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The Prevention and Treatment of Complications of Diabetes Mellitus A Guide for Primary Care Practitioners

Department of Health and Human Services, Public Health Service, Centers for Disease Control, National Center for Chronic Disease Prevention and Health Promotion, Division of Diabetes Translation

Publication date: 01/01/1991


Table of Contents

Foreword

Preface

Psychosocial Problems
Prevention
Detection
Treatment
References

Acute Glycemic Complications
Diabetic Ketoacidosis; Background
Prevention
Guidelines for Sick Days
Record for Sick Days
Detection
Treatment
Hyperglycemic Hyperosmolar Nonketotic Coma
Prevention
Detection
Treatment
Hypoglycemia
Prevention
Detection
Treatment
Teaching Patients to Avoid Acute Glycemic Complications
References

Adverse Outcomes of Pregnancy
Pregestational and Gestational Diabetes; Background
Caring for the Patient With Pregestational Diabetes
Treatment
Caring for the Patient With Gestational Diabetes
Treatment
References

Disease
Prevention
Detection
Treatment
References

Eye Disease
Prevention of Diabetic Retinopathy
Detection and Monitoring of Diabetic Retinopathy
Treatment and Referral
References

Kidney Disease
Prevention
Detection
Treatment
References

Cardiovascular Disease
Prevention
Detection
Treatment
References

Neuropathy
Prevention
Detection
Differential Diagnosis
Treatment
References

Foot Problems
Prevention
Detection and Monitoring
Treatment
References

Appendix A, Office Guide

Acknowledgments

POINT OF CONTACT FOR THIS DOCUMENT:

Tables
Clinical Manifestations Of Eye Diseases
Example of An Office Guide

Figures
Natural History Of Diabetic Nephropathy In Persons With Insulin


Foreword

The 1982 publication of The Prevention and Treatment of Five Complications of Diabetes: A Guide for Primary Care Practitioners was an initial attempt to provide straightforward and practical information that primary care practitioners could immediately apply in their practice in the diagnosis and prevention of complications of diabetes. In the eight years since that publication was released, over 200,000 copies have been distributed. The emphasis on early application of currently available preventive measures or treatments has resulted in the widespread use of the document.

The scope of the present revised edition has been broadened to cover nine complications of diabetes, and the recommendations for the previous five. We anticipate continued widespread use of this guide in assisting practitioners in the care of their patients with diabetes. The recommendations are clear, practical, and based upon scientific evidence, and they can be generally implemented in an office practice. We believe that they are conceptually consistent with the American Medical Association's new emphasis on practice parameters.

Although this publication is meant to provide freestanding and practical assistance in an office practice, the most appropriate use is in continuing education programs and workshops. In these settings, the practical application of the recommendations can be discussed and barriers to their application in individual practices overcome.

We congratulate the Centers for Disease Control in its efforts to update this guide and wish it the same success as the previous edition.

Charles M. Clark, Jr., M.D.
Indiana University School of Medicine
Indianapolis, Indiana


Preface

This publication is designed to help the primary care practitioner in the day-to-day management of patients with diabetes. The recommendations relate to the prevention, detection, and treatment of the major complications of diabetes. The emphasis is on early application of currently available measures that, if systematically applied, may reduce the incidence or severity of these complications. Because of the need for brevity and practicality, we have neither discussed areas of controversy nor provided in-depth discussions of pathophysiology and the scientific rationale for treatment.

An office guide is included as an appendix. The office guide is a brief synopsis of the recommendations contained in the body of the text and is designed so that it may be photocopied and placed in the patient's medical record.

A companion publication entitled Take Charge of Your Diabetes: A Guide for Patients is available. It is written in nontechnical language and emphasizes the same preventive measures and treatments. The sequence of the chapters corresponds with the sequence in this document.

William H. Herman, M.D.
University of Michigan Medical Center
Ann Arbor, Michigan


Psychosocial Problems

Background--

Description. Like other chronic illnesses, diabetes mellitus poses a wide range of problems for patients and their family members. These problems include pain, hospitalization, changes in lifestyle and vocation, physical disabilities, and threatened survival. Direct psychological consequences can arise from any one of these factors, making it harder for patients to treat their diabetes and live productive, enjoyable lives.

Populations at risk --

Diabetes itself does not cause changes in personality or psychiatric illness, but particular subgroups of the diabetic population appear to be at risk for developing psychosocial problems. Young people with insulin- dependent diabetes mellitus (IDDM) may have a higher prevalence of eating disorders, such as anorexia nervosa and bulimia, and adults with longstanding diabetes and major medical complications have a higher prevalence of symptoms of depression and anxiety. Elderly persons who have non-insulin-dependent diabetes mellitus (NIDDM) and other symptomatic medical conditions may also have a higher risk of developing psychological problems.

Patients with IDDM diagnosed before age 5 and older patients with NIDDM may have associated alterations in cognitive or intellectual functioning. The pathophysiology of these cognitive changes is not well understood. In the young patients, these cognitive changes may be linked to recurring episodes of severe hypoglycemia. In the older patients, both microvascular and artherosclerotic disease are possible factors.

Barriers to self-care.

Research has indicated that psychological and social factors can profoundly influence a patient's success at adhering to a prescribed regimen of self- care. Patients may fail to care for themselves if they have certain attitudes or beliefs, including the following:

Several other psychosocial factors can influence how well patients care for themselves:

Prevention

To help anticipate or identify psychosocial problems that could interfere with a patient's self-care regimen, the practitioner should strive to establish an ongoing, therapeutic alliance with the patient. The stronger the alliance, the more likely the patient is to share inner concerns and psychosocial issues. This leads to improved detection and permits more rapid institution of treatment.

This therapeutic alliance will take shape over time, through discussions identifying the patient's expectations of, and feelings about, treatment. Although the patient should not be forced to set particular goals, the practitioner may be able to broaden or refine existing objectives to include improving the patient's adjustment to having diabetes.

Over time, this alliance may lead to better glycemic control by helping the patient address such self-care barriers as low motivation, preconceived judgments about treatment, and fears about diabetes.

Detection

The practitioner should be sensitive to possible psychosocial issues when diabetes is first diagnosed and when complications, however minor, first develop.

Some psychosocial barriers stem from personal, family, and cultural beliefs that may conflict with suggested treatment. A patient may resist following a prescribed diet, for instance, because of certain cultural beliefs about weight. Such beliefs should be given their due respect; patients respond best to advice that does not seem to prejudge their beliefs.

Certain medical conditions can be reliable indicators of Psychosocial barriers. Recurrent hypoglycemia, frequent episodes of diabetic ketoacidosis, and very high glycosylated hemoglobin levels should each be recognized as a possible sign of personal or family problems. Although brittle, or unstable, diabetes can sometimes have a metabolic basis, interrupted or erratic self-care is by far a more common cause--and psychosocial problems may underlie this cause.

To help uncover problem areas, the practitioner may want to conduct discussions along the following lines:

The practitioner may then be able to counsel patients and provide useful solutions.

Treatment

Try to actively engage the patient in determining as well as pursuing a course of treatment. Ask the patient both specific and open-ended questions. Open-ended questions may elicit information that can help detect problems as well as tailor the course of treatment. Such discussions may identify individual strengths and problem-solving strategies that have helped the patient successfully face previous challenges.

The practitioner will need to identify, for possible referral, mental health professionals who are knowledgeable about diabetes and who can serve as collaborators in treating the patient. If these individuals are not familiar with diabetes, they can be given materials (such as this guide) that provide basic information.

Refer the following persons:

Remember that diabetes is a chronic illness. Even if treatment activities fail to bring change within a short time, remaining involved with the patient and the patient's family and providing an accepting atmosphere may lead to increased motivation for change.

Encourage patients and their families to attend group sessions. Medical and psychosocial information can be given at these sessions, which can also provide a forum for discussion of personal concerns. These sessions can be led by health care professionals, including physicians, nurses, and dietitians, and may meet several times a year. Local diabetes organizations may sponsor or know of such groups.

Patient Education Principles:

References

Bradley C. Psychological aspects of diabetes. In: Alberti KGMM, Krall LP, eds. The Diabetes Annual/1. New York: Elsevier, 1985.

Feste C. The Physician Within. Minneapolis: Diabetes Center, 1987.

Jacobson AM, Hauser ST. Behavioral and psychological aspects of diabetes. In: Ellenberg M, Rifkin H, eds. Diabetes Mellitus: Theory and Practice. 3rd ed. Vol. 2. New Hyde Park, New York: Medical Examination, 1983.


Acute Glycemic Complications

Introduction--

In diabetes mellitus, severe hyperglycemia may result from absolute or relative insulin deficiency. In some patients, the condition may culminate in diabetic ketoacidosis or hyperglycemic hyperosmolar nonketotic coma. Profound hypoglycemia may result from a relative excess of insulin. Symptoms associated with acute hyperglycemia generally develop more slowly (over hours or days) than do symptoms associated with an acute fall in the level of blood glucose (over minutes).

Diabetic Ketoacidosis; Background

Definition. Diabetic ketoacidosis (DKA) develops when absolute insulin deficiency and excess contra-insulin hormones increase hepatic glucose production, decrease peripheral glucose utilization, and stimulate release of fatty acids from fat cells and production of ketones by the liver. These changes cause hyperglycemia, osmotic diuresis, volume depletion, and acidosis.

Occurrence. The annual incidence of DKA ranges from three to eight episodes per 1,000 persons with diabetes. It is much more common among persons with insulin-dependent diabetes mellitus (IDDM) than among those with non-insulin-dependent diabetes mellitus (NIDDM).

DKA may be the initial manifestation of previously unrecognized IDDM. More often, DKA develops in persons known to have diabetes. Patients with IDDM who fail to take insulin or who do not receive extra insulin during flulike illness, pneumonia, or myocardial infarction may develop DKA. Patients with NIDDM who experience severe stress may secrete more contra-insulin hormones; these further compromise limited insulin secretion, which may in turn lead to DKA.

Morbidity and mortality. Before insulin was available, patients with diabetes often died of DKA; now, the mortality rate associated with DKA is less than 5%. However, persons who develop DKA experience pain and suffering, lose time from school or work, have increased hospitalization rates, and have high medical costs. Serious medical sequelae include cerebral edema (in young people), aspiration pneumonia, and adult respiratory distress syndrome.

Prevention

Why DKA occurs. Ultimately, DKA results from lack of insulin. Early recognition of metabolic disarray, by monitoring glucose and ketones and by properly using exogenous insulin and fluids, can prevent further decompensation. Thus, DKA should be considered preventable. Said differently, when DKA occurs, a breakdown in care has occurred that should have been prevented.

Three general circumstances may allow DKA to develop:

Index of suspicion. Many people may not know the signs and symptoms of diabetes. At times, even when a person seeks medical help, a health care provider may fail to recognize the warning signs of hyperglycemia--particularly when the patient is very young (an infant), is very old (such as an octogenarian), or has unusual symptoms (such as mental deterioration without nausea or vomiting).

Therefore, to prevent DKA or to minimize its extent, the health care provider must have a high index of suspicion for DKA. In emergency rooms, clinics, and physicians' offices, routine use of a glucose/ketone urine dipstick may allow for early identification of decompensating diabetes.

Inappropriate cessation of insulin therapy. Under circumstances such as those described below, insulin therapy may be inappropriately discontinued.

Intercurrent illness. Both patients and health care providers may incorrectly assume that when no food or fluid is consumed, no insulin should be taken. However, when ill or stressed, the patient with diabetes should promptly test the glucose level in blood and/or urine and test the urine for ketones. The patient should follow a sick-day protocol and consult with the health care provider. Both patients and providers must understand the proper management of diabetes during intercurrent illness. (See "Guidelines for Sick Days".)

Analysis and referral. For the patient who has experienced DKA, the health care provider should do the following:

When recurrent episodes of DKA occur, the practitioner should determine the medical and psychosocial components of the episodes. Patients with difficult-to-manage IDDM should be referred to a diabetologist. Patients with underlying psychosocial problems should be referred to a mental health professional.

The guidelines and record for sick days on the following page are adapted from Take Charge of Your Diabetes: A Guide for Patients. Review these guidelines and discuss them with patients before illness occurs. Explain how to keep a record, and stress the importance of self-monitoring.

Guidelines for Sick Days

Keep a daily record of your sick days by following the guidelines below. If you feel too sick to follow any of these guidelines, ask a family member or a friend to help you. By following these instructions and by keeping a diary, you can work with your health care provider to feel better.

Health care provider's name:

Health care provider's telephone number:

1. If you feel too sick to eat normally, call your health care provider right away. Describe in detail how you feel. 2. Keep taking insulin when you feel sick. Don't stop taking insulin even if you can't eat. Your health care provider may change your insulin dose or may tell you to drink liquids that have sugar in them.
3. Weigh yourself every day and write down your weight. 4. Take your temperature every morning and evening. Write down the readings. (For small children or for someone who is breathing through the mouth, use a rectal thermometer.) If your temperature is above normal (99 F), drink extra liquids.
5. If you weigh 80 pounds or more, try to drink at least 12 eight- ounce glasses of liquid per day. Write down how much you drink. If you throw up, call your health care provider right away. You may need to go to the hospital or have special medical treatment. 6. Every 4 hours or before every meal, measure the glucose level in your blood. Write down the results. If the level is less than 60 mg/dL or consistently higher than 240 mg/dL, call your health care provider. Every 4 hours or each time you pass urine, test your urine for ketones and write down the results.
7. If you start to have trouble breathing, call your health care provider (or have someone do it for you) or go to a nearby emergency room. 8. Every 4 to 6 hours, write down whether you feel awake or sleepy. If you feel very sleepy or can't concentrate, have someone call your health care provider right away.
9. If your health care provider asks you to, call every day to describe your daily record (see "Record for Sick Days" below). Your health care provider may adjust your daily insulin dosage.

Record for Sick Days

How often                Question                      Answer
Every day           How much do you weigh
                    today?                             _____ pounds
Every evening       How much did you drink
                    today?                             _____ glasses
Every morning       What is your temperature?          AM ______
and every evening                                      PM ______
Every 4 hours       How much medication                Time        Dose
or before           did you take?                      ______      ______
every meal                                             ______      ______
                                                       ______      ______
                                                       ______      ______
                                                       ______      ______
                                                       ______      ______

Every 4 hours       What is the level of                Time      Level
or before           glucose in your blood?             ______     ______
every meal                                             ______     ______
                                                       ______     ______
                                                       ______     ______
                                                       ______     ______
                                                       ______     ______

Every 4 hours       What is the level of                Time      Level
or each time        ketones in your urine?              ______    ______
you pass urine                                          ______    ______
                                                        ______    ______
                                                        ______    ______
                                                        ______    ______
                                                        ______    ______

Every 4 to          How are you                         Time      Condition
6  hours             breathing?                         ______    ______
                                                        ______    ______
                                                        ______    ______
                                                        ______    ______
                                                        ______    ______
                                                        ______    ______

If you feel unusually sleepy or can't concentrate, have someone call your health care provider or take you to an emergency room.

Detection

Symptoms. Suspect diabetes and DKA in any person at any age who has symptoms compatible with hyperglycemia and ketosis, including:
Results of a simple glucose/ketone urine dipstick may give guiding information about the presence of diabetes or DKA. If glucose or ketones are present in the urine, the blood glucose level must be measured.

Monitoring. All patients with IDDM should be taught to prevent DKA. Encourage patients to monitor their blood glucose level and advise them to monitor the urine for ketones when the blood glucose level is 240 mg/dL or more and/or acute illness develops.

Insist that patients contact you promptly when the blood glucose level remains at 240 mg/dL or more, ketonuria develops, or acute illness persists.

Periodically assess how proficient patients are with self- monitoring and reassess their understanding of self-care during acute illness. (See "Guidelines for Sick Days".)

Treatment

Identify the causes of DKA by taking a thorough history, performing a physical examination, and requesting appropriate laboratory tests. In adult patients, an electrocardiogram should be performed to rule out a silent acute myocardial infarction. Treatment should be initiated while this information is being collected.

If DKA is mild and the patient is quickly responding to therapy, replacement of fluids, electrolytes, and insulin may occur in the emergency room. If DKA is more severe, hospitalize the patient at once to ensure adequate treatment and monitoring of the clinical state until recovery ensues. An intensive care unit is the preferred site for the treatment of severe DKA.

Health care providers whose experience with DKA is episodic and infrequent should not hesitate to arrange for the patient's prompt referral to a specialist experienced in the care of patients with DKA. A detailed summary of the treatment of DKA is available in the American Diabetes Association's Physician's Guide to Insulin- Dependent (Type 1) Diabetes.

Note: See "Patient Education Principles".

Hyperglycemic Hyperosmolar Nonketotic Coma

Background--

Definition. Hyperglycemic hyperosmolar nonketotic coma (HHNKC) is characterized by severe hyperglycemia (glucose level typically greater than 600 to 800 mg/dL), dehydration, and altered mental status -- in the absence of ketosis. In HHNKC, hyperglycemia causes glycosuria. Osmotic diuresis results in volume contraction and a reduction in both the glomerular filtration rate and glucose excretion. Worsening hyperglycemia causes further extracellular hypertonicity and intracellular dehydration.

Central nervous system dysfunction in persons with HHNKC is probably due to hyperosmolarity. The absence of ketosis has not been entirely explained but may be due to the secretion of insulin in amounts sufficient to suppress ketogenesis.

Occurrence. HHNKC occurs most often among persons over 60 years of age. Most persons with HHNKC have a history of NIDDM, but in a sizable minority, NIDDM is undiagnosed or untreated. When persons who are chronically ill, debilitated, or institutionalized have mild renal insufficiency and lack normal thirst mechanisms or access to water, they are at risk of developing HHNKC. Acute illnesses (stroke, myocardial infarction, or pneumonia), drugs (diuretics or glucocorticoids), surgery, and, occasionally, large glucose loads (through enteral or parenteral nutrition or peritoneal dialysis) may precipitate HHNKC.

Severity. The mortality rate for HHNKC has been reported to be as high as 50%, primarily because of the age of the population most at risk and the acute precipitating causes.

Prevention

Be alert to the elderly patient who:
For persons with several of these characteristics, periodically monitor the glucose level in the urine or blood. (Monitoring blood glucose is preferred.) If the fasting blood glucose level is above 200 mg/dL, monitor the glucose level more frequently and initiate or adjust hypoglycemic medications as necessary.

Early diagnosis of diabetes or early identification of worsening hyperglycemia will permit appropriate therapy that will prevent the development of HHNKC.

Detection

The patient with HHNKC has severe hyperglycemia and azotemia without ketoacidosis. The intravascular volume is contracted, and the patient shows signs and symptoms of hypovolemia and severe dehydration. Both diffuse and focal central nervous system deficits may occur. These may include hallucinations, aphasia, nystagmus, hemianopsia, hemiplegia, hemisensory deficits, and focal or grand mal seizures. Coma may ensue.

Treatment

Therapy is primarily directed at replacement of fluid and electrolytes while supportive care is given. Insulin therapy is designed to slowly --over 24 to 48 hours--return the blood glucose level to a near normal range.

When therapy is successful, the patient may be significantly sensitive to further insulin. Ultimately, the patient may achieve metabolic control through diet and/or oral agents.

Note: See "Patient Education Principles".

Hypoglycemia

Background--

Occurrence. Any person with diabetes who takes an oral hypoglycemic agent or insulin may experience low blood glucose. Severe hypoglycemia occurs more often in patients who are following an intensified insulin therapy protocol (with the target glucose level near the normal range), whose diet and activity vary widely, who have a long duration of diabetes, and/or who have autonomic neuropathy. Patients with a history of severe hypoglycemia are at increased risk for future episodes. Often the cause is multifactorial. A delay or decrease in food intake, vigorous physical activity, and alcohol consumption all may contribute.

Prevention

Patient education and self-monitoring of blood glucose are the best approaches to preventing hypoglycemia.

By emphasizing the relation between hypoglycemia and delayed or decreased food intake or increased physical activity, you may help patients anticipate and avoid the condition. If patients regularly and correctly monitor their blood glucose level, impending hypoglycemia may be avoided. Patients who know how to treat hypoglycemia can reduce its impact and severity.

To minimize the risk of hypoglycemia, cooperation is required between the patient, family members, other persons close to the patient (including friends, teachers, and colleagues), and health care providers. Stress the importance of such persons knowing the signs and symptoms of hypoglycemia and how to treat it.

Detection

Clinical hypoglycemia (blood glucose level below approximately 60 mg/dL) is associated with adrenergic symptoms (apprehension, tremors, sweating, or palpitations) and neuroglycopenic symptoms (fatigue, headache, confusion, coma, or seizure). Usually, the symptoms of low blood glucose are mild, related to catecholamine release, and easily treated by the patient.

Severe hypoglycemia occurs when the patient ignores, inappropriately treats, lacks, or does not recognize the early warning signs or when glucose counterregulation fails to return the blood glucose level to normal.

Treatment

Guidelines for treating hypoglycemia are as follows:

Person                             Action
_________________________________________________________________________

Patient        Eat 10 to 15 grams of rapidly absorbable carbohydrate (3 to
               5 pieces of hard candy, 2 to 3 packets of sugar, or 4 ounces
               of fruit juice) to abort the episode. Repeat in 15 minutes,
               as necessary.

Friend or     If the patient is unable to treat himself or herself,
family        administer oral carbohydrate.  If the patient is unable to
member        swallow, administer glucagon subcutaneously or
              intramuscularly. For children younger than 3 years of age,
              give 0.5 mg glucagon; for children 3 years of age and older
              and for adults, give 1.0 mg.

Practitioner  If the patient shows signs and symptoms of severe
              hypoglycemia, administer glucagon or inject 25 grams of
              sterile 50% glucose intravenously.

              Analyze the cause of the episode. Often, a modest reduction
              in the insulin dosage should be advised. Reeducate the
              patient about preventing hypoglycemia by discussing the
              timing of meals and physical activity, the use of alcohol,
              and the frequency of self-monitoring of blood glucose.

              Those patients who develop hypoglycemia while taking oral
              hypoglycemic agents should be closely monitored for at least
              48 to 72 hours to prevent a possible recurrence.

Teaching Patients to Avoid Acute Glycemic Complications

Thorough and repetitive patient education is essential to preventing the development of acute glycemic complications. In particular, teach patients how to care for themselves when they are ill and how to monitor themselves.

Patient Education Principles:
For patients with diabetic ketoacidosis--

For patients with hyperglycemic hyperosmolar nonketotic coma--

For patients with hypoglycemia--

References

Bergenstal RM. Diabetic ketoacidosis. Postgraduate Medicine. 1985;77:151-161.

Butts DE. Fluid and electrolyte disorders associated with diabetic ketoacidosis and hyperglycemic hyperosmolar nonketotic coma. Nursing Clinics of North America. 1987;22:827-836.

Carroll P, Matz R. Uncontrolled diabetes in adults. Diabetes Care. 1983;6:579-585.

Casparie AF, Elzing LD. Severe hypoglycemia in diabetic patients. Diabetes Care. 1985;8:141-145.

Consensus statement of self-monitoring of blood glucose. Diabetes Care. 1987;10:95-99.

The DCCT Research Group. Diabetes Control and Complications Trial (DCCT): results of feasibility study. Diabetes Care. 1987;10:1-19.

Foster DW, McGarry JD. The metabolic derangements and treatment of diabetic ketoacidosis. New England Journal of Medicine. 1983;309:159-169.

Keller U. Diabetic ketoacidosis: current views on pathogenesis and treatment. Diabetologia. 1986;29:71-77.

Kitabchi AE, Matteri R, Murphy MB. Optimal insulin delivery in diabetic ketoacidosis and hyperglycemic, hyperosmolar nonketotic coma. Diabetes Care. 1982;5(suppl 1):78-87.

Physician's Guide to Insulin-Dependent (Type I) Diabetes: Diagnosis and Treatment. Alexandria, Virginia: American Diabetes Association, 1988.

Physician's Guide to Non-Insulin-Dependent (Type II) Diabetes: Diagnosis and Treatment. 2nd ed. Alexandria, Virginia: American Diabetes Association, 1988.

Sperling MA. Diabetic ketoacidosis. Pediatric Clinics of North America. 1984;31:591-610.


Adverse Outcomes of Pregnancy

Introduction--

When a woman who is known to have diabetes becomes pregnant, she is said to have pregestational diabetes. When a woman develops diabetes during pregnancy or is first recognized as having this condition during pregnancy, she is said to have gestational diabetes. Each year, approximately 10,000 infants are born to women with pregestational diabetes, and 60,000 to 90,000 infants are born to women with gestational diabetes.

The factor most important to the outcome of pregnancy is how well the mother's glucose level is controlled before and during pregnancy. When women with diabetes receive optimal care, the perinatal mortality rate for their offspring approaches the corresponding rate for the general population. However, when pregnant women with diabetes do not receive expert treatment, the perinatal mortality rate for their offspring more than doubles.

Pregestational and Gestational Diabetes; Background

Metabolic changes. Normal pregnancy is characterized by increasing insulin resistance, which is probably due to human placental lactogen, a growth-hormone-like protein secreted by the placenta. Although pregnant women develop compensatory hyperinsulinemia, postprandial glucose levels increase significantly throughout pregnancy. During late pregnancy, fasting glucose levels fall because of increased glucose consumption by the placenta and the fetus.

Human placental lactogen reaches its peak late in pregnancy; during the third trimester, insulin requirements rise. Gestational diabetes most often appears during this period of maximum insulin resistance, and ketoacidosis may be seen -- particularly in patients with insulin-dependent diabetes mellitus who do not increase their insulin dose appropriately.

Effect on the fetus. Because glucose crosses the placenta by facilitated diffusion, maternal hyperglycemia produces fetal hyperglycemia. Fetal hyperinsulinemia occurs in response to this abnormal metabolic environment. Hyperinsulinemia, combined with hyperglycemia, leads to excessive fetal growth. It may also contribute to intrauterine fetal death, delayed fetal pulmonary maturation, and neonatal hypoglycemia.

The incidence of major congenital malformations is increased approximately fourfold among infants of women with pregestational diabetes. Approximately 9% of pregnancies complicated by pregestational diabetes result in the birth of infants with central nervous system, cardiac, renal, skeletal, and other malformations. Major malformations may occur in 20% to 25% of infants born to women with very poor glycemic control during organogenesis, as evidenced by markedly elevated glycosylated hemoglobin levels during the first trimester.

Other factors that may increase the risk for fetal anomalies include early age at onset of maternal diabetes and microvascular disease in the mother. The earlier the age at onset of pregestational diabetes, the worse the prognosis is for successful pregnancy.

Effect on the mother. Pregnancy may be associated with exacerbation of diabetic eye disease, especially in women with unrecognized or untreated proliferative diabetic retinopathy. Diabetic women with nephropathy and hypertension are at greater risk for preeclampsia and fetal growth retardation than are women without nephropathy. Death has been reported among pregnant women with diabetes and coronary artery disease.

Caring for the Patient With Pregestational Diabetes

Prevention --

The outcome of pregnancy complicated by pregestational diabetes is improved when care begins before conception. Each visit with a woman of childbearing age who has diabetes should be considered a preconceptional visit. Discuss family planning and ask the patient her thoughts about a future pregnancy.

Results of a glycosylated hemoglobin test provide overall assessment of glycemic control. Pregnancy should be deferred until excellent glycemic control is achieved, as indicated by a normal or near normal glycosylated hemoglobin level. Counsel patients about nutrition and teach them how to monitor their blood glucose levels and how to adjust their insulin treatment.

For patients who are planning to become pregnant, establish baseline data that can be used to assess maternal and perinatal risk, including the following:

Patients whose pregnancy is complicated by diabetes often experience significant emotional and financial stresses. Assess the patient's emotional or psychosocial support and financial resources through discussion with the patient, her partner, and her family.

Emphasize the dangers of smoking and of consuming alcohol when pregnant.

Treatment

Health care team. An experienced health care team is required to care for a patient with pregestational diabetes. The team should include the following persons:

Every effort should be made to refer patients to medical centers that can provide comprehensive support. If such referral is not possible, members of the health care team should frequently consult with each other by telephone.

Glucose level. Excellent control of maternal diabetes is a critical objective both before and during pregnancy. During normal pregnancy, mean maternal plasma glucose levels rarely exceed 120 mg/dL and range from fasting levels of 60 mg/dL to 2-hour postprandial levels of 120 mg/Dl. Use these values as the therapeutic objective for patients whose pregnancies are complicated by pregestational diabetes.

Diet. During the latter half of pregnancy, the patient with pregestational diabetes needs to eat approximately 35 kilocalories per kilogram of her ideal prepregnancy body weight each day, or approximately 2200 to 2400 calories per day. A weight gain of 24 to 28 pounds is recommended for most patients; however, for obese patients with noninsulin-dependent diabetes mellitus, the preferred daily dietary intake is 25 kilocalories per kilogram of ideal prepregnancy body weight, or approximately 1600 to 1800 calories per day.

The calories should be derived as follows: approximately 50% from complex carbohydrates, 30% from fats, and 20% from proteins. Patients will require three meals and up to three snacks each day. A bedtime snack is particularly important to decrease the risk of nocturnal hypoglycemia.

Monitoring. Patients with insulin-treated diabetes should monitor their blood glucose levels at least four times a day -- either before or 2 hours after each meal and at bedtime. Before breakfast, patients should test for ketones in their urine. Ask patients to record results in a log book and to note any changes in diet and exercise and any problems with hypoglycemia.

Measure the glycosylated hemoglobin level at least once each trimester to assess overall glycemic control.

Insulin therapy. Patients treated with oral hypoglycemic agents should be switched to insulin before they become pregnant. Human insulin should generally be used. Patients with insulin-treated diabetes require an individualized insulin regimen based on their exercise plan and blood glucose levels.

Most patients will require at least two injections a day of a mixture of intermediate-acting (NPH or lente) and short-acting (regular) insulin. Selected patients may be treated with multiple daily injections (that is, regular insulin before each meal and an injection of intermediate- or long-acting ultralente| insulin at bedtime). For some patients, continuous subcutaneous insulin infusion is an option, but it appears to offer no significant advantage over multiple daily injections. Patients who prefer the flexibility offered by the pump may be started on such therapy, and those who have used a pump before pregnancy may continue to do so.

Fetal assessment. Maintain a program of fetal assessment throughout pregnancy. Measure the maternal serum alpha-fetoprotein level at 16 weeks of gestation to screen for neural tube defects and other fetal anomalies. Perform a detailed ultrasonographic examination at 16 to 18 weeks of gestation. If indicated, assess the fetal cardiac structure by echocardiography at 20 weeks of gestation. When performed by experienced professionals, such tests allow detection of most major fetal malformations. If an anomaly is found, skilled counseling must be provided for the patient.

During the third trimester, assessment of fetal growth and well- being becomes most important. Fetal growth may be evaluated by serial ultrasonographic examination every 4 to 6 weeks. Fetal well-being may be determined by a variety of techniques, including the following:

Although these tests may be initiated at 28 weeks of gestation, they are most often begun at 32 weeks and performed once or twice a week until delivery.

Delivery. If the patient maintains excellent glucose control, if her blood pressure is normal, and if antepartum fetal testing shows no evidence of fetal compromise, delivery may occur at term. If delivery is planned before term, assess fetal pulmonary maturation by measuring the ratio of amniotic fluid lecithin to sphingomyelin (L/S) and the level of acidic phospholipid phosphatidyglycerol. If ultrasound suggests excessive fetal size, delivery by cesarean section may be elected.

Delivery must take place where expert maternal and neonatal care are available. Breast-feeding should be encouraged.

Postpartum care. In the immediate postpartum period, reassess the patient's meal plan and adjust her treatment program. Maternal insulin requirements fall significantly, usually to- or even below- prepregnancy levels.

During the patient's postpartum follow-up visit, encourage her to diet, if necessary, to achieve her ideal body weight. Contraception should be discussed. Low-dose oral contraceptives or a progestin-only pill may be offered to patients who have no evidence of hypertension or vascular disease. For patients with hypertension or vascular disease, a barrier method of contraception, such as a diaphragm, is preferred. If the patient has completed her family or if she has serious vascular disease, sterilization should be discussed.

Caring for the Patient With Gestational Diabetes

Detection --

Screening. All pregnant women should be screened for gestational diabetes. If only those patients with recognized historical or clinical risk factors are screened, a significant number of cases of gestational diabetes will be missed.

Timing. Screen for gestational diabetes at approximately 24 to 28 weeks of gestation. Screening may be indicated before 24 weeks if the patient has a history of any of the following:

Method for screening. Patients need not be fasting when the screening test is performed. Use a 50-gram oral glucose load and measure the patient's glucose level after one hour. If the venous plasma glucose is 140 mg/dL or higher, schedule a 100-gram oral glucose tolerance test (see next paragraph).

Method for diagnosis. In pregnancy, the oral glucose tolerance test should be performed as follows:

___________________________________________________________________________

   Time of                  Glucose
   Test                     Concentration
___________________________________________________________________________
     Fasting                  105 mg/dL
     After glucose
        1 hour                190 mg/dL
        2 hours               165 mg/dL
        3 hours               145 mg/dL
___________________________________________________________________________


Although blood glucose measurements using glucose-oxidase-impregnated test strips are useful for monitoring treatment, they are not sufficiently precise for diagnostic purposes. Glycosuria and glycosylated hemoglobin tests are also not sensitive enough to be used to diagnose gestational diabetes.

Treatment

Most women with gestational diabetes can be cared for as outpatients. The patient should be seen at 1- to 2-week intervals to assess glucose control, weight gain, and blood pressure. The patient may need to be hospitalized if she does not maintain acceptable glucose control or if she develops hypertension or an infectious complication such as pyelonephritis.

Diet. Dietary therapy is the mainstay of treatment for patients with gestational diabetes. The daily dietary plan should contain approximately 2000 to 2400 calories distributed among three meals and a bedtime snack.

Monitoring. Ideally, the efficacy of the diet is assessed by daily self-monitoring of blood glucose. Weekly measurements of fasting and postprandial glucose levels are also an acceptable method of monitoring.

Pharmacologic therapy. If the fasting plasma glucose level exceeds 105 mg/dL and/or the 2-hour postprandial value exceeds 120 mg/dL, treatment with human insulin should be initiated. Patients who require insulin should be instructed in glucose self-monitoring.

Oral hypoglycemic agents should not be used during pregnancy.

Fetal assessment. Patients with insulin-treated gestational diabetes require a program of fetal surveillance identical to that recommended for patients with pregestational diabetes (see the earlier discussion). Begin fetal surveillance by 34 weeks of gestation for patients with non-insulin-treated gestational diabetes who develop preeclampsia or have a history of intrauterine death. Begin fetal surveillance at 40 weeks of gestation for patients with uncomplicated non-insulin-treated gestational diabetes who have not delivered.

Postpartum care. All patients with gestational diabetes should undergo a 75-gram oral glucose tolerance test at 6 to 8 weeks postpartum to determine whether abnormal carbohydrate metabolism has persisted.

The glucose tolerance test should be performed as follows:

__________________________________________________________________________
                       Glucose Concentration
__________________________________________________________________________
                   Normal              Impaired
Time of            Glucose             Glucose            Diabetes
Test               Tolerance           Tolerance          Mellitus
___________________________________________________________________________

Fasting             <115 mg/dL          <140 mg/dL          >140 mg/dL
                      and                   and                 or
After glucose       <200 mg/dL          1 value >200        1 value>200
(30, 60, and           mg/dl               mg/dL               mg/dL
90 minutes)             and                 and                 and
120 minutes        <140 mg/dL           >140 mg/dL          >200 mg/dL
                                          but <200
                                           mg/dL
--------------------------------------------------------------------------

Encourage patients to achieve their ideal body weight to decrease their likelihood of developing non-insulin-dependent diabetes mellitus. Patients with a history of gestational diabetes should be annually evaluated for onset of diabetes.

For contraception, patients may use low-dose oral contraceptive pills, progestin-only pills, or barrier methods.

Patient Education Principles:
For patients with pregestational diabetes

For patients with gestational diabetes --

For patients with a history of gestational diabetes--

References

Freinkel N, Dooley SL, Metzger BE. Care of the pregnant woman with insulin-dependent diabetes mellitus. New England Journal of Medicine. 1985;313:96-101.

Freinkel N, Gabbe SG, Hadden DR, et al. Summary and recommendations of the Second International Workshop-Conference on Gestational Diabetes Mellitus. Diabetes. 1985 ;34(suppl 2):123-126.

Fuhrmann K, Reiher H, Semmler K, Fischer F, Fischer M, Glockner E. Prevention of congenital malformations in infants of insulin- dependent diabetic mothers. Diabetes Care. 1983;6:219-223.

Gabbe SG. Management of diabetes mellitus in pregnancy. American Journal of Obstetrics and Gynecology. 1985;153:824-828.

Greene MF, Hare JW, Cloherty JP, et al. First-trimester hemoglobin A(1) and risk for major malformation and spontaneous abortion in diabetic pregnancy. Teratology. 1989;39:225-231.

Landon MB, Gabbe SG. Glucose monitoring and insulin administration in the pregnant diabetic patient. Clinical Obstetrics and Gynecology. 1985;28:496-506.

Mills JL, Knopp RH, Simpson JL. et al. Lack of relation of increased malformation rates in infants of diabetic mothers to glycemic control during organogenesis. New England Journal of Medicine. 1988;318:671-676.

Mills JL, Simpson JL, Driscoll SG, et al. Incidence of spontaneous abortion among normal women and insulin-dependent diabetic women whose pregnancies were identified within 21 days of conception. New England Journal of Medicine. 1988;319:1617-1623.

Schwartz R. The infant of the diabetic mother. In: Davidson JK, ed. Clinical Diabetes Mellitus. New York: Thieme. 1986.

Steel JM. Prepregnancy counseling and contraception in the insulin- dependent diabetic patient. Clinical Obstetrics and Gynecology. 1985;28:553-566.


Disease

Background

Definition. The term periodontal disease describes a group of localized infections that affect the tissue surrounding and supporting the teeth.

The two most common forms of periodontal disease are gingivitis and periodontitis. Gingivitis, an early and reversible condition, is an inflammation of the soft tissues surrounding the teeth. Persons with gingivitis have tender, edematous, red gums that may bleed upon gentle pressure, such as from toothbrushing.

Periodontitis is a progressive inflammatory condition that destroys periodontal ligament fibers and alveolar bone and can eventually cause tooth loss. Although gingivitis usually precedes periodontitis, not all gingivitis progresses to periodontitis.

For all persons, the keys to preventing periodontal disease are good oral hygiene and regular dental care. A third element crucial to persons with diabetes is good glycemic control; poorly controlled diabetes can invite or promote periodontal disease.

Occurrence. disease is widely prevalent. Forty to 50% of U.S. adults report gingival bleeding, and over 80% of adults have objective evidence of previous periodontal disease. The prevalence and severity of periodontal disease increase markedly with age. Eight percent of adults younger than age 65 and 34% of adults 65 and older have evidence of advanced periodontal destruction.

Among children and adolescents with poorly controlled insulin- dependent diabetes mellitus and among adults with poorly controlled non-insulin-dependent diabetes mellitus, the prevalence of periodontal disease is considerably greater than it is among their nondiabetic peers. The severity of periodontal disease is also usually greater among persons with diabetes.

Pathophysiology. disease is initiated by the toxic

metabolic products of bacteria in dental plaque. Other associated factors include smoking, vitamin C deficiency, dental restorations, and prostheses.

disease appears to be aggravated by increased levels of blood glucose and by other conditions associated with poor glycemic control. Altered microbial flora, impaired immunity, vascular changes, and abnormal collagen metabolism may contribute to the development and severity of periodontal disease among persons with diabetes.

Prevention

Effective self-care is essential to periodontal health. To ensure that patients with diabetes are aware of the importance of maintaining good glycemic control as well as an effective regimen of oral hygiene, the health care provider should do the following:

To ensure that patients receive the regular professional dental care critical to preventing periodontal disease, the health care provider should do the following:

Efficient brushing and flossing removes the more superficial supragingival dental plaque. Subgingival plaque, as well as calculus (hard deposits of plaque, also called tartar), will require professional removal. For some patients, the dentist may prescribe antiplaque rinses, such as chlorhexidene.

To evaluate personal oral hygiene, the dentist or dental hygienist should ask patients to demonstrate how they remove plaque. Patients can then be shown, if necessary, how to more effectively care for their teeth.

Detection

To determine whether a patient is at increased risk for developing periodontal disease, the health care provider should ask about the patient's oral hygiene habits. Does the patient brush and floss twice daily? Does the patient use any other devices for cleaning teeth? When did the patient last see a dentist? Is the patient experiencing any of the following: bad taste in the mouth, bad breath, sore gums, swollen or red gums, bleeding gums, difficulty chewing, loose teeth, or oral pain?

The health care provider should inspect the patient's mouth for the following signs of dental disease:

Patients showing these possible indicators of periodontal disease should be referred to a dentist.

Severe periodontal disease can be present without obvious inflammation. A complete dental examination, including periodontal probing of gum pockets, is necessary to determine the presence and severity of periodontal infection.

Treatment

The health care provider can treat periodontal disease by helping the patient achieve good glycemic control. Further measures fall to the dental health professional, who initially treats periodontal disease by removing plaque from infected areas of the patient's mouth. If infection or destruction has progressed too far, the dentist may prescribe antibiotic treatment, perform restorative procedures, perform surgery, or extract teeth.

The health care provider should work with the dentist in planning treatment and scheduling dental appointments. The health care provider should also be consulted before the patient is pretreated with an antibiotic or is hospitalized.

Patient Education Principles:

References

Epidemiology and Oral Disease Prevention Program, National Institute of Dental Research. Oral Health of United States Adults-- The National Survey of Oral Health in US Employed Adults and Seniors: 1985-1986. Bethesda, Maryland: US Department of Health and Human Services, Public Health Service, 1987. Publication NIH 87-2868.

Manouchehr-Pour M, Bissada NF. disease in juvenile and adult diabetic patients: a review of the literature. Journal of the American Dental Association. 1983;107:766-770.

Murrah VA. Diabetes mellitus and associated oral manifestations: a review. Journal of Oral Pathology. 1985;14:271-281.

National Institute of Dental Research. Detection and Prevention of Disease in Diabetes. Bethesda, Maryland: US Department of Health and Human Services, Public Health Service, 1986. Publication NIH 86-1148.

Williams RC. Periodontal disease. New England Journal of Medicine. 1990;322:373-382.


Eye Disease

Background --

Diabetes mellitus is a major cause of blindness in the United States and is the leading cause of new blindness in working-aged Americans. Diabetic retinopathy alone accounts for at least 12% of new cases of blindness each year in the United States. People with diabetes are 25 times more at risk for blindness than the general population. The estimated annual incidence of new cases of proliferative diabetic retinopathy and diabetic macular edema are 65,000 and 75,000, respectively. Approximately 700,000 Americans have proliferative diabetic retinopathy --the most sight- threatening form of retinopathy -- and 500,000 have diabetic macular edema. Over a lifetime, 70% of people with insulin- dependent diabetes mellitus (IDDM) will develop proliferative diabetic retinopathy, and 40% will develop macular edema. Both complications, if untreated, frequently lead to serious visual loss and disability.

Diabetic retinopathy is often asymptomatic in its most treatable stages. Unfortunately, only about half of persons with diabetes receive adequate eye care. Early detection of diabetic retinopathy is critical.

The results of National Eye Institute-supported multicenter clinical trials of laser surgery and vitrectomy surgery have demonstrated that the risk of blindness from diabetes can be reduced.

Diabetic retinopathy and macular edema. The process by which diabetes results in retinopathy and macular edema is not fully understood. It is known that diabetes causes the retinal capillaries to become functionally less competent. Five clinical pathological processes can be recognized in diabetic retinopathy:

Nonproliferative and proliferative diabetic retinopathy and macular edema have several clinical manifestations (Table 1). Diabetic macular edema can be associated with any stage of diabetic retinopathy.

Cataracts. Cataracts are 1.6 times more common in people with diabetes than in those without diabetes. Furthermore, cataracts occur at a younger age and progress more rapidly in people with diabetes. Young people with IDDM occasionally develop snowflake or metabolic cataracts. These may lessen or resolve with improved glycemic control. Fortunately, cataract extraction with or without lens implantation is 90% to 95% successful in restoring useful vision, but the surgery is not without potential complications that are more frequent in patients with diabetes.

Open-angle glaucoma. Open-angle glaucoma is 1.4 times more common in the diabetic population. The prevalence of glaucoma increases with the patient's age and with the length of time the patient has had diabetes. Medical therapy for open-angle glaucoma is generally effective. Argon laser trabeculoplasty may normalize intraocular pressure in over 80% of patients in whom medical therapy has proven ineffective.

Neovascular glaucoma. Neovascular glaucoma is a more severe type of glaucoma that most commonly occurs among patients with severe proliferative diabetic retinopathy and retinal detachments. It occasionally follows vitrectomy or cataract surgery. Early recognition and emergency panretinal laser surgery may prevent full development of this devastating type of glaucoma. Diagnosis and evaluation require slit-lamp examination of the iris and gonioscopic evaluation of the filtration angle.

Prevention of Diabetic Retinopathy

Epidemiological studies have suggested that diabetic retinopathy and diabetic macular edema are associated with poorer glycemic control and higher blood pressure levels. Health care providers should work with their patients to achieve good blood glucose and blood pressure control. While the National Institute of Health-sponsored Diabetes Control and Complications Trial is investigating whether very strict control of blood glucose levels is effective in preventing development of retinopathy and slowing its progression, it is prudent to maintain good control of blood glucose levels without causing significant hypoglycemia.

Because coexisting medical problems -- including hypertension and renal disease -- may affect the development and progression of diabetic retinopathy, blood pressure should be routinely measured. If hypertension exists even at borderline levels, it should be monitored and treated as needed. Aspirin treatment (650 mg per day) neither alters the progression of diabetic retinopathy nor increases the risk of vitreous hemorrhage. Therefore, diabetic retinopathy is not a contraindication for the medical use of aspirin.

Because diabetic retinopathy and diabetic macular edema cannot be prevented, routine early evaluation, timely laser surgery, and careful follow-up are critical.

Detection and Monitoring of Diabetic Retinopathy

Laser surgery, as defined by the National Eye Institute- sponsored Diabetic Retinopathy Study and Early Treatment Diabetic Retinopathy Study, can ameliorate the devastating effects of diabetic retinal disease, particularly when laser surgery is initiated at the most treatable stages. Emphasis, therefore, must be placed on early detection of diabetic retinopathy and timely referral to ophthalmologists experienced in the management of diabetic eye disease. Because mild, moderate, and even severe retinopathy may be present without any symptoms, the responsibility to screen or examine the patient with diabetes for retinopathy is significant.

The following examination schedule is designed to ensure the early detection and monitoring of diabetic eye disease:

The practitioner may elect to perform the examination, but because proper stereoscopic examination requires dilation of the pupils and specialized techniques, such as binocular indirect ophthalmoscopy, referral to ophthalmologists or optometrists appropriately trained and skilled in the diagnosis and classification of diabetic eye disease is preferred.

After the initial eye examination, persons with diabetes should receive complete examinations once a year, unless more frequent examinations are indicated by the presence of abnormalities.

The patient should be under the care of a retinal specialist or ophthalmologist experienced in the treatment of diabetic retinopathy when any of the following conditions are identified (see Table 1 for definitions):

People with any degree of retinal disease--including those who have lost vision from retinopathy--should continue to receive regular eye care. Vitrectomy surgery may restore usable vision for some individuals who have lost sight from vitreous hemorrhage or fibrous tissue proliferation with traction detachment. Postsurgical treatment requires proper refraction, low vision evaluation, optical aids, and other techniques and devices to enable the person to use even severely limited vision. Referral to optometrists or ophthalmologists specializing in low vision may be appropriate. Support groups for the visually challenged and organizations providing vocational rehabilitation are available in most areas. All practitioners should be familiar with appropriate rehabilitative referral sources for their patients with visual impairment.

Treatment and Referral

Patients with high-risk proliferative diabetic retinopathy (see (Table 1) for definition) should receive immediate laser photocoagulation surgery. Some patients with diabetic macular edema are candidates for immediate macular laser surgery. If careful follow-up can be maintained, it is safe to defer treatment in those with severe nonproliterative diabetic retinopathy and non- high-risk proliferative retinopathy until it approaches or reaches the high-risk stage. Alternatively, in patients with bilateral non-high-risk proliferative retinopathy, one eye may be considered for laser surgery prior to the high-risk stage.

Certain patients with vitreous hemorrhage or recent traction retinal detachment may be candidates for vitrectomy. Laser surgery and vitrectomy surgery should be performed by a retinal specialist or other ophthalmologist experienced in laser surgery and the management of diabetic eye disease.

Patients with functionally decreased visual acuity should be referred for low vision evaluation and appropriate visual, vocational, and psychosocial rehabilitation.

Patient Education Principles:

References

Aiello LM, Rand LI. Sebestyen JG, et al. The eyes and diabetes. In: Marble A, Krall LP. Bradley RS, Christlieb AR, Soeldner JS, eds. Joslin's Diabetes Mellitus. 12th ed. Philadelphia: Lea & Febiger, 1985.

Diabetic Retinopathy Study Research Group. Photocoagulation treatment of proliferative diabetic retinopathy: clinical application of Diabetic Retinopathy Study (DRS) findings, DRS report no. 8. Ophthalmology. 1981;88:583-600.

Early Treatment Diabetic Retinopathy Study Research Group. Photocoagulation for diabetic macular edema: Early Treatment Diabetic Retinopathy Study report no. 1. Archives of Ophthalmology. 1985;103:1796-1806.

Klein BEK, Moss SE, Klein R. Effect of pregnancy on progression of diabetic retinopathy. Diabetes Care. 1990:13:34-40.

Klein R. The epidemiology of diabetic retinopathy: findings from the Wisconsin Epidemiologic Study of Diabetic Retinopathy. International Ophthalmology Clinics. 1987;27:230-238.

Klein R, Klein BEK, Moss SE, et al. The Wisconsin Epidemiologic Study of Diabetic Retinopathy. II. Prevalence and risk of diabetic retinopathy when age at diagnosis is less than 30 years. Archives of Ophthalmology. 1984:102:520-526.

Klein R, Klein BEK, Moss SE. et al. The Wisconsin Epidemiologic Study of Diabetic Retinopathy. III. Prevalence and risk of diabetic retinopathy when age at diagnosis is 30 or more years. Archives of Ophthalmology. 1984;102:527-532.

Klein R, Moss SE, Klein BEK. et al. The Wisconsin Epidemiologic Study of Diabetic Retinopathy. XI. The incidence of macular edema. Ophthalmology. 1989;96:1501-1510.

Preferred Practice Pattern--Diabetic Retinopathy. San Francisco: American Academy of Ophthalmology, 1989.


Kidney Disease

Background --

Description. Diabetic nephropathy represents a distinct clinical syndrome characterized by albuminuria, hypertension, and progressive renal insufficiency. Diabetic nephropathy can lead to end-stage renal disease (ESRD), a serious condition in which a patient's survival depends on either dialysis or kidney transplantation.

Occurrence. Among persons who have had insulin-dependent diabetes mellitus (IDDM) for 20 years, the incidence of ESRD approaches 40%. Among whites, the incidence of ESRD is lower among those with non- insulin-dependent diabetes mellitus (NIDDM) than among those with IDDM. Because NIDDM is much more common than IDDM, the number of whites with NIDDM who develop renal failure each year is about the same as for those with IDDM. In certain populations--including blacks, Hispanics, and Native Americans--persons with NIDDM have a higher incidence of ESRD.

About a third of new cases of ESRD in the United States are attributed to diabetes. These persons account for about a third of the $2.8 billion per year that is spent for the care of patients with ESRD.

Pathophysiology--IDDM. The natural history of renal involvement in persons with IDDM has been well characterized. See (Figure 1). When diabetes is first diagnosed, the histological appearance of the kidney is normal. Within three years, however, the typical changes of diabetic glomerulosclerosis appear: thickening of the glomerular basement membrane and mesangial expansion.

Renal blood flow and the glomerular filtration rate (GFR) are characteristically elevated, correlating with an increase in kidney size and weight. Mild albuminuria may be present if glycemia is not well regulated. Because of renal hyperfiltration, serum creatinine and urea nitrogen concentrations are usually slightly reduced.

After 10 to 15 years, the first laboratory evidence of renal damage may appear with the presence of persistent microalbuminuria (30 to 300 mg per 24 hours). In IDDM, the prevalence of hypertension increases markedly in patients with microalbuminuria, and hypertension clearly contributes to the progression of renal disease.

Clinical diabetic nephropathy is said to be present when a patient who has had diabetes for more than five years and has evidence of diabetic retinopathy develops clinically apparent albuminuria (>300 mg per 24 hours) and has no evidence of any other cause of kidney disease. When these criteria are fulfilled, a clinical diagnosis of diabetic nephropathy can generally be made without performing a renal biopsy.

About four years after the onset of clinical diabetic nephropathy, the serum creatinine level rises to 2 mg/dL or greater. Within an additional three years, about one-half of patients will have developed ESRD.

Pathophysiology--NIDDM. The natural history of renal

involvement in persons with NIDDM is not well established. Although microalbuminuria has been shown to be associated with the development of clinical diabetic nephropathy, the precise level of microalbuminuria that reliably predicts this condition has yet to be determined. Some individuals with low levels of albuminuria do not develop renal failure. In these persons, albuminuria may be due to the presence of other complicating renal diseases, such as obstructive uropathy, hypertension, or arteriolosclerosis, or may reflect an age-related increase in urinary albumin excretion.

Prevention

At present, strategies for preventing diabetic nephropathy must be viewed as limited in their effectiveness, since the exact pathogenic factors responsible for this condition are unknown.

In patients with albuminuria, blood pressure regulation is of critical importance in slowing the progression to renal failure. Other strategies that may slow the progression of renal disease include limiting the patient's protein intake, maintaining good glycemic control, promptly treating urinary tract infections, and avoiding potentially nephrotoxic drugs and radiographic dyes.

Detection

At the time of initial diagnosis, all diabetic patients should have a urinalysis performed. If bacteria or white blood cells are seen, a culture should be obtained.

Each year, obtain a sensitive quantitative measure of urinary albumin or protein excretion. In general, the protein excretion rate is about one third greater than that for albumin. Thus, a protein excretion rate of approximately 400 mg per 24 hours would correspond to an albumin excretion rate of 300 mg per 24 hours.

Measure renal function (serum creatinine and/or creatinine clearance) each year.

Before establishing a diagnosis of diabetic nephropathy, exclude other possible causes of renal disease--particularly, obstructive uropathy and infection. If diabetic retinopathy is not present, suspect a nondiabetic cause of renal disease.

Hypertension is a common development with the onset of diabetic nephropathy or shortly thereafter. If the patient's initial blood pressure is higher than 140/90 mm Hg, at least three additional readings should be obtained over the next month.

Treatment

At present, no known interventions have been shown to reverse clinical diabetic nephropathy. However, practitioners can take several actions to monitor and perhaps slow the progress of this complication:

Patients who have developed ESRD will require kidney transplantation, hemodialysis, or peritoneal dialysis to prolong their lives. Because diabetic complications -- especially retinopathy and neuropathy -- progress more rapidly with the onset of renal failure, dialysis is usually instituted earlier (when the concentration of serum creatinine reaches about 6 mg/dL) for people with diabetes than for those without diabetes. Kidney transplantation is preferable to dialysis when a living relative of the patient is available as a donor; the patient's chances of survival are otherwise about equal among these three courses of treatment. The ultimate choice will require the input of the patient, the patient's family, the primary health care provider, and a nephrologist.

Patient Education Principles:

References

American Diabetes Association. Nutritional recommendations and principles for individuals with diabetes mellitus: 1986. Diabetes Care. 1987;10:126-132.

Consensus statement. Proceedings from the International Symposium on Preventing the Kidney Disease of Diabetes Mellitus: public health perspectives. American Journal of Kidney Diseases. 1989;13:2-6.

DeFronzo RA. Diabetes and the kidney: an update. In: Olefsky JM, Sherwin RS, eds. Diabetes Mellitus: Management and Complications. New York: Churchill Livingstone, 1985.

Kaplan NM, Rosenstock J, Raskin P. A differing view of treatment of hypertension in patients with diabetes mellitus. Archives of Internal Medicine. 1987;147:1160-1162.

Mogensen CE, Schmitz A, Christensen CK. Comparative renal pathophysiology relevant to IDDM and NIDDM patients. Diabetes/Metabolism Reviews. 1988;4:453-483.

Viberti GC, Walker JD. Diabetic nephropathy: etiology and prevention. Diabetes/ Metabolism Reviews. 1988;4:147-162.

The Working Group on Hypertension in Diabetes. Statement on hypertension in diabetes mellitus. Archives of Internal Medicine. 1987; 147: 830-842.


Cardiovascular Disease

Background --

Occurrence. Cardiovascular disease is the leading cause of morbidity and mortality among persons with diabetes. In the United States in 1986, approximately 80,000 deaths from cardiovascular disease were associated with diabetes.

The annual risk for death from cardiovascular disease is two to three times greater for persons with diabetes than for persons without diabetes. For persons with diabetes, the risk for cerebrovascular disease and for coronary artery disease is two to three times greater, and the risk for peripheral vascular disease is five times greater. Among persons without diabetes, women have a lower rate of cardiovascular disease than men do; among persons with diabetes, women are not preferentially spared.

Risk factors. In persons with diabetes, smoking is a powerful risk factor for cardiovascular disease, and the prevalence of smoking appears to be higher in young people (less than 21 years old) with diabetes than in young people without diabetes.

Hypertension, also a strong risk factor for cardiovascular disease, occurs two to three times more often in persons with diabetes than in persons without diabetes. The risk for cardiovascular disease increases linearly with increases in blood pressure.

Abnormalities in the concentration of lipids and lipoproteins in plasma have been reported to occur in almost 30% of persons with diabetes. The risk for cardiovascular disease is directly proportional to the concentration of low-density lipoprotein (LDL) cholesterol and inversely proportional to the concentration of high-density lipoprotein (HDL) cholesterol. Although hypertriglyceridemia is common among persons with non-insulin- dependent diabetes mellitus, whether the triglyceride level independently predicts cardiovascular disease is uncertain.

The precise relationship between hyperglycemia and atherosclerosis is also unknown. Among persons with diabetes, several concomitant conditions may affect the etiology of atherosclerosis: obesity, inactivity, hyperinsulinemia, abnormalities in platelet function, and defects in blood coagulation and flow.

Among persons with diabetes, part of the increased likelihood of cardiovascular disease appears to be a consequence of the increased frequency of risk factors. Yet diabetes itself is an independent risk factor for cardiovascular disease.

Prevention

Although the benefit of controlling smoking, hypertension, and hypercholesterolemia has not been well studied in diabetic populations, there is no reason to believe that persons with diabetes will not benefit from controlling these risk factors. However, the precise benefit that can be achieved is not known.

Smoking. Smoking cessation may be the most important modification in behavior that can be made to reduce the risk for cardiovascular disease. Stress to patients the importance of not smoking. Encourage those who smoke to quit, and remind those who do not smoke not to start.

Blood pressure. Blood pressure should be closely monitored in patients with diabetes. When blood pressure is increased over 140/90 mm Hg, nonpharmacologic therapy should be instituted. Medication may need to be initiated early, depending on the blood pressure level. When selecting drugs for treating hypertension, consider their potential adverse effects on other risk factors for cardiovascular disease.

Plasma lipids. The incidence of atherosclerotic heart disease and the morbidity associated with this condition can be decreased in nondiabetic populations by reducing the plasma cholesterol level. When the total cholesterol is more than 200 mg/dL and the LDL cholesterol is more than 130 mg/dL, nonpharmacologic therapy should be instituted.

Plasma glucose. The relationship between plasma glucose and the development of cardiovascular disease is less clear. However, poor glycemic control is often associated with hyperlipidemia. Improved glycemic control has been shown to lower the concentration of cholesterol and triglycerides in plasma and to raise the concentration of HDL cholesterol in persons with diabetes who are either hyperlipidemic or normolipidemic.

Weight, exercise, and aspirin therapy. Additional recommendations for preventing cardiovascular disease in diabetic patients include weight loss (for obese persons) and an increased level of physical activity. For patients who have had cardiovascular events, aspirin therapy may help to prevent mortality or additional morbidity from cardiovascular disease.

Detection

The following guidelines may help in the detection of cardiovascular disease.

At every office visit (at least four times a year)

___________________________________________________________________________
Condition                          Symptoms such as
___________________________________________________________________________
Cerebral vascular disease          Transient blindness, dysarthria, or
                                   unilateral weakness.

Coronary artery disease            Chest pain or pressure, dyspnea,  and
congestive heart                   orthopnea, paroxysmal nocturnal
failure                            dyspnea, or edema.(Painless myocardial
                                   infarction is common among diabetic
                                   patients, and they may have angina
                                   or myocardial infarction with atypical
                                   symptoms.)

Peripheral vascular disease        Intermittent claudication or foot ulcers
                                   that do not heal.
---------------------------------------------------------------------------

At least once a year

Once a year

Treatment

Smoking. Strongly advise patients who smoke to quit. Both the health hazards of smoking and the improved health that patients will enjoy when they stop smoking should be emphasized. Work with each patient to set a quit date, and follow up after that date. Nicotine gum may be used for physiological dependency. Behavioral treatment is recommended for psychological and social dependency. Health care providers should refer patients to smoking cessation programs in the community that are appropriate to patients' individual needs.

Hypertension. If the patient's blood pressure exceeds 140/90 mm Hg at two visits, begin nonpharmacologic therapy, including a low- sodium, alcohol-restricted diet designed for weight reduction. Regular exercise has also been shown to have a beneficial effect on blood pressure. Blood pressure should be maintained below 140/90 mm Hg. For individual patients, consider earlier pharmacologic intervention when indicated by clinical conditions (for example, diastolic blood pressure greater than 110 mm HG) and the presence of other risk factors (such as albuminuria).

After three months of nonpharmacologic therapy, if the diastolic blood pressure remains above 90 mm Hg, begin pharmacologic treatment. Select drugs that do not worsen other risk factors for cardiovascular disease (including lipids) and that do not induce or worsen autonomic neuropathic complications of diabetes (including hypoglycemia unawareness, orthostatic hypotension, or impotence).

Hyperlipidemia. When the calculated LDL cholesterol level is greater than 130 mg/dL, consider the following guidelines for glycemic control, diet, and exercise.

Glycemic control. Glycemic control should be improved through diet, use of sulfonylureas, or insulin therapy. Weigh the benefits of improved glycemic control against the potential risk for hypoglycemia.

Dietary therapy. Dietary therapy should be instituted to reduce the weight of obese patients and to try to lower the LDL cholesterol level to below 130 mg/dL. Consider the following restrictions on diet:

Exercise. Weigh the potential benefits of exercise against the risks and recommend an exercise program, if appropriate. Regular aerobic exercise has been shown to be a useful adjunct to weight loss and to have a beneficial effect on lipids, especially levels of triglycerides and HDL cholesterol. Exercise may also cause a modest drop in the LDL cholesterol level. Before patients begin an exercise program, determine whether they have hypoglycemia unawareness, postural hypotension, proliferative retinopathy, painless myocardial ischemia, or insensitive feet. An exercise stress test is recommended for all diabetic patients over 40 years old who are considering an exercise program.

Reevaluation. After six months of therapy, if a patient's LDL cholesterol level is above 160 mg/Dl, consider drug therapy. Drugs used to treat patients with hypercholesterolemia include bile acid sequestrants (cholestyramine or colestipol), HMGCoA reductase inhibitors (lovastatin), fibric acid derivatives (gemfibrozil or clofibrate), nicotinic acid, and probucol. Drugs used to treat patients with hypertriglyceridemia include fibric acid derivatives (gemfibrozil or clofibrate) and nicotinic acid.

Existing cardiovascular disease. Clinically apparent cardiovascular disease poses considerable diagnostic and therapeutic challenges to the practitioner. Consider consulting with specialists (such as cardiologists, neurologists, and vascular surgeons) early in the course of such disease. The guidelines below address some of the cardiovascular diseases common among persons with diabetes.

Cerebral vascular disease. Patients with signs or symptoms of cerebral vascular disease should be referred for specialized diagnostic tests, including noninvasive Doppler flow studies and, if necessary, carotid arteriography. Caution should be used with dye studies in patients with preexisting renal disease and/or dehydration. Patients with symptomatic cerebral vascular disease may be treated with aspirin and anticoagulants. If symptoms persist despite pharmacological treatment and if correctable vascular lesions are present, surgery may be considered.

Coronary artery disease. Heart disease due to coronary atherosclerosis is the most common cause of morbidity and mortality in patients with diabetes. Patients with signs or symptoms of coronary artery disease should receive a complete evaluation, including exercise testing and, if

necessary, coronary arteriography. Contrast-dye studies should be used with caution because of the possible coexistence of diabetic nephropathy. Nitrates, calcium channel blockers, and beta blockers may be prescribed for patients with angina. Consider coronary angioplasty or bypass surgery for patients with appropriate coronary lesions or intractable angina. Unless contraindicated, aspirin should be given after acute myocardial infarction. Because of their ability to prevent reinfarction in nondiabetic subjects, beta blockers may be used in patients with diabetes after myocardial infarction--with attention to possible hypoglycemia and/or hyperlipidemia.

Peripheral vascular disease. Generally, no effective medical treatment is available for patients with peripheral vascular disease, although some patients may benefit from pentoxifylline. Patients who have incapacitating symptoms of peripheral vascular disease (such as rest pain) or who have foot lesions that are poorly healing require careful evaluation. To detect surgically correctable peripheral vascular disease, first use clinical examination of the pulses and then consider noninvasive means (Doppler flow study). Contrast-dye studies should be used with caution because of the possible coexistence of diabetic nephropathy. Refer patients for surgery, as appropriate.

Patient Education Principles:

References

American Diabetes Association. Nutritional recommendations and principles for individuals with diabetes mellitus: 1986. Diabetes Care. 1987;10:126-132.

Kannel WB, McGee DL. Diabetes and cardiovascular disease: the Framingham Study. Journal of the American Medical Association. 1979;241:2035-2038.

Kaplan NM, Rosenstock J, Raskin P. A differing view of treatment of hypertension in patients with diabetes mellitus. Archives of Internal Medicine. 1987;147:1160-1162.

Lipid Research Clinics Program. The Lipid Research Clinics Coronary Primary Prevention Trial results. II: the relationship of reduction in incidence of coronary heart disease to cholesterol lowering. Journal of the American Medical Association. 1984;251:365-374.

National Diabetes Data Group. Diabetes in America. Bethesda, Maryland: US Department of Health and Human Services, 1985. Publication NIH 85-1468.

1984 report of the Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure. Archives of Internal Medicine. 1984;144: 1045-1057.

Steering Committee of the Physicians' Health Study Research Group. Preliminary report: findings from the aspirin component of the ongoing physicians' health study. New England Journal of Medicine. 1988;318:262-264.

Working Group on Diabetes in Hypertension. Statement on hypertension in diabetes mellitus. Archives of Internal Medicine. 1987;147:830-842.


Neuropathy

Background--

Persons with diabetes who develop neuropathy may have no symptoms or may experience pain, sensory loss, weakness, and autonomic dysfunction. Neuropathy may result in significant morbidity and may contribute to other major complications, such as lower extremity amputation.

There are three major types of diabetic neuropathy:

Distal symmetrical polyneuropathy. This most common of the diabetic neuropathies is characterized by insidious onset, symmetrical distribution, and progressive course. Although its cause is unclear, distal symmetrical polyneuropathy is believed to result from abnormal neural metabolism, generalized neural ischemia, or both. The onset and course of illness cannot be predicted for an individual patient, but increasing age, male sex, increasing height, longer duration of diabetes, poorer glucose control, hypertension, alcohol consumption, and smoking may be independent risk factors.

Estimates of the prevalence of distal symmetrical polyneuropathy differ greatly, but approximately 12% of patients have this condition when diabetes is diagnosed, and nearly 60% have it after 25 years.

Three overlapping clinical syndromes have been described:

Focal neuropathy. Focal neuropathy is an uncommon condition believed to occur after the acute occlusion of a blood vessel produces ischemia in a nerve or group of nerves. The characteristics of focal diabetic neuropathy are sudden onset, an asymmetrical nature, and a self-limited course. Near total recovery generally occurs within two weeks to 18 months. Examples of focal diabetic neuropathies are cranial neuropathies, truncal neuropathies, mononeuropathies, radiculopathies, and plexopathies. Both sensory and motor components may be present.

Autonomic neuropathy. This troubling complication of diabetes encompasses multiple disturbances affecting the following systems: sudomotor (possible symptoms include heat exhaustion), pupillary (poor night vision), adrenomedullary (hypoglycemia unawareness), cardiovascular (orthostatic hypotension and painless myocardial ischemia), gastrointestinal (gastroparesis, constipation, diarrhea, and fecal incontinence), and

urogenital (bladder dysfunction and sexual         dysfunction).

The following complications can occur with autonomic neuropathy:

___________________________________________________________________________
Condition                     Description
___________________________________________________________________________
Orthostatic                Suspect this condition when a patient reports
hypotension                having postural faintness, weakness, visual
                           impairment, or syncope. In patients whose
                           intravascular volume is not depleted,
                           autonomic neuropathy may be diagnosed if the
                           systolic blood pressure falls more than 30
                           Hg or if the diastolic blood pressure falls
                           more than 10 mm Hg when the patient changes
                           from a lying to a standing position.

Gastroparesis              May be associated with symptoms of anorexia,
                           early satiety, bloating, abdominal pain,
                           nausea, and vomiting. Signs may include
                           weight loss and erratic glycemic control.

Constipation               A common manifestation that may be difficult
                           to treat.
                           
Diabetic diarrhea          May last from a few hours to several weeks.
                           May be severe and watery, is generally worse
                           at night, and is often preceded by abdominal
                           cramps. During remissions, the patient may
                           report constipation.

Fecal incontinence         Associated with a reduced threshold of
                           conscious rectal sensation, low basal
                           internal sphincter pressure, and reduced
                           voluntary control of the external anal
                           sphincter.

Diabetic bladder           Associated with defective perception of
dysfunction                bladder filling and decreased
                           reflex bladder emptying. Patients may strain
                           to initiate a stream, may be unable to
                           completely void, may dribble when urinating,
                           and may have recurrent urinary tract infections.

Sexual dysfunction         Men may experience impotence.  Women may
                           experience decreased vaginal lubrication and
                           dyspareunia.
---------------------------------------------------------------------------

Prevention

Studies have not firmly established that glucose control is effective in preventing or treating diabetic neuropathy. It seems prudent, however, to promote good glycemic control until the benefits and risks of trying to achieve euglycemia are clarified by large clinical trials.

Practitioners should urge patients to avoid other risk factors associated with the development of peripheral polyneuropathy. These include consumption of alcohol, poor nutrition, exposure to chemical toxins, use of certain drugs, and physical injury to the nerves (such as entrapment and compression).

Detection

Interview. The practitioner should conduct an interview at each visit--at least four times a year--to determine whether the patient is experiencing the following:
Physical examination. The practitioner should inspect the feet at each visit--at least four times a year. At least once a year, the practitioner should perform a physical examination to assess neurologic function. The practitioner should measure blood pressure and pulse rate--both when the patient is lying down and standing--and should assess the patient's muscle strength, deep tendon reflexes, and sense of touch. Four modalities of touch should be assessed.

Distal temperature sensation. Touch a cool piece of metal (such as a tuning fork) to the patient's foot; ask the patient to describe the object's temperature. Another method is to alternately touch the patient's foot with a test tube containing cool water and another containing warm water; ask the patient to distinguish between these objects.

Distal pinprick or pressure sensation. Have the patient close his or her eyes. Hold a pin lightly between your thumb and forefinger and touch it to the patient's foot. Ask the patient to say when a sensation is felt and whether the sensation is sharp or dull. Clarify a doubtful response by alternately touching the patient with the point and the head of the pin. As an alterative, pressure sensation can be assessed with a monofilament.

Distal vibratory sensation. Tap a 128 hz tuning fork and place the end of the handle on a bony surface of the patient, such as the distal first metatarsal head or the malleoli of the ankles. Ask the patient to say when the vibration ceases.

Position sense. Have the patient close his or her eyes. Grasp between your thumb and index finger the lateral and medial sides of the patient's toe. Ask the patient to describe the toe's position as you alternately flex and extend it.

Differential Diagnosis

The practitioner should exclude other potential causes of neuropathy before attributing a patient's neuropathy to diabetes.

Distal symmetrical polyneuropathy. The differential diagnosis includes the following:

Focal neuropathy. The differential diagnosis includes the following:

___________________________________________________________________________
Type                          Differential Diagnosis
___________________________________________________________________________
Cranial neuropathy       Increased intracranial pressure, aneurysm, tumor.
Truncal neuropathy       Cardiopulmonary disease, degenerative joint
                         disease, disc disease, tumor, Paget's disease.

Mononeuropathy           Trauma, hemorrhage, tumor.
                         multiplex
___________________________________________________________________________
Autonomic neuropathy.    The differential diagnosis includes the following:
___________________________________________________________________________
Manifestation                 Differential Diagnosis
___________________________________________________________________________
Hypoglycemia                 Medications, lack of knowledge about
unawareness                  hypoglycemia
Orthostatic hypotension      Medications, hypovolemia, panhypopituitarism,
                             pheochromocytoma, Shy-Drager syndrome.

Gastroparesis                Medications, ketoacidosis, gastric or
                             intestinal obstruction.
Constipation                 Medications, dehydration, intestinal
                             obstruction.
Diarrhea                     Medications, dietary sorbitol or lactose,
                             enteric pathogens, bacterial overgrowth,
                             primary intestinal diseases, pancreatic
                             exocrine insufficiency.

Impotence                    Medications, hormonal abnormalities, vascular
                             disease, psychogenic disease.
___________________________________________________________________________

Treatment

Distal symmetrical polyneuropathy. Often the pain resolves. For patients with painful neuropathy, the practitioner should institute rigorous glucose control. If pain continues, consider using pharmacologic agents such as amitriptyline, imipramine, nortriptyline plus fluphenazine, carbamazepine, mexiletine, or capsaicin.

Inform patients with distal sensory or motor abnormalities about foot care. Tell patients who have lost sensation in their feet to wear special protective footwear and to avoid activities (such as jogging) that can traumatize the feet (see "Foot Problems").

If painful neuropathy persists or worsens, consider referring the patient to a diabetologist.

Focal neuropathy. After other causes are excluded (see previous section under differential diagnosis), management is palliative. Spontaneous resolution generally occurs within a period of months but may persist over years.

Autonomic neuropathy. Various treatments are available for autonomic neuropathy. If signs or symptoms of autonomic neuropathy are present, consider referring the patient to a diabetologist.

Hypoglycemia unawareness. If necessary, alter patients' targeted goals for glycemic control. Encourage patients to monitor their blood glucose regularly. Instruct patients to carry with them a source of simple sugar and to wear a necklace or bracelet that identifies them as having diabetes. Patients should also have glucagon available; their family and friends need to know how and when to use it.

Orthostatic hypotension. Patients may benefit from improved glycemic control (to reduce glycosuria), from volume and salt repletion, and from mechanical support with waist-high elastic stockings. Vasoconstrictors may be indicated.

Gastroparesis. Patients may benefit from correction of metabolic abnormalities (including hyperglycemia, ketosis, and hypokalemia), from dietary modification (eating small, liquid, low-fiber, low-fat meals), and from a prokinetic agent such as metoclopramide.

Constipation. Patients may benefit from correction of glycosuria, adequate hydration, a high-fiber diet, and psyllium.

Diarrhea. Patients may benefit from a bowel program that includes ingesting dietary fiber and making regular efforts to move the bowels. Another possible treatment is a short-term trial of an antidiarrheal agent (such as loperamide or diphenoxylate hydrochloride and atropine sulfate) or a broad-spectrum antibiotic with anaerobic coverage (such as tetracycline or metronidazole hydrochloride). Metoclopramide may occasionally be beneficial.

Fecal incontinence. Patients may be candidates for biofeedback training.

Diabetic bladder dysfunction. Patients may benefit from treatment to improve bladder emptying and to reduce the risk of urinary tract infection.

Impotence. Patients may benefit from noninvasive devices to assist erection, from a semirigid or inflatable penile prosthesis, or from papaverine injections.

Patient Education Principles:

References

Broadstone VL, Cyrus J, Pfeifer MA, Greene DA. Diabetic peripheral neuropathy, part I: sensorimotor neuropathy. The Diabetes Educator. 1987; 13:30-35.

Cyrus J, Broadstone VL, Pfeifer MA, Greene DA. Diabetic peripheral neuropathy, part II: autonomic neuropathies. The Diabetes Educator. 1987; 13:111-114.

Dyck P J, Thomas PK, Asbury AK, Winegrad AI, Porte D Jr, eds. Diabetic Neuropathy. Philadelphia: W.B. Saunders, 1987.

Pfeifer MA, Greene DA. Diabetic Neuropathy. Kalamazoo, Michigan: The Upjohn Company, 1985. (Current Concepts booklet).

Physician's Guide to Insulin-Dependent (Type 1) Diabetes: Diagnosis and Treatment. Alexandria, Virginia: American Diabetes Association, 1988.


Foot Problems

Background--

Persons with diabetes are at significant risk for lower extremity amputations; such procedures are 15 times more common among persons with diabetes than among those without diabetes. Yet if patients whose feet are particularly at risk are aggressively sought out and treated, up to 50% of amputations can be prevented.

Pathophysiology. Peripheral neuropathy, peripheral vascular disease, and infection all may contribute to amputation in patients with diabetes. Peripheral neuropathy may contribute to loss of sensation in the feet and to the development of foot deformities. In insensitive feet, deformities can cause pressure points that are vulnerable to ulceration. Inadequate blood supply and infection can then lead to osteomyelitis and gangrene.

Many persons with diabetes who undergo a lower extremity amputation have an amputation of the contralateral leg within a few years. This occurs not only because of peripheral neuropathy and peripheral vascular disease but also because the remaining foot bears increased pressure and frequently develops ulceration and infection.

The in-hospital mortality rate for diabetic patients who receive an amputation is higher than the rate for nondiabetic patients. In general, morbidity and mortality are high among diabetic patients who have amputations. All diabetic patients who undergo amputation require close supervision for other medical problems, particularly coronary artery disease.

Occurrence. Persons with diabetes account for approximately 50,000 (or 50%) of all nontraumatic amputations performed in the United States each year. The risk is greater for patients over 40 years old who have had diabetes for more than 10 years.

Cost. Although there is some variation, the average hospital stay for an amputation is approximately 25 days, and the average in- hospital cost is $25,000.

Prevention

Saving the diabetic foot and preventing amputation requires the following:
Achieving these goals requires patient and family education in the care of the foot, frequent foot inspection, and teamwork among medical disciplines.

Identification of feet at risk. The diabetic patient with distal symmetrical polyneuropathy and peripheral vascular disease has feet at risk for problems. At each visit, the health care provider should inquire for symptoms of peripheral neuropathy, including pain, burning, tingling, and numbness. Patients with insensitive feet may not be aware of ulcerations or lesions. Therefore, the shoes and stockings must be removed at every visit--at least four times a year--and the feet inspected for dryness, calluses, corns, and ulcers. The health care provider should also inspect between the toes and inspect for deformities. At least once a year, the health care provider should assess the patient's ability to sense temperature, pinprick or pressure, touch, and vibration and should test muscle strength and deep tendon reflexes (see chapter 8, "Neuropathy").

At every visit, the health care provider should also ask the patient about symptoms of intermittent claudication. In persons with diabetes and neuropathy, severe ischemia may exist without symptoms. At least once a year, the health care provider should palpate the following pulses: dorsalis pedis, posterior tibial, popliteal, and femoral.

Prevention of foot ulcers. Diabetic patients with feet at risk must learn foot hygiene and how to protect their feet. Changes in activity may be needed. Patients with foot deformities almost always require specially molded, extra-depth shoes. Deformed feet will not fit into ordinary shoes, although the patient, because of loss of sensation, may think they fit. The wearing of ordinary shoes on deformed feet may result in abrasions, ulcerations, and infection, which can lead to gangrene and amputation. If the patient's circulation is good, prophylactic correction of foot deformities should be considered.

Peripheral polyneuropathy may have a number of etiologies, such as drugs, alcohol, chemical toxins, and uremia. These must always be considered in the differential diagnosis of neuropathy in the patient with diabetes.

Factors that contribute to peripheral vascular disease should be avoided or treated. Smoking, the most significant risk factor for peripheral vascular disease, is associated with atherosclerosis, and even one cigarette can cause vasoconstriction that lasts for an hour or longer. Other risk factors for peripheral vascular disease should be treated, including hypertension, hypercholesterolemia, and perhaps hyperglycemia.

Rest pain and night pain are major indications for vascular surgery. Other indications are ulcers that will not heal, infections resistant to treatment, and incipient gangrene. In recent years, there has been an increase in the success of vascular surgical procedures. There are, however, risks to persons with diabetes who undergo vascular surgery, including the risk of angiography (see "Kidney Disease"). Conservative measures should thus always be considered before vascular surgery. Pentoxifylline may improve the circulation in patients with peripheral vascular disease; aspirin and dipyridamole have not been

conclusively shown to be effective. Oral vasodilators are ineffective in improving blood flow, and sympathectomy is not helpful in these patients.

Treatment of foot ulcers. Carefully evaluate and vigorously debride foot ulcers to establish the depth of the ulcer. Use X-ray studies to help exclude the possibility of imbedded foreign objects or osteomyelitis. If osteomyelitis is suspected, use follow-up radiographs and appropriate scans to help establish the diagnosis. Where there is significant infection, use parenteral antibiotics. Since anaerobes frequently occur in the foot ulcers of diabetic patients, take both aerobic and anaerobic bacterial cultures to help select antibiotics.

Ulcers that occur in areas other than the usual plantar area, that cannot be explained by previous trauma or ill-fitting shoes, or that do not respond to aggressive treatment should be biopsied.

Ensure that patients do not put weight on the affected foot. Patients who do not feel pain will likely continue to walk; the resulting pressure on the foot will prevent healing. Total bed rest or the use of crutches may be required. Total-contact casts have been shown to help patients with foot ulcers ambulate while ulcers heal; the casts redistribute pressure so that the area of the ulcer bears much less weight than it would otherwise.

Good glycemic control also may help the patient's foot to heal. Topical use of hyperbaric oxygen, however, is not effective.

If foot ulcers do not respond to therapy, vascular surgery must be considered.

Prevention of recurrence of foot ulcers. Without special post- ulcer care, recurrence of the ulcer is almost certain. Such care may entail a change in job, a change in walking habits, and most importantly, special shoes. Extra-depth shoes with molded plastic insoles help redistribute weight and may prevent recurrent ulcers. In one study, ulcers recurred in only about 20% of patients who wore these special shoes, whereas ulcers recurred in 80% of patients who resumed wearing ordinary shoes.

If ulcers recur despite protective shoes, the most likely cause is a bony deformity. If the patient's circulation is good, orthopedic procedures to repair such deformities may help prevent recurrence of the ulcer.

Detection and Monitoring

All patients with diabetes should be given a complete foot examination at each visit (or at least four times a year).

The health care provider should ensure that these patients are instructed in proper foot care (see "For Patients With Diabetes: How to Care for Your Feet," on pages 83-84). A member of the health care team should instruct patients to do the following:

If these patient instructions cannot be given during regular office visits, the health care provider should arrange to collaborate with another qualified specialist.

Treatment

Calluses. Assess the shoes of patients who have calluses. Teach patients to manage calluses with an emery board, callus file, or pumice stone--but strongly caution patients against trying to perform "home surgery" on calluses.

Deformities. If the foot is deformed, the patient will likely need consultation and should benefit from having specially molded shoes. Surgical correction should be considered for bunions, claw toes, or hammer toes--if the patient's circulation is good.

Neuropathic ulcers. When a neuropathic ulcer is present, consultation may be necessary, and the patient may need to be hospitalized where resources for proper treatment are available. Whenever a patient is hospitalized for any reason or is put at bed rest, heel protection should be used; the heels must be checked daily for evidence of pressure injury.

Additional considerations. Caring for the feet of persons with diabetes is complex. The expertise of professionals from many disciplines is often required. Health care providers may not be able to manage all aspects of foot care by themselves and may need to consult with other professionals:

For Patients With Diabetes: How to Care for Your Feet

Wash your feet daily. Dry them carefully, especially between the toes. Don't soak your feet (unless instructed to do so by your health care provider). If your feet are dry, apply a very thin coat of lubricant (oil or cream) to them after bathing and drying them. Don't put oil or cream between your toes.

Inspect your feet daily. Use an unbreakable mirror to help see the bottom of your feet. If your vision is impaired, ask someone to check your feet for you. Check for scratches, cuts, or blisters. Always check between your toes.

Cut your toenails by following the contour of the nail. Smooth the corners with an emery board. Don't trim into the corners of your toenails or cut ingrown toenails. If redness appears around your toenails, see your health care provider immediately.

Don't cut corns or calluses. Don't use corn plasters or chemicals for removing corns or calluses. Don't use strong antiseptic solutions or adhesive tape on your feet.

Avoid extreme temperatures. Test water with your hand or elbow before bathing. Don't walk on hot surfaces, such as sand at the beach or cement around swimming pools. In winter, wear wool socks and protective foot gear, such as fleece-lined boots. Don't apply hot water bottles or heating pads to your feet. If your feet are cold at night, wear socks.

Don't walk barefooted--even indoors. Don't wear sandals with thongs between your toes. Don't wear shoes without stockings or socks. Inspect the inside of your shoes every day for foreign objects, nail points, torn linings, and rough areas. Shoes should be comfortable at the time of purchase. Don't buy shoes that are too tight and depend on them to stretch out. Break in new shoes before wearing them regularly. Ask your health care provider or podiatrist about the types of shoes most appropriate for you.

Don't wear restrictive clothing (such as leg garters). Avoid crossing your legs; doing so can cause pressure on the nerves and blood vessels in the legs.

Don't smoke.

Don't drink alcohol excessively.

See your health care provider regularly and be sure your feet are examined at least four times a year.

Tell your health care provider or podiatrist at once if you develop a blister or sore on your foot. Be sure to tell your podiatrist that you have diabetes.

Patient Education Principles:

References

Bild DE, Selby JV, Sinnock P, Browner WS, Braveman P, Showstack JA. Lower-extremity amputation in people with diabetes: epidemiology and prevention. Diabetes Care. 1989;12:24-31.

Boulton AJM, Bowker JH, Gadia M, et al. Use of plaster casts in the management of diabetic neuropathic foot ulcers. Diabetes Care. 1986;9:149-152.

Edmonds ME, Blundell MP, Morris ME. Thomas EM, Cotton LT, Watkins PJ. Improved survival of the diabetic foot: the role of a specialised foot clinic. Quarterly Journal of Medicine. 1986;60:763-771.

Levin ME, O' NeaI LW, eds. The Diabetic Foot. 4th ed. St. Louis: CV Mosby, 1988.


Appendix A, Office Guide

The office guide is a brief synopsis of the recommendations contained in the body of the text and is designed so that it may be photocopied and placed in the patient's medical record.

(Table 2) Example of an office guide.


Acknowledgments

This publication was prepared by the Department of Health and Human Services, Centers for Disease Control, National Center for Chronic Disease Prevention and Health Promotion, Division of Diabetes, under the general editorship of William Herman: Alacia Lyons was the project coordinator.

The following persons prepared chapters of this publication: Jerry Cavallerano, Ralph DeFronzo, Steven Gabbe, Alan Jacobson, Marvin Levin, Michael Pfeifer, Philip Raskin, Susan Szpunar, and Fred Whitehouse.

The following persons served as primary reviewers of the draft chapters: Harry Bennert, Stephen Corbin, Donald Coustan, Daniel Cox, Allen Drash, Catherine Feste, Douglas Greene, William Herman, Ronald Klein, Robert Luke, David Nathan, Pasquale Palumbo, Roger Pecoraro, Anthony Rizzo, Peter Savage, and F. William Wagner, Jr.

The following organizations have lent their support in the development of this publication: the American Association of Diabetes Educators, the American Diabetes Association, the American Dietetic Association, the Juvenile Diabetes Foundation, the National Diabetes Advisory Board, and the Technical Advisory Committee of the Division of Diabetes Translation.

The following persons have also assisted in the preparation of this publication: Robert Anderson, David Ballard, Elizabeth Barrett-Connor, Diane Bild, Alton Brown, Frank DeStefano, Joycelyn EIders, Mary Anne Farrell, Catherine Feste, Florence Fiori, Earl Ford. Richard Hamman, Maureen Harris, Carlos Hernandez, Saunders Hupp, Sharon Johnson, William Jubiz, Richard Kahn, Barbara Klein, Raymond Kuehne, Daniel Lorber, Maria Ludi, James Marks, Robert Moran, Ben Muneta, Jeffrey Newman. John O'Brian, James Pichert, Gayle Reiber, Alice Ring, William Robinson, Dawn Satterfield, Richard Scheffler, Maria Segarra, Stephen Sepe, Mohamed Shakir, Karl Sussman, Frank Vinicor, John Waller, Jr., Scott Wetterhall, Julie Will, and Deborah Wingard.

The editor acknowledges with gratitude Charles M. Clark, Jr., Dorothy Gohdes, and Fran Wood for contributing critical reviews of the entire manuscript and Kelly Fearer for her secretarial assistance.

Division of Diabetes Translation, Department of Health and Human Services, Public Health Service, Centers for Disease Control, National Center for Chronic Disease Prevention and Health Promotion, Atlanta, Georgia


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Table 1

             Table 1.  Clinical Manifestations of Eye Diseases
===============================================================================
_
        Nonproliferative Diabetic Retinopathy

           Nonproliferative Diabetic Retinopathy

           -  Retinal microaneurysms.
           -  Occasional blot hemorrhages.
           -  Hard exudates.
           -  One or two soft exudates.

           Preproliferative Diabetic Retinopathy

           -  Presence of venous beading.
           -  Significant areas of large retinal blot hemorrhages.
           -  Multiple cotton wool spots (nerve fiber infarcts).
           -  Multiple intraretinal microvascular abnormalities.

           Prolliferative Diabetic Retinopathy

           -  New vessels on the disc (NVD).
           -  New vessels elsewhere on the retina (NVE).
           -  Preretinal or vitreous hemorrhage.
           -  Fibrous tissue proliferation.

           High-Risk Proliferative Diabetic Retinopathy

           -  NVD with or without preretinal or vitreous hemorrhage.
           -  NVE with preretinal or vitreous hemorrhage.

           Dibetic Macular Edema

           -  Any thickening of retina <2 disc diameters from center of
              macula.

           -  Any hard exudate <2 disc diameters from center of macula with
              associated thickening of the retina.

           -  Any nonperfused retina inside the temporal vessel arcades.

           -  Any combination of the above.
===============================================================================

Table 2

                       Table 2. Example of an Office Guide
===============================================================================
                                  Office Guide

Patient's Name:_______________________________________________

Address:______________________________________________________

Phone: home (    )_______________________
       work (    )_______________________

Date of birth:   _______/_______/________
                  mo      day     year

Year of diagnosis:_______________________

Type od diabetes: IDDM___ NIDDM___ Other________________________

Diet:  calories______________________
       meals and snacks (circle)
              breakfast  snack   lunch   snack   dinner   snack   snack

Exercise:     type__________  frequency_______________/week
              duration______minutes  time of day____________________

Monitoring:   blood glucose_____  urine glucose_____  urine ketones_____
              frequency_______________________________________/day

Oral hypoglycemia agent:________________________________________________

Insulin:________________________________________________________________

Other medications:______________________________________________________
===============================================================================



Figure 1

Natural History Of Diabetic Nephropathy In Persons With Insulin

Prevention Guidelines Image




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