Standards of Medical Care for Patients With Diabetes Mellitus

AMERICAN DIABETES ASSOCIATION

Originally approved 1988.  Revised 1994, 1996, and 1997.  The recommendations in this paper are based on the evidence reviewed in the following publication: Standards of care for diabetes (Technical Review).
  Diabetes Care 17:1514-22, 1994.  Reprinted with permission from Diabetes Care (Suppl. 1): 21:S23-35,1998.

Diabetes is a chronic illness that requires continuing medical care and education to prevent acute complications and to reduce the risk of long-term complications. People with diabetes should receive their treatment and care from a physician-coordinated team. Such teams include, but are not limited to, physicians, nurses, dietitians, and mental health professionals with expertise and a special interest in diabetes.

The following standards define basic medical care for people with diabetes. These standards are not intended to preclude more extensive evaluation and management of the patient by other specialists as needed.

These standards of diabetes care seek to provide:

1. Physicians and other health care professionals who treat people with diabetes with a means to

• Set treatment goals
• Assess the quality of diabetes treat- ment provided
• Identify areas where more attention or self-management training is needed
• Define timely and necessary referral patterns to appropriate specialists

2. People with diabetes with a means to

• Assess the quality of medical care they receive
• Develop expectations for their role in the medical treatment
• Compare their treatment outcomes with standard goals

For more detailed information, refer to Santiago (Ed.): Medical Management of Insulin-Dependent (Type I) Diabetes and Raskin (Ed.): Medical Management of Non-Insulin-Dependent (Type II) Diabetes (see bibliography).

GENERAL PRINCIPLES
Persistent hyperglycemia is the hallmark of all forms of diabetes. Treatment aimed at lowering blood glucose to or near normal levels in all patients is mandated by the following proven benefits:

1. The danger of acute decompensation due to diabetic ketoacidosis (DKA) or hyperosmolar hyperglycemic nonketotic syndrome, with their accompanying morbidity and mortality, is markedly reduced.
2. The symptoms of blurred vision are alleviated, and the risk of polyuria, polydipsia, fatigue, weight loss with polyphagia, vaginitis, or balanitis may be decreased.
3. The risks of development or progression of diabetic retinopathy, nephropathy, and neuropathy are all greatly decreased. It is possible that these complications may even be prevented by early normalization of metabolic status.
4. Near normalization of blood glucose has been demonstrated to be associated with a less atherogenic lipid profile.

With many types of diabetes, achieving near normal or normal blood glucose levels in patients requires comprehensive training in self-management and, for most individuals, intensive treatment programs. Such programs include the following components according to individual patient need:

• Appropriate frequency of self-monitoring of blood glucose (SMBG)
• Medical nutrition therapy (MNT)
• Regular exercise
• Physiologically based insulin regimens, i.e., multiple daily injections of rapid- (e.g., lispro), short- (e.g., regu- lar), intermediate- (e.g., NPH or lente), or long-acting (e.g., ultralente) insulins or continuous subcutaneous insulin infusion, in type 1 and some type 2 patients
• Less-complex insulin regimens or oral glucose-lowering agents in some type 2 patients
• Instruction in the prevention and treatment of hypoglycemia and other acute and chronic complications
• Continuing education and reinforcement
• Periodic assessment of treatment goals

To be effective, treatment programs require ongoing support from the clinical care team.

SPECIFIC GOALS OF TREATMENT
Type 1 Diabetes
Setting individual patient glycemic targets should take into account the results of prospective randomized clinical trials, most notably the Diabetes Control and Complications Trial (DCCT). This trial conclusively demonstrated that in patients with type 1 diabetes the risk of development or progression of retinopathy, nephropathy, and neuropathy is reduced 50–75% by intensive treatment regimens when compared with conventional treatment regimens. These benefits were observed with an average HbA_1c of 7.2% in intensively treated groups of patients compared with 9.0% in conventionally treated groups of patients. The reduction in risk of these complications correlated continuously with the reduction in HbA_1c produced by intensive treatment. This relationship implies that complete normalization of glycemic levels may prevent complications. The nondiabetic reference range for the HbA_1c in the DCCT was 4.0–6.0. Because GHb values differ in different laboratories, diabetes treatment teams should adjust their GHb values to account for local differences in assay methodology and nondiabetic reference ranges.

SMBG targets in the DCCT were 70–120 mg/dl (3.9–6.7 mmol/l) before meals and at bedtime and <180 mg/dl (<10.0 mmol/l) when measured 1.5–2.0 h postprandially. However, these goals were associated with a threefold increased risk of severe hypoglycemia. Therefore, it may be appropriate to increase these targets (e.g., 80–120 mg/dl [4.4–6.7 mmol/l] before meals and 100–140 mg/dl [5.6–7.8 mmol/l] at bedtime) (Table 1). These targets should be further adjusted in patients with a history of recurrent severe or unrecognized hypoglycemia.

Individual treatment goals should take into account the patient’s capacity to understand and carry out the treatment regimen, the patient’s risk for severe hypoglycemia, and other patient factors that may increase risk or decrease benefit (e.g., very young or old age, end-stage renal disease (ESRD), advanced cardiovascular or cerebrovascular disease, or other coexisting diseases that will materially shorten life expectancy).

The desired outcome of glycemic control in type 1 diabetes is to lower GHb (or any equivalent measure of chronic glycemia) so as to achieve maximum prevention of complications with due regard for patient safety. To achieve these goals with intensive management, the following may be necessary:

• Frequent SMBG (at least three or four times per day)
• MNT
• Training in self-management and problem solving
• Possible hospitalization for initiation of therapy

In situations where resources are unavailable or insufficient, referral to a diabetes care team for consultation and/or comanagement is recommended.

Type 2 Diabetes
In type 2 diabetes, considerable epidemiological evidence exists for a relationship between microvascular disease and hyperglycemia similar to that proven for type 1 diabetes. A randomized trial similar in design to the DCCT but involving fewer subjects (110 vs. 1,440) showed that improvement in glucose control to levels mimicking those in the DCCT resulted in a comparable reduction in microvascular complications in lean Japanese patients with type 2 diabetes. It is reasonable to expect that therapy that achieves glycemic goals similar to those in the DCCT will provide similar benefits with regard to long-term microvascular and neurological complications. There are some observational studies showing fewer cardiovascular events and less mortality in better controlled type 2 diabetes; however, no randomized studies have been completed to support these findings.

In setting treatment goals for type 2 diabetes (Table 1), the same individual patient characteristics should be considered as for type 1 diabetes: the patient’s capacity to understand and carry out the treatment regimen, the patient’s risk for severe hypoglycemia, and other patient factors that may increase risk or decrease benefit (e.g., advanced age, ESRD, advanced cardiovascular or cerebrovascular disease, or other coexisting diseases that will materially shorten life expectancy).

Daily SMBG is especially important for patients treated with insulin or sulfonylureas to monitor for and prevent asymptomatic hypoglycemia. The optimal frequency of SMBG for patients with type 2 diabetes is not known, but it should be sufficient to facilitate reaching glucose goals. The role of SMBG in stable diet-treated patients with type 2 diabetes is not known.

Type 2 diabetes treatment methods should emphasize diabetes management as a multiple risk factor approach including MNT, exercise, weight reduction when indicated, and use of oral glucose-lowering agents and/or insulin, with careful attention given to cardiovascular risk factors, including hypertension, smoking, dyslipidemia, and family history. Whether treated with insulin or oral glucose-lowering agents, or a combination, goals remain those outlined in Table 1. There is less certainty that the risk-to-benefit ratio of intensive insulin treatment is as favorable in type 2 patients as in type 1 patients.

INITIAL VISIT
Medical History
The comprehensive medical history can uncover symptoms that will help establish the diagnosis in the patient with previously unrecognized diabetes. If the diagnosis of diabetes has already been made, the history should confirm the diagnosis, review the previous treatment, allow evaluation of the past and present degrees of glycemic control, determine the presence or absence of the chronic complications of diabetes, assist in formulating a management plan, and provide a basis for continuing care. Elements of the medical history of particular concern in patients with diabetes include the following:

• Symptoms, results of laboratory tests, and special examination results related to the diagnosis of diabetes
• Prior GHb records
• Eating patterns, nutritional status, and weight history; growth and development in children and adolescents
• Details of previous treatment programs, including nutrition and diabetes self-management training
• Current treatment of diabetes, including medications, meal plan, and results of glucose monitoring and patients’ use of the data
• Exercise history
• Frequency, severity, and cause of acute complications such as ketoacidosis and hypoglycemia
• Prior or current infections, particularly skin, foot, dental, and genitourinary infections
• Symptoms and treatment of chronic eye; kidney; nerve; genitourinary (including sexual), bladder, and gastrointestinal function; heart; peripheral vascular; foot; and cerebrovascular complications associated with diabetes
• Other medications that may affect blood glucose levels
• Risk factors for atherosclerosis: smoking, hypertension, obesity, dyslipidemia, and family history
• History and treatment of other conditions, including endocrine and eating disorders
• Family history of diabetes and other endocrine disorders
• Gestational history: hyperglycemia, delivery of an infant weighing >9 lb, toxemia, stillbirth, polyhydramnios, or other complications of pregnancy
• Lifestyle, cultural, psychosocial, educational, and economic factors that might influence the management of diabetes

Physical Examination
A physical examination should be performed during the initial evaluation. People with diabetes have a high risk of developing eye, kidney, foot, nerve, cardiac, and vascular complications. Patients with type 1 diabetes have an increased frequency of autoimmune disorders, especially thyroid disease. All individuals with poorly controlled diabetes are at increased risk for infections. Children with poorly controlled diabetes may have delayed growth and maturation. Therefore, certain aspects of the detailed physical examination should be performed. These include the following:

• Height and weight measurement (and comparison to norms in children and adolescents)
• Sexual maturation staging (during peripubertal period)
• Blood pressure determination (with orthostatic measurements when indicated) and comparison to age-related norms
• Ophthalmoscopic examination (preferably with dilation)
• Oral examination
• Thyroid palpation
• Cardiac examination
• Abdominal examination (e.g., for hepatomegaly)
• Evaluation of pulses (by palpation and auscultation)
• Hand/finger examination
• Foot examination
• Skin examination (including insulin-injection sites)
• Neurological examination

The clinician should also be alert for signs of diseases that can cause secondary diabetes, e.g., hemochromatosis, pancreatic disease, and endocrine disorders such as acromegaly, pheochromocytoma, and Cushing’s syndrome.

Laboratory Evaluation
Blood glucose testing and urine ketone testing should be available in the office for immediate use as needed. In addition, each patient should undergo laboratory tests that are appropriate to the evaluation of the individual’s general medical condition. Certain tests should be performed to establish the diagnosis of diabetes (see the American Diabetes Association’s "Report of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus" in this supplement for a complete discussion on this subject), determine the degree of glycemic control, and define associated complications and risk factors. These include the following:

• Fasting plasma glucose (a random plasma glucose test may be performed in an undiagnosed symptomatic patient for diagnostic purposes)
• GHb
• Fasting lipid profile: total cholesterol, HDL cholesterol, triglycerides, and LDL cholesterol
• Serum creatinine in adults; in children if proteinuria is present
• Urinalysis: glucose, ketones, protein, sediment
• Test for microalbuminuria (e.g., timed specimen or the albumin-to-creatinine ratio) in pubertal and post-pubertal type 1 patients who have had diabetes for at least 5 years and in all patients with type 2 diabetes
• Urine culture if sediment is abnormal or symptoms are present
• Thyroid function test(s) when indicated
• Electrocardiogram in adults

Management Plan
A complete, organized medical record system is essential to providing ongoing care of people with diabetes. The records must always be accessible to the diabetes treatment team and organized so that they not only document what has occurred but also serve as a reminder of what should be done at appropriate intervals.

The management plan should be formulated as an individualized therapeutic alliance among the patient and family, the physician, and other members of the health care team skilled in the management of diabetes to achieve the desired level of diabetes control. Patient self-management should be emphasized. To this end, the management plan should be formulated in collaboration with the patient, and the plan should emphasize the involvement of the patient in problem solving as much as possible. A variety of strategies and techniques should be employed to provide adequate education and development of problem-solving skills in the various aspects of diabetes management.

In formulating this management plan, consideration should be given to the patient’s age, school or work schedule and conditions, physical activity, eating patterns, social situation and personality, cultural factors, and presence of complications of diabetes or other medical conditions. Implementation of the management plan requires that each aspect be understood and agreed on by the patient and the care providers and that the goals and treatment plan are reasonable. The management plan should include the following:

• Statement of short- and long-term goals
• Medications (insulin, oral glucose-lowering agents, glucagon, antihypertensive and lipid-lowering agents, aspirin therapy, other endocrine drugs, and other medications)
• Individualized nutrition recommendations and instructions, preferably by a registered dietitian familiar with the components of diabetes MNT
• Recommendations for appropriate lifestyle changes (e.g., exercise, smoking cessation)
• Patient and family education for self-management that is consistent with the National Standards for Diabetes Self-Management Education Programs, preferably provided by a Certified Diabetes Educator
• Monitoring instructions: SMBG, urine ketones, and use of a record system. Frequency of SMBG should be individualized according to clinical circumstances, the form of treatment employed, and the response to treatment. Urine glucose may be considered as an alternative only if the patient is unable or unwilling to perform blood glucose testing or if the only goal is avoidance of symptomatic hyperglycemia.
• Annual comprehensive dilated eye and visual examinations by an ophthalmologist or optometrist for all patients of age 10 years and older who have had diabetes for 3–5 years, all patients diagnosed after age 30 years, and any patient with visual symptoms and/or abnormalities
• Consultation for podiatry services as indicated
• Consultation for specialized services as indicated
• Agreement on continuing support, follow-up, and return appointments
• Instructions on when and how to contact the physician or other members of the health care team when the patient has not been able to solve problems and when management of acute problems is required
• For women of childbearing age, discussion of contraception and emphasis on the necessity of optimal blood glucose control before conception and during pregnancy
• Dental hygiene

See Table 2 for a summary of the initial visit.

CONTINUING CARE
Continuing care is essential in the management of every patient with diabetes. At each visit, the patient’s progress in achieving treatment goals should be evaluated by the health care team, and problems that have occurred should be reviewed. If goals are not being met, the management plan needs to be revised and/or the goals need to be reassessed.

Visit Frequency
The frequency of patient visits depends on the following:

• Type of diabetes
• Blood glucose goals and the degree to which they are achieved
• Changes in the treatment regimen
• Presence of complications of diabetes or other medical conditions

Patients initiating insulin therapy or having a major change in their insulin program may need to be in contact with their health care providers as often as daily until glucose control is achieved, the risk of hypoglycemia is low, and they are competent and comfortable implementing the treatment plan. Some patients may require hospitalization for initiation or change of therapy.

Patients beginning treatment with MNT or oral glucose-lowering agents may need to be contacted as often as weekly until reasonable glucose control is achieved and they are competent to conduct the treatment program. Regular visits should be scheduled for all patients with diabetes. Patients should generally be seen at least quarterly until achievement of treatment goals. Thereafter, the frequency of visits may be decreased as long as patients continue to achieve all treatment goals. More frequent contact also may be required if patients are undergoing intensive insulin therapy, not meeting glycemic or blood pressure goals, or have evidence of progression in microvascular or macrovascular complications. Patients must be taught to recognize problems with their glucose control as indicated by their SMBG records and to promptly report concerns to the health care team to clarify and strengthen their self-management skills. They also should be taught to recognize early signs and symptoms of acute and chronic complications and to report these immediately. Severe hypoglycemic reactions requiring the assistance of another person must be reported as soon as possible.

Medical History
An interim history should be obtained at each visit and should include the following:

• Frequency, causes, and severity of hypoglycemia or hyperglycemia
• Results of SMBG
• Adjustments by the patient of the therapeutic regimen
• Problems with adherence
• Symptoms suggesting development of the complications of diabetes
• Other medical illnesses
• Current medications
• Psychosocial issues
• Lifestyle changes

Physical Examination
The quarterly examination should include the following:

• Height (until maturity)
• Weight
• Blood pressure
• Sexual maturation (in peripubertal patients)
• Funduscopy in patients at risk (referral if retinopathy detected)
• Foot examination in patients at risk

If abnormalities are identified, more frequent follow-up may be required.

Comprehensive dilated eye and visual examinations should be performed annually by an ophthalmologist or optometrist who is knowledgeable and experienced in the management of diabetic retinopathy for all patients age 10 years and older who have had diabetes for 3–5 years, all patients diagnosed after age 30, and any patient with visual symptoms and/or abnormalities. For further discussion, see the American Diabetes Association’s position statement "Diabetic Retinopathy."

Laboratory Evaluation
A GHb determination should be performed routinely in all patients with diabetes, first to document the degree of glycemic control at initial assessment, then as part of continuing care. Since GHb reflects mean glycemia over the preceding 2–3 months, measurement approximately every 3 months is required to determine whether a patient’s metabolic control has remained continuously within the target range. Thus, regular measurements of GHb permit detection of departures from the target range in a timely fashion. For any individual patient, the frequency of GHb testing should depend on the treatment regimen employed and the judgment of the clinician. In the absence of well-controlled studies that suggest a definite testing protocol, expert opinion recommends GHb testing at least twice a year in patients who are meeting treatment goals and who have stable glycemic control and more frequently (quarterly assessment) in patients whose therapy has changed or who are not meeting glycemic goals.

Adult patients with diabetes should be tested annually for lipid disorders with fasting serum cholesterol, triglyceride, HDL cholesterol, and calculated LDL cholesterol measurements. Lower-risk, borderline, and higher-risk lipid levels for adults are shown in Table 3. Tests resulting in borderline or abnormal values should be repeated for confirmation. Tests resulting in abnormal values requiring institution of therapy should be repeated, following the National Cholesterol Education Program recommendations. Lipid values should be reevaluated in the presence of a macrovascular event.

A lipid profile should be performed on children older than 2 years after diagnosis of diabetes and when glucose control has been established. Tests resulting in borderline or abnormal values should be repeated for confirmation. If values fall within accepted risk levels, assessment should be repeated every 5 years. Tests resulting in abnormal values requiring institution of therapy should be repeated, following the National Cholesterol Education Program recommendations for children and adolescents.

Routine urinalysis should be performed yearly in adults. If the urinalysis is positive for protein, a quantitative measure is frequently helpful in the development of a treatment plan. If the urinalysis is negative for protein, a test for the presence of microalbumin is necessary. Screening for microalbuminuria in individuals with type 1 diabetes should begin with puberty and after 5 years’ duration of the disease. Because of the difficulty in precise dating of the onset of type 2 diabetes, such screening should begin at the time of diagnosis. Screening for microalbuminuria can be performed by three methods:

1. Measurement of the albumin-to-creatinine ratio in a random, spot collection
2. 24-h collection with creatinine, allowing the simultaneous measurement of creatinine clearance
3. Timed (e.g., 4-h or overnight) collection

The first method is often found to be the easiest in an office setting and generally provides accurate information. First-void or other morning collections are preferred because of the known diurnal variation in albumin excretion, but if this timing cannot be used, uniformity of timing for different collections in the same individual should be employed.

Management Plan
The management plan should be reviewed at each regular visit to determine progress in meeting goals and to identify problems. This review should include the control of blood glucose levels, assessment of complications, control of blood pressure, control of dyslipidemia, nutrition assessment, frequency of hypoglycemia, adherence to all aspects of self-care, evaluation of the exercise regimen, follow-up of referrals, and psychosocial adjustment. In addition, knowledge of diabetes and self-management skills should be reassessed at least annually. Continuing education should be provided or encouraged.

See Table 4 on for a summary of continuing care.

SPECIAL CONSIDERATIONS
Children and Adolescents
Approximately three-quarters of all newly diagnosed cases of type 1 diabetes occur in individuals younger than 18 years. Care of this group requires integration of diabetes management with the complicated physical and emotional growth needs of children, adolescents, and their families. Diabetes care for children of this age-group should be provided by a team that can deal with these special medical, educational, nutritional, and behavioral issues.

At the time of initial diagnosis, it is extremely important to establish the goals of care and to begin diabetes self-management training. A firm educational base should be provided so that the individual and family can become increasingly independent in the self-management of diabetes. Glycemic goals may need to be modified to take into account the fact that most children younger than 6 or 7 years have a form of "hypoglycemic unawareness," in that they lack the cognitive capacity to recognize and respond to hypoglycemic symptoms. Intercurrent illnesses are more frequent in young children. Sick-day management rules must be established and taught to prevent severe hyperglycemia and DKA that require hospitalization. A nutritional assessment should be performed at diagnosis, and at least annually thereafter, by an individual experienced with the nutritional needs of the growing child and the behavioral issues that have an impact on adolescent diets. Caution must be exercised to avoid overaggressive dietary manipulation in the very young. Assessment of lifestyle needs should be accompanied by possible modifications of the diabetic regimen. For example, an adolescent who requires more flexibility might be switched to a three– or four–insulin-injection program when needed.

A major issue deserving emphasis in this age-group is that of "adherence." No matter how sound the medical regimen, it can only be as good as the ability of the family and/or individual to implement it. Health care providers who care for children and adolescents, therefore, must be capable of evaluating the behavioral, emotional, and psychosocial factors that interfere with implementation and then must work with the individual and family to resolve problems that occur and/or to modify goals as appropriate.

Information should be supplied to the school or day care setting so that school personnel are aware of the diagnosis of diabetes in the student and of the signs, symptoms, and treatment of hypoglycemia. It is desirable that blood glucose testing be performed at the school or day care setting before lunch and when signs or symptoms of abnormal blood glucose levels are present.

Referral for Diabetes Management
For a variety of reasons (e.g., intercurrent illness, DKA, recurrent hypoglycemia), it may not be possible to provide care that meets these standards or achieves the desired goals of treatment (Table 1). In such instances, additional actions suggested may include enhanced education of diabetes self-management, comanagement with a diabetes team, or referral to an endocrinologist.

Intercurrent Illness
The stress of illness frequently aggravates glycemic control and necessitates more frequent monitoring of blood glucose and urine ketones. Marked hyperglycemia requires temporary adjustment of the treatment program, and, if accompanied by ketosis, frequent interaction with the diabetes care team. The patient treated with oral glucose-lowering agents or MNT alone may temporarily require insulin. Adequate fluid and caloric intake must be assured. Infection or dehydration is more likely to necessitate hospitalization of the person with diabetes than the person without diabetes. The hospitalized patient should be treated by a physician with expertise in the management of diabetes.

Diabetic Ketoacidosis and Hyperosmolar
Hyperglycemic Nonketotic Syndrome
These conditions represent decompensation in diabetic control and require immediate treatment. Careful evaluation of the patient for associated or precipitating events must be undertaken (e.g., infection, medications, vascular events), and associated problems must be treated appropriately. Depending on the severity of the illness and available resources, treatment can be initiated in the physician’s office, but it is best carried out in the emergency room, hospital room, or intensive care unit. Because of the potential morbidity and mortality of DKA and the hyperosmolar hyperglycemic nonketotic syndrome, prompt consultation with a diabetologist/ endocrinologist is recommended when the initial clinical and/or biochemical state is markedly abnormal, when the initial response to standard therapy is unsatisfactory, or when metabolic complications or cerebral edema occur. Recurrence of DKA demands a detailed psychosocial and educational evaluation by a diabetes specialist.

Severe or Frequent Hypoglycemia
The occurrence of severe, frequent, or unexplained episodes of hypoglycemia may be due to a number of factors such as defective counterregulation, hypoglycemic unawareness, insulin dose errors, and excessive alcohol intake. Hypoglycemia may also be a consequence of the therapeutic regimen and always requires evaluation of both the management plan and its execution by the patient. Family members and close associates of the patient who uses insulin should be taught to use glucagon.

The successful accomplishment of these goals requires more frequent patient contacts during readjustment of the treatment program and patient/family reeducation.

PREGNANCY
To reduce the risk of fetal malformations and maternal and fetal complications, pregnant women and women planning to become pregnant require excellent blood glucose control. These women need to be seen frequently by a multidisciplinary team, including a diabetologist, internist or family practice physician, obstetrician, diabetes educators, including a nurse, registered dietitian, and social worker, and other specialists as necessary. In addition, these women must be trained in SMBG and may require specialized laboratory and diagnostic tests. For further discussion, see the American Diabetes Association’s position statement "Preconception Care of Women with Diabetes."

Because of the need for prepregnancy planning and excellent glucose control, every pregnancy in a woman with diabetes should be planned in advance. Therefore, any diabetic woman who is not currently attempting to conceive should be informed of and offered acceptable and effective methods of contraception.

RETINOPATHY
In addition to undergoing the annual retinal examination by an ophthalmologist or optometrist who is knowledgeable and experienced in the management of diabetic retinopathy, patients with any level of macular edema, severe nonproliferative retinopathy, or any proliferative retinopathy require the prompt care of an ophthalmologist who is knowledgeable and experienced in the management of diabetic retinopathy. (For further discussion, see the American Diabetes Association’s position statement "Diabetic Retinopathy" in this supplement.)

HYPERTENSION
Hypertension contributes to the development and progression of chronic complications of diabetes. In patients with type 1 diabetes, persistent hypertension is often a manifestation of diabetic nephropathy, as indicated by concomitant elevated levels of urinary albumin and, in later stages, by a decrease in the glomerular filtration rate (GFR). In patients with type 2 diabetes, hypertension often is part of a syndrome that includes glucose intolerance, insulin resistance, obesity, dyslipidemia, and coronary artery disease. Isolated systolic hypertension may occur with long duration of either type of diabetes and is in part due to inelasticity of atherosclerotic large vessels. Control of hypertension has been demonstrated to reduce the rate of progression of diabetic nephropathy and to reduce the complications of hypertensive nephropathy, cerebrovascular disease, and cardiovascular disease.

General Principles
Lifestyle modifications should initially be employed to reduce blood pressure unless hypertension is at an urgent level. Such modifications include weight loss, exercise, reduction of dietary sodium, and limits on alcohol consumption. If lifestyle modifications do not achieve specified goals, medications should be added in a stepwise fashion until blood pressure goals are reached. Several medications in patients with albuminuria (e.g., ACE inhibitors) appear to have selective benefit in patients with diabetes. Other cardiovascular risk factors, such as smoking, inactivity, and elevated LDL cholesterol levels, should also be managed concomitantly.

Specific Goals of Treatment
Hypertension in adults has traditionally been defined as a systolic blood pressure >140 mmHg and/or a diastolic blood pressure >90 mmHg. Most epidemiological studies have suggested that risk due to elevated blood pressure is a continuous function, so these cutoff levels are arbitrary. In the general population, the risks for end-organ damage appear to be lowest when the systolic blood pressure is <120 mmHg and the diastolic blood pressure is <80 mmHg.

The primary goal of therapy for adults should be to decrease blood pressure to <130/85 mmHg. In children, blood pressure should be decreased to the corresponding age-adjusted 90th percentile values.

For patients with an isolated systolic hypertension of >180 mmHg, the goal is a blood pressure <160 mmHg. For those with systolic blood pressure of 160–179, the goal is a reduction of 20 mmHg. If these goals are achieved and well tolerated, further lowering to 140 mmHg may be appropriate. (For more detailed information, see the consensus statement "Treatment of Hypertension in Diabetes.")

NEPHROPATHY
General Principles
Persistent albuminuria in the range of 30–300 mg/24 h (microalbuminuria) has been shown to be the earliest stage of diabetic nephropathy. Patients with microalbuminuria will likely progress to clinical albuminuria (>300 mg/24 h) and decreasing GFR over a period of years. Once clinical albuminuria occurs, the risk for ESRD is high in type 1 diabetes and significant in type 2 diabetes. If untreated, hypertension can hasten the progression of renal disease. Over the past several years, a number of interventions have been demonstrated to retard the initial development or rate of progression of renal disease.

Specific Goals of Treatment
Intensive diabetes management with the goal of achieving near normoglycemia has been proved to delay the onset of microalbuminuria, and the progression of microalbuminuria to clinical albuminuria, in patients with type 1 diabetes.

Lowering blood pressure to <130/85, by any effective means, should be the goal in hypertensive individuals. A reduction in blood pressure will also decrease the rate of progression of diabetic nephropathy.

In hypertensive patients with either type 1 or type 2 diabetes who have microalbuminuria or clinical albuminuria, treatment with ACE inhibitors has been shown to delay progression from microalbuminuria to clinical albuminuria and to slow the decline in GFR in clinical albuminuria. Because of the high proportion of patients who progress from microalbuminuria to overt nephropathy and subsequently to ESRD, the use of ACE inhibitors is recommended for all type 1 patients with microalbuminuria, even if they are normotensive. However, because of the more variable rate of progression from microalbuminuria to overt nephropathy and ESRD in patients with type 2 diabetes, the use of ACE inhibitors in normotensive type 2 diabetic patients is not as well substantiated as in normotensive type 1 diabetic patients. Therefore, treatment with ACE inhibitors in normotensive type 2 patients should be based on physician assessment. Should such a patient show progression of albuminuria or develop hypertension, then ACE inhibitors would clearly be indicated.

Measurement of urine albumin should be done on a 24-h or other timed urine collection. Alternatively, the albumin-to-creatinine ratio can be measured in a random urine specimen. There is also marked day-to-day variability in albumin excretion, so that at least two of three collections measured in a 3- to 6-month period should show elevated levels before a patient is designated as having microalbuminuria.

Assessment of the creatinine clearance should be performed by using the serum creatinine and formulas that take into account the patient’s age, sex, and body size or by measuring creatinine in serum and in a timed urine specimen.

Repeat timed or overnight urine collections or measurements of albumin-to-creatinine ratios should be obtained periodically to document the effect of treatment on albumin excretion and to detect the rare case of a deleterious effect of drug therapy. If ACE inhibitors are used, serum potassium levels should also be monitored for the development of hyperkalemia, with an increased frequency of monitoring when there is a progressive decrease in GFR or in patients with hyporeninemic hypoaldosteronism.

Protein restriction to 0.8 g . kg^-1 body wt . day^-1 (~10% of daily calories), the current adult recommended daily allowance for protein, should be instituted with the onset of overt nephropathy. However, it has been suggested that once the GFR begins to fall, further restriction to 0.6 g . kg^-1 body wt . day^-1 may prove useful in slowing the decline of GFR in selected patients. On the other hand, nutritional deficiency may occur in some individuals and may be associated with muscle weakness. Protein-restricted meal plans should be designed by a registered dietitian familiar with all components of the dietary management of diabetes.

Referral to a physician experienced in the care of diabetic renal disease should be considered when the GFR has fallen to either <70 ml . min^-1 . 1.73 m^-2, when serum creatinine has increased to >2.0 mg/dl (>180 µmol/l), or when difficulties occur in management of hypertension or hyperkalemia. (For a complete discussion on the treatment of nephropathy, see the American Diabetes Association’s position statement "Diabetic Nephropathy" in this supplement.)

CARDIOVASCULAR DISEASE
Evidence of cardiovascular disease, such as angina, claudication, decreased pulses, carotid bruits, and electrocardiogram abnormalities, requires efforts to correct contributing risk factors (e.g., obesity, smoking, hypertension, sedentary lifestyle, dyslipidemia, poorly regulated diabetes) in addition to specific treatment of the cardiovascular problem. Daily intake of aspirin has been shown to reduce cardiovascular events in patients with diabetes. (For specific recommendations and further discussion, see the American Diabetes Association’s position statement "Aspirin Therapy in Diabetes" in this supplement.)

DYSLIPIDEMIA
General Principles
Diabetes increases the risk for atherosclerotic vascular disease. This risk is greatest in people who have other known risk factors, such as dyslipidemia, hypertension, smoking, and obesity. Furthermore, in type 2 diabetes there is an additional increased risk for obesity and lipid abnormalities independent of the level of glycemic control. A common abnormal lipid pattern in such patients is an elevation of VLDL, a reduction in HDL, and an LDL fraction that contains a greater proportion of small, dense atherogenic LDL particles.

Data about treatment of dyslipidemia in people with diabetes, especially in children, are limited. However, current recommendations from the National Cholesterol Education Program Adult Treatment Panel II Report and the Expert Panel on Blood Cholesterol Levels in Children and Adolescents Report on the general management of elevated cholesterol and triglycerides have set increasingly stringent treatment targets based on the number of cardiovascular risk factors and the presence of coronary heart disease (CHD). Risk factors include age (men >45 years or women >55 years, or premature menopause without estrogen replacement therapy), diabetes mellitus, hypertension, HDL cholesterol <35 mg/dl (<0.90 mmol/l), smoking, and a family history of premature CHD. Because diabetes appears to eliminate the protective effect of female sex against CHD, all adults with diabetes are candidates for progressively aggressive therapy.

The following recommendations are designed to achieve two major goals as a result of treatment of dyslipidemia: 1) to reduce the risk for development of CHD in people without documented CHD and 2) to reduce the risk for progression of CHD or to cause regression in people with known CHD.

A meal plan designed both to lower glucose levels and to alter lipid patterns and regular physical activity are the cornerstones in the management of lipid disorders. The goal of MNT should focus on three major strategies: weight loss if indicated, increased physical activity, and MNT individualized for the patient.

Weight loss is achieved by reducing total caloric and fat intake and by increasing physical activity. Recommendations for increased physical activity, however, need to be made in the context of the patient’s history and medical status. The recommendations should detail a frequency, duration, and intensity of exercise. Lipid-lowering pharmacological agents are indicated if there is an inadequate response to a trial of MNT, exercise, and improved glucose control. (For a complete discussion of the treatment of lipid disorders, see the American Diabetes Association’s position statement "Diabetic Dyslipidemia" in this supplement.)

The primary emphasis in children and adolescents with serum lipid abnormalities should be on glucose control, MNT, and exercise. Because there are important considerations regarding the efficacy and safety of drug therapy for dyslipidemia in children and adolescents, drug therapy in these individuals should be undertaken only in consultation with a physician experienced in the area of lipid disorders in children.

Specific Goals of Treatment
The primary goal of therapy for adult patients with diabetes is to lower LDL cholesterol to <130 mg/dl (<3.35 mmol/l). The primary goal of therapy in people with known CHD is to lower the LDL cholesterol to <100 mg/dl (<2.60 mmol/l) and triglycerides to <200 mg/dl (<2.30 mmol/l).

People with diabetes who have triglyceride levels >1,000 mg/dl (>11.3 mmol/l) are at risk of pancreatitis and other manifestations of the hyperchylomicronemic syndrome. These individuals need special, immediate attention to lower triglyceride levels to <400 mg/dl (<4.50 mmol/l). Further reduction to Adult Treatment Panel II goals of <200 mg/dl (<2.30 mmol/l) may be beneficial.

A secondary goal of therapy is to raise HDL cholesterol to >35 mg/dl (>0.90 mmol/l) in men and >45 mg/dl (>1.15 mmol/l) in women.

The primary goal of therapy for children with risk factors in addition to diabetes is to lower LDL cholesterol to <110 mg (<2.80 mmol/l), following the recommendations of the National Cholesterol Education Program’s Report of the Expert Panel on Blood Cholesterol Levels in Children and Adolescents.

NEUROPATHY
Peripheral diabetic neuropathy may result in pain, loss of sensation, and muscle weakness. Autonomic involvement can affect gastrointestinal, cardiovascular, and genitourinary function. Each condition may require special diagnostic testing and consultation with an appropriate medical specialist. Improvement in neuropathy should be sought by increased attention to blood glucose control. Relief can be provided by various medications, alterations in MNT, or specialized procedures.

FOOT CARE
Problems involving the feet may require care by a podiatrist, orthopedic surgeon, vascular surgeon, or rehabilitation specialist experienced in the management of people with diabetes. All patients, especially those with evidence of sensory neuropathy and/or peripheral vascular disease, must be educated about the risk and prevention of foot problems, and this education must be regularly reinforced.

Patients with a history of previous foot lesions, especially those with prior amputations, require preventive foot care and lifelong surveillance, preferably by a foot care specialist. (For a complete discussion on foot care, see the American Diabetes Association’s position statement "Foot Care in Patients With Diabetes Mellitus" in this supplement.)

BIBLIOGRAPHY

American Diabetes Association: Aspirin therapy in diabetes (Position Statement). Diabetes Care 21 (Suppl. 1):S45–46, 1998.

American Diabetes Association: Diabetic dyslipidemia (Position Statement). Diabetes Care 21 (Suppl. 1):S36–39, 1998.

American Diabetes Association: Diabetic nephropathy (Position Statement). Diabetes Care 21 (Suppl. 1):S50–53, 1998.

American Diabetes Association: Diabetic retinopathy (Position Statement). Diabetes Care 21 (Suppl. 1):S47–49, 1998.

American Diabetes Association: Foot care in patients with diabetes mellitus (Position Statement). Diabetes Care 21 (Suppl. 1): S54–55, 1998.

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American Diabetes Association: Nutrition recommendations and principles for people with diabetes mellitus (Position Statement). Diabetes Care 21 (Suppl. 1):S32–35, 1998.

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Raskin P (Ed.): Medical Management of Non-Insulin-Dependent (Type II) Diabetes. 3rd ed. Alexandria, VA, American Diabetes Association, 1994.

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