Concise Update to Managing Adult Diabetes. (Featured CME Topic: Diabetes Mellitus).

THE PREVALENCE of type 2 diabetes and obesity has reached epidemic proportions in the United States. (1) Diabetes is the seventh leading cause of death and accounts for approximately 15% of health care expenditures in the United States. While the prevalence of diabetes has been estimated at 6%, in many populations, such as veterans, the elderly, and minorities, the prevalence is considerably higher and has disproportionately severe consequences to both the patient and health care resources. Cardiovascular disease accounts for 75% to 80% of the mortality in diabetic patients. In the United Kingdom Prospective Diabetes Study, (2) a 14% reduction in myocardial infarction was linked to every 1% reduction in hemoglobin [A.sub.1c] ([HbA.sub.1c]) level. In the same study, no increase in cardiovascular disease resulted from intensive insulin use, despite previous data implicating hyperinsulinemia as a cardiovascular risk factor. (3) It is clear that early intervention with insulin is justified to achieve better diabe tic control. Uncontrolled blood sugar remains perhaps the most underrated cardiovascular risk factor; moreover, glucose intolerance is a significant risk factor for cardiac disease. The screening criteria for type 2 diabetes should help to detect a large number of undiagnosed type 2 diabetic patients (see Selected Guidelines, page 35).

INITIAL EVALUATION

The history and physical examination remain essential to the management of diabetes and are summarized in Table 1. The initial visit of a diabetic patient allows the primary care provider to discuss the concerns and wishes of the patient in the context of achieving good diabetic control. In rare instances, the patient may decline intensive treatment despite information regarding the consequences of protracted hyperglycemia; moreover, the presence of disabling hypoglycemia with lack of hypoglycemic awareness may prevent intensive control of blood sugar. Laboratory testing is an integral part of the initial evaluation. A list of desired laboratory tests is shown with ideal values in Table 2.

GENERAL MANAGEMENT

Avoidance of diabetic complications with excellent blood sugar control and minimal hypoglycemia is the desired goal in diabetes management. This process needs to be individualized and is dependent upon active patient participation. Documenting an individualized plan and the level of patient participation expected is a helpful addition to the patient's chart. A copy of such a document signed by the patient and physician may enhance communication and facilitate better outcomes.

ACHIEVING AN OPTIMAL [HBA.sub.1c] LEVEL

The importance of achieving an excellent glycosylated hemoglobin [A.sub.1c] level has now become widely recognized. Studies in both type 1 and type 2 diabetic patients confirm the benefits of tight blood sugar control. While optimal control has been defined as an [HbA.sub.1c] level <7%, more recently this value has been lowered to <6.5% by the American Association of Clinical Endocrinologists. In many cases, access to a multidisciplinary team specializing in diabetes care is needed to achieve this level of blood sugar control. The need for continuing patient participation and education is recognized as essential for achieving optimal glucose control.

NONPHARMACOLOGIC THERAPY

Diet remains a cornerstone in the management of all diabetic patients. The goal of nutritional intervention is to assist in achieving desired glucose and lipid values. These goals are achieved by regulating daily intake with consistent carbohydrate intake and promoting healthy eating habits. In our experience, teaching the patient to count carbohydrates forms the basis for successful dietary intervention in diabetes. This method of counting carbohydrates makes the assumption that carbohydrates are the major influence on blood sugar levels; it therefore focuses on carbohydrate intake when planning a meal. It also assumes that all carbohydrates have a similar effect on blood sugar levels. A summary of the guidelines for diet is given in Table 3.

Exercise can reduce cardiovascular risk, enhance well-being, and increase endurance while assisting with weight reduction. The risks of exercise include hypoglycemia, cardiac events, vitreous hemorrhage, and soft tissue injuries. The blood sugar profile may worsen with exercise if initial glycemic control is poor. The guideline for exercise in patients with diabetes is given in Table 4. The importance of diet and exercise is underscored by recent data indicating that diabetes may be prevented by regular exercise and dietary modification. (4)

PHARMACOLOGIC TREATMENT

The use of drugs to aid weight loss in the management of diabetes has been of recent interest. The use of sibutramine (Meridia) has resulted in significant metabolic benefit in type 2 diabetes Mellitus. (5) A similar outcome may be expected with the use of orlistat (Xenical), and these studies are pending.

Any diabetic patient with symptoms of hyperglycemia and/or persistent blood sugar levels of >300 mg/dL should initially be started on insulin. A persistently high blood sugar level is toxic to the beta cells and may contribute to peripheral insulin resistance. The usual daily starting dose for insulin is 0.5 to 1.0 unit per kilogram of body weight. Once the glycemic profile has improved with symptom relief, a transition to oral antidiabetic medication can be considered in appropriate type 2 patients. Patients with less severe hyperglycemia despite diet and exercise are normally started on oral antidiabetic agents. A wide range of oral agents for treating diabetes is now available. A guideline for initial use of oral hypoglycemic agents is shown in Figure 1.

Monotherapy may not be sufficient to achieve optimal diabetic control, and the addition of a second oral agent is often helpful. Useful oral dual-agent combinations are given in Figure 2. In some situations, a third oral agent may enhance glycemic control. Cost and patient compliance issues need to be considered before triple-agent antidiabetic therapy is begun.

Failure to achieve glycemic control with oral agents is an indication for insulin. In many cases, the addition of a bedtime injection of NPH insulin is sufficient to improve glycemic control. The approximate initial dose of bedtime NPH insulin can be calculated as 25% of patient weight in kilograms (eg, a 100 kilogram patient will receive 25 units of NPH at bedtime).

Progressive deterioration of beta cell function may require multiple insulin injections. In many instances when insulin is added the use of sulfonylureas and/or meglitinides can be discontinued. Insulin-sensitizing agents should be continued, however, and may enable the dose of insulin required for glycemic control to be minimized. Traditionally, most physicians have focused on preprandial or fasting hyperglycemia in the quest for optimizing glycemic control. Newer information indicates that postprandial hyperglycemia may also need intensive intervention. (6) In some patients, failure to achieve adequate [HbA.sub.lc] levels despite a good fasting blood sugar profile may indicate pronounced postprandial hyperglycemia. In these situations, agents that target postprandial blood sugar levels such as the meglitinides, [alpha]-glucosidase inhibitors, and rapid-acting insulin (Novolog and Humalog) may be considered. A value of less than 140 to 160 mg/dL in the postprandial period may be optimal but difficult to achi eve. Figure 3 provides an outline of the insulin regimens used in the treatment of diabetes based on the desired glucose goals.

The newer insulin glargine (Lantus) provides a 24-hour basal insulin requirement and may be associated with less nocturnal hypoglycemia. (7) Early results indicate good success combining glargine with a rapid-acting insulin (Humalog /Novolog) to cover meal-related blood sugar excursions. The basal coverage provided by insulin glargine and postprandial coverage with rapid-acting insulin is similar to the concept of the insulin pump. The rapid-acting insulin can also be used for supplemental insulin requirements via a sliding scale.

ACHIEVING OPTIMAL LIPID PARAMETERS

The death rate from myocardial infarction in diabetic patients is similar to the death rate in nondiabetic patients with preexisting cardiac disease; thus, the presence of diabetes can be considered risk equivalent to established coronary artery disease. (8) An intensive effort to achieve the desired goals for lipid parameters (Table 3) is mandatory. It is important to note that lipid lowering is as effective (and possibly more effective) in reducing coronary artery disease in diabetic patients as it is in nondiabetic patients. Postprandial hyperlipidemia may also contribute to the increased atherogenic risk in diabetes. (9) Statin therapy may be combined with fibric acid derivatives or niacin for optimal lipid levels. Statins appear to be interesting agents, with potential promise in reducing the prevalence of diabetes in addition to their cardioprotective effects. The latter may include benefits in the setting of acute coronary ischemia.

Treatment with nicotinic acid should be considered in diabetic patients, especially if they have a combined hyperlipidemia and a good [HbA.sub.lc] level (ie, <7%). (10) Nicotinic acid is a potent agent for raising high-density lipoprotein (HDL) levels and any potential effect on glucose tolerance can be monitored by close supervision of glucose levels and [HbA.sub.lc] levels. The addition of omega-3 fatty acids (1,000 to 3,000 mg daily) in the form of fish oil or flaxseed oil may also be beneficial in reducing elevated triglyceride levels. (11) Additional benefits of omega-3 fatty acids may include reduced coronary events (12) and reduced mortality, though further studies are needed.

ACHIEVING OPTIMAL BLOOD PRESSURE READINGS

Inadequately controlled blood pressure remains a frequent problem in many outpatient clinics. The target blood pressure goal should be less than 130/80 mm Hg. A blood pressure level lower than this, such as 120/80 mm Hg, may be desirable in selected patients. Although the evidence is less convincing in older people, reduction of blood pressure to similar levels in older diabetic hypertensive patients may be desirable if the medication is tolerated. In a recent study of diabetic patients, (2) a modest reduction in systolic blood pressure on the order of 10 to 15 mm Hg was associated with a 10% to 15% reduction in death, myocardial infarction, and microvascular complications. A progressive reduction in cardiovascular events with concurrent reduction in diastolic blood pressure was also noted. (13)

The choice of antihypertensive agents in diabetes has been widely discussed. Angiotensin-converting enzyme inhibitors remain agents of choice for hypertension and / or the presence of microalbuminuria / proteinuria. New information also indicates that they can offer benefits in diabetic patients in the context of acute coronary ischemia. (14) The Heart Outcomes Prevention Evaluation (HOPE) study (15) indicated a 25% reduction of cardiovascular death, stroke, and myocardial infarction in high-risk patients given ramipril. The beneficial effects of ramipril were demonstrable even after adjusting for blood pressure effects.

PREVENTIVE MEASURES AND OUTCOMES

Diabetic patients are generally considered hypercoagulable and an aspirin a day (81 to 325 mg/day) is recommended for patients older than 30 years of age. Flu vaccinations, pneumococcal vaccinations, and smoking cessation programs should be offered to diabetic patients. Recent information suggests that these simple measures are relatively underutilized.

The best outcome in terms of diabetes management will result from a concerted team effort to achieve and maintain the desired blood sugar levels, lipid parameters, and blood pressure levels in diabetic patients. Failure to achieve desired objectives is an indication for an appropriate subspecialty consultation.

Many advances such as nasal insulin, insulin analogues, new glucose sensors (transcutaneous as well as implantable) and islet cell transplantation offer potential significant quality of life improvements to the diabetic patient. Newer medications and new uses of existing medications (such as thiazolidinediones being used for their beneficial endothelial effects) may offer enhanced cardioprotection to diabetic patients.

References

(1.) Mokdad AH, Bowman BA, Ford ES, et al: The continuing epidemics of obesity and diabetes in the United States. JAMA 2001;286:1195-2000

(2.) Adler AI, Stratton IM, Neil HA, et al: Association of systolic blood pressure with macrovascular and microvascular cmplications of type 2 diabetes (UKPDS 35): prospective observational study. BMJ 2000; 321:412-419

(3.) Stratton IM, Adler AI, Neil HA, et al: Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study. BMJ 2000; 321:405-412

(4.) Fruchter O: Prevention of type 2 diabetes mellitus by changes in lifestyle. N Engl J Med 2001; 345:696-697

(5.) Gokcel A, Karakose H, Ertorer EM, et al: Effects of sibutramine in obese female subjects with type 2 diabetes and poor blood glucose control. Diabetes Care 2001; 24:1957-1960

(6.) Bell DS: Importance of postprandial glucose control. South Med J 2001; 94:804-809

(7.) Rosenstock J, Schwartz SL, Clark CM Jr, et al: Basal insulin therapy in type 2 diabetes: 28-week comparison of insulin glargine (HOE 901) and NPH insulin. Diabetes Care 2001; 24:631-636

(8.) LaRosa JC: Prevention and treatment of coronary heart disease: who benefits? Circulation 2001; 104:1688-1692

(9.) Ginsberg HN, Illingworth DR: Postprandial dyslipidemia: an atherogenic disorder common in patients with diabetes mellitus. Am J Cardiol 2001; 88:9H-15H

(10.) Elam MB, Hunninghake DB, Davis KB, et al: Effect of niacin on lipid and lipoprotein levels and glycemic control in patients with diabetes and peripheral arterial disease: the ADMIT study: a randomized trial. Arterial Disease Multiple Intervention Trial. JAMA 2000; 284:1263-1270

(11.) Sirtori CR, Crepaldi G, Manzato E, et al: One-year treatment with ethyl esters of n-3 fatty acids in patients with hypertriglyceridemia and glucose intolerance: reduced triglyceridemia, total cholesterol, and increased HDL-C without glycemic alterations. Atherosclerosis 1998; 137:419-427

(12.) Harris WS, Isley WL: Clinical trial evidence for the cardio-protective effects of omega-3 fatty acids. Curr Atheroscler Rep 2001; 3:174-179

(13.) Elliott WJ: Intensive antihypertensive treatment to the new lower blood pressure targets. Curr Hypertens Rep 1999; 1:313-319

(14.) Zuanetti C, Latini R, Maggioni AP, et al: Effect of the ACE inhibitor lisinopril on mortality in diabetic patients with acute myocardial infarction: data from the GISSI-3 study. Circulation 1997; 96:4239-4245

(15.) Yusuf S, Sleight P, Pogue J, et al: Effects of an angiotensinconverting enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. The Heart Outcomes Prevention Evaluation Study Investigators. N Engl J Med 2000; 342:145-153

TABLE 1.

History and Physical Diagnosis

History

1. Presenting symptoms; evidence of hypoglycemia or hyperglycemia

2. Previous laboratory evaluations and results pertaining to diagnosis
   of diabetes

3. Record of previous [HbA.sub.1c] evaluations

4. Previous treatment programs; dietary history and evaluation of
   diabetic education and level of understanding

5. Active diabetic treatment; drugs, dietary measures, monitoring,
   and integration of information with self-care by patient

6. Exercise history

7. History of acute diabetic complications; frequency and
   precipitants (to include evaluation of patient, family,
   and caregiver response)

8. History of foot, skin, dental, and genitourinary infections

9. Evaluation of chronic complications of diabetes, eg, ophthalmologic,
   podiatric, neurologic, and cardiac

10. Evaluation of patient's medications that impact diabetic control

11. Evaluation for risk factors of atherosclerosis

12. Family history of diabetes

13. Gestational diabetes and history of macrosomia, polyhydramnios,
    and still-births

14. Assessment of sociocultural factors with an influence on diabetic
    management, eg, education level

15. Use of alcohol and tobacco

16. Comorbid conditions

17. Family history and ethnicity

Physical Examination:

1. Height, weight, and body habitus

2. Attainment of developmental milestones (in children and adolescents)

3. Determination of blood pressure (including orthostatic measurements)

4. Fundoscopic evaluation (under dilatation)

5. Oropharyngeal examination under direct visiualization

6. Thyroid palpation

7. Cardiovascular system evaluation (to include evaluation for
   peripheral circulation and assessment for abdominal bruits)

8. Abdominal examination (eg, for hepatomegaly)

9. Evaluation of extremities for adequacy of circulation, signs
   of infection , and morphology of joints

10. Skin; injection sites, pigmentation, body hair patterns, and
    striae

11. Neurologic assessment

12. Hand and foot examination

Adapted from Diabetes Care 2001; 24 (suppl 1)
TABLE 2.

Laboratory Testing

Test                    Ideal Value

[HbA.sub.1c]            <7% (*)
Triglycerides           <200 mg/dL
LDL cholesterol         <100 mg/dL
Fasting blood glucose   <120 mg/dL
Bedtime glucose         <140 mg/dL
Urine microalbumin (+)  Negative
Urine protein           Negative
Liver function (**)     Normal

(*)<6.5% per American Associationof Clinical Endocrinology

(+)May be screened with albumin/creatinine ratio, normal <30, or
assessed with a timed urine collecton

(**)The possibility of hepatic steatosis and potential use of oral
agents influenced by liver dysfunction make a liver panel desirable
in type 2 diabetes.
TABLE 3.

Prescribing a Diet for the Diabetic Patient

1. Determine the ideal body weight

2. Calculate basal calorie ingestion (can be approximately 30 cal/kg)

3. Determine desired daily calorie intake based on ideal body weight,
   physical activity, and lifestyle (individualize calorie needs)

4. Recommended daily amount:

   Carbohydrate             55%-60% of total calories
   Protein                  15%-20% of total calories
   Fat                      <30% of total calories
   Cholesterol              <300 mg/day
   Sodium                   <2,400-3,000 mg/day
   Fiber                    35-40 g/day

5. Carbohydrate calories per day = total calories x % carbohydrate

6. Carbohydrate grams per day = carbohydrate calories/4 calories/g

7. Allocate carbohydrates throughout the day and teach the patient
   to count carbohydrates (15 grams = 1 carb)

Examples of 15 gram carbohydrate portions: 1/2 cup orange juice,
1/2 cup Coca-Cola, 1 cup Gatorade, 1/2 cup cream soup, 3 graham
cracker squares, 1/2 cup regular ginger ale
TABLE 4.

Exercise and Diabetes

1. Screening before exercise
   * Perform physical evaluation

   * Assess glycemic control

   * Consider exercise stress test if patient is at high risk for
     cardiac disease

   * Perform retinal and podiatric examinations

2. Recommendations for diabetic patients

   * Start exercise cautiously and avoid unplanned, spontaneous
     exercise

   * Monitor blood glucose before, during, and after exercise, and
     consume extracarbohydrates for unplanned exercise (20 to 30 grams
     per 30 mm of exercise)

   * Exercise 1 to 3 hours after meals and consume extra carbohydrates
     before strenuous exercise

   * Reduce insulin dosages by 20% to 30% for planned exercise

   * Exercise with partners who can assist if needed

   * Exercise should have a consistent pattern (time of day, relation
     to meals, etc)

   * Ensure adequate pre-exercise hydration, appropriate level of
     warm-up, and adequate cool-down

   * People with preexisting complications should exercise extra caution

3. Goal

   * Minimum of 20 to 30 minutes of aerobic activity daily