Insulin therapy for type 2 diabetes: rescue, augmentation, and replacement of beta-cell function.

Type 2 diabetes is characterized by progressive beta-cell failure. Indications for exogenous insulin therapy in patients with this condition include acute illness or surgery, pregnancy, glucose toxicity, contraindications to or failure to achieve goals with oral antidiabetic medications, and a need for flexible therapy. Augmentation therapy with basal insulin is useful if some beta-cell function remains. Replacement therapy with basal-bolus insulin is required for beta-cell exhaustion. Rescue therapy using replacement regimens for several weeks may reverse glucose toxicity. Replacement insulin therapy should mimic normal release patterns. Basal insulin, using long-acting insulins (i.e., neutral protamine Hagedorn [NPH], ultralente, glargine) is injected once or twice a day and continued on sick days. Bolus (or mealtime) insulin, using short-acting or rapid-acting insulins (i.e., regular, aspart, lispro) covers mealtime carbohydrates and corrects the current glucose level. The starting dose of 0.15 units per kg per day for augmentation or 0.5 units per kg per day for replacement can be increased several times as needed. About 50 to 60 percent of the total daily insulin requirement should be a basal type, and 40 to 50 percent should be a bolus type. The mealtime dose is the sum of the corrective dose plus the anticipated requirements for the meal and exercise. Adjustments should be made systematically, starting with the fasting, then the preprandial and, finally, the postprandial glucose levels. Basal therapy with glargine insulin provides similar to lower A1C levels with less hypoglycemia than NPH insulin. Insulin aspart and insulin lispro provide similar A1C levels and quality of life, but lower postprandial glucose levels than regular insulin.

The epidemiology of lower-extremity disease in veterans with diabetes.

OBJECTIVE: To describe the epidemiology of lower-extremity complications of diabetes in veterans who are users of the Department of Veterans Affairs (VA). RESEARCH DESIGN AND METHODS: Hospital discharge records for care provided in all VA hospitals in 1998 were obtained. All hospitalizations for lower-extremity ulceration, peripheral vascular procedures, and amputation were analyzed using frequency tables. A diabetes denominator was defined as a veteran with at least three ambulatory care visits with at least one diabetes diagnosis code. Age-specific and total age-adjusted rates of discharge with ulceration, vascular procedures, and amputation were calculated. RESULTS: Veterans with diabetes comprised over half of all hospitalizations for lower-extremity ulceration, one-third of all hospitalizations for peripheral vascular procedures, and two-thirds of all hospitalizations for amputation. The age-specific discharge rate per 1,000 diabetic persons for age 0-64 years, 65-74 years, and 75 years and older for ulceration were 28.4, 31.0, and 37.9; for vascular procedures, the rates were 3.5, 4.4, and 4.4; and for amputation, the rates were 7.3, 9.0, and 10.0, respectively. CONCLUSIONS: Veterans with diabetes comprise a significant proportion of hospitalizations for lower-extremity ulceration, peripheral vascular bypass, and amputation. Age-specific rates of diabetic amputation in veterans are lower than U.S. rates.

Relationship of medial arterial calcinosis to autonomic neuropathy and adverse outcomes in a diabetic veteran population.

STATEMENT OF THE PROBLEM: Medial arterial calcinosis (MAC) is associated with neuropathy, amputation, and mortality through an unknown mechanism. We hypothesized that MAC was a marker of autonomic neuropathy rather than a risk factor and that the outcomes were due to autonomic neuropathy. METHODS: All subjects in an ongoing prospective study of diabetic foot conditions in a diabetic veteran cohort who received a foot radiograph between 11/7/90 and 11/5/93 were included. Autonomic neuropathy measured as either heart rate variability with timed respiration or postural hypotension. A logistic model predicted the presence of MAC at baseline and Cox proportional models assessed the relative contribution of autonomic neuropathy and traditional risk factors for the outcomes of ulceration, amputation, and death. RESULTS: MAC was identified in 181 subjects, no MAC in 253 subjects, and 39 were excluded due to disagreement between observers. Both measures of autonomic neuropathy were independent predictors of MAC at baseline, even after adjustment for vibration sensation loss in a logistic model. MAC was associated with an increased risk for ulceration (hazards ratio, HR: 2.1, 95% confidence intervals, CI, 1.4-3.1), amputation (HR 3.3, 95% CI 1.5-7.4), and mortality (HR 1.6, 95% CI 1.1-2.2). The addition of either autonomic measure of neuropathy did not change the MAC HR or significantly improved the fit of the model. CONCLUSIONS: Our hypothesis that the excess mortality, amputation, and ulceration in persons with MAC could be explained by autonomic neuropathy measured as postural hypotension or heart rate variability with measured respiration was not supported.