Use of insulin aspart, a fast-acting insulin analog, as the mealtime insulin in the management of patients with type 1 diabetes.

OBJECTIVE: To compare long-term glycemic control and safety of using insulin aspart (IAsp) with that of regular human insulin (HI). RESEARCH DESIGN AND METHODS: This was a multicenter randomized open-label 6-month study (882 subjects) with a 6-month extension period (714 subjects) that enrolled subjects with type 1 diabetes. Subjects administered IAsp immediately before meals or regular HI 30 min before meals; basal NPH insulin was taken as a single bedtime dose in the majority of subjects. Glycemic control was assessed with HbA1c values and 8-point blood glucose profiles at 3-month intervals. RESULTS: Mean postprandial blood glucose levels (mg/dl +/- SEM) were significantly lower for subjects in the IAsp group compared with subjects in the HI group after breakfast (156 +/- 3.4 vs. 185 +/- 4.7), lunch (137 +/- 3.1 vs. 162 +/- 4.1), and dinner (153 +/- 3.1 vs. 168 +/- 4.1), when assessed after 6 months of treatment. Mean HbA1c values (% +/- SEM) were slightly, but significantly, lower for the IAsp group (7.78% +/- 0.03) than for the regular HI group (7.93% +/- 0.05, P = 0.005) at 6 months. Similar postprandial blood glucose and HbA1c values were observed at 12 months. Adverse events and overall hypoglycemic episodes were similar for both treatment groups. CONCLUSIONS: Postprandial glycemic control was significantly better with IAsp compared with HI after 6 and 12 months of treatment. The improvement was not obtained at an increased risk of hypoglycemia. HbA1c was slightly, but significantly, lower for IAsp compared with HI at 6 and 12 months.

Neurological disease in xeroderma pigmentosum. Documentation of a late onset type of the juvenile onset form.

Xeroderma pigmentosum (XP) is an autosomal recessive, neurocutaneous disorder characterized by sunlight-induced skin cancers and defective DNA repair. Many XP children develop a primary neuronal degeneration. We describe 2 unusual XP patients who had a delayed onset of XP neurological disease. Somatic cell genetic studies indicated that they have the same defective DNA repair gene and are both in XP complementation group A. These 2 patients, together with a group A patient previously reported from London, establish as a distinct clinical entity the late onset type of the juvenile onset form of XP neurological disease. The functional capacity of these patients' cultured fibroblast strains to survive after treatment with ultraviolet radiation indicates that their DNA repair defect is less severe than that of typical group A patients who have a more severe neurodegeneration with an earlier symptomatic onset. The premature death of nerve cells in XP patients (which is presumably due to their inherited defects in DNA repair mechanisms) suggests that normal repair of damaged DNA in neurons is required to maintain integrity of the human nervous system.

New approaches to improve diabetes control.

Knowledge about diabetes mellitus and its management has steadily increased since the discovery of insulin in 1921. Specific therapies for both type I and type II diabetes have resulted in greater normalization of plasma glucose levels. Information obtained from self-monitoring of blood glucose levels has given physicians a firmer base on which to make management decisions concerning the safe control of diabetes.

Approach to management.

This paper describes a physiologic approach to diabetes management called pattern therapy and compares it with the sliding scale or "catch-up" type of management. Pattern therapy differs from the sliding scale approach in that it anticipates rather than reflects insulin needs, and it relies heavily on intensive patient education and intelligent self-management. Frequent blood glucose monitoring is also a key aspect of pattern therapy.

Changes in cortical functioning with acute hypoglycemia and hyperglycemia in type I diabetes.

In this study, 18 type I (insulin-dependent) diabetic subjects aged 22-35 yr (mean age 29.3) and within 10 yr of diagnosis (mean 7.7) performed a battery of cognitive and psychomotor tasks under conditions of hypoglycemia (50 mg/dl), normoglycemia (100 mg/dl), and hyperglycemia (300 mg/dl). Blood glucose levels during testing were precisely maintained at the preselected level via a Biostator insulin/glucose-infusion system. The order of glycemic level was counterbalanced across subjects in a single-blinded design. Performance on tasks requiring visual tracking, visuomotor speed, concentration, and planning ability (pursuit rotor and trails B) were significantly impaired under conditions of hypoglycemia compared with normoglycemic levels. Visual reaction time was not significantly impaired under conditions of hypoglycemia or hyperglycemia.

Self-monitoring of blood glucose: an important adjunct to diabetes therapy.

Therapy for diabetes mellitus, especially type I diabetes mellitus, is changing rapidly. Several developments and discoveries have contributed to this change. Most important, the data relating to the relationship between vascular disease and neuropathy and control of blood sugar and the developments in monitoring of glucose control have had a major impact on concepts of therapy. The development of new and purer insulins and new delivery systems have also improved diabetic control. The major concept that has evolved in recent years has been that the vascular disease and neuropathy of diabetes are related to control of the blood glucose and, therefore, it is important to deliver insulin in a physiologic way that duplicates the pattern of control found in nature. Techniques to better accomplish this goal are now evolving.

Effect of dietary fiber in insulin-dependent diabetics: insulin requirements and serum lipids.

Four young adult (18 to 26 years old), nonobese human subjects (two men and two women) with insulin-dependent diabetes mellitus volunteered to consume a series of three diets: baseline (normal daily intake), wheat bran (normal daily intake + 78 gm wheat bran per day), and cellulose (normal daily intake + 30 gm cellulose per day). Wheat bran and cellulose diets both contained 60 gm dietary fiber, with 50% of the dietary fiber from wheat bran or cellulose, respectively. Each patient served as his or her own control. Randomized diets were of 6 weeks' duration, separated by a 4-week "recovery" period. At the conclusion of each diet, subjects were hospitalized and underwent 12 hours of computer-controlled, insulin-glucose infusions. Significant decreases were seen in fasting cholesterol (p less than .05), but the decreases seemed to result largely from the significant reductions in high-density lipoprotein cholesterol. A large reduction in triglycerides was noted with cellulose feeding but not with wheat bran. The mean daily insulin dose decreased (p less than .05) in response to fiber addition (8% and 10% decrease for wheat bran and cellulose feeding, respectively). Mean biostator insulin requirements decreased 11% with wheat bran (p less than .05) but not with cellulose. During biostator monitoring, subjects experienced delayed postprandial blood glucose and insulin-infusion rate peaks with both wheat bran and cellulose feeding. The wheat bran diet reduced peak blood glucose concentration and peak insulin infusion rate in comparison with baseline and cellulose diets. The data suggest that high levels of cellulose or wheat bran are of marginal benefit to insulin-dependent diabetic subjects.

Capillary basement membrane changes in adolescents with type 1 diabetes.

Measurements were made of muscle capillary basement membrane thickness (CBMT) in 95 normal boys and girls and 167 postpubescent insulin-dependent diabetics. Of 110 diabetics in whom "higher" degrees of metabolic control were maintained, only two had increased CBMT values. Of 57 diabetics in whom "lower" degrees of metabolic control were maintained, 26 had increased CBMT values. Two or more muscle biopsies were done in each of 65 diabetic subjects: Mean CBMT values of 24 subjects with "higher" degrees of metabolic control for two to nine years remained within the normal range; values of 23 subjects with "lower" degrees of metabolic control for only one to three years increased from 858 +/- 142 A to 1,155 +/- 227 A: values of 13 subjects who had been in "lower" degrees of control decreased from 1,255 +/- 232 A to 869 +/- 135 A after maintaining "improved" metabolic control for about a year. In postpubescent diabetics, the CBMT is labile and progresses or regresses depending on the degree of metabolic control.

Retinopathy in adolescents and young adults with onset of insulin-dependent diabetes in childhood.

Retinal studies were done in 181 postpubescent, insulin-dependent diabetic patients who developed diabetes before the age of 20. Retinal studies included serial direct ophthalmoscopic examinations, stereoscopic fundus photography and fluorescein angiography. At the time of retinal studies, muscle biopsies also were done to measure capillary basement membrane thickness (CBMT) as an index of early microvascular changes in skeletal muscles. Assessment of clinical metabolic control, interpretation of retinal findings, and CBMT were done independently. No retinopathy was detected in patients observed continuously and known to have been in higher degrees of metabolic control. Twenty-five patients in lower degrees of control for extended periods had retinopathy. CBMT was found to be labile and to progress or regress within a year depending on the degree of control. All patients in lower degrees of control with retinopathy had increased CBMT, but if they subsequently attained and maintained a high degree of control for a year, then CBMT diminished and there was no progression of retinopathy. Our study demonstrates that a high degree of metabolic control delays, and may prevent, microvascular changes, and confirms other studies indicating that most postpubescent, insulin-dependent diabetic patients will develop retinopathy within 15 years unless a relatively high degree of control is maintained.