The use of information technology for the management of intensive insulin therapy in type 1 diabetes mellitus.

OBJECTIVE: The purpose of the study was to evaluate the safety of a computer program used by the patient for the adjustment of insulin doses to achieve tight glycemic control in type 1 diabetic subjects on intensive insulin therapy. METHODS: Ten type 1 diabetic patients participated in the study. Using the basal-bolus (UL-Humalog) insulin regimen, they were randomized in a crossover design to 2 intensive treatment periods of 8 weeks each, one with and the other without the assistance of a computer program via the Internet. They measured their capillary blood glucose regularly, and the results were entered on a daily basis into their log-book or in the computer. During intensive treatment with the computer, the software would provide recommendation for insulin dose adjustment according to specific algorithms. When on intensive treatment without computer assistance, they would adjust their own insulin dose according to the same algorithms. RESULTS: The study subjects followed 89% of the recommendations made by the computer. With the computer, subjects made more insulin dose adjustments (98 versus 50) than without. Intensive treatments with and without computer assistance resulted in a similar improvement of pre-meal/post-prandial capillary blood glucose from 7.6 +/- 2.7/9.5 +/- 2.5 to 6.7 +/- 2.3/8.8 +/- 2.5 and 6.7 +/- 2.6/9.0 +/- 2.6 mmol/L, respectively. Glygated hemoglobin also improved from 7.7 +/- 0.9% to 7.2 +/- 0.7 and 7.3 +/- 0.8%, respectively. The incidence of minor hypoglycemia was similar under both intensive treatments (7.9 +/- 4.0 and 7.1 +/- 5.0/patient/28 days, respectively). Both treatments increased patient behavior while patient knowledge of their disease was improved only during computer assistance. There was no effect on quality of life. The study subjects greatly appreciated the software and wanted to continue using it. CONCLUSIONS: The study demonstrated that the use of computer software by the patient to adjust insulin doses for intensive insulin therapy is feasible and is not associated with increased adverse events.

Effects of meal carbohydrate content on insulin requirements in type 1 diabetic patients treated intensively with the basal-bolus (ultralente-regular) insulin regimen.

OBJECTIVE: In this study, we evaluated the effects of high-(55%) and low-(40%) carbohydrate diets on insulin requirements in nine type 1 diabetic subjects treated intensively with ultralente as basal insulin and regular insulin as premeal insulin adjusted to the carbohydrate content of meals. RESEARCH DESIGN AND METHODS: Nine subjects were randomized in a crossover design to follow two diets consecutively for a period of 14 days each. A 3-day food diary was completed for each diet with the amount of carbohydrate in the mixed meals ranging from 21 to 188 g. Preprandial (5.9 vs. 6.1 mmol/l) and postprandial (8 vs. 8.9 mmol/l) capillary glucose and fructosamine (310 vs. 316 mumol/l) were comparable on both the low- and high-carbohydrate diets. RESULTS: The assessment of meal carbohydrate content by the patients was excellent, with > 85% of cases falling within 15% of computer-assisted evaluation. When premeal regular insulin was prescribed in U/10 g of carbohydrate, the postprandial glycemic rise remained constant (2.4 +/- 2.8 mmol/l) over a wide range of carbohydrate ingested (21-188 g) and was not affected by the glycemic index, fiber, and caloric and lipidic content of the meals. This tight control was maintained during the low- and high-carbohydrate diet without any change in insulin requirements (breakfast, 1.5 vs. 1.5 U/10 g of carbohydrate; lunch, 1.0 vs. 1.0; supper, 1.1 vs. 1.2) and in basal ultralente insulin requirements (22.5 vs. 21.4 U/day). CONCLUSIONS: These results indicate that in type 1 diabetic subjects 1) increasing the amount of carbohydrate intake does not influence glycemic control if premeal regular insulin is adjusted to the carbohydrate content of the meals; 2) algorithms based on U/10 g of carbohydrate are effective and safe, whatever the amount of carbohydrate in the meal; 3) the glycemic index, fiber, and lipidic and caloric content of the meals do not affect premeal regular insulin requirements; 4) wide variations in carbohydrate intake do not modify basal (ultralente) insulin requirements; and, finally 5) the ultralente-regular insulin regimen allows dissection between basal and prandial insulin requirements, so that each can be adjusted accurately and independently.

Glucose metabolism during exercise in man: the role of insulin and glucagon in the regulation of hepatic glucose production and gluconeogenesis.

This study was designed to further characterize the role of insulin and glucagon in the regulation of glucose production and gluconeogenesis during a 2-h mild intensity exercise (40% VO2max) in 14 h fasted healthy male subjects. Endogenous insulin and glucagon secretions were suppressed by the infusion of somatostatin. The pancreatic hormones were replaced singly or in combination to match the hormonal concentrations observed during exercise in control subjects. Glucose turnover was determined by a tracer method using the stable isotope D-[2,3,4,6,6-2H]glucose. Gluconeogenesis was estimated by the simultaneous infusion of L-[1,2,3-13C]alanine to follow the conversion of alanine to glucose. Hepatic glucose production significantly increased from a resting rate of 12.1 +/- 0.2 to 27.6 +/- 1.4 mumol.kg-1.min-1 during exercise (p < 0.05). In the absence of glucagon, this increase in hepatic glucose production during exercise was totally abolished (p < 0.05). When insulin was made deficient, in the presence of glucagon, there was an overshoot in the increase in hepatic glucose production during exercise to 36.4 +/- 1.6 mumol.kg-1.min-1 (p < 0.05). The normal increase in hepatic glucose output during exercise was reproduced when both insulin and glucagon were replaced. Exercise increased gluconeogenesis by 47% above the resting level (p < 0.05). When glucagon was made deficient, in the absence or presence of insulin, this increase in gluconeogenesis was totally suppressed (p < 0.05). Furthermore, glucagon replacement during exercise in the absence of insulin resulted in a further increase in gluconeogenesis to 93% above resting value (p < 0.05). From these observations, it is concluded that during prolonged mild intensity exercise in healthy subjects, the rise in glucagon is essential for the increase in hepatic glucose production and the increase in gluconeogenesis. It is also suggested that the lower level of insulin during exercise still exerts a restraining effect on glucagon-stimulated glucose production and gluconeogenesis, thus preventing hyperglycemia.

Glucose metabolism during exercise in man: the role of insulin in the regulation of glucose utilization.

The present study was designed to characterize further the role of insulin in the regulation of glucose utilization during a 2-h exercise at 40% VO2max in 14 h fasted, healthy subjects. Endogenous insulin and glucagon were suppressed by somatostatin infusion and replaced singly or in combination to match the hormonal concentrations observed during similar exercise in saline-treated control subjects. Glucose kinetics were determined by a tracer method using D-[2,3,4,6,6-2H]glucose. In the exercising controls, during the last hour of the exercise, plasma glucose remained stable (4.26 +/- 0.06 mmol/L) and glucose utilization (Rd) increased significantly (p < 0.05) from 12.2 +/- 0.2 to 28.6 +/- 1.3 mumol.kg-1.min-1. During insulin deficiency without glucagon replacement, plasma glucose was maintained at 3.74 +/- 0.10 mmol/L by dextrose infusion, but with glucagon replacement plasma glucose increased to 6.69 +/- 0.24 mmol/L (p < 0.05). These hormonal changes were associated with an increase in Rd to 18.6 +/- 1.1 mumol.kg-1.min-1 (p = ns versus resting controls) and to 37.9 +/- 1.9 mumol.kg-1.min-1 (p < 0.05 versus resting controls), respectively. When insulin was replaced without glucagon replacement, plasma glucose was maintained at 3.85 +/- 0.06 mmol/L by dextrose infusion and Rd increased significantly (p < 0.05) from the resting value to 25.9 +/- 0.7 mumol.kg-1.min-1. When insulin was replaced together with glucagon, the plasma glucose (4.29 +/- 0.15 mmol/L) and the Rd (32.1 +/- 0.9 mumol.kg-1.min-1, p < 0.05 versus the resting value) obtained were similar to the values from the saline exercising control. Glucose metabolic clearance rate (MCR) significantly increased (p < 0.05) during exercise in all protocols. When insulin was made deficient, MCR increased 2-fold (p < 0.05) during exercise (2.7 to 4.8 and 5.4 mL.kg-1.min-1, respectively, with and without glucagon deficiency). However, when insulin was present, with and without glucagon deficiency, it increased further to 6.7 and 7.5 mL.kg-1.min-1, respectively, and values were different (p < 0.05) from glucose MCRs during insulin deficiencies. It is concluded that in 14 h fasted, healthy subjects, exercise per se can stimulate whole body glucose uptake even when insulin is made deficient. Insulin is necessary, however, for optimal glucose utilization during prolonged mild intensity exercise.