Lispro or regular insulin for multiple injection therapy in adolescence. Differences in free insulin and glucose levels overnight.
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OBJECTIVE: Regular insulin given with the evening meal could contribute to the risk of nocturnal hypoglycemia in adolescents with type 1 diabetes using a multiple injection regimen. To test this hypothesis, we compared glucodynamics and free insulin levels on two separate study nights. RESEARCH DESIGN AND METHODS: A total of 14 adolescents were recruited. On both nights, identical doses of regular insulin or insulin lispro were administered 30 min or 10 min, respectively, before the evening meal, using a double-blind randomized crossover study design. Doses of NPH insulin and carbohydrate content of the evening meal and snack were kept identical. Blood samples were taken every 15 min for blood glucose and every 60 min for free insulin and ketones. RESULTS: After insulin lispro administration, glucose levels were significantly lower between the evening meal and the bedtime snack (analysis of variance [ANOVA] P = 0.02), and four hypoglycemic episodes were recorded. This corresponded to a higher (458 +/- 48 vs. 305 +/- 33 pmol/l, P = 0.02), earlier (64 +/- 4.6 vs. 103 +/- 12 min, P = 0.01), and shorter-lasting (245 +/- 21 vs. 365 +/- 39 min, P = 0.01) insulin peak in contrast to regular insulin. After the bedtime snack, glucose levels increased dramatically during the lispro night and stayed higher, up to 0300 in the morning (ANOVA P = 0.01), corresponding to lower mean insulin levels (146 +/- 20 vs. 184 +/- 27 pmol/l, P = 0.04). No differences were seen in glucose and insulin levels between 0300 and 0800. Four episodes of nocturnal hypoglycemia were documented after the bedtime snack during the regular insulin night, in contrast to one episode after insulin lispro. No differences in ketone levels were observed. CONCLUSIONS: The replacement of regular insulin with insulin lispro may reduce the risk of late hypoglycemia, but redistribution of the evening carbohydrate may be needed to ensure good metabolic control and prevent early postprandial hypoglycemia. (+info)
Efficacy of metformin in the treatment of NIDDM. Meta-analysis.
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OBJECTIVE: The results differ concerning randomized controlled trials of the effects of metformin on blood glucose regulation and body weight. To get a systematic overview, a meta-analysis of the efficacy of metformin was performed by comparing metformin with placebo and sulfonylurea. RESEARCH DESIGN AND METHODS: All randomized controlled trials published since 1957 were selected by searching the Current List of Medical Literature, Cumulated Index Medicus, Medline, and Embase, Meta-analysis was performed calculating weighted mean difference (WMD) of fasting blood glucose, glycosylated hemoglobin, and body weight. RESULTS: Nine randomized controlled trials comparing metformin with placebo and ten comparing metformin with sulfonylurea were identified. The WMD between metformin and placebo after treatment for fasting blood glucose was -2.0 mmol/l (95% CI -2.4 to -1.7) and for glycosylated hemoglobin -0.9% (95% CI -1.1 to -0.7). Body weight WMD was not significant after treatment. Sulfonylurea and metformin lowered blood glucose and glycosylated hemoglobin equally, while there was a significant WMD of body weight (-2.9 kg [95% CI -4.4 to -1.1]) because of a 1.7-kg mean increase after sulfonylurea and a 1.2-kg mean decrease after metformin. CONCLUSIONS: Metformin lowers blood glucose and glycosylated hemoglobin significantly, compared with placebo. Metformin and sulfonylurea have an equal effect on fasting blood glucose and glycosylated hemoglobin, but the body weight is significantly lower after metformin compared with sulfonylurea treatment because of an increase in body weight after sulfonylurea treatment. (+info)
First 20 months' experience with use of metformin for type 2 diabetes in a large health maintenance organization.
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OBJECTIVE: To assess adherence to prescribing guidelines, continuation rates, population effects on glycemic control, and occurrence of lactic acidosis during the first 20 months of the availability of metformin in a large health maintenance organization. RESEARCH DESIGN AND METHODS: A retrospective cohort study was performed in the 90,000-member diabetes registry of Kaiser Permanente, northern California. Principal study measures were the proportions of patients started on metformin who met prescribing guidelines (previously on sulfonylureas, HbA1c, obesity, creatinine), the change in HbA1c at 6 months after starting metformin, and hospitalization rates for lactic acidosis. RESULTS: A total of 9,875 patients received metformin during this interval. At least 74% were previously treated with sulfonylureas alone, 81% had baseline HbA1c > or = 8.5%, 71% were obese, and 99% had a serum creatinine < or = 1.5 mg/dl. Among patients on sulfonylureas at baseline, those starting metformin had significantly lower HbA1c levels 6 months later than those not started, after adjustment for age, sex, and the higher baseline levels in those started (adjusted difference: 0.5%, P < 0.0001). Patients starting metformin as initial monotherapy also improved significantly, but patients previously treated with insulin (with or without sulfonyl-ureas) had slightly higher follow-up HbA1c levels than similar patients not starting metformin. Continuation of metformin at 12 months was significantly higher for patients previously treated with sulfonylureas than other groups. One probable case of lactic acidosis was identified during 4,502 person-years on metformin. CONCLUSIONS: Adherence to prescribing guidelines was relatively high during metformin's first 20 months of availability. Glycemic control improved substantially for patients previously treated with sulfonylureas. Lactic acidosis was rare. (+info)
Effect of repaglinide addition to metformin monotherapy on glycemic control in patients with type 2 diabetes.
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OBJECTIVE: To compare the effect of repaglinide in combination with metformin with monotherapy of each drug on glycemic control in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: A total of 83 patients with type 2 diabetes who had inadequate glycemic control (HbA1c > 7.1%) when receiving the antidiabetic agent metformin were enrolled in this multicenter, double-blind trial. Subjects were randomized to continue with their prestudy dose of metformin (n = 27), to continue with their prestudy dose of metformin with the addition of repaglinide (n = 27), or to receive repaglinide alone (n = 29). For patients receiving repaglinide, the optimal dose was determined during a 4- to 8-week titration and continued for a 3-month maintenance period. RESULTS: In subjects receiving combined therapy, HbA1c was reduced by 1.4 +/- 0.2%, from 8.3 to 6.9% (P = 0.0016) and fasting plasma glucose by 2.2 mmol/l (P = 0.0003). No significant changes were observed in subjects treated with either repaglinide or metformin monotherapy in HbA1c (0.4 and 0.3% decrease, respectively) or fasting plasma glucose (0.5 mmol/l increase and 0.3 mmol/l decrease respectively). Subjects receiving repaglinide either alone or in combination with metformin, had an increase in fasting levels of insulin between baseline and the end of the trial of 4.04 +/- 1.56 and 4.23 +/- 1.50 mU/l, respectively (P < 0.02). Gastrointestinal adverse events were common in the metformin group. An increase in body weight occurred in the repaglinide and combined therapy groups (2.4 +/- 0.5 and 3.0 +/- 0.5 kg, respectively; P < 0.05). CONCLUSIONS: Combined metformin and repaglinide therapy resulted in superior glycemic control compared with repaglinide or metformin monotherapy in patients with type 2 diabetes whose glycemia had not been well controlled on metformin alone. Repaglinide monotherapy was as effective as metformin monotherapy. (+info)
Optimal administration of lispro insulin in hyperglycemic type 1 diabetes.
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OBJECTIVE: Lispro is a new rapidly absorbed insulin analog. At present, there are no recommendations for the optimal injection time of lispro insulin in hyperglycemic patients. In contrast to normoglycemic patients with diabetes, we hypothesized that injection of lispro insulin 15-30 min before meal ingestion would improve postprandial glucose excursion in hyperglycemic diabetic subjects. RESEARCH DESIGN AND METHODS: In 48 randomized overnight studies, 12 healthy adult type 1 diabetic patients received lispro insulin 0.15 U/kg admixed with human ultralente 0.2 U/kg (as background insulin) subcutaneously at minutes (-30, -15, 0, and +15) relative to the ingestion of an American Diabetes Association breakfast of 8.6 kcal/kg. Pre-breakfast hyperglycemia of 10.2 +/- 0.2 mmol/l was established before the study by continuous overnight infusion of intravenous insulin, which was stopped 30 min before lispro insulin injection. Glucose and insulin levels were measured every 30 min for 5 h after breakfast. RESULTS: Results demonstrated that postprandial glucose excursion was reduced when lispro insulin was administered 15 or 30 min before the meal compared with lispro insulin injected at the meal (P < 0.002). The postprandial glucose excursion (millimoles per liter per hour) was -6.4 +/- 3 for the -30-min group, -5.1 +/- 2.9 for the -15-min group, 3.4 +/- 4.1 for the 0-min group, and 5.7 +/- 4.4 for the +15-min group. Although injecting lispro insulin at 30 min before the meal resulted in a significant reduction in postprandial glycemia, it was accompanied by loss of glucose control at 4 h postmeal in two subjects. CONCLUSIONS: Optimization of lispro insulin in hyperglycemic patients requires timing of the insulin injection at least 15 min before the meal. (+info)
Accuracy of pen injectors versus insulin syringes in children with type 1 diabetes.
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OBJECTIVE: To compare the accuracy and precision of insulin syringes and pen devices used by children with type 1 diabetes and their parents. RESEARCH DESIGN AND METHODS: There were 48 subjects (32 patients, a parent of an additional 16 patients) instructed to measure out morning insulin doses three times from vials and/or cartridges containing saline mixed with small amounts of [14C]glucose (solution used as regular insulin) and [3H]glucose (solution used as NPH insulin) and to dispense the contents into a scintillation vial. Statistical analysis was used to determine the accuracy and precision of both methods of insulin delivery. RESULTS: The absolute error in measuring out doses of regular insulin < 5 U was greater with insulin syringes compared with pen injection devices (9.9 +/- 2.4 vs. 4.9 +/- 1.6%, respectively). Both were comparable for regular insulin doses > 5 U (3.2 +/- 0.6 vs. 2.2 +/- 0.4% for syringes and pens, respectively). The accuracy in drawing up NPH doses was similar for low and high insulin doses (mean percent error of 7.5 +/- 1.5 vs. 5.6 +/- 1.1%). CONCLUSIONS: Pen devices are more accurate than insulin syringes in measuring out insulin at low insulin doses. The accuracy of insulin syringes improves when higher doses of regular insulin are measured out and becomes comparable to pen devices. (+info)
Multicenter randomized trial of a comprehensive prepared meal program in type 2 diabetes.
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OBJECTIVE: To evaluate the clinical effects of a comprehensive prepackaged meal plan, incorporating the overall dietary guidelines of the American Diabetes Association and other national health organizations, relative to those of a self-selected diet based on exchange lists in free-living individuals with type 2 diabetes. RESEARCH DESIGN AND METHODS: A total of 202 women and men (BMI < or = 42 kg/m2) whose diabetes was treated with diet alone or an oral hypoglycemic agent were enrolled at 10 medical centers. After a 4-week baseline period, participants were randomized to a nutrient-fortified prepared meal plan or a self-selected exchange-list diet for 10 weeks. On a caloric basis, both interventions were designed to provide 55-60% carbohydrate, 20-30% fat, and 15-20% protein. At intervals, 3-day food records were completed, and body weight, glycemic control, plasma lipids, and blood pressure were assessed. RESULTS: Food records showed that multiple nutritional improvements were achieved with both diet plans. There were significant overall reductions in body weight and BMI, fasting plasma glucose and serum insulin, fructosamine, HbA1c, total and LDL cholesterol, and blood pressure (P < 0.001 or better for all). In general, differences in major end points between the diet plans were not statistically significant. CONCLUSIONS: Glycemic control and cardiovascular risk factors improve in individuals with type 2 diabetes who consume diets in accordance with the American Diabetes Association guidelines. The prepared meal program was as clinically effective as the exchange-list diet. The prepared meal plan has the additional advantages of being easily prescribed and eliminating the complexities of meeting the multiple dietary recommendations for type 2 diabetes management. (+info)
Effects of a thiazolidinedione compound on body fat and fat distribution of patients with type 2 diabetes.
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OBJECTIVE: To examine the effects of a thiazolidinedione (600 mg troglitazone) insulin-sensitizing treatment on total body fat measured by underwater weighing, on intra- and extra-abdominal fat mass using magnetic resonance imaging (MRI), and on anthropometric measures. RESEARCH DESIGN AND METHODS: Type 2 diabetic outpatients were studied in a double-blind randomized trial carried out at Glasgow Royal Infirmary, Scotland. RESULTS: Groups who received troglitazone (8 men, 3 women) and placebo (8 men, 2 women) were well matched for age, BMI, total body fat percentage by underwater weighing, and intra-abdominal fat (kilograms) by MRI. After 12 weeks, body weight changes in the troglitazone group (mean +0.66 kg [95% CI -0.71 to 2.04], P = 0.31) and the placebo group (mean +0.25 kg [-0.64 to 1.13], P = 0.55) were not statistically different. Changes in total body fat with troglitazone (mean +1.02% body wt [-1.13 to 3.17], P = 0.32) and placebo (mean -0.54% body wt [-1.68 to 0.59], P = 0.31) were not significantly different. There was, however, a decrease in intra-abdominal fat mass in the troglitazone-treated group (mean -0.47 kg [-0.79 to -0.13], P = 0.01), and this was significantly different (P = 0.03) from placebo treatment (mean -0.41 kg [-0.77 to -0.05]). CONCLUSIONS: Treatment with the thiazolidinedione troglitazone in human patients with type 2 diabetes decreases intra-abdominal fat mass but does not affect total body fat or weight. This potentially valuable effect points to a differential action on insulin sensitivity in different adipose tissue depots. (+info)