The Effect of Rosiglitazone on Overweight Subjects With Type 1 Diabetes

Abstract

OBJECTIVE -To evaluate the safety and effectiveness of rosiglitazone in the treatment of overweight subjects with type 1 diabetes.RESEARCH DESIGN AND METHODS -A total of 50 adult type 1 diabetic subjects with a baseline BMI Ն27 kg/m 2 were randomly assigned in a double-blind fashion to take insulin and placebo (n ϭ 25) or insulin and rosiglitazone 4 mg twice daily (n ϭ 25) for a period of 8 months. Insulin regimen and dosage were modified in all subjects to achieve near-normal glycemic control.RESULTS -Both groups experienced a significant reduction in HbA 1c (A1C) level (rosiglitazone: 7.9 Ϯ 1.3 to 6.9 Ϯ 0.7%, P Ͻ 0.0001; placebo: 7.7 Ϯ 0.8 to 7.0 Ϯ 0.9%, P ϭ 0.002) and a significant increase in weight (rosiglitazone: 97.2 Ϯ 11.8 to 100.6 Ϯ 16.0 kg, P ϭ 0.008; placebo: 96.4 Ϯ 12.2 to 99.1 Ϯ 15.0, P ϭ 0.016). Baseline measures of BMI (P ϭ 0.001), total daily insulin dose (P ϭ 0.002), total cholesterol (P ϭ 0.005), HDL cholesterol (P ϭ 0.00l), and LDL cholesterol (P ϭ 0.02) were predictors of improvement in A1C level only in the group treated with rosiglitazone. Total daily insulin dose increased in subjects taking placebo (74.0 Ϯ 33.8 to 82.0 Ϯ 48.9 units, P Ͻ 0.05 baseline vs. week 32), but it decreased slightly in subjects taking rosiglitazone (77.5 Ϯ 28.6 to 75.3 Ϯ 33.1 units). Both systolic blood pressure (137.4 Ϯ 15.6 vs. 128.8 Ϯ 14.8 mmHg, baseline vs. week 32, P Ͻ 0.02) and diastolic blood pressure (87.2 Ϯ 9.4 vs. 79.4 Ϯ 7.2 mmHg, P Ͻ 0.0001) improved in the group treated with rosiglitazone. The total incidence of hypoglycemia did not differ between groups.CONCLUSIONS -Rosiglitazone in combination with insulin resulted in improved glycemic control and blood pressure without an increase in insulin requirements, compared with insulin-and placebo-treated subjects, whose improved glycemic control required an 11% increase in insulin dose. Weight gain and hypoglycemia were similar in both groups at the end of the study. The greatest effect of rosiglitazone occurred in subjects with more pronounced markers of insulin resistance. Diabetes Care 28:1562-1567, 2005R esearch in the past decade has conclusively demonstrated that improved blood glucose control is of benefit in preventing the microvascular complications of diabetes (1,2). Although new insulin analogs and intensive insulin treatment regimens are effective in improving glycemic control, these treatments involve considerable effort and cost (3) and can result in weight gain and increased risk for severe and asymptomatic hypoglycemia (4). Faced with the challenge of balancing aggressive insulin replacement therapy against the risk for the potentially serious consequences of excessive weight gain and insulininduced hypoglycemia, investigators continue to search for treatments that address both the treatment of insulin deficiency as well as other metabolic abnormalities that are associated with diabetes (5).Insulin resistance, a metabolic abnormality common in type 2 diabetes, appears to be present in individuals with type 1 diabetes, as well. Although insuli...

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“…Destaca-se, entretanto, que, nesta situação, a utilização de agentes sensibilizadores à insulina talvez mereça ser considerada, em conjunto com ênfase em mudanças no estilo de vida, de forma a contribuir para uma melhora no perfil metabó-lico desses pacientes (18).…”

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“…10-12 A recent placebo-controlled trial of rosiglitazone in conjunction with standard care in adults with type 1 diabetes showed similar improvements in A1c in the groups but with less insulin required in the rosiglitazone-treated compared with the placebo group. 13 The mechanism of action of thiazolidinediones on metabolic control is primarily through enhancement of peripheral glucose utilization with some suppression of hepatic glucose production. 12 Adolescents with type 1 diabetes have reduced peripheral insulin sensitivity as measured by hyperinsulinemic-euglycemic clamp studies.…”