Pioglitazone as adjunctive therapy in adolescents with type 1 diabetes

OBJECTIVE: To determine whether the addition of the thiazoladinedione, pioglitazone, to standard therapy improves metabolic control in adolescents with type 1 diabetes (T1D) and clinical evidence of insulin resistance. STUDY DESIGN: Randomized, placebo-controlled 6-month 2-site trial of pioglitazone therapy in 35 adolescents with T1D, high insulin requirements (>0.9 U/kg/d), and suboptimal metabolic control (A1c 7.5%-11%), with the primary outcome of change in A1c. Secondary outcomes include change in insulin dose, body mass index (BMI), lipids, and waist and hip circumference. RESULTS: Metabolic control (A1c) was improved at 6 months in all subjects (P = .02). There was no significant difference between the pioglitazone and placebo treatment groups at 6 months in either change in A1c (-0.4% +/- 0.9% and -0.5% +/- 1.2%, respectively) or insulin dose. BMI SDS increased by 0.3 +/- 0.3 (kg/m(2)) in the pioglitazone group and remained unchanged in the placebo group (P = .01). There was no significant difference in change in any lipid parameters between the pioglitazone and placebo groups at 6 months. CONCLUSIONS: Adjunctive pioglitazone therapy was not effective in improving glycemic control in adolescents with T1D. Pioglitazone was associated with increased BMI.     

Death caused by hyperglycemic hyperosmolar state at the onset of type 2 diabetes

Seven obese African American youth were considered to have died from diabetic ketoacidosis (DKA) due to type 1 diabetes, despite meeting the criteria for hyperglycemic hyperosmolar state and not for DKA. All had previously unrecognized type 2 diabetes, and death may have been prevented with earlier diagnosis or treatment.     

Fatal cerebral infarctions in diabetic ketoacidosis in a child with previously unknown heterozygosity for factor V Leiden deficiency

An 11-year-old boy with poorly controlled diabetes had sudden collapse after the development of lower extremity deep venous thrombosis, with fatal cerebral infarctions. He was heterozygous for factor V Leiden deficiency. This case emphasizes the value of cranial imaging after initial resuscitative treatment of neurologic collapse in diabetic ketoacidosis.     

Classification of Type 1 and Type 2 Diabetes Mellitus from Studies of ICA, HLA and Insulin Secretory Capacity

We studied ICA, HLA and insulin secretory capacity in 87 children with positive urinary screening and more than 2 points in the oral glucose tolerance test in order to establish criteria by which they could be classified into type 1 or type 2 diabetes mellitus. Fifty-five non-obese, ketosis-prone insulin dependent diabetic children were used as controls for type 1 diabetes mellitus. Our conclusions were as follows: 1. Type 1 diabetics were non-obese (on insulin therapy), ICA positive, ketosis-prone, had an insulin secretory capacity (Z IRI) of less than 100/nU/ml, and most of them possessed HLA-Bw54-DR4 or DRw9, DRw53 but did not possess Bw52-DR2 haplotype. 2. In the patients who were treated by dietary regimens alone for certain periods, however, insulin secretory capacities gradually deteriorated and they finally became insulin dependent. The children of this group who were not obese during insulin therapy and possessed an HLA haplotype identical to that in type 1 diabetes, regardless of ICA, might be classified as having slowly progressive type 1 diabetes. 3. The major difference between type 1 and slowly progressive type 1 diabetes was a family history of diabetes. Genetic factors might modify the clinical course of type 1 diabetes mellitus. 4. If the sensitivity of ICA or related autoantibodies to islet cells can be detected more readily, it should become easier to distinguish between type 1 and 2 diabetes.