Effects of a diet higher in carbohydrate/lower in fat versus lower in carbohydrate/higher in monounsaturated fat on postmeal triglyceride concentrations and other cardiovascular risk factors in type 1 diabetes.

OBJECTIVE: To compare the effects of a eucaloric diet higher in carbohydrate/lower in fat versus lower in carbohydrate/higher in monounsaturated fat on postmeal triglyceride (TG) concentrations and other cardiovascular disease risk factors in nonobese subjects with type 1 diabetes and in good glycemic control. RESEARCH DESIGN AND METHODS: In a parallel group design study, 30 subjects were randomly assigned and completed one of the two eucaloric diets. Assessments included: BMI, blood pressure, A1C, plasma lipids, and markers of oxidation, thrombosis, and inflammation. At 6 months, subjects were hospitalized for 24 h to measure plasma TG excursions. RESULTS: There were no significant differences between groups other than decreased plasminogen activator inhibitor 1 (PAI-1) levels and weight gain in the lower-carbohydrate/higher-monounsaturated fat group. During the 24-h testing, the lower-carbohydrate/higher-monounsaturated fat group had a lower plasma TG profile. CONCLUSIONS: A diet lower in carbohydrate/higher in monounsaturated fat could offer an appropriate choice for nonobese type 1 diabetic individuals with good metabolic and weight control.

Randomized study to characterize glycemic control and short-term pulmonary function in patients with type 1 diabetes receiving inhaled human insulin (exubera).

OBJECTIVE: Previous studies with inhaled human insulin [Exubera (EXU); insulin human (recombinant DNA origin) Inhalation Powder, Pfizer Inc., New York, NY; Nektar Therapeutics, San Carlos, CA) show comparable efficacy to sc insulin and small declines in pulmonary function in type 1 and 2 diabetes. This is a detailed characterization of short-term efficacy and pulmonary safety profile of EXU. RESEARCH DESIGN AND METHODS: In a 24-wk multicenter study, 226 nonsmoking patients with type 1 diabetes and normal lung function were randomized to intensive regimens of premeal EXU or sc insulin for 12 wk (comparative phase), followed by sc insulin for 12 wk (washout phase). Glycosylated hemoglobin, hypoglycemia, general adverse events, and pulmonary function were measured. Forced expiratory volume in 1 sec and carbon monoxide diffusion capacity were measured using standardized equipment and methodology. RESULTS: Comparable declines from baseline in glycosylated hemoglobin were observed in both groups (0.5%) and sustained throughout the study. There was a higher rate of hypoglycemia (risk ratio 1.23; 90% confidence interval 1.16, 1.30) but a lower rate of severe hypoglycemia (risk ratio 0.51; 90% confidence interval 0.30, 0.86) with EXU vs. sc insulin. The treatment group differences in changes from baseline in forced expiratory volume in 1 sec and carbon monoxide diffusion capacity were small, occurred within 2 wk of EXU initiation, and were reversible shortly after discontinuation. More patients reported mild cough with EXU vs. sc insulin (30.9% vs. 7.8%, respectively). CONCLUSIONS: Three months of EXU therapy is as effective and well tolerated as intensive sc insulin therapy. This study supports the role of EXU in type 1 diabetes.

Reduced histone biotinylation in multiple carboxylase deficiency patients: a nuclear role for holocarboxylase synthetase.

The attachment of biotin to apocarboxylases is catalyzed by holocarboxylase synthetase (HCS). An inherited deficiency of HCS results in the disorder 'multiple carboxylase deficiency', which is characterized by reduced activity of all biotin-dependent carboxylases. Here we show that the majority of HCS localizes to the nucleus rather than the cytoplasm based on immunofluorescence studies with antibodies to peptides and full length HCS and on the expression of recombinant HCS. Subnuclear fractionations indicate that HCS is associated with chromatin and the nuclear lamina, the latter in a discontinuous distribution in high salt-extracted nuclear membranes. During mitosis, HCS resolves into ring-like particles which co-localize with lamin B. Nuclear HCS retains its biotinylating activity and was shown to biotinylate purified histones in vitro. Significantly, fibroblasts from patients with HCS deficiency are severely deficient in histone biotinylation in addition to the deficiency of carboxylase activities. We propose that the role of HCS in histone modification may be linked to the participation of biotin in the regulation of gene expression or cell division and that affected patients may have additional disease beyond that due to the effect on carboxylases.