Effect of Optimization of Glycaemic Control on Mannan-Binding Lectin in Type 1 Diabetes.

OBJECTIVE: Mannan-binding lectin (MBL) concentration in plasma is increased in subjects with type 1 diabetes and associated with increased mortality and risk of diabetic nephropathy. Recent findings show that pancreas transplantation reduces MBL concentration. Whether the increased MBL concentration is reversed by improved glycaemic control remains unknown. We investigated the effects of improved glycaemic control on MBL concentration in patients with type 1 diabetes. METHODS: We measured MBL, fructosamine, and HbA1cat baseline and after 6 weeks in 52 type 1 diabetic patients following the change from conventional insulin therapy to insulin pump therapy. RESULTS: After initiation of insulin pump therapy, the total daily insulin dose was significantly reduced (from 51 ± 18 IE/day to 39 ± 13 IE/day, P < 0.0001). There was a significant decrease in HbA1c from 8.6% to 7.7% (from 70 mmol/mol to 61 mmol/mol, P < 0.0001) and in fructosamine levels (from 356 µmol/L to 311 µmol/L, P < 0.0001). MBL levels decreased by 10% from 2165 µg/L (IQR 919-3389 µg/L) at baseline to 1928 µ/L (IQR 811-2758 µg/L) at follow-up (P = 0.005), but MBL change was not significantly correlated with changes in insulin dose, HbA1c, or fructosamine. CONCLUSIONS: MBL concentration decreased following the initiation of insulin pump therapy in patients with type 1 diabetes and did not correlate with changes in glycaemic control.

Six months of diazoxide treatment at bedtime in newly diagnosed subjects with type 1 diabetes does not influence parameters of {beta}-cell function and autoimmunity but improves glycemic control.

OBJECTIVE Continuous beta-cell rest with diazoxide preserves residual endogenous insulin production in type 1 diabetes. However, side effects have hampered therapeutic usefulness. In a double-blind study, we tested whether lower, intermittent dosing of diazoxide had beneficial effects on insulin production, metabolic control, and autoimmunity markers in the absence of side effects. RESEARCH DESIGN AND METHODS Forty-one newly diagnosed type 1 diabetic patients were randomized to 6 months of treatment with placebo or 100 mg diazoxide at bedtime. A1C, C-peptide (fasting and glucagon stimulated), and FoxP3(+) regulatory T-cells (Tregs) were measured. Patients were followed for 6 months after intervention. RESULTS Of six dropouts, three were due to perceived side effects; one subject in the diazoxide group experienced rash, another dizziness, and one in the placebo group sleep disturbance. Adverse effects in others were absent. Diazoxide treatment reduced A1C from 8.6% at baseline to 6.0% at 6 months and 6.5% at 12 months. Corresponding A1C value in the placebo arm were 8.3, 7.3, and 7.5% (P < 0.05 for stronger reduction in the diazoxide group). Fasting and stimulated C-peptide decreased during 12 months similarly in both arms (mean -0.30 and -0.18 nmol/l in the diazoxide arm and -0.08 and -0.09 nmol/l in the placebo arm). The proportion of Tregs was similar in both arms and remained stable during intervention but was significantly lower compared with nondiabetic subjects. CONCLUSIONS Six months of low-dose diazoxide was without side effects and did not measurably affect insulin production but was associated with improved metabolic control.