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Objective: Long-acting basal insulin analogs have demonstrated positive effects on the balance between effective glycemic control and risk of hypoglycemia versus neutral protamine Hagedorn (NPH) insulin in randomized controlled trials. Evidence of severe hypoglycemic risk with insulin detemir, insulin glargine, or NPH insulin is presented from a nationwide retrospective database study., Research Design and Methods: Data from hospital and secondary healthcare visits due to hypoglycemic coma from 75 682 insulin-naïve type 1 or 2 diabetes patients initiating therapy with NPH insulin, insulin glargine, or insulin detemir in Finland between 2000 and 2009 were analyzed. Incidence rates with 95% confidence intervals (CIs) were calculated using Poisson regression. Hazard ratios were estimated using Cox's regression with adjustments for relevant background variables., Results: The adjusted risk of hospital/secondary healthcare visits due to the first severe hypoglycemic event was 21.7% (95% CI 9.6-32.1%, p < 0.001) lower for insulin detemir and 9.9% (95% CI 1.5-17.6%, p = 0.022) lower for insulin glargine versus NPH insulin. Risk of hypoglycemic coma recurrence was 36.3% (95% CI 8.9-55.5%, p = 0.014) lower for detemir and 9.5% but not significantly (95% CI -10.2 to 25.7%, p = 0.318) lower for glargine versus NPH insulin. Risk of all hypoglycemic coma events was 30.8% (95% CI 16.2-42.8%, p-value <0.001) lower for detemir and 15.6% (95% CI 5.1-25.0%, p-value 0.005) lower for glargine versus NPH. Insulin detemir had a significantly lower risk for first (13.1% lower [p = 0.034]), recurrent (29.6% lower [p = 0.021]), and all (17.9% lower [p = 0.016]) severe hypoglycemic events than insulin glargine., Conclusions: There were considerable differences in risk of hospitalization or secondary healthcare visits due to hypoglycemic coma between basal insulin treatments in real-life clinical practice., (© 2013 The Authors. Pharmacoepidemiology and Drug Safety published by John Wiley & Sons, Ltd.)

Normal insulin action in vivo involves a decrease in stiffness of large arteries (a decrease in aortic pressure augmentation). We determined whether the ability of insulin to decrease arterial stiffness is altered in uncomplicated type 1 diabetes. Nine type 1 diabetic men (age 28+/-2 years, body mass index 24+/-1 kg/m(2)) and 9 matched normal men were studied under normoglycemic hyperinsulinemic (sequential 2-hour insulin infusions of 1 [step 1] and 2 [step 2] mU x kg(-1) x min(-1)) conditions. Central aortic pressure waveforms were synthesized from those recorded in periphery with applanation tonometry on the radial artery and a validated reverse transfer function to construct the central aortic pressure wave every 30 minutes. This allowed the determination of aortic augmentation (the pressure difference between the first and the second systolic peaks) and the augmentation index (augmentation divided by pulse pressure), as the measure of stiffness of large arteries. Whole-body glucose uptake was 44% (step 1) and 37% (step 2) lower (P<0.001) in the diabetic patients than in the normal subjects. At baseline, before the insulin infusion, augmentation averaged 0+/-1 and 2+/-1 mm Hg (NS) and the augmentation index was -1.5+/-4.5% and 4.0+/-3.7% (NS) in the normal and diabetic subjects, respectively. After 1 hour of hyperinsulinemia, the augmentation index had decreased significantly (P<0.01) to -9.5+/-4.8% in the normal subjects but remained at 4.4+/-4.2% in the diabetic patients. A significant decrease was not observed in the diabetic patients until 150 minutes (-1.2+/-4.1%, P<0.05 versus baseline). Whole-body glucose uptake was significantly inversely correlated with the change in the augmentation index during step 1 (r=-0.61, P<0.01). Insulin resistance in type 1 diabetes involves a defect in the ability of insulin to decrease central aortic pressure. This defect could predispose these patients to premature stiffening of large arteries.

A total of 75 in vivo endothelial function tests (intrabrachial artery infusions of endothelium-dependent [acetylcholine] and -independent [sodium nitroprusside] vasoactive agents) were performed in 18 type 2 diabetic patients (aged 58+/-2 years, body mass index 28.5+/-0.6 kg/m(2), and fasting plasma glucose 229+/-11 mg/dL) and 27 matched normal subjects. These tests were performed before and 6 months after combination therapy with insulin and metformin and before and 6 months after metformin therapy only. Before insulin therapy, blood flow responses to acetylcholine (15 microg/min) were significantly blunted in type 2 diabetic patients (7.5+/-0.7 mL x dL(-1) x min(-1)) compared with normal subjects (11.6+/-0.9 mL x dL(-1) x min(-1), P<0.01). During insulin therapy, the acetylcholine response increased by 44% to 10.8+/-1.6 mL x dL(-1) x min(-1) (P<0.05). Insulin therapy also significantly increased the blood flow responses to both low and high doses of sodium nitroprusside. We conclude that insulin therapy improves endothelium-dependent and -independent vasodilatation. These data support the idea that insulin therapy has beneficial rather than harmful effects on vascular function.

Aims/hypothesis: To determine causes of weight gain during insulin therapy with and without metformin in Type II (non-insulin-dependent) diabetes mellitus., Methods: Twenty-six patients with Type II diabetes (body mass index 28+/-1 kg/m2) were treated with insulin alone (n = 13) or insulin and with metformin (n = 13). Components of energy balance (basal metabolic rate, energy intake, glucosuria) were measured at 0 and 12 months., Results: Glycaemic control improved similarly in patients using (HbA1c 10.5+/-0.3 vs 7.6+/-0.2%, p<0.001) and not using (10.2+/-0.3 vs 7.8+/-0.3%, p < 0.001) metformin. The metformin group required 47 % less insulin than the group not using metformin (p < 0.001). Body weight increased by 3.8+/-0.8 and 7.5+/-1.6 kg (p < 0.05), respectively. Basal metabolic rate and glucosuria were similar at 0 and 12 months in both groups but the metformin group decreased energy intake by 1.12+/-0.46 MJ/day, whereas it remained unchanged in the other group (0.15+/-0.42 MJ/day). Changes in body weight and glycaemia were statistically significant independent determinants of basal metabolic rate. Their change in opposite directions explained why basal metabolic rate remained unchanged., Conclusion/interpretation: Improved glycaemia promotes weight gain by decreasing both basal metabolic rate and glucosuria. Use of metformin decreases weight gain by reducing energy intake and is therefore a useful adjunct to insulin therapy in patients with Type II diabetes.