SAFETY AND EFFICACY AT NORMALIZING FASTING GLUCOSE WITH BEDTIME NPH INSULIN ALONE IN NIDDM

OBJECTIVE - To examine the safety and overall clinical effects of norm alizing the fasting plasma glucose (FPG) level with bedtime NPH insuli n alone in patients with non-insulin-dependent diabetes mellitus (NIDD M) that is poorly controlled with maximal doses of sulfonylureas. RESE ARCH DESIGN AND METHODS - Twelve obese male NIDDM subjects were treate d for 16 weeks with bedtime insulin after a 4-week sulfonylurea washou t. The insulin dosage was increased until the FPG level was normalized . The 24-h plasma glucose profiles and lipid and HbA(1c) levels were m easured at the beginning and end of the study, and the incidence and s everity of hypoglycemic episodes were closely monitored. In addition, hyperglycemic clamp studies were performed to assess insulin secretion and provide an indirect measurement of insulin sensitivity. RESULTS - FPG (14.6 +/- 0.9 mmol/l at week 0) was normalized (<6.4 mmol/l) with in 6 weeks (5.9 +/- 0.6 mmol/l) and remained at target levels until th e end of the study (4.0 +/- 0.03 mmol/l at week 16, P < 0.001). The in sulin dose was 80 +/- 9 U/day (0.86 +/- 0.10 U/kg). Improved glycemic control was confirmed by a reduction in HbA(1c)(10.9 +/- 0.05 vs. 7.2 +/- 0.2%, P < 0.001) and mean 24-h glucose (17.2 +/- 0.2 vs. 7.4 +/- 0 .2 mmol/l, P < 0.001). The incidence of mild or moderate hypoglycemic episodes was 3.4 +/- l/patient for the entire 16-week study, and no pa tient experienced severe hypoglycemia. Bedtime insulin significantly i mproved total cholesterol, low-density lipoprotein cholesterol, very-l ow-density lipoprotein cholesterol, and triglyceride levels (P < 0.01) . Weight gain was 2.4 +/- 0.7 kg, and blood pressure was unchanged. Du ring the hyperglycemic clamp, there was an improvement in the first ph ase (P < 0.001) and in the second phase (P < 0.01) of insulin secretio n. There also was an increase in the rate of exogenous glucose infused (M) (P < 0.01) and in the M/C-peptide ratio (P < 0.02), suggesting en hanced insulin sensitivity. CONCLUSIONS - NPH insulin given at bedtime in amounts sufficient to achieve a normal FPG level does not cause ex cessive or severe hypoglycemia and does lead to good glycemic and lipi d control in NIDDM. Bedtime insulin therapy also is accompanied by imp roved insulin secretion and insulin sensitivity. We conclude that a si ngle dose of insulin alone at bedtime merits consideration as a therap eutic strategy in patients with poorly controlled NIDDM.