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Nocturnal Glucose Metabolism after Bedtime Injection of Insulin Glargine or Neutral Protamine Hagedorn Insulin in Patients with Type 2 Diabetes

3rd Medical Clinic (T.L., B.F., N.S., M.E., R.G.B.) and Institute of Nutrition (T.L., J.E., C.K.), Justus Liebig University Giessen, 35385 Giessen, Germany

Address all correspondence and requests for reprints to: Professor Thomas Linn, Clinical Research Unit, 3rd Medical Clinic and Policlinic, Rodthohl 6, 35385 Giessen, Germany. E-mail: thomas.linn{at}innere.med.uni-giessen.de.

Aims/Hypothesis: Insulin glargine is a long-acting human insulin analog often administered at bedtime to patients with type 2 diabetes. It reduces fasting blood glucose levels more efficiently and with less nocturnal hypoglycemic events compared with human neutral protamine Hagedorn (NPH) insulin. Therefore, bedtime injections of insulin glargine and NPH insulin were compared overnight and in the morning.

Methods: In 10 type 2 diabetic patients, euglycemic clamps were performed, including [6,6']²H₂ glucose, to study the rate of disappearance (Rd) and endogenous production (EGP) of glucose during the night. On separate days at bedtime (2200 h), patients received a sc injection of insulin glargine, NPH insulin, or saline in a randomized, double-blind fashion.

Results: Similar doses of both insulins had different metabolic profiles. NPH insulin had a greater effect on both Rd and EGP in the night compared with insulin glargine. By contrast, in the morning, insulin glargine was more effective, increasing Rd by 5.8 µmol/kg^–1·min^–1 (95% confidence interval 4.7–6.9) and reducing EGP –5.7 (–5.0 to –6.4) compared with NPH insulin. Nearly 80% of the glucose lowering effect in the morning was due to insulin glargine’s reduction of EGP. Its injection was associated with one-third lower morning glucagon levels compared with NPH insulin (P = 0.021).

Conclusion/Interpretation: Nocturnal variations of EGP and Rd explain the reduced incidence of hypoglycemia and lower fasting glucose levels reported for insulin glargine compared with human NPH insulin.