Nocturnal glucose metabolism after bedtime injection of insulin glargine or neutral protamine hagedorn insulin in patients with type 2 diabetes.
OBJECTIVE
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'](2)H(2) 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 micromol/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).


CONCLUSIONS
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.
Linn
Thomas
T
Clinical Research Unit, 3rd Medical Clinic and Policlinic, Rodthohl 6, 35385 Giessen, Germany. thomas.linn@innere.med.uni-giessen.de
Fischer
Britta
B
Soydan
Nedim
N
Eckhard
Michael
M
Ehl
Julia
J
Kunz
Clemens
C
Bretzel
Reinhard G
RG
D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000378:metabolism*; D002940:Circadian Rhythm / Q000502:physiology*; D018592:Cross-Over Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage; D007279:Injections, Subcutaneous; D007328:Insulin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000069036:Insulin Glargine; D007336:Insulin, Isophane / Q000008:administration & dosage*; D049528:Insulin, Long-Acting; D008297:Male; D008875:Middle Aged; D010919:Placebos
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D049528:Insulin, Long-Acting; D010919:Placebos; D000069036:Insulin Glargine; D007336:Insulin, Isophane