Acute hyperinsulinemia decreases plasma osteoprotegerin with diminished effect in type 2 diabetes and obesity.
OBJECTIVE
Osteoprotegerin (OPG) is a soluble tumour necrosis factor-receptor-like molecule present in connective tissues, especially bone and vasculature. It is known to accumulate in the arterial wall in diabetes. As its synthesis in vascular cells is decreased by insulin, we wanted to elucidate the acute effects of insulin on plasma OPG concentrations in individuals with type 2 diabetes and obese individuals compared with lean controls.


METHODS
The study population consisted of ten type 2 diabetic, ten obese subjects, and ten lean subjects with no family history of diabetes.


METHODS
All subjects underwent a 4-h euglycemic-hyperinsulinemic clamp. Plasma OPG, insulin, lactate, HbA1c, cholesterol, triglycerides, free fatty acids (FFA), and glucose disposal rate were measured before and at the end of the clamp.


RESULTS
Baseline OPG concentrations did not differ significantly between groups. Insulin infusion decreased plasma OPG concentrations in all groups (P<0.01); however, the fall in OPG was 50% less in obese and type 2 diabetic individuals (P=0.007). Baseline OPG correlated with fasting insulin, baseline lactate, and low density lipoprotein cholesterol in the diabetic group, and with baseline FFA in the lean group. The relative change of OPG in response to insulin correlated inversely with HbA1c and baseline FFA in the lean group.


CONCLUSIONS
Acute hyperinsulinemia decreases plasma OPG, but with diminished effect in individuals with type 2 diabetes and obesity. Increased levels of OPG in arteries and plasma in diabetes together with the capability of plasma OPG as a cardiovascular risk predictor may be related to the described effects of insulin.
Jørgensen
Gitte Maria
GM
Department of Biochemistry, Pharmacology and Genetics, Odense University Hospital, Sdr. Boulevard 29, DK-5000 Odense, Denmark.
Vind
Birgitte
B
Nybo
Mads
M
Rasmussen
Lars Melholt
LM
Højlund
Kurt
K
D000208:Acute Disease; D001835:Body Weight; D002318:Cardiovascular Diseases / Q000453:epidemiology / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology / Q000378:metabolism*; D005260:Female; D015309:Glucose Clamp Technique; D006801:Humans; D006946:Hyperinsulinism / Q000453:epidemiology / Q000378:metabolism*; D007328:Insulin / Q000097:blood; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000453:epidemiology / Q000378:metabolism*; D053244:Osteoprotegerin / Q000097:blood*; D012307:Risk Factors
D007328:Insulin; D053244:Osteoprotegerin; C506030:TNFRSF11B protein, human