Increased circulating leptin concentrations in insulin-resistant first-degree relatives of patients with non-insulin-dependent diabetes mellitus: relationship to body composition and insulin sensitivity but not to family history of non-insulin-dependent diabetes mellitus.
OBJECTIVE
To explore a possible association between serum concentration of leptin, insulin sensitivity and non-insulin-dependent diabetes mellitus (NIDDM).


METHODS
Forty first-degree relatives of NIDDM patients and 35 control subjects matched for age, gender and body mass index underwent a hyperinsulinaemic (insulin infusion rate 0.6 mU/kg per min) euglycaemic clamp combined with indirect calorimetry. Serum leptin was measured in fasting blood samples obtained before the clamp.


RESULTS
All subjects had a normal oral glucose tolerance test. Insulin-stimulated glucose uptake (M) was decreased in the relatives compared with the control subjects (4.58 +/- 0.27 versus 6.06 +/- 0.25 mg/kg per min, P < 0.001). Conversely, serum leptin was increased in the relatives (9.6 x/divided by 1.1 versus 6.1 x/divided by 1.2 ng/ml (geometric mean x/divided by antilog S.E.M.), P < 0.05). A positive correlation was observed between circulating levels of leptin and percentage body fat (P < 0.001) and inverse correlations were found between leptin, M (P < 0.01), maximal aerobic capacity (VO2 max) (P < 0.01), and energy expenditure (P < or = 0.01) in both groups. In multiple linear regression analysis, percentage body fat, gender and M significantly determined the level of leptin (r2 = 0.71, P < 0.001) whereas family history of NIDDM and VO2 max did not.


CONCLUSIONS
Serum leptin is increased in insulin-resistant offspring of NIDDM patients. The association between leptin, anthropometric measures and insulin sensitivity is, however, comparable with that of a control group. The increased concentrations of serum leptin in the relatives appear to be associated with the insulin resistance, but not with a family history of NIDDM.
Nyholm
B
B
Department of Medicine M (Endocrinology and Diabetes), University Hospital of Aarhus, Denmark.
Fisker
S
S
Lund
S
S
Møller
N
N
Schmitz
O
O
D000284:Administration, Oral; D000328:Adult; D001823:Body Composition; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D005260:Female; D005947:Glucose / Q000378:metabolism; D005951:Glucose Tolerance Test; D006706:Homeostasis; D006801:Humans; D007328:Insulin / Q000494:pharmacology; D007333:Insulin Resistance; D020738:Leptin; D008297:Male; D008499:Medical Records; D008875:Middle Aged; D009994:Osmolar Concentration; D011506:Proteins / Q000032:analysis*; D012016:Reference Values; D012044:Regression Analysis
D007328:Insulin; D020738:Leptin; D011506:Proteins; D005947:Glucose