Insulin resistance in the first-degree relatives of persons with type 2 diabetes.
BACKGROUND
Type 2 diabetes is characterized by impaired insulin secretion and insulin resistance. Both genetic and environmental factors are thought to play a role in the pathogenesis of this disease. Obesity is associated with increased risk of type 2 diabetes, but some metabolic abnormalities may also be present in lean, predisposed subjects. The aim of the present study was to assess insulin sensitivity in lean normoglycemic offspring of parents with type 2 diabetes.


METHODS
We examined 17 lean offspring (BMI<25 kg x m-2) whose parents had type 2 diabetes, and 17 age, sex and BMI-matched subjects without family history of diabetes as controls. Anthropometric and biochemical measurements, oral glucose tolerance test (OGTT), and euglycemic hyperinsulinemic clamp were performed.


RESULTS
The subjects did not differ in anthropometric measurements, and all had normal glucose tolerance according to WHO criteria. Offspring of type 2 diabetic parents were markedly more hyperinsulinemic (p<0.05) and insulin resistant (p<0.005). The ratio of the increase in insulin to the increase in glucose during the first 30 minutes of the OGTT, a crude index of first-phase insulin secretion, did not differ between groups. Insulin sensitivity was negatively related to fasting plasma insulin (r=-0.67, p<0.001) and non-esterified fatty acids (r=-0.43, p<0.02).


CONCLUSIONS
Insulin resistance is present even in young lean subjects at high risk to develop type 2 diabetes. Our data suggest that insulin resistance may be a primary abnormality in the pathogenesis of this disease.
Straczkowski
Marek
M
Department of Endocrinology, Diabetology and Internal Medicine, Medical Academy, Białystok, Poland. mstraczkowski@poczta.onet.pl
Kowalska
Irina
I
Stepień
Agnieszka
A
Dzienis-Straczkowska
Stella
S
Szelachowska
Małgorzata
M
Kinalska
Ida
I
Krukowska
Agnieszka
A
Konicka
Marta
M
D000328:Adult; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D015309:Glucose Clamp Technique; D005951:Glucose Tolerance Test; D006801:Humans; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000235:genetics* / Q000502:physiology; D008297:Male
D007328:Insulin