Metabolic impact of a family history of Type 2 diabetes. Results from a European multicentre study (EGIR).
BACKGROUND
Insulin resistance was found in some but not in all previous studies of non-diabetic first degree relatives of Type 2 diabetic patients. Small study groups, ethnic differences and/or non-optimal techniques may explain the conflicting results.


OBJECTIVE
To study the impact of a family history of Type 2 diabetes on insulin action in a large group of non-diabetic Europeans using the 'gold standard' euglycaemic hyperinsulinaemic clamp technique.


METHODS
Non-diabetic subjects (n = 235) with a positive family history of Type 2 diabetes (FH+) and 564 subjects with no family history of diabetes (FH-) were recruited from The European Group of Insulin Resistance (EGIR) database. This database includes measurements of insulin action using the insulin clamp technique (1 mU/kg per min) in normal glucose-tolerant individuals from 20 different European centres. In a subset of subjects the measurements were performed in combination with indirect calorimetry (n = 80 vs. 213 with and without family history of Type 2 diabetes).


RESULTS
The body mass index (BMI) was slightly higher in FH+ compared with FH- (26.7 +/- 4.6 vs. 25.1 +/- 4.7 kg/m(2); P < 0.02). After correction for covariates according to differences between investigators and subject characteristics including BMI (multiple regression analysis), insulin-stimulated glucose disposal was lower in FH+ compared with FH- (P < 0.00001). Insulin-stimulated glucose oxidation was slightly increased in FH+ compared with FH-, and insulin-stimulated non-oxidative glucose metabolism was consequently markedly reduced in FH+ compared with FH- (P < 0.0005).


CONCLUSIONS
Insulin resistance is present in European non-diabetic relatives of Type 2 diabetic patients. The insulin resistance is independent of degree of obesity and is restricted solely to the pathway of non-oxidative glucose metabolism. Diabet. Med. 18, 533-540 (2001)
Vaag
A
A
Steno Diabetes Center, Gentofte, Denmark. avaa@novo.dk
Lehtovirta
M
M
Thye-Rönn
P
P
Groop
L
L
D000328:Adult; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism*; D001827:Body Height; D015992:Body Mass Index; D002784:Cholesterol / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000235:genetics*; D004734:Energy Metabolism; D005215:Fasting; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D005947:Glucose / Q000378:metabolism; D015309:Glucose Clamp Technique; D005951:Glucose Tolerance Test; D006801:Humans; D006946:Hyperinsulinism / Q000097:blood; D007262:Infusions, Intravenous; D007328:Insulin / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D007333:Insulin Resistance / Q000235:genetics / Q000502:physiology*; D008099:Liver / Q000378:metabolism; D008297:Male; D012016:Reference Values; D012044:Regression Analysis; D014280:Triglycerides / Q000097:blood
D001786:Blood Glucose; D008076:Cholesterol, HDL; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D014280:Triglycerides; D002784:Cholesterol; D005947:Glucose