Beta-cell dysfunction, rather than insulin insensitivity, is the primary defect in familial type 2 diabetes.
Continuous infusion of glucose with model assessment was used to measure glucose tolerance, beta-cell function, and insulin sensitivity in 154 first-degree relatives of 55 patients with type-2 diabetes. The plasma glucose achieved at 1 h was normally distributed in normal control subjects, but 31 (20%) of relatives of type-2 diabetics had values above the normal distribution mean +2 SD. Insulin secretion, assessed from the first or second phase plasma-C-peptide responses, was significantly lower in the glucose-intolerant relatives than in normoglycaemic relatives of similar sex, age, and obesity. beta-cell function, estimated by means of model analysis, was severely impaired in the glucose-intolerant relatives but was not impaired in the normoglycaemic relatives (geometric mean 41% and 109% of normal beta-cell response, respectively). Reduced beta-cell function was found with all degrees of glucose intolerance, whereas only the more severely hyperglycaemic relatives had impaired insulin sensitivity. This suggests that the primary defect in familial type-2 diabetes is beta-cell dysfunction.
D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D002096:C-Peptide / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000235:genetics* / Q000503:physiopathology; D005260:Female; D005951:Glucose Tolerance Test; D006801:Humans; D007263:Infusions, Parenteral; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D007515:Islets of Langerhans / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged
D001786:Blood Glucose; D002096:C-Peptide; D007328:Insulin