Impaired glucose effectiveness (i.e., a diminished ability of glucose per se to facilitate its own metabolism), increased gluconeogenesis, and endogenous glucose release are, together with insulin resistance and β-cell abnormalities, established features of type 2 diabetes. To explore aspects of the pathophysiology behind type 2 diabetes, we assessed in a group of healthy people prone to develop type 2 diabetes (n = 23), namely first-degree relatives of type 2 diabetic patients (FDR), 1) endogenous glucose release and fasting gluconeogenesis measured using the 2H2O technique and 2) glucose effectiveness. The FDR group was insulin resistant when compared with an age-, sex-, and BMI-matched control group without a family history of type 2 diabetes (n = 14) (M value, clamp: 6.07 ± 0.48 vs. 8.06 0.69 mg. kg-1 lean body weight (lbw) · min-1; P = 0.02). Fasting rates of gluconeogenesis (1.28 ± 0.06 vs. 1.41 0.07 mg · kg-1 lbw · min-1 FDR vs. control subjects, P = 0.18) did not differ in the two groups and accounted for 53 ± 2 and 60 ± 3% of total endogenous glucose release. Glucose effectiveness was examined using a combined somatostatin and insulin infusion (0.17 vs. 0.14 mU· kg-1 · min-1, FDR vs. control subjects), the latter replacing serum insulin at near baseline levels. In addition, a 360-min labeled glucose infusion was given to simulate a prandial glucose profile. After glucose infusion, the integrated plasma glucose response above baseline (1817 · 94 vs. 1789 ± 141 mmol/l per 6 h), the ability of glucose to simulate its own uptake (1.50 ± 0.13 vs. 1.32 · 0.16 ml · kg-1 lbw · min-1), and the ability of glucose per se to suppress endogenous glucose release did not differ between the FDR and control group. In conclusion, in contrast to overt type 2 diabetic patients, healthy people at high risk of developing type 2 diabetes are characterized by normal glocuse effectiveness at near-basal insulinemia and normal fasting rates of gluconeogenesis.
ASJC Scopus subject areas
- Internal Medicine
- Endocrinology, Diabetes and Metabolism