[Hepatic and peripheral insulin resistance as a cause of hyperglycemia in non-insulin-dependent (type 2) diabetes mellitus: a review].

In diabetic patients, fasting hyperglycaemia is attributed to both, reduced clearance by peripheral tissues and augmented endogenous glucose release. In normal-weight, non-insulin-dependent diabetic patients, basal hepatic glucose production (HGP) was determined by means of tracer kinetic analysis. HGP was enhanced to 3.00 +/- 0.20 mg/kg X min as compared to 1.90 +/- 0.05 in healthy, non-diabetic subjects, even though hyperglycaemia and fasting hyperinsulinaemia prevailed. HGP correlated positively with fasting blood glucose (r = 0.577; P less than 0.01). Glucose clearance rate was reduced by 20%. Marked hyperinsulinaemia during an isoglycaemic (0.75 mU/kg X min) insulin clamp study suppressed HGP by only 82% as compared to greater than 95% in healthy subjects. Furthermore, significant residual HGP was also observed when hyperglycaemia was augmented by exogenous glucose administration. Thus, in the fasting state, HGP is increased and directly correlated with severity of hyperglycaemia. Due to a reduction in glucose clearance, blood glucose concentration rises until glucose utilization rate equals HGP. Under conditions of hyperinsulinaemia and hyperglycaemia, suppressibility of HGP is diminished. Thereby, HGP and diminished glucose clearance by peripheral tissues contribute to basal as well as postprandial hyperglycaemia in type 2 diabetic patients.