Peripheral tissue glucose uptake is not reduced after an oral glucose load in Southern Italian subjects at risk of developing non-insulin-dependent diabetes mellitus

Metabolism. 1999 Jan;48(1):80-5. doi: 10.1016/s0026-0495(99)90014-8.


Studies searching for the inherited defects that cause non-insulin-dependent diabetes mellitus (NIDDM) have been performed mostly in Northern European subjects using the hyperinsulinemic clamp technique. The conclusion drawn from most of these studies is that peripheral insulin resistance is likely a primary inherited defect. Our aim was to examine early defects in glucose metabolism using a more physiological technique in a different ethnic group. For this, a double-label oral glucose tolerance test (OGTT) was performed in young diabetes-prone Southern Italian subjects who had both parents with NIDDM (relatives) and in subjects with no family history of NIDDM (matched for age, weight, and ethnicity). Fasting plasma glucose and insulin in the relatives were normal; however, they had impaired glucose tolerance during the OGTT. This was due to reduced hepatic glucose uptake (17.9+/-2.8 v. 28.1+/-2.3 g, P<.02). No defects were found in the metabolic clearance rate (MCR) of glucose or endogenous glucose production. During an intravenous glucose tolerance test (IVGTT), insulin sensitivity was again found to be normal (3.04+/-0.65 in relatives v. 2.33+/-0.38 min(-1) per micromol x L(-1) x min in controls), with a marked reduction in first-phase insulin secretion in the relatives (110+/-12 v. 211+/-18 pmol x L(-1) x min per mmol x L(-1), P<.001). A strong correlation was found between hepatic glucose uptake and insulin secretion (r = .81, P<.001), which may suggest that the same abnormality operates in both the liver and pancreas. Therefore, the metabolic defect that causes hyperglycemia in diabetes-prone subjects is not always a reduced peripheral insulin sensitivity. The genetic basis of NIDDM may differ between different ethnic groups.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Diabetes Mellitus, Type 2 / ethnology
  • Diabetes Mellitus, Type 2 / etiology
  • Diabetes Mellitus, Type 2 / metabolism*
  • Fatty Acids, Nonesterified / blood
  • Glucose / metabolism*
  • Glucose Tolerance Test
  • Humans
  • Insulin / metabolism
  • Insulin Resistance*
  • Insulin Secretion
  • Italy
  • Liver / metabolism
  • Metabolic Clearance Rate
  • Risk


  • Fatty Acids, Nonesterified
  • Insulin
  • Glucose