Background: First-degree offspring (OFF) of type 2 diabetic (T2DM) patients bear a approximately 40% lifetime risk of developing T2DM. They are insulin resistant and carry a risk of premature atherosclerosis, the extent of which can be estimated by intima media thickness (IMT) of the carotid artery (CA). Thus, this study examines parameters of glucose and lipid metabolism, insulin sensitivity, beta cell function (BCF) and IMT with their interrelationships in middle-aged OFF.
Materials and methods: T2DM-OFF (n = 18, 14f/4m, 45.6 +/- 2.1 years, BMI: 26 +/- 1 kg m(-2)) were compared with 18 matching humans without a family history of diabetes (CON; 14f/4m, 44.5 +/- 2.1 years, BMI: 24 +/- 1 kg m(-2); each P > 0.30), all with normal glucose tolerance as tested by three-hour (75 g) oral glucose tolerance tests (OGTT). Two-hour hyperinsulinaemic (40 mU min(-1).m(-2))isoglycaemic clamp tests were performed with simultaneous measurement of endogenous glucose (D-[6,6-(2)H(2)]glucose) production (EGP). IMT [internal (ICA), common CA, and bulb] were measured sonographically. BCF was assessed by Adaptation Index (AI).
Results: Before and during OGTT, both groups were similar in plasma glucose, insulin, C-peptide and free fatty acids (FFA), whereas OFF showed ~30% lower (P < 0.03) fasting plasma triglycerides before OGTT. During hyperinsulinaemic clamps, insulin sensitivity was approximately 38% lower (P < 0.03) in OFF who showed higher plasma FFA (44 +/- 9 micromol L(-1)) than CON (26 +/- 3 micromol L(-1), P < 0.05) after 90 min. EGP was similar in both groups. OFF had 38% (P < 0.007) reduced AI. ICA-IMT was approximately 18% higher in OFF (P < 0.002), but did not correlate with insulin sensitivity.
Conclusion: The data obtained show middle-aged T2DM-OFF with normal glucose tolerance displaying reduced total insulin sensitivity and impaired beta cell function, which relates to impaired insulin-dependent suppression of plasma FFA and increased ICA-IMT.