Central and peripheral pathogenetic forms of type 2 diabetes: a proof-of-concept study

Abstract

Hypothesis

Previous studies provide evidence that glycated haemoglobin (HbA _1c) and fasting plasma glucose (FPG) should not be considered as interchangeable alternatives in the diagnosis of the same type 2 diabetes, but as indicators of its different pathogenetic subtypes. This study was conducted to determine whether a particularly high amount of glucose in either HbA _1c form or in fasting plasma would be found in diabetic patients genetically predisposed for either intensive cognitive or intensive muscle metabolic activity, respectively.

Methods

HbA _1c and FPG levels, polymorphisms of genes indicating the predisposition to different cognitive activity (the dopamine D2 receptor ( DRD2/ANKK1)), muscle activity (peroxisome proliferator-activated receptor gamma, coactivator 1 alpha ( PGC1A( PPARGC1A))), and vascular regulation of general metabolic activity (the angiotensin 1 converting enzyme ( ACE)) were assessed in diabetic patients and nondiabetic controls.

Results

DRD2/ANKK1 polymorphism that affects baseline central arousal determined HbA _1c variations uncorrelated with FPG in total and clinical groups. The mutation of PGC1A mainly affecting peripheral glucose metabolism had an effect on FPG correlated or uncorrelated with HbA _1c depending on the effect assessment in the total sample or in the nondiabetic group, respectively. ACE insertion/deletion (I/D) gene polymorphism was associated with both HbA _1c and FPG fluctuations, but only in diabetic patients.

Conclusion

The findings provide evidence that the HbA _1c and FPG may predict the risks for different subtypes of type 2 diabetes associated with either brain or muscle metabolic activity in genetically vulnerable people.