title: Central and peripheral pathogenetic forms of type 2 diabetes: a proof-of-concept study.
abstract: OBJECTIVE
  Previous studies provide evidence that glycated haemoglobin (HbA1c) 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 HbA1c form or in fasting plasma would be found in diabetic patients genetically predisposed for either intensive cognitive or intensive muscle metabolic activity, respectively.
  
  
  METHODS
  HbA1c 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 HbA1c 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 HbA1c 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 HbA1c and FPG fluctuations, but only in diabetic patients.
  
  
  CONCLUSIONS
  The findings provide evidence that the HbA1c 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.
authors: Laboratory of NeuroimmunopathologyInstitute of General Pathology and Pathophysiology, Russian Academy of Medical Sciences, Moscow, Russia d.m.davydov@gmail.com.
authors: Dmitry M
authors: DM
authors: Davydov
authors: Laboratory of SociogenomicsMoscow State Pedagogical University, Moscow, Russia.
authors: Malik K
authors: MK
authors: Nurbekov
keywords: ACE; DRD2/ANKK1; PGC1A; central arousal; fasting plasma glucose; gene polymorphism; glycated haemoglobin; muscle activity; type 2 diabetes; vascular resistance