Association of subclinical inflammation with deterioration of glycaemia before the diagnosis of type 2 diabetes: the KORA S4/F4 study

Diabetologia. 2015 Oct;58(10):2269-77. doi: 10.1007/s00125-015-3679-4. Epub 2015 Jul 9.

Abstract

Aims/hypothesis: The role of biomarkers of subclinical inflammation in the early deterioration of glycaemia before type 2 diabetes is largely unknown. We hypothesised that increased levels of circulating proinflammatory biomarkers and decreased circulating adiponectin would be associated with 7 year increases of HbA(1c) in non-diabetic individuals.

Methods: This study was based on individuals who participated in the prospective Cooperative Health Research in the Region of Augsburg (KORA) S4 survey (1999-2001) and the 7 year follow-up KORA F4 (2006-2008) survey. Individuals with type 2 diabetes at baseline or with a diagnosis of diabetes in the period between both surveys were excluded, which left a sample of 850 men and women. Multivariable linear regression analyses were performed to assess associations among baseline values of leucocyte count and levels of acute-phase proteins (high-sensitivity C-reactive protein [hsCRP], serum amyloid A [SAA] and fibrinogen), IL-6 and adiponectin with changes in HbA1c between baseline and follow-up.

Results: A high leucocyte count and high hsCRP, SAA and IL-6 levels were positively associated with changes in HbA(1c) after adjusting for age, sex, lifestyle factors and baseline HbA(1c). In contrast, the adiponectin level was inversely associated with changes in HbA(1c) (p value between <0.0001 and 0.020). The associations of leucocyte count and levels of hsCRP and SAA with HbA(1c) changes remained significant after additional adjustment for waist circumference and circulating lipids at baseline and for the 7 year change in waist circumference (p value between 0.004 and 0.045).

Conclusions/interpretation: An elevated leucocyte count and elevated hsCRP and SAA were associated with early deterioration of glycaemia before the diagnosis of type 2 diabetes. These associations were largely independent of baseline abdominal adiposity and increases in waist circumference.

Keywords: Adiponectin; Cohort study; Cytokines; Glycaemia; HbA1c; Inflammation; Type 2 diabetes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute-Phase Proteins / metabolism
  • Adiponectin / blood*
  • Aged
  • Biomarkers / blood
  • Blood Glucose*
  • C-Reactive Protein / metabolism*
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / diagnosis*
  • Female
  • Fibrinogen / metabolism
  • Humans
  • Inflammation / blood
  • Inflammation / complications
  • Inflammation / diagnosis*
  • Interleukin-6 / blood
  • Male
  • Middle Aged
  • Prospective Studies
  • Serum Amyloid A Protein / metabolism

Substances

  • ADIPOQ protein, human
  • Acute-Phase Proteins
  • Adiponectin
  • Biomarkers
  • Blood Glucose
  • Interleukin-6
  • Serum Amyloid A Protein
  • Fibrinogen
  • C-Reactive Protein