Association of Changes in Inflammation with Changes in Glycemia, Insulin Resistance and Secretion: a DIRECT study based on KORA

AIMS: Subclinical systemic inflammation may contribute to the development of type 2 diabetes, but its association with early progression of glycemic deterioration in persons without diabetes has not been fully investigated. Our primary aim was to assess longitudinal associations of changes in pro- (leukocytes, high-sensitivity C-reactive protein (hsCRP)) and anti-inflammatory (adiponectin) markers with changes in markers that assessed glycemia, insulin resistance and secretion (HbA1c , HOMA-IR, HOMA-ß). Furthermore, we aimed to directly compare longitudinal with cross-sectional associations.

MATERIALS AND METHODS: This study includes 819 initially non-diabetic individuals with repeated measurements from the KORA S4/F4 cohort study (median follow-up: 7.1 years). Longitudinal and cross-sectional associations were simultaneously examined using linear mixed growth models. Changes in markers of inflammation were used as independent and changes in markers of glycemia/insulin resistance/insulin secretion as dependent variables. Models were adjusted for age, sex and major lifestyle and metabolic risk factors for diabetes using time-varying variables in the final model.

RESULTS: Changes of leukocyte count were positively associated with changes in HbA1c and HOMA-ß while changes in adiponectin were inversely associated with changes in HbA1c . All examined cross-sectional associations were statistically significant; they were generally stronger and mostly directionally consistent to the longitudinal association estimates.

CONCLUSIONS: Adverse changes in low-grade systemic inflammation go along with glycemic deterioration and increased insulin secretion independently of changes in other risk factors, suggesting that low-grade inflammation may contribute to the development of hyperglycemia and a compensatory increase in insulin secretion.