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

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)(2000)(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 HbA 1c 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).Electronic supplementary material The online version of this article (doi:10.1007/s00125-015-3679-4) contains peer-reviewed but unedited supplementary material, which is available to authorised users. 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.

Biomarkers of subclinical inflammation and increases in glycaemia, insulin resistance and beta-cell function in non-diabetic individuals: the Whitehall II study

“…Furthermore, the sample size for the HbA 1c analysis was smaller than that for other glycaemic traits. Our data are only partly in line with previous observations in the KORA study showing a positive association between hsCRP and 7-year changes in HbA 1c , but no association between adiponectin and HbA 1c (9). There are no obvious differences in baseline characteristics between the two studies, so the relevance of subclinical inflammation for HbA 1c levels in non-diabetic individuals merits further studies.…”

“…To date, two small studies have failed to provide evidence for an association of proinflammatory cytokines or adiponectin with incident IFG or IGT (6,7). An alternative approach with higher statistical power is to investigate whether baseline levels of biomarkers of subclinical inflammation are associated with subsequent changes in measures of glucose metabolism (8,9).…”

MASP1, THBS1, GPLD1 and ApoA-IV are novel biomarkers associated with prediabetes: the KORA F4 study

“…As summarised by Wang et al [37], ApoA-IV has potent antioxidant and anti-inflammatory properties, and has been suggested to reduce food intake by increasing satiety (at least in animal models). These properties all have the potential to prevent type 2 diabetes development [3,38,39]. In support of this notion, we observed associations between increased ApoA-IV levels and both decreased 2 h glucose levels and decreased prediabetes prevalence independent of all investigated covariables.…”

“…Biomarkers associated with this 'prediabetic' state (impaired fasting glucose and/or impaired glucose tolerance) may help to elucidate the pathophysiological pathways leading to type 2 diabetes [2,3].…”

Clinical and metabolic factors associated with chronic low-grade inflammation in type 2 diabetic patients

“…Последние становятся источником провоспалительных цитокинов, которые могут вмеши-ваться в реализацию сигнала инсулина в перифериче-ских тканях и индуцировать дисфункцию β-клеток [2]. Проспективные исследования показывают, что уве-личение количества лейкоцитов и содержания мар-керов воспаления в сыворотке крови ассоциировано с повышением гликемии на ранних стадиях развития СД2 [3,4].…”