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Measuring Relative Insulin Secretion using a Co-Secreted Luciferase Surrogate

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Association of changes in inflammation with variation in glycaemia, insulin resistance and secretion based on the

Tonia de Las Heras Gala^1,2, Christian Herder^2,3,4, Femke Rutters⁵

¹Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.

Diabetes/Metabolism Research and Reviews

|August 17, 2018

Abstract

Aims:

Subclinical systemic inflammation may contribute to the development of type 2 diabetes, but its association with early progression of glycaemic deterioration in persons without diabetes has not been fully investigated. Our primary aim was to assess longitudinal associations of changes in pro-inflammatory (leukocytes, high-sensitivity C-reactive protein (hsCRP)) and anti-inflammatory (adiponectin) markers with changes in markers that assessed glycaemia, insulin resistance, and secretion (HbA_1c , HOMA-IR, and HOMA-ß). Furthermore, we aimed to directly compare longitudinal with cross-sectional associations.

Materials And Methods:

This study includes 819 initially nondiabetic individuals with repeated measurements from the Cooperative Health Research in the Region of Augsburg (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 glycaemia/insulin resistance/insulin secretion as dependent variables. Models were adjusted for age, sex, 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 HbA_1c and HOMA-ß while changes in adiponectin were inversely associated with changes in HbA_1c . 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 glycaemic deterioration and increased insulin secretion independently of changes in other risk factors, suggesting that low-grade inflammation may contribute to the development of hyperglycaemia and a compensatory increase in insulin secretion.

Keywords:

HbA1c glycaemic deterioration inflammation insulin resistance ß-cell function

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