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

Tonia de las Heras Gala; Christian Herder; Femke Rutters; Maren Carstensen-Kirberg; Cornelia Huth; Coen D. A. Stehouwer; Giel Nijpels; Casper Schalkwijk; Allan Flyvbjerg; Paul W. Franks; Jacqueline Dekker; Christa Meisinger; Wolfgang Koenig; Michael Roden; Wolfgang Rathmann; Annette Peters; Barbara Thorand; IMI DIRECT Consortium

doi:10.1002/dmrr.3063

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

Tonia de las Heras Gala, Christian Herder, Femke Rutters, Maren Carstensen-Kirberg, Cornelia Huth, Coen D. A. Stehouwer, Giel Nijpels, Casper Schalkwijk, Allan Flyvbjerg, Paul W. Franks, Jacqueline Dekker, Christa Meisinger, Wolfgang Koenig, Michael Roden, Wolfgang Rathmann, Annette Peters, Barbara Thorand^*, IMI DIRECT Consortium

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

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-beta). Furthermore, we aimed to directly compare longitudinal with cross-sectional associations. Materials and methods Results 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. Changes of leukocyte count were positively associated with changes in HbA(1c) and HOMA-beta 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.

Original language	English
Article number	3063
Number of pages	9
Journal	Diabetes-metabolism Research and Reviews
Volume	34
Issue number	8
DOIs	https://doi.org/10.1002/dmrr.3063
Publication status	Published - Nov 2018

Keywords

glycaemic deterioration
HbA(1c)
inflammation
insulin resistance
beta-cell function
BETA-CELL FUNCTION
SUBCLINICAL INFLAMMATION
ADIPONECTIN LEVELS
CARDIOVASCULAR-DISEASE
GLUCOSE-TOLERANCE
DIABETES-MELLITUS
S4/F4 COHORT
TNF-ALPHA
HIGH-RISK
SENSITIVITY

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10.1002/dmrr.3063

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Gala, T. D. L. H., Herder, C., Rutters, F., Carstensen-Kirberg, M., Huth, C., Stehouwer, C. D. A., Nijpels, G., Schalkwijk, C., Flyvbjerg, A., Franks, P. W., Dekker, J., Meisinger, C., Koenig, W., Roden, M., Rathmann, W., Peters, A., Thorand, B., & IMI DIRECT Consortium (2018). Association of changes in inflammation with variation in glycaemia, insulin resistance and secretion based on the KORA study. Diabetes-metabolism Research and Reviews, 34(8), Article 3063. https://doi.org/10.1002/dmrr.3063

@article{96d7001937cf4e65a59d67bfc6dc95ab,

title = "Association of changes in inflammation with variation in glycaemia, insulin resistance and secretion based on the KORA study",

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-beta). Furthermore, we aimed to directly compare longitudinal with cross-sectional associations. Materials and methods Results 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. Changes of leukocyte count were positively associated with changes in HbA(1c) and HOMA-beta 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 = "glycaemic deterioration, HbA(1c), inflammation, insulin resistance, beta-cell function, BETA-CELL FUNCTION, SUBCLINICAL INFLAMMATION, ADIPONECTIN LEVELS, CARDIOVASCULAR-DISEASE, GLUCOSE-TOLERANCE, DIABETES-MELLITUS, S4/F4 COHORT, TNF-ALPHA, HIGH-RISK, SENSITIVITY",

author = "Gala, {Tonia de las Heras} and Christian Herder and Femke Rutters and Maren Carstensen-Kirberg and Cornelia Huth and Stehouwer, {Coen D. A.} and Giel Nijpels and Casper Schalkwijk and Allan Flyvbjerg and Franks, {Paul W.} and Jacqueline Dekker and Christa Meisinger and Wolfgang Koenig and Michael Roden and Wolfgang Rathmann and Annette Peters and Barbara Thorand and {IMI DIRECT Consortium}",

year = "2018",

month = nov,

doi = "10.1002/dmrr.3063",

language = "English",

volume = "34",

journal = "Diabetes-metabolism Research and Reviews",

issn = "1520-7560",

publisher = "Wiley",

number = "8",

}

Gala, TDLH, Herder, C, Rutters, F, Carstensen-Kirberg, M, Huth, C, Stehouwer, CDA, Nijpels, G, Schalkwijk, C, Flyvbjerg, A, Franks, PW, Dekker, J, Meisinger, C, Koenig, W, Roden, M, Rathmann, W, Peters, A, Thorand, B & IMI DIRECT Consortium 2018, 'Association of changes in inflammation with variation in glycaemia, insulin resistance and secretion based on the KORA study', Diabetes-metabolism Research and Reviews, vol. 34, no. 8, 3063. https://doi.org/10.1002/dmrr.3063

TY - JOUR

T1 - Association of changes in inflammation with variation in glycaemia, insulin resistance and secretion based on the KORA study

AU - Gala, Tonia de las Heras

AU - Herder, Christian

AU - Rutters, Femke

AU - Carstensen-Kirberg, Maren

AU - Huth, Cornelia

AU - Stehouwer, Coen D. A.

AU - Nijpels, Giel

AU - Schalkwijk, Casper

AU - Flyvbjerg, Allan

AU - Franks, Paul W.

AU - Dekker, Jacqueline

AU - Meisinger, Christa

AU - Koenig, Wolfgang

AU - Roden, Michael

AU - Rathmann, Wolfgang

AU - Peters, Annette

AU - Thorand, Barbara

AU - IMI DIRECT Consortium

PY - 2018/11

Y1 - 2018/11

N2 - 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-beta). Furthermore, we aimed to directly compare longitudinal with cross-sectional associations. Materials and methods Results 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. Changes of leukocyte count were positively associated with changes in HbA(1c) and HOMA-beta 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.

AB - 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-beta). Furthermore, we aimed to directly compare longitudinal with cross-sectional associations. Materials and methods Results 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. Changes of leukocyte count were positively associated with changes in HbA(1c) and HOMA-beta 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.

KW - glycaemic deterioration

KW - HbA(1c)

KW - inflammation

KW - insulin resistance

KW - beta-cell function

KW - BETA-CELL FUNCTION

KW - SUBCLINICAL INFLAMMATION

KW - ADIPONECTIN LEVELS

KW - CARDIOVASCULAR-DISEASE

KW - GLUCOSE-TOLERANCE

KW - DIABETES-MELLITUS

KW - S4/F4 COHORT

KW - TNF-ALPHA

KW - HIGH-RISK

KW - SENSITIVITY

U2 - 10.1002/dmrr.3063

DO - 10.1002/dmrr.3063

M3 - Article

SN - 1520-7560

VL - 34

JO - Diabetes-metabolism Research and Reviews

JF - Diabetes-metabolism Research and Reviews

IS - 8

M1 - 3063

ER -