Adipokines and inflammatory markers in elderly subjects with high risk of type 2 diabetes and cardiovascular disease

Abstract

Inflammation plays a significant role in pathogenesis of diabetes and atherosclerosis. Increased adiposity with an upregulation of cytokines in prediabetes has been associated with vascular inflammation and considered a leading causal factor for type 2 diabetes (T2D). Information on adipokines and inflammatory markers in prediabetes, defined by hemoglobin A1C (HbA1c) 5.7-6.4% in addition to impaired fasting glucose (IFG) and impaired glucose tolerance (IGT), are sparse. We conducted a population-based cross-sectional study (part of a follow-up study) of inhabitants of Oulu, Finland, born in 1935. Inflammatory markers and traditional risk markers of 367 subjects were measured. The glucose status was determined by an oral glucose tolerance test (OGTT) and HbA1c. Inflammatory markers and glycemic levels were analysed using analysis of covariance (ANCOVA). Of the participants, 193 were normoglycemic, 82 had prediabetes and 40 T2D. Inflammatory cytokines were significantly higher in subjects with prediabetes as compared to normoglycemic subjects: IL-4 (14.9 vs 5.9 pg/ml, p = 0.041), IP-10 (251 vs 209 pg/ml, p = 0.05), TNF-α (10.4 vs 6.9 pg/ml, p = 0.027), RANTES (43.3 vs 33.1 pg/ml, p = 0.009), CD40L (3708 vs 1671 pg/ml, p = 0.010) and VEGF (269 vs 174 pg/ml, p = 0.013). These inflammatory cytokines remained significant even after adjustment for waist circumference. The differences in inflammatory markers in prediabetic and T2D subjects were not statistically significant. Prediabetes was associated with low-grade inflammation with increased inflammatory cytokine levels, while the levels in prediabetic subjects were comparable to those in T2D subjects. The associations were independent of visceral adiposity.

Figure 1

Flow chart of the study.

Figure 2

Spearman correlation coefficients between inflammatory markers, diabetes and cardiovascular risk factors. Red or blue color indicates the respective positive or negative correlation coefficient value intensities. Indices: BMI, Body mass index; DIA, Diastolic blood pressure; SYS, Systolic blood pressure, 2 H GLUC, 2 hour glucose; fS-GLUC, Fasting glucose, fS-INS, Fasting insulin; HbA1c, Hemoglobin A1c; HOMA-IR, Homeostasis model assessment for insulin resistance; HDL, High density lipoprotein; Trigly, Triglycerides; Waist, Waist circumference; IL-1α, Interleukin 1α; IL-1β, Interleukin 1β, IL-1ra, Interleukin 1 receptor antagonist; IL-4, Interleukin 4; IL-6, Interleukin 6; IL-8, Interleukin 8; IL-17, Interleukin 17; IP-10, Interferon gamma-induced protein 10; TNF-α, Tumor necrosis factor α; MCP-1, Monocyte chemoattractant protein-1; active PAI-1, plasminogen activators inhibitor type 1 – activity; RANTES, Regulated on activation, normal T-cell and expressed and secreted; MPO, Myeloperoxidase; CD40L, Ligand for CD40; ICAM-1, Intercellular Adhesion Molecule 1; VCAM-1, Vascular Cell Adhesion Molecule 1; VEGF, Vascular endothelial growth factor; DPPIV, Dipeptidyl peptidase IV. Units please see Table 2.

Figure 3

Correlation Network. The thickness of the lines represent the strength of the correlation. Green lines – positive correlation. Red lines – negative correlation. There are strong positive correlations between BMI, waist circumference, HOMA-IR, systolic and diastolic blood pressure. In the cytokines, there are four positive correlated clusters: (1) IL-1α, IL-1β, IL-1Ra, IL-4, and IL-6; (2) VEGF, IP-10, TNF-α, IL-8 and IL-17; (3) MPO, RANTES and CD40L; (4) E-selectin, ICAM-1 and VCAM-1. Adiponectin and HDL cholesterol are positively correlated while HDL is negative with fasting insulin (fS-INS), waist circumference and triglycerides. BMI, Body mass index; DIA, Diastolic pressure; SYS, Systolic blood pressure, 2 H GLUC, 2 hour glucose; fS-GLUC, Fasting glucose, fS-INS, Fasting insulin; HbA1c, Hemoglobin A1c; HOMA, Homeostasis model assessment for insulin resistance; HDL, High density lipoprotein; Trigly, Triglycerides; Waist, Waist circumference; IL-1α, Interleukin 1α; IL-1α, Interleukin 1β, IL-1ra, Interleukin 1 receptor antagonist; IL-4, Interleukin 4; IL-6, Interleukin 6; IL-8, Interleukin 8; IL-17, Interleukin 17; IP-10, Interferon gamma-induced protein 10; TNF-α, Tumor necrosis factor α; MCP-1, Monocyte chemoattractant protein-1; active PAI-1, plasminogen activators inhibitor type 1 – activity; RANTES, Regulated on activation, normal T-cell and expressed and secreted; MPO, Myeloperoxidase; CD40L, Ligand for CD40; ICAM-1, Intercellular Adhesion Molecule 1; VCAM-1, Vascular Cell Adhesion Molecule 1; VEGF, Vascular endothelial growth factor; DPPIV, Dipeptidyl peptidase IV.