Low-grade inflammation in type 2 diabetes: a cross-sectional study from a Danish diabetes outpatient clinic

Abstract

Objectives: To investigate low-grade inflammation in type 2 diabetes and explore associations to clinical aspects as well as microvascular and macrovascular complications.

Design: Cross-sectional analysis.

Setting: The outpatient diabetes clinic at the Department of Endocrinology at Aalborg University Hospital, Denmark.

Participants: 100 participants with type 2 diabetes confirmed by a haemoglobin A1c (HbA1c)≥6.5% for a minimum of 1 year and 21 healthy controls.

Outcome measures: Serum levels of 27 inflammation-related biomarkers measured by immunoassay. Associations with microvascular and macrovascular complications, body weight, glycaemic control, medication and sex were investigated in the diabetes cohort.

Results: Serum levels of tumour necrosis factor (TNF)-α and eotaxin were elevated in type 2 diabetes (p<0.05), while interleukin (IL)-7 was decreased (p<0.001). IL-12/IL-23p40, IL-15, macrophage-derived chemokine (MDC) and C reactive protein (CRP) levels were increased with body weight (p<0.05), while eotaxin and TNF-α were increased with elevated HbA1c levels (p<0.04). Dipeptidyl peptidase-4 inhibitor therapy was associated with lower levels of induced protein-10, MDC and thymus and activation regulated chemokine (p<0.02), while females had higher levels of MDC (p=0.027). Individuals with ≥3 diabetic complications had elevated levels of IL-6, IL-10, IL-12/IL-23p40, IL-15 and CRP compared with those with ≤3 (p<0.05).

Conclusion: The level of low-grade inflammation in type 2 diabetes is associated with obesity, glycaemic regulation, therapeutical management, sex and complications. Our results underline the importance of addressing inflammatory issues in type 2 diabetes, as these may predispose for crippling comorbidities.

Keywords: DIABETES & ENDOCRINOLOGY; Diabetic neuropathy; IMMUNOLOGY.

Figure 1

Volcano plot displaying pairwise comparisons of inflammatory factors in type 2 diabetes and healthy controls. Vertical dashed lines indicate threshold for twofold differences among groups. Horizontal dashed lines indicate p value thresholds of 0.05, 0.01 and 0.001, respectively. ●Significantly different after adjustment for age and BMI, ◓significantly different in the unadjusted model,○ above significance threshold in both models. Only significant analytes are labelled. BMI, body mass index; CRP, C reactive protein; IL, interleukin; MDC, macrophage-derived chemokine; MIP, macrophage inflammatory protein; TNF, tumour necrosis factor.

Figure 2

Box plots displaying plasma concentrations of biomarkers in individuals with type 2 diabetes and 0 (n=20), 1 (n=43), 2 (n=28), or 3 or more (n=7) diabetic comorbidities (retinopathy, nephropathy, neuropathy, cardiac autonomic neuropathy). Only analytes with p values below 0.05 are shown. *P<0.05, **p<0.01. CRP, C reactive protein; IL, interleukin.