Profile of the Immune and Inflammatory Response in Individuals With Prediabetes and Type 2 Diabetes

Abstract

OBJECTIVEThe inflammatory and immune systems are altered in type 2 diabetes. Here, the aim was to profile the immune and inflammatory response in subjects with prediabetes and diabetes in a large population-representative sample. RESEARCH DESIGN AND METHODSIn total, 15,010 individuals were analyzed from the population-based Gutenberg Health Study. Glucose status was classified according to HbA 1c concentration and history of diagnosis. All samples were analyzed for white blood cells (WBCs), granulocytes, lymphocytes, monocytes, platelets, C-reactive protein (CRP), albumin, fibrinogen, and hematocrit. Interleukin-18 (IL-18), IL-1 receptor antagonist (IL-1RA), and neopterin concentrations were determined in a subcohort. RESULTSIn total, 7,584 men and 7,426 women were analyzed (range 35-74 years), with 1,425 and 1,299 having prediabetes and diabetes, respectively. Biomarkers showed varying dynamics from normoglycemic via subjects with prediabetes to subjects with diabetes: 1) gradual increase (WBCs, granulocytes, monocytes, IL-1RA, IL-18, and fibrinogen), 2) increase with subclinical disease only (lymphocytes and CRP), 3) increase from prediabetes to diabetes only (neopterin), and 4) no variation with glucose status (hematocrit). The strongest relative differences were found for CRP, IL-1RA, and fibrinogen concentrations. Several inflammatory and immune markers were associated with the glucose status independent from cardiovascular risk factors and comorbidities, varied with disease severity and the presence of disease-specific complications in the diabetes subcohort. CONCLUSIONSThe inflammatory and immune biomarker profile varies with the development and progression of type 2 diabetes. Markers of inflammation and immunity enable differentiation between the early preclinical and clinical phases of the disease, disease complications, and progression.Type 2 diabetes and its disease-associated complications represent an important and increasing public health burden worldwide (1). Obesity, which leads to metabolic and adipocyte stress, is the most important predisposing factor for type 2 diabetes (2). Obesity-associated insulin resistance, activation of the innate immune system, and chronic increased production of cytokines and adipokines are an

Endoplasmic reticulum stress and the unfolded protein response in pancreatic islet inflammation

“…In line with this, elevated circulating levels of pro-inflammatory cytokines characterize the early (or pre-clinical) stages of T2D and exhibit a graded increase with the disease progression (Duncan et al 2003, Grossmann et al 2015. Interestingly, recent studies also suggest links between inflammation and ER stress in T2D patients at the level of the immune system.…”

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

“…Regarding circulating C-reactive protein (CRP), for example, higher levels were observed in prediabetes (i.e., impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT)) compared with normal glucose tolerance (NGT), whereas only minor differences in CRP levels were observed between people with prediabetes and type 2 diabetes (3). In contrast, systemic levels of interleukin (IL)-6 or IL18 seemed to be similar in individuals with NGT and prediabetes, but higher in those with type 2 diabetes compared with those with prediabetes (3,4). Thus, different biomarkers of subclinical inflammation are related to early vs late stages of glycaemic deterioration, but little is known about the underlying pathophysiology (5).…”

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“…Grossmann et al in 2015, noted that neopterin level was positively associated with the prevalence of the diabetes disease 13 . As well, neopterin considered as a marker of diabetic progression and complication 14 .…”