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

Abstract

Objective: Higher systemic levels of pro-inflammatory biomarkers and low adiponectin are associated with increased risk of type 2 diabetes, but their associations with changes in glycaemic deterioration before onset of diabetes are poorly understood. We aimed to study whether inflammation-related biomarkers are associated with 5-year changes in glucose and insulin, HbA1c, insulin sensitivity and beta-cell function before the diagnosis of type 2 diabetes and whether these associations may be bidirectional. Design and methods: We used multiple repeat measures (17 891 person-examinations from 7683 non-diabetic participants) from the Whitehall II study to assess whether circulating high-sensitivity C-reactive protein (hsCRP), interleukin-6 (IL6), IL1 receptor antagonist (IL1Ra) and adiponectin are associated with subsequent changes in glycaemia, insulin, insulin resistance and beta-cell function (based on oral glucose tolerance tests). We examined bidirectionality by testing if parameters of glucose metabolism at baseline are associated with changes in inflammation-related biomarkers. Results: Higher hsCRP and IL6 were associated with increases in fasting insulin, insulin resistance and, for IL6, with beta-cell function after adjustment for confounders. Higher adiponectin was associated with decreases in fasting glucose, HbA1c, fasting insulin, insulin resistance and beta-cell function. The reverse approach showed that 2-h glucose and insulin sensitivity were associated with changes in IL1Ra. Fasting insulin and insulin resistance showed inverse associations with changes in adiponectin. Conclusions: Subclinical inflammation is associated with development of increased glycaemia, insulin resistance and beta-cell function in non-diabetic individuals. These findings are consistent with the hypothesis that inflammationrelated processes may increase insulin resistance and lead to a compensatory upregulation of beta-cell function. European Journal of Endocrinology175:5 368 Clinical Study C Herder and others Inflammation and glucose metabolism

Relationships of serum high-sensitivity C-reactive protein and body size with insulin resistance in a Japanese cohort

“…These findings were almost concordant with previous reports [36,37]. Festa et al [36] reported that inflammation in the prediabetic state was related to increased insulin resistance rather than decreased insulin secretion.…”

“…Festa et al [36] reported that inflammation in the prediabetic state was related to increased insulin resistance rather than decreased insulin secretion. Herder et al [37] have recently reported that higher hs-CRP and interleukin (IL)-6 were associated with increases in fasting insulin and insulin resistance and IL-6 (but not hs-CRP) was associated with HOMA-β. Although we have no data on IL-6, it has been reported that IL-6 can stimulate insulin secretion through glucagon-like peptide-1 (GLP-1) production and secretion in animal models of type 2 diabetes [38].…”

Association of child maltreatment subtypes and long-term physical health in a German representative sample

“…Long-term alterations in the regulation of the HPA axis and its final product, cortisol, are a known consequence of the enormous stress caused by maltreatment during childhood (Carpenter et al, 2007), and are linked to health outcomes such as cancer and cardiovascular and metabolic diseases (Kumari, Shipley, Stafford, & Kivimaki, 2011; Volden & Conzen, 2013). Furthermore, chronic inflammatory processes, encompassing increased levels of pro-inflammatory cytokines and oxidative stress, are a demonstrated long-term consequence of child maltreatment (Boeck et al, 2016) and are known to play a role in the pathomechanisms of cancer (Taniguchi & Karin, 2018), cardiovascular diseases (Harrington, 2017), diabetes and other metabolic diseases (Herder et al, 2016). As well as biological mechanisms, socioeconomic and behavioural aspects are considered to be relevant for the demonstrated link between child maltreatment and health conditions in adulthood.…”

Cardiovascular and Metabolic Diseases Comorbid with Psoriasis: Beyond the Skin

“…The close association of systemic inflammation with cardiovascular diseases (CVD) and metabolic syndrome is a recent topic in medicine (1-3). Inflammatory skin diseases such as psoriasis are an integral part of diseases causing systemic inflammation (4).…”