Type 2 diabetes mellitus and inflammation: Prospects for biomarkers of risk and nutritional intervention

Abstract

Obesity is a major risk factor for type 2 diabetes mellitus (T2DM), which is a significant health problem worldwide. Active disease is associated with low-grade chronic inflammation resulting in part from the activation of the innate immune system. In obesity, this activation leads to the release of pro-inflammatory cytokines such as tumor necrosis factor-α, interleukin-1β and interleukin-6 that block major anabolic cascades downstream of insulin signaling and thus disrupt insulin homeostasis and action. Cytokines also trigger the production of acute-phase reactants such as C-reactive protein, plasminogen activator inhibitor-1, serum amyloid-A, and haptoglobin. The elevated synthesis of pro-inflammatory cytokines and acute-phase proteins (inflammatory network) characterizes the early (or pre-clinical) stages of T2DM and exhibits a graded increase with the disease progression. Current evidence suggests that understanding inflammatory networks can point to new biomarkers that may permit capturing the interaction between genetic and environmental risk factors in the pathogenesis of T2DM. Such biomarkers have a significant public health potential in the prediction of disease occurrence beyond risk factors presently monitored, such as family history, lifestyle assessment and standard clinical chemistry profiles. Furthermore, inflammatory markers may assist in the evaluation of novel strategies for prevention, particularly in relation to micronutrients. This review discusses the current knowledge linking T2DM risk to inflammatory signaling pathways interacting with the innate immunity system and the prospect of inflammatory markers serving as molecular targets for prevention and/or biomarkers for early risk prediction of T2DM. The potential of micronutrients replenishment to improve insulin action by attenuating inflammation is also evaluated in the context of the public health relevance of this approach.

Data-analytically derived flexible HbA1c thresholds for type 2 diabetes mellitus diagnostic

“…HT is a known circumstance abetting development of T2DM, so much that the precursor of the two: namely, HT in addition to hyperglycaemia and/or dyslipidaemia is recognised as metabolic syndrome (MS) -a distinct condition. [17,43] However, HT is strongly associated with obesity [51] and obesity with T2DM. [28,29,43] In this regard, the little deflection of the "HT and CVD" line where the "HT absent" line joins it in Figure 6 -the inflection point in Figure 5 past 5.9% seems to be more on the part of the actual phenomenon than due to the limited knowledge of the data given by a single set.…”

“…C-reactive protein (CRP) and interleukin-6 (IL-6) are known to be indicators of inflammation processes associated with T2DM [17] and are routinely collected for diagnostic of the disease. In brief, the inflammation is caused by expansion of adipose tissue with vasculature development falling behind, which is also known to increase BP.…”

“…Thus, elevated IL-6 is one of the signs of increasing adiposity and therefore is a marker of obesity. IL-6 is not only present in obesity but actually abets T2DM by indirectly contributing to insulin resistance, [17] that is, before the glycation of cellular receptors is effective. Issue of this proinflammatory cytokine also stimulates hepatic production of CRP -an acute-phase response agent to inflammation, part of the innate immunity, which contributes to the autoimmune suppression of insulin producing β-cells in pancreas, [17] and this is not only abetting T2DM but in a long run makes it less and less reversible.…”

“…In fact, many anti-T2DM drugs attenuate CRP levels, directly or indirectly. [17] In this connection, while all rules in Table 1 offer mitigations of the HbA1c-only rule, whether the standard or the optimal, in view of the general discussion about their applicability, we would be more interested in modified rules extending the HbA1c useful range, that is, helping early detection of T2DM. This means smaller 'from' values of the indecision interval in Table 1.…”

“…[12] This may explain that varied results are obtained world-wide for HbA1c as a clinical marker in T2DM diagnostic. [8] Beyond protein glycation, DM progression is linked to markers of endothelial [13,14] and autonomic nervous system (ANS) dysfunction, [15,16] inflammatory [17,18] and oxidative stress [19,20] biomarkers. Recent literature reports that presence of 8-hydroxy-2'-deoxy-guanosine (8-OHdG) in blood or urine samples is indicative of oxidative stress and deoxyribonucleic acid (DNA) damage due to minor increases in the PG level.…”