Betatrophin is a recently identified hormone, the circulating concentrations of which are unaltered in human insulin resistance but correlate significantly with atherogenic lipid profiles in high-risk cohorts with morbid obesity or type 2 diabetes. Betatrophin could therefore be a novel pathomechanistic player in dysfunctional lipid metabolism associated with high cardiovascular risk.

Obesity-induced chronic low-grade inflammation originates from adipose tissue and is crucial for obesity-driven metabolic deterioration, including insulin resistance and type 2 diabetes. Chronic inflammation may be a consequence of a failure to actively resolve inflammation and could result from a lack of local specialized proresolving lipid mediators (SPMs), such as resolvins and protectins, which derive from the n-3 polyunsaturated fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). We assessed obesity-induced changes of n-3–derived SPMs in adipose tissue and the effects of dietary EPA/DHA thereon. Moreover, we treated obese mice with SPM precursors and investigated the effects on inflammation and metabolic dysregulation. Obesity significantly decreased DHA-derived 17-hydroxydocosahexaenoic acid (17-HDHA, resolvin D1 precursor) and protectin D1 (PD1) levels in murine adipose tissue. Dietary EPA/DHA treatment restored endogenous biosynthesis of n-3–derived lipid mediators in obesity while attenuating adipose tissue inflammation and improving insulin sensitivity. Notably, 17-HDHA treatment reduced adipose tissue expression of inflammatory cytokines, increased adiponectin expression, and improved glucose tolerance parallel to insulin sensitivity in obese mice. These findings indicate that impaired biosynthesis of certain SPM and SPM precursors, including 17-HDHA and PD1, contributes to adipose tissue inflammation in obesity and suggest 17-HDHA as a novel treatment option for obesity-associated complications.

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Expression of IL-33 and its receptor ST2 in human adipose tissue is predominantly detectable in endothelial cells and increased by severe obesity indicating an autocrine action. Thus, the adipose tissue microvasculature could participate in obesity-associated inflammation and related complications via IL-33/ST2.

which in turn accelerates β-cell death. Both innate and adaptive immune system components, specifically macrophages and self-reactive T cells, contribute to an increased secretion of inflammatory cytokines involved in inflammatory and autoimmune processes. However, the extent to which inflammation overlaps with autoimmunity is not known. Our review focuses on autoimmune involvement in T2DM, with an emphasis on LADA and the humoral immune response, on the involvement of chronic inflammation in autoimmunity, and specifically the role of B and T cells as links between inflammatory and autoimmune reactions. We will further stress the consequences of autoimmune activation for T2DM patients and present novel therapeutic approaches for T2DM management that rely on immune modulation.

Obesity and type 2 diabetes mellitus have reached an epidemic level, thus novel treatment concepts need to be identified. Myostatin, a myokine known for restraining skeletal muscle growth, has been associated with the development of insulin resistance and type 2 diabetes mellitus. Yet, little is known about the regulation of myostatin in human obesity and insulin resistance. We aimed to investigate the regulation of myostatin in obesity and uncover potential associations between myostatin, metabolic markers and insulin resistance/sensitivity indices. Circulating active myostatin concentration was measured in the serum of twenty-eight severely obese non-diabetic patients compared to a sex and age matched lean and overweight control group (n=22). Insulin resistance/sensitivity was assessed in the obese group. Skeletal muscle and adipose tissue specimens from the obese group were collected during elective bariatric surgery. Adipose tissue samples from lean and overweight subjects were collected during elective abdominal surgery. Myostatin concentration was increased in obese compared to lean individuals, while myostatin adipose tissue expression did not differ. Muscle myostatin gene expression strongly correlated with expression of metabolic genes such as ,, . Circulating myostatin concentration correlated positively with insulin resistance indices and negatively with insulin sensitivity indices. The best correlation was obtained for the oral glucose insulin sensitivity index. Our results point to an interesting correlation between myostatin and insulin resistance/sensitivity in humans, and emphasize its need for further evaluation as a pharmacological target in the prevention and treatment of obesity-associated metabolic complications.

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Postprandial hypoglycemia is a complication following gastric bypass surgery, which frequently remains undetected. Severe hypoglycemic episodes, however, put patients at risk, e.g., for syncope. A major cause of hypoglycemia following gastric bypass is hyperinsulinemic nesidioblastosis. Since pancreatic islets in nesidioblastosis overexpress insulin-like growth factor 1 (IGF-1) receptor α and administration of recombinant IGF-1 provokes hypoglycemia, our main objective was to investigate the occurrence of post-load hypoglycemia one year after bariatric surgery and its relation to pre- and post-operative IGF-1 serum concentrations. We evaluated metabolic parameters including 2 h 75 g oral glucose tolerance test (OGTT) and measured IGF-1 serum concentration in thirty-six non-diabetic patients (29 f/7 m), aged 41.3±2.0 y with a median (IQR) BMI of 30.9 kg/m2 (27.5–34.3 kg/m2), who underwent elective bariatric surgery (predominantly gastric bypass, 83%) at our hospital. Post-load hypoglycemia as defined by a 2 h glucose concentration <60 mg/dl was detected in 50% of patients. Serum insulin and C-peptide concentration during the OGTT and HOMA-IR (homeostatic model assessment–insulin resistance) were similar in hypoglycemic and euglycemic patients. Strikingly, pre- and post-operative serum IGF-1 concentrations were significantly higher in hypoglycemic patients (p = 0.012 and p = 0.007 respectively). IGF-1 serum concentration before surgery negatively correlated with 2 h glucose concentration during the OGTT (rho = −0.58, p = 0.0003). Finally, IGF-1 serum concentrations before and after surgery significantly predicted post-load hypoglycemia with odds ratios of 1.28 (95%CI:1.03–1.55, p = 0.029) and 1.18 (95%CI:1.03–1.33, p = 0.015), respectively, for each 10 ng/ml increment. IGF-1 serum concentration could be a valuable biomarker to identify patients at risk for hypoglycemia following bariatric surgery independently of a diagnostic OGTT. Thus, IGF-1 testing could help to prevent a significant complication of gastric bypass surgery.