Novel Insight into the Mechanism of Metabolic Surgery Causing the Diversity in Glycemic Status in Type 2 Diabetes

Metabolic surgery results in diverse glycemic status in patients with type 2 diabetes (T2D), including hyperglycemia without remission, significant amelioration of hyperglycemia with partial remission, complete restoration of euglycemia, or with prolonged remission, hyperglycemia recurrence in relapses after remission, or post-bariatric hypoglycemia. Unfortunately, it is not known how metabolic surgery leads to this diverse consequence. Here, we discuss the diversity of glycemic status associated with metabolic surgery and the potential mechanisms of T2D remission. We also highlight the relationship between the change in low-grade inflammation and T2D remission after metabolic surgery. We hypothesize that the level of inflammatory and anti-inflammatory cytokines controls the efficacy of metabolic surgery in patients with T2D. This hypothesis may provide further insight into the mechanism of the beneficial effects of metabolic surgery patients with T2D.

Ceramides Are Early Responders In Metabolic Syndrome Development In Rhesus Monkeys

Metabolic syndrome increases risk of complicating co-morbidities. Current clinical indicators reflect established metabolic impairment, preventing earlier intervention strategies. Here we show that circulating sphingolipids are altered in the very early stages of insulin resistance development. The study involved 16 overweight but healthy, euglycemic monkeys, one-half of which spontaneously developed metabolic syndrome over the course of 2 years while the other half remained healthy. As previously reported, adiposity and glycemic status were equivalent across the cohort and did not explain divergent health outcomes. Using mass spectrometry, we detected and quantified circulating ceramides and other sphingolipids in healthy and impaired animals at both time points. Several ceramides were significantly different between healthy and impaired at time of diagnosis. Correlation analysis revealed differences in the interactions among ceramides in impaired animals at diagnosis and even pre-diagnosis, when animals were clinically indistinguishable from healthy controls. Importantly, correlations between ceramides and diacylglycerols and non-esterified fatty acids were distinct for healthy and impaired states, indicative of coordinated changes in lipid handling. Impaired animals displayed extensive differences in correlations among sphingolipids even in advance of loss of insulin sensitivity. These data suggest that circulating ceramides are clinically relevant in identifying disease risk and in devising preventative strategies.

Assessment of structural and functional myocardial characteristics in patients with chronic coronary artery disease and various glycemic status

Aim. To study the structural and functional myocardial characteristics in patients with exertional angina and type 2 diabetes in comparison with those without diabetes to identify combined hemodynamic changes.Material and methods. Patients were divided into two groups depen - ding on the glycemic status. The first group consisted of 49 patients (mean age, 57,9±1,04 years; male/female, 35/14) with coronary artery disease (CAD) and type 2 diabetes, while the second one (control) — 51 patients (60,2±0,9 years, 34/17) with CAD and without diabetes. Patients were surveyed using a standard questionnaire that included socio-demographic parameters, behavioral risk factors, clinical status, medications received, and comorbidities. Diagnostic investigations were carried out, including resting electrocardiography, transthoracic echocardiography and cycle ergometry.Results. Among patients with CAD and type 2 diabetes, hypertension occurred 20% more often compared with the control group — 98 vs 78% (p<0,004). According to the electrocardiography, the combination of diabetes and CAD was characterized by various arrhythmias, which were recorded 2,8 times more often than in the group without diabetes. According to echocardiography, signs of left ventricular hypertrophy, systolic and diastolic dysfunction prevailed in people with diabetes. Mean pulmonary artery pressure in patients with diabetes were higher than in patients without carbohydrate metabolism disorders (p<0,004). According to the stress test, exercise tolerance in experimental group patients was lower than in patients in the control group.Conclusion. The combination of chronic CAD and type 2 diabetes is cha - racterized by a more common combination with hypertension, impaired central and intracardiac hemodynamics, as well as left ventricular hypertrophy. In people with diabetes, impaired systolic and diastolic myocardial function is combined with reduced exercise tolerance.

Plasma Metabolomics and Lipidomics Differentiate Obese Individuals by Peripheral Neuropathy Status

Context Peripheral neuropathy (PN) is a frequent prediabetes and type 2 diabetes (T2D) complication. Multiple clinical studies reveal that obesity and dyslipidemia can also drive PN progression, independent of glycemia, suggesting a complex interplay of specific metabolite and/or lipid species may underlie PN. Objective This work aimed to identify the plasma metabolomics and lipidomics signature that underlies PN in an observational study of a sample of individuals with average class 3 obesity. Methods We performed plasma global metabolomics and targeted lipidomics on obese participants with (n = 44) and without PN (n = 44), matched for glycemic status, vs lean nonneuropathic controls (n = 43). We analyzed data by Wilcoxon, logistic regression, partial least squares–discriminant analysis, and group-lasso to identify differential metabolites and lipids by obesity and PN status. We also conducted subanalysis by prediabetes and T2D status. Results Lean vs obese comparisons, regardless of PN status, identified the most significant differences in gamma-glutamyl and branched-chain amino acid metabolism from metabolomics analysis and triacylglycerols from lipidomics. Stratification by PN status within obese individuals identified differences in polyamine, purine biosynthesis, and benzoate metabolism. Lipidomics found diacylglycerols as the most significant subpathway distinguishing obese individuals by PN status, with additional contributions from phosphatidylcholines, sphingomyelins, ceramides, and dihydroceramides. Stratifying the obese group by glycemic status did not affect discrimination by PN status. Conclusion Obesity may be as strong a PN driver as prediabetes or T2D in a sample of individuals with average class 3 obesity, at least by plasma metabolomics and lipidomics profile. Metabolic and complex lipid pathways can differentiate obese individuals with and without PN, independent of glycemic status.