Myocardial mechano-energetic efficiency is not impaired in patients with metabolically healthy overweight and obesity.

OBJECTIVE: Reduced myocardial mechano-energetic efficiency (MEE) was associated with BMI. Subgroups of individuals with increased BMI but favorable cardiovascular risk profile were identified as individuals with "metabolically healthy overweight" (MHOW) and "metabolically healthy obesity" (MHO), respectively. We aim to investigate whether those with MHOW/MHO, defined as those having none of the components of metabolic syndrome, exhibit impaired MEE compared with their unhealthy counterparts. METHODS: Myocardial MEE per gram of left ventricular mass (MEEi) was assessed by echocardiography in 2190 nondiabetic individuals participating in the CATAnzaro MEtabolic RIsk factors (CATAMERI) study who were divided, according to BMI and metabolic status, into groups of individuals with metabolically healthy normal weight (MHNW), metabolically unhealthy normal weight (MUNW), MHOW, metabolically unhealthy overweight (MUOW), MHO, and metabolically unhealthy obesity (MUO). RESULTS: After adjusting for age and sex, no differences in myocardial MEEi were observed among individuals with MHNW, MHOW, and MHO (p = 0.56). Myocardial MEEi was comparable among individuals with MUNW, MUOW, and MUO (p = 0.21). Individuals with MHNW, MHOW, and MHO displayed significantly higher myocardial MEEi compared with their unhealthy counterparts. CONCLUSIONS: Increased BMI is not an obligate determinant for reduced myocardial MEEi. Other known components of metabolic syndrome rather than increased BMI contributed to reduced myocardial MEEi.

Erythrocyte membrane fluidity: A novel biomarker of residual cardiovascular risk in type 2 diabetes.

AIMS: Improving the composition of circulating fatty acids (FA) leads to a reduction in cardiovascular diseases (CVD) in high-risk individuals. The membrane fluidity of red blood cells (RBC), which reflects circulating FA status, may be a valid biomarker of cardiovascular (CV) risk in type 2 diabetes (T2D). METHODS: Red blood cell membrane fluidity, quantified as general polarization (GP), was assessed in 234 subjects with T2D, 86 with prior major CVD. Based on GP distribution, a cut-off of .445 was used to divide the study cohort into two groups: the first with higher GP, called GEL, and the second, defined as lower GP (LGP). Lipidomic analysis was performed to evaluate FA composition of RBC membranes. RESULTS: Although with comparable CV risk factors, the LGP group had a greater percentage of patients with major CVD than the GEL group (40% vs 24%, respectively, p < .05). Moreover, in a logistic regression analysis, a lower GP value was independently associated with the presence of macrovascular complications. Lipidomic analysis showed a clear shift of LGP membranes towards a pro-inflammatory condition due to higher content of arachidonic acid and increased omega 6/omega 3 index. CONCLUSIONS: Increased membrane fluidity is associated with a higher CV risk in subjects with T2D. If confirmed in prospective studies, membrane fluidity could be a new biomarker for residual CV risk assessment in T2D.

Liver fibrosis is associated with an increased risk of non-fatal myocardial infarction.

INTRODUCTION: Liver fibrosis is a risk factor for liver-related adverse outcomes and cardiovascular disease (CVD). Recently, the non-invasive Hepamet fibrosis score (HFS) has been validated as a tool capable to identify with good diagnostic accuracy subjects with advanced liver fibrosis. It is unsettled whether HFS is capable to identify individuals at higher risk of CVD. To investigate whether individuals with liver fibrosis measured with HFS have higher risk of myocardial infarction (MI) in adults participating in the CATAnzaro MEtabolic RIsk factors (CATAMERI) study. METHODS: Participants (n = 2948) were divided into three groups according to HFS: low risk of fibrosis (<0.12); intermediate risk of fibrosis (≥0.12 to <0.47); high risk of fibrosis (≥0.47). The association between the liver fibrosis risk and MI was analysed by a logistic regression analysis. RESULTS: As compared with those having the lowest risk (5.3%), a higher proportion of subjects with moderate or high risk of liver fibrosis had MI (12.9% and 24.4%, respectively; p < 0.001). In a logistic regression analysis, individuals at increased risk of liver fibrosis exhibited a threefold increased risk of having MI as compared to those with low risk (OR 3.18; 95% CI 1.31-7.70) independently of confounders including smoking, cholesterol, triglycerides, anti-hypertensive, lipid-lowering and glucose-lowering therapies. CONCLUSIONS: In this cross-sectional study, individuals with higher values of HFS show a higher risk of MI, suggesting that HFS may be a useful tool to identify not only individuals with liver fibrosis but also those at the increased risk of CVD.

ß-Cell Fate in Human Insulin Resistance and Type 2 Diabetes: A Perspective on Islet Plasticity.

Although it is well established that type 2 diabetes (T2D) is generally due to the progressive loss of ß-cell insulin secretion against a background of insulin resistance, the actual correlation of reduced ß-cell mass to its defective function continues to be debated. There is evidence that a compensatory increase in ß-cell mass, and the consequent insulin secretion, can effectively cope with states of insulin resistance, until hyperglycemia supervenes. Recent data strongly indicate that the mechanisms by which islets are able to compensate in response to insulin resistance in peripheral tissues is secondary to hyperplasia, as well as the activation of multiple cellular machineries with diverse functions. Importantly, islet cells exhibit plasticity in altering their endocrine commitment; for example, by switching from secretion of glucagon to secretion of insulin and back (transdifferentiation) or from an active secretory state to a nonsecretory quiescent state (dedifferentiation) and back. Lineage tracing (a method used to track each cell though its differentiation process) has demonstrated these potentials in murine models. A limitation to drawing conclusions from human islet research is that most studies are derived from human autopsy and/or organ donor samples, which lack in vivo functional and metabolic profiling. In this review, we specifically focus on evidence of islet plasticity in humans-from the normal state, progressing to insulin resistance to overt T2D-to explain the seemingly contradictory results from different cross-sectional studies in the literature. We hope the discussion on this intriguing scenario will provide a forum for the scientific community to better understand the disease and in the long term pave the way for personalized therapies.

Sotagliflozin, the first dual SGLT inhibitor: current outlook and perspectives.

Sotagliflozin is a dual sodium-glucose co-transporter-2 and 1 (SGLT2/1) inhibitor for the treatment of both type 1 (T1D) and type 2 diabetes (T2D). Sotagliflozin inhibits renal sodium-glucose co-transporter 2 (determining significant excretion of glucose in the urine, in the same way as other, already available SGLT-2 selective inhibitors) and intestinal SGLT-1, delaying glucose absorption and therefore reducing post prandial glucose. Well-designed clinical trials, have shown that sotagliflozin (as monotherapy or add-on therapy to other anti-hyperglycemic agents) improves glycated hemoglobin in adults with T2D, with beneficial effects on bodyweight and blood pressure. Similar results have been obtained in adults with T1D treated with either continuous subcutaneous insulin infusion or multiple daily insulin injections, even after insulin optimization. A still ongoing phase 3 study is currently evaluating the effect of sotagliflozin on cardiovascular outcomes (ClinicalTrials.gov NCT03315143). In this review we illustrate the advantages and disadvantages of dual SGLT 2/1 inhibition, in order to better characterize and investigate its mechanisms of action and potentialities.

Metabolic consequences of the occlusion of the main pancreatic duct with acrylic glue after pancreaticoduodenectomy.

BACKGROUND: Pancreaticoduodenectomy represents the major treatment for pancreatic and periampullary neoplasms. Complications related to pancreaticojejunostomy are still the leading cause of morbidity and mortality. A solution proposed by some surgeons is the occlusion of main pancreatic duct by acrylic glue, avoiding pancreaticojejunostomy. Nevertheless, the consequences of this procedure on glucose metabolism are not well-defined. METHODS: We retrospectively analyzed a cohort of 50 patients who underwent pancreaticoduodenectomy and had metabolic assessments available. The metabolic evaluation included the following: body composition and clinical evaluation, an oral glucose tolerance test, and an hyperinsulinemic euglycemic clamp procedure. RESULTS: Twenty-three patients underwent pancreatic duct occlusion and were compared with 27 patients, well-matched controls, who underwent pancreaticojejunostomy. Pancreatic duct occlusion leads to a greater impairment in insulin secretion compared with classic pancreaticojeunostomy. CONCLUSION: Pancreatic duct occlusion is associated with a greater reduction in insulin secretion but does not lead to meaningful differences in the management of patients with diabetes.