Empagliflozin improves left ventricular ejection fraction and end systolic volume in patients with type 2 diabetes mellitus and coronary artery disease: a post-hoc analysis of EMPA-CARD trial.

Background: Sodium glucose co-transporter2 (SGLT2) inhibitors have exhibited cardioprotective properties in diabetes patients. The aim of this study was to investigate the effect of Empagliflozin on changes in echocardiographic parameters.

Methods: This was a post hoc analysis of the EMPA-CARD trial which was a multicenter, triple-blind randomized controlled trial.

Ultra-stable insulin-glucagon fusion protein exploits an endogenous hepatic switch to mitigate hypoglycemic risk.

Unlabelled: The risk of hypoglycemia and its serious medical sequelae restrict insulin replacement therapy for diabetes mellitus. Such adverse clinical impact has motivated development of diverse glucose-responsive technologies, including algorithm-controlled insulin pumps linked to continuous glucose monitors ("closed-loop systems") and glucose-sensing ("smart") insulins. These technologies seek to optimize glycemic control while minimizing hypoglycemic risk.

The effect of sodium-glucose co-transporter-2 (SGLT2) inhibitors on blood interleukin-6 concentration: a systematic review and meta-analysis of randomized controlled trials.

Background: The low-grade chronic inflammation in diabetes plays an important role in development of cardiovascular and renal complications. Sodium-glucose co-transporter-2 (SGLT2) inhibitors are recognized as protective agents for cardio-renal complications. Interleukin-6 (IL-6) is positively associated with the pathophysiology of metabolic-related pathologies.

Effect of Empagliflozin and Pioglitazone on left ventricular function in patients with type two diabetes and nonalcoholic fatty liver disease without established cardiovascular disease: a randomized single-blind clinical trial.

Background: Nonalcoholic fatty liver disease (NAFLD) is a complex metabolic disorder that increases the risk for cardiovascular disease in patients with type 2 diabetes mellitus (T2DM). Global longitudinal strain (GLS) is an indicator of left ventricular (LV) mechanics and can detect subclinical myocardial dysfunction. We compared the effects of pioglitazone and empagliflozin on GLS in patients with T2DM and NAFLD without established atherosclerotic cardiovascular disease.

Beta-cell function in type 2 diabetes (T2DM): Can it be preserved or enhanced?

Type 2 diabetes (T2DM) is a complex metabolic disorder manifested by hyperglycemia, insulin resistance, and deteriorating beta-cell function. A way to prevent progression of the disease might be to enhance beta-cell function and insulin secretion. However, most previous studies examined beta-cell function while patients were using glycemia-lowering agents without an adequate period off medications (washout).

Comparative Effects of Glucose-Lowering Medications on Kidney Outcomes in Type 2 Diabetes: The GRADE Randomized Clinical Trial.

Importance: Type 2 diabetes (T2D) is the leading cause of kidney disease in the US. It is not known whether glucose-lowering medications differentially affect kidney function.

Objective: To evaluate kidney outcomes in the Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness (GRADE) trial comparing 4 classes of glucose-lowering medications added to metformin for glycemic management in individuals with T2D.

The effect of EMPAgliflozin on markers of inflammation in patients with concomitant type 2 diabetes mellitus and Coronary ARtery Disease: the EMPA-CARD randomized controlled trial.

Systemic inflammation and oxidative burden in patients with type 2 diabetes mellitus (T2DM) causes deleterious cardiovascular outcomes. We sought to investigate the clinical antioxidative and anti-inflammatory effects of empagliflozin. Platelet function, oxidant and antioxidant biomarkers and pro-inflammatory agents at baseline and at 26 weeks were measured.

Peptide Model of the Mutant Proinsulin Syndrome. I. Design and Clinical Correlation.

The mutant proinsulin syndrome is a monogenic cause of diabetes mellitus due to toxic misfolding of insulin's biosynthetic precursor. Also designated (MIDY), this syndrome defines molecular determinants of foldability in the endoplasmic reticulum (ER) of β-cells. Here, we describe a peptide model of a key proinsulin folding intermediate and variants containing representative clinical mutations; the latter perturb invariant core sites in native proinsulin (Leu→Pro, Leu→Pro, and Phe→Ser).

The cross-sectional association of cognition with diabetic peripheral and autonomic neuropathy-The GRADE study.

Background: Studies examining whether measures of cognition are related to the presence of diabetic peripheral neuropathy (DPN) and/or cardiovascular autonomic neuropathy (CAN) are lacking, as are data regarding factors potentially explaining such associations.

Methods: Participants were from the Glycemia Reduction Approaches in Diabetes Study (GRADE) that examined 5047 middle-aged people with type 2 diabetes of <10 years of known duration. Verbal learning and immediate and delayed recall (memory) were assessed with the Spanish English Verbal Learning Test; frontal executive function and processing speed with the Digit Symbol Substitution Test; and ability to concentrate and organize data with word and animal fluency tests.

Shape of the OGTT glucose response curve: relationship with β-cell function and differences by sex, race, and BMI in adults with early type 2 diabetes treated with metformin.

Introduction: The shape of the glucose curve during an oral glucose tolerance test (OGTT) reflects β-cell function in populations without diabetes but has not been as well studied in those with diabetes. A monophasic shape has been associated with higher risk of diabetes, while a biphasic pattern has been associated with lower risk. We sought to determine if phenotypic or metabolic characteristics were associated with glucose response curve shape in adults with type 2 diabetes treated with metformin alone.

Study rationale and design of a study of EMPAgliflozin's effects in patients with type 2 diabetes mellitus and Coronary ARtery disease: the EMPA-CARD randomized controlled trial.

Background: Recent trials have revealed that sodium-glucose co-transporter 2 inhibitors (SGLT2-i) are effective against hyperglycemia and also reduce micro- and macro-vascular complications in patients with type 2 diabetes mellitus (T2DM). Most of the beneficial cardiovascular effects have been investigated in patients with heart failure and coronary artery disease (CAD). Yet, few human studies have been conducted to investigate the molecular mechanisms underlying these clinically beneficial effects in patients with CAD.

Association of glycemia with insulin sensitivity and β-cell function in adults with early type 2 diabetes on metformin alone.

Aims: Evaluate the relationship between measures of glycemia with β-cell function and insulin sensitivity in adults with early type 2 diabetes mellitus (T2DM).

Methods: This cross-sectional analysis evaluated baseline data from 3108 adults with T2DM <10 years treated with metformin alone enrolled in the Glycemia Reduction Approaches in Diabetes. A Comparative Effectiveness (GRADE) Study.

Empagliflozin Improves Liver Steatosis and Fibrosis in Patients with Non-Alcoholic Fatty Liver Disease and Type 2 Diabetes: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial.

Introduction: To evaluate the efficacy of empagliflozin compared to pioglitazone in patients with non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes (T2DM).

Methods: In this prospective randomized, double-blind, placebo-controlled trial, we assigned 106 patients with NAFLD and T2DM to receive empagliflozin 10 mg (n = 35), pioglitazone 30 mg (n = 34), or placebo (n = 37) for 24 weeks. Liver fat content and liver stiffness were measured using fibroscans.

Association of Baseline Characteristics With Insulin Sensitivity and β-Cell Function in the Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness (GRADE) Study Cohort.

Objective: We investigated sex and racial differences in insulin sensitivity, β-cell function, and glycated hemoglobin (HbA) and the associations with selected phenotypic characteristics.

Research Design And Methods: This is a cross-sectional analysis of baseline data from 3,108 GRADE (Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study) participants. All had type 2 diabetes diagnosed <10 years earlier and were on metformin monotherapy.

Evolution of insulin at the edge of foldability and its medical implications.

Proteins have evolved to be foldable, and yet determinants of foldability may be inapparent once the native state is reached. Insight has emerged from studies of diseases of protein misfolding, exemplified by monogenic diabetes mellitus due to mutations in proinsulin leading to endoplasmic reticulum stress and β-cell death. Cellular foldability of human proinsulin requires an invariant Phe within a conserved crevice at the receptor-binding surface (position B24).

Effect of Empagliflozin on Liver Steatosis and Fibrosis in Patients With Non-Alcoholic Fatty Liver Disease Without Diabetes: A Randomized, Double-Blind, Placebo-Controlled Trial.

Introduction: Despite the high prevalence of non-alcoholic fatty liver disease (NAFLD) and its associated co-morbidities, no efficient treatment in a high percentage of individuals is available. Beneficial effects of sodium-glucose co-transporter 2 inhibitors on fatty liver have been investigated in people with type 2 diabetes (T2DM). The aim of this study was to explore the effect of empagliflozin on liver steatosis and fibrosis in patients with NAFLD without T2DM.

Factors leading to high morbidity and mortality of COVID-19 in patients with type 2 diabetes.

Coronavirus disease 2019 (COVID-19) is a recent pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel coronavirus. Diabetes (mostly type 2 diabetes mellitus, T2DM) and hyperglycemia are among the major comorbidities in patients with COVID-19 leading to poor outcomes. Reports show that patients with diabetes and COVID-19 are at an increased risk for developing severe complications including acute respiratory distress syndrome, multi-organ failure, and death.

Challenging Issues in the Management of Cardiovascular Risk Factors in Diabetes During the COVID-19 Pandemic: A Review of Current Literature.

The COVID-19 outbreak was declared a pandemic on March 2020. Many patients with SARS-CoV-2 infection have underlying chronic medical conditions such as diabetes, cardiovascular disease (CVD), and hypertension. Patient-related outcomes are worse if there are associated comorbidities.

Intermittent fasting and 'metabolic switch': Effects on metabolic syndrome, prediabetes and type 2 diabetes.

Various intermittent fasting (IF) dietary plans have gained popularity among obese individuals in recent years as a means of achieving weight loss. However, studies evaluating the effect of IF regimens in people with metabolic syndrome, prediabetes and type 2 diabetes (T2D) are limited. The aim of the present review was to briefly elucidate the biochemical and physiological mechanisms underlying the positive effects of IF, especially the effect of the proposed 'metabolic switch' on metabolism.

Glucocorticoid-Induced Fatty Liver Disease.

Glucocorticoids (GCs) are commonly used at high doses and for prolonged periods (weeks to months) in the treatment of a variety of diseases. Among the many side effects are increased insulin resistance with disturbances in glucose/insulin homeostasis and increased deposition of lipids (mostly triglycerides) in the liver. Here, we review the metabolic pathways of lipid deposition and removal from the liver that become altered by excess glucocorticoids.

Connecting Rodent and Human Pharmacokinetic Models for the Design and Translation of Glucose-Responsive Insulin.

Despite considerable progress, development of glucose-responsive insulins (GRIs) still largely depends on empirical knowledge and tedious experimentation-especially on rodents. To assist the rational design and clinical translation of the therapeutic, we present a Pharmacokinetic Algorithm Mapping GRI Efficacies in Rodents and Humans (PAMERAH) built upon our previous human model. PAMERAH constitutes a framework for predicting the therapeutic efficacy of a GRI candidate from its user-specified mechanism of action, kinetics, and dosage, which we show is accurate when checked against data from experiments and literature.

Impaired fasting glucose and major adverse cardiovascular events by hypertension and dyslipidemia status: the Golestan cohort study.

Background: Whether pre-diabetes in the absence of hypertension (HTN) or dyslipidemia (DLP) is a risk factor for occurrence of major adverse cardiovascular events (MACE) is not fully established. We investigated the effect of impaired fasting glucose (IFG) alone and in combination with HTN, DLP or both on subsequent occurrence of MACE as well as individual MACE components.

Methods: This longitudinal population-based study included 11,374 inhabitants of Northeastern Iran.