Effect of dapagliflozin on renal haemodynamics in hyperfiltering T2D patients.

Aims: To investigate the effect of sodium-glucose co-transporter 2 inhibitor [SGLT-2i] therapy on renal haemodynamics in T2D patients with glomerular hyperfiltration.

Materials And Methods: Sixty T2D patients with elevated [HYPER] and normal [NORMO] GFR were randomized to dapagliflozin 10 mg/day [DAPA/HYPER, n = 15; DAPA/NORMO, n = 15] or to metformin/glipizide [CONTROL/HYPER, n = 15; CONTROL/NORMO, n = 15] to reach similar glycaemic control after 4 months. GFR was measured with Iohexol and hyperfiltration was empirically defined as >125 mL/min/1.

Effect of Hyperketonemia on Myocardial Function in Patients With Heart Failure and Type 2 Diabetes.

We examined the effect of increased levels of plasma ketones on left ventricular (LV) function, myocardial glucose uptake (MGU), and myocardial blood flow (MBF) in patients with type 2 diabetes (T2DM) with heart failure. Three groups of patients with T2DM (n = 12 per group) with an LV ejection fraction (EF) ≤50% received incremental infusions of β-hydroxybutyrate (β-OH-B) for 3-6 h to increase the plasma β-OH-B concentration throughout the physiologic (groups I and II) and pharmacologic (group III) range. Cardiac MRI was performed at baseline and after each β-OH-B infusion to provide measures of cardiac function.

Effect of weight-maintaining ketogenic diet on glycemic control and insulin sensitivity in obese T2D subjects.

Introduction: Low carbohydrate ketogenic diets have received renewed interest for the treatment of obesity and type 2 diabetes. These diets promote weight loss, improve glycemic control, and reduce insulin resistance. However, whether the improvements in glycemic control and insulin sensitivity are secondary to the weight loss or result from a direct effect of hyperketonemia is controversial.

Advances and counterpoints in type 2 diabetes. What is ready for translation into real-world practice, ahead of the guidelines.

This review seeks to address major gaps and delays between our rapidly evolving body of knowledge on type 2 diabetes and its translation into real-world practice. Through updated and improved best practices informed by recent evidence and described herein, we stand to better attain A1c targets, help preserve beta cell integrity and moderate glycemic variability, minimize treatment-emergent hypoglycemia, circumvent prescribing to "treatment failure," and prevent long-term complications. The first topic addressed in this review concerns updates in the 2023 and 2024 diabetes treatment guidelines for which further elaboration can help facilitate integration into routine care.

Pre-Prediabetes: Insulin Resistance is Associated with Cardiometabolic Risk in Non-obese Patients (STOP DIABETES).

Background/aim: To examine if insulin resistance is associated with markers of glycemic, cardiometabolic and atherosclerotic risk in non-obese, non-prediabetic individuals compared to insulin sensitive subjects matched for BMI, gender, and age.

Methods: Of 1860 patients from STOP DIABETES study, 624 had normal fasting plasma glucose, body mass index < 30, and HbA1c < 5.7%.

Managing insulin resistance: the forgotten pathophysiological component of type 2 diabetes.

Glucagon-like peptide-1 (GLP-1) receptor agonists have gained widespread use in the treatment of individuals with type 2 diabetes because of their potent weight loss promoting effect, ability to augment β-cell function, and cardiovascular protective effects. However, despite causing impressive weight loss, GLP-1 receptor agonists do not normalise insulin sensitivity in people with type 2 diabetes and obesity, and the long-term effects of this class of antidiabetic medication on muscle mass, frailty, and bone density have been poorly studied. Although GLP-1 receptor agonists improve insulin sensitivity secondary to weight loss, the only true direct insulin-sensitising drugs are thiazolidinediones.

Study protocol for a prospective, multicentre study of hypercortisolism in patients with difficult-to-control type 2 diabetes (CATALYST): prevalence and treatment with mifepristone.

Introduction: Even with recent treatment advances, type 2 diabetes (T2D) remains poorly controlled for many patients, despite the best efforts to adhere to therapies and lifestyle modifications. Although estimates vary, studies indicate that in >10% of individuals with difficult-to-control T2D, hypercortisolism may be an underlying contributing cause. To better understand the prevalence of hypercortisolism and the impact of its treatment on T2D and associated comorbidities, we describe the two-part Hyper ortisolism in P ients with Difficult to Control Type 2 Di betes Despite Receiving Standard-of-Care Therapies: Preva ence and Treatment with Korl m (Mifepri one) (CATALYST) trial.

Unexplained Residual Risk In Type 2 Diabetes: How Big Is The Problem?

Purpose Of Review: What is new? Cardiovascular disease (CVD) is the leading cause of mortality in type 2 diabetes (T2D) individuals. Of the major risk factors for CVD, less than 10% of T2D people meet the American Diabetes Association/American Heart Association recommended goals of therapy. The present review examines how much of the absolute cardiovascular (CV) risk in type 2 diabetes patients can be explained by major CV intervention trials.

Effect of Dapagliflozin on Renal and Hepatic Glucose Kinetics in T2D and NGT Subjects.

Acute and chronic sodium-glucose cotransporter 2 (SGLT-2) inhibition increases endogenous glucose production (EGP). However, the organ-liver versus kidney-responsible for the increase in EGP has not been identified. In this study, 20 subjects with type 2 diabetes (T2D) and 12 subjects with normal glucose tolerance (NGT) received [3-3H]glucose infusion (to measure total EGP) combined with arterial and renal vein catheterization and para-aminohippuric acid infusion for determination of renal blood flow.

Empagliflozin Reduces Liver Fat in Individuals With and Without Diabetes.

Objective: To examine the effect of empagliflozin on liver fat content in individuals with and without type 2 diabetes (T2D) and the relationship between the decrease in liver fat and other metabolic actions of empagliflozin.

Research Design And Methods: Thirty individuals with T2D and 27 without were randomly assigned to receive in double-blind fashion empagliflozin or matching placebo (2:1 ratio) for 12 weeks. Participants underwent 75-g oral glucose tolerance testing and measurement of liver fat content with MRS before therapy and at study end.

Longitudinal Effects of Glucose-Lowering Medications on β-Cell Responses and Insulin Sensitivity in Type 2 Diabetes: The GRADE Randomized Clinical Trial.

Objective: To compare the long-term effects of glucose-lowering medications (insulin glargine U-100, glimepiride, liraglutide, and sitagliptin) when added to metformin on insulin sensitivity and β-cell function.

Research Design And Methods: In the Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study (GRADE) cohort with type 2 diabetes (n = 4,801), HOMA2 was used to estimate insulin sensitivity (HOMA2-%S) and fasting β-cell function (HOMA2-%B) at baseline and 1, 3, and 5 years on treatment. Oral glucose tolerance test β-cell responses (C-peptide index [CPI] and total C-peptide response [incremental C-peptide/incremental glucose over 120 min]) were evaluated at the same time points.

Impact of Insulin Sensitivity and β-Cell Function Over Time on Glycemic Outcomes in the Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study (GRADE): Differential Treatment Effects of Dual Therapy.

Objective: To compare the effects of insulin sensitivity and β-cell function over time on HbA1c and durability of glycemic control in response to dual therapy.

Research Design And Methods: GRADE participants were randomized to glimepiride (n = 1,254), liraglutide (n = 1,262), or sitagliptin (n = 1,268) added to baseline metformin and followed for mean ± SD 5.0 ± 1.

Emergence of a New Glucoregulatory Mechanism for Glycemic Control With Dapagliflozin/Exenatide Therapy in Type 2 Diabetes.

Context: This study addresses the development of a new glucoregulatory mechanism in type 2 diabetes (T2D) patients treated with SGLT-2 inhibitors, which is independent of glucose, insulin and glucagon. The data suggest the presence of a potential trigger factor (s) arising in the kidney that stimulates endogenous glucose production (EGP) during sustained glycosuria.

Objective: To investigate effects of SGLT-2 inhibitor therapy together with GLP-1 receptor agonist on EGP and glucose kinetics in patients with T2D.

Plasma insulin is required for the increase in plasma angiopoietin-like protein 8 in response to nutrient ingestion.

Background: Plasma levels of angiopoietin-like protein 8 (ANGPTL8) are regulated by feeding and they increase following glucose ingestion. Because both plasma glucose and insulin increase following food ingestion, we aimed to determine whether the increase in plasma insulin and glucose or both are responsible for the increase in ANGPTL8 levels.

Methods: ANGPTL8 levels were measured in 30 subjects, 14 with impaired fasting glucose (IFG), and 16 with normal fasting glucose (NFG); the subjects received 75g glucose oral Glucose tolerance test (OGTT), multistep euglycaemic hyperinsulinemic clamp and hyperglycaemic clamp with pancreatic clamp.

Distinct Mechanisms Responsible for the Increase in Glucose Production and Ketone Formation Caused by Empagliflozin in T2DM Patients.

Objective: To examine the mechanisms responsible for the increase in glucose and ketone production caused by empagliflozin in patients with type 2 diabetes mellitus (T2DM).

Research Design And Methods: Twelve subjects with T2DM participated in two studies performed in random order. In study 1, endogenous glucose production (EGP) was measured with 8-h infusion of 6,6,D2-glucose.

Chronic physiologic hyperglycemia impairs insulin-mediated suppression of plasma glucagon concentration in healthy humans.

Background And Aims: Hyperglucagonemia is a characteristic feature of type 2 diabetes mellitus (T2DM). We examined the effect of chronic (48-72 h) physiologic increase (+50 mg/dl) in plasma glucose concentration on suppression of plasma glucagon concentration by insulin and by hyperglycemia in normal glucose tolerance (NGT) individuals.

Materials And Methods: Study One: 16 NGT subjects received OGTT and 3-step hyperinsulinemic (10, 20, 40 mU/m·min) euglycemic clamp before and after 48 hour glucose infusion to increase plasma glucose by ~50 mg/dl.

Early intervention and intensive management of patients with diabetes, cardiorenal, and metabolic diseases.

Increasing rates of obesity and diabetes have driven corresponding increases in related cardiorenal and metabolic diseases. In many patients, these conditions occur together, further increasing morbidity and mortality risks to the individual. Yet all too often, the risk factors for these disorders are not addressed promptly in clinical practice, leading to irreversible pathologic progression.

Pioglitazone reduces epicardial fat and improves diastolic function in patients with type 2 diabetes.

Aims: To examine the effect of pioglitazone on epicardial (EAT) and paracardial adipose tissue (PAT) and measures of diastolic function and insulin sensitivity in patients with type 2 diabetes mellitus (T2DM).

Methods: Twelve patients with T2DM without clinically manifest cardiovascular disease and 12 subjects with normal glucose tolerance (NGT) underwent cardiac magnetic resonance imaging to quantitate EAT and PAT and diastolic function before and after pioglitazone treatment for 24 weeks. Whole-body insulin sensitivity was measured with a euglycaemic insulin clamp and the Matsuda Index (oral glucose tolerance test).

Metabolic syndrome predictors of brain gray matter volume in an age-stratified community sample of 776 Mexican- American adults: Results from the genetics of brain structure image archive.

Introduction: This project aimed to investigate the association between biometric components of metabolic syndrome (MetS) with gray matter volume (GMV) obtained with magnetic resonance imaging (MRI) from a large cohort of community-based adults ( = 776) subdivided by age and sex and employing brain regions of interest defined previously as the "Neural Signature of MetS" (NS-MetS).

Methods: Lipid profiles, biometrics, and regional brain GMV were obtained from the Genetics of Brain Structure (GOBS) image archive. Participants underwent T1-weighted MR imaging.

Bromocriptine-QR Therapy Reduces Sympathetic Tone and Ameliorates a Pro-Oxidative/Pro-Inflammatory Phenotype in Peripheral Blood Mononuclear Cells and Plasma of Type 2 Diabetes Subjects.

Bromocriptine-QR is a sympatholytic dopamine D2 agonist for the treatment of type 2 diabetes that has demonstrated rapid (within 1 year) substantial reductions in adverse cardiovascular events in this population by as yet incompletely delineated mechanisms. However, a chronic state of elevated sympathetic nervous system activity and central hypodopaminergic function has been demonstrated to potentiate an immune system pro-oxidative/pro-inflammatory condition and this immune phenotype is known to contribute significantly to the advancement of cardiovascular disease (CVD). Therefore, the possibility exists that bromocriptine-QR therapy may reduce adverse cardiovascular events in type 2 diabetes subjects via attenuation of this underlying chronic pro-oxidative/pro-inflammatory state.