Glycemic Benefit of Insulin Degludec/Insulin Aspart Compared to Basal Insulin in Type 2 Diabetes Mellitus Associated with Impaired Glucagon-Like Peptide-1 Response: A Randomized Crossover Trial.

Background: We aimed to confirm that once-daily insulin degludec/insulin aspart (IDegAsp) is superior to basal insulin therapy in participants with type 2 diabetes mellitus (T2DM) exhibiting signs of overbasalization. Additionally, we analyzed incretin profiles in relation to the benefits of IDegAsp, providing insights into the underlying mechanisms.

Methods: A prospective study was conducted in participants receiving basal insulin therapy, with a fasting plasma glucose (FPG) level lower than predicted from their glycosylated hemoglobin (HbA1c).

Multi-ancestry polygenic risk scores for the prediction of type 2 diabetes and complications in diverse ancestries.

Background: Polygenic risk scores (PRSs) improve type 2 diabetes (T2D) prediction beyond clinical risk factors but perform poorly in non-European populations, where T2D burden is often higher, undermining their global clinical utility.

Methods: We conducted the largest global effort to date to harmonize T2D genome-wide association study (GWAS) meta-analyses across five ancestries-European (EUR), African/African American (AFR), Admixed American (AMR), South Asian (SAS), and East Asian (EAS)-including 360,000 T2D cases and 1·8 million controls (41% non-EUR). We constructed ancestry-specific and multi-ancestry PRSs in training datasets including 11,000 T2D cases and 32,000 controls, and validated their performance in independent datasets including 39,000 T2D cases and 126,000 controls of diverse ancestries.

SENP2 regulates UCP1-dependent thermogenesis in brown adipocytes via deSUMOylation of ERRα.

Brown adipose tissue (BAT) is responsible for energy homeostasis and adaptive thermogenesis. SUMO-specific protease 2 (SENP2) plays an essential role in adipogenesis; however, the role of SENP2 in BAT metabolism has not been explored. Here we investigated the role of SENP2 in mature brown adipocytes with a brown adipocyte-specific SENP2 knockout (Senp2-BKO) mouse model generated using the uncoupling protein 1 (Ucp1)-Cre.

The brown fat-specific overexpression of RBP4 improves thermoregulation and systemic metabolism by activating the canonical adrenergic signaling pathway.

Retinol-binding protein 4 (RBP4), the sole specific carrier for retinol (vitamin A) in circulation, is highly expressed in liver and adipose tissues. Previous studies have demonstrated that RBP4 plays a role in cold-mediated adipose tissue browning and thermogenesis. However, the role of RBP4 in brown adipose tissue and its metabolic significance remain unclear.

Real-time continuous glucose monitoring improves postoperative glucose control in people with type 2 diabetes mellitus undergoing coronary artery bypass grafting: A randomized clinical trial.

Background: Effective glycaemic control following cardiac surgery improves clinical outcomes, and continuous glucose monitoring (CGM) might be a valuable tool in achieving this objective. We investigated the effect of real-time CGM and telemonitoring on postoperative glycaemic control in people with type 2 diabetes (T2D) after coronary artery bypass grafting (CABG).

Methods: In this randomized clinical trial (RCT), adults with T2D undergoing CABG were assigned to either a test group utilizing real-time CGM (Dexcom G6) and telemetry for glycaemic control, or a control group with blinded CGM measures, relying on point-of-care measures.

In Vivo Differentiation of Endogenous Bone Marrow-Derived Cells into Insulin-Producing Cells Using Four Soluble Factors.

Four soluble factors-putrescine, glucosamine, nicotinamide, and signal transducer and activator of transcription 3 (STAT3) inhibitor BP-1-102-were shown to differentiate bone marrow mononucleated cells (BMNCs) into functional insulin-producing cells (IPCs) in vitro. Transplantation of these IPCs improved hyperglycemia in diabetic mice. However, the role of endogenous BMNC regeneration in this effect was unclear.

Long-term efficacy and safety of enavogliflozin in Korean people with type 2 diabetes: A 52-week extension of a Phase 3 randomized controlled trial.

Aims: To evaluate the long-term safety and efficacy of enavogliflozin monotherapy (0.3 mg/day) in individuals with type 2 diabetes mellitus (T2DM).

Materials And Methods: Following a 24-week randomized, double-blind treatment period with enavogliflozin 0.

Dual add-on therapy of gemigliptin and dapagliflozin in patients with type 2 diabetes inadequately controlled with metformin alone: The SOLUTION 2 study.

Aim: To evaluate the efficacy and safety of gemigliptin and dapagliflozin dual add-on therapy (GEMI + DAPA) to metformin in type 2 diabetes (T2D) patients who had inadequate glycaemic control on metformin alone, compared with a single add-on of either gemigliptin (GEMI) or dapagliflozin (DAPA) to metformin.

Materials And Methods: In this randomized, double-blind, double-dummy, active-controlled, parallel-group, phase 3 study, 469 T2D patients treated with a stable dose of metformin for 8 weeks or longer were randomized to receive GEMI + DAPA (n = 157) and either GEMI (n = 156) or DAPA (n = 156). The primary endpoint was change in HbA1c levels from baseline at week 24.

Higher Genetic Risk for Type 2 Diabetes Is Associated With a Faster Decline of β-Cell Function in an East Asian Population.

Objective: While most genetic variants of type 2 diabetes (T2D) are suggested to be associated with β-cell dysfunction cross sectionally, their association with the longitudinal change of β-cell function remains largely unknown.

Research Design And Methods: We analyzed data from 6,311 participants without T2D at baseline (mean [SD] age 51.6 [8.

Clinical Characteristics of Diabetes in People with Mitochondrial DNA 3243A>G Mutation in Korea.

Maternally inherited diabetes and deafness (MIDD) is a rare mitochondrial disorder primarily resulting from m.3243A>G mutation. The clinical characteristics of MIDD exhibit significant heterogeneity.

Partial Deletion of Perk Improved High-Fat Diet-Induced Glucose Intolerance in Mice.

Although pancreatic endoplasmic reticulum kinase (PERK) is indispensable to beta cells, low-dose PERK inhibitor improved glucose- stimulated insulin secretion (GSIS) and hyperglycemia in diabetic mice. Current study examined if partial deletion of Perk (Perk+/-) recapitulated the effects of PERK inhibitor, on the contrary to the complete deletion. Perk+/- mice and wild-type controls were fed with a high-fat diet (HFD) for 23 weeks.

Periostin deficiency attenuates kidney fibrosis in diabetic nephropathy by improving pancreatic β-cell dysfunction and reducing kidney EMT.

Diabetic nephropathy (DN) is associated with kidney fibrosis. A previous study revealed that periostin (POSTN) contributes to kidney fibrosis. This study examined the role of POSTN in DN.

SUMO-specific protease 2 regulates lipid droplet size through ERRα-mediated CIDEA expression in adipocytes.

Lipid droplets are not only lipid storage sites but also are closely related to lipid metabolism. Lipid droplet growth increases lipid storage capacity and suppresses lipolysis via lipase associated with the lipid droplet surface. The cell death-inducing DFF45-like effector (CIDE) family of proteins mediates lipid droplet fusion, which mainly contributes to lipid droplet growth.

Glucolipotoxicity Suppressed Autophagy and Insulin Contents in Human Islets, and Attenuation of PERK Activity Enhanced Them in an ATG7-Dependent Manner.

Backgruound: Administration of pancreatic endoplasmic reticulum kinase inhibitor (PERKi) improved insulin secretion and hyperglycemia in obese diabetic mice. In this study, autophagic balance was studied whether to mediate it.

Methods: Human islets were isolated from living patients without diabetes.

Triglyceride-Glucose Index Predicts Future Atherosclerotic Cardiovascular Diseases: A 16-Year Follow-up in a Prospective, Community-Dwelling Cohort Study.

Backgruound: While the triglyceride-glucose (TyG) index is a measure of insulin resistance, its association with cardiovascular disease (CVD) has not been well elucidated. We evaluated the TyG index for prediction of CVDs in a prospective large communitybased cohort.

Methods: Individuals 40 to 70 years old were prospectively followed for a median 15.

Direct Differentiation of Bone Marrow Mononucleated Cells Into Insulin-Producing Cells Using 4 Specific Soluble Factors.

Bone marrow-derived stem cells are self-renewing and multipotent adult stem cells that differentiate into several types of cells. Here, we investigated a unique combination of 4 differentiation-inducing factors (DIFs), including putrescine (Put), glucosamine (GlcN), nicotinamide, and BP-1-102, to develop a differentiation method for inducing mature insulin-producing cells (IPCs) and apply this method to bone marrow mononucleated cells (BMNCs) isolated from mice. BMNCs, primed with the 4 soluble DIFs, were differentiated into functional IPCs.

Multi-ancestry genome-wide study in >2.5 million individuals reveals heterogeneity in mechanistic pathways of type 2 diabetes and complications.

Type 2 diabetes (T2D) is a heterogeneous disease that develops through diverse pathophysiological processes. To characterise the genetic contribution to these processes across ancestry groups, we aggregate genome-wide association study (GWAS) data from 2,535,601 individuals (39.7% non-European ancestry), including 428,452 T2D cases.

Efficacy and safety of monotherapy with enavogliflozin in Korean patients with type 2 diabetes mellitus: Results of a 12-week, multicentre, randomized, double-blind, placebo-controlled, phase 2 trial.

Aims: The study aimed to evaluate and compare the efficacy and safety of enavogliflozin, a newly developed sodium-glucose cotransporter 2 inhibitor, with placebo in Korean patients with type 2 diabetes mellitus.

Materials And Methods: Patients with glycated haemoglobin (HbA1c) of 7.0-10.

Earlier Age at Type 2 Diabetes Diagnosis Is Associated With Increased Genetic Risk of Cardiovascular Disease.

Objective: We investigated genetic risk of cardiovascular disease (CVD) by age at type 2 diabetes (T2D) diagnosis.

Research Design And Methods: We compared incident CVD events by age at T2D diagnosis using UK Biobank (N = 12,321) and the Seoul National University Hospital (SNUH) cohort (N = 1,165). Genetic risk was quantified using polygenic risk score (PRS).

Efficacy and safety of enavogliflozin, a novel SGLT2 inhibitor, in Korean people with type 2 diabetes: A 24-week, multicentre, randomized, double-blind, placebo-controlled, phase III trial.

Aims: To evaluate the efficacy and safety of a novel sodium-glucose cotransporter 2 inhibitor, enavogliflozin 0.3 mg monotherapy, in Korean people with type 2 diabetes mellitus (T2DM) inadequately controlled with diet and exercise.

Materials And Methods: This study was a randomized, double-blind, placebo-controlled trial conducted in 23 hospitals.

Role of SUMO-Specific Protease 2 in Leptin-Induced Fatty Acid Metabolism in White Adipocytes.

Background: Leptin is a 16-kDa fat-derived hormone with a primary role in controlling adipose tissue levels. Leptin increases fatty acid oxidation (FAO) acutely through adenosine monophosphate-activated protein kinase (AMPK) and on delay through the SUMO-specific protease 2 (SENP2)-peroxisome proliferator-activated receptor δ/γ (PPARδ/γ) pathway in skeletal muscle. Leptin also directly increases FAO and decreases lipogenesis in adipocytes; however, the mechanism behind these effects remains unknown.