Diabetes care最新文献

Objective: Automated insulin delivery (AID) requiring manual premeal boluses are the standard of care for people with type 1 diabetes (T1D). We evaluated the safety and feasibility of the Automated Insulin Delivery as an Adaptive NETwork (AIDANET) system used without meal announcements in both supervised and home settings across a diverse population of people with T1D.

Research design and methods: Adults (age >25 years), young adults (age 18-25 years), and adolescents (age 14-18 years) were enrolled at three sites in the U.S. to compare the AIDANET system used in fully closed-loop (FCL) with usual care (UC) in a randomized crossover study. Participants spent ∼5 days using FCL in a supervised environment followed by ∼7 days of use at home. The prespecified primary outcome was defined as the change in mean sensor glucose (MSG) between the 2nd week of UC and the week of the FCL at-home period.

Results: Overall, 34 participants (12 adults, 10 young adults, 12 adolescents; mean age 25.4 ± 12.6 years; 62% female; mean HbA1c 8.0 ± 1.1%; 94% hybrid closed loop users during UC) completed the study. MSG improved from 178 to 164 mg/dL (UC vs. FCL P = 0.0058). The percentages of time in range (70-180 mg/dL), time in tight range (70-140 mg/dL), and time above range (>180 mg/dL and >250 mg/dL) also significantly improved, primarily overnight. The percentage of time <70 and <54 mg/dL were significantly noninferior in FCL compared with UC.

Conclusions: FCL therapy with the AIDANET system can significantly improve average glycemic control while removing the need for mealtime bolusing for a broad population of people with T1D.

Objective: Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common chronic liver disease in children and is linked to type 2 diabetes. This study evaluates whether longitudinal changes in liver chemistries-γ-glutamyl transferase (GGT), aspartate aminotransferase (AST), and alanine aminotransferase (ALT)-can serve as biomarkers of increased type 2 diabetes risk in children with MASLD.

Research design and methods: This multicenter longitudinal cohort study followed 1,035 children with biopsy-confirmed MASLD, without type 2 diabetes at baseline, for a mean of 3.9 years. Liver chemistries were measured annually, and type 2 diabetes was diagnosed based on fasting glucose, HbA1c, and clinical diagnosis. Extended Cox models with inverse probability weighting were used to evaluate associations between liver enzyme trajectories and type 2 diabetes risk.

Results: The cumulative incidence of type 2 diabetes was 12.3%. Increases in GGT (hazard ratio [HR]: 1.55; 95% CI: 1.34-1.80), AST (HR: 1.31; 95% CI: 1.20-1.43), and ALT (HR: 1.13; 95% CI: 1.07-1.20) were associated with a higher risk of developing type 2 diabetes in the independent models. In the mutual model with all three liver chemistries, only GGT and AST remained significant.

Conclusions: A 30-unit increase in GGT over time was associated with a substantially higher risk of developing type 2 diabetes in children with MASLD. Together with AST, GGT may provide clinicians with concrete, routinely available parameters to monitor for early risk stratification. Further validation in independent cohorts is needed to confirm these findings and inform clinical application.

Objective: The Centers for Medicare & Medicaid Services (CMS) requires a low C-peptide level for insulin pump coverage unless the individual is β-cell autoantibody positive, which precludes coverage of automated insulin delivery (AID) systems for many people with type 2 diabetes.

Research design and methods: In the Randomized Trial Evaluating the Efficacy and Safety of Control-IQ+ Technology in Adults With Type 2 Diabetes Using Basal-Bolus Insulin Therapy study evaluating the t:slim X2 insulin pump with Control-IQ+ technology, adults with insulin-treated type 2 diabetes were categorized into high C-peptide (n = 195) and low C-peptide (n = 59) groups based on CMS criteria.

Results: In the AID group, mean HbA1c decreased from baseline by 0.8%, which was significantly greater than in the control group with both high (P < 0.001) and low (P = 0.02) C-peptide levels. Results were similar in participants ≥65 years old.

Conclusions: The benefit of AID is present with high and low C-peptide levels. Thus, requiring a low C-peptide level as a prerequisite for AID therapy is not warranted.

Background: Evidence that type 2 diabetes can be reversed has been limited by the understanding and implementation of these interventions.

Purpose: We assessed the effect of nonsurgical randomized controlled trials (RCTs) on type 2 diabetes remission and characterized core components.

Data sources: We reviewed articles from MEDLINE and Embase (inception to April 2025).

Study selection: RCTs of multimodal pharmacological or nonpharmacological type 2 diabetes remission interventions for adults with type 2 diabetes were included.

Data extraction: Study characteristics and outcomes for clinical/population health, patient-reported, and adverse event were extracted.

Data synthesis: We performed a random-effects multilevel meta-analysis of studies, grouped based on type of intervention and by length of follow-up. A total of 18 studies were included in this review from 11 different countries. There was a higher likelihood of achieving type 2 diabetes remission through multimodal interventions (risk ratio [RR] 1.75 [95% CI 1.49-2.04]) and for nonpharmacological interventions (RR 5.80 [95% CI 4.28-7.87]), compared with the control group. Other significant outcomes for intervention groups compared with control groups included change in A1C, weight loss, and quality of life and improvements in adverse events of hypoglycemia.

Limitations: There was heterogeneity in our small pool of included studies (diversity of nonpharmacological components), stringent intervention protocols, narrow participant selection criteria, and lack of consistent diabetes remission definitions.

Conclusions: With specific protocols, a variety of tailored approaches can induce type 2 diabetes remission for patients with newly diagnosed type 2 diabetes who are able to subscribe to strict protocols. Consideration of long-term sustainability and effectiveness is needed in future research, along with patient preferences.

Objective: In many individuals, type 2 diabetes (T2D) remains poorly controlled despite taking multiple glucose-lowering therapies. Several studies have demonstrated that endogenous hypercortisolism is prevalent among these individuals. We tested whether cortisol-directed therapy improves their glycemic control.

Research design and methods: In this prospective, multicenter, double-blind study, 136 individuals with T2D (hemoglobin A1c [HbA1c] 7.5%-11.5% [58-102 mmol/mol] on multiple medications) and hypercortisolism (by dexamethasone suppression test) were randomized 2:1 to the glucocorticoid receptor antagonist mifepristone (300-900 mg once daily; n = 91) or placebo (n = 45) for 24 weeks, with stratification by presence/absence of an adrenal imaging abnormality. The primary end point was the change in HbA1c. Secondary end points included changes in glucose-lowering medications, weight, and waist circumference and safety.

Results: Mean baseline HbA1c in the study cohort was 8.55% (69.9 mmol/mol). At 24 weeks, the least squares mean (LSM) difference from placebo in HbA1c was -1.32% (95% CI -1.81 to -0.83; P < 0.001). Participants receiving mifepristone experienced reductions in body weight and waist circumference (placebo-adjusted LSM differences of -5.12 kg [95% CI -8.20 to -2.03] and -5.1 cm [-8.23 to -1.99], respectively). Of participants on mifepristone, 46% discontinued therapy, compared with 18% on placebo. Adverse events with mifepristone (>10% of participants) included hypokalemia, fatigue, nausea, vomiting, headache, peripheral edema, diarrhea, and dizziness, consistent with mifepristone's known tolerability profile. Increases in blood pressure also occurred.

Conclusions: In individuals with inadequately controlled T2D and hypercortisolism, cortisol-directed medical therapy with mifepristone reduced HbA1c, with a manageable tolerability profile.

Objective: Despite the use of multiple glucose-lowering medications, glycemic targets are not met in a significant fraction of people with type 2 diabetes. In this prospective, observational study we assessed the prevalence of hypercortisolism, a potential contributing factor to inadequate glucose control.

Research design and methods: Individuals with type 2 diabetes and HbA1c 7.5%-11.5% (58-102 mmol/mol) on two or more glucose-lowering medications with or without micro-/macrovascular complications or taking multiple blood pressure-lowering medications were screened with a 1-mg dexamethasone suppression test. Common causes of false-positive DSTs were excluded. The primary end point was the prevalence of hypercortisolism, defined as post-DST cortisol >1.8 μg/dL (50 nmol/L). Characteristics associated with hypercortisolism were assessed with multiple logistic regression. The percentage and characteristics of participants with hypercortisolism and adrenal imaging abnormalities were also assessed.

Results: Post-DST cortisol was unsuppressed in 252 of 1,057 participants (prevalence 23.8%; 95% CI 21.3, 26.5). Hypercortisolism prevalence was 33.3% among participants with cardiac disorders and 36.6% among those taking three or more blood pressure-lowering medications. Adrenal imaging abnormalities were reported in 34.7% of participants with hypercortisolism. Use of sodium-glucose cotransporter 2 inhibitors (odds ratio 1.558), maximum-dose glucagon-like peptide 1 receptor agonists (1.544), tirzepatide (1.981), or a higher number of blood pressure-lowering medications (1.390); older age (1.316); BMI <30 kg/m2 (1.639); non-Latino/Hispanic ethnicity (3.718); and use of fibrates (2.676) or analgesics (1.457) were associated with higher prevalence (all P < 0.03).

Conclusions: Hypercortisolism was associated with hyperglycemia in approximately one-quarter of individuals with inadequately controlled type 2 diabetes despite multiple medications.

Objective: To assess the effect of automated insulin delivery (AID) on glycemic and insulin outcomes in adults with insulin-treated type 2 diabetes using a glucagon-like peptide-1 receptor agonist (GLP-1 RA).

Research design and methods: In a randomized trial comparing Control-IQ+ AID versus continuation of prestudy insulin delivery method plus continuous glucose monitoring (CGM group), 143 (45%) of the 319 participants were using a GLP-1 RA at baseline, which was continued during the trial.

Results: Among GLP-1 RA users, mean HbA1c decreased by 0.8% from a baseline of 8.0 ± 1.2% with AID, which represented a mean improvement of -0.5% (95% CI -0.8 to -0.3, P < 0.001) compared with the CGM group. Time-in-range 70-180 mg/dL and other CGM metrics reflective of hyperglycemia also showed comparable statistically significant improvements using AID when added to GLP-1 RA use. For GLP-1 RA users, there was no significant difference in weight after 13 weeks with AID compared with the CGM group (0.9 kg, 95% CI -0.2 to 2.1, P = 0.10), whereas, in GLP-1 RA nonusers, there was a mean weight gain of 1.9 kg with AID compared with CGM (95% CI 0.5 to 3.2, P = 0.007).

Conclusions: The benefits of AID appear to be substantial for a broad spectrum of insulin-treated patients with type 2 diabetes, including those already receiving contemporary and guideline-directed therapy, such as a GLP-1 RA medication. These additive benefits of AID in GLP-1 RA users included significant reductions in HbA1c levels with simultaneous reduction in insulin use, along with no statistical increase in weight despite very significant improvements in glycemic control.

Objective: Patients with type 2 diabetes (T2D) are at increased risk of acute pancreatitis (AP) and biliary events. Evidence remains mixed regarding the association between incretin-based therapies, such as glucagon-like peptide 1 receptor agonists (GLP-1RAs) and dipeptidyl peptidase 4 inhibitors (DPP-4is), and these outcomes. We examined the association between incretin medication use and risk of incident AP or biliary disease in patients with T2D.

Research design and methods: Using Medicare Fee-for-Service (FFS) and two U.S. commercial claims databases (2014-2021), we identified three pairwise cohorts of propensity score (PS)-based fine stratification-weighted patients aged ≥18 years (≥65 years in Medicare FFS) with T2D without prior AP or biliary disease who initiated treatment with GLP-1RAs versus sodium-glucose cotransporter 2 inhibitors (SGLT2is), DPP-4is versus SGLT2is, or GLP-1RAs versus DPP-4is. PS was estimated using 92 covariates. Weighted hazard ratios (HRs) with 95% CIs for hospitalization because of AP and biliary events were estimated using Cox models.

Results: Each cohort included >1.2 million patients. After weighting, GLP-1RA and DPP-4i initiators had similar risk of AP compared with SGLT2i initiators (HR 1.01; 95% CI 0.90-1.13 and HR 1.00; 95% CI 0.85-1.15, respectively). However, both GLP-1RA and DPP-4i initiators showed a modestly increased risk of biliary disease compared with SGLT2i initiators (HR 1.15; 95% CI 1.05-1.26 and HR 1.22; 95% CI 1.03-1.46, respectively), equivalent to fewer than one additional event per 1,000 person-years. There was no difference in risk of AP (HR 1.08; 95% CI 0.95-1.22) or biliary disease (HR 0.95; 95% CI 0.86-1.04) between GLP-1RAs and DPP-4is.

Conclusions: In patients with T2D, GLP-1RAs and DPP-4is were associated with a small increase in risk of biliary disease, but not of AP, compared with SGLT2is.

Objective: This secondary analysis of the Semaglutide Treatment Effect in People with obesity (STEP) TEENS (NCT04102189) study investigated the effect of semaglutide 2.4 mg versus placebo on insulin sensitivity and cardiometabolic risk factors.

Research design and methods: The STEP TEENS phase 3a randomized study in adolescents (aged 12 to <18 years) with obesity demonstrated that once-weekly subcutaneous semaglutide 2.4 mg provided a significantly greater percentage reduction in BMI than placebo at week 68 (estimated difference -16.7 percentage points; P = 0.0001). This analysis investigated changes in insulin sensitivity and cardiometabolic risk factors from baseline to week 68.

Results: Overall, 193 participants without type 2 diabetes were included in the analysis. Participants receiving semaglutide 2.4 mg (n = 129) compared with those receiving placebo (n = 64) had greater reductions from baseline in fasting serum insulin (-33.6% vs. -10.1%; P = 0.0012), homeostatic model assessment for insulin resistance (HOMA-IR) score (-35.0% vs. -5.3%; P = 0.0002), glycemic measures (glycated hemoglobin: P < 0.0001; fasting plasma glucose: P = 0.0181), alanine aminotransferase (ALT; -17.9% vs. -3.3%; P = 0.0232), waist-to-height ratio (P < 0.0001), triglycerides (P < 0.0001), LDL cholesterol (P = 0.0105), and total cholesterol (P < 0.0001). Moreover, greater improvements in insulin sensitivity, glycemic measures, and cardiometabolic risk factors were seen in semaglutide 2.4 mg recipients with BMI reductions of ≥20% versus <20%.

Conclusions: These novel data support semaglutide 2.4 mg as an efficacious obesity treatment in adolescents with obesity and advance its application by showing associated improvements in insulin sensitivity, glycemic measures, ALT, and other cardiometabolic risk factors.

The worldwide incidence of type 1 diabetes continues to rise at an alarming rate. One hundred years after the introduction of insulin, the long-entertained hope of moving from symptomatic treatment to disease-modifying therapies is finally taking shape with regulatory approval of teplizumab to delay the onset of stage 3 disease. Here we review teplizumab's mechanism of action, setting it against the background of emerging disease-modifying therapies for clinical practice, in language accessible to practicing clinicians. A clinical diagnosis of type 1 diabetes and insulin dependence results from progressive autoimmune destruction of pancreatic β-cells as part of a complicated dialogue between the immune system and the islet. Infusion with teplizumab, a humanized monoclonal antibody that binds the ε-chain of the T lymphocyte CD3 molecule, delays progression from stage 2 to clinical stage 3 type 1 diabetes by almost 3 years. The mechanism of action of teplizumab involves partial agonistic signaling via CD3/TCR and subsequent deactivation, promoting exhaustion of pancreatic β-cell-reactive CD8+ T lymphocytes and induction of regulatory T lymphocytes, thereby restoring self-tolerance. With regulatory approval of this agent, clinical practice has entered a new era for treating people with type 1 diabetes, in which disease modification can become the new standard of care. Implementation of global screening for autoantibodies and dysglycemia is underway, enabling efforts to intervene during asymptomatic stages of the disease before insulin treatment is required.