Daily Endocrinology Research Analysis

BACKGROUND: Current treatment options for youth-onset type 2 diabetes are limited and have demonstrated lower glycaemic efficacy than those for adult-onset type 2 diabetes. We aimed to assess the safety and efficacy of tirzepatide, a glucose-dependent insulinotropic polypeptide and GLP-1 receptor agonist, compared with placebo in youth-onset type 2 diabetes. METHODS: We conducted a phase 3, double-blind, placebo-controlled, multicentre (39 sites), multinational (eight countries) trial over 30 weeks, followed by an open-label extension for 22 weeks in which all participants received tirzepatide. Participants aged 10 to <18 years with youth-onset type 2 diabetes inadequately controlled with metformin and/or basal insulin were randomly assigned (1:1:1) to receive tirzepatide 5 mg, 10 mg, or placebo administered by subcutaneous injection with a single-dose pen. Randomisation was stratified by age group (≤14 years or >14 years) and antihyperglycaemic medication use (metformin, basal insulin, or both). All participants, investigators, and the sponsor were masked to treatment assignment during the 30-week double-blind period. The primary endpoint was change in glycated haemoglobin (HbA FINDINGS: Between April 12, 2022, and Dec 27, 2023, 146 participants were screened, of whom 99 (60 [61%] female, 39 [39%] male; mean age 14·7 years [SD 1·8]; mean baseline HbA INTERPRETATION: Tirzepatide demonstrated significant improvements in glycaemic control and BMI compared with placebo. These effects were sustained over 1 year. FUNDING: Eli Lilly and Company.

BACKGROUND: Diagnosis of dysglycemia is traditionally based on classical criteria, such as those outlined by the American Diabetes Association (ADA), which rely on isolated glucose measurements. However, these static assessments may not fully capture an individual's dynamic glycemic profile. Continuous glucose monitoring (CGM) offers an alternative approach that provides a more comprehensive and accurate reflection of glycemic status over time. Women with a history of gestational diabetes mellitus (GDM) represent a particularly high-risk group. Compared with women who maintained normoglycemia during pregnancy, those with prior GDM have a significantly increased risk of developing dysglycemia. In addition to altered glucose metabolism, they frequently exhibit a cluster of cardiometabolic abnormalities, including obesity, dyslipidemia, hypertension, and early cardiac dysfunction. OBJECTIVE: To compare continuous glucose monitoring to American Diabetes Association criteria, in the postpartum period in women who had developed gestational diabetes mellitus during their recent pregnancy, for diagnosis of type 2 diabetes mellitus complicated by clinical obesity. STUDY DESIGN: Between September 2023 and April 2025, we conducted a multiproposal cohort study at King's College Hospital, London, UK. We invited consecutive women with and without gestational diabetes mellitus at 5 months postpartum. Gestational diabetes mellitus patients were also invited for a 1-year follow-up clinic. Blinded continuous glucose monitoring (Dexcom G7; Dexcom, San Diego, CA) was performed for 10 days. The primary outcome was type 2 diabetes mellitus with clinical obesity, defined by first, the American Diabetes Association criteria (hemoglobin A1c ≥6.5%, fasting plasma glucose ≥126 mg/dL, or 2-hour oral glucose tolerance test of ≥200 mg/dL), and second, continuous glucose monitoring average glucose ≥131.5 mg/dL, which is the mean+2 standard deviation of our nongestational diabetes mellitus group. Clinical obesity was defined by the recently published The Lancet Diabetes and Endocrinology Commission, as excess body fat directly affecting the function of organs and tissues. RESULTS: We examined 1118 women, including 276 (24.7%) nongestational diabetes mellitus controls at 5 months postpartum, 539 (48.2%) postgestational diabetes mellitus at 5 months postpartum, and 303 (27.1%) postgestational diabetes mellitus at 1 year postpartum. In the nongestational diabetes mellitus group, the mean+2 standard deviation average glucose was ≥131.5 mg/dL. At 5 months postpartum in the gestational diabetes mellitus group, continuous glucose monitoring classified 8.9% (48/539) women as diabetes mellitus type 2 with clinical obesity and the respective value by the American Diabetes Association criteria was 4.3% (23/539). Women diagnosed by continuous glucose monitoring but not the American Diabetes Association criteria (n=35) had a worse cardiometabolic profile than those diagnosed by the American Diabetes Association criteria alone (n=10). Of the 35 additional cases, classified only by continuous glucose monitoring, 26 attended to the 1-year postnatal clinic and all still had an average glucose ≥131.5 mg/dL measured by continuous glucose monitoring and abnormal cardiometabolic profile. CONCLUSION: Postpartum follow-up in women who had gestational diabetes mellitus should not only focus on dysglycemia but also on their cardiometabolic profile. In this respect, continuous glucose monitoring is superior to American Diabetes Association criteria for diagnosis of diabetes mellitus type 2 with clinical obesity.

Type 2 diabetes (T2D) is a heterogeneous condition, but its phenotypic variation and links with mortality are unclear. We apply the discriminative dimensionality reduction with trees (DDRTree) algorithm to seven clinical variables in 10,091 adults with newly diagnosed T2D from a nationally representative Chinese cohort. Distinct mortality patterns are observed across phenotypes. Cardiovascular mortality is highest in the most hypertensive and obese individuals, while diabetic ketoacidosis/coma mortality is largely driven by the combination of hyperglycemia and dyslipidemia. Additionally, chronic obstructive pulmonary disease mortality is higher in those with elevated high-density lipoprotein (HDL) and total cholesterol levels. These patterns are similar in UK Biobank, though cardiovascular mortality is highest in those with dyslipidemia and obesity. Predictive models incorporating these variables show good performance and an online tool is provided for individual risk prediction. Overall, this study visualizes phenotypic variation in T2D and its impact on mortality, underscoring the need for personalized treatment strategies.