Diabetes care最新文献

Objective: Understanding the pathophysiology of type 2 diabetes subtypes (severe insulin-deficient diabetes, severe insulin-resistant diabetes, mild obesity-related diabetes, and mild age-related diabetes) before diagnosis can enable precision prevention. We estimated the associations of seven biomarkers with type 2 diabetes subtypes prior to diagnosis.

Research design and methods: We analyzed 69,725 observations from 9,661 adults without diabetes (median follow-up 10 years [range 0-17 years]) from four U.S. cohorts. Time-dependent Cox models estimated cause-specific hazard ratios (HRs) of seven pathophysiological biomarkers (BMI [kg/m2], systolic blood pressure [SBP] [per 10 mmHg], HbA1c [%], LDL cholesterol [per 10 mg/dL], homeostatic indices [HOMA2 of β-cell function (HOMA2-%B) (per 10 units) and HOMA2 of insulin resistance (HOMA2-IR)], and estimated glomerular filtration rate [eGFR] [per 10 mL/min/1.73 m2]) with incidence of type 2 diabetes and subtypes, adjusting for demographic and clinical covariates. Model performance was evaluated using participants' first and random visits before last follow-up.

Results: Of the pooled cohort, 1,569 individuals developed type 2 diabetes. BMI (HR 1.03 [95% CI 1.02, 1.04]), SBP (HR 1.09 [95% CI 1.05, 1.13]), HbA1c (HR 2.46 [95% CI 1.73, 3.52]), HOMA2-%B (0.89 [95% CI 0.87, 0.91]), HOMA2-IR (HR 1.92 [95% CI 1.78, 2.07]), and LDL cholesterol (HR 1.02 [95% CI 1.00, 1.04]), but not eGFR (HR 1.02 [95% CI 0.98, 1.07]), were independently associated with diabetes. Associations were similar across subtypes. Models based on single time points demonstrated a high C-index (0.81-0.90) but modest F1 scores (0.26-0.51) and varying sensitivity and calibration (slope 0.22-1.24).

Conclusions: Pathophysiological biomarkers were prospectively associated with type 2 diabetes and subtypes, but single-time-point measurements before diagnosis could not reliably distinguish subtypes at diagnosis.

Objective: We aimed to identify plasma metabolites significantly associated with existing type 2 diabetes (T2D), further characterize their associations with T2D-related laboratory measures and lifestyle-related risk factors, and evaluate their potential mediating and predictive roles for incident T2D.

Research design and methods: We performed metabolomic profiling in 10,163 Finnish men in the Metabolic Syndrome in Men (METSIM) study at baseline. Of these participants, 1,412 had prevalent T2D and 1,234 developed incident T2D during an average follow-up period of 13.6 years. We tested for associations of 979 named metabolites with prevalent T2D. For significant metabolites, we further evaluated their associations with 24 T2D-related laboratory measures of five groups and five T2D lifestyle-related risk factors. We performed an exploratory mediation analysis to examine the mediation effects of metabolites on incident T2D for the five risk factors. We evaluated metabolite associations with incident T2D and built exploratory metabolite predictive models for incident T2D.

Results: We identified 193 plasma metabolites significantly associated with prevalent T2D at baseline, including 71 previously unreported. Of these 193 metabolites, 88 were associated with incident T2D. In participants with prevalent T2D, the 193 metabolites showed associations with zero to 24 (mean 10.2) T2D-related laboratory measures. Eighty-one metabolites partially mediated the associations of the five risk factors with T2D onset under standard mediation assumptions. The significant metabolites showed improved predictive ability for future T2D.

Conclusions: This study identifies T2D plasma metabolic biomarkers for further investigation in women and other populations. The findings enhance our understanding of T2D biology.

Objective: Sodium-glucose cotransporter 2 inhibitors (SGLT2is) lower serum urate and are associated with a lower risk of recurrent gout flares. We used target trial emulation to compare rates of allopurinol initiation and use of anti-inflammatories (high-dose glucocorticoids, nonsteroidal anti-inflammatory drugs [NSAIDs], colchicine) and diuretics (prototypic serum urate-raising medication) among patients with gout using SGLT2is versus dipeptidyl peptidase 4 inhibitors (DPP-4is) (primary comparator), with glucagon-like peptide 1 receptor agonists (GLP-1RAs) as an alternative comparator.

Research design and methods: From a general population database, we identified patients with gout and comorbid type 2 diabetes and used Cox proportional hazards and Poisson regressions with inverse probability of treatment weighting to emulate randomization to SGLT2i or DPP-4i/GLP-1RA. We also replicated the analysis in an electronic health record data set with further adjustment for serum urate and BMI.

Results: Among 26,739 adults with gout and type 2 diabetes (mean age 66 years), 67% had polypharmacy. Allopurinol initiation was lower among SGLT2i initiators than DPP-4i, with a hazard ratio of 0.62 (95% CI 0.52-0.73). Associations were stronger among those using diuretics at baseline (P for interaction = 0.03) and persisted when comparing SGLT2i with GLP-1RA and accounting for serum urate and BMI in the secondary data set. SGLT2i was also associated with lower rates of high-dose glucocorticoid, NSAID, colchicine, and diuretic dispensing, with rate ratios of 0.78 (95% CI 0.74-0.83), 0.85 (95% CI 0.80-0.92), 0.87 (95% CI 0.83-0.92), and 0.87 (95% CI 0.85-0.89), respectively.

Conclusions: For patients with gout and type 2 diabetes, SGLT2is may reduce gout-related medication use, which could, in turn, reduce exposure to the harmful cardiovascular-kidney-metabolic effects of NSAIDs and glucocorticoids in this high-risk population.

Objective: This nationwide study aimed to identify factors associated with 1-year mortality following a first diabetic foot ulcer (DFU) using the French National Health Data System (SNDS). A secondary objective was to analyze mortality after major lower-limb amputation within the same timeframe.

Research design and methods: A retrospective cohort analysis was conducted using SNDS data to identify adults with incident DFUs between January 2017 and December 2018, with 12 months of follow-up. Inclusion criteria combined hospitalization records and community care data. Cox proportional hazards models were used to estimate associations with mortality, adjusting for demographic, clinical, treatment, and care access variables.

Results: Among 133,791 individuals with incident DFU, 14.6% died within 1 year, and 3.5% underwent a major amputation. Of those amputated, 28.8% died within a year. Independent predictors of 1-year mortality included male sex, older age, hospital-acquired DFU, insulin, major amputation, cardiovascular disease, cancer, dementia, ESKD, and liver disease. Protective factors included lipid-lowering therapy, GLP-1 receptor agonists, and prior consultations with diabetologists, ophthalmologists, and podiatrists. Similar patterns were observed for postamputation mortality, with GLP-1 receptor agonists showing a consistent survival benefit.

Conclusions: One-year mortality after DFU remains high and is strongly linked to age and comorbidities. Community-based identification highlights the vulnerability of these patients, even outside hospital settings. Glucagon-like peptide 1 receptor agonists and structured, multidisciplinary follow-up are associated with better survival and should be prioritized. These findings underline the urgent need to reinforce preventive care and optimize care pathways for high-risk diabetic populations.

Objective: Sodium-glucose cotransporter inhibitors (SGLTi) in type 1 diabetes increase diabetic ketoacidosis (DKA) risk but may offer kidney protection. This study assesses whether a reduced estimated glomerular filtration rate (eGFR) increases DKA risk even without SGLTi.

Research design and methods: Time-varying eGFR and hazard of first DKA event were analyzed from 35-year data in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications study using Poisson and extended Cox proportional hazards models.

Results: Of 1,441 participants, 297 experienced 488 DKA events. Unadjusted and adjusted DKA rates in individuals with eGFR between 30 and 90 mL/min/1.73 m2 showed no statistical difference compared with those with eGFR 90-120 mL/min/1.73 m2 (incidence rate of 0.65 events per 100 person-years).

Conclusions: A reduced eGFR (between 30 and 90 mL/min/1.73 m2) alone was not associated with increased DKA risk. This finding supports further research into potential kidney-protection benefits of SGLTi for selected individuals with type 1 diabetes.

Objective: To investigate the association of sex hormones at baseline and 1 year after a lifestyle intervention on cardiovascular (CV) risk in type 2 diabetes (T2D).

Research design and methods: This prospective study, following the Look AHEAD: Action for Health in Diabetes (LookAHEAD) trial, of 2,260 adults with T2D, included measurements of sex hormones and sex hormone binding globulin (SHBG). Baseline levels and 1-year changes were divided into sex-specific tertiles to assess the association with CV events (n = 488 events) and weight loss interactions.

Results: In men, higher baseline total testosterone was associated with lower CV risk (hazard ratio [HR] = 0.74; 95% CI 0.56-0.97). In men with ≥7% weight loss, SHBG increases were inversely associated with CV risk (HR = 0.47; 95% CI 0.26-0.85). In men with <7% weight loss, increases in estradiol were associated with CV risk (second vs. first estradiol tertile: HR = 1.64 [95% CI 1.13-2.38]; third vs. first estradiol tertile: HR = 1.88 [95% CI 1.29-2.73]). No associations were detected in women.

Conclusions: In men with T2D, but not women with T2D, sex hormones were associated with CV events.

The 10-year Action for Health in Diabetes (Look AHEAD) clinical trial compared a multidomain intensive lifestyle intervention to a diabetes support and education program with respect to major cardiovascular disease events (primary outcome) and other diabetes- and obesity-related outcomes. Follow-up of the cohort continues to add other aging-related outcomes and conditions to identify the long-term consequences of factors related to lifestyle and medical care. In this transition to a study of aging among individuals at risk for accelerated aging due to type 2 diabetes and overweight or obesity, the investigators have retrospectively reframed the study using the perspective of geroscience. This perspective strengthens the importance of lifestyle changes as a core component for medical care for these individuals to slow biological aging.

Objective: The Islet Autoantibody Standardization Program (IASP) evaluates type 1 diabetes autoantibody assays through international interlaboratory comparison studies. This report describes 2024 IASP workshop results for multiplex assays that simultaneously measure multiple islet autoantibodies, increasingly adopted for population screening programs.

Research design and methods: Participating laboratories analyzed coded sera from individuals with new-onset type 1 diabetes (n = 50), blood donors with no diabetes (n = 98), and replicate samples (n = 3). Performance was assessed using sensitivity, specificity, adjusted sensitivity at 95%, 99%, and 100% specificity, area under the receiver operating characteristic curve analysis (ROC-AUC), and partial ROC-AUC at 95% specificity (pAUC95).

Results: Fifteen laboratories contributed results from 19 multiplex assays using five formats: antibody-dependent agglutination PCR (ADAP) (n = 6), bridge-ELISA (n = 8), electrochemiluminescence (n = 2), luciferase immunoprecipitation system (LIPS) (n = 1), and protein A luciferase/solid-phase capture LIPS (n = 2). Median ROC-AUC was 0.98 across all platforms, with a pAUC95 of 0.048 against a theoretical maximum of 0.05. Laboratory-reported sensitivity ranged from 86% to 96% with specificity 81% to 100%. Standardized adjusted sensitivity at 99% specificity thresholds eliminated most false positives without compromising sensitivity, achieving 93-97% adjusted sensitivity. Bridge-ELISA platforms demonstrated potential for universal cutoff standardization, while ADAP showed substantial interlaboratory threshold variation.

Conclusions: Multiplex assays demonstrated good overall performance for detecting islet autoantibodies and discriminating case subjects from control subjects. However, interlaboratory variability and platform-specific recognition patterns necessitate further standardization efforts. While not directly tested in this workshop, the results suggest that sequential testing strategies using complementary platforms may be necessary to achieve the stringent specificity required when these assays are used in a screening context.

Objective: Oral administration of an antigen can induce immunological tolerance. Insulin is an autoantigen in childhood type 1 diabetes (T1D). We tested the effect of treatment with high-dose oral insulin on disease progression and immune response to insulin in children with stage 1 T1D.

Research design and methods: We conducted a phase 2 randomized placebo-controlled double-blind trial in children with stage 1 T1D who received daily oral insulin (7.5 mg/day for 3 months and 67.5 mg/day for 9 months; n = 110) or placebo (n = 110) for 12 months. The coprimary outcomes were 1) time from baseline to dysglycemia or clinical diabetes and 2) increased immune response to insulin within 12 months of treatment (assessed in the first 90 participants).

Results: Of 220 participants (n = 112 girls; median age 4.8 years; interquartile range 3.6, 6.2), 179 completed the trial. Dysglycemia or diabetes developed in 87 participants (n = 46 receiving oral insulin and n = 41 receiving placebo; hazard ratio 1.07; 95% CI 0.66-1.73; P = 0.74). The 5-year progression rate was 40% (95% CI 30-51%) in each group. A modest treatment interaction was found with the INS rs689 genotype (P = 0.03). Increased immune response to insulin was observed in 11 (25%) of 44 participants in the oral insulin group and 13 (31%) of 42 in the placebo group (P = 0.63). Oral insulin was well tolerated. No significant study-related adverse events occurred.

Conclusions: In children with stage 1 T1D, 1 year of high-dose oral insulin did not alter progression to dysglycemia or diabetes or immune response to insulin.

Objective: To determine whether extending sleep improves insulin sensitivity in people with overweight/obesity, insulin resistance, and habitual short sleep schedules (<7 h/night).

Research design and methods: Participants were randomized to habitual sleep (HS; n = 15) or extended sleep (ES; n = 14) for ∼6 weeks. Multiorgan (whole-body [primarily muscle], hepatic, and adipose tissue) insulin sensitivity (assessed by the hyperinsulinemic-euglycemic clamp procedure with tracer infusions) and glycemic control (assessed by 24-h serial plasma glucose and insulin concentrations during wakefulness) were determined.

Results: Time-in-bed and sleep duration increased more in the ES group (1.3 ± 0.6 and 1.1 ± 0.5 h/night) than in the HS group (0.3 ± 0.8 and 0.0 ± 0.4 h/night). Day-to-day variability in sleep and subjective measures of sleep health improved more in the ES than HS group, without differences in multiorgan insulin sensitivity or glycemic control between groups.

Conclusions: Extending sleep by ∼1 h/night for ∼6 weeks in people with overweight/obesity and short sleep schedules improves sleep health but not insulin sensitivity or glycemic control.