Diabetes care最新文献

Objective: Diabetes prevention in real-world settings is affected by the challenge of intervention adherence and difficulty in sustaining behavior change. This study evaluated the effectiveness of a stepped care prevention program, enhanced with financial incentives, in reducing the risk of diabetes conversion in a multiethnic prediabetes cohort in Singapore.

Research design and methods: The Pre-Diabetes Interventions and Continued Tracking to Ease Out Diabetes (Pre-DICTED) trial was a randomized controlled trial involving 751 overweight or obese individuals with impaired glucose tolerance, impaired fasting glucose, or both. Participants were assigned to standard care (control arm) or a stepped care intervention program, starting with lifestyle interventions for 6 months before adding metformin for participants who remained at high risk of diabetes conversion based on study visit assessments. Intervention arm participants also received financial incentives for attending lifestyle sessions and for achieving ≥5% weight loss. The primary end point was the proportion of participants developing diabetes at 3 years in the modified intention-to-treat population.

Results: After 3 years, 34.8% of participants in the intervention arm developed diabetes compared with 47.3% in the control arm (adjusted risk difference -10.93%; 95% CI -18.04 to -3.81; P = 0.003). The adjusted relative risk was 0.74 (95% CI 0.62-0.88; P < 0.001). In the intervention arm, 26.4% of participants received metformin, and 45.1% received cash incentives. Adverse events were more common in the intervention arm, mainly because of metformin-related gastrointestinal symptoms.

Conclusions: A stepped care diabetes prevention program, enhanced with financial incentives, effectively reduced diabetes conversion in a multiethnic Asian prediabetes cohort.

Objective: To describe the prevalence and incidence of electrocardiogram (ECG) abnormalities and ECG-derived cardiovascular autonomic neuropathy (CAN) in the GRADE cohort of adults with type 2 diabetes (T2D) <10 years.

Research design and methods: Individuals with T2D taking metformin alone were randomly assigned to add insulin glargine, glimepiride, liraglutide, or sitagliptin. Resting ECGs were completed at the baseline, 2-year, and 4-year study visits and analyzed for minor and major abnormalities and CAN assessed with heart rate variability (HRV) in 4,769 participants. Incidence of new major, minor, and any ECG abnormalities and CAN by treatment group was analyzed using logistic repeated-measures models at years 2 and 4 adjusted for baseline risk factors.

Results: At baseline, participants were a mean age of 57.2 ± 10.0 years, 36.3% were women, mean diabetes duration was 4.3 ± 2.8 years, and mean HbA1c was 7.5 ± 0.5%. Participants with ECG abnormalities at baseline (57.1%) and ECG-derived CAN (52.8%) were older and had more severe cardiovascular risk factors. The incidence of minor and major ECG abnormalities was similar among all treatment groups. However, at year 4, major ECG abnormalities were fewer in the liraglutide versus nonliraglutide groups (9% vs. 13%; P = 0.03). The incidence of CAN did not differ between the liraglutide and nonliraglutide groups across visits (P = 0.42); however, one measure of HRV (SD of normal-to-normal R-R intervals) was higher at year 2 in the liraglutide versus nonliraglutide groups (P = 0.02).

Conclusions: ECG abnormalities, including those reflecting CAN, are common in individuals with T2D <10 years and more so in those with certain cardiovascular risk factors. The development of major ECG abnormalities may be lower with liraglutide.

Objective: Glucose-6-phosphate dehydrogenase (G6PD) deficiency presents silently and is not routinely screened. It is associated with markedly lower HbA1c for the prevailing glucose levels. Since HbA1c is internationally recommended to diagnose and manage type 2 diabetes (T2D), we investigated the population-level impact of undiagnosed G6PD deficiency on T2D diagnosis and complications in the U.K.

Research design and methods: We used whole-exome sequencing and electronic health record data from UK Biobank (n = 467,368) and Genes & Health (n = 43,011) cohorts.

Results: In the U.K., we estimated that ∼1 in 7 Black and 1 in 63 Asian males carry G6PD deficiency alleles, compared with fewer than 1 in 10,000 White males. Despite this, less than 1 in 50 G6PD-deficient men are clinically recognized. Male G6PD carriers have considerably lower average HbA1c (0.9% [International Federation of Clinical Chemistry and Laboratory Medicine: 10.0 mmol/mol]) compared with noncarriers, while differences in average glucose were negligible. G6PD-deficient men had 1.37 (95% CI: 1.01, 1.86) higher odds of developing diabetes-related microvascular complications than noncarriers. Although risk factors were similar prior to diagnosis, male G6PD carriers diagnosed with T2D since 2011 were, on average, 4.1 years (95% CI: 0.6, 7.7) older at diagnosis compared with noncarriers. In addition, lower mean HbA1c values in G6PD carriers falsely underestimated their 10-year T2D risk.

Conclusions: Undiagnosed G6PD deficiency has significant impact on T2D diagnosis with HbA1c and associates with increased risk of diabetes complications. This has major implications for global populations using HbA1c for diagnosis and monitoring, and could contribute significantly to inequalities in diabetes outcomes.

Objective: White matter hyperintensities (WMHs) moderate the association between diabetes and cognition, but the underlying mechanisms remain unknown. This study investigated the interaction effect between diabetes and WMHs on brain atrophy, the resulting atrophy patterns, and whether brain atrophy mediates the effect of diabetes on cognition.

Research design and methods: This study included individuals without dementia from two independent memory clinic-based cohorts: Harmonization (primary analysis, n = 112 case subjects with diabetes, n = 284 control subjects) and Alzheimer's Disease Neuroimaging Initiative (ADNI) (secondary analysis, n = 64 case subjects with diabetes, n = 600 control subjects). Participants underwent longitudinal brain MRI and cognitive assessments, along with plasma pTau181 measurement as a marker of Alzheimer's disease (AD). WMHs and brain atrophy were quantified, with Schwarz signature, McEvoy signature, and hippocampal volume used as AD-specific atrophy measures.

Results: Diabetes was not associated with brain atrophy cross-sectionally or longitudinally. Instead, an interactive effect between diabetes and WMHs on brain atrophy was observed. In Harmonization, this interaction was significant in cross-sectional analyses, affecting cortical gray matter and the frontal lobe. No interactive effect was found for AD-specific atrophy, and the observed interactive effect remained significant after adjusting for plasma pTau181. Cortical gray matter mediated the effect of diabetes on cognition at higher WMHs burden. These results were replicated in ADNI, where diabetes and WMHs interacted to accelerate brain atrophy over time.

Conclusions: Our study demonstrated diabetes and WMHs synergistically contribute to brain atrophy independent of AD, suggesting diabetes-associated cognitive impairment is primarily driven by cerebrovascular disease rather than Alzheimer pathology.

Objective: In the TrialNet 10 Anti-CD3 Prevention (TN-10) trial, teplizumab delayed onset of stage 3 type 1 diabetes in U.S. and Canadian individuals with stage 2 disease who had a relative with type 1 diabetes. Here, the generalizability of the population risk in TN-10 to a European population with or without first-degree relatives (FDRs) with type 1 diabetes was investigated.

Research design and methods: This retrospective study used data from participants with stage 2 type 1 diabetes from the TN-10 placebo arm and the Fr1da population-based screening program in Germany (Fr1da group) to investigate time to progression from stages 2-3 type 1 diabetes. The study only had sufficient power to detect large differences.

Results: Risk of progression to stage 3 type 1 diabetes was comparable between the TN-10 placebo arm (n = 32) and the Fr1da group (n = 152; hazard ratio [HR] = 1.3 [95% CI 0.8-2.1]). Once prognostic factors significantly associated with progression in this study (anti-IA-2 antibodies, HbA1c >5.7%, and 120-min oral glucose tolerance test) were included in the model, the adjusted HR was 1.1 (95% CI 0.6-2.1). Fr1da group participants with (n = 45) and without (n = 107) FDRs with type 1 diabetes had similar time to progression to stage 3. Age-based subanalysis demonstrated minimal impact of age on progression time.

Conclusions: Time to progression to stage 3 appeared similar between the TN-10 placebo arm and the Fr1da group and between participants with and without FDRs with disease. Results suggest progression risk from the TN-10 trial may be generalizable to European populations with or without FDRs with type 1 diabetes.

This article summarizes the current understanding of the heterogeneity of type 1 diabetes from a June 2024 international Expert Forum organized by the editors of Diabetes, Diabetes Care, and Diabetologia. The Forum reviewed key factors contributing to the development and progression of type 1 diabetes and outlined specific, high-priority research questions. Knowledge gaps were identified, and, notably, opportunities to harness disease heterogeneity to develop personalized therapies were outlined. Herein, we summarize our discussions and review the heterogeneity of genetic risk and immunologic and metabolic phenotypes that influence and characterize type 1 diabetes progression (presented as a palette of risk factors). We discuss how these age-related factors determine disease aggressiveness (along gradients) and describe how variable immunogenetic pathways aggregate (into networks) to affect β-cell and other pancreatic pathologies to cause clinical disease at different ages and with variable severity (described as disease-related thresholds). Heterogeneity of pathogenesis and clinical severity opens avenues to prevention and intervention, including the potential of disease-modifying immunotherapy and islet cell replacement. We conclude with a call for 1) continued research to identify more factors contributing to the disease, both overall and in specific subgroups; 2) investigations focusing on both individuals who surpass metabolic and immune thresholds and develop diabetes and those who remain disease free with the same level of immunogenetic risk; and 3) efforts to identify where the current type 1 diabetes staging system may fall short and determine how it can be improved to capture and leverage heterogeneity in prevention and intervention strategies.