Diabetes care最新文献

Objective: To examine the associations between patient out-of-pocket (OOP) costs and nonadherence to glucagon-like peptide 1 receptor agonists (GLP-1RA), and the consequent impact on adverse outcomes, including hospitalizations and emergency department (ED) visits.

Research design and methods: This retrospective cohort study used MarketScan Commercial data (2016-2021). The cohort included nonpregnant adults aged 18-64 years with type 2 diabetes who initiated GLP-1RA therapy. Participants were continuously enrolled in the same private insurance plan for 6 months before the prescription date and 1 year thereafter. Exposures included average first 30-day OOP costs for GLP-1RA, categorized into quartiles (lowest [Q1] to highest [Q4]). Primary outcomes were the annual proportion of days covered (PDC) for GLP-1RA and nonadherence, defined as PDC <0.8. Secondary outcomes included diabetes-related and all-cause hospitalizations and ED visits 1 year after GLP-1RA initiation.

Results: Among 61,907 adults who initiated GLP-1RA, higher 30-day OOP costs were associated with decreased adherence. Patients in the highest OOP cost quartile (Q4: $80-$3,375) had significantly higher odds of nonadherence (odds ratio [OR] 1.25; 95% CI 1.19-1.31) compared with those in Q1 ($0-$21). Nonadherence was linked to increased incidence rates of diabetes-related hospitalizations or ED visits (incidence rate ratio [IRR] 1.86; 95% CI 1.43-2.42), cumulative length of hospitalization (IRR 1.56; 95% CI 1.41-1.72), all-cause ED visits (IRR 1.38; 95% CI 1.32-1.45), and increased ED-related costs ($69.81, 95% CI $53.54-$86.08).

Conclusions: Higher OOP costs for GLP-1RA were associated with reduced adherence and increased rates of adverse outcomes among patients with type 2 diabetes.

In 2025, the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) at the National Institutes of Health celebrates 75 years of leadership in diabetes research. The NIDDK serves people of the U.S. affected by or at risk for many chronic diseases, including diabetes and other endocrine, metabolic, and digestive disorders, by funding innovative research to develop better treatment and prevention and a cure for these conditions. Autoimmunity that leads to type 1 diabetes or celiac disease or thyroid autoimmunity affects 1 in 20 children and adolescents in the U.S. While treatments are available, prevention of these common autoimmune diseases has been elusive due to poor understanding of the environmental causes and their interactions with common predisposing or protective genetic variants. In 2002, the NIDDK established The Environmental Determinants of Diabetes in the Young (TEDDY) consortium to advance understanding of the causes and the natural history of type 1 diabetes and other autoimmune diseases. The overarching goal of TEDDY is to inform novel approaches to primary prevention of autoimmunity. In this large international prospective birth cohort study, standardized information has been collected concerning candidate environmental exposures along with serial blood, stool, nasal swab, and other biosamples, with creation of a central repository of data and biologic samples for hypothesis-based research. This review summarizes TEDDY's major contributions to our understanding of environmental triggers, drivers, and modifiers of autoimmunity, and gene-environment interactions, leading to type 1 diabetes.

Objective: To compare rates of and risk factors for hospitalizations among Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study (GRADE) participants taking metformin and randomly assigned to insulin glargine U-100, glimepiride, liraglutide, or sitagliptin.

Research design and methods: Intention-to-treat (ITT) (N = 5,047) and on-assigned-treatment (AT) (N = 4,830) data sets were used. Baseline differences between those hospitalized versus those not hospitalized were assessed. Kaplan-Meier analysis was used to determine incidence for time to first hospitalization, and log-rank tests were used to determine treatment group differences. Time-to-event analyses were used to examine factors affecting subsequent hospitalization risk.

Results: During GRADE, 1,636 participants (32.4%) were hospitalized at least once and 751 (14.9%) were hospitalized more than once. Hospitalized participants were older, less likely to be Hispanic, more likely to be White, and more likely to have a history of hypertension and had higher baseline BMI. There were no treatment group differences in incidence for time to first hospitalization in the ITT data set (P = 0.148), but a reduced hazard rate was observed for those taking liraglutide versus those taking glimepiride in the AT data set (hazard ratio 0.78 [95% CI 0.66, 0.92]; P = 0.022). Factors increasing the risk for subsequent hospitalizations included meeting the secondary outcome (HbA1c >7.5%, confirmed), each prior hospitalization, and change from assigned treatment (29%, 41%, and 56% increase in risk, respectively). Assignment to liraglutide versus glimepiride reduced this risk by 13%.

Conclusions: Hospitalizations were common in GRADE, and rates were nearly identical across treatment groups. The small, but significant, reduction in risk for subsequent hospitalizations among participants assigned to liraglutide versus glimepiride may influence treatment decisions in populations similar to GRADE participants.

Objective: Exposure to maternal gestational diabetes mellitus (GDM) is associated with childhood BMI. Among youth, we explored whether three different glucagon-like peptide 1 receptor gene (GLP-1R) polymorphisms modified the associations between 1) GDM and BMI trajectories and 2) GDM and markers of glucose-insulin homeostasis.

Research design and methods: For 464 participants from the Exploring Perinatal Outcomes Among Children (EPOCH) study, microarray genotyping was performed during childhood (∼10 years). BMI trajectories across childhood and adolescence were characterized using repeated measurements from research visits and medical record abstraction. Markers of glucose-insulin homeostasis were derived from one oral glucose tolerance test in adolescence (∼16 years). Linear models assessed effect modification by GLP-1R polymorphisms.

Results: Among youth with at least one minor allele of rs10305420 (CT or TT) or rs1042044 (CA or AA), but not among major allele homozygotes, exposure to GDM was associated with higher average BMI. For rs6923761, participants who were exposed to GDM and were major allele homozygotes (i.e., genotype GG) had significantly higher average BMI than all other participants in the cohort. No polymorphisms modified the association between GDM and markers of glucose-insulin homeostasis during adolescence.

Conclusions: GLP-1R polymorphisms modify the association between GDM and BMI growth among youth. Further studies are needed to replicate these findings, and to better understand the mechanisms by which GLP-1R polymorphisms lead to heterogeneity in offspring BMI growth.

The current-day epidemic of type 2 diabetes, largely driven by increased adiposity and reduced physical activity in the setting of genetic susceptibility, is a major public health challenge. The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) presciently proposed the Diabetes Prevention Program (DPP), a multicenter randomized clinical trial, designed by investigators in conjunction with NIDDK staff and initiated in 1996. The primary goal of DPP was to determine whether an intensive lifestyle intervention (ILS) or metformin in comparison with placebo would reduce the development of diabetes in a high-risk population with prediabetes. After mean 2.8 years, ILS reduced diabetes risk by 58% and metformin by 31%, leading to study termination ahead of schedule due to demonstrated efficacy of both interventions. In 2002, an extension of the DPP study, the Diabetes Prevention Program Outcomes Study (DPPOS), was initiated for examination of the longer-term course and consequences of diabetes prevention. Over 21 years of median total follow-up, in comparison with the placebo group, cumulative diabetes incidence was reduced by 24% and 17% in the original ILS and metformin groups, respectively, with median increases in diabetes-free survival of 3.5 and 2.5 years/person. During long-term follow-up, there were no significant effects of the original DPP interventions on microvascular or cardiovascular outcomes. However, compared with prevalence of microvascular outcomes among participants who progressed to diabetes, prevalence among those who did not progress was significantly lower. Longer-term follow-up of the cohort continues with examination of relationships between diabetes and prediabetes and an expanded array of diabetes- and aging-related morbidities.

Objective: The National Institute of Diabetes and Digestive and Kidney Diseases Diabetic Foot Consortium tested the hypothesis that compromised restoration of the skin barrier function of closed diabetic foot ulcers (DFUs), as measured by high transepidermal water loss (TEWL), is associated with an increased risk of DFU recurrence.

Research design and methods: This was a multicenter noninterventional study measuring TEWL in 418 adult participants with diabetes and a recently healed DFU. TEWL was measured at the center of the closed wound and at an anatomically similar reference area on the contralateral foot within 2 weeks of wound closure (visit 1); measurements were repeated at a wound closure confirmation visit 2 weeks later (visit 2). Participants were observed for up to 16 weeks to assess for wound recurrence. Participant self-reported and clinician assessments of DFU wound recurrence were recorded.

Results: DFU recurrence by week 16 occurred in 21.5% of participants. Mean TEWL at the center of the healed DFU at visit 1 was higher for those with recurrence compared with those without (P = 0.006). Among participants with high TEWL (>30.05 g · m-2 · h-1), 35% reported wound recurrence by 16 weeks versus 17% of those with low TEWL. The odds ratio for recurrence for participants with high TEWL was 2.66 (P < 0.001). Self-reported wound recurrence was highly concordant with clinician assessment of wound recurrence.

Conclusions: Compromised wound healing mechanisms culminating in wound closure associated with defective skin barrier function is associated with increased risk of DFU recurrence. Measurement of TEWL has value as a predictor of functional wound healing and could affect clinical practice, leading to better outcomes.

Objective: Weight gain with glucose-lowering medications may interfere with effective type 2 diabetes (T2D) management. We evaluated weight change and the effect of weight gain on outcomes over 5 years on four diabetes medications.

Research design and methods: The Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study (GRADE) randomized trial compared the addition of insulin glargine, glimepiride, liraglutide, or sitagliptin to metformin in participants with T2D. We report weight change and hazard ratio (HR) per kilogram of weight change for HbA1c >7.5%; cardiovascular disease (CVD), kidney disease, and neuropathy outcomes; and diabetes treatment satisfaction.

Results: Participants (n = 4,980) were 57 ± 10 years, 44% non-White, with HbA1c 7.5% ± 0.5%, and BMI 34.3 ± 6.8 kg/m2. Mean (95% CI) weight change (kg) during the first year was -3.5 (-3.8,-3.2) with liraglutide,-1.07 (-1.4,-0.78) with sitagliptin, 0.45 (0.16, 0.74) with glargine, and 0.89 (0.60, 1.2) with glimepiride (P < 0.0001). Thereafter, weight decreased in all groups. Weight gain within the first 6 months was associated with increased risk of HbA1c >7.5%, with modest differences by treatment, and with subsequent CVD (HR 1.03 [95% CI 1.005, 1.06]). Weight gain at 1 year was associated with increased risk of HbA1c >7.5% (HR 1.05 [1.04, 1.07]) and kidney disease (HR 1.03 [1.01, 1.06]). Baseline weight, but not weight gain, was associated with new-onset neuropathy. Weight gain was associated with lower diabetes treatment satisfaction.

Conclusions: Liraglutide and sitagliptin were associated with initial weight loss and glargine and glimepiride with slight weight gain, followed by weight loss in metformin-treated T2D. Weight gain was associated with worsening glycemia and increased risk of cardiovascular and kidney outcomes largely independent of treatment.