Diabetes care最新文献

Objective: Women with a history of gestational diabetes mellitus (GDM) are at increased risk of developing type 2 diabetes (T2D). It remains unclear whether genetic information improves prediction of incident T2D in these women.

Research design and methods: Using five independent cohorts representing four different ancestries (n = 1,895), we investigated whether a genome-wide T2D polygenic risk score (PRS) is associated with increased risk of incident T2D. We also calculated the area under the receiver operating characteristics curve (AUROC) and continuous net reclassification improvement (NRI) following the incorporation of T2D PRS into clinical risk models to assess the diagnostic utility.

Results: Among 1,895 women with previous history of GDM, 363 (19.2%) developed T2D in a range of 2 to 30 years. T2D PRS was higher in those who developed T2D (-0.08 vs. 0.31, P = 2.3 × 10-11) and was associated with an increased risk of incident T2D (odds ratio 1.52 per 1-SD increase, 95% CI 1.05-2.21, P = 0.03). In a model that includes age, family history of diabetes, systolic blood pressure, and BMI, the incorporation of PRS led to an increase in AUROC for T2D from 0.71 to 0.74 and an intermediate improvement of NRI (0.32, 95% CI 0.15-0.49, P = 3.0 × 10-4). Although there was variation, a similar trend was observed across study cohorts.

Conclusions: In cohorts of GDM women with diverse ancestry, T2D PRS was significantly associated with future development of T2D. A significant but small improvement was observed in AUROC when T2D PRS was integrated into clinical risk models to predict incident T2D.

Objective: To compare postprandial glucose excursions following a bolus with inhaled technosphere insulin (TI) or subcutaneous rapid-acting analog (RAA) insulin.

Research design and methods: A meal challenge was completed by 122 adults with type 1 diabetes who were using multiple daily injections (MDI), a nonautomated pump, or automated insulin delivery (AID) and who were randomized to bolus with their usual RAA insulin (n = 61) or TI (n = 61).

Results: The primary outcome, the treatment group difference in area under the curve for glucose >180 mg/dL over 2 h, was less with TI versus RAA (adjusted difference -12 mg/dL, 95% CI -22 to -2, P = 0.02). With TI, the glucose excursion was smaller (P = 0.01), peak glucose lower (P = 0.01), and time to peak glucose shorter (P = 0.006). Blood glucose <70 mg/dL occurred in one participant in each group.

Conclusions: Postmeal glucose excursion was smaller with TI than with RAA insulin in a cohort that included both AID and MDI users.

Objective: To investigate quantitative and qualitative changes in retinal structure using optical coherence tomography (OCT) and their associations with systemic or other risk factors in individuals with type 1 diabetes (T1D).

Research design and methods: In the Epidemiology of Diabetes Interventions and Complications (EDIC) study, OCT images were obtained during study years 25-28 (2019-2022) in 937 participants; 54% and 46% were from the original intensive (INT) and conventional (CONV) glycemic management treatment groups, respectively.

Results: Average age for participants was 61 years old, diabetes duration 39 years, and HbA1c 7.6%. Participants originally in the CONV group were more likely to have disorganization of retinal inner layers (DRIL) (CONV 27.3% vs. INT 18.7%; P = 0.0003), intraretinal fluid (CONV 24.4% vs. INT 19.2%; P = 0.0222), and intraretinal cysts (CONV 20.8% vs. INT 16.6%; P = 0.0471). In multivariable models, sex, age, smoking, mean updated systolic blood pressure, and history of "clinically significant" macular edema (CSME) and of anti-VEGF treatment were independently associated with changes in central subfield thickness, while HbA1c, BMI, and history of CSME and of ocular surgery were associated with DRIL. Visual acuity (VA) decline was associated with significant thinning of all retinal subfields except for the central and inner nasal subfields.

Conclusions: Early intensive glycemic management in T1D is associated with a decreased risk of DRIL. This important morphological abnormality was associated with a history of macular edema, a history of ocular surgery, and worse VA. This study reveals benefits of intensive glycemic management on the retina beyond features detected by fundus photographs and ophthalmoscopy.

Objective: To explore if oral insulin could delay onset of stage 3 type 1 diabetes (T1D) among patients with stage 1/2 who carry HLA DR4-DQ8 and/or have elevated levels of IA-2 autoantibodies (IA-2As).

Research and methods: Next-generation targeted sequencing technology was used to genotype eight HLA class II genes (DQA1, DQB1, DRB1, DRB3, DRB4, DRB5, DPA1, and DPB1) in 546 participants in the TrialNet oral insulin preventative trial (TN07). Baseline levels of autoantibodies against insulin (IAA), GAD65 (GADA), and IA-2A were determined prior to treatment assignment. Available clinical and demographic covariables from TN07 were used in this post hoc analysis with the Cox regression model to quantify the preventive efficacy of oral insulin.

Results: Oral insulin reduced the frequency of T1D onset among participants with elevated IA-2A levels (HR 0.62; P = 0.012) but had no preventive effect among those with low IA-2A levels (HR 1.03; P = 0.91). High IA-2A levels were positively associated with the HLA DR4-DQ8 haplotype (OR 1.63; P = 6.37 × 10-6) and negatively associated with the HLA DR7-containing DRB1*07:01-DRB4*01:01-DQA1*02:01-DQB1*02:02 extended haplotype (OR 0.49; P = 0.037). Among DR4-DQ8 carriers, oral insulin delayed the progression toward stage 3 T1D onset (HR 0.59; P = 0.027), especially if participants also had high IA-2A level (HR 0.50; P = 0.028).

Conclusions: These results suggest the presence of a T1D endotype characterized by HLA DR4-DQ8 and/or elevated IA-2A levels; for those patients with stage 1/2 disease with such an endotype, oral insulin delays the clinical T1D onset.

Objective: To evaluate the impact of prolonged hybrid closed loop (HCL) use in children with type 1 diabetes (T1D) on glucose control and BMI throughout pubertal progression.

Research design and methods: We used a prospective multicenter extension study following the Free-Life Kid AP (FLKAP) HCL trial. The 9-month previously reported FLKAP trial included 119 prepubertal children (aged 6-12 years). During the extension study, participants could continue to use HCL for 30 months (M9 to M39). HbA1c values were collected every 3 months up to M39, while continuous glucose monitoring metrics, BMI z scores, and Tanner stages were collected up to M24. Noninferiority tests were performed to assess parameter sustainability over time.

Results: One hundred seventeen children completed the extension study, with mean age 10.1 years (minimum to maximum, 6.8-14.0) at the beginning. Improvement of HbA1c obtained in the FLKAP trial was significantly sustained during extension (median [interquartile range], M9 7.0% [6.8-7.4], and M39 7.0% [6.6-7.4], P < 0.0001 for noninferiority test) and did not differ between children who entered puberty at M24 (Tanner stage ≥2; 54% of the patients) and patients who remained prepubertal. BMI z score also remained stable (M9 0.41 [-0.29 to 1.13] and M24 0.48 [-0.11 to 1.13], P < 0.0001, for noninferiority test). No severe hypoglycemia and one ketoacidosis episode not related to the HCL system occurred.

Conclusions: Prolonged use of HCL can safely and effectively mitigate impairment of glucose control usually associated with pubertal progression without impact on BMI in children with T1D.

Objective: To update state-specific estimates of diabetes-attributable costs in the U.S. and assess changes in spending from 2013 to 2021.

Research design and methods: We used an attributable fraction approach to estimate direct medical costs of diagnosed diabetes using the 2021 State Health Expenditure Accounts, the 2021 Behavioral Risk Factor Surveillance System, and the Centers for Medicare and Medicaid Services 2018-2019 Minimum Data Set. We estimated diabetes-attributable productivity losses from morbidity and mortality using the 2016-2021 National Health Interview Survey and the 2021 mortality data from the Centers for Disease Control and Prevention. Costs were adjusted to 2021 U.S. dollars.

Results: Total diabetes-attributable cost in 2021 was $640 billion ($335 billion in direct medical costs and $305 billion in indirect costs). The median state-level total diabetes-attributable cost was $8.2 billion (range $842 million to $81 billion). The median state-level per-person cost was $21,082, ranging from $17,452 to $37,090. Total diabetes-attributable cost increased by a median of 33% between 2013 and 2021, ranging from 16 to 68% across states. Medical costs increased by 50% overall (range 33-79%) and by 27% (range 15-41%) for per person with diabetes. Costs paid by Medicaid experienced the highest increase between 2013 and 2021 (median 153%; range 41-483%).

Conclusions: State economic costs of diagnosed diabetes are substantial and increased over the last decade. These costs and their growth vary considerably across states. These findings may help state policy makers in developing evidenced-based public health interventions in their respective states to prevent and control the prevalence of diabetes.

Objective: To estimate lifetime incremental medical spending attributed to incident type 2 diabetes (T2D) among Medicare beneficiaries by age at diagnosis, sex, and race/ethnicity.

Research design and methods: We used the 1999-2019 100% Medicare fee-for-service claims database to identify a cohort of beneficiaries with newly diagnosed T2D in 2001-2003 using ICD codes. We matched this cohort with a nondiabetes cohort using a propensity score method and then followed the two cohorts until death, disenrollment, or the end of 2019. Lifetime medical spending for each cohort was the sum of expected annual spending, a product of actual annual spending multiplied by the annual survival rate, from the age at T2D diagnosis to death. Lifetime incremental medical spending was calculated as the difference in lifetime medical spending between the two cohorts. All spending was standardized to 2019 U.S. dollars.

Results: Medicare beneficiaries with newly diagnosed T2D, despite having a shorter life expectancy, had 36-40% higher lifetime medical spending compared with a comparable group without diabetes. Lifetime incremental medical spending ranged from $16,115 to $122,146, depending on age at diagnosis, sex, and race/ethnicity, declining with age at diagnosis, and being highest for Asian/Pacific Islander and non-Hispanic Black beneficiaries.

Conclusions: The large lifetime incremental medical spending associated with incident T2D underscores the need for preventing T2D among Medicare beneficiaries. Our results could be used to estimate the potential financial benefit of T2D prevention programs both overall and among subgroups of beneficiaries.