Chromosome 6 was imputed using SNP2HLA, with conditional analysis performed in type 1 diabetes case subjects (n = 1,985) and control subjects (n = 2,219). The same approach was applied to a LADA cohort (n = 1,428) using population-based control subjects (n = 2,850) and in a separate replication cohort (656 type 1 diabetes case, 823 LADA case, and 3,218 control subjects).

The strongest associations in the MHC class II region (rs3957146, β [SE] = 1.44 [0.05]), as well as the independent effect of MHC class I genes, on type 1 diabetes risk, particularly HLA-B*39 (β [SE] = 1.36 [0.17]), were confirmed. The conditional analysis in LADA versus control subjects showed significant association in the MHC class II region (rs3957146, β [SE] = 1.14 [0.06]); however, we did not observe significant independent effects of MHC class I alleles in LADA.

In LADA, the independent effects of MHC class I observed in type 1 diabetes were not observed after conditioning on the leading MHC class II associations, suggesting that the MHC class I association may be a genetic discriminator between LADA and childhood-onset type 1 diabetes.

Before and after 1 year of gender-affirming hormone therapy, body composition and oral glucose tolerance tests (OGTTs) were evaluated.

In TM, body weight (2.8 ± 1.0 kg; P < 0.01), fat-free mass (FFM) (3.1 ± 0.9 kg; P < 0.01), and waist-to-hip ratio (–0.03 ± 0.01; P < 0.01) increased. Fasting insulin (–1.4 ± 0.8 mU/L; P = 0.08) and HOMA of insulin resistance (HOMA-IR) (2.2 ± 0.3 vs. 1.8 ± 0.2; P = 0.06) tended to decrease, whereas fasting glucose (–1.6 ± 1.6 mg/dL), glucose-dependent insulinotropic polypeptide (GIP) (–1.8 ± 1.0 pmol/L), and glucagon-like peptide 1 (GLP-1) (–0.2 ± 1.1 pmol/L) were statistically unchanged. Post-OGTT areas under the curve (AUCs) for GIP (2,068 ± 1,134 vs. 2,645 ± 1,248 [pmol/L] x min; P < 0.01) and GLP-1 (2,352 ± 796 vs. 2,712 ± 1,015 [pmol/L] x min; P < 0.01) increased. In TW, body weight tended to increase (1.4 ± 0.8 kg; P = 0.07) with decreasing FFM (–2.3 ± 0.4 kg; P < 0.01) and waist-to-hip ratio (–0.03 ± 0.01; P < 0.01). Insulin (3.4 ± 0.8 mU/L; P < 0.01) and HOMA-IR (1.7 ± 0.1 vs. 2.4 ± 0.2; P < 0.01) rose, fasting GIP (–1.4 ± 0.8 pmol/L; P < 0.01) and AUC GIP dropped (2,524 ± 178 vs. 1,911 ± 162 [pmol/L] x min; P < 0.01), but fasting glucose (–0.3 ± 1.4 mg/dL), GLP-1 (1.3 ± 0.8 pmol/L), and AUC GLP-1 (2,956 ± 180 vs. 2,864 ± 93 [pmol/L] x min) remained unchanged.

In this cohort of transgender persons, insulin sensitivity but also post-OGTT incretin responses tend to increase with masculinization and to decrease with feminization.

A post hoc analysis was performed of the SWITCH (SWITCH 1: n = 501, type 1 diabetes; SWITCH 2: n = 721, type 2 diabetes) and DEVOTE (n = 7,637, type 2 diabetes) trials utilizing the IHSG low glucose definitions. Patients in all trials were randomized to either insulin degludec or insulin glargine 100 units/mL. In the main analysis, the following definitions were compared: 1) American Diabetes Association (ADA) 2005 (plasma glucose [PG] confirmed ≤3.9 mmol/L with symptoms); and 2) IHSG level 2 (PG confirmed <3.0 mmol/L, independent of symptoms).

In SWITCH 2, the estimated rate ratios of hypoglycemic events indicated increasing differences between treatments with decreasing PG levels until 3.0 mmol/L, following which no additional treatment differences were observed. Similar results were observed for the SWITCH 1 trial. In SWITCH 2, the IHSG level 2 definition produced a rate ratio that was lower than the ADA 2005 definition.

The IHSG level 2 definition was validated in a series of clinical trials, demonstrating its ability to discriminate between basal insulins. This definition is therefore recommended to be uniformly adopted by regulatory bodies and used in future clinical trials.

Patients with diabetes and chronic DFUs were randomized (double-blind) to either active TWO2 therapy or sham control therapy—both in addition to optimal SOC. The primary outcome was the percentage of ulcers in each group achieving 100% healing at 12 weeks. A group sequential design was used for the study with three predetermined analyses and hard stopping rules once 73, 146, and ultimately 220 patients completed the 12-week treatment phase.

At the first analysis point, the active TWO2 arm was found to be superior to the sham arm, with a closure rate of 41.7% compared with 13.5%. This difference in outcome produced an odds ratio (OR) of 4.57 (97.8% CI 1.19, 17.57), P = 0.010. After adjustment for University of Texas Classification (UTC) ulcer grade, the OR increased to 6.00 (97.8% CI 1.44, 24.93), P = 0.004. Cox proportional hazards modeling, also after adjustment for UTC grade, demonstrated >4.5 times the likelihood to heal DFUs over 12 weeks compared with the sham arm with a hazard ratio of 4.66 (97.8% CI 1.36, 15.98), P = 0.004. At 12 months postenrollment, 56% of active arm ulcers were closed compared with 27% of the sham arm ulcers (P = 0.013).

This sham-controlled, double-blind randomized controlled trial demonstrates that, at both 12 weeks and 12 months, adjunctive cyclical pressurized TWO2 therapy was superior in healing chronic DFUs compared with optimal SOC alone.

People with type 1 diabetes (n = 100) investigated at the University Hospital of Montpellier (France) underwent continuous glucose monitoring (CGM) on two consecutive days, providing a total of 200 24-h glycemic profiles. The following parameters were computed: MDG concentration, within-day glycemic variability (coefficient of variation for glucose [%CV]), and risk of hypoglycemia (presented as the percentage of time spent below three glycemic thresholds: 3.9, 3.45, and 3.0 mmol/L).

MDG was significantly higher, and %CV significantly lower (both P < 0.001), when comparing the 24-h glycemic profiles according to whether no time or a certain duration of time was spent below the thresholds. Univariate regression analyses showed that MDG and %CV were the two explanatory variables that entered the model with the outcome variable (time spent below the thresholds). The classification and regression tree procedure indicated that the predominant predictor for hypoglycemia was %CV when the threshold was 3.0 mmol/L. In people with mean glucose ≤7.8 mmol/L, the time spent below 3.0 mmol/L was shortest (P < 0.001) when %CV was below 34%.

In type 1 diabetes, short-term glycemic variability relative to mean glucose (i.e., %CV) explains more hypoglycemia than does mean glucose alone when the glucose threshold is 3.0 mmol/L. Minimizing the risk of hypoglycemia requires a %CV below 34%.

A Stepped Insulin Secretion Test with Arginine was used to quantify functional β-cell capacity by hyperglycemia and arginine stimulation. Thirty-nine of 57 participants initially achieved remission (HbA_1c <6.5% [<48 mmol/mol] and fasting plasma glucose <7 mmol/L on no antidiabetic drug therapy) with a 16.4 ± 7.7 kg weight loss and were followed up with supportive advice on avoidance of weight regain. At 2 years, 20 participants remained in remission in the study. A nondiabetic control (NDC) group, matched for age, sex, and weight after weight loss with the intervention group, was studied once.

During remission, median (interquartile range) maximal rate of insulin secretion increased from 581 (480–811) pmol/min/m² at baseline to 736 (542–998) pmol/min/m² at 5 months, 942 (565–1,240) pmol/min/m² at 12 months (P = 0.028 from baseline), and 936 (635–1,435) pmol/min/m² at 24 months (P = 0.023 from baseline; n = 20 of 39 of those initially in remission). This was comparable to the NDC group (1,016 [857–1,507] pmol/min/m²) by 12 (P = 0.064) and 24 (P = 0.244) months. Median first-phase insulin response increased from baseline to 5 months (42 [4–67] to 107 [59–163] pmol/min/m²; P < 0.0001) and then remained stable at 12 and 24 months (110 [59–201] and 125 [65–166] pmol/min/m², respectively; P < 0.0001 vs. baseline) but lower than that of the NDC group (250 [226–429] pmol/min/m²; P < 0.0001).

A gradual increase in assessed functional β-cell capacity occurred after weight loss, becoming similar to that of NDC group participants by 12 months. This result was unchanged at 2 years with continuing remission of type 2 diabetes.

DPN was assessed with the Michigan Neuropathy Screening Instrument Questionnaire (MNSIQ) in adults with ≥5 years of type 1 diabetes duration. A score of ≥4 defined DPN. Associations of demographic, clinical, and laboratory factors with DPN were assessed.

Among 5,936 T1D Exchange participants (mean ± SD age 39 ± 18 years, median type 1 diabetes duration 18 years [interquartile range 11, 31], 55% female, 88% non-Hispanic white, mean glycated hemoglobin [HbA_1c] 8.1 ± 1.6% [65.3 ± 17.5 mmol/mol]), DPN prevalence was 11%. Compared with those without DPN, DPN participants were older, had higher HbA_1c, had longer duration of diabetes, were more likely to be female, and were less likely to have a college education and private insurance (all P < 0.001). DPN participants also were more likely to have cardiovascular disease (CVD) (P < 0.001), worse CVD risk factors of smoking (P = 0.008), hypertriglyceridemia (P = 0.002), higher BMI (P = 0.009), retinopathy (P = 0.004), reduced estimated glomerular filtration rate (P = 0.02), and Charcot neuroarthropathy (P = 0.002). There were no differences in insulin pump or continuous glucose monitor use, although DPN participants were more likely to have had severe hypoglycemia (P = 0.04) and/or diabetic ketoacidosis (P < 0.001) in the past 3 months.

The prevalence of DPN in this national cohort with type 1 diabetes is lower than in prior published reports but is reflective of current clinical care practices. These data also highlight that nonglycemic risk factors, such as CVD risk factors, severe hypoglycemia, diabetic ketoacidosis, and lower socioeconomic status, may also play a role in DPN development.