Diabetes care最新文献

Objective: There is a need for early detection of β-cell decline in people with newly diagnosed (ND) type 1 diabetes. The gold standard mixed-meal tolerance test (MMTT) is an invasive and time-consuming procedure that requires participants to travel to clinical sites. We assessed the feasibility of measuring dried blood spot (DBS) C-peptide levels collected at home as an alternative to the MMTT to detect early β-cell decline.

Research design and methods: Individuals with ND type 1 diabetes were recruited within 6 weeks of diagnosis as part of the INNODIA cohort. They collected finger-prick DBS C-peptide data at home, both while fasting and 60 min after a liquid meal. At 12 months, an MMTT was conducted to measure the area under the curve (AUC) of venous C-peptide.

Results: Data of 292 people were analyzed (mean age 12.7 years; range 1.2-43.8 years). The median number of DBS card pairs per participant was 6.5 (interquartile range = 2, 9) over 12 months. The slopes of stimulated DBS C-peptide levels in the first 6 months significantly predicted venous MMTT AUC C-peptide and peak C-peptide levels at 12 months (P < 0.01). The models were adjusted for simultaneous glucose levels, age, and baseline fasting C-peptide level. However, the 6-month fasting DBS C-peptide slope did not predict 12-month MMTT AUC C-peptide.

Conclusions: Home DBS C-peptide assessment is a feasible method to monitor β-cell function in ND type 1 diabetes. The early prognostic utility of stimulated DBS C-peptide highlights its potential for optimizing trial design. However, further validation is needed to confirm its reliability and broader applicability.

Objective: Pathogenic variants of HNF1A cause maturity-onset diabetes of the young type 3 (HNF1A-MODY; also known as MODY3). Individuals with HNF1A-MODY are primarily treated with sulfonylureas; however, little is known about the effect of sodium-glucose cotransporter 2 (SGLT2) inhibitors in HNF1A-MODY. Interestingly, HNF1A-MODY is associated with increased glucosuria, which has been attributed to lower expression of SGLT2 as observed in HNF1A-knockout mice. We investigated the impact of acute SGLT2 inhibition on glucosuria in individuals with HNF1A-MODY or type 2 diabetes.

Research design and methods: In a randomized, double-blind, crossover study, individuals with HNF1A-MODY or type 2 diabetes underwent two three-step hyperglycemic clamps targeted at 1-h periods of 10, 14, and 18 mmol/L glucose with and without acute SGLT2 inhibition (25 mg empagliflozin or placebo administrated 2 h before clamp procedures).

Results: Eleven individuals with HNF1A-MODY (age [mean ± SD] 49 ± 15 years; glomerular filtration rate [GFR; mean ± SD] 113 ± 18 mL/min) and 10 individuals with type 2 diabetes (age 63 ± 7 years; GFR 103 ± 27 mL/min) were included. During the 3-h hyperglycemic clamp, SGLT2 inhibition increased urinary glucose excretion in both groups (HNF1A-MODY: 24.5 g [95% CI 20.6, 28.3]; type 2 diabetes: 23.5 g [95% CI 20.4, 26.5]). The effect of SGLT2 inhibition was not significantly different between the groups (1.0 g [95% CI -3.5, 5.6]; P = 0.6).

Conclusions: The robust effect of SGLT2 inhibition on urinary glucose excretion in participants with HNF1A-MODY points to SGLT2 inhibition as a relevant glucose-lowering treatment strategy in individuals with HNF1A-MODY.

Objective: To compare the efficacy of enabling Activity feature 60 (AF-60) or 30 min (AF-30) before prolonged exercise versus the automated mode (Auto) in adults and adolescents with type 1 diabetes wearing the Omnipod 5 System.

Research design and methods: In this three-way crossover study, 38 participants (age 30 ± 15 years; BMI 24.7 ± 4.1 kg/m2; HbA1c 7.5% ± 0.9% [58 ± 11 mmol/mol]) from the extension phase of the pivotal trial of the Omnipod 5 System completed a 70-min treadmill session at 64-76% maximum heart rate in a postabsorptive state under each of the three conditions. Auto was resumed after exercise, and glycemia and insulin delivery metrics were examined in the 4-h postexercise period.

Results: The percentage of participants who developed hypoglycemia during exercise did not differ significantly between Auto (42%) and AF-60 (29%; P = 0.34) or AF-30 (24%; P = 0.14). However, AF-60 and AF-30 reduced insulin delivery compared with Auto in the hour before (P < 0.001) and during exercise (P < 0.001). There was also a favorable attenuation in glucose drop during exercise when comparing Auto (-57 ± -35 mg/dL) with AF-60 (-44 ± -33 mg/dL; P = 0.02) and AF-30 (-36 ± -34 mg/dL; P = 0.01). In the postexercise period, glycemia and insulin delivery were comparable.

Conclusions: Enabling the Activity feature either 60 or 30 min before exercise reduced insulin delivery and attenuated glucose drops relative to Auto, but hypoglycemia incidence was not different across the three conditions. These findings support the use of the Omnipod 5 System for exercise but highlight the importance of using additional strategies, such as earlier use of Activity feature and/or carbohydrate intake to further reduce hypoglycemia risk.

Objective: Continuous glucose monitoring (CGM) is increasingly used in gestational diabetes mellitus (GDM), but optimal metrics, ranges, and targets in this population are undefined. We assessed associations between CGM metrics and pregnancy outcomes in GDM.

Research design and methods: During the DiGest study, 425 women with GDM (diagnosed at median [IQR] 25.1 [18.3-27.7] weeks) and BMI ≥25 kg/m2 received a dietary intervention, with masked Dexcom G6 CGM at 29 (n = 361), 32 (n = 215), and 36 (n = 227) weeks' gestation. For this secondary analysis, we used logistic regression, receiver operating characteristic curves, and the Youden index to assess associations and predictive ability of CGM metrics, including pregnancy-specific time in range (TIRp) (63-140 mg/dL [3.5-7.8 mmol/L]) and pregnancy outcomes.

Results: CGM metrics at 29 weeks were significantly associated with large for gestational age (LGA) and small for gestational age (SGA). Participants achieving mean glucose <110 mg/dL (6.1 mmol/L), TIRp ≥90%, or pregnancy-specific time above range (TARp) <10% at 29 weeks had a significantly lower risk of LGA (odds ratio [OR] 0.41 [95% CI 0.22, 0.77], 0.38 [0.20, 0.70], and 0.39 [0.20, 0.73], respectively) and SGA (0.26 [0.08, 0.79], 0.30 [0.10, 0.91], and 0.19 [0.06, 0.62], respectively). TARp <10% and mean nocturnal glucose <110 mg/dL (6.1 mmol/L) were associated with a reduced odds of preterm birth (OR 0.40 [0.17, 0.94] and 0.42 [0.19, 0.97], respectively). A stricter range (63-120 mg/dL [3.5-6.7 mmol/L]) had similar performance overall, but had no single statistically robust TIR/TAR target across all outcomes.

Conclusions: In women with GDM, CGM mean glucose <110 mg/dL (6.1 mmol/L), ≥90% TIRp, or <10% TARp using a range of 63-140 mg/dL (3.5-7.8 mmol/L) at 29 weeks' gestation was associated with a low risk of suboptimal offspring outcomes.

Objective: We tested associations of type 2 diabetes genetic risk score (T2D-GRS) and exposure to maternal hyperglycemia with childhood impaired glucose tolerance (IGT) and T2D and glycemic outcomes in youth from the Hyperglycemia and Adverse Pregnancy Outcome Follow-Up Study.

Research design and methods: We calculated T2D-GRS using 1,150 known genetic variants associated with T2D in adults. In utero exposures included gestational diabetes mellitus (GDM) and sum-of-glucose z scores during oral glucose tolerance test at ∼28 weeks' gestation. IGT + T2D and continuous glycemic outcomes were measured when children were 10-14 years old.

Results: In 3,444 children (mean age, 11.4 years), higher maternal sum-of-glucose z scores and child T2D-GRS were both associated with higher glucose levels. In children exposed to GDM and with T2D-GRS >75th percentile, 15.9% had IGT + T2D, compared with 5.6% in nonexposed children.

Conclusions: High genetic risk for diabetes and in utero exposure to maternal hyperglycemia are additively associated with IGT + T2D and glycemic outcomes in youth.