One-year postpartum weight retention and glucose intolerance in women with prediabetes after gestational diabetes.

AIMS: To determine risk factors for 1-year postpartum weight retention (PPWR) and glucose intolerance (prediabetes + diabetes) in women with a previous history of gestational diabetes (GDM) and prediabetes in early postpartum. METHODS: In this exploratory analysis of the MELINDA randomized controlled trial, we report data of 167 women with prediabetes at the 6-16 weeks (early) postpartum oral glucose tolerance test after a recent history of GDM. RESULTS: Of all participants, 45% (75) had PPWR >0 kg at 1-year postpartum. Compared to women without PPWR, women with PPWR had higher gestational weight gain [10.5 ± 6.4 vs. 6.5 ± 4.5 kg, p < 0.001], higher BMI (p < 0.01) and a worse metabolic profile (higher waist circumference, worse lipid profile and more insulin resistance) (all p < 0.05) both in early and late postpartum. Of all women with PPWR, 40.0% developed metabolic syndrome, compared to 18.9% of women without late PPWR (p = 0.003). The only independent predictor for late PPWR was weight retention in early postpartum (p < 0.001). Of all participants, 55.1% (92) had glucose intolerance (84 prediabetes, 8 diabetes) 1-year postpartum. Independent predictors for late postpartum glucose intolerance were lower gestational age at start insulin therapy in pregnancy and delivery by caesarean section (resp. p = 0.044 and 0.014). CONCLUSIONS: In women with a previous history of GDM and prediabetes in early postpartum, PPWR in early postpartum was a strong independent predictor for late PPWR, while earlier start of insulin therapy during pregnancy and delivery by caesarean section were independent predictors of glucose intolerance in late postpartum.

Perspectives and Behaviors of People with Diabetes toward Time in Range and Glucose Control in Diabetes Management: An Online Survey.

INTRODUCTION: This study assessed experiences, attitudes, and behaviors of people with diabetes (PwD) regarding diabetes self-management and glucose control, and their level of awareness, knowledge, and attitudes toward time in range (TIR). METHODS: This quantitative survey was conducted using an online questionnaire across seven countries. Respondents were PwD classified into three subgroups: type 1 (T1), type 2 insulin (T2 insulin), and type 2 not on insulin (T2 N/insulin). RESULTS: Respondents included 621 people in the T1, 780 people in the T2 insulin, and 735 people in the T2 N/insulin subgroups. Awareness of TIR was low, particularly in the T2 N/insulin subgroup (T1 53%, T2 insulin 29%, T2 N/insulin 9%). Despite a lower current use of continuous glucose monitoring (CGM) among the T2 insulin and T2 N/insulin participants (38% and 9%, respectively), versus T1 participants (64%), most (> 70%) were positive toward utilizing new tools and measures to self-manage blood glucose. Recommendations from their healthcare professionals (HCPs) were cited as a strong motivator to try new measures for analyzing glucose levels. The main barriers cited were limited access to CGM and lack of understanding of TIR benefits. Cost was the main reason given by ≥ 40% of respondents for stopping CGM use. CONCLUSIONS: There is an unmet need in diabetes management, and TIR and CGM offer a potential solution. PwD are motivated to manage their blood glucose levels and are positive toward utilizing new tools and measures to achieve this goal. HCPs play a pivotal role in informing and guiding PwD on new measures for analyzing glucose.

Metabolic dysfunction-associated steatotic liver disease is associated with worse time in ranges in type 1 diabetes.

AIM: To investigate the relationship between continuous glucose monitoring (CGM)-derived glucometrics and metabolic dysfunction-associated steatotic liver disease (MASLD) in type 1 diabetes (T1D). METHODS: A cross-sectional study collecting data on anthropometrics, glucometrics and MASLD in adults with T1D using a CGM device was conducted. MASLD was assessed by abdominal ultrasound and the presence of at least one cardiometabolic criterion. Backward multivariable logistic regression models were applied to define variables independently associated with MASLD. RESULTS: A total of 302 consecutive participants were included (median age 49 [34-61] years, male sex 58%, median diabetes duration 29 [17-38] years, mean time in range [TIR] 55% ± 16%). MASLD was present in 17% of cases, and 32% had metabolic syndrome (MetS). MetS was significantly more prevalent in the MASLD group (65% vs. 25%, P < .0001). TIR (P = .038) and time below range (TBR) (P = .032) were lower and time above range (TAR) was higher (P = .006), whereas HbA1c did not reach significance (P = .068). No differences were found for the glycaemia risk index. TIR (P = .028), TAR (P = .007), TBR (P = .036), waist circumference (P < .001) and systolic blood pressure (P = .029) were independently associated with MASLD, while sex, age, aspartate aminotransferase/alanine aminotransferase ratio, gamma-glutamyl transferase, high-density lipoprotein cholesterol and triglycerides were not. CONCLUSIONS: TIR, TAR, TBR, waist circumference and systolic blood pressure were independently associated with MASLD.

Impact of breastfeeding on risk of glucose intolerance in early postpartum after gestational diabetes.

Aims: To determine the impact of breastfeeding on the risk of postpartum glucose intolerance in women with gestational diabetes. Methods: Sub-analysis of two multi-centric prospective cohort studies (BEDIP-N and MELINDA) in 1008 women with gestational diabetes. Data were collected during pregnancy and at a mean of 12 weeks postpartum. Multivariate logistic regression was used to estimate the effect of breastfeeding on glucose intolerance, with adjustment for ethnicity, education, income, professional activity and BMI. Results: Of all participants, 56.3% (567) breastfed exclusively, 10.1% (102) gave mixed milk feeding and 33.6% (339) did not breastfeed. Mean breastfeeding duration was 3.8 ± 2.4 and 3.7 ± 2.1 months in the breastfeeding and mixed milk feeding groups (p=0.496). The rate of glucose intolerance was lower in both the breastfeeding [22.3% (126)] and mixed milk feeding [25.5% (26)] groups compared to the no breastfeeding group [29.5% (100)], with an adjusted OR of 0.7 (95% CI 0.5-1.0) for glucose intolerance in the breastfeeding group compared to no breastfeeding group and an adjusted OR of 0.7 (95% CI 0.4-1.2) for the mixed milk feeding group compared to the no breastfeeding group. Postpartum, breastfeeding women had a lower BMI, less often postpartum weight retention, lower fasting triglycerides, less insulin resistance and a higher insulin secretion-sensitivity index-2 than the mixed milk feeding and no breastfeeding group. The mixed milk feeding group was more often from an non-White background, had a lower blood pressure and lower fasting triglycerides compared to the no breastfeeding group. Conclusions: Breastfeeding (exclusive and mixed milk feeding) is associated with less glucose intolerance and a better metabolic profile in early postpartum in women with gestational diabetes.

Early feasibility study with an implantable near-infrared spectroscopy sensor for glucose, ketones, lactate and ethanol.

OBJECTIVE: To evaluate the safety and performance of an implantable near-infrared (NIR) spectroscopy sensor for multi-metabolite monitoring of glucose, ketones, lactate, and ethanol. RESEARCH DESIGN AND METHODS: This is an early feasibility study (GLOW, NCT04782934) including 7 participants (4 with type 1 diabetes (T1D), 3 healthy volunteers) in whom the YANG NIR spectroscopy sensor (Indigo) was implanted for 28 days. Metabolic challenges were used to vary glucose levels (40-400 mg/dL, 2.2-22.2 mmol/L) and/or induce increases in ketones (ketone drink, up to 3.5 mM), lactate (exercise bike, up to 13 mM) and ethanol (4-8 alcoholic beverages, 40-80g). NIR spectra for glucose, ketones, lactate, and ethanol levels analyzed with partial least squares regression were compared with blood values for glucose (Biosen EKF), ketones and lactate (GlucoMen LX Plus), and breath ethanol levels (ACE II Breathalyzer). The effect of potential confounders on glucose measurements (paracetamol, aspartame, acetylsalicylic acid, ibuprofen, sorbitol, caffeine, fructose, vitamin C) was investigated in T1D participants. RESULTS: The implanted YANG sensor was safe and well tolerated and did not cause any infectious or wound healing complications. Six out 7 sensors remained fully operational over the entire study period. Glucose measurements were sufficiently accurate (overall mean absolute (relative) difference MARD of 7.4%, MAD 8.8 mg/dl) without significant impact of confounders. MAD values were 0.12 mM for ketones, 0.16 mM for lactate, and 0.18 mM for ethanol. CONCLUSIONS: The first implantable multi-biomarker sensor was shown to be well tolerated and produce accurate measurements of glucose, ketones, lactate, and ethanol. TRIAL REGISTRATION: Clinical trial identifier: NCT04782934.

The association of chronic complications with time in tight range and time in range in people with type 1 diabetes: a retrospective cross-sectional real-world study.

AIMS/HYPOTHESIS: The aim of this study was to evaluate the association of chronic complications with time in tight range (TITR: 3.9-7.8 mmol/l) and time in range (TIR: 3.9-10.0 mmol/l) in people with type 1 diabetes. METHODS: The prevalence of microvascular complications (diabetic retinopathy, diabetic nephropathy and diabetic peripheral neuropathy [DPN]) and macrovascular complications according to sensor-measured TITR/TIR was analysed cross-sectionally in 808 adults with type 1 diabetes. Binary logistic regression was used to evaluate the association between TITR/TIR and the presence of complications without adjustment, with adjustment for HbA1c, and with adjustment for HbA1c and other confounding factors (sex, age, diabetes duration, BMI, BP, lipid profile, smoking, and use of statins and renin-angiotensin-aldosterone system inhibitors). RESULTS: The mean TITR and TIR were 33.9 ± 12.8% and 52.5 ± 15.0%, respectively. Overall, 46.0% had any microvascular complication (34.5% diabetic retinopathy, 23.8% diabetic nephropathy, 16.0% DPN) and 16.3% suffered from any macrovascular complication. The prevalence of any microvascular complication, diabetic retinopathy, diabetic nephropathy and a cerebrovascular accident (CVA) decreased with increasing TITR/TIR quartiles (all ptrend<0.05). Each 10% increase in TITR was associated with a lower incidence of any microvascular complication (OR 0.762; 95% CI 0.679, 0.855; p<0.001), diabetic retinopathy (OR 0.757; 95% CI 0.670, 0.856; p<0.001), background diabetic retinopathy (OR 0.760; 95% CI 0.655, 0.882; p<0.001), severe diabetic retinopathy (OR 0.854; 95% CI 0.731, 0.998; p=0.048), diabetic nephropathy (OR 0.799; 95% CI 0.699, 0.915; p<0.001), DPN (OR 0.837; 95% CI 0.717, 0.977; p=0.026) and CVA (OR 0.651; 95% CI 0.470, 0.902; p=0.010). The independent association of TITR with any microvascular complication (OR 0.867; 95% CI 0.762, 0.988; p=0.032), diabetic retinopathy (OR 0.837; 95% CI 0.731, 0.959; p=0.010), background diabetic retinopathy (OR 0.831; 95% CI 0.705, 0.979; p=0.027) and CVA (OR 0.619; 95% CI 0.426, 0.899; p=0.012) persisted after adjustment for HbA1c. Similar results were obtained when controlling for HbA1c and other confounding factors. CONCLUSIONS/INTERPRETATION: TITR and TIR are inversely associated with the presence of microvascular complications and CVA in people with type 1 diabetes. Although this study was not designed to establish a causal relationship, this analysis adds validity to the use of TITR and TIR as key measures in glycaemic management. TRIAL REGISTRATION: ClinicalTrials.gov NCT02601729 and NCT02898714.

Continuous Glucose Monitoring-Derived Glucometrics in Adults with Type 1 Diabetes When Switching Basal Insulins.

Context: Limited evidence is available on the real-world effect of insulin degludec (IDeg) in type 1 diabetes (T1D), using continuous glucose monitoring (CGM)-derived metrics. Objective: To assess the real-world effect of switching to IDeg from other long-acting insulins on time in ranges (TIRs) measured by CGM, metabolic control, and insulin dose for people with T1D. Design: This retrospective multicenter study encompassed five time points during a 12-month pre-switch of IDeg and a 12-month follow-up period. For each visit, clinical and CGM data were collected to evaluate temporal trends in glycemic outcomes. Participants: Of 753 persons with T1D who were assessed for eligibility, 486 persons were included, mostly men (61.5%), 47.4 (16.9) years old and diabetes duration of 23.8 (14.2) years at IDeg-initiation. Main Outcome Measure: Primary outcome was the evolution of percent TIR (70-180 mg/dL or 3.9-10.0 mmol/L, TIR) before versus after switch to IDeg. Results: TIR over 24 h increased at 12 months versus baseline (56.7% vs. 52.3%, P < 0.001), mostly during daytime. Time <54 mg/dL (<3.0 mmol/L) over 24 h decreased at 12 months versus baseline (2.02% vs. 2.86%, P < 0.001), mostly during nighttime. Glycated hemoglobin (7.9% vs. 8.1%, P < 0.001) and coefficient of variation (40.0% vs. 41.5%, P < 0.001) improved at 12 months versus baseline. Mean daily basal, bolus and total insulin doses decreased at 12 months (P < 0.001 for all vs. baseline). Conclusions: This retrospective real-world study reports that switching basal insulin significantly improved time spent in glucometric ranges and glycemic variability in the studied population of people with T1D. Clinical Trial Registration number: NCT05434559.

Metabolic Dysfunction-Associated Fibrosis 5 (MAF-5) Score Predicts Liver Fibrosis Risk and Outcome in the General Population With Metabolic Dysfunction.

BACKGROUND & AIMS: There is an unmet need for noninvasive tests to improve case-finding and aid primary care professionals in referring patients at high risk of liver disease. METHODS: A metabolic dysfunction-associated fibrosis (MAF-5) score was developed and externally validated in a total of 21,797 individuals with metabolic dysfunction in population-based (National Health and Nutrition Examination Survey 2017-2020, National Health and Nutrition Examination Survey III, and Rotterdam Study) and hospital-based (from Antwerp and Bogota) cohorts. Fibrosis was defined as liver stiffness ≥8.0 kPa. Diagnostic accuracy was compared with FIB-4, nonalcoholic fatty liver disease fibrosis score (NFS), LiverRisk score and steatosis-associated fibrosis estimator (SAFE). MAF-5 was externally validated with liver stiffness measurement ≥8.0 kPa, with shear-wave elastography ≥7.5 kPa, and biopsy-proven steatotic liver disease according to Metavir and Nonalcoholic Steatohepatitis Clinical Research Network scores, and was tested for prognostic performance (all-cause mortality). RESULTS: The MAF-5 score comprised waist circumference, body mass index (calculated as kg / m2), diabetes, aspartate aminotransferase, and platelets. With this score, 60.9% was predicted at low, 14.1% at intermediate, and 24.9% at high risk of fibrosis. The observed prevalence was 3.3%, 7.9%, and 28.1%, respectively. The area under the receiver operator curve of MAF-5 (0.81) was significantly higher than FIB-4 (0.61), and outperformed the FIB-4 among young people (negative predictive value [NPV], 99%; area under the curve [AUC], 0.86 vs NPV, 94%; AUC, 0.51) and older adults (NPV, 94%; AUC, 0.75 vs NPV, 88%; AUC, 0.55). MAF-5 showed excellent performance to detect liver stiffness measurement ≥12 kPa (AUC, 0.86 training; AUC, 0.85 validation) and good performance in detecting liver stiffness and biopsy-proven liver fibrosis among the external validation cohorts. MAF-5 score >1 was associated with increased risk of all-cause mortality in (un)adjusted models (adjusted hazard ratio, 1.59; 95% CI, 1.47-1.73). CONCLUSIONS: The MAF-5 score is a validated, age-independent, inexpensive referral tool to identify individuals at high risk of liver fibrosis and all-cause mortality in primary care populations, using simple variables.

The 13C glucose breath test accurately identifies insulin resistance in people with type 1 diabetes.

OBJECTIVE: This study investigated whether the delta-over-baseline of exhaled 13CO2 (Δ13CO2), generated from a 13C glucose breath test (13C-GBT), measured insulin resistance (IR) in people with type 1 diabetes, using the hyperinsulinemic-euglycemic clamp (HEC) as reference method. Secondary objective was to compare the 13C-GBT with the estimated glucose disposal rate (eGDR). METHODS: A 40 mU/m2/min HEC and two separate 13C-GBTs (euglycemic with insulin bolus and hyperglycemic without bolus) were consecutively performed in 44 adults with type 1 diabetes with varying body compositions. eGDR was calculated based on HbA1c, presence of hypertension and waist circumference. RESULTS: Mean M-value was 5.9 ± 3.1 mg/kg/min, mean euglycemic Δ13CO2 was 6.4 ± 2.1 δ‰, while median eGDR was 5.9 [4.3 - 9.8] mg/kg/min. The hyperglycemic Δ13CO2 did not correlate with the M-value, while the euglycemic Δ13CO2 and the M-value correlated strongly (r = 0.74, p < 0.001). Correlation between M-value and eGDR was more moderate (Spearman's rho = 0.63, p < 0.001). Linear regression showed an association between Δ13CO2 and M-value, adjusted for age, sex and HbA1c (adjusted R² = 0.52, B = 1.16, 95% CI 0.80 - 1.52, p < 0.001). The AUROC for Δ13CO2 to identify subjects with IR (M-value < 4.9 mg/kg/min) was 0.81 (95% CI 0.68 - 0.94, p < 0.001). The optimal cut-off for Δ13CO2 to identify subjects with IR was ≤ 5.8 δ‰. CONCLUSIONS: Under euglycemic conditions, the 13C-GBT accurately identified individuals with type 1 diabetes and concurrent IR, suggesting its potential as a valuable non-invasive index.

Effectiveness of a blended mobile-based lifestyle intervention in women with glucose intolerance after a recent history of gestational diabetes (MELINDA): a 1-year, prospective, multicentre, randomised controlled trial.

Background: Women with glucose intolerance after gestational diabetes mellitus (GDM) are at high risk to develop type 2 diabetes. Traditional lifestyle interventions in early postpartum have limited impact. We investigated the efficacy of a blended mobile-based lifestyle intervention in women with glucose intolerance after a recent history of GDM. Methods: Prospective, double-arm, non-masked, multicentre randomised controlled trial (RCT) in which women with glucose intolerance, diagnosed 6-16 weeks after a GDM-complicated pregnancy, were assigned 1:1 to a one-year blended-care, telephone- and mobile-based lifestyle program (intervention) or usual care (control). Primary endpoint was the proportion of women able to achieve their weight goal (≥5% weight loss if prepregnancy BMI ≥ 25 kg/m2 or return to prepregnancy weight if prepregnancy BMI < 25 kg/m2) in the intention-to-treat sample. Key secondary outcomes were frequency of glucose intolerance, diabetes and metabolic syndrome, and lifestyle-related outcomes assessed with self-administered questionnaires. The study was registered in ClinicalTrials.gov (NCT03559621). Findings: Between April 10th 2019 and May 13th 2022, 240 participants were assigned to the intervention (n = 121) or control group (n = 119), of which 167 (n = 82 in intervention and n = 85 in control group) completed the study. Primary outcome was achieved by 46.3% (56) of intervention participants compared to 43.3% (52) in the control group [odds ratio (OR) 1.13, 95% confidence interval (CI) 0.63-2.03, p = 0.680; risk ratio 1.07, 95% CI (0.78-1.48)]. Women in the intervention group developed significantly less often metabolic syndrome compared to the control group [7.3% (6) vs. 16.5% (14), OR 0.40, CI (0.22-0.72), p = 0.002], reported less sedentary behaviour and higher motivation for continuing healthy behaviours. In the intervention group, 84.1% (69) attended at least eight telephone sessions and 70.7% (58) used the app at least once weekly. Interpretation: A blended, mobile-based lifestyle intervention was not effective in achieving weight goals, but reduced the risk to develop metabolic syndrome. Funding: Research fund of University Hospitals Leuven, Novo Nordisk, Sanofi, AstraZeneca, Boehringer-Ingelheim, Lilly.

Evaluation of Glucose Metrics in Adults with Type 1 Diabetes Switching to Insulin Glargine 300 U/mL: A Retrospective, Propensity-Score Matched Study.

Objectives: To study real-world effect of switching to Insulin Glargine 300 U/mL (Gla-300) on glucose metrics in people with type 1 diabetes. Methods: This retrospective secondary-use study compared 151 adults who switched to Gla-300 from first-generation long-acting insulins (Switchers) to 281 propensity-score matched controls (Non-switchers) who continued first-generation long-acting insulins. Primary endpoint was difference in time in range (TIR) evolution. A fictive "switching" date was assigned to Non-switchers to facilitate between-group comparisons. Results: In the period before switching, TIR decreased numerically for people in whom Gla-300 was eventually initiated (-0.05%/month [-0.16 to 0.07]), while it increased for matched controls (0.08%/month [0.02 to 0.015]; between-group difference P = 0.047). After Gla-300-initiation, Switchers had similar TIR increase compared to Non-switchers (P = 0.531). Switchers used higher basal dose than before switch (Δ0.012 U/[kg·d] [0.006 to 0.018]; P < 0.0001). Conclusion: In real-life, Gla-300 was typically initiated in people where TIR was decreasing, which was reversed after switch using slightly higher basal insulin dose. ClinicalTrials: ClinicalTrials.gov number NCT05109520.

Cost-utility analysis of Dexcom G6 real-time continuous glucose monitoring versus FreeStyle Libre 1 intermittently scanned continuous glucose monitoring in adults with type 1 diabetes in Belgium.

AIMS/HYPOTHESIS: The aim of this study was to assess the long-term cost-effectiveness of Dexcom G6 real-time continuous glucose monitoring (rtCGM) with alert functionality compared with FreeStyle Libre 1 intermittently scanned continuous glucose monitoring (isCGM) without alerts in adults with type 1 diabetes in Belgium. METHODS: The IQVIA CORE Diabetes Model was used to estimate cost-effectiveness. Input data for the simulated baseline cohort were sourced from the randomised ALERTT1 trial (ClinicalTrials.gov. REGISTRATION NO: NCT03772600). The age of the participants was 42.9 ± 14.1 years (mean ± SD), and the baseline HbA1c was 57.8 ± 9.5 mmol/mol (7.4 ± 0.9%). Participants using rtCGM showed a reduction in HbA1c of 3.6 mmol/mol (0.36 percentage points) based on the 6-month mean between-group difference. In the base case, both rtCGM and isCGM were priced at €3.92/day (excluding value-added tax [VAT]) according to the Belgian reimbursement system. The analysis was performed from a Belgian healthcare payer perspective over a lifetime time horizon. Health outcomes were expressed as quality-adjusted life years. Probabilistic and one-way sensitivity analyses were used to account for parameter uncertainty. RESULTS: In the base case, rtCGM dominated isCGM, resulting in lower diabetes-related complication costs and better health outcomes. The associated main drivers favouring rtCGM were lower HbA1c, fewer severe hypoglycaemic events and reduced fear of hypoglycaemia. The results were robust under a wide range of one-way sensitivity analyses. In models where the price of rtCGM is €5.11/day (a price increase of 30.4%) or €12.34/day (a price increase of 214.8%), rtCGM was cost-neutral or reached an incremental cost-effectiveness ratio of €40,000 per quality-adjusted life year, respectively. CONCLUSIONS/INTERPRETATION: When priced similarly, Dexcom G6 rtCGM with alert functionality has both economic and clinical benefits compared with FreeStyle Libre 1 isCGM without alerts in adults with type 1 diabetes in Belgium, and appears to be a cost-effective glucose monitoring modality. Trial registration ClinicalTrials.gov NCT03772600.

Tirzepatide Improved Markers of Islet Cell Function and Insulin Sensitivity in People With T2D (SURPASS-2).

CONTEXT: In previous SURPASS studies tirzepatide reduced hemoglobin glycated A1c (HbA1c) and body weight and improved markers of insulin sensitivity and ß-cell function to a greater extent than comparators. OBJECTIVE: Explore changes in biomarkers of ß-cell function and insulin sensitivity and in efficacy profiles in baseline biomarker quartile analyses with tirzepatide compared to semaglutide. DESIGN: Post hoc analysis of SURPASS-2 phase 3 trial (participants randomly assigned to receive weekly subcutaneous tirzepatide or semaglutide for 40 weeks). SETTING: Post hoc analysis of 128 sites in 8 countries. PARTICIPANTS: A total of 1879 participants with type 2 diabetes. INTERVENTIONS: Once-weekly tirzepatide (5, 10, 15 mg) or semaglutide 1 mg. MAIN OUTCOMES MEASURES: Change in homeostatic model assessment indices for pancreatic ß-cell function (HOMA2-B) and for insulin resistance (HOMA2-IR), fasting glucagon, fasting C-peptide, and fasting insulin. RESULTS: At week 40, a greater increase in HOMA2-B was seen with tirzepatide (5, 10, 15 mg) doses (96.9-120.4%) than with semaglutide 1 mg (84.0%) (P < .05). There was a greater reduction in HOMA2-IR with all doses of tirzepatide (15.5%-24.0%) than with semaglutide 1 mg (5.1%) (P < .05). Tirzepatide 10 and 15 mg resulted in a significant reduction in both fasting C-peptide (5.2%-6.0%) and fasting glucagon (53.0%-55.3%) compared with an increase of C-peptide (3.3%) and a reduction of glucagon (47.7%) with semaglutide 1 mg (P < .05). HbA1c and body weight reductions were greater with all tirzepatide doses than semaglutide within each HOMA2-B and HOMA2-IR baseline quartile. CONCLUSION: In this post hoc analysis, improvements in HbA1c and weight loss were consistent and significantly higher with tirzepatide, regardless of baseline ß-cell function and insulin resistance, compared with semaglutide.

Insulin resistance and CGM-derived parameters in people with type 1 diabetes: are they associated?

BACKGROUND: Insulin resistance (IR) is increasingly more prevalent in people with type 1 diabetes (T1D). We investigated whether IR is associated with continuous glucose monitor (CGM)-derived parameters (glucometrics) such as time in range (TIR), time above range (TAR), time below range (TBR) and glycaemic variability (CV). METHODS: This is a retrospective analysis of two databases: IR was quantified according to the estimated glucose disposal rate (eGDR) (NCT04664036) and by performing a hyperinsulinaemic-euglycaemic clamp (HEC) (NCT04623320). All glucometrics were calculated over 28 days. RESULTS: A total of 287 subjects were included. Mean age was 46 ± 17 years, 55% were male, TIR was 57 ± 14% and eGDR was 7.6 (5.6 - 9.3) mg/kg min. The tertile of people with the lowest eGDR (highest level of IR) had a higher TAR compared to the tertile with the highest eGDR (39 ± 15% versus 33 ± 14, p = 0.043). Using logistic regression, a higher eGDR was associated with a higher chance to fall in a higher TIR- (OR 1.251, p < 0.001), a lower TAR- (OR 1.281, p < 0.001) and a higher TBR-tertile (OR 0.893, p = 0.039), adjusted for age, sex, diabetes duration, smoking status and alcohol intake. In the 48 people undergoing a HEC, no significant association between glucometrics and the HEC-determined glucose disposal rate (M-value) was observed. CONCLUSION: In people with T1D, an association between IR, measured by eGDR, and worse CGM profiles was observed.

Basal metabolic rate using indirect calorimetry among individuals living with overweight or obesity: The accuracy of predictive equations for basal metabolic rate.

BACKGROUND & AIMS: Weight reduction programs in people with overweight or obesity can be informed by indirect calorimetry (IC) which is the gold standard to measure basal metabolic rate (BMR). Since IC is labor intensive and expensive, predictive equations are often used as an alternative. In this study the accuracy rate was assessed and bias statistics of predictive equations were compared to IC among subjects with overweight or obesity. Secondly, differences in clinical features between individuals with over-, accurate or underestimation of their BMR were evaluated. METHODS: This cross sectional study included 731 subjects from the outpatient obesity clinic of the Antwerp University Hospital, Belgium. Fourteen equations were evaluated. Overestimation and underestimation was defined as >10 % and <10 % of measured BMR. RESULTS: In the total population, mean age was 43 ± 13 years, mean BMI 35.6 ± 5.8 kg/m2 and 79.5 % were female. The highest accuracy rates were reached by the Henry (73 %), Ravussin (73 %) and Mifflin St. Jeor (73 %) equations. In the total population, the Mifflin St. Jeor and Henry equation were unbiased. The Akern, Livingston and Ravussin equations were biased to underestimation. All other equations were biased to overestimation. Subjects with an underestimation of BMR had significantly higher waist-hip ratio (1.02 ± 0.13 vs 0.91 ± 0.11; P < 0.001), higher visceral adipose tissue (239 ± 96 vs 162 ± 93; P < 0.001), lower fat free mass (kg) (67.6 (45.4-95.9) vs 54.0 (39.6-95.5); P < 0.001) and a higher prevalence of the Metabolic Syndrome (24 (77.4) vs 112 (37.5); P < 0.001). Individuals with an overestimation of BMR had significantly higher subcutaneous adipose tissue (545 ± 149 vs 612 ± 149; P < 0.05), lower fasting plasma insulin (81 (10-2019) vs 67 (27-253); P < 0.001) and lower 2-h plasma glucose (132 (30-430) vs 116 (43-193); P < 0.001) during OGTT. CONCLUSIONS: In this study, the Henry and Mifflin St. Jeor equations have the highest accuracy and lowest bias to estimate the basal metabolic rate in a Caucasian, predominantly female, population living with overweight or obesity. Visceral and subcutaneous adipose tissue and presence of metabolic syndrome were significantly different in individuals with over- or underestimation of BMR.

Baseline plasma proinsulin response to glucose for predicting therapeutic response to otelixizumab in recent-onset type 1 diabetes.

AIMS: In recent-onset type 1 diabetes, clamp-derived C-peptide predicts good response to anti-CD3. Elevated proinsulin and proinsulin/C-peptide ratio (PI/CP) suggest increased metabolic/inflammatory beta cell burden. We reanalyzed trial data to compare the ability of baseline acutely glucose-stimulated proinsulin, C-peptide and PI/CP to predict functional outcome. METHODS: Eighty recent-onset type 1 diabetes patients participated in the placebo-controlled otelixizumab (GSK; NCT00627146) trial. Hyperglycemic clamps were performed at baseline, 6, 12 and 18 months, involving 3 h of induced euglycemia, followed by acutely raising and maintaining glycemia to ≥ 10 mmol/l for 140 min. Plasma proinsulin, C-peptide and PI/CP were determined after acute (minute 0 at 10 mmol/l; PI0, CP0, PI/CP0) and sustained glucose stimulation (AUC between minutes 60-140). Outcome was assessed as change in AUC60-140 C-peptide from baseline. RESULTS: In multiple linear regression, higher baseline (≥median [P50]) PI0 independently predicted preservation of beta cell function in response to anti-CD3 and interacted significantly with IAA. During follow-up, anti-CD3 tempered a further increase in PI/CP0, but not in PI0. CP0 outperformed PI0 and PI/CP0 for post-treatment monitoring. CONCLUSIONS: In recent-onset type 1 diabetes, elevated acutely glucose-stimulated proinsulin may complement or replace acutely or sustainedly stimulated C-peptide release for identifying good responders to anti-CD3, but not as outcome measure.

Healthcare Professionals' Knowledge of and Attitudes Towards the Use of Time in Range in Diabetes Management: Online Survey Across Seven Countries.

INTRODUCTION: Time in range (TIR) is a metric of glycaemic target management derived from continuous glucose monitoring (CGM) data. This study aimed to understand knowledge of and attitudes towards use of TIR among healthcare professionals (HCPs), and gain insights into benefits and barriers to its use in clinical practice. METHODS: An online survey was disseminated across seven countries. Participants were sampled from online HCP panels and were aware of TIR (defined as amount of time in, below, and above target range). Participants were HCPs classified as specialists (SP), generalists (GP), or allied HCPs (AP; diabetes nurse specialists, diabetes educators, general nurses, nurse practitioners/physician assistants). RESULTS: Respondents included 741 SP, 671 GP and 307 AP. Most HCPs (approximately 90%) agreed TIR is likely/somewhat likely to become the standard of diabetes management. Perceived benefits of TIR included helping to optimise medication regimen (SP, 71%; GP, 73%; AP, 74%), giving HCPs the knowledge and insights to make informed clinical decisions (SP, 66%; GP, 61%; AP, 72%), and empowering people with diabetes with information to successfully manage their diabetes (SP, 69%; GP, 77%; AP, 78%). Barriers to wider adoption included limited CGM access (SP, 65%; GP, 74%; AP, 69%) and lack of HCP training/education (SP, 45%; GP, 59%; AP, 51%). Most participants considered integration of TIR into clinical guidelines, recognition of TIR by regulators as a primary clinical endpoint, and recognition of TIR by payers as a parameter for diabetes treatment evaluation as key factors for increased use. CONCLUSIONS: Overall, HCPs agreed on the benefits of using TIR for diabetes management. Besides raising awareness among HCPs and people with diabetes, more training and healthcare system updates are needed to facilitate increased TIR use. In addition, integration into clinical guidelines and recognition by regulators and payers are needed.

'Time in range' is the proportion of time in a day that a person's glucose level is within a particular range. The purpose of this study was to understand knowledge of and attitudes towards use of TIR among healthcare professionals. The study was carried out using an online survey and participants from seven countries were included. Participants were healthcare professionals classified as specialists (SP), generalists (GP), or allied healthcare professionals (AP; diabetes nurse specialists, diabetes educators, general nurses, nurse practitioners, or physician assistants). Overall, 1719 participants were included in the study. Most healthcare professionals (approximately 90%) agreed that time in range is likely/somewhat likely to become the standard of diabetes management. Participants reported the following benefits of time in range: helping to optimise medication regimen, giving healthcare professionals the knowledge and insights to make informed clinical decisions, and empowering people with diabetes with information to successfully manage their diabetes. The most common barrier to wider time in range adoption was limited access to continuous glucose monitoring (SP, 65%; GP, 74%; AP, 69%), followed by lack of healthcare professionals' training/education (SP, 45%; GP, 59%; AP, 51%). Most participants considered integration of time in range into clinical guidelines, recognition of time in range by regulators as a primary clinical endpoint, and recognition of time in range by payers as a parameter for evaluation of diabetes treatment as key factors for the increased use of time in range.

Normal glucose tolerant women with low glycemia during the oral glucose tolerance test have a higher risk to deliver a low birth weight infant.

Background: Data are limited on pregnancy outcomes of normal glucose tolerant (NGT) women with a low glycemic value measured during the 75g oral glucose tolerance test (OGTT). Our aim was to evaluate maternal characteristics and pregnancy outcomes of NGT women with low glycemia measured at fasting, 1-hour or 2-hour OGTT. Methods: The Belgian Diabetes in Pregnancy-N study was a multicentric prospective cohort study with 1841 pregnant women receiving an OGTT to screen for gestational diabetes (GDM). We compared the characteristics and pregnancy outcomes in NGT women according to different groups [(<3.9mmol/L), (3.9-4.2mmol/L), (4.25-4.4mmol/L) and (>4.4mmol/L)] of lowest glycemia measured during the OGTT. Pregnancy outcomes were adjusted for confounding factors such as body mass index (BMI) and gestational weight gain. Results: Of all NGT women, 10.7% (172) had low glycemia (<3.9 mmol/L) during the OGTT. Women in the lowest glycemic group (<3.9mmol/L) during the OGTT had compared to women in highest glycemic group (>4.4mmol/L, 29.9%, n=482), a better metabolic profile with a lower BMI, less insulin resistance and better beta-cell function. However, women in the lowest glycemic group had more often inadequate gestational weight gain [51.1% (67) vs. 29.5% (123); p<0.001]. Compared to the highest glycemia group, women in the lowest group had more often a birth weight <2.5Kg [adjusted OR 3.41, 95% CI (1.17-9.92); p=0.025]. Conclusion: Women with a glycemic value <3.9 mmol/L during the OGTT have a higher risk for a neonate with birth weight < 2.5Kg, which remained significant after adjustment for BMI and gestational weight gain.

Prevalence, risk factors and diagnostic accuracy of non-invasive tests for NAFLD in people with type 1 diabetes.

Background & Aims: The epidemiology of non-alcoholic fatty liver disease (NAFLD) in people with type 1 diabetes (T1D) is not yet elucidated. This study aimed to assess the diagnostic accuracy of non-invasive tests for NAFLD, to investigate the prevalence and severity of NAFLD, and to search for factors contributing to NAFLD in people with T1D. Methods: In this prospective cohort study, we consecutively screened 530 adults with T1D from a tertiary care hospital, using ultrasound (US), vibration-controlled transient elastography equipped with liver stiffness measurement (LSM) and controlled attenuation parameter, and the fatty liver index. Magnetic resonance spectroscopy (MRS) was performed in a representative subgroup of 132 individuals to validate the diagnostic accuracy of the non-invasive tests. Results: Based on MRS as reference standard, US identified individuals with NAFLD with an AUROC of 0.98 (95% CI 0.95-1.00, sensitivity: 1.00, specificity: 0.96). The controlled attenuation parameter was also accurate with an AUROC of 0.85 (95% CI 0.77-0.93). Youden cut-off was ≥270 dB/m (sensitivity: 0.90, specificity: 0.74). The fatty liver index yielded a similar AUROC of 0.83 (95% CI 0.74-0.91), but the conventional cut-off used to rule in (≥60) had low sensitivity and specificity (0.62, 0.78). The prevalence of NAFLD in the overall cohort was 16.2% based on US. Metabolic syndrome was associated with NAFLD (OR: 2.35 [1.08-5.12], p = 0.031). The overall prevalence of LSM ≥8.0 kPa indicating significant fibrosis was 3.8%, but reached 13.2% in people with NAFLD. Conclusions: NAFLD prevalence in individuals with T1D is 16.2%, with approximately one in 10 featuring elevated LSM. US-based screening could be considered in people with T1D and metabolic syndrome. Impact and Implications: We aimed to report on the prevalence, disease severity, and risk factors of NAFLD in type 1 diabetes (T1D), while also tackling which non-invasive test for NAFLD is the most accurate. We found that ultrasound is the best test to diagnose NAFLD. NAFLD prevalence is 16.2%, and is associated with metabolic syndrome and BMI. Elevated liver stiffness indicating fibrosis is overall not prevalent in people with T1D (3.8%), but it reaches 13.2% in those with T1D and NAFLD.

Weight retention and glucose intolerance in early postpartum after gestational diabetes.

OBJECTIVES: To determine risk factors for early postpartum weight retention (PPWR) and glucose intolerance (GI) in women with gestational diabetes (GDM). DESIGN & METHODS: Prospective, multicenter (n=8) cohort study in 1201 women with a recent history of GDM. Pregnancy and postpartum characteristics, and data from self-administered questionnaires were collected at the 6-16 weeks postpartum 75g OGTT. RESULTS: Of all participants, 38.6% (463) had moderate (>0 and ≤5 kg) and 15.6% (187) had high (>5kg) PPWR. Independent predictors for early PPWR were excessive gestational weight gain (GWG), lack of breastfeeding, higher dietary fat intake, insulin use during pregnancy, multiparity, lower prepregnancy BMI, and lower education degree. Compared to PPWR <5 kg, women with high PPWR had a more impaired postpartum metabolic profile, breastfed less often, had higher depression rates [23.1% (43) vs. 16.0% (74), p=0.035] and anxiety levels, and lower quality of life. Of all participants, 28.0% (336) had GI [26.1% (313) prediabetes and 1.9% (23) diabetes]. Women with high PPWR had more often GI compared to women without PPWR [33.7% (63) vs. 24.9% (137), p=0.020]. Only 12.9% (24) of women with high PPWR perceived themselves at high risk for diabetes but they were more often willing to change their lifestyle than women with moderate PPWR. CONCLUSIONS: Modifiable risk factors such as lifestyle, prepregnancy BMI, GWG, and mental health can be used to identify a subgroup of women with GDM at the highest risk of developing early PPWR, allowing for a more personalized follow-up.