Huttasch M, Kahl S, Mori T
… +11 more, Heilmann G, Schön M, Trenkamp S, Kupriyanova Y, Schrauwen-Hinderling V, Wewer Albrechtsen NJ, Westhoff P, Schrauwen P, Wagner R, Roden M, GDS Group*
Diabetes Care
· 2026 Jun · PMID 41931030
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OBJECTIVE: Glucagon-based polyagonists improve metabolic dysfunction-associated steatotic liver disease (MASLD), which could result from glucagon-stimulated hepatic lipid oxidation. Nevertheless, people with long-standin...OBJECTIVE: Glucagon-based polyagonists improve metabolic dysfunction-associated steatotic liver disease (MASLD), which could result from glucagon-stimulated hepatic lipid oxidation. Nevertheless, people with long-standing type 2 diabetes (T2D) exhibit a paradoxical rise in both hepatic lipid content (HLC) and glucagon levels, which has been related to disturbed hepatic metabolism generating glucagonotropic metabolites such as amino acids and nonesterified fatty acids (NEFAs). We examined these relationships in individuals with normal glucose tolerance (NGT) and newly diagnosed T2D. RESEARCH DESIGN AND METHODS: Fifty individuals with newly diagnosed T2D and 50 age-, sex-, and BMI-matched individuals with NGT underwent liquid mixed-meal tolerance tests to measure glucagon and metabolites, hyperinsulinemic-euglycemic clamps with stable isotope dilution, indirect calorimetry to assess insulin sensitivity and lipid oxidation, and 1H/31P magnetic resonance spectroscopy and MRI to quantify HLC, ATP, and visceral adipose tissue (VAT) volume. RESULTS: Individuals with T2D had an ∼65% higher HLC as well as higher fasting and postprandial glucagonemia (∼30% and ∼75%) than those with NGT. Multivariable linear regression analyses revealed that the presence of MASLD, but not T2D, was associated with higher fasting glucagonemia. Interestingly, postprandial glucagon was related to HLC only in T2D, leading to ∼47% higher early postprandial glucagonemia in individuals with combined MASLD and T2D. These differential associations were independent of insulin sensitivity or VAT volume, and neither were mediated by amino acids or NEFAs. CONCLUSIONS: Hyperglucagonemia in the face of higher HLC in early T2D is not due to differences in insulin sensitivity or glucagonotropic metabolites but could suggest hepatic glucagon resistance.
Diabetes Care
· 2026 Jun · PMID 41931023
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OBJECTIVE: To investigate previous gestational diabetes mellitus (GDM) as a potential risk factor for diabetic retinopathy (DR) in women with diabetes, including the potential role of GDM severity and hypertension after...OBJECTIVE: To investigate previous gestational diabetes mellitus (GDM) as a potential risk factor for diabetic retinopathy (DR) in women with diabetes, including the potential role of GDM severity and hypertension after pregnancy. RESEARCH DESIGN AND METHODS: A nationwide, register-based cohort study included all women giving birth in Denmark in 1997-2018. We defined GDM and DR using ICD-10 codes. GDM severity was a proxy based on insulin treatment during GDM pregnancy. Subsequent diabetes and hypertension were based on ICD-10 codes and/or medication postpregnancy. Statistical analyses included Cox regression. RESULTS: The complete study population comprised 708,250 women. The GDM prevalence was 3.4%, and the overall median follow-up was 12 years. Diabetes developed subsequently in 18,556 women, and DR occurred in 655 of these. In the women who developed diabetes, previous GDM was associated with a threefold higher risk of DR (adjusted hazard ratio [aHR] 3.0 [95% CI 2.6-3.6]). The risk increased with increasing GDM severity (aHRs 5.6 [95% CI 4.5-6.9] and 2.4 [95% CI 2.0-2.9]) in women with previous GDM with and without insulin treatment, respectively, compared with women without previous GDM [reference group]). In women with subsequent hypertension, GDM exposure was associated with a 2.7-fold higher DR risk (aHR 2.7 [95% CI 2.1-3.5]). CONCLUSIONS: This large population-based study identified GDM as a significant risk factor for DR in parous women with diabetes, a risk that increased with increasing GDM severity and postpregnancy hypertension development. On the basis of this study, planning of DR screening strategies should include awareness of GDM history.
Karakus KE, Clayton MG, Baschal EE
… +8 more, McDaniel KA, Yu L, Haider Z, Polsky S, Akturk HK, Gottlieb PA, Garg SK, Michels AW
Diabetes Care
· 2026 Jul · PMID 41925716
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OBJECTIVE: Adult-onset type 1 diabetes is not well characterized, especially after 40 years of age, and is commonly misdiagnosed as type 2 diabetes. We evaluated the differences in clinical presentation, islet autoantibo...OBJECTIVE: Adult-onset type 1 diabetes is not well characterized, especially after 40 years of age, and is commonly misdiagnosed as type 2 diabetes. We evaluated the differences in clinical presentation, islet autoantibodies, and HLA genetics between pediatric- and adult-onset type 1 diabetes. RESEARCH DESIGN AND METHODS: Individuals who were newly diagnosed with type 1 diabetes were tested for islet autoantibodies within 1 year of diagnosis in this retrospective study. Islet autoantibodies against GAD, insulin, islet antigen 2, and zinc transporter 8 were measured using fluid-phase radiobinding assays. High-resolution HLA class I (n = 655) and II (n = 1,196) typing was performed in a subset of participants. RESULTS: In total, 414 adults (aged ≥20 years) and 2,000 children were included. Adults were aged 20-76 years and had a mean BMI of 23.5 ± 4.7 kg/m2 at onset. Compared with children, adults presented with diabetic ketoacidosis (DKA) less frequently (32.6% vs. 56.0%; P < 0.001) and with slightly lower HbA1c values (11.3% ± 2.6% vs. 12.0% ± 2.4%; P < 0.001). Notably, adults older than 40 years (n = 84) presented with DKA only 13.1% of the time. Adults more often presented with zero or one islet autoantibodies compared with children (43.0% vs. 20.2%; P < 0.001). There were no differences in high-risk HLA haplotypes between adults and children (DR4-DQ8: 57.1% vs. 63.7%; P = 0.060; DR3-DQ2: 43.6% vs. 46.1%; P = 0.482). CONCLUSIONS: Adult-onset type 1 diabetes is characterized by a reduced frequency of DKA and by fewer total islet autoantibodies. Our findings can help in the accurate diagnosis of type 1 diabetes in adults.
Bergenstal RM, Crandall JP, Rosin SP
… +13 more, Butera NM, Bantle A, Desouza C, Duran-Valdez E, Hall S, Herman WH, Johnson ML, Lagari V, Larkin ME, Phillips LS, Willis HJ, Krause-Steinrauf H, GRADE Research Group*
Diabetes Care
· 2026 Jun · PMID 41925680
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OBJECTIVE: Glycemic management metrics derived from continuous glucose monitoring (CGM) are increasingly recognized as important therapeutic targets. We performed one of the first comparisons of CGM metrics and achieveme...OBJECTIVE: Glycemic management metrics derived from continuous glucose monitoring (CGM) are increasingly recognized as important therapeutic targets. We performed one of the first comparisons of CGM metrics and achievement of CGM targets among four classes of glucose-lowering medications in combination with metformin. RESEARCH DESIGN AND METHODS: The Glycemia Reduction Approaches in Diabetes (GRADE) study randomly assigned participants with type 2 diabetes and taking metformin to add one of four glucose-lowering medications (insulin glargine, glimepiride, liraglutide, or sitagliptin) and followed them for glycemic outcomes for 5 ± 1.3 years. A 2-week masked CGM analysis was conducted midstudy in 1,080 participants to evaluate CGM metrics, 24-h ambulatory glucose profile, and achievement of consensus goals. Treatment effects among the four groups were compared. RESULTS: The sitagliptin and liraglutide groups had the highest time in range 70-180 mg/dL (TIR70-180) and the lowest time below range <70 mg/dL (TBR<70) and percentage coefficient of variation (%CV). The glimepiride group had the lowest TIR70-180, and the highest %CV, TBR<70, and number of CGM-derived hypoglycemic events (P < 0.001), and was the only drug showing daytime hypoglycemia. Sitagliptin and liraglutide were best for achieving consensus goals of very low TBR<54 <1% and the combined metric of TIR70-180 >70% and TBR<70 <4% (P < 0.001). When stratified by HbA1c, mean glucose did not differ among treatments, but %CV and TBR<70 were higher with glargine and glimepiride within each HbA1c stratum. CONCLUSIONS: Incretin class drugs had the lowest %CV, the least hypoglycemia, and best achievement of CGM-based glycemic targets. CGM metrics and profiles provide clinical insights, beyond HbA1c, to guide diabetes management.
Wan Y, Alessa HB, Guasch-Ferré M
… +6 more, Tobias DK, Lee KH, Manson JE, Willett WC, Sun Q, Hu FB
Diabetes Care
· 2026 Jun · PMID 41920710
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OBJECTIVE: To examine the association between fiber from various food sources and type 2 diabetes (T2D) risk, as well as the molecular profiles involved. RESEARCH DESIGN AND METHODS: Using data from three large prospecti...OBJECTIVE: To examine the association between fiber from various food sources and type 2 diabetes (T2D) risk, as well as the molecular profiles involved. RESEARCH DESIGN AND METHODS: Using data from three large prospective U.S. cohorts comprising 195,222 participants observed for up to 34 years, we evaluated the association between fiber from various food sources and T2D risk. We also assessed the association between fiber intake, plasma metabolic biomarkers, and a metabolomic profile indicative of T2D risk. Additionally, we examined gut microbial features related to fiber intake and the T2D metabolomic profile. RESULTS: During follow-up, we documented 18,369 incident T2D cases. Higher intakes of total fiber (hazard ratio [HR] comparing extreme quintiles 0.88; 95% CI 0.82, 0.94), cereal fiber (HR 0.77; 95% CI 0.73, 0.82), and fruit fiber (HR 0.82; 95% CI 0.78, 0.87) were each associated with a lower T2D risk. Greater intakes of total fiber, cereal fiber, and fruit fiber, but not vegetable fiber, were linked to more favorable plasma profiles of insulinemic, lipid, and inflammatory biomarkers and a metabolomic profile indicative of a lower T2D risk. We also identified multiple gut microbial species, such as Faecalibacterium prausnitzii, Ruminococcus lactaris, and Gemmiger formicilis, along with relevant butyric acid-producing enzymes, all of which were associated with higher fruit fiber intake and a metabolomic profile indicating a lower likelihood of T2D development. CONCLUSIONS: Higher intakes of total, cereal, and fruit fiber are associated with a lower risk of T2D and a more favorable metabolic profile, with the gut microbiome potentially contributing to the beneficial association of fruit fiber.
Daultrey HE, Oliver NS, Chakera AJ
… +3 more, de la Cruz Libardi A, Iwuji CC, Gasparrini A
Diabetes Care
· 2026 Mar · PMID 41915489
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OBJECTIVE: To investigate the short-term association between ambient temperature and risk of hypoglycemia in adults with type 1 diabetes mellitus (T1DM). We hypothesized that higher ambient temperature would increase the...OBJECTIVE: To investigate the short-term association between ambient temperature and risk of hypoglycemia in adults with type 1 diabetes mellitus (T1DM). We hypothesized that higher ambient temperature would increase the odds of hypoglycemia developing. RESEARCH DESIGN AND METHODS: We applied a case time series design to assess the longitudinal association between ambient temperature and hypoglycemia measured using routine continuous glucose monitoring data from individuals with T1DM. A quasi-binomial fixed-effect regression with distributed lag nonlinear models was used to estimate potentially nonlinear and lagged risks of nonoptimal temperature on hypoglycemic episodes, defined as ≥15 min of glucose concentration <3.9 mmol/L. The model was adjusted for long-term trends, seasonality, day of the week, and public holidays. A secondary outcome was change in daily mean glucose concentration. RESULTS: We analyzed 32,966,282 glucose readings from 679 adults with T1DM attending two National Health Service clinics in Sussex, England, between 2017 and 2024. Higher ambient temperatures were associated with an increased risk of hypoglycemia. The risk increased nonlinearly for temperatures above 13°C, with the odds ratio reaching 1.26 (95% CI 1.13-1.26) at 25°C. The strongest effect was observed on the same day of the exposure, and it diminished over subsequent days. In the secondary analysis, higher temperatures were associated with lower mean glucose levels. CONCLUSIONS: Elevated ambient temperature significantly increases the short-term risk of hypoglycemia in adults with T1DM. These findings are specific to the U.K. population and climate, which may limit generalizability. Our results support anticipatory insulin adjustments during hot weather and consideration of ambient temperature in hybrid closed-loop insulin algorithms.
Lizoain A, Vettoretti M, Ferreira A
… +8 more, Schönenberger KA, Streicher O, Rolfes E, Braunack-Mayer V, Facchinetti A, Herzig D, Rothenbühler M, Bally L
Diabetes Care
· 2026 Jun · PMID 41915461
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OBJECTIVE: Although continuous glucose monitors (CGMs) are increasingly used to detect and manage postbariatric hypoglycemia (PBH) and associated glucose variability, data on their accuracy in this population remain scar...OBJECTIVE: Although continuous glucose monitors (CGMs) are increasingly used to detect and manage postbariatric hypoglycemia (PBH) and associated glucose variability, data on their accuracy in this population remain scarce. RESEARCH DESIGN AND METHODS: We retrospectively assessed the accuracy of the Dexcom G6 CGM system in adults with PBH after Roux-en-Y gastric bypass (RYGB) surgery (n = 70). Glucose excursions were induced using a standardized solid mixed-meal test, and reference blood glucose (BG) values were obtained through repeated venous whole-blood sampling. CGM accuracy was analyzed separately during stable and dynamic postmeal glucose periods, with dynamic phases stratified according to magnitude and direction of the rate of change (RoC). We further estimated the lag time for each sensor and examined predictive factors affecting CGM accuracy. RESULTS: A total of 1,822 CGM-BG pairs obtained with 70 individuals were included in the analysis. Mean absolute relative differences at stable and dynamic levels were 9.6% and 16.4%, respectively. After the meal test, 67.6% of pairs had CGM values within 15%, or 15 mg/dL of the reference BG; 78.0% within 20%, or 20 mg/dL; and 90.8% within 30%, or 30 mg/dL. Performance was worse at rapid plasma glucose decline (>1.5 mg/dL/min), and CGM values at the time of plasma glucose nadir were systematically higher (bias, 8.2 mg/dL). Plasma-interstitium time delay was estimated at 9.8 min. No participant or sensor characteristic had a significant impact on CGM accuracy. CONCLUSIONS: Meal-induced glucose dynamics, particularly rapid declines, challenge CGM accuracy in people with PBH and must be carefully considered when diagnosing or managing the condition.
Gupta RM, Ismail HM, Siller AF
… +4 more, Pesikoff J, Devaraj S, Balasubramanyam A, Redondo MJ
Diabetes Care
· 2026 Mar · PMID 41915459
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Type 1 diabetes arises from the interplay of genetic susceptibility and environmental exposures, leading to autoimmune β-cell destruction. Although disease-modifying therapies (DMTs) can delay progression to clinical (st...Type 1 diabetes arises from the interplay of genetic susceptibility and environmental exposures, leading to autoimmune β-cell destruction. Although disease-modifying therapies (DMTs) can delay progression to clinical (stage 3) type 1 diabetes, treatment responses remain inconsistent and transient. The marked heterogeneity of type 1 diabetes, shaped by age, sex, race/ethnicity, and genetic background, underscores the need to elucidate distinct mechanistic pathways. Among environmental contributors, obesity stands out as a compelling modifiable target. Data from The Environmental Determinants of Diabetes in the Young (TEDDY), Type 1 Diabetes TrialNet, and other longitudinal cohorts link BMI and adiposity to the onset of islet autoimmunity, progression through preclinical stages, and development of stage 3 type 1 diabetes. These associations are not uniform; heightened susceptibility to adiposity-related risk is seen among younger children, Hispanic populations, and individuals with specific HLA genotypes. Despite robust epidemiologic evidence, the biological pathways connecting elevated BMI to autoimmune β-cell destruction remain incompletely defined. Emerging data implicate a network of immunologic and metabolic disturbances, including insulin resistance, β-cell stress, chronic adipose tissue inflammation, altered adipokine signaling, and gut microbiome changes, that collectively heighten β-cell vulnerability, amplify autoreactive immune responses, and drive metabolic decompensation toward clinical disease. Elucidating these mechanisms and identifying related biomarkers are critical to advancing precision prevention. In future studies, investigators should evaluate whether modifying elevated BMI or targeting obesity-associated immunologic and metabolic pathways can alter the preclinical trajectory of type 1 diabetes. Such mechanistic understanding may help curb type 1 diabetes incidence and improve outcomes for populations most vulnerable to obesity-related risk.
Pan M, Al-Sharify D, Engström G
… +6 more, Ahlqvist E, Lotta L, Nilsson J, Goncalves I, Sun J, Edsfeldt A
Diabetes Care
· 2026 May · PMID 41912451
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OBJECTIVE: Diabetes significantly increases the risk for atherosclerotic complications, including coronary artery disease (CAD). Previous studies have suggested that adult-onset diabetes can be classified into five diffe...OBJECTIVE: Diabetes significantly increases the risk for atherosclerotic complications, including coronary artery disease (CAD). Previous studies have suggested that adult-onset diabetes can be classified into five different clinical subtypes, including moderate obesity-related diabetes (MOD). The aim of this study was to investigate the genetic associations between the five diabetes subtypes and the risk of developing CAD and diabetes in the general population. RESEARCH DESIGN AND METHODS: The Malmö Diet and Cancer cohort (N = 24,025) was used to assess whether polygenic risk scores (PRSs) for the five diabetes subtypes could predict future diabetes and CAD. Genetic correlations and causal effects of the MOD subtype on CAD were investigated using data from large genome-wide association studies of the MOD subtype (N = 4,116) and CAD (N = 296,525). RESULTS: During follow-up, 4,105 participants (17.1%) developed diabetes (median follow-up 24.0 years) and 3,841 (16.0%) developed CAD (median follow-up 24.6 years). PRS for MOD (PRSMOD) was associated with incident diabetes and CAD. In addition, participants in the third tertile of PRSMOD had a 1.10-fold higher risk of developing CAD compared with those in the first tertile. A positive genetic correlation between MOD and CAD was observed, and Mendelian randomization analyses suggested a causal effect of MOD on CAD. CONCLUSIONS: The current study showed that the genetic susceptibilities for all five diabetes subtypes were associated with incident diabetes. However, only the MOD subtype was associated with incident CAD. These findings underscore the significance of a high genetic risk for MOD as an early marker for CAD.
Kok N, Williamson WT, Lee JM
… +1 more, Gaynanova I
Diabetes Care
· 2026 Jun · PMID 41911328
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OBJECTIVE: Consensus guidelines recommend at least 14 consecutive days of continuous glucose monitoring (CGM) with 70% completeness to represent 90-day glycemic exposure. This study quantifies bias and uncertainty introd...OBJECTIVE: Consensus guidelines recommend at least 14 consecutive days of continuous glucose monitoring (CGM) with 70% completeness to represent 90-day glycemic exposure. This study quantifies bias and uncertainty introduced into downstream analyses by using CGM metrics from incomplete or reduced monitoring, relative to a 90-day complete profile. RESEARCH DESIGN AND METHODS: Using a type 1 diabetes cohort with 1,010 complete 90-day CGM profiles, we simulated incomplete profiles by varying monitoring duration and data completeness. Consensus CGM metrics were computed on incomplete and complete profiles to quantify measurement error, which was propagated into two downstream regression models: 1) CGM metric is an outcome for a binary treatment (clinical trial setting); 2) CGM metric is an explanatory variable (covariate) for another continuous outcome. Bias was quantified using observed-to-true effect size ratios and uncertainty by the sample size increase required to maintain precision. RESULTS: In the clinical trial setting, treatment effects remain unbiased but lose precision; for time in range (TIR), 14 days required ≥16% more participants versus 90 days; 30 days required ≥6.5%. When the CGM metric is a covariate, associations with outcomes are attenuated (biased toward zero up to 14% at 14 days and 6% at 30 days for TIR) and less precise. CONCLUSIONS: Representing 90 days of glycemic exposure with 14 days can lead to bias and loss of precision in downstream analyses. We recommend study protocols require at least 30 days of CGM with 70% completeness. If 30 days is not feasible, studies should plan for increased sample sizes.
Maher MD, Vigers T, Kohler C
… +4 more, Stecenko AA, Moran A, Chan CL, Phillips LS
Diabetes Care
· 2026 May · PMID 41911242
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OBJECTIVE: Cystic fibrosis (CF)-related diabetes (CFRD) affects nearly half of adults with CF, but screening rates with the recommended oral glucose tolerance test (OGTT) are low. We evaluated the utility of a nonfasting...OBJECTIVE: Cystic fibrosis (CF)-related diabetes (CFRD) affects nearly half of adults with CF, but screening rates with the recommended oral glucose tolerance test (OGTT) are low. We evaluated the utility of a nonfasting, 50-g, 1-h oral glucose challenge test (GCT) as first-line screening for CFRD and pre-CFRD. The objectives were to define a cutoff that provides high sensitivity and reasonable specificity, and to determine how GCT compares with other opportunistic tests. RESEARCH DESIGN AND METHODS: Participants with CF ≥10 years old, without known diabetes, had baseline random plasma and capillary glucose (RPG and RCG), then underwent an in-clinic GCT for collection of 1-h plasma glucose (GCTpl). This was followed by hemoglobin A1C (HbA1c) and OGTT on a separate day. Receiver operating characteristic (ROC) curves were generated for identifying CFRD and pre-CFRD. RESULTS: Of 185 participants, 94 had normal glucose tolerance, 81 had pre-CFRD, and 10 had CFRD. For detecting pre-CFRD or CFRD, GCTpl had an area under the ROC curve (ROC-AUC) of 0.73 (95% CI 0.65-0.80), higher than ROC-AUCs for RPG of 0.56 (0.48-0.65, P = 0.003), RCG of 0.55 (0.46 = 0.63, P = 0.002), and HbA1c of 0.62 (0.53-0.67, P = 0.02). The ROC-AUC for detecting CFRD was 0.75 (0.64-0.86) for GCTpl, 0.64 (0.42-0.87) for RPG, and 0.56 (0.39-0.73) for HbA1c. A GCTpl of 147 mg/dL provides 90% sensitivity and 58% specificity for detecting CFRD and could reduce the OGTTs needed by 56%. CONCLUSIONS: GCT offers a practical, in-clinic method for CFRD screening. This spares low-risk individuals from OGTT, while maintaining high sensitivity for CFRD.
Klein KR, Menacher A, Buse JB
… +6 more, Mann JFE, Tuttle KR, Kvist K, Andersen MR, Mayrdorfer M, Lingvay I
Diabetes Care
· 2026 Jun · PMID 41893299
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OBJECTIVE: People receiving dialysis are at high risk of cardiovascular and all-cause mortality. Semaglutide reduces major adverse cardiovascular events (MACE) in people with type 2 diabetes (T2D) and those without T2D w...OBJECTIVE: People receiving dialysis are at high risk of cardiovascular and all-cause mortality. Semaglutide reduces major adverse cardiovascular events (MACE) in people with type 2 diabetes (T2D) and those without T2D with obesity and high cardiovascular risk. Data to establish safety and efficacy in dialysis-dependent kidney failure are scarce. We aimed to assess the safety of semaglutide in people who initiate dialysis. RESEARCH DESIGN AND METHODS: In this post hoc analysis of four randomized, placebo-controlled trials (Trial to Evaluate Cardiovascular and Other Long-term Outcomes With Semaglutide in Subjects With Type 2 Diabetes [SUSTAIN-6], Semaglutide Effects on Cardiovascular Outcomes in People with Overweight or Obesity [SELECT], Evaluate Renal Function With Semaglutide Once Weekly [FLOW], and Semaglutide Cardiovascular Outcomes [SOUL]), we evaluated systematically collected adverse events (AEs) from participants who initiated dialysis during study follow-up. We compared the proportion and event rates of systematically collected serious AEs (SAEs), including adjudicated MACE, and AEs leading to permanent treatment discontinuation in participants originally randomized to semaglutide or placebo who remained on treatment after dialysis initiation. RESULTS: Among 34,064 participants randomized across the trials, 307 initiated dialysis, of whom 165 participants randomized to semaglutide (n = 71) or placebo (n = 94) remained on treatment. After dialysis initiation, SAEs were reported in 32 of 71 (45%) and 54 of 94 (57%) participants, and the proportion of participants who permanently discontinued trial medication was 8.5% and 10.6% in the semaglutide and placebo groups, respectively. The MACE event rates were 9.7 and 16.1 events per 100 person-years, and all-cause mortality event rates were 13.8 and 18.1 events per 100 person-years, in the semaglutide and placebo groups, respectively. CONCLUSIONS: Although more evidence is needed, continuation of semaglutide after dialysis initiation appears safe and warrants efficacy testing regarding reduction in MACE and death.
Bragg F, Alegre-Diaz J, Trichia E
… +19 more, Torres JM, Baca P, Garcilazo-Ávila A, González-Carballo C, Ramirez-Reyes R, Rivas F, Aguilar-Ramirez D, Gnatiuc Friedrichs L, Herrington WG, Hill M, Hubbard T, Vergara A, Wade R, Collins R, Peto R, Berumen J, Kuri-Morales P, Tapia-Conyer R, Emberson JR
Diabetes Care
· 2026 May · PMID 41892798
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OBJECTIVE: The Mexican population experiences a notably high prevalence of type 2 diabetes (T2D) and high T2D-associated disease risks. We used targeted plasma nuclear magnetic resonance metabolomics data within a Mendel...OBJECTIVE: The Mexican population experiences a notably high prevalence of type 2 diabetes (T2D) and high T2D-associated disease risks. We used targeted plasma nuclear magnetic resonance metabolomics data within a Mendelian randomization framework to characterize the metabolomic profile of genetically predicted liability to T2D in this population. RESEARCH DESIGN AND METHODS: Between 1998 and 2004, 50,000 men and 100,000 women aged ≥35 years were recruited from Mexico City. Mendelian randomization analyses used a genetic risk score (GRS) comprising 1,055 established T2D-associated risk variants and eight pathway-specific T2D GRSs constructed from nonoverlapping subsets of these variants to estimate associations with 143 metabolic biomarkers (including lipids, lipoproteins, fatty acids, amino acids, ketone bodies, and other low-molecular-weight biomarkers). RESULTS: Among 125,587 included participants, the T2D GRS explained 6.0% of T2D liability and was not associated with major potential confounders of the relationships of T2D with the circulating metabolome. Genetically predicted liability to T2D was strongly positively associated with concentrations of VLDL particles and lipids within these, with triglycerides, branched-chain amino acids, and glycoprotein acetyls, and more modestly positively associated with intermediate-density lipoprotein and LDL, particularly small LDL, particles. Inverse associations were found with relative concentrations of several fatty acids. Pathway-specific T2D GRSs all associated with higher T2D risk but showed differential relationships with circulating metabolic biomarkers. CONCLUSIONS: T2D is associated with widespread changes in the circulating metabolome among adults in Mexico, reflecting diverse biological mechanisms and highlighting the importance of effective T2D management, including control of T2D-associated dyslipidemia, in this population.
Leohr JK, Abitbol A, Turner LV
… +4 more, Smith LaBell E, Ghosh A, Coutant DE, Riddell MC
Diabetes Care
· 2026 Jul · PMID 41885780
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OBJECTIVE: To compare the glycemic response and pharmacokinetics (PK) of ultra-rapid lispro (URLi) versus lispro during manual basal rate reductions (BRRs) before exercise with conventional continuous subcutaneous insuli...OBJECTIVE: To compare the glycemic response and pharmacokinetics (PK) of ultra-rapid lispro (URLi) versus lispro during manual basal rate reductions (BRRs) before exercise with conventional continuous subcutaneous insulin infusion (CSII) in active adults with type 1 diabetes. RESEARCH DESIGN AND METHODS: This study was a double-blind, four-period, crossover, randomized controlled trial. Exercise (60 min walking at 45-55% VO2max) was performed 4 h after a standardized meal, with either a 50% (-60 min) or 100% (-15 min) BRR before exercise using URLi or lispro. The primary end point was the change in glucose during exercise, and insulin lispro PK was the secondary end point. RESULTS: Twenty-five participants (mean ± SD age 36.7 ± 10.3 years; mean ± SD HbA1c 50.4 ± 8.5 mmol/mol [6.76 ± 0.8%]; 48% female) completed the study. URLi significantly attenuated the reduction in glucose level compared with lispro during both the 50% BRR (-26.8 ± 37 vs. -39.0 ± 39 mg/dL; P < 0.05) and the 100% BRR (-46.9 ± 32 vs. -60.5 ± 39 mg/dL; P < 0.01). Circulating insulin lispro concentrations rose in the first 15 min of exercise, but maximum concentration was lower with URLi versus lispro within each BRR strategy. Numerically less hypoglycemia was observed during exercise with URLi (6%) compared with lispro (16%). Following a postexercise meal, faster insulin absorption of URLi resulted in an earlier postprandial glucose lowering compared with lispro. CONCLUSIONS: Using URLi in conventional CSII pump therapy provides more effective BRRs prior to exercise compared with lispro, with fewer hypoglycemic events in active adults with type 1 diabetes.
Dupenloup P, Chen Y, Prahalad P
… +8 more, Johari R, Addala A, Zaharieva DP, Lee MY, Maahs DM, Scheinker D, Brandeau ML, 4T Research Team*
Diabetes Care
· 2026 May · PMID 41879358
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OBJECTIVE: The use of continuous glucose monitoring (CGM) with remote patient monitoring (RPM) continues to grow. We evaluated the cost-effectiveness of CGM with RPM compared with self-monitoring of blood glucose (SMBG)...OBJECTIVE: The use of continuous glucose monitoring (CGM) with remote patient monitoring (RPM) continues to grow. We evaluated the cost-effectiveness of CGM with RPM compared with self-monitoring of blood glucose (SMBG) and CGM alone. RESEARCH DESIGN AND METHODS: We simulated type 1 diabetes progression with a Markov model in 5-year-old patients over a 20-year, 50-year, and lifetime horizon. We tracked diabetic ketoacidosis (DKA), severe hypoglycemia (SH), and seven chronic complications: retinopathy, neuropathy, nephropathy, cardiovascular disease, end-stage renal disease, lower-extremity amputation, and blindness. We compared three interventions: SMBG, CGM, and CGM with RPM. Efficacy estimates were derived from meta-analyses of pediatric CGM studies and the results of the Teamwork, Targets, Technology, and Tight Glycemia Study (4T Study 1). We evaluated quality-adjusted life years (QALYs) and health care costs (2022 U.S. dollars) discounted at 3% annually. We performed extensive sensitivity analyses. RESULTS: Compared with SMBG, CGM increased QALYs by 0.09 and costs by $8,900 over 20 years; CGM with RPM increased QALYs by 0.37, and costs by $10,300. CGM with RPM yielded more QALYs at a lower incremental cost-effectiveness ratio compared with CGM ($27,400/QALY vs. $103,700/QALY, respectively). Results were robust across sensitivity analyses and time horizons. CGM with RPM remained cost-effective when achieving at least 30% of 4T's clinical efficacy. CONCLUSIONS: CGM with RPM delivers superior health outcomes compared with SMBG and CGM and is likely cost-effective for patients with newly diagnosed type 1 diabetes. Despite higher intervention costs, CGM with RPM can reduce complications costs and generate net health care savings.
Brown CJ, Roesch SC, Rosas CE
… +8 more, McCurley JL, Cordero C, Trifan G, Testai F, Zhao B, Cai J, Isasi CR, Gallo LC
Diabetes Care
· 2026 May · PMID 41875073
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OBJECTIVE: Social determinants of health (SDoHs) account for more than half of the variance in racial and ethnic disparities in health. However, few studies have examined how SDoHs may cluster in ways that affect health....OBJECTIVE: Social determinants of health (SDoHs) account for more than half of the variance in racial and ethnic disparities in health. However, few studies have examined how SDoHs may cluster in ways that affect health. We aimed to identify patterns of social adversity and their differential associations with both diabetes status at baseline and change in diabetes status across ∼12 years among Hispanic/Latino adults. RESEARCH DESIGN AND METHODS: Participants were from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL; N = 16,415; aged 18-74 years). Diabetes status (defined as normoglycemia, prediabetes, or diabetes per American Diabetes Association criteria) was measured by clinical assessment and self-reported medications at baseline (2008-2011) and two follow-up visits (2014-2017 and 2020-2024). SDoHs were assessed at baseline and as part of the HCHS/SOL Sociocultural Ancillary Study (2010-2012). RESULTS: Latent class analyses of nine SDoHs (income, education, employment status, home ownership, language and social acculturation, chronic stressors, family cohesion, and social support) revealed four distinct patterns of social adversity: 1) low adversity, 2) social/educational strengths, 3) acculturated and underresourced, and 4) high adversity. Compared with the low-adversity group, the high-adversity group had the highest odds of worse diabetes status at baseline and had greater odds of worsening diabetes status over time. CONCLUSIONS: SDoHs cluster in distinct ways that affect diabetes outcomes; social adversities must be addressed to mitigate diabetes burden among Hispanic/Latino adults.
Starling AP, Burjak M, Nzegwu AW
… +27 more, Xun X, Adgate JL, Barrett ES, Bennett DH, Chatzi L, Colicino E, Dabelea D, Dunlop AL, Eick SM, Farzan SF, Ferrara A, Fleisch AF, Geiger SD, Hedderson MM, Kahn LG, Karagas MR, Kelly RS, Liang D, Lin PI, O'Connor TG, Padula AM, Peterson AK, Romano ME, Sathyanarayana S, Zhu Y, Valvi D, ECHO Cohort Consortium*
Diabetes Care
· 2026 May · PMID 41875060
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OBJECTIVE: Exposure to per- and polyfluoroalkyl substances (PFAS) may increase the risk of gestational diabetes mellitus (GDM), with adverse consequences for pregnant women and their offspring. However, epidemiologic stu...OBJECTIVE: Exposure to per- and polyfluoroalkyl substances (PFAS) may increase the risk of gestational diabetes mellitus (GDM), with adverse consequences for pregnant women and their offspring. However, epidemiologic studies have shown inconsistent results. We addressed this question in a large, pooled sample of U.S. women. RESEARCH DESIGN AND METHODS: Participants (n = 5,229) from 16 cohorts had singleton pregnancies. PFAS were quantified in a single plasma or serum sample during pregnancy (1999-2021); six PFAS detected in ≥60% of participants were analyzed. The primary outcome was GDM diagnosis based on self-report or medical record documentation. The secondary outcome, among 1,213 participants, was fasting glucose. We estimated associations between each PFAS and GDM using generalized estimating equations models with Poisson distribution and robust variance, and estimated associations between each PFAS and fasting glucose using generalized estimating equations models for linear regression. Effect modification by prepregnancy BMI or race and ethnicity was evaluated via interaction terms and stratification. We quantified the combined effect of the PFAS mixture using quantile-based g-computation. RESULTS: Associations between individual PFAS and GDM were null or weakly inverse; the association with the six-PFAS mixture was negative (prevalence ratio [95% CI] per quartile increase: 0.75 [0.58, 0.96]). Certain PFAS were more strongly negatively associated with GDM among participants with BMI <25 kg/m2. Associations between PFAS and fasting glucose were largely null, although both positive and negative associations were observed in specific race and ethnicity strata. CONCLUSIONS: In a large, pooled sample of U.S. pregnant women, greater concentrations of PFAS were not associated with higher prevalence of GDM.