OBJECTIVE: To investigate the change in prevalence of impaired awareness of hypoglycemia (IAH) and severe hypoglycemia (SH) across three cohorts (2002, 2015, and 2024) in youth with type 1 diabetes. RESEARCH DESIGN AND M...OBJECTIVE: To investigate the change in prevalence of impaired awareness of hypoglycemia (IAH) and severe hypoglycemia (SH) across three cohorts (2002, 2015, and 2024) in youth with type 1 diabetes. RESEARCH DESIGN AND METHODS: Youth (12-18 years old) completed a Modified Clarke questionnaire to assess IAH. Prevalence of IAH and recent SH was compared across cohorts. Continuous glucose monitoring (CGM)-derived metrics were compared between those with and without IAH in 2024. RESULTS: IAH prevalence was 15.9% compared with 33.1% in 2002 (P < 0.001) and 21.4% in 2015 (P = 0.051). The 2024 SH rate was 0.92 per 100 patient-years, 3.5-fold lower (95% CI 1.2, 12.5) than in 2015 and 30-fold lower (12.7, 98.9) than in 2002 despite HbA1c reduction across cohorts (P < 0.001). Hypoglycemia exposure did not differ between IAH and non-IAH when analyzing CGM metrics (P > 0.05). CONCLUSIONS: IAH and SH have declined substantially over two decades, reflecting improved diabetes care. However, ongoing IAH signifies the need for routine screening.
Luk AOY, O CK, Fan B
… +19 more, Lau ESH, Fan Y, Lim C, Lui JNM, Wong KTC, Tsoi STF, Poon EWM, Lai WY, Wan R, Wong SYS, Wang MH, Lee EKP, Ho JPY, Cheung E, Chow E, Ozaki R, Kong APS, Ma RCW, Chan JCN
Diabetes Care
· 2026 Jul · PMID 42118608
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OBJECTIVE: Young-onset type 2 diabetes (YOD) results from complex causes, calling for precision management. RESEARCH DESIGN AND METHODS: The Precision Medicine to Redefine Insulin Secretion and Monogenic Diabetes (PRISM)...OBJECTIVE: Young-onset type 2 diabetes (YOD) results from complex causes, calling for precision management. RESEARCH DESIGN AND METHODS: The Precision Medicine to Redefine Insulin Secretion and Monogenic Diabetes (PRISM) study was a single-center, two-arm, 3-year randomized controlled trial in which Chinese individuals aged 18 to 50 years with non-type 1 diabetes diagnosed at age ≤40 years were randomly assigned to intervention (Joint Asia Diabetes Evaluation [JADE]-PRISM) or usual clinic-based care (JADE only). The intervention included technologically guided assessment and use of biogenetic markers (autoantibodies, C-peptide, and common and rare genetic variants) to classify diabetes for 1-year intensified, algorithm-based treatment followed by two annual reviews by an endocrinologist-led multidisciplinary team. The primary end point was a composite of incident or progression of all diabetes-related complications. Secondary end points included attainment of three or more treatment targets (HbA1c <6.2%, blood pressure <120/75 mmHg, LDL cholesterol <1.2 mmol/L, triglycerides <1.2 mmol/L, and waist circumference <80 [women] or <85 cm [men]), proxies of β-cell function, and patient-reported outcome measures (PROMs). RESULTS: During 2020 to 2021, 884 participants (mean [SD] age 40.7 [6.5] years; mean [SD] age at diagnosis 32.5 [6.8] years; autoantibody positivity [n = 46]; monogenic diabetes [n = 23]; C-peptide <200 pmol/L [n = 82]; central obesity [n = 699]; dyslipidemia [n = 669]; hypertension [n = 588]; albuminuria [n = 313]; insulin treated [n = 250]) were randomly assigned to the JADE-PRISM (n = 441) or JADE-only group (n = 443). During the 3-year study, the primary end point developed in 116 participants (26.3%) in the JADE-PRISM group versus 125 (28.2%) in the JADE-only group (odds ratio 0.908 [95% CI 0.675-1.221]). In the JADE-PRISM group, 104 participants (23.8%) versus 54 in the JADE-only group (12.2%; P < 0.001) reached three or more treatment targets, with improved proxies of β-cell function and reduced emotional distress. CONCLUSIONS: A 3-year technology-enhanced, multicomponent program improved cardiometabolic status, proxies of β-cell function, and PROMs in individuals with YOD but did not reduce complications.
OBJECTIVE: To determine whether less invasive C-peptide tests, urine C-peptide-to-creatinine ratio (UCPCR) and dried blood spot (DBS), could replace the mixed-meal tolerance test (MMTT) in the context of an interventiona...OBJECTIVE: To determine whether less invasive C-peptide tests, urine C-peptide-to-creatinine ratio (UCPCR) and dried blood spot (DBS), could replace the mixed-meal tolerance test (MMTT) in the context of an interventional clinical trial (Ustekinumab in Adolescents With Recent-Onset Type 1 Diabetes [USTEKID]). RESEARCH DESIGN AND METHODS: C-peptide was assessed at screening and weeks 28 and 52 using a 2-h MMTT. UCPCR samples were taken after each MMTT. Fasting and 60-min postmeal DBS samples were collected weekly to week 28 and then monthly to week 52. UCPCR and glucose-adjusted DBS results were compared with MMTT results. Weekly DBS averages were calculated and differences between treatment groups assessed using a mixed linear model, bootstrap one-sample t tests, and autoregressive integrated moving averages. Six months of weekly DBS data were used to predict 12-month C-peptide levels. RESULTS: Unlike MMTT C-peptide, UCPCR did not change in the first 6 months, before decreasing by 12 months. The DBS area under the curve from 0 to 60 min declined steadily over 12 months. The DBS C-peptide decline in the intervention group was significantly less than that in the control group by week 20 (P < 0.05). This was not apparent with UCPCR and did not become evident until 52 weeks with MMTT. The slope from 6 months of DBS could predict 12-month MMTT C-peptide in the control but not in the intervention group, consistent with the increasing impact of the intervention from 6 to 12 months indicated by the MMTT data. CONCLUSIONS: Frequently sampled glucose-adjusted DBS was more sensitive to early change than MMTT and could serve as a home-based marker of β-cell function, whereas UCPCR was not sensitive to change in the early period.
Jagannathan R, Kondal D, Tiwari P
… +17 more, Deepa M, Gujral UP, Patel SA, Mohan S, Anjana RM, Staimez LR, Gupta R, Beyh YS, Oguntade AS, Chang HH, Ali MK, Quyyumi A, Sun YV, Prabhakaran D, Tandon N, Mohan V, Narayan KMV
Diabetes Care
· 2026 May · PMID 42102359
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OBJECTIVE: Current definitions of type 2 diabetes (T2D) and prediabetes do not capture their pathophysiological heterogeneity. We investigated data-driven subtypes of T2D and prediabetes and evaluated their associations...OBJECTIVE: Current definitions of type 2 diabetes (T2D) and prediabetes do not capture their pathophysiological heterogeneity. We investigated data-driven subtypes of T2D and prediabetes and evaluated their associations with mortality. RESEARCH DESIGN AND METHODS: We analyzed data from 14,036 South Asian participants from the CArdiometabolic Risk Reduction cohort using unsupervised k-means clustering based on five variables: age, BMI, HbA1c, insulin resistance, and β-cell dysfunction. For each subtype of T2D or prediabetes, we estimated Cox hazard ratios (HRs) for all-cause and cardiovascular disease (CVD) mortality and excess years of life lost compared with normal glucose tolerance. RESULTS: Among 2,639 participants with T2D, three subtypes emerged: severe insulin-deficient diabetes (SIDD; 23.0%), mild insulin-deficient diabetes (MIDD; 54.5%), and severe insulin-resistant diabetes (SIRD; 22.5%). Among 4,992 participants with prediabetes, two subtypes were identified: insulin-deficient prediabetes (IDPD; 66.0%) and insulin-resistant prediabetes (IRPD; 34.0%). Over a median follow-up of 10.6 years, 1,076 deaths occurred (405 due to CVD). Compared with normal glucose tolerance, SIDD had the highest all-cause mortality (HR 3.34; 95% CI 2.39-4.68), followed by MIDD (1.39; 95% CI 1.05-1.84), and SIRD (1.67; 95% CI 1.15-2.41). Among prediabetes subtypes, IDPD was associated with increased all-cause (HR 1.32; 95% CI 1.03-1.68) and CVD mortality (HR 1.53; 95% CI 1.00-2.34), whereas IRPD was not. Excess years of life lost were greatest for SIDD (17.7 years), followed by MIDD (12.8 years) and SIRD (12.0 years). CONCLUSIONS: Insulin-deficient subtypes made up a high proportion of individuals with T2D and prediabetes and were associated with higher mortality hazards and excess years of life lost.
Templeman EL, Thomas N, Martin S
… +13 more, Wherett DK, Redondo MJ, Sherr J, Petrelli A, Jacobsen LM, Salami F, Lonier J, Evans-Molina C, Sosenko J, Barroso I, Oram RA, Sims EK, Ferrat LA
Diabetes Care
· 2026 Jul · PMID 42090204
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OBJECTIVE: HbA1c thresholds used to define dysglycemia in autoantibody-positive individuals at risk for type 1 diabetes do not account for age-related increases in HbA1c and may overestimate progression risk in adults. W...OBJECTIVE: HbA1c thresholds used to define dysglycemia in autoantibody-positive individuals at risk for type 1 diabetes do not account for age-related increases in HbA1c and may overestimate progression risk in adults. We evaluated whether age-adjusted HbA1c or a higher HbA1c threshold improves risk stratification across age-groups. RESEARCH DESIGN AND METHODS: We analyzed 5,024 autoantibody-positive relatives (3,720 children and 1,304 adults) participating in the TrialNet Pathway to Prevention study. Age-related HbA1c effects were modeled using 6,273 adults from the population-based Exeter 10000 cohort. Progression risk was compared using the standard dysglycemia threshold (HbA1c ≥5.7% [39 mmol/mol]), age-adjusted HbA1c, and an alternative threshold of HbA1c ≥6.0% (42 mmol/mol). RESULTS: Using HbA1c ≥5.7% (39 mmol/mol), children had higher 1-year progression risk than adults among single autoantibody-positive participants (38% [95% CI 28, 47] vs. 13% [7.2, 19]) and multiple autoantibody-positive participants (55% [49, 60] vs. 38% [27, 47]) (both P < 0.001). Age adjustment reduced these differences; progression risk was similar among single autoantibody-positive participants (38% [28, 47] vs. 27% [13, 39]; P = 0.32), with attenuated differences among multiple autoantibody-positive participants. An HbA1c threshold ≥6.0% (42 mmol/mol) yielded comparable progression risk between adults and children across autoantibody subgroups. In post hoc analyses, adults aged <30 years had progression risk similar to children (P = 0.1). CONCLUSIONS: Age-related variation in HbA1c influences dysglycemia classification in adults at risk for type 1 diabetes. Age-adjusted HbA1c or a higher HbA1c threshold (≥6.0% [42 mmol/mol]) in adults aged ≥30 years identifies individuals with progression risk comparable to children and may improve age-specific risk stratification in prevention settings.
OBJECTIVE: We assessed whether 1) severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination is associated with the risk of type 1 diabetes and 2) SARS-CoV-2 vaccination or infection is associated with dise...OBJECTIVE: We assessed whether 1) severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination is associated with the risk of type 1 diabetes and 2) SARS-CoV-2 vaccination or infection is associated with disease severity at type 1 diabetes diagnosis. RESEARCH DESIGN AND METHODS: Every Finnish child aged 5-14 years diagnosed with type 1 diabetes (case subjects, n = 433) during a 16-month period (September 2021 to December 2022) were compared with three control subjects matched for age, sex, and municipality. Information on coronavirus disease 2019 (COVID-19) vaccinations was obtained from the National Vaccination Register. SARS-CoV-2 infections were identified based on circulating antibody titer in samples obtained soon after the diagnosis of type 1 diabetes. RESULTS: COVID-19 vaccinations preceding type 1 diabetes diagnosis were not associated with risk of type 1 diabetes (hazard ratio 1.30, 95% CI 0.97-1.72, P = 0.076). Vaccinations were linked to less severe symptoms at the time of diagnosis. Children with protective HLA genotypes were more common among the vaccinated case subjects compared with unvaccinated case subjects. Vaccinations were inversely associated with insulin autoantibody positivity. There was no association between SARS-CoV-2 and type 1 diabetes symptoms or autoantibodies at the time of type 1 diabetes diagnosis. CONCLUSIONS: There was no significant association between SARS-CoV-2 vaccination and risk of type 1 diabetes. Neither COVID-19 vaccinations nor SARS-CoV-2 infections explain the more severe symptoms at type 1 diabetes diagnosis observed in Finnish children after the beginning of the COVID-19 pandemic. Parents who vaccinate their children are more likely to seek medical care. This may result in less severe symptoms in their children at diagnosis of diabetes.
Weber D, Modeste J, Peeling S
… +5 more, Foster TP, Bruggeman BS, Jacobsen LM, Schatz DA, Haller MJ
Diabetes Care
· 2026 Jul · PMID 42085576
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OBJECTIVE: To evaluate the real-world feasibility and efficacy of low-dose antithymocyte globulin (ATG) by an exploratory modified quantitative response (mQR) of C-peptide in type 1 diabetes. RESEARCH DESIGN AND METHODS:...OBJECTIVE: To evaluate the real-world feasibility and efficacy of low-dose antithymocyte globulin (ATG) by an exploratory modified quantitative response (mQR) of C-peptide in type 1 diabetes. RESEARCH DESIGN AND METHODS: Individuals with stage 2 (n = 6) or stage 3 (n = 33) diabetes were treated clinically with low-dose ATG (2.5 mg/kg) and asked to obtain C-peptide via a commercial laboratory 90 min postconsumption of 6 mL/kg Boost. Thirty individuals (77%) completed 1 year of follow-up, with 22 (73% of those) providing pre-ATG and 1-year-post-ATG C-peptides. Area under the curve C-peptide was estimated from 90-min values to calculate mQR. RESULTS: In the 22 evaluable patients, average mQR at 1 year was 0.072. Average HbA1c decreased from 7.1% (54 mmol/mol) to 6.0% (42 mmol/mol). There were 15 responders (+mQR) and 7 nonresponders (-mQR). There were no unexpected side effects. CONCLUSIONS: C-peptide mQR was feasible and produced expected responder frequencies following low-dose ATG in a clinical practice setting.
OBJECTIVE: Discordance between the glucose management indicator (GMI) and hemoglobin A1c (HbA1c) is frequently observed in diabetes, yet its physiological basis remains unclear. This study investigated how specific gluco...OBJECTIVE: Discordance between the glucose management indicator (GMI) and hemoglobin A1c (HbA1c) is frequently observed in diabetes, yet its physiological basis remains unclear. This study investigated how specific glucose excursion patterns captured by continuous glucose monitoring (CGM) contribute to this discordance in individuals with type 1 diabetes. RESEARCH DESIGN AND METHODS: Ninety-day CGM traces from 611 adults with type 1 diabetes were paired with HbA1c results obtained within ±15 days. Glucose excursions were quantified using the glucose rate increase detector (GRID) algorithm with varied peak glucose and time-to-peak thresholds. Discordance was defined using GMI-to-HbA1c and updated GMI (uGMI)-to-HbA1c ratios, and associations with GRID-derived excursion metrics were evaluated alongside conventional CGM-derived variability metrics. RESULTS: Excursions with peak glucose ≥250 mg/dL and time to peak ≥90 min were significantly associated with higher uGMI-to-HbA1c ratios after adjustment for age, sex, estimated glomerular filtration rate, and HbA1c group, with consistent findings across CGM devices (sensor type 1: β = 0.174, 95% CI 0.147-0.201; sensor type 2: β = 0.102, 95% CI 0.068-0.136; both P < 0.001) and alternative GMI formulations. In restricted cubic spline analyses, adjustment for GRID-derived excursion metrics differentially reshaped the associations of HbA1c, GMI, and uGMI with albuminuria and elevated triglyceride-glucose index in an outcome- and context-dependent manner, preferentially enhancing the informativeness of GMI and uGMI but not HbA1c. CONCLUSIONS: Frequent high and prolonged glucose excursions were consistently associated with GMI-HbA1c discordance across devices, HbA1c strata, and analytic conditions. GRID-derived excursion metrics modify the relationship between GMI/uGMI and glycemia-associated risk.
OBJECTIVE: To investigate the associations of baseline general and abdominal adiposity, as well as their longitudinal changes, with risks of any-site, major osteoporotic, and site-specific fractures in individuals with t...OBJECTIVE: To investigate the associations of baseline general and abdominal adiposity, as well as their longitudinal changes, with risks of any-site, major osteoporotic, and site-specific fractures in individuals with type 2 diabetes. RESEARCH DESIGN AND METHODS: Individuals with type 2 diabetes who underwent structured assessments in the Hong Kong Hospital Authority between August 2001 and February 2022 were followed for incident fractures until June 2024. Multivariable Cox regression and restricted cubic spline analyses were used to evaluate the associations of baseline BMI, waist circumference, and their 2-year percentage changes with fracture risk. RESULTS: Among 436,929 individuals (mean ± SD age 61.9 ± 11.8 years, median [interquartile range] diabetes duration 1 [0-6] years, 53.1% men) followed for a median of 8.3 years, underweight was associated with 30-77% higher risks of any-site, major osteoporotic, hip, and pelvis fractures, whereas class II obesity was associated with 21-36% higher risks of humerus, upper leg, and ankle fractures. Waist circumference residuals from BMI were positively associated with fracture risk. Among 247,540 individuals with 2-year adiposity measurements, weight change showed U-shaped associations with any-site, major osteoporotic, hip, and humerus fractures, with the lowest risks at -1.5% to 2.3% weight change. Increases in waist circumference were positively associated with risks of any-site, major osteoporotic, hip, rib, humerus, and elbow fractures. CONCLUSIONS: In individuals with type 2 diabetes, general adiposity showed site-specific associations with fracture risk, with its longitudinal changes demonstrating U-shaped relationships, whereas abdominal adiposity and its increases were independently associated with higher fracture risk.
The regulatory approval and growing pipeline of disease-modifying therapies for presymptomatic type 1 diabetes have sparked an increase in screening for the presence of islet autoantibodies in individuals who may not hav...The regulatory approval and growing pipeline of disease-modifying therapies for presymptomatic type 1 diabetes have sparked an increase in screening for the presence of islet autoantibodies in individuals who may not have yet developed clinical symptoms of disease. The staging system that is currently employed to define type 1 diabetes diagnosis in presymptomatic and symptomatic phases is based on the presence of islet autoantibodies and glycemic status. Here, we make the case to consider using C-peptide values to provide context for glycemia. Inclusion of C-peptide could result in better prediction of progression to clinical disease and more specificity for features typically associated with type 1 diabetes (and, thus, be less susceptible to confounding influences on glycemia like age and insulin resistance). It also could more rapidly identify responses to disease-modifying therapies. The implementation and translation of these findings will be key to long-term success in type 1 diabetes prediction and disease modification strategies.
Chong KH, Ahmadi MN, Biswas RK
… +8 more, Francois ME, Koemel NA, Sabag A, Gibala MJ, Keating SE, Little J, Thøgersen-Ntoumani C, Stamatakis E
Diabetes Care
· 2026 Jun · PMID 42048576
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OBJECTIVE: To examine dose-response associations of vigorous intermittent lifestyle physical activity (VILPA; bouts ≤1 min) and its moderate- to vigorous-intensity equivalent (MV-ILPA; bouts ≤3 min) with incident type 2...OBJECTIVE: To examine dose-response associations of vigorous intermittent lifestyle physical activity (VILPA; bouts ≤1 min) and its moderate- to vigorous-intensity equivalent (MV-ILPA; bouts ≤3 min) with incident type 2 diabetes. RESEARCH DESIGN AND METHODS: Prospective data from UK Biobank accelerometry substudy participants who reported no leisure-time exercise and had no type 2 diabetes at baseline were analyzed. Daily duration and frequency of VILPA and MV-ILPA were derived from wrist-worn accelerometers. Incident type 2 diabetes was ascertained through linked primary care, hospital, and death records. Dose-response associations were examined using multivariable-adjusted Fine-Gray subdistribution hazard models accounting for competing risks. RESULTS: Among 22,706 participants (mean age 62.3 years; 56.4% female), 665 developed type 2 diabetes over an average follow-up of 7.9 years. Daily durations of VILPA and MV-ILPA showed inverse, nonlinear L-shaped associations with incident type 2 diabetes. Median durations of 3.9 min/day of VILPA and 25.3 min/day of MV-ILPA were associated with 36% and 46% lower risks of type 2 diabetes, respectively, compared with no VILPA or 3.9 min/day of MV-ILPA. Daily VILPA frequency showed a near-linear inverse association, with 10.4 bouts/day (median) corresponding to a hazard ratio (HR) of 0.64 (95% CI 0.51-0.81) compared with 0 bouts/day. Daily MV-ILPA frequency showed a U-shaped pattern, with risk reductions plateauing at approximately 56 bouts/day (HR 0.54; 95% CI 0.39-0.76). CONCLUSIONS: Among adults who do not engage in leisure-time exercise, accruing brief, intermittent bouts of moderate- to vigorous-intensity physical activity during day-to-day routines may be a promising strategy for prevention of type 2 diabetes.
Qiang J, Pathmaraj M, Lo T
… +4 more, Uleryk EM, Huszti E, Abrahamyan L, Pinto AD
Diabetes Care
· 2026 Jun · PMID 42030121
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BACKGROUND: Prediabetes is a precursor of type 2 diabetes mellitus (T2DM), and lifestyle modifications are key preventive strategies. Primary care is central to prevention efforts, including screening, diagnosis, and fol...BACKGROUND: Prediabetes is a precursor of type 2 diabetes mellitus (T2DM), and lifestyle modifications are key preventive strategies. Primary care is central to prevention efforts, including screening, diagnosis, and follow-up. PURPOSE: This systematic review and meta-analysis aimed to evaluate the effectiveness of lifestyle interventions delivered in primary care to patients at elevated risk of developing T2DM. DATA SOURCES: We searched Medline and Embase from inception to 28 March 2024. STUDY SELECTION: We screened 639 records and included 14 eligible studies of lifestyle-based diabetes prevention programs. Eligible participants had prediabetes or high diabetes risk scores, and interventions were delivered in primary care. DATA EXTRACTION: Outcomes included diabetes incidence, glycemic and anthropometric indicators, physical activity, and diet. DATA SYNTHESIS: Pooled mean differences (MD) were estimated using inverse variance methods; leave-one-out cross-validation (LOOCV) addressed heterogeneity (>50%). Meta-analysis found no significant effects on diabetes incidence (relative risk 0.82; 95% CI 0.65-1.02), and pooled MD on HbA1c (MD -0.41, 95% CI -0.94 to 0.12), fasting glucose, 2-h glucose, body weight, BMI, waist circumference (MD -1.13, 95% CI -2.40 to 0.13), or systolic and diastolic blood pressure. LOOCV identified one study driving heterogeneity in several outcomes. LIMITATIONS: English-only publications may reduce generalizability. CONCLUSIONS: This review found no significant differences in diabetes incidence or other key indicators of T2DM, with certainty of evidence varying from moderate to low. Future studies should test integrated screening, referral, and social support strategies in routine care for high-risk groups.
Guo T, Li H, Liu Z
… +17 more, Yang Y, Xie J, Ren J, He M, Chu C, Li C, Yan Y, Sun Y, Wang D, Hu G, Du M, Jia H, Yan Y, Zhao M, Magnussen CG, Xi B, Mu J
OBJECTIVE: To examine the associations between cumulative BMI burden from childhood to adulthood and the risk of adult metabolic multimorbidity. RESEARCH DESIGN AND METHODS: This prospective cohort study used data from t...OBJECTIVE: To examine the associations between cumulative BMI burden from childhood to adulthood and the risk of adult metabolic multimorbidity. RESEARCH DESIGN AND METHODS: This prospective cohort study used data from the Hanzhong Adolescent Hypertension Study (1987-2023). A total of 2,446 participants with at least two BMI measurements in both childhood (6-18 years) and adulthood (19-52 years) were included. Cumulative BMI exposure was quantified using total and incremental area under the curve (AUC). Outcomes included metabolic multimorbidity, defined as the presence of two or more or three or more metabolic diseases, specifically hypertension, diabetes, dyslipidemia, elevated liver enzymes/bilirubin, and kidney damage. RESULTS: Higher total and incremental BMI AUC during childhood, adulthood, and over the life course were consistently associated with an increased risk of adult metabolic multimorbidity (two or more diseases). For total AUC, odds ratios (ORs) ranged from 1.51 to 2.59 (all P < 0.05); for incremental AUC, ORs ranged from 1.94 to 4.33 (all P < 0.05). Compared with total AUC, incremental AUC showed a stronger association with metabolic multimorbidity in childhood (OR 4.33 [95% CI 2.93, 6.40] vs. 1.51 [1.17, 1.95], respectively). Conversely, total AUC exhibited a stronger association in adulthood than in childhood (OR 2.51 [2.08, 3.04] vs. 1.94 [1.62, 2.31]). Furthermore, the associations for adulthood and life course BMI AUC were significantly stronger in males than in females (P for interaction < 0.05). CONCLUSIONS: These findings highlight the importance of life stage-specific strategies: curbing rapid BMI gain in childhood and maintaining long-term weight control throughout adulthood.
Curto A, Konieczna J, Colom A
… +16 more, Abete I, de Hoogh K, Hoek G, Salas-Salvadó J, Martín-Sánchez JV, Estruch R, Vidal J, Toledo E, García-Gavilán JF, de Paz JA, Casas R, Goñi-Ruiz N, Vázquez-Lorente H, Fitó M, Martínez JA, Romaguera D
Diabetes Care
· 2026 Jun · PMID 42012390
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OBJECTIVE: To examine the relationship between long-term air pollution exposure, including black carbon (BC), fine particulate matter (PM2.5), and nitrogen dioxide (NO2), and total fat mass, visceral fat mass, and lean m...OBJECTIVE: To examine the relationship between long-term air pollution exposure, including black carbon (BC), fine particulate matter (PM2.5), and nitrogen dioxide (NO2), and total fat mass, visceral fat mass, and lean mass in older adults with overweight or obesity and metabolic syndrome. RESEARCH DESIGN AND METHODS: We included 1,454 older adults (aged 54-75 years; 48% female) from the PREDIMED-Plus trial in Spain who underwent baseline DXA scans at recruitment (2013-2016) and at 1- and 3-year follow-up. Annual air pollution exposure was assigned at participants' baseline residential address at 100 m resolution. We used linear mixed-effect regression models with interaction terms for exposure and time to examine longitudinal associations with body composition, also stratifying by sex, age, and physical activity. RESULTS: At baseline, a 1 × 10-5/m increase in BC was associated with 1.01% (95% CI 0.31-1.71) higher body fat percentage, -0.97% (95% CI -1.64 to -0.30) lower lean mass percentage, and -0.74 kg (95% CI -1.37 to -0.12) lower lean mass. PM2.5 and NO2 showed similar relationships with body fat and lean mass percentage at baseline. These associations persisted in years 1 and 3 for BC and PM2.5. In age-stratified analyses, associations with visceral fat mass were observed only in participants younger than 65 years. Associations did not meaningfully differ by sex or physical activity. CONCLUSIONS: Long-term air pollution exposure was adversely associated with body composition over 3 years. Results indicate air pollution is associated with fat accumulation and lean mass loss in metabolically vulnerable older adults.