Exome sequencing of 20,791 cases of type 2 diabetes and 24,440 controls.

Protein-coding genetic variants that strongly affect disease risk can yield relevant clues to disease pathogenesis. Here we report exome-sequencing analyses of 20,791 individuals with type 2 diabetes (T2D) and 24,440 non-diabetic control participants from 5 ancestries. We identify gene-level associations of rare variants (with minor allele frequencies of less than 0.5%) in 4 genes at exome-wide significance, including a series of more than 30 SLC30A8 alleles that conveys protection against T2D, and in 12 gene sets, including those corresponding to T2D drug targets (P = 6.1 × 10-3) and candidate genes from knockout mice (P = 5.2 × 10-3). Within our study, the strongest T2D gene-level signals for rare variants explain at most 25% of the heritability of the strongest common single-variant signals, and the gene-level effect sizes of the rare variants that we observed in established T2D drug targets will require 75,000-185,000 sequenced cases to achieve exome-wide significance. We propose a method to interpret these modest rare-variant associations and to incorporate these associations into future target or gene prioritization efforts.

Pre-exercise protein intake is associated with reduced time in hypoglycaemia among adolescents with type 1 diabetes.

AIM: Secondary analyses were conducted from a randomized trial of an adaptive behavioural intervention to assess the relationship between protein intake (g and g/kg) consumed within 4 h before moderate-to-vigorous physical activity (MVPA) bouts and glycaemia during and following MVPA bouts among adolescents with type 1 diabetes (T1D). MATERIALS AND METHODS: Adolescents (n = 112) with T1D, 14.5 (13.8, 15.7) years of age and 36.6% overweight/obese, provided measures of glycaemia using continuous glucose monitoring [percentage of time above range (>180 mg/dl), time in range (70-180 mg/dl), time below range (TBR; <70 mg/dl)], self-reported physical activity (previous day physical activity recalls), and 24 h dietary recall data at baseline and 6 months post-intervention. Mixed effects regression models adjusted for design (randomization assignment, study site), demographic, clinical, anthropometric, dietary, physical activity and timing covariates estimated the association between pre-exercise protein intake on percentage of time above range, time in range and TBR during and following MVPA. RESULTS: Pre-exercise protein intakes of 10-19.9 g and >20 g were associated with an absolute reduction of -4.41% (p = .04) and -4.83% (p = .02) TBR during physical activity compared with those who did not consume protein before MVPA. Similarly, relative protein intakes of 0.125-0.249 g/kg and ≥0.25 g/kg were associated with -5.38% (p = .01) and -4.32% (p = .03) absolute reductions in TBR during physical activity. We did not observe a significant association between protein intake and measures of glycaemia following bouts of MVPA. CONCLUSIONS: Among adolescents with T1D, a dose of ≥10 g or ≥0.125 g/kg of protein within 4 h before MVPA may promote reduced time in hypoglycaemia during, but not following, physical activity.

Associations of Dietary Intake with the Intestinal Microbiota and Short-Chain Fatty Acids Among Young Adults with Type 1 Diabetes and Overweight or Obesity.

BACKGROUND: Diet, a key component of type 1 diabetes (T1D) management, modulates the intestinal microbiota and its metabolically active byproducts-including SCFA-through fermentation of dietary carbohydrates such as fiber. However, the diet-microbiome relationship remains largely unexplored in longstanding T1D. OBJECTIVES: We evaluated whether increased carbohydrate intake, including fiber, is associated with increased SCFA-producing gut microbes, SCFA, and intestinal microbial diversity among young adults with longstanding T1D and overweight or obesity. METHODS: Young adult men and women with T1D for ≥1 y, aged 19-30 y, and BMI of 27.0-39.9 kg/m2 at baseline provided stool samples at baseline and 3, 6, and 9 mo of a randomized dietary weight loss trial. Diet was assessed by 1-2 24-h recalls. The abundance of SCFA-producing microbes was measured using 16S rRNA gene sequencing. GC-MS measured fecal SCFA (acetate, butyrate, propionate, and total) concentrations. Adjusted and Bonferroni-corrected generalized estimating equations modeled associations of dietary fiber (total, soluble, and pectins) and carbohydrate (available carbohydrate, and fructose) with microbiome-related outcomes. Primary analyses were restricted to data collected before COVID-19 interruptions. RESULTS: Fiber (total and soluble) and carbohydrates (available and fructose) were positively associated with total SCFA and acetate concentrations (n = 40 participants, 52 visits). Each 10 g/d of total and soluble fiber intake was associated with an additional 8.8 µmol/g (95% CI: 4.5, 12.8 µmol/g; P = 0.006) and 24.0 µmol/g (95% CI: 12.9, 35.1 µmol/g; P = 0.003) of fecal acetate, respectively. Available carbohydrate intake was positively associated with SCFA producers Roseburia and Ruminococcus gnavus. All diet variables except pectin were inversely associated with normalized abundance of Bacteroides and Alistipes. Fructose was inversely associated with Akkermansia abundance. CONCLUSIONS: In young adults with longstanding T1D, fiber and carbohydrate intake were associated positively with fecal SCFA but had variable associations with SCFA-producing gut microbes. Controlled feeding studies should determine whether gut microbes and SCFA can be directly manipulated in T1D.

More hypoglycemia not associated with increasing estimated adiposity in youth with type 1 diabetes.

BACKGROUND: Despite the widespread clinical perception that hypoglycemia may drive weight gain in youth with type 1 diabetes (T1D), there is an absence of published evidence supporting this hypothesis. METHODS: We estimated the body fat percentage (eBFP) of 211 youth (HbA1c 8.0-13.0%, age 13-16) at baseline, 6, and 18 months of the Flexible Lifestyles Empowering Change trial using validated equations. Group-based trajectory modeling assigned adolescents to sex-specific eBFP groups. Using baseline 7-day blinded continuous glucose monitoring data, "more" vs. "less" percent time spent in hypoglycemia was defined by cut-points using sample median split and clinical guidelines. Adjusted logistic regression estimated the odds of membership in an increasing eBFP group comparing youth with more vs. less baseline hypoglycemia. RESULTS: More time spent in clinical hypoglycemia (defined by median split) was associated with 0.29 the odds of increasing eBFP in females (95% CI: 0.12, 0.69; p = 0.005), and 0.33 the odds of stable/increasing eBFP in males (95% CI: 0.14, 0.78; p = 0.01). CONCLUSIONS: Hypoglycemia may not be a major driver of weight gain in US youth with T1D and HbA1c ≥8.0. Further studies in different sub-groups are needed to clarify for whom hypoglycemia may drive weight gain and focus future etiological studies and interventions. IMPACT: We contribute epidemiological evidence that hypoglycemia may not be a major driver of weight gain in US youth with type 1 diabetes and HbA1c ≥8.0% and highlight the need for studies to prospectively test this hypothesis rooted in clinical perception. Future research should examine the relationship between hypoglycemia and adiposity together with psychosocial, behavioral, and other clinical factors among sub-groups of youth with type 1 diabetes (i.e., who meet glycemic targets or experience a frequency/severity of hypoglycemia above a threshold) to further clarify for whom hypoglycemia may drive weight gain and progress etiological understanding of and interventions for healthy weight maintenance.

Weight management in young adults with type 1 diabetes: The advancing care for type 1 diabetes and obesity network sequential multiple assignment randomized trial pilot results.

AIMS: Co-management of weight and glycaemia is critical yet challenging in type 1 diabetes (T1D). We evaluated the effect of a hypocaloric low carbohydrate, hypocaloric moderate low fat, and Mediterranean diet without calorie restriction on weight and glycaemia in young adults with T1D and overweight or obesity. MATERIALS AND METHODS: We implemented a 9-month Sequential, Multiple Assignment, Randomized Trial pilot among adults aged 19-30 years with T1D for ≥1 year and body mass index 27-39.9 kg/m2 . Re-randomization occurred at 3 and 6 months if the assigned diet was not acceptable or not effective. We report results from the initial 3-month diet period and re-randomization statistics before shutdowns due to COVID-19 for primary [weight, haemoglobin A1c (HbA1c), percentage of time below range <70 mg/dl] and secondary outcomes [body fat percentage, percentage of time in range (70-180 mg/dl), and percentage of time below range <54 mg/dl]. Models adjusted for design, demographic and clinical covariates tested changes in outcomes and diet differences. RESULTS: Adjusted weight and HbA1c (n = 38) changed by -2.7 kg (95% CI -3.8, -1.5, P < .0001) and -0.91 percentage points (95% CI -1.5, -0.30, P = .005), respectively, while adjusted body fat percentage remained stable, on average (P = .21). Hypoglycaemia indices remained unchanged following adjustment (n = 28, P > .05). Variability in all outcomes, including weight change, was considerable (57.9% were re-randomized primarily due to loss of <2% body weight). No outcomes varied by diet. CONCLUSIONS: Three months of a diet, irrespective of macronutrient distribution or caloric restriction, resulted in weight loss while improving or maintaining HbA1c levels without increasing hypoglycaemia in adults with T1D.

Estimating incidence of type 1 and type 2 diabetes using prevalence data: the SEARCH for Diabetes in Youth study.

BACKGROUND: Incidence is one of the most important epidemiologic indices in surveillance. However, determining incidence is complex and requires time-consuming cohort studies or registries with date of diagnosis. Estimating incidence from prevalence using mathematical relationships may facilitate surveillance efforts. The aim of this study was to examine whether a partial differential equation (PDE) can be used to estimate diabetes incidence from prevalence in youth. METHODS: We used age-, sex-, and race/ethnicity-specific estimates of prevalence in 2001 and 2009 as reported in the SEARCH for Diabetes in Youth study. Using these data, a PDE was applied to estimate the average incidence rates of type 1 and type 2 diabetes for the period between 2001 and 2009. Estimates were compared to annual incidence rates observed in SEARCH. Precision of the estimates was evaluated using 95% bootstrap confidence intervals. RESULTS: Despite the long period between prevalence measures, the estimated average incidence rates mirror the average of the observed annual incidence rates. Absolute values of the age-standardized sex- and type-specific mean relative errors are below 8%. CONCLUSIONS: Incidence of diabetes can be accurately estimated from prevalence. Since only cross-sectional prevalence data is required, employing this methodology in future studies may result in considerable cost savings.

Associations of disordered eating with the intestinal microbiota and short-chain fatty acids among young adults with type 1 diabetes.

BACKGROUND AND AIMS: Disordered eating (DE) in type 1 diabetes (T1D) includes insulin restriction for weight loss with serious complications. Gut microbiota-derived short chain fatty acids (SCFA) may benefit host metabolism but are reduced in T1D. We evaluated the hypothesis that DE and insulin restriction were associated with reduced SCFA-producing gut microbes, SCFA, and intestinal microbial diversity in adults with T1D. METHODS AND RESULTS: We collected stool samples at four timepoints in a hypothesis-generating gut microbiome pilot study ancillary to a weight management pilot in young adults with T1D. 16S ribosomal RNA gene sequencing measured the normalized abundance of SCFA-producing intestinal microbes. Gas-chromatography mass-spectrometry measured SCFA (total, acetate, butyrate, and propionate). The Diabetes Eating Problem Survey-Revised (DEPS-R) assessed DE and insulin restriction. Covariate-adjusted and Bonferroni-corrected generalized estimating equations modeled the associations. COVID-19 interrupted data collection, so models were repeated restricted to pre-COVID-19 data. Data were available for 45 participants at 109 visits, which included 42 participants at 65 visits pre-COVID-19. Participants reported restricting insulin "At least sometimes" at 53.3% of visits. Pre-COVID-19, each 5-point DEPS-R increase was associated with a -0.34 (95% CI -0.56, -0.13, p = 0.07) lower normalized abundance of genus Anaerostipes; and the normalized abundance of Lachnospira genus was -0.94 (95% CI -1.5, -0.42), p = 0.02 lower when insulin restriction was reported "At least sometimes" compared to "Rarely or Never". CONCLUSION: DE and insulin restriction were associated with a reduced abundance of SCFA-producing gut microbes pre-COVID-19. Additional studies are needed to confirm these associations to inform microbiota-based therapies in T1D.

Disparities in Food Security and Glycemic Control Among People with Type 2 Diabetes During the COVID-19 Pandemic.

Background: Little is known about the differing impacts of food insecurity on HbA1c by race in type 2 diabetes (T2D). Predictions around increased food insecurity from COVID-19 exacerbating racial disparities led us to estimate its prevalence and associations with HbA1c by race during the COVID-19 pandemic. Methods: Data came from medical records and surveys among a clinic-based sample of T2D patients. Linear regression models estimated associations between food insecurity and HbA1c and between change in food insecurity and change in HbA1c. Likelihood ratio tests and examination of stratum-specific estimates assessed effect modification by race. Results: Our sample was 59% White, 59% female, and mean age was 60.8 ± 12.6. During the pandemic, food insecurity prevalence and HbA1c were significantly (p < .05) higher among non-Whites (39%, 8.4% ± 2.1) compared to Whites (15%, 7.8% ±1.6). HbA1c among those who were very food insecure was 1.00% (95% CI: 0.222, 1.762, p = .01) higher than those who were food secure. Those with increased food insecurity had a 0.58% (95% CI: 0.024, 1.128, p = .04) higher HbA1c increase than among those experiencing no change. No effect modification was detected. Limitations: Convenience sampling in an endocrinology clinic, recall bias, and inadequate power may underlie null effect modification results. Conclusion: Although effect modification was not detected, racial disparities in HbA1c and food insecurity warrant further investigation. These disparities, combined with the significant impact of food insecurity on HbA1c, suggest that prioritization of resources to high-risk populations should be considered early during public emergencies to minimize short- and long-term health consequences.

Mindfulness, disordered eating, and impulsivity in relation to glycemia among adolescents with type 1 diabetes and suboptimal glycemia from the Flexible Lifestyles Empowering Change (FLEX) intervention trial.

OBJECTIVE: To assess the relationship between mindfulness and glycemia among adolescents with type 1 diabetes (T1D) with suboptimal glycemia, and evaluate the potential mediation by ingestive behaviors, including disordered eating, and impulsivity. RESEARCH DESIGN AND METHODS: We used linear mixed models for hemoglobin A1c (HbA1c) and linear regression for continuous glucose monitoring (CGM) to study the relationship of mindfulness [Child and Adolescent Mindfulness Measure (CAMM)] and glycemia in adolescents with T1D from the 18-month Flexible Lifestyles Empowering Change (FLEX) trial. We tested for mediation of the mindfulness-glycemia relationship by ingestive behaviors, including disordered eating (Diabetes Eating Problem Survey-Revised), restrained eating, and emotional eating (Dutch Eating Behavior Questionnaire); and impulsivity (total, attentional, and motor, Barrett Impulsiveness Scale). RESULTS: At baseline, participants (n = 152) had a mean age of 14.9 ± 1.1 years and HbA1c of 9.4 ± 1.2% [79 ± 13 mmol/mol]. The majority of adolescents were non-Hispanic white (83.6%), 50.7% were female, and 73.0% used insulin pumps. From adjusted mixed models, a 5-point increase in mindfulness scores was associated with a -0.19% (95%CI -0.29, -0.08, p = 0.0006) reduction in HbA1c. We did not find statistically significant associations between mindfulness and CGM metrics. Mediation of the relationship between mindfulness and HbA1c by ingestive behaviors and impulsivity was not found to be statistically significant. CONCLUSIONS: Among adolescents with T1D and suboptimal glycemia, increased mindfulness was associated with lower HbA1c levels. Future studies may consider mindfulness-based interventions as a component of treatment for improving glycemia among adolescents with T1D, though more data are needed to assess feasibility and efficacy.

A longitudinal assessment of diabetes autoantibodies in the SEARCH for diabetes in youth study.

To assess changes in diabetes autoantibodies (DAs) over time in children and young adults with diabetes and determine whether observed changes were associated with demographic characteristics, clinical parameters and diabetes complications. Participants had DAs measured at baseline (10.3 ± 7.1 months after diabetes diagnosis) and at 12, 24 months and ≥5 years after the baseline measurement. At the ≥5-year follow-up, the presence of diabetes complications was assessed. We examined the associations between change in number of positive DAs and changes in individual DA status with the participants' characteristics and clinical parameters over time. Out of 4179 participants, 62% had longitudinal DA data and 51% had complications and longitudinal DA data. In participants with ≥1 baseline positive DA (n = 1699), 83.4% remained positive after 7.3 ± 2.3 years duration of diabetes. Decrease in number of positive DAs was associated with longer diabetes duration (p = 0.003 for 1 baseline positive DA; p < 0.001 for 2 baseline positive DAs) and younger age at diagnosis (p < 0.001 for 2 baseline positive DAs). No associations were found between change in number of positive DAs in participants with ≥1 baseline positive DA (n = 1391) and HbA1c, insulin dose, acute, or chronic complications after 7.7 ± 1.9 years duration of diabetes. DA status likely remains stable in the first 7 years after diabetes diagnosis. Younger age at diabetes diagnosis and longer duration were associated with less persistence of DAs. Measuring DAs after initial presentation may aid in diabetes classification but not likely in predicting the clinical course.

Comparison of the incidence of diabetes in United States and Indian youth: An international harmonization of youth diabetes registries.

OBJECTIVE: Incidence of youth-onset diabetes in India has not been well described. Comparison of incidence, across diabetes registries, has the potential to inform hypotheses for risk factors. We sought to compare the incidence of diabetes in the U.S.-based registry of youth onset diabetes (SEARCH) to the Registry of Diabetes with Young Age at Onset (YDR-Chennai and New Delhi regions) in India. METHODS: We harmonized data from both SEARCH and YDR to the Observational Medical Outcomes Partnership (OMOP) Common Data Model. Data were from youth registered with incident diabetes (2006-2012). Denominators were from census and membership data. We calculated diabetes incidence by averaging the total cases across the entire follow-up period and dividing this by the estimated census population corresponding to the source population for case ascertainment. Incidence was calculated for each of the registries and compared by type and within age and sex categories using a 2-sided, skew-corrected inverted score test. RESULTS: Incidence of type 1 was higher in SEARCH (21.2 cases/100 000 [95% CI: 19.9, 22.5]) than YDR (4.9 cases/100 000 [95% CI: 4.3, 5.6]). Incidence of type 2 diabetes was also higher in SEARCH (5.9 cases/100 000 [95% CI: 5.3, 6.6] in SEARCH vs 0.5/cases/100 000 [95% CI: 0.3, 0.7] in YDR). The age distribution of incident type 1 diabetes cases was similar across registries, whereas type 2 diabetes incidence was higher at an earlier age in SEARCH. Sex differences existed in SEARCH only, with a higher rate of type 2 diabetes among females. CONCLUSION: The incidence of youth-onset type 1 and 2 diabetes was significantly different between registries. Additional data are needed to elucidate whether the differences observed represent diagnostic delay, differences in genetic susceptibility, or differences in distribution of risk factors.

Changes to care delivery at nine international pediatric diabetes clinics in response to the COVID-19 global pandemic.

BACKGROUND: Pediatric diabetes clinics around the world rapidly adapted care in response to COVID-19. We explored provider perceptions of care delivery adaptations and challenges for providers and patients across nine international pediatric diabetes clinics. METHODS: Providers in a quality improvement collaborative completed a questionnaire about clinic adaptations, including roles, care delivery methods, and provider and patient concerns and challenges. We employed a rapid analysis to identify main themes. RESULTS: Providers described adaptations within multiple domains of care delivery, including provider roles and workload, clinical encounter and team meeting format, care delivery platforms, self-management technology education, and patient-provider data sharing. Providers reported concerns about potential negative impacts on patients from COVID-19 and the clinical adaptations it required, including fears related to telemedicine efficacy, blood glucose and insulin pump/pen data sharing, and delayed care-seeking. Particular concern was expressed about already vulnerable patients. Simultaneously, providers reported 'silver linings' of adaptations that they perceived as having potential to inform care and self-management recommendations going forward, including time-saving clinic processes, telemedicine, lifestyle changes compelled by COVID-19, and improvements to family and clinic staff literacy around data sharing. CONCLUSIONS: Providers across diverse clinical settings reported care delivery adaptations in response to COVID-19-particularly telemedicine processes-created challenges and opportunities to improve care quality and patient health. To develop quality care during COVID-19, providers emphasized the importance of generating evidence about which in-person or telemedicine processes were most beneficial for specific care scenarios, and incorporating the unique care needs of the most vulnerable patients.

Treatment regimens and glycosylated hemoglobin levels in youth with Type 1 and Type 2 diabetes: Data from SEARCH (United States) and YDR (India) registries.

OBJECTIVE: To compare treatment regimens and glycosylated hemoglobin (A1c) levels in Type 1 (T1D) and Type 2 diabetes (T2D) using diabetes registries from two countries-U.S. SEARCH for Diabetes in Youth (SEARCH) and Indian Registry of youth onset diabetes in India (YDR). METHODS: The SEARCH and YDR data were harmonized to the structure and terminology in the Observational Medical Outcomes Partnership Common Data Model. Data used were from T1D and T2D youth diagnosed <20 years between 2006-2012 for YDR, and 2006, 2008, and 2012 for SEARCH. We compared treatment regimens and A1c levels across the two registries. RESULTS: There were 4003 T1D (SEARCH = 1899; YDR = 2104) and 611 T2D (SEARCH = 384; YDR = 227) youth. The mean A1c was higher in YDR compared to SEARCH (T1D:11.0% ± 2.9% vs 7.8% ± 1.7%, P < .001; T2D:9.9% ± 2.8% vs 7.2% ± 2.1%, P < .001). Among T1D youth in SEARCH, 65.1% were on a basal/bolus regimen, whereas in YDR, 52.8% were on once/twice daily insulin regimen. Pumps were used by 16.2% of SEARCH and 1.5% of YDR youth with T1D. Among T2D youth, in SEARCH and YDR, a majority were on metformin only (43.0% vs 30.0%), followed by insulin + any oral hypoglycemic agents (26.3% vs 13.7%) and insulin only (12.8% vs 18.9%), respectively. CONCLUSION: We found significant differences between SEARCH and YDR in treatment patterns in T1D and T2D. A1c levels were higher in YDR than SEARCH youth, for both T1D and T2D, irrespective of the regimens used. Efforts to achieve better glycemic control for youth are urgently needed to reduce the risk of long-term complications.

Diabetic ketoacidosis at diagnosis among youth with type 1 and type 2 diabetes: Results from SEARCH (United States) and YDR (India) registries.

BACKGROUND: There is significant global variation in the prevalence of diabetic ketoacidosis (DKA) at diagnosis among youth with type 1 diabetes (T1D). However, data for youth with type 2 diabetes (T2D) are limited, even in developed countries. We compared the prevalence of DKA at diagnosis among individuals with T1D and T2D from the SEARCH for Diabetes in Youth (SEARCH) and the Registry of Youth Onset Diabetes in India (YDR) registries. METHODS: We harmonized the SEARCH and YDR registries to the structure and terminology in the Observational Medical Outcome Partnership Common Data Model. Data used were from youth with T1D and T2D diagnosed before 20 years and newly diagnosed between 2006 and 2012 in YDR and 2009 and 2012 in SEARCH. RESULTS: There were 5366 US youth (4078 with T1D, 1288 with T2D) and 2335 Indian youth (2108 with T1D, 227 with T2D). More than one third of T1D youth enrolled in SEARCH had DKA at diagnosis which was significantly higher than in YDR (35.3% vs 28.7%, P < .0001). The burden of DKA in youth with T1D was significantly higher among younger age groups; this relationship was similar across registries (P = .4). The prevalence of DKA among T2D in SEARCH and YDR were 5.5% and 6.6% respectively (P = .4). CONCLUSIONS: There is significant burden of DKA at diagnosis with T1D among youth from United States and India, especially among the younger age groups. The reasons for this high prevalence are largely unknown but are critical to developing interventions to prevent DKA at diagnosis.

Clinical profile at diagnosis with youth-onset type 1 and type 2 diabetes in two pediatric diabetes registries: SEARCH (United States) and YDR (India).

BACKGROUND: Over the last decades, diabetes in youth has increased in both India and the United States, along with the burden of long-term complications and healthcare costs. However, there are limited standardized population-based data in contemporary youth cohorts for comparison of clinical and demographic characteristics of diabetes for both type 1 (T1D) and type 2 (T2D). METHODS: In partnership, we harmonized demographic and clinical data from the SEARCH for Diabetes in Youth (SEARCH) registry in the United States and the Registry of People with Diabetes with Youth Age at Onset (YDR) in India to the structure and terminology of the Observational Medical Outcomes Partnership Common Data Model. Data were from youth with T1D and T2D, aged <20 years and newly diagnosed between 2006 and 2010. We compared key characteristics across registries using χ2 tests and t-tests. RESULTS: In total, there were 9650 youth with T1D and 2406 youth with T2D from 2006 to 2012. SEARCH youth were diagnosed at younger ages than YDR youth for T1D and T2D (10.0 vs 10.5 years, P < .001 and 14.7 vs 16.1 years, P < .001, respectively). For T2D, SEARCH had a higher proportion of females and significantly lower proportion of youth of high socioeconomic status compared to YDR. For T1D and T2D, SEARCH youth had higher BMI, lower blood pressure, and lower A1c compared to YDR youth. CONCLUSIONS: These data offer insights into the demographic and clinical characteristics of diabetes in youth across the two countries. Further research is needed to better understand why these differences exist.

Metabolic effects of high-intensity interval training and essential amino acids.

High-intensity interval training (HIIT) promotes positive cardiometabolic and body composition changes. Essential amino acids (EAA) may support changes associated with HIIT, but evaluation of potential synergistic effects is lacking. The purpose of this study was to compare independent and combined effects of HIIT and EAA on total body composition and metabolism in men and women considered overweight/obese; an exploratory aim was to evaluate the modulatory effects of sex. Sixty-six healthy adults (50% female; Age: 36.7 ± 6.0 years; BMI: 32.0 ± 4.2 kg/m2) completed 8 weeks of: (1) HIIT, 2 days/weeks; (2) EAA supplementation, 3.6 g twice daily; (3) HIIT + EAA; or (4) control. Body composition, resting metabolic rate (RMR), substrate metabolism (respiratory exchange ratio; RER), and cardiorespiratory fitness were measured at baseline, 4 weeks, and 8 weeks; cardiometabolic blood markers were measured at baseline and 8 weeks. Differences between groups were assessed by linear mixed models covaried for baseline values, followed by 95% confidence intervals (CI) on adjusted mean change scores. There were no significant changes in body composition (p > 0.05) for any group. Changes in RER, but not RMR, occurred with HIIT (mean change; [95% CI]: - 0.04; [- 0.07, - 0.02]) and EAA (- 0.03; [- 0.06, - 0.01]) after 8 weeks. Cardiorespiratory fitness increased following 8 weeks of HIIT (+ 5.1 ml/kg/min [3.3,6.8]) and HIIT + EAA (+ 4.1 ml/kg/min [1.0,6.4]). Changes with HIIT + EAA were not significantly different from HIIT. There were no changes in cardiometabolic markers (p > 0.05) and no sex interaction (p > 0.05). HIIT is efficacious for promoting positive changes in cardiorespiratory fitness and resting substrate metabolism in adults considered overweight/obese. Addition of EAA did not significantly enhance HIIT-induced adaptations. ClinicalTrials.gov ID#NCT04080102.

Trends in Prevalence of Type 1 and Type 2 Diabetes in Children and Adolescents in the US, 2001-2017.

Importance: Changes in the prevalence of youth-onset diabetes have previously been observed. Objective: To estimate changes in prevalence of type 1 and type 2 diabetes in youths in the US from 2001 to 2017. Design, Setting, and Participants: In this cross-sectional observational study, individuals younger than 20 years with physician-diagnosed diabetes were enumerated from 6 areas in the US (4 geographic areas, 1 health plan, and select American Indian reservations) for 2001, 2009, and 2017. Exposures: Calendar year. Main Outcomes and Measures: Estimated prevalence of physician-diagnosed type 1 and type 2 diabetes overall and by race and ethnicity, age, and sex. Results: Among youths 19 years or younger, 4958 of 3.35 million had type 1 diabetes in 2001, 6672 of 3.46 million had type 1 diabetes in 2009, and 7759 of 3.61 million had type 1 diabetes in 2017; among those aged 10 to 19 years, 588 of 1.73 million had type 2 diabetes in 2001, 814 of 1.85 million had type 2 diabetes in 2009, and 1230 of 1.85 million had type 2 diabetes in 2017. The estimated type 1 diabetes prevalence per 1000 youths for those 19 years or younger increased significantly from 1.48 (95% CI, 1.44-1.52) in 2001 to 1.93 (95% CI, 1.88-1.98) in 2009 to 2.15 (95% CI, 2.10-2.20) in 2017, an absolute increase of 0.67 per 1000 youths (95%, CI, 0.64-0.70) and a 45.1% (95% CI, 40.0%-50.4%) relative increase over 16 years. The greatest absolute increases were observed among non-Hispanic White (0.93 per 1000 youths [95% CI, 0.88-0.98]) and non-Hispanic Black (0.89 per 1000 youths [95% CI, 0.88-0.98]) youths. The estimated type 2 diabetes prevalence per 1000 youths aged 10 to 19 years increased significantly from 0.34 (95% CI, 0.31-0.37) in 2001 to 0.46 (95% CI, 0.43-0.49) in 2009 to 0.67 (95% CI, 0.63-0.70) in 2017, an absolute increase of 0.32 per 1000 youths (95% CI, 0.30-0.35) and a 95.3% (95% CI, 77.0%-115.4%) relative increase over 16 years. The greatest absolute increases were observed among non-Hispanic Black (0.85 per 1000 youths [95% CI, 0.74-0.97]) and Hispanic (0.57 per 1000 youths [95% CI, 0.51-0.64]) youths. Conclusions and Relevance: In 6 areas of the US from 2001 to 2017, the estimated prevalence of diabetes among children and adolescents increased for both type 1 and type 2 diabetes.

Impact of Hurricane Matthew on Diabetes Self-Management and Outcomes.

BACKGROUND: Individuals with diabetes require extensive self-management. Little is known about how Hurricane Matthew (Matthew) or Hurricane Florence (Florence) impacted diabetes self-management and outcomes in Robeson County, North Carolina. METHODS: Mixed methods were used to assess the impact of hurricanes on diabetes self-management and outcomes. Individuals with diabetes were recruited for focus groups to understand the perceived impact on diabetes self-management. Health care providers were recruited for parallel key informant interviews. Mean hemoglobin A1c (HbA1c) and frequency of diabetic ketoacidosis (DKA) from hospital data six months before and after Matthew were compared using Student t-tests. RESULTS: A demographic breakdown of 34.25% white, 21.70% Black or African American, and 21.38% American Indian or Alaska Native was observed from focus groups. Qualitative results highlight a limited access to a balanced diet and medications. No significant differences were found between mean HbA1c values before and after Matthew (before Matthew: mean HbA1c 8.34 ± 1.87%; after Matthew: mean HbA1c 8.31 ± 1.93 %; P = .366). The period prevalence (PP) of DKA was higher after Matthew than before (before Matthew: 39 cases out of 4,025 visits, PP = .010; after Matthew: 87 cases out of 3,779 visits, PP = .023; P <.0001). LIMITATIONS: Limitations include non-random sampling and limited sample sizes. Also, the cross-sectional panel approach did not follow the same individuals over time. CONCLUSIONS: The period prevalence of DKA was higher in the six-month time period following Matthew compared to before the hurricane. Future interventions may improve outcomes via increased access to foods and medications recommended for those with diabetes.

Temporal trends in diabetic ketoacidosis at diagnosis of paediatric type 1 diabetes between 2006 and 2016: results from 13 countries in three continents.

AIMS/HYPOTHESIS: The aim of this work was to evaluate geographical variability and trends in the prevalence of diabetic ketoacidosis (DKA), between 2006 and 2016, at the diagnosis of childhood-onset type 1 diabetes in 13 countries over three continents. METHODS: An international retrospective study on DKA at diagnosis of diabetes was conducted. Data on age, sex, date of diabetes diagnosis, ethnic minority status and presence of DKA at diabetes onset were obtained from Australia, Austria, Czechia, Denmark, Germany, Italy, Luxembourg, New Zealand, Norway, Slovenia, Sweden, USA and the UK (Wales). Mean prevalence was estimated for the entire period, both overall and by country, adjusted for sex and age group. Temporal trends in annual prevalence of DKA were estimated using logistic regression analysis for each country, before and after adjustment for sex, age group and ethnic minority status. RESULTS: During the study period, new-onset type 1 diabetes was diagnosed in 59,000 children (median age [interquartile range], 9.0 years [5.5-11.7]; male sex, 52.9%). The overall adjusted DKA prevalence was 29.9%, with the lowest prevalence in Sweden and Denmark and the highest in Luxembourg and Italy. The adjusted DKA prevalence significantly increased over time in Australia, Germany and the USA while it decreased in Italy. Preschool children, adolescents and children from ethnic minority groups were at highest risk of DKA at diabetes diagnosis in most countries. A significantly higher risk was also found for females in Denmark, Germany and Slovenia. CONCLUSIONS/INTERPRETATION: DKA prevalence at type 1 diabetes diagnosis varied considerably across countries, albeit it was generally high and showed a slight increase between 2006 and 2016. Increased awareness of symptoms to prevent delay in diagnosis is warranted, especially in preschool children, adolescents and children from ethnic minority groups.

Incidence Trends of Type 1 and Type 2 Diabetes among Youths, 2002-2012.

BACKGROUND: Diagnoses of type 1 and type 2 diabetes in youths present a substantial clinical and public health burden. The prevalence of these diseases increased in the 2001-2009 period, but data on recent incidence trends are lacking. METHODS: We ascertained cases of type 1 and type 2 diabetes mellitus at five study centers in the United States. Denominators (4.9 million youths annually) were obtained from the U.S. Census or health-plan member counts. After the calculation of annual incidence rates for the 2002-2012 period, we analyzed trends using generalized autoregressive moving-average models with 2-year moving averages. RESULTS: A total of 11,245 youths with type 1 diabetes (0 to 19 years of age) and 2846 with type 2 diabetes (10 to 19 years of age) were identified. Overall unadjusted estimated incidence rates of type 1 diabetes increased by 1.4% annually (from 19.5 cases per 100,000 youths per year in 2002-2003 to 21.7 cases per 100,000 youths per year in 2011-2012, P=0.03). In adjusted pairwise comparisons, the annual rate of increase was greater among Hispanics than among non-Hispanic whites (4.2% vs. 1.2%, P<0.001). Overall unadjusted incidence rates of type 2 diabetes increased by 7.1% annually (from 9.0 cases per 100,000 youths per year in 2002-2003 to 12.5 cases per 100,000 youths per year in 2011-2012, P<0.001 for trend across race or ethnic group, sex, and age subgroups). Adjusted pairwise comparisons showed that the relative annual increase in the incidence of type 2 diabetes among non-Hispanic whites (0.6%) was lower than that among non-Hispanic blacks, Asians or Pacific Islanders, and Native Americans (P<0.05 for all comparisons) and that the annual rate of increase among Hispanics differed significantly from that among Native Americans (3.1% vs. 8.9%, P=0.01). After adjustment for age, sex, and race or ethnic group, the relative annual increase in the incidence of type 1 diabetes was 1.8% (P<0.001) and that of type 2 diabetes was 4.8% (P<0.001). CONCLUSIONS: The incidences of both type 1 and type 2 diabetes among youths increased significantly in the 2002-2012 period, particularly among youths of minority racial and ethnic groups. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and the Centers for Disease Control and Prevention.).