Glycoprotein Acetyls Associate With Intraglomerular Hemodynamic Dysfunction, Albuminuria, Central Adiposity, and Insulin Resistance in Youth With Type 1 Diabetes.

OBJECTIVES: Glycoprotein acetyls (GlycA's) are biomarkers of systemic inflammation and cardiovascular disease, yet little is known about their role in type 1 diabetes (T1D). In this study we examined the associations among GlycA's, central adiposity, insulin resistance, and early kidney injury in youth with T1D. METHODS: Glomerular filtration rate and renal plasma flow by iohexol and p-aminohippurate clearance, urine albumin-to-creatinine ratio (UACR), central adiposity by dual-energy x-ray absorptiometry, and estimated insulin sensitivity were assessed in 50 youth with T1D (16±3.0 years of age, 50% female, glycated hemoglobin 8.7±1.3%, T1D duration 5.7±2.6 years). Concentrations of GlycA were quantified by targeted nuclear magnetic resonance spectroscopy. Correlation and multivariable linear regression analyses were performed. RESULTS: GlycA's were higher in girls vs boys (1.05±0.26 vs 0.84±0.15 mmol/L, p=0.001) and in participants living with overweight/obesity vs normal weight (1.12±0.23 vs 0.87±0.20 mmol/L, p=0.0004). GlycA's correlated positively with estimated intraglomerular pressure (r=0.52, p=0.001), UACR (r=0.53, p<0.0001), and trunk mass (r=0.45, p=0.001), and inversely with estimated insulin sensitivity (r=-0.36, p=0.01). All relationships remained significant after adjustment for age, sex, and glycated hemoglobin. CONCLUSIONS: As biomarker of inflammation, GlycA's were higher in girls and those with overweight or obese body habitus in T1D. GlycA's associated with parameters of early kidney dysfunction, central adiposity, and insulin resistance.

Physical Activity According to Diabetes and Metropolitan Status, U.S., 2020 and 2022.

INTRODUCTION: Physical activity can reduce morbidity and mortality among adults with diabetes. Although rural disparities in physical activity exist among the general population, it is not known how these disparities manifest among adults with diabetes. METHODS: Data from the 2020 and 2022 National Health Interview Survey were analyzed in 2023 to assess the prevalence of meeting aerobic and muscle-strengthening recommendations according to the 2018 Physical Activity Guidelines for Americans during leisure time. Physical activity prevalence was computed by diabetes status, type of physical activity, and urban/rural residence (large central metropolitan, large fringe metropolitan, medium/small metropolitan, and nonmetropolitan). Logistic regression models were used to estimate prevalence and prevalence ratios of meeting physical activity recommendations by urban/rural residence across diabetes status. RESULTS: Among adults with diabetes in nonmetropolitan counties, only 23.8% met aerobic, 10.9% met muscle-strengthening, and 6.2% met both physical activity recommendations. By contrast, among adults with diabetes in large fringe metropolitan counties, 32.1% met aerobic, 19.7% met strengthening, and 12.0% met both guidelines. Multivariable adjusted prevalence of meeting muscle-strengthening recommendations was higher among participants with diabetes in large fringe metropolitan than among large central metropolitan counties (prevalence ratio=1.27; 95% CI=1.03, 1.56). Among those without diabetes, adjusted prevalence of meeting each recommendation or both was lower in nonmetropolitan and small/medium metropolitan than in large central metropolitan counties. CONCLUSIONS: Adults with diabetes are less likely to meet the physical activity recommendations than those without, and differences exist according to urban/rural status. Improving physical activity among rural residents with diabetes may mitigate disparities in diabetes-related mortality.

Assessing trends and variability in outpatient dual testing for chronic kidney disease with urine albumin and serum creatinine, 2009-2018: a retrospective cohort study in the Veterans Health Administration System.

BACKGROUND: Simultaneous urine testing for albumin (UAlb) and serum creatinine (SCr), that is, 'dual testing,' is an accepted quality measure in the management of diabetes. As chronic kidney disease (CKD) is defined by both UAlb and SCr testing, this approach could be more widely adopted in kidney care. OBJECTIVE: We assessed time trends and facility-level variation in the performance of outpatient dual testing in the integrated Veterans Health Administration (VHA) system. DESIGN, SUBJECTS AND MAIN MEASURES: This retrospective cohort study included patients with any inpatient or outpatient visit to the VHA system during the period 2009-2018. Dual testing was defined as UAlb and SCr testing in the outpatient setting within a calendar year. We assessed time trends in dual testing by demographics, comorbidities, high-risk (eg, diabetes) specialty care and facilities. A generalised linear mixed-effects model was applied to explore individual and facility-level predictors of receiving dual testing. KEY RESULTS: We analysed data from approximately 6.9 million veterans per year. Dual testing increased, on average, from 17.4% to 21.2%, but varied substantially among VHA centres (0.3%-43.7% in 2018). Dual testing was strongly associated with diabetes (OR 10.4, 95% CI 10.3 to 10.5, p<0.0001) and not associated with VHA centre complexity level. However, among patients with high-risk conditions including diabetes, <50% received dual testing in any given year. As compared with white veterans, black veterans were less likely to be tested after adjusting for other individual and facility characteristics (OR 0.93, 95% CI 0.92 to 0.93, p<0.0001). CONCLUSIONS: Dual testing for CKD in high-risk specialties is increasing but remains low. This appears primarily due to low rates of testing for albuminuria. Promoting dual testing in high-risk patients will help to improve disease management and patient outcomes.

Estimation of mortality rate ratios for chronic conditions with misclassification of disease status at death.

Estimation of mortality rates and mortality rate ratios (MRR) of diseased and non-diseased individuals is a core metric of disease impact used in chronic disease epidemiology. Estimation of mortality rates is often conducted through retrospective linkage of information from nationwide surveys such as the National Health Interview Survey (NHIS) and death registries. These surveys usually collect information on disease status during only one study visit. This infrequency leads to missing disease information (with right censored survival times) for deceased individuals who were disease-free at study participation, and a possibly biased estimation of the MRR because of possible undetected disease onset after study participation. This occurrence is called "misclassification of disease status at death (MicDaD)" and it is a potentially common source of bias in epidemiologic studies. In this study, we conducted a simulation analysis with a high and a low incidence setting to assess the extent of MicDaD-bias in the estimated mortality. For the simulated populations, MRR for diseased and non-diseased individuals with and without MicDaD were calculated and compared. Magnitude of MicDaD-bias depends on and is driven by the incidence of the chronic disease under consideration; our analysis revealed a noticeable shift towards underestimation for high incidences when MicDaD is present. Impact of MicDaD was smaller for lower incidence (but associated with greater uncertainty in the estimation of MRR in general). Further research can consider the amount of missing information and potential influencers such as duration and risk factors of the disease.

Prevalence of Cardiometabolic Diseases Among Racial and Ethnic Subgroups in Adults - Behavioral Risk Factor Surveillance System, United States, 2013-2021.

Although diabetes and cardiovascular disease account for substantial disease prevalence among adults in the United States, their prevalence among racial and ethnic subgroups is inadequately characterized. To fill this gap, CDC described the prevalence of diagnosed cardiometabolic diseases among U.S. adults, by disaggregated racial and ethnic subgroups, among 3,970,904 respondents to the Behavioral Risk Factor Surveillance System during 2013-2021. Prevalence of each disease (diabetes, myocardial infarction, angina or coronary heart disease, and stroke), stratified by race and ethnicity, was based on self-reported diagnosis by a health care professional, adjusting for age, sex, and survey year. Overall, mean respondent age was 47.5 years, and 51.4% of respondents were women. Prevalence of cardiometabolic diseases among disaggregated race and ethnicity subgroups varied considerably. For example, diabetes prevalence within the aggregated non-Hispanic Asian category (11.5%) ranged from 6.3% in the Vietnamese subgroup to 15.2% in the Filipino subgroup. Prevalence of angina or coronary heart disease for the aggregated Hispanic or Latino category (3.8%) ranged from 3.1% in the Cuban subgroup to 6.3% in the Puerto Rican subgroup. Disaggregation of cardiometabolic disease prevalence data by race and ethnicity identified health disparities among subgroups that can be used to better help guide prevention programs and develop culturally relevant interventions.

Risk Factors Amenable to Primary Prevention of Type 2 Diabetes Among Disaggregated Racial and Ethnic Subgroups in the U.S.

OBJECTIVE: Race and ethnicity data disaggregated into detailed subgroups may reveal pronounced heterogeneity in diabetes risk factors. We therefore used disaggregated data to examine the prevalence of type 2 diabetes risk factors related to lifestyle behaviors and barriers to preventive care among adults in the U.S. RESEARCH DESIGN AND METHODS: We conducted a pooled cross-sectional study of 3,437,640 adults aged ≥18 years in the U.S. without diagnosed diabetes from the Behavioral Risk Factor Surveillance System (2013-2021). For self-reported race and ethnicity, the following categories were included: Hispanic (Cuban, Mexican, Puerto Rican, Other Hispanic), non-Hispanic (NH) American Indian/Alaska Native, NH Asian (Chinese, Filipino, Indian, Japanese, Korean, Vietnamese, Other Asian), NH Black, NH Pacific Islander (Guamanian/Chamorro, Native Hawaiian, Samoan, Other Pacific Islander), NH White, NH Multiracial, NH Other. Risk factors included current smoking, hypertension, overweight or obesity, physical inactivity, being uninsured, not having a primary care doctor, health care cost concerns, and no physical exam in the past 12 months. RESULTS: Prevalence of hypertension, lifestyle factors, and barriers to preventive care showed substantial heterogeneity among both aggregated, self-identified racial and ethnic groups and disaggregated subgroups. For example, the prevalence of overweight or obesity ranged from 50.8% (95% CI 49.1-52.5) among Chinese adults to 79.8% (73.5-84.9) among Samoan adults. Prevalence of being uninsured among Hispanic subgroups ranged from 11.4% (10.9-11.9) among Puerto Rican adults to 33.0% (32.5-33.5) among Mexican adults. CONCLUSIONS: These findings underscore the importance of using disaggregated race and ethnicity data to accurately characterize disparities in type 2 diabetes risk factors and access to care.

Diabetes Prevalence and Incidence Inequality Trends Among U.S. Adults, 2008-2021.

INTRODUCTION: This study examined national trends in age, sex, racial and ethnic, and socioeconomic inequalities for diagnosed diabetes prevalence and incidence among U.S. adults from 2008 to 2021. METHODS: Adults (aged ≥18 years) were from the National Health Interview Survey (2008-2021). The annual between-group variance (BGV) for sex, race, and ethnicity; and the slope index of inequality (SII) for age, education, and poverty-to-income ratio along with the average annual percentage change (AAPC) were estimated in 2023 to assess trends in inequalities over time in diabetes prevalence and incidence. For BGV and SII, a value of 0 represents no inequality, whereas a value further from 0 represents greater inequality. RESULTS: On average over time, poverty-to-income ratio inequalities in diabetes prevalence worsened (SII= -8.24 in 2008 and -9.80 in 2021; AAPC for SII= -1.90%, p=0.003), whereas inequalities in incidence for age (SII=17.60 in 2008 and 8.85 in 2021; AAPC for SII= -6.47%, p<0.001), sex (BGV=0.09 in 2008, 2.05 in 2009, 1.24 in 2010, and 0.27 in 2021; AAPC for BGV= -12.34%, p=0.002), racial and ethnic (BGV=4.80 in 2008 and 2.17 in 2021; AAPC for BGV= -10.59%, p=0.010), and education (SII= -9.89 in 2008 and -2.20 in 2021; AAPC for SII=8.27%, p=0.001) groups improved. CONCLUSIONS: From 2008 to 2021, age, sex, racial and ethnic, and education inequalities in the incidence of diagnosed diabetes improved but persisted. Income-related diabetes prevalence inequalities worsened over time. To close these gaps, future research could focus on identifying the factors driving these trends, including the contribution of morbidity and mortality.

Risk of Cardiovascular Disease After COVID-19 Diagnosis Among Adults With and Without Diabetes.

Background Growing evidence suggests incident cardiovascular disease (CVD) may be a long-term outcome of COVID-19 infection, and chronic diseases, such as diabetes, may influence CVD risk associated with COVID-19. We evaluated the postacute risk of CVD >30 days after a COVID-19 diagnosis by diabetes status. Methods and Results We included adults ≥20 years old with a COVID-19 diagnosis from March 1, 2020 through December 31, 2021 in a retrospective cohort study from the IQVIA PharMetrics Plus insurance claims database. A contemporaneous control group comprised adults without recorded diagnoses for COVID-19 or other acute respiratory infections. Two historical control groups comprised patients with or without an acute respiratory infection. Cardiovascular outcomes included cerebrovascular disorders, dysrhythmia, inflammatory heart disease, ischemic heart disease, thrombotic disorders, other cardiac disorders, major adverse cardiovascular events, and any CVD. The total sample comprised 23 824 095 adults (mean age, 48.4 years [SD, 15.7 years]; 51.9% women; mean follow-up, 8.5 months [SD, 5.8 months]). In multivariable Cox regression models, patients with a COVID-19 diagnosis had a significantly greater risk of all cardiovascular outcomes compared with patients without a diagnosis of COVID-19 (hazard ratio [HR], 1.66 [1.62-1.71], with diabetes; HR, 1.75 [1.73-1.78], without diabetes). Risk was attenuated but still significant for the majority of outcomes when comparing patients with COVID-19 to both historical control groups. Conclusions In patients with COVID-19 infection, postacute risk of incident cardiovascular outcomes is significantly higher than among controls without COVID-19, regardless of diabetes status. Therefore, monitoring for incident CVD may be essential beyond the first 30 days after a COVID-19 diagnosis.

Prevalence of anemia and associated All-Cause mortality among adults with Diabetes: The role of chronic kidney disease.

AIMS: Among adults with diabetes in the United States, we evaluated anemia prevalence by CKD status as well as the role of CKD and anemia, as potential risk factors for all-cause mortality. METHODS: In a retrospective cohort study, we included 6,718 adult participants with prevalent diabetes from the 2003-March 2020 National Health and Nutrition Examination Survey (NHANES), a nationally representative sample of the non-institutionalized civilian population in the United States. Cox regression models evaluated the role of anemia and CKD, alone or combined, as predictors of all-cause mortality. RESULTS: Anemia prevalence among adults with diabetes and CKD was 20%. Having anemia or CKD alone, compared with having neither condition, was significantly associated with all-cause mortality (anemia: HR = 2.10 [1.49-2.96], CKD: HR = 2.24 [1.90-2.64]). Having both conditions conferred a greater potential risk (HR = 3.41 [2.75-4.23]). CONCLUSIONS: Approximately one-quarter of the adult US population with diabetes and CKD also has anemia. The presence of anemia, with or without CKD, is associated with a two- to threefold increased risk of death by compared with adults who have neither condition, suggesting that anemia may be a strong predictor of death among adults with diabetes.

Changes in racial and ethnic disparities in glucose-lowering drug utilization and glycated haemoglobin A1c in US adults with diabetes: 2005-2018.

AIM: To examine changes in racial and ethnic disparities in glucose-lowering drugs (GLD) use and glycated haemoglobin A1c in US adults with diabetes from 2005 to 2018. METHODS: We conducted pooled cross-sectional analysis using data from the 2005-2018 Medical Expenditure Panel Surveys, and the 2005-2018 National Health and Nutrition Examination Survey. Individuals ≥18 years with diabetes were included. Racial and ethnic disparities were measured in (a) newer non-insulin GLD use; (b) insulin analogue use; (c) non-insulin GLDs adherence; (d) insulin adherence; and (e) glucose management, along with (f) the proportion of the disparities explained by potential contributing factors. RESULTS: From 2005 to 2018, racial and ethnic disparities persisted in newer GLD use, non-insulin GLDs adherence, insulin analogue use and glucose management. In 2018, compared with non-Hispanic white adults, non-Hispanic black, Hispanic and other race/ethnicity groups had lower rates of using newer GLDs (adjusted risk ratio: 0.44, 0.52, 0.64, respectively; p < .05 for all) and insulin analogues (adjusted risk ratio: 0.93, 0.89, 0.95, respectively; p < .05 for all except other groups), lower non-insulin GLD adherence (proportion of days covered: -4.5%, -5.6%, -4.3%, respectively; p < .05 for all), higher glycated haemoglobin A1c (0.29%, 0.32%, 0.02%, respectively; p < .05 for all except other group), and similar insulin adherences. Socioeconomic and health status were the main contributors to these disparities. CONCLUSIONS: Our findings provide evidence of racial and ethnic disparities in newer GLD use and quality of care in glucose management. Our study results can inform decision-makers of the status of racial and ethnic disparities and identify ways to reduce these disparities.

Youth-onset type 2 diabetes mellitus: an urgent challenge.

The incidence and prevalence of youth-onset type 2 diabetes mellitus (T2DM) and its complications are increasing worldwide. Youth-onset T2DM has been reported in all racial and ethnic groups, but Indigenous peoples and people of colour are disproportionately affected. People with youth-onset T2DM often have a more aggressive clinical course than those with adult-onset T2DM or those with type 1 diabetes mellitus. Moreover, the available treatment options for children and adolescents with T2DM are more limited than for adult patients. Intermediate complications of youth-onset T2DM, such as increased albuminuria, often develop in late childhood or early adulthood, and end-stage complications, including kidney failure, develop in mid-life. The increasing frequency, earlier onset and greater severity of childhood obesity in the past 50 years together with increasingly sedentary lifestyles and an increasing frequency of intrauterine exposure to diabetes are important drivers of the epidemic of youth-onset T2DM. The particularly high risk of the disease in historically disadvantaged populations suggests an important contribution of social and environmental factors, including limited access to high-quality health care, healthy food choices and opportunities for physical activity as well as exposure to stressors including systemic racism and environmental pollutants. Understanding the mechanisms that underlie the development and aggressive clinical course of youth-onset T2DM is key to identifying successful prevention and management strategies.

Plasma levels of carboxylic acids are markers of early kidney dysfunction in young people with type 1 diabetes.

BACKGROUND: We compared plasma metabolites of amino acid oxidation and the tricarboxylic acid (TCA) cycle in youth with and without type 1 diabetes mellitus (T1DM) and related the metabolites to glomerular filtration rate (GFR), renal plasma flow (RPF), and albuminuria. Metabolites associated with impaired kidney function may warrant future study as potential biomarkers or even future interventions to improve kidney bioenergetics. METHODS: Metabolomic profiling of fasting plasma samples using a targeted panel of 644 metabolites and an untargeted panel of 19,777 metabolites was performed in 50 youth with T1DM ≤ 10 years and 20 controls. GFR and RPF were ascertained by iohexol and p-aminohippurate clearance, and albuminuria calculated as urine albumin to creatinine ratio. Sparse partial least squares discriminant analysis and moderated t tests were used to identify metabolites associated with GFR and RPF. RESULTS: Adolescents with and without T1DM were similar in age (16.1 ± 3.0 vs. 16.1 ± 2.9 years) and BMI (23.4 ± 5.1 vs. 22.7 ± 3.7 kg/m2), but those with T1DM had higher GFR (189 ± 40 vs. 136 ± 22 ml/min) and RPF (820 ± 125 vs. 615 ± 65 ml/min). Metabolites of amino acid oxidation and the TCA cycle were significantly lower in adolescents with T1DM vs. controls, and the measured metabolites were able to discriminate diabetes status with an AUC of 0.82 (95% CI: 0.71, 0.93) and error rate of 0.21. Lower glycine (r:-0.33, q = 0.01), histidine (r:-0.45, q < 0.001), methionine (r: -0.29, q = 0.02), phenylalanine (r: -0.29, q = 0.01), serine (r: -0.42, q < 0.001), threonine (r: -0.28, q = 0.02), citrate (r: -0.35, q = 0.003), fumarate (r: -0.24, q = 0.04), and malate (r: -0.29, q = 0.02) correlated with higher GFR. Lower glycine (r: -0.28, q = 0.04), phenylalanine (r:-0.3, q = 0.03), fumarate (r: -0.29, q = 0.04), and malate (r: -0.5, q < 0.001) correlated with higher RPF. Lower histidine (r: -0.28, q = 0.02) was correlated with higher mean ACR. CONCLUSIONS: In conclusion, adolescents with relatively short T1DM duration exhibited lower plasma levels of carboxylic acids that associated with hyperfiltration and hyperperfusion. TRIAL REGISTRATION: ClinicalTrials.gov NCT03618420 and NCT03584217 A higher resolution version of the Graphical abstract is available as Supplementary information.

Proinflammatory Diets and Risk of ESKD in US Adults with CKD.

Background: Inflammation may affect long-term kidney function. Diet may play a role in chronic inflammation. We hypothesized that proinflammatory diets increase the risk of progression to kidney failure with replacement therapy (KFRT), and systemic inflammation is a mediator of the effect of diet on progression to KFRT. Methods: In the 1988-1994 National Health and Nutrition Examination Survey linked to the national ESKD registry, in adults with CKD (eGFR 15-59 ml/min per 1.73 m2), aged ≥20 years, we calculated the Adapted Dietary Inflammatory Index (ADII) at baseline from a 24-hour dietary recall and an inflammation score (IS) using average of z scores of four inflammation biomarkers. We explored the association of the ADII and IS with risk of incident KFRT using Cox proportional model, adjusting for sociodemographics, physical activity, Framingham risk score, eGFR, and urinary ACR. We evaluated whether, and to what extent, IS mediated the effect of the ADII on KFRT incidence, using causal mediation analysis. Results: Of 1084 adults with CKD, 109 (10%) developed KFRT. The ADII was associated with increased risk of KFRT (relative hazard [RH] per SD increase (2.56): 1.4 [1.04-1.78]). IS was also associated with KFRT (RH: 1.12; 95% CI, 1.02 to 1.25). Approximately 36% of the association between the ADII and KFRT was explained by IS. Conclusions: Among adults with CKD, a proinflammatory diet was associated with risk of KFRT, and that association was partially explained by an increase in inflammatory markers. Dietary interventions that reduce inflammation may offer an approach for preventing KFRT.

Age-Related Association between Multimorbidity and Mortality in US Veterans with Incident Chronic Kidney Disease.

INTRODUCTION: Mortality is an important long-term indicator of the public health impact of chronic kidney disease (CKD). We investigated the role of individual comorbidities and multimorbidity on age-specific mortality risk among US veterans with new-onset CKD. METHODS: The cohort included 892,005 veterans aged ≥18 years with incident CKD stage 3 between January 2004 and April 2018 in the US Veterans Health Administration (VHA) system and followed until death, December 2018, or up to 10 years. Incident CKD was defined as the first-time estimated glomerular filtration rate (eGFR) was <60 mL/min/1.73 m2 for >3 months. Comorbidities were ascertained using inpatient and outpatient clinical records in the VHA system and Medicare claims. We estimated death rates for any cardiovascular disease (CVD, a composite of 6 CVD conditions) and 15 non-CVD comorbidities, and adjusted risks of death (hazard ratio [HR], 95% confidence interval [CI]) overall and by age group at CKD incidence. RESULTS: At CKD incidence, the mean age was 72 years, and 97% were male; the mean eGFR was 52 mL/min/1.73 m2, and 95% had ≥2 comorbidities (median, 4) in addition to CKD. During a median follow-up of 4.5 years, among the 16 comorbidities, CVD was associated with the highest relative risk of death in younger veterans (HR 1.96 [95% CI: 1.61-2.37] in ages 18-44 years and HR 1.66 [1.63-1.70] in ages 45-64 years). Dementia was associated with the highest relative risk of death among older veterans (HR 1.71 [1.68-1.74] in ages 65-84 years and HR 1.69 [1.65-1.73] in ages 85-100 years). The additive effect of multimorbidity on risk of death was stronger in younger than older veterans. Compared to having 1 or no comorbidity at CKD onset, the risk of death with ≥5 comorbidities was >7-fold higher among veterans aged 18-44 years and >2-fold higher among veterans aged 85-100 years. CONCLUSION: The large burden of comorbidities in US veterans with newly identified CKD places them at the risk of premature death. Compared with older veterans, younger veterans with multiple comorbidities, particularly with CVD, at CKD onset are at an even higher relative risk of death.

Lifetime risk, life expectancy, and years of life lost to type 2 diabetes in 23 high-income jurisdictions: a multinational, population-based study.

BACKGROUND: Diabetes is a major public health issue. Because lifetime risk, life expectancy, and years of life lost are meaningful metrics for clinical decision making, we aimed to estimate these measures for type 2 diabetes in the high-income setting. METHODS: For this multinational, population-based study, we sourced data from 24 databases for 23 jurisdictions (either whole countries or regions of a country): Australia; Austria; Canada; Denmark; Finland; France; Germany; Hong Kong; Hungary; Israel; Italy; Japan; Latvia; Lithuania; the Netherlands; Norway; Scotland; Singapore; South Korea; Spain; Taiwan; the UK; and the USA. Our main outcomes were lifetime risk of type 2 diabetes, life expectancy in people with and without type 2 diabetes, and years of life lost to type 2 diabetes. We modelled the incidence and mortality of type 2 diabetes in people with and without type 2 diabetes in sex-stratified, age-adjusted, and calendar year-adjusted Poisson models for each jurisdiction. Using incidence and mortality, we constructed life tables for people of both sexes aged 20-100 years for each jurisdiction and at two timepoints 5 years apart in the period 2005-19 where possible. Life expectancy from a given age was computed as the area under the survival curves and lifetime lost was calculated as the difference between the expected lifetime of people with versus without type 2 diabetes at a given age. Lifetime risk was calculated as the proportion of each cohort who developed type 2 diabetes between the ages of 20 years and 100 years. We estimated 95% CIs using parametric bootstrapping. FINDINGS: Across all study cohorts from the 23 jurisdictions (total person-years 1 577 234 194), there were 5 119 585 incident cases of type 2 diabetes, 4 007 064 deaths in those with type 2 diabetes, and 11 854 043 deaths in those without type 2 diabetes. The lifetime risk of type 2 diabetes ranged from 16·3% (95% CI 15·6-17·0) for Scottish women to 59·6% (58·5-60·8) for Singaporean men. Lifetime risk declined with time in 11 of the 15 jurisdictions for which two timepoints were studied. Among people with type 2 diabetes, the highest life expectancies were found for both sexes in Japan in 2017-18, where life expectancy at age 20 years was 59·2 years (95% CI 59·2-59·3) for men and 64·1 years (64·0-64·2) for women. The lowest life expectancy at age 20 years with type 2 diabetes was observed in 2013-14 in Lithuania (43·7 years [42·7-44·6]) for men and in 2010-11 in Latvia (54·2 years [53·4-54·9]) for women. Life expectancy in people with type 2 diabetes increased with time for both sexes in all jurisdictions, except for Spain and Scotland. The life expectancy gap between those with and without type 2 diabetes declined substantially in Latvia from 2010-11 to 2015-16 and in the USA from 2009-10 to 2014-15. Years of life lost to type 2 diabetes ranged from 2·5 years (Latvia; 2015-16) to 12·9 years (Israel Clalit Health Services; 2015-16) for 20-year-old men and from 3·1 years (Finland; 2011-12) to 11·2 years (Israel Clalit Health Services; 2010-11 and 2015-16) for 20-year-old women. With time, the expected number of years of life lost to type 2 diabetes decreased in some jurisdictions and increased in others. The greatest decrease in years of life lost to type 2 diabetes occurred in the USA between 2009-10 and 2014-15 for 20-year-old men (a decrease of 2·7 years). INTERPRETATION: Despite declining lifetime risk and improvements in life expectancy for those with type 2 diabetes in many high-income jurisdictions, the burden of type 2 diabetes remains substantial. Public health strategies might benefit from tailored approaches to continue to improve health outcomes for people with diabetes. FUNDING: US Centers for Disease Control and Prevention and Diabetes Australia.

Prevalence and Characteristics of CKD in the US Military Health System: A Retrospective Cohort Study.

Rationale & Objective: The US Military Health System (MHS) is a global health care network with a diverse population that is more representative of the US population than other study cohorts and with fewer disparities in health care access. We aimed to examine the prevalence of chronic kidney disease (CKD) in the MHS and within demographic subpopulations. Study Design: Multiple cross-sectional analyses of demographic and claims-based data extracted from the MHS Data Repository, 1 for each fiscal year from 2006-2015. Setting & Population: Multicenter health care network including active-duty military, retirees, and dependents. The average yearly sample size was 3,285,348 individuals. Exposures: Age, sex, race, active-duty status, and active-duty rank (a surrogate for socioeconomic status). Outcome: CKD, defined as the presence of matching International Classification of Diseases, Ninth Revision, codes on either 1 or more inpatient or 2 or more outpatient encounters. Analytical Approach: t test for continuous variables and χ2 test for categorical variables; multivariable logistic regression for odds ratios. Results: For 2015, the mean (standard deviation) age was 38 (16). Crude CKD prevalence was 2.9%. Age-adjusted prevalence was 4.9% overall-1.9% active-duty and 5.4% non-active-duty individuals. ORs for CKD were calculated with multiple imputations to account for missing data on race. After adjustment, the ORs for CKD (all P < 0.001) were 1.63 (95% CI, 1.62-1.64) for an age greater than 40 years, 1.16 (95% CI, 1.15-1.17) for Black race, 1.15 (95% CI, 1.14-1.16) for senior enlisted rank, 0.94 (95% CI, 0.93-0.95) for women, and 0.50 (95% CI, 0.49-0.51) for active-duty status. Limitations: Retrospective study based on International Classification of Diseases, Ninth Revision, coding. Conclusions: Within the MHS, older age, Black race, and senior enlisted rank were associated with a higher risk of CKD, whereas female sex and active-duty status were associated with a lower risk.

Aminoaciduria and metabolic dysregulation during diabetic ketoacidosis: Results from the diabetic kidney alarm (DKA) study.

OBJECTIVE: We examined changes in the excretion of various amino acids and in glycolysis and ketogenesis-related metabolites, during and after diabetic ketoacidosis (DKA) diagnosis, in youth with known or new onset type 1 diabetes (T1D). METHODS: Urine samples were collected from 40 youth with DKA (52% boys, mean age 11 ± 4 years, venous pH 7.2 ± 0.1, blood glucose 451 ± 163 mg/dL) at 3 time points: 0-8 h and 12-24 h after starting an insulin infusion, and 3 months after hospital discharge. Mixed-effects models evaluated the changes in amino acids and other metabolites in the urine. RESULTS: Concentrations of urine histidine, threonine, tryptophan, and leucine per creatinine were highest at 0-8 h (148.8 ± 23.5, 59.5 ± 12.3, 15.4 ± 1.4, and 24.5 ± 2.4% of urine creatinine, respectively), and significantly decreased over 3 months (p = 0.028, p = 0.027, p = 0.019, and p < 0.0001, respectively). Urine histidine, threonine, tryptophan, and leucine per urine creatinine decreased by 10.6 ± 19.2, 0.7 ± 0.9, 1.3 ± 0.9, and 0.5 ± 0.3-fold, respectively, between 0 and 8 h and 3 months. CONCLUSIONS: In our study, DKA was associated with profound aminoaciduria, suggestive of proximal tubular dysfunction analogous to Fanconi syndrome.