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.

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 Self-Reported Diagnosed Diabetes Among Adults, by County Metropolitan Status and Region, United States, 2019-2022.

Introduction: Previous research suggests that rural-urban disparities in diabetes mortality, hospitalization, and incidence rates may manifest differently across US regions. However, no studies have examined disparities in diabetes prevalence by metropolitan residence and region. Methods: We used data from the 2019-2022 National Health Interview Survey to compare diabetes status, socioeconomic characteristics, and weight status among adults in each census region (Northeast, Midwest, South, West) according to county metropolitan status of residence (large central metro, large fringe metro, small/medium metro, and nonmetro). We used χ2 tests and logistic regression models to assess the association of metropolitan residence with diabetes prevalence in each region. Results: Diabetes prevalence ranged from 7.0% in large fringe metro counties in the Northeast to 14.8% in nonmetro counties in the South. Compared with adults from large central metro counties, those from small/medium metro counties had significantly higher odds of diabetes in the Midwest (age-, sex-, and race and ethnicity-adjusted odds ratio [OR] = 1.24; 95% CI, 1.06-1.45) and South (OR = 1.15; 95% CI, 1.02-1.30). Nonmetro residence was also associated with diabetes in the South (OR = 1.62 vs large central metro; 95% CI, 1.43-1.84). After further adjustment for socioeconomic and body weight status, small/medium metro associations with diabetes became nonsignificant, but nonmetro residence in the South remained significantly associated with diabetes (OR = 1.22; 95% CI, 1.07-1.39). Conclusion: The association of metropolitan residence with diabetes prevalence differs across US regions. These findings can help to guide efforts in areas where diabetes prevention and care resources may be better directed.

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.

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.

Mortality trends in type 1 diabetes: a multicountry analysis of six population-based cohorts.

AIMS/HYPOTHESIS: Mortality has declined in people with type 1 diabetes in recent decades. We examined how the pattern of decline differs by country, age and sex, and how mortality trends in type 1 diabetes relate to trends in general population mortality. METHODS: We assembled aggregate data on all-cause mortality during the period 2000-2016 in people with type 1 diabetes aged 0-79 years from Australia, Denmark, Latvia, Scotland, Spain (Catalonia) and the USA (Kaiser Permanente Northwest). Data were obtained from administrative sources, health insurance records and registries. All-cause mortality rates in people with type 1 diabetes, and standardised mortality ratios (SMRs) comparing type 1 diabetes with the non-diabetic population, were modelled using Poisson regression, with age and calendar time as quantitative variables, describing the effects using restricted cubic splines with six knots for age and calendar time. Mortality rates were standardised to the age distribution of the aggregate population with type 1 diabetes. RESULTS: All six data sources showed a decline in age- and sex-standardised all-cause mortality rates in people with type 1 diabetes from 2000 to 2016 (or a subset thereof), with annual changes in mortality rates ranging from -2.1% (95% CI -2.8%, -1.3%) to -5.8% (95% CI -6.5%, -5.1%). All-cause mortality was higher for male individuals and for older individuals, but the rate of decline in mortality was generally unaffected by sex or age. SMR was higher in female individuals than male individuals, and appeared to peak at ages 40-70 years. SMR declined over time in Denmark, Scotland and Spain, while remaining stable in the other three data sources. CONCLUSIONS/INTERPRETATION: All-cause mortality in people with type 1 diabetes has declined in recent years in most included populations, but improvements in mortality relative to the non-diabetic population are less consistent.

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.

Reported Cases of End-Stage Kidney Disease - United States, 2000-2019.

End-stage kidney disease (ESKD) (kidney failure requiring dialysis or transplantation) is a costly and disabling condition that often results in premature death (1). During 2019, Medicare fee-for-service expenditures for ESKD were $37.3 billion, accounting for approximately 7% of Medicare paid claims costs (1). Diabetes and hypertension remain the leading causes of ESKD, accounting for 47% and 29%, respectively, of patients who began ESKD treatment in 2019 (1). Compared with White persons, Black, Hispanic, and American Indian or Alaska Native persons are more likely to develop ESKD (1,2) and to have diagnosed diabetes (3). After declining for more than a decade, the incidence rate of ESKD with diabetes reported as the primary cause (ESKD from diabetes) has leveled off since 2010 (1,4). Further, after increasing for many years, the prevalence of diagnosed diabetes has also leveled off (4). Although these flattening trends in rates are important from a population perspective, the trend in the number of ESKD cases is important from a health systems resources perspective. Using United States Renal Data System (USRDS) 2000-2019 data, CDC examined trends in the number of incident and prevalent ESKD cases by demographic characteristics and by primary cause of ESKD. During 2000-2019, the number of incident ESKD cases increased by 41.8%, and the number of prevalent ESKD cases increased by 118.7%. Higher percentage changes in both incident and prevalent ESKD cases were among Asian, Hispanic, and Native Hawaiian or other Pacific Islander persons and among cases with hypertension or diabetes as the primary cause. Interventions to improve care and better manage ESKD risk factors among persons with diabetes and hypertension, along with increased use of therapeutic agents such as angiotensin-converting enzyme (ACE) inhibitors, angiotensin-receptor blockers (ARB), and sodium-glucose cotransporter 2 (SGLT2) inhibitors shown to have kidney-protective benefits (5,6) might slow the increase and eventually reverse the trend in incident ESKD cases.

Risk for Newly Diagnosed Diabetes >30 Days After SARS-CoV-2 Infection Among Persons Aged <18 Years - United States, March 1, 2020-June 28, 2021.

The COVID-19 pandemic has disproportionately affected people with diabetes, who are at increased risk of severe COVID-19.* Increases in the number of type 1 diabetes diagnoses (1,2) and increased frequency and severity of diabetic ketoacidosis (DKA) at the time of diabetes diagnosis (3) have been reported in European pediatric populations during the COVID-19 pandemic. In adults, diabetes might be a long-term consequence of SARS-CoV-2 infection (4-7). To evaluate the risk for any new diabetes diagnosis (type 1, type 2, or other diabetes) >30 days† after acute infection with SARS-CoV-2 (the virus that causes COVID-19), CDC estimated diabetes incidence among patients aged <18 years (patients) with diagnosed COVID-19 from retrospective cohorts constructed using IQVIA health care claims data from March 1, 2020, through February 26, 2021, and compared it with incidence among patients matched by age and sex 1) who did not receive a COVID-19 diagnosis during the pandemic, or 2) who received a prepandemic non-COVID-19 acute respiratory infection (ARI) diagnosis. Analyses were replicated using a second data source (HealthVerity; March 1, 2020-June 28, 2021) that included patients who had any health care encounter possibly related to COVID-19. Among these patients, diabetes incidence was significantly higher among those with COVID-19 than among those 1) without COVID-19 in both databases (IQVIA: hazard ratio [HR] = 2.66, 95% CI = 1.98-3.56; HealthVerity: HR = 1.31, 95% CI = 1.20-1.44) and 2) with non-COVID-19 ARI in the prepandemic period (IQVIA, HR = 2.16, 95% CI = 1.64-2.86). The observed increased risk for diabetes among persons aged <18 years who had COVID-19 highlights the importance of COVID-19 prevention strategies, including vaccination, for all eligible persons in this age group,§ in addition to chronic disease prevention and management. The mechanism of how SARS-CoV-2 might lead to incident diabetes is likely complex and could differ by type 1 and type 2 diabetes. Monitoring for long-term consequences, including signs of new diabetes, following SARS-CoV-2 infection is important in this age group.

Is dietary intake of advanced glycation end products associated with mortality among adults with diabetes?

BACKGROUND AND AIMS: Prior studies suggest a positive association between dietary AGEs and adverse health outcomes but have not well-characterized AGEs intake and its association with mortality in a general adult population in the United States. METHODS AND RESULTS: We included 5474 adults with diabetes from the 2003 to 2018 National Health and Nutrition Examination Survey, a nationally representative sample of the non-institutionalized civilian population in the United States. Concordance to dietary guidelines (Healthy Eating Index 2015 [HEI-2015]) and intake of the AGE Nϵ-(carboxymethyl)lysine (CML) were estimated using an existing database and two 24-h food recalls. Multivariable Cox regression evaluated the association between AGEs intake and all-cause mortality. A secondary analysis measured CML, Nϵ-(1-carboxyethyl)lysine (CEL), and Nδ-(5-hydro-5-methyl-4-imidazolon-2-yl)-ornithine (MGH1) from an alternative database. Higher AGEs intake was associated with lower concordance to dietary guidelines (Means and standard errors of HEI-2015 score, by quartiles of AGEs intake: Q1 = 55.2 ± 0.6, Q2 = 54.1 ± 0.5, Q3 = 52.1 ± 0.5, Q4 = 49.0 ± 0.5; p < 0.001). There were 743 deaths among 3884 adults in the mortality analysis (mean follow-up = 3.8 years). AGEs intake was not significantly associated with all-cause mortality (Q2 vs. Q1: Hazard Ratio [HR] = 0.91 [0.69-1.21], Q3 vs. Q1: HR = 0.90 [0.63-1.27], Q4 vs. Q1: HR = 1.16 [0.84-1.60]). Results were similar in secondary analyses. CONCLUSION: While dietary AGEs intake was associated with concordance to dietary guidelines, it was not significantly associated with all-cause mortality among adults with diabetes. Further research may consider other health outcomes as well as the evaluating specific contribution of dietary AGEs to overall AGEs burden.

Comprehensive Search for Novel Circulating miRNAs and Axon Guidance Pathway Proteins Associated with Risk of ESKD in Diabetes.

BACKGROUND: Mechanisms underlying the pro gression of diabetic kidney disease to ESKD are not fully understood. METHODS: We performed global microRNA (miRNA) analysis on plasma from two cohorts consisting of 375 individuals with type 1 and type 2 diabetes with late diabetic kidney disease, and targeted proteomics analysis on plasma from four cohorts consisting of 746 individuals with late and early diabetic kidney disease. We examined structural lesions in kidney biopsy specimens from the 105 individuals with early diabetic kidney disease. Human umbilical vein endothelial cells were used to assess the effects of miRNA mimics or inhibitors on regulation of candidate proteins. RESULTS: In the late diabetic kidney disease cohorts, we identified 17 circulating miRNAs, represented by four exemplars (miR-1287-5p, miR-197-5p, miR-339-5p, and miR-328-3p), that were strongly associated with 10-year risk of ESKD. These miRNAs targeted proteins in the axon guidance pathway. Circulating levels of six of these proteins-most notably, EFNA4 and EPHA2-were strongly associated with 10-year risk of ESKD in all cohorts. Furthermore, circulating levels of these proteins correlated with severity of structural lesions in kidney biopsy specimens. In contrast, expression levels of genes encoding these proteins had no apparent effects on the lesions. In in vitro experiments, mimics of miR-1287-5p and miR-197-5p and inhibitors of miR-339-5p and miR-328-3p upregulated concentrations of EPHA2 in either cell lysate, supernatant, or both. CONCLUSIONS: This study reveals novel mechanisms involved in progression to ESKD and points to the importance of systemic factors in the development of diabetic kidney disease. Some circulating miRNAs and axon guidance pathway proteins represent potential targets for new therapies to prevent and treat this condition.

Impact of age at type 2 diabetes mellitus diagnosis on mortality and vascular complications: systematic review and meta-analyses.

AIMS/HYPOTHESIS: Few studies examine the association between age at diagnosis and subsequent complications from type 2 diabetes. This paper aims to summarise the risk of mortality, macrovascular complications and microvascular complications associated with age at diagnosis of type 2 diabetes. METHODS: Data were sourced from MEDLINE and All EBM (Evidence Based Medicine) databases from inception to July 2018. Observational studies, investigating the effect of age at diabetes diagnosis on macrovascular and microvascular diabetes complications in adults with type 2 diabetes were selected according to pre-specified criteria. Two investigators independently extracted data and evaluated all studies. If data were not reported in a comparable format, data were obtained from authors, presented as minimally adjusted ORs (and 95% CIs) per 1 year increase in age at diabetes diagnosis, adjusted for current age for each outcome of interest. The study protocol was recorded with PROSPERO International Prospective Register of Systematic Reviews (CRD42016043593). RESULTS: Data from 26 observational studies comprising 1,325,493 individuals from 30 countries were included. Random-effects meta-analyses with inverse variance weighting were used to obtain the pooled ORs. Age at diabetes diagnosis was inversely associated with risk of all-cause mortality and macrovascular and microvascular disease (all p < 0.001). Each 1 year increase in age at diabetes diagnosis was associated with a 4%, 3% and 5% decreased risk of all-cause mortality, macrovascular disease and microvascular disease, respectively, adjusted for current age. The effects were consistent for the individual components of the composite outcomes (all p < 0.001). CONCLUSIONS/INTERPRETATION: Younger, rather than older, age at diabetes diagnosis was associated with higher risk of mortality and vascular disease. Early and sustained interventions to delay type 2 diabetes onset and improve blood glucose levels and cardiovascular risk profiles of those already diagnosed are essential to reduce morbidity and mortality. Graphical abstract.

Tubular injury in diabetic ketoacidosis: Results from the diabetic kidney alarm study.

OBJECTIVE: Glomerular injury is a recognized complication of diabetic ketoacidosis (DKA), yet the tubular lesions are poorly understood. The aim of this prospective study was to evaluate the presence and reversibility of tubular injury during DKA in children with type 1 diabetes (T1D). RESEARCH DESIGN AND METHODS: Blood and urine samples were collected from 40 children with DKA (52% boys, mean age 11 ± 4 years, venous pH 7.2 ± 0.1, glucose 451 ± 163 mg/dL) at three timepoints: 0-8 and 12-24 h after starting insulin, and 3 months after discharge. Mixed-effects models evaluated the changes in tubular injury markers over time (neutrophil gelatinase-associated lipocalin [NGAL], kidney injury molecule 1 [KIM-1], and interleukin 18 [IL-18]). We also evaluated the relationships among the tubular injury biomarkers, copeptin, a vasopressin surrogate, and serum uric acid (SUA). RESULTS: Serum NGAL, KIM-1, and IL-18 were highest at 0-8 h (306.5 ± 45.9 ng/mL, 128.9 ± 10.1 pg/mL, and 564.3 ± 39.2 pg/mL, respectively) and significantly decreased over 3 months (p = 0.03, p = 0.01, and p < 0.001, respectively). There were strong relationships among increases in copeptin and SUA and rises in tubular injury biomarkers. At 0-8 h, participants with acute kidney injury (AKI) [17%] showed significantly higher concentrations of tubular injury markers, copeptin, and SUA. CONCLUSIONS: DKA was characterized by tubular injury, and the degree of injury associated with elevated copeptin and SUA. Tubular injury biomarkers, copeptin and SUA may be able to predict AKI in DKA.

A systematic review of trends in all-cause mortality among people with diabetes.

AIMS/HYPOTHESIS: We examined all-cause mortality trends in people with diabetes and compared them with trends among people without diabetes. METHODS: MEDLINE, EMBASE and CINAHL databases were searched for observational studies published from 1980 to 2019 reporting all-cause mortality rates across ≥2 time periods in people with diabetes. Mortality trends were examined by ethnicity, age and sex within comparable calendar periods. RESULTS: Of 30,295 abstracts screened, 35 studies were included, providing data on 69 separate ethnic-specific or sex-specific populations with diabetes since 1970. Overall, 43% (3/7), 53% (10/19) and 74% (32/43) of the populations studied had decreasing trends in all-cause mortality rates in people with diabetes in 1970-1989, 1990-1999 and 2000-2016, respectively. In 1990-1999 and 2000-2016, mortality rates declined in 75% (9/12) and 78% (28/36) of predominantly Europid populations, and in 14% (1/7) and 57% (4/7) of non-Europid populations, respectively. In 2000-2016, mortality rates declined in 33% (4/12), 65% (11/17), 88% (7/8) and 76% (16/21) of populations aged <40, 40-54, 55-69 and ≥70 years, respectively. Among the 33 populations with separate mortality data for those with and without diabetes, 60% (6/10) of the populations with diabetes in 1990-1999 and 58% (11/19) in 2000-2016 had an annual reduction in mortality rates that was similar to or greater than in those without diabetes. CONCLUSIONS/INTERPRETATION: All-cause mortality has declined in the majority of predominantly Europid populations with diabetes since 2000, and the magnitude of annual mortality reduction matched or exceeded that observed in people without diabetes in nearly 60% of populations. Patterns of diabetes mortality remain uncertain in younger age groups and non-Europid populations. REGISTRATION: PROSPERO registration ID CRD42019095974. Graphical abstract.

Do sodium-glucose cotransporter-2 inhibitors affect renal hemodynamics by different mechanisms in type 1 and type 2 diabetes?

Cardiovascular and renal outcome trials demonstrate nephroprotection with sodium-glucose cotransporter-2 inhibitors in people with type 2 diabetes. Attenuation of hyperfiltration is believed to be responsible for the nephroprotection, and studies in young adults with type 1 diabetes suggest that afferent arteriolar vasoconstriction induced by a tubuloglomerular feedback mechanism may be responsible for this effect. The study by van Bommel et al. suggests that this mechanism may not hold true in older adults with type 2 diabetes, who instead attenuate elevated glomerular filtration rate via post-glomerular vasodilation.

US Trends in Hospitalizations for Dialysis-Requiring Acute Kidney Injury in People With Versus Without Diabetes.

RATIONALE & OBJECTIVE: Dialysis-requiring acute kidney injury (AKI-D) has increased substantially in the United States. We examined trends in and comorbid conditions associated with hospitalizations and in-hospital mortality in the setting of AKI-D among people with versus without diabetes. STUDY DESIGN: Cross-sectional study. SETTING & PARTICIPANTS: Nationally representative data from the National Inpatient Sample and National Health Interview Survey were used to generate 16 cross-sectional samples of US adults (aged ≥18 years) between 2000 and 2015. EXPOSURE: Diabetes, defined using International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) diagnosis codes. OUTCOME: AKI-D, defined using ICD-9-CM diagnosis and procedure codes. ANALYTICAL APPROACH: Annual age-standardized rates of AKI-D and AKI-D mortality were calculated for adults with and without diabetes, by age and sex. Data were weighted to be representative of the US noninstitutionalized population. Trends were assessed using join point regression with annual percent change (Δ/y) reported. RESULTS: In adults with diabetes, AKI-D increased between 2000 and 2015 (from 26.4 to 41.1 per 100,000 persons; Δ/y, 3.3%; P < 0.001), with relative increases greater in younger versus older adults. In adults without diabetes, AKI-D increased between 2000 and 2009 (from 4.8 to 8.7; Δ/y, 6.5%; P < 0.001) and then plateaued. AKI-D mortality significantly declined in people with and without diabetes. In adults with and without diabetes, the proportion of AKI-D hospitalizations with liver, rheumatic, and kidney disease comorbid conditions increased between 2000 and 2015, while the proportion of most cardiovascular comorbid conditions decreased. LIMITATIONS: Lack of laboratory data to corroborate AKI diagnosis; National Inpatient Sample data are hospital-level rather than person-level data; no data for type of diabetes; residual unmeasured confounding. CONCLUSIONS: Hospitalization rates for AKI-D have increased considerably while mortality has decreased in adults with and without diabetes. Hospitalization rates for AKI-D remain substantially higher in adults with diabetes. Greater AKI risk-factor mitigation is needed, especially in young adults with diabetes.

CKD Awareness Among US Adults by Future Risk of Kidney Failure.

RATIONALE & OBJECTIVE: Persons with chronic kidney disease (CKD) are often unaware of their disease status. Efforts to improve CKD awareness may be most effective if focused on persons at highest risk for progression to kidney failure. STUDY DESIGN: Serial cross-sectional surveys. SETTING & PARTICIPANTS: Nonpregnant adults (aged≥20 years) with CKD glomerular filtration rate categories 3-4 (G3-G4) who participated in the National Health and Nutrition Examination Survey from 1999 to 2016 (n = 3,713). PREDICTOR: 5-year kidney failure risk, estimated using the Kidney Failure Risk Equation. Predicted risk was categorized as minimal (<2%), low (2%-<5%), intermediate (5%-<15%), or high (≥15%). OUTCOME: CKD awareness, defined by answering "yes" to the question "Have you ever been told by a doctor or other health professional that you had weak or failing kidneys?" ANALYTICAL APPROACH: Prevalence of CKD awareness was estimated within each risk group using complex sample survey methods. Associations between Kidney Failure Risk Equation risk and CKD awareness were assessed using multivariable logistic regression. CKD awareness was compared with awareness of hypertension and diabetes during the same period. RESULTS: In 2011 to 2016, unadjusted CKD awareness was 9.6%, 22.6%, 44.7%, and 49.0% in the minimal-, low-, intermediate-, and high-risk groups, respectively. In adjusted analyses, these proportions did not change over time. Awareness of CKD, including among the highest risk group, remains consistently below that of hypertension and diabetes and awareness of these conditions increased over time. LIMITATIONS: Imperfect sensitivity of the "weak or failing kidneys" question for ascertaining CKD awareness. CONCLUSIONS: Among adults with CKD G3-G4 who have 5-year estimated risks for kidney failure of 5%-<15% and≥15%, approximately half were unaware of their kidney disease, a gap that has persisted nearly 2 decades.

Exploring reasons for state-level variation in incidence of dialysis-requiring acute kidney injury (AKI-D) in the United States.

BACKGROUND: There is considerable state-level variation in the incidence of dialysis-requiring acute kidney injury (AKI-D). However, little is known about reasons for this geographic variation. METHODS: National cross-sectional state-level ecological study based on State Inpatient Databases (SID) and the Behavioral Risk Factor Surveillance System (BRFSS) in 2011. We analyzed 18 states and six chronic health conditions (diabetes mellitus [diabetes], hypertension, chronic kidney disease [CKD], arteriosclerotic heart disease [ASHD], cancer (excluding skin cancer), and chronic obstructive pulmonary disease [COPD]). Associations between each of the chronic health conditions and AKI-D incidence was assessed using Pearson correlation and multiple regression adjusting for mean age, the proportion of males, and the proportion of non-Hispanic whites in each state. RESULTS: The state-level AKI-D incidence ranged from 190 to 1139 per million population. State-level differences in rates of hospitalization with chronic health conditions (mostly < 3-fold difference in range) were larger than the state-level differences in prevalence for each chronic health condition (mostly < 2.5-fold difference in range). A significant correlation was shown between AKI-D incidence and prevalence of diabetes, ASHD, and COPD, as well as between AKI-D incidence and rate of hospitalization with hypertension. In regression models, after adjusting for age, sex, and race, AKI-D incidence was associated with prevalence of and rates of hospitalization with five chronic health conditions--diabetes, hypertension, CKD, ASHD and COPD--and rates of hospitalization with cancer. CONCLUSIONS: Results from this ecological analysis suggest that state-level variation in AKI-D incidence may be influenced by state-level variations in prevalence of and rates of hospitalization with several chronic health conditions. For most of the explored chronic conditions, AKI-D correlated stronger with rates of hospitalizations with the health conditions rather than with their prevalences, suggesting that better disease management strategies that prevent hospitalizations may translate into lower incidence of AKI-D.

Global trends in diabetes complications: a review of current evidence.

In recent decades, large increases in diabetes prevalence have been demonstrated in virtually all regions of the world. The increase in the number of people with diabetes or with a longer duration of diabetes is likely to alter the disease profile in many populations around the globe, particularly due to a higher incidence of diabetes-specific complications, such as kidney failure and peripheral arterial disease. The epidemiology of other conditions frequently associated with diabetes, including infections and cardiovascular disease, may also change, with direct effects on quality of life, demands on health services and economic costs. The current understanding of the international burden of and variation in diabetes-related complications is poor. The available data suggest that rates of myocardial infarction, stroke and amputation are decreasing among people with diabetes, in parallel with declining mortality. However, these data predominantly come from studies in only a few high-income countries. Trends in other complications of diabetes, such as end-stage renal disease, retinopathy and cancer, are less well explored. In this review, we synthesise data from population-based studies on trends in diabetes complications, with the objectives of: (1) characterising recent and long-term trends in diabetes-related complications; (2) describing regional variation in the excess risk of complications, where possible; and (3) identifying and prioritising gaps for future surveillance and study.