RATIONALE & OBJECTIVE: Patients with kidney failure from racial and ethnic minority groups and older patients have reduced access to the transplant waitlist relative to White and younger patients. Although racial disparities in the waitlisting group have declined after the 2014 kidney allocation system change, whether there is intersectionality of race and age in waitlisting access is unknown. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: 439,455 non-Hispanic White and non-Hispanic Black US adults initiating dialysis between 2015 and 2019 were identified from the United States Renal Data System, and followed through 2020. EXPOSURES: Patient race and ethnicity (non-Hispanic White and non-Hispanic Black) and age group (18-29, 30-49, 50-64, and 65-80 years). OUTCOMES: Placement on the United Network for Organ Sharing deceased donor waitlist. ANALYTICAL APPROACH: Age- and race-stratified waitlisting rates were compared. Multivariable Cox proportional hazards models, censored for death, examined the association between race and waitlisting, and included interaction term for race and age. RESULTS: Over a median follow-up period of 1 year, the proportion of non-Hispanic White and non-Hispanic Black patients waitlisted was 20.7% and 20.5%, respectively. In multivariable models, non-Hispanic Black patients were 14% less likely to be waitlisted (aHR, 0.86, 95% CI, 0.77-0.95). Relative differences between non-Hispanic Black and non-Hispanic White patients were different by age group. Non-Hispanic Black patients were 27%, 12%, and 20% less likely to be waitlisted than non-Hispanic White patients for ages 18-29 years (aHR, 0.73; 95% CI, 0.61-0.86), 50-64 (aHR, 0.88; 95% CI, 0.80-0.98), and 65-80 years (aHR, 0.80; 95% CI, 0.71-0.90), respectively, but differences were attenuated among patients aged 30-49 years (aHR, 0.89; 95% CI, 0.77-1.02). LIMITATIONS: Race and ethnicity data is physician reported, residual confounding, and analysis is limited to non-Hispanic White and non-Hispanic Black patients. CONCLUSIONS: Racial disparities in waitlisting exist between non-Hispanic Black and non-Hispanic White individuals and are most pronounced among younger patients with kidney failure. Results suggest that interventions to address inequalities in waitlisting may need to be targeted to younger patients with kidney failure. PLAIN-LANGUAGE SUMMARY: Research has shown that patients from racial and ethnic minority groups and older patients have reduced access to transplant waitlisting relative to White and younger patients; nevertheless, how age impacts racial disparities in waitlisting is unknown. We compared waitlisting between non-Hispanic Black and non-Hispanic White patients with incident kidney failure, within age strata, using registry data for 439,455 US adults starting dialysis (18-80 years) during 2015-2019. Overall, non-Hispanic Black patients were less likely to be waitlisted and relative differences between the two racial groups differed by age. After adjusting for patient-level factors, the largest disparity in waitlisting was observed among adults aged 18-29 years. These results suggest that interventions should target younger adults to reduce disparities in access to kidney transplant waitlisting.

INTRODUCTION: Heart failure (HF) is a major contributor to cardiovascular morbidity and mortality in people with diabetes. In this study, we estimated trends in the incidence of HF inpatient admissions and emergency department (ED) visits by diabetes status. RESEARCH DESIGN AND METHODS: Population-based age-standardized HF rates in adults with and without diabetes were estimated from the 2006-2017 National Inpatient Sample, Nationwide ED Sample and year-matched National Health Interview Survey, and stratified by age and sex. Trends were assessed using Joinpoint. RESULTS: HF inpatient admissions did not change in adults with diabetes between 2006 and 2013 (from 53.9 to 50.4 per 1000 persons; annual percent change (APC): -0.3 (95% CI -2.5 to 1.9) but increased from 50.4 to 62.3 between 2013 and 2017 (APC: 4.8 (95% CI 0.3 to 9.6)). In adults without diabetes, inpatient admissions initially declined (from 14.8 in 2006 to 12.9 in 2014; APC -2.3 (95% CI -3.2 to -1.2)) and then plateaued. Patterns were similar in men and women, but relative increases were greatest in young adults with diabetes. HF-related ED visits increased overall, in men and women, and in all age groups, but increases were greater in adults with (vs without) diabetes. CONCLUSIONS: Causes of increased HF rates in hospital settings are unknown, and more detailed data are needed to investigate the aetiology and determine prevention strategies, particularly among adults with diabetes and especially young adults with diabetes.

INTRODUCTION: Little is known about the role diabetes (type 1 (T1D) and type 2 (T2D)) plays in modifying prognosis among kidney transplant recipients. Here, we compare mortality among transplant recipients with T1D, T2D and non-diabetes-related end-stage kidney disease (ESKD). RESEARCH DESIGN AND METHODS: We included 254 188 first-time single kidney transplant recipients aged ≥18 years from the US Renal Data System (2000-2018). Diabetes status, as primary cause of ESKD, was defined using International Classification of Disease 9th and 10th Clinical Modification codes. Multivariable-adjusted Cox regression models (right-censored) computed risk of death associated with T1D and T2D relative to non-diabetes. Trends in standardized mortality ratios (SMRs) (2000-2017), relative to the general US population, were assessed using Joinpoint regression. RESULTS: A total of 72 175 (28.4%) deaths occurred over a median survival time of 14.6 years. 5-year survival probabilities were 88%, 85% and 77% for non-diabetes, T1D and T2D, respectively. In adjusted models, mortality was highest for T1D (HR=1.95, (95% CI: 1.88 to 2.03)) and then T2D (1.65 (1.62 to 1.69)), as compared with non-diabetes. SMRs declined for non-diabetes, T1D, and T2D. However, in 2017, SMRs were 2.38 (2.31 to 2.45), 6.55 (6.07 to 7.06), and 3.82 (3.68 to 3.98), for non-diabetes, T1D and T2D, respectively. CONCLUSIONS: In the USA, diabetes type is an important modifier in mortality risk among kidney transplant recipients with highest rates among people with T1D-related ESKD. Development of effective interventions that reduce excess mortality in transplant recipients with diabetes is needed, especially for T1D.

OBJECTIVE: Diabetes is a leading cause of nontraumatic lower-extremity amputation (NLEA) in the U.S. After a period of decline, some national U.S. data have shown that diabetes-related NLEAs have recently increased, particularly among young and middle-aged adults. However, the trend for older adults is less clear. RESEARCH DESIGN AND METHODS: To examine NLEA trends among older adults with diabetes (≥67 years), we used 100% Medicare claims for beneficiaries enrolled in Parts A and B, also known as fee for service (FFS). NLEA was defined as the highest-level amputation per patient per calendar year. Annual NLEA rates were estimated from 2000 to 2017 and stratified by age-group, sex, race/ethnicity, NLEA level (toe, foot, below-the-knee amputation [BKA], above-the-knee amputation [AKA]), and state. All rates were age and sex standardized to the 2000 Medicare population. Trends over time were assessed using Joinpoint regression and annual percent change (APC) reported. RESULTS: NLEA rates (per 1,000 people with diabetes) decreased by half from 8.5 in 2000 to 4.4 in 2009 (APC -7.9, P < 0.001). However, from 2009 onward, NLEA rates increased to 4.8 (APC 1.2, P < 0.01). Trends were similar across most age, sex, and race/ethnic groups, but absolute rates were highest in the oldest age-groups, blacks, and men. By NLEA type, overall increases were driven by increases in rates of toe and foot NLEAs, while BKA and AKA continued to decline. The majority of U.S. states showed recent increases in NLEA, similar to national estimates. CONCLUSIONS: This study of the U.S. Medicare FFS population shows that recent increases in diabetes-related NLEAs are also occurring in older populations but at a less severe rate than among younger adults (<65 years) in the general population. Preventive foot care has been shown to reduce rates of NLEA among adults with diabetes, and the findings of the study suggest that those with diabetes-across the age spectrum-could benefit from increased attention to this strategy.

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.

Accumulating data suggest that type 2 diabetes mellitus (T2DM) in younger people (aged <40 years), referred to as young-onset T2DM, has a more rapid deterioration of beta-cell function than is seen in later-onset T2DM. Furthermore, individuals with young-onset T2DM seem to have a higher risk of complications than those with type 1 diabetes mellitus. As the number of younger adults with T2DM increases, young-onset T2DM is predicted to become a more frequent feature of the broader diabetes mellitus population in both developing and developed nations, particularly in certain ethnicities. However, the magnitude of excess risk of premature death and incident complications remains incompletely understood; likewise, the potential reasons for this excess risk are unclear. Here, we review the evidence pertaining to young-onset T2DM and its current and future burden of disease in terms of incidence and prevalence in both developed and developing nations. In addition, we highlight the associations of young-onset T2DM with premature mortality and morbidity.

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 (Delta/y) reported. RESULTS: In adults with diabetes, AKI-D increased between 2000 and 2015 (from 26.4 to 41.1 per 100,000 persons; Delta/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; Delta/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.

OBJECTIVE: To assess what proportions of studies reported increasing, stable, or declining trends in the incidence of diagnosed diabetes. DESIGN: Systematic review of studies reporting trends of diabetes incidence in adults from 1980 to 2017 according to PRISMA guidelines. DATA SOURCES: Medline, Embase, CINAHL, and reference lists of relevant publications. ELIGIBILITY CRITERIA: Studies of open population based cohorts, diabetes registries, and administrative and health insurance databases on secular trends in the incidence of total diabetes or type 2 diabetes in adults were included. Poisson regression was used to model data by age group and year. RESULTS: Among the 22 833 screened abstracts, 47 studies were included, providing data on 121 separate sex specific or ethnicity specific populations; 42 (89%) of the included studies reported on diagnosed diabetes. In 1960-89, 36% (8/22) of the populations studied had increasing trends in incidence of diabetes, 55% (12/22) had stable trends, and 9% (2/22) had decreasing trends. In 1990-2005, diabetes incidence increased in 66% (33/50) of populations, was stable in 32% (16/50), and decreased in 2% (1/50). In 2006-14, increasing trends were reported in only 33% (11/33) of populations, whereas 30% (10/33) and 36% (12/33) had stable or declining incidence, respectively. CONCLUSIONS: The incidence of clinically diagnosed diabetes has continued to rise in only a minority of populations studied since 2006, with over a third of populations having a fall in incidence in this time period. Preventive strategies could have contributed to the fall in diabetes incidence in recent years. Data are limited in low and middle income countries, where trends in diabetes incidence could be different. SYSTEMATIC REVIEW REGISTRATION: Prospero CRD42018092287.

OBJECTIVE: Vascular complications of diabetes have declined substantially over the past 20 years. However, the impact of modern medical treatments on infectious diseases in people with diabetes remains unknown. RESEARCH DESIGN AND METHODS: We estimated rates of infections requiring hospitalizations in adults (>/=18 years) with versus without diabetes, using the 2000-2015 National Inpatient Sample and the National Health Interview Surveys. Annual age-standardized and age-specific hospitalization rates in groups with and without diabetes were stratified by infection type. Trends were assessed using Joinpoint regression with the annual percentage change (Delta%/year) reported. RESULTS: In 2015, hospitalization rates remained almost four times as high in adults with versus without diabetes (rate ratio 3.8 [95% CI 3.8-3.8]) and as much as 15.7 times as high, depending on infection type. Overall, between 2000 and 2015, rates of hospitalizations increased from 63.1 to 68.7 per 1,000 persons in adults with diabetes and from 15.5 to 16.3 in adults without diabetes. However, from 2008, rates declined 7.9% in adults without diabetes (from 17.7 to 16.3 per 1,000 persons; Delta%/year -1.5, P < 0.01), while no significant decline was noted in adults with diabetes. The lack of decline in adults with diabetes in the later period was driven by significant increases in rates of foot infections and cellulitis as well as by lack of decline for pneumonia and postoperative wound infections in young adults with diabetes. CONCLUSIONS: Findings from this study highlight the need for greater infectious risk mitigation in adults with diabetes, especially young adults with diabetes.

AIMS/HYPOTHESIS: Cancer-related death is higher among people with vs without diabetes. However, it is not known if this excess risk has changed over time or what types of cancer may be driving these changes. METHODS: To estimate rates of site-specific cancer mortality in adults with vs without self-reported diagnosed diabetes, we used data from adults aged >/=18 years at the time of the interview who participated in the 1985-2012 National Health Interview Survey. Participants' data were linked to the National Death Index by the National Center for Health Statistics to determine vital status and cause of death through to the end of 2015. Cancer deaths were classified according to underlying cause of death. Death rates for five time periods (1988-1994, 1995-1999, 2000-2004, 2005-2009, 2010-2015) were estimated using discrete Poisson regression models adjusted for age, sex and race/ethnicity with p for linear trend reported (ptrend). Site-specific cancer mortality rates were stratified by diabetes status and period, and total cancer mortality rates were additionally stratified by sex, race/ethnicity, education and BMI status. RESULTS: Among adults with diabetes, age-adjusted cancer mortality rates (per 10,000 person-years) declined 25.5% from 39.1 (95% CI 30.1, 50.8) in 1988-1994 to 29.7 (26.6, 33.1) in 2010-2015, ptrend < 0.001. Among adults without diabetes, rates declined 25.2% from 30.9 (28.6, 33.4) in 1988-1994 to 23.2 (22.1, 24.2) in 2010-2015, ptrend < 0.01. Adults with diabetes remained approximately 30% more likely to die from cancer than people without diabetes, and this excess risk did not improve over time. In adults with diabetes, cancer mortality rates did not decline in some population subgroups (including black people, people with lower levels of education and obese people), and the excess risk increased for obese adults with vs without diabetes. Declines in total cancer mortality rates in adults with diabetes appear to be driven by large relative declines in cancers of the pancreas (55%) and breast (65%), while for lung cancer, declines are modest (7%). CONCLUSIONS/INTERPRETATION: Declines in cancer mortality rates were observed in adults with and without diabetes. However, adults with diabetes continue to be more likely to die from cancer than people without diabetes. This study highlights the continued need for greater cancer risk-factor mitigation, especially in adults with diabetes.

OBJECTIVE: Nontraumatic lower-extremity amputation (NLEA) is a complication of end-stage renal disease (ESRD) and diabetes. Although recent data show that NLEA rates in the U.S. ESRD population are declining overall, trends in diabetes and diabetes subgroups remain unclear. RESEARCH DESIGN AND METHODS: We estimated annual rates of NLEA hospitalizations during 2000-2015 among >2 million adults (>/=18 years) with ESRD from the U.S. Renal Data System. Age, sex, and race-adjusted NLEA rates were stratified by diabetes status, age, sex, race, and level of amputation (toe, foot, below the knee, and above the knee). Time trends were assessed using Joinpoint regression with annual percent changes (APC) reported. RESULTS: Among adults with diabetes, NLEA rates declined 43.8% between 2000 and 2013 (from 7.5 to 4.2 per 100 person-years; APC -4.9, P < 0.001) and then stabilized. Among adults without diabetes, rates of total NLEAs declined 25.5% between 2000 and 2013 (from 1.6 to 1.1; APC -3.0, P < 0.001) and then stabilized. These trends appear to be driven by a slowing or stagnation in declines of minor NLEAs (toe and foot) in more recent years, while major NLEAs (above the knee) continue to decline. CONCLUSIONS: Despite an initial period of decline, this analysis documents a stall in progress in NLEA trends in recent years in a high-risk population with both ESRD and diabetes. Increased attention to preventive foot care in the ESRD population should be considered, particularly for those with diabetes.

Purpose: To estimate prevalence and severity of diabetic retinopathy (DR) among U.S. adults with diabetes and with or without chronic kidney disease (CKD), and assess associated risk of mortality. Design(s): Cross-sectional study with national survey data. Method(s): The cohort included adults >=40 years old with diabetes in the National Health and Nutrition Examination Surveys (NHANES) 2005-2008. Vital status was determined through December 31, 2011. We defined diabetes as hemoglobin A1c >=6.5% or self-report and CKD by urinary albumin/creatinine >=30 mg/g or glomerular filtration rate <60 mL/min/1.73 m2. The main outcomes were DR and mortality. Result(s): Prevalence of DR was 27.8% (95% CI 24.3-31.7), 36.2% (95%CI 30.1-42.7), and 23.4% (95% CI 19.2-28.1), overall, with and without CKD. Prevalence of vision-threatening DR was 4.2% (95% CI 3.2-5.5), 8.2% (95% CI 5.4-12.2), and 2.0% (95% CI 1.2-3.5), respectively. In a multivariable adjusted model, DR was positively but nonsignificantly associated with CKD (OR = 1.1, 95% CI 0.7-1.7), was 40% higher per 1% increase in hemoglobin A1c (OR = 1.4, 95% CI 1.1-1.6), was 30% higher per 5 years additional diabetes duration (OR = 1.3, 95% CI 1.1-1.5), was 30% higher per 10 mm Hg increase in systolic blood pressure (OR = 1.3, 95% CI 1.1-1.5), and was 6-fold higher with insulin treatment (OR = 6.2, 95% CI 2.6-14.8). Compared with diabetic participants with neither DR nor CKD, those with DR and CKD had a 3.6-fold (95% CI 1.5-9.1) increased adjusted risk for all-cause mortality. Conclusion(s): Over one third of persons with diabetes and CKD had DR. The risk of death was higher with than without CKD and DR. Many of the studied risk factors associated with DR are modifiable.

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.

Acute kidney injury is a sudden decrease in kidney function with or without kidney damage, occurring over a few hours or days. Diabetes, hypertension, and advanced age are primary risk factors for acute kidney injury. It is increasingly recognized as an in-hospital complication of sepsis, heart conditions, and surgery (1,2). Its most severe stage requires treatment with dialysis. Acute kidney injury is also associated with higher likelihood of long-term care, incidence of chronic kidney disease and hospital mortality, and health care costs (1,2). Although a number of U.S. studies have indicated an increasing incidence of dialysis-treated acute kidney injury since the late 1990s (3), no data are available on national trends in diabetes-related acute kidney injury. To estimate diabetes- and nondiabetes-related acute kidney injury trends, CDC analyzed 2000-2014 data from the National Inpatient Sample (NIS) (4) and the National Health Interview Survey (NHIS) (5). Age-standardized rates of acute kidney injury hospitalizations increased by 139% (from 23.1 to 55.3 per 1,000 persons) among adults with diagnosed diabetes, and by 230% (from 3.5 to 11.7 per 1,000 persons) among those without diabetes. Improving both patient and provider awareness that diabetes, hypertension, and advancing age are frequently associated with acute kidney injury might reduce its occurrence and improve management of the underlying diseases in an aging population.