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OBJECTIVE: The impact of age of diabetes diagnosis on dementia risk across the life course is poorly characterized. We estimated the lifetime risk of dementia by age of diabetes diagnosis. RESEARCH DESIGN AND METHODS: We included 13,087 participants from the Atherosclerosis Risk in Communities Study who were free from dementia at age 60 years. We categorized participants as having middle age–onset diabetes (diagnosis <60 years), older-onset diabetes (diagnosis 60–69 years), or no diabetes. Incident dementia was ascertained via adjudication and active surveillance. We used the cumulative incidence function estimator to characterize the lifetime risk of dementia by age of diabetes diagnosis while accounting for the competing risk of mortality. We used restricted mean survival time to calculate years lived without and with dementia. RESULTS: Among 13,087 participants, there were 2,982 individuals with dementia and 4,662 deaths without dementia during a median follow-up of 24.1 (percentile 25–percentile 75, 17.4–28.3) years. Individuals with middle age–onset diabetes had a significantly higher lifetime risk of dementia than those with older-onset diabetes (36.0% vs. 31.0%). Compared with those with no diabetes, participants with middle age–onset diabetes also had a higher cumulative incidence of dementia by age 80 years (16.1% vs. 9.4%) but a lower lifetime risk (36.0% vs. 45.6%) due to shorter survival. Individuals with middle age–onset diabetes developed dementia 4 and 1 years earlier than those without diabetes and those with older-onset diabetes, respectively. CONCLUSIONS: Preventing or delaying diabetes may be an important approach for reducing dementia risk throughout the life course. [ABSTRACT FROM AUTHOR]

Objective: To predict adverse kidney outcomes for use in optimizing medical management and clinical trial design.Research Design and Methods: In this meta-analysis of individual participant data, 43 cohorts (N = 1,621,817) from research studies, electronic medical records, and clinical trials with global representation were separated into development and validation cohorts. Models were developed and validated within strata of diabetes mellitus (presence or absence) and estimated glomerular filtration rate (eGFR; ≥60 or <60 mL/min/1.73 m2) to predict a composite of ≥40% decline in eGFR or kidney failure (i.e., receipt of kidney replacement therapy) over 2-3 years.Results: There were 17,399 and 24,591 events in development and validation cohorts, respectively. Models predicting ≥40% eGFR decline or kidney failure incorporated age, sex, eGFR, albuminuria, systolic blood pressure, antihypertensive medication use, history of heart failure, coronary heart disease, atrial fibrillation, smoking status, and BMI, and, in those with diabetes, hemoglobin A1c, insulin use, and oral diabetes medication use. The median C-statistic was 0.774 (interquartile range [IQR] = 0.753, 0.782) in the diabetes and higher-eGFR validation cohorts; 0.769 (IQR = 0.758, 0.808) in the diabetes and lower-eGFR validation cohorts; 0.740 (IQR = 0.717, 0.763) in the no diabetes and higher-eGFR validation cohorts; and 0.750 (IQR = 0.731, 0.785) in the no diabetes and lower-eGFR validation cohorts. Incorporating the previous 2-year eGFR slope minimally improved model performance, and then only in the higher-eGFR cohorts.Conclusions: Novel prediction equations for a decline of ≥40% in eGFR can be applied successfully for use in the general population in persons with and without diabetes with higher or lower eGFR. [ABSTRACT FROM AUTHOR]

Objective: Confirmatory testing is recommended for diabetes diagnosis in clinical practice. However, national estimates of undiagnosed diabetes are based on single elevated test measures, potentially resulting in overestimation. Our objective was to update trends in undiagnosed diabetes using definitions consistent with clinical practice.Research Design and Methods: We included 30,492 adults (aged ≥20 years) from the National Health and Nutrition Examination Survey (1988-2020). Among adults without diagnosed diabetes, confirmed undiagnosed diabetes was defined as having both elevated levels of fasting plasma glucose (FPG) (≥126 mg/dL) and elevated glycated hemoglobin (HbA1c; ≥6.5%), and persistent undiagnosed diabetes was defined as having elevated HbA1c or FPG levels, adjusted for the within-person variability in HbA1c and FPG tests.Results: From the periods 1988-1994 to 2017 to March 2020, there was an increase in the prevalence of diagnosed diabetes (from 4.6% to 11.7%), but no change in prevalence of persistent undiagnosed diabetes (from 2.23% to 2.53%) or confirmed undiagnosed diabetes (from 1.10% to 1.23%). Consequently, the proportion of all undiagnosed diabetes cases declined from 32.8% to 17.8% (persistent undiagnosed diabetes) and from 19.3% to 9.5% (confirmed undiagnosed diabetes). Undiagnosed diabetes was more prevalent in older and obese adults, racial/ethnic minorities, and those without health care access. Among persons with diabetes, Asian Americans and those without health care access had the highest proportion of undiagnosed cases, with rates ranging from 23% to 61%.Conclusions: From 1988 to March 2020, the proportion of undiagnosed diabetes cases declined substantially, suggesting major improvements in diabetes screening and detection. Undiagnosed diabetes currently affects 1-2% of US adults; up to 90% of all cases are diagnosed. [ABSTRACT FROM AUTHOR]

Objective: Clinical guidelines for people with diabetes recommend chronic kidney disease (CKD) testing at least annually using estimated glomerular filtration rate (eGFR) and urinary albumin-to-creatinine ratio (uACR). We aimed to understand CKD testing among people with type 2 diabetes in the U.S.Research Design and Methods: Electronic health record data were analyzed from 513,165 adults with type 2 diabetes receiving primary care from 24 health care organizations and 1,164 clinical practice sites. We assessed the percentage of patients with both one or more eGFRs and one or more uACRs and each test individually in the 1, 2, and 3 years ending September 2019 by health care organization and clinical practice site. Elevated albuminuria was defined as uACR ≥30 mg/g.Results: The 1-year median testing rate across organizations was 51.6% for both uACR and eGFR, 89.5% for eGFR, and 52.9% for uACR. uACR testing varied (10th-90th percentile) from 44.7 to 63.3% across organizations and from 13.3 to 75.4% across sites. Over 3 years, the median testing rate for uACR across organizations was 73.7%. Overall, the prevalence of detected elevated albuminuria was 15%. The average prevalence of detected elevated albuminuria increased linearly with uACR testing rates at sites, with estimated prevalence of 6%, 15%, and 30% at uACR testing rates of 20%, 50%, and 100%, respectively.Conclusions: While eGFR testing rates are uniformly high among people with type 2 diabetes, testing rates for uACR are suboptimal and highly variable across and within the organizations examined. Guideline-recommended uACR testing should increase detection of CKD. [ABSTRACT FROM AUTHOR]

Objective: Hypoglycemia has been postulated to contribute to falls risk in older adults with type 2 diabetes. However, few studies have prospectively examined the association between severe hypoglycemia and falls, both important causes of morbidity and mortality.Research Design and Methods: We conducted a prospective cohort analysis of participants from the Atherosclerosis Risk in Communities (ARIC) study with diagnosed diabetes at visit 4 (1996-1998). Episodes of severe hypoglycemia requiring medical treatment were identified using ICD-9 codes from hospitalizations, emergency department visits, and ambulance calls; total falls were identified from medical claims using E-codes from 1996 to 2013. Secondary analyses examined hospitalized falls and falls with fracture. We calculated incidence rates and used Cox regression models to evaluate the independent association of severe hypoglycemia with falls occurring after visit 4 through 2013.Results: Among 1,162 participants with diabetes, 149 ever had a severe hypoglycemic event before baseline or during the median of 13.1 years of follow-up. The crude incidence rate of falls among persons without severe hypoglycemia was 2.17 per 100 person-years (PY) (95% CI 1.93-2.44) compared with 8.81 per 100 PY (6.73-11.53) with severe hypoglycemia. After adjustment, severe hypoglycemia was associated with a more than twofold higher risk of falls (hazard ratio 2.23, 95% CI 1.61-3.07). Associations were consistent in subgroups defined by age, sex, race, BMI, duration of diabetes, or functional difficulty.Conclusions: Severe hypoglycemia was associated with a substantially higher risk of falls in this community-based population of adults with diabetes. Fall risk should be considered when individualizing glycemic treatment in older adults. Assessing hypoglycemia history and future hypoglycemia risk could also improve multifactorial fall prevention interventions for older adults with diabetes. [ABSTRACT FROM AUTHOR]

Objective: Diabetes in older age is heterogeneous, and the treatment approach varies by patient characteristics. We characterized the short-term all-cause and cardiovascular mortality risk associated with hyperglycemia in older age.Research Design and Methods: We included 5,791 older adults in the Atherosclerosis Risk in Communities Study who attended visit 5 (2011-2013; ages 66-90 years). We compared prediabetes (HbA1c 5.7% to <6.5%), newly diagnosed diabetes (HbA1c ≥6.5%, prior diagnosis <1 year, or taking antihyperglycemic medications <1 year), short-duration diabetes (duration ≥1 year but <10 years [median]), and long-standing diabetes (duration ≥10 years). Outcomes were all-cause and cardiovascular mortality (median follow-up of 5.6 years).Results: Participants were 58% female, and 24% had prevalent cardiovascular disease. All-cause mortality rates, per 1,000 person-years, were 21.2 (95% CI 18.7, 24.1) among those without diabetes, 23.7 (95% CI 20.8, 27.1) for those with prediabetes, 33.8 (95% CI 25.2, 45.5) among those with recently diagnosed diabetes, 29.6 (95% CI 25.0, 35.1) for those with diabetes of short duration, and 48.6 (95% CI 42.4, 55.7) for those with long-standing diabetes. Cardiovascular mortality rates, per 1,000 person-years, were 5.8 (95% CI 4.6, 7.4) among those without diabetes, 6.6 (95% CI 5.2, 8.5) for those with prediabetes, 11.5 (95% CI 7.0, 19.1) among those with recently diagnosed diabetes, 8.2 (95% CI 5.9, 11.3) for those with diabetes of short duration, and 17.3 (95% CI 13.8, 21.7) for those with long-standing diabetes. After adjustment for other cardiovascular risk factors, prediabetes and newly diagnosed diabetes were not significantly associated with a higher risk of all-cause mortality (hazard ratio [HR] 1.03 [95% CI 0.85, 1.23] and HR 1.31 [95% CI 0.94, 1.82], respectively) or cardiovascular mortality (HR 1.00 [95% CI 0.70, 1.43] and HR 1.35 [95% CI 0.74, 2.49], respectively). Excess mortality risk was primarily concentrated among those with long-standing diabetes (all-cause: HR 1.71 [95% CI 1.40, 2.10]; cardiovascular: HR 1.72 [95% CI 1.18, 2.51]).Conclusions: In older adults, long-standing diabetes has a substantial and independent effect on short-term mortality. Older individuals with prediabetes remained at low mortality risk over a median 5.6 years of follow-up. [ABSTRACT FROM AUTHOR]

Objective: There is suggestive evidence linking hypoglycemia with cardiovascular disease, but few data have been collected in a community-based setting. Information is lacking on individual cardiovascular outcomes and cause-specific mortality.Research Design and Methods: We conducted a prospective cohort analysis of 1,209 participants with diagnosed diabetes from the Atherosclerosis Risk in Communities (ARIC) study (analytic baseline, 1996-1998). Severe hypoglycemic episodes were identified using first position ICD-9 codes from hospitalizations, emergency department visits, and ambulance calls through 2013. Cardiovascular events and deaths were captured through 2013. We used adjusted Cox regression models with hypoglycemia as a time-varying exposure.Results: There were 195 participants with at least one severe hypoglycemic episode during a median fellow-up of 15.3 years. After severe hypoglycemia, the 3-year cumulative incidence of coronary heart disease was 10.8% and of mortality was 28.3%. After adjustment, severe hypoglycemia was associated with coronary heart disease (hazard ratio [HR] 2.02, 95% CI 1.27-3.20), all-cause mortality (HR 1.73, 95% CI 1.38-2.17), cardiovascular mortality (HR 1.64, 95% CI 1.15-2.34), and cancer mortality (HR 2.49, 95% CI 1.46-4.24). Hypoglycemia was not associated with stroke, heart failure, atrial fibrillation, or noncardiovascular and noncancer death. Results were robust within subgroups defined by age, sex, race, diabetes duration, and baseline cardiovascular risk.Conclusions: Severe hypoglycemia is clearly indicative of declining health and is a potent marker of high absolute risk of cardiovascular events and mortality. [ABSTRACT FROM AUTHOR]