Trends in all-cause mortality among people with diagnosed diabetes in high-income settings: a multicountry analysis of aggregate data.

BACKGROUND: Population-level trends in mortality among people with diabetes are inadequately described. We aimed to examine the magnitude and trends in excess all-cause mortality in people with diabetes. METHODS: In this retrospective, multicountry analysis, we collected aggregate data from 19 data sources in 16 high-income countries or jurisdictions (in six data sources in Asia, eight in Europe, one from Australia, and four from North America) for the period from Jan 1, 1995, to Dec 31, 2016, (or a subset of this period) on all-cause mortality in people with diagnosed total or type 2 diabetes. We collected data from administrative sources, health insurance records, registries, and a health survey. We estimated excess mortality using the standardised mortality ratio (SMR). FINDINGS: In our dataset, there were approximately 21 million deaths during 0·5 billion person-years of follow-up among people with diagnosed diabetes. 17 of 19 data sources showed decreases in the age-standardised and sex-standardised mortality in people with diabetes, among which the annual percentage change in mortality ranged from -0·5% (95% CI -0·7 to -0·3) in Hungary to -4·2% (-4·3 to -4·1) in Hong Kong. The largest decreases in mortality were observed in east and southeast Asia, with a change of -4·2% (95% CI -4·3 to -4·1) in Hong Kong, -4·0% (-4·8 to -3·2) in South Korea, -3·5% (-4·0 to -3·0) in Taiwan, and -3·6% (-4·2 to -2·9) in Singapore. The annual estimated change in SMR between people with and without diabetes ranged from -3·0% (95% CI -3·0 to -2·9; US Medicare) to 1·6% (1·4 to 1·7; Lombardy, Italy). Among the 17 data sources with decreasing mortality among people with diabetes, we found a significant SMR increase in five data sources, no significant SMR change in four data sources, and a significant SMR decrease in eight data sources. INTERPRETATION: All-cause mortality in diabetes has decreased in most of the high-income countries we assessed. In eight of 19 data sources analysed, mortality decreased more rapidly in people with diabetes than in those without diabetes. Further longevity gains will require continued improvement in prevention and management of diabetes. FUNDING: US Centers for Disease Control and Prevention, Diabetes Australia Research Program, and Victoria State Government Operational Infrastructure Support Program.

Prevalence and incidence of microvascular and macrovascular complications over 15 years among patients with incident type 2 diabetes.

INTRODUCTION: Type 2 diabetes (T2D) is a common condition that, if left untreated or poorly managed, can lead to adverse microvascular and macrovascular complications. We estimated the prevalence and incidence of microvascular and macrovascular complications among patients newly diagnosed with T2D within a US integrated healthcare system. RESEARCH DESIGN AND METHODS: We conducted a retrospective cohort study among patients newly diagnosed with T2D between 2003 and 2014. We evaluated 13 complications, including chronic kidney disease (CKD), cardiovascular disease (CVD), and all-cause mortality through 2018. Multivariable Cox proportional hazards models were used to study factors associated with complications. RESULTS: We identified 135 199 patients with incident T2D. The mean age was 58 years, and 48% were women. The prevalence of CKD was the highest of the complications at the time of T2D diagnosis (prevalence=12.3%, 95% CI 12.2% to 12.5%), while the prevalence of CVD was among the lowest at 3.3% (95% CI 3.2% to 3.3%). The median time to incidence of a T2D complication ranged from 3.0 to 5.2 years. High incidence rates (95% CI) of T2D complications included peripheral neuropathy (26.9, 95% CI 26.5 to 27.3 per 1000 person-years (PY)), CKD (21.2, 95% CI 20.9 to 21.6 per 1000 PY), and CVD (11.9, 95% CI 11.7 to 12.2 per 1000 PY). The trend of 5-year incidence rates of T2D complications by diagnosis year decreased over time (p value<0.001). Older age, non-Hispanic white race/ethnicity, sex, higher A1C, smoking, and hypertension were associated with increased CKD and CVD incidence. CONCLUSION: Though incidence rates of T2D complications were lower in more recent years (2010-2014), a significant proportion of patients had complications at T2D diagnosis. Earlier preventive therapies as well as managing modifiable factors may help delay the development and progression of T2D complications.

Predictors of Hyperkalemia and Hypokalemia in Individuals with Diabetes: a Classification and Regression Tree Analysis.

BACKGROUND: Both hyperkalemia and hypokalemia can lead to cardiac arrhythmias and are associated with increased mortality. Information on the predictors of potassium in individuals with diabetes in routine clinical practice is lacking. OBJECTIVE: To identify predictors of hyperkalemia and hypokalemia in adults with diabetes. DESIGN: Retrospective cohort study, with classification and regression tree (CART) analysis. PARTICIPANTS: 321,856 individuals with diabetes enrolled in four large integrated health care systems from 2012 to 2013. MAIN MEASURES: We used a single serum potassium result collected in 2012 or 2013. Hyperkalemia was defined as a serum potassium ≥ 5.5 mEq/L and hypokalemia as < 3.5 mEq/L. Predictors included demographic factors, laboratory measurements, comorbidities, medication use, and health care utilization. KEY RESULTS: There were 2556 hypokalemia events (0.8%) and 1517 hyperkalemia events (0.5%). In univariate analyses, we identified concordant predictors (associated with increased probability of both hyperkalemia and hypokalemia), discordant predictors, and predictors of only hyperkalemia or hypokalemia. In CART models, the hyperkalemia "tree" had 5 nodes and a c-statistic of 0.76. The nodes were defined by prior potassium results and eGFRs, and the 5 terminal "leaves" had hyperkalemia probabilities of 0.2 to 7.2%. The hypokalemia tree had 4 nodes and a c-statistic of 0.76. The hypokalemia tree included nodes defined by prior potassium results, and the 4 terminal leaves had hypokalemia probabilities of 0.3 to 17.6%. Individuals with a recent potassium between 4.0 and 5.0 mEq/L, eGFR ≥ 45 mL/min/1.73m2, and no hypokalemia in the previous year had a < 1% rate of either hypokalemia or hyperkalemia. CONCLUSIONS: The yield of routine serum potassium testing may be low in individuals with a recent serum potassium between 4.0 and 5.0 mEq/L, eGFR ≥ 45 mL/min/1.73m2, and no recent history of hypokalemia. We did not examine the effect of recent changes in clinical condition or medications on acute potassium changes.

High rates of severe hypoglycemia among African American patients with diabetes: the surveillance, prevention, and Management of Diabetes Mellitus (SUPREME-DM) network.

AIMS: Seven-year surveillance study (2005-2011) to evaluate race/ethnic differences in the trends in rates of severe hypoglycemia (SH) in a population of insured, at-risk adults with diabetes. METHODS: SH events were identified via any primary or principal diagnosis from emergency department or inpatient encounters among African American, Asian, Latino and White adult diabetes patients treated with insulin or secretagogues (Sulfonylureas or Meglitinides), receiving care from integrated healthcare delivery systems across the United States. We calculated age- and sex-standardized annual SH rates and average annual percent change (AAPC) in SH rates. RESULTS: Annual SH rates ranged from 1.8% to 2.1% during this 7-year observation period (2,200,471 person-years). African Americans had consistently higher SH rates compared with Whites, while Latinos and Asians had consistently lower rates compared with Whites in each of the 7 years (all p < 0.01). The trend increased significantly only among African Americans (AAPC = +4.3%; 95% CI: +2.1, +6.5%); in the other groups, the AAPC was not significantly different from zero. CONCLUSIONS: Surveillance efforts should monitor the racial/ethnic-specific rates. The factors underlying substantially higher rates of hypoglycemia in African Americans should be evaluated. Clinically and culturally-appropriate strategies to reduce the risk of SH need to be developed and tested.

Cardiometabolic Risk Factors Among 1.3 Million Adults With Overweight or Obesity, but Not Diabetes, in 10 Geographically Diverse Regions of the United States, 2012-2013.

INTRODUCTION: Various phenotypes of overweight and obesity pose various health risks. The objective of this study was to determine the prevalence of 4 commonly measured cardiometabolic risk factors (CRFs) among adults with overweight or obesity, but not diabetes, at the time of the study. METHODS: We analyzed data for 1,294,174 adults (aged ≥20 y) who were members of one of 4 integrated health systems. Each cohort member had a body mass index in 2012 or 2013 that indicated overweight or obesity. We determined the presence of 4 CRFs within 1 year of the first BMI measurement: elevated blood pressure (systolic ≥130 mm Hg or diastolic >85 mm Hg or ICD-9-CM [International Classification of Diseases, Ninth Revision, Clinical Modification] diagnosis code 401.0-405.9); elevated triglycerides (≥150 mg/dL or ICD-9-CM 272.1); low high-density lipoprotein cholesterol (<40 mg/dL for men or <50 mg/dL for women or ICD-9-CM 272.5); and prediabetes (fasting glucose 100-125 mg/dL or HbA1c 5.7%-6.4% or ICD-9-CM 790.2x). We tested the risk of having 1 or more CRFs after adjusting for obesity class and demographic characteristics with multivariable logistic regression. RESULTS: Among participants with overweight (52.5% of the sample), 18.6% had none of the 4 CRFs. Among the 47.5% of participants with obesity, 9.6% had none; among participants with morbid obesity, 5.8% had none. Age was strongly associated with CRFs in multivariable analysis. CONCLUSION: Almost 10% of participants with obesity had no CRFs. Overweight or obesity increases cardiometabolic risk, but the number and type of CRFs varied substantially by age, even among participants with morbid obesity.

Effect of Combination Cholesterol-Lowering Therapy and Triglyceride-Lowering Therapy on Medical Costs in Patients With Type 2 Diabetes Mellitus.

High triglyceride (TG) levels among patients with type 2 diabetes mellitus (DM) are associated with higher medical costs. We analyzed the economic impact of TG-lowering therapies and whether the association between medical costs and therapy differed according to TG reduction. We conducted an observational cohort study of 184,932 patients with diabetes mellitus who had a TG measurement between January 2012 and June 2013 and a second TG measurement 3 to 15 months later. We identified 4 therapy groups (statin monotherapy, TG-specific monotherapy, statin/TG-specific combination therapy, or no therapy) and stratified those groups by percent change in TG (increased ≥5%, change of ≤4.9%, decreased 5% to 29%, decreased ≥30%). We compared change in medical costs between the year before and after therapy, adjusted for demographic and clinical characteristics. Of the 184,932 total patients, 143,549 (77.6%) received statin monotherapy, 900 (0.5%) received TG-specific monotherapy, 1,956 (1.1%) received statin and TG-specific combination therapy, and 38,527 (20.8%) received no prescription lipid agents. After covariate adjustment, statin/TG-specific agent recipients had a mean 1-year total cost reduction of $1,110. The greatest cost reduction was seen among statin/TG-specific combination therapy patients who reduced TG levels by ≥30% (-$2,859). Statin monotherapy patients who reduced TG by ≥30% also had a large reduction in adjusted costs (-$1,079). In conclusion, we found a substantial economic benefit to treating diabetic patients with statin/TG-specific combination lipid therapy compared with monotherapy of either type or no lipid pharmacotherapy. A TG reduction of ≥30% produced a particularly large reduction in 1-year medical costs.

Severe Hypoglycemia Requiring Medical Intervention in a Large Cohort of Adults With Diabetes Receiving Care in U.S. Integrated Health Care Delivery Systems: 2005-2011.

OBJECTIVE: Appropriate glycemic control is fundamental to diabetes care, but aggressive glucose targets and intensive therapy may unintentionally increase episodes of hypoglycemia. We quantified the burden of severe hypoglycemia requiring medical intervention in a well-defined population of insured individuals with diabetes receiving care in integrated health care delivery systems across the U.S. RESEARCH DESIGN AND METHODS: This observational cohort study included 917,440 adults with diabetes receiving care during 2005 to 2011 at participating SUrveillance, PREvention, and ManagEment of Diabetes Mellitus (SUPREME-DM) network sites. Severe hypoglycemia rates were based on any occurrence of hypoglycemia-related ICD-9 codes from emergency department or inpatient medical encounters and reported overall and by age, sex, comorbidity status, antecedent A1C level, and medication use. RESULTS: Annual rates of severe hypoglycemia ranged from 1.4 to 1.6 events per 100 person-years. Rates of severe hypoglycemia were higher among those with older age, chronic kidney disease, congestive heart failure, cardiovascular disease, depression, and higher A1C levels, and in users of insulin, insulin secretagogues, or ß-blockers (P < 0.001 for all). Changes in severe hypoglycemia occurrence over time were not clinically significant in the cohort as a whole but were observed in subgroups of individuals with chronic kidney disease, congestive heart failure, and cardiovascular disease. CONCLUSIONS: Risk of severe hypoglycemia in clinical settings is considerably higher in identifiable patient subgroups than in randomized controlled trials. Strategies that reduce the risk of hypoglycemia in high-risk patients are needed.

Prevalence of chronic kidney disease among individuals with diabetes in the SUPREME-DM Project, 2005-2011.

AIMS: Diabetes is a leading cause of chronic kidney disease (CKD). Different methods of CKD ascertainment may impact prevalence estimates. We used data from 11 integrated health systems in the United States to estimate CKD prevalence in adults with diabetes (2005-2011), and compare the effect of different ascertainment methods on prevalence estimates. METHODS: We used the SUPREME-DM DataLink (n = 879,312) to estimate annual CKD prevalence. Methods of CKD ascertainment included: diagnosis codes alone, impaired estimated glomerular filtration rate (eGFR) alone (eGFR < 60 mL/min/1.73 m(2)), albuminuria alone (spot urine albumin creatinine ratio > 30 mg/g or equivalent), and combinations of these approaches. RESULTS: CKD prevalence was 20.0% using diagnosis codes, 17.7% using impaired eGFR, 11.9% using albuminuria, and 32.7% when one or more method suggested CKD. The criteria had poor concordance. After age- and sex-standardization to the 2010 U.S. Census population, prevalence using diagnosis codes increased from 10.7% in 2005 to 14.3% in 2011 (P < 0.001). The prevalence using eGFR decreased from 9.7% in 2005 to 8.6% in 2011 (P < 0.001). CONCLUSIONS: Our data indicate that CKD prevalence and prevalence trends differ according to the CKD ascertainment method, highlighting the necessity for multiple sources of data to accurately estimate and track CKD prevalence.

Preventable major cardiovascular events associated with uncontrolled glucose, blood pressure, and lipids and active smoking in adults with diabetes with and without cardiovascular disease: a contemporary analysis.

OBJECTIVE: The objective of this study was to assess the incidence of major cardiovascular (CV) hospitalization events and all-cause deaths among adults with diabetes with or without CV disease (CVD) associated with inadequately controlled glycated hemoglobin (A1C), high LDL cholesterol (LDL-C), high blood pressure (BP), and current smoking. RESEARCH DESIGN AND METHODS: Study subjects included 859,617 adults with diabetes enrolled for more than 6 months during 2005-2011 in a network of 11 U.S. integrated health care organizations. Inadequate risk factor control was classified as LDL-C ≥100 mg/dL, A1C ≥7% (53 mmol/mol), BP ≥140/90 mm Hg, or smoking. Major CV events were based on primary hospital discharge diagnoses for myocardial infarction (MI) and acute coronary syndrome (ACS), stroke, or heart failure (HF). Five-year incidence rates, rate ratios, and average attributable fractions were estimated using multivariable Poisson regression models. RESULTS: Mean (SD) age at baseline was 59 (14) years; 48% of subjects were female, 45% were white, and 31% had CVD. Mean follow-up was 59 months. Event rates per 100 person-years for adults with diabetes and CVD versus those without CVD were 6.0 vs. 1.7 for MI/ACS, 5.3 vs. 1.5 for stroke, 8.4 vs. 1.2 for HF, 18.1 vs. 40 for all CV events, and 23.5 vs. 5.0 for all-cause mortality. The percentages of CV events and deaths associated with inadequate risk factor control were 11% and 3%, respectively, for those with CVD and 34% and 7%, respectively, for those without CVD. CONCLUSIONS: Additional attention to traditional CV risk factors could yield further substantive reductions in CV events and mortality in adults with diabetes.

Trends in diabetes incidence among 7 million insured adults, 2006-2011: the SUPREME-DM project.

An observational cohort analysis was conducted within the Surveillance, Prevention, and Management of Diabetes Mellitus (SUPREME-DM) DataLink, a consortium of 11 integrated health-care delivery systems with electronic health records in 10 US states. Among nearly 7 million adults aged 20 years or older, we estimated annual diabetes incidence per 1,000 persons overall and by age, sex, race/ethnicity, and body mass index. We identified 289,050 incident cases of diabetes. Age- and sex-adjusted population incidence was stable between 2006 and 2010, ranging from 10.3 per 1,000 adults (95% confidence interval (CI): 9.8, 10.7) to 11.3 per 1,000 adults (95% CI: 11.0, 11.7). Adjusted incidence was significantly higher in 2011 (11.5, 95% CI: 10.9, 12.0) than in the 2 years with the lowest incidence. A similar pattern was observed in most prespecified subgroups, but only the differences for persons who were not white were significant. In 2006, 56% of incident cases had a glycated hemoglobin (hemoglobin A1c) test as one of the pair of events identifying diabetes. By 2011, that number was 74%. In conclusion, overall diabetes incidence in this population did not significantly increase between 2006 and 2010, but increases in hemoglobin A1c testing may have contributed to rising diabetes incidence among nonwhites in 2011.

Prescription medication burden in patients with newly diagnosed diabetes: a SUrveillance, PREvention, and ManagEment of Diabetes Mellitus (SUPREME-DM) study.

OBJECTIVE: To understand the burden of medication use for patients with newly diagnosed diabetes both before and after diabetes diagnosis and to identify subpopulations of patients with newly diagnosed diabetes who face a relatively high drug burden. DESIGN: Retrospective cohort study. SETTING: 11 integrated health systems in the United States. PARTICIPANTS: 196,654 insured adults 20 years of age or older newly diagnosed with type 1 or type 2 diabetes from January 2005 through December 2009. MAIN OUTCOME MEASURES: Number of unique therapeutic classes of drugs dispensed in the 12 months before and 12 months after diagnosis of diabetes in five categories: overall, antihypertensive agents, antihyperlipidemic agents, mental health agents, and antihyperglycemic agents (in the postdiagnosis period only). RESULTS: The mean number of drug classes used by newly diagnosed patients with diabetes is high before diagnosis (5.0) and increases significantly afterward (6.6). Of this increase, 81% is due to antihyperglycemic initiation and increased use of medications to control hypertension and lipid levels. Multivariate analyses showed that overall drug burden after diabetes diagnosis was higher in women, older, white, and obese patients, as well as among those with higher glycosylated hemoglobin concentrations and comorbidity levels (significant for all comparisons). The overall number of drug classes used by newly diagnosed patients with diabetes after diagnosis decreased slightly but significantly between 2005 and 2009. CONCLUSION: Patients newly diagnosed with diabetes face a substantially increased burden of medications used to control diabetes and other comorbidities. This study shows an increased focus on cardiovascular disease risk factor control after diagnosis of diabetes. However, total drug burden may be slightly decreasing over time.

Construction of a multisite DataLink using electronic health records for the identification, surveillance, prevention, and management of diabetes mellitus: the SUPREME-DM project.

INTRODUCTION: Electronic health record (EHR) data enhance opportunities for conducting surveillance of diabetes. The objective of this study was to identify the number of people with diabetes from a diabetes DataLink developed as part of the SUPREME-DM (SUrveillance, PREvention, and ManagEment of Diabetes Mellitus) project, a consortium of 11 integrated health systems that use comprehensive EHR data for research. METHODS: We identified all members of 11 health care systems who had any enrollment from January 2005 through December 2009. For these members, we searched inpatient and outpatient diagnosis codes, laboratory test results, and pharmaceutical dispensings from January 2000 through December 2009 to create indicator variables that could potentially identify a person with diabetes. Using this information, we estimated the number of people with diabetes and among them, the number of incident cases, defined as indication of diabetes after at least 2 years of continuous health system enrollment. RESULTS: The 11 health systems contributed 15,765,529 unique members, of whom 1,085,947 (6.9%) met 1 or more study criteria for diabetes. The nonstandardized proportion meeting study criteria for diabetes ranged from 4.2% to 12.4% across sites. Most members with diabetes (88%) met multiple criteria. Of the members with diabetes, 428,349 (39.4%) were incident cases. CONCLUSION: The SUPREME-DM DataLink is a unique resource that provides an opportunity to conduct comparative effectiveness research, epidemiologic surveillance including longitudinal analyses, and population-based care management studies of people with diabetes. It also provides a useful data source for pragmatic clinical trials of prevention or treatment interventions.