Weight loss is recommended for overweight or obese patients with type 2 diabetes on the basis of short-term studies, but long-term effects on cardiovascular disease remain unknown. We examined ...whether an intensive lifestyle intervention for weight loss would decrease cardiovascular morbidity and mortality among such patients.
In 16 study centers in the United States, we randomly assigned 5145 overweight or obese patients with type 2 diabetes to participate in an intensive lifestyle intervention that promoted weight loss through decreased caloric intake and increased physical activity (intervention group) or to receive diabetes support and education (control group). The primary outcome was a composite of death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for angina during a maximum follow-up of 13.5 years.
The trial was stopped early on the basis of a futility analysis when the median follow-up was 9.6 years. Weight loss was greater in the intervention group than in the control group throughout the study (8.6% vs. 0.7% at 1 year; 6.0% vs. 3.5% at study end). The intensive lifestyle intervention also produced greater reductions in glycated hemoglobin and greater initial improvements in fitness and all cardiovascular risk factors, except for low-density-lipoprotein cholesterol levels. The primary outcome occurred in 403 patients in the intervention group and in 418 in the control group (1.83 and 1.92 events per 100 person-years, respectively; hazard ratio in the intervention group, 0.95; 95% confidence interval, 0.83 to 1.09; P=0.51).
An intensive lifestyle intervention focusing on weight loss did not reduce the rate of cardiovascular events in overweight or obese adults with type 2 diabetes. (Funded by the National Institutes of Health and others; Look AHEAD ClinicalTrials.gov number, NCT00017953.).
The frequency of remission of type 2 diabetes achievable with lifestyle intervention is unclear.
To examine the association of a long-term intensive weight-loss intervention with the frequency of ...remission from type 2 diabetes to prediabetes or normoglycemia.
Ancillary observational analysis of a 4-year randomized controlled trial (baseline visit, August 2001-April 2004; last follow-up, April 2008) comparing an intensive lifestyle intervention (ILI) with a diabetes support and education control condition (DSE) among 4503 US adults with body mass index of 25 or higher and type 2 diabetes.
Participants were randomly assigned to receive the ILI, which included weekly group and individual counseling in the first 6 months followed by 3 sessions per month for the second 6 months and twice-monthly contact and regular refresher group series and campaigns in years 2 to 4 (n=2241) or the DSE, which was an offer of 3 group sessions per year on diet, physical activity, and social support (n=2262).
Partial or complete remission of diabetes, defined as transition from meeting diabetes criteria to a prediabetes or nondiabetic level of glycemia (fasting plasma glucose <126 mg/dL and hemoglobin A1c <6.5% with no antihyperglycemic medication). RESULTS Intensive lifestyle intervention participants lost significantly more weight than DSE participants at year 1 (net difference, -7.9%; 95% CI, -8.3% to -7.6%) and at year 4 (-3.9%; 95% CI, -4.4% to -3.5%) and had greater fitness increases at year 1 (net difference, 15.4%; 95% CI, 13.7%-17.0%) and at year 4 (6.4%; 95% CI, 4.7%-8.1%) (P < .001 for each). The ILI group was significantly more likely to experience any remission (partial or complete), with prevalences of 11.5% (95% CI, 10.1%-12.8%) during the first year and 7.3% (95% CI, 6.2%-8.4%) at year 4, compared with 2.0% for the DSE group at both time points (95% CIs, 1.4%-2.6% at year 1 and 1.5%-2.7% at year 4) (P < .001 for each). Among ILI participants, 9.2% (95% CI, 7.9%-10.4%), 6.4% (95% CI, 5.3%-7.4%), and 3.5% (95% CI, 2.7%-4.3%) had continuous, sustained remission for at least 2, at least 3, and 4 years, respectively, compared with less than 2% of DSE participants (1.7% 95% CI, 1.2%-2.3% for at least 2 years; 1.3% 95% CI, 0.8%-1.7% for at least 3 years; and 0.5% 95% CI, 0.2%-0.8% for 4 years).
In these exploratory analyses of overweight adults, an intensive lifestyle intervention was associated with a greater likelihood of partial remission of type 2 diabetes compared with diabetes support and education. However, the absolute remission rates were modest. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00017953.
Knowledge of trends in the incidence of and survival after myocardial infarction (MI) in a community setting is important to understanding trends in coronary heart disease (CHD) mortality rates.
We ...estimated race- and gender-specific trends in the incidence of hospitalized MI, case fatality, and CHD mortality from community-wide surveillance and validation of hospital discharges and of in- and out-of-hospital deaths among 35- to 74-year-old residents of 4 communities in the Atherosclerosis Risk in Communities (ARIC) Study. Biomarker adjustment accounted for change from reliance on cardiac enzymes to widespread use of troponin measurements over time. During 1987-2008, a total of 30 985 fatal or nonfatal hospitalized acute MI events occurred. Rates of CHD death among persons without a history of MI fell an average 4.7%/y among men and 4.3%/y among women. Rates of both in- and out-of-hospital CHD death declined significantly throughout the period. Age- and biomarker-adjusted average annual rate of incident MI decreased 4.3% among white men, 3.8% among white women, 3.4% among black women, and 1.5% among black men. Declines in CHD mortality and MI incidence were greater in the second decade (1997-2008). Failure to account for biomarker shift would have masked declines in incidence, particularly among blacks. Age-adjusted 28-day case fatality after hospitalized MI declined 3.5%/y among white men, 3.6%/y among black men, 3.0%/y among white women, and 2.6%/y among black women.
Although these findings from 4 communities may not be directly generalizable to blacks and whites in the entire United States, we observed significant declines in MI incidence, primarily as a result of downward trends in rates between 1997 and 2008.
The prevalence of type 2 diabetes in youth has increased substantially, yet the genetic underpinnings remain largely unexplored. To identify genetic variants predisposing to youth-onset type 2 ...diabetes, we formed ProDiGY, a multiethnic collaboration of three studies (TODAY, SEARCH, and T2D-GENES) with 3,006 youth case subjects with type 2 diabetes (mean age 15.1 ± 2.9 years) and 6,061 diabetes-free adult control subjects (mean age 54.2 ± 12.4 years). After stratifying by principal component-clustered ethnicity, we performed association analyses on ∼10 million imputed variants using a generalized linear mixed model incorporating a genetic relationship matrix to account for population structure and adjusting for sex. We identified seven genome-wide significant loci, including the novel locus rs10992863 in
(
= 3.2 × 10
; odds ratio OR = 1.23). Known loci identified in our analysis include rs7903146 in
(
= 8.0 × 10
; OR 1.58), rs72982988 near
(
= 4.4 × 10
; OR 1.53), rs200893788 in
(
= 1.1 × 10
; OR 1.32), rs2237892 in
(
= 4.8 × 10
; OR 1.59), rs937589119 in
(
= 3.1 × 10
; OR 1.34), and rs113748381 in
(
= 4.1 × 10
; OR 1.04). Secondary analysis with 856 diabetes-free youth control subjects uncovered an additional locus in
(
= 3.2 × 10
; OR 2.1) and consistent direction of effect for diabetes risk. In conclusion, we identified both known and novel loci in the first genome-wide association study of youth-onset type 2 diabetes.
Diabetes is one of the most common chronic diseases among persons aged <20 years (1). Onset of diabetes in childhood and adolescence is associated with numerous complications, including diabetic ...kidney disease, retinopathy, and peripheral neuropathy, and has a substantial impact on public health resources (2,3). From 2002 to 2012, type 1 and type 2 diabetes incidence increased 1.4% and 7.1%, respectively, among U.S. youths (4). To assess recent trends in incidence of diabetes in youths (defined for this report as persons aged <20 years), researchers analyzed 2002-2015 data from the SEARCH for Diabetes in Youth Study (SEARCH), a U.S. population-based registry study with clinical sites located in five states. The incidence of both type 1 and type 2 diabetes in U.S. youths continued to rise at constant rates throughout this period. Among all youths, the incidence of type 1 diabetes increased from 19.5 per 100,000 in 2002-2003 to 22.3 in 2014-2015 (annual percent change APC = 1.9%). Among persons aged 10-19 years, type 2 diabetes incidence increased from 9.0 per 100,000 in 2002-2003 to 13.8 in 2014-2015 (APC = 4.8%). For both type 1 and type 2 diabetes, the rates of increase were generally higher among racial/ethnic minority populations than those among whites. These findings highlight the need for continued surveillance for diabetes among youths to monitor overall and group-specific trends, identify factors driving these trends, and inform health care planning.
Abstract Objective Severe obesity (body mass index BMI ≥40 kg/m2 ) is a serious public health concern. Although bariatric surgery is an efficacious treatment approach, it is limited in reach; thus, ...nonsurgical treatment alternatives are needed. We examined the 4-year effects of an intensive lifestyle intervention on body weight and cardiovascular disease risk factors among severely obese, compared with overweight (25 ≤BMI <30), class I (30 ≤BMI <35), and class II obese (35 ≤BMI <40) participants. Methods There were 5145 individuals with type 2 diabetes (45-76 years, BMI ≥25 kg/m2 ) randomized to an intensive lifestyle intervention or diabetes support and education. The lifestyle intervention group received a behavioral weight loss program that included group and individual meetings, a ≥10% weight loss goal, calorie restriction, and increased physical activity. Diabetes support and education received a less intense educational intervention. Four-year changes in body weight and cardiovascular disease risk factors were assessed. Results Across BMI categories, 4-year changes in body weight were significantly greater in lifestyle participants compared with diabetes support and education ( P s <.05). At year 4, severely obese lifestyle participants lost 4.9% ± 8.5%, which was similar to class I (4.8% ± 7.2%) and class II obese participants (4.4% ± 7.6%), and significantly greater than overweight participants (3.4% ± 7.0%; P <.05). Four-year changes in low-density-lipoprotein cholesterol, triglycerides, diastolic blood pressure, HbA1c , and blood glucose were similar across BMI categories in lifestyle participants; however, the severely obese had less favorable improvements in high-density-lipoprotein cholesterol (3.1 ± 0.4 mg/dL) and systolic blood pressure (−1.4 ± 0.7 mm Hg) compared with the less obese ( P s <.05). Conclusion Lifestyle interventions can result in important long-term weight losses and improvements in cardiovascular disease risk factors among a significant proportion of severely obese individuals.
To evaluate differences in amyloid deposition in a community-based cohort without dementia by age, sex, race, education, and APOE ε4 allele status.
Recruited from the longitudinal Atherosclerosis ...Risk in Communities study, 329 participants without dementia, ages 67-88 years, were imaged using florbetapir PET at 3 US community sites (Washington County, Maryland; Forsyth County, North Carolina; and Jackson, Mississippi). Standardized uptake value ratios (SUVRs) were calculated; global cortical SUVR >1.2 was evaluated as the primary outcome. Age, race, sex, education level, and number of APOE ε4 alleles were evaluated in multivariable models including vascular risk factors, brain white matter hyperintensity and total intracranial volume, and cognitive status.
A total of 141 of the participants (43%) were black. In multivariable models, odds of elevated SUVR was increased in participants with increasing age (odds ratio OR 1.63, 95% confidence interval CI 1.01-2.65 per 10 years of age) and black race (OR 2.08, 95% CI 1.23-3.51) but did not differ by educational level. Each ε4 allele was associated with increased odds of elevated SUVR (OR 2.65, 95% CI 1.61-4.39).
In this community-based cohort without dementia, florbetapir uptake is associated with older age and APOE genotype. Black race was associated with higher SUVR, after adjusting for demographics, vascular risk factors, cognitive status, white matter hyperintensity volume, and APOE genotype, with effect sizes nearing those seen for APOE ε4. Replication of these findings is needed in other cohorts, and reasons for and consequences of these observed differences by race warrant further study.
We reevaluated the Action for Health in Diabetes (Look AHEAD) intervention, incorporating diabetes subgroups, to identify whether intensive lifestyle intervention (ILI) is associated with ...differential risk for cardiovascular disease (CVD) by diabetes subgroup.
In the Look AHEAD trial, 5,145 participants, aged 45-76 years, with type 2 diabetes (T2D) and overweight or obesity were randomly assigned to 10 years of ILI or a control condition of diabetes support and education. The ILI focused on weight loss through decreased caloric intake and increased physical activity. To characterize diabetes subgroups, we applied k-means clustering to data on age of diabetes diagnosis, BMI, waist circumference, and glycated hemoglobin. We examined whether relative intervention effects on the trial's prespecified CVD outcomes varied among diabetes subgroups.
We characterized four subgroups related to older age at diabetes onset (42% of sample), poor glucose control (14%), severe obesity (24%), and younger age at diabetes onset (20%). We observed interactions (all
< 0.05) between intervention and diabetes subgroups for three separate composite cardiovascular outcomes. Randomization to ILI was associated with increased risk for each cardiovascular outcome only among the poor-glucose-control subgroup (hazard ratio >1.32). Among the three other diabetes subgroups, ILI was not associated with increased risk for CVD.
Among overweight and obese adults with T2D, a lifestyle intervention was associated with differential risk for CVD that was dependent on diabetes subgroup. Diabetes subgroups may be important to identify the patients who would achieve benefit and avoid harm from an ILI.
The TG/HDL-C ratio is used as a marker of insulin resistance (IR) in Caucasians; however, there is limited data in other ethnic groups. We hypothesized that the TG/HDL-C ratio is associated with IR ...in Hispanics and African Americans (AA).
Data from the Insulin Resistance Atherosclerosis Family Study was examined for associations between TG/HDL-C ratio and IR, β-cell function and incident diabetes in non-diabetic Hispanics (n = 872, 63% female) and AA (n = 371, 61% female). Insulin sensitivity index (SI) and disposition index (DI) from frequently-sampled intravenous glucose tolerance tests were used as markers of IR and β-cell function respectively. Incident type 2 diabetes was determined by fasting glucose ≥ 126 mg/dl or initiation of anti-hyperglycemia agents over 5 year follow-up.
Higher TG/HDL-C ratio was associated with IR in Hispanic and AA men and women (P < 0.0002), as well as β-cell function in Hispanic women and AA men and women (P < 0.02). TG/HDL-C predicted incident type 2 diabetes in women (area under the curves 0.703 and 0.795 for Hispanics and AA respectively).
Similar to Caucasians, the TG/HDL-C ratio can be used to identify IR in Hispanics and AA, and may predict type 2 diabetes in women.
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