Effects of visceral adipose tissue reduction on CVD risk factors independent of weight loss: The Look AHEAD study.

OBJECTIVES: To determine if the reduction of visceral adipose tissue (VAT) volume by lifestyle intervention improved risk factors for cardiovascular disease (CVD) independent of weight loss amount. DESIGN: Ancillary study of randomized-controlled trial. SETTING: Data analysis using multivariable regression models. PARTICIPANTS: Participants of the Look AHEAD (Action for HEAlth in Diabetes) Fatty Liver Ancillary Study. MAIN OUTCOME MEASURES: Correlations between changes in VAT and in CVD risk factors, while adjusting for weight loss and treatment (intensive lifestyle intervention [ILI] vs. diabetes support and education [DSE]). RESULTS: Of 100 participants analyzed, 52% were women, and 36% were black, with a mean age of 61.1 years. In the DSE group, mean weight and VAT changed by 0.1 % (p=0.90) and 4.3% (p=0.39), respectively. In the ILI group, mean weight and VAT decreased by 8.0% (p<0.001) and 7.7% (p=0.01), respectively. Across both groups, mean weight decreased by 3.6% (p<0.001), and mean VAT decreased by 1.2% (p=0.22); the decrease in VAT was correlated with the increase in HDL-cholesterol (HDL-C; R=-0.37; p=0.03). There were no correlations between changes in VAT and blood pressure, triglycerides, LDL-C, glucose, or HbA1c. After adjusting for age, race, gender, baseline metabolic values, fitness, and treatment group, changes in HDL-C were not associated with changes in VAT, while weight changes were independently associated with decrease in glucose, HbA1c, and increase in HDL-C. CONCLUSIONS: VAT reduction was not correlated with improvements of CVD risk factors in a sample of overweight and obese adults with type 2 diabetes after adjusting for weight loss.

Cardiovascular effects of intensive lifestyle intervention in type 2 diabetes.

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.).

Comparative effectiveness of weight-loss interventions in clinical practice.

BACKGROUND: Obesity and its cardiovascular complications are extremely common medical problems, but evidence on how to accomplish weight loss in clinical practice is sparse. METHODS: We conducted a randomized, controlled trial to examine the effects of two behavioral weight-loss interventions in 415 obese patients with at least one cardiovascular risk factor. Participants were recruited from six primary care practices; 63.6% were women, 41.0% were black, and the mean age was 54.0 years. One intervention provided patients with weight-loss support remotely--through the telephone, a study-specific Web site, and e-mail. The other intervention provided in-person support during group and individual sessions, along with the three remote means of support. There was also a control group in which weight loss was self-directed. Outcomes were compared between each intervention group and the control group and between the two intervention groups. For both interventions, primary care providers reinforced participation at routinely scheduled visits. The trial duration was 24 months. RESULTS: At baseline, the mean body-mass index (the weight in kilograms divided by the square of the height in meters) for all participants was 36.6, and the mean weight was 103.8 kg. At 24 months, the mean change in weight from baseline was -0.8 kg in the control group, -4.6 kg in the group receiving remote support only (P<0.001 for the comparison with the control group), and -5.1 kg in the group receiving in-person support (P<0.001 for the comparison with the control group). The percentage of participants who lost 5% or more of their initial weight was 18.8% in the control group, 38.2% in the group receiving remote support only, and 41.4% in the group receiving in-person support. The change in weight from baseline did not differ significantly between the two intervention groups. CONCLUSIONS: In two behavioral interventions, one delivered with in-person support and the other delivered remotely, without face-to-face contact between participants and weight-loss coaches, obese patients achieved and sustained clinically significant weight loss over a period of 24 months. (Funded by the National Heart, Lung, and Blood Institute and others; ClinicalTrials.gov number, NCT00783315.).

Non-traditional risk factors are important contributors to the racial disparity in diabetes risk: the atherosclerosis risk in communities study.

BACKGROUND: Traditional risk factors, particularly obesity, do not completely explain the excess risk of diabetes among African Americans compared to whites. OBJECTIVE: We sought to quantify the impact of recently identified, non-traditional risk factors on the racial disparity in diabetes risk. DESIGN: Prospective cohort study. PARTICIPANTS: We analyzed data from 2,322 African-American and 8,840 white participants without diabetes at baseline from the Atherosclerosis Risk in Communities (ARIC) Study. MAIN MEASURES: We used Cox regression to quantify the association of incident diabetes by race over 9 years of in-person and 17 years of telephone follow-up, adjusting for traditional and non-traditional risk factors based on literature search. We calculated the mediation effect of a covariate as the percent change in the coefficient of race in multivariate models without and with the covariate of interest; 95 % confidence intervals (95 % CI) were calculated using boot-strapping. KEY RESULTS: African American race was independently associated with incident diabetes. Body mass index (BMI), forced vital capacity (FVC), systolic blood pressure, and serum potassium had the greatest explanatory effects for the difference in diabetes risk between races, with mediation effects (95 % CI) of 22.0 % (11.7 %, 42.2 %), 21.7 %(9.5 %, 43.1 %), 17.9 % (10.2 %, 37.4 %) and 17.7 % (8.2 %, 39.4 %), respectively, during 9 years of in-person follow-up, with continued effect over 17 years of telephone follow-up. CONCLUSIONS: Non-traditional risk factors, particularly FVC and serum potassium, are potential mediators of the association between race and diabetes risk. They should be studied further to verify their importance and to determine if they mark causal relationships that can be addressed to reduce the racial disparity in diabetes risk.

Body-Mass Index and All-Cause Mortality in US Adults With and Without Diabetes.

BACKGROUND: Previous studies found normal weight compared to overweight/obese adults with type 2 diabetes had a higher mortality risk, and body-mass index (BMI)-mortality studies do not typically account for baseline diabetes status. OBJECTIVE: To determine if diabetes influences the BMI-mortality relationship. DESIGN: Using a prospective study design, we analyzed data from a nationally representative sample of US adults participating in the National Health Interview Survey from 1997 to 2002, and followed for mortality through 2006. PARTICIPANTS: Excluding those with heart disease or cancer, our final analytic sample included 74,710 (34,805 never smoker) adults. MAIN MEASURES: BMI was calculated from self-reported height and weight. Diabetes status was based on self-reported diagnosis from a health professional. We used direct age standardization to calculate all-cause mortality rates and adjusted Cox models for all-cause mortality hazard ratios by BMI quintile; this was done separately for adults with diabetes and without diabetes. KEY RESULTS: Among never smokers, mean age was 50.1 years and 43 % were men. Mean BMI was 27.4 kg/m(2), 26 % were obese, and 2,035 (5 %) reported diagnosed diabetes. After 9 years, there were 4,355 deaths (754 of 4,740 with diabetes; 3,601 of 69,970 without) among 74,710 participants, and 1,238 (247 of 2,035 with diabetes; 991 of 32,770 without) among 34,805 never smokers. We observed a qualitative interaction with diabetes on the BMI-mortality relationship (p = 0.002). Death rates were substantially higher among participants with diabetes compared to those without diabetes across all BMI quintiles. However, death rates in participants with diabetes fell with increasing BMI quintile, while rates followed a J-shaped curve among those without diabetes. In adjusted Cox models, BMI was positively associated with mortality in adults without diabetes, but inversely associated with mortality among participants with diabetes. CONCLUSIONS: Mortality increased with increasing BMI in adults without diabetes, but decreased with increasing BMI among their counterparts with diabetes. Future studies need to be better designed to answer the question of whether normal weight adults with diabetes have a higher risk of mortality, by minimizing the possibility of reverse causation. Future studies should also account for prevalent diabetes in all investigations of the BMI-mortality relationship.

The use of clinical guidelines highlights ongoing educational gaps in physicians' knowledge and decision making related to diabetes.

BACKGROUND: Clinical guidelines for type 2 diabetes are a resource for providers to manage their patients and may help highlight specific areas in need of further education and training. We sought to determine how often guidelines are used and the relationship to physicians' diabetes-related knowledge and decision making. METHODS: Existing users of electronic clinical support tools were invited to complete an online questionnaire. A knowledge score was calculated for five questions related to prevention of diabetes and treatment of its complications. We explored the association of clinical guideline use with diabetes-related knowledge and self-reported decision making using logistic regression models, adjusted for key covariates. RESULTS: Of 383 physicians completing the questionnaire, 53% reported using diabetes guidelines routinely. Mean diabetes knowledge score for guideline users (GU) was significantly higher than non-guideline users (NGU) (3.37 ± 0.072 vs. 2.76 ± 0.084; p < 0.001). GU were significantly more likely to report a good understanding of type 2 diabetes medications (OR = 2.99, 95% CI 1.95-4.61; p < 0.001). GU were less likely to report their unfamiliarity with insulin as an important barrier to early insulin use (OR = 0.41, 0.21-0.80; p = 0.007) and with pharmacologic options as a barrier to prescribing intensive multifactorial interventions (OR = 0.32, 0.17-0.58; p < 0.001). Associations remained significant after adjusting for physician specialty, practice volume and frequency diagnosing or treating diabetes patients. CONCLUSIONS: Significant gaps exist in diabetes-related knowledge and decision making among practicing physicians, as highlighted by clinical guideline use. The development of educational and training strategies to address these needs may ultimately improve outcomes for patients with diabetes and should be investigated in the future.

Prevalence of nonalcoholic fatty liver disease in the United States: the Third National Health and Nutrition Examination Survey, 1988-1994.

Previous estimates of the prevalence of nonalcoholic fatty liver disease (NAFLD) in the US population relied on measures of liver enzymes, potentially underestimating the burden of this disease. We used ultrasonography data from 12,454 adults who participated in the Third National Health and Nutrition Examination Survey, conducted in the United States from 1988 to 1994. We defined NAFLD as the presence of hepatic steatosis on ultrasonography in the absence of elevated alcohol consumption. In the US population, the rates of prevalence of hepatic steatosis and NAFLD were 21.4% and 19.0%, respectively, corresponding to estimates of 32.5 (95% confidence interval: 29.9, 35.0) million adults with hepatic steatosis and 28.8 (95% confidence interval: 26.6, 31.2) million adults with NAFLD nationwide. After adjustment for age, income, education, body mass index (weight (kg)/height (m)²), and diabetes status, NAFLD was more common in Mexican Americans (24.1%) compared with non-Hispanic whites (17.8%) and non-Hispanic blacks (13.5%) (P = 0.001) and in men (20.2%) compared with women (15.8%) (P < 0.001). Hepatic steatosis and NAFLD were also independently associated with diabetes, with insulin resistance among people without diabetes, with dyslipidemia, and with obesity. Our results extend previous national estimates of the prevalence of NAFLD in the US population and highlight the burden of this disease. Men, Mexican Americans, and people with diabetes and obesity are the most affected groups.

The association of plasma lactate with incident cardiovascular outcomes: the ARIC Study.

We examined the association of plasma lactate at rest, a marker of oxidative capacity, with incident cardiovascular outcomes in 10,006 participants in the Atherosclerosis Risk in Communities (ARIC) Study visit 4 (1996-1998). We used Cox proportional-hazards models to estimate hazard ratios of incident coronary heart disease, stroke, heart failure, and all-cause mortality by quartiles of plasma lactate (Q1, ≤5.3 mg/dL; Q2, 5.4-6.6; Q3, 6.7-8.6; and Q4 ≥8.7). During a median follow-up time of 10.7 years, there were 1,105 coronary heart disease cases, 379 stroke cases, 820 heart failure cases, and 1,408 deaths. A significant graded relation between lactate level and cardiovascular events was observed in the demographically adjusted model (all P for trend < 0.001). After further adjustment for traditional and other potential confounders, the association remained significant for heart failure (Q4 vs. Q1: hazard ratio (HR) = 1.35, 95% confidence interval (CI): 1.07, 1.71) and all-cause mortality (HR = 1.27, 95% CI: 1.07, 1.51) (P for trend < 0.02 for these outcomes) but not for coronary heart disease (HR = 1.02, 95% CI: 0.84, 1.24) and stroke (HR = 1.26, 95% CI: 0.91, 1.75). The results for heart failure were robust across multiple subgroups, after further adjustment for N-terminal pro-B-type natriuretic peptide and after exclusion of participants with incident heart failure within 3 years. The independent associations of plasma lactate with heart failure and all-cause mortality suggest an important role for low resting oxidative capacity.

Glycated hemoglobin, diabetes, and cardiovascular risk in nondiabetic adults.

BACKGROUND: Fasting glucose is the standard measure used to diagnose diabetes in the United States. Recently, glycated hemoglobin was also recommended for this purpose. METHODS: We compared the prognostic value of glycated hemoglobin and fasting glucose for identifying adults at risk for diabetes or cardiovascular disease. We measured glycated hemoglobin in whole-blood samples from 11,092 black or white adults who did not have a history of diabetes or cardiovascular disease and who attended the second visit (occurring in the 1990-1992 period) of the Atherosclerosis Risk in Communities (ARIC) study. RESULTS: The glycated hemoglobin value at baseline was associated with newly diagnosed diabetes and cardiovascular outcomes. For glycated hemoglobin values of less than 5.0%, 5.0 to less than 5.5%, 5.5 to less than 6.0%, 6.0 to less than 6.5%, and 6.5% or greater, the multivariable-adjusted hazard ratios (with 95% confidence intervals) for diagnosed diabetes were 0.52 (0.40 to 0.69), 1.00 (reference), 1.86 (1.67 to 2.08), 4.48 (3.92 to 5.13), and 16.47 (14.22 to 19.08), respectively. For coronary heart disease, the hazard ratios were 0.96 (0.74 to 1.24), 1.00 (reference), 1.23 (1.07 to 1.41), 1.78 (1.48 to 2.15), and 1.95 (1.53 to 2.48), respectively. The hazard ratios for stroke were similar. In contrast, glycated hemoglobin and death from any cause were found to have a J-shaped association curve. All these associations remained significant after adjustment for the baseline fasting glucose level. The association between the fasting glucose levels and the risk of cardiovascular disease or death from any cause was not significant in models with adjustment for all covariates as well as glycated hemoglobin. For coronary heart disease, measures of risk discrimination showed significant improvement when glycated hemoglobin was added to models including fasting glucose. CONCLUSIONS: In this community-based population of nondiabetic adults, glycated hemoglobin was similarly associated with a risk of diabetes and more strongly associated with risks of cardiovascular disease and death from any cause as compared with fasting glucose. These data add to the evidence supporting the use of glycated hemoglobin as a diagnostic test for diabetes.

Association between variants in or near PNPLA3, GCKR, and PPP1R3B with ultrasound-defined steatosis based on data from the third National Health and Nutrition Examination Survey.

BACKGROUND & AIMS: A genome-wide association study associated 5 genetic variants with hepatic steatosis (identified by computerized tomography) in individuals of European ancestry. We investigated whether these variants were associated with measures of hepatic steatosis (HS) in non-Hispanic white (NHW), non-Hispanic black, and Mexican American (MA) participants in the US population-based National Health and Nutrition Examination Survey III, phase 2. METHODS: We analyzed data from 4804 adults (1825 NHW, 1442 non-Hispanic black, and 1537 MA; 51.7% women; mean age at examination, 42.5 y); the weighted prevalence of HS was 37.3%. We investigated whether ultrasound-measured HS, with and without increased levels of alanine aminotransferase (ALT), or level of ALT alone, was associated with rs738409 (patatin-like phospholipase domain-containing protein 3 [PNPLA3]), rs2228603 (neurocan [NCAN]), rs12137855 (lysophospholipase-like 1), rs780094 (glucokinase regulatory protein [GCKR]), and rs4240624 (protein phosphatase 1, regulatory subunit 3b [PPP1R3B]) using regression modeling in an additive genetic model, controlling for age, age-squared, sex, and alcohol consumption. RESULTS: The G allele of rs738409 (PNPLA3) and the T allele of rs780094 (GCKR) were associated with HS with a high level of ALT (odds ratio [OR], 1.36; P = .01; and OR, 1.30; P = .03, respectively). The A allele of rs4240624 (PPP1R3B) and the T allele of rs2228603 (NCAN) were associated with HS (OR, 1.28; P = .03; and OR, 1.40; P = .04, respectively). Variants of PNPLA3 and NCAN were associated with ALT level among all 3 ancestries. Some single-nucleotide polymorphisms were associated with particular races or ethnicities: variants in PNPLA3, NCAN, GCKR, and PPP1R3B were associated with NHW and variants in PNPLA3 were associated with MA. No variants were associated with NHB. CONCLUSIONS: We used data from the National Health and Nutrition Examination Survey III to validate the association between rs738409 (PNPLA3), rs780094 (GCKR), and rs4240624 (PPP1R3B) with HS, with or without increased levels of ALT, among 3 different ancestries. Some, but not all, associations between variants in NCAN, lysophospholipase-like 1, GCKR, and PPP1R3B with HS (with and without increased ALT level) were significant within subpopulations.

Early response to preventive strategies in the Diabetes Prevention Program.

BACKGROUND: Recommendations for diabetes prevention in patients with prediabetes include lifestyle modification and metformin. However, the significance of early weight loss and glucose measurements when monitoring response to these proven interventions is unknown. OBJECTIVE: To quantify the relationship between early measures of weight and glucose and subsequent diabetes in patients undergoing diabetes prevention interventions. DESIGN: Analysis of results from a randomized controlled trial in 27 academic medical centers in the United States. PARTICIPANTS/INTERVENTIONS: 3,041 adults with hyperglycemia randomized to lifestyle (n = 1,018), metformin (n = 1,036), or placebo (n = 987) with complete follow-up in The Diabetes Prevention Program. MAIN MEASURES: Independent variables were weight loss at 6 and 12 months; fasting glucose (FG) at 6 months; hemoglobin A1c (HbA1c) at 6 months; and post-load glucose at 12 months. The main outcome was time to diabetes diagnosis. KEY RESULTS: After 6 months, 604 participants developed diabetes in the lifestyle (n = 140), metformin (n = 206), and placebo (n = 258) arms over 2.7 years. In the lifestyle arm, 6-month weight loss predicted decreased diabetes risk in a graded fashion: adjusted HR (95 % CI) 0.65 (0.35-1.22), 0.62 (0.33-1.18), 0.46 (0.24-0.87), 0.34 (0.18-0.64), and 0.15 (0.07-0.30) for 0-<3 %, 3-<5 %, 5-<7 %, 7-<10 %, and ≥10 % weight loss, respectively (reference: weight gain). Attainment of optimal 6-month FG and HbA1c and 12-month post-load glucose predicted >60 % lower diabetes risk across arms. We found a significant interaction between 6-month weight loss and FG in the lifestyle arm (P = 0.038). CONCLUSION: Weight and glucose at 6 and 12 months strongly predict lower subsequent diabetes risk with a lifestyle intervention; lower FG predicts lower risk even with substantial weight loss. Early reduction in glycemia is a stronger predictor of future diabetes risk than weight loss for metformin. We offer the first evidence to guide clinicians in making interval management decisions for high-risk patients undertaking measures to prevent diabetes.

Creating a transdisciplinary research center to reduce cardiovascular health disparities in Baltimore, Maryland: lessons learned.

Cardiovascular disease (CVD) disparities continue to have a negative impact on African Americans in the United States, largely because of uncontrolled hypertension. Despite the availability of evidence-based interventions, their use has not been translated into clinical and public health practice. The Johns Hopkins Center to Eliminate Cardiovascular Health Disparities is a new transdisciplinary research program with a stated goal to lower the impact of CVD disparities on vulnerable populations in Baltimore, Maryland. By targeting multiple levels of influence on the core problem of disparities in Baltimore, the center leverages academic, community, and national partnerships and a novel structure to support 3 research studies and to train the next generation of CVD researchers. We also share the early lessons learned in the center's design.

Glycated hemoglobin and cancer incidence and mortality in the Atherosclerosis in Communities (ARIC) Study, 1990-2006.

Diabetes is a risk factor for many cancers; chronic hyperglycemia is hypothesized to be, in part, explanatory. We evaluated the association between glycated hemoglobin, a time-integrated glycemia measure, and cancer incidence and mortality in nondiabetic and diabetic men and women. We conducted a prospective study of 12,792 cancer-free participants attending the second visit (1990-1992) of the Atherosclerosis Risk in Communities (ARIC) Study. We measured glycated hemoglobin in whole-blood samples using HPLC. Incident cancers were ascertained from registries and hospital records through 2006. We estimated multivariable-adjusted hazard ratios (HR) of cancer incidence and mortality for nondiabetic participants with values ≥ 5.7% (elevated), nondiabetic participants with <5.0% (low) and diabetic participants all compared with nondiabetic participants with 5.0-5.6% (normal). We ascertained 2,349 incident cancer cases and 887 cancer deaths. Compared with nondiabetic women with normal glycated hemoglobin, nondiabetic women with elevated values had an increased risk of cancer incidence (HR:1.24; 95% CI:1.07,1.44) and mortality (HR:1.58; 95% CI:1.23,2.05) as did diabetic women (incidence, HR:1.30; 95% CI:1.06,1.60, mortality, HR:1.96; 95% CI:1.40,2.76). Nondiabetic women with low values also had increased risk. Diabetic women with good glycemic control (<7.0%) had a lower cancer risk than those with higher values. Glycated hemoglobin in nondiabetic and diabetic men, and diabetes were not statistically significantly associated with total cancer risk. Our findings support the hypothesis that chronic hyperglycemia, even in the nondiabetic range, increases cancer risk in women. Maintaining normal glycated hemoglobin overall, and good glycemic control among diabetic adults, may reduce the burden of cancer, especially in women.

Diagnostic accuracy and reliability of ultrasonography for the detection of fatty liver: a meta-analysis.

UNLABELLED: Ultrasonography is a widely accessible imaging technique for the detection of fatty liver, but the reported accuracy and reliability have been inconsistent across studies. We aimed to perform a systematic review and meta-analysis of the diagnostic accuracy and reliability of ultrasonography for the detection of fatty liver. We used MEDLINE and Embase from October 1967 to March 2010. Studies that provided cross-tabulations of ultrasonography versus histology or standard imaging techniques, or that provided reliability data for ultrasonography, were included. Study variables were independently abstracted by three reviewers and double checked by one reviewer. Forty-nine (4720 participants) studies were included for the meta-analysis of diagnostic accuracy. The overall sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio of ultrasound for the detection of moderate-severe fatty liver, compared to histology (gold standard), were 84.8% (95% confidence interval: 79.5-88.9), 93.6% (87.2-97.0), 13.3 (6.4-27.6), and 0.16 (0.12-0.22), respectively. The area under the summary receiving operating characteristics curve was 0.93 (0.91-0.95). Reliability of ultrasound for the detection of fatty liver showed kappa statistics ranging from 0.54 to 0.92 for intrarater reliability and from 0.44 to 1.00 for interrater reliability. Sensitivity and specificity of ultrasound was similar to that of other imaging techniques (i.e., computed tomography or magnetic resonance imaging). Statistical heterogeneity was present even after stratification for multiple clinically relevant characteristics. CONCLUSION: Ultrasonography allows for reliable and accurate detection of moderate-severe fatty liver, compared to histology. Because of its low cost, safety, and accessibility, ultrasound is likely the imaging technique of choice for screening for fatty liver in clinical and population settings.

Comorbid diabetes and end-of-life expenditures among Medicare beneficiaries with heart failure.

BACKGROUND: Diabetes is associated with increased risk of mortality in heart failure. We examined the association of diabetes with expenditures, hospitalizations, and procedures among Medicare beneficiaries with heart failure during the last 6 months of life. METHODS AND RESULTS: In a 5% national Medicare sample, the prevalence of diabetes was 41.7% among 16,613 beneficiaries who died in 2007 with a diagnosis of heart failure. Diabetes was associated with higher expenditures during the last 6 months of life (mean $39,042 vs $29,003; P < .001), even after adjusting for covariates, including age, sex, race, geographic location, comorbidities, and preceding hospitalizations (cost ratio 1.08, 95% CI 1.05-1.12). For both diabetic and nondiabetic adults, more than one-half of Medicare expenditures were related to hospitalization costs (mean $22,516 vs $15,721; P < .001). Compared with their counterparts without diabetes, beneficiaries with diabetes had higher rates of hospitalization (adjusted incidence rate ratio 1.09, 95% CI 1.05-1.12) and days spent in the intensive care unit. CONCLUSIONS: Comorbid diabetes was common in heart failure and associated with higher expenditures, much of which was driven by increased rates of hospitalizations. Programs that focus on prevention of hospitalizations may reduce the substantial costs associated with heart failure near the end of life.

Midcourse correction to a clinical trial when the event rate is underestimated: the Look AHEAD (Action for Health in Diabetes) Study.

The Look AHEAD (Action for Health in Diabetes) Study is a long-term clinical trial that aims to determine the cardiovascular disease (CVD) benefits of an intensive lifestyle intervention (ILI) in obese adults with type 2 diabetes. The study was designed to have 90% statistical power to detect an 18% reduction in the CVD event rate in the ILI Group compared to the Diabetes Support and Education (DSE) Group over 10.5 years of follow-up. The original power calculations were based on an expected CVD rate of 3.125% per year in the DSE group; however, a much lower-than-expected rate in the first 2 years of follow-up prompted the Data and Safety Monitoring Board (DSMB) to recommend that the Steering Committee undertake a formal blinded evaluation of these design considerations. The Steering Committee created an Endpoint Working Group (EPWG) that consisted of individuals masked to study data to examine relevant issues. The EPWG considered two primary options: (1) expanding the definition of the primary endpoint and (2) extending follow-up of participants. Ultimately, the EPWG recommended that the Look AHEAD Steering Committee approve both strategies. The DSMB accepted these modifications, rather than recommending that the trial continue with inadequate statistical power. Trialists sometimes need to modify endpoints after launch. This decision should be well justified and should be made by individuals who are fully masked to interim results that could introduce bias. This article describes this process in the Look AHEAD study and places it in the context of recent articles on endpoint modification and recent trials that reported endpoint modification.

Primary prevention of type 2 diabetes: integrative public health and primary care opportunities, challenges and strategies.

Type 2 diabetes imposes a large and growing burden on the public's health. This burden, combined with the growing evidence for primary prevention from randomized controlled trials of structured lifestyle programs leads to recommendations to include caloric reduction, increased physical activity and specific assistance to patients in problem solving to achieve modest weight loss as well as pharmacotherapy. These recommendations demand exploration of new ways to implement such primary prevention strategies through more integrated community organization, medical practice and policy. The US experience with control of tobacco use and high blood pressure offers valuable lessons for policy, such as taxation on products, and for practice in a variety of settings, such as coordination of referrals for lifestyle supports. We acknowledge also some notable exceptions to their generalizability. This paper presents possible actions proposed by an expert panel, summarized in Table 1 as recommendations for immediate action, strategic action and research. The collaboration of primary care and public health systems will be required to make many of these recommendations a reality. This paper also provides information on the progress made in recent years by the Division of Diabetes Translation at the US Centers for Disease Control and Prevention (CDC) to implement or facilitate such integration of primary care and public health for primary prevention.

Gestational diabetes and subsequent growth patterns of offspring: the National Collaborative Perinatal Project.

Our objective was to test the hypothesis that intrauterine exposure to gestational diabetes [GDM] predicts childhood growth independent of the effect on infant birthweight. We conducted a prospective analysis of 28,358 mother-infant pairs who enrolled in the National Collaborative Perinatal Project between 1959 and 1965. The offspring were followed until age 7. Four hundred and eighty-four mothers (1.7%) had GDM. The mean birthweight was 3.2 kg (range 1.1-5.6 kg). Maternal characteristics (age, education, race, family income, pre-pregnancy body mass index and pregnancy weight gain) and measures of childhood growth (birthweight, weight at ages 4, and 7) differed significantly by GDM status (all P < 0.05). As expected, compared to their non-diabetic counterparts, mothers with GDM gave birth to offspring that had higher weights at birth. The offspring of mothers with GDM were larger at age 7 as indicated by greater weight, BMI and BMI z-score compared to the offspring of mothers without GDM at that age (all P < 0.05). These differences at age 7 persisted even after adjustment for infant birthweight. Furthermore, the offspring of mothers with GDM had a 61% higher odds of being overweight at age 7 compared to the offspring of mothers without GDM after adjustment for maternal BMI, pregnancy weight gain, family income, race and birthweight [OR = 1.61 (95%CI:1.07, 1.28)]. Our results indicate that maternal GDM status is associated with offspring overweight status during childhood. This relationship is only partially mediated by effects on birthweight.

Racial differences in glycemic markers: a cross-sectional analysis of community-based data.

BACKGROUND: Although differences between black and white persons in hemoglobin A(1c) (HbA(1c)) values are well established, recent studies suggest that this might not reflect differences in glycemia. OBJECTIVE: To investigate racial disparities in glycemic markers, including those that reflect biological processes independent of hemoglobin glycation and erythrocyte turnover. DESIGN: Cross-sectional. SETTING: Community-based. PARTICIPANTS: 1376 nondiabetic and 343 diabetic adults in a substudy of the Atherosclerosis Risk in Communities Study. MEASUREMENTS: Hemoglobin A(1c), fasting glucose, glycated albumin, fructosamine, and 1,5-anhydroglucitol levels. RESULTS: Among persons with and without diabetes, black persons had significantly higher HbA(1c), glycated albumin, and fructosamine levels than white persons before and after adjustment for covariates and fasting glucose concentration. Serum 1,5-anhydroglucitol levels, which are reduced in the setting of hyperglycemia-induced glycosuria, were lower in black persons than in white persons, although this difference was statistically significant only in nondiabetic adults. LIMITATION: The design was cross-sectional, a limited number of participants with a history of diabetes was included, and the study did not include integrated measures of circulating nonfasting glycemia. CONCLUSION: Differences between black and white persons in glycated albumin, fructosamine, and 1,5-anhydroglucitol levels parallel differences between these groups in HbA(1c) values. Racial differences in hemoglobin glycation and erythrocyte turnover cannot explain racial disparities in these serum markers. The possibility that black persons have systematically higher levels of nonfasting glycemia warrants further study. PRIMARY FUNDING SOURCE: National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases.

Admixture mapping of 15,280 African Americans identifies obesity susceptibility loci on chromosomes 5 and X.

The prevalence of obesity (body mass index (BMI) > or =30 kg/m(2)) is higher in African Americans than in European Americans, even after adjustment for socioeconomic factors, suggesting that genetic factors may explain some of the difference. To identify genetic loci influencing BMI, we carried out a pooled analysis of genome-wide admixture mapping scans in 15,280 African Americans from 14 epidemiologic studies. Samples were genotyped at a median of 1,411 ancestry-informative markers. After adjusting for age, sex, and study, BMI was analyzed both as a dichotomized (top 20% versus bottom 20%) and a continuous trait. We found that a higher percentage of European ancestry was significantly correlated with lower BMI (rho = -0.042, P = 1.6x10(-7)). In the dichotomized analysis, we detected two loci on chromosome X as associated with increased African ancestry: the first at Xq25 (locus-specific LOD = 5.94; genome-wide score = 3.22; case-control Z = -3.94); and the second at Xq13.1 (locus-specific LOD = 2.22; case-control Z = -4.62). Quantitative analysis identified a third locus at 5q13.3 where higher BMI was highly significantly associated with greater European ancestry (locus-specific LOD = 6.27; genome-wide score = 3.46). Further mapping studies with dense sets of markers will be necessary to identify the alleles in these regions of chromosomes X and 5 that may be associated with variation in BMI.