Bianca Porneala

Mortality Among Homeless Adults in Boston Shifts in Causes of Death Over a 15-Year Period

BACKGROUND Homeless persons experience excess mortality, but US-based studies on this topic are outdated or lack information about causes of death. To our knowledge, no studies have examined shifts in causes of death for this population over time. METHODS We assessed all-cause and cause-specific mortality rates in a cohort of 28 033 adults 18 years or older who were seen at Boston Health Care for the Homeless Program from January 1, 2003, through December 31, 2008. Deaths were identified through probabilistic linkage to the Massachusetts death occurrence files. We compared mortality rates in this cohort with rates in the 2003-2008 Massachusetts population and a 1988-1993 cohort of homeless adults in Boston using standardized rate ratios with 95% confidence intervals. RESULTS A total of 1302 deaths occurred during 90 450 person-years of observation. Drug overdose (n = 219), cancer (n = 206), and heart disease (n = 203) were the major causes of death. Drug overdose accounted for one-third of deaths among adults younger than 45 years. Opioids were implicated in 81% of overdose deaths. Mortality rates were higher among whites than nonwhites. Compared with Massachusetts adults, mortality disparities were most pronounced among younger individuals, with rates about 9-fold higher in 25- to 44-year-olds and 4.5-fold higher in 45- to 64-year-olds. In comparison with 1988-1993 rates, reductions in deaths from human immunodeficiency virus (HIV) were offset by 3- and 2-fold increases in deaths owing to drug overdose and psychoactive substance use disorders, resulting in no significant difference in overall mortality. CONCLUSIONS The all-cause mortality rate among homeless adults in Boston remains high and unchanged since 1988 to 1993 despite a major interim expansion in clinical services. Drug overdose has replaced HIV as the emerging epidemic. Interventions to reduce mortality in this population should include behavioral health integration into primary medical care, public health initiatives to prevent and reverse drug overdose, and social policy measures to end homelessness.

Association of Smoking Cessation and Weight Change With Cardiovascular Disease Among Adults With and Without Diabetes

IMPORTANCE Smoking cessation reduces the risks of cardiovascular disease (CVD), but weight gain that follows quitting smoking may weaken the CVD benefit of quitting. OBJECTIVE To test the hypothesis that weight gain following smoking cessation does not attenuate the benefits of smoking cessation among adults with and without diabetes. DESIGN, SETTING, AND PARTICIPANTS Prospective community-based cohort study using data from the Framingham Offspring Study collected from 1984 through 2011. At each 4-year examination, self-reported smoking status was assessed and categorized as smoker, recent quitter (≤ 4 years), long-term quitter (>4 years), and nonsmoker. Pooled Cox proportional hazards models were used to estimate the association between quitting smoking and 6-year CVD events and to test whether 4-year change in weight following smoking cessation modified the association between smoking cessation and CVD events. MAIN OUTCOME MEASURE Incidence over 6 years of total CVD events, comprising coronary heart disease, cerebrovascular events, peripheral artery disease, and congestive heart failure. RESULTS After a mean follow-up of 25 (SD, 9.6) years, 631 CVD events occurred among 3251 participants. Median 4-year weight gain was greater for recent quitters without diabetes (2.7 kg [interquartile range {IQR}, -0.5 to 6.4]) and with diabetes (3.6 kg [IQR, -1.4 to 8.2]) than for long-term quitters (0.9 kg [IQR, -1.4 to 3.2] and 0.0 kg [IQR, -3.2 to 3.2], respectively, P < .001). Among participants without diabetes, age- and sex-adjusted incidence rate of CVD was 5.9 per 100 person-examinations (95% CI, 4.9-7.1) in smokers, 3.2 per 100 person-examinations (95% CI, 2.1-4.5) in recent quitters, 3.1 per 100 person-examinations (95% CI, 2.6-3.7) in long-term quitters, and 2.4 per 100 person-examinations (95% CI, 2.0-3.0) in nonsmokers. After adjustment for CVD risk factors, compared with smokers, recent quitters had a hazard ratio (HR) for CVD of 0.47 (95% CI, 0.23-0.94) and long-term quitters had an HR of 0.46 (95% CI, 0.34-0.63); these associations had only a minimal change after further adjustment for weight change. Among participants with diabetes, there were similar point estimates that did not reach statistical significance. CONCLUSIONS AND RELEVANCE In this community-based cohort, smoking cessation was associated with a lower risk of CVD events among participants without diabetes, and weight gain that occurred following smoking cessation did not modify this association. This supports a net cardiovascular benefit of smoking cessation, despite subsequent weight gain.

Polygenic type 2 diabetes prediction at the limit of common variant detection.

Genome-wide association studies (GWAS) may have reached their limit of detecting common type 2 diabetes (T2D)–associated genetic variation. We evaluated the performance of current polygenic T2D prediction. Using data from the Framingham Offspring (FOS) and the Coronary Artery Risk Development in Young Adults (CARDIA) studies, we tested three hypotheses: 1) a 62-locus genotype risk score (GRSt) improves T2D prediction compared with previous less inclusive GRSt; 2) separate GRS for β-cell (GRSβ) and insulin resistance (GRSIR) independently predict T2D; and 3) the relationships between T2D and GRSt, GRSβ, or GRSIR do not differ between blacks and whites. Among 1,650 young white adults in CARDIA, 820 young black adults in CARDIA, and 3,471 white middle-aged adults in FOS, cumulative T2D incidence was 5.9%, 14.4%, and 12.9%, respectively, over 25 years. The 62-locus GRSt was significantly associated with incident T2D in all three groups. In FOS but not CARDIA, the 62-locus GRSt improved the model C statistic (0.698 and 0.726 for models without and with GRSt, respectively; P < 0.001) but did not materially improve risk reclassification in either study. Results were similar among blacks compared with whites. The GRSβ but not GRSIR predicted incident T2D among FOS and CARDIA whites. At the end of the era of common variant discovery for T2D, polygenic scores can predict T2D in whites and blacks but do not outperform clinical models. Further optimization of polygenic prediction may require novel analytic methods, including less common as well as functional variants.

Metabolite Traits and Genetic Risk Provide Complementary Information for the Prediction of Future Type 2 Diabetes

OBJECTIVE A genetic risk score (GRS) comprised of single nucleotide polymorphisms (SNPs) and metabolite biomarkers have each been shown, separately, to predict incident type 2 diabetes. We tested whether genetic and metabolite markers provide complementary information for type 2 diabetes prediction and, together, improve the accuracy of prediction models containing clinical traits. RESEARCH DESIGN AND METHODS Diabetes risk was modeled with a 62-SNP GRS, nine metabolites, and clinical traits. We fit age- and sex-adjusted logistic regression models to test the association of these sources of information, separately and jointly, with incident type 2 diabetes among 1,622 initially nondiabetic participants from the Framingham Offspring Study. The predictive capacity of each model was assessed by area under the curve (AUC). RESULTS Two hundred and six new diabetes cases were observed during 13.5 years of follow-up. The AUC was greater for the model containing the GRS and metabolite measurements together versus GRS or metabolites alone (0.820 vs. 0.641, P < 0.0001, or 0.820 vs. 0.803, P = 0.01, respectively). Odds ratios for association of GRS or metabolites with type 2 diabetes were not attenuated in the combined model. The AUC was greater for the model containing the GRS, metabolites, and clinical traits versus clinical traits only (0.880 vs. 0.856, P = 0.002). CONCLUSIONS Metabolite and genetic traits provide complementary information to each other for the prediction of future type 2 diabetes. These novel markers of diabetes risk modestly improve the predictive accuracy of incident type 2 diabetes based only on traditional clinical risk factors.

Tobacco-, Alcohol-, and Drug-Attributable Deaths and Their Contribution to Mortality Disparities in a Cohort of Homeless Adults in Boston

OBJECTIVES We quantified tobacco-, alcohol-, and drug-attributable deaths and their contribution to mortality disparities among homeless adults. METHODS We ascertained causes of death among 28 033 adults seen at the Boston Health Care for the Homeless Program in 2003 to 2008. We calculated population-attributable fractions to estimate the proportion of deaths attributable to tobacco, alcohol, or drug use. We compared attributable mortality rates with those for Massachusetts adults using rate ratios and differences. RESULTS Of 1302 deaths, 236 were tobacco-attributable, 215 were alcohol-attributable, and 286 were drug-attributable. Fifty-two percent of deaths were attributable to any of these substances. In comparison with Massachusetts adults, tobacco-attributable mortality rates were 3 to 5 times higher, alcohol-attributable mortality rates were 6 to 10 times higher, and drug-attributable mortality rates were 8 to 17 times higher. Disparities in substance-attributable deaths accounted for 57% of the all-cause mortality gap between the homeless cohort and Massachusetts adults. CONCLUSIONS In this clinic-based cohort of homeless adults, over half of all deaths were substance-attributable, but this did not fully explain the mortality disparity with the general population. Interventions should address both addiction and non-addiction sources of excess mortality.

Race-ethnic differences in the association of genetic loci with HbA1c levels and mortality in U.S. adults: the third National Health and Nutrition Examination Survey (NHANES III)

BackgroundHemoglobin A1c (HbA1c) levels diagnose diabetes, predict mortality and are associated with ten single nucleotide polymorphisms (SNPs) in white individuals. Genetic associations in other race groups are not known. We tested the hypotheses that there is race-ethnic variation in 1) HbA1c-associated risk allele frequencies (RAFs) for SNPs near SPTA1, HFE, ANK1, HK1, ATP11A, FN3K, TMPRSS6, G6PC2, GCK, MTNR1B; 2) association of SNPs with HbA1c and 3) association of SNPs with mortality.MethodsWe studied 3,041 non-diabetic individuals in the NHANES (National Health and Nutrition Examination Survey) III. We stratified the analysis by race/ethnicity (NHW: non-Hispanic white; NHB: non-Hispanic black; MA: Mexican American) to calculate RAF, calculated a genotype score by adding risk SNPs, and tested associations with SNPs and the genotype score using an additive genetic model, with type 1 error = 0.05.ResultsRAFs varied widely and at six loci race-ethnic differences in RAF were significant (p < 0.0002), with NHB usually the most divergent. For instance, at ATP11A, the SNP RAF was 54% in NHB, 18% in MA and 14% in NHW (p < .0001). The mean genotype score differed by race-ethnicity (NHW: 10.4, NHB: 11.0, MA: 10.7, p < .0001), and was associated with increase in HbA1c in NHW (β = 0.012 HbA1c increase per risk allele, p = 0.04) and MA (β = 0.021, p = 0.005) but not NHB (β = 0.007, p = 0.39). The genotype score was not associated with mortality in any group (NHW: OR (per risk allele increase in mortality) = 1.07, p = 0.09; NHB: OR = 1.04, p = 0.39; MA: OR = 1.03, p = 0.71).ConclusionAt many HbA1c loci in NHANES III there is substantial RAF race-ethnic heterogeneity. The combined impact of common HbA1c-associated variants on HbA1c levels varied by race-ethnicity, but did not influence mortality.

Diabetes Differentially Affects Depression and Self-Rated Health by Age in the U.S.

OBJECTIVE To determine whether the relationship between age and physical and mental health varies by diabetes status in older U.S. adults. RESEARCH DESIGN AND METHODS Using data from the National Social Life, Health, and Aging Project, a national sample of 3,005 adults aged 57–85 years, we tested the significance of the interaction between age and diabetes in association with health states. RESULTS Respondents with diabetes in the youngest age cohort had more medical conditions than those without diabetes, a difference that narrowed with age (P for interaction <0.01). The youngest cohort with diabetes had a higher rate of depression compared to those without diabetes (14 vs. 8%). Depression declined with age and did not differ by diabetes status in the oldest respondents (P = 0.01 for age-diabetes interaction). CONCLUSIONS Diabetes differentially affects self-rated overall health and depression by age, with convergence in the oldest age-group with and without diabetes.

Disparities in Cancer Incidence, Stage, and Mortality at Boston Health Care for the Homeless Program.

INTRODUCTION Homeless people have a high burden of cancer risk factors and suboptimal rates of cancer screening, but the epidemiology of cancer has not been well described in this population. We assessed cancer incidence, stage, and mortality in homeless adults relative to general population standards. METHODS We cross-linked a cohort of 28,033 adults seen at Boston Health Care for the Homeless Program in 2003-2008 to Massachusetts cancer registry and vital registry records. We calculated age-standardized cancer incidence and mortality ratios (SIRs and SMRs). We examined tobacco use among incident cases and estimated smoking-attributable fractions. Trend tests were used to compare cancer stage distributions with those in Massachusetts adults. Analyses were conducted in 2012-2015. RESULTS During 90,450 person-years of observation, there were 361 incident cancers (SIR=1.13, 95% CI=1.02, 1.25) and 168 cancer deaths (SMR=1.88, 95% CI=1.61, 2.19) among men, and 98 incident cancers (SIR=0.93, 95% CI=0.76, 1.14) and 38 cancer deaths (SMR=1.61, 95% CI=1.14, 2.20) among women. For both sexes, bronchus and lung cancer was the leading type of incident cancer and cancer death, exceeding Massachusetts estimates more than twofold. Oropharyngeal and liver cancer cases and deaths occurred in excess among men, whereas cervical cancer cases and deaths occurred in excess among women. About one third of incident cancers were smoking-attributable. Colorectal, female breast, and oropharyngeal cancers were diagnosed at more-advanced stages than in Massachusetts adults. CONCLUSIONS Efforts to reduce cancer disparities in homeless people should include addressing tobacco use and enhancing participation in evidence-based screening.

Genetically Driven Hyperglycemia Increases Risk of Coronary Artery Disease Separately From Type 2 Diabetes

OBJECTIVE This study tested the hypothesis that genetically raised hyperglycemia increases coronary artery disease (CAD) risk separately from the risk conferred by type 2 diabetes as a whole. RESEARCH DESIGN AND METHODS We conducted a Mendelian randomization (MR) analysis using summary-level statistics from the largest published meta-analyses of genome-wide association studies (GWAS) for fasting glucose (FG) (n = 133,010 participants free of diabetes) and CAD (n = 63,746 case subjects and 130,681 control subjects) of predominantly European ancestry. FG-increasing variants associated with type 2 diabetes from the largest GWAS for type 2 diabetes were excluded. Variants with pleiotropic effects on other CAD risk factors (blood lipids, blood pressure, and obesity) were excluded using summary-level data from the largest published GWAS. Data from the Framingham Heart Study were used to validate the MR instrument and to build an FG genetic risk score (GRS). RESULTS In an instrumental variable analysis comprising 12 FG-raising variants, a 1 mmol/L increase in FG revealed an effect-size estimate of 1.43 CAD odds (95% CI 1.14–1.79). The association was preserved after excluding variants for heterogeneity and pleiotropic effects on other CAD risk factors (odds ratio [OR] 1.33 [95% CI 1.02–1.73]). The 12 FG-increasing variants did not significantly increase type 2 diabetes risk (OR 1.05 [95% CI 0.91–1.23]), and its prevalence was constant across FG GRS quintiles (P = 0.72). CONCLUSIONS Our data support that genetic predisposition to hyperglycemia raises the odds of CAD separately from type 2 diabetes and other CAD risk factors. These findings suggest that modulating glycemia may provide cardiovascular benefit.

Improving diabetes outcomes through lifestyle change – A randomized controlled trial

To compare a diabetes group lifestyle intervention (GLI) with dietitian referral for medical nutrition therapy (RD) for weight loss in the usual care setting.