Reexamining the Association of Body Mass Index With Overall Survival Outcomes After Liver Transplantation.

BACKGROUND: Several studies have shown that obese patients undergoing liver transplantation (LT) have an increased risk of mortality regardless of Model of End Stage Liver Disease (MELD) scores. The purpose of this study is to identify the range of body mass index (BMI) at LT associated with the lowest risks of posttransplant mortality by MELD category. METHODS: A retrospective cohort of patients aged 18 years or older from the Organ Procurement and Transplantation Network database undergoing LT between February 27, 2002, and December 31, 2013, was identified and followed up through March 14, 2014. Patients' MELD score at the time of transplantation was categorized into 10 or lower (MELD1), 11 to 18 (MELD2), 19 to 24 (MELD3), and 25 or higher (MELD4). Multivariable adjusted Cox proportional hazard analyses were conducted. RESULTS: Among 48 226 patients in the analytic cohort (14.8% were in MELD1, 33.7% were in MELD2, 19.6% were in MELD3, and 32.0% were in MELD4), 25% died with mean follow-up of 1371 days. For MELD1, patient BMI ranging from 30 to 33 was associated with a better survival outcome than BMI less than 30 or 33 or greater; for MELD2, BMI ranging from 28 to 37 had a better survival outcome than BMI less than 28 or 37 or greater; for MELD3, the survival outcome improved with an increasing BMI; for MELD4, the survival outcome was not associated with patient BMI. CONCLUSIONS: This study provides evidence that obesity in LT patients is not necessarily associated with higher posttransplantation mortality and highlights the importance of the interaction between BMI and MELD category to determine their survival likelihood.

Racial disparity in life expectancies and life years lost associated with multiple obesity-related chronic conditions.

OBJECTIVE: This study investigated racial disparity in life expectancies (LEs) and life years lost (LYL) associated with multiple obesity-related chronic conditions (OCCs). METHODS: Data from the Medical Expenditure Panel Survey, 2008-2012, were used. Four OCCs were studied: diabetes, hypertension, coronary heart disease (CHD), and stroke. LE for each subpopulation was simulated by Markov modelling. LYL associated with a disease for a subpopulation was computed by taking the difference between LEs for members of that subpopulation without disease and LEs for members of that subpopulation who had that disease. Racial disparities were measured in the absolute differences in LE and LYL between black women/men and white women/men. RESULTS: Black individuals had higher risks of developing diabetes, hypertension, and stroke. This disparity in LE between white and black participants was largest in men age 40 to 49 with at least stroke: black men lived 3.12 years shorter than white men. The disparity in LYL between white and black participants was largest in women age 70 to 79 with at least CHD: black women had 1.98 years more LYL than white women. CONCLUSIONS: Racial disparity exists in incident disease and mortality risks, LEs, and LYL associated with multiple OCCs. Efforts targeting subpopulations with large disparities are required to reduce disparities in the burden of multiple OCCs.

The Burden of Obesity on Diabetes in the United States: Medical Expenditure Panel Survey, 2008 to 2012.

BACKGROUND: Diabetes is one of the most prevalent and costly chronic diseases in the United States. OBJECTIVES: To analyze the risk of developing diabetes and the annual cost of diabetes for a US general population. METHODS: Data from the Medical Expenditure Panel Survey, 2008 to 2012, were used to analyze 1) probabilities of developing diabetes and 2) annual total health care expenditures for diabetics. The age-, sex-, race-, and body mass index (BMI)-specific risks of developing diabetes were estimated by fitting an exponential survival function to age at first diabetes diagnosis. Annual health care expenditures were estimated using a generalized linear model with log-link and gamma variance function. Complex sampling designs in the Medical Expenditure Panel Survey were adjusted for. All dollar values are presented in 2012 US dollars. RESULTS: We observed a more than 6 times increase in diabetes risks for class III obese (BMI ≥ 40 kg/m2) individuals compared with normal-weight individuals. Using age 50 years as an example, we found a more than 3 times increase in annual health care expenditures for those with diabetes ($13,581) compared with those without diabetes ($3,954). Compared with normal-weight (18.5 ≤ BMI < 25 kg/m2) individuals, class II obese (35 ≤ BMI < 40 kg/m2) and class III obese (BMI ≥ 40 kg/m2) individuals incurred an annual marginal cost of $628 and $756, respectively. The annual health care expenditure differentials between those with and without diabetes of age 50 years were the highest for individuals with class II ($12,907) and class III ($9,703) obesity. CONCLUSIONS: This article highlights the importance of obesity on diabetes burden. Our results suggested that obesity, in particular, class II and class III (i.e., BMI ≥ 35 kg/m2) obesity, is associated with a substantial increase in the risk of developing diabetes and imposes a large economic burden.

Obesity and the Transformation of Monoclonal Gammopathy of Undetermined Significance to Multiple Myeloma: A Population-Based Cohort Study.

Background: Multiple myeloma (MM) is one of the most common hematologic malignancies in the United States and is consistently preceded by monoclonal gammopathy of undetermined significance (MGUS). This study investigates the role of obesity in the progression of MGUS to MM. Methods: A retrospective identified cohort of patients in the US Veterans Health Administration database diagnosed with MGUS between October 1, 1999, and December 31, 2009, was followed through August 6, 2013. Patient-level clinical data were reviewed to verify MM diagnosis, if any. Survival analyses utilizing interval-censored data were used to investigate the risk of progression of MGUS to MM. Statistical tests were two-sided. Results: The analytic cohort consisted of 7878 MGUS patients with a median follow-up of 68 months. Within the cohort, 39.8% were overweight and 33.8% were obese; 64.1% were of white race. During follow-up, 329 MGUS patients (4.2%) progressed to MM: 72 (3.5%) normal-weight patients (median follow-up = 61.9 months), 144 (4.6%) overweight patients (median follow-up = 69.1 months), and 113 (4.3%) obese patients (median follow-up = 70.6 months). In the multivariable analysis, overweight (hazard ratio [HR] = 1.55, 95% confidence interval [CI] = 1.16 to 2.06) and obesity (HR = 1.98, 95% CI = 1.47 to 2.68) were associated with an increased risk of transformation of MGUS to MM. Moreover, black race was associated with a higher risk of MM (HR = 1.98, 95% CI = 1.55 to 2.54). Conclusions: Obesity and black race are risk factors for transformation of MGUS to MM. Future clinical trials should examine whether weight loss is a way to prevent the progression to MM in MGUS patients.

Associations of individual characteristics and lifestyle factors with metabolism of di-2-ethylhexyl phthalate in NHANES 2001-2012.

BACKGROUND: Previous studies suggest that a higher ratio of primary to secondary metabolites of di-2-ethylhexyl phthalate (DEHP), reflective of a slower DEHP conversion rate, is associated with a greater physiologic effect. We examined associations of several individual characteristics and lifestyle factors with the ratio of mono-2-ethylhexyl phthalate to mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHP:MEHHP) and %MEHP (the ratio of MEHP to the sum of the secondary metabolites). METHODS: We used the data from the National Health and Nutrition Examination Survey, 2001-2012. The study included adults with BMI<30 and no diabetes. Pregnant women were excluded. We examined associations of age, race, gender, Body Mass Index, smoking, alcohol and caffeine consumption, medication use, cancer history, and menopausal status and postmenopausal hormone use (in women) with MEHP:MEHHP and %MEHP using multivariable linear regression. The values for %MEHP were log-transformed in the analysis. RESULTS: In multivariable analysis, non-Caucasian individuals had higher %MEHP (non-Hispanic Blacks: ß=0.114, 95% Confidence interval [CI]: 0.050, 0.177; Hispanic: ß=0.089, 95% CI: 0.024, 0.154; other race: ß=0.126, 95% CI: 0.033, 0.219). Age was inversely associated with MEHP:MEHHP (ß=-0.001, 95% CI: -0.002, -0.001) and %MEHP (ß=-0.006, 95% CI: -0.008, -0.004). Overweight individuals had lower MEHP: MEHHP and lower %MEHP (ß=-0.035, 95% CI: 0.062, -0.008 and ß=-0.104, 95% CI: -0.162, -0.046, respectively). Alcohol consumption was inversely associated with %MEHP among men (p-trend=0.03). CONCLUSIONS: Individual and lifestyle characteristics are associated with differences in DEHP metabolism. Understanding underlying biological mechanisms could help to identify individuals at a greater risk of adverse effects from DEHP exposure.

Association between metformin use and progression of monoclonal gammopathy of undetermined significance to multiple myeloma in US veterans with diabetes mellitus: a population-based retrospective cohort study.

BACKGROUND: Multiple myeloma is one of the most common haematological malignancies in the USA and is consistently preceded by monoclonal gammopathy of undetermined significance (MGUS). We aimed to assess the association between metformin use and progression of MGUS to multiple myeloma. METHODS: We did a retrospective cohort study of patients registered in the US Veterans Health Administration database and diagnosed with MGUS between Oct 1, 1999, and Dec 31, 2009. We included patients (aged >18 years) with at least one International Classification of Diseases (9th revision) code for diabetes mellitus and one treatment for their diabetes before MGUS diagnosis. We reviewed patient-level clinical data to verify diagnoses and extract any available data for size of baseline M-protein and type of MGUS. We defined metformin users as patients with diabetes who were given metformin consistently for 4 years after their diabetes diagnosis and before multiple myeloma development, death, or censorship. Our primary outcome was time from MGUS diagnosis to multiple myeloma diagnosis. We used Kaplan-Meier curves and Cox models to analyse the association between metformin use and MGUS progression. FINDINGS: We obtained data for 3287 patients, of whom 2003 (61%) were included in the final analytical cohort. Median follow-up was 69 months (IQR 49­96). 463 (23%) participants were metformin users and 1540 (77%) participants were non-users. 13 (3%) metformin users progressed to multiple myeloma compared with 74 (5%) non-users. After adjustment, metformin use was associated with a reduced risk of progression to multiple myeloma (hazard ratio 0·47, 95% CI 0·25­0·87). INTERPRETATION: For patients with diabetes diagnosed with MGUS, metformin use for 4 years or longer was associated with a reduced risk of progression of MGUS to multiple myeloma. Prospective studies are needed to establish whether this association is causal and whether these results can be extrapolated to non-diabetic individuals. FUNDING: Barnes-Jewish Hospital Foundation, National Institutes of Health, Agency for Healthcare Research and Quality, American Cancer Society.