Nils P. Carlsson

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 49–96). 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 0·25–0·87). 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.

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 (

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

13,581) compared with those without diabetes (

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

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

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

628 and

Reexamining the association of body mass index with overall survival outcomes after liver transplantation

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 (

15+ year weight change outcomes and complications after Roux-en-Y gastric bypass: a single-center study

12,907) and class III (

Risk Of Diabetes With Or Without The Presence Of Other Obesity-Related Comorbidities (Hypertension, Stroke And Coronary Heart Disease): National Health And Nutrition Examination Survey, 2007-2010

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.

Major early complications following Bariatric Surgery: a systematic review and meta-analysis

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: β=0.114, 95% Confidence interval [CI]: 0.050, 0.177; Hispanic: β=0.089, 95% CI: 0.024, 0.154; other race: β=0.126, 95% CI: 0.033, 0.219). Age was inversely associated with MEHP:MEHHP (β=-0.001, 95% CI: -0.002, -0.001) and %MEHP (β=-0.006, 95% CI: -0.008, -0.004). Overweight individuals had lower MEHP: MEHHP and lower %MEHP (β=-0.035, 95% CI: 0.062, -0.008 and β=-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.

Joint Estimation Of Markov Chain Transition Probabilities Using Survival Models And Constrained Optimization: A Case Study On Diabetes And Mortality And Their Association With Body Mass Index, Age, And Gender

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.