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Item Adult BMI change and risk of Breast Cancer: National Health and Nutrition Examination Survey (NHANES) 2005-2010(Springer-Verlag, 2015-11) Gathirua-Mwangi, Wambui G.; Zollinger, Terrell W.; Murage, Mwangi J.; Pradhan, Kamnesh R.; Champion, Victoria L.; Department of Epidemiology, Richard M. Fairbanks School of Public HealthOBJECTIVE: Breast cancer is the second leading cause of cancer mortality among women in the developed world. This study assessed the association between occurrence of breast cancer and body mass index (BMI) change from age 25 to age closest to breast cancer diagnosis while exploring the modifying effects of demographic variables. METHODS: The National Health and Nutrition Examination Survey data were used. Women included were ≥50 years, not pregnant and without a diagnosis of any cancer but breast. The total sample included 2895 women (172 with breast cancer and 2723 controls with no breast cancer diagnosis). Multivariate logistic regression was used to estimate the OR and 95 % CIs and interaction evaluated by including an interaction term in the model. RESULTS: Women whose BMI increased from normal or overweight to obese compared to those who remained at a normal BMI were found to have a 2 times higher odds (OR = 2.1; 95 % CI 1.11-3.79) of developing breast cancer. No significant association was observed for women who increased to overweight. However, a more pronounced association was observed in non-Hispanic black women (OR = 6.6; 95 % CI 1.68-25.86) and a significant association observed when they increased from normal to overweight (OR = 4.2; 95 % CI 1.02-17.75). CONCLUSIONS: Becoming obese after age 25 is associated with increased risk of breast cancer in women over 50 years old, with non-Hispanic black women being at greatest risk.Item Association of Body Mass Index With Colorectal Cancer Risk by Genome-Wide Variants(Oxford University Press, 2021) Campbell, Peter T.; Lin, Yi; Bien, Stephanie A.; Figueiredo, Jane C.; Harrison, Tabitha A.; Guinter, Mark A.; Berndt, Sonja I.; Brenner, Hermann; Chan, Andrew T.; Chang-Claude, Jenny; Gallinger, Steven J.; Gapstur, Susan M.; Giles, Graham G.; Giovannucci, Edward; Gruber, Stephen B.; Gunter, Marc; Hoffmeister, Michael; Jacobs, Eric J.; Jenkins, Mark A.; Marchand, Loic Le; Li, Li; McLaughlin, John R.; Murphy, Neil; Milne, Roger L.; Newcomb, Polly A.; Newton, Christina; Ogino, Shuji; Potter, John D.; Rennert, Gad; Rennert, Hedy S.; Robinson, Jennifer; Sakoda, Lori C.; Slattery, Martha L.; Song, Yiqing; White, Emily; Woods, Michael O.; Casey, Graham; Hsu, Li; Peters, Ulrike; Epidemiology, School of Public HealthBackground: Body mass index (BMI) is a complex phenotype that may interact with genetic variants to influence colorectal cancer risk. Methods: We tested multiplicative statistical interactions between BMI (per 5 kg/m2) and approximately 2.7 million single nucleotide polymorphisms with colorectal cancer risk among 14 059 colorectal cancer case (53.2% women) and 14 416 control (53.8% women) participants. All analyses were stratified by sex a priori. Statistical methods included 2-step (ie, Cocktail method) and single-step (ie, case-control logistic regression and a joint 2-degree of freedom test) procedures. All statistical tests were two-sided. Results: Each 5 kg/m2 increase in BMI was associated with higher risks of colorectal cancer, less so for women (odds ratio [OR] = 1.14, 95% confidence intervals [CI] = 1.11 to 1.18; P = 9.75 × 10-17) than for men (OR = 1.26, 95% CI = 1.20 to 1.32; P = 2.13 × 10-24). The 2-step Cocktail method identified an interaction for women, but not men, between BMI and a SMAD7 intronic variant at 18q21.1 (rs4939827; Pobserved = .0009; Pthreshold = .005). A joint 2-degree of freedom test was consistent with this finding for women (joint P = 2.43 × 10-10). Each 5 kg/m2 increase in BMI was more strongly associated with colorectal cancer risk for women with the rs4939827-CC genotype (OR = 1.24, 95% CI = 1.16 to 1.32; P = 2.60 × 10-10) than for women with the CT (OR = 1.14, 95% CI = 1.09 to 1.19; P = 1.04 × 10-8) or TT (OR = 1.07, 95% CI = 1.01 to 1.14; P = .02) genotypes. Conclusion: These results provide novel insights on a potential mechanism through which a SMAD7 variant, previously identified as a susceptibility locus for colorectal cancer, and BMI may influence colorectal cancer risk for women.Item Association of the First 1,000 Days Systems-Change Intervention on Maternal Gestational Weight Gain(Wolters Kluwer, 2020-05) Blake-Lamb, Tiffany; Boudreau, Alexy Arauz; Matathia, Sarah; Perkins, Meghan E.; Roche, Brianna; Cheng, Erika R.; Kotelchuck, Milton; Shtasel, Derri; Taveras, Elsie M.; Pediatrics, School of MedicineObjective: To examine the associations of a clinical and public health systems-change intervention on the prevalence of excess gestational weight gain among high-risk, low-income women. Methods: In a quasi-experimental trial, we compared the prevalence of excess gestational weight gain among women before (n=643) and after (n=928) implementation of the First 1,000 Days program in two community health centers in Massachusetts. First 1,000 Days is a systematic program starting in early pregnancy and lasting through the first 24 months of childhood to prevent obesity among mother-child pairs. The program includes enhanced gestational weight gain tracking and counseling, screening for adverse health behaviors and sociocontextual factors, patient navigation and educational materials to support behavior change and social needs, and individualized health coaching for women at high risk for excess gestational weight gain based on their prepregnancy body mass index (BMI) or excess first-trimester weight gain. The primary outcome was gestational weight gain greater than the 2009 Institute of Medicine (now known as the National Academy of Medicine) guidelines according to prepregnancy BMI. Results: Among 1,571 women in the analytic sample, mean (SD) age was 30.0 (5.9) years and prepregnancy BMI was 28.1 (6.1); 65.8% of women started pregnancy with BMIs of 25 or higher, and 53.2% were Hispanic. We observed a lower prevalence (55.8-46.4%; unadjusted odds ratio [OR] 0.69, 95% CI 0.49-0.97), similar to results in a multivariable analysis (adjusted OR 0.69, 95% CI 0.49-0.99), of excess gestational weight gain among women with prepregnancy BMIs between 25 and 29.9. Among women who were overweight at the start of pregnancy, the lowest odds of excess gestational weight gain were observed among those with the most interaction with the program's components. Program enrollment was not associated with reduced excess gestational weight gain among women with prepregnancy BMIs of 30 or higher. Conclusions: Implementation of a systems-change intervention was associated with modest reduction in excess gestational weight gain among women who were overweight but not obese at the start of pregnancy.Item Associations of Muscle Mass and Strength with All-Cause Mortality among US Older Adults(Lippincott, Williams & Wilkins, 2018-03) Li, Ran; Xia, Jin; Zhang, Xi; Gathirua-Mwangi, Wambui Grace; Guo, Jianjun; Li, Yufeng; McKenzie, Steve; Song, Yiqing; Epidemiology, School of Public HealthINTRODUCTION: Recent studies suggested that muscle mass and muscle strength may independently or synergistically affect aging-related health outcomes in older adults; however, prospective data on mortality in the general population are sparse. METHODS: We aimed to prospectively examine individual and joint associations of low muscle mass and low muscle strength with all-cause mortality in a nationally representative sample. This study included 4449 participants age 50 yr and older from the National Health and Nutrition Examination Survey 1999 to 2002 with public use 2011 linked mortality files. Weighted multivariable logistic regression models were adjusted for age, sex, race, body mass index (BMI), smoking, alcohol use, education, leisure time physical activity, sedentary time, and comorbid diseases. RESULTS: Overall, the prevalence of low muscle mass was 23.1% defined by appendicular lean mass (ALM) and 17.0% defined by ALM/BMI, and the prevalence of low muscle strength was 19.4%. In the joint analyses, all-cause mortality was significantly higher among individuals with low muscle strength, whether they had low muscle mass (odds ratio [OR], 2.03; 95% confidence interval [CI], 1.27-3.24 for ALM; OR, 2.53; 95% CI, 1.64-3.88 for ALM/BMI) or not (OR, 2.66; 95% CI, 1.53-4.62 for ALM; OR, 2.17; 95% CI, 1.29-3.64 for ALM/BMI). In addition, the significant associations between low muscle strength and all-cause mortality persisted across different levels of metabolic syndrome, sedentary time, and LTPA. CONCLUSIONS: Low muscle strength was independently associated with elevated risk of all-cause mortality, regardless of muscle mass, metabolic syndrome, sedentary time, or LTPA among US older adults, indicating the importance of muscle strength in predicting aging-related health outcomes in older adults.Item Comparison of Commercial and Self-Initiated Weight Loss Programs in People With Prediabetes: A Randomized Control Trial(American Public Health Association, 2016-05) Marrero, David G.; Palmer, Kelly N. B.; Phillips, Erin O.; Miller-Kovach, Karen; Foster, Gary D.; Saha, Chandan K.; Medicine, School of MedicineTo determine if a widely available weight-management program (Weight Watchers) could achieve sufficient weight loss in persons with prediabetes compared with a Diabetes Prevention Program-based individual counseling program supported by National Diabetes Education Program materials. METHODS: We conducted an individual, randomized intervention trial in Indianapolis, Indiana, in 2013 to 2014, in 225 persons with prediabetes. We compared the Weight Watchers weight-management program (n = 112) with Your Game Plan to Prevent Type 2 Diabetes, a program developed by the National Diabetes Education Program. Outcomes were weight and metabolic markers measured at baseline, 6 months, and 12 months. RESULTS: Intervention participants lost significantly more weight than controls at 6 months (5.5% vs 0.8%) and 12 months (5.5% vs 0.2%; both P < .001). The intervention group also had significantly greater improvements in hemoglobin A1c and high-density lipoprotein cholesterol level than did controls. CONCLUSIONS: A large weight-management program is effective for achieving lifestyle changes associated with diabetes prevention. Such programs could significantly increase the availability of diabetes prevention programs worldwide making an immediate and significant public health impact.Item Dental maturity of Caucasian children in the Indianapolis area(American Academy of Pediatric Dentistry, 2011-05) Weddell, Lauren S.; Hartsfield, James K.; Department of Pediatric Dentistry, School of DentistryPURPOSE: The purpose of this study was to compare chronologic and dental age using Demirjian's method. METHODS: Two hundred and fifty-seven panoramic radiographs of healthy 5- to 17.5-year-old Caucasian children in the Indianapolis area were evaluated using Demirjian's 7 tooth method. RESULTS: The intraclass correlation coefficient (ICC) for agreement with Demirjian was 0.94 (95% confidence interval [CI]: 0.87, 0.97). The ICC for repeatability of the investigator was 0.97 (95% CI=0.95, 0.99). Calculated dental age was significantly greater than chronologic age by 0.59 years (P<.001). There was no significant difference in the mean difference in ages between sexes (P=.73). Medicaid subjects had a significantly higher (P<.001) mean difference (0.82 years) than private insurance subjects (0.32 years). There was a significant negative correlation between the chronologic age and the difference in ages (r=-0.29, P<.001). Overweight (P<.001) and obese (P=.004) subjects were significantly more dentally advanced than normal (P=.35) and underweight (P=.42) subjects. CONCLUSIONS: Demirjian's method has high inter- and intraexaminer repeatability. Caucasian children in the Indianapolis area are more advanced dentally than the French-Canadian children studied by Demirjian. Difference between dental age and chronologic age varies depending on the age of the child, socioeconomic status, and body mass index.Item Effects of Proximity to Supermarkets on a Randomized Trial Studying Interventions for Obesity(American Public Health Association, 2016-03) Fiechtner, Lauren; Kleinman, Ken; Melly, Steven J.; Sharifi, Mona; Marshall, Richard; Block, Jason; Cheng, Erika R.; Taveras, Elsie M.; Department of Pediatrics, IU School of MedicineOBJECTIVES: To determine whether proximity to a supermarket modified the effects of an obesity intervention. METHODS: We examined 498 children aged 6 to 12 years with a body mass index (BMI) at or above the 95th percentile participating in an obesity trial in Massachusetts in 2011 to 2013. The practice-based interventions included computerized clinician decision support plus family self-guided behavior change or health coaching. Outcomes were 1-year change in BMI z-score, sugar-sweetened beverage intake, and fruit and vegetable intake. We examined distance to the closest supermarket as an effect modifier. RESULTS: Distance to supermarkets was an effect modifier of 1-year change in BMI z-score and fruit and vegetable intake but not sugar-sweetened beverage intake. With each 1-mile shorter distance to a supermarket, intervention participants increased their fruit and vegetable intake by 0.29 servings per day and decreased their BMI z-score by -0.04 units relative to controls. CONCLUSIONS: Living closer to a supermarket is associated with greater improvements in fruit and vegetable intake and weight status in an obesity intervention.Item Estimation of glomerular filtration rate for drug dosing in patients with very high or low body mass index(Wiley, 2022) Donker, Erik M.; Bet, Pierre; Nurmohamed, Azam; Serné, Erik; Burchell, George Louis; Friedman, Allon N.; Bouquegneau, Antoine; Lemoine, Sandrine; Ebert, Natalie; Cirillo, Massimo; van Agtmael, Michiel A.; Bartelink, Imke H.; Medicine, School of MedicineAn accurate estimated glomerular filtration rate (eGFR) is essential in drug dosing. This study demonstrates the limitations of indexed (ml/min/1.73 m2 ) and de-indexed (ml/min) eGFR based drug dosing in patients with obesity or underweight. This systematic study aimed to determine the most appropriate approach to estimate the GFR for standardized eGFR based drug dosing in these patients. (Raw) data of 12 studies were selected to investigate the accuracy and bias of both the indexed and de-indexed estimations of the Modification of Diet in Renal Disease (MDRD) study equation and the Chronic Kidney Disease Epidemiology Collaboration equation (CKD-EPI), and of the Cockcroft-Gault (CG) in patients with obesity or underweight. Accuracy was calculated as the proportion of eGFR values within 30% of the measured GFR (P30) using an inert tracer (e.g., iohexol, inulin, 51 Cr-EDTA, or iothalamate clearance). An accuracy of at least 80% was considered acceptable. GFR values estimated with the CG, MDRD, and CKD-EPI differ significantly within a patient with obesity or underweight regardless of whether it is indexed or de-indexed. All studies, with two exceptions, show that all three equations are inaccurate for patients with underweight or class II obesity (P30: 55%-94%). De-indexing eGFR improves not or modestly the accuracy, and mostly remains below the 80% (P30: 62%-100%). CG was highly inaccurate in obese and underweight patients (P30: 7%-82%). Although these results show that CG is obsolete, the accuracy of MDRD and CKD-EPI is low in patients with obesity or underweight and de-indexing is not the solution. Better education and more accurate methods for appropriate drug dosing (e.g., measured GFR with inert tracer, therapeutic drug monitoring, or 24-h creatinine clearance) are recommended.Item Excess BMI Accelerates Islet Autoimmunity in Older Children and Adolescents(American Diabetes Association, 2020-03) Ferrara-Cook, Christine; Geyer, Susan Michelle; Evans-Molina, Carmella; Libman, Ingrid M.; Becker, Dorothy J.; Gitelman, Stephen E.; Jose Redondo, Maria; Medicine, School of MedicineObjective: Sustained excess BMI increases the risk of type 1 diabetes (T1D) in autoantibody-positive relatives without diabetes of patients. We tested whether elevated BMI also accelerates the progression of islet autoimmunity before T1D diagnosis. Research design and methods: We studied 706 single autoantibody-positive pediatric TrialNet participants (ages 1.6-18.6 years at baseline). Cumulative excess BMI (ceBMI) was calculated for each participant based on longitudinally accumulated BMI ≥85th age- and sex-adjusted percentile. Recursive partitioning analysis and multivariable modeling defined the age cut point differentiating the risk for progression to multiple positive autoantibodies. Results: At baseline, 175 children (25%) had a BMI ≥85th percentile. ceBMI range was -9.2 to 15.6 kg/m2 (median -1.91), with ceBMI ≥0 kg/m2 corresponding to persistently elevated BMI ≥85th percentile. Younger age increased the progression to multiple autoantibodies, with age cutoff of 9 years defined by recursive partitioning analysis. Although ceBMI was not significantly associated with progression from single to multiple autoantibodies overall, there was an interaction with ceBMI ≥0 kg/m2, age, and HLA (P = 0.009). Among children ≥9 years old without HLA DR3-DQ2 and DR4-DQ8, ceBMI ≥0 kg/m2 increased the rate of progression from single to multiple positive autoantibodies (hazard ratio 7.32, P = 0.004) and conferred a risk similar to that in those with T1D-associated HLA haplotypes. In participants <9 years old, the effect of ceBMI on progression to multiple autoantibodies was not significant regardless of HLA type. Conclusions: These data support that elevated BMI may exacerbate islet autoimmunity prior to clinical T1D, particularly in children with lower risk based on age and HLA. Interventions to maintain normal BMI may prevent or delay the progression of islet autoimmunity.Item Immune reconstitution in ART treated, but not untreated HIV infection, is associated with abnormal beta cell function(Public Library of Science, 2018-05-24) Sims, Emily K.; Park, Grace; Mather, Kieren J.; Raghavendra, G. Mirmira; Liu, Ziyue; Gupta, Samir K.; Pediatrics, School of MedicineHIV infection has been associated with increased diabetes risk, but prior work has mostly focused on insulin resistance, as opposed to beta cell effects, or included patients on antiretroviral therapies (ART) directly linked to metabolic toxicity. In this analysis, we measured markers of glucose homeostasis and beta cell function, stress, and death in fasting sera from a cross section of HIV+ individuals off ART (n = 43), HIV+ individuals on ART (n = 23), and HIV- controls (n = 39). Markers included glucose, HOMA%S, HOMA%B, proinsulin:C-peptide ratio (PI:C ratio), and circulating preproinsulin (INS) DNA. We performed multiple linear regressions with adjustments for age, sex, race, BMI, and smoking status. Compared to HIV- controls, HIV+ participants off ART exhibited similar beta cell function and insulin sensitivity, without increases in markers of beta cell stress or death. Specifically, in HIV+ participants with CD4 counts <350 cells/μL, PI:C ratios were lower than in HIV- controls (p<0.01), suggesting a reduction in intrinsic beta cell stress among this group. By contrast, HIV+ participants on ART had higher fasting glucose (p<0.0001) and lower HOMA%B (p<0.001) compared to HIV- controls. Among the entire HIV+ population, higher HIV RNA correlated with lower fasting glucose (r = -0.57, p<0.001), higher HOMA%B (r = 0.40, p = 0.001), and lower PI:C ratios (r = -0.42, p<0.001), whereas higher CD4 counts correlated with higher PI:C ratios (r = 0.2, p = 0.00499). Our results suggest that HIV seropositivity in the absence of ART does not worsen beta cell function or glucose homeostasis, but immune reconstitution with ART may be associated with worsened beta cell function.