Showing papers by "David Melzer published in 2010"
TL;DR: It is demonstrated that genetic studies of glycemic traits can identify type 2 diabetes risk loci, as well as loci containing gene variants that are associated with a modest elevation in glucose levels but are not associated with overt diabetes.
Abstract: Levels of circulating glucose are tightly regulated. To identify new loci influencing glycemic traits, we performed meta-analyses of 21 genome-wide association studies informative for fasting glucose, fasting insulin and indices of beta-cell function (HOMA-B) and insulin resistance (HOMA-IR) in up to 46,186 nondiabetic participants. Follow-up of 25 loci in up to 76,558 additional subjects identified 16 loci associated with fasting glucose and HOMA-B and two loci associated with fasting insulin and HOMA-IR. These include nine loci newly associated with fasting glucose (in or near ADCY5, MADD, ADRA2A, CRY2, FADS1, GLIS3, SLC2A2, PROX1 and C2CD4B) and one influencing fasting insulin and HOMA-IR (near IGF1). We also demonstrated association of ADCY5, PROX1, GCK, GCKR and DGKB-TMEM195 with type 2 diabetes. Within these loci, likely biological candidate genes influence signal transduction, cell proliferation, development, glucose-sensing and circadian regulation. Our results demonstrate that genetic studies of glycemic traits can identify type 2 diabetes risk loci, as well as loci containing gene variants that are associated with a modest elevation in glucose levels but are not associated with overt diabetes.
2,022 citations
Journal Article•
1,766 citations
TL;DR: Higher BPA exposure, reflected in higher urinary concentrations of BPA, is consistently associated with reported heart disease in the general adult population of the USA.
Abstract: Background
Bisphenol A (BPA) is a high production volume chemical widely used in food and drinks packaging. Associations have previously been reported between urinary BPA concentrations and heart disease, diabetes and liver enzymes in adult participants of the National Health and Nutrition Examination Survey (NHANES) 2003/04. We aimed to estimate associations between urinary BPA concentrations and health measures in NHANES 2005/06 and in data pooled across collection years.
493 citations
TL;DR: Low levels of vitamin D were associated with substantial cognitive decline in the elderly population studied over a 6-year period, which raises important new possibilities for treatment and prevention.
Abstract: Background: To our knowledge, no prospective study has examined the association between vitamin D and cognitive decline or dementia. Methods: We determined whether low levels of serum 25-hydroxyvitamin D (25[OH]D) were associated with an increased risk of substantial cognitive decline in the InCHIANTI population–based study conducted in Italy between 1998 and 2006 with follow-up assessments every 3 years. A total of 858 adults 65 years or older completed interviews, cognitive assessments, and medical examinations and provided blood samples. Cognitive decline was assessed using the Mini-Mental State Examination (MMSE), and substantial decline was defined as 3 or more points. The Trail-Making Tests A and B were also used, and substantial decline was defined as the worst 10% of the distribution of decline or as discontinued testing. Results: The multivariate adjusted relative risk (95% confidence interval [CI]) of substantial cognitive decline on the MMSE in participants who were severely serum 25 (OH)D deficient (levels25 nmol/L) in comparison with those with sufficient levels of 25(OH)D (75 nmol/L) was 1.60 (95% CI, 1.19-2.00). Multivariate adjusted random-effects models demonstrated that the scores of participants who were severely 25(OH)D deficient declined by an additional 0.3 MMSE points per year more than those with sufficient levels of 25(OH)D. The relative risk for substantial decline on Trail-Making Test B was 1.31 (95% CI, 1.03-1.51) among those who were severely 25(OH)D deficient compared with those with sufficient levels of 25(OH)D. No significant association was observed for Trail-Making Test A. Conclusion: Low levels of vitamin D were associated with substantial cognitive decline in the elderly population studied over a 6-year period, which raises important new possibilities for treatment and prevention. Arch Intern Med. 2010;170(13):1135-1141
413 citations
TL;DR: Higher concentrations of serum PFOA and PFOS are associated with current thyroid disease in the U.S. general adult population and more work is needed to establish the mechanisms involved and to exclude confounding and pharmacokinetic explanations.
Abstract: BackgroundPerfluorooctanoic acid (PFOA, also known as C8) and perfluorooctane sulfonate (PFOS) are stable compounds with many industrial and consumer uses. Their persistence in the environment plus...
406 citations
TL;DR: Higher daily BPA excretion was associated with higher total testosterone concentrations in men, in models adjusted for age and study site, and in models additionally adjusted for smoking, measures of obesity, and urinary creatinine concentrations.
Abstract: BackgroundBisphenol A (BPA) is a high production volume chemical widely used in packaging for food and beverages. Numerous studies have demonstrated that BPA can alter endocrine function in animals...
199 citations
TL;DR: English baby boomers are moving toward retirement with improved cardiovascular health, however, the baby-boomer cohort has a higher prevalence of mental illness diagnoses and shows no improvement in self-rated health compared to the wartime birth cohort.
Abstract: Background: The baby-boom generation is entering retirement. Having experienced unprecedented prosperity and improved medical technology, they should be the healthiest generation ever. Methods: We compared prevalence of disease and risk factors at ages 50–61 years in baby boomers with the preceding generation and attributed differences to period or cohort effects. Data were from the Health Survey for England (HSE) from 1994 to 2007 (n = 48,563). Logistic regression models compared health status between birth cohorts. Age-period-cohort models identified cohort and period effects separately. Results: Compared to the wartime generation, the baby-boomer group was heavier (3.02 kg; 95% confidence interval [CI], 2.42–3.63; p < 0.001) and reported more diagnoses of hypertension (odds ratio [OR] = 1.48; CI, 1.27–1.72; p < 0.001), diabetes (OR = 1.71; CI, 1.37–2.12; p < 0.001), and mental illness (OR = 1.90; CI, 1.54–2.53; p < 0.001). Baby boomers reported fewer heart attacks (OR = 0.61; CI, 0.47–0.79; p ...
50 citations
26 citations
TL;DR: P pig-meat consumption remained independently associated with mortality from CLD in developed countries in the 1990–2000 period, but HCV seroprevalence was not.
Abstract: A correlation between national pig-meat consumption and mortality rates from chronic liver disease (CLD) across developed countries was reported in 1985. One possible mechanism explaining this may be hepatitis E infection spread via pig meat. We aimed to re-examine the original association in more recent international data. Regression models were used to estimate associations between national pig-meat consumption and CLD mortality, adjusting for confounders. Data on CLD mortality, alcohol consumption, hepatitis B virus (HBV) and hepatitis C virus (HCV) seroprevalence for 18 developed countries (1990-2000) were obtained from WHO databases. Data on national pig-meat and beef consumption were obtained from the UN database. Univariate regression showed that alcohol and pig-meat consumption were associated with mortality from CLD, but beef consumption, HBV and HCV seroprevalence were not. A 1 litre per capita increase in alcohol consumption was associated with an increase in mortality from CLD in excess of 1.6 deaths/100,000 population. A 10 kg higher national annual average per capita consumption of pork meat was associated with an increase in mortality from CLD of between 4 and 5 deaths/100,000 population. Multivariate regression showed that alcohol, pig-meat consumption and HBV seroprevalence were independently associated with mortality from CLD, but HCV seroprevalence was not. Pig-meat consumption remained independently associated with mortality from CLD in developed countries in the 1990-2000 period. Further work is needed to establish the mechanism.
22 citations
TL;DR: The mechanisms underlying the associations with cognitive impairment and LOAD require further elucidation, but both genes are interesting candidates for involvement in age-related cognitive impairment.
9 citations
TL;DR: This work states that delirium within three days of stroke in a cohort of elderly patients in the first days of acute stroke is likely to be a cause for concern and further research is needed to establish a causative factor.
Abstract: 1. Inouye SK, Fearing MA, Marcantonio ER. Delirium. In: Halter JB, Ouslander JG, Tinetti ME et al., editors. Hazzard’s Geriatric Medicine and Gerontology, 6th Ed. New York: McGraw Hill Medical, 2009, pp 647–658. 2. Reichel W, Arenson C, Scherger JE. Essential principles in the care of the elderly. In: Arenson C, Busby-Whitehead J, Brummel-Smith K et al., editors. Reichel’s Care of the Elderly: Clinical Aspects of Aging, 6th Ed. Cambridge: Cambridge University Press, 2009, pp 1–13. 3. Benbadis SR, Sila CA, Cristea RL. Mental status changes and stroke. J Gen Intern Med 1994;9:485–487. 4. Dasgupta M, Hillier LM. Factors associated with prolonged delirium: A systematic review. Int Psychogeriatr 2010;22:373–394. 5. McManus J, Pathansali R, Stewart R et al. Delirium post-stroke. Age ageing 2007;36:613–618. 6. Caeiro L, Ferro JM, Albuquerque R et al. Delirium in the first days of acute stroke. J Neurol 2004;251:171–178. 7. Sheng AZ, Shen Q, Cordato D et al. Delirium within three days of stroke in a cohort of elderly patients. J Am Geriatr Soc 2006;54:1192–1198. 8. Lanna ME, Madeira DM, Alves G et al. Vascular dementia by thalamic strategic infarct. Arq Neuropsiquiatr 2008;66:412–414. 9. McManus J, Pathansali R, Hassan H et al. The course of delirium in acute stroke. Age ageing 2009;38:385–389.
06 Dec 2010
01 Jan 2010
TL;DR: As part of the In Vitro Diagnostics sector, genetic tests fall under the broader statutory regimes for the regulation of medical devices.
Abstract: • As part of the In Vitro Diagnostics (IVD) sector, genetic tests fall under the broader statutory regimes for the regulation of medical devices. The EU IVD Directive governs the safety, quality and performance of devices by setting out requirements for: placing a product on the market, production, labelling, clinical evaluation/investigation and post-marketing surveillance.
[...]
TL;DR: The chemical glyphosate is found in many plastic food containers, but mounting evidence about its safety is being ignored, according to experts.