GAD antibody positivity predicts type 2 diabetes in an adult population.
Diabetes. 2010 Feb;59(2):416-22
Authors: Lundgren VM, Isomaa B, Lyssenko V, Laurila E, Korhonen P, Groop LC, Tuomi T,
OBJECTIVE: To evaluate the significance of GAD antibodies (GADAs) and family history for type 1 diabetes (FH(T1)) or type 2 diabetes (FH(T2)) in nondiabetic subjects. RESEARCH DESIGN AND METHODS: GADAs were analyzed in 4,976 nondiabetic relatives of type 2 diabetic patients or control subjects from Finland. Altogether, 289 (5.9%) were GADA(+)-a total of 253 GADA(+) and 2,511 GADA(-) subjects participated in repeated oral glucose tolerance tests during a median time of 8.1 years. The risk of progression to diabetes was assessed using Cox regression analysis. RESULTS: Subjects within the highest quartile of GADA(+) (GADA(+)(high)) had more often first-degree FH(T1) (29.2 vs. 7.9%, P < 0.00001) and GADA(+) type 2 diabetic (21.3 vs. 13.7%, P = 0.002) or nondiabetic (26.4 vs. 13.3%, P = 0.010) relatives than GADA(-) subjects. During the follow-up, the GADA(+) subjects developed diabetes significantly more often than the GADA(-) subjects (36/253 [14.2%] vs. 134/2,511 [5.3%], P < 0.00001). GADA(+)(high) conferred a 4.9-fold increased risk of diabetes (95% CI 2.8-8.5) compared with GADA(-)-seroconversion to positive during the follow-up was associated with 6.5-fold (2.8-15.2) and first-degree FH(T1) with 2.2-fold (1.2-4.1) risk of diabetes. Only three subjects developed type 1 diabetes, and others had a non-insulin-dependent phenotype 1 year after diagnosis. GADA(+) and GADA(-) subjects did not clinically differ at baseline, but they were leaner and less insulin resistant after the diagnosis of diabetes. CONCLUSIONS: GADA positivity clusters in families with type 1 diabetes or latent autoimmune diabetes in adults. GADA positivity predicts diabetes independently of family history of diabetes, and this risk was further increased with high GADA concentrations.
PMID: 19864397 [PubMed - indexed for MEDLINE]
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Association between a literature-based genetic risk score and cardiovascular events in women.
JAMA. 2010 Feb 17;303(7):631-7
Authors: Paynter NP, Chasman DI, Paré G, Buring JE, Cook NR, Miletich JP, Ridker PM
CONTEXT: While multiple genetic markers associated with cardiovascular disease have been identified by genome-wide association studies, their aggregate effect on risk beyond traditional factors is uncertain, particularly among women. OBJECTIVE: To test the predictive ability of a literature-based genetic risk score for cardiovascular disease. DESIGN, SETTING, AND PARTICIPANTS: Prospective cohort of 19 313 initially healthy white women in the Women’s Genome Health Study followed up over a median of 12.3 years (interquartile range, 11.6-12.8 years). Genetic risk scores were constructed from the National Human Genome Research Institute’s catalog of genome-wide association study results published between 2005 and June 2009. MAIN OUTCOME MEASURE: Incident myocardial infarction, stroke, arterial revascularization, and cardiovascular death. RESULTS: A total of 101 single nucleotide polymorphisms reported to be associated with cardiovascular disease or at least 1 intermediate cardiovascular disease phenotype at a published P value of less than 10(-7) were identified and risk alleles were added to create a genetic risk score. During follow-up, 777 cardiovascular disease events occurred (199 myocardial infarctions, 203 strokes, 63 cardiovascular deaths, 312 revascularizations). After adjustment for age, the genetic risk score had a hazard ratio (HR) for cardiovascular disease of 1.02 per risk allele (95% confidence interval [CI], 1.00-1.03/risk allele; P = .006). This corresponds to an absolute cardiovascular disease risk of 3% over 10 years in the lowest tertile of genetic risk (73-99 risk alleles) and 3.7% in the highest tertile (106-125 risk alleles). However, after adjustment for traditional factors, the genetic risk score did not improve discrimination or reclassification (change in c index from Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults [ATP III] risk score, 0; net reclassification improvement, 0.5%; [P = .24]). The genetic risk score was not associated with cardiovascular disease risk (ATP III-adjusted HR/allele, 1.00; 95% CI, 0.99-1.01). In contrast, self-reported family history remained significantly associated with cardiovascular disease in multivariable models. CONCLUSION: After adjustment for traditional cardiovascular risk factors, a genetic risk score comprising 101 single nucleotide polymorphisms was not significantly associated with the incidence of total cardiovascular disease.
PMID: 20159871 [PubMed - in process]
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Community-Based Participatory Research in Boston’s Neighborhoods: A Review of Asthma Case Examples.
Arch Environ Occup Health. 2010 Jan-Mar 1;65(1):38-44
Authors: Brugge D, Rivera-Carrasco E, Zotter J, Leung A
Three case examples of asthma studies that differ in terms of community and involvement are considered. The Boston Chinatown studies faced limited funding that restricted the level of community involvement, but resulted in some of the first published evidence about asthma in Asian American children. These studies led to an asthma education program grant to a local Asian clinic and elementary school. The public housing study was a well-funded multi-year study of asthma and pest management with city, university and community partners. Residents were trained to collect data and participated throughout the study. Follow up pest management and pesticide buy-back programs headed by the city and community partners have been funded. The Dorchester case had more limited funding, but had the greatest level of involvement of parents of asthmatic children in all phases of the research. This survey led to an interesting novel finding of lower asthma prevalence in foreign born black residents.
PMID: 20147002 [PubMed - in process]
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