JAMA. 2008;300(2):182-188.
Context Fetuin-A is a hepatic secretory protein that binds the insulin receptor and inhibits insulin action in vitro. In prior cross-sectional studies in humans, higher fetuin-A levels were associated with insulin resistance. However, the longitudinal association of fetuin-A with incident type 2 diabetes mellitus is unknown. Objective To determine whether fetuin-A levels are associated with incident diabetes in older persons. Design, Setting, and Participants Observational study among 3075 well-functioning persons aged 70 to 79 years. In this case-cohort study, we retrospectively measured fetuin-A levels in baseline serum among 406 randomly selected participants without prevalent diabetes, and all participants who developed incident diabetes mellitus during a 6-year follow-up (to August 31, 2005). Main Outcome Measure Incident diabetes mellitus. Results Incident diabetes developed in 135 participants (10.1 cases/1000 person-years). Participants with fetuin-A levels within the highest tertile (> 0.97 g/L) had an increased risk of incident diabetes (13.3 cases/1000 person-years) compared with participants in the lowest tertile ( 0.76 g/L) (6.5 cases/1000 person-years) in models adjusted for age, sex, race, waist circumference, body weight, physical activity, blood pressure level, fasting glucose level, high-density lipoprotein cholesterol concentration, triglyceride concentration, and C-reactive protein level (adjusted hazard ratio, 2.41; 95% confidence interval, 1.28-4.53; P = .007). The association was not affected by adipocytokine levels but was moderately attenuated by adjustment for visceral adiposity (adjusted hazard ratio of highest vs lowest tertile 1.72; 95% confidence interval, 0.98-3.05; P = .06). Conclusion Among well-functioning older persons, serum fetuin-A is associated with incident diabetes, independent of other markers of insulin resistance.
JAMA. 2003;289:2709-2716.
Researchers, clinicians, and policy makers face 3 challenges in writing about race and ethnicity: accounting for the limitations of race/ethnicity data; distinguishing between race/ethnicity as a risk factor or as a risk marker; and finding a way to write about race/ethnicity that does not stigmatize and does not imply a we/they dichotomy between health professionals and populations of color. Josurnals play an important role in setting standards for research and policy literature. The authors outline guidelines that might be used when race and ethnicity are addressed in biomedical publications.
JAMA. 2002;288:1632-1639.
ABSTRACT
Polyarteritis nodosa (PAN) is regarded rightly as the grandfather of the vasculitides. In this Grand Rounds, the case of a 30-year-old man with a 12-year illness is described. The patient presented with daily fevers, tachycardia, and cutaneous ulcers on his distal extremities. He eventually developed mononeuritis multiplex. Because of the striking pattern of his fevers, he was diagnosed for many years as having adult-onset Still disease. Following the addition of daily cyclophosphamide to his long-standing regimen of prednisone, the patient's disease entered remission for the first time in more than a decade. He was ultimately able to discontinue all of his immunosuppressive medications. The case is discussed in the context of the first patient ever described with PAN, the classic report of Kussmaul and Maier.
JAMA. 2007;297:196-204.
Ms M, a 74-year-old woman with type 2 diabetes of 6 years' duration, has a glycated hemoglobin (HbA1C) value of 7.4% despite taking 3 oral antidiabetic medications, as well as coexistent hypertension and abdominal obesity. She has no known microvascular or macrovascular complications of diabetes and is otherwise healthy. She is reluctant to commence insulin treatment as she dislikes the idea of injections and wonders if there are any alternate options if she is to get her HbA1C value below 7%. The natural history of type 2 diabetes, reasons why many patients begin requiring insulin over time, rationale for tight glycemic control, and therapeutic options for Ms M are discussed.
JAMA. 2008;299(20):2423-2436.
Context Continuing advances in genotyping technologies and the inclusion of DNA collection in observational studies have resulted in an increasing number of genetic association studies. Objective To evaluate the overall progress and contribution of candidate gene association studies to current understanding of the genetic susceptibility to cancer. Data Sources We systematically examined the results of meta-analyses and pooled analyses for genetic polymorphisms and cancer risk published through March 2008. Study Selection We identified 161 meta-analyses and pooled analyses, encompassing 18 cancer sites and 99 genes. Analyses had to meet the following criteria: include at least 500 cases, have cancer risk as outcome, not be focused on HLA antigen genetic markers, and be published in English. Data Extraction Information on cancer site, gene name, variant, point estimate and 95% confidence interval (CI), allelic frequency, number of studies and cases, tests of study heterogeneity, and publication bias were extracted by 1 investigator and reviewed by other investigators. Results These 161 analyses evaluated 344 gene-variant cancer associations and included on average 7.3 studies and 3551 cases (range, 508-19 729 cases) per investigated association. The summary odds ratio (OR) for 98 (28%) statistically significant associations (P value <.05) were further evaluated by estimating the false-positive report probability (FPRP) at a given prior probability and statistical power. At a prior probability level of 0.001 and statistical power to detect an OR of 1.5, 13 gene-variant cancer associations remained noteworthy (FPRP <0.2). Assuming a very low prior probability of 0.000001, similar to a probability assumed for a randomly selected single-nucleotide polymorphism in a genome-wide association study, and statistical power to detect an OR of 1.5, 4 associations were considered noteworthy as denoted by an FPRP value <0.2: GSTM1 null and bladder cancer (OR, 1.5; 95% CI, 1.3-1.6; P = 1.9 x 10–14), NAT2 slow acetylator and bladder cancer (OR, 1.46; 95% CI, 1.26-1.68; P = 2.5 x 10–7), MTHFR C677T and gastric cancer (OR, 1.52; 95% CI, 1.31-1.77; P = 4.9 x 10–8), and GSTM1 null and acute leukemia (OR, 1.20; 95% CI, 1.14-1.25; P = 8.6 x 10–15). When the OR used to determine statistical power was lowered to 1.2, 2 of the 4 noteworthy associations remained so: GSTM1 null with bladder cancer and acute leukemia. Conclusion In this review of candidate gene association studies, nearly one-third of gene-variant cancer associations were statistically significant, with variants in genes encoding for metabolizing enzymes among the most consistent and highly significant associations.