This Week in JAMA, pdfs

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Hi All, This week's JAMA issue, most abstract and citations can be viewed from: http://jama.ama-assn.org/current.dtl Two papers may be worth mention, below. The glycemic index paper rings bells. Although my test results in the CR cohort at WUSTL showed slightly higher than average fasting insulin values, my LDL was very low and my fasting glucose levels were significantly lower, in line with the not significantly lower fasting glucose values shown in the below paper. pdfs of all papers are availed. This Week in JAMAJAMA. 2007;297:2053. Insulin and Low–Glycemic Load vs Low-Fat Diets Differing physiological characteristics may be an explanation for inconsistent outcomes of dietary interventions for weight loss. Ebbeling

and colleagues investigated whether insulin secretion affects weight loss in obese young adults who were randomly assigned to either a low–glycemic load or a low-fat diet. At the 18-month follow-up, the authors found that among participants whose insulin secretion at baseline was above the median, loss of weight and body fat were greater in persons assigned to the low–glycemic load vs the low-fat diet. The low–glycemic load diet was associated with greater improvements in high-density lipoprotein cholesterol and triglyceride levels and the low-fat diet with more improvement in low-density lipoprotein cholesterol levels. Effects of a Low–Glycemic Load vs Low-Fat Diet in Obese Young Adults: A Randomized TrialCara B. Ebbeling; M. Leidig; Henry A. Feldman; Margaret M. Lovesky; S. LudwigJAMA. 2007;297:2092-2102. ABSTRACT Context The results of

clinical trials involving diet in the treatment of obesity have been inconsistent, possibly due to inherent physiological differences among study participants. Objective To determine whether insulin secretion affects weight loss with 2 popular diets. Design, Setting, and Participants Randomized trial of obese young adults (aged 18-35 years; n = 73) conducted from September 2004 to December 2006 in Boston, Mass, and consisting of a 6-month intensive intervention period and a 12-month follow-up period. Serum insulin concentration at 30 minutes after a 75-g dose of oral glucose was determined at baseline as a measure of insulin secretion. Outcomes were assessed at 6, 12, and 18 months. Missing data were imputed conservatively. Interventions A low–glycemic load (40% carbohydrate and 35% fat) vs low-fat (55% carbohydrate and 20% fat) diet. Main Outcome Measures Body weight, body fat percentage determined by dual-energy x-ray absorptiometry, and cardiovascular disease risk factors. Results Change in body weight and body fat percentage did not differ between the diet groups overall. However, insulin concentration at 30 minutes after a dose of oral glucose was an effect modifier (group x time x insulin concentration at 30 minutes: P = .02 for body weight and P = .01 for body fat percentage). For those with insulin concentration at 30 minutes above the median (57.5 µIU/mL; n = 28), the low–glycemic load diet produced a greater decrease in weight (–5.8 vs –1.2 kg; P = .004) and body fat percentage (–2.6% vs –0.9%; P = .03) than the low-fat diet at 18 months. There were no significant differences in these end points between diet groups for those with insulin concentration at 30 minutes below the median level (n = 28). Insulin concentration at 30 minutes after a dose

of oral glucose was not a significant effect modifier for cardiovascular disease risk factors. In the full cohort, plasma high-density lipoprotein cholesterol and triglyceride concentrations improved more on the low–glycemic load diet, whereas low-density lipoprotein cholesterol concentration improved more on the low-fat diet. Conclusions Variability in dietary weight loss trials may be partially attributable to differences in hormonal response. Reducing glycemic load may be especially important to achieve weight loss among individuals with high insulin secretion. Regardless of insulin secretion, a low–glycemic load diet has beneficial effects on high-density lipoprotein cholesterol and triglyceride concentrations but not on low-density lipoprotein cholesterol concentration. This Week in JAMAJAMA. 2007;297:2053. Medical News & Perspectives A newly

discovered common genetic variant could play a major role in predisposing some individuals to obesity and type 2 diabetes. NEWS AND ANALYSIS Medical News & Perspectives Common Gene Variant Linked to Obesity HamptonJAMA. 2007;297:2063-2064. A large meta-analysis of research articles has pointed to a common variant of a gene that may predispose some individuals to obesity. While the variant was associated with only a modest increase in weight gain, it appears to cause obesity in a population already experiencing excess weight gain, the study investigators said (Frayling TM et al. Science. doi:10.1126/science.1141634 [published online April 12, 2007]). WEIGHTY GENE It was during a genome-wide search for type 2 diabetes susceptibility genes that a team of scientists, primarily in the United Kingdom, first

identified this variant, which lies within the FTO gene on chromosome 16. A recent meta-analysis has found a common genetic variant that helps expain why some individuals are more prone to obesity than others. (Photo credit: Simon Fraser http://www.sciencesource.com) "Using groundbreaking microchip technology, we were able to look at over 500 000 points in the genome, and we found that at one particular position in the human DNA sequence, there was quite a big difference between people with type 2 diabetes and people without," said first author Frayling, PhD, of the Peninsula Medical School in Exeter, England. Frayling and colleagues found that the variant predisposes individuals to diabetes via an effect on body mass index. The next logical question was whether this variant also influences weight in the general population. To

get at the question, the researchers analyzed 13 studies involving a total of 38 759 white Europeans of all ages and found that the common gene variant increased an individual's risk of obesity by approximately 67%. In the populations that were studied, about 16% of adults had both copies of this gene variant, and, compared with individuals with no copies of the variant, they weighed on average 3 kg more and had about 15% more fat mass. This association occurred in people aged 7 years or older. "The key thing about this finding is that this is a common variant which is present in over half of the population," said co–principal investigator Hattersley, FRCP, DM, also of the Peninsula Medical School. "And approximately one sixth of the population has 2 copies of the variant." The study may help explain why some individuals are heavier than others. Hattersley added that by predisposing people to increased weight gain, having 2 copies of

the variant predisposes them to obesity and type 2 diabetes. CLINICAL IMPLICATIONS The name for the human FTO gene originated from recent and unrelated studies involving mutant mice that have fused toes—Ft mutant mice have a 1.6 megabase deletion of DNA on chromosome 8 that encompasses several genes, including Fto, the mouse version of the human FTO gene (Anselme I et al. Dev Biol. 2007;304:208-220). Because multiple genes are deleted in these mice, they do not make a good model for studying the role of altered Fto activity; currently, neither isolated inactivation nor overexpression of Fto has been described. The role of FTO is a mystery, so researchers have much more work ahead before any sort of clinical therapies are envisioned based on these latest findings. "FTO is a gene about which we know very little, and it hasn't been implicated in obesity or any related

conditions to date," said coprincipal investigator Mark McCarthy, FRCP, MD, of the University of Oxford in Oxford, England. "That's both a curse and a blessing." The curse lies in the absence of knowledge about how the variant influences weight regulation and how it predisposes people to obesity. But the blessing comes with the discovery of a new pathway that, when disrupted, has profound effects on fat development, weight regulation, obesity, and type 2 diabetes risk. Follow-up studies may help researchers design novel ways of treating and preventing obesity and type 2 diabetes, said McCarthy. "There's a definite and massive unmet clinical need for new therapeutic and interventional strategies," he said. Although research into FTO's role is in its early stages, "understanding how variation in the FTO gene region is associated with adiposity may provide insights into novel

pathways involved in the control of adiposity," the authors wrote. -- Al Pater, alpater@...

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