PrimeCuts: This Week in the Journals

July 13, 2009

shrimp1Ami Jhaveri MD

Faculty Peer Reviewed

A low calorie diet, high adiponectin levels, new anti-cancer agents, and for patients on erythropoietin, hemoglobin levels between 9-12 g/dL are on the prescription pad this summer.

The New York Times reported that a low calorie diet may extend life in primates. Researchers at the University of Wisconsin have been studying rhesus monkeys and the effects of low calorie diets on their health and mortality. As the average lifespan of rhesus monkeys is 27 years, the study started over 20 years ago and is still ongoing. Monkeys on low calorie diets, defined as 30% less calories than regular diets, have had fewer incidences of diabetes, cancer, and cardiovascular disease.

We already know that low calorie diets and decreased obesity prevent diabetes. However, having high levels of adiponectin, a hormone secreted only by fat cells, may also protect against diabetes. A meta-analysis published in JAMA of 13 prospective studies of plasma adiponectin levels before the onset of diabetes in patients showed that higher adiponectin levels are associated with a lower risk of type 2 diabetes. For every 1-log ug/ml increment increase in adiponectin level, the study found a decreased relative risk of type 2 diabetes of 0.72. Adiponectin is an insulin sensitizer, and adiponectin levels are inversely related to the amount of adipocytes. This study’s findings suggest that low adiponectin levels predict the development of type 2 diabetes.

A novel agent, olaparib, may be effective in breast, ovarian, and prostate cancers associated with BRCA1 or BRCA2 mutations. This new drug is hot because it represents a new way of targeting cancer cells by having a specific therapeutic window for BRCA-deficient cells. Olaparib inhibits poly (adenosine diphosphate ribose) polymerases (PARPs), which lead to selective cellular damage in BRCA-deficient cancer cells. PARPs are enzymes that repair DNA single-strand breaks; therefore, the inhibition of PARPs results in DNA and thus cell damage. Cells without BRCA alleles are significantly more susceptible to additional insults of the DNA-repair pathway such as that resulting from PARP inhibition. In a NEJM study published this week, olaparib treatment led to stable or improved disease in both radiology studies and tumor markers. Olaparib has significantly more tolerable side effects than previous chemotherapy agents. The implications of this novel method of introducing a defect in already susceptible cells are discussed in an editorial in the same NEJM issue. Although this trial is a small, phase I study, it signifies a new method of targeting cancer cells without harming other cells.

A study by the Nordic Cochrane Centre published in the British Medical Journal addressed ramifications of breast cancer screening. Researchers in this study found that one in three breast cancers is overdiagnosed when organized screening programs are used. This meta-analysis reviewed changes in breast cancer incidence before and after the implementation of breast cancer screening programs and found a rise in breast cancer incidence associated with the introduction of a screening program. Further studies will need to investigate whom to screen and which lesions need work-up to avoid the physiologic, psychological, and economic consequences of overdiagnosis.

Target hemoglobin levels in patients with chronic kidney disease on erythropoietin treatments have been a topic of debate for several years. A meta-analysis of 11 randomized controlled trials investigated the health-related quality of life in patients on erythropoietin-stimulating agents as related to low to intermediate (9.0-12.9 g/dL) versus high (>12 g/dL) hemoglobin target levels. The study, published in Archives of Internal Medicine, found that hemoglobin levels greater than 12g/dL did not significantly improve patient quality of life and concluded that target levels of 9.0 to 12.0 g/dL is better for patients with chronic kidney disease. Quality of life if often cited as a reason for having higher goals of hemoglobin levels, and this study shows otherwise.

Dr. Jhaveri is a second year internal medicine resident at NYU Medical Center.

Peer reviewed by Barbara Porter, MD MPH,  Clinical Assistant Professor of Medicine, NYU Medical Center

References:
1. Wade N. Dieting Monkeys Offer Hope for Living Longer. The New York Times. 2009 July 11.
2. Li S, Shin HJ, Ding EL, van Dam RM. Adiponectin Levels and Risk of Type 2 Diabetes: A Systematic Review and Meta-analysis. JAMA. 2009;302(2):179-188.
3. Fong PC, Boss DS, Yap TA, et al. Inhibition of Poly(ADP-Ribose) Polymerase in Tumors from BRCA Mutation Carriers. N Engl J Med. 2009;361(2):123-134.
4. Iglehart JD, Silver DP. Synthetic Lethality — A New Direction in Cancer-Drug Development. N Engl J Med. 2009;361(2):189-191.
5. Jorgensen KJ, Gotzsche PC. Overdiagnosis in publicly organised mammography screening programmes: systematic review of incidence trends. BMJ. 2009;339(jul09_1):b2587.
6.Clement FM, Klarenbach S, Tonelli M, Johnson JA, Manns BJ. The Impact of Selecting a High Hemoglobin Target Level on Health-Related Quality of Life for Patients With Chronic Kidney Disease: A Systematic Review and Meta-analysis. Arch Intern Med. 2009;169(12):1104-1112.

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