Also Appearing in This Issue of JAMA


Study Finds Association Between Weight of Pancreas and Potential Diabetes Biomarker

Autopsy and imaging studies suggest that among adults with type 1 diabetes (T1D), their pancreas is smaller and weighs less than the pancreas of adults without the disease. However, it is unknown when pancreatic atrophy begins in T1D. Martha Campbell-Thompson, D.V.M., Ph.D., of the University of Florida, Gainesville, and colleagues conducted a study to examine pancreas weight early in the natural history of T1D from at-risk individuals without diabetes but with disease-associated autoantibodies, obtained through the Network for Pancreatic Organ Donors with Diabetes program. All donors were identified by organ procurement organizations that coordinate organ and tissue donations for clinical transplantation or research.

As reported in a Research Letter, the final analysis included 51 donors (no diabetes, n = 23; positive for autoantibody only, n = 8; type 1 diabetes, n = 20). The authors found that the average weight of pancreata (plural form of pancreas) from those without diabetes (controls) was 81.4 g compared with 61.3 g from the group positive for a single autoantibody only and 44.9 g from the T1D group.

“In this study, the weight of pancreata in individuals without T1D, but with serum markers that potentially precede the clinical manifestations, as well as in individuals with T1D, was less than in controls. This suggests that early atrophy of the organ may be an important subclinical feature of T1D pathogenesis,” the authors write. “Future studies should include validation and analysis of the potential mechanisms underlying this observation to understand whether early pancreatic atrophy contributes to the pathogenesis of T1D.”

(JAMA. 2012;308[22]:2337-2339. Available pre-embargo to the media at


Viewpoints in This Week’s JAMA

Lixivaptan for Hyponatremia – The Numbers Game

Ryan T. Borne, M.D., and Mori J. Krantz, M.D., of the Denver Health Hospital and Authority, examine the approval of the drug lixivaptan for the treatment of hyponatremia (abnormally low level of sodium in the blood) and the questions regarding the benefit of this class of drugs (vasopressin receptor antagonist).

“Sole reliance on laboratory surrogates can lead to widespread adoption of ineffective or harmful treatments. Regulators should create a landscape that supports evaluation of safety and efficacy across all phases of development and exhibit caution when making inferences based on predictive data from epidemiologic studies. Therapeutically modifying a given surrogate marker tightly linked in epidemiologic studies with improved outcomes cannot guarantee clinical efficacy,” they write. “… in the case of the vasopressin receptor antagonist class, it remains dubious that an increase in serum sodium levels will ultimately be demonstrated to improve outcomes in clinical trials given the myriad etiologies for hyponatremia. The manufacturers of lixivaptan sought approval for use in less severe hyponatremia and even among outpatients. The potential risks and benefits of lixivaptan and this expanded label are being carefully considered by the FDA.”

(JAMA. 2012;308[22]:2345-2346. Available pre-embargo to the media at

Editor’s Note: Please see the articles for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.

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