The Journal of Clinical Endocrinology & Metabolism Vol. 94, No. 11 17a-18a
Copyright © 2009 by The Endocrine Society
Endocrinology & Metabolism News
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Endocrine Discovery
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In a 14-week trial of 500 patients with type 2 diabetes randomly assigned to glargine insulin, metformin, combined metformin and glargine insulin, or placebo, no changes in inflammatory biomarkers hsCRP, IL-6, or sTNFr2 compared to placebo were detected, despite improvements in glycemic control with all active therapy regimens.
(JAMA [September 16, 2009] 302 (11):1186)
In a 36-month trial, 58 newly diagnosed type 2 diabetes patients treated with insulin and metformin for three months were then randomized to continue or switch to metformin, pioglitazone, and glyburide. No differences in hypoglycemic events, compliance, A1C, weight, quality of life, or treatment satisfaction were found.
(Diabetes Care [October 2009] 32 (10):1789)
Normal values for 10 body composition parameters were established from NHANES data, including a proposed replacement for BMI.
(PLoS One [September 2009] 4 (9):e7038)
Metabolic syndrome was associated with a 62% increased risk of future peripheral artery disease in women (hazard ratio, 1.6; 95% CI, 1.1–2.4) in a prospective cohort study of more than 27,000 women free of baseline cardiovascular disease.
(Circulation [September 22, 2009) 120 (12):1041)
Among women in the Women’s Health Initiative study, treatment with estrogen plus progestin was associated with nearly twice as many lung cancer deaths.
(Lancet [October 10, 2009] 374 (9697):1243)
The potassium channel subunit KCNE2—previously known to control cardiac electrical activity—was found, with its partner KCNQ1, to be expressed in mouse and human thyroid epithelial cells. In mice, Kcne2 deficiency decreases thyroid hormone biosynthesis.
(Nat Med [October 2009] 15 (10):1186)
The obesity susceptibility gene Cpe links FoxO1 signaling in hypothalamic pro-opiomelanocortin neurons with regulation of food intake.
(Nat Med [October 2009] 15 (10):1195)
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Level of Plasma SHBG Linked to Type 2 Diabetes Risk
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Sex hormone–binding globulin (SHBG), which regulates the concentration of free androgens and estrogens in plasma, has other important functions. These include signal transduction at the plasma membrane, buffering of the effects of intracellular androgens and estrogens, and the possibility that it may enhance the movement of androgens and estrogens into the cell. A number of previous epidemiologic studies have implicated SHBG in impaired glucose control. The studies are difficult to interpret, though, because they are largely cross sectional, and because of the confounders, particularly obesity, which are associated with both alterations in plasma SHBG and type 2 diabetes mellitus.
In a new study, researchers led by Eric Sing and Yiqing Song reexamined these associations in a nested case-control study and confirmed that SHBG seems to play a causal role in the development of type 2 diabetes mellitus. The study was drawn from the Women’s Health Study from which the authors matched 359 patients newly diagnosed with type 2 diabetes mellitus with 359 controls from the same cohort. The results were impressive: multivariable odds ratios were 1.00 for the first (lowest) quartile of plasma SHBG levels, 0.16 the second quartile, 0.04 for the third quartile, and 0.09 for the fourth (highest) quartile.
To confirm these results from another set of premises, the authors took advantage of the fact that two variant alleles in the SHBG gene resulted in either a 10% decrease in plasma SHBG (rs6257) or a 10% increase in plasma SHBG (rs6259) compared to wild type SHBG. Variants of both single-nucleotide polymorphisms (SNPs) were associated with a risk of type 2 diabetes mellitus in directions corresponding to their associated SHBG concentrations in plasma. There was no association between SHBG polymorphisms and BMI in these two cohorts, consistent with the hypothesis that the effects of the SHBG gene on the risk of type 2 diabetes mellitus are independent of the effect of BMI.
In a replication study, conducted within the Physicians’ Health Study II of men, type 2 diabetes mellitus developed in 170 men during 8 years of follow up. Using 170 matched controls, the results confirmed the strong inverse association between SHBG and the risk of type 2 diabetes mellitus observed in women.
The authors speculate that their observations "support the notion that sex hormone–binding globulin may play an important role in the development of type 2 diabetes at both the genomic and phenotypic levels and that sex hormone–binding globulin could be an important target in stratification for the risk of type 2 diabetes and early intervention."
William Rosner, M.D., Professor of Medicine at Columbia University and St. Luke’s-Roosevelt Hospital Center, said that among a number of similar studies, this is the best of the lot. "It shows that there seems to be a predictive value between plasma sex hormone–binding globulin and subsequent occurrence of type 2 diabetes. Although the authors make a strong case that it is unlikely the changes in SHBG are an epiphenomenon, e.g., a basic risk factor for diabetes also causes alterations in plasma SHBG, that possibility remains viable. Elucidation of a mechanism whereby SHBG signaling impacts glucose homeostasis would go a long way toward solidifying this hypothesis."
(N Engl J Med [September 17, 2009] 361 (12):1152)
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Milestones in Endocrinology
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One hundred years ago, David Marine established that iodine is necessary for thyroid function.
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In the Journal 25 Years Ago
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Transient hypogonadotropic hypogonadism caused by critical illness. Woolf PD, Hamill RW, McDonald JV, Lee LA, Kelly M.
J Clin Endocrinol Metab [March 1985] 60 (3):444
"In summary, patients who are critically ill develop temporary hypogonadotropic gonadal insufficiency regardless of the nature of their illness. In men, it is manifested by low testosterone levels, while estradiol levels in young women fall into the postmenopausal range."
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FIG. 1. "Elucidation of a mechanism whereby SHBG signaling impacts glucose homeostasis would go a long way toward solidifying this hypothesis," commented William Rosner, M.D., on a recent study suggesting that the protein sex hormone-binding globulin may predict type 2 diabetes mellitus.
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FIG. 2. Matthew Ringel
Matthew Ringel, of the Ohio State University College of Medicine, was awarded the American Thyroid Association’s 2009 Van Meter Award at their 80th Annual meeting.
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FIG. 3. Paul Walfish
Paul Walfish has received the 2009 John B. Stanbury award of the American Thyroid Association at their 80th Annual meeting.
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Footnotes
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Readers are encouraged to suggest items for Endocrinology and Metabolism News by email (sherman{at}endo-society.org). Submissions will be considered.
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Level of Plasma SHBG...
