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Endocrinology & Metabolism News

	Endocrine Discovery

Top Endocrine Discovery Reexamining Treatment for Mild... Endocrine Practice Milestones in Endocrinology In the Journal 25...

 
Alum-formulated glutamic acid decarboxylase contributed to the preservation of insulin secretion in patients with recent-onset type 1 diabetes, but it did not change the insulin requirement. (N Engl J Med [published ahead of print October 8, 2008])

Among 1,148 British patients with newly diagnosed type 2 diabetes and hypertension, improvement in blood-pressure control, if maintained, was associated with a reduced risk of micro- and macrovascular complications. (N Engl J Med [October 9, 2008] 359 (15):1565)

Young women with type 1 diabetes have lower total hip, femoral neck, and whole body bone mineral density than control patients, which persist over time, especially in women over 20 years of age, suggesting that screening may be important in this group. (Diabetes Care [September 2008] 31 (9):1729)

A large prospective study including white, black, Hispanic, and Chinese men and women found that an empirically derived dietary pattern characterized by high intake of whole grains, fruit, nuts/seeds, and green leafy vegetables was inversely associated with risk of incident type 2 diabetes, suggesting that multiple food groups collectively influence type 2 diabetes risk beyond that of individual food groups. (Diabetes Care [September 2008] 31 (9):1777)

Pramlintide treatment, when used over 12 months as an adjunct to lifestyle intervention and at either a low-dose three-times daily or a higher-dose two-times daily regimen, helped obese patients achieve greater initial weight loss and maintain weight loss. (Diabetes Care [September 2008] 31 (9):1816)

In a follow up study of 249 participants who were aged 13–19 years at entry in the Diabetes Control and Complications Trial (DCCT), there was no evidence that severe hypoglycemia or intensive therapy affected cognitive performance over an 18 year follow up period. (Diabetes Care [October 2008] 31 (10):1933)

In a study of 487 women, any degree of abnormal glucose homeostasis in pregnancy independently predicted an increased risk at 3 months postpartum of glucose intolerance. Standard antepartum screening for gestational diabetes mellitus identified four metabolically distinct tolerance groups for pregnancy, whose differences in insulin sensitivity, β-cell function, and glucose tolerance persisted at 3 months postpartum. (Diabetes Care [October 2008] 31 (10):2026)

A 23-year prospective study of 21,841 U.S. male physicians found that diabetes is not a preceding risk factor for Parkinson’s disease. (Diabetes Care [October 2008] 31 (10):2003)

A retrospective cohort study of 2,574 patients aged 21–75 years found that a weight-loss pattern after a new diagnosis of type 2 diabetes predicted improved glycemic and blood pressure control despite weight regain. (Diabetes Care [October 2008] 31 (10):1960)

Iron deficiency was involved with increased A1C levels in late pregnancy, but had no effect on serum glycated albumin, suggesting that the latter may be a better index for monitoring glycemic control in pregnancy. (Diabetes Care [October 2008] 31 (10):1945)

Two studies examining cognitive function in children with type 1 diabetes found that impaired cognitive effects are most pronounced and pervasive for those with early-onset diabetes and that those on intensive glucose control for 18 years, with its risk of severe hypoglycemia, did not affect cognitive function. (Diabetes Care [September 2008] 31 (9):1892 and Diabetes Care [October 2008] 31(10):1933)

A randomized, 52-week, phase III, double-blind, parallel-treatment trial found that liraglutide was more effective than glimepiride for use as initial pharmacological therapy in reducing HbA1c levels, weight, hypoglycemia, and blood pressure in patients with type 2 diabetes. (Lancet [published ahead of print September 25, 2008])

In a randomized trial of inhaled insulin or placebo, given to 244 children with genetic susceptibility to diabetes and positive autoantibodies, there was no evidence that inhaled insulin given for a median of 1.8 years prevented or delayed the development of type 1 diabetes. (Lancet [published ahead of print September 22, 2008])

In a 30-week, randomized trial of weekly long-acting exenatide versus twice daily exenatide, there was a greater improvement in HbA1c, a greater proportion of patients achieving a HbA1c less than 7%, and similar weight reduction with the long acting preparation (77% vs. 61%). (Lancet [October 4, 2008] 372 (9645):1240)

Overactive endocannabinoid signaling in mice elicited an increase in plasma triglyceride levels associated with reduced plasma triglyceride clearance and an accumulation in plasma of apolipoprotein E-depleted triglyceride-rich lipoproteins, suggesting a role of cannabinoid receptor type 1 activation in the pathogenesis of obesity-related hypertriglyceridemia and the possible efficacy of receptor antagonists in treating metabolic disease. (Proc Natl Acad Sci USA [September 23, 2008] 105 (38):14561)

A prospective case–control study of 244 young women with and without multiple fibroadenomas identified a gain-of function mutation in the prolactin receptor, PrlR_I146L, linking for the first time prolactin receptor to a human disease. (Proc Natl Acad Sci USA [September 23, 2008] 105 (38):14533)

Liver-specific deletion of Bmal1, an essential circadian clock component, in mice caused hypoglycemia restricted to the fasting phase of the daily feeding cycle, exaggerated glucose clearance, and loss of rhythmic expression of hepatic glucose regulatory genes, implying that this peripheral tissue circadian clock regulates glucose homeostasis in a time-of-day dependent manner. (Proc Natl Acad Sci USA [September 30, 2008] 105 (39):15172)

Electrophysiological studies have shown that estrogen directly potentiates neuronal L-type voltage-gated Ca²⁺ channels, which could have implications in modulating synaptic plasticity, neuroprotection, and memory formation. (Proc Natl Acad Sci USA [September 30, 2008] 105 (39):15148)

Examination of 23,146 postmenopausal women previously hospitalized with a hip fracture revealed that most do not take anti-osteoporotic therapy after the fracture. Those who did start aldendronate decreased their adherence such that only 41% continued the treatment after one year. (J Bone Joint Surg Am [October 2008] 90A (10):2142)

Comorbid depression in 10,704 Medicare beneficiaries with diabetes (mean age 75.6 years) participating in a disease management program was associated with an increased risk for all-cause mortality over a 2-year follow-up period by 36%–38%. (J Gen Intern Med [October 2008] 23 (10):1571)

Insulin-secreting islet-like clusters can be generated from skin fibroblasts, pointing to the possibility that patient-specific induced pluripotent stem cells could provide potential diabetes treatment. (J Biol Chem [published online September 9, 2008])

A case–control study of 472 postmenopausal women with a BRCA1 mutation found that hormone therapy was not associated with increased breast cancer risk. (J Nat Cancer Inst [October 1, 2008] 100 (19):1361)

In a quantitative systematic review of controlled trials, premixed insulin analogues were found to provide glycemic control similar to that seen with premixed human insulin. (Ann Intern Med [published ahead of print September 16, 2008])

In continued observations of the original Diabetes Control and Complications Trial (DCCT) cohort, the Epidemiology of Diabetes Intervention and Complications (EDIC) study found that intensive insulin therapy reduced the risk of developing hypertension over a 16 year follow up period. (Arch Intern Med [September 22, 2008]168 (17):1867)

Current tamoxifen use substantially reduced osteoporotic fractures in a population-based case-control study of Canadian women 50 years of age or older. (J Clin Oncol [published ahead of print October 6, 2008])

In postmenopausal women and aged-matched men, two weeks of topical estradiol treatment stimulated collagen I and III production in sun-protected hip skin, but not in photoaged forearm or face skin. (Arch Dermatol [September 2008] 144 (9):1129)

White adipocyte progenitor cells have been identified that are capable of proliferating and differentiating into an adipose tissue depot in A-Zip lipodystrophic transgenic mice. (Cell [October 17, 2008] 135:1)

In mice, obesity could be prevented by virally or genetically inhibiting the IKKβ/NF-B pathway, an innate immune pathway in the hypothalamus that is overactivated in obese individuals. (Cell [October 3, 2008] 135:61)

White fat progenitor cells have been found to reside solely in the mural cell compartment of the adipose vasculature. (Science [published online September 18, 2008])

	Reexamining Treatment for Mild Hypothyroidism

Top Endocrine Discovery Reexamining Treatment for Mild... Endocrine Practice Milestones in Endocrinology In the Journal 25...

 
A new study may help set the threshold as to when to treat individuals with subclinical hypothyroidism. Subclinical hyperthyroidism—conditions with high or low levels of TSH, respectively, but normal free thyroxine levels—increase in prevalence in age, with more than 10% of the aging population affected. These states have also been tenuously linked by several studies to cardiac dysfunction, yet screening and treatment remain a hotbed of controversy.

Determining the exact TSH boundary for treatment has some serious implications. If this limit is set too high, some patients below the cut-off may develop cardiovascular problems that might have been prevented with thyroxine treatment. On the other hand, if the treatment limit is set too low, then patients could be inappropriately treated with thyroxine without benefit while also placing them at risk of subclinical hyperthyroidism, which has been associated with atrial fibrillation and increased fracture risk.

Looking to quell this roiling debate, Nicolas Rodondi, M.D., M.A.S, head of the cardiovascular prevention and lipid clinic at the University of Lausanne in Switzerland, and colleagues performed a 12-year observational study on the cardiac changes of 3,044 adults over 65 years of age who were initially free of heart failure. The participants were divided into four groups: those who were euthyroid (TSH between 0.45–4.5 mU/l), those with subclinical hypothyroidism (TSH between 4.5–9.9 mU/l and those above 10 mU/l), and those with subclinical hyperthyroidism (TSH 0.10–0.45 mU/l).

In a recent article published by the Journal of the American College of Cardiology, the researchers found that compared to euthyroid participants, those having a TSH 10 mU/l had almost a two-fold risk of heart failure incidence. Two echocardiographic measurements, an increase in peak E velocity at baseline—a measurement of diastolic function—and in left ventricular mass over 5 years were also altered in the subclinical hypothyroidism subgroup with TSH 10 mU/l compared to euthyroid participants.

Their findings are mixed, according to Dr. Rodondi. "They give further strength to some guidelines that recommend treatment above 10 mU/l," he said. "But it also gives further information that below 10 mU/l, we don’t know if there is increased risk for cardiovascular disease."

He and others suggest that a large randomized clinical trial would give firmer diagnosis and treatment guidelines.

"Based upon this study, a prospective study would be warranted to determine whether treatment was able to reverse those changes," commented Irwin Klein, M.D., Professor of Medicine and Cell Biology at North Shore University Hospital and the Feinstein Institute for Medical Research, in Manasset, New York.

In the meantime, Dr. Klein added, a TSH screen for thyroid disease should be performed in the elderly.

"It used to be thought that patients labeled ‘subclinical’ did not have any classic symptoms of dysfunction," he said. "That may be a misnomer, especially in the cardiovascular sphere, because it’s really a function of how carefully you look for these clinical and metabolic changes and symptoms." (J Am Coll Cardiol [September 30, 2008] 52 (14):1152)

	Endocrine Practice

Top Endocrine Discovery Reexamining Treatment for Mild... Endocrine Practice Milestones in Endocrinology In the Journal 25...

 
As of September 5, 2008, Alza Pharmaceuticals discontinued the manufacture of Neutra-phos, used in the treatment of X-linked hypophosphatemic rickets. The Lawson Wilkins Pediatric Endocrine Society recommends the following phosphate alternatives: K-phos Neutral tablets (Beach Pharmaceuticals), Phos-NaK packets (Cyprus Pharmaceuticals), and phospho soda. (For more information log on to http://lwpes.org/)

The American Diabetes Association introduced a new adult diabetes prevention toolkit for community-based and faith-based organizations in the Hispanic/Latino community. The Por Tu Familia Adult Prevention Toolkit provides comprehensive and culturally relevant information on diabetes and healthy living and comes with educational materials, including bilingual brochures, recipe samplers, posters, and tip sheets. These organizations can order a free copy by calling 1-800-DIABETES.

The National Institute of Diabetes and Digestive and Kidney Diseases has produced four new fact sheets for consumers and health care providers about thyroid disorders. The fact sheets separately discuss hyperthyroidism, hypothyroidism, Graves’ Disease, and pregnancy and thyroid disease. To obtain copies, please visit www.endocrine.niddk.nih.gov/pubs/Hyperthyroidism; www.endocrine.niddk.nih.gov/pubs/Hypothryoidism; www.endocrine.niddk.nih.gov/pubs/graves; and www.endocrine.niddk.nih.gov/pubs/pregnancy.

	Milestones in Endocrinology

Top Endocrine Discovery Reexamining Treatment for Mild... Endocrine Practice Milestones in Endocrinology In the Journal 25...

 
100 years ago, William MacCallum reported from Johns Hopkins that parathyroidectomized dogs, who were already known to develop tetany, had a low blood calcium level and the injection of calcium salts could improve their condition.

	In the Journal 25 Years Ago

Top Endocrine Discovery Reexamining Treatment for Mild... Endocrine Practice Milestones in Endocrinology In the Journal 25...

 
Pregnancy-associated changes in the thyroid-stimulating antibody of Graves’ disease and the relationship to neonatal hyperthyroidism. Zakarija M, MCKenzie JM. J Clin Endocrinol Metab [November 1983] 57(5):1036

"These results in 20 pregnancies indicate that a maternal value of TSAb greater than 500% in the third trimester leads to the development of neonatal hyperthyroidism."

View larger version (76K): [in this window] [in a new window]   FIG. 1. "It used to be thought that patients labeled ‘subclinical’ did not have any classic symptoms of dysfunction. That may be a misnomer, especially in the cardiovascular sphere...Based upon this study, a prospective study would be warranted to determine whether treatment was able to reverse those changes," commented Irwin Klein, M.D., about the latest study to establish a TSH screening threshold for subclinical hypothyroidism.

View larger version (118K): [in this window] [in a new window]   FIG. 2. Francine Kaufman

View larger version (132K): [in this window] [in a new window]   FIG. 3. E. Chester Ridgway

View larger version (69K): [in this window] [in a new window]   FIG. 4. Furio Pacini

View larger version (112K): [in this window] [in a new window]   FIG. 5. Yun-Bo Shi Francine Kaufman began a three-year term as chair of the National Diabetes Education Program. E. Chester Ridgway was awarded the John B. Stanbury Thyroid Pathophysiology Medal, Furio Pacini received the Paul Starr Award, and Yun-Bo Shi was awarded the Van Meter Award at the American Thyroid Association’s 79th Annual meeting.

	Footnotes

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