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Endocrine Discovery |
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 Top Endocrine Discovery Endocrine PracticeMilestones in EndocrinologyIn the Journal 25... |
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In 1276 adults with type 1 or type 2 diabetes, there was no evidence of an effect of either aspirin or antioxidant therapy on development of cardiovascular disease or mortality in those who did not have symptomatic cardiovascular disease, but did have evidence of peripheral vascular disease in a 7 year prospective, placebo-controlled, randomized double blind trial. (BMJ [November 1, 2008] 337 (7677):a1840)
When 71 pregnant women with type 1 or 2 diabetes were randomly allocated to antenatal care with or without continuous glucose monitoring, the addition of this monitoring was associated with improved glycemic control, lower birth weight, and a reduction in macrosomia. (BMJ [October 18, 2008] 337 (7675):a1680)
In a group of older patients with type 2 diabetes, microalbuminuria was a risk factor for dementia or cognitive decline, whereas the use of drugs that inhibit the renin-angiotensin system was associated with a decrease in cognitive deficits (OR 0.28 [CI 0.12–0.65], P = 0.003). (Diabetes Care [November 2008] 31 (11):2103)
Candesartan treatment, 32 mg daily, in type 2 diabetes patients was associated with a small but statistically significant improvement in retinopathy (OR 1.17 [95% CI 1.05–1.30] P=0.003) in a randomized, double-blind, placebo-controlled trial enrolling 1905 patients with mild to moderately severe retinopathy. (Lancet [October 18, 2008] 372 (9647):1385)
In a 10-year follow-up of patients originally enrolled in the United Kingdom Prospective Diabetes Study (UKPDS), persistent reductions in microvascular disease end points, myocardial infarction, and all cause mortality were seen in patients who had been randomized to either sulfonylurea or metformin therapy compared to controls, despite the lack of differences in glycohemoglobin within one year of the end of the active intervention phase of the study. (N Engl J Med [October 9, 2008] 359 (15):1577)
A population-based study of 6823 young U.S. adult males found that those who used anabolic-androgenic steroids reported greater involvement in violent behaviors, even after controlling for key demographic variables, previous violent behavior, and polydrug use. (Am J Pub Health [published online October 15, 2008])
Axitinib, a selective vascular endothelial growth factor receptor inhibitor, was shown in a single-arm Phase II trial to be active in all histologic subtypes of metastatic thyroid cancer, with an observed response rate of 30% and a median progression-free survival time of 18 months. An additional 38% of patients experienced stable disease for 16 or more weeks. (J Clin Oncol [October 10, 2008] 26 (29):4708)
Patients with poorly controlled type 2 diabetes had similar glycemic control with the addition of either neutral protamine lispro or glargine insulin. (Ann Int Med [October 21, 2008] 149 (8):531)
Twice-daily insulin detemir dosage had no clinically significant advantage over a once-daily dosage in patients with type 1 diabetes. (Diabetes Care [published online October 22, 2008])
Vitamin K1 supplementation of 5 mg daily for 2–4 years did not protect against age-related decline in bone mineral density in postmenopausal women with osteopenia. (PLoS Medicine [published online October 14, 2008])
A population-based study of 12,376 U.S. patients found a link between self-reported thyroid problems and glaucoma. (Br J Ophthalmol [published online October 16, 2008])
Patients with diabetes took longer to clear the tuberculosis mycobacterium during treatment than those without diabetes in a retrospective study of 469 culture-positive patients. (Am J Trop Med Hyg [October 2008] 79 (4):541)
Older men with low serum estradiol and high serum sex hormone binding globulin had an increased risk of fractures in a prospective study of 2639 Swedish men with a mean age of 75 years. (J Bone Miner Res [October 2008] 23:1552)
Low cortisol concentrations in extremely low birth weight infants at 12–48 hours and day 5–7 of postnatal life did not identify the infants at highest risk for adverse outcomes. In contrast, high cortisol levels were associated with severe intraventricular hemorrhage, with infants in the
90th percentile linked with higher rates of mortality, periventricular leukomalacia, gastrointestinal perforation, and severe retinopathy of prematurity. (Pediatrics [October 4, 2008] 122 (4):775)
A meta-analysis study revealed that obesity may increase the risk of miscarriage, both in the general population (OR:1.67) and possibly after ovulation induction (OR:5.11) and oocyte donation (OR:1.52). (Fertility and Sterility [September 2008] 90 (3):714)
Women with human chorionic gonadotropin level in the top tertile tended to have a lower risk of breast cancer than those with the lowest tertile levels in a case–control study of 567 first-trimester pregnant women. (Am J Epidemiol [published online October 20, 2008])
Two functional magnetic resonance imaging studies showed that individuals with blunted striatal activation during food intake are at risk for obesity, particularly those at genetic risk for compromised dopamine signaling in brain regions implicated in food reward. (Science [October 17, 2008] 322 (5900):449)
Bariatric surgery in morbidly obese patients with diabetes resulted in an improvement in carbohydrate metabolism and a significant increase in IgG and IgM anti-oxidized low-density lipoprotein antibodies. (Diabetes Care [published online October 3, 2008])
A significant association was identified between transsexualism and an androgen receptor allele having longer CAG repeat lengths. (Biol Psychiatry [published online October 26, 2008])
A population-based study of 2,011 European patients, ages 30–70, found that metabolic syndrome is significantly higher in patients with type 2 diabetes than in patients with latent adult-onset autoimmune diabetes or type 1 diabetes. (Diabetes Care [published online October 22, 2008])
In French non-institutionalized elderly subjects aged 65 years and older, the presence of metabolic syndrome at baseline was associated with an increased risk of incident vascular dementia over 4 years in a prospective study, but not all-cause dementia or Alzheimer’s disease. (Diabetes Care [published online October 22, 2008])
Production of lipid messenger oleoylehanolamide was disrupted and the satiety response induced by fat was abrogated in mutant mice lacking the membrane fatty-acid transporter CD36, suggesting that pharmacological intervention against this lipid-sensing mechanism might be useful in treating obesity and other eating disorders. (Cell Metab [October 8, 2008]8:281)
Combination therapy with an angiotensin II type 1 receptor blocker and a vitamin D analog significantly ameliorated renal injury in the streptozotocin-induced diabetic mice due to the blockade of the compensatory renin rise by the vitamin D analog, leading to more effective renin-angiotensin system inhibition. (Proc Natl Acad Sci USA [October 14, 2008] 105 (41):15896)
Monogamous male prairie voles separated 4–5 days from their bonded female partner had activation of their hypothalamic-pituitary-adrenal axis along with a passive stress-coping behavior. (Neuropsychopharmacology [published online October 15, 2008])
Revised Consensus Algorithm for Type 2 Diabetes Recently Published
A newly revised joint consensus statement on the medical management of type 2 diabetes in the nonpregnant adult, taking into account newer medications and the most current clinical data, has been published.
Co-published by the American Diabetes Association and the European Association for the Study of Diabetes, the consensus statement builds upon the first statement, published in August 2006, which called for the intensive glucose management targeted to bring hemoglobin A1c levels lower than 7%. This statement was first updated in January 2008 in order to address the safety issues surrounding thiazolidinediones, such as the risk of fluid retention, bone loss, and congestive heart failure with rosiglitazone.
"In our original algorithm, we recommended several departures from what the usual therapy had been," said David Nathan, M.D., director of the Diabetes Center at Massachusetts General in Boston and chair of the joint panel which published this current statement. "Most diabetes treatments are lente or very slow. However if we treat early in the course of the disease, we can take advantage of better β-cell function, and the treatments work better and longer."
The current consensus statement continues to endorse the achievement of normoglycemia or an A1c of less than 7% in patients with type 2 diabetes, but also came out with a tiered algorithm in order to counter these patients’ elevated levels of blood glucose. The first tier, which is characterized as the most established and preferred route, calls for diet and exercise lifestyle interventions to promote weight loss or at least avoid weight gain, as well as the concurrent use of metformin, a relatively inexpensive and tolerated drug, at the time of diabetes diagnosis. The A1c level should be checked every 3 months until it reaches the target goal of less than 7%, and then at least every 6 months. If the lifestyle intervention and metformin fail, the next step includes the addition of basal insulin or sulfonylurea. Lastly, if lifestyle, metformin, and sulfonylurea or basal insulin do not achieve target glycemia, then the panel suggests discontinuing sulfonylurea and starting the patient on intensive insulin therapy. For patients in whom hypoglycemia is particularly undesirable, such as those with hazardous jobs, the algorithm recommends second tier or less well-validated therapies such as the addition of pioglitazone or a GLP-1 agonist to lifestyle changes and metformin; if neither of these medications work, then they are discontinued and addition of sulfonylurea or intensive insulin therapy should be considered.
"There was an element of the pocket book that entered in our decision," said Dr. Nathan, when explaining the choice of medication used in the algorithm, noting that ironically the three oldest drugs—insulin, sulfonylurea, and metformin—were just as powerful if not more so than the newer ones.
Most diabeticians laud the new algorithm for its judiciousness and rationale.
"I think it’s applicable for the clinician and the patient and I think the patients will accept it by and large," said Saul Genuth, M.D. professor of medicine at the endocrine division in Case Western Reserve University, Cleveland, Ohio. "It provides excellent rational for every recommendation and the reference list is very impressive."
However, some expressed several reservations.
"The algorithm is an excellent and instructive starting point, but perhaps is a little oversimplified in terms of the decision-making we actually do as we care for these patients," said Robert Smith, M.D., director of The Hallett Center for Diabetes and Endocrinology in Providence, Rhode Island, who often finds himself working with patients that would use the tier 2 steps in the algorithm. "In caring for type 2 diabetes patients, which is a pretty heterogeneous disorder, we’re in fact making decisions that are on a somewhat individualized basis. Very often we’re confronting problems with intolerance of first tier medications. It is quite common for patients to be unable to take metformin because of renal insufficiency or GI side effects and hypoglycemia with sulfonylureas can cause problems."
Another impediment to this algorithm, according to Dr. Genuth, is clinical inertia, in which the management of diabetes is maintained at the status quo rather than pursuing an aggressive algorithm.
"All physicians have been confronted with at best reluctance and worst refusal to start insulin with the promise ‘I’ll do better with diet and exercise’ or ‘I didn’t tell you but I missed some of my oral doses,’" he said. "I think gradually there will be earlier use of insulin. Publishing the algorithm will help to make this change." (Diabetes Care [December 2008] 31 (12):1) (Diabetologia [published online October 22, 2008])
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Endocrine Practice |
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Milestones in Endocrinology |
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In the Journal 25 Years Ago |
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TopEndocrine DiscoveryEndocrine PracticeMilestones in EndocrinologyIn the Journal 25... |
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"The above data indicate that in patients with idiopathic central hypothyroidism due to biologically inactive TSH there is an excess of circulating TSH-β and suggest that TRH is implicated in the secretion of TSH of full biological potency."
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