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What's new in endocrinology and diabetes mellitus
All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Apr 2012. | This topic last updated: Mar 28, 2012.

The following represent additions to UpToDate since the last version of What’s New that were considered by the authors and editors to be of particular interest.

DIABETES

Microvascular complications type 1 diabetes — In the Epidemiology of Diabetes Interventions and Complications (EDIC) follow-up study to the Diabetes Control and Complications Trial (DCCT), intensive insulin therapy compared with conventional therapy for 6.5 years during the DCCT significantly reduced the risk of developing impaired renal function over a median follow-up period of 22 years [1]. This decreased risk occurred despite an absence of a difference in A1C values during the post-DCCT trial period. This phenomenon has been called "metabolic memory." (See "Glycemic control and vascular complications in type 1 diabetes mellitus", section on 'Nephropathy'.)

VITAMIN D

Fractures — A meta-analysis of five trials comparing vitamin D (400 to 1370 units/day) with placebo in over 14,500 elderly men and women showed that vitamin D supplementation alone did not reduce fracture risk [2]. However, a meta-analysis of 11 trials comparing combined supplementation with calcium (500 to 1200 mg/day) plus vitamin D (300 to 1100 units/day) with placebo showed a reduction in fracture risk [2]. In a subgroup analysis, the risk reduction was larger among institutionalized than community dwelling older individuals. These findings suggest that supplementation with both calcium and vitamin D is required to reduce the risk of fracture. (See "Calcium and vitamin D supplementation in osteoporosis", section on 'Calcium versus vitamin D'.)

Colon cancer — The relationship between vitamin D deficiency and risk of cancer is controversial. In a meta-analysis of nine case-control studies, there was a link between poor vitamin D status and risk of colon cancer [2]. For each 4 ng/mL (10 nmol/L) increase in pre-diagnosis serum 25OHD concentration, there was a 6 percent reduction in colorectal cancer. (See "Vitamin D and extraskeletal health", section on 'Cancer'.)

OSTEOPOROSIS

Repeat screening for bone mineral density — Data regarding the frequency of follow-up bone mineral density (BMD) testing in women who have had an initial screening test are limited. Two studies provide new related data:

  • Whether the rate of BMD loss is an independent risk factor for fracture has been uncertain. In a retrospective cohort study using a database of all clinical BMD results from Manitoba, Canada, 146 women sustained one or more osteoporotic fractures after the second BMD test [3]. The annualized percentage change in BMD did not differ in women who did and did not sustain major osteoporotic fractures.
  • In an analysis of data from the Study of Osteoporotic Fractures (SOF), 4957 women (67 years and older) who did not have osteoporosis at baseline testing were followed for up to 15 years [4]. The interval for 10 percent of participants to make the transition from normal BMD or osteopenia at baseline to osteoporosis (before a hip or clinical vertebral fracture occurred and before initiation of osteoporosis treatment) was estimated. For women with normal (T-score -1.0 or better) or slightly low (T-score -1.01 to -1.49) bone mass at baseline, the interval between baseline testing and the development of osteoporosis was approximately 17 years.

These data suggest that healthy women 65 years of age and older at baseline screening, with normal or slightly low bone mass (T-score -1.01 to -1.49), and with no risk factors for accelerated bone loss, do not require repeat testing for 17 years. These results are not applicable to women with osteoporosis (T-scores below -2.5) at baseline, women already receiving osteoporosis treatment, or women younger than 65 years of age at time of first bone density screening. Women younger than 65 years of age with clinical risk factors for fracture (table 1) may require more frequent monitoring of bone density, depending upon risk factors. (See "Screening for osteoporosis", section on 'Repeat BMD measurements'.)

Solid organ transplantation — A meta-analysis of nine trials evaluating the effect of treatment with bisphosphonates versus control (placebo or no treatment) on fracture outcomes after solid organ (liver, heart, kidney) transplantation showed a reduction in the proportion of patients with fracture after treatment with bisphosphonates [5]. (See "Osteoporosis after solid organ or stem cell transplantation", section on 'Bisphosphonates'.)

Historically, post-transplantation fracture incidence rates have been very high, ranging from 10 to 65 percent. The rate of post-transplantation fracture is decreasing in some studies. In a retrospective review of over 500 patients undergoing liver transplantation at a single center between 1998 and 2008 (following the introduction of a protocol for bone health assessment and management) fractures occurred in only 3.5 percent after transplantation [6]. The spine and the wrist were the two most common fracture sites. Possible reasons for the lower fracture incidence include a reduction in the dose and duration of glucocorticoid therapy, use of bone protective medications (predominantly bisphosphonates), which nearly 30 percent of patients took after transplantation, and improvement in pre- and post-transplantation nutrition. (See "Osteoporosis after solid organ or stem cell transplantation", section on 'Fractures'.)

Postmenopausal women — A meta-analysis of 43 randomized trials (4320 participants) of exercise and bone mineral density (BMD) in postmenopausal women showed a small but significant positive effect of exercise on BMD at the lumbar spine and trochanter compared with controls [7]. Various exercise types, including resistance training, jogging, jumping, and walking, were effective. The most effective type of exercise for BMD of the femoral neck was non-weight bearing high force exercise (eg, progressive resistance strength training), whereas a combined program (mixture of more than one exercise type) was most effective for lumbar spine BMD. (See "Overview of the management of osteoporosis in postmenopausal women", section on 'Exercise'.)

MALE REPRODUCTION

New testosterone preparations — Several new testosterone preparations are available for androgen replacement therapy in hypogonadal men, including two higher concentrations of testosterone gel that allow use of a smaller volume of gel (applied to the upper arm) [8-10] and a topical testosterone solution that is applied to the underarm [11]. (See "Testosterone treatment of male hypogonadism", section on 'Testosterone gels'.)

FEMALE REPRODUCTION

Progestins associated with an increased risk of thrombosis — In a study that assessed the risk of cardiovascular events in over 800,000 women, use of combined contraceptives containing drospirenone, norelgestromin, or etonogestrel (newer progestins used in an oral contraceptive, transdermal patch, and vaginal ring, respectively) was associated with a significantly higher risk of venous thrombosis compared with use of standard low-estrogen combined hormonal contraceptives [12]. When the analysis was restricted to new users, only drospirenone was associated with a significantly higher risk of venous thrombosis. (See "Risks and side effects associated with estrogen-progestin contraceptives", section on 'Venous thromboembolic disease'.)

Early menopause after hysterectomy — Hysterectomy without oophorectomy may be associated with early menopause. In a prospective cohort study of 871 premenopausal women, those who had undergone hysterectomy had nearly a twofold higher risk of early ovarian failure than those who had not [13]. The risk for ovarian failure was higher in women who had undergone a unilateral oophorectomy with their hysterectomy. (See "Overview of hysterectomy", section on 'Earlier menopause'.)

Postmenopausal hormone therapy and melanoma risk — Although some epidemiologic studies have suggested that postmenopausal hormone therapy is associated with an increased risk of melanoma, no excess risk of either melanoma or nonmelanoma skin cancer was observed in a post-hoc analysis of the Women’s Health Initiative (for unopposed estrogen or combined estrogen-progestin therapy) [14]. (See "Postmenopausal hormone therapy: Benefits and risks", section on 'Skin'.)

THYROID DISORDERS

Hypothyroidism during pregnancy — A randomized trial compared neurocognitive outcomes in children of women with subclinical hypothyroidism who were or were not treated with levothyroxine during pregnancy [15]. 21,846 pregnant women (gestational age <15 weeks), without known thyroid disease, were randomly assigned to a screening or control group. All women had blood drawn for TSH and free T4, but only serum samples from the screening group were immediately assayed. Serum samples from the control group were stored and assayed after delivery. Patients in the screening group who had TSH above the 97.5th percentile (>3.65 mU/L), serum free T4 below the 2.5th percentile, or both were treated with levothyroxine to achieve a TSH between 0.1 and 1.0 mU/L. IQ testing was performed in the children of mothers in the screening and control groups who had tested positive for thyroid dysfunction. There was no difference in the IQ of the children at three years of age or in the proportion of children with IQ score <85. (See "Hypothyroidism during pregnancy: Clinical manifestations, diagnosis, and treatment", section on 'Cognitive impairment'.)

Antineoplastic agents and thyroid dysfunction — Newer antineoplastic agents, such as targeted therapies and immunotherapies, are associated with thyroid dysfunction. Oral tyrosine kinase inhibitors (eg, sunitinib, sorafenib, imatinib) used for the treatment of gastrointestinal stromal tumors, renal cell carcinoma, hepatocellular cancer, chronic myeloid leukemia, and in other cancers can cause hypothyroidism in patients with previously normal function and increase thyroid hormone requirements in patients with preexisting hypothyroidism [16]. Hypophysitis and panhypopituitarism, including central hypothyroidism, may also occur as a complication of ipilimumab (anti-CTLA-4) immunotherapy used for the treatment of metastatic melanoma. Hyperthyroidism may occur after treatment with denileukin diftitox, ipilimumab, and alemtuzumab. Possible mechanisms include changes in thyroid hormone clearance, impaired iodine uptake, or destructive thyroiditis. (See "Drug interactions with thyroid hormones", section on 'Drugs that cause hypothyroidism' and "Drug interactions with thyroid hormones", section on 'Drugs that cause hyperthyroidism'.)

OBESITY

Investigational drugs — Serotonin reduces food intake in animals and human beings, and therefore agonists to appropriate serotonin receptors are potentially valuable drugs for weight reduction. Lorcaserin is a selective agonist of the serotonin 2C receptor. In a randomized trial in 4008 patients, a significantly greater proportion of patients assigned to lorcaserin (10 mg twice daily or once daily) compared with placebo lost at least 5 percent of baseline body weight [17]. There was no significant increase in the incidence of serotonin-associated valvulopathy (as assessed by echocardiography at week 52) or in neuropsychiatric side effects. The trial was limited by a high dropout rate, which approached 50 percent. (See "Drug therapy of obesity", section on 'Lorcaserin'.)

Maintenance of weight loss — Achieving and maintaining weight loss is made difficult by the reduction in energy expenditure that is induced by weight loss. In addition, weight loss induces changes in peripheral hormone signals that regulate appetite. Gastrointestinal peptides, such as ghrelin and gastric inhibitory polypeptide, increase after diet-induced weight loss. Ghrelin stimulates appetite, and gastric inhibitory peptide promotes energy storage. Other circulating mediators that inhibit intake (eg, leptin, peptide YY, cholecystokinin, pancreatic polypeptide) decrease. In an observational study of 50 patients who lost a mean of 14 kg through dieting, the hormonal adaptations favoring weight gain were still present one year after initial weight loss [18]. (See "Dietary therapy for obesity", section on 'Maintenance of weight loss'.)

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REFERENCES

  1. DCCT/EDIC Research Group, de Boer IH, Sun W, et al. Intensive diabetes therapy and glomerular filtration rate in type 1 diabetes. N Engl J Med 2011; 365:2366.
  2. Chung M, Lee J, Terasawa T, et al. Vitamin D with or without calcium supplementation for prevention of cancer and fractures: an updated meta-analysis for the U.S. Preventive Services Task Force. Ann Intern Med 2011; 155:827.
  3. Leslie WD, Morin SN, Lix LM, for the Manitoba Bone Density Program. Rate of Bone Density Change Does Not Enhance Fracture Prediction in Routine Clinical Practice. J Clin Endocrinol Metab 2012; 97:1211.
  4. Gourlay ML, Fine JP, Preisser JS, et al. Bone-density testing interval and transition to osteoporosis in older women. N Engl J Med 2012; 366:225.
  5. Stein EM, Ortiz D, Jin Z, et al. Prevention of fractures after solid organ transplantation: a meta-analysis. J Clin Endocrinol Metab 2011; 96:3457.
  6. Premaor MO, Das TK, Debiram I, et al. Fracture incidence after liver transplantation: results of a 10-year audit. QJM 2011; 104:599.
  7. Howe TE, Shea B, Dawson LJ, et al. Exercise for preventing and treating osteoporosis in postmenopausal women. Cochrane Database Syst Rev 2011; :CD000333.
  8. Miller J, Britto M, Fitzpatrick S, et al. Pharmacokinetics and relative bioavailability of absorbed testosterone after administration of a 1.62% testosterone gel to different application sites in men with hypogonadism. Endocr Pract 2011; 17:574.
  9. Kaufman JM, Miller MG, Garwin JL, et al. Efficacy and safety study of 1.62% testosterone gel for the treatment of hypogonadal men. J Sex Med 2011; 8:2079.
  10. A new testosterone gel (fortesta) for hypogonadism. Med Lett Drugs Ther 2011; 53:29.
  11. Wang C, Ilani N, Arver S, et al. Efficacy and safety of the 2% formulation of testosterone topical solution applied to the axillae in androgen-deficient men. Clin Endocrinol (Oxf) 2011; 75:836.
  12. FDA Office of Surveillance and Epidemiology. Combined Hormonal Contraceptives (CHCs) and the Risk of Cardiovascular Disease Endpoints. http://www.fda.gov/downloads/Drugs/DrugSafety/UCM277384.pdf (Accessed on February 03, 2012).
  13. Moorman PG, Myers ER, Schildkraut JM, et al. Effect of hysterectomy with ovarian preservation on ovarian function. Obstet Gynecol 2011; 118:1271.
  14. Tang JY, Spaunhurst KM, Chlebowski RT, et al. Menopausal hormone therapy and risks of melanoma and nonmelanoma skin cancers: women's health initiative randomized trials. J Natl Cancer Inst 2011; 103:1469.
  15. Lazarus JH, Bestwick JP, Channon S, et al. Antenatal thyroid screening and childhood cognitive function. N Engl J Med 2012; 366:493.
  16. Hamnvik OP, Larsen PR, Marqusee E. Thyroid dysfunction from antineoplastic agents. J Natl Cancer Inst 2011; 103:1572.
  17. Fidler MC, Sanchez M, Raether B, et al. A one-year randomized trial of lorcaserin for weight loss in obese and overweight adults: the BLOSSOM trial. J Clin Endocrinol Metab 2011; 96:3067.
  18. Sumithran P, Prendergast LA, Delbridge E, et al. Long-term persistence of hormonal adaptations to weight loss. N Engl J Med 2011; 365:1597.
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