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What's new in endocrinology and diabetes mellitus
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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: Oct 2017. | This topic last updated: Nov 08, 2017.

The following represent additions to UpToDate from the past six months that were considered by the editors and authors to be of particular interest. The most recent What's New entries are at the top of each subsection.

DIABETES MELLITUS

Continuous glucose monitoring in patients with type 2 diabetes receiving multiple daily injections of insulin (October 2017)

In patients with type 1 diabetes, continuous glucose monitoring (CGM) can modestly improve glycemic control and reduce the frequency of biochemical hypoglycemia (glucose <70 mg/dL [3.9 mmol/L]). In a recent trial evaluating CGM or usual care (self-monitoring of blood glucose at least four times daily) in 158 adults with type 2 diabetes receiving multiple daily injections of insulin, the reduction in glycated hemoglobin (A1C) at 24 weeks was greater with CGM (0.8 versus 0.5 percentage points, respectively) [1]. There was no difference in hypoglycemia, which was infrequent in both groups, or in quality-of-life measures. CGM may be beneficial in selected patients with type 2 diabetes receiving multiple daily insulin injections. (See "Self-monitoring of blood glucose in management of adults with diabetes mellitus", section on 'Efficacy'.)

Continuous glucose monitoring in pregnant women with type 1 diabetes (October 2017)

Good glycemic control before and during pregnancy in women with type 1 diabetes is a key factor impacting pregnancy outcome, but whether frequent daily capillary glucose monitoring or continuous glucose monitoring (CGM) results in better glycemic control and pregnancy outcome has not been established. In two parallel open-label trials, 325 women (215 pregnant, 110 planning pregnancy) with type 1 diabetes receiving intensive insulin therapy were randomly assigned to either CGM plus capillary glucose monitoring or capillary glucose monitoring alone [2]. In women planning pregnancy, glycemic control at the end of the trial was similar in both groups. In pregnant women, glycemic control and some newborn outcomes (eg, frequency of hypoglycemia, large for gestational age) were better in the CGM group. Although the improvement in neonatal hypoglycemia with CGM appears promising, the lack of blinding may have biased decisions regarding neonatal management. Also, it is unclear whether the high level of maternal compliance with CGM in this trial could be achieved in other populations. (See "Pregestational diabetes mellitus: Glycemic control during pregnancy", section on 'Self-monitoring of blood glucose'.)

Sotagliflozin as adjunctive therapy for type 1 diabetes (October 2017)

Sotagliflozin, an investigational dual sodium-glucose co-transporter (SGLT) 1 and 2 inhibitor, was evaluated as an adjunct to insulin therapy in 1400 patients with type 1 diabetes who were randomly assigned to sotagliflozin or placebo [3]. After 24 weeks, the proportion of patients who achieved a glycated hemoglobin (A1C) <7 percent and no severe hypoglycemia or diabetic ketoacidosis was greater in the sotagliflozin group (28.6 versus 15.2 percent). However, the rate of diabetic ketoacidosis was higher in the sotagliflozin group (3 versus 0.6 percent) as was the frequency of dehydration and genital infections. Whether the increased risk for treatment-related complications is balanced by the modest lowering of A1C is unclear. (See "Management of blood glucose in adults with type 1 diabetes mellitus", section on 'Adjunctive therapy'.)

SGLT2 inhibitors and risk of acute kidney injury (October 2017)

In postmarketing reports, sodium-glucose co-transporter 2 (SGLT2) inhibitors used for the treatment of type 2 diabetes have been associated with acute kidney injury, with some patients requiring hospitalization and dialysis. However, a recent analysis of two different cohorts of diabetic patients, including both SGLT2 users and nonusers, did not show an increased risk of acute kidney injury [4]. Nevertheless, renal function should be assessed prior to initiation of SGLT2 inhibitors and monitored during treatment. (See "Sodium-glucose co-transporter 2 inhibitors for the treatment of type 2 diabetes mellitus", section on 'Acute kidney injury'.)

Roux-en-Y gastric bypass versus sleeve gastrectomy in patients with type 2 diabetes (September 2017)

Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) comprise over 95 percent of bariatric procedures performed in patients with type 2 diabetes in North America, but the optimal procedure to maximize glycemic control is unclear. In one study, diabetes remission (glycated hemoglobin [A1C] <6.5 percent off medications) was achieved in 49 percent of patients after RYGB and 28 percent after SG at a median of seven years [5]. By classifying diabetes preoperatively as mild, moderate, or severe by a nomogram based on four variables, the authors found that RYGB resulted in a higher rate of diabetes remission than SG for patients with moderate diabetes and a similar rate as SG for those with mild diabetes. For patients with severe diabetes, both procedures had low rates of diabetes remission. We believe the choice between RYGB and SG should be based on clinical factors in addition to glucose control, such as the patient's overall surgical risk and whether the patient has severe acid reflux, Crohn disease, or requires organ transplantation. (See "Laparoscopic sleeve gastrectomy", section on 'Diabetes mellitus'.)

Liraglutide and renal outcomes in type 2 diabetes (September 2017)

In an earlier report of a randomized trial comparing liraglutide with placebo in patients with type 2 diabetes and coexisting cardiovascular disease, liraglutide reduced the incidence of the composite cardiovascular endpoint. In a separate analysis of the secondary microvascular endpoints in the trial, liraglutide reduced the incidence of the renal outcome (a composite of new-onset persistent macroalbuminuria, persistent doubling of the serum creatinine level, end-stage renal disease, or death due to renal disease) [6]. The results were driven by a lower incidence of new-onset persistent macroalbuminuria. Trials of longer duration with primary microvascular outcomes and in patients who are not at high cardiovascular risk are required in order to better understand the microvascular effects of GLP-1 receptor agonists. (See "Glucagon-like peptide-1 receptor agonists for the treatment of type 2 diabetes mellitus", section on 'Microvascular outcomes'.)

Effect of insulin degludec and insulin glargine on hypoglycemia and CVD outcomes (July 2017)

Long-acting basal insulin preparations include glargine, detemir, and degludec. Several recent studies have compared outcomes for insulin degludec and insulin glargine.

In two similarly designed crossover trials comparing once-daily insulin degludec with insulin glargine in patients with type 1 and type 2 diabetes mellitus at high risk for hypoglycemia, the rate of overall symptomatic and nocturnal hypoglycemia was lower with degludec [7,8]. Limitations of the trials include a high rate of loss to follow-up and lack of generalizability to patients at lower risk for hypoglycemia.

In a two-year noninferiority trial comparing once-daily insulin degludec with insulin glargine in over 7500 patients with type 2 diabetes and cardiovascular disease, the primary cardiovascular composite outcome (death from cardiovascular causes, or first occurrence of a nonfatal myocardial infarction or nonfatal stroke) occurred in a similar proportion of patients (8.5 and 9.3 percent of the patients receiving degludec and glargine, respectively) [9]. Glycemic control was similar throughout the trial; rates of severe and nocturnal hypoglycemia were lower in patients taking degludec.

The choice of basal insulin (NPH, glargine, detemir, or degludec) primarily depends upon patient preference, lifestyle, and cost issues. (See "Insulin therapy in type 2 diabetes mellitus", section on 'Cardiovascular effects' and "Insulin therapy in type 2 diabetes mellitus", section on 'Basal insulin' and "Management of blood glucose in adults with type 1 diabetes mellitus", section on 'Basal insulin'.)

Racial variation in glycated hemoglobin (July 2017)

Several studies have shown that glycated hemoglobin (A1C) concentrations are higher in black than in white persons with diabetes, although it is uncertain if the difference is due to worse glycemic control or racial variation in the glycation of hemoglobin. In a prospective, 12-week study comparing A1C with mean glucose values measured by continuous glucose monitoring (CGM) in black and white persons with type 1 diabetes, both average CGM glucose (191 versus 180 mg/dL [10.6 versus 10 mmol/L]) and A1C (9.1 versus 8.3 percent) were higher in black than white individuals [10]. The mean A1C in black compared with white individuals was 0.4 percentage points higher for any given mean glucose concentration. The racial variation explained only a proportion of the difference in mean A1C levels between the two groups, with higher mean glucose values likely accounting for the rest. The small difference in A1C has not been shown to modify the association between A1C and microvascular and macrovascular outcomes, and diagnostic criteria and target A1C goals remain unchanged. (See "Estimation of blood glucose control in diabetes mellitus", section on 'Racial variation'.)

Canagliflozin in diabetic individuals with overt CVD (June 2017)

The cardiovascular effects of diabetes drugs have been evaluated in a growing number of trials. Two trials evaluated the effects of canagliflozin, compared with placebo, on cardiovascular, renal, and safety outcomes in patients with type 2 diabetes and high cardiovascular risk [11]. The primary composite cardiovascular outcome (cardiovascular mortality, nonfatal myocardial infarction, or nonfatal stroke), as well as progression of albuminuria, occurred in fewer patients in the canagliflozin group. However, there was an increase in the risk of lower limb amputations and fractures in the canagliflozin group, tempering enthusiasm for this drug. (See "Sodium-glucose co-transporter 2 inhibitors for the treatment of type 2 diabetes mellitus", section on 'Cardiovascular effects'.)

GLP-1-based therapies for type 2 diabetes and overall mortality (June 2017)

The effect of glucagon-like peptide-1 (GLP-1)-based therapies (GLP-1 receptor agonists and dipeptidyl peptidase-4 [DPP-4] inhibitors) on overall mortality in patients with type 2 diabetes is uncertain. In a systematic review and meta-analysis of 189 trials, there was no difference in all-cause mortality between any GLP-1-based therapy versus control (placebo or other antidiabetic drug) [12]. In subgroup analyses of the cardiovascular outcomes trials, there was a suggestion of reduced all-cause mortality with GLP-1 receptor agonists versus placebo, but no difference with DPP-4 inhibitors versus placebo. Further studies examining the effect of GLP-1 receptor agonists on overall mortality are warranted. (See "Glucagon-like peptide-1 receptor agonists for the treatment of type 2 diabetes mellitus" and "Dipeptidyl peptidase-4 (DPP-4) inhibitors for the treatment of type 2 diabetes mellitus".)

Screening interval for diabetic retinopathy (May 2017)

There are few data evaluating the optimal frequency of follow-up retinal examinations after initial screening in patients with diabetes, particularly type 1 diabetes. In an analysis of almost 24,000 retinopathy examinations over 24 years in the Diabetes Control and Complications Trial and Epidemiology of Diabetes Interventions and Complications study, the probability of progressing from lower to higher categories of retinopathy was dependent upon the previous retinal exam and glycated hemoglobin (A1C), with optimal screening intervals ranging from every three months among patients with severe nonproliferative retinopathy to every four years among those who had no retinopathy [13]. Compared with annual or biannual examinations, this model for an individualized schedule resulted in an overall reduction in the frequency of eye examinations and a substantial reduction in cost. (See "Diabetic retinopathy: Screening", section on 'Frequency of examinations'.)

FEMALE REPRODUCTION

Ovarian biomarkers for predicting ability to conceive (October 2017)

Serum anti-Müllerian hormone (AMH) and follicle stimulation hormone (FSH) levels are commonly measured to assess ovarian reserve in women wishing to conceive. However, a large prospective cohort study of women age 30 to 44 years, without a history of infertility, reported similar conception rates for women with normal and abnormal AMH and FSH levels [14]. This study adds to the body of evidence suggesting that AMH and FSH levels do not predict the probability of pregnancy in women without a diagnosis of infertility, even among women of older age. The study did not address conception rates for women with a known diagnosis of infertility. For women in this age group with known infertility who are considering in vitro fertilization, these tests do have some prognostic value. (See "Evaluation and management of infertility in women of advancing age", section on 'Diminished ovarian reserve'.)

Polycystic ovary syndrome: No role for metformin in ovulation induction (September 2017)

Metformin was widely used in the past for women with polycystic ovary syndrome (PCOS) for ovulation induction and prevention of miscarriage, multiple gestations, and pregnancy complications. However, the American Society for Reproductive Medicine now suggests that there is insufficient evidence to recommend metformin for any of these indications [15]. Unlike the first-line ovulation induction agents letrozole and clomiphene, which improve live birth rates, metformin increases ovulatory rates and pregnancy rates, but not live birth rates. (See "Metformin for treatment of the polycystic ovary syndrome", section on 'Anovulatory infertility'.)

Fertility preservation with cryopreserved ovarian tissue transplantation (July 2017)

For women at risk of ovarian failure due to planned gonadotoxic therapy and who desire fertility preservation, increasing evidence supports use of ovarian tissue cryopreservation followed by autotransplantation (OTT) after completion of therapy. In a 2017 meta-analysis, endocrine function was restored for at least four months after OTT in over 60 percent of women [16]. OTT was associated with similar live birth rates as conventional frozen embryo transfer, and over 60 percent of women who conceived after an orthotopic transplant conceived naturally. (See "Fertility preservation in patients undergoing gonadotoxic treatment or gonadal resection", section on 'Outcomes'.)

Menopausal hot flashes: A novel nonhormonal treatment (July 2017)

A neurokinin 3 receptor (NK3R) antagonist is a potential new nonhormonal therapy for menopausal hot flashes. In a randomized, crossover trial of an oral NK3R antagonist or placebo administered for four weeks each in symptomatic postmenopausal women, the average total weekly number of hot flashes decreased from approximately 85 at baseline to 20 and 50 in the treatment and placebo groups, respectively [17]. Residual hot flashes in the treatment group were also less severe and less bothersome. Three subjects in the treatment group had transient increases in transaminases that were asymptomatic and returned to baseline post-trial. Although results of this trial are encouraging, larger and longer duration trials are needed to determine the efficacy and safety of this drug. (See "Menopausal hot flashes", section on 'Neurokinin 3 receptor antagonist'.)

Primary ovarian insufficiency: ACOG statement on hormone therapy (June 2017)

Many clinicians have become reluctant to prescribe estrogen to women of any age based upon the safety concerns raised by clinical trials performed in older postmenopausal women (the Women's Health Initiative, WHI). The American College of Obstetrics and Gynecology issued a Committee Opinion on the importance of long-term hormone therapy in women with primary ovarian insufficiency (POI, menopause before age 40), for whom the results of the WHI are not applicable [18]. They recommend systemic hormone therapy for all women with POI without contraindications until age 50/51 years (the average age of natural menopause) for the multiple issues associated with estrogen deficiency (eg, treatment of symptoms [hot flashes, genitourinary atrophy, diminished quality of life], prevention of adverse health consequences [osteoporosis, early coronary heart disease, and dementia], and maintenance of normal sexual function). (See "Management of spontaneous primary ovarian insufficiency (premature ovarian failure)", section on 'Estrogen therapy'.)

Oral contraceptives and ovarian cancer risk (June 2017)

Use of oral estrogen-progestin contraceptives is associated with a reduction in risk of ovarian cancer. In the largest and longest duration study of oral contraceptive use, the Royal College of General Practitioners’ Oral Contraception Study followed over 46,000 women for up to 44 years and found that ever-use of oral contraceptives was associated with a 33 percent reduction in ovarian cancer risk [19]. This finding supports previous data and our recommendation for use of oral contraceptives in women who desire ovarian cancer risk reduction who have not undergone risk reduction surgery and who are not trying to conceive. (See "Risk-reducing bilateral salpingo-oophorectomy in women at high risk of epithelial ovarian and fallopian tubal cancer" and "Epithelial carcinoma of the ovary, fallopian tube, and peritoneum: Epidemiology and risk factors", section on 'Oral contraceptives'.)

Oral GnRH antagonist for endometriosis-related pain (May 2017)

Endometriosis can cause chronic debilitating dysmenorrhea and pelvic pain. In phase 3 trials, elagolix (a novel oral gonadotropin-releasing [GnRH] antagonist) reduced endometriosis-related dysmenorrhea and noncyclic pelvic pain compared with placebo at three months of treatment, and these reductions were sustained at six months of treatment [20]. Oral GnRH antagonists, such as elagolix, provide a treatment option for women who do not respond to standard oral therapies and are more convenient than intramuscular GnRH agonists. However, they are associated with hypoestrogenic side effects. (See "Endometriosis: Treatment of pelvic pain", section on 'Gonadotropin-releasing hormone (GnRH) antagonists'.)

OSTEOPOROSIS

Romosozumab for the treatment of postmenopausal osteoporosis (September 2017)

Romosozumab, an investigational sclerostin inhibitor, was compared with alendronate in a trial in over 4000 postmenopausal women with osteoporosis and a prior fragility fracture [21]. The experimental group received romosozumab monthly for 12 months followed by weekly alendronate for an additional 12 months; the control group received alendronate alone for 24 months. Radiographic vertebral fractures, as well as clinical fractures (nonvertebral and hip) were less frequent in the romosozumab group, but serious cardiovascular events (cardiac ischemia and stroke) occurred more commonly in the romosozumab group (0.8 versus 0.3 percent). Further investigation is warranted. (See "Overview of the management of osteoporosis in postmenopausal women", section on 'Emerging therapies'.)

Bisphosphonates not protective against breast cancer in postmenopausal women (August 2017)

Although some studies have suggested a protective effect of bisphosphonates against breast cancer, others, including a large observational cohort of over 64,000 postmenopausal women followed for approximately seven years [22], have not. Studies may be confounded by the frequent use of bisphosphonates to treat osteoporosis, and women with osteoporosis are more likely to have a lower estrogen environment and therefore a lower baseline risk of breast cancer regardless of bisphosphonate exposure. (See "Factors that modify breast cancer risk in women", section on 'Bisphosphonates'.)

THYROID DISORDERS

Thyroid hormone assay interference with biotin supplements (October 2017)

A growing number of reports have noted that ingestion of 5 to 10 mg of biotin (marketed over the counter to prevent hair loss) can cause artifactually low serum thyroid stimulating hormone (TSH) and high triiodothyronine (T3) and thyroxine (T4) in assays using biotin-streptavidin affinity systems in their design [23,24]. Thyroid tests should be repeated at least two days after discontinuation of biotin supplements. (See "Laboratory assessment of thyroid function", section on 'Assay interference with biotin ingestion'.)

VITAMIN D

Vitamin D and all-cause mortality in patients with advanced heart failure (August 2017)

Some, but not all, observational studies suggest that low 25-hydroxyvitamin D levels (especially <10 to 20 ng/mL [25 to 50 nmol/L]) are associated with higher mortality. There are few randomized trials of vitamin D supplementation with mortality as a primary endpoint. In one such trial, vitamin D supplementation (4000 international units daily for three years) compared with placebo did not reduce overall mortality in patients with advanced heart failure and baseline vitamin D levels <30 ng/dL (75 nmol/L) [25]. (See "Vitamin D and extraskeletal health", section on 'Mortality'.)

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REFERENCES

  1. Beck RW, Riddlesworth TD, Ruedy K, et al. Continuous Glucose Monitoring Versus Usual Care in Patients With Type 2 Diabetes Receiving Multiple Daily Insulin Injections: A Randomized Trial. Ann Intern Med 2017; 167:365.
  2. Feig DS, Donovan LE, Corcoy R, et al. Continuous glucose monitoring in pregnant women with type 1 diabetes (CONCEPTT): a multicentre international randomised controlled trial. Lancet 2017.
  3. Garg SK, Henry RR, Banks P, et al. Effects of Sotagliflozin Added to Insulin in Patients with Type 1 Diabetes. N Engl J Med 2017.
  4. Nadkarni GN, Ferrandino R, Chang A, et al. Acute Kidney Injury in Patients on SGLT2 Inhibitors: A Propensity-Matched Analysis. Diabetes Care 2017; 40:1479.
  5. Aminian A, Brethauer SA, Andalib A, et al. Individualized Metabolic Surgery Score: Procedure Selection Based on Diabetes Severity. Ann Surg 2017; 266:650.
  6. Mann JFE, Ørsted DD, Brown-Frandsen K, et al. Liraglutide and Renal Outcomes in Type 2 Diabetes. N Engl J Med 2017; 377:839.
  7. Lane W, Bailey TS, Gerety G, et al. Effect of Insulin Degludec vs Insulin Glargine U100 on Hypoglycemia in Patients With Type 1 Diabetes: The SWITCH 1 Randomized Clinical Trial. JAMA 2017; 318:33.
  8. Wysham C, Bhargava A, Chaykin L, et al. Effect of Insulin Degludec vs Insulin Glargine U100 on Hypoglycemia in Patients With Type 2 Diabetes: The SWITCH 2 Randomized Clinical Trial. JAMA 2017; 318:45.
  9. Marso SP, McGuire DK, Zinman B, et al. Efficacy and Safety of Degludec versus Glargine in Type 2 Diabetes. N Engl J Med 2017; 377:723.
  10. Bergenstal RM, Gal RL, Connor CG, et al. Racial Differences in the Relationship of Glucose Concentrations and Hemoglobin A1c Levels. Ann Intern Med 2017; 167:95.
  11. Neal B, Perkovic V, Mahaffey KW, et al. Canagliflozin and Cardiovascular and Renal Events in Type 2 Diabetes. N Engl J Med 2017; 377:644.
  12. Liu J, Li L, Deng K, et al. Incretin based treatments and mortality in patients with type 2 diabetes: systematic review and meta-analysis. BMJ 2017; 357:j2499.
  13. DCCT/EDIC Research Group, Nathan DM, Bebu I, et al. Frequency of Evidence-Based Screening for Retinopathy in Type 1 Diabetes. N Engl J Med 2017; 376:1507.
  14. Steiner AZ, Pritchard D, Stanczyk FZ, et al. Association Between Biomarkers of Ovarian Reserve and Infertility Among Older Women of Reproductive Age. JAMA 2017; 318:1367.
  15. Practice Committee of the American Society for Reproductive Medicine. Electronic address: ASRM@asrm.org, Practice Committee of the American Society for Reproductive Medicine. Role of metformin for ovulation induction in infertile patients with polycystic ovary syndrome (PCOS): a guideline. Fertil Steril 2017; 108:426.
  16. Pacheco F, Oktay K. Current Success and Efficiency of Autologous Ovarian Transplantation: A Meta-Analysis. Reprod Sci 2017; 24:1111.
  17. Prague JK, Roberts RE, Comninos AN, et al. Neurokinin 3 receptor antagonism as a novel treatment for menopausal hot flushes: a phase 2, randomised, double-blind, placebo-controlled trial. Lancet 2017; 389:1809.
  18. Committee on Gynecologic Practice. Committee Opinion No. 698: Hormone Therapy in Primary Ovarian Insufficiency. Obstet Gynecol 2017; 129:e134.
  19. Iversen L, Sivasubramaniam S, Lee AJ, et al. Lifetime cancer risk and combined oral contraceptives: the Royal College of General Practitioners' Oral Contraception Study. Am J Obstet Gynecol 2017; 216:580.e1.
  20. Taylor HS, Giudice LC, Lessey BA, et al. Treatment of Endometriosis-Associated Pain with Elagolix, an Oral GnRH Antagonist. N Engl J Med 2017; 377:28.
  21. Saag KG, Petersen J, Brandi ML, et al. Romosozumab or Alendronate for Fracture Prevention in Women with Osteoporosis. N Engl J Med 2017; 377:1417.
  22. Fournier A, Mesrine S, Gelot A, et al. Use of Bisphosphonates and Risk of Breast Cancer in a French Cohort of Postmenopausal Women. J Clin Oncol 2017; 35:3230.
  23. Li D, Radulescu A, Shrestha RT, et al. Association of Biotin Ingestion With Performance of Hormone and Nonhormone Assays in Healthy Adults. JAMA 2017; 318:1150.
  24. Sharma A, Baumann NA, Shah P. Biotin-Induced Biochemical Graves Disease: A Teachable Moment. JAMA Intern Med 2017; 177:571.
  25. Zittermann A, Ernst JB, Prokop S, et al. Effect of vitamin D on all-cause mortality in heart failure (EVITA): a 3-year randomized clinical trial with 4000 IU vitamin D daily. Eur Heart J 2017; 38:2279.
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