THE EFFECTS OF PERIOPERATIVE DEXAMETHASONE ON GLYCEMIC CONTROL AND POSTOPERATIVE OUTCOMES.

Objective: Perioperative glucocorticoids are commonly given to reduce pain and nausea in patients undergoing surgery. However, the glycemic effects of steroids and the potential effects on morbidity and mortality have not been systematically evaluated. This study investigated the association between perioperative dexamethasone and postoperative blood glucose, hospital length of stay (LOS), readmission rates, and 90-day survival. Methods: Data from 4,800 consecutive orthopedic surgery patients who underwent surgery between 2000 and 2016 within a single health system were analyzed retrospectively. Results: Patients with and without diabetes mellitus (DM) who were given a single dose of dexamethasone had higher rates of hyperglycemia during the first 24 hours after surgery as compared to those who did not receive dexamethasone (hazard ratio [HR] was 1.81, and 95% confidence interval [CI] was [1.46, 2.24] for the DM cohort; HR 2.34, 95% CI [1.66, 3.29] for the nonDM cohort). LOS was nearly 1 day shorter in patients who received dexamethasone (geometric mean ratio [GMR] 0.79, 95% CI [0.75, 0.83] for patients with DM; GMR 0.75, 95% CI [0.72, 0.79] for patients without DM), and there was no difference in 90-day readmission rates. In patients without DM, dexamethasone was associated with a higher 90-day overall survival (99.07% versus 96.90%; P = .004). Conclusion: In patients with and without DM who undergo orthopedic surgery, perioperative dexamethasone was associated with a transiently higher risk of hyperglycemia. However, dexamethasone treatment was associated with a shorter LOS in patients with and without DM, and a higher overall 90-day survival rate in patients without DM, compared to patients who did not receive dexamethasone. Abbreviations: BMI = body mass index; CAD = coronary artery disease; CI = confidence interval; DM = diabetes mellitus; GMR = geometric mean ratio; HR = hazard ratio; IV = intravenous; LOS = length of stay; POD = postoperative day.

Development and Implementation of a Perioperative Blood Glucose Monitoring Protocol for Patients Undergoing Spinal Surgery.

PURPOSE: Stress-induced hyperglycemia during the perioperative period is associated with adverse outcomes after spinal surgery, which increases both patient-related burden and hospital costs. This quality improvement project describes the development and implementation of a perioperative blood glucose monitoring protocol for patients undergoing spinal surgery. DESIGN: An evidence-based perioperative blood glucose monitoring protocol was developed by a multidisciplinary committee of specialists in endocrinology and anesthesiology with utilization of the American Diabetes Association diabetes screening criteria. METHODS: The protocol was implemented in the perioperative areas of a regional hospital in the Southeastern United States. The project sample included patients with and without a prior diagnosis of diabetes who met protocol inclusion criteria during a 3-month implementation period. FINDINGS: Preoperative glycated hemoglobin (HbA1c) testing identified more than 54% of previously undiagnosed patients with levels consistent with either prediabetes or diabetes according to the American Diabetes Association criteria for diagnosis. Patients with diabetes and those without diabetes experienced a perioperative increase in blood glucose with levels remaining elevated above preoperative baseline through postoperative day 1. CONCLUSIONS: A perioperative blood glucose monitoring protocol enables preoperative identification of patients with undiagnosed prediabetes and diabetes, allowing for optimization before elective surgery and establishment of appropriate postoperative follow-up care. In addition, a blood glucose monitoring protocol increases the detection of perioperative hyperglycemia and may lead to a reduction in postoperative complications after spinal surgery.

Technosphere insulin: inhaled prandial insulin.

INTRODUCTION: Insulin therapy is a mainstay for treatment of diabetes mellitus; however, many barriers to insulin exist. Insulin human inhalation powder (technosphere insulin) is a new FDA-approved alternative to subcutaneous bolus insulin. AREAS COVERED: This is an overview of technosphere insulin (TI). Pharmacokinetics, clinical efficacy, safety and tolerability are discussed. EXPERT OPINION: TI is more quickly absorbed than subcutaneous insulin therapies and has a shorter duration of action. It appears to be noninferior compared with subcutaneous insulin regimens, and is associated with less hypoglycemia. Thus, it may serve as an alternative insulin agent in patients reluctant to administer multiple subcutaneous injections of insulin daily or in patients who experience late postprandial hypoglycemia with subcutaneous insulin. Cough is the most common side effect, but tends to be mild and transient. A small decrease in the forced expiratory volume has been demonstrated, but does not appear to progress and is reversible. Patients should have periodic pulmonary function tests. TI is contraindicated in patients with chronic lung disease. The long-term risk of lung cancer is being monitored but at this point does not appear to be higher than the expected incidence of lung cancer in this population.

Review of nonalcoholic fatty liver disease in women with polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in reproductive-aged women. Women with PCOS frequently have metabolic complications including insulin resistance (IR), early diabetes, hypertension and dyslipidemia. Recent studies have demonstrated an association between PCOS and another metabolic complication: nonalcoholic fatty liver disease (NAFLD). NAFLD occurs as a result of abnormal lipid handling by the liver, which sensitizes the liver to injury and inflammation. It can progress to nonalcoholic steatohepatitis (NASH), which is characterized by hepatocyte injury and apoptosis. With time and further inflammation, NASH can progress to cirrhosis. Thus, given the young age at which NAFLD may occur in PCOS, these women may be at significant risk for progressive hepatic injury over the course of their lives. Many potential links between PCOS and NAFLD have been proposed, most notably IR and hyperandrogenemia. Further studies are needed to clarify the association between PCOS and NAFLD. In the interim, clinicians should be aware of this connection and consider screening for NAFLD in PCOS patients who have other metabolic risk factors. The optimal method of screening is unknown. However, measuring alanine aminotransferase and/or obtaining ultrasound on high-risk patients can be considered. First line treatment consists of lifestyle interventions and weight loss, with possible pharmacologic interventions in some cases.

Polycystic ovary syndrome: update on diagnosis and treatment.

Polycystic ovary syndrome is now a well-recognized condition affecting 6%-25% of reproductive-aged women, depending on the definition. Over the past 3 decades, research has launched it from relative medical obscurity to a condition increasingly recognized as common in internal medicine practices. It affects multiple systems, and requires a comprehensive perspective on health care for effective treatment. Metabolic derangements and associated complications include insulin resistance and diabetes, hyperlipidemia, hypertension, fatty liver, metabolic syndrome, and sleep apnea. Reproductive complications include oligo-/amenorrhea, sub-fertility, endometrial hyperplasia, and cancer. Associated psychosocial concerns include depression and disordered eating. Additionally, cosmetic issues include hirsutism, androgenic alopecia, and acne. This review organizes this multi-system approach around the mnemonic "MY PCOS" and discusses evaluation and treatment options for the reproductive, cosmetic, and metabolic complications of this condition.

Screening for glucose intolerance in polycystic ovary syndrome: hemoglobin A1C, fasting blood glucose or oral glucose tolerance test?

Polycystic ovary syndrome (PCOS) is a chronic condition with many reproductive, metabolic and psychological manifestations. Insulin resistance puts women with PCOS at an increased risk for developing impaired glucose tolerance (IGT) and diabetes (T2D). An oral glucose tolerance test is the preferred IGT/T2D screening test, since it is most sensitive for detecting early glucose abnormalities. The goals in detecting IGT in these women are to avoid progression to T2D, modify cardiovascular risk and prevent gestational diabetes. Periodic IGT/T2D rescreening is necessary, given their propensity for more rapid deterioration in glucose tolerance. Lifestyle intervention is first-line therapy for PCOS women with IGT. Metformin is an option if lifestyle intervention fails to have an impact, while bariatric surgery is reserved for a select set of morbidly obese patients.

Higher high-density lipoprotein cholesterol in African-American women with polycystic ovary syndrome compared with Caucasian counterparts.

CONTEXT: Studies have demonstrated lipid differences among African-Americans and Caucasians and between women with polycystic ovary syndrome (PCOS) and normally ovulating women. However, few studies have examined racial differences in lipoprotein levels in women with PCOS. OBJECTIVE: This study compared lipoprotein levels in African-American and Caucasian women with PCOS. DESIGN AND SETTING: We performed a retrospective chart review of 398 subjects seen as new patients for PCOS at the Duke University Medical Center Endocrinology Clinic in Durham, NC. PATIENTS: We identified 126 charts appropriate for review, based on a diagnosis of PCOS (using the 1990 National Institutes of Health criteria), a self-reported race of either Caucasian or African-American, and a body mass index (BMI) higher than 25. We excluded patients taking glucophage, oral contraceptives, or lipid-lowering medications. MAIN OUTCOME MEASURE: Age, BMI, total cholesterol, high-density lipoprotein (HDL) cholesterol, non-HDL cholesterol, random triglycerides (TG), and oral glucose tolerance test measurements were collected and included in the analysis. RESULTS: African-American women with PCOS had higher HDL cholesterol levels (52.6 vs. 47.5 mg/dl, P = 0.019), lower non-HDL cholesterol (134.1 vs. 154.6 mg/dl, P = 0.046), and lower TG levels (97.5 vs. 168.2 mg/dl, P < 0.001) than Caucasian women. These differences could not be attributed to age, BMI, or differences in insulin resistance as determined by homeostasis model assessment of insulin resistance. CONCLUSION: African-American women with PCOS appear to have a more favorable lipid profile than Caucasian women with PCOS having higher HDL cholesterol, lower non-HDL cholesterol, and lower TG when BMI and insulin resistance are equal.

Effects of exercise on lipoprotein particles in women with polycystic ovary syndrome.

PURPOSE: Women with polycystic ovary syndrome (PCOS) commonly have insulin resistance. Insulin resistance is associated with marked abnormalities of lipoprotein size and subclass particle concentration. The purpose of this study was to examine the effects of a moderate-intensity exercise program without weight loss on lipoprotein profiles in women with PCOS. METHODS: Thirty-seven sedentary PCOS women were randomized to either an 8- to 12-wk ramp-up followed by a 12-wk moderate-intensity exercise program (16-24 wk total, approximately 228 min x wk at 40-60% peak V x O2, n = 21) or control (no change in lifestyle, n = 16). PCOS was defined as or=8). Fasting lipoprotein profiles were obtained before and after the intervention. Nuclear magnetic resonance spectroscopy was used to quantify the following: average particle size, total and subclass concentrations of HDL, LDL, and VLDL particles, and calculated HDL cholesterol, triglycerides, and VLDL triglycerides. Wilcoxon exact rank sums tests were used to compare changes in these parameters in the exercise group relative to controls. RESULTS: Twenty women (8 exercisers, 12 controls) completed the study. Comparing exercisers to controls, significant changes were seen in concentrations of the following lipoprotein parameters that are associated with decreased insulin resistance: decreased large VLDL (P = 0.007), calculated triglycerides (P = 0.003), VLDL triglycerides (P = 0.003), and medium/small HDL (P = 0.031) and increased large HDL (P = 0.002) and average HDL size (P = 0.001). CONCLUSIONS: In this trial, moderate-intensity exercise without significant weight loss improved several components of the lipoprotein profiles of women with PCOS. These findings support the beneficial role of moderate exercise in this high-risk population.

Polycystic ovary syndrome: diagnosis and treatment.

Polycystic ovary syndrome affects 6%-7% of reproductive-aged women, making it the most common endocrine disorder in this population. It is characterized by chronic anovulation and hyperandrogenism. Affected women may present with reproductive manifestations such as irregular menses or infertility, or cutaneous manifestations, including hirsutism, acne, or male-pattern hair loss. Over the past decade, several serious metabolic complications also have been associated with polycystic ovary syndrome including type 2 diabetes mellitus, metabolic syndrome, sleep apnea, and possibly cardiovascular disease and nonalcoholic fatty liver disease. In addition to treating symptoms by regulating menstrual cycles and improving hyperandrogenism, it is imperative that clinicians recognize and treat metabolic complications. Lifestyle therapies are first-line treatment in women with polycystic ovary syndrome, particularly if they are overweight. Pharmacological therapies are also available and should be tailored on an individual basis. This article reviews the diagnosis, clinical manifestations, metabolic complications, and treatment of the syndrome. A table summarizing treatment recommendations is provided.

Nonalcoholic steatohepatitis and nonalcoholic Fatty liver disease in young women with polycystic ovary syndrome.

CONTEXT: Nonalcoholic fatty liver disease and polycystic ovary syndrome (PCOS) are both associated with insulin resistance. Thus, women with PCOS may have an increased prevalence of nonalcoholic fatty liver disease, including nonalcoholic steatohepatitis (NASH). OBJECTIVE: The objective of the study was to determine the prevalence and characteristics of NASH and abnormal aminotransferase activity in women with PCOS. DESIGN: The study is a retrospective chart review. SETTING: The setting is an academic endocrinology clinic. PATIENTS: Patients were 200 women with PCOS, defined as irregular menses and hyperandrogenism. MAIN OUTCOME MEASURES: Biopsy-documented NASH and aminotransferase levels were the main outcome measures. RESULTS: Fifteen percent (29 of 200) had aspartate aminotransferase and/or alanine aminotransferase more than 60 U/liter. Women with aminotransferase elevations had lower high-density lipoprotein (HDL) (41 vs. 50 mg/dl, P = 0.006), higher triglycerides (174 vs. 129 mg/dl, P = 0.024), and higher fasting insulin (21 vs. 12 microIU/ml, P = 0.036) compared with women with normal aminotransferases. Six women (mean age 29 yr) with persistent aminotransferase elevations underwent liver biopsy. All six had NASH with fibrosis. Compared with the 194 of 200 PCOS women who did not undergo biopsy, women with biopsy-documented NASH had lower HDL (median 34 vs. 50 mg/dl, P < 0.001), and higher triglycerides (245 vs. 132 mg/dl, P = 0.025), fasting insulin (26 vs. 13 microIU/ml, P = 0.038), aspartate aminotransferase (144 vs. 22 U/liter, P < 0.001), and alanine aminotransferase (143 vs. 28 U/liter, P < 0.001). CONCLUSION: Abnormal aminotransferase activity is common in women with PCOS. Low HDL, high triglycerides, and high fasting insulin were associated with abnormal aminotransferase activity. Some women already had evidence of NASH with fibrosis. Further studies are needed to evaluate whether to screen PCOS women for liver disease at an earlier age than is currently recommended for the general population.

Polycystic ovary syndrome and severe nonalcoholic steatohepatitis: beneficial effect of modest weight loss and exercise on liver biopsy findings.

OBJECTIVE: To report a case of biopsy-documented nonalcoholic steatohepatitis (NASH), which improved appreciably through moderate exercise and weight loss in a young woman with polycystic ovary syndrome (PCOS) and insulin resistance. METHODS: We present a detailed case report, including laboratory and pathologic findings. In addition, we review the recent literature regarding the association of insulin resistance with NASH and PCOS. RESULTS: A 24-year-old woman was referred to the Duke Gastroenterology Clinic for evaluation of long-term high serum aminotransferase levels. She also reported a history of chronically irregular menses, infertility, and hirsutism and was diagnosed with PCOS. Subsequent glucose tolerance testing suggested the presence of insulin resistance. Liver biopsy findings were consistent with severe nonalcoholic steatohepatitis. Under the supervision of her physician and an exercise physiologist, the patient initiated a diet and exercise program that resulted in an 11.5% weight loss during approximately 8 months and yielded normalization of her aminotransferase levels. A repeat liver biopsy done 13 months after the initial biopsy revealed a substantial decrease in steatosis and a reduction in inflammation. CONCLUSION: Women with PCOS and insulin resistance have an increased risk of developing many of the consequences of the dysmetabolic syndrome, including type 2 diabetes, hypertension, and hyperlipidemia. This case report suggests that fatty liver and NASH may be other important diseases to identify in such women. It also demonstrates the improvement in this condition with moderate exercise and weight loss.