Tracy L. Setji

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 menses per year and hyperandrogenism (biochemical or clinical with Ferriman-Gallwey score >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.

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 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.

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.

Sodium–Glucose Cotransporter 2 Inhibitors and Diabetic Ketoacidosis: A Case Series From Three Academic Institutions

Sodium–glucose cotransporter 2 inhibitors (SGLT2i) have recently been associated with diabetic ketoacidosis (DKA). Initial case reports were largely among patients using SGLT2i off label in the setting of type 1 diabetes and were unusual because of limited associated hyperglycemia (1). More recently, the problem has been specifically noted in patients with type 2 diabetes (2). Meta-analysis of data from initial randomized controlled trials of SGLT2i suggests little risk of DKA (<0.1%) in patients with type 2 diabetes (3). To better define the scope of the problem in clinical practice, we conducted a search of three academic health care systems’ electronic health records. The study was approved by institutional review boards. Patients were selected from all emergency and inpatient encounters between 1 January 2013 and 30 April 2016 that contained the diagnosis codes for ketosis or acidosis (ICD-9 …

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.

Albiglutide: clinical overview of a long-acting GLP-1 receptor agonist in the treatment of Type 2 diabetes

Glucagon-like peptide-1 receptor agonists have become an important therapeutic option for patients with Type 2 diabetes because of their ability to lower blood glucose and help patients lose weight. There are currently three glucagon-like peptide-1 receptor agonists on the market. In the near future, albiglutide will undergo review by the US FDA for possible approval. Results from Phase I/II trials have demonstrated that albiglutide is a safe and efficacious medication for treating Type 2 diabetes. It lowers hemoglobin A1c and decreases bodyweight. It appears to have fewer gastrointestinal side effects than liraglutide. The once-weekly (or possibly longer duration) dosing of albiglutide may improve adherence. Several Phase III trials are expected to be completed in 2013. These trials will shed further light on the safety and efficacy of albiglutide.

Managing hyperglycemia and diabetes in patients receiving enteral feedings: A health system approach

Abstract Evidence of poor outcomes in hospitalized patients with hyperglycemia has led to new and revised guidelines for inpatient management of diabetes. As providers become more aware of the need for better blood glucose control, they are finding limited guidance in the management of patients receiving enteral nutrition. To address the lack of guidelines in this population, Duke University Health System has developed a consistent practice for managing such patients. Here, we present our practice strategies for insulin use in patients receiving enteral nutrition. Essential factors include assessing the patients’ history of diabetes, hyperglycemia, or hypoglycemia and timing and type of feedings. Insulin practices are then designed to address these issues keeping in mind patient safety in the event of abrupt cessation of nutrition. The outcome of the process is a consistent and safe method for glucose control with enteral nutrition.

Effect of A1C and Glucose on Postoperative Mortality in Noncardiac and Cardiac Surgeries

OBJECTIVE Hemoglobin A1c (A1C) is used in assessment of patients for elective surgeries because hyperglycemia increases risk of adverse events. However, the interplay of A1C, glucose, and surgical outcomes remains unclarified, with often only two of these three factors considered simultaneously. We assessed the association of preoperative A1C with perioperative glucose control and their relationship with 30-day mortality. RESEARCH DESIGN AND METHODS Retrospective analysis on 431,480 surgeries within the Duke University Health System determined the association of preoperative A1C with perioperative glucose (averaged over the first 3 postoperative days) and 30-day mortality among 6,684 noncardiac and 6,393 cardiac surgeries with A1C and glucose measurements. A generalized additive model was used, enabling nonlinear relationships. RESULTS A1C and glucose were strongly associated. Glucose and mortality were positively associated for noncardiac cases: 1.0% mortality at mean glucose of 100 mg/dL and 1.6% at mean glucose of 200 mg/dL. For cardiac procedures, there was a striking U-shaped relationship between glucose and mortality, ranging from 4.5% at 100 mg/dL to a nadir of 1.5% at 140 mg/dL and rising again to 6.9% at 200 mg/dL. A1C and 30-day mortality were not associated when controlling for glucose in noncardiac or cardiac procedures. CONCLUSIONS Although A1C is positively associated with perioperative glucose, it is not associated with increased 30-day mortality after controlling for glucose. Perioperative glucose predicts 30-day mortality, linearly in noncardiac and nonlinearly in cardiac procedures. This confirms that perioperative glucose control is related to surgical outcomes but that A1C, reflecting antecedent glycemia, is a less useful predictor.

Patient Self-Management of Diabetes Care in the Inpatient Setting: Pro.

Patients should be allowed to manage their diabetes in the hospital. Diabetes mellitus is a common and sometimes difficult to control medical issue in hospitalized patients. Oftentimes patients who have been controlling their diabetes well as an outpatient are not allowed to continue this management on the inpatient setting, which can lead to hypo- and hyperglycemia. Involving the patient in his or her diabetes care, including self-management in select patients, may provide a safe and effective way of improving glycemic control and patient satisfaction. This may particularly benefit the dosing and coordination of meal-time