Ann J. Brown

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.

Constitutional rearrangements of chromosome 22 as a cause of neurofibromatosis 2.

Neurofibromatosis type 2 (NF2) is an autosomal dominant condition characterised by vestibular schwannomas, schwannomas of other cranial nerves, meningiomas, and other low grade brain malignancies.1 The severity of NF2 is variable, with some patients having early onset disease and more rapidly growing tumours that occur in greater numbers. The NF2 gene is on chromosome 22q12.2,3 The protein product (termed merlin or schwannomin) is a cell cytoskeleton associating protein. Genotype−phenotype correlations have been demonstrated, with missense mutations and large deletions causing mild disease, and nonsense or frameshift mutations causing severe disease.4,5 The current mutation screening techniques of single strand conformation polymorphism analysis (SSCP), protein truncation test, and denaturing gradient gel electrophoresis detect 33–65% of mutations, although adding a deletion strategy increases the proportion to 80%.6 However, deletion testing and chromosome analysis are rarely reported in studies of NF2 mutations. In this study, we present five NF2 patients for whom chromosome analysis, usually following routine molecular screening, revealed the underlying genetic aberration. ### Case 1 A 20 year old female was referred with a large diffuse goitre commencing early in puberty, moderate learning difficulties, and bilateral sensorineural hearing loss, which resembles the phenotype of Pendred’s syndrome. She was born after a normal pregnancy and delivery. Her physical and mental development during early infancy was not remarkable, but developmental delay became apparent in the second year of life. Growth parameters were within the normal range. She began to walk at the age of 3 years. Six months later, audiometric tests showed no hearing impairment although chronic otitis media was diagnosed on one side. According to the parents, her communication had been improving with age, but her speech remained dysarthric and her articulation was very poor. In primary school, she had sub-average grades in all subjects. Her affect was good and …

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.

Can individuals meet multiple physical activity and dietary behavior goals

OBJECTIVES To examine whether participants with the most behavioral goals to achieve were more likely to meet more goals than those given fewer goals. METHODS Eight hundred ten participants were randomly assigned to advice-only, established guidelines for blood pressure control (reduced sodium, increased physical activity), or established guidelines plus the DASH diet (increased fruits, vegetables, low-fat dairy, reduced fat). RESULTS At 6 months, 11.7% of Advice-Only, 19.3% of Established, and 44.6% of Established plus DASH met at least 3 goals (P<0.0001). At 18 months, 33.5% of Established plus DASH met at least 3 goals. CONCLUSIONS Those with the most goals to achieve reached the most goals.

Depression and insulin resistance: applications to polycystic ovary syndrome.

In healthy people, depression can cause or exacerbate clinical symptoms such as fatigue, poor sleep, and changes in appetite and weight. But in those with chronic illness, depression can have more insidious consequences, influencing the expression and course of disease. One important and common disorder that underlies many different chronic diseases is insulin resistance. This disorder of carbohydrate and fat metabolism is a precursor to type 2 diabetes and contributes to chronic illnesses such as coronary heart disease, hypertension, hyperlipidemia, and the metabolic syndrome. Insulin resistance also has plausible physiologic links with depression, perhaps through a common responsiveness to agents such as cortisol, epinephrine and norepinephrine, and serotonin. Interesting clinical evidence linking depression with insulin-resistant disorders has been published in recent years, strengthening the association between these 2 common conditions. This review will discuss the epidemiologic and clinical trial data exploring insulin resistance, diabetes, and depression. It will highlight one facet of this literature: the association between depression and polycystic ovary syndrome (PCOS), a common insulin-resistant condition affecting young women.

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.

Multidisciplinary Mentoring Programs to Enhance Junior Faculty Research Grant Success

PROBLEM Junior faculty face challenges in establishing independent research careers. Declining funding combined with a shift to multidisciplinary, collaborative science necessitates new mentorship models and enhanced institutional support. APPROACH Two multidisciplinary mentorship programs to promote grant success for junior faculty were established at the Duke University School of Medicine beginning in 2011. These four-month programs-the Path to Independence Program (PtIP) for National Institutes of Health (NIH) R applicants and the K Club for NIH K applicants-use multiple senior faculty mentors and professional grant-writing staff to provide a 20-hour joint curriculum comprising a series of lectures, hands-on workshops, career development counseling, peer groups, and an internal study section. In March 2016, the authors analyzed the success rate for all NIH grants submitted by participants since program enrollment. In a 2015 postprogram survey, participants rated their feelings of support and competency across six skill factors. OUTCOMES From October 2011 to March 2016, the programs engaged 265 senior faculty mentors, 145 PtIP participants, and 138 K Club participants. Success rates for NIH grant applications were 28% (61 awards/220 decisions) for PtIP participants-an increase over the 2010 Duke University junior faculty baseline of 11%-and 64% (38/59) for K Club participants. Respondents reported significantly increased feelings of support and self-ratings for each competency post program. NEXT STEPS The authors plan to expand the breadth of both the mentorship pool and faculty served. Broad implementation of similar programs elsewhere could bolster success, satisfaction, and retention of junior faculty investigators.

Challenges and opportunities for recruiting a new generation of neurosurgeons.

SEVERAL FACTORS HAVE converged to raise concern among program directors about attracting and training the next generation of neurosurgeons. These include the relatively new duty-hour regulations, the projected physician shortage, and the preference of many current medical students for controllable lifestyles. Attracting top talent into training programs may require innovations geared to Generation X such as policies supporting work–life balance, flexible work options, lots of feedback, mentoring programs, talented leadership, and standardized communication strategies during patient handoffs. Larger programmatic changes may also be needed such as “competency-based” training and additional years of training for mastery of highly specialized procedures.

Sexual Dysfunction in Women with Type 2 Diabetes

Many women with type 2 diabetes report symptoms of female sexual dysfunction (FSD). Although sexual dysfunction is a well-established complication of type 2 diabetes in men, it has not been well-studied in women with diabetes. Information on the prevalence and etiology of FSD in diabetes is increasing but still sparse. Because few studies have examined FSD in type 2 diabetes exclusively, in this chapter we review available literature in both type 1 and type 2 diabetes.