Edmond P. Wickham

Sex hormone-binding globulin and type 2 diabetes mellitus

Sex hormone-binding globulin (SHBG) has emerged as one of the multiple genetic and environmental factors that potentially contribute to the pathophysiology of type 2 diabetes mellitus (T2DM). In addition to epidemiologic studies demonstrating a consistent relationship between decreased levels of serum SHBG and incident T2DM, recent genetic studies also reveal that transmission of specific polymorphisms in the SHBG gene influence the risk of T2DM. At the molecular level, the multiple interactions between SHBG and its receptors in various target tissues suggest physiologic roles for SHBG that are more complex than the simple transport of sex hormones in serum. Taken together, these data provide support for an expanded role of SHBG in the pathophysiology of insulin resistance and T2DM.

Polymorphisms in the SHBG Gene Influence Serum SHBG Levels in Women with Polycystic Ovary Syndrome

CONTEXT Single-nucleotide polymorphisms (SNPs) in the SHBG gene are associated with type 2 diabetes mellitus. SHBG has also been proposed as a candidate gene for the polycystic ovary syndrome (PCOS). OBJECTIVE The study aims were 1) to determine whether any of four SHBG SNPs (rs1779941, rs6297, rs6259, and rs727428) are associated with PCOS and 2) to determine whether SNP genotype influences SHBG levels in PCOS women. DESIGN Using the transmission disequilibrium test, evidence of associations between SHBG SNPs and PCOS were analyzed. Additionally, correlations between SHBG levels and SNP genotype, body mass index, non-SHBG-bound testosterone, and insulin resistance estimated by the homeostasis model were determined. SETTING The study was conducted at academic medical centers. PATIENTS OR OTHER PARTICIPANTS A total of 430 families having a proband with PCOS were included in the family-based study. Associations between SNP genotypes, SHBG, and metabolic parameters were determined in 758 women with PCOS including probands from the family cohort. MAIN OUTCOME MEASURES Primary outcome measures included transmission frequency of SNP alleles and correlation coefficients between SHBG and allele frequency/metabolic parameters. RESULTS No evidence of association between SNPs of interest and PCOS was found. However, in multivariate analyses, SHBG levels varied significantly with rs1799941 and rs727428 genotype after controlling for body mass index, non-SHBG-bound testosterone, and homeostasis model for insulin resistance. CONCLUSIONS Although SHBG SNPs associated with type 2 diabetes mellitus do not appear to be associated with PCOS status, rs1799941 and rs727428 genotypes are associated with SHBG levels independent of the effects of insulin resistance and obesity.

Motivational interviewing targeting diet and physical activity improves adherence to paediatric obesity treatment: results from the MI Values randomized controlled trial.

Adherence is a challenge in obesity treatment. Motivational interviewing (MI) may promote patient adherence. MI Values is a randomized controlled trial of MI implemented as an adjunct to an adolescent obesity treatment [Teaching Encouragement Exercise Nutrition Support (T.E.E.N.S.)].

Prevalence of the metabolic syndrome among obese adolescents enrolled in a multidisciplinary weight management program: clinical correlates and response to treatment.

OBJECTIVE The aim of this study was to determine the prevalence of the metabolic syndrome at baseline and after 6 months of lifestyle modification among obese adolescents referred to a multidisciplinary weight management program. METHODS A total of 165 obese adolescents were evaluated at baseline, and measurements were repeated in 57 subjects who completed 6 months of the program. Metabolic syndrome was defined as having three or more of the following: a body mass index (BMI) >97(th) percentile, hypertension, low high-density lipoprotein cholesterol (HDL-C), hypertriglyceridemia, and impaired fasting glucose (IFG). RESULTS The prevalence of a BMI >97(th) percentile, hypertension, hypertriglyceridemia, low HDL-C, and IFG was 92.7, 54.5, 29.1, 26.7, and 2.4%, respectively. The prevalence of the metabolic syndrome at baseline was 30.3%. After 6 months of lifestyle modification, BMI z scores, percent body fat, total cholesterol, and low-density lipoprotein cholesterol (LDL-C) decreased significantly from baseline; however, there was no significant change in the number of subjects demonstrating >or=three criteria of the metabolic syndrome. CONCLUSIONS Approximately one third of the study subjects met the criteria of the metabolic syndrome, emphasizing the growing concern for the future development of premature cardiovascular disease in this high-risk population. Our data suggest that new strategies for lifestyle modification may be needed to improve cardiovascular risk factors significantly among adolescents with obesity.

Evaluation of a 6-month multi-disciplinary healthy weight management program targeting urban, overweight adolescents: Effects on physical fitness, physical activity, and blood lipid profiles

This study evaluated preliminary physical fitness, physical activity, and blood lipid profile data obtained from overweight adolescents upon enrolling in a healthy weight management program and following 6 months of program participation. One hundred and sixty-eight participants (13.4+/-1.8 years, 37.9+/-8.3 kg/m(2), 59.5% female and 76.2% African-American) enrolled in the program. The intervention addressed factors related to nutrition, physical activity, and other behaviors related to weight management. Sixty-four participants (38.1%) completed 6 months of program participation. While there was no significant reduction in body mass or body mass index (BMI), BMI z-score was reduced by 1.2% (p < 0.05), cardiorespiratory fitness was increased by 10.8% (p = 0.001), body fat percentage was reduced by 2.6% (p = 0.001), total cholesterol was reduced by 7.2% (p < 0.001), and low density lipoprotein (LDL-C) was reduced by 8.4% (p < 0.001) at 6 months. Continued development and evaluation of programs designed to prevent and treat child and adolescent overweight is warranted to address this major public health issue.

Total and High-Molecular Weight Adiponectin in Women with the Polycystic Ovary Syndrome

Adiponectin, an adipokine with antidiabetic properties, forms multimers; and the high-molecular weight (HMW) form most closely correlates with insulin sensitivity (S(i)). Therefore, we hypothesize that HMW adiponectin levels are decreased in women with polycystic ovary syndrome (PCOS), a condition characterized by insulin resistance, compared with healthy controls and that HMW adiponectin correlates with testosterone and S(i). A cross-sectional study involving 13 women with PCOS and 13 age- and body mass index-matched healthy controls was performed. Waist-to-hip ratios (WHRs), glucose, insulin, sex hormone-binding globulin, total testosterone, and total and HMW adiponectin levels were measured after an overnight fast. Free testosterone was calculated from sex hormone-binding globulin and total testosterone, and S(i) was determined using a frequently sampled intravenous glucose tolerance test. The studys primary outcomes were differences in total and HMW adiponectin between women with PCOS and healthy control women. Total adiponectin (P < .01), HMW adiponectin (P < .01), and the ratio of HMW to total adiponectin (P = .03) were lower in women with PCOS compared with healthy women. Total and HMW adiponectin levels correlated inversely with WHR (P < .01) and free testosterone (P < .01) and positively with S(i) (P < .001). Using forward stepwise multivariate analysis, HMW adiponectin and WHR, but not PCOS status, were independent predictors of S(i). Women with PCOS have lower total and HMW adiponectin levels compared with healthy women. High-molecular weight adiponectin also comprises a smaller proportion of total circulating adiponectin in women with PCOS. Alterations in HMW adiponectin levels in women with PCOS may contribute to the insulin resistance intrinsic to the syndrome.

Six-Month Dietary Changes in Ethnically Diverse, Obese Adolescents Participating in a Multidisciplinary Weight Management Program

This study’s objective was to examine dietary and metabolic changes in obese adolescents who completed 6 months of participation in an outpatient multidisciplinary weight management program (N = 67). Participants (75% African American, 66% female, mean age = 13.7 years) completed 24-hour dietary recalls and underwent measurement of anthropometrics and fasting blood lipid parameters at baseline and after 6 months of participation. General linear models suggested that participants significantly reduced total energy, total fat, saturated fat, carbohydrate, sodium, and sugar intakes, and increased fiber and fruit and vegetable intake (P < .05). Gender-stratified models showed differences in fruit/vegetable intake, percentage calories from fat, sodium, and dietary cholesterol intakes by gender. Significant improvements in body mass index percentile and lipid profiles were also found, lending objective support to the dietary changes participants made. Findings suggest that participation in this multidisciplinary treatment helped participants make behaviorally based dietary changes, which were associated with improved dietary intakes and health status.

Divergent Effects of a Combined Hormonal Oral Contraceptive on Insulin Sensitivity in Lean versus Obese Women

OBJECTIVE To evaluate the effects of a commonly used combined hormonal oral contraceptive (OC) on carbohydrate metabolism in obese as compared with lean women. DESIGN 6-month prospective study. SETTING Clinical research center at an academic medical center. PATIENT(S) Premenopausal nondiabetic women with body mass index <25 kg/m(2) (n = 15) or >30 kg/m(2) (n = 14). INTERVENTION(S) Ethinyl estradiol (35 μg) and norgestimate (0.18/0.215/0.25 mg) for 6 cycles. MAIN OUTCOME MEASURE(S) Insulin sensitivity by frequent sampling intravenous glucose tolerance test; other indices of insulin sensitivity (homeostatic model assessment of insulin sensitivity index [ISI HOMA], the Matsuda index); fasting lipid panel. RESULT(S) Insulin sensitivity changed from 6.62 ± 3.69 min(-1)/mIU/L (baseline) to 8.23 ± 3.30 min(-1)/mIU/L (6 months) in lean women, and from 4.36 ± 2.32 to 3.82 ± 2.32 min(-1)/mIU/L in obese women. Divergent effects on insulin sensitivity were also observed with ISI HOMA and the Matsuda index. Low-density lipoprotein increased by approximately 20 mg/dL in both the lean and obese groups. CONCLUSION(S) Lean and obese women exhibit differential changes in insulin sensitivity when given 6 months of a commonly used oral contraceptive. The mechanisms of these differences and whether these divergent effects persist in the long term require further investigation.

Pediatric Health Care Provider Perceptions of Weight Loss Surgery in Adolescents

This study explored pediatric health care providers’ obesity treatment practices and perceptions about adolescent weight loss surgery (WLS). Surveys were e-mailed to pediatric listservs. After descriptive analyses, correlations, chi-squares, and one-way analyses of variance compared responses by provider characteristics. Surveys were completed by 109 providers. Almost half do not routinely measure body mass index. Providers typically counsel patients about lifestyle change, with limited perceived benefit; <10% have ever referred patients for WLS, citing cost (20%), risk (49%), or “not indicated in pediatrics” (17%) as reasons. However, when presented with patient scenarios of different ages and comorbidities, likeliness to refer for WLS increased substantially. Surgeons, younger providers and those with fewer years of experience were more likely to refer for WLS (P < .05). Despite expert consensus recommendations supporting WLS as part of a comprehensive obesity treatment plan, significant pediatric provider resistance to refer obese adolescents remains. Improved referral and management practices are needed.

The Stress Process and Eating Pathology Among Racially Diverse Adolescents Seeking Treatment for Obesity

OBJECTIVE This study examined the associations of weight-related teasing and daily hassles with eating pathology, as well as potential mediators of these relations, among a racially diverse sample of adolescents. METHODS Participants were 92 primarily African American 11-17-year-olds seeking treatment for obesity. Data were collected at baseline. RESULTS Both daily hassles and weight-related teasing were significantly correlated with eating pathology at r = .22 and r = .25, respectively. Feeling upset about teasing mediated the associations of daily hassles (PE = .0093, SE = .0054, 95% BCa bootstrap CI of .0001-.0217) and teasing (PE = .0476, SE = .0198, 95% BCa bootstrap CI of .0093-.0873) with eating pathology. CONCLUSIONS These results highlight the importance of psychological interventions in the treatment of weight-loss among adolescents, as stressors may impact eating behaviors.