Barbara A. Gower

Postmenopausal hormone therapy: An endocrine society scientific statement

OBJECTIVE Our objective was to provide a scholarly review of the published literature on menopausal hormonal therapy (MHT), make scientifically valid assessments of the available data, and grade the level of evidence available for each clinically important endpoint. PARTICIPANTS IN DEVELOPMENT OF SCIENTIFIC STATEMENT: The 12-member Scientific Statement Task Force of The Endocrine Society selected the leader of the statement development group (R.J.S.) and suggested experts with expertise in specific areas. In conjunction with the Task Force, lead authors (n = 25) and peer reviewers (n = 14) for each specific topic were selected. All discussions regarding content and grading of evidence occurred via teleconference or electronic and written correspondence. No funding was provided to any expert or peer reviewer, and all participants volunteered their time to prepare this Scientific Statement. EVIDENCE Each expert conducted extensive literature searches of case control, cohort, and randomized controlled trials as well as meta-analyses, Cochrane reviews, and Position Statements from other professional societies in order to compile and evaluate available evidence. No unpublished data were used to draw conclusions from the evidence. CONSENSUS PROCESS A consensus was reached after several iterations. Each topic was considered separately, and a consensus was achieved as to content to be included and conclusions reached between the primary author and the peer reviewer specific to that topic. In a separate iteration, the quality of evidence was judged using the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) system in common use by The Endocrine Society for preparing clinical guidelines. The final iteration involved responses to four levels of additional review: 1) general comments offered by each of the 25 authors; 2) comments of the individual Task Force members; 3) critiques by the reviewers of the Journal of Clinical Endocrinology & Metabolism; and 4) suggestions offered by the Council and members of The Endocrine Society. The lead author compiled each individual topic into a coherent document and finalized the content for the final Statement. The writing process was analogous to preparation of a multiauthored textbook with input from individual authors and the textbook editors. CONCLUSIONS The major conclusions related to the overall benefits and risks of MHT expressed as the number of women per 1000 taking MHT for 5 yr who would experience benefit or harm. Primary areas of benefit included relief of hot flashes and symptoms of urogenital atrophy and prevention of fractures and diabetes. Risks included venothrombotic episodes, stroke, and cholecystitis. In the subgroup of women starting MHT between ages 50 and 59 or less than 10 yr after onset of menopause, congruent trends suggested additional benefit including reduction of overall mortality and coronary artery disease. In this subgroup, estrogen plus some progestogens increased the risk of breast cancer, whereas estrogen alone did not. Beneficial effects on colorectal and endometrial cancer and harmful effects on ovarian cancer occurred but affected only a small number of women. Data from the various Womens Health Initiative studies, which involved women of average age 63, cannot be appropriately applied to calculate risks and benefits of MHT in women starting shortly after menopause. At the present time, assessments of benefit and risk in these younger women are based on lower levels of evidence.

Relation between visceral fat and disease risk in children and adolescents

This review examines whether the relations and metabolic parameters necessary for the development of syndrome X are present in children and whether the metabolic complications of obesity in children are explained by excess intraabdominal adipose tissue (IAAT), or visceral fat. Despite the limited use of imaging techniques in research studies, an increasing number of studies reported on IAAT and its relation to disease risk in children and adolescents. For this article we reviewed studies that documented the early accumulation of IAAT in children and adolescents and the factors that contribute to variation in the degree of IAAT accumulation. We also reviewed studies that showed the clinical relevance of IAAT in children and adolescents through significant relations with adverse health effects including dyslipidemia and glucose intolerance in obese and nonobese children and adolescents of different ethnic groups.

Dietary carbohydrate restriction as the first approach in diabetes management: Critical review and evidence base

The inability of current recommendations to control the epidemic of diabetes, the specific failure of the prevailing low-fat diets to improve obesity, cardiovascular risk, or general health and the persistent reports of some serious side effects of commonly prescribed diabetic medications, in combination with the continued success of low-carbohydrate diets in the treatment of diabetes and metabolic syndrome without significant side effects, point to the need for a reappraisal of dietary guidelines. The benefits of carbohydrate restriction in diabetes are immediate and well documented. Concerns about the efficacy and safety are long term and conjectural rather than data driven. Dietary carbohydrate restriction reliably reduces high blood glucose, does not require weight loss (although is still best for weight loss), and leads to the reduction or elimination of medication. It has never shown side effects comparable with those seen in many drugs. Here we present 12 points of evidence supporting the use of low-carbohydrate diets as the first approach to treating type 2 diabetes and as the most effective adjunct to pharmacology in type 1. They represent the best-documented, least controversial results. The insistence on long-term randomized controlled trials as the only kind of data that will be accepted is without precedent in science. The seriousness of diabetes requires that we evaluate all of the evidence that is available. The 12 points are sufficiently compelling that we feel that the burden of proof rests with those who are opposed.

Prediction of intra-abdominal and subcutaneous abdominal adipose tissue in healthy pre-pubertal children

OBJECTIVE: To examine the relationship of intra-abdominal adipose tissue (IAAT) and subcutaneous abdominal adipose tissue (SAAT) with body composition and anthropometry in children.DESIGN: Cross-sectional data analysis.SUBJECTS: 113 healty Caucasian and African-American, pre-pubertal children aged 4–10 y.MEASUREMENTS: IAAT and SAAT by single slice computed tomography at the level of the umbilicus; total fat and trunk fat by dual energy X-ray absorptiometry (DEXA); anthropometric evaluation by skinfolds and circumferences.RESULTS: IAAT was most strongly correlated with abdominal skinfold (r=0.88) and trunk fat by DEXA (r=0.87), and SAAT with trunk fat by DEXA (r=0.96), total fat by DEXA (r=0.93) and waist circumference (r=0.93). In stepwise regression, IAAT was best predicted by trunk fat from DEXA, total fat from DEXA, and abdominal skinfold (R2=0.85); SAAT was best predicted by trunk fat from DEXA, body weight, waist circumference and abdominal skinfold (R2=0.96). In the absence of DEXA data, IAAT was best predicted by abdominal skinfold, ethnicity and subscapular skinfold (R2=0.82) and SAAT was best predicted by waist circumference subscapular skinfold, height and abdominal skinfold (R2=0.92). The prediction equations with and without DEXA were successfully cross-validated in an independent sample of 12 additional measures of IAAT and SAAT.CONCLUSION: These data provide useful information that can help in the interpretation of anthropometric data with regard to body fat distribution. IAAT and SAAT can be accurately estimated in Caucasian and African-American prepubertal children from anthropometry with and without the availability of DEXA data.

Predicting body composition from anthropometry in pre-adolescent children

The objectives of this paper were to: a) evaluate the accuracy and precision of previously published pediatric body composition prediction equations and b) develop additional prediction equations from a large, heterogeneous group of Caucasian (n=133) and African-American (n=69) children. The combined cohort of 202 children included a wide range of ages (4.0–10.9 y), weights (14.0–70.8 kg), fat mass (FM: 1.2–28.5 kg) and percent body fat (% body fat: 6.2–49.6%). Skinfold measurements were obtained using a Lange caliper and body fat was measured with a Lunar DPX-L densitometer. The previously published equations of Slaughter et al and Goran et al did not accurately predict body fat. The entire cohort was randomly divided into two sub-groups for purposes of deriving and cross-validating a new prediction equation. In stepwise regression analysis in the development group (n=135), weight, triceps skinfold, gender, ethnicity and abdominal skinfold estimated FM measured by dual energy x-ray absorptiometry (DEXA) with a model R2 of 0.95. The new prediction equation was cross-validated in the control group (n=67) and each ethnic and gender subgroup. We conclude that a) the equations of Slaughter et al and Goran et al did not accurately predict FM in a heterogeneous group of children and b) a new anthropometric prediction equation is proposed that may provide accurate estimates of FM in both Caucasian and African-American children aged 4–10 y with a wide range of FM and body composition.

Polymorphism in the Transcription Factor 7-Like 2 (TCF7L2) Gene Is Associated With Reduced Insulin Secretion in Nondiabetic Women

Recently, the transcription factor 7-like 2 (TCF7L2) gene on chromosome 10q25.2 has been linked with type 2 diabetes among Caucasians, with disease associations noted for single nucleotide polymorphisms (SNPs) rs12255372 and rs7903146. To investigate mechanisms by which TCF7L2 could contribute to type 2 diabetes, we examined the effects of these SNPs on clinical and metabolic traits affecting glucose homeostasis in 256 nondiabetic female subjects (138 European Americans and 118 African Americans) aged 7–57 years. Outcomes included BMI, percent body fat, insulin sensitivity (Si), acute insulin response to glucose (AIRg), and the disposition index (DI). Homozygosity for the minor allele (TT) of SNP rs12255372 occurred in 9% of individuals and was associated with a 31% reduction in DI values in a recessive model. The at-risk allele TT was also associated with lower AIRg adjusted for Si in both ethnic groups, whereas rs12255372 genotype was not associated with measures of adiposity or with Si. The T allele of rs12255372 was also associated with increased prevalence of impaired fasting glucose. Genotypes at rs7903146 were not associated with any metabolic trait. Lower Si and higher AIRg observed in the African-American compared with the European-American subgroup could not be explained by the TCF7L2 genotype. Our data suggest that the TCF7L2 gene is an important factor regulating insulin secretion, which could explain its association with type 2 diabetes.

Resistance Training Conserves Fat-free Mass and Resting Energy Expenditure Following Weight Loss

Objective: To determine what effect diet‐induced ∼12 kg weight loss in combination with exercise training has on body composition and resting energy expenditure (REE) in premenopausal African‐American (AA) and European‐American (EA) women.

Threshold for Effects of Vitamin D Deficiency on Glucose Metabolism in Obese Female African-American Adolescents

CONTEXT Vitamin D status can influence insulin resistance. OBJECTIVE The aim of the study was to determine the prevalence of vitamin D deficiency in obese African-American (AA) adolescent females in a southeastern latitude and to determine the relationship of 25-hydroxyvitamin D [25(OH)D] with insulin and glucose dynamics. DESIGN We conducted a cross-sectional study in a University Childrens Hospital. METHODS Serum 25(OH)D, fasting glucose, PTH, serum calcium, serum lipids, serum transaminases, and C-reactive protein were assessed. Indices of insulin sensitivity and resistance were determined from an oral glucose tolerance test. Subjects were classified as vitamin D deficient or sufficient, based on the traditional vitamin D deficiency definition [serum 25(OH)D <20 ng/ml] and also by a lower 25(OH)D cut-point of 15 ng/ml or less. RESULTS A total of 51 AA adolescent females (body mass index, 43.3 +/- 9.9 kg/m(2); age, 14 +/- 2 yr) were studied. Serum 25(OH)D concentrations were 20 ng/ml or less in 78.4% and 15 ng/ml or less in 60.8% of subjects. There were no significant group differences in the metabolic outcomes when subjects were classified using the traditional vitamin D deficiency definition. The Matsuda index of insulin sensitivity was significantly lower (P = 0.02), and insulin area under the curve was significantly higher (P = 0.04) in subjects with 25(OH)D concentrations of 15 ng/ml or less vs. those with higher concentrations. CONCLUSIONS Vitamin D deficiency is highly prevalent in obese, AA female adolescents and may promote insulin resistance. Our data suggest that a 25(OH)D concentration of 15 ng/ml or less may be the threshold by which vitamin D deficiency confers negative effects on insulin sensitivity.

Exercise Training Prevents Regain of Visceral Fat for 1 Year Following Weight Loss

The purpose of this study was to determine what effect aerobic and resistance exercise training has on gain of visceral fat during the year following weight loss. After being randomly assigned to aerobic training, resistance training, or no exercise training, 45 European‐American (EA) and 52 African‐American (AA) women lost 12.3 ± 2.5 kg on a 800 kcal/day diet. Computed tomography was used to measure abdominal subcutaneous and visceral adipose tissue, whereas total fat and regional fat (leg, arm, and trunk) were measured by dual energy X‐ray absorptiometry after weight loss and 1 year following the weight loss. Because not all the subjects adhered to the 2 time/week 40 min/day exercise training during the 1‐year follow‐up, subjects were divided into five groups for analysis: aerobic adherers, aerobic nonadherers, resistance adherers, resistance nonadherers, and no exercise. No significant differences were observed between the aerobic training and resistance training adherers for any variable. However, the aerobic (3.1 kg) and resistance (3.9 kg) exercise adherers gained less weight than any of the other three groups (all >6.2 kg). In addition, the two exercise adherence groups did not significantly increase visceral fat (<0.8%) as compared with the 38% increase for the two nonadhering exercise groups and the 25% for the nonexercise group. In conclusion, as little as 80 min/week aerobic or resistance training had modest positive effects on preventing weight regain following a diet‐induced weight loss. More importantly, both aerobic and resistance training prevented regain of potentially harmful visceral fat.

Insulin Sensitivity and Blood Pressure in Black and White Children

Although insulin sensitivity is correlated with high blood pressure in adults, it is unclear whether such a relationship exists in children across ethnic groups. Therefore, the aims of the study were to establish (1) if body composition and insulin sensitivity were related to blood pressure in children, and (2) if any differences in blood pressure between white and black children were explained by body composition and/or insulin sensitivity. Insulin sensitivity and the acute insulin response were established by the minimal model and body composition by dual-energy X-ray absorptiometry. Blood pressure was recorded in the supine position. Body composition, fasting insulin (P <0.01), and the acute insulin response (P <0.05) were positively related to systolic blood pressure but not to diastolic blood pressure, and insulin sensitivity (P <0.001) was negatively related to systolic blood pressure but not to diastolic blood pressure. Insulin sensitivity was negatively associated with systolic and diastolic blood pressure after adjustment for body composition (P <0.01). Black children had higher systolic (110±9.2 versus 105±8.5 mm Hg, P =0.01) and diastolic (59±7.0 versus 54±8.0 mm Hg, P <0.01) blood pressure than did white children. The ethnic difference in blood pressure was not explained by body composition, fasting insulin, acute insulin response, or insulin sensitivity. In conclusion, the relationship between insulin sensitivity and systolic blood pressure is evident early in life. Black ethnicity and low insulin sensitivity contribute independently to higher blood pressure in children.