Elizabeth R. Stamm

Leg Muscle Mass and Composition in Relation to Lower Extremity Performance in Men and Women Aged 70 to 79: The Health, Aging and Body Composition Study

OBJECTIVES: The loss of muscle mass with aging, or sarcopenia, is hypothesized to be associated with the deterioration of physical function. Our aim was to determine whether low leg muscle mass and greater fat infiltration in the muscle were associated with poor lower extremity performance (LEP).

Genetic Epidemiology of Insulin Resistance and Visceral Adiposity ☆: The IRAS Family Study Design and Methods

PURPOSE Insulin resistance and visceral adiposity are associated with increased risk of type 2 diabetes. In this report, we describe the methods of the IRAS Family Study, which was designed to identify the genetic and environmental risk factors for insulin resistance and visceral adiposity. METHODS Families from two ethnic groups (African American and Hispanic) have been recruited from three clinical sites. Blood samples for DNA as well as other standard measures were collected. A CT scan (visceral adiposity) and a frequently sampled glucose tolerance test (insulin resistance) were performed. Preliminary estimates of heritability for indirect measures related to insulin resistance and visceral adiposity were obtained using a variance components approach in the first 93 families (approximately 1000 individuals). RESULTS Estimates of heritability ranged from low (0.08) for fasting insulin and HOMA, to moderate (0.28) for fasting glucose, to high (0.54) for BMI. After adjustment for age, gender and ethnicity, all heritability estimates were significantly greater than zero (p < 0.05). CONCLUSIONS These results are consistent with the expectation that intermediate measures of insulin resistance and visceral adiposity are heritable, and that the IRAS Family Study has statistical power to detect these intermediate phenotypes of type 2 diabetes and atherosclerosis.

Fat distribution and metabolic changes are strongly correlated and energy expenditure is increased in the HIV lipodystrophy syndrome

ObjectiveTo examine the relationships between protease inhibitor (PI) therapy, body fat distribution and metabolic disturbances in the HIV lipodystrophy syndrome. DesignCross-sectional study. SettingHIV primary care practices. PatientsPI-treated patients with lipodystrophy (n = 14) and PI-treated (n = 13) and PI-naive (n = 5) patients without lipodystrophy. Main outcome measuresBody composition was assessed by physical examination, dual-energy X-ray absorptiometry and computed tomography. Insulin sensitivity (SI) was measured using the insulin-modified frequently sampled intravenous glucose tolerance test. Lipid profiles, other metabolic parameters, duration of HIV infection, CD4 lymphocyte counts, HIV-1 RNA load and resting energy expenditure (REE) were also assessed. ResultsPI-treated patients with lipodystrophy were significantly less insulin sensitive than PI-treated patients and PI-naive patients without any changes in fat distribution (SI(22) × 10−4 (min−1/μU/ml) versus 3.2 × 10−4 and 4.6 × 10−4 (min−1/μU/ml), respectively;P < 0.001). Visceral adipose tissue area and other measures of central adiposity correlated strongly with metabolic disturbances as did the percent of total body fat present in the extremities; visceral adipose tissue was an independent predictor of insulin sensitivity and high density lipoprotein cholesterol levels. REE per kg lean body mass was significantly higher in the group with lipodystrophy compared to the groups without lipodystrophy (36.9 versus 31.5 and 29.4 kcal/kg lean body mass;P < 0.001), and SI was strongly correlated with and was an independent predictor of REE in this population. ConclusionsBody fat distribution and metabolic disturbances are strongly correlated in the HIV lipodystrophy syndrome and REE is increased.

Body Size and Shape Changes and the Risk of Diabetes in the Diabetes Prevention Program

The researchers conducted this study to test the hypothesis that risk of type 2 diabetes is less following reductions in body size and central adiposity. The Diabetes Prevention Program (DPP) recruited and randomized individuals with impaired glucose tolerance to treatment with placebo, metformin, or lifestyle modification. Height, weight, waist circumference, and subcutaneous and visceral fat at L2-L3 and L4-L5 by computed tomography were measured at baseline and at 1 year. Cox proportional hazards models assessed by sex the effect of change in these variables over the 1st year of intervention upon development of diabetes over subsequent follow-up in a subset of 758 participants. Lifestyle reduced visceral fat at L2-L3 (men −24.3%, women −18.2%) and at L4-L5 (men −22.4%, women −17.8%), subcutaneous fat at L2-L3 (men −15.7%, women −11.4%) and at L4-L5 (men −16.7%, women −11.9%), weight (men −8.2%, women −7.8%), BMI (men −8.2%, women −7.8%), and waist circumference (men −7.5%, women −6.1%). Metformin reduced weight (−2.9%) and BMI (−2.9%) in men and subcutaneous fat (−3.6% at L2-L3 and −4.7% at L4-L5), weight (−3.3%), BMI (−3.3%), and waist circumference (−2.8%) in women. Decreased diabetes risk by lifestyle intervention was associated with reductions of body weight, BMI, and central body fat distribution after adjustment for age and self-reported ethnicity. Reduced diabetes risk with lifestyle intervention may have been through effects upon both overall body fat and central body fat but with metformin appeared to be independent of body fat.

Correlates and heritability of nonalcoholic fatty liver disease in a minority cohort.

Nonalcoholic fatty liver disease (NAFLD) is associated with obesity and insulin resistance. The condition disproportionately affects Hispanic Americans. The aims of this study were to examine the risk factors and heritability of NAFLD in 795 Hispanic American and 347 African‐American adults participating in the Insulin Resistance Atherosclerosis Study (IRAS) Family Study. Computed tomography (CT) scans of the abdomen were evaluated centrally for measures of liver–spleen (LS) density ratio and abdominal fat distribution. Other measures included insulin sensitivity (SI) calculated from a frequently sampled intravenous glucose tolerance test and various laboratory measures. Statistical models which adjust for familial relationships were estimated separately for the two ethnic groups. Heritability was calculated using a variance components approach. The mean age of the cohort was 49 years (range 22–84); 66% were female. NAFLD (LS ratio <1) was more common in Hispanic Americans (24%) than African Americans (10%). NAFLD was independently associated with SI and visceral adipose tissue (VAT) area in both ethnic groups, although the proportion of explained variance was considerably higher in the Hispanic models. Adiponectin contributed significantly in the African‐American models whereas triglycerides (TGs) and plasminogen activator inhibitor 1 (PAI‐1) contributed only in the Hispanic models. Liver density was modestly heritable in both ethnic groups (h2 ∼0.35). In summary, the prevalence of NAFLD was twofold greater in Hispanic than African Americans. Certain correlates of NAFLD were similar between the ethnic groups, whereas others were distinct. NAFLD was modestly heritable. These findings suggest that NAFLD may have a differing environmental and/or genetic basis in these ethnic groups.

The long-term impact of intrauterine growth restriction in a diverse U.S. cohort of children: the EPOCH study

To explore the long‐term impact of intrauterine growth restriction (IUGR) among a diverse, contemporary cohort of US children.

Fat redistribution following suction lipectomy: defense of body fat and patterns of restoration.

No randomized studies in humans have examined whether fat returns after removal or where it returns. We undertook a prospective, randomized‐controlled trial of suction lipectomy in nonobese women to determine if adipose tissue (AT) is defended and if so, the anatomic pattern of redistribution. Healthy women with disproportionate AT depots (lower abdomen, hips, or thighs) were enrolled. Baseline body composition measurements included dual‐energy X‐ray absorptiometry (DXA) (a priori primary outcome), abdominal/limb circumferences, subcutaneous skinfold thickness, and magnetic resonance imaging (MRI) (torso/thighs). Participants (n = 32; 36 ± 1 year) were randomized to small‐volume liposuction (n = 14, mean BMI: 24 ± 2 kg/m2) or control (n=18, mean BMI: 25 ± 2) following baseline. Surgery group participants underwent liposuction within 2–4 weeks. Identical measurements were repeated at 6 weeks, 6 months, and 1 year later. Participants agreed not to make lifestyle changes while enrolled. Between‐group differences were adjusted for baseline level of the outcome variable. After 6 weeks, percent body fat (%BF) by DXA was decreased by 2.1% in the lipectomy group and by 0.28% in the control group (adjusted difference (AD): −1.82%; 95% confidence interval (CI): −2.79% to −0.85%; P = 0.0002). This difference was smaller at 6 months, and by 1 year was no longer significant (0.59% (control) vs. −0.41% (lipectomy); AD: −1.00%; CI: −2.65 to 0.64; P = 0.23). AT reaccumulated differently across various sites. After 1 year the thigh region remained reduced (0.77% (control) vs. −1.83% (lipectomy); AD: −2.59%; CI: −3.91 to −1.28; P = 0.0001), but AT reaccumulated in the abdominal region (0.64% (control) vs. 0.42% (lipectomy); AD: −0.22; CI: −2.35 to 1.91; P = 0.84). Following suction lipectomy, BF was restored and redistributed from the thigh to the abdomen.

Effects of Maintained Weight Loss on Sleep Dynamics and Neck Morphology in Severely Obese Adults

The goals of the study were to determine if moderate weight loss in severely obese adults resulted in (i) reduction in apnea/hypopnea index (AHI), (ii) improved pharyngeal patency, (iii) reduced total body oxygen consumption (VO2) and carbon dioxide production (VCO2) during sleep, and (iv) improved sleep quality. The main outcome was the change in AHI from before to after weight loss. Fourteen severely obese (BMI > 40 kg/m2) patients (3 males, 11 females) completed a highly controlled weight reduction program which included 3 months of weight loss and 3 months of weight maintenance. At baseline and postweight loss, patients underwent pulmonary function testing, polysomnography, and magnetic resonance imaging (MRI) to assess neck morphology. Weight decreased from 134 ±6.6 kg to 118 ± 6.1 kg (mean ± s.e.m.; F = 113.763, P < 0.0001). There was a significant reduction in the AHI between baseline and postweight loss (subject, F = 11.11, P = 0.007). Moreover, patients with worse sleep‐disordered breathing (SDB) at baseline had the greatest improvements in AHI (group, F = 9.00, P = 0.005). Reductions in VO2 (285 ± 12 to 234 ±16 ml/min; F = 24.85, P < 0.0001) and VCO2 (231 ± 9 to 186 ± 12 ml/min; F = 27.74, P < 0.0001) were also observed, and pulmonary function testing showed improvements in spirometry parameters. Sleep studies revealed improved minimum oxygen saturation (minSaO2) (83.4 ± 61.9% to 89.1 ± 1.2%; F = 7.59, P = 0.016), and mean SaO2 (90.4 ± 1.1% to 93.8 ± 1.0%; F = 6.89, P = 0.022), and a significant increase in the number of arousals (8.1 ± 1.4 at baseline, to 17.1 ± 3.0 after weight loss; F = 18.13, P = 0.001). In severely obese patients, even moderate weight loss (∼10%) boasts substantial benefit in terms of the severity of SDB and sleep dynamics.

Adiposity, Fat Patterning, and the Metabolic Syndrome among Diverse Youth: The EPOCH Study

OBJECTIVES To assess fat distribution, prevalence of obesity, and the metabolic syndrome among diverse 6-13-year-old Colorado youth to better understand racial/ethnic influences on adiposity and metabolic syndrome. STUDY DESIGN We measured body mass index, subscapular-to-triceps skinfold ratio, waist circumference, dietary fat, and physical activity in 422 youth (47% non-Hispanic White, 44% Hispanic, and 9% African-American). Visceral adipose tissue, subcutaneous adipose tissue, and intramyocellular lipid were measured with magnetic resonance techniques. Multiple-linear regression was used to assess associations between race/ethnicity and adiposity patterns. RESULTS Hispanic and African-American youth had a higher prevalence of obesity and metabolic syndrome compared with non-Hispanic White youth. Both groups displayed a more centralized fat distribution and larger volumes of subcutaneous tissue, compared with non-Hispanic White youth. After controlling for body mass index, these differences were attenuated, and for a given body size, African-American youth showed significantly lower visceral adipose tissue than non-Hispanic White youth. However, both Hispanic and African-American youth showed higher intermyocellular lipid in skeletal muscle compared with non-Hispanic Whites, independent of body size. CONCLUSIONS Racial/ethnic minorities experience higher overall adiposity, and may also have an increased risk for early development of metabolic syndrome relative to non-Hispanic White youth, beyond their increased obesity risk.

Frequency of ovarian cysts in patients with autosomal dominant polycystic kidney disease

Extrarenal cysts occur in patients with autosomal dominant polycystic kidney disease (ADPKD) most frequently in the liver. Ovarian cysts have been reported in women with ADPKD, but their frequency has not been determined. Therefore, we analyzed the historical data in our database of 337 women with ADPKD and 199 of their unaffected female family members (NADPKD). In addition, we prospectively studied 25 nonpregnant, premenopausal women with ADPKD and 25 nonpregnant, premenopausal, age-matched control women recruited from the general population to assess the occurrence of ovarian cysts. No women in either the control or ADPKD groups were receiving exogenous estrogen or progesterone. All women underwent sonographic examination using a 5- or 7.5-MHz vaginal probe. A normal ovarian follicle was defined as a fluid-filled structure less than 2 cm in average diameter, and an ovarian cyst as one of 2 cm or greater. From the historical data, 28% of the women with ADPKD gave a history of ovarian cysts compared with 18% of the NADPKD women (P < 0.05). In the prospective study, the mean age of the women with ADPKD was not different from that of the control women (40.9 +/- 1.2 v 39.3 +/- 1.2 years; P = not significant [NS]). There was no difference in frequency of normal follicles found in women with ADPKD or controls (80% v 96%; P = NS), nor was there a difference in the frequency of ovarian cysts found in women with ADPKD or controls (12% v 12%; P = NS). There was no difference in the calculated ovarian volumes between the women with ADPKD and controls (9.9 +/- 2. 5 v 7.2 +/- 1.2 cm3). Among the women with ADPKD, there was no correlation between mean ovarian volume and mean renal volume, nor was there a significant relationship between the occurrence of hepatic cystic disease and ovarian cysts. Therefore, a prospective imaging study suggests that ovarian cysts have no increased frequency in women with ADPKD compared with women in the general population.