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Weight loss intervention is the principal nonpharmacological method for prevention and treatment of type 2 diabetes. However, little is known whether it influences insulin sensitivity directly or via its anti-inflammatory effect. The aim of this study was to assess the independent role of changes in inflammation status and weight loss on insulin sensitivity in this population. Overweight and obese nondiabetic participants without co-morbidities underwent a one-year weight loss intervention focused on caloric restriction and behavioral support. Markers of inflammation, body composition, anthropometric para meters, and insulin sensitivity were recorded at baseline, 6, and 12 months. Insulin sensitivity was assessed with frequently sampled intravenous glucose tolerance test and Minimal Model. Twenty-eight participants (F: 15, M: 13, age 39 ± 5 years, BMI 33.2 ± 4.6 kg/m2 ) completed the study, achieving 9.4 ± 6.9 % weight loss, which was predominantly fat mass (7.7 ± 5.6 kg, p < 0.0001). Dietary intervention resulted in significant decrease in leptin, leptin-to-adiponectin ratio, hs-CRP, and IL-6 (all p < 0.02), and improvement in HOMA-IR and Insulin Sensitivity Index (SI) (both p < 0.001). In response to weight loss IL-1α, IL-2, leptin, and resistin were significantly associated with insulin, sensitivity, whereas sICAM-1 had only marginal additive effect. Moderate weight loss in otherwise healthy overweight and obese individuals resulted in an improvement in insulin sensitivity and in the overall inflammation state; the latter played only a minimal independent role in modulating insulin sensitivity. [ABSTRACT FROM AUTHOR]

Objective: To determine whether insulin resistance and secretion differ in obese premenopausal African-American women with and without glucose intolerance.Research Design and Methods: A total of 63 women underwent oral glucose tolerance tests (OGTTs). A total of 48 women underwent frequently sampled intravenous glucose tolerance tests (FSIGTs). Insulin resistance was determined from the insulin sensitivity index (S(I)) from the FSIGT. Insulin secretion during the OGTT was determined by (I(30 min) - I(0 min))/(G(30 min) - G(0 min)) and during the FSIGT by the acute insulin response to glucose (AIRg). The disposition index, the product of AIRg and S(I), was used to determine whether AIRg was adequate to compensate for insulin resistance. Statistical analyses included one-way analysis of variance with Bonferroni corrections for multiple comparisons and regression analyses.Results: The women were divided into three groups: nonobese glucose tolerant (n = 32), obese glucose tolerant (n = 17), and obese glucose intolerant (n = 14). The BMI of the three groups were 24.8 +/- 2.3, 37.8 +/- 5.5, and 42.0 +/- 7.6 kg/m(2) (mean +/- SD), respectively (P < 0.0001). The ages of the three groups were 34.9 +/- 8.4, 32.1 +/- 5.0, and 41.1 +/- 6.3 years (P = 0.011). S(I) was higher in the nonobese women than in the obese glucose-tolerant women (3.99 +/- 1.44 vs. 2.66 +/- 2.14 l x mU(-1) x min(-1), P = 0.03). S(I) was similar in the obese glucose-intolerant and obese glucose-tolerant women (2.12 +/- 1.27 vs. 2.66 +/- 2.14 l x mU(-1) x min(-1), P = 0.9). OGTT showed that insulin secretion was lower in the glucose-intolerant than the obese glucose-tolerant women (1.73 +/- 1.38 vs. 3.62 +/- 2.11, P = 0.005). FSIGT showed that AIRg was not significantly lower in glucose-intolerant than in obese glucose-tolerant women (807 +/- 665 vs. 1,253 +/- 655 mU x l(-1) x min, P = 0.078). The disposition index was lower in glucose-intolerant than in obese glucose-tolerant women (1,324 +/- 1,061 vs. 2,656 +/- 1,415, P = 0.014).Conclusions: Obese premenopausal African-American women with and without glucose intolerance have a similar degree of insulin resistance but differ in insulin secretion. [ABSTRACT FROM AUTHOR]

Background: Troglitazone promotes adipocyte differentiation in vitro and increases insulin sensitivity in vivo. Therefore, troglitazone may have therapeutic benefit in lipoatrophic diabetes.Objective: To determine whether troglitazone ameliorates hyperglycemia and hypertriglyceridemia or increases fat mass in lipoatrophic patients.Design: Open-labeled prospective study.Setting: United States and Canada.Patients: 20 patients with various syndromes associated with lipoatrophy or lipodystrophy.Intervention: 6 months of therapy with troglitazone, 200 to 600 mg/d.Measurements: Levels of hemoglobin A1c triglycerides, free fatty acids, and insulin; respiratory quotient; percentage of body fat; liver volume; and regional fat mass.Results: In the 13 patients with diabetes who completed 6 months of troglitazone therapy, hemoglobin A1c levels decreased by a mean of 2.8% (95% CI, 1.9% to 3.7%; P < 0.001). In all 19 study patients, fasting triglyceride levels decreased by 2.6 mmol/L (230 mg/dL) (CI, 0.7 to 4.5 mmol/L [62 to 398 mg/dL]; P = 0.019) and free fatty acid levels decreased by 325 micromol/L (CI, 135 to 515 micromol/L; P = 0.035). The respiratory quotient decreased by a mean of 0.12 (CI, 0.08 to 0.16; P < 0.001), suggesting that troglitazone promoted oxidation of fat. Body fat increased by a mean of 2.4 percentage points (CI, 1.3 to 4.5 percentage points; P = 0.044). Magnetic resonance imaging showed an increase in subcutaneous adipose tissue but not in visceral fat. In one patient, the serum alanine aminotransferase level increased eightfold during the 10th months of troglitazone treatment but normalized 3 months after discontinuation of treatment Liver biopsy revealed an eosinophilic infiltrate, suggesting hypersensitivity reaction as a cause of hepatotoxicity.Conclusion: Troglitazone therapy improved metabolic control and increased body fat in patients with lipoatrophic diabetes. The substantial benefits of troglitazone must be balanced against the risk for hepatotoxicity, which can occur relatively late in the treatment course. [ABSTRACT FROM AUTHOR]

Abstract Background Physical activity is being studied as a breast cancer prevention strategy. Women at risk of breast cancer report interest in lifestyle modification, but recruitment to randomized physical activity intervention studies is challenging. Methods We conducted an analysis of recruitment techniques used for a prospective, randomized pilot study of physical activity in women at risk of breast cancer. We evaluated differences in proportion of eligible patients, enrolled patients, and successful patients identified by each individual recruitment method. The Fisher-Freeman-Halton test (an extension of Fisher's exact test from 2 × 2 tables to general row by column tables) was used to compare the success of different recruitment strategies. Results We received 352 inquiries from women interested in participating, of whom 171 (54%) were eligible. Ninety-nine women completed a baseline activity evaluation, and 58 (34% of eligible; 16% of total inquiries) were randomized. Recruitment methods fell into three broad categories: media techniques, direct contact with potential participants, and contacts with health care providers. Recruitment strategies differed significantly in their ability to identify eligible women (p = 0.01), and women who subsequently enrolled in the study (p = 0.02). Conclusion Recruitment techniques had varying success. Our data illustrate the challenges in recruiting to behavior modification studies, and provide useful information for tailoring future recruitment efforts for lifestyle intervention trials. Trial Registration No(s) CDR0000393790, NCI-04-C-0276, NCI-NAVY-B05-001

Determines whether treating lipoatrophy with troglitazone lowers blood sugar and triglyceride levels and increases the amount of body fat. Association of lipoatrophy with abnormally small amounts of body fat; Measurements of the patients' levels of triglycerides, body fat and hemoglobin A; Improvement of blood sugar levels, triglyceride levels and body fat content with troglitazone; Potential side effect.

Background: It is commonly asserted that the average American gains 5 lb (2.3 kg) or more over the holiday period between Thanksgiving and New Year's Day, yet few data support this statement.Methods: To estimate actual holiday-related weight variation, we measured body weight in a convenience sample of 195 adults. The subjects were weighed four times at intervals of six to eight weeks, so that weight change was determined for three periods: preholiday (from late September or early October to mid-November), holiday (from mid-November to early or mid-January), and postholiday (from early or mid-January to late February or early March). A final measurement of body weight was obtained in 165 subjects the following September or October. Data on other vital signs and self-reported health measures were obtained from the patients in order to mask the main outcome of interest.Results: The mean (+/-SD) weight increased significantly during the holiday period (gain, 0.37+/-1.52 kg; P<0.001), but not during the preholiday period (gain, 0.18+/-1.49 kg; P=0.09) or the postholiday period (loss, 0.07+/-1.14 kg; P=0.36). As compared with their weight in late September or early October, the study subjects had an average net weight gain of 0.48+/-2.22 kg in late February or March (P=0.003). Between February or March and the next September or early October, there was no significant additional change in weight (gain, 0.21 kg+/-2.3 kg; P=0.13) for the 165 participants who returned for follow-up.Conclusions: The average holiday weight gain is less than commonly asserted. Since this gain is not reversed during the spring or summer months, the net 0.48-kg weight gain in the fall and winter probably contributes to the increase in body weight that frequently occurs during adulthood. [ABSTRACT FROM AUTHOR]

Aim: Maximal oxygen uptake (VO(2max)), the gold standard for measurement of cardiorespiratory fitness, is frequently difficult to assess in overweight individuals due to physical limitations. Reactance and resistance measures obtained from bioelectrical impedance analysis (BIA) have been suggested as easily obtainable predictors of cardiorespiratory fitness, but the accuracy with which ht(2)/Z can predict VO(2max) has not previously been examined in overweight adolescents., Methods: The impedance index was used as a predictor of VO(2max) in 87 overweight girls and 47 overweight boys ages 12 to 17 with mean BMI of 38.6 + or - 7.3 and 42.5 + or - 8.2 in girls and boys respectively. The Bland Altman procedure assessed agreement between predicted and actual VO(2max)., Results: Predicted VO(2max) was significantly correlated with measured VO(2max) (r(2)=0.48, P<0.0001). Using the Bland Altman procedure, there was significant magnitude bias (r(2)=0.10; P<0.002). The limits of agreement for predicted relative to actual VO(2max) were -589 to 574 mL O(2)/min., Conclusions: The impedance index was highly correlated with VO(2max) in overweight adolescents. However, using BIA data to predict maximal oxygen uptake over-predicted VO(2max) at low levels of oxygen consumption and under-predicted VO(2max) at high levels of oxygen consumption. This magnitude bias, along with the large limits of agreement of BIA-derived predicted VO(2max), limit its usefulness in the clinical setting for overweight adolescents.

Context: Osteoporosis primarily affects postmenopausal women. However, young women with estrogen deficiency also are at increased risk for low bone density., Objective: The aim of the study was to assess bone density and associated risk factors for reduced bone density in young, estrogen-deficient women using primary ovarian insufficiency (POI) as the disease model., Design and Setting: We conducted a cross-sectional study at a tertiary care research center., Participants: We studied women with POI (n = 442), concurrent controls (n = 70), and matched controls from NHANES III (n = 353)., Primary Outcome Measure: We measured bone mineral density (BMD) using dual-energy x-ray absorptiometry., Results: Patients on average had 2-3% lower BMD at L1-L4, femoral neck, and total hip (P < 0.01 at all sites). The modifiable risk factors for BMD below the expected range for age (Z-score <-2) were: more than 1-yr delay in diagnosis of estrogen deficiency (P = 0.018), low (<32 ng/ml) vitamin D levels (P = 0.002), estrogen replacement nonadherence (P = 0.002), low calcium intake (P = 0.005), and lack of exercise (P = 0.005). As compared to Caucasians, African-American and Asian women with POI were 3.18 and 4.34 times more likely, respectively, to have Z-scores below -2 (P = < 0.0001 for both). Race was an overall risk factor, but on regression modeling, not an independent predictor of low bone density., Conclusions: Women with POI have lower bone density compared to regularly menstruating women. Compared to Caucasians, minority women with estrogen deficiency are more likely to have BMD below the expected range for age. This racial disparity appears to be related to a combined effect of several modifiable risk factors. Delay in diagnosis of POI also contributes to reduced bone density by delaying proper therapy.

Background: Physical activity is being studied as a breast cancer prevention strategy. Women at risk of breast cancer report interest in lifestyle modification, but recruitment to randomized physical activity intervention studies is challenging., Methods: We conducted an analysis of recruitment techniques used for a prospective, randomized pilot study of physical activity in women at risk of breast cancer. We evaluated differences in proportion of eligible patients, enrolled patients, and successful patients identified by each individual recruitment method. The Fisher-Freeman-Halton test (an extension of Fisher's exact test from 2 x 2 tables to general row by column tables) was used to compare the success of different recruitment strategies., Results: We received 352 inquiries from women interested in participating, of whom 171 (54%) were eligible. Ninety-nine women completed a baseline activity evaluation, and 58 (34% of eligible; 16% of total inquiries) were randomized. Recruitment methods fell into three broad categories: media techniques, direct contact with potential participants, and contacts with health care providers. Recruitment strategies differed significantly in their ability to identify eligible women (p = 0.01), and women who subsequently enrolled in the study (p = 0.02)., Conclusion: Recruitment techniques had varying success. Our data illustrate the challenges in recruiting to behavior modification studies, and provide useful information for tailoring future recruitment efforts for lifestyle intervention trials. TRIAL REGISTRATION NO(S): CDR0000393790, NCI-04-C-0276, NCI-NAVY-B05-001.

Major depressive disorder (MDD) is one of the most common psychiatric illnesses in the adult population. It is often associated with an increased risk of cardiovascular disease. We measured body fat distribution as well as plasminogen activator inhibitor-1 (PAI-1) concentration and factor VIII (fVIII) activity at 8:00 am and 8:00 pm in 45 premenopausal women with MDD vs 28 healthy controls (age, 37 +/- 6.8 vs 35 +/- 6.5; weight [kg], 75.3 +/- 17.2 vs 67.9 +/- 10.2; mean +/- SD] participating in a prospective study of bone turnover, the POWER Study. At the time of evaluation, women with MDD were mildly depressed and mostly in clinical remission on antidepressants. After adjusting for body weight, women with MDD had greater waist circumference and abdominal fat as well as significantly higher evening (8:00 pm) PAI-1 and fVIII levels than controls. Even when age-, race-, and body mass index-matched subsets were compared, the MDD group continued to exhibit statistically higher PAI-1 and fVIII levels. The observed alterations in body fat distribution (increased abdominal fat) and prothrombotic factors (increased PAI-1 and fVIII) may be in part responsible for the increased risk of cardiovascular disease reported in association with major depression.

Alkaptonuria, a rare autosomal recessive disorder caused by mutations in the HGD gene and deficiency of homogentisate 1,2 dioxygenase, is characterized by ochronosis, arthritis, and daily excretion of gram quantities of homogentisic acid (HGA). Nitisinone, an inhibitor of the enzyme 4-hydroxyphenylpyruvate dioxygenase, can drastically reduce urinary excretion of HGA in individuals with alkaptonuria. We investigated the safety and the HGA-depleting efficacy of nitisinone in an open-label, single-center study of 9 alkaptonuria patients (5 women, 4 men; 35-69 years of age) over the course of 3 to 4 months. Each patient received nitisinone in incremental doses, 0.35 mg bid followed by 1.05 mg bid, and remained on this dosage and a regular diet for 3 months. Nitisinone reduced urinary HGA levels from an average of 4.0 +/- 1.8 (SD) g/day to 0.2 +/- 0.2 g/day ( P < .001). The average plasma tyrosine concentration, initially 68 +/- 18 mmicro mol/L, rose to 760 +/- 181 micro mol/L ( P < .001). During the final week of the study, 5 patients adhered to a protein-restricted diet (40 g/day), and their mean plasma tyrosine level fell from 755 +/- 167 to 603 +/- 114 mu mol/L. Six of the 7 patients who received nitisinone for more than 1 week reported decreased pain in their affected joints. Weekly ophthalmologic examinations showed no signs of corneal toxicity. Adverse events included the passing of kidney stones, the recognition of symptoms related to aortic stenosis, and elevation of liver transaminase levels. We conclude that low-dose nitisinone effectively reduced urinary HGA levels in patients with alkaptonuria. Future long-term clinical trials are planned to determine the benefits of nitisinone in preventing joint deterioration and providing pain relief, and its long-term side effects.

Recombinant methionyl human leptin (r-metHuLeptin) therapy has shown clear efficacy in the treatment of severe insulin resistance associated with lipodystrophy syndromes and low leptin levels. We treated two siblings with Rabson-Mendenhall syndrome (severe insulin resistance and presumed insulin receptor mutations). The brother and sister, aged 13 and 11 yr, respectively, had severe acanthosis nigricans, insulin resistance, and diabetes. Both were taking 2000 mg metformin and 2 mg rosiglitazone daily; the brother was also taking 300 U regular insulin daily. In contrast to our lipoatrophic patients treated with r-metHuLeptin, these two patients had a higher percent body fat and low-normal fasting triglycerides [42 mg/dl (0.37 mmol/liter), male sibling, and 33 mg/dl (0.47 mmol/liter), female sibling]. The siblings were treated with r-metHuLeptin therapy for 10 months and demonstrated a 40-60% decrease in fasting serum glucose and insulin levels and improved glycosylated hemoglobin. There was corresponding improvement in glucose and insulin tolerance during leptin therapy. This is the first report of a partial, but significant, effect of r-metHuLeptin administration in patients with extreme insulin resistance with a presumed insulin receptor mutation and low serum triglyceride levels.

Leptin, an adipocyte hormone, when replaced in patients with lipodystrophy, improves insulin resistance, hyperglycemia, dyslipidemia, and hepatic steatosis. Changes in body composition accompany this metabolic improvement. We studied 14 patients (3 men and 11 women); 12 of who had generalized lipodystrophy (7 congenital, 5 acquired), and 2 patients had partial lipodystrophy. Body composition and related parameters were evaluated at baseline and after 4 and 12 months of leptin therapy. Baseline body mass index (BMI) was 21.7 +/- 0.8 kg/m(2), the percent body fat was 9.5% +/- 1.6%, and the serum leptin level was 1.7 +/- 0.3 ng/mL. On treatment, serum leptin levels increased by 10-fold. All patients reported a decrease in appetite on therapy. After 4 months, both daily caloric intake and resting energy expenditure (REE) decreased. The liver volume decreased (baseline = 3,055 +/- 281 cm(3); 4 months = 2,433 +/- 243 cm(3), P =.006). Dual energy x-ray absorptiometry (DEXA) demonstrated significant decreases in fat mass (5.4 +/- 0.8 kg to 5.0 +/- 0.8 kg; P =.003) and lean body mass (51.2 +/- 3.2 kg to 48.3 +/- 3.4 kg; P =.003) at 4 months on therapy. There was no impact of leptin therapy on bone mineral content, mineral density, and metabolism. Changes in body composition occurred during the first 4 months of leptin therapy, but then stabilized and were sustained thereafter.

Background: The quantity and type of dietary polyunsaturated fatty acids (PUFAs) can alter essential fatty acid metabolism in humans. Diets rich in 20- and 22-carbon PUFAs may inhibit desaturase expression or activity and decrease the synthesis of long-chain unsaturated fatty acids., Objective: It was theorized that the fat content of a fish-based diet would inhibit the kinetics of the in vivo metabolism of n-3 fatty acids compared with a beef-based diet., Design: A compartmental model was used to determine the coefficients of the kinetic rate constants from the plasma concentration time curves of pentadeuterated (d(5)) 18:3n-3, 20:5n-3, 22:5n-3, and 22:6n-3 of 10 subjects who subsisted on 3 diets with different long-chain PUFA contents. For 3 wk, subjects reported their food intake from their usual diets and then consumed a beef-based diet for 3 wk and then a fish-based diet for an additional 3 wk. Subjects consumed 1 g d(5)-18:3n-3 ethyl ester at weeks 3, 6, and 9. Blood was drawn over 168 h and the plasma analyzed for fatty acids. The coefficients of the kinetic constants of n-3 fatty acid metabolism and the percentage utilization of the substrates were determined., Results: Across all diets, < 1% of plasma 18:3n-3 was utilized for long-chain PUFA synthesis. There was a 70% reduction in the value of the rate constant coefficient that regulated transfer of the isotope from the 22:5n-3 compartment to 22:6n-3 when the fish-based diet was compared with the beef-based diet. The turnover rate of plasma d(5)-22:6n-3 also decreased., Conclusions: The primary effect of a fish-based diet on the kinetics of n-3 metabolism involves processes that inhibit the synthesis of 22:6n-3 from 22:5n-3. These processes may involve a system of feedback control mechanisms responsive to the plasma concentration of 22:6n-3.

Leptin is important in regulating energy homeostasis. Severe lipodystrophy is associated with leptin deficiency and insulin resistance, hypertriglyceridemia, and hepatic steatosis. Leptin deficiency is also associated with abnormalities of the pituitary hormones in rodent models and patients with congenital absence of leptin. We inquired whether similar abnormalities are seen in patients with lipodystrophy and whether replacement of leptin will make an impact on the regulation of pituitary hormones. Seven female patients (aged 15-42 yr, all diabetic) with lipodystrophy and serum leptin levels less than 4 mg/liter were treated with recombinant methionyl-human leptin (recombinant leptin) in physiological doses in an open-labeled study. The following parameters were evaluated before and at 4 months of leptin treatment: menstrual history, pelvic ultrasonogram, LHRH, TRH, and CRH tests. While on recombinant leptin, mean serum leptin concentration increased from 1.3 +/- 0.3 mg/liter to 11.1 +/- 2.5 mg/liter. Only one of five patients who had intact reproductive systems was cycling normally before leptin therapy, and all five had normal menses by the fourth month of leptin therapy. Serum E2 concentrations increased (110 +/- 44 pmol/liter vs. 546 +/- 247 pmol/liter, P = 0.002), serum T concentrations decreased (3.5 +/- 3.0 nmol/liter vs. 1.3 +/- 0.7 nmol/liter, P = 0.055), and the attenuated LH response to LHRH was corrected with therapy. Serum T(3) and free T(4) were in the normal range before leptin therapy and did not change. However, serum TSH concentrations fell from 2.2 +/- 1.1 microU/ml to 1.2 +/- 0.7 microU/ml (P < 0.001). The percent increase in TSH following TRH administration was similar before (560%) and at 4 months (580%) of leptin therapy. The mean nonstimulated ACTH and cortisol concentrations were, respectively, 6.0 +/- 3.4 pmol/liter and 680 +/- 280 nmol/liter before leptin and did not change after 4 months of therapy (4.2 +/- 1.2 pmol/liter, P = 0.11 and 453 +/- 142 nmol/liter, P = 0.13, respectively). The ACTH and cortisol responses to CRH stimulation were normal both before and after therapy. Leptin replacement improved menstrual abnormalities and low E2 levels and corrected the attenuated LH response to LHRH in a group of young women with lipodystrophy and leptin deficiency. These results add to the growing body of evidence that metabolic signals such as leptin play a role in neuroendocrine regulation.

The purpose of this study was to determine the ability of air displacement plethysmography (ADP) to estimate body fatness in prepubertal and early pubertal African American and white children. One hundred nineteen nonoverweight and overweight boys (N = 56) and girls (N = 63), age (mean +/- SD) 9.8 +/- 1.7 y, body mass index 25.9 +/- 7.6 kg/m2 (range, 14.2-47.0 kg/m2), and mean percent body fat (%BF) by dual-energy x-ray absorptiometry (DXA) 39.2 +/- 11.7% (range, 12.2-57.5%), were studied. %BF by ADP was compared with DXA %BF estimates and with body fat by several field methods: skinfold thicknesses using the Slaughter et al. equations (Hum Biol 60: 709-723, 1988), bioelectrical impedance analysis (BIA) using the Houtkooper et al. equation (J Appl Physiol 72: 366-373, 1992), and a predictive equation using skinfold thicknesses, BIA, and weight (Goran et al.: Am J Clin Nutr 63: 299-305, 1996). All methods used to estimate %BF were significantly correlated with DXA (all p < 0.0001), with r2 ranging from 0.85 (skinfold measurements) to 0.95 (ADP). ADP using the Siri equation underestimated %BF by -1.9% (p < 0.001); the Bland-Altman limits of agreement (defined as +/-2 SD) were +/-7.4%. %BF by ADP-Siri underestimated %BF by DXA by 3.0% for girls (p < 0.001) and by 0.6% for boys (NS). Agreement between body fat estimation by ADP and DXA did not vary with age, race, or pubertal stage. Application of the age-adjusted Lohman model to ADP significantly increased the magnitude of the underestimation to -6.9% (p < 0.0001). Prediction of %BF by the Slaughter skinfold thickness equation showed no significant mean bias for the overall data, but significantly underestimated %BF in girls (-3.7%) while overestimating %BF in boys (+2.4%) with wide limits of agreement (+/-17.7%, p < 0.01 versus ADP). %BF by the Houtkooper BIA equation or Goran model underestimated %BF to a significantly greater degree than ADP (Houtkooper, -8.1%; Goran, -10.1%; both p < 0.0001 versus DXA or ADP). Determination of %BF from ADP using the Siri model slightly underestimates %BF as determined by DXA in girls, but appears to be superior to existing field methods both in accuracy and limits of agreement. Because of the ease with which it can be performed, ADP may prove useful for investigations of adiposity in children.

Objectives: Acanthosis nigricans (AN) has been proposed as a reliable marker of hyperinsulinemia, but its utility for predicting hyperinsulinism has not been systematically evaluated in overweight children. We examined the relationship of AN to hyperinsulinemia and body adiposity., Study Design: One hundred thirty-nine children underwent physical examination for AN, body composition studies, an oral glucose tolerance test, and a hyperglycemic clamp., Results: Thirty-five children (25%) had AN. AN was more prevalent in African Americans (50.1%) than in white subjects (8.2%, P < .001). Independent of race, children with AN had greater body weight and body fat mass (P < .001); greater basal and glucose-stimulated insulin levels during oral glucose tolerance test (P < .001); greater first-phase, second-phase, and steady-state insulin levels (P < .001); and lower insulin sensitivity (P < .001) during the hyperglycemic clamp. After adjusting for body fat mass and age, none of these differences remained significant. When categorized by fasting insulin, 35% with fasting insulin levels > 20 microU/mL and 50% with fasting insulin levels > 15 microU/mL did not have AN. Eighty-eight percent of children with fasting insulin levels > or = 15 microU/mL had a body mass index SD score > or = 3.0., Conclusions: AN is not a reliable marker for hyperinsulinemia in overweight children. Children with a race-, sex-, and age-specific body mass index SD scores > or = 3.0 should be screened for hyperinsulinemia, whether or not they have AN.

Objectives: African American children have greater bone mineral density (BMD) and bone mineral content (BMC) than white children. We examined the hypothesis that differences in insulin-like growth factors (IGFs) are important determinants of BMD during childhood., Methods: We measured IGFs and IGF binding proteins in 59 African American and 59 white girls matched for age, body mass index, socioeconomic status, and pubertal stage. BMD and BMC were determined by dual emission x-ray absorptiometry., Results: African American girls had greater total BMD (P <.001), BMC (P <.01), total IGF-1 (P <.001), and free IGF-1 (P <.01) than white girls. IGFBP-1, IGFBP-2, and IGFBP-3 were similar in both groups or lower in African Americans. IGF-1 was positively correlated with IGF-2 in white girls (P =.012) but was negatively correlated with IGF-2 in African Americans (P =.015). IGF-1 and free IGF-1 were positively correlated with BMD/BMC. Multiple regression analyses showed 80% of the variance in BMC could be accounted for by the use of body weight, height, and IGF-1 in the model. When IGF-1 was included as a factor, race did not add to the model's predictive power., Conclusion: IGF-1 and free IGF-1 are greater in African American than in white girls and may contribute to the greater BMD of African Americans.

Background: HAART has been associated with metabolic abnormalities (hyperlipidemia, insulin resistance, alterations in cortisol metabolism) and fat redistribution., Setting: A prospective study of 26 Caucasian men (median age 43.5 years) with HIV-1 viral loads < 500 copies/ml for 12 months while on highly active antiretroviral therapy (HAART) who interrupted treatment for a median of 7.0 weeks (range 4.9-10.3 weeks). Seventeen (65.4%) patients reported at least one fat redistribution symptom at baseline., Method: Serum lipids, glucose and insulin levels during an oral glucose tolerance test, 24-h urinary free cortisol and 17-hydroxycorticosteroids, and anthropometric parameters were measured before HAART cessation and prior to its reinstitution., Results: When baseline values were compared with those obtained after HAART interruption (means +/- SD), there was a significant decrease in total cholesterol (194+/-47.3 versus 159+/-29.3 mg/dl; P < 0.0001), low density lipoprotein (LDL) cholesterol (114+/-32.6 versus 96+/-24.7 mg/dl; P = 0.0013), triglycerides (261+/-244.3 versus 185+/-165.4 mg/dl; P = 0.008), and 24-hour urinary 17-hydroxycorticosteroids (15+/-7.9 versus 5+/-2.5 mg/24 h, P < 0.0001) and a significant increase in 24-hour urinary free cortisol (45+/-34.1 versus 62+/-32.2 microg/24 h; P = 0.016). There were no significant changes in glucose or insulin levels or in anthropometric measurements., Conclusions: A relatively brief interruption of HAART resulted in significant improvements in total cholesterol, LDL cholesterol, and triglyceride levels. No changes were observed in insulin resistance profiles or anthropometric measurements, perhaps because of the brief duration of HAART interruption. These results suggest that hyperlipidemia and alterations in corticosteroid metabolism in the setting of HAART are a direct drug effect that reverses with drug withdrawal. However, glucose metabolism and fat redistribution do not change over the short term.

Background: Little is known about genes that affect childhood body weight., Objective: The objective of this study was to examine the association between alleles of the mitochondrial uncoupling protein 2 (UCP2) gene and obesity because UCP2 may influence energy expenditure., Design: We related UCP2 genotype to body composition and resting energy expenditure in 105 children aged 6-10 y. Overweight children and nonoverweight children of overweight parents were genotyped for a 45-base pair deletion/insertion (del/ins) in 3'-untranslated region of exon 8 and for an exon 4 C to T transition., Results: Eighty-nine children were genotyped for the exon 8 allele: 50 children had del/del, 33 had del/ins, and 6 had ins/ins. Mean (+/-SD) body mass index (BMI; in kg/m(2)) was greater for children with del/ins (24.1 +/- 5.9) than for children with del/del (20.4 +/- 4.8; P < 0.001). BMI of ins/ins children (23.7 +/- 7.8) was not significantly different from that of del/ins children. A greater BMI in del/ins children was independent of race and sex. Body composition was also different according to UCP2 genotype. All body circumferences and skinfold thicknesses examined were significantly greater in del/ins than in del/del children. Body fat mass as determined by dual-energy X-ray absorptiometry was also greater in del/ins than in del/del children (P < 0.005). For 104 children genotyped at exon 4, no significant differences in BMI or body composition were found among the 3 exon 4 genotypes. Neither resting energy expenditure nor respiratory quotient were different according to UCP2 exon 4 or exon 8 genotype., Conclusions: The exon 8 ins/del polymorphism of UCP2 appears to be associated with childhood-onset obesity. The UCP2/UCP3 genetic locus may play a role in childhood body weight.

A 72-h fast in normal weight women during the follicular phase results in transient alterations in neuroendocrine function, but follicle development and follicular phase length remain unaltered. In this study we evaluated neuroendocrine and ovulatory function in lean women (body fat, < or = 20%) undergoing a similar 72-h fast. Compared to fed controls, fasted lean women experienced significant weight loss, blunting of the diurnal variation of cortisol, suppression of the nocturnal TSH rise, and a decrease in T3 levels after a 72-h fast. In contrast to similarly fasted, normal weight women, lean women have significantly higher evening cortisol levels and do not exhibit a normal nocturnal TSH rise after the fast. Lean fasted women exhibited a 19% decrease in the number of LH pulses over 24 h compared to fed women (12.9 +/- 1.3 vs. 16.0 +/- 1.9; P < 0.05). Fasting did not result in significant differences in mean LH, LH amplitude, LH area under the curve, and mean FSH levels in these lean women. Of the seven fasted cycles, two were anovulatory. In the five women studied in fed and fasted cycles, one had interrupted lead follicle development with anovulation, and four had significant lengthening of the follicular phase compared to those during their fed cycles (14.4 +/- 1.2 vs. 13.2 +/- 1.0 days; P = 0.01). The clinical observations made in this small sample of lean women showing more profound changes in neuroendocrine function, anovulation, and lengthened follicular phase after fasting suggest that lean women may be more vulnerable to fasting stress than normal weight women.

The nutrient content of the diet of edentulous patients who have various oral prostheses is of concern. This study compared baseline food records to those records kept semiannually for 3 years after treatment to ascertain whether nutrient intake of edentulous patients changed after they received new implant-supported mandibular dentures (n = 41) or new conventional dentures (n = 30). No significant differences in intake of calories or of 27 nutrients were noted between the two groups (p > 0.01). A decline in the percent of calories from fat with a corresponding increase in carbohydrate calories within both groups (p < 0.01) reflected a national trend; a slight decrease in calories was similarly observed (p < 0.02). More than 40% of patients in both groups were found to have inadequate intakes of dietary fiber, calcium, or both, and 25% to 50% had low intakes of vitamins A, E, D, B6 and/or magnesium. Intakes were similar to those reported for two age-matched populations.

Because binge eating in obese individuals has been postulated to be a reaction to dietary restriction, we examined the recorded food intake of 17 obese women with and 16 obese women without binge eating disorder (BED) during 1-week periods before and 3 months after a very low calorie diet program in order to determine the effects of dietary restriction on binge eating frequency and severity. Before weight loss, rather than reporting severe caloric restriction, women with BED reported greater average energy intake than nonbinge eaters on both a total (2707 vs. 1869 k cal/day, p < .01) and weight-adjusted (25.1 vs. 18.1 kcal/kg, p < .01) basis, with both higher intake on nonbinge days and an increased frequency of binge days. After weight loss, there was no significant difference in energy intake, on either a total or weight-adjusted basis, between subjects with and without BED. Although average daily energy intake fell for both groups after weight loss, only subjects with BED reported significantly decreased energy intake when adjusted for change in body weight. This resulted from decreased intake on nonbinge days and a decreased frequency of binge days. Before weight loss, subjects with BED reported an average energy intake equivalent to 94% of their predicted energy expenditure. Whereas subjects without BED reported intake only 64% of predicted (p = .002). After weight loss, there was no significant difference between subjects with and without BED in the percentage of predicted energy expenditure reported as intake (64% vs. 58%). Restraint was similar in both groups before weight loss, but those with BED reported greater hunger and disinhibition. After weight loss treatment, restraint increased significantly, whereas disinhibition and hunger remained elevated in subjects with BED. Disinhibition, rather than restraint, appears to be a major contributor to the disordered eating of these individuals. Unlike normal-weight women with bulimia nervosa, dietary restriction does not appear to worsen symptoms of binge eating in obese women with BED. Over the short term, subjects with BED may respond to a standard weight loss treatment program with improvements in binge eating behaviors.