Adiponectin is inversely related to adiposity and positively correlated with insulin sensitivity (S(i)). Sparse data exist on the contributions of ethnicity and body fat distribution to variance in serum adiponectin. Hypotheses tested were that adiponectin would be lower in African Americans compared with Caucasians; that adiponectin would be inversely related to central, not peripheral, fat; that adiponectin would be positively associated with S(i); and that baseline adiponectin would predict change in S(i) over 2 years in 150 African-American and Caucasian youth. Multiple linear regression modeling showed that adiponectin was lower in African-American versus Caucasian children (adjusted means 10.8 +/- 0.5 vs. 12.3 +/- 0.5 microg/ml, respectively; P < 0.05); inversely related to trunk fat (P < 0.05); and positively related to limb fat (P < 0.01). Addition of the acute insulin response to glucose to the model eliminated the significance of ethnicity. S(i), which was positively related to adiponectin (P < 0.05), was lower in African Americans (P < 0.001) and girls (P < 0.05). Baseline adiponectin did not predict change in S(i) over 2 years. In conclusion, adiponectin was positively correlated with S(i), inversely related to central fat, and positively related to peripheral fat. In addition, higher acute insulin response to glucose explained lower adiponectin among African-American children.

OBJECTIVE:To determine whether eucaloric diets either enriched with monounsaturated fatty acids (MUFA; 17% energy) or low in carbohydrates (Low CHO; 43% energy) would increase insulin sensitivity (Si) and decrease circulating insulin concentrations, relative to a standard diet (STD; 56% CHO, 31% fat, 16% protein), among women with polycystic ovary syndrome (PCOS).DESIGN:Crossover.SETTING:Academic research environment.PATIENT(S):Healthy women with PCOS not on hormonal or insulin-sensitizing therapy.INTERVENTION(S):Subjects consumed three, 16-day, eucaloric diets, each separated by a 3-week washout period. A frequently sampled, intravenous, glucose tolerance test was administered at baseline and following each diet.MAIN OUTCOME MEASURE(S):Fasting glucose, insulin, the acute insulin response to glucose (AIRg), Si, sex hormone-binding globulin (SHBG), dehydroepiandrosterone sulfate (DHEAS), total testosterone (T), free T, A4, total cholesterol, high-density lipoprotein cholesterol (HDL-C), tryglycerides (TG), and free fatty acids (FFA).RESULT(S):Fasting insulin was lower following the Low CHO diet relative to the STD diet; AIRg was lower following the Low CHO diet relative to the MUFA diet. Fasting glucose, Si, and the circulating concentrations of reproductive hormones were not significantly affected by the intervention.CONCLUSION(S):A moderate reduction in dietary carbohydrate reduced the fasting and postchallenge insulin concentrations among women with PCOS, which, over time, may improve reproductive/endocrine outcomes.

BACKGROUND:Moderate alcohol consumption increases plasma HDL and lowers cardiovascular disease risk while transiently enhancing postprandial lipemia.OBJECTIVE:We hypothesized that the alcohol-mediated increase in postprandial triacylglycerol-rich lipoproteins (TRLs) and their clearance elevate HDL cholesterol and reverse cholesterol transport.DESIGN:We determined the effect in normolipidemic humans (n = 14) of postprandial lipemia produced 4 h after a test meal (M) or a test meal + 0.5 g alcohol/kg body wt (M+A) on postprandial changes in plasma lipids and on the balance of cholesterol between TRL and the cholesterol-rich LDL and HDL fractions (CRL) or red blood cells (RBCs) in fresh and incubated plasma or blood.RESULTS:Postprandial lipemia after the M and M+A test meals caused a 56% and 89% increase in plasma triacylglycerol, a 30% and 74% increase in TRL cholesterol, and a 3.8% and 6.6% decrease in CRL cholesterol, respectively. In vitro reaction of endogenous lecithin:cholesterol acyltransferase (EC 2.3.1.43) and cholesteryl ester transfer proteins via incubation of fasting plasma samples and postprandial M and M+A plasma samples for 16 h increased TRL cholesterol by 22.8% (0.08 mmol/L), 32.6% (0.16 mmol/L), and 45.8% (0.28 mmol/L) in plasma and by 71.1% (0.27 mmol/L), 89.4% (0.45 mmol/L), and 112.5% (0.70 mmol/L) in RBC-enriched blood, respectively. After the in vitro lipolysis of TRL, the elevation of HDL cholesterol in postprandial M+A plasma, but not in postprandial M plasma, was significantly greater than in fasting plasma.CONCLUSION:The alcohol-mediated increase in postprandial TRL flux and the hepatic removal of postprandial TRL after the acceptance of cholesterol from CRL and cell membranes contribute to increased HDL cholesterol and enhancement of reverse cholesterol transport in humans.

Questions remain concerning the effect of variations in cholesterol intake on plasma cholesterol concentration, as well as on the role of factors modulating the metabolic impact of this dietary intervention. To define the impact of wide variations in dietary cholesterol intake on plasma total and low-density lipoprotein (LDL) cholesterol concentrations, as well as testing the hypothesis that resistance to insulin-mediated glucose disposal would accentuate the increase in plasma total and LDL cholesterol concentrations in response to a given increment in dietary cholesterol intake, we performed a prospective, randomized study comparing diets varying in cholesterol content in 65 healthy, postmenopausal women, 31 defined as insulin-resistant and 34 as insulin-sensitive. The changes in total and LDL cholesterol in response to increments in dietary cholesterol of up to approximately 800 mg/day were modest in magnitude, without evidence of a statistically significant diet-induced increase in cholesterol concentration, or of any difference in the responses of insulin-resistant as compared with insulin-sensitive women. These results indicate that relatively large increments in dietary cholesterol intake had little effect on total or LDL cholesterol concentrations in healthy, postmenopausal women, irrespective of whether they were insulin-resistant or insulin-sensitive.

Objective: This study was designed to determine if serum leptin concentrations (adjusted for fat mass) after weight loss on a low-calorie diet predict subsequent weight gain,Research Methods and Procedures: Body composition and serum leptin concentrations were determined on 14 moderately obese, postmenopausal, nondiabetic women with a familial predisposition to obesity. Assessments were obtained under tightly controlled metabolic ward conditions of macronutrient intake and weight maintenance both before (obese state) and after a mean weight loss of 12.0 kg to normal body weight (postobese state).:Four years later, without intervention, body weight and body composition were reassessed.Results: Weight loss resulted in significant decreases in fat mass (29.7 +/- 5.4 vs. 20.3 +/- 4.7; kg), body mass index (27.7 +/- 1.6 vs. 23.0 +/- 1.5; kg/m(2)), percent body fat (40.7 +/- 4.3 vs. 33.1 +/- 5.0), and serum leptin concentrations (31.8 +/- 16.0 vs. 11.5 +/- 5.4; ng/mL). Serum leptin concentrations a ere positively correlated (p<0.05) with fat mass in both the obese and postobese states (r = 0.67 and r = 0.56, respectively). However, residual serum leptin concentrations (adjusted for fat mass) in the obese and postobese states were not related to changes in body weight (p = 0.61 and 0.52), fat mass (p = 0.72 and 0.42), body mass index (p = 0.59 and 0.33), or percent body fat (p = 0.84 and 0.46) over the follow-up period.Discussion: These finding do not support the hypothesis that relatively low concentrations of leptin predict weight regain after weight loss. However, because the number of subjects in this study was limited, further studies are warranted.

It is not known whether the decrease in the thermic effect of food (TEF) in obesity is a consequence of obesity or a factor contributing to the development of obesity. The resting energy expenditure (REE) of 24 obese, nondiabetic, postmenopausal women was 5481 +/- 110 kJ/24 h (1310 +/- 26.4 kcal/24 h). After weight loss (12.7 +/- 0.45 kg) the REE was significantly decreased (4858 +/- 94 kJ/24 h, or 1161 +/- 22.4 kcal/24 h) and equivalent to the REE of 4866 +/- 119 kJ/24 h (1163 +/- 28.5 kcal/24 h) in 24 never-obese, postmenopausal women. The TEF, expressed as a percentage of the calories ingested, was 8.2 +/- 0.50% for obese subjects, 8.7 +/- 0.57% for postobese subjects, and 9.8 +/- 0.54% for never-obese subjects. Compared with never-obese subjects, the TEF was significantly reduced in obese subjects (P = 0.043) and remained unchanged after weight loss (P = 0.341). These findings indicate that the lower TEF in the obese subjects is uncorrected by weight loss, and thus it is a contributor to obesity rather than a consequence of obesity.

Delayed-type hypersensitivity (DTH) skin testing as an assay of immune competence is a widely used technique. Accordingly, clinical situations frequently occur which require that skin tests be performed many times on the same patient. In the present investigation, in vivo and in vitro immune responses were studied over a 7-month period in 22 normal human volunteers, each of whom were skin tested 6 times at monthly intervals with multiple antigens. Patterns of responses to the 7 specific skin test antigens observed during repeated skin testing in vivo indicated non-significant, but detectable, declines in skin test reactivity to tetanus, diphtheria and streptococcus antigens and increases in reactivity to trichophyton, tuberculin, candida and proteus antigens. In vitro lymphocyte transformation assays (LTAs) of cell-mediated immune (CMI) activities revealed that repeated skin testing, e.g., 3-5 serial skin tests, induced significantly increased levels of CMI reactions with 3 of the 4 skin test antigens used as challenge antigens. Since no significant changes in in vitro CMI responses were detected using 3 control "non-skin test" antigens, the effects observed were confirmed to be antigen specific. Increased IgG antibody responses were detected for only the toxoid antigens during the skin testing period. For the group of 22 normal volunteers, positive statistical correlations were not observed between any individual skin test antigen and the immune reactions assayed specifically for that antigen, including DTH responses and levels of circulating antigen-specific antibodies. Short term differences were detected between tetanus, diphtheria and streptococcus antigens in their LTA response patterns.(ABSTRACT TRUNCATED AT 250 WORDS)

The activity of natural killer cells in the synovial fluid, the synovial tissue and the peripheral blood was studied in 23 patients with active rheumatoid arthritis and was found to be significantly lower than that in the blood of 28 controls. This decrease was inversely related to the erythrocyte sedimentation rate. The preincubation of mononuclear cells with indomethacin significantly increased the natural killer activity in the blood of the controls and the patients with rheumatoid arthritis, but did not have any effect in the synovial compartment. The elimination of the adherent cells increased the natural killer activity in the blood of the controls and the patients with rheumatoid arthritis, but decreased this activity in the synovium. The stimulatory effect of synovial macrophages and the suppressor effect of the blood macrophages on the natural killer activity were confirmed when the adherent and non-adherent populations were mixed and these effects were reproduced by using supernatants of total mononuclear cells. The stimulation of the natural killer activity by interleukin 2 and poly-I:C, an interferon inducer, is independent of the macrophages in rheumatoid arthritis. These results suggest a deficient natural killer activity in active rheumatoid arthritis and a difference in the modulation of these natural killer cells by macrophages in rheumatoid synovium and normal or rheumatoid arthritis blood.

Several aspects of interleukin-2 (IL-2) generation and function were studied employing mononuclear cells from synovial fluid (SF), synovial tissue (ST) and peripheral blood (PB) of patients with rheumatoid arthritis (RA). Decreased PHA stimulated IL-2 production by lymphocytes from rheumatoid ST, SF (P less than 0.02), and PB (P less than 0.01) was observed when compared to normal blood and SF of patients with gout. The proliferative response of rheumatoid lymphocyte blasts exposed to exogenous IL-2 was also defective (P less than 0.05-0.001). This defect was greater in SF than in rheumatoid PB (P less than 0.05-0.001). In addition to the proliferative response, the effect of IL-2 on interferon-gamma (IFN-gamma) production was also examined. Rheumatoid lymphocytes from both PB and SF produced less IFN-gamma after overnight treatment with IL-2 than did normal PB lymphocytes. This decreased IFN-gamma induction was discordant with the excellent enhancement by IL-2 of natural killer activity. Removal of adherent cells in synovial fluid did not correct this deficit. Abnormalities in the biology of IL-2 and IFN-gamma suggest that impaired T cell function could contribute to the immunopathogenesis of RA.