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The association between premature pubarche (PP) and metabolic syndrome is controversial and not supported by some authors. The aim of this study was to determine insulin resistance syndrome, plasma adiponectin, and fatty acid profile in PP girls to discern potential confounder variables and markers of metabolic disturbances. We studied 22 prepubertal girls with a diagnosis of PP and 20 healthy controls who differed in body mass index (BMI) (19.33 +/- 0.71 vs 17.30 +/- 0.60). We evaluated insulin resistance syndrome components and postprandial response of adiponectin, nonesterified fatty acids, and fatty acid profile after consumption of a standardized breakfast. No lipid disturbances were detected in the PP group. High-density lipoprotein to low-density lipoprotein cholesterol ratio tended to be lower in PP girls (P = .052), but this effect disappeared when data were adjusted for both BMI and age (P = .480). Insulin levels tended to be higher at 2 hours in PP girls, who showed significantly higher C-peptide area under the curve. In contrast, adiponectin at 3 hours after the meal and postprandial adiponectin area under the curve were significantly lower. The PP girls showed significantly higher percentages of eicosapentaenoic acid in total plasma and plasma phospholipids. No differences were found in the postprandial fatty acid clearance rate. In conclusion, PP girls and controls differed in postprandial plasma adiponectin response and in postprandial plasma C-peptide response after both BMI and age adjustment. Cholesterol plasma disturbances were mainly attributable to their higher BMI, although n-3 polyunsaturated fatty acids were higher because of the PP.
Abstract. Henneman P, Janssens ACJW, Carola Zillikens M, Frolich M, Frants RR, Oostra BA, van Duijn CM, van Dijk KW (Leiden University Medical Center, Leiden; Erasmus Medical Center, Rotterdam, The Netherlands). Menopause impacts the relation of plasma adiponectin levels with the metabolic syndrome. J Intern Med 2009; doi: 10.1111/j.1365-2796.2009.02162.xObjective. Plasma adiponectin is negatively correlated with metabolic syndrome (MetS) components obesity and insulin sensitivity. Here, we set out to evaluate the effect of menopause on the association of plasma adiponectin with MetS. Design. Data on plasma adiponectin and MetS were available from 2256 individuals participating in the Erasmus Rucphen Family study. Odds ratios for MetS were calculated by logistic regression analysis using plasma adiponectin quartiles. The discriminative accuracy of plasma adiponectin for MetS was determined by calculating the area under the curve (AUC) of receiver operator. Analyses were performed in women and men, pre- and postmenopausal women and younger and older men. Results. Virtually all determinants of MetS differed significantly between groups. Low plasma adiponectin showed the highest risk for MetS in postmenopausal women (odds ratio = 18.6, 95% CI = 7.9-44.0). We observed a high discriminative accuracy of age and plasma adiponectin for MetS not only in postmenopausal women (AUC = 0.76) but also in other subgroups (AUC from 0.67 to 0.87). However, in all groups, the discriminative accuracy of age and body mass index (BMI) for MetS was similar to the discriminative accuracy of age and plasma adiponectin. Conclusions. Low plasma levels of adiponectin are associated with increased prevalence of MetS, especially in postmenopausal women. Age and BMI have similar discriminatory accuracies for presence of MetS when compared with age and plasma adiponectin. Thus, we conclude that the association of plasma adiponectin with MetS is significantly affected by menopause but challenge the additional value of adiponectin for the discriminatory accuracy for presence of MetS.
OBJECTIVE: Adiponectin is negatively associated with leptin, insulin and obesity in children and adults. Whereas increases in fetal insulin and leptin are associated with increased weight and adiposity at birth, the role of adiponectin in fetal growth has not yet been determined. The aims of this study were to examine the relationships between adiponectin and insulin, leptin, weight and adiposity at birth in healthy term infants. DESIGN AND METHODS: Anthropometric parameters including weight, length, circumferences and skinfold thickness were measured, and plasma lipid profiles, insulin, leptin and adiponectin concentrations in cord blood samples from 226 singleton infants born at term after uncomplicated pregnancies were assayed. RESULTS: Cord plasma adiponectin, leptin and insulin levels correlated significantly and positively with birthweight (P = 0.001, P 0.001, P 0.001, respectively) and the sum of skinfold thicknesses (P 0.001, P 0.001, P 0.001, respectively). Mean cord plasma adiponectin and leptin levels, but not insulin level, were significantly higher in large-for-gestational-age (LGA) infants compared with appropriate-for-gestational-age (AGA) infants. Cord plasma leptin concentration, but not adiponectin concentration, was significantly higher in female infants than in male infants (P = 0.003 and P = 0.94, respectively). Cord plasma adiponectin concentration correlated positively with leptin level (P = 0.007) but not with insulin level (P = 0.78). CONCLUSIONS: High adiponectin levels are present in the cord blood. Cord plasma adiponectin and leptin levels are positively correlated with birthweight and adiposity. This suggests that adiponectin may be involved in regulating fetal growth.
OBJECTIVE: The relationship of visceral adiposity with adipocytokines and low-density lipoprotein (LDL) particle distribution and oxidation in Asian metabolically obese, normal-weight (MONW) individuals has not been evaluated. We aimed to investigate the association between visceral adiposity and adipocytokines and cardiovascular disease (CVD) risk factors in MONW Korean women with normal glucose tolerance. METHODS AND PROCEDURES: We examined the metabolic characteristics of 135 non-obese (BMI 25 kg/m(2)) women aged 25-64 years. Twenty-five women (BMI 25 kg/m(2) and visceral fat adiposity (VFA) > or =100 cm(2)) were classified as MONW and 25 women (BMI 25 kg/m(2) and VFA 100 cm(2)), pair-matched for age, weight, height, and menopausal status, as control group. Plasma lipid profiles and adipocytokines were evaluated in these two groups. RESULTS: MONW subjects had higher systolic (P 0.05) and diastolic blood pressure (P 0.005) and higher concentrations of triacylglycerol (TG) (P 0.005), insulin (P 0.01), and free fatty acid (FFA) (P 0.05) than control subjects. There was no significant difference between two groups in LDL-cholesterol (LDL-C) concentrations; however, MONW subjects had smaller LDL particles (P 0.01) and higher concentrations of oxidized LDL (ox-LDL) (P 0.05) compared with controls. Moreover, MONW subjects had higher concentrations of tumor necrosis factor-alpha (TNF-alpha) (P 0.05), interleukin-6 (IL-6) (P 0.05) and leptin (P 0.05), and lower plasma adiponectin concentrations (P 0.05). Higher intake of saturated fat with lower ratio of polyunsaturated fatty acids (PUFAs) to saturated fatty acids (SFA) and lower fiber intake than normal subjects were found in MONW women. DISCUSSION: We found an unfavorable inflammatory profile and a more atherogenic LDL profile in MONW female subjects even in the absence of a known CVD risk factors. Moreover, MONW consumed more saturated fat and less fiber than the control group.
Insulin resistance is a key pathogenic factor of type 2 diabetes (T2DM); in contrast, in type 1 diabetes (T1DM) it is considered a secondary alteration. Increased intramyocellular lipid (IMCL) content accumulation and reduced plasma adiponectin were suggested to be pathogenic events of insulin resistance in T2DM. This study was designed to assess whether IMCL content and plasma adiponectin were also associated with the severity of insulin resistance in T1DM. We studied 18 patients with T1DM, 7 older and overweight/obese patients with T2DM, and 15 nondiabetic, insulin-resistant offspring of T2DM parents (OFF) and 15 healthy individuals (NOR) as appropriate control groups matched for anthropometric features with T1DM patients by means of the euglycemic hyperinsulinemic clamp combined with the infusion of [6,6-2H2]glucose and 1H magnetic resonance spectroscopy of the calf muscles. T1DM and T2DM patients showed reduced insulin-stimulated glucose metabolic clearance rate (MCR: 5.1 +/- 0.6 and 3.2 +/- 0.8 ml x kg(-1) min(-1)) similar to OFF (5.3 +/- 0.4 ml x kg(-1) x min(-1)) compared with NOR (8.5 +/- 0.5 ml x kg(-1) min(-1), P 0.001). Soleus IMCL content was increased in T1DM (112 +/- 15 AU), T2DM (108 +/- 10 AU) and OFF (82 +/- 13 AU) compared with NOR (52 +/- 7 AU, P 0.05) and the result was inversely proportional to the MCR (R2 = 0.27, P 0.001); an association between IMCL content and Hb A1c was found only in T1DM (R2 = 0.57, P 0.001). Fasting plasma adiponectin was reduced in T2DM (7 +/- 1 microg/ml, P = 0.01) and OFF (11 +/- 1 microg/ml, P = 0.03) but not in T1DM (25 +/- 6 microg/ml), whose plasma level was increased with respect to both OFF (P = 0.03) and NOR (16 +/- 2 microg/ml, P = 0.05). In conclusion, in T1DM, T2DM, and OFF, IMCL content was associated with insulin resistance, demonstrating that IMCL accretion is a marker of insulin resistance common to both primary genetically determined and secondary metabolic (chronic hyperglycemia) alterations. The increased adiponectin levels in insulin-resistant patients with T1DM, in contrast to the reduced levels found in patients with T2DM and in OFF, demonstrated that the relationship of adiponectin to insulin resistance in humans is still unclear.
Humans respond to an acute excess of ingested energy by storing the surplus energy as triglyceride in white adipose tissue. To study the energetic response to acute overfeeding in human subjects with limited adipose tissue capacity, we recruited seven subjects with lipodystrophy and seven lean healthy controls. Total fat mass was approximately 70% lower in lipodystrophic subjects (mean, 6.1 kg) than in body mass index-matched lean controls (mean, 22.0 kg). Energy expenditure and macronutrient oxidation rates were assessed in chamber calorimeters on two separate occasions for 40 h, during which time subjects consumed either an energy-balanced diet or a diet incorporating 30% excess energy as fat. On the energy-balanced diet, total daily energy expenditure and basal metabolic rate were linearly associated with lean mass in both groups (r(2) = 0.83) and were not significantly different between groups when corrected for lean mass. In response to the fat challenge, total energy expenditure did not increase significantly in healthy controls (9,472 +/- 1,069 to 9,724 +/- 1,114 kJ/d; P = 0.189). Substrate oxidation results confirm that excess fat was predominantly stored. In contrast, lipodystrophic subjects significantly increased total daily energy expenditure (11,081 +/- 1,226 to 11,730 +/- 1,374 kJ/d; P 0.005). This was largely attributable to a 29% increase in fat oxidation. Thus, subjects with lipodystrophy uniquely respond to an acute hypercaloric load with a higher energy expenditure increment and by increasing fat oxidation. Insight into the molecular mechanisms responsible for this phenomenon may yield novel therapeutic approaches for obesity.
AIM: The tryptophan to arginine change in position 64 (Trp64Arg) polymorphism of the beta3-adrenergic receptor (beta3AR) gene has been associated with an increased prevalence of obesity, insulin resistance and type 2 diabetes. In this, decreased rates of energy expenditure and impaired insulin secretion could play a role. METHODS: In 10 male twin pairs discordant for the Trp64Arg polymorphism, we examined insulin response to glucose by an oral glucose tolerance test (OGTT), a frequently sampled intravenous glucose tolerance test (FSIGT), body composition by the bioimpedance method, dual-energy X-ray absorptiometry scanning and energy expenditure by indirect and direct calorimetry. RESULTS: Twins heterozygous for the Trp64Arg polymorphism showed significantly lower fat mass independent of the method used, and significantly lower fasting insulin and glucose concentrations compared with their homozygous wild-type co-twins. Correspondingly, insulin resistance and insulin secretion determined by homeostasis model assessment were significantly lower in twins carrying the Trp64Arg polymorphism. However, there were no significant differences in adiponectin levels, insulinogenic index assessed by OGTT, or insulin sensitivity, acute insulin response to glucose, glucose effectiveness or insulin disposition index assessed by minimal modelling of the FSIGT. Furthermore, there were no differences in sleeping, resting or post-prandial energy expenditure. CONCLUSIONS: In male twins with a high similarity in genetic and environmental background, the Trp64Arg polymorphism of the beta3AR gene is associated with lower fat mass, fasting insulin levels and an appropriate insulin response to glucose. Thus, heterozygosity for the Trp64Arg variant is unlikely to increase the risk of obesity, insulin resistance or type 2 diabetes.