Objective: The aim of this study is to assess the association between the degree of insulin resistance and the different components of the metabolic syndrome among Chinese children and adolescents. Moreover, to determine the cut-off values for homeostasis model assessment of insulin resistance (HOMA-IR) at MS risk.Methods: 3203 Chinese children aged 6 to 18 years were recruited. Anthropometric and biochemical parameters were measured. Metabolic syndrome (MS) was identified by a modified Adult Treatment Panel III (ATP III) definition. HOMA-IR index was calculated and the normal reference ranges were defined from the healthy participants. Receiver operating characteristic (ROC) analysis was used to find the optimal cutoff of HOMA-IR for diagnosis of MS.Results: With the increase of insulin resistance (quintile of HOMA-IR value), the ORs of suffering MS or its related components were significantly increased. Participants in the highest quintile of HOMA-IR were about 60 times more likely to be classified with metabolic syndrome than those in the lowest quintile group. Similarly, the mean values of insulin and HOMA-IR increased with the number of MS components. The present HOMA-IR cutoff point corresponding to the 95th percentile of our healthy reference children was 3.0 for whole participants, 2.6 for children in prepubertal stage and 3.2 in pubertal period, respectively. The optimal point for diagnosis of MS was 2.3 in total participants, 1.7 in prepubertal children and 2.6 in pubertal adolescents, respectively, by ROC curve, which yielded high sensitivity and moderate specificity for a screening test. According to HOMA-IR > 3.0, the prevalence of insulin resistance in obese or MS children were 44.3% and 61.6% respectively.Conclusions: Our data indicates insulin resistance is common among Chinese obese children and adolescents, and is strongly related to MS risk, therefore requiring consideration early in life. As a reliable measure of insulin resistance and assessment of MS risk, the optimal HOMA-IR cut-off points in this cohort were developed with variation regarding puberty. HOMA-IR may be useful for early evaluating insulin resistance in children and teenagers and could have a long-term benefit of preventive and diagnostic therapeutic intervention.

Article published by the Endocrine Society Article published by the Endocrine Society

Breast milk (BM) hormones have been hypothesised as a nutritional link between maternal and infant metabolic health. This study aimed to evaluate hormone concentrations in BM of women with and without gestational diabetes mellitus (GDM), and the relationship between maternal factors, BM hormones and infant growth. We studied ninety-six nulliparous women with (n 48) and without GDM and their exclusively breastfed term singletons. Women with GDM received dietary therapy or insulin injection for euglycaemia during pregnancy. Hormone concentrations in BM, maternal BMI and infant growth were longitudinally evaluated on postnatal days 3, 42 and 90. Mothers with GDM had decreased concentrations of adiponectin (P_colostrum<0·001; P_mature-milk=0·009) and ghrelin (P_colostrum=0·011; P_mature-milk<0·001) and increased concentration of insulin in BM (P_colostrum=0·047; P_mature-milk=0·021). Maternal BMI was positively associated with adiponectin (β=0·06; 95 % CI 0·02, 0·1; P=0·001), leptin (β=0·16; 95 % CI 0·12, 0·2; P<0·001) and insulin concentrations (β=0·06; 95 % CI 0·02, 0·1; P<0·001), and inversely associated with ghrelin concentration in BM (β=–0·08; 95 % CI –0·1, –0·06; P<0·001). Among the four hormones, adiponectin was inversely associated with infant growth in both the GDM (β_{weight-for-height}=–2·49; 95 % CI –3·83, –1·15; P<0·001; β_{head-circumference}=–0·39; 95 % CI –0·65, –0·13; P=0·003) and healthy groups (β_{weight-for-height}=–1·42; 95 % CI –2·38, –0·46; P=0·003; β_{head-circumference}=–0·15; 95 % CI –0·27, –0·03; P=0·007). Maternal BMI and GDM are important determinants of BM hormone concentrations. Milk-borne adiponectin is determined by maternal metabolic status and plays an independent down-regulating role in early infant growth.

An adverse intrauterine environment, induced by a chromium-restricted diet, is a potential cause of metabolic disease in adult life. Up to now, the relative mechanism has not been clear. C57BL female mice were time-mated and fed either a control diet (CD), or a chromium-restricted diet (CR) throughout pregnancy and the lactation period. After weaning, some offspring continued the diet diagram (CD-CD or CR-CR), while other offspring were transferred to another diet diagram (CD-CR or CR-CD). At 32 weeks of age, glucose metabolism parameters were measured, and the liver from CR-CD group and CD-CD group was analyzed using a gene array. Quantitative real-time polymerase chain reaction (qPCR) and Western blot were used to verify the result of the gene array. A maternal chromium-restricted diet resulted in obesity, hyperglycemia, hyperinsulinemia, increased area under the curve (AUC) of glucose in oral glucose tolerance testing and homeostasis model assessment of insulin resistance (HOMA-IR). There were 463 genes that differed significantly (>1.5-fold change, p < 0.05) between CR-CD offspring (264 up-regulated genes, 199 down-regulated genes) and control offspring. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and STRING (Search Tool for the Retrieval of Interacting Genes/Proteins) analysis revealed that the insulin signaling pathway and Wnt signaling pathway were in the center of the gene network. Our study provides the first evidence that maternal chromium deficiency influences glucose metabolism in pups through the regulation of insulin signaling and Wnt signaling pathways.

Background: Although attention to metabolic syndrome (MetS) in children has increased, there is still no universally accepted definition and its pathogenesis remains unclear. Our aim was to compare the current definitions of childhood MetS in a Chinese cohort and to examine the clustering pattern of MetS risk factors, particularly inclusion of leptin and adiponectin as additional components. Methods: 3373 schoolchildren aged 6 to 18 years were recruited. Anthropometric and biochemical parameters and adipokines were measured. MetS was identified using both the International Diabetes Federation (IDF) and a modified Adult Treatment Panel III (ATP III) definitions. Exploratory factor analysis was performed to establish grouping of metabolic characteristics. Results: For children ≥10 years, the prevalence of MetS was 14.3% in the obese group and 3.7% in the overweight group according to the new IDF definition, and 32.3% in the obese group and 8.4% in the overweight group according to the modified ATPIII definition. Frequency of hypertriglyceridemia, low high-density lipoprotein cholesterol (HDL-C), impaired fasting glucose, elevated blood pressure, and central obesity according to the new IDF definition was 16.7%, 20.7%, 15.8%, 25.5% and 75.5% in obese boys and 14.7%, 24.0%, 12.0%, 11.0% and 89.0% in obese girls, respectively. Metabolic abnormalities in children under 10 years of age were also noted. Using factor analysis on eight conventional variables led to the extraction of 3 factors. Waist circumference (WC) provided a connection between two factors in boys and all three factors in girls, suggesting its central role in the clustering of metabolic risk factors. Addition of leptin and adiponectin also led to the extraction of 3 factors, with leptin providing a connection between two factors in girls. When using WC, mean arterial pressure, triglyceride/HDL-C ratio, HOMA-IR and leptin/adiponectin ratio as variables, a single-factor model was extracted. WC had the biggest factor loading, followed by leptin/adiponectin ratio. Conclusions: MetS was highly prevalent amongst obese children and adolescents in this cohort, regardless of the definition used. Central obesity is the key player in the clustering of metabolic risk factors in children, supporting the new IDF definition. Moreover, our findings suggest that a common factor may underlie MetS. Leptin/adiponectin ratio as a possible component of MetS deserves further consideration.

Berberine is known to inhibit the differentiation of 3T3-L1 cellsin vitro,improve glycemic control, and attenuate dyslipidemia in clinical study. The aim of this study was to investigate the effects of berberine on preadipocytes isolated from human omental fat and in metabolic syndrome patients treated with berberine for 3 months. We have shown that treatment with 10 μM berberine resulted in a major inhibition of human preadipocyte differentiation and leptin and adiponectin secretion accompanied by downregulation of PPARγ2, C/EBPα, adiponectin, and leptin mRNA expression. After 3 months of treatment, metabolic syndrome patients showed decrease in their BMI (31.5±3.6versus27.4±2.4 kg/m²) and leptin levels (8.01 versus 5.12 μg/L), as well as leptin/adiponectin ratio and HOMA-IR. These results suggest that berberine improves insulin sensitivity by inhibiting fat store and adjusting adipokine profile in human preadipocytes and metabolic syndrome patients.