Cardiometabolic risk factors among children who are affected by overweight, obesity and severe obesity.

Background: The increasing severity of obesity is expected to lead to more serious health effects. However, there is limited information on the prevalence and clinical characteristics of cardiometabolic risk factors in severely children affected by obesity in Malaysia. This baseline study aimed to investigate the prevalence of these factors and their association with obesity status among young children. Methods: In this study, a cross-sectional design was employed using the baseline data obtained from the My Body Is Fit and Fabulous at school (MyBFF@school) intervention program involving obese school children. Obesity status was defined using the body mass index (BMI) z-score from the World Health Organization (WHO) growth chart. Cardiometabolic risk factors presented in this study included fasting plasma glucose (FPG), triglycerides (TGs), total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), blood pressure, acanthosis nigricans, insulin resistance (IR), and MetS. MetS was defined using the International Diabetes Federation (IDF) 2007 criteria. Descriptive data were presented accordingly. The association between cardiometabolic risk factors, such as obesity status, and acanthosis nigricans with MetS was measured using multivariate logistic regression, which was adjusted for gender, ethnicity, and strata. Results: Out of 924 children, 38.4% (n = 355) were overweight, 43.6% (n = 403) were obese, and 18% (n = 166) were severely obese. The overall mean age was 9.9 ± 0.8 years. The prevalence of hypertension, high FPG, hypertriglyceridemia, low HDL-C, and the presence of acanthosis nigricans among severely children affected by obesity was 1.8%, 5.4%, 10.2%, 42.8%, and 83.7%, respectively. The prevalence of children affected by obesity who were at risk of MetS in <10-year-old and MetS >10-year-old was observed to be similar at 4.8%. Severely children affected by obesity had higher odds of high FPG [odds ratio (OR) = 3.27; 95% confdence interval (CI) 1.12, 9.55], hypertriglyceridemia (OR = 3.50; 95%CI 1.61, 7.64), low HDL-C (OR = 2.65; 95%CI 1.77, 3.98), acanthosis nigricans (OR = 13.49; 95%CI 8.26, 22.04), IR (OR = 14.35; 95%CI 8.84, 23.30), and MetS (OR = 14.03; 95%CI 3.97, 49.54) compared to overweight and children affected by obesity. The BMI z-score, waist circumference (WC), and percentage body fat showed a significant correlation with triglycerides, HDL-C, the TG: HDL-C ratio, and the homeostatic model assessment for IR (HOMA-IR) index. Conclusions: Severely children affected by obesity exhibit a higher prevalence of and are more likely to develop cardiometabolic risk factors compared to overweight and children affected by obesity. This group of children should be monitored closely and screened periodically for obesity-related health problems to institute early and comprehensive intervention.

Changes in Mitochondrial Epigenome in Type 2 Diabetes Mellitus.

Type 2 Diabetes Mellitus is a major chronic metabolic disorder in public health. Due to mitochondria's indispensable role in the body, its dysfunction has been implicated in the development and progression of multiple diseases, including Type 2 Diabetes mellitus. Thus, factors that can regulate mitochondrial function, like mtDNA methylation, are of significant interest in managing T2DM. In this paper, the overview of epigenetics and the mechanism of nuclear and mitochondrial DNA methylation were briefly discussed, followed by other mitochondrial epigenetics. Subsequently, the association between mtDNA methylation with T2DM and the challenges of mtDNA methylation studies were also reviewed. This review will aid in understanding the impact of mtDNA methylation on T2DM and future advancements in T2DM treatment.

Postprandial glucose-lowering effects by sago (Metroxylon sagu Rottb.) resistant starch in spontaneously type 2 diabetes, Goto-Kakizaki rat.

Introduction: The beneficial effects of resistant starch (RS) consumption on health in terms of reducing postprandial hyperglycaemia are evident. However, the potential of local Sarawak sago RS in regulating glucose has not been extensively studied. Objectives: This study aims to identify glucose-lowering effects of Sarawak sago RS, namely native (RS2) and chemically modified (RS4). Methodology: An oral glucose tolerance test (OGTT) was performed before and after 1 month treatment with sago RS2 and RS4 in spontaneously type 2 diabetes (T2D), Goto-Kakizaki (GK) rat. The mechanisms involved were further explored by screening the in vitro inhibitory activities of α-glucosidase and dipeptidyl peptidase (DPP)-IV. Histopathology examination for pancreas, kidney and liver tissues was done in response to sago RS intake using haematoxylin and eosin (H&E) staining. Results and discussion: The incremental area under the curve (iAUC) for blood glucose in RS-treated groups was decreased and significant in RS2-treated group (p < 0.05). Improved iAUC for insulin and higher glucagon-like peptide (GLP-1) levels were observed in all RS-treated groups (p < 0.05). Both sago RS may have potential roles in regulating glucose via α- glucosidase and DPP-IV inhibitory activities by reducing intestinal glucose absorption. For histopathology, although insignificant, sago RS2 and RS4 attenuated lesion scores of pancreatic tissue whereas the liver and kidney tissues significantly showed lesser lesion scores compared to the control diabetic group suggesting the potential of RS in reducing cell degeneration. Conclusion: Findings of this study indicates that RS2 showed greater glucose-lowering effect when compared to RS4, thus the therapeutic potential in the T2D management should be further explored.

TG: HDL-C Ratio as Insulin Resistance Marker for Metabolic Syndrome in Children With Obesity.

Insulin resistance (IR) is an important variable in the diagnosis of metabolic syndrome (MetS). Currently, IR is not part of the existing pediatric definition of MetS, instead elevated fasting blood glucose (FBG) is measured as an indicator of hyperglycemia. Arguably, many obese children with severe IR are still able to regulate their FBG well. Hence, this study aimed to assess the utility of triglyceride-to-high-density lipoprotein cholesterol (TG : HDL-C) ratio as an IR marker in the modeling of pediatric MetS among children with obesity using structural equation modeling (SEM). A total of 524 blood samples from children with obesity (age 10-16 years old) were analyzed for FBG, lipids, insulin, leptin, and adiponectin. Both exploratory (EFA) and confirmatory factor analysis (CFA) were used to examine TG : HDL-C ratio as an IR marker in pediatric MetS. EFA shows that TG: HDL-C ratio (standardized factor loading = 0.904) groups together with homeostasis model assessment-estimated insulin resistance (HOMA-IR) (standardized factor loading = 0.664), indicating a strong correlation to the IR factor. Replacing FBG with TG: HDL-C ratio improved the modeling of MetS structure in children with obesity. Our MetS model of TG: HDL-C ratio as IR component shows comparable model fitness indices (goodness of fit, Akaike's information criterion, and Bayesian information criterion) with leptin:adiponectin ratio (platinum standard for adiposity:IR marker) model. The least model fit was seen when using FBG as an IR surrogate. TG : HDL-C ratio performed better as IR surrogate in MetS structures (standardized factor loading = 0.39) compared to FBG (standardized factor loading = 0.27). TG: HDL-C ratio may be considered as an IR component in pediatric MetS.

Weight Change and Its Association with Cardiometabolic Risk Markers in Overweight and Obese Women.

Objectives: To examine the association of weight loss magnitude with changes in cardiometabolic risk markers in overweight and obese women from low socioeconomic areas engaged in a lifestyle intervention. Methods: Analyses were performed on 243 women (mean body mass index 31.27 ± 4.14 kg/m2) who completed a 12-month lifestyle intervention in low socioeconomic communities in Klang Valley, Malaysia. Analysis of covariance (ANCOVA) was used to compare changes of cardiometabolic risk factors across weight change categories (2% gain, ±2% maintain, >2 to <5% loss, and 5 to 20% loss) within intervention and control group. Results: A graded association for changes in waist circumference, fasting insulin, and total cholesterol (p=0.002, for all variables) across the weight change categories were observed within the intervention group at six months postintervention. Participants who lost 5 to 20% of weight had the greatest improvements in those risk markers (-5.67 cm CI: -7.98 to -3.36, -4.27 µU/mL CI: -7.35, -1.19, and -0.59 mmol/L CI: -.99, -0.19, respectively) compared to those who did not. Those who lost >2% to <5% weight reduced more waist circumference (-4.24 cm CI: -5.44 to -3.04) and fasting insulin (-0.36 µU/mL CI: -1.95 to 1.24) than those who maintained or gained weight. No significant association was detected in changes of risk markers across the weight change categories within the control group except for waist circumference and adiponectin. Conclusion: Weight loss of >2 to <5% obtained through lifestyle intervention may represent a reasonable initial weight loss target for women in the low socioeconomic community as it led to improvements in selected risk markers, particularly of diabetes risk.

Gene Expression Profiling associated with Hepatoxicity in Pregnant Rats treated with Ubi Gadong (Dioscorea hispida) Extract.

Dioscorea hispida (D.hispida) is the most well-known starchy tuber in Malaysia and called 'ubi gadong'. Despite concerns over toxicity effects, the tuber is known to possess therapeutic values due to the presence of bioactive compounds such as saponins. This study was performed to identify the changes in gene expression profiles associated with hepatoxicity in pregnant rat treated with D.hispida using RT² Profiler PCR Array. The identification of steroidal saponins from D.hispida was carried out by UHPLC/MS method. Treatment of D.hispida caused mortality when dosage above 2000 mg/kg b.w. was given to pregnant rats. The PCR array showed that several genes were significantly up and down-regulated upon treatment with D.hispida. Treatment of D.hispida at 2000 mg/kg b.w leads to significant upregulation of several genes such as Btg2, Gsr, L2hgdn, S100a8, Slc17a3, Bhmt, Cd68, Cyp1a2 whereas several genes were downregulated such as Abcb1a, Aldoa, Cdc14b, Icam1, Krt18, Hpn and Maob. The consumption of D.hispida extract when taken at lower dosage of 2000 mg/kg may not be harmful to rats. D.hispida extract given at the highest dosage to pregnant rats caused alterations of several genes categorized in different hepatotoxic group functions such as necrosis, cholestasis and phospholipodisis.

Electrophoretic Techniques for the Detection of Human Microsatellite D19S884.

BACKGROUND: The detection and analysis of microsatellites is very important for the mapping of genetic diseases because they are commonly used as genetic markers. Microsatellite marker D19S884 has been associated with polycystic ovary syndrome (PCOS), the most common reproductive endocrine disease of women in their childbearing years. It is responsible for an estimated 70% of cases of anovulatory infertility. In this work, we detected microsatellites in DNA extracted from the blood of PCOS patients. METHODS: DNA microsatellites were amplified by polymerase chain reaction (PCR) using a pair of specific primers tagged with fluorescence to yield products of 160-200 base pairs in length. Alleles were separated on 4% low-melting agarose gels; stained with a safe gel staining, GelRed™, which is an alternative to ethidium bromide; and visualised by ultraviolet illumination. RESULTS: Bands were observed, but their base-pairs differences were difficult to distinguish. To identify each allele clearly, the PCR products were also analysed using capillary gel electrophoresis for fragment analysis where it was possible to discriminate even in case of difference between two pairs of bases between the alleles. CONCLUSION: In this article, we present a protocol that combines the use of gel electrophoresis and fragment analysis in the identification of genetic biomarkers for PCOS.

Labisia pumila Upregulates Peroxisome Proliferator-Activated Receptor Gamma Expression in Rat Adipose Tissues and 3T3-L1 Adipocytes.

Peroxisome proliferator-activated receptor gamma (PPARgamma) is a ligand-activated transcription factor that regulates lipid and glucose metabolism. We investigated the effects of Labisia pumila (LP) standardized water extract on PPARgamma transcriptional activity in adipocytes in vitro and in vivo. We used a rat model of dihydrotestosterone- (DHT-) induced polycystic ovary syndrome (PCOS), a condition characterized by insulin resistance. At 9 weeks of age, the PCOS rats were randomly subdivided into two groups: PCOS-LP (50 mg/kg/day of LP) and PCOS-control (1 mL of deionised water) for 4-5 weeks on the same schedule. Real-time RT-PCR was performed to determine the PPARgamma mRNA levels. LP upregulated PPARgamma mRNA level by 40% in the PCOS rats. Western blot analysis further demonstrated the increased PPARgamma protein levels in parallel with upregulation in mRNA. These observations were further proven by adipocytes culture. Differentiated 3T3-L1 adipocytes were treated with final concentration of 100 µ g/mL LP and compared to untreated control and 10 µ M of rosiglitazone (in type of thiazolidinediones). LP increased PPARgamma expressions at both mRNA and protein levels and enhanced the effect of glucose uptake in the insulin-resistant cells. The data suggest that LP may ameliorate insulin resistance in adipocytes via the upregulation of PPARgamma pathway.