Molecular, Metabolic, and Nutritional Changes after Metabolic Surgery in Obese Diabetic Patients (MoMen): A Protocol for a Multicenter Prospective Cohort Study.

Metabolic surgery is an essential option in the treatment of obese patients with type 2 diabetes (T2D). Despite its known advantages, this surgery still needs to be introduced in Malaysia. In this prospective study, the pathophysiological mechanisms at the molecular level will be studied and the metabolomics pathways of diabetes remission will be explored. The present study aims to evaluate the changes in the anthropometric measurements, body composition, phase angle, diet intake, biochemistry parameters, adipokines, microRNA, and metabolomics, both pre- and post-surgery, among obese diabetic patients in Malaysia. This is a multicenter prospective cohort study that will involve obese patients (n = 102) with a body mass index (BMI) of ≥25 kg/m2 (Asian BMI categories: WHO/IASO/IOTF, 2000) who will undergo metabolic surgery. They will be categorized into three groups: non-diabetes, prediabetes, and diabetes. Their body composition will be measured using a bioimpedance analyzer (BIA). The phase angle (PhA) data will be analyzed. Venous blood will be collected from each patient for glycated hemoglobin (HbA1c), lipids, liver, renal profile, hormones, adipokines, and molecular and metabolomics analyses. The serum microRNA will be measured. A gene expression study of the adipose tissue of different groups will be conducted to compare the groups. The relationship between the 1HNMR-metabolic fingerprint and the patients' lifestyles and dietary practices will be determined. The factors responsible for the excellent remission of T2D will be explored in this study.

Mechanisms and Outcomes of Metabolic Surgery in Type 2 Diabetes.

This review is aimed at synthesizing the mechanisms and outcomes of metabolic surgery on the endocrine system, microbiome, metabolomics, and at the molecular level. We review the hormonal, adipokine, microbiota, microRNA, and metabolomic changes in human and animal models following metabolic surgery for the treatment of obesity and diabetes. The most relevant studies in this area over the past 17 years have been considered for this review. In most cases, metabolic procedures, especially those that include intestinal bypass components, showed the remission of type 2 diabetes. This involves a variety of weight-independent mechanisms to improve glucose homeostasis, improving insulin sensitivity and secretion, gut microbiota, and bile acid cross-talk.

Effectiveness of a community-based intervention for weight loss on cardiometabolic risk factors among overweight and obese women in a low socio-economic urban community: findings of the MyBFF@home.

BACKGROUND: The effectiveness of lifestyle intervention for weight loss on cardiometabolic risk factors among overweight and obese individuals in the community setting remains inconclusive. This study aimed to evaluate the effect of a 6-month weight loss lifestyle intervention on cardiometabolic risk factors among overweight and obese women and the sustainability of the changes in those markers at 12-month follow-up, comparing an intervention group with a control group. METHODS: A total of 243 participants from MyBFF@home were included in this study. Fasting blood samples at baseline, 6- and 12-month were assessed for fasting plasma glucose (FPG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and triglycerides. The effect of the intervention on cardiometabolic risk markers were investigated within and between study groups using t-test and general linear model (GLM) repeated measure ANOVA. RESULTS: Results from repeated measures ANOVA showed intervention effect only in TC where significant reduction was found in the intervention group (- 0.26 mmol/L [95% CI: - 0.47 to - 0.06], p < 0.01) compared to the control group (- 0.06 mmol/L [95% CI: - 0.28 to 0.17]) at 12 months. At 6 months, TC was reduced significantly in both groups but only intervention group retained the reduction in maintenance phase while, the level increased significantly in the control group (0.22 mmol/L [95% CI: 0.06 to 0.38]). This attributed to significant increase in TC/HDL-C ratio in the control group during maintenance phase (0.32 [95% CI: 0.15 to 0.50], p < 0.001). The intervention group also showed trend of reduction in FPG at 6 months and further decreased during maintenance phase (- 0.19 mmol/L [95% CI: - 0.32 to - 0.06], p < 0.01). At 6 months HDL-C was maintained in the intervention group but reduced significantly in the control group (- 0.05 mmol/L [95% CI: - 0.10 to - 0.01], p < 0.05). No significant difference was detected in both markers when compared between groups. CONCLUSIONS: In the context of low socio-economic communities, this study supports that weight loss related lifestyle modifications over a 6-month period could improve selected cardiometabolic risk factors, particularly fasting glucose, TC and HDL-C in overweight and obese women with favourable sustainability over a 12-month period.

Prediction of body fat loss in relation to change in nutrient intake among housewives participating in the MyBFF@home study.

BACKGROUND: Diet compositions are likely to be one of the influential factors for body fat deposition. The aim of this paper was to determine the nutrient changes and its association to body fat loss among the overweight and obese housewives in the MyBFF@home study. METHODS: Data of participants in the MyBFF@home study (intervention and control groups) were analysed. Participants in the intervention group received personalised dietary counselling consisted of reduced calorie diet 1200-1500 kcal/day, while the control group was assigned to receive women's health seminars. The dietary assessment was done during the intervention phase at baseline, 1 month (m), 2 m, 3 m and 6 m using a 3-day food diary. Body fat was measured using a bioelectrical impedance analyser (In-body 720) at baseline and at the end of the intervention phase. The mean differences of nutrient intake and body compositions during the intervention phase were measured with paired t-test. The changes in body fat and nutrients intake were calculated by subtracting baseline measurements from those taken at 6 months. Multiple linear regression analysis was conducted to determine the extent to which the changes in each gram of nutrients per 1000 kcal were predictive of changes in body fat mass. RESULTS: There were significant reductions in energy, all macronutrients, dietary fibre, calcium and iron intake in both study groups after the intervention phase (p <  0.05). In the intervention group, body fat loss increased with the reduction of each gram of carbohydrate, protein and fat per 1000 kcal, (p <  0.05), and decreased with the reduction of each gram of calcium and fibre intake per 1000 kcal (p <  0.05). In the control group, body fat loss increased with the reduction of each gram fat per 1000 kcal (p <  0.05) and decreased with the reduction of each gram iron per 1000 kcal. CONCLUSION: Changes in the intake of various nutrients have different effects on body fat loss between the intervention and control group.

Impact of community lifestyle intervention on anthropometric parameters and body composition among overweight and obese women: findings from the MyBFF@home study.

BACKGROUND: The prevalence of overweight and obesity among Malaysian women remained high over the past three decades. Collaboration with existing community at-risk may be feasible for wide-scale prevention of overweight and obesity in the country. The aims of this study were to examine the impact of community-based lifestyle intervention among overweight and obese women on their anthropometric and body composition changes as compared to the usual care group. METHODS: This was a quasi-experimental study conducted in low-cost flats in Kuala Lumpur, Malaysia. A total of 255 overweight and obesity individuals aged between 18 to 59 years old were assigned to either the lifestyle intervention group (n = 169) or the usual care group (n = 146) over a period of 6 months. Individuals in the intervention group received 6 individual lifestyle counselling comprised of physical activity, diet counselling and self-monitoring components aimed to achieve at least 5% weight loss while individuals in the usual care group obtained six sessions of health care seminars from health care providers. These individuals were then followed-up for another 6 months without any intervention as part of maintenance period. RESULTS: An intention-to-treat analysis of between-groups at 6-month of intervention (ß, 95% CI) revealed greater changes in weight among intervention individuals' (- 1.09 kg vs. -0.99; p < 0.018) as compared to the control group. These changes were not sustained during the maintenance phase (between 6 and 12 months). Overall significant improvement at 12th month was found for visceral fat (- 0.78 vs. -0.64; p-value = 0.017), although no significant changes between groups were detected either during intervention or maintenance phase (p > 0.05). Individuals in the intervention group showed a significant increase for skeletal muscle mass (0.13 kg) than those individuals in the control group (- 0.37 kg), p = 0.033, throughout the study period. CONCLUSION: This study provides evidence that an overweight and obesity prevention program can be implemented in a community setting, with some reduction of several anthropometric and body composition parameters.

Effects of weight loss intervention on body composition and blood pressure among overweight and obese women: findings from the MyBFF@home study.

BACKGROUND: Obesity is related to the increased incidence of hypertension and in healthy individuals, blood pressure changes with age and body mass. The aims of this paper were to evaluate the effectiveness of the weight loss intervention on body composition and blood pressure, and to evaluate the relationship between these factors among housewives in the MyBFF@home study. METHODS: MyBFF@home intervention was a quasi-experimental study which involved 328 overweight and obese housewives aged 18-59 years old (Control group: 159, Intervention group: 169). Data of the control and intervention group (pre and post intervention who completed the body composition and blood pressure measurements were analysed. Body compositions were measured using the Body Impedance Analyser (InBody 720) and blood pressure (Systolic and Diastolic) was taken using the blood pressure monitoring device (Omron HEM 907) at baseline, 6 month and 12 month. Data analyses (Pearson's correlation test and ANOVA) were performed and analysed using SPSS Statistics for Windows, version 22.0. RESULTS: Visceral fat area, fat mass and body fat percentage, were all significantly decreased in the intervention group compared to the control group after 6 month intervention (p < 0.05). Systolic blood pressure was reduced significantly by - 6.81 mmHg (95% CI: -9.72,-3.90; p < 0.01) in the intervention and by - 7.95 mmHg (95% CI: -11.69,-4.20; p < 0.01) in the control group after 6 month intervention. Diastolic blood pressure was significantly correlated with BMI (r = 0.19), waist circumference (r = 0.23), body fat mass (r = 0.22), body fat percentage (r = 0.18) visceral fat area (r = 0.22) and skeletal muscle mass (r = 0.14) with p < 0.05. At 12-month follow-up, no significant changes of blood pressure were detected in both groups. CONCLUSION: There were significant changes in the body fat and systolic blood pressure over 6 month among the participants in the intervention group compared to the control group. However, both groups were unable to sustain the positive changes in the body fats during the maintenance phase. There was a relationship between the body composition and blood pressure during the weight loss intervention and weight loss maintenance phase. Participation among obese housewives in a community-based intervention programme led to the improvements in blood pressure and body composition.

Effect of physical activity on fasting blood glucose and lipid profile among low income housewives in the MyBFF@home study.

BACKGROUND: Regular physical activity has always been strongly recommended for good cardiovascular health. This study aimed to determine the effect of physical activity on fasting blood glucose and lipid profile among low income housewives in Klang Valley. METHODS: Data of 328 eligible housewives who participated in the MyBFF@Home study was used. Intervention group of 169 subjects were provided with an intervention package which includes physical activity (brisk walking, dumbbell exercise, physical activity diary, group exercise) and 159 subjects in control group received various health seminars. Physical activity level was assessed using short-International Physical Activity Questionnaire. The physical activity level was then re-categorized into 4 categories (active intervention, inactive intervention, active control and inactive control). Physical activity, blood glucose and lipid profile were measured at baseline, 3rd month and 6th month of the study. General Linear Model was used to determine the effect of physical activity on glucose and lipid profile. RESULTS: At the 6th month, there were 99 subjects in the intervention and 79 control group who had complete data for physical activity. There was no difference on the effect of physical activity on the glucose level and lipid profile except for the Triglycerides level. Both intervention and control groups showed reduction of physical activity level over time. CONCLUSION: The effect of physical activity on blood glucose and lipid profile could not be demonstrated possibly due to physical activity in both intervention and control groups showed decreasing trend over time.

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 extract down-regulates hydroxysteroid (11-beta) dehydrogenase 1 expression and corticosterone levels in ovariectomized rats.

We evaluated the effects of a standardized Labisia pumila var. alata (LPva) extract on body weight change, hydroxysteroid (11-beta) dehydrogenase 1 (HSD11B1) expressions and corticosterone (CORT) level in ovariectomized (OVX) rats. The decoction of LPva has been used for generations among Malay women in Malaysia to maintain a healthy reproductive system.Thirty-six Sprague-Dawley OVX rats were treated orally with LPva extract (10, 20 or 50 mg/kg/day) or estrogen replacement (ERT) for 30 days. Sham operated rats were used as controls. Compared to untreated OVX rats, LPva-treated rats showed less weight gain and had significantly down-regulated HSD11B1 mRNA in liver tissues. HSD11B1 mRNA in adipose tissues increased by 55% (p < 0.05) in OVX rats but normalized in rats treated with LPva. Similarly, there was significant down-regulation (p < 0.05) of protein levels of HSD11B1 in both liver and adipose tissue of LPva and ERT groups, and CORT levels were significantly reduced in both groups of rats. This is the first study ever conducted to evaluate the beneficial effects of LPva in relation to weight gain caused by estrogen insufficiency. Results implied that the bioactive components in LPva extract affect not only HSD11B1 expressions in both adipose and liver tissues but also decrease circulating CORT. The extract should be explored for its potential use as a natural remedy for weight management.

Labisia pumila var. alata reduces bacterial load by inducing uroepithelial cell apoptosis.

ETHNOPHARMACOLOGICAL RELEVANCE: Labisia pumila var. alata (LPva) is a traditional medicinal herb used by Malaysian women to treat many ailments of the genitourinary tract. Its phytoestrogenic properties suggest potential to prevent recurrent urinary tract infection (UTI) in women post menopause. The aim of this study was therefore to investigate the mechanisms of action of LPva in an in vitro model of UTI. MATERIALS AND METHODS: Bladder epithelial cell lines T24 and 5637 and uropathogenic Escherichia coli (UPEC) strain CFT073 were used to model uroepithelial infection. The ability of LPva to induce programmed cell death was tested using the Annexin-V-FLUOS and TUNEL assays. Expression of caveolin-1, ß1 integrin and antimicrobial peptides HBD-2 and LL-37 in response to LPva treatment and/or infection, was assessed using RT real-time PCR. Effects on protein expression were confirmed by Western blot analysis. Sensitivity and yeast agglutination assays were employed to determine if LPva had antimicrobial activities and/or interacted with type 1 fimbriae, respectively. Finally, bacterial adherence and invasion to cells treated with LPva was examined. RESULTS: LPva induced uroepithelial apoptosis which was coupled with upregulated expression of caveolin-1 and downregulation of ß1 integrin. LPva did not exhibit direct antimicrobial properties and did not influence antimicrobial peptide levels in cells. Additionally, LPva did not interact with type 1 fimbriae and did not affect adherence in comparison to non-treated control cells. However, LPva significantly reduced the number of intracellular UPEC in bladder epithelial cells. CONCLUSIONS: Our findings suggest that LPva has beneficial applications against UPEC infection due to its ability to induce programmed cell death and reduce bacterial invasion of the uroepithelium.

Labisia pumila extract regulates body weight and adipokines in ovariectomized rats.

OBJECTIVE: We investigated the effects of a standardized water extract of Labisia pumila var. alata (LPva), and compared to estrogen replacement (ERT), on body weight gain, uterus weight, adipose tissue mRNA and protein levels of adipokines in ovariectomized (OVX) rats. METHODS: Eight-week-old OVX Sprague-Dawley rats were administered orally with either 10 mg/kg/day (LPva10), 20 mg/kg/day (LPva20) or 50 mg/kg/day (LPva50) of LPva for 30 days. Sham-operated (Sham) and estrogen-treated OVX rats (ERT, 0.625 mg/kg/day) served as controls. Plasma adipokines were measured, and mRNA expressions of the adipokines were determined in the adipose tissues. RESULTS: ERT- and LPva50-treated OVX rats showed significantly less (p<0.05) weight gain compared to untreated OVX rats. Ovariectomy caused plasma leptin levels to decrease significantly (p<0.05), but when treated with LPva or ERT, plasma leptin increased significantly to levels higher or comparable to that seen in the Sham group. The mRNA expression of leptin was higher in the LPva-treated animals than in all other groups. In contrast, the elevated plasma resistin concentrations in OVX rats were significantly reduced in rats given ERT (p<0.05) and LPva extracts (p<0.05). There was no difference in adiponectin levels in all groups. The uterus to body weight ratio of untreated OVX rats was significantly low compared to Sham (p<0.05), but showed dose-dependent increase upon treatment with LPva. CONCLUSION: The present study provides first evidence that LPva exerts uterotrophic effect and regulates body weight gain by modulating secretion of leptin and resistin, and expression of the adipokines in adipose tissues.