The Effect of a Combined Intermittent Fasting Healthy Plate Intervention on Anthropometric Outcomes and Body Composition Among Adults With Overweight and Obesity: Nonrandomized Controlled Trial.

BACKGROUND: Adult obesity and overweight pose a substantial risk to global public health and are associated with various noncommunicable diseases. Although intermittent fasting (IF) is increasingly used as a relatively new dietary strategy for weight loss, the effectiveness of 2 days per week of dry fasting remains unknown. OBJECTIVE: This study aims to evaluate the effectiveness of a combined dry IF and healthy plate (IFHP) and healthy plate (HP) intervention in improving anthropometric outcomes and body composition. METHODS: This nonrandomized controlled trial involved 177 adults who were overweight and obese. Among them, 91 (51.4%) were allocated to the IFHP group and 86 (48.6%) were allocated to the HP group. The overall study duration was 6 months (October 2020 to March 2021). The intervention was divided into 2 phases: supervised (3 months) and unsupervised (3 months). The data were collected at baseline, after the supervised phase (month 3), and after the unsupervised phase (month 6). Anthropometric (weight, height, waist circumference, and hip circumference) and body composition (body fat percentage, body fat mass, skeletal muscle mass, and visceral fat area) data were measured at all 3 data collection points. Sociodemographic data were obtained using a questionnaire at baseline. RESULTS: Most participants were female (147/177, 83.1%) and Malay (141/177, 79.7%). After 3 months, there were significant reductions in weight (difference -1.68; P<.001), BMI (difference -0.62; P<.001), body fat percentage (difference -0.921; P<.001), body fat mass (difference -1.28; P<.001), and visceral fat area (difference -4.227; P=.008) in the IFHP group, whereas no significant changes were observed in the HP group. Compared to baseline, participants in the IFHP group showed a significant decrease in weight (difference -1.428; P=.003), BMI (difference -0.522; P=.005), body fat percentage (difference -1.591; P<.001), body fat mass (difference -1.501; P<.001), visceral fat area (difference -7.130; P<.001), waist circumference (difference -2.304; P=.001), and hip circumference (difference -1.908; P=.002) at month 6. During the unsupervised phase, waist (IFHP difference -3.206; P<.001, HP difference -2.675; P=.004) and hip (IFHP difference -2.443; P<.001; HP difference -2.896; P<.001) circumferences were significantly reduced in both groups (P<.01), whereas skeletal muscle mass (difference 0.208; P=.04) and visceral fat area (difference -2.903; P=.003) were significantly improved in the IFHP group only. No significant difference in the between-group comparison was detected throughout the intervention (all P>.05). CONCLUSIONS: A combined IFHP intervention was effective in improving anthropometric outcomes and body composition in adults with overweight and obesity. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.2196/33801.

Recent Progress in Genetics and Epigenetics Research on Diabetic Nephropathy in Malaysia.

Diabetic nephropathy is a multifactorial disease. Gene susceptibility, as well as environmental exposure, plays an important role in disease progression. Malaysia is reported to be among the world's second-fastest-growing rates of kidney failure. Diabetic nephropathy has become the main cause of end-stage renal disease in Malaysia. This article is aimed at reviewing genetic studies conducted among diabetic nephropathy patients in the Malaysian population. This review was conducted by searching PubMed, MEDLINE, and Google Scholar databases to identify all relevant papers published in English from March 2022 to April 2022, using the following keywords: diabetes, type 2 diabetes, diabetic nephropathy, diabetic kidney disease, and Malaysia. The case-control study among diabetic patients with and without diabetic nephropathy showed a significant association with diabetic nephropathy in CNDP1, NOS3, and MnSOD genes. In the ethnic subgroup analysis, significant differences for diabetic nephropathy in terms of diabetes duration (≥10 years) were observed for CCL2 rs3917887, CCR5 rs1799987, ELMO1 rs74130, and IL8 rs4073. The IL8 rs4073 was associated only with the Indians, while the CCR5 rs1799987 was associated with the Chinese. In Malays, SLC12A3 Arg913Gln polymorphism and ICAM1 K469E (A/G) polymorphism were found to be associated with diabetic nephropathy. Studies on gene-environment interactions have suggested significant genetic and environmental factors such as smoking, waist circumference, and sex for eNOS rs2070744, PPARGC1A rs8192678, KCNQ1 rs2237895, and KCNQ1 rs2283228 with kidney disease. The genetic variants' contributions differed across ethnic groups. Therefore, a study to validate the genetic variants that are found to be associated with different ethnicities in Malaysia may be important in future studies.

Cardiometabolic and Anthropometric Outcomes of Intermittent Fasting Among Civil Servants With Overweight and Obesity: Study Protocol for a Nonrandomized Controlled Trial.

BACKGROUND: Overweight and obesity among adults are a growing global public health threat and an essential risk factor for various noncommunicable diseases. Although intermittent fasting is a generally new dietary approach to weight management that has been increasingly practiced worldwide, the effectiveness of 2 days per week dry fasting remains unclear. OBJECTIVE: The Cardiometabolic and Anthropometric Outcomes of Intermittent Fasting study aims to determine the cardiometabolic, anthropometric, dietary intake, and quality of life changes among civil servants with overweight and obesity, following combined intermittent fasting and healthy plate (IFHP) and healthy plate (HP) and explore the participants' experiences. METHODS: We designed a mixed methods quasi-experimental study to evaluate the effectiveness of the IFHP and HP methods among adults with overweight and obesity. A total of 177 participants were recruited for this study, of which 91 (51.4%) were allocated to the IFHP group and 86 (48.6%) to the HP group. The intervention comprised 2 phases: supervised (12 weeks) and unsupervised (12 weeks). Data collection was conducted at baseline, after the supervised phase (week 12), and after the unsupervised phase (week 24). Serum and whole blood samples were collected from each participant for analysis. Data on sociodemographic factors, quality of life, physical activity, and dietary intake were also obtained using questionnaires during data collection. RESULTS: Most of the participants were female (147/177, 83.1%) and Malay (141/177, 79.7%). The expected outcomes of this study are changes in body weight, body composition, quality of life, physical activity, dietary intake, and cardiometabolic parameters such as fasting blood glucose, 2-hour postprandial blood glucose, hemoglobin A1c, fasting insulin, and lipid profile. CONCLUSIONS: The Cardiometabolic and Anthropometric Outcomes of Intermittent Fasting study is a mixed methods study to evaluate the effectiveness of combined IFHP and HP interventions on cardiometabolic and anthropometric parameters and explore participants' experiences throughout the study. TRIAL REGISTRATION: ClinicalTrials.gov NCT05034653; https://clinicaltrials.gov/ct2/show/NCT05034653. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR1-10.2196/33801.

Genetic, epigenetic and protein analyses of intercellular adhesion molecule 1 in Malaysian subjects with type 2 diabetes and diabetic nephropathy.

AIMS: Recent research has implicated that the inflammation may be a key pathophysiological mechanism in diabetic nephropathy (DN). Intercellular adhesion molecule 1 (ICAM-1) is an acute phase marker of inflammation. In the present study, we carried out genetic, epigenetic and protein analyses of ICAM-1 in a Malaysian population, including normal glucose tolerance (NGT) subjects and type 2 diabetes (T2D) patients with or without DN in order to evaluate its role in DN. METHODS: Analyses of DNA polymorphism and methylation in the ICAM1 gene were performed with TaqMan allelic discrimination and pyrosequencing, respectively. Plasma ICAM-1 levels were determined using an enzyme-linked immune-sorbent assay kit. RESULTS: We found that the ICAM1 K469E(A/G) polymorphism (rs5498) was significantly associated with DN. Particularly, 86.1% of T2D patients with DN carried heterozygous genotype compared to the patients without DN (68.6%). Furthermore, plasma ICAM-1 levels were increased from NGT subjects to T2D patients without and with DN (P<0.001). The NGT subjects carrying heterozygous genotype had significantly lower plasma ICAM-1 levels compared to the K469(A/A) genotype carriers (P=0.009). In the ICAM1 gene promoter, DNA methylation levels of CpG sites were low, and no association of the ICAM1 DNA methylation alteration with DN was detected. CONCLUSION: The present study provided evidence that the ICAM1 K469E(A/G) polymorphism with high heterozygous index and elevation of plasma ICAM-1 levels were associated with DN in a Malaysian population. Further prospective study of ICAM-1 protein according to the ICAM1 K469E(A/G) genotypes is necessary for predicting the susceptibility to T2D and DN.

Genetic and biological effects of sodium-chloride cotransporter (SLC12A3) in diabetic nephropathy.

BACKGROUND/AIMS: Solute carrier family 12 member 3 (SLC12A3) encodes a sodium/chloride transporter in kidneys. Previous reports suggest that Arg913Gln polymorphism in this gene is associated with diabetic nephropathy (DN), but the data appear to be inconsistent. Up to now, there is no biological evidence concerning the effects of SLC12A3 in DN. In this study, we aim to evaluate the genetic effects of the SLC12A3 gene and its Arg913Gln polymorphism with genetic and functional analyses. METHODS: We genotyped SLC12A3 genetic polymorphisms including Arg913Gln in 784 non-diabetes controls and 633 type 2 diabetes (T2D) subjects with or without DN in a Malaysian population and performed a meta-analysis of the present and previous studies. We further analyzed the role of slc12a3 in kidney development and progress of DN in zebrafish and db/db mice. RESULTS: We found that SLC12A3 Arg913Gln polymorphism was associated with T2D (p = 0.028, OR = 0.772, 95% CI = 0.612-0.973) and DN (p = 0.038, OR = 0.547, 95% CI = 0.308-0.973) in the Malaysian cohort. The meta-analysis confirmed the protective effects of SLC12A3 913Gln allele in DN (Z-value = -1.992, p = 0.046, OR = 0.792). Furthermore, with knockdown of zebrafish ortholog, slc12a3 led to structural abnormality of kidney pronephric distal duct at 1-cell stage. Slc12a3 mRNA and protein expression levels were upregulated in kidneys of db/db mice from 6, 12, and 26 weeks at the age. CONCLUSION: The present study provided the first biological and further genetic evidence that SLC12A3 has genetic susceptibility in the development of DN, while the minor 913Gln allele in this gene confers a protective effect in the disease.

Evaluation of the association of plasma pentraxin 3 levels with type 2 diabetes and diabetic nephropathy in a Malay population.

Recent reports have demonstrated that elevated plasma long pentraxin 3 (PTX3) levels are associated with cardiovascular and chronic kidney diseases. In the current study, we investigated the plasma PTX3 levels in 296 Malay subjects including the subjects with normal glucose tolerance (NGT) and type 2 diabetes (T2DM) patients with or without DN by using an enzyme-linked immune-sorbent assay. Results showed that in males, plasma PTX3 levels in T2DM patients without DN were lower than that in the subjects with NGT (2.78 versus 3.98 ng/mL; P = 0.021). Plasma PTX3 levels in T2DM patients with DN were decreased compared to the patients without DN (1.63 versus 2.78 ng/mL; P = 0.013). In females, however, no significant alteration of plasma PTX3 levels among NGT subjects and T2DM patients with and without DN was detected. Furthermore, an inverse correlation between PTX3 and body mass index was found in male subjects with NGT (P = 0.012; r = -0.390), but not in male T2DM patients, neither in all females. The current study provided the first evidence that decreased plasma PTX3 levels are associated with T2DM and DN in Malay men and also suggested that PTX3 may have different effects in DN and chronic kidney diseases.

Impact of the hypoxia-inducible factor-1 α (HIF1A) Pro582Ser polymorphism on diabetes nephropathy.

OBJECTIVE: Hypoxia plays a major pathogenic role in diabetic nephropathy (DN). We have investigated in this study the effect of hypoxia-inducible factor 1 α subunit (HIF1A) genetic polymorphisms on the development of DN. RESEARCH DESIGN AND METHODS: In 1,165 American type 1 diabetic patients with and without DN selected from the Genetics of Kidneys in Diabetes (GoKinD) study, the HIF1A genetic polymorphisms were genotyped with TaqMan allelic discrimination. The regulation of HIF-1α in the kidneys of diabetic mice was appreciated by immunohistochemistry, and the effect HIF1A Pro582Ser polymorphism on HIF-1α sensitivity to glucose was evaluated in vitro. RESULTS: We identified a protective association between HIF1A Pro582Ser polymorphism and DN in male subjects. We also provided mechanistic insights that HIF-1α is repressed in the medulla of diabetic mice despite hypoxia and that Pro582Ser polymorphism confers less sensitivity to the inhibitory effect of glucose during a hypoxic challenge. CONCLUSIONS: The current study demonstrates for the first time that HIF1A Pro582Ser polymorphism has an effect on DN, possibly by conferring a relative resistance to the repressive effect of glucose on HIF-1α.

Increased expression of adenylyl cyclase 3 in pancreatic islets and central nervous system of diabetic Goto-Kakizaki rats: a possible regulatory role in glucose homeostasis.

Adenylyl cyclase 3 (AC3) is expressed in pancreatic islets of the Goto-Kakizaki (GK) rat, a spontaneous animal model of type 2 diabetes (T2D), and also exerts genetic effects on the regulation of body weight in man. In addition to pancreatic islets, the central nervous system (CNS) plays an important role in the pathogenesis of T2D and obesity by regulating feeding behavior, body weight and glucose metabolism. In the present study, we have investigated AC3 expression in pancreatic islets, striatum and hypothalamus of GK rats to evaluate its role in the regulation of glucose homeostasis. GK and Wistar rats at the age of 2.5 mo were used. A group of GK rats were implanted with sustained insulin release chips for 15 d. Plasma glucose and serum insulin levels were measured. AC3 gene expression levels in pancreatic islets, striatum and hypothalamus were determined by using real-time RT-PCR. Results indicated that plasma glucose levels in Wistar rats were found to be similar to insulin-treated GK rats, and significantly lower compared with non-treated GK rats. AC3 expression levels in pancreatic islets, striatum and hypothalamus of GK rats were higher compared with Wistar rats, while the levels were intermediate in insulin-treated GK rats. The AC3 expression display patterns between pancreatic islets and striatum-hypothalamus were similar. The present study thus provides the first evidence that AC3 is overexpressed in the regions of striatum and hypothalamus of brain, and similarly in pancreatic islets of GK rats suggesting that AC3 plays a role in regulation of glucose homeostasis via CNS and insulin secretion.