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Fulltext Determination of Cutoff Values for the Screening of Osteosarcopenia in Obese Postmenopausal Women

Abidin NZ, Mitra SR

Curr Gerontol Geriatr Res, 2021;2021:6634474.
PMID: 33790963 DOI: 10.1155/2021/6634474

Osteosarcopenic obesity (OSO) describes the concurrent presence of obesity, low bone mass, and low muscle mass in an individual. Currently, no established criteria exist to diagnose OSO. We hypothesized that obese individuals require different cut-points from standard cut-points to define low bone mass and low muscle mass due to their higher weight load. In this study, we determined cutoff values for the screening of osteosarcopenia (OS) in obese postmenopausal Malaysian women based on the measurements of quantitative ultrasound (QUS), bioelectrical impedance analysis (BIA), and functional performance test. Then, we compared the cutoff values derived by 3 different statistical modeling methods, (1) receiver operating characteristic (ROC) curve, (2) lowest quintile of the study population, and (3) 2 standard deviations (SD) below the mean value of a young reference group, and discussed the most suitable method to screen for the presence of OS in obese population. One hundred and forty-one (n = 141) postmenopausal Malaysian women participated in the study. Bone density was assessed using calcaneal quantitative ultrasound. Body composition was assessed using bioelectrical impedance analyzer. Handgrip strength was assessed using a handgrip dynamometer, and physical performance was assessed using a modified Short Physical Performance Battery test. ROC curve was determined to be the most suitable statistical modeling method to derive the cutoffs for the presence of OS in obese population. From the ROC curve method, the final model to estimate the probability of OS in obese postmenopausal women is comprised of five variables: handgrip strength (HGS, with area under the curve (AUC) = 0.698 and threshold ≤ 16.5 kg), skeletal muscle mass index (SMMI, AUC = 0.966 and threshold ≤ 8.2 kg/m2), fat-free mass index (FFMI, AUC = 0.946 and threshold ≤ 15.2 kg/m2), broadband ultrasonic attenuation (BUA, AUC = 0.987 and threshold ≤ 52.85 dB/MHz), and speed of sound (SOS, AUC = 0.991 and threshold ≤ 1492.15 m/s). Portable equipment may be used to screen for OS in obese women. Early identification of OS can help lower the risk of advanced functional impairment that can lead to physical disability in obese postmenopausal women.
Fulltext The Combined Effect of Polygenic Risk from FTO and ADRB2 Gene Variants, Odds of Obesity, and Post-Hipcref Diet Differences

Tan PY, Mitra SR

Lifestyle Genom, 2020;13(2):84-98.
PMID: 32101872 DOI: 10.1159/000505662

BACKGROUND: Computing polygenic risk scores (PRS) to predict the degree of risk for obesity may contribute to weight management programs strategically.
OBJECTIVES: To investigate the combined effect of FTO rs9930501, rs9930506, and rs9932754 and ADRB2 rs1042713 and rs1042714 using PRS on (1) the odds of obesity and (2) post-intervention differences in dietary, anthropometric, and cardiometabolic parameters in response to high-protein calorie-restricted, high-vitamin E, high-fiber (Hipcref) diet intervention in Malaysian adults.
METHODS: Both a cross-sectional study (n = 178) and a randomized controlled trial (RCT) (n = 128) were conducted to test the aforementioned objectives. PRS was computed as the weighted sum of the risk alleles possessed by each individual participant. Participants were stratified into first (PRS 0-0.64), second (PRS 0.65-3.59), and third (PRS 3.60-8.18) tertiles.
RESULTS: The third tertile of PRS was associated with significantly higher odds of obesity: 2.29 (95% CI = 1.11-4.72, adjusted p = 0.025) compared to the first tertile. Indians (3.9 ± 0.3) had significantly higher PRS compared to Chinese (2.1 ± 0.4) (p = 0.010). In the RCT, a greater reduction in high-sensitivity C-reactive protein (hsCRP) levels was found in second and third tertiles after Hipcref diet intervention compared to the control diet (p interaction = 0.048).
CONCLUSION: Higher PRS was significantly associated with increased odds of obesity. Individuals with higher PRS had a significantly greater reduction in hsCRP levels after Hipcref diet compared to the control diet.
Effect of an individualised high-protein, energy-restricted diet on anthropometric and cardio-metabolic parameters in overweight and obese Malaysian adults: a 6-month randomised controlled study

Mitra SR, Tan PY

Br J Nutr, 2019 05;121(9):1002-1017.
PMID: 30761964 DOI: 10.1017/S0007114519000345

The aim of this study was to investigate the effectiveness of the Hipcref (high-protein, energy-restricted, high-vitamin E and high-fibre) diet in Malaysian adults on body composition and metabolic parameters after an intervention period of 6 months. Overweight/obese Malaysian adults (n 128; BMI≥23 kg/m2) were randomised to the Hipcref (n 65) or control diet (n 63). The intervention group received Hipcref diet charts based on their personal preferences. The control group followed a generalised dietary advice based on Malaysian Dietary Guidelines, 2010. All participants were responsible for preparing their own meals. There was a significant treatment group×time effect on anthropometric parameters (P<0·05) on an intention-to-treat basis. Pairwise comparisons revealed that Hipcref diet participants had significant reduction in weight, BMI, waist circumference, fat mass and percentage body fat at months 3 and 6 compared with baseline (P<0·001). The control group had significant increase in weight and BMI at months 3 and 6 compared with baseline (P<0·05). The Hipcref diet group had higher reduction in fasting insulin, insulin resistance and C-reactive protein levels compared with the control group at month 6 (P<0·05). Post-intervention, compared with the control group, the Hipcref diet group was found to consume significantly higher percentage energy from protein, and PUFA, higher energy-adjusted vitamin E (mg) and fibre (g), and lower total energy, lower percentage energy from fat and carbohydrate (P<0·05). The success of the Hipcref diet on overweight/obese Malaysian adults may be due to the combined effect of the nutrient composition of the Hipcref diet.
Fulltext Association of ADRB2 rs1042713 with Obesity and Obesity-Related Phenotypes and Its Interaction with Dietary Fat in Modulating Glycaemic Indices in Malaysian Adults

Mitra SR, Tan PY, Amini F

J Nutr Metab, 2019;2019:8718795.
PMID: 31007954 DOI: 10.1155/2019/8718795

Gene-diet interaction studies have reported that individual variations in phenotypic traits may be due to variations in individual diet. Our study aimed to evaluate (i) the association of ADRB2 rs1042713 with obesity and obesity-related metabolic parameters and (ii) the effect of dietary nutrients on these associations in Malaysian adults. ADRB2 genotyping, dietary, physical activity, anthropometric, and biochemical data were collected from 79 obese and 99 nonobese individuals. Logistic regression revealed no association between ADRB2 rs1042713 and obesity (p=0.725). However, the carriers of G allele (AG + GG genotypes) of rs1042713 were associated with increased odds of insulin resistance, 2.83 (CI = 1.04-7.70, adjusted p=0.042), in the dominant model, even after adjusting for potential confounders. Obese individuals carrying the G allele were associated with higher total cholesterol (p=0.011), LDL cholesterol levels (p=0.008), and total cholesterol/HDL cholesterol ratio (p=0.048), compared to the noncarriers (AA), even after adjusting for potential confounders. Irrespective of obesity, the carriers of GG genotype had significantly lower fasting glucose levels with low saturated fatty acid intake (<7.3% of TE/day) (4.92 ± 0.1 mmol/L vs 5.80 ± 0.3 mmol/L, p=0.011) and high intake of polyunsaturated fatty acid:saturated fatty acid ratio (≥0.8/day) (4.83 ± 0.1 mmol/L vs 5.93 ± 0.4 mmol/L, p=0.006). Moreover, the carriers of GG genotype with high polyunsaturated fatty acid intake (≥6% of TE/day) had significantly lower HOMA-IR (1.5 ± 0.3 vs 3.0 ± 0.7, p=0.026) and fasting insulin levels (6.8 ± 1.6 µU/mL vs 11.4 ± 2.1 µU/mL, p=0.036). These effects were not found in the noncarriers (AA). In conclusion, G allele carriers of ADRB2 rs1042713 were associated with increased odds of insulin resistance. Obese individuals carrying G allele were compromised with higher blood lipid levels. Although it is premature to report gene-diet interaction on the regulation of glucose and insulin levels in Malaysians, we suggest that higher quantity of PUFA-rich food sources in regular diet may benefit overweight and obese Malaysian adults metabolically. Large-scale studies are required to replicate and confirm the current findings in the Malaysian population.
Effect of FTO rs9930506 on obesity and interaction of the gene variants with dietary protein and vitamin E on C-reactive protein levels in multi-ethnic Malaysian adults

Mitra SR, Tan PY, Amini F

J Hum Nutr Diet, 2018 12;31(6):758-772.
PMID: 30141234 DOI: 10.1111/jhn.12593

BACKGROUND: Individual variations of obesity-related traits can be a consequence of dietary influence on gene variants.
METHODS: This cross-sectional study aimed to evaluate (i) the effect of FTO rs9930506 on obesity and related parameters and (ii) the influence of diet on the above association in Malaysian adults. In total, 79 obese and 99 nonobese Malaysian adults were recruited.
RESULTS: In comparison with Chinese and Malays, Indians had significantly higher waist circumference (P ≤ 0.001 and P = 0.016), waist-hip ratio (P = 0.001 and P < 0.001), body fat percentage (P = 0.001 and P = 0.042), fasting insulin (P = 0.001 and P = 0.001), homeostatic model assessment-insulin resistance (P = 0.001 and P = 0.001) and lower high-density lipoprotein-cholesterol levels (P < 0.001 and P < 0.001), respectively. Indians consumed significantly lower dietary cholesterol (P = 0.002), percentage energy from protein (P < 0.001) and higher fibre (P = 0.006) compared to the other two groups. Malaysian Indians expressed the highest risk allele frequency (G) of FTO rs9930506 compared to the Malays and the Chinese (P < 0.001). No significant association was found between FTO rs9930506 and obesity (dominant model). Risk allele carriers (G) consumed significantly lower vitamin E (P = 0.020) and had a higher fibre intake (P = 0.034) compared to the noncarriers (A). Gene-diet interaction analysis revealed that risk allele carriers (G) had lower high sensitivity C-reactive protein (hsCRP) levels with higher energy from protein (≥14% day-1 ; P = 0.049) and higher vitamin E (≥5.4 mg day-1 ; P = 0.038).
CONCLUSIONS: The presence of the risk allele (G) of FTO rs9930506 was not associated with an increased risk of obesity. Malaysian Indians had a significantly higher frequency of the risk allele (G). Indian participants expressed higher atherogenic phenotypes compared to Chinese and Malays. FTO rs9930506 may interact with dietary protein and vitamin E and modulate hsCRP levels.
Fulltext Lifestyle Interventions for Weight Control Modified by Genetic Variation: A Review of the Evidence

Tan PY, Mitra SR, Amini F

Public Health Genomics, 2018;21(5-6):169-185.
PMID: 31117103 DOI: 10.1159/000499854

BACKGROUND/AIMS: Excess weight gain is a result of the interaction between diet, environment, and genes. Evidence suggests that responses to lifestyle interventions to manage weight are partially modified by genetic factors. This review is aimed at summarizing the current evidence from studies done on gene variants - single nucleotide polymorphisms (SNPs) - and intervention outcomes on weight loss and obesity-related traits.
METHODS: Intervention studies published in English between 2000 and August 2018 were retrieved from PubMed, Google Scholar, and Web of Science using various keywords.
RESULTS: This article is a review of 36 studies conducted in 13 different countries which included a total of 15,931 participants between 19 and 70 years of age. The effect of 26 genes and 64 SNPs on the reduction of body weight and metabolic risk factors in response to diet, exercise, and lifestyle interventions was reviewed.
CONCLUSION: Gene-lifestyle interaction studies on the same candidate gene in different populations have reported information which is challenging to interpret. Thus, it is difficult to arrive at a particular model for a strategy on weight management at this point in time. Most of the intervention studies focus on the effect of variants of a single candidate gene on weight loss. Further evidence from large-scale studies is necessary to assess the effect of multiple candidate genes to compute a gene score that could be used in a model intervention programme. Our review suggests that a healthy lifestyle with a balanced diet and regular physical activity will benefit individuals who carry the risk alleles of the obesity-related candidate genes. This message should be the mainstay of the recommendations and guidelines published by nutrition societies across the world.
Dietary protein interacts with polygenic risk scores and modulates serum concentrations of C-reactive protein in overweight and obese Malaysian adults

Tan PY, Amini F, Mitra SR

Nutr Res, 2022 Nov;107:75-85.
PMID: 36206635 DOI: 10.1016/j.nutres.2022.09.002

Dietary intake may interact with gene variants and modulate inflammatory status. This study aimed to investigate the combined effect of fat mass and obesity-associated rs9930501, rs9930506, and rs9932754 and beta-2 adrenergic receptor rs1042713 on C-reactive protein (CRP) concentrations using polygenic risk scores (PRS), and modulatory effect of dietary nutrients on these associations. We hypothesized that higher protein intake is associated with lower inflammatory status in individuals genetically predisposed to obesity. PRS was computed as the weighted sum of the risk alleles possessed and stratified into first (0-0.64), second (0.65-3.59), and third (3.60-8.18) tertiles. A total of 128 overweight and obese Malaysian adults were dichotomized into groups of low and elevated inflammatory status (CRP concentrations ≤3 and >3 mg/L, respectively). One-half of the study participants (51%) were found to have elevated inflammatory status. Second- and third-tertile PRS were significantly associated with increased odds of elevated inflammatory status, 7.56 (95% confidence interval [CI], 1.98-28.80; adjusted P = .003) and 3.87 (95% CI, 1.10-13.60; adjusted P = .035), respectively. Individuals in the third-tertile PRS had significantly lower CRP concentrations (4.61 ± 1.3 mg/L vs 9.60 ± 2.6 mg/L, P = .019) when consuming ≥14% energy from protein (with an average of 18.0% ± 2.4%, 43.0% ± 7.7%, and 39.0% ± 8.0% energy from protein, carbohydrate, and fat per day). In conclusion, third-tertile PRS was significantly associated with increased odds of elevated CRP; higher protein intake may alleviate inflammatory status and reduce CRP concentrations systemically in those individuals.
Fulltext Daily Consumption of a Fruit and Vegetable Smoothie Alters Facial Skin Color

Tan KW, Graf BA, Mitra SR, Stephen ID

PLoS One, 2015;10(7):e0133445.
PMID: 26186449 DOI: 10.1371/journal.pone.0133445

Consumption of dietary carotenoids or carotenoid supplements can alter the color (yellowness) of human skin through increased carotenoid deposition in the skin. As fruit and vegetables are the main dietary sources of carotenoids, skin yellowness may be a function of regular fruit and vegetable consumption. However, most previous studies have used tablets or capsules to supplement carotenoid intake, and less is known of the impact of increased fruit and vegetable consumption on skin color. Here, we examined skin color changes in an Asian population (Malaysian Chinese ethnicity) over a six week dietary intervention with a carotenoid-rich fruit smoothie. Eighty one university students (34 males, 47 females; mean age 20.48) were assigned randomly to consuming either a fruit smoothie (intervention group) or mineral water (control group) daily for six weeks. Participants' skin yellowness (CIELab b*), redness (a*) and luminance (L*) were measured at baseline, twice during the intervention period and at a two-week follow-up, using a handheld reflectance spectrophotometer. Results showed a large increment in skin yellowness (p<0.001) and slight increment in skin redness (p<0.001) after 4 weeks of intervention for participants in the intervention group. Skin yellowness and skin redness remained elevated at the two week follow up measurement. In conclusion, intervention with a carotenoid-rich fruit smoothie is associated with increased skin redness and yellowness in an Asian population. Changes in the reflectance spectrum of the skin suggest that this color change was caused by carotenoid deposition in the skin.