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Tan, Pui Yee (2020) An intervention programme for weight management in overweight and obese Malaysian adults. PhD thesis, University of Nottingham.

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Abstract

The prevalence of obesity and its co-morbidities in the Malaysian population has been increasing dramatically through the past decade, and has now become the leading preventable cause of morbidity and mortality in the Malaysian population. The main aim of this doctoral thesis was to develop a dietary intervention programme tailored according to an individual’s food preference, cultural habit and genetic makeup (namely fat mass and obesity-associated gene (FTO) and beta 2-adrenergic receptor (ADRB2) gene). Further, this project aimed to manage body weight and reduce metabolic risk factors through, the modelled dietary intervention in overweight and obese Malaysian adults (Malaysian Malays, Chinese and Indians) (Chapter 6). Thereafter, this project investigated the individual and combined response of the gene variants (FTO and ADRB2 genes) on the post-intervention (6-month period) differences in anthropometric and cardio-metabolic parameters (Chapters 7 & 8).

Baseline investigation of 178 multi-ethnic Malaysian adults revealed that Malaysian Indians had significantly higher BMI, WC, fat mass, body fat percent, fasting insulin, HOMA-IR and lower HDL cholesterol levels, compared to the Chinese and Malays (Chapter 4). Interestingly, dietary analysis revealed that Malaysian Indians consumed lower dietary cholesterol and higher fibre, compared to their Malaysian Chinese and Malays counterpart (p<0.05). With respect to the risk of obesity and gene variants of FTO and ADRB2, our results revealed contrasting differences (Chapter 5). In case of FTO gene variants (n=178), the risk alleles carriers of FTO rs9930501 (GG), rs9930506 (GG), and rs9932754 (CC) were associated with increased odds of obesity 3.03 (CI=1.23-7.49, p=0.016), 2.87 (CI=1.14-7.19, p=0.025) and 3.04 (CI=1.22-7.59, p=0.017) compared to AA, AA and TT genotypes, respectively, in the additive model. Moreover, the risk allele carriers of FTO rs9930501 (G), rs9930506 (G) and rs9932754 (C) had significantly higher BMI, WC, WHR, fat mass, body fat percent, hsCRP levels and lower HDL cholesterol levels compared to the non-carriers (AA, AA and TT, respectively) (p<0.05). Interestingly, we found that Malaysian Indians expressed significantly higher frequency of the risk alleles of FTO rs9930501 (G), rs9930506 (G) and rs9932754 (C) when compared to Chinese and Malays (p<0.001).

With respect to ADRB2 (n=178), our results revealed that ADRB2 rs1042713 and rs1042714 were not associated with increased odds of obesity (p>0.025). However, we found that the risk allele carriers of ADRB2 rs1042713 (GG) were associated with increased odds of insulin resistance, 4.43 (CI=1.31-15.0, p=0.016) compared to the non-carriers (AA), in the additive model. Obese individuals carrying the G allele of rs1042713 had significantly higher total cholesterol and LDL cholesterol levels compared to the non-carriers (A), whereas obese individuals carrying the G allele of rs1042714 had significantly higher WHR compared to the non-carriers (C) (p<0.025). However, such differences were not observed in non-obese individuals (p>0.025). Furthermore, Malaysian Chinese had significantly lower frequency of the risk allele (G) of ADRB2 rs1042714 compared to Malaysian Malays and Malaysian Indians combined (11.9% vs 28.7%) (p=0.028).

Gene-diet interaction analysis (n=126) revealed that individuals carrying the risk alleles of FTO rs9930501 (G), rs9930506 (G) and rs9932754 (C) showed significantly lower hsCRP levels with higher vitamin E intake (≥5.4mg/day of energy adjusted vitamin E intake) (p=0.036, p=0.038 and p=0.036, respectively) and higher percent energy from protein (≥14%/day) (p=0.034, p=0.049 and p=0.034, respectively). Individuals carrying the risk allele of ADRB2 rs1042713 (G) had significantly lower fasting glucose levels with intake of relatively higher PUFA: SFA ratio (≥0.8/day) (p=0.006) and lower SFA intake (<7.3% of TE/day) (p=0.011). Moreover, the latter had significantly lower fasting insulin levels (p=0.036) and HOMA-IR (p=0.026) when consuming higher PUFA intake (≥6% of TE/day).

Hipcref (high-protein, calorie-restricted, high vitamin E and normal fibre) dietary intervention was formulated and developed to reduce body weight and cardio-metabolic risk factors in Malaysian adults (Chapter 6). A 6-month RCT revealed that overweight and obese Malaysian adults following Hipcref diet (n=65) had greater reduction in obesity-related anthropometric parameters (BMI, WC, WHR, fat mass and percent body fat) and better metabolic health outcomes (fasting insulin, HOMA-IR and hsCRP levels) compared to the generalised dietary instruction on weight loss based on Malaysian Dietary Guidelines (MDG) 2010 (n=63) (p<0.05). After 6 months of intervention, Hipcref diet group was found to consume significantly higher percent energy from protein, higher percent energy from PUFA, higher vitamin E (mg), higher fibre (g), lower total energy, lower percent energy from fat and lower percent energy from carbohydrate (p<0.05). We opine that the success of the Hipcref diet in achieving positive outcomes in overweight/obese Malaysian adults may be, due to the combined effect of the nutrient composition of the Hipcref diet.

Further, the effect of the interaction between gene variants (FTO and ADRB2 genes) and dietary intervention on the post-intervention differences in dietary, anthropometric and cardio-metabolic parameters was assessed (Chapter 7). In the individual SNP analysis, general linear regression analysis revealed that the haplotype of FTO rs9930501, rs9930506 and rs9932754 were not associated with any post-intervention differences in dietary intake, anthropometric and cardio-metabolic parameters after 6 months of dietary intervention (p>0.05). However, significant effect of the interaction between ADRB2 rs1042714 x dietary group was found on the post-intervention differences in fasting insulin (p interaction =0.012) and HOMA-IR (p interaction =0.021), in response to a 6-month Hipcref dietary intervention. Individuals carrying both the risk allele (CG+GG) and the non-risk allele (CC) of rs1042714 had significantly greater reduction in fasting insulin (p<0.001 and p=0.001, respectively) and HOMA-IR (p<0.001 and p=0.006, respectively) after a Hipcref diet compared to a control diet. With respect to dietary intake, individuals carrying the risk allele of rs1042713 (AG+GG) had significantly greater reduction in SFA intake (p=0.006) and MUFA intake (p=0.019) after a Hipcref diet. Further, we assessed the combined response of FTO and ADRB2 gene variants on the above aspect by computing polygenic risk scores (PRS) (Chapter 8). General liner regression analysis revealed significant effect of the interaction between PRS x dietary group on the post-intervention difference in hsCRP levels (p interaction=0.048). Participants from the second and third tertiles of PRS had significantly greater reduction in hsCRP levels with Hipcref diet compared to the control diet (-2.5 ± 0.9mg/L vs -0.03 ± 0.6mg/L, p=0.025; and -2.4 ± 1.0mg/L vs 0.8 ± 1.0mg/L, p=0.025, respectively), after 6 months of intervention period. Such difference was not observed in the first tertile of PRS (p>0.05).

In conclusion, the findings from this project suggest that gene variants may affect individual’s susceptibility to obesity-related phenotypes and it may interact with dietary intakes and modulate the effect of obesity-related phenotypes, in Malaysian adults. Individualised dietary intervention (Hipcref diet) tailored according to individual’s food preferences, cultural habits and genetic makeup had positive impact on body composition and cardio-metabolic parameters compared to generalised weight loss advice based on Malaysian Dietary Guidelines (MDG) 2010. Personalisation seems to be an important factor when developing strategies for weight management, especially in a multi-ethnic Malaysian population. Furthermore, individuals with different gene variants responded differently to the dietary intervention programme with respect to body composition and cardio-metabolic parameters.

Item Type:	Thesis (University of Nottingham only) (PhD)
Supervisors:	Mitra, Soma Roy Amini, Farahnaz
Keywords:	obesity-related phenotypes, FTO gene, ADRB2 gene,Hipcref dietary intervention, gene-diet interactions, polygenic risk scores
Subjects:	R Medicine > RM Therapeutics. Pharmacology
Faculties/Schools:	University of Nottingham, Malaysia > Faculty of Science and Engineering — Science > School of Biosciences
Item ID:	59495
Depositing User:	TAN, PUI YEE
Date Deposited:	22 Feb 2020 04:40
Last Modified:	21 Feb 2022 04:30
URI:	https://eprints.nottingham.ac.uk/id/eprint/59495

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