CONTEXT:Type 2 diabetes (T2D) is a major global concern, with Asia at its epicenter in recent years. Proteins, products of gene transcription, serve as dynamic biomarkers for pinpointing perturbed pathways in disease development. Previous T2D proteomic association studies primarily focused on European populations. OBJECTIVE:The aim of this study was to investigate the relationship between plasma proteins and the incidence of T2D in Asian individuals. METHODS:We examined the association of 4775 plasma proteins with incident T2D in a Singapore multi-ethnic cohort of 1659 Asian individuals (539 cases and 1120 controls) using logistic regression. We used 2-sample mendelian randomization and colocalization analysis to evaluate the causal relationship between proteins and T2D. RESULTS:Our analysis revealed 522 proteins that were associated with incident T2D after adjusting for age, sex, and ethnicity, and 17 proteins that remained statistically significantly associated after adjusting for other T2D risk factors such as fasting glucose, waist circumference, and triglycerides. Among the 522 proteins associated with incident T2D, the change in 205 plasma proteins, observed in parallel with the development of T2D at baseline and 6-year follow-up, were further associated with incident T2D. The associated proteins showed enrichment in neuron generation, glycosaminoglycan binding, and insulin-like growth factor binding. Two-sample mendelian randomization analysis suggested 3 plasma proteins, GSTA1, INHBC, and FGL1, play causal roles in the development of T2D, with colocalization evidence supporting GSTA1 and INHBC. CONCLUSION:Our findings reveal plasma protein profiles linked to the onset of T2D in Asian populations, offering insights into the biological mechanisms of T2D development.

The biomarkers connecting obesity and cardiometabolic diseases are not fully understood. We aimed to (i) evaluate the associations between body mass index (BMI), waist circumference (WC), and ~5,000 plasma proteins (SomaScan v4), (ii) identify protein signatures of BMI and WC, and (iii) evaluate the associations between the protein signatures and cardiometabolic health including metabolically unhealthy obesity and type 2 diabetes incidence in the Singapore Multi-Ethnic Cohort (MEC1). Among 410 BMI-associated and 385 WC-associated proteins, we identified protein signatures of BMI and WC and validated them in an independent dataset across two timepoints and externally in the Atherosclerosis Risk in Communities (ARIC) study. The BMI- and WC-protein signatures were highly correlated with total and visceral body fat, respectively. Furthermore, the protein signatures were significantly associated with cardiometabolic risk factors and metabolically unhealthy obesity. In prospective analyses, the protein signatures were strongly associated with type 2 diabetes risk in MEC1 (odds ratio per SD increment in WC-protein signature = 2.84, 95% CI 2.47 to 3.25) and ARIC (hazard ratio = 1.98, 95% CI 1.88 to 2.08). Our protein signatures have potential uses for the monitoring of metabolically unhealthy obesity.

BACKGROUND:Diet affects the development of chronic diseases such as type 2 diabetes, but the underlying biological mechanisms are only partly understood. OBJECTIVES:This study aimed to identify proteomic markers of the Alternative Healthy Eating Index (AHEI) and the Dietary Approaches to Stop Hypertension (DASH) diet and their association with type 2 diabetes risk. METHODS:We examined the associations between the AHEI and DASH diet quality scores and 1317 plasma proteins in African American participants of the Jackson Heart Study (JHS, n = 1878). These findings were validated in a Singapore Multi-Ethnic Cohort (n = 2395) and examined in relation to type 2 diabetes incidence (n = 539 cases). We adjusted for multiple testing by using false discovery rate-adjusted q values. RESULTS:We identified 13 proteins consistently associated with the AHEI or DASH scores with the strongest associations for the AHEI score and epidermal growth factor receptor (β:0.089; SE: 0.017; q < 0.001) and for the DASH score and tissue factor (β: -0.114; SE: 0.022; q < 0.001). Most of these proteins were related to inflammation, thrombosis, adipogenesis, and glucose metabolism. Concentrations of myeloperoxidase, epidermal growth factor receptor, hepatocyte growth factor receptor, coagulation factor Xa, contactin 4, kynureninase, neurogenic locus notch homolog protein 1, and vesicular integral-membrane protein VIP36 were associated with the risk of type 2 diabetes in the Asian cohort. The diabetes odds ratio for a 2-fold higher protein abundance concentration ranged from 0.03 (95% CI: 0.01, 0.08) for neurogenic locus notch homolog protein 1 to 3.04 (95% CI: 2.13, 4.33) for kynureninase. Furthermore, genetic markers for myeloperoxidase and hepatocyte growth factor receptor were significantly associated with diabetes risk. CONCLUSIONS:Our study across geographically and ethnically diverse populations identified robust protein biomarkers for healthy dietary patterns. Furthermore, our findings suggest novel biological mechanisms linking dietary patterns with type 2 diabetes development.

Type 2 diabetes (T2D) is a major global concern, with Asia at its epicenter in recent years. Proteins, products of gene transcription, serve as dynamic biomarkers for pinpointing perturbed pathways in disease development. To understand the protein function in incident T2D, we examined the association of 4,775 plasma proteins with incident T2D in a Singapore multi-ethnic cohort of 1,659 Asian participants (539 cases and 1,120 controls). Our analysis revealed 522 proteins that were associated with incident T2D after adjusting for age, sex, and ethnicity. Among the 522 proteins associated with incident T2D, the change in 205 plasma proteins, observed in parallel with the development of T2D at baseline and six-years follow-up, were further associated with incident T2D. The associated proteins showed enrichment in neuron generation, glycosaminoglycan binding, and insulin-like growth factor binding. Two-sample Mendelian randomization analysis suggested three plasma proteins, GSTA1, INHBC, and FGL1, play causal roles in the development of T2D, with colocalization evidence supporting GSTA1 and INHBC. Our findings reveal plasma protein profiles linked to the onset of T2D in Asian populations, offering insights into the biological mechanisms of T2D development.

AIMS:To assess three well-established type 2 diabetes (T2D) risk prediction models based on fasting plasma glucose (FPG) in Chinese, Malays, and Indians, and to develop simplified risk models based on either FPG or HbA1c. METHODS:We used a prospective multiethnic Singapore cohort to evaluate the established models and develop simplified models. 6,217 participants without T2D at baseline were included, with an average follow-up duration of 8.3 years. The simplified risk models were validated in two independent multiethnic Singapore cohorts (N = 12,720). RESULTS:The established risk models had moderate-to-good discrimination (area under the receiver operating characteristic curves, AUCs 0.762 - 0.828) but a lack of fit (P-values < 0.05). Simplified risk models that included fewer predictors (age, BMI, systolic blood pressure, triglycerides, and HbA1c or FPG) showed good discrimination in all cohorts (AUCs ≥ 0.810), and sufficiently captured differences between the ethnic groups. While recalibration improved fit the simplified models in validation cohorts, there remained evidence of miscalibration in Chinese (p ≤ 0.012). CONCLUSIONS:Simplified risk models including HbA1c or FPG had good discrimination in predicting incidence of T2D in three major Asian ethnic groups. Risk functions with HbA1c performed as well as those with FPG.

BACKGROUND:Metabolic syndrome (MetS) is a precursor to cardiovascular diseases and type 2 diabetes. Existing MetS prediction models relied heavily on biochemical measures and those based on non-invasive predictors such as lifestyle behaviours were limited. We aim to (1) develop a weighted lifestyle risk index for MetS and (2) externally validate this index using two Asian-based cohorts in Singapore. METHODS:Using data from the Multi-Ethnic Cohort (MEC) 1 (n = 2873, 41% male), multiple logistic regression was used to identify predictors associated with MetS. A weighted lifestyle risk index was generated using coefficients of the selected predictors in the development cohort (MEC1). Subsequently, the performance of the lifestyle risk index in predicting the occurrence of MetS within 10 years was assessed by discrimination and calibration in an external validation cohort (MEC2) (n = 6070, 43% male). RESULTS:A lifestyle risk index for MetS with nine predictors was developed (age, sex, ethnicity, having a family history of diabetes, BMI, diet, physical activity, smoking status, and screen time). This index demonstrated acceptable discrimination in the development cohort [AUC (95% CI) = 0.74 (0.71, 0.76)] and the validation cohort [AUC (95% CI) = 0.79 (0.77, 0.81)]. CONCLUSION:This lifestyle risk index exhibits potential for risk stratification in population-based screening programmes. Future research could apply a similar methodology to develop disease-specific lifestyle risk indices using nationwide registry-based data.

Introduction: Cardiovascular diseases (CVDs) are a major cause of deaths worldwide, but prospective data on dietary risk factors for CVD in South and Southeast Asian populations are sparse. Objective: We aimed to evaluate the relation between macronutrient and food intakes and incidence of major adverse cardiovascular events (MACE) in a multi-ethnic Asian population. Methods: We used data from the Singapore Multi-ethnic cohort ( n = 12,408), a prospective cohort of ethnic Chinese, Malay and Indian adults aged 21–65 years recruited between 2004 to 2010. Dietary intakes were assessed using a validated food frequency questionnaire, and the incidence of MACE was ascertained through data linkage with national registries. Cox proportional hazards model was used to evaluate the associations between dietary intakes and MACE risk. Results: Over 125,241 person-years, 746 incident cases of MACE were documented. We observed a direct association between carbohydrate intake and MACE risk (HR 1.35, 95% CI 1.07, 1.71 highest vs. lowest quartile, P -trend 0.001). Replacing 5% of energy from carbohydrate with polyunsaturated fat (HR 0.79, 95% CI 0.69, 0.91), but not saturated fat (HR 0.95, 95% CI 0.83, 1.08), was significantly associated with a lower MACE risk. In terms of food groups, replacing 1 serving per day of refined grains with fruit (HR 0.93, 95% CI 0.87, 0.99), vegetables (HR 0.93, 95% CI 0.86, 1.00), and dairy (HR 0.93, 95% CI 0.87, 0.99) was associated with lower MACE risk. Cholesterol intake was associated with a higher MACE risk in ethnic Indians (HR 2.37, 95% CI 1.52, 3.71 highest vs. lowest quartile, P -trend <0.001), but not in ethnic Malay or Chinese ( P -interaction 0.016). Conclusions: Moderating carbohydrate intakes by increasing polyunsaturated fat intake and replacing refined grains with fruits, vegetables, and dairy may lower CVD risk in Asian populations.

BACKGROUNDThe prevalence of obesity is increasing in many Asian countries. However, longitudinal data on the impacts of dietary factors on weight gain in Asian populations are sparse.OBJECTIVESWe evaluated the relationship between changes in intakes of nutrients, foods, and beverages and diet quality and long-term changes in body weight.METHODSWe used data (n = 3064) from the Singapore Multi-Ethnic Cohort, a prospective cohort including Chinese, Indian, and Malay residents aged 21-65 years. Dietary intakes were assessed using an FFQ, and body weight and waist circumference were measured during health examinations. Diet quality was evaluated using the Dietary Approaches to Stop Hypertension (DASH) and Alternative Healthy Eating Index (AHEI-2010) scores. Data were collected at baseline (2004-2010) and follow-up (2011-2016), with a mean follow-up of 6.0 years. Linear regression was used to assess the associations between dietary changes and weight change, adjusted for socio-demographic and lifestyle variables.RESULTSImprovements in dietary quality scores (DASH, -0.34 kg per 5 points; AHEI-2010, -0.35 kg per 10 points) and replacement of carbohydrates with protein (-0.44 kg per 5% of energy) were significantly associated with less weight gain. Increased intakes of white rice (+0.25 kg per serving/d), soft drinks (+0.69 kg), red meat (+0.58 kg), and poultry with skin (+0.74 kg) were directly associated with weight gain. The replacement of 1 serving per day of white rice with whole grains (-0.68 kg), vegetables (-0.33 kg), poultry without skin (-0.79 kg), and eggs (-0.87 kg) was associated with less weight gain. Similar associations were observed between changes in dietary factors and changes in waist circumference.CONCLUSIONSAmong Asian adults, increasing dietary quality, reducing soft drink consumption, and replacing white rice with whole grains, vegetables, and selected high-protein foods was associated with less weight gain.

Novel staple foods are staple foods that are modified with the purpose of improving their nutritional properties. However, consumers' acceptance towards novel staple foods remains to be evaluated, especially in Asian populations where staple foods like white rice are a major source of energy. The objective of this study was to explore consumers' attitudes and perceptions towards novel staple foods in a multi-ethnic Asian population. We conducted 11 focus group discussions, with 37 healthy participants and 22 participants with diabetes recruited through newspaper, email and poster advertisement and in-person recruitment at a clinic. Thematic analysis using the general inductive approach was performed. We found that participants' conceptual understanding of the modification process affected their acceptance towards novel staple foods. Plant-based modifications were considered natural and acceptable while genetic modification and use of chemicals were unnatural and undesirable. Participants expected novel staple foods to be more expensive and less tasty and this was largely due to their perceptions and experiences with healthy eating. Participants with diabetes or family history of diabetes were generally more willing to compromise taste and cost for healthier staple foods, and this appeared to be driven by concerns about diabetes and its related co-morbidities. The appearance of food was an important influence on participants' initial impression of the food, which appeared to be mediated by taste expectations. Participants' trust of novel staple foods was largely influenced by their trust in food industry, governmental authorities and nutrition science that was mediated through pathways of information and food safety.

BACKGROUND:Attitudes and beliefs regarding food are known to influence dietary behaviours and may reflect cultural traditions. Therefore, understanding the food culture in the population is important to inform culturally relevant and acceptable public health interventions.OBJECTIVE:(1) To evaluate attitudes towards pleasure and health with regard to eating and its association with healthy eating intentions. (2) To assess traditional beliefs about 'hot-cold balance' and its influence on food choice.METHODS:We conducted a cross-sectional study using an online research panel comprising of 787 male and female adults of Chinese, Malay and Indian ethnicity recruited from population-based cohorts and public housing estates in Singapore. A self-administered questionnaire was used to assess beliefs and attitudes towards food. To evaluate the association of beliefs and attitudes with socio-demographic determinants and potential consequences for healthy eating intentions, multivariable logistic regression was used with adjustment for age, gender and ethnicity.RESULTS:Beliefs about the importance of considering hot-cold balance for food choice were common among all three Asian ethnic groups and most prominent among the Chinese ethnic group (56.3% Malay, 64.5% Indian and 72.4% Chinese). The majority of participants (73.8%) often consider the effects of diet on health, but also value eating pleasure greatly (84.9%). Older age was associated with a shift in attitudes from valuing eating pleasure towards health. Valuing the importance of food for health was associated with a wide range of healthy eating intentions, whereas highly valuing eating pleasure was associated with a lower intention to reduce salt intake.CONCLUSION:In a cosmopolitan Asian population, both eating for health and eating for pleasure were valued highly and traditional beliefs regarding the hot-cold balance were held by the majority.