association of ethnicity, inflammation, and obesity in ... · inflammation (c-reactive protein...

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S Liu 1 , JJ Liu 1 , MC Moh 1 , DSM Wong 1 , CF Sum 2, 3 , S Tavintharan 2, 3 , LY Yeoh 3 , SC Lim 2, 3 1 Clinical Research Unit, 2 Diabetes Centre, 3 Department of Medicine, Khoo Teck Puat Hospital, Singapore Association of Ethnicity, Inflammation, and Obesity in Multiethnic Asians with Type 2 Diabetes and Preserved Renal Function Obesity is associated with elevated systemic inflammation and contributes to pathogenesis of type 2 diabetes mellitus (T2DM) and increased risk of cardiovascular disease (CVD). Our earlier studies showed that among the multiethnic Asians, Malays and Indians withT2DM had higher CVD risk as compared to Chinese but the underlying mechanisms remain incompletely understood. We aim to study the relationship of ethnicity, systemic inflammation (C-reactive protein (CRP) as a biomarker) and obesity in multiethnic Asians with T2DM. INTRODUCTION 1467 T2DM subjects from SMART2D (Singapore Study of MAcro-angiopathy and Micro-vascular Reactivity in Type 2 Diabetes) cohort with CKD-EPI eGFR 60 ml/min/1.73m 2 were included in this study. Plasma high-sensitivity CRP (hs-CRP) was quantified by solid phase sandwich enzyme-linked immunosorbent assay (ELISA) kits. Relationship between ethnicity, hs-CRP and obesity was studied using general linear model after adjusting for multiple potential confounders. METHODS The proportion of Chinese, Malays and Indians in this study was 55%, 21% and 24%, respectively. Among them, hs-CRP concentration was significantly higher in Malay (2.0 (0.7-4.1) μg/ml) and Indian (2.8 (1.1-4.7) μg/ml) as compared with Chinese (1.3 (0.4-3.0) μg/ml, p<0.0001). Malays and Indians had higher BMI (Malays 29.5±5.6, Indians 27.5±4.5 and Chinese 26.3±4.4 kg/m 2 , p<0.0001) and greater waist circumference (Malays 99.2±14.2, Indians 97.8±12.1 and Chinese 93.1±12 cm, p<0.0001) than Chinese. Bivariate correlation showed that hs-CRP was positively correlated with BMI (ρ=0.385, p<0.0001) and waist circumference (ρ=0.372, p<0.0001). Interestingly, general linear model revealed that the differences in hs-CRP levels between Malay and Chinese were weakened after adjusting for either BMI or waist circumference whereas the difference in hs- CRP levels between Chinese and Indian was not significantly altered. RESULTS High systemic inflammation in Malays and Indians with T2DM may partly explain their high CVD risk. The increased levels of inflammation in Malays may be attributed to obesity. However, the mechanism underlying high inflammation in Indians remains to be fully elucidated. DISCUSSION 1. Ridker, P.M. Cardiology Patient Page. C-reactive protein: a simple test to help predict risk of heart attack and stroke. Circulation 2003.108: e81e85. 2. Khoo, C.M, et al. Ethnicity modifies the relationships of insulin resistance, inflammation, and adiponectin with obesity in a multiethnic Asian population. Diabetes Care 2011.34: 11201126. 3. Sinha S.K, et al. Association of race/ethnicity, inflammation, and albuminuria in patients with diabetes and early chronic kidney disease. Diabetes Care 2014.37: 10601068. REFERENCES Acknowledgement This study was supported by the Singapore National Medical Research Council Grant [PPG/AH(KTPH)/2011]. Figure 1. Adipose tissue inflammation contributes to obesity- related metabolic dysfunction. Obesity (adipose tissue) Type 2 diabetes Cardiovascular disease Inflammatory markers Table 1. Clinical and biochemical characteristics of subjects with type 2 diabetes stratified by ethnicity. HbA1c, glycated hemoglobin; TC, total cholesterol; HDL, high density lipoprotein; LDL, low density lipoprotein; eGFR, estimated glomerular filtration rate; uACR, urinary albumin-to-creatinine ratio. Table 2. Variables associated with plasma hs-CRP variations in general linear regression models in subjects with T2DM (N=1467). B, unstandardized regression coefficient; HbA1c, glycated hemoglobin; FPG, fasting plasma glucose; SBP, systolic blood pressure; HDL, high density lipoprotein; LDL, low density lipoprotein; TG, triglycerides; eGFR, estimated glomerular filtration rate; uACR, urinary albumin-to-creatinine ratio. a Male gender and Chinese ethnicity were taken as reference. TG, uACR and hs-CRP were natural logarithmically transformed. b No usage of medication was used as a reference.

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Page 1: Association of Ethnicity, Inflammation, and Obesity in ... · inflammation (C-reactive protein (CRP) as a biomarker) and obesity in multiethnic Asians with T2DM. INTRODUCTION 1467

S Liu1, JJ Liu1, MC Moh1, DSM Wong1, CF Sum2, 3, S Tavintharan2, 3, LY Yeoh3, SC Lim2, 3

1Clinical Research Unit, 2Diabetes Centre, 3Department of Medicine, Khoo Teck Puat Hospital, Singapore

Association of Ethnicity, Inflammation, and Obesity in Multiethnic

Asians with Type 2 Diabetes and Preserved Renal Function

Obesity is associated with elevated systemic inflammation and contributes

to pathogenesis of type 2 diabetes mellitus (T2DM) and increased risk of

cardiovascular disease (CVD). Our earlier studies showed that among the

multiethnic Asians, Malays and Indians withT2DM had higher CVD risk as

compared to Chinese but the underlying mechanisms remain incompletely

understood. We aim to study the relationship of ethnicity, systemic

inflammation (C-reactive protein (CRP) as a biomarker) and obesity in

multiethnic Asians with T2DM.

INTRODUCTION

1467 T2DM subjects from SMART2D (Singapore Study of MAcro-angiopathy and Micro-vascular Reactivity in Type 2 Diabetes) cohort

with CKD-EPI eGFR ≥ 60 ml/min/1.73m2 were included in this study. Plasma high-sensitivity CRP (hs-CRP) was quantified by solid phase

sandwich enzyme-linked immunosorbent assay (ELISA) kits. Relationship between ethnicity, hs-CRP and obesity was studied using

general linear model after adjusting for multiple potential confounders.

METHODS

The proportion of Chinese, Malays and Indians in

this study was 55%, 21% and 24%, respectively.

Among them, hs-CRP concentration was

significantly higher in Malay (2.0 (0.7-4.1) µg/ml)

and Indian (2.8 (1.1-4.7) µg/ml) as compared with

Chinese (1.3 (0.4-3.0) µg/ml, p<0.0001). Malays

and Indians had higher BMI (Malays 29.5±5.6,

Indians 27.5±4.5 and Chinese 26.3±4.4 kg/m2,

p<0.0001) and greater waist circumference

(Malays 99.2±14.2, Indians 97.8±12.1 and Chinese

93.1±12 cm, p<0.0001) than Chinese. Bivariate

correlation showed that hs-CRP was positively

correlated with BMI (ρ=0.385, p<0.0001) and waist

circumference (ρ=0.372, p<0.0001). Interestingly,

general linear model revealed that the differences

in hs-CRP levels between Malay and Chinese

were weakened after adjusting for either BMI or

waist circumference whereas the difference in hs-

CRP levels between Chinese and Indian was not

significantly altered.

RESULTS

High systemic inflammation in Malays and Indians with

T2DM may partly explain their high CVD risk. The

increased levels of inflammation in Malays may be

attributed to obesity. However, the mechanism underlying

high inflammation in Indians remains to be fully elucidated.

DISCUSSION

1. Ridker, P.M. Cardiology Patient Page. C-reactive protein: a

simple test to help predict risk of heart attack and stroke.

Circulation 2003.108: e81–e85.

2. Khoo, C.M, et al. Ethnicity modifies the relationships of

insulin resistance, inflammation, and adiponectin with obesity

in a multiethnic Asian population. Diabetes Care 2011.34:

1120–1126.

3. Sinha S.K, et al. Association of race/ethnicity, inflammation,

and albuminuria in patients with diabetes and early chronic

kidney disease. Diabetes Care 2014.37: 1060–1068.

REFERENCES

AcknowledgementThis study was supported by the Singapore National Medical Research Council Grant [PPG/AH(KTPH)/2011].

Figure 1. Adipose tissue inflammation contributes to obesity-

related metabolic dysfunction.

Obesity

(adipose tissue) Type 2 diabetes

Cardiovascular disease

Inflammatory markers ↑

Table 1. Clinical and biochemical characteristics of subjects with type 2 diabetes stratified

by ethnicity.

HbA1c, glycated hemoglobin; TC, total cholesterol; HDL, high density lipoprotein; LDL, low density lipoprotein; eGFR,

estimated glomerular filtration rate; uACR, urinary albumin-to-creatinine ratio.

Table 2. Variables associated with plasma hs-CRP variations in general linear regression

models in subjects with T2DM (N=1467).

B, unstandardized regression coefficient; HbA1c, glycated hemoglobin; FPG, fasting plasma glucose; SBP, systolic

blood pressure; HDL, high density lipoprotein; LDL, low density lipoprotein; TG, triglycerides; eGFR, estimated

glomerular filtration rate; uACR, urinary albumin-to-creatinine ratio.a Male gender and Chinese ethnicity were taken as reference. TG, uACR and hs-CRP were natural logarithmically

transformed.b No usage of medication was used as a reference.