The association between dyslipidaemia and obesity in Chinese men after adjustment for insulin resistance

Atherosclerosis 138 (1998) 153 – 161

The association between dyslipidaemia and obesity in Chinese men after adjustment for insulin resistance Gary T.C. Ko *, Juliana C.N. Chan, Clive S. Cockram Department of Medicine and Therapeutics, The Chinese Uni6ersity of Hong Kong, The Prince of Wales Hospital, Shatin, N.T., Hong Kong Received 6 May 1997; received in revised form 15 December 1997; accepted 24 December 1997

Abstract Obesity is associated with dyslipidaemia characterised by increased fasting triglyceride and decreased high-density lipoprotein (HDL) concentrations. Causes for obesity-associated dyslipidaemia include insulin resistance, excessive caloric intake, increased free fatty acid production and disturbances in the counter-regulatory hormones. We examined the relationships between lipid parameters and obesity before and after adjustment of insulin resistance in 902 Hong Kong Chinese men. After adjustment for age, smoking and insulin resistance, increasing body mass index (BMI) and waist-to-hip ratio (WHR) remained closely associated with increased concentrations of triglyceride and apolipoprotein B (apo B), increased ratios between low-density lipoprotein (LDL) and HDL (LDL/HDL), and that between apo B and LDL (apo B/LDL), increased fasting and 2-h plasma glucose and insulin, as well as decreased concentrations of HDL, HDL2 and apolipoprotein A-I (apo A-I). On stepwise multiple regression analysis using age, BMI, WHR, insulin resistance and fasting plasma glucose as independent variables, BMI and WHR were the major determinants for the variance of triglyceride, HDL and its subfractions, LDL/HDL, apo B and apo B/LDL. Age was the most important predictor for total cholesterol and LDL. Insulin resistance only explained less than 1% of the variance in triglyceride and apo B. This was compared to a variance between 10 and 16% in these parameters as explained by BMI and/or WHR. In conclusion, obesity is associated with dyslipidaemia in Chinese men, characterised by increased plasma triglyceride, apo B, LDL/HDL, apo B/LDL, and decreased HDL, HDL2 and apo A-I concentrations. Obesity independent of insulin resistance, in particular central adiposity as reflected by increased WHR, was the most important independent variable for many of these lipid abnormalities. Our results emphasised the multifactorial linkage between obesity and dyslipidaemia. © 1998 Elsevier Science Ireland Ltd. All rights reserved. Keywords: Obesity; Dyslipidaemia; Insulin resistance; Chinese men

1. Introduction The incidence of death due to ischaemic heart disease increases significantly in obese subjects [1,2]. Obesity, especially central obesity, is associated with dyslipidaemia characterised by increased triglyceride and decreased high-density lipoprotein (HDL) concentrations [3 – 6]. The plasma triglyceride concentrations are dependent on the rate of hepatic synthesis and peripheral * Corresponding author. Tel.: + 852 26323131; fax: + 852 26375396

clearance of very low-density lipoprotein (VLDL) [7,8]. Insulin resistance in obesity is associated with increased hepatic VLDL synthesis [9–11] and impaired lipoprotein lipase (LPL) activity which is involved in VLDL catabolism and formation of HDL [12,13]. Apart from insulin resistance, other factors such as excessive caloric intake [14,15], increased free fatty acid production [8,16,17] and alterations in the counter-regulatory hormones, as seen in visceral obesity [18], may also contribute to the dyslipidaemia in obese subjects. There are not sufficient reports in the literature on lipoproteins and their relationship to obesity, especially

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154

G.T.C. Ko et al. / Atherosclerosis 138 (1998) 153–161

in the Chinese population. In this analysis, we examined the relationships between lipid parameters and obesity in 902 Chinese men. We also tried to assess the role of insulin resistance in explaining the association between dyslipidaemia and obesity.

2. Subjects and methods

2.1. Subjects This is a subgroup analysis of a population-based survey for prevalence of cardiovascular risk factors in Hong Kong Chinese [19,20]. All employees from a public utility company and a regional hospital were invited to participate. A total of 1470 subjects were recruited. There were 902 men and 568 women. We excluded the female data in this present analysis due to the possible effects of menopause on lipid parameters [21,22]. The methodology of the survey has been described in detail [19,20]. In brief, all subjects attended their worksites after an overnight fast on the study day. Demographic and clinical data including past medical history and tobacco intake were recorded. Height and weight (measured to the nearest 0.1 kg) were measured with the subject in light clothing without shoes. Body mass index (BMI) was calculated as the weight (kg) divided by the square of the height (m2). Waist circumference (WC) was taken as the minimum circumference between the umbilicus and xiphoid process and measured to the nearest 0.5 cm. Hip circumference was measured as the maximum circumference around the buttocks posteriorly and the symphysis pubis anteriorly and measured to the nearest 0.5 cm. Waist-to-hip ratio (WHR) was then calculated [23]. Although there are papers suggesting waist circumference is more reliable in reflecting central adiposity than WHR, we have found in Chinese subjects that waist circumference and WHR are equally good in their association with cardiovascular risk factor [20]. We used WHR in this analysis as the index of central adiposity since it is still the most widely used parameter. Blood was taken after a 12-h fast for measurement of plasma total cholesterol (TC), triglyceride (TG), highdensity lipoprotein cholesterol and its subfractions (HDL, HDL2, HDL3), low-density lipoprotein cholesterol (LDL), apolipoprotein A-I (apo A-I) and apolipoprotein B (apo B). Since every LDL particle has only one apo B molecule [24], the ratio between apo B and LDL (apo B/LDL) provides an estimate of the size of LDL particles. The higher the ratio, the smaller and denser the LDL particles are. All subjects underwent a 75-g oral glucose tolerance test (OGTT). Fasting and 2-h plasma glucose and insulin were measured during the OGTT. The various laboratory assays have been described previously [19]. In short, TC and TG were

assayed enzymatically with commercial reagents (Baker Instruments Corporation, Allentown, PA, USA) on a Cobas Mira analyzer (Hoffmann-La Roche and Co., Basle, Switzerland). HDL and its subfractions were determined after fractional precipitation with dextran sulphate–MgCl2. LDL was calculated using the Friedewald’s formula [25]. Apo A-I and apo B were assayed by rate immunonephelometry (Array analyser and reagents, Beckman Instruments Inc., Bera, CA, USA). Interassay coefficients of variation (CV) were: TC, 1.9% at 6.4 mmol/l; TG, 2.6% at 1.9 mmol/l; HDL, 5.4% at 0.86 mmol/l; apo A-I, 2.2% at 1.36 g/l; apo B, 2.8% at 0.85 g/l. Plasma glucose was measured using a glucose oxidase method (Diagnostic Chemicals reagent kit). The intra-assay CV of glucose was 2% at 6.6 mmol/l. Insulin assay was performed using a radioimmunoassay kit (Pharmacia Insulin RIA 100, Pharmacia diagnostics AB, Uppsala, Sweden). The lower limit of detection was B 2 mU/ml. The inter-assay CV was 5%. Insulin resistance (IR) was calculated using a computer-solved homeostasis model assessment (HOMA) method: IR= fasting serum insulin/(22.5e − ln fasting plasma glucose) [26]. Lean and obese subjects were defined as those having a BMIB 22 kg/m2 or ] 27 kg/m2, respectively [27].

2.2. Statistical analysis Statistical analysis was performed using the SPSS (version 6.0) software on an IBM-compatible computer. Plasma triglyceride and insulin concentrations were logarithmically transformed due to skewed distributions. All results are expressed as mean9S.E.M. or geometric mean (95% confidence intervals) where appropriate. The analysis of covariance (ANCOVA) was used for between group comparisons with age, smoking, BMI, WHR and IR as covariates where appropriate. Stepwise multiple regression analysis was used to assess the significance of age, BMI, WHR, IR and fasting PG on the variance of various lipid parameters. A p-value B0.05 (two-tailed) was considered to be significant.

3. Results Table 1 summarises the clinical and biochemical characteristics of the 902 men. We divided the subjects into four quartiles based on BMI and WHR to assess the associations between lipid parameters, insulin resistance and obesity. After adjustment for age, smoking and IR, increasing BMI and WHR remained closely associated with increased concentrations of TG, apo B, LDL/HDL, apo B/LDL, fasting and 2-h PG and insulin, as well as decreased concentrations of HDL, HDL2 and apo A-I (Tables 1 and 2). We examined the relationships between IR and lipid parameters in the lean (BMIB22 kg/m2, n= 306) and

Total (BMI: 16.09– 42.47 kg/m2, n= 902)

5.85 9 0.17

39.7 (35.6, 43.1) 2.036 90.81 27.8 93.0

5.05 90.11 6.6 (6.3, 7.0) 35.3 (32.3, 38.6) 1.523 9 0.051 17.9 9 2.6

4.919 0.12 5.5 (5.2, 5.8) 28.8 (28.0, 31.9) 1.2549 0.046 20.0 9 2.7

7.5 (7.1, 7.9)

5.15 9 0.10

84.3 91.4 252.3 97.1

78.5 91.3 238.7 9 2.9

74.39 1.3 235.7 9 4.7 4.78 9 0.03

38.7 90.6 2 4.10 9 0.04 0.887 90.003 5.379 0.07 1.24 (1.16, 1.34) 1.21 9 0.02 0.34 90.02 0.87 9 0.01 3.50 9 0.07 3.07 9 0.07 122.4 91.5

35.8 90.6 22.24 90.03 0.864 90.003 5.16 9 0.06 1.06 (0.99, 1.13) 1.26 90.02 0.39 9 0.02 0.87 9 0.01 3.34 90.06 2.82 9 0.07 125.6 91.8

34.59 0.6 19.799 0.08 0.8329 0.003 5.1190.07 0.87 (0.82, 0.92) 1.41 9 0.02 0.54 9 0.02 0.8790.01 3.269 0.06 2.44 9 0.06 130.3 9 1.6

4.6890.12

Quartile 3 (BMI: 23.11 – 25.25 kg/m2, n =227)

Quartile 2 (BMI: 21.38 – 23.10 kg/m2, n =224)

Quartile 1 (BMI: 16.09–21.36 kg/m2, n= 225)

2.794 9 0.169 25.7 92.9

60.0 (54.1, 66.7)

10.3 (9.6, 11.0)

6.21 9 0.17

5.07 9 0.06

86.7 91.3 263.8 96.0

38.0 90.6 27.25 90.15 0.919 90.003 5.35 9 0.07 1.43 (1.34, 1.53) 1.10 90.02 0.26 90.01 0.85 9 0.01 3.48 9 0.07 3.27 9 0.08 120.0 91.5

Quartile 4 (BMI: 25.26 – 42.47 kg/m2, n = 226)

B0.001

B0.001

B0.001 —

B0.001

B0.001

B0.001 0.040

B0.001

B0.001

B0.001 0.003

— B0.001 B0.001 0.163 B0.001 B0.001 B0.001 0.131 0.186 B0.001 B0.001

— —

B0.001

B0.001

B0.001

B0.001

B0.001 0.022

— B0.001 B0.001 0.328 B0.001 B0.001 B0.001 0.318 0.281 B0.001 B0.001

p values after adjust- p values after adjustment for age and ment for age, smoksmoking ing and IR

B0.001

B0.001

B0.001 B0.001

B0.001 B0.001 B0.001 0.007 B0.001 B0.001 B0.001 0.157 0.015 B0.001 B0.001

p values

BMI, body mass index; WHR, waist-to-hip ratio; TC, total cholesterol; TG, triglyceride; HDL, HDL2, HDL3, high-density lipoprotein and its subfractions; LDL, low-density lipoprotein; apo A-I, apo B, apolipoprotein A-I and B; PG, plasma glucose; IR, insulin resistance. a Geometric mean (95% CI).

Age (years) 36.89 0.3 BMI (kg/m2) 23.3590.10 WHR 0.8759 0.002 TC (mmol/l) 5.259 0.03 TG (mmol/l)a 1.13 (1.09, 1.17) HDL (mmol/l) 1.259 0.01 HDL2 (mmol/l) 0.3890.01 HDL3 (mmol/l) 0.8790.01 LDL (mmol/l) 3.4090.03 LDL/HDL 2.9090.04 Apo A-I 124.59 0.8 (mg/dl) Apo B (mg/dl) 81.090.7 Apo B/LDL 247.79 2.7 (g/mol) fasting PG 4.929 0.03 (mmol/l) 2-h PG (mmol/ 5.509 0.08 l) Fasting insulin 7.3 (7.1, 7.5) (mU/ml)a 2-h insulin 39.5 (37.4, 41.7) (mU/ml)a IR 1.9059 0.067 Smoking (%) 22.8 9 1.4

Variables

Table 1 Clinical and biochemical characteristics of the 902 Chinese men divided into four quartiles based on BMI

G.T.C. Ko et al. / Atherosclerosis 138 (1998) 153–161 155

Quartile 1 (WHR: 0.745–0.834, n= 221)

6.63 9 0.20

58.1 (51.3, 65.9) 2.911 90.221 32.0 93.3

5.71 90.16 7.4 (6.9, 7.9) 43.9 (39.5, 48.9) 1.923 9 0.141 25.7 92.9

5.129 0.11 6.9 (6.6, 7.3) 36.6 (33.5, 39.8) 1.6299 0.057 17.09 2.4

10.0 (9.4, 10.8)

5.37 9 0.11

90.2 91.5 272.5 99.0

83.8 9 1.3 247.0 9 3.7

78.79 1.1 243.294.4 4.90 90.05

42.5 90.7 25.88 9 0.21 0.949 90.002 5.48 9 0.07 1.54 (1.44, 1.64) 1.10 9 0.02 0.26 9 0.02 0.84 9 0.01 3.57 9 0.07 3.41 9 0.08 119.3 91.7

38.3 90.6 24.23 90.16 0.894 90.001 5.31 90.06 1.20 (1.12, 1.29) 1.20 90.02 0.33 9 0.01 0.88 9 0.01 3.47 90.06 3.03 90.07 124.4 9 1.7

35.09 0.5 22.599 0.14 0.85590.001 5.22 90.06 1.13 (1.06, 1.20) 1.269 0.02 0.409 0.02 0.879 0.01 3.369 0.06 2.809 0.06 124.491.5

4.80 9 0.04

Quartile 4 (WHR: 0.916 – 1.211, n = 206)

Quartile 3 (WHR: 0.876 – 0.915, n =222)

Quartile 2 (WHR: 0.835–0.875, n=253)

B0.001

B0.001

B0.001 —

B0.001

B0.001

B0.001 B0.001

B0.001

B0.001

B0.001 B0.001

— B0.001 B0.001 0.159 B0.001 B0.001 B0.001 0.015 0.300 B0.001 B0.001

p values after adjustment for age and smoking

B0.001

B0.001

B0.001 B0.001

B0.001 B0.001 B0.001 B0.001 B0.001 B0.001 B0.001 0.067 B0.001 B0.001 B0.001

p values

— —

B0.001

B0.001

B0.001

0.199

B0.001 B0.001

— B0.001 B0.001 0.366 B0.001 B0.001 B0.001 0.038 0.457 B0.001 B0.001

p values after adjustment for age, smoking and IR

BMI, body mass index; WHR, waist-to-hip ratio; TC, total cholesterol; TG, triglyceride; HDL, HDL2, HDL3, high-density lipoprotein and its subfractions; LDL, low-density lipoprotein; apo A-I, apo B, apolipoprotein A-I and B; PG, plasma glucose; IR, insulin resistance. a Geometric mean (95% CI).

Age (years) 31.99 0.5 BMI (kg/m2) 20.989 0.15 WHR 0.8109 0.001 TC (mmol/l) 5.019 0.07 TG (mmol/l)a 0.81 (0.77, 0.86) HDL (mmol/l) 1.409 0.02 HDL2 (mmol/l) 0.5390.02 0.8790.01 HDL3 (mmol/l) LDL (mmol/l) 3.2090.06 LDL/HDL 2.41 90.07 Apo A-I 129.79 1.7 (mg/dl) Apo B (mg/dl) 72.19 1.3 Apo B/LDL 230.49 3.2 (g/mol) Fasting PG 4.669 0.02 (mmol/l) 2-h PG 4.719 0.10 (mmol/l) Fasting insulin 5.6 (5.3, 5.9) (mU/ml)a 2-h insulin 26.9 (24.5, 29.6) (mU/ml)a IR 1.2519 0.035 Smoking (%) 18.1 92.6

Variables

Table 2 Clinical and biochemical characteristics of the 902 Chinese men divided into four quartiles based on WHR

156 G.T.C. Ko et al. / Atherosclerosis 138 (1998) 153–161

G.T.C. Ko et al. / Atherosclerosis 138 (1998) 153–161

obese subjects (BMI=27 kg/m2, n =90). In both groups, subjects with an IR] 1.905 (the mean IR of the whole population) had higher BMI, WHR, TG, fasting and 2-h PG and insulin than subjects with IRB1.905. These differences in TG, PG and insulin persisted after adjustment for age, BMI, WHR and smoking. In the lean group, the more insulin-resistant subjects also had a lower HDL2 concentration than those with a lower IR (Table 3). On stepwise multiple regression analysis using age, BMI, WHR, IR and fasting PG as independent variables, BMI and WHR were the major determinants for the variance of TG, HDL and its subfractions, LDL/ HDL, apo B and apo B/LDL. Age was the most important predictor for TC and LDL. Insulin resistance only explained less than 1% of the variance in TG and apo B. This was compared to a variance between 10 and 16% in these parameters as explained by BMI and/or WHR (Table 4). In the lean subjects with BMIB 22 kg/m2 (n =306), WHR and IR both contributed to the variance of TG, HDL, HDL2, LDL/ HDL and apo B. Age and FPG explained much of the variance of TC, LDL and, to a lesser extent, apo B. In subjects with a BMI\22 kg/m2, the variance of all parameters were entirely explained by BMI, WHR and, to a lesser extent, FPG and age.

4. Discussion Associations between obesity and a wide range of lipid abnormalities have previously been reported [3–6]. In agreement with these findings, our study showed that increasing BMI or WHR were associated with increased triglyceride, LDL/HDL, apo B, apo B/LDL and decreased HDL, HDL2 and apo A-I concentrations after adjustment for age and smoking. We also found that both increasing BMI and WHR in Chinese men were associated with increased fasting and 2-h insulin levels and insulin resistance. Due to the pluripotent effects of insulin on intermediary metabolism, insulin resistance has often been proposed as the common linking factor for the frequent, but not invariable, clustering of obesity, glucose intolerance, dyslipidaemia, atherosclerosis and hypertension [14]. In the present analysis, we also found that the more insulin-resistant subjects had higher TG concentrations than subjects with a lower IR index based on the HOMA model [26] after adjustment for age, obesity and smoking. These associations between insulin resistance and dyslipidaemia were observed in both lean (BMI B22 kg/m2) and obese subjects (BMI]27 kg/m2). In addition, in the lean group, the insulin-resistant subjects with a high IR index had a lower HDL2 concentration than those with a low IR index.

157

Despite these associations between IR and dyslipidaemia, obesity as measured by BMI and WHR was the major determinant for the various lipid abnormalities even after adjustment for IR. Although insulin resistance may contribute to the dyslipidaemia in obesity, other factors may also be important [3,8,14–18]. A maladaptive response to stress may lead to increased glucocorticoid production [18]. Glucocorticoids may increase VLDL and apo B production, as well as decrease the activity of LDL receptor [28]. Alterations in sex steroid levels such as reduced testosterone concentrations in men and increased testosterone concentrations in women are also associated with visceral obesity [3,29,30]. The underlying mechanism may be due to change in the hepatic lipase and LPL activity [31–33]. Visceral adipocytes have increased lipolytic activity and centrally obese subjects often have increased free fatty acid (FFA) level. The latter provide a substrate for the hepatic synthesis of triglyceride and secretion of VLDL [8,17,34]. Similarly, excessive caloric intake can also provide an abundant substrate to the liver for triglyceride synthesis and contribute to the dyslipidaemic state in obesity [14]. Against this background and using stepwise multiple regression analysis, we found that central obesity, as reflected by WHR, was the most important explanatory variable for the variance in plasma triglyceride, LDL/ HDL, apo B and apo B/LDL ratios. Body mass index was the most important determinant for the variance in HDL, HDL2 and apo A-I levels while age explained most of the variance in plasma total cholesterol and LDL. Although insulin resistance also explained some of the variations in plasma triglyceride and apo B, this was only small compared to that explained by BMI and/or WHR. Nevertheless, in lean subjects with BMI less than 22 kg/m2, the effects of insulin resistance became more important, although WHR remained an important explanatory variable. In this study, we are using an indirect index, the HOMA model [26], to determine IR rather than using euglycaemic clamp, the gold standard for assessing IR. Although this might affect the precision in the interpretation, the high significance of our results emphasised the multifactorial linkage between obesity and dyslipidaemia. Small, dense LDL is a strong and independent risk factor for cardiovascular disease [35–37]. In this respect, there were significant associations between BMI, WHR and apo B/LDL ratio. Apo B/LDL ratio provides a good estimate of the size of LDL particles, although it is confounded by the apo B present in the VLDL molecules. These results therefore suggest that obesity is associated with both quantitative and qualitative changes in lipid parameters which contribute to the increased cardiovascular risk of these subjects. In addition, in obese subjects with BMI]27 kg/m2, fasting plasma glucose was the main determinant for apo B/

G.T.C. Ko et al. / Atherosclerosis 138 (1998) 153–161

158

Table 3 Comparison between subjects with IR]1.905 and IRB1.905 for those who were lean (BMIB22 kg/m2) or obese (BMI]27 kg/m2) Variables

Total (n =306)

(A) Lean subjects with BMIB22 kg/m 2 Age (years) 34.790.5 BMI, kg/m2 0.299 0.07 WHR 0.8409 0.001 TC (mmol/l) 5.129 0.06 TG (mmol/l)a 0.91 (0.85, 0.96) HDL (mmol/l) 1.399 0.02 HDL2 (mmol/l) 0.529 0.02 HDL3 (mmol/l) 0.87 90.01 LDL (mmol/l) 3.259 0.05 LDL/HDL 2.4790.05 Apo A-I (mg/dl) 130.491.5 Apo B (mg/dl) 74.99 1.1 Apo B/LDL (g/mol) 237.29 3.7 Fasting PG (mmol/l) 4.7190.03 2-h PG (mmol/l) 4.909 0.10 Fasting insulin (mU/ 5.8 (5.5, 6.0) ml)a 2-h insulin (mU/ml)a 29.4 (27.1, 31.8) IR 1.329 0.05 Smoking (%) 18.3 92.2 (B) Obese subjects with BMI]27 kg/m 2 Age (years) 36.29 1.0 BMI (kg/m2) 29.1090.25 WHR 0.9309 0.010 TC (mmol/l) 5.309 0.12 TG (mmol/l)a 1.41 (1.27, 1.55) HDL (mmol/l) 1.109 0.02 HDL2 (mmol/l) 0.26 90.02 HDL3 (mmol/l) 0.8590.01 LDL (mmol/l) 3.459 0.12 LDL/HDL 3.259 0.13 Apo A-I (mg/dl) 119.892.3 Apo B (mg/dl) 85.392.0 Apo B/LDL (g/mol) 265.29 9.1 Fasting PG (mmol/l) 4.9890.08 2-h PG (mmol/l) 6.0690.25 Fasting insulin (mU/ 11.7 (10.4, 13.2) ml)a 2-h insulin (mU/ml)a 64.7 (54.1, 77.5) IR 3.049 0.22 Smoking (%) 22.29 4.4

IR]1.905 (n = 37)

IRB1.905 (n =269)

p values

p values after adjustment for age, BMI, WHR and smoking

34.79 1.9 20.91 9 0.16 0.8529 0.008 5.039 0.14 1.17 (0.98, 1.39) 1.28 9 0.05 0.399 0.04 0.899 0.02 3.12 9 0.12 2.559 0.13 130.79 3.5 77.2 9 2.9 249.79 5.8 5.019 0.11 5.609 0.30 11.5 (10.3, 12.8)

34.79 0.5 20.209 0.08 0.83490.002 5.13 9 0.06 0.88 (0.83, 0.93) 1.40 9 0.02 0.54 9 0.02 0.87 9 0.01 3.279 0.06 2.46 9 0.06 130.3 9 1.6 74.6 91.2 235.5 94.1 4.67 9 0.03 4.80 9 0.10 5.2 (5.0, 5.4)

0.970 B0.001 0.010 0.549 0.001 0.024 0.003 0.620 0.343 0.565 0.944 0.439 0.211 0.003 0.009 B0.001

— — — 0.336 0.011 0.153 0.040 0.665 0.169 0.720 0.709 0.881 0.330 B0.001 0.010 B0.001

54.3 (43.7, 67.4) 2.739 0.23 16.296.1

27.1 (24.8, 29.6) 1.13 9 0.02 18.6 92.4

B0.001 B0.001 0.728

B0.001 B0.001 0.759

36.5 9 1.2 29.509 0.34 0.9399 0.006 5.41 9 0.12 1.59 (1.44, 1.76) 1.0990.03 0.24 9 0.02 0.859 0.02 3.509 0.13 3.34 9 0.15 119.29 3.0 86.39 2.3 264.0 9 12.0 5.149 0.10 6.629 0.33 14.9 (13.4, 16.5)

35.5 9 1.9 28.21 9 0.24 0.900 90.009 5.04 90.27 1.07 (0.88, 1.29) 1.14 90.04 0.30 90.03 0.85 9 0.02 3.35 9 0.26 3.05 90.28 121.2 9 3.8 83.3 93.8 268.0 9 14.0 4.62 90.08 4.81 90.20 6.5 (5.8, 7.3)

0.635 0.003 0.001 0.145 B0.001 0.229 0.132 0.962 0.562 0.318 0.699 0.490 0.845 0.002 B0.001 B0.001

— — — 0.142 0.004 0.206 0.207 0.695 0.366 0.189 0.505 0.399 0.780 0.014 0.025 B0.001

82.2 (67.8, 99.6) 3.719 0.26 24.29 5.5

35.9 (26.4, 48.9) 1.3890.07 17.9 97.4

B0.001 B0.001 0.509

0.001 B0.001 —

BMI, body mass index; WHR, waist-to-hip ratio; TC, total cholesterol; TG, triglyceride; HDL, HDL2, HDL3, high-density lipoprotein and its subfractions; LDL, low-density lipoprotein; apo A-I, apo B, apolipoprotein A-I and B; PG, plasma glucose; IR, insulin resistance. a Geometric mean (95% CI).

LDL. Other workers have shown a two-fold increase in the prevalence of small, dense LDL in diabetic subjects [38,39]. In a prospective study, small, dense LDL were associated with a more than two-fold increased risk of subsequent development of diabetes [40]. On the other hand, an association between small, dense LDL and insulin resistance has also been described [41,42]. All these findings point to intimate and complex relationships between obesity, abnormal fat and glucose metabolism, insulin resistance and increased cardiovascular risks. In conclusion, among Chinese men, obesity is associ-

ated with dyslipidaemia characterised by increased plasma triglyceride, apo B, LDL/HDL and apo B/LDL, decreased HDL, HDL2 and apo A-I concentrations. Insulin resistance was associated with increased plasma triglyceride and decreased HDL2 concentrations especially in lean subjects. Obesity independent of insulin resistance, in particular central adiposity as reflected by increased WHR, was the most important independent variable for many of these lipid abnormalities. Our results emphasised the multifactorial linkage between obesity and dyslipidaemia.

R2

Age

b p — 2.977 −0.035 −0.033 — 0.021 0.043 −1.115 — — — — — — — — — — — — — 0.050 −0.038 −0.029 — — — — — — — — — — — — — — — —

— — — — — — — — — — — 0.014 0.030a 0.034a — — — — — — — — — — — — — — — —

b

— 0.015 0.111a 0.152a — 0.003 0.008 0.017a — —

R2

BMI

— — — — — — — — — —

— 0.003 B0.001 B0.001 — — — — — —

— — — — — — — — — —

— B0.001 B0.001 B0.001 — 0.043 0.003 B0.001 — —

p

— 0.054a — — — — — — — —

— 0.085a 0.003 0.008 0.009a — 0.053a — 0.030 0.050a

— 0.083a 0.062a 0.096a — — 0.093a 0.011a 0.050a —

0.006 0.157a 0.022 0.025 0.007a — 0.105a — 0.102a 0.035a

R2

WHR

— — — — — — — —

— 2.476

3.175 −0.731 −0.497 −0.315 — 5.282 — 0.478 42.14

—

7.099 −80.99 113.44 —

— —

3.852 −2.167 −2.279

120.51 28.67

6.523

1.625 3.933 −1.094 −0.977 −0.266

—

—

—

b

0.018 — — — — — — — —

—

— B0.001 0.010 0.018 0.022 — B0.001 — B0.001 B0.001

— B0.001 B0.001 B0.001 — — B0.001 0.038 B0.001 —

0.012 B0.001 B0.001 B0.001 0.007 — B0.001 — B0.001 B0.001

p

— — — — — — — — — —

— — — — — — — — — —

— 0.033 0.019 0.028 — — 0.009 — 0.016 —

— 0.003 — — — — — — 0.004 —

R2

IR

0.694

0.020

— — — — — — — — — —

— — — — — — — — — —

0.125 −0.062 −0.061 — — 0.126 — 3.634 —

—

—

— — — — — —

—

b

— — — — — — — — — —

— — — — — — — — — —

— B0.001 0.008 0.002 — — 0.046 — 0.012 —

— 0.026 — — — — — — 0.038 —

p

— — — — — — — — — 0.041a

— — — — — — — — 0.012 —

0.015 — — — — 0.015 — — 0.014 —

— — — — — — — — — —

R2

FPG

— — — — — — — — — 2.640

— — — — — — — — 2.192 —

−0.293 — — — — −0.270 — — 5.510 —

— — — — — — — — — —

b

— — — — — — — — — 0.033

— — — — — — — — 0.005 —

0.016 — — — — 0.017 — — 0.019 —

— — — — — — — — — —

p

BMI, body mass index; WHR, waist-to-hip ratio; TC, total cholesterol; TG, triglyceride; HDL, HDL2, HDL3, high-density lipoprotein and its subfractions; LDL, low-density lipoprotein; apo A-I, apo B, apolipoprotein A-I and B; PG, plasma glucose; IR, insulin resistance. a The first independent variable which enters the regression model.

(A) Total population (n= 902) TC 0.063a 0.027 B0.001 TG 0.004 0.004 0.027 HDL — — — HDL2 — — — HDL3 0.001 0.047 0.003 LDL 0.045a 0.022 B0.001 LDL/HDL 0.009 0.013 0.001 — — — Apo A-I 0.443 B0.001 Apo B 0.033 Apo B/LDL — — — (B) BMI B22 kg/m 2 (n= 306) a TC 0.060 0.028 B0.001 TG — — — HDL 0.018 0.006 0.009 HDL2 — — — a HDL3 0.030 0.003 0.002 LDL 0.042 0.022 B0.001 — LDL/HDL — — Apo A-I 0.374 0.043 0.010 Apo B 0.020 0.356 0.007 Apo B/LDL — — — (C) BMI]22 and B27 kg/m 2 (n= 506) TC 0.065a 0.027 B0.001 TG — — — HDL — — — HDL2 — — — HDL3 — — — LDL 0.051a 0.023 B0.001 LDL/HDL 0.019 0.018 0.001 Apo A-I — — — 0.675 B0.001 Apo B 0.092a Apo B/LDL — — — 2 (D) BMI]27 kg/m (n= 90) TC — — — TG — — — HDL — — — HDL2 — — — HDL3 — — — LDL — — — LDL/HDL — — — Apo A-I — — — Apo B 0.045a 0.477 0.028 Apo B/LDL — — —

Lipid

Table 4 Stepwise multiple regression analysis using age, BMI, WHR, IR and fasting PG as independent variables to explain the variance in various lipid parameters

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