Postprandial lipid metabolism and insulin sensitivity in young Northern Europeans, South Asians and Latin Americans in the UK

Atherosclerosis 159 (2001) 441– 449 www.elsevier.com/locate/atherosclerosis

Pilot study

Postprandial lipid metabolism and insulin sensitivity in young Northern Europeans, South Asians and Latin Americans in the UK Martha L. Cruz a,b, Kevin Evans c, Keith N. Frayn a,* a

Oxford Lipid Metabolism Group, Oxford Centre for Diabetes, Endocrinology and Metabolism, Nuffield Department of Clinical Medicine, Radcliffe Infirmary, Oxford OX2 6HE, UK b Uni6ersidad del Valle, Cali, Colombia c Department of Clinical Chemistry, Staffordshire General Hospital, Stafford, UK Received 4 April 2000; received in revised form 14 February 2001; accepted 30 March 2001

Abstract The aim of this study was to determine whether the higher susceptibility to coronary heart disease and diabetes in South Asian immigrants to the United Kingdom compared with the Caucasian population may reflect insulin resistance and altered postprandial lipid metabolism. We also wished to study Latin Americans, an ethnic group that has not been previously studied in the United Kingdom. The intention was to carry out a detailed study in a relatively small number of subjects to provide essential baseline information for larger epidemiological studies. Postprandial lipaemia was measured in 25 subjects (eight South Asians, eight Latin Americans and nine Northern Europeans) who resided in the United Kingdom. Results from the postprandial studies were correlated to insulin sensitivity measured by the insulin tolerance test, food intake, anthropometry and adipose tissue fatty acid composition. In South Asians, postprandial glucose and insulin concentrations were greater than in the other groups (PB 0.01 and B0.05, respectively), although there were no differences in postprandial triacylglycerol concentrations or in insulin sensitivity assessed with the insulin tolerance test. The decreased glucose tolerance in this group could not be explained by differences in percentage body fat, body mass index, or by dietary intake measured by food records or adipose tissue fatty acid composition. We conclude that postprandial lipaemia is not affected in young South Asians compared to Northern Europeans although glucose intolerance is detectable. The results from the present study should help in the design of further postprandial lipid studies in different ethnic groups. © 2001 Elsevier Science Ireland Ltd. All rights reserved. Keywords: Ethnic; Postprandial lipaemia; Insulin sensitivity; South Asians; Northern Europeans; Latin Americans

1. Introduction Abbre6iations: AUC, area under the postprandial plasma concentration versus time curve; IAUC, incremental area under the postprandial plasma concentration versus time curve; BMI, body mass index; BMR, basal metabolic rate; CVD, cardiovascular disease; NEFA, non-esterified fatty acids; PAL, physical activity level; SEM, standard error of the mean; SITT, short insulin tolerance test; TG, triacylglycerols; VLDL, very low density lipoprotein; HDL, high density lipoprotein; LDL, low density lipoprotein; UK, United Kingdom; US, United States. * Corresponding author. Tel.: + 44-1865-224180; fax: + 44-1865224652. E-mail address: [email protected] (K.N. Frayn).

High coronary disease rates and mortality appear to be common to South Asian groups of different geographical origin, religion and language [1]. In England and Wales, male and female migrants from the Indian subcontinent (Gujarati, Hindus, Punjabi, Sikhs and Muslims from Pakistan and Bangladesh) have higher morbidity and mortality from coronary heart disease than the native Caucasian population [2,3]. This may be due to insulin resistance [4,5] when genetically predisposed individuals adopt a sedentary

0021-9150/01/$ - see front matter © 2001 Elsevier Science Ireland Ltd. All rights reserved. PII: S 0 0 2 1 - 9 1 5 0 ( 0 1 ) 0 0 5 2 3 - 8

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lifestyle and a high energy intake [6,7]. McKeigue and co-workers [3] have provided evidence for the existence of an insulin resistance syndrome in South Asians, associated with a pronounced tendency to central obesity. Similarly, Hispanics in the US are centrally obese [8], and insulin resistant, and display a consistent relationship between impaired insulin-mediated glucose disposal and dyslipidaemia [9]. Insulin resistance and the development of cardiovascular disease (CVD) are probably linked through changes in lipid and lipoprotein metabolism. Alterations in lipid metabolism commonly associated with insulin resistance and with an increased risk for CVD are: elevated plasma triacylglycerol (TG) concentration (particularly elevation of VLDL-TG), decreased plasma HDL-cholesterol concentration, elevation of plasma non-esterified fatty acids (NEFA, particularly impaired postprandial suppression) and small dense LDL particle distribution. An underlying theme may be an impairment of postprandial lipid metabolism [10]. A delay in plasma lipoprotein TG clearance allows for cholesterol esters to be passed on from LDL and HDL to TG-rich particles, making them potentially atherogenic. Deficits in insulin suppression of NEFA have been demonstrated in persons with impaired glucose tolerance, patients with NIDDM, in South Asians compared with individuals of European origin, in women and men with upper body obesity and in sedentary men [11]. Insulin plays a central role in determining TG clearance via activation of lipoprotein lipase, and also TG output, through effects on the synthesis and secretion of VLDL. The ability of an individual to cope with a fat meal may be especially important in the development of coronary heart disease. Measurement of postprandial lipaemia may help to explain differences in coronary heart disease mortality between ethnic groups as suggested by a recent study, which compared Northern and Southern European subjects [12]. It has been suggested that the influence of postprandial lipid metabolism on development of CVD is gradual, and reflects the effect of successive bouts of increased postprandial lipaemia [13]. Therefore it would be interesting to investigate postprandial lipid metabolism at an earlier age than that at which CVD becomes evident. As most studies of ethnic differences in metabolism have been conducted in middle-aged subjects, we felt it would be relevant to study younger subjects to see if changes could be observed that might, over a period of time, lead to development of later CVD. Large epidemiological studies are expensive and labour-intensive. Detailed study of postprandial metabolism is not readily applicable in such studies. It has been suggested that measurement of plasma TG concentrations at 6-8 h after a lipid load might provide the best discrimination between healthy subjects and those with CVD [14], but the timing of events in the

postprandial period has not been investigated in different ethnic groups. Therefore it would be valuable to have detailed information from a pilot study on which to base future, larger-scale epidemiological studies. To address these issues we designed a pilot study in healthy young adults belonging to three ethnic groups and who were residents in the UK.

2. Subjects and methods

2.1. Subjects Twenty-five subjects (15 males) participated. They were recruited mainly from among the student population at the University of Oxford, in response to advertisements placed in local Colleges and through personal communication. They were originally from South Asia (India, Sri Lanka; five males, three females) Latin America (Colombia, Mexico, Brazil; five males, three females) or Northern Europe (UK; five males, four females). To participate in the study the subject was required to have lived a minimum of 1 year in the UK and both his/her parents and grandparents should share a common ethnic background which was self-determined by a questionnaire. The inclusion criteria were age: 22–40 years, BMI 19–27 kg/m2, no family history of heart disease or diabetes, no medication or weightlosing diet. The average age, body mass index (BMI) and percentage body fat for the subjects, are shown in Table 1. All subjects had normal fasting plasma TG, glucose, insulin and NEFA concentrations and they were non-smokers (Table 2). Ethical approval for the study was provided by the Central Oxford Research Ethics Committee, and all subjects gave informed consent.

2.2. Experimental design Subjects were asked to refrain from performing exercise or drinking alcoholic beverages 24 h before a study. They were requested to eat a low fat (B1% fat) meal 14 h before the study and to avoid eating or drinking anything except water after this period. Twenty-five subjects completed the postprandial studies; however, due to voluntary withdrawal, only 21 completed the short insulin tolerance test and other measurements.

2.3. Postprandial response to a fatty meal After a 12 h fast, subjects attended the investigation unit at 08:00 h. A retrograde intravenous cannula was inserted into a dorsal hand vein under lignocaine anaesthesia and kept patent by a continuous slow infusion of saline (9 g/l NaCl). The hand was placed in a hot box maintained at 65°C to arterialise the venous blood.

M.L. Cruz et al. / Atherosclerosis 159 (2001) 441–449

After two fasting blood samples had been taken, the subjects ate a high-fat test meal. This consisted of corn flakes, macadamia nuts, skimmed milk and banana which provided 52% of energy as fat, 40% as carbohydrate and 8% as protein. Additional samples were taken at 20, 40, 60, 90, 120, 180, 240, 300, 360, 420 and 480 min after breakfast for measurement of postprandial plasma TG, glucose, insulin and NEFA. Plasma chylomicron and VLDL TG were measured at 0, 120, 180, 240, 300, 360, 420 and 480 min after the meal.

2.4. Short insulin tolerance test In order to assess subjects’ overall tissue insulin sensitivity we performed a short insulin tolerance test (SITT) at least one week apart from the postprandial tests. On the morning of each experiment, subjects attended the laboratory at 08:00 h after a 12 h overnight fast. A 20 gauge intravenous cannula was positioned in a dorsal hand vein and the hand kept in a hot box as described above. A second cannula was placed in an arm vein for insulin injection. After taking two basal samples, a bolus of insulin (Humulin S., Lilly, France), 0.05 U/kg body weight, was administered intravenously. Further blood samples were taken at 3, 5, 7, 9, 11, 13, and 15 min after the injection of insulin for measurement of plasma glucose. The test was terminated 15 min after the insulin bolus with a 75 g glucose solution given orally and the subject was given a light breakfast. The blood glucose was checked before departure. Insulin sensitivity was derived from the linear slope of the blood glucose concentration from 3–15 min [15].

2.5. Anthropometric measurements After an overnight fast weight was recorded to 9 0.2 kg with a digital scale, with subjects wearing light clothing and no shoes. Height was recorded to 9 0.5

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cm with a height bar fixed on the wall, with subjects standing with a straight back and heels together pressed to the wall. Four subcutaneous skinfold measurements (biceps, triceps, suprailiac and subscapular) were recorded to 9 2 mm with a Lange caliper and three circumferences (hip, waist, mid-arm) to 9 5 mm with a sewing tape. All measurements were made by one investigator. Weight (kg) and height (m) were used to calculate BMI. Biceps, triceps subscapular and suprailiac skinfold thickness were used to estimate whole body fat content from standard tables [16]. Waist/hip ratio and waist circumference were used to estimate body fat distribution [17].

2.6. Dietary record and adipose tissue biopsy The energy and nutrient intake was investigated by using a self-administered 7-day food record designed by the Glostrup Population Studies [18]. The record provides standard portion size photographs for the guidance of the subjects. Average weights are given for 19 foodstuffs. The entries are made in grams, estimated as accurately as possible. Nutrient content was analysed with the PC program Foodbase (Institute of Brain Chemistry, London). The long-term average dietary fatty acid [19,20] and carbohydrate [21] intake was estimated by measuring the fatty acid profile of adipose tissue. Needle biopsies were taken from subcutaneous fat in the lower abdominal region [22]. Samples were stored at − 20°C.

2.7. Analytical methods Plasma was separated rapidly at 4°C and portions of 1 ml were used for preparing a chylomicron-rich fraction by layering under a solution of density 1.006 g/l and centrifugation at 12 600× g for 120 min as described previously [23]. Chylomicron, VLDL and

Table 1 Details and anthropometric measurement of subjects Ethnic group

Age (years) Weight (kg) Height (m) BMI (kg/m2) Waist circumference (cm) Hip circumference (cm) Waist/Hip ratio Midarm circumference (cm) Body fat (%)

Latin Americans (n = 8)

South Asians (n = 8)

Northern Europeans (n = 9)

Mean

Range

Mean

Range

Mean

Range

31.4 71.6 1.7 24.5 83.5 99.2 0.84 28.1 26.1

25–35 44.0–92.8 1.44–1.85 21.2–26.7 68.0–94.0 87.0–111.4 0.78–0.91 23.5–30.6 17.5–36.0

28.5 70.9 1.8 22.9 83.8 100.6 0.83 29.5 24.2

22–38 49.9–85.5 1.55–1.92 19.9–27.2 64.8–101.1 91.3–114.5 0.71–0.89 26.3–33.5 13.0–36.9

30.4 66.1 1.7 22.5 75.6 96.6 0.78 27.4 24.4

23–40 46.5–80.0 1.60–1.88 17.7–27 62.5–90.3 86.5–103.5 0.71–0.88 22–32 16.0–31.0

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Table 2 Fasting plasma concentration of lipids, glucose and insulin measured on the postprandial day Ethnic group

Triacylglycerol (mmol/l) VLDL-TG (mmol/l) NEFA (mmol/l) Glucose (mmol/l) Insulin (mU/l)

Latin Americans (n= 8)

South Asians (n =8)

Northern Europeans (n =9)

Mean

SEM

Mean

SEM

Mean

SEM

1174 546 431 5.0 7.4

208 125 50 0.1 1.2

892 399 467 5.0 8.8

107 71 41 0.1 1.3

1168 452 469 4.8 6.2

243 105 67 0.1 0.78

Values are not statistically significant, P\0.05. TG, triacylglycerol; NEFA, non-esterified fatty acids.

plasma TG were measured by an enzymatic method on an IL Monarch centrifugal analyser (Instrumentation Laboratory, Warrington, UK). Plasma NEFA was determined by an enzymatic method (WAKO NEFA C kit, Alpha laboratories Ltd, Eastleigh, UK). Glucose concentrations were measured using a hexokinase method. Plasma insulin was measured by a double antibody radioimmunoassay (Kabi Pharmacia, Milton Keynes, UK). Adipose tissue biopsies were extracted with chloroform:methanol (2:1 by volume) containing butylated hydroxytoluene as antioxidant. TG in the extract was separated from the phospholipids by thin layer chromatography and transesterified to form fatty acid methyl esters. Fatty acid composition was analysed by capillary gas chromatography as described previously [23]. A Chrompack 9000 gas chromatograph equipped with a 25× 0.32 mm fused silica capillary column (FFAP-CB) from Chrompack (Milharbour, London, UK) was used.

2.8. Statistical analysis All data were analysed using the program SPSS version 8.0 (SPSS UK Ltd, Chertsey, UK). For most statistical analysis, postprandial measurements were assessed as area under the curve (AUC) [24]. Incremental areas under the curve (IAUC) were calculated as the total AUC minus the mean baseline value, extrapolated over the 8-h postprandial period. Total AUC and IAUC were then divided by the appropriate time base to give time-averaged values. Differences in AUCs between ethnic groups were then analysed by analysis of variance (ANOVA). Postprandial insulin data were log (10) transformed to achieve a normal distribution. TG AUCs were non-normally distributed, although TG concentrations were not significantly so. Each was analysed with and without log-transformation with similar statistical results. For simplicity of presentation, all results are presented as arithmetic mean with standard error (SEM). ANOVA was used to assess differences

between ethnic groups in the fasting levels of lipids, glucose and insulin as well as in anthropometric measurements, dietary food intake and adipose tissue fatty acid profiles. Differences in insulin sensitivity (slope of blood glucose concentration against time) were determined by multifactorial analysis of variance. All results were tested for the effect of ethnic group and gender. 3. Results

3.1. Anthropometry and diet Table 1 shows the mean values for age, height, weight, percentage body fat, mid-arm circumference, waist circumference, waist/hip ratio and BMI for each ethnic group. Although there were no statistical differences due to ethnicity, gender differences were found for weight, height, midarm circumference, percentage body fat (ANOVA PB 0.001) and for waist and hip circumference and waist/hip ratio (ANOVA PB0.01) (results not shown). All subjects had a similar dietary intake as shown by the analysis of the recorded food diaries. The daily mean9SEM total energy intake was 10.49 0.7 MJ and the mean9 SEM percentage energy derived from carbohydrate, protein and fat was 479 2.9, 16.39 0.91 and 369 3.1. Energy intake was validated against calculated basal metabolic rate estimated from the equations of Schofield [25] and compared with the mean energy requirement of the population, also expressed as a multiple of the basal metabolic rate (physical activity level or PAL). The Golberg equation [26] was used to evaluate under-reporting of energy intake for each subject. Under-reporters were defined as those subjects with an energy intake:basal metabolic rate ratio below a cut-off that assumed an energy requirement of 1.55×BMR. Using this level of PAL only one subject appeared to be under-reporting. At higher energy expenditures (PAL of 1.86 for men and 1.66 for women) three subjects appeared to be underreporting.

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Table 3 Adipose tissue fatty acid composition (percent by weight) Ethnic group Latin Americans

12:0 14:0 16:0 16:1 18:0 18:1n-9a 18:2n-6 18:3n-6 18:3n-3 20:0a,b 20:4n-6 20:5n-3 22:5n-3 22:6n-3 Total SFA Total MUFAa Total PUFA

South Asians

Northern Europeans

Mean

SEM

Mean

SEM

Mean

SEM

0.59 3.78 25.66 4.13 5.01 44.78 13.38 0.10 0.99 0.17 0.24 0.04 0.15 0.09 35.26 49.58 15.16

0.04 0.20 0.92 0.57 0.54 0.77 0.84 0.01 0.07 0.04 0.05 0.01 0.03 0.03 1.47 0.73 0.82

0.62 3.97 25.61 3.51 5.47 42.83 15.03 0.10 1.13 0.21 0.29 0.07 0.14 0.07 35.95 47.05 17.00

0.05 0.23 0.75 0.24 0.35 0.45 0.88 0.01 0.08 0.03 0.03 0.01 0.02 0.04 0.70 0.60 0.90

0.70 3.65 24.13 3.49 6.00 45.44 13.55 0.06 1.16 0.30 0.22 0.05 0.14 0.07 34.86 49.74 15.41

0.05 0.16 0.62 0.27 0.29 0.75 0.81 0.01 0.08 0.03 0.01 0.01 0.03 0.04 0.55 0.81 0.82

SFA, saturated fatty acids; MUFA, monounsaturated fatty acids; PUFA, polyunsaturated fatty acids. a Values are statistically different for ethnic group (ANOVA PB0.05); South Asians are different from Northern Europeans (Multiple comparisons using Bonferoni post hoc tests PB0.05). b Latin Americans are different from Northern Europeans and from South Asians (Multiple comparisons using Bonferoni post hoc tests PB0.05).

3.2. Adipose tissue fatty acid profiles Table 3 shows the fatty acid composition of abdominal subcutaneous adipose tissue by ethnic group. Total saturated and polyunsaturated fatty acids were not different between ethnic groups. Likewise the fatty acid content of linoleic acid, a strong biomarker of polyunsaturated fatty acid intake [27], was not statistically significant between groups. The adipose tissue monounsaturated fatty acid content, as well as the content of oleic and 20:0 acids were different between ethnic groups (ANOVA P B0.05). Finally, saturated fatty acid content was lower in adipose tissue of women than men (ANOVA PB0.05).

Total plasma TG, chylomicron-TG (Fig. 1) and VLDLTG also peaked at 4 h and declined steadily until 8 h after the meal, at which time the initial fasting values were reached. Although Latin Americans appeared to have a greater postprandial TG response to the meal, particularly in the chylomicron fraction, this did not

3.3. Fasting plasma 6alues Fasting plasma concentrations of glucose, insulin, total TG, VLDL-TG and NEFA are shown in Table 2. Lipid values, except NEFA were significantly different by gender (ANOVA P B0.05) but were similar by ethnic group.

3.4. Postprandial response to a fatty meal In all three ethnic groups, the appearance of dietary fat in plasma reached its peak 4 h after the meal as evidenced by the concentration of chylomicron TG.

Fig. 1. Triacylglycerol (TG) concentrations in plasma (A) and the chylomicron fraction (B) after overnight fast and following a high-fat test meal in North Europeans (“), Latin Americans () and South Asians (). Values are mean 9SEM; overlapping standard error bars have been omitted for clarity.

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Table 4 Areas (AUC) and Incremental areas (IAUC) under the plasma postprandial response curves following the meal Ethnic group

AUC Total TG (mmol/l) IAUC Total TG (mmol/l) Chylomicron-TG (mmol/l) AUC VLDL-TG (mmol/l) IAUC VLDL-TG (mmol/l) AUC NEFA (mmol/l) IAUC NEFA (mmol/l) AUC Glucose (mmol/l) IAUC Glucose (mmol/l) AUC Insulin (mU/l) IAUC Insulin (mU/l)

Latin Americans (n= 8)

South Asians (n = 8)

Northern Europeans (n = 9)

Mean

SEM

Mean

SEM

Mean

SEM

1667 494 258 735 132 380 −52 5.9 0.9 42 35

355 175 74 172 70 24 42 0.12 0.1 12 11

1211 320 161 505 64 400 −68 6.6a 1.6c 64b 55

114 43 19 83 51 48 35 0.24 0.2 17 16

1360 192 137 501 −5 425 −44 5.9 1.0 29 23

289 105 29 115 42 38 76 0.15 0.2 3 3

Total and incremental AUCs were divided by the time baseline to give average values. Incremental AUCs represent the average change from baseline over 8-h postprandial period. TG, triacylglycerol; NEFA, non-esterified fatty acids. a Values are significantly different from Latin Americans and Northern Europeans (post hoc Bonferoni Test PB0.05). b Log(10) transformed values are significantly different for Northern Europeans (post hoc Bonferoni Test PB0.05). c Values are significantly different from Latin Americans and Northern Europeans (post hoc Bonferoni Test PB0.01).

reach statistical significance. This finding was consistent whether results were expressed as AUC or IAUC for total TG, chylomicron-TG or VLDL-TG (Table 4). South Asians had similar postprandial lipid values to Northern Europeans. Women had a lower postprandial TG response than men (ANOVA P B 0.001). Plasma NEFA concentration dropped immediately after the meal in all three groups and gradually increased until 8 h after the meal. Results were not statistically different by ethnic group (Fig. 2) or gender (results not shown). After the meal, plasma glucose and insulin concentrations peaked at 40 min after the meal and returned to normal fasting values by 120 min (Fig. 3). Although South Asians did not have an altered postprandial lipid response to the meal, the postprandial concentration of plasma glucose in this group, estimated from the AUC and IAUC between 0 and 120 min (Table 4), was significantly higher than in the Latin American and Northern European groups (ANOVA P B 0.01). Interestingly, the postprandial response in plasma insulin was also higher in the South Asian group (ANOVA P B 0.05) (Fig. 3) (Table 4). The mean9 SEM for the log(10) transformed AUC plasma insulin values were as follows: 1.549 0.09; 1.729 0.10; 1.459 0.04 for Latin Americans, South Asians and Northern Europeans respectively. Statistical differences were found only between the last two groups (Post Hoc Tests P B0.05). The IAUC for the log(10) plasma insulin was not different between ethnic groups (mean values9 SEM were 1.449 0.10; 1.6390.11; 1.359 0.05 for Latin Americans, South Asians and Northern Europeans).

3.5. Short insulin tolerance test (SITT) The ability of exogenous insulin to lower the blood glucose concentration was also decreased in South Asians compared to the other ethnic groups. The mean slope of the curve (9SEM) derived from the linear regression of blood glucose concentration after the short insulin tolerance test was −0.14690.019, −0.1719 0.015 and −0.1849 0.012 respectively for South Asians, Latin Americans and Northern Europeans. However results did not reach statistical significance. The fall in plasma glucose in response to insulin injection was correlated with body fat and BMI (Pear-

Fig. 2. Plasma non-esterified fatty acid (NEFA) concentrations after overnight fast and following a high-fat test meal, in North Europeans (“), Latin Americans () and South Asians (). Values are mean 9 SEM; overlapping standard error bars have been omitted for clarity.

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Fig. 3. Plasma glucose (A) and insulin (B) concentrations after overnight fast and following a high-fat test meal, in North Europeans (“), Latin Americans () and South Asians (). Values are mean 9 SEM; overlapping standard error bars have been omitted for clarity.

son correlation coefficients were 0.619 and 0.466, PB 0.01 and B 0.05, respectively) when all three ethnic groups were pooled together. Backward multiple linear regression analysis using slope of the curve as the dependent variable revealed that body fat, not BMI, was responsible for the majority of variation in insulin sensitivity between subjects (b coefficient 0.649, PB 0.001). Percentage body fat in South Asians was highly correlated to the slope of the curve derived from the fall in plasma glucose during the SITT (Pearson correlation coefficient 0.965, P B 0.001) and backward multiple linear regression using slope as the dependent variable and all anthropometric measurements as independent variables confirmed that percentage body fat in this group could predict most of the variation in insulin sensitivity (b coefficient 0.965, P B 0.001).

4. Discussion Although both South Asians in various parts of the world and Latin Americans in the US have been reported to have higher fasting plasma glucose and TG concentrations, our study does not support this finding in young healthy subjects. In fact South Asians and Latin Americans had normal fasting glucose and TG concentrations. The lipaemic response to a fatty meal was also not different in duration and magnitude between the three ethnic groups. The difference in our findings compared to previously reported studies could

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be due to the characteristics of the subjects studied. All volunteers were fairly young (between the ages of 23– 40 years), healthy, had a normal body weight and similar dietary fat intake estimated from food diaries. Although physical activity was not recorded, most subjects engaged in exercise on a regular basis, were nonsmokers and belonged to a privileged socio-economic class. Long term dietary fat intake estimated by adipose tissue fatty acid content was not different between ethnic groups. The polyunsaturated fatty acid content of adipose tissue, which is highly correlated with polyunsaturated fat intake, was similar between groups. Although the monounsaturated fatty acid content, as well as the content of oleic and 20:0 acids, were different between ethnic groups, the significance of these findings in relation to dietary fatty acid intake is unclear. In adipose tissue, monounsaturated fatty acids tend to be over-represented [28] while saturated fatty acids can be desaturated and possibly preferentially oxidized. The postprandial glucose and insulin concentrations in Latin Americans and Northern Europeans were similar. However, South Asians had a significant increase in the postprandial glucose and insulin response to the meal compared to Northern Europeans. The insulinstimulated fall in plasma glucose was also decreased, although this did not reach statistical significance These results point to a degree of insulin resistance in young South Asians compared to Northern Europeans which has been documented previously in middle-aged subjects [3,29]. The decreased insulin-stimulated glucose uptake measured in the postprandial state could not be explained by differences in BMI, percentage body fat, waist to hip circumference or habitual dietary intake estimated by either food diaries or by adipose tissue fatty acid composition. In addition, the decreased tissue sensitivity to the action of insulin only appeared to affect carbohydrate metabolism after the meal, and did not affect postprandial lipid metabolism or the antilipolytic effect of the hormone on adipose tissue which has been found to be suppressed in middle-aged South Asian men [29]. Body fat, particularly abdominal fat, is correlated to insulin sensitivity in South Asian immigrants, Northern Europeans [3,30], and in Hispanic immigrants in the US [31]. The presence of central obesity has been proposed as one of the major risk factors for the development of both diabetes in Mexican Americans [8] and for diabetes and cardiovascular disease in South Asians in the UK [3,30,32]. The only indicator of central fat accumulation measured in this study was derived from the waist circumference and the waist to hip ratio; these variables were not different between ethnic groups when men and women were pooled together. The small number of subjects in this study made gender compari-

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sons between ethnic groups impossible and it is most likely that correlation between these variables and insulin sensitivity is therefore concealed. Our results confirm the presence of insulin resistance in young South Asians in the UK, despite the lack of differences in anthropometric measurements and diet. Insulin resistance appears to affect carbohydrate metabolism after the meal but there were no detectable changes in postprandial fat metabolism. Interestingly, an increase in postprandial plasma glucose has been associated with myocardial infarction in South Asians with normal glucose tolerance [33]. It is possible that detectable changes in postprandial lipid metabolism require a greater degree of insulin resistance brought about by age and fat accumulation [34]. Although the number of subjects in this study was small, the results obtained should help in the design of further postprandial lipid studies in different ethnic groups.

[10] [11] [12]

[13] [14]

[15]

[16]

[17]

[18]

Acknowledgements The authors thank the research volunteers, without whose patience and willing participation this study would not have been possible. M.L. Cruz was supported by a Wellcome Trust Travelling Research Fellowship.

[19]

[20]

[21]

References [1] McKeigue PM, Miller GJ, Marmot MG. Coronary heart disease in South Asians overseas: a review. J Clin Epidemiol 1989;42:597 – 609. [2] Dhawan J. Coronary heart disease risks in Asian Indians. Curr Opin Lipidol 1996;7:196 –8. [3] McKeigue PM, Shah B, Marmot MG. Relation of central obesity and insulin resistance with high diabetes prevalence and cardiovascular risk in South Asians. Lancet 1991;6:337 –82. [4] Elliott TG, Viberti G. Relationship between insulin resistance and coronary heart disease in diabetes mellitus and the general population: a critical appraisal. Baillie`res Clin Endocrinol Metab 1993;7:1079 – 103. [5] Despre´ s JP, Marette A. Relation of components of the insulin resistance syndrome to coronary disease risk. Curr Opin Lipidol 1994;5:274 – 89. [6] Olefsky J, Reaven GM, Farquhar JW. Effects of weight reduction on obesity. Studies of lipid and carbohydrate metabolism in normal and hyperlipoproteinemic subjects. J Clin Invest 1974;53:64 – 76. [7] Cappuccio FP. Ethnicity and cardiovascular risk: variations in people of African ancestry and South Asian origin. J Hum Hypertens 1997;11:571 –6. [8] Reichley KB, Mueller WH, Hanis CL, Joos SK, Tulloch BR, Barton S, Schull WJ. Centralized obesity and cardiovascular disease risk in Mexican Americans. Am J Epidemiol 1987;125:373 – 86. [9] Howard BV, Mayer-Davis EJ, Goff D, et al. Relationship between insulin resistance and lipoproteins in nondiabetic

[22]

[23]

[24]

[25]

[26]

[27]

[28]

African-Americans, Hispanics, and non Hispanic Whites: The Insulin Resistance Atherosclerosis Study. Metabolism 1998;47:1174 – 9. Frayn KN. Insulin resistance and lipid metabolism. Curr Opin Lipidol 1993;4:197 – 204. Laws A. Free fatty acids insulin resistance and lipoprotein metabolism. Curr Opin Lipidol 1996;7:172 – 7. Zampelas A, Roche H, Knapper JME, et al. Differences in postprandial lipaemic response between Northern Europeans and Southern Europeans. Atherosclerosis 1998;139:83 –93. Hardman AE. The influence of exercise on postprandial triacylglycerol metabolism. Atherosclerosis 1998;141:S93 – S100. Patsch JR, Miesenbo¨ ck G, Hopferwieser T, et al. Relation of triglyceride metabolism and coronary artery disease. Studies in the postprandial state. Arterioscler Thromb 1992;12:1336 –45. Gelding SV, Robinson S, Lowe S, Nithyananthan R, Johnston DG. Validation of the low dose short insulin tolerance test for evaluation of insulin sensitivity. Clin Endocrinol 1994;40:611 –5. Durnin JV, Womersley J. Body fat assessed from total body density and its estimation from skinfold thickness; measurements on 481 men and women aged 16 – 72 years. Br J Nutr 1974;32:77 – 97. Lean ME, Han TS, Deurenberg P. Predicting body composition by densitometry from simple anthropometric measurements. Am J Clin Nutr 1996;63:4 – 14. Jorgensen LM, Isaksson B, Schroll M. Reproducibility and validity of 7-day food record questionnaire. Eur J Clin Nutr 1992;46:729 – 34. van Staveren WA, Deurenberg P, Katan MB, Burema J, de Groot LCPGM, Hoffmans DAF. Validity of the fatty acid composition of the subcutaneous fat tissue microbiopsies as an estimate of the long term average fatty acid composition of the diet of separate individuals. Am J Epidemiol 1986;123:455 –63. Riemersma RA, Wood DA, Butler S, et al. Linoleic acid content in adipose and coronary heart disease. Br Med J 1986;292:1423 – 7. Rubba P, Fidanza F, Gautiero G, Leccia G, Cozzolino G, Mancini M. Influence of dietary intake of energy and carbohydrate on the proportion of saturated and monounsaturated fatty acids in adipose tissue of middle aged men. Int J Vitam Nutr Res 1990;60:383 – 91. Beynen AC, Katan MB. Rapid sampling and long term storage of subcutaneous adipose tissue biopsies for determination of fatty acid composition. Am J Clin Nutr 1985;42:317 – 22. Griffiths JA, Humphreys SM, Clark ML, Fielding BA, Frayn KN. Immediate metabolic availability of dietary fat in combination with carbohydrate. Am J Clin Nutr 1994;59:53 – 9. Matthews JNS, Altman DG, Campbell MJ, Royston P. Analysis of serial measurements in medical research. Br Med J 1990;300:230 – 5. Schofield W, Schofield C, James WP. Basal metabolic rate: review and prediciton, together with an annotaded bibliography of source material, Hum Nutr Clin Nutr 1985; 39c, suppl 1: Black AE, Bingham SA, Johansson G, Coward WA. Validation of dietary intakes of protein and energy against 24 hour urinary N and DLW energy expenditure in middle-aged women, retired men and post-obese subjects: comparisons with validations against presumed energy requirements. Eur J Clin Nutr 1997;51:405 – 13. Jacobsen BK, Trygg K, Hjermann I, Thomassen MS, Real C, Norum KR. Acyl pattern of adipose tissue glycerides plasma free fatty acids and diet of group of men participating in a primary coronary prevention program (The Oslo Study). Am J Clin Nutr 1983;38:906 – 13. London SJ, Sacks FM, Caesar J, Stampfer MJ, Siguel E, Willett WC. Fatty acid composition of subcutaneous adipose tissue and diet in postmenopausal US women. Am J Clin Nutr 1991;54:340 – 5.

M.L. Cruz et al. / Atherosclerosis 159 (2001) 441–449 [29] Zoratti R, Godsland IF, Chaturvedi N, Crook D, Stevenson JC, McKeigue PM. Relation of plasma lipids to insulin resistance, nonesterified fatty acid levels, and body fat in men from three different ethnic groups: relevance to variation in risk of diabetes and coronary disease. Metabolism 2000;49:245 – 52. [30] Dhawan J, Bray CL, Warburton R, Ghambhir DS, Morris J. Insulin resistance, high prevalence of diabetes and cardiovascular risk in immigrant Asians. Br Heart J 1994;72:413 –21. [31] Haffner SM, D’Agostino R, Saad MF, et al. Increased insulin resistance and insulin secretion in nondiabetic African-Americans and Hispanics compared with non-Hispanic whites. The

449

Insulin Resistance Atherosclerosis Study. Diabetes 1996;45:742 – 8. [32] Greenhalgh PM. Diabetes in British South Asians: Nature, nurture and culture. Diabet Med 1997;14:10 – 8. [33] Gerstein HC, Pais P, Pogue J, Yusuf F. Relationship of glucose and insulin levels to the risk of myocardial infarction: a case control study. J Am Coll Cardiol 1999;33:612 – 9. [34] Jeppesen J, Hollenbeck CB, Zhou MY, Coulston AM, Jones C, Chen YDI, Reaven GM. Relation between insulin resistance, hyyperinsulinemia, postheparin plasma lipoprotein lipase activity, and postprandial lipemia. Arterioscler Thromb Vasc Biol 1995;15:320 – 4.