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EVIEW ARTICLE

Insulin Resistance Syndrome(Metabolic Syndrome) and Obesity in Asian

Indians: Evidence and ImplicationsAnoop Misra, MD, and Naval K. Vikram, MD

From the Department of Medicine, All India Institute of Medical Sciences, New Delhi, IndiaOBJECTIVES: This review describes prevalence, determinants, and possible pathophysiologic mechanismsand suggests management and research directions for insulin resistance syndrome (metabolic syndrome)in Asian Indians.METHOD: We reviewed the topic using the terms Asian Indians, Asians, South Asians, and Indians coupledwith the terms insulin resistance, hyperinsulinemia, metabolic syndrome, and obesity from the databasesPubmed (National Library of Medicine, Bethesda, MD, USA) and Current Contents (Institute forScientific Information, Thomson Scientific, Philadelphia, PA, USA) and from non-indexed publicationsof the medical research and governmental institutions in India.RESULTS: Asian Indians have a high prevalence of insulin resistance syndrome that may underlie theirgreater than normal tendency to develop diabetes mellitus and early atherosclerosis. Important reasonscould be their excess body fat and adverse body fat patterning including abdominal adiposity even whenthe body mass index is within the currently defined normal limits. Some of these features have beenreported at birth and childhood. Whether Asian Indians also have tendency to develop insulin resistancede novo, independent of total or regional adiposity, needs further investigation. Underlying genetictendency or early-life adverse events may contribute to such a phenotype, but lifestyle factors alone ormodulated by inherited factors appear to play an important role because obesity and dyslipidemia becomeworse with urbanization and migration. Systemic stress may contribute to insulin resistance syndrome inthe intra-country and inter-country migrant Asian Indians.CONCLUSIONS: High prevalences of excess body fat, adverse body fat patterning, hypertriglyceridemia,and insulin resistance beginning at a young age have been consistently recorded in Asian Indiansirrespective of their geographic locations. These data suggest that primary prevention strategies should beinitiated early in this ethnic group. Nutrition 2004;20:482–491. ©Elsevier Inc. 2004

KEY WORDS: Asian Indians, insulin resistance syndrome, obesity, abdominal obesity, hypertriglyceride-mia, high-density lipoprotein cholesterol, physical activity, coronary heart disease

NTRODUCTION

igher cardiovascular mortality1–3 and higher prevalence of met-bolic syndrome4–7 have been recorded in Asian Indians settled inarious countries as compared with other ethnic groups. Urbanndia is in a “second stage” of epidemiologic transition, accumu-ating a high burden of non-communicable diseases.8,9 Recenteports have indicated that prevalence rates for coronary heartisease (CHD) and diabetes mellitus have risen sharply inndia.10–12

Because Asian Indians have settled in several countries, it ismportant that they are labeled uniformly for academic research.eople belonging to heterogeneous ethnicities from various coun-

ries in the Indian subcontinent (India, Pakistan, Sri Lanka,angladesh, Nepal, etc.) have been classified as “South Asians”nd the observations have been generalized to Asian Indians.13

ther ambiguous terms such as “Asians” and “Asian and Pacific

his study was supported in part by a financial grant from Science andociety Division, Department of Science and Technology, Ministry ofcience and Technology, Government of India.

orrespondence to: Anoop Misra, MD, Department of Internal Medicine,ll India Institute of Medical Sciences, New Delhi 110 029, India. E-mail:

noopmisra@metabolicresearchindia.com

utrition 20:482–491, 2004Elsevier Inc., 2004. Printed in the United States. All rights reserved.

Islanders,” encompassing a wide range of ethnic groups, have beencommonly used. In the following discussion we use the descriptiveterms as used in the quoted studies; otherwise, the term “AsianIndians” is used.

The migrant Asian Indian populations have been increasing inseveral countries. In the United Kingdom, South Asians are thelargest minority ethnic group.14 In Canada, Asian Indians consti-tute the second largest migrant ethnic group, having increased byapproximately 25% during the previous 5 y.15 In the United StatesAsian and Pacific Islanders number 10.9 million, approximately4% of the population in 1999.16 Asian Indians constitute approx-imately 12% of this population and are one of the fastest growingethnic minorities in the United States.17 However, relatively lessresearch has been done on many non-communicable disease-linked and ethnic-specific lifestyle factors of Asian Indians. Anunderstanding of the issues presented in the following discussionthus will help physicians and dieticians in designing and executingproper preventive and management strategies for insulin resistancesyndrome-related disorders in Asian Indians.

A literature search has been done by using the terms insulinresistance, hyperinsulinemia, metabolic syndrome, obesity, andhyperlipidemia in Asian Indians, South Asians, and Asians in themedical search databases Pubmed (National Library of Medicine,Bethesda, MD, USA), from 1966 to May 2003, and CurrentContents (Institute for Scientific Information, Thomson Scientific,

Philadelphia, PA, USA). A manual search of the relevant quoted

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Nutrition Volume 20, Number 5, 2004 483Insulin Resistance Syndrome in Asian Indians

eferences was also carried out from the retrieved articles. Data-ases, non-indexed publications, and Web sites of reputed medicalesearch institutions and government health agencies in IndiaIndian Council of Medical Research, New Delhi; Nationalnstitute of Nutrition, Hyderabad: Department of Science andechnology, Ministry of Science and Technology, Governmentf India, New Delhi; and Ministry of Health, Government ofndia, New Delhi) were also researched. We also tabulatedeasures of obesity in several ethnic groups (Table I) from the

elevant data. These data may not be strictly comparable; none-heless, interesting inter-ethnic differences were observed, asiscussed later.

LUSTERING OF RISK FACTORS, INSULINESISTANCE SYNDROME, AND CHD

eaven initially proposed that the coexistence of obesity, glucosentolerance, dyslipidemia, and hypertension be termed insulin re-istance syndrome (metabolic syndrome, syndrome X).18 The con-ept of insulin resistance syndrome has been expanded to includeany new associations such as procoagulant tendency and endo-

helial dysfunction. Debate continues as to whether it is the causer the consequence of atherosclerosis, although several studiesave shown a close association.

The Expert Panel of National Cholesterol Education ProgramNCEP), Adult Treatment Panel III, has proposed criteria for thelinical identification of metabolic syndrome.19 However, theseriteria were based on data from white populations and may notppropriately identify metabolic syndrome for Asian Indians andther Asian ethnic groups. The major problem is the definingevels of waist circumference as given by the NCEP Expert Panel,hich, as discussed later, may be lower than that suggested.

McKeigue et al.4–7,20 identified the dimensions of insulin re-istance syndrome in South Asians in the United Kingdom andeported higher prevalences of glucose intolerance, abdominalbesity, hyperinsulinemia, and hypertriglyceridemia as comparedith whites.4–7 According to the subsequent investigations, therevalence of insulin resistance in Asian Indians has ranged from% to 50%.6,7,21–31 Marked variations in the prevalence of insulinesistance syndrome could be accounted for by different method-

TA

AVERAGE VALUES OF VARIOUS MEASURES OF OB

arameters

Asian Indians (n)

Rural*Urbanslums† Urban‡

ody mass index (kg/m2) 19.6 (3674) 20.9 (674) 22.4 (111,722)ercentage of body fat 20.4 (149) 24.4 (674) 28.2 (273)aist circumference (cm) 79.4 (149) 83.7 (142) 85.2 (273)aist-to-hip ratio 0.87 (3674) 0.92 (142) 0.87 (12,124)

Ramachandran et al.,170 Reddy et al.,78 and Lubree et al.90

Misra et al.79 and Lubree et al.90

Ramachandran et al,170 Reddy et al.,78 Dudeja et al.,114 Ramachandran eDowse et al.,227 McKeigue et al.6,7 (includes populations from other Sou

ther South Asian countries), Tan et al.,3 and Deurenberg-Yap et al.223

Popkin et al.,228 Patel et al.,98 Deurenberg et al.,223 Jia et al.,229 and BellMcKeigue et al.,6,7 (includes populations from other South Asian countrurn et al.233

Gallagher et al.,231 Okosun et al.,234 Bell et al.,230 and Luke et al.235

* Haffner et al.,236 Bell et al.,230 and Chumlea et al.237

logies used for the assessment of insulin resistance, different age r

roups and socioeconomic strata of the subjects, variations in theietary and physical activity profiles, and, notably, inclusion ofisparate ethnic groups having ancestral origins from several coun-ries in South Asia. Urban Asian Indian women may have an equalr higher prevalence of insulin resistance and other cardiovascularisk factors as compared with men.28,32–36 Overall, however, therevalence of insulin resistance syndrome in Asian Indians wasigher than in the other ethnic groups, in particular whites.23,24,26,37

Insulin resistance syndrome in Asian Indians manifests early inife. Conflicting reports are available regarding umbilical cordnsulin levels,38,39 but hyperinsulinemia has been reported in post-ubertal children and young adults.29,37,40,41 Young adult Asianndians had the highest levels of postprandial insulin and lowernsulin sensitivity as compared with four other ethnic groups.42

he relation of adiposity to fasting hyperinsulinemia also wastronger for prepubertal South Asian children than for whitehildren.37

We recently reviewed associations of insulin resistance syn-rome in Asian Indians.43 These included high procoagulant ten-ency (high levels of plasminogen activator inhibitor-1, fibrino-en, etc.),37,44–47 hypertension,48 high levels of proinflammatoryytokines (tumor necrosis factor-� and interleukin-6),49 high levelsf soluble intercellular adhesion molecule-1,50 impaired flow-ediated, endothelium-dependent dilatation,51 polycystic ovarian

yndrome,52 and high oxidative stress.53 Plasma leptin was notssociated54 or weakly associated55 with insulin resistance insian Indians. Overall, Asian Indians fared worse than other

thnic groups.Asians Indians with CHD or premature myocardial infarction

re commonly insulin resistant and have clustering of cardiovas-ular risk factors.5,31,56–68 Healthy sons of Asian Indians withngiographically proved CHD also had a higher magnitude ofyperinsulinemia than did sons of white CHD patients.69 Lowernsulin-stimulated glucose uptake in the adipocytes from Asiansith CHD has been reported as compared to whites.70 Contribu-

ions of insulin resistance syndrome and associated factors to theathogenesis of cerebrovascular and peripheral vascular athero-clerosis in Asian Indians have not been fully investigated; how-ver, high levels of procoagulant factors and decreased fibrinolysisssociated with insulin resistance have been reported in Southsian patients with ischemic stroke71–74 and in their first-degree

75,76

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IN ASIAN INDIANS AND OTHER ETHNIC GROUPS

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(7686) 22.8 (11,360) 26.3 (7489) 28.5 (12,480) 25.7 (2906)(107) 29.5 (108) 26.6 (1190) 29.7 (1256) 48.8 (4792)(1837) 78.2 (11,360) 91.3 (4335) 83.9 (12,480) 94.5 (2906)(7686) 0.84 (11,360) 0.91 (7489) 0.86 (11,426) 0.92 (2906)

6 Lubree et al.,90 and Shukla et al.99

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484 Misra and Vikram Nutrition Volume 20, Number 5, 2004

THEROGENIC DYSLIPIDEMIA

yperinsulinemia and consequent insulin resistance are commonlyssociated with hypertriglyceridemia and low levels of high-ensity lipoprotein cholesterol (HDL-C).77 In addition to this com-ination of lipid abnormalities,6,7,28,29,31,55,68,78–84 Asian Indianslso have high levels of small-dense low-density lipoprotein,56,85

nd lipoprotein (a).86,87 Interethnic comparison showed higherevels of serum triacylglycerols in adult Asian Indians,88 which

anifests at a young age.37,41,88,89 Hypertriglyceridemia in Asianndians was observed predominantly in people belonging to highocioeconomic strata78,90 and in migrant South Asians7,91 as com-ared with the low socioeconomic strata rural populations.88,92

Low HDL-C levels are also characteristically seen in Asianndians of both sexes.32,44,85,88,91,93–95 For example, Tai et al.95

eported that 33% of subjects with isolated low HDL-C levels inhe multi-ethnic population in Singapore were Asian Indians wholso had more clustering of risk factors than did Chinese andalays.95 The average level of HDL-C in rural populations in

ndia was higher than that in urban Asian Indian and migrant Asianndians. However, rural Asian Indians had a lower average HDL-Cevel than did whites.88

ETEROGENEITY OF RISK FACTORS AMONG ASIANNDIANS AND SOUTH ASIANS

nterestingly, average body mass index (BMI) was lower andnsulin sensitivity higher in subjects living in India as comparedith their siblings living in west London.96 On comparison be-

ween Asian Indians living in the United Kingdom and in Indiaith angiographically defined CHD, fasting insulin concentrationsere higher in the former.63 Further, differences in body compo-

ition and cardiovascular risk profile have been reported amongouth Asian populations with ancestral origins in India,angladesh, Pakistan, and Sri Lanka.97,98 It appears that, besidesthnicity, variegated lifestyle factors may account for some ofhese observed differences: Bangladeshis are non-vegetarians, fisheing their staple dietary item and many are smokers, whereasunjabi Sikhs are generally vegetarian and non-smokers. Further,any people who live in the borderline regions of India, Pakistan,angladesh, and Sri Lanka may share several dietary and lifestyle

eatures. Further investigation of these issues is clearly needed.

OTENTIAL DETERMINANTS OF DYSLIPIDEMIA ANDETABOLIC SYNDROME IN SOUTH ASIAN AND ASIAN

NDIANS

besity and Body Fat Distribution

ost studies have shown that the prevalence of obesity is 2% to5% in urban,99–101 and 0% to 6% in rural populations inndia100,102 by using the current definition (BMI � 30 kg/m2),103

ut a higher prevalence of obesity has been seen in migrant Asianndians.7 Further, there is a peculiar admixture of obesity andalnutrition in economically poor people, constituting “twin

urden” of under- and overnutrition.11,104 An increasing trendf obesity also has been seen in Asian Indian children, ado-escents,105–107 and women.28,79,80,101,108,109

The average value of BMI in Asian Indians appears to increaseith urbanization and migration, but is still less than that seen inhites, Mexican-Americans, and blacks (Table I). Asian Indiansave a higher percentage of body fat in relation to BMI,39,90,110–118

nd there is stepwise increase of percentage of body fat in Asianndians from rural to urban and migrant populations. Migrantsian Indians have higher percentage of body fat at lower BMI as

118

ompared with whites and blacks (Table I). Further, as com- d

ared with whites, Asian Indians have lower fat-free mass119,120

Table II). The combination of higher body fat and relatively lowerean body mass does not allow an appreciable increase in theverage value of BMI that may remain below 25 kg/m.2,118

A significant proportion (9% to 52%) of Asian Indians havebdominal obesity,6,7,44,79,80,108,115,121,122 as also reported in non-bese subjects.115,121 It appears that the waist circumference ofsian Indians may be less but that the waist-to-hip ratio may be

imilar to that in other ethnic groups (Table I). As compared withhites and other ethnic groups, Asian Indians have a greater

mount of intra-abdominal fat113,123 and thicker truncal skin-olds.41,82,93,113,119,120,124 Excess body fat, abdominal adiposity,nd body fat patterning appear to be important determinants ofnsulin resistance28,56,79,113,122–126 and dyslipidemia.113,119,124

Non-obese” Asian Indians with insulin resistance29,30,42,119,123 areikely to have relatively high body fat and are “metabolicallybese.”127

iet

sian Indian diets are markedly heterogeneous.128 Asian Indiansn India consumed relatively more carbohydrates (�60% to 67%f energy intake)36,80,129 as compared with the migrant Asianndians in the United Kingdom (�46% of energy intake)130 andhe United States (�56% to 58% of energy intake).119,131 Higharbohydrate intake has been reported to induce hypertriglyceri-emia80,131 and postglucose load hyperinsulinemia in Asianndians.130

The dietary fat intake in migrant south Asians was higher thann urban Asian Indians in India80,82,104,119,129–131 and similar inhites,82,119,130,132 although, in comparison, south Asians pur-

hased a higher amount of fat.133 The increase in the consumptionf fat, in particular animal fat, in the semi-urban and urban areasf India over the past three decades134 has been an importantomponent of “dietary westernization” and nutrition transi-ion.135,136 Rural-based Asian Indians, however, consume low-fatiets.135 Intake of saturated fat did not correlate with hyperinsu-inemia in South Asians130 but may cause weight gain, excessccumulation of body fat, and abdominal adiposity.131 Unevenistribution of meals and consumption of large amounts of calories

TABLE II.

BODY COMPOSITION OF ASIAN INDIANS

horter height*ower body mass index*xcess body fat in relation to body mass index†bdominal adiposityHigh waist-to-hip ratio‡Normal waist circumference*§High intra-abdominal fat*

runcal adiposityThick subscapular skinfold thickness*More abdominal subcutaneous fat*�

ess lean body mass*¶

As compared with whites or blacks.High body fat per unit of body mass index.This may be due to less lean mass at the hips resulting in a smallerip circumference.Average value of waist circumference usually does not exceed the cur-

ently accepted cutoff values for abdominal obesity.As estimated by skinfold thickness measurements or imaging tech-iques.Particularly in the lower extremities.

uring the evening meal may be other factors responsible for

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Nutrition Volume 20, Number 5, 2004 485Insulin Resistance Syndrome in Asian Indians

yslipidemia131; however, their effects on insulin resistance anddiposity are not known.

Low dietary intake and low plasma levels of �-3 polyunsatu-ated fatty acids in Asian Indians have been reported in severaltudies,80,82,130,137–139 particularly in vegetarians.139 In costal areasf India, where fish is widely consumed, people have lower aver-ge levels of serum triacylglycerols and high levels of HDL-C.140–143

ow levels of long-chain polyunsaturated fatty acids may increaseevels of tumor necrosis factor-� and other proinflammatoryytokines,144–146 and thus have the potential to induce insulinesistance. An optimum ratio of �-6 to �-3 polyunsaturated fattycids has been recommended for Asian Indians,147 but its long-erm effects on insulin sensitivity and atherosclerosis are notnown. Another consistently recorded observation in Asian Indi-ns has been low intake of dietary fiber,80,132,148 but its metabolicnd clinical correlates remain to be studied.

Nearly 50% of the urban population in India is vegetarian.149

owever, vegetarian diets do not confer a great deal of protectiongainst cardiovascular risk. For example, as compared with whiteegetarians, Asian Indian vegetarians have higher generalized andruncal adiposity.148 Vegetarian Asian Indians also have higherMI and body fat than do non-vegetarian Asian Indians.131,149 A

ipid profile of vegetarian Asian Indians was reported to be similaro that of non-vegetarians150; however, higher carbohydrate intakey vegetarians may potentially elevate serum triacylglycerol lev-ls.131 Further, the fiber intake of Asian Indian vegetarian womenas much lower than in white vegetarians and similar in whitemnivores.148 Although the impact of vegetarian diets on insulinensitivity in Asian Indians remains to be systematically investi-ated, significantly more postglucose load hyperinsulinemia haseen reported in Asian Indians as compared with white vegetari-ns.151 Finally, hyperhomocysteinemia may be more prevalentmong the vegetarian Asian Indians.152,153

Due to acculturation, the dietary habits of migrant Asian Indi-ns are rapidly changing. An important determinant of thesehanges is the period of residence in the adopted country. Con-umption of margarine, juice, chips, fruits, cola, alcohol, and fastoods has been shown to be increased, whereas consumption ofome traditional foods has decreased in migrant Asian Indians inhe United States.154 Implications of these dietary changes in theevelopment of obesity and metabolic syndrome remain to bescertained, although these may contribute to the higher preva-ence of obesity in those migrant Asian Indians who have residedonger in the United States.155 Similar to the “westernization” ofietary habits of urban Asian Indians, intra-country migrants havecquired adverse dietary habits.80,156 Many Asian Indians arenaware of balanced diets and their health implications despitedequate public health campaigns and publicity.157

hysical Inactivity

onsistently, South Asians and Asian Indians have been shown toe less physically active when compared with other ethnicroups.109,119,157–161 South Asian women are particularly seden-ary.33,79,108,119 Migration, urbanization, and affluence are impor-ant determinants of physical inactivity,100,162 but sedentary life-tyle has been reported in rural populations.102 Of considerableoncern, approximately 75% of urban adolescents and youngdults were recently reported to be sedentary.163 Sedentary Asianndians had higher average values of BMI,109,162 serum tricylglyc-rol levels, and blood pressure162 and higher future risk for devel-pment of hyperglycemia.164 Sedentary lifestyle could be an im-ortant risk factor for insulin resistance in Asian Indians andhould be investigated further.

igration and Stress

igration to another habitat, psychosocial stress due to a feeling of

nequality or maladjustment in the society, and adverse socioeco- c

omic milieu may cause intermittent or persistent systemic stress.hronic stress may lead to hypothalamic-pituitary-adrenocorticalnd sympathoadrenal activations.165 Excessive cortisol level166

nd cytokine activation may be potential links between stress andnsulin resistance syndrome,165,167 as observed recently in Southsians.168

Contrary to the above hypothesis, the prevalence of insulinesistance syndrome was less frequent in people belonging toower socioeconomic status (�7%) than in higher socioeconomictatus (19%) in South India.169 Further, the prevalences ofbesity90,100–102,170 and type 2 diabetes90,102,170 are consistentlyow in rural populations in India. Physically active lifestyle andonsumption of diets low in calories and saturated fat may offsethe adverse physiology initiated by stress in the rural population. Its also possible that, as compared with people of low socioeco-omic status residing in large cities, those in the rural areas haveess severe stress. Adverse metabolic milieu171,172 and a change inhe physical activity pattern173 have been reported in people withow socioeconomic status living in the inner city areas of largeities in the developed countries. An analogous population subsetf many developing countries consists of intra-country migrantsrom rural areas who have resettled in the urban areas. The level oftress in these people is very high because of poverty, relocation,ob insecurity, and unfamiliarity with the urban environment. As aonsequence, considerable changes in lifestyle occur; physicalnactivity, smoking, and alcohol intake increase, and the dietsecome imbalanced. High prevalence rates of type 2 diabetes,79

eneralized and abdominal obesity,79,80,174 hypertension,79 athero-enic dyslipidemia,79,80 hyperhomocysteinemia,153,175 endothelialysfunction,50 and a high prevalence of insulin resistance28 haveeen recently shown in this population by us. Many of thesebservations are similar to those reported in the shantytown dwell-rs in cities of other developing countries; Sao Paulo, Brazil176 andangkok, Thailand.177 Interestingly, this intra-country migrantopulation in India and migration of Asian Indian to other coun-ries may have similar magnitudes of systemic stress and societalaladjustment. However, proportional contributions of excessive

tress on migration, increasing affluence, and lifestyle changes tohe development of insulin resistance syndrome in inter-countryigrant Asian Indians are not known.

arly-Life Adverse Events

arly-life adverse events, mostly malnutrition, and their relationso adult-onset metabolic syndrome and atherosclerosis have beenhown in various populations including Asian Indians.178–184 Thisssue is particularly relevant to India, where approximately 23% ofhildren are born with a low birth weight and 60% of childrenounger than 3 y have stunted growth.185 Asian Indian babies bornn India had lower ponderal index and triceps skinfold thicknesshan did white babies; however, their higher subscapular skinfoldhickness was accompanied by more severe hyperinsulinemia.116

urther, similar to studies in other ethnic groups,186,187 Asianndian children born with a low birth weight showed insulinesistance and dyslipidemia when they gained weight in earlyhildhood.182,186,188 Due to unchanging adverse socioeconomicilieu, chronic stress may become a synergistic or dominant factor

or Asian Indians born with a low birth weight.Although plausible, this concept fails to explain the low prev-

lence of obesity and insulin resistance syndrome in people withow socioeconomic status in rural areas of India, where early-lifedverse events and low birth weight are exceedingly common. Itould be speculated that those born small in rural areas remainnderweight and do not rapidly gain weight during childhood,hich has been shown to increase cardiovascular risk factors in

dulthood. Many rural Gambian children did not have any impair-ent of glucose-insulin metabolism or increase in the cardiovas-

ular risk factors during adulthood after early-life growth retarda-

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486 Misra and Vikram Nutrition Volume 20, Number 5, 2004

ion due to undernutrition, and this might be explained by theirdherence to a traditional and frugal lifestyle not conducive to theevelopment of obesity.189 Further, an equal or higher prevalencef insulin resistance syndrome in a second or subsequent genera-ion of migrant Indians who had received adequate perinatal andeonatal care and nutrition and consequently suffered less oftenrom early-life adverse events is unexplained by this hypothesis.hus, studies comparing adult consequences of low birth weight in

ural and urban populations of India and migrant Asian Indians arelearly warranted. More importantly, it would be interesting totudy weight gain and diet and physical activity patterns of suchopulations during childhood and their effects on body composi-ion and metabolic parameters in adulthood. Some reports havendicated that breast-feeding may be protective against develop-ent of insulin resistance and glucose tolerance.190,191 Interest-

ngly, Asian Indian mothers residing in rural areas of Indian areikely to breast feed their children for a prolonged period,192 but aimilar practice was seen in migrant Asian Indians in the Unitedtates.193

enetic and Metabolic Factors

enetic propensity to develop dyslipidemia,81,194–196 obesity,81,197

nd CHD,86,198–200 has been shown in Asian Indians, but insulinesistance syndrome has been inadequately studied. A recent studyas shown a correlation of polymorphism of hepatic glucokinaseromoter to hepatic insulin resistance in Asian Indians.201 Sometudies have indicated that Asian Indians have greater hyperinsu-inemia or lower insulin sensitivity even when adiposity and someeasures of abdominal obesity are matched with those of other

thnic groups, indicating de novo insulin resistance.124

ECENT CONCEPTS IN INSULIN RESISTANCE:MPLICATIONS FOR FUTURE RESEARCH IN ASIANNDIANS

ith the growing interest in the research on insulin resistance andelated metabolic diseases, there is a great scope for research inusceptible ethnic groups such as Asian Indians. Clearly, there is aeed for international cooperation so that data and resources mighte pooled together for multicenter trials.

First, firm guidelines should be established by the World Healthrganization and other international bodies for defining cutoffs forarious measures of obesity, e.g., BMI, waist circumference, waisto hip ratio, and percentage of body fat in Asian Indians.117,118

uch an action would resolve ongoing uncertainty regarding diag-oses of overweight and obesity and would lead to more rationaluidelines for the prevention and management of insulin resistanceyndrome in Asian Indians.

Second, there is a dearth of in-depth genetic and metabolicnvestigations of insulin resistance syndrome in Asian Indians. Theecent discovery of novel proteins including adiponectin and re-istin linked to insulin resistance may provide important insights.diponectin is abundantly expressed in the adipose tissue, and low

diponectin levels have been related to excess adiposity and insu-in resistance.202–204 Adiponectin levels in Indo-Asians have beeneported to be lower than in whites in one study,205 however, itselations to body fat patterning and regional adiposity in Asianndians are not known. The role of resistin in the pathogenesis ofuman insulin resistance is less clear, and no studies are availablen Asian Indians. Further, the contribution of postinsulin receptorberrations to the pathogenesis of insulin resistance in Asianndians remains to be investigated.

Besides a possible role for the hypothalamic-pituitary-adrenalxis and cortisol excess in the pathogenesis of abdominal adipositynd insulin resistance in Asian Indians, generation of active cor-

isol in adipose tissue by 11-�-hydroxysteroid dehydrogenase type

may be important. Increased activity of this enzyme has beeninked to abdominal adiposity and metabolic syndrome in Pimandians and whites.206 Further, recent studies have also shown thencreased role of growth hormone in determination of body fatistribution and lean body mass. These issues should be investi-ated in Asian Indians.

Considering that some aspects of body composition may beetermined during the intrauterine period, more research is neededn the role of macro- and micronutrients during intrauterine andeonatal periods in relation to subsequent development of obesitynd insulin resistance syndrome. Similarly, frequent infections inarly life, commonly seen in Asian Indians in India, may triggerroinflammatory cytokines such as tumor necrosis factor-� andnterleukein-6 and cause endothelial activation. This hypothesiss supported by preliminary data,49,50 but more studies are re-uired. Gene-environment interaction is another useful area foresearch. For example pro-12-Ala polymorphism of peroxisomeroliferator-activated receptor-�2 gene is known to modify birtheight due to adverse early life events207 and response of serum

riacylglycerols to oral supplementation of �-3 polyunsaturatedatty acids208 and should be investigated more vigorously in Asianndians.

More focus is needed for non-fat body tissues and their rela-ions to body fat in Asian Indians. For example, it is not knownhether, in addition to less mass, skeletal muscle is physiologi-

ally altered due to protein malnutrition in early life. Further, theathophysiologic correlates of high intramyocellular lipid contentf soleus muscle in Asian Indians are incompletely known. Goodorrelation of intramyocellular lipid with insulin resistance haseen reported in whites209,210 but not in Asian Indians.209,210

natomic and physiologic studies of liver in relation to adversearly-life nutrition and events are also needed.211 Moreover, theelation of hepatic steatosis to insulin resistance is known in otherthnic groups212 but remains uninvestigated in Asian Indians.

There is recent evidence that subclinical inflammation (high-reactive protein levels) is linked to insulin resistance213,214 andredicts future development of type 2 diabetes and CHD in otherthnic groups.215–217 High C-reactive protein levels have beeneported in adult South Asians and Asian Indians34,218 and post-ubertal children and young adults.89 Further research in thismerging important area is clearly needed, particularly in relationo insulin resistance, premature atherosclerosis, and type 2 diabetesellitus in Asian Indians.

REVENTION AND CONTROL OF INSULIN RESISTANCEYNDROME IN ASIAN INDIANS

ppropriate measures should be undertaken early, particularly inigh-risk groups such as those with the family history of type 2iabetes or premature coronary heart disease. The following sum-arizes the recommendations based on the current knowledge;

1. Therapeutic lifestyle changes should be encouraged fromchildhood. Improvements in obesity, regional adiposity, andinsulin sensitivity occur after calorie restriction219 and reg-ular physical activity.219,220 Change of sedentary lifestyle toregular physical exercise will result in global benefits in themetabolic profile. Progression from impaired glucose toler-ance to diabetes also can be effectively prevented withregular physical activity,221 which may be particularly im-portant for high-risk ethnic groups such as Asian Indians.Beneficial effects of meditation and Yoga have been re-ported in patients with CHD222; however, investigations areneeded to assess its effects on insulin resistance.

2. The optimal weight should be maintained. Based on therecent data121,223 and provisional recommendations,224 indi-viduals should be instructed to maintain BMI between 18.5

2

and 23 kg/m . Waist circumference should be maintained

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Nutrition Volume 20, Number 5, 2004 487Insulin Resistance Syndrome in Asian Indians

within the optimum limits, less than 90 cm for men and 80cm for women.224 The same guidelines for the maintenanceof BMI and waist circumference should be followed formanaging type 2 diabetes mellitus with lifestyle measuresand drugs (e.g. metformin).225 Physicians should be madeaware that these provisional limits for defining normal BMIand waist circumference might be revised in the future.Particular emphasis should be placed on prevention of obe-sity during childhood.

3. A vigorous public information campaign should be launchedto create awareness of adverse effects of a sedentary life-style and obesity for the general public in India and forAsian Indians worldwide. The campaign should specificallypromote aerobic sports and physical activity duringchildhood.

4. Obese individuals should be actively managed to loseweight. Detection of one component of insulin resistancesyndrome should lead to the search for and management ofother components.

5. Greater care should be taken to provide adequate nutritionduring the intrauterine period and to prevent early-life ad-verse events. People with low socioeconomic status in par-ticular should be targeted.

6. National control programs for diabetes and cardiovasculardiseases should be adequately strengthened and modified inview of recent knowledge and guidelines. In countries withsizable migrant Asian Indian populations, culturally appro-priate and specifically targeted guidelines for the preventionand management of insulin resistance syndrome and relateddiseases should be formulated by the national governmenthealth institutes and policy-making bodies.

CKNOWLEDGMENTS

he authors sincerely thank Mrs. Vinita Sharma (Ministry ofcience and Technology, Government of India) for supporting oureveral research projects. They thank Dr Bela Shah, Dr. Rakeshittal, and Dr. Tooteja (Indian Council of Medical Research, Newelhi, India) for helpful suggestions. They appreciate help from

he Ministry of Health, Government of India, the Regional Officef World Health Organization, New Delhi, the Diabetes Founda-ion (India), and the Center for Human Nutrition, The Universityf Texas Southwestern Medical Center at Dallas.

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