Obesity, Diabetes and Cardiovascular Diseases in : Public Health Challenges

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Current Diabetes Reviews, 2017, 13, 65-80

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ISSN: 1573-3998 eISSN: 1875-6417

Obesity, Diabetes and Cardiovascular Diseases in India: Public Health Challenges

BENTHAM SCIENCE

U. Shrivastava1-3, A. Misra*1-4, V. Mohan5, R. Unnikrishnan5 and D. Bachani6

1Centre for Public Health India, New , India; 2National Diabetes, Obesity and Cholesterol Foundation, New Delhi, India; 3Diabetes Foundation (India), New Delhi, India; 4Fortis C-DOC Hospital for Diabetes, Metabolic Diseases and Endocrinology, New Delhi, India; 5Dr. Mohan’s Diabetes Specialties Centre and Madras Diabetes Research Founda- tion, Chennai, India; 6Ministry of Health and Family Welfare,

Abstract: Non-communicable diseases (NCDs; including coronary heart disease and type 2 diabe- tes) are rapidly increasing in India causing nearly 5.8 million deaths per year. Primary reasons for rise in NCDs in India are nutrition and lifestyle transitions. Further, presence of higher body fat, ab- dominal fat, liver and pancreatic fat and lower lean mass than whites, contribute to heightened meta- bolic and cardiovascular risk in Asian Indians. Importantly, conversion from pre-diabetes to diabetes A R T I C L E H I S T O R Y occurs more rapidly, and reversion to normal glucose regulation with appropriate lifestyle measures Received: May 30, 2016 is more difficult in Asian Indians than white population. Huge number of patients with diabetes and Revised: July 11, 2016 Accepted: July 28, 2016 with complications increase morbidity, mortality and pose substantial economic burden. It is diffi- cult, though not impossible, to decrease pace of rapidly expanding juggernaut of NCDs in India. DOI: 10.2174/1573399812666160805153 Only concerted efforts from multiple stakeholders, consistently sincere efforts and intensely focused 328 attention from health officialdom and clear political will may help counter this increasingly difficult challenge. Finally, all prevention and management approaches should be cost-effective, pragmatic, and focused on children and underprivileged populations. Keywords: Asian Indians, diabetes, cardio-vascular diseases, hypertension, metabolic syndrome, obesity.

BACKGROUND contribute to 52% of mortality in South Asia, and have been projected to account for 72% of total mortality in this region NCDs have emerged as a major public health threat for by 2030 (Fig. 1) [1]. all strata of the society worldwide. They account for 38 mil- lion deaths in 2012, and this number is expected to rise to 52 million by 2030 [1]. In 2014 alone, 1.9 billion adults were SEARCH STRATEGY overweight (>=25 kg/m2) of whom 600 million were obese A literature search was conducted in the electronic data- (>=30 kg/m2) [1]. As of 2015, more than 415 million people bases (PubMed, Embase, and Google Scholar) and was lim- worldwide have diabetes. Globally, diabetes accounted for ited to articles published in English. The search terms in- 4.9 million deaths in 2014 [2]. Finally, cardiovascular dis- cluded “diabetes”, “cardio-vascular disease”, “obesity” and eases (CVD) accounted for 31% of all global deaths (17.5 “India”, in combination with “risk factors”, “economic con- million) in 2012 [1]. sequences” and “prevention”. This process yielded 284 ref- South Asian region, which is home to more than 1.7 bil- erences, including reports from national and international lion people, is currently experiencing marked demographic organizations, government reports, review articles and re- transition characterised by declining birth and death rates search studies. After further review, of these, 123 references and an increasingly aging population [3]. This increase in were selected by US, VM, RU, DB and AM. The final re- longevity has led to a rapid increase in the prevalence of view of the articles was performed by AM. NCDs like CVD, diabetes (78 million cases in 2015), cancer, and chronic pulmonary disease, due in large part to increas- MAGNITUDE OF NCDs IN INDIA: SOME FACTS ing lifetime exposure to risk factors. NCDs already In India, NCDs accounted for 60% of all deaths and 44% of disability-adjusted life-years (DALYs) lost in 2011 [1]. They were estimated to be responsible for 40% of all hospi- tal admissions and 35% of all out-patient visits in 2004 in *Address correspondence to this author at the Fortis-C-DOC Hospital for India [4]. Estimates from the Global Burden of Disease Diabetes, Metabolic Diseases and Endocrinology, B-16, Chirag Enclave, New Delhi, India; Tel: +011-493-01222; Fax: +011-493-01200; Study 2013 have shown increase in number of deaths for E-mail: [email protected] most of the leading NCDs increased by 42% between 1990

1875-6417/17 $58.00+.00 © 2017 Bentham Science Publishers Current Diabetes Reviews 66 Current Diabetes Reviews, 2017, Vol. 13, No. 1 Shrivastava et al.

Mortality in 2008 Mortality in 2030

11.9% 10% 24% Injuries

Cardio-vascular diseases 12.1% 35.9% Cancers

Respiratory diseases 6% 37% Diabetes

Other NCDs 19.1% 11% Communicable, maternal, perinatal, 2% and nutritional 10% conditions 21.0% Fig. (1). Non-communicable diseases and proportional mortality in India 2008 and 2030. Reproduced with permission from [1]. and 2013 (from 27·0 million [UI 26·3-27·6] in 1990, to 38·3 [8, 9]. Obesity affects more than 135 million individuals in million [37·2-39·4] in 2013) in India. The common NCDs India. Prevalence rates of obesity in India differ depending are interlinked; for instance, it is estimated that about 44% of on various factors including age, gender, place of residence, the diabetes burden and 23% of the CVD burden can be socio-economic status, and criteria used for the measurement attributed to overweight and obesity in India [5-7]. of obesity (Table 1) [11, 12]. According to the nationwide, population-based Indian Council of Medical Research-India OBESITY Diabetes (ICMR-INDIAB) study, the prevalence of general- ized obesity (defined as BMI 25 kg/m2), varied from 11.8% Serial National surveys in India have demonstrated an in- in () to 31.3% in Chandigarh (north In- creasing trend in the prevalence of obesity (NFHS 2 and 3) dia) [10]. The urban population has higher prevalence rates

Table 1. Prevalence of Obesity in Asian Indians residing in India.

Location (geographical Sample populationCriteria of obesity Diabetes Prevalence (%) Studies Age (year) 2 and urban/rural) Males Females (BMI in kg/m and WC in cm) Males Females

Dhurandhar et al. 1992 West India (Urban) >15 791 791 BMI: >30 4.8 7.8 [21]

Gupta et al. 2003 [22] (Urban) 20 532 559 WC: >102 (M), 88 (F) 21.8 44.0

Misra et al. 2001 [7] North India (Urban) ** >18 170 362 BMI: >25 13.3 15.6

Gupta et al. 2004 [23] North India (Urban) >20 960 840 WC: 102 (M); 88 (F) 25.6 44.0

Prabhakaran et al. 2005 North India BMI: >25 35.0 * 20–59 2935 * [24] (industrial population) WC: 90 (M); 80 (F) 43.0 *

Misra et al. 2005 [25] North India (Urban) 38.9 640 * WC: 90 (M); 80 (F) 10.1 25.9

Mean: Gupta et al. 2007 [26] North India (Urban) *** 43.2 (M) 226 232 BMI: 30, WC: 102 (M); 88 (F) 20.8 34.5 44.7 (F)

Chow et al. 2008 [27] (Rural) 20–90 4535 * BMI: >25 WC: 90 (M); 80 (F) 32.4 41.4

Bhardwaj et al. 2011 [20] North India (urban) >18 217 242 BMI: >25, WC: 90 (M); 80 (F) 50.2 50

Gupta et al. 2012 [13] West India (Urban) 35–70 4621 WC: 102 (M); 88 (F) 14.4

South India (Tamilnadu) 1047 2521 20.6 28.4 West India () ICMR-INDIAB-3 [10] 20 1215 2594 BMI25 15.7 17.6 East India (Jharkhand) 921 2286 14.7 19.1 North India (Chandigarh) 880 2336 24.2 38.7

22.5# 45.6 @ Mohan et al. 2016 [14] Multi-centric 35-70 6853 BMI25 57.4@@

*: Overall including male and female; ** Data from urban slum population of New Delhi, north India; *** Data from Punjabi Bhatia community in north India; M, Male; # Rural; @ Urban poor; @@ Urban middle class; F, Female; BMI, Body mass index; WC, Waist circumference; ICMR-INDIAB, The Indian Council of Medical Research–India Diabetes. Adapted from reference 12, with additional data from references 10 and 14. Obesity, Diabetes and Cardiovascular Diseases in India Current Diabetes Reviews, 2017, Vol. 13, No. 1 67

250 *p < 0.05 *p < 0.01 *p < 0.01 200 3 *p < 0.01 150 *p < 0.01

*p < 0.01

100

50 Abdominal fat & pancreatic volume (cm ) 0

s ta o a dn bcu a e u rp ioe r su t n o s subcut neous t subcut neous Intra-peri one l sct r Ret o er t n al To al ab omi all ub u aneou Live span (mm) Pancreatic v lume Deep a Tota n pi ta ra-a d mi al A terior subcutPosterio neous Su a erf cial To l Int b o n Abdominal fat depots

Fig. (2). Abdominal fat depots, pancreatic volume & liver span measured by MRI (1.5 Tesla) in non-obese patients with type 2 diabetes (n = 93, shown in black bars) & non-obese non-diabetic subjects (n = 40, shown in box filled with crossed lines). Reproduced with permission from [16]. of obesity as compared to the rural population [6, 7, 14]. DIABETES Further, the prevalence of obesity is observed to be higher in women than men [12]. In a multi-site study conducted in India has more than 69 million people with T2DM, and India on 4608 women over 35 years of age using WHO cut- these numbers are expected to rise to 140 million by 2040, offs for obesity, 33.2% of rural and 46.6% of the urban and an almost half of them remain undiagnosed [3]. Moreo- women were overweight [13]. Recent study conducted on ver, Asian Indians have one of the highest incidence rates of rural, urban-poor and urban-middle class women reported pre-diabetes and diabetes among all major ethnic groups, and the prevalence of overweight/obesity (BMI >25 kg/m2) as the conversion from pre-diabetes to diabetes occurs more 22.5, 45.6 and 57.4%, respectively [14]. rapidly in this population [28]. The prevalence of diabetes has increased significantly in the past four decades; while the Obesity in south Asians has certain characteristic fea- first ICMR multi-centric study conducted in the early 1970s tures: for any given level of body-mass index (BMI), south estimated prevalence rates of 2.3% and 1.5% in the urban Asians tend to have higher body fat, abdominal fat, liver fat and rural areas, respectively [29], the latest studies show an (see below) and pancreatic fat and lower lean mass along almost tenfold increase in prevalence rates (Table 2). The with increased insulin resistance and dysmetabolic state than CARRS (Center for cArdio-metabolic Risk Reduction in whites [11, 15]. Interestingly, even non-obese patients with South Asia) Study has shown that the overall prevalence of diabetes have excess fat in all abdominal compartments (e.g. diabetes in 3 major cities of south Asia was Chennai (south excess intra-abdominal fat) and abdominal organs (e.g. liver) India): 22.8% (21.5-24.1%); Delhi (north India): 25.2% (Fig. 2) [16]. Therefore, categorization of obesity based on (23.6-26.8%); and Karachi (Pakistan): 16.3% (15.2-17.3%) BMI levels as used in white populations does not accurately [30]. There is marked heterogeneity in prevalence of diabetes reflect the metabolic risk in Asian Indians. Ethnic-specific according to location of residence (less in rural areas), and cut-offs of BMI for the diagnosis of obesity in Asian Indians socio-economic strata (less in low socio-economic stratum). have been suggested (23–24.9 kg/m2 and 25 kg/m2 for According to the ICMR-INDIAB study, the prevalence of diabetes varied from 3% in rural Jharkhand, east India to overweight and obesity, respectively) [17] and have now 13.7% in urban , south India [28]. The rate of been accepted for use in migrant Asian Indians in the United increase in diabetes prevalence has been shown to be higher Kingdom [18]. in men (3.33 per 1000 per year) as compared with women In Asian Indians, abdominal obesity has been recognized (0.88 per 1000 per year) [11]. as an important risk factor for T2DM and CVD [11, 12, 19]. The prevalence of abdominal obesity was found to be high CARDIO-VASCULAR DISEASES AND RISK FAC- even in underprivileged populations residing in the urban TORS slums of Delhi [7]. Another recent study reported that 68.9% Reports of increased CHD risk and higher cardiovascular subjects (62.2% males and 74.8% females) of the urban mortality among South Asians than other ethnic groups were population of Delhi had abdominal obesity [20] (Table 1). first reported from UK, Singapore and Fiji and then from According to the ICMR-INDIAB study, the prevalence of Canada and USA [48, 49]. South Asian migrants face an abdominal obesity varied from 16.9% in Jharkhand to 36.3% increased risk of premature CVD as compared to other ethnic in Chandigarh [10]. populations [50]. The prevalence of CVD is constantly rising 68 Current Diabetes Reviews, 2017, Vol. 13, No. 1 Shrivastava et al.

Table 2. Prevalence of .

Prevalence (%) Year Author Place Urban Rural

1972 [29] Ahuja et al. Multi-centric 2.3 1.5

1991 [31] Ahuja et al. New Delhi (North India) 6.7

1992 [32] Ramachandran et al. Chennai (South India) 8.2 2.4

2001 [33] Ramachandran et al. National Urban Diabetes Study 12.1

2001 [7] Misra et al. New Delhi (North India) 10.3

2004 [34] Sadikot et al. (PODIS)* Multi-centric 4.6 1.9

2008 [35] Ramachandran et al. Chennai (South India) 18.6 9.2

2011 [28] ICMR-INDIAB# Chandigarh (North India) 14.2 8.3 Tamil Nadu (South India) 13.7 7.8 Maharashtra (West India) 10.9 6.5 Jharkhand (East India) 13.5 3.0

2014 [36] Gupta et al. Multi-centric 15.7

2015 [30] CARRS@ Chennai (South India) 22.8 Delhi (North India) 25.2 Karachi(Pakistan) 16.3

*PODIS, Prevalence of Diabetes in India Study; #ICMR-INDIAB, The Indian Council of Medical Research–India Diabetes; @CARRS, The Center for cArdio-metabolic Risk Reduc- tion in South Asia. in India and is higher in urban areas. A systematic review of diabetes, Odds Ratio (OR) 2.52 with 95% confidence inter- studies on CVD in Asian Indians from January 1969 to Oc- val (CI) (2.07 to 3.07); hypertension, 2.92 (2.46 to 3.48); tober 2012 has documented that the prevalence in urban ar- high waist-hip ratio (WHR), 2.44 (2.05 to 2.91); and ApoB eas was 2.5%-12.6% and in rural areas, 1.4%-4.6% [51]. The 100/Apo A-I ratio, 2.57 (2.03 to 3.26) [52]. It is likely that overall prevalence of CVD in south Indian population is es- ectopic fat deposition in various abdominal compartments timated to be 11%, a 10-fold increase as compared to the and liver (see below) may contribute to this risk [11, 15]. prevalence in urban India in the 1970s [42]. The Jaipur Heart Watch (carried out in state of , north India) studies DIET AND PHYSICAL INACTIVITY have also recorded high prevalence of both coronary heart The intake of saturated fatty acids, n-6 polyunsaturated disease (CHD) and cardiovascular risk factors (Table 3). fatty acids and trans-fatty acids is higher, and that of n-3 Mortality rates in India due to acute myocardial infarction polyunsaturated fatty acids lower in Asian Indians as com- (AMI) were 141 per 100,000 in males and 136 per 100,000 pared to other populations [54]. It has been observed that the in females, which were much higher than those recorded in use of ghee (clarified butter), vegetable ghee (partially hy- other countries e.g., China (66 per 100,000 in males and 69 drogenated vegetable oil, popularly known as ‘Vanaspati’) per 100,000 in females) [52]. Age-adjusted CVD mortality in and coconut oil, with high content of saturated fatty acids urban India is almost twice that of the United States (Fig. 3) and trans-fatty acids in cooking may also contribute to dys- [37]. CVD mortality rates vary from 75-100 per 100,000 in metabolic state in south Asians [55]. the sub-Himalayan states of , , Himachal Increase in sugar consumption (from both traditional Pradesh and to a high of 360-430 per 100,000 in sources and from sugar sweetened beverages) has been re- , Tamil Nadu, Punjab and [53]. Data corded in India [56]. INTERHEART study has shown that regarding relationship of diabetes and CVD in India are Asian Indians in comparison to the people residing in 47 scarce. non-South-Asian countries had a lower daily intake of fruits The risk factors for acute myocardial infarction (AMI) do and vegetables [57]. High intake of refined cereals such as not differ between south Asians and other races, however, polished white rice has also been shown to increase the risk the relative importance of some of these factors may vary. A of type 2 diabetes and metabolic syndrome in this population case-control study (INTERHEART) of 1732 cases with first [58]. A study conducted on south Asian migrants in UK AMI and 2204 controls matched by age and sex from various showed that the average energy intake was 2100 kcal/day countries including 5 from South Asia showed higher preva- and the energy distribution was 57%, 14% and 30% for car- lence of risk factors for myocardial infarction in this region bohydrates, protein and total fat, respectively. Although the [49]. The risk of CVD associated with these risk factors was: percentage energy from fats was not found to be above the Obesity, Diabetes and Cardiovascular Diseases in India Current Diabetes Reviews, 2017, Vol. 13, No. 1 69

Table 3. Prevalence of Cardio-vascular Diseases and Risk Factors.

Prevalence (%)

Study Period n Setting Major risk factors CHD HTN DM High cholesterol Smoking

Raman Kutty et al. [39] 1993 1253 R 7 18.8 4a – 21.9

Chadha et al. [40] 1997 14.886 U/R U 9.7/R 2.7 10.6 1.5a 43.7 18.1

Singh et al. [41] 1997 3575 U/R U 9/R 3.3 23.4 4.5 22 19.7

Mohan et al. [42] 2001 1262 U 11.0 M – 14.9 M – 12.4 M – 24.2 M – 5.6 L – 8.4. L – 6.5 L – 14.2 L – 17.9

Gupta et al. [43] 2002 1123 U 8.2 36.9 12.2 39.1 23.9

Kamili et al. [44] 2007 3128 U/R 7.54 - - - - U 8.3/ R 6.7

Thankappan et al. [45] 2010 7449 U/R – 28.8 14.8 54.1 42

CSI , CRP study [46] 2011 5193 U/R 15.7 39 21 23 31

Krishnan et al*. [47] 2011 5167 U/R 12.5 49.59 15.23 52.31 28.05

Mohan et al. [14] 2004- 6853 UM/UP/R - 2007 2229 UM - 59.0 17.7 37.4 41.6 and 2006- 2008 UR - 48.2 9.3 27.7 19.6 2010 2616 R - 31.6 2.2 13.5 9.4

U, urban; R, rural; UM, urban middle class; UR, urban poor; R, rural; CHD, Coronary heart disease; HTN, Hypertension; DM, Diabetes mellitus; M, Middle income; L, Low income; CSI Kerala CRP study, Cardiology Society of India, Kerala Chapter Coronary Artery Disease and its Risk Factors Prevalence study; *Diagnosed by history only. Modified from 14, 38, 45.

Rates/100 000 Men Women 600 Urban India 525 500 490

400 Rural India 299 283 300 255 246 225 231 200 145

100

0 1987 Andhra 2006 Kerala 2010 Mumbai 2010 United States 2005 n = 750 n = 180 162 n = 161 942 n = 148 713

Fig. (3). Prospective studies of cardiovascular mortality in urban and rural populations in India. Reproduced with permission from [37]. recommended level but the distribution of types of fat was into account the above issues and ethnic dietary practices, a not ideal and thus, the potential benefits of mono-unsaturated consensus statement on dietary guidelines for Indians have fatty acids (MUFA) may have been lost. It is interesting that been published [61]. one of the major sources of this macronutrient were vegeta- Physical activity levels are uniformly lower in Asian In- bles and vegetable dishes [59, 60]. CVD mortality rates in dians in comparison with other ethnic groups (Table 4) [11, India have positive correlation with dietary consumption of 62-66]. Studies on immigrant South Asians in US have fats, milk and its products and sugars and negative correla- shown that only 51.8 % are physically active [71]. A study tion with intake of green leafy vegetable intake [57]. Taking conducted on Asian Indians in UK also showed that 67.62% 70 Current Diabetes Reviews, 2017, Vol. 13, No. 1 Shrivastava et al.

Table 4. Differences in Physical Activity patterns in South Asians/Asian Indians vs Whites/Europeans.

Physical activity crite- Study N South Asians/Asian Indians Whites/Europeans ria/parameter

Mohanty 555AIs and 87 846 Per cent reporting vigorous 33.0% 40.7%* et al. [62] non-Hispanic Whites@ activity

Hayes 684 SA@@ (259 Indian, Never active or active less than 67.0% 59.3%* M,48%; et al. [63] 305 Pakistani, once a week Indians: M, 29%, F,37% 120 Bangladeshi) and 30-min moderate activity most F, 17%; @@ weekdays 825 Europeans Pakistanis: M, 12%F. 19%, Bangla- deshis: 52% M, 13% F, 9%; Guidelines of PA activity index Indians, 71%; not met by Pakistanis, 88%; Bangladeshis, 87%

Lean 63 SA migrants, 56 SA born Participated in sport or other 23%$$$,17%^ 50% @@@ et al. [64] in UK, and 50 Europeans recreational exercise

Shaukat 89 AIs and 82 Caucasian# PA index### 8.5 13.7 et al. [65] Daily distance(km) walked 1.78 2.39 for1week$

Rudat et al. 1017 AIs, 935 Pakistanis and Reported general physical activ- Indian:M,12%;F,5% Pakista- M,17%; F,19% e $$ [66] 667 Bangladeshis ity ni:M,8%;F,8% Bangladeshi:M,4%;F,4%

Reported sporting activity Indians:M,36%; F,15% M,43%;F,37% Pakistanis:M,26%; F,10% Bangladeshis: M,18%; F,2%

Abbreviations: AI, Asian Indian; F, female; M, male; N, number of sample study population; PA, Physical activity; SA, South Asian; UK, United Kingdom; @Non-Hispanic Whites; @@Aged 25–70 years; @@@Women aged 20–42 years; #Sons of patients with Coronary Heart Disease aged 15–30 years; ##Aged 16–74 years; ###Developed by authors; $Measured by pedometer; $$activities undertaken to maintain or improve health; $$$SA born in UK; ^Migrant South Asians;* P=0.004. Adapted from [11]. were sedentary [59]. The levels of recreational physical ac- obesity, low level of high density lipoprotein-cholesterol tivity were also reported to be low [67]. Asian Indian and (HDL-c), hypertriglyceridemia, hypertension, insulin resis- South Asian women are not able to engage in daily exercise tance and/or glucose intolerance, pro-inflammatory and pro- [68] and do not appreciate the mode and intensity of activity thrombotic states. All the studies from India using any crite- that is appropriate and safe due to certain beliefs [70]. Impor- ria have reported higher prevalence of metabolic syndrome tantly, during exercise, in south Asians as compared with in Asian Indian women in comparison with men [74]. Over- matched Europeans, there is lower cardio-respiratory fitness all, about one third of the urban population in large cities in and capacity for fat oxidation [69]. Physical activity guide- India has metabolic syndrome [75]. lines for Asian Indians have been designed keeping the high A study conducted in Delhi, north India, it was observed metabolic and CVD risk in mind [72]. In Asian Indians, they that 66% of men and 88% of women, classified as “non- recommend daily physical activity of 60 min duration, with obese” using the international cutoff of body mass index inclusion of 10-15 min of resistance exercise and work- (BMI), had 1 cardiovascular risk factor(s), including dyslip- related activity [72]. In a study conducted on 30 Asian Indi- idemia [76]. Various studies have shown that the overall ans with T2DM, effects of supervised progressive resistance- prevalence of dyslipidemia in India ranges from 10% to 73% exercise training were evaluated for 12 weeks. Improvement [77]. The ICMR-INDIAB study has shown that 72.3% of the in insulin sensitivity, glycosylated hemoglobin, lipids, and Indian population has low levels of HDL-c, 13.9% have hy- truncal and peripheral subcutaneous adipose tissue compart- percholesterolemia, 29.5% have hypertriglyceridemia and ments were noticed [73]. 11.8% have high low density-cholesterol (LDL-c). Regional disparities were observed in the prevalence rates with highest METABOLIC SYNDROME AND DYSLIPIDEMIA rates of hypercholesterolemia (18.3%) and LDL-c (15.8%) in Tamilnadu, south India, highest rates of hypertriglyceridemia Metabolic syndrome (MS) is a condition in which there is in Chandigarh, north India (38.6%), and lowest rates of HDL a clustering of metabolic abnormalities including: abdominal in Jharkhand, east India [78]. In particular, the prevalence of Obesity, Diabetes and Cardiovascular Diseases in India Current Diabetes Reviews, 2017, Vol. 13, No. 1 71 dyslipidemia is rising in rural areas, though the rates remain (men: 35.6%, women: 29.1%) and lowest in Kolkata in east- lower than in urban areas [12, 13]. ern India (men: 24.0%, women: 22.4%) [96]. A study on urban slum dwellers from North India showed comparable The combination of hypertriglyceridemia and low HDL, prevalence rates of hypertension in men (11.8%) and women termed as “atherogenic dyslipidemia” [79], is particularly prevalent in Asian Indians. In various studies, the levels of (11.6%) [7]. HDL have been reported to be lower in Asian Indians than in White Caucasians [6, 12]. Further, Asian Indians also have NON-ALCOHOLIC FATTY LIVER DISEASE significantly higher prevalence of atherogenic small, dense (NAFLD) LDL in comparison to white Caucasians in USA (44% vs. 21%; p < 0.05) which may contribute to an increase in risk NAFLD is an important component of the metabolic ab- of CVD [80]. normalities, closely associated with insulin resistance and CVD. It is estimated that approximately one third of Asian Indians residing in urban areas have NAFLD [97]. It is likely HYPERTENSION that the high prevalence of NAFLD in Asian Indians is re- A population-based study conducted on 4608 women lated to increasing obesity, higher magnitude of insulin resis- (2005-2008) from four urban and five rural locations in India tance than other races and/or inherent genetic predisposition. showed age adjusted prevalence of hypertension as 39.2% Of particular interest, Asian Indians have higher hepatic (urban : 48.2%; and rural :31.5%) [13]. According to the triglycerides associated with lower adiponectin levels than ICMR-INDIAB study, the overall age-standardized preva- white Caucasians [11]. The presence of NAFLD has been lence of hypertension was 26.3% and almost four-fifths of shown to be independently related to sub-clinical inflamma- the population was unaware about it (Table 5) [81]. In a re- tion in Indian population. In a case-control study, the asso- cent study involving 6940 individuals from five cities of ciation between high sensitivity C-reactive protein (hs-CRP) India, the difference in prevalence of hypertension between and NAFLD was statistically significant [adjusted men and women was highest in Mumbai in OR = 1.17, 95% CI = 1.05–1.29] [98]. In another case

Table 5. Prevalence of Hypertension in India.

First author Year Place Age (yr) Sample size Prevalence (%)

Urban Populations

Gupta et al. [82] 1995 Jaipur (West India) 20 2212 30.9

Anand et al. [83] 2000 Mumbai (West India) 30-60 1662 34.0

Gupta et al. [84] 2002 Jaipur (West India) 20 1123 33.4

Shanthirani et al. [85] 2003 Chennai (South India) 20 1262 21.1

Gupta et al. [86] 2004 Mumbai (West India) 35 88653 47.9

Prabhakaran et al. [87] 2005 Delhi (North India) 20-59 2935 30.0

Reddy et al. [88] 2006 National 20-69 19973 27.2

Mohan et al. [89] 2007 Chennai (South India) 20 2350 20.0

Kaur et al. [90] 2007 Chennai (South India) 18-69 2262 27.2

Rural Populations

Gupta et al. [86] 1994 Rajasthan (West India) 20 3148 16.9

Kusuma et al. [91] 2004 Andhra (South India) 20 1316 21.0

Hazarika et al. [92] 2004 (North East 30 3180 33.3 India)

Krishnan et al. [93] 2008 (North India) 15-64 2828 9.3

Todkar et al. [94] 2009 Maharashtra (West 20 1297 7.2 India)

Bhardwaj et al. [95] 2010 Himachal (North In- 18 1092 35.9 dia)

ICMR-INDIAB Study [81] 2014 National 20 14059 26.3

Modified in part from [81,86]. 72 Current Diabetes Reviews, 2017, Vol. 13, No. 1 Shrivastava et al. control study, overweight/obese non-diabetic Asian Indians [106]. Increased hs-CRP levels have been shown to have with NAFLD have been shown to have excess abdominal positive correlation with generalized and abdominal adipos- and subcutaneous fat, and multiple other phenotypic markers ity in Asian Indians [98]. In south Asians, significance and of insulin resistance. This group of subjects also had higher prognostic value of elevated hs-CRP still remains unclear, prevalence of insulin resistance, glycemia, dyslipidemia and since it could also be elevated in the presence of infections subclinical inflammation than those without NAFLD (Table that are highly prevalent in this population group [107]. 6) [99]. Finally, it has also been observed that low levels of 25-hydroxy vitamin D levels show positive correlation with ENDOTHELIAL DYSFUNCTION increased NAFLD in Asian Indians residing in north India [100]. NAFLD has also been shown to be associated with Endothelial dysfunction includes several pathological elevated total leukocyte count, hyperglutathionemia and hy- conditions, including altered anticoagulant and anti- poadiponectinemia in the south Indian population [101-104]. inflammatory properties of the endothelium dysregulation of vascular remodeling and impaired modulation of vascular While association of NAFLD and CVD is emerging, growth. Impaired endothelium-dependent vasodilation has studies on Indian population are few. Asian Indians prognostic implications and also predicts adverse cardiovas- with NAFLD were estimated to be having higher average cular events [108]. Endothelial-dependent dilatation and the and maximum carotid intima media thickness (CIMT) circulating numbers of endothelial progenitor cells (EPCs) (0.6 ± 0.12 and 0.684 ± 0.16 mm vs. 0.489 ± 0.1 and and EPC colony-forming units (indicating dysfunctional en- 0.523 ± 0.1 mm, respectively; p < 0.05), and prevalence of dothelium) were significantly lower in south Asians as com- atherosclerotic plaques in them was higher than controls pared to the White Caucasians [7]. Further, Chambers et al (20% vs. 5%, p < 0.05). It was observed that even after ad- [109] reported that visceral obesity, insulin resistance and justing for insulin resistance, obesity, lipid parameters and dyslipidemia were common in Asian Indians with vascular metabolic syndrome, the presence of NAFLD remains an endothelial dysfunction as compared with European Whites. independent predictor of high average CIMT (OR 4.8; 95% Finally, south Asians have higher pro-coagulant tendency; CI: 1.8-12.8), high maximum CIMT (OR 5.4; 95% CI: 2.0- increased plasminogen activator inhibitor-1 and fibrinogen 14.4) and impaired flow mediated dilation (FMD) (OR 11.7; and decreased tissue plasminogen activator levels in com- 95% CI: 1.4-96.5) [105, 106]. Clearly, further data are re- parison with European and North American White popula- quired in this important research area. tions [7].

SUBCLINICAL INFLAMMATION TOBACCO CONSUMPTION Chronic inflammatory states including those related with Tobacco production and consumption have increased obesity are closely associated with insulin resistance, endo- significantly over the years in India. Tobacco is consumed in thelial dysfunction, diabetes and CVD. Specifically, south various forms in south Asia, including smokeless varieties Asians have a higher hs-CRP level than White Caucasians in [110]. They include: smoking, chewing tobacco, sniffing UK, matched for total body fat and truncal subcutaneous fat tobacco and consumption after mixing with other products

Table 6. Biochemical Cardio-vascular Risk Factors in Non-diabetic Subjects with and without Non-alcoholic Fatty Liver Disease.

Variables With NAFLD Without NAFLD p value

Total cholesterol (mg/dl) 189.1± 31.2 179.4± 26.8 0.002

Serum triglycerides (mg/dl) 172.0±78.0 148.0±65.3 0.002

HDL-C (mg/dl) 39.1± 6.2 39.3± 10.8 0.7

LDL-C (mg/dl) 110.5± 22.9 104.9± 24.1 0.03

VLDL (mg/dl) 33.4 ± 14.3 29.0 ± 14.0 0.01

ALT (IU/L) 38.7 ± 21.0 35.0 ± 13.7 0.05

AST (IU/L) 35.7 ± 19.2 33.6 ± 11.3 0.2

GGT (IU/L) 22.1±11.6 18.1± 6.8 0.0001

Fasting Insulin (U/ml)* 9.7 (0.3–48.9) 6.7 (0.8–24.4) 0.0008

HOMA-IR* 2.5 (0.1–13.2) 1.6 (0.2–5.1) 0.009

hs-CRP (g/l) * 3.2 (0.03–14.3) 2.0 (0.25–13.5) 0.02

All values except that mentioned in line 2 are from fasting plasma levels. Values are given as the mean ±standard deviation. *Wilcoxon rank-sum (Mann-Whitney) test, Median (minimum- maximum). P value <0.05 is statistically significant. LDL-C, low-density lipoprotein cholesterol; HDL-C, high-density lipoprotein cholesterol; VLDL, very-low density lipoprotein; ALT, alanine transaminase; AST, aspartate transaminase; GGT, glutamyl transpeptidase; HOMA-IR, homoeostasis modal assessment for insulin resistance; hs-CRP, high sensitive C- reactive protein. Reproduced with permission from [99] Obesity, Diabetes and Cardiovascular Diseases in India Current Diabetes Reviews, 2017, Vol. 13, No. 1 73

A B F G

C D E H I

Fig. (4). Forms of Tobacco Consumption in India. Legend: A=Cigarette packet; B= Cigarettes; C= Beedi is a thin, roll filled with tobacco flake and wrapped in a tendu leaf tied with a string at one end; D=Gutkha is a preparation of crushed areca nut, tobacco, catechu, paraffin wax, slaked lime and sweet or savory flavorings with tobacco; E=Pan masala, this is a powder of crushed betel nut, catechu, lime, cardamom seeds, sandal or other flavorings with tobacco; F= Paan is a preparation combining betel leaf with areca nut and sometimes also with tobacco. It is chewed for its stimulant and psychoactive effects. After chewing it is either spat out or swallowed; G= Khaini, is a powdered tobacco used as for chewing or sometimes as snuff; H=Chillum, is a straight conical pipe with end-to-end channel, traditionally made of clay to smoke; I=Hookah, is a water pipe with a smoke chamber, a bowl, a pipe and a hose used for smoking tobacco mixed with water.

(zarda, gutkha etc.) (Fig. 4). Cigarettes are displacing beedi cial consequences. The mean cost of hospitalization for CVD (a thin, roll filled with tobacco flake and wrapped in tendu has been shown to be approximately INR 13143 (USD 219) leaf tied with a string at one end) smoking, most notably per patient. The median out of pocket expenditure for CVD among young adult men and illiterate men [113]. treatment incurred by households in India has been estimated to be INR 175020 (USD2917). The outpatient expenditure In India in 2010, the number of tobacco users were esti- on CVD without hospitalization constituted 16% of the total mated to be 274.9 million, out of these 163.7 million were household expenditure, and majority of this was spent on using smokeless forms of tobacco and 68.9 million were medication (65%) [115]. smokers [111]. Death toll attributable to tobacco is estimated to rise from 1.4% in 1990 to 13.3% in 2020 in India [112]. Expenditure incurred for diabetes and its complications Importantly, age-standardized prevalence of any form of in south Asia has been estimated to be USD 6 billion. In In- smoking in men at ages 15–69 years fell from about 27% in dia, annual direct and indirect cost of diabetes care was esti- 1998 to 24% in 2010 [113]. Despite a modest decrease in mated to be 1541.4 billion INR (USD 31.9 billion) in 2010 smoking prevalence, the absolute numbers of male smokers [122]. Increase in economic burden of diabetes in India from aged 15–69 years has increased substantially over the last 15 2012–30 is projected to be nearly USD 0.15 trillion in 2030 years [113]. Indian government’s campaign regarding to- (Fig. 5) [116]. The annual median expenditure incurred by bacco intake and smoking is being aggressively pursued patients on diabetes care is INR 10 000 (USD 227) in the [114]. urban areas and INR 6260 (USD 142) in the rural areas. Es- timates have shown that nearly 25–35% of the annual in- ECONOMIC CONSEQUENCES OF NCDs come of low-income group is spent on diabetes care [117]. The economic consequences of obesity and its associated In case of complications or when insulin treatment is re- NCDs are far-reaching and pose a significant drain on the quired or admission to hospital or surgery are necessary, the economy of individuals, families and the nation. In south cost of diabetes care is observed to increase manifolds [118]. Asia, individuals tend to develop type 2 diabetes and CVD at In Asian Indians, inadequate resources and medical reim- a younger age, thus increasing their risk of morbidity and bursement, insufficient healthcare budget, and socio- mortality during the peak years of their productive life, with economic barriers contribute to the rising cost of diabetes devastating social and financial consequences. The costs of and CVD management. treatment, combined with loss of earnings when the bread- winner is affected by disease, forces many households into PREVENTION borrowing loans and sale of assets including land and pushes South Asian developing countries face a ‘double burden’ many of them into poverty [115]. due to the persistence of infectious diseases on one hand, and Type 2 diabetes and CVD necessitate life-long treatment the emergence of NCDs on the other. NCDs have to compete with high associated costs. Since, most individuals are not with infectious diseases and maternal and child health prob- covered by health insurance and health expenditures are paid lems for scarce healthcare resources in terms of finances and out of pocket in India, treatment costs can have major finan- personnel. The only cost-effective solutions, therefore, lie in 74 Current Diabetes Reviews, 2017, Vol. 13, No. 1 Shrivastava et al.

24

2010 Total (CMH1) 20 2010 Total (CMH3) 2010 Total (VSL)

16

12

8 Trillions (2010 USD$)

4

- High Income Upper Middle Income Lower Middle Income Low Income World Fig. (5). Non- communicable Disease Cost burden is likely to double from 2010 to 2030 in India (CMH1, CMH3 and VSL estimates). The CMH1 (Commission on Macro-economics and Health) method refers to multiplying DALYs by one times GDP (Gross Domestic Product) per capita; the CMH3 method refers to multiplying DALYs by three times GDP per capita; VSL= value of statistical life. (Reproduced with permission from [116]). prevention and early detection. It is important to invest in prevention strategies which will yield long lasting benefits Behavioral Disease and pay off in the long run with reduction in overall costs RF Physiological RF Outcomes Heart disease associated with burden of disease. Tobacco BMI (obesity) Alcohol Blood pressure Stroke Physical Blood glucose Diabetes PROGRAMS/PROJECTS FOR PREVENTION OF inactivity Cholesterol Cancer Diet Chronic resp OBESITY, DIABETES AND CVD IN INDIA disease

The first phase of the National Program for Control of Secondary Cancer, Diabetes, Cardiovascular Disease and Stroke Primary Prevention Tertiary Care Prevention (Early Diagnosis (Case Management & (NPCDCS) (Fig. 6) [119] was launched by Government of (Health and Rehabilitation) India in 100 districts in 2010, with strong screening and Case Management) monitoring components, and it was subsequently strength- Fig. (6). Risk Factors (RF) and Level of NCD Prevention and Man- ened in 2013–2014 (Fig. 7) [119]. Further, a programme for agement. (Reproduced with permission from Booklet of National adolescent health named Rashtriya Kishor Swasthya Karyak- Programme for Prevention and Control of Cancer, Diabetes, Car- ram (RKSK) was launched by Government of India in Janu- diovascular diseases and Stroke (NPCDCS), Government of India, ary, 2014 with focus on improving nutrition, mental health, page 4 [119]). and for prevention of NCDs (Fig. 8) [120]. Impact of these programs remains to be researched. Pakistani line of control Jammu & Chinese Other initiatives were led largely by non-governmental line of Kashmir control organizations, include a large project entitled ‘‘Medical edu- Srinagar Jammu Himach cation for children/Adolescents for Realistic prevention of Pradesh Poona Shimla obesity and diabetes and for healthy aGeing’’(MARG; Hindi Chandigarh Dehra Dun Uttaranchal Arunachal for ‘‘path’’) focused on nutrition and physical activity of haryana Pradesh New Delhi Delhi Sikkim Itanagar school children of north India. Within this project, a multi- Gangtok Assam Nagaland Lucknow Dispur Jaipur Kohima component intervention model over 6 months including nu- Rajasthan Uttar Shiliong Pradesh Patna Meghalaya Imphal trition and lifestyle education on behavior modification, an- Agartala Aizawl Jharahand West Gandhinagar Madhya Ranchi Bengal thropometry and metabolic risk profile of adolescents re- Bhopal Kolkata Gujarat Pradesh (Calcutta) sulted in better lifestyle practices (less TV viewing, eating Chhattis- garh Orissa Daman Diu Daman Maharashtra Raipur Bhubaneswar more fruits, etc.), a significant decrease in waist–hip ratio, Silvassa Dadra & Nagar Haveil better insulin sensitivity, and significantly lower high- Mumbai (Bombay) sensitivity C-reactive protein (hs-CRP) levels compared to Hyderabad Pondicherry Arabian Sea 15 control group (Fig. 9) [121]. More innovation and research Anbhra Bay of Bengal 15 Panaji Pradesh Goa in this area and expanded public health programs focused on Andaman Islands Chennal (Madras) Bangalore school children are needed. Port Blair Pondicherry Pondicherry Pondicherry Tamil One innovation in public health area in area of diabetes, Kavaratti Nadu Pondicherry Andaman and Nicobar Islands Andaman Sea customized mobile units (Fig. 10) can be used for early de- Lakshadweep Kerala Thiruvananthapuram tection of NCDs and providing standard care and manage- Nicobar Islands ment at the doorsteps of the under privileged population. Laccadive Sea 75 Indian Ocean 90 Consultation with experts at tertiary centres through skype Maldives Fig. (7). National Program for Control of Cancer, Diabetes, Car- and transmission of electro-cardiograms, fundus images diovascular Disease and Stroke (NPCDCS). (Reproduced with (retinopathy), vibration perception testing (neuropathy), foot permission from Booklet of National Programme for Prevention ulcers can help in early detection of complications and expert and Control of Cancer, Diabetes, Cardiovascular diseases and advice (Fig. 11a and b) [122]. Stroke (NPCDCS), Government of India, page 7 [119]). Obesity, Diabetes and Cardiovascular Diseases in India Current Diabetes Reviews, 2017, Vol. 13, No. 1 75

Nutrition i. Awareness messages ii. Diabetes education particularly for women iii. Mass screening iv. Management and advice v. Foot evaluation including minor surgical procedures vi. Fundus evaluation and transmission of images 2 Malnutrition prevention and vii. Skype consultation with experts at tertiary care centres management viii. Distribution of free medicines ix. Transport of sick patients Content IDA prevention and x. Linkages with other mobile health programmes particularly eated to ophthalmic management conditions

Sexual and Mental Health Reproductive Health Promotion and Care Fig. (10). Customized Mobile Units for Delivering Prevention and Management of Diabetes at the Doorsteps of Community: Key Benefits. Successful programmes in Delhi, North India and Chen- nai, South India. Ref. [122, 123].

a) Address mental health concerns of adolescents

Knowledge, attitudes, behaviour, practice building Substance Misuse Prevention of teenage pregnancy Prevention

Improve birth preparedness and complication readiness in adolescents

Management of unwanted pregnancy Increase awareness of Prevention and management of the adverse effects and Reproductive Tract Infections consequences of substance (RTIs) and STIs misuse

NCD Prevention Injuries and Violence, Including Gender- b) based Violence

Promote behaviour change in Promote favourable attitudes for adolescents preventing injuries and violence

Fig. (8). Components of Rashtriya Kishor Swasthya Karyakram (RKSK) for Adolescent Health in relation to NCDs. (Reproduced with permission from Booklet of Rashtriya Kishor Swasthya Kar- yakram, Government of India, page 64 [120]).

10

Fig. (11). Photographs of Customized Mobile Unit (Delhi). a). A 5 patient undergoing ECG inside a Customized Mobile Diabetes Unit

e

g in Trilokpuri, East Delhi, North India. His fundus photo using a n a

h 0 Forus Tri-netra camera is seen on the laptop screen and will be sent c

e

g to tertiary care centre for expert advice. b). A Diabetes Health a I h C o t C C D I R i R G C M ig A H t T B - n A C B a - L B W U th S - r F e D - T W t W H Camp in Mongolpuri, West Delhi, North India for the underprivi- c 5 M id H

r - M e W leged population. A Customized Mobile Diabetes Unit, in Hindi, P “Diabetes Rath”, seen in the background. Ref. [122]. 10 SOME SUGGESTED PUBLIC HEALTH SOLUTIONS 15 FOR PREVENTION OF DIABETES AND CVD Intervention children Control children There is a clear need for planning strategies with an inte- grated approach to tackle the burden of obesity, diabetes and Fig. (9). Percentage Change in Anthropometric and Biochemical CVD in India (Table 7). Comprehensive, persistent and in- Parameters in Intervention and Control School Children. MUAC, mid-upper arm circumference; SAD, sagittal abdominal diameter; ter-linked efforts from multiple stakeholders, focused atten- Tr, triceps skinfold thickness; Bic, biceps skinfold thickness; W-Ht, tion from health officialdom and clear political will can waist to- height; W-TR, waist-to-thigh ratio. (Reproduced with make some inroads in this increasingly difficult challenge. A permission from [121]). countrywide concerted approach, like carried out in China, is 76 Current Diabetes Reviews, 2017, Vol. 13, No. 1 Shrivastava et al.

Table 7. Steps Suggested at Various Levels of Health Care for Tackling Epidemic of Diabetes and Cardio-Vascular diseases in Asian Indians.

Level of Intervention Strategies Action/Remarks

Community • Enhancing health awareness for Involvement of different stakeholders and inter-ministerial coordination# nutrition and physical activity for provision of culturally appropriate low-cost food items, open spaces • Opportunistic screening for diabe- for walks, open gyms (Fig. 12), bicycle tracks etc. tes and hypertension • Screening using appropriate cut offs of body mass index (BMI) and waist circumference • Target vulnerable groups

Local self-governance institu- More active involvement of civil society Participation of: * tions for health promotion and prevention • Resident Welfare Associations in urban areas • Panchayati Raj institutions in rural areas

Individual/Patient • Efforts to enhance awareness Life style modifications: healthy diets, increased physical activity, avoid- • Consistent drug compliance and ance of addictions e.g. tobacco, alcohol adherence Availability of low cost drugs

Health care provider¥ • Standardized treatment of Standardized protocol for diagnosis, management and rehabilitation hyperglycemia Appropriate referral, rehabilitation and follow up, resource enhancement • Coordinated and effective man- and strengthening agement of complications

Governmental Health System • Uniform and standard protocols • Setting up of diagnostic, treatment and referral facilities Response (Centre and State) for diagnosis and treatment • Targeted approach for vulnerable groups including elderly and • Cost effective interventions under-privileged • Mobile services to provide stan- • Provision of customized mobile units (Figs. 10, 11a and b) dard health care at door-steps of • Drug adherence and compliance under privileged • Inter-linked approach for health promotion and disease prevention • Availability of medicines • Training of health care providers at primary, secondary and tertiary • # Inter-ministerial coordination levels • Prioritization of resources in dif- • Increase taxation on SSBs and ban their use in schools ferent governmental programmes • Food labeling • Regulations • Ban on advertising of junk food and SSBs during prime time tele- vision

Media (print, electronic and Dissemination of culturally acceptable • Stress on healthy life style, nutrition, physical activity etc. social media) simple messages for the community • Promotion of self-referrals

Public private partnership@ Inter-linked efforts • Coordination in implementation of health programmes • Uniform approach to combat health challenges of non- communicable diseases • Coordinated approach to school-based intervention and worksite interventions

At any level of health care Use of technology • Introduce electronic health cards¶ • Use e-health and m-health© • Digital platform¶¶ • Text alerts using smart phones for promotion of healthy lifestyle • Consultations using telemedicine

Legend: Local self-governance institutions *,institutions in which the citizens of a smaller area control their own affairs and become part of governance mechanisms; Health care provider ¥ includes doctors from governmental institutions, corporate hospitals and private practitioners; Public private@ partnership, coordination in government and private sector health care providers ; electronic health cards¶, electronic health cards can help in tracking and evaluation of patient profile by health care providers at different levels of health care in government and private hospitals;e-health, use of information and communication technologies (ICT) for health; ©m-health, mobile health, a term used for the practice of medicine and public health supported by mobile devices; Digital platform¶¶, web based interface to track weight, nutritional intake, physical activity; Inter-ministerial coordination#, ministries of health, women and child development, information and broadcasting, agriculture, food processing, water resources, chemicals and fertilizers, urban development, rural develop- ment and environment education, sports, information and broadcasting; SSBs, sugar sweetened beverages. Obesity, Diabetes and Cardiovascular Diseases in India Current Diabetes Reviews, 2017, Vol. 13, No. 1 77

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