Diabetes in India - Nature Jan 2011

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6. Harmr, S. L.  Annu. Rev. Plant Biol. 60, 357–377 (2009). 7. Bass, J. & T akahashi, J. S. Science 330, 1349–1354 (2010). 8. Ruttr, J., Rick, M. & McKnight, S. L.  Annu. Rev. Biochem. 71, 307–331 (2002). 9. Nakahata, Y. et al. Cell 134, 329–340 (2008). 10. Ashr , G. et al. Cell 134, 317–328 (2008). 11. Ramsy, K. M. et al. Science 324, 651–654 (2009). 12. Nakahata, Y., Sahar, S., Astarita, G., Kaluzova, M. & Sasson-Corsi, P . Science 324, 654–657 (2009). 13. Ashr , G. et al. Cell 142, 943–953 (2010). 14. Lamia, K . A. et al. Science 326, 437–440 (2009). 15. Rddy, A. B. et al. Curr. Biol. 16, 1107–1115 (2006). 16.Nakajima, M. et al. Science 308, 414–415 (2005). 17.Kitayama, Y., Nishiwaki, T., Trauchi, K. & Kondo, T. Genes Dev. 22, 1513–1521 (2008).  J.B. declares competing financial interests. S onlin articl for dtails. MEDICINE Diabet es i n India Wih h sad of fas-food ouls and mo sdnay lifsyls, h valnc of diabs in India is ising alamingly. Bu h suboulaio ns a isk and h symoms of h disas diff fom hos in h Ws. JarED DIaMoND I ndia, the world’s second most populous country, now has more people with type 2 diabetes (more than 50 million) than any other nation. The problem has been well docu- mented in a battery of recent papers 1–6 . These publications were foreshadowed by studies of previously Westernized Indian populations elsewhere, and they illuminate distinctive features of diabetes in India. Type 2 diabetes results from a genetic predis- position and from lifestyle factors, especially those of the so-called Western lifestyle, char- acterized by high calorie intake and little exer- cise. Also known as non-insulin-dependent or adult-onset diabetes, this form of the disease is far more common than type 1 (insulin- dependent or juvenile-onset) diabetes. Until recently, type 2 diabetes — henceforth simply diabetes’ — was v iewed as a diseas e of overfed, sedentary people of European ancestry . But it is now exploding around the world owing to the spread of Western habits. Hints of trouble ahead came from observa- tions of diabetes epidemics in emigrant Indian communities that achieved affluence long before Indians in India 1–3, 7 . Those communi- ties include ones in Fiji, Mauritius, Singapore, South Africa, Surinam, T anzania and Britain. For instance, in the 1830s, Indi ans were brought to Mauritius for physically demanding work on sugar plantations. By the 1980s, the decline in world sugar prices had led the Mauritian government to promote industrialization and the export of manufactured goods, which in turn led to increasing affluence and decreasing physical activity for the local population. As a result, between 1982 and 1986 deaths due to diabetes tripled, and by 1987 reached 13% in the Mauritius Indian community 7,8 . (By contrast, prevalence remained much lower in the even more affluent Mauritius European community , illustrating the role of genetic factors.) Today , Mauritius enj oys a per capita income four times that of India but suf fers from the world’s second highest national prevalence of diabetes, 24%. Those develop- ments led Zimmet 8 to prophesy in 1996: “If over the next few decades the people in India become modernize d to a similar level of those in Mauritius and other countries inhabited by Asian Indians, one could expect dramatically increased di abetes rates in India.” That prophecy has already been grimly fulfilled. In 2010, the average age-adjusted prevalence of diabetes in India was 8%, higher than that in most European countries 1 . By con- trast, surve ys in 1938 and 1959, in large Indian cities that are today diabetes strongholds, yielded prevalences of just 1% or less. Only in the 1980s did those numbers start to rise, first slowly and now explosively 5,6,9,10 . The reasons are those behind the diabetes epidemic worldwide. One set of factors is urbanization, a rise in living standards and the spread of calorie-rich, fatty, fast foods cheapl y available in cities to rich and poor alike. Another is the increased sedentariness that has resulted from the replacement of manual labour by service jobs, and from the advent of video games, television and comput- ers that keep people seated lethargically watch- ing screens for hours every day . Although the specific role of TV has not been quantified in India, a study in Australia 11 found that each hour per day spent watching TV is associated with an 18% increase in cardiovascular mortal- ity (much of it associated with diabetes), even after controlling for other risk factors such as waist circumference, smoking, alcohol intake and diet. But those factors notoriously increase with TV watching time, so the true figure must be even larger than the 18% estimate. In India, a wide range of outcomes for differ- ent groups 9,10 is buried within the average dia- betes prevalence of 8%. Prevalence is only 0.7% for non-obese, physically active, rural Indians. It reaches 11% for obese, sedentary, urban Indians; and it peaks at 20% in the Ernakulam district of Kerala, one of India’ s most urbanized states. Among lifestyle factors predicting the incidence of diabetes in Indi a, some are famil- iar from the West, whereas others turn expecta- tions upside down 9,10 . As in the West, diabetes in India is associated with obesity, high blood pressure and sedentariness. But prevalence of the disease is higher among affluent, educated, urban Indians than among poor, uneducated, rural people: exactly the opposite of trends in the West, although similar to the situation in other developing countries. For inst ance, Indians with diabetes are more likely to have undergone higher education, and less likely to be illiterate, than their healthy compatriots. In 2004, the prevalence of diabetes averaged 16% Figure 1 | Raising awareness of diabetes. Participants on a ‘walkathon’ in Bangalore, India, in November 2010.    D  .    S    A    R    K    A    R    /    A    F    P    P    H    O    T    O    /    G    e    T    T    Y 478 | NATURE | VOL 469 | 27 JANUARy 2011 NEWS & VIEWS RESEaRch

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6. Harm r, S. L. Annu. Rev. Plant Biol. 60, 357–377(2009).

7. Bass, J. & Takahashi, J. S. Science 330, 1349–1354(2010).

8. Rutt r, J., R ick, M. & McKnight, S. L. Annu. Rev.Biochem. 71, 307–331 (2002).

9. Nakahata, Y. et al. Cell 134, 329–340 (2008).10. Ash r, G. et al. Cell 134, 317–328 (2008).11. Rams y, K. M. et al. Science 324, 651–654 (2009).12. Nakahata, Y., Sahar, S., Astarita, G., Kaluzova, M. &

Sasson -Corsi, P. Science 324, 654–657 (2009).13. Ash r, G. et al. Cell 142, 943–953 (2010).14. Lamia, K. A. et al. Science 326, 437–440 (2009).15. R ddy, A. B. et al. Curr. Biol. 16, 1107–1115 (2006).16. Nakajima, M. et al. Science 308, 414–415 (2005).17. Kitayama, Y., Nishiwaki, T., T rauchi, K. & Kondo, T.

Genes Dev. 22, 1513–1521 (2008).

J.B. declares competing financial interests. Sonlin articl for d tails.

M E D I C I N E

Diabetes in IndiaWi h h s ad of fas -food ou l s and mo s d n a y lif s yl s, h val ncof diab s in India is ising ala mingly. Bu h sub o ula ions a isk and hsym oms of h dis as diff f om hos in h W s .

J a r E D D I a M o N D

India, the world’s second most populouscountry, now has more people with type 2diabetes (more than 50 million) than any

other nation. The problem has been well docu-mented in a battery of recent papers 1–6. Thesepublications were foreshadowed by studies of previously Westernized Indian populationselsewhere, and they illuminate distinctivefeatures of diabetes in India.

Type 2 diabetes results from a genetic predis-position and from lifestyle factors, especially those of the so-called Western lifestyle, char-acterized by high calorie intake and little exer-cise. Also known as non-insulin-dependent oradult-onset diabetes, this form of the diseaseis far more common than type 1 (insulin-dependent or juvenile-onset) diabetes. Untilrecently, type 2 diabetes — henceforth simply

‘diabetes’ — was viewed as a disease of overfed,

sedentary people of European ancestry. But itis now exploding around the world owing tothe spread of Western habits.

Hints of trouble ahead came from observa-tions of diabetes epidemics in emigrant Indiancommunities that achieved affluence longbefore Indians in India 1–3, 7. Those communi-ties include ones in Fiji, Mauritius, Singapore,South Africa, Surinam, Tanzania and Britain.For instance, in the 1830s, Indians were broughtto Mauritius for physically demanding workon sugar plantations. By the 1980s, the declinein world sugar prices had led the Mauritiangovernment to promote industrialization andthe export of manufactured goods, which inturn led to increasing affluence and decreasingphysical activity for the local population.

As a result, between 1982 and 1986 deathsdue to diabetes tripled, and by 1987 reached

13% in the Mauritius Indian community 7,8. (By contrast, prevalence remained much lower inthe even more affluent Mauritius Europeancommunity, illustrating the role of geneticfactors.) Today, Mauritius enjoys a per capitaincome four times that of India but suffersfrom the world’s second highest nationalprevalence of diabetes, 24%. Those develop-

ments led Zimmet8

to prophesy in 1996: “If over the next few decades the people in Indiabecome modernized to a similar level of thosein Mauritius and other countries inhabited by Asian Indians, one could expect dramatically increased diabetes rates in India.”

That prophecy has already been grimly fulfilled. In 2010, the average age-adjustedprevalence of diabetes in India was 8%, higherthan that in most European countries 1. By con-trast, surveys in 1938 and 1959, in large Indiancities that are today diabetes strongholds,yielded prevalences of just 1% or less. Only inthe 1980s did those numbers start to rise, first

slowly and now explosively 5,6,9,10

.The reasons are those behind the diabetesepidemic worldwide. One set of factors isurbanization, a rise in living standards andthe spread of calorie-rich, fatty, fast foodscheaply available in cities to rich and pooralike. Another is the increased sedentarinessthat has resulted from the replacement of manual labour by service jobs, and from theadvent of video games, television and comput-ers that keep people seated lethargically watch-ing screens for hours every day. Although thespecific role of TV has not been quantified inIndia, a study in Australia 11 found that eachhour per day spent watching TV is associatedwith an 18% increase in cardiovascular mortal-ity (much of it associated with diabetes), evenafter controlling for other risk factors such aswaist circumference, smoking, alcohol intakeand diet. But those factors notoriously increasewith TV watching time, so the true figure mustbe even larger than the 18% estimate.

In India, a wide range of outcomes for differ-ent groups 9,10 is buried within the average dia-betes prevalence of 8%. Prevalence is only 0.7%for non-obese, physically active, rural Indians.It reaches 11% for obese, sedentary, urbanIndians; and it peaks at 20% in the Ernakulamdistrict of Kerala, one of India’s most urbanizedstates. Among lifestyle factors predicting theincidence of diabetes in India, some are famil-iar from the West, whereas others turn expecta-tions upside down 9,10. As in the West, diabetesin India is associated with obesity, high bloodpressure and sedentariness. But prevalence of the disease is higher among affluent, educated,urban Indians than among poor, uneducated,rural people: exactly the opposite of trendsin the West, although similar to the situationin other developing countries. For instance,Indians with diabetes are more likely to haveundergone higher education, and less likely tobe illiterate, than their healthy compatriots. In2004, the prevalence of diabetes averaged 16%Figure 1 | Raising awareness of diabetes. Participants on a ‘walkathon’ in Bangalore, India, in November 2010.

D .

S A R K A R / A F P P H O T O / G e T T Y

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in urban India and only 3% in rural India 10.That urban concentration of diabetes has alsobeen reported in many other Asian countries.

The likely explanation for these paradoxes istwofold. First, in the West, poor rural peopleare better able to afford fast foods than theirIndian counterparts. Second, educated West-erners with access to fast foods and with sed-

entary jobs are by now often well aware thatfast foods are unhealthy and that one shouldexercise, whereas that advice has not yet madewide inroads among educated Indians (Fig. 1).Nearly 25% of Indian city dwellers (the sub-population most at risk) haven’t even heard of diabetes 9.

In India, as in the West, diabetes is ulti-mately due to chronically high levels of bloodglucose, and some of the clinical consequencesare similar. But whereas Westerners thinkof type 2 diabetes as an adult-onset diseaseappearing especially after the age of 50, Indi-ans (and Chinese, Japanese and Aboriginal

Australians) with diabetes exhibit symptomsat an age one or two decades younger thanthat. The age of onset in India has been shiftingtowards ever-younger people even within thepast decade 9 — among Indians in theirlate teens, ‘adult-onset’ diabetes already mani-fests itself more often than does ‘juvenile-onset’ diabetes. In Britain, the prevalence of type 2 diabetes is 14 times higher in Asian thanEuropean children. And although obesity is arisk factor for diabetes both in India and in theWest, the disease appears at a lower thresholdof obesity in India, as is also the case in China,Japan and other Asian countries 10.

Symptoms also differ between Indians andWesterners: Indians with diabetes are lesslikely to develop blindness and kidney dis-ease, but much more likely to suffer coronary artery disease at a relatively young age 9,12. Justas Indians can’t be lumped in with people of European ancestry, differences also appearamong Asians: some, but not all, distinctivefeatures of Indian diabetes apply to other Asianpopulations. For example, by worldwide stand-ards, Chinese people with diabetes experiencea low prevalence of coronary artery disease buta high prevalence of retinal and kidney dam-age. The relative roles of genetic and lifestylefactors in these ethnic differences remain tobe teased out.

Although poor Indians are currently at lowerrisk than affluent Indians, the rapid spread of fast food exposes even urban Indian slum-dwellers to the risk of diabetes. Sandeep andcolleagues of the Madras Diabetes ResearchFoundation 13 summarize the situation as fol-lows: “diabetes [in India] is no longer a dis-ease of the affluent or a rich man’s disease. Itis becoming a problem even among the mid-dle income and poorer sections of the society.Studies have shown that poor diabetic subjectsare more prone to complications as they haveless access to quality health care. This presentsan alarming picture…” Alas, that’s true. ■

Jared Diamond is in the GeographyDepartment, University of California,Los Angeles, California 90095-1524, USA.e-mail: [email protected]

1. Shaw, J. e., Sicr , R. A. & Zimm t, P. Z. DiabetesRes. Clin. Practice 87, 4–14 (2010).

2. Magliano, D. J. et al. Diabetes Care 33, 1983–1989(2010).

3. Jow tt, J. B. et al. Twin Res. Hum. Genet . 12, 44–52(2009).

4. Ramachandran, A., Ma, R. C. W. & Sn halatha, C.Lancet 375, 408–418 (2010).

5. Mohan, V. et al. Indian J. Med. Res . 131, 369–372(2010).

6. Prad pa, R. et al. Diabetes Technol. Therapeutics 12, 755–761 (2010).

7. Dows , G. K. et al. Diabetes 39, 390–396 (1990).8. Zimm t, P. IDF Bull. 36, 29–32 (1996).9. Mohan, V. et al. Indian J. Med. Res . 125, 217–230

(2007).10. Mohan, V. et al. Diabetes Res. Clin. Practice 80,

159–168 (2008).11. Dunstan, D. W. et al. Circulation 121, 384–391

(2010).

12. Unnikrishnan, R. et al. Diabetes Care 30, 2019–2024 (2007).13. Sand p, S., Gan san, A. & Mohan, V. Development

and Updation of the Diabetes Atlas of India www.whoindia.org/LinkFil s/NMH_R sourc s_ Diab l t s_atlas.pdf (2010).

CoSMoLoGY

A glimpse of the

first galaxiesTh c n ly fu bish d Hubbl S ac T l sco v als a galaxy f om a imwh n h Univ s was jus 500 million y a s old, oviding insigh s in o h fi s

h o s of galaxy fo ma ion and h ioniza ion of h Univ s . See Letter p.504

N a v E E N a . r E D D Y

Acentral focus of cosmology is tounderstand how the primordialdensity fluctuations imprinted by the

Big Bang gave rise to the galaxies and largerstructures we observe today. Just as archae-ologists sift through deeper layers of sand touncover the past, cosmologists use large tele-scopes and sensitive detectors to study galax-ies at ever greater distances from Earth and,because of the finite speed of light, to peerfarther back in time. On page 504 of this issue,Bouwens et al. 1 take another step in this direc-tion by exploiting the deepest near-infraredimages of the sky, which were obtained withthe reserviced Hubble Space Telescope and itsnew Wide Field Camera 2. On the basis of thesedata, the authors report the plausible detectionof the most distant galaxy yet discovered. Thegalaxy would have existed when the Universewas just 4% of its current age and when one of the most important phase transitions of gas inthe Universe occurred.

Building on previous studies, Bouwens andcolleagues used the well-established Lymanbreak technique 3 to select galaxies at the larg-est distances, or redshifts. The method relieson the absorption, by neutral hydrogen withina galaxy or by intervening hydrogen clouds,of photons that are more energetic thanLyman-α photons (10.2 eV, corresponding toa wavelength of 1,216 ångströms). The result-ing decrease in flux bluewards of the Lyman-αwavelength results in a characteristic ‘break’ inthe spectrum of a galaxy. Galaxies at differentredshifts can then be located by searching for

objects that are detected in one filter but thatdisappear, or are very faint, in a bluer filter.

Until now, the primary obstacle to identi-fying galaxies beyond redshift 6 — when theUniverse was less than 1 billion years old —has been that the Lyman break shifts to theobserved near-infrared, where the emissionfrom the sky background is several hundredtimes higher than it is in the visible range of the spectrum. This higher background inhib-its the ability to obtain deep imaging, and hasmotivated observations from above Earth’satmosphere. A breakthrough came with theinstallation of the Wide Field Camera onHubble; the camera’s increased field of viewand sensitivity over the previous near-infraredinstrument on Hubble results in an increaseby a factor of more than 30 in its capacity forfinding faint galaxies at high redshift.

Using multi-filter imaging from Hubble andthe Lyman break technique, Bouwens and col-laborators 1 report the discovery of one candi-date galaxy at a redshift of about 10 (Fig. 1).Comparing the number density of galaxies atredshift 10, inferred from their observations,with that determined at lower redshifts, they find that the average galaxy increases in lumi-nosity by more than a factor of 10 during thefirst 2 billion years of galaxy formation. Takenone step further, this finding suggests a closeconnection between galaxy formation and theassembly of dark matter in the early Universe.

In contrast to the prevailing theory of cold dark matter and its relative success inreproducing the large-scale structure of theUniverse, the physics of the development andevolution of visible matter is difficult to model:

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