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Diabetes in China 2
Causes of type 2 diabetes in China
Ronald Ching Wan Ma, Xu Lin, Weiping Jia

The prevalence of diabetes in China has increased substantially over recent decades, with more than 100 million Lancet Diabetes Endocrinol 2014
people estimated to be affected by the disease presently. During this period there has been an increase in the rates of Published Online
obesity and a reduction in physical activity. Many of the changes in lifestyle and diet are a result of increased September 11, 2014
http://dx.doi.org/10.1016/
economic development and urbanisation. In addition to an increasingly westernised diet, the traditional Chinese
S2213-8587(14)70145-7
diet also plays a part, with the quantity and quality of rice intake linked to the risk of type 2 diabetes. Familial factors
See Online/Comment
including inherited genetic variants are important, although differences in the genetic architecture suggest a http://dx.doi.org/10.1016/
different combination of genetic variants could be most relevant in Chinese when compared with Europeans. Recent S2213-8587(14)70154-8
advances have also emphasised the role of early life factors in the epidemic of diabetes and non-communicable This is the second in a Series of
diseases: maternal undernutrition, maternal obesity, and gestational diabetes are all linked to increased risk of three papers about diabetes in
diabetes in offspring. A mismatch between developmentally programmed biology and the modern environment is China

relevant for countries like China where there has been rapid economic transformation. Multisectoral efforts to Department of Medicine and
Therapeutics, Hong Kong
address the risks will be needed at different stages throughout the lifecourse to reduce the burden of diabetes. Institute of Diabetes and
Obesity, and The Li Ka Shing
Introduction of socioeconomic factors to the disease epidemic in Institute of Health Sciences,
There is a worldwide epidemic of type 2 diabetes. China, and its relevance to prevention, care, and The Chinese University of
Hong Kong, Hong Kong SAR,
Prevalence of diabetes in China has increased sub- management is covered in more detail in another paper China (Prof R C W Ma FRCP);
stantially over the last 30 years, in parallel with rapid in this Series.10 International Diabetes
economic and demographic transition. Compared with a In this Series paper, we focus on other factors that are Federation Centre of
reported prevalence of about 1% in the 1980s, the rate contributing to the increase in diabetes prevalence in the Education, The Chinese
University of Hong Kong,
had increased to 5·5% by 2001.1,2 More recent nationwide Chinese population, and explore secular trends that Prince of Wales Hospital,
surveys reported a prevalence of diabetes of 9·7% in could have driven this epidemic. We focus on Hong Kong SAR, China
20083 and 11·6% in 2010.4 Furthermore, the prevalence of epidemiological studies done in China, but also draw on (Prof R C W Ma); Key
prediabetes has also increased substantially.3 Projections insights from studies in other populations. Although Laboratory of Nutrition and
Metabolism, Institute for
based on these surveys suggest that up to 113·9 million many factors we discuss have been identified from Nutritional Sciences, Shanghai
adults in China have diabetes.4 This substantial increase association studies, few can be labelled as definite casual Institutes for Biological
means that China has the largest number of individuals factors according to traditional definitions.11 Better Sciences, Chinese Academy of
Sciences and Graduate
with diabetes in the world. understanding of the factors that are causing the diabetes
University of the Chinese
A particularly worrying feature of the diabetes epidemic epidemic will be key to future prevention programmes Academy of Sciences,
in China is the high percentage of young people affected and interventional efforts. Shanghai, China
by the disease. In the latest nationwide study, the (Prof X Lin PhD); and
Department of Endocrinology
prevalence of diabetes in the 18–29 age group was 4·5%, Susceptibility to type 2 diabetes in the Chinese and Metabolism, Shanghai
and as high as 6·6% in the 30–39 age group.4 Given the population Diabetes Institute, Shanghai
increased risk of long-term complications in patients Similar to other populations, the major underlying Jiao Tong University Affiliated
with young-onset diabetes,5,6 the potential economic and pathophysiology of type 2 diabetes in the Chinese Sixth People’s Hospital,
Shanghai, China
health burden associated with this epidemic in China is population is impaired β-cell function and insulin
(Prof W Jia PhD)
very alarming. Notably, type 2 diabetes has overtaken resistance. Additionally, α-cell dysfunction, diminished
Correspondence to:
type 1 diabetes as the predominant form of diabetes in incretin effect, and other disturbances contribute to the Prof Ronald Ma, Department of
children in Taiwan and Hong Kong.7 pathophysiology of the disease.1,12 Ethnic differences exist Medicine and Therapeutics,
Social determinants of disease are increasingly being in susceptibility to type 2 diabetes.7,13 For example, Chinese The Chinese University of Hong
Kong, Prince of Wales Hospital,
identified as important for worldwide efforts to combat people develop type 2 diabetes at considerably lower BMI
Shatin, Hong Kong SAR, China
chronic diseases. Socioeconomic factors not only affect compared with European populations: the mean BMI of rcwma@cuhk.edu.hk
the risk of diabetes, but also affect access to care, quality newly diagnosed diabetes in the latest nationwide study in or
of care, comorbidities, and mortality. Social determinants China was only 23·7 kg/m², compared with over 27 kg/m² Prof Xu Lin, Key Laboratory of
of diabetes include education, social stratification, and in most US studies.14 Increased risk of diabetes at lower Nutrition and Metabolism,
urbanisation.8 In a study of more than 7000 adults in BMI was partly attributed to the tendency to visceral Institute for Nutritional Sciences,
Tianjin, China, it was noted that individuals with lower adiposity in east Asian populations including the Chinese Shanghai Institutes for Biological
Sciences, Chinese Academy of
income had about 4·5 times increased risk of diabetes population. With increasing adiposity, east Asians have Sciences, Shanghai 200031,
compared with individuals of higher income, and the the largest accumulation of visceral fat compared with China
results remained significant after the analysis was deep subcutaneous fat among the groups in an xlin@sibs.ac.cn
stratified by education and occupation.9 The contribution international study of intra-abdominal adiposity.15 This

www.thelancet.com/diabetes-endocrinology Published online September 11, 2014 http://dx.doi.org/10.1016/S2213-8587(14)70145-7 1

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or
Prof Weiping Jia, Department of
Endocrinology and Metabolism,
Shanghai Diabetes Institute,
Shanghai Jiao Tong University
Affiliated Sixth People’s Hospital,
Shanghai 200233, China
wpjia@sjtu.edu.cn
2 www.thelancet.com/diabetes-endocrinology Published online September 11, 2014 http://dx.doi.org/10.1016/S2213-8587(14)70145-7
tendency to visceral adiposity is present early in life, and is insulin sensitivity and insulin response noted that east
associated with an altered profile of adipocytokines Asians have higher insulin sensitivity but much lower
including adiponectin.7,10,15 insulin response compared with white and African
The importance of β-cell dysfunction in the patho- people, suggesting that a small decline in β-cell function
genesis of type 2 diabetes has been emphasised in several could be enough to precipitate progression to overt type 2
studies.16 In a study comparing insulin sensitivity and diabetes in east Asians.19
β-cell function in multi-ethnic women without diabetes,
women of east Asian origin (including Chinese Risk factors for type 2 diabetes in the Chinese
Americans) had lower indices of β-cell function than population
non-Hispanic white women, after controlling for waist Urbanisation
circumference and other risk factors.17 Individuals who Rapid economic development and urbanisation across
had fasting plasma glucose in the upper range had China since the 1980s has led to a population shift to
decreased β-cell function and decreased insulin urban areas, with about half of the Chinese population
sensitivity before the onset of diabetes.18 A meta-analysis now living in cities and towns compared with 20% in the
examining ethnic differences in the relation between late 1970s.20 Together with the associated changes in
lifestyle, urbanisation has led to a substantial increase in
A obesity and diabetes and other non-communicable
40 Adults diseases.21 The average daily calorie intake has remained
Children stable over recent decades, suggesting that reduced
35 physical activity and changes in dietary behaviour are the
33·9
31
main reasons for the increase in obesity (figures 1, 2).22
30 Increasing life expectancy leading to an ageing
29
Prevalence of overweight (%)
25·5
27·1 population in China is an important contributing factor
25
21·8 to the recent increase in diabetes.26 From 2000 to 2010,
the proportion of people aged over 65 years grew from
20 17·1 7·0% to 8·9%,20 and is estimated to reach 25% by 2050.21
17·4 Combined with the decreased birth rate there has been a
15 16 12·4 marked change in the demographic structure of the
13·7
12·2 Chinese population (figure 3). For example, the number
10
of people in China aged under 25 will decrease by 47%
8·8
8·4 between 2007 and 2026, whereas the number of people
5 6·9
6·3 aged over 40 will increase by 31% from 566 million to 740
0
million over the same period.27 Given the marked
increase in risk of type 2 diabetes with increasing age,
B changes in the population structure will substantially
400
increase the proportion of people at risk of the disease.
380
Several traditional risk factors for type 2 diabetes are
360 associated with the disease in Chinese adults, including
340 increasing age, male sex, urban residency, parental
MET hours per week
320 history of diabetes, obesity or central obesity, low
300 educational level, raised systolic blood pressure, hyper-
280 cholesterolaemia, or raised triglycerides.3,4 Obesity,
260 hypertension, and dyslipidaemia are consistently
240
associated with risk of incident type 2 diabetes in
prospective studies, suggesting they have a direct role in
220
the causal pathway. Smoking increases the risk of type 2
200
1990 1995 2000 2005 2010
diabetes by about 45%,28 and smoking rates are high in
Year
China, especially in men. China has more than
300 million smokers, and an additional 530 million are
Figure 1: Secular trends in several factors associated with the increasing exposed to passive smoking.22 In the Shanghai Men’s
prevalence of diabetes in China
Health Study (SMHS), smoking more than 20 cigarettes
(A) Prevalence of overweight in adults (aged 18–65) and children (aged 6–19) in
the China Health and Nutrition Survey, 1991–2011. Adult overweight was defined per day was associated with increased risk of incident
according to WHO definition for Asians, with BMI ≥23 kg/m². Overweight in diabetes (HR 1·41, 95% CI 1·13–1·77), after adjustment
children was defined according to the Chinese age-specific and sex-specific cut-offs for age, energy intake, alcohol intake, occupation,
proposed by the Group of China Obesity Task Force. Data from Gordon-Larsen and
colleagues.23 (B) Mean occupational physical activity in adult men in the China
physical activity, hypertension, and family history of
Health and Nutrition Survey, 1991–2011. Data from Ng and colleagues.24 diabetes; the association persisted after further
MET=metabolic equivalent of task. adjustment for baseline BMI.29 Several risk scores have
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been developed to predict the risk of type 2 diabetes in no physical activity.38 Therefore, the available data
the Chinese population (panel, table). underscore that increasing physical activity has a
potential role in counteracting the epidemic of type 2
Obesity diabetes in China.
The prevalence of overweight (BMI ≥25 kg/m²) and
obesity (BMI ≥30 kg/m²), according to WHO definitions, Diet
has increased by 4·1 times in China from 3·7% in 1982 to Dietary pattern
19·0% in 2002,32 and a review in 2014 suggested that this China has experienced a rapid nutrition transition
upward trend has continued (figure 1).23 Many factors characterised by increased energy intake from animal
contribute to increasing obesity, including changes in foods, dietary fat, and refined grains, and reduced
diet, increased affluence, reduced physical activity, and consumption of cereals (figure 2).39 Between 1992 and
increased urbanisation. Central obesity has also become 2002 energy intake from dietary fat increased from 22%
more common. For example, during the 10-year period to 29·8% and animal foods from 9·3% to 13·7%. By
between 1998 and 2008, two population-based cross- contrast average daily cereal intake decreased by 130 g
sectional surveys noted an increase in central obesity per capita from 1989 to 2000, although carbohydrates
from 19·5% to 27·3% in Chinese men in Shanghai.33 The
tendency to visceral adiposity, coupled with low muscle
A
mass, leading to a metabolically obese phenotype might 30 Cooking oil (left axis) Grains (right axis) 180
explain the high prevalence of diabetes in Asian Meats (pork, beef, mutton, and lamb; left axis) Vegetables (right axis)
populations despite the low prevalence of obesity Poultry (left axis) 160
compared with European populations. Prevalence of 25
childhood obesity has also increased in the last 140
Per capita food consumption (kg)

Per capita food consumption (kg)

two decades (figure 1). Given the key role of central 20 120
obesity and visceral adiposity in the pathogenesis of
type 2 diabetes, this increase in central obesity can 100
promote the development of overt type 2 diabetes in those 15
80
with inherited susceptibility.
10 60
Physical activity
Physical activity is a key lifestyle factor for the prevention 40
and control of type 2 diabetes.34 However, only 11·9% of 5
20
Chinese adults exercised routinely (≥3 times per week
and ≥10 min each time) in 2010.35 Reduction in physical 0 0
activity has been driven by a decline in occupational 1982 1985 1990 1995 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010
physical activity, and metabolic equivalent of task (MET)-
minutes per week decreased from 382 to 264 in men and B
420 to 243 in women based on the 1991–2011 China 18 300
Health and Nutrition Survey from nine provinces
(figure 1).24 Findings from the Guangzhou Biobank 16
250
Cohort Study (n=28 946) showed an inverse association
14
between moderate-to-vigorous physical activity and the
Per capita food consumption (kg)
Per capita food consumption (kg)

risk of type 2 diabetes, particularly in women with 12 200

abdominal obesity.36 In the SMHS (51 464 Chinese men,
1304 new cases of type 2 diabetes during a mean 5·4 years 10
150
follow-up) and the Shanghai Women’s Health Study
8
(SWHS; 70 658 Chinese women, 1973 incident cases of
type 2 diabetes during a mean 4·6 years follow-up), 6 100
physical activity from leisure-time exercise or daily
activity was associated with reduced risk of diabetes: for 4
example, men in the highest physical activity quintile 50
2
had a 27% reduced risk compared with those in the
lowest quintile over 5·4 years.29,37 In the Nutrition and 0 0
Health of Aging Population in China (NHAPC) study, 1978 1980 1985 1990 1995 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010
participants with high physical activity had a 30% lower Year
risk of metabolic syndrome and more favourable profiles
of inflammatory and adipocytokines individually and Figure 2: Secular trends of dietary pattern in (A) urban and (B) rural China over the past decades
collectively compared with their counterparts with low or Data from Zhou and colleagues.25

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or sugar-sweetened drinks), reduced the risk of

A
≥80 Female
developing type 2 diabetes in a recent systematic review
75–79 Male and meta-analysis of cohort studies.41,42 Although most
70–74 studies were done in American and European
65–69 populations, the SWHS showed that compared with
60–64 those clustered by highest intake of staple foods, those
55–59
with the highest intake of dairy milk had a 22% lower
50–54
45–49 risk of type 2 diabetes.43 In Hong Kong, findings from a
study of 690 adults followed up for 9–14 years, showed
Age

40–44
35–39 that a diet enriched with vegetables, fruits, and fish was
30–34 associated with a 14% lower risk of diabetes per 1 SD
25–29
increase in dietary pattern score, whereas a diet enriched
20–24
15–19
with meat and dairy products was associated with a 39%
10–14 higher type 2 diabetes risk per 1 SD.44
5–9
0–4 Carbohydrates
Rice accounts for about 30% daily energy intake in the
B
≥80 Chinese population.45 However, the quality of rice has
75–79 shifted from less processed to more refined in recent
70–74 decades.46 Asian populations including Chinese had
65–69 much higher white rice consumption compared with
60–64
American and Australian populations (average intake of
55–59
50–54
three to four servings per day compared with one to
45–49 two servings per week).47 High glycaemic index could be
a dietary trigger for type 2 diabetes in Chinese48 as well as
Age

40–44
35–39
30–34
25–29
20–24
15–19
10–14
5–9
0–4
80 000 60 000 40 000 20 000 0 20 000 40 000 60 000 80 000
Population (thousands)
Figure 3: Changes in population structure in China
Population by age group and sex: (A) 1980 and (B) 2010. Data derived from World population prospects: the 2012
revision. DVD edition. UN Department of Economic and Social Affairs, Population Division. Copyright 2013 United
Nations.26 Adapted with the permission of the United Nations.
Panel: Predicting the risk of diabetes in the Chinese population
Several risk scores have been developed to predict the risk of type 2 diabetes in the Chinese
population. These scores include well-established risk factors and newer scores also
incorporate genetic factors. The different clinical and laboratory variables included, and the
performance of these risk scores, are summarised in the table. Review of these risk scores
emphasises the importance of several known clinical risk factors, such as age, (central)
obesity, hypertension, dyslipidaemia, positive family history, and smoking. The consistent
ability of these risk factors to predict incident diabetes suggests that they are likely to be
causally related. Although the genetic variants identified have limited ability to predict
future risk of diabetes on their own, they do provide marginal improvement over predictions
based on clinical factors alone. Notably, individuals with high genetic susceptibility seem to
be most affected by obesity, detrimental lifestyle, and environmental factors,30,31
emphasising the importance of gene–environment interactions.
still contributed about 60% of total energy in 2004.40
A healthy diet (ie, high consumption of fibre-rich foods
or fish but low consumption of red meat, refined grains,
in studies from the US and Australia.49 In the SWHS,
women in the highest quintile of rice intake had 78%
increased risk of type 2 diabetes than those in the lowest
quintile;48 in this study, rice contributed to about 74% of
glycaemic load. Chinese people have 60% greater
glycaemic response to rice than Europeans, measured by
incremental area under the glucose curve.50 In addition,
results from the NHAPC study showed significant
correlations between a high carbohydrate to fat intake
ratio and erythrocyte fatty acids in the de novo lipogenesis
pathway.51 Higher concentrations of palmitoleic acid and
other fatty acids from the de novo lipogenesis pathway
were independently associated with increased 6-year
incidences of metabolic syndrome and type 2 diabetes.51
Few intervention trials have assessed the health benefit
of replacing white rice with brown rice. Substituting
white rice with brown rice for 5 consecutive days in Asian
Indians reduced the 5-day change of plasma glucose by
19·8% and 5-day percentage change in fasting insulin by
57%.52 In a 16-week randomised trial, patients with
diabetes in the brown rice group had lower diastolic
blood pressure and marginally higher reversion rate of
low serum HDL cholesterol than their counterparts in
the white rice group, but no difference between the two
groups in fasting glucose or insulin concentrations.45
Effects of sugar-sweetened beverages on cardiometabolic
health have attracted increasing attention because of their
high content of rapidly absorbable carbohydrates. Existing
studies from the USA and other countries suggested that
sugar-sweetened beverages that include naturally derived
caloric sweeteners like sucrose, high-fructose corn syrup,
or fruit-juice concentrates,53 were associated with

4 www.thelancet.com/diabetes-endocrinology Published online September 11, 2014 http://dx.doi.org/10.1016/S2213-8587(14)70145-7

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Scores incorporating noninvasive measures
Qingdao Diabetes Risk Score
New Chinese Diabetes Risk
Score
Scores incorporating laboratory measures
National Taiwan University
Taiwan MJ Longitudinal
health check-up-based
Population Database
(MJLPD)
Chinese University of Hong
Kong
Chinese PLA General
Hospital
Nutrition and Health of
Aging Population in China
(NHAPC)
Nutrition and Health of
Aging Population in China
(NHAPC)
Scores incorporating genetic markers
Shanghai Jiao Tong
University Affiliated Sixth
People’s Hospital
Nutrition and Health of
Aging Population in China
(NHAPC)
Ruijin Hospital, Shanghai
Shanghai Diabetes GWAS
Study (SDGS),
Shanghai Women’s Health
Study (SWHS),
Shanghai Men’s Health
Study (SMHS)
Chinese University of Hong
Kong
Population characteristics Variables selected in risk score Performance of risk score Reference*
1986, 62·7% female, Chinese, aged 20–74 years Age, WC, FH AUC 0·64 Gao and colleagues
2007–08, 16 525 men, 25 284 women, Age, sex, BMI, SBP, FH AUC 0·748 Zhou and colleagues
Chinese, aged 20–74 years
1990–2000, 548 out of 2960 developed Age, FBG, BMI, TG, WBC count, HDL cholesterol AUC 0·702 Chien and colleagues
incident type 2 diabetes during median 10-year
follow-up, Taiwan
Longitudinal health check-up information, Age, sex, education, FH, current smoking status, BMI, WC, AUC 0·848 Sun and colleagues
73 961 participants, aged 35–74 years, median hypertension, FBG
follow-up 3·15 years, Taiwan
Risk factor matching cohort of 2448 subjects Age, BMI, hypertension, dyslipidaemia (high TC, high TG or low AUC 0·735 Ko and colleagues
from Hong Kong, median age 36 years, two HDL), FH, gestational diabetes
other cohorts used for validation
10-year prospective health checkup-based Age, hypertension, history of high blood glucose, BMI, FBG, AUC 0·909 Liu and colleagues
population, 1851 Chinese individuals free of TG, HDL
diabetes at baseline, validated in cross-
sectional sample of 699
3189 Shanghai and Beijing residents aged Conventional risk factors (age, sex, region, residence, smoking, AUC 0·76 (for conventional Wu and colleagues
50–70 years from the Nutrition and Health of alcohol use, physical activity, FH, BMI), adiponectin, PAI-1, CRP, risk factors), AUC 0·81 (for
Aging Population in China in 2005 IL-6, ferritin risk factors plus weighted
biomarker risk score)
1912 Shanghai and Beijing residents, free of Female sex, hypertension, BMI, AUC 0·728 Ye and colleagues
diabetes (diagnosed by fasting glucose and fasting glucose, HbA1c, CRP
HbA1c) in 2005 and followed up in 2011
1849 patients with type 2 diabetes, PPARG rs1801282, KCNJ11 rs5219, WFS1 rs10010131, CDKAL1 AUC 0·614 for clinical, GRS Hu and colleagues
1795 controls aged >40 years, from in-patient rs7756992, CDKN2A/B rs10811161, IDE-HHEX rs10748582, 0·621, 0·668 combined
department of hospital in Shanghai IGFBP2 rs7651090, SLC30A8 rs13266634, FTO rs8050136,
KCNQ1 rs2237892, TCF2 rs4430796, age, sex, BMI
3210 Chinese (1423 men, 1787 women) aged 17 variants, fasting glucose, HbA1c, HOMA-S, insulin, HOMA-B, AUC 0·62 for GRS, 0·77 Qi and colleagues
50–70 years BMI, smoking, alcohol, physical activity, FH conventional, 0·79
combined
Case-control cohort of 1825 patients with type CDKAL1 rs7756992, SLC30A8 (rs13266634, rs2466293), AUC 0·714 for clinical risk Xu and colleagues
2 diabetes, 1487 with IGR, 2200 controls from CDKN2A/2B (rs10811661) and KCNQ1 (rs2237892), age, sex, factors, 0·73 for genetic+
Shanghai, recruited 2004–08. Prospective BMI, FH, current smoking, alcohol intake clinical risk factors
cohort of 734 participants without diabetes
recruited in 2005, of which 67 developed type
2 diabetes over 3·5 years
2679 patients with type 2 diabetes, GRS including 14 variants (IGFBP2 rs4402960, CDKAL1 ·· Villegas and
3322 controls, middle-aged Chinese Han from rs7756992, rs10440833, KCNK15 rs3734618, TP53INP1 colleagues
Shanghai rs896854, SLC30A8 rs13266634, CDKN2A/B rs10811661,
CDC123 rs12779790, HHEX rs1111875, rs5015480, KCNQ1
rs2237892, KCNJ11 rs5215, SPRY2 rs1215468, HNF1B
rs4430796), exercise, BMI, WHR
5882 with type 2 diabetes, 2569 controls, GRS including 8 variants (CDKAL1 rs7756992, IGF-BP2 Clinical 0·75, clinical and Tam and colleagues
Chinese Han in Hong Kong, case-control rs4402960, WFS1 rs734312, SLC30A8 rs1326634, CDKN2A/B genetic 0·77, net
rs10811661, reclassification
HHEX rs1111875, TCF7L2 rs7903146, KCNQ1 rs2237892), age, improvement 11%
sex, BMI

*References are listed in the appendix (pp 14–15). WC=waist circumference. FH=family history. AUC=area under receiver operating characteristic curve. SBP=systolic blood pressure. FBG=fasting blood glucose.
WBC=white blood cell. TC=total cholesterol. TG=triglyceride. PAI-1=plasminogen activator inhibitor 1. CRP=C-reactive protein. IL-6=interleukin 6. HOMA=homoeostatic model assessment. GRS=genetic risk
score. IGR=impaired glucose regulation. WHR=waist-to-hip ratio.

Table: Risk scores for type 2 diabetes in the Chinese population

increased risks of metabolic syndrome and type 2
diabetes.14,54,55 Although the underlying mechanisms are
not fully understood, high intake of sugar-sweetened
beverages could lead to insulin resistance, β-cell
dysfunction, and inflammation.55 National consumption
data for sugar-sweetened beverages are not presently
available for China. A survey of 10 216 children and See Online for appendix
adolescents from four large cities in mainland China
showed that consumption of soft drinks and fruit juice
increased from 477 mL per day in 1999 to about 715 mL per
day in 2008.56 The Singapore Chinese Health Study
(SCHS, 43 580 particpiants) found that higher intake

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(≥2 per week) of soft drinks and juice were associated with
higher incident risk of incident type 2 diabetes (42% with
soft drinks and 29% with juice).57 Moreover, heightened
risk of diabetes was more pronounced in participants in
the group with the highest soft drink consumption and
5-year weight gain.
Dietary fat and fatty acids
Evidence is accumulating that not only the quantity but
also the quality of dietary fat could have a distinct effect
on health outcomes. High consumption of fish, fish oil,
or eicosapentaenoic acid, and docosahexaenoic acid, and
low intake of trans fatty acids, have cardiovascular
benefits.58,59 However, their effects on type 2 diabetes
remain controversial. In the SWHS and SMHS, women
in the highest quintile of intake of long chain n-3 fatty
acids had 16% lower risk of type 2 diabetes than those in
the lowest quintile after a 9-year follow-up, whereas only
shellfish intake was significantly associated with reduced
risk of type 2 diabetes in both men and women.60 In the
SCHS, individuals in the highest quintile of intake of
total n-3 fatty acids had 22% lower risk of type 2 diabetes
than those in the lowest quintile after a 5·7-year follow-
up.61 Intake of trans fatty acids are low in Chinese people,
with dairy and bakery products being the main sources.
Vitamins and minerals
Certain vitamins and minerals, including carotenoids,
vitamin C, vitamin D, magnesium, selenium, chromium,
and zinc might reduce the risk of type 2 diabetes owing to
their antioxidant properties.62 Inadequate intake of
vitamin E, magnesium, selenium, and zinc was found in
10–69% of Chinese adults.63 The relation of these micro-
nutrients to the risk of type 2 diabetes, however, has not
been well studied in the Chinese population. In the SWHS,
higher intake of calcium was associated with 26% lower
risk of incident type 2 diabetes, and magnesium with 14%
lower risk, when the extreme quintiles were compared.64
Vitamin D deficiency is recognised as a worldwide
nutritional problem.65 Vitamin D status, its metabolism,
and its relation to diseases varies across ethnic groups.66
In a prospective study in South Korea, low vitamin D
(<20 ng/mL) was associated with increased risk of
incident type 2 diabetes during follow-up.67 No nationally
representative vitamin D data, measured by blood
25-hydroxyvitamin D (25(OH)D), is available in China. In
the NHAPC study, the proportion of vitamin D deficiency
(plasma 25(OH)D <50 nmol/L) was 69·2%, and
insufficiency (plasma 25(OH)D of 50 to <75 nmol/L)
24·4%. Lower plasma 25(OH)D concentrations were
significantly associated with higher risk of metabolic
syndrome and insulin resistance, and these associations
were more pronounced in overweight and obese
individuals.68
Iron overload indicated by raised concentrations of
circulating ferritin increased the risk of type 2 diabetes in
US studies,69 but little is known from China, a country
6 www.thelancet.com/diabetes-endocrinology Published online September 11, 2014 http://dx.doi.org/10.1016/S2213-8587(14)70145-7
with a high prevalence of iron deficiency.70 The upwards
trend of increased red meat intake might increase iron
overload and related type 2 diabetes in men and
postmenopausal women in China. Several cross-sectional
studies in Chinese individuals showed that participants
in the highest ferritin quartile had one to two times
higher prevalence of type 2 diabetes compared with those
in the lowest quartile.71,72 More recently, in the NHAPC
study, raised plasma ferritin concentrations at baseline
were associated with a 59% heightened risk for 6-year
incident diabetes comparing extreme quintiles,
independent of BMI, inflammation, and many con-
founders.73 Therefore, iron overload seems to be an
independent risk factor for type 2 diabetes, even in
China, where there is a high prevalence of iron deficiency.
Collectively, a shift to a westernised diet, with increased
intake of sugar-sweetened beverages, dietary fats, and red
meat, and a change towards refined grains, seem to play
an important part in the type 2 diabetes epidemic in
China. Of the different dietary risk factors, changes in
carbohydrate intake, including white rice intake and
sugar-sweetened beverages, and increased unhealthy fat
intake, probably have the most effect given their common
consumption.
Other risk factors
Associations between diabetes and several other risk
factors, such as chronic infections and low-grade
inflammation, have also been observed in the Chinese
population. Tuberculosis is endemic in China, and cases
in China account for 17% of cases worldwide.74
Epidemiological studies in many countries have shown
that diabetes increases the risk of tuberculosis by about
three times,75 and vice versa;76 this double burden poses
substantial public health challenges. Indeed, in a
prospective study of 6382 newly diagnosed patients with
tuberculosis in rural areas of China, the prevalence of
diabetes was 6·3%, and was significantly higher than in
non-tuberculosis controls (4·7%, p<0·001).74 Helicobacter
pylori infection, which is highly prevalent in the Chinese
population, was also associated with about two times
increased risk of diabetes in a meta-analysis of 37 case-
control studies and two cohort studies.77 H pylori titres
have been associated with glucose concentrations and
β-cell function.78 Various inflammatory markers,
including white blood cell count, C-reactive protein, and
interleukin 6, have been associated with insulin
resistance, impaired glycaemic status,79 and incident
diabetes in Chinese people.80
Adipocytokines produced from adipose tissue have
many effects, and might partly mediate the association
between adiposity, cardiometabolic abnormalities, and
vascular risk. Several adipocytokines, including
adiponectin, have been associated with risk of diabetes
in cross-sectional and prospective studies, both in China
and elsewhere. The concentrations of adipocytokines are
correlated with indices of visceral adiposity, and some

have been incorporated into risk scores for predicting
diabetes (table).
Several other common diseases have also been linked
to diabetes risk. About 25% of urban adults in China
have non-alcoholic fatty liver disease,81 which is strongly
associated with diabetes.82 In a study using magnetic
resonance spectroscopy, the proportion of the general
adult population in Hong Kong with non-alcoholic fatty
liver disease was 27%.83 Polycystic ovary syndrome, a
common endocrine disorder in women of reproductive
age, is associated with increased diabetes and cardio-
metabolic risk.84 Finally, both major depression and
generalised anxiety disorder, which are increasing in
China, have been noted to be associated with a two times
increased risk of diabetes in the Chinese population.22,85
Increasing evidence also suggests an association
between sleep disturbances or disrupted circadian
rhythm and increased risk of diabetes.86 Reduced sleeping
hours were associated with increased risk of obesity in
Chinese working men,87 children, and adolescents.88 With
rapid urbanisation and an increasingly fast-paced
lifestyle, the tendency for less sleep has become more
common in China.
Several classes of drugs, notably anti-psychotics,
antiretrovirals, and others have been associated with
increased risk of diabetes.89 Chinese patients with chronic
schizophrenia have been reported to have about a four
times increased risk of type 2 diabetes, similar to that
reported in other populations.90 Given the health
transition and increasing burden from mental illness
and HIV in recent decades, these factors could be
important in the future.91
Carbon dioxide emissions in China have increased
from 1·5 tons per capita in 1980 to 6·7 tons per capita in
2011,92 with air pollution becoming a major health
problem. Environmental exposure to chlorinated
persistent organic pollutants and endocrine disruptors
such as bisphenol A has been linked to increased risk of
obesity or diabetes.93,94 In a cross-sectional study of more
than 3000 adults in Shanghai, raised urinary bisphenol A
was associated with obesity, central obesity, and insulin
resistance, although no definite association between
urinary bisphenol A and prevalent type 2 diabetes was
detected.94,95 Import and export of bisphenol A has
increased in China, with estimated volume of
consumption increasing from 106 000 tonnes in 2001 to
570 000 tonnes in 2007.96
Developmental origins of diabetes
Early life events and the intrauterine environment can
have a persistent effect on the risk of many chronic
diseases later in life. Barker and Hales’97 finding that
birthweight is associated with risk of diabetes and
cardiovascular disease in adulthood has been confirmed
in many studies across different ethnic groups. The
concept of fetal origin of disease has now evolved into a
conceptual framework of developmental origins of health
www.thelancet.com/diabetes-endocrinology Published online September 11, 2014 http://dx.doi.org/10.1016/S2213-8587(14)70145-7
Series
and disease, drawing on evidence from epidemiological
and animal studies.98 China has undergone a very rapid
economic transition, which was accompanied by a rapid
nutritional transition. This change in nutritional status
across as little as one to two generations has resulted in a
marked mismatch between the nutritional states of
mothers during pregnancy, compared with the high-fat,
calorie-dense diets that modern Chinese children are
exposed to following birth. A low-protein diet has
detrimental effects on pancreatic β cells in experimental
animal models, including increased oxidative stress,
fibrosis, decreased HNF4A expression, mitochondrial
dysfunction, and increased differentiation instead of
proliferation of cells in adult offspring.99 Thus, maternal
malnutrition could fuel the epidemic of obesity and
diabetes in many developing countries. Offspring of
mothers exposed to the Chinese famine of 1959–61 have
a 3·9 times increased risk of diabetes or hyperglycaemia
as adults, and the risk is even higher if the offspring has
high economic status later in life or is overweight.100
Maternal undernutrition, maternal over-nutrition, and
low rates of breastfeeding are early life factors associated
with increased risk of obesity and diabetes.101 Gestational
diabetes is also an important risk factor for diabetes in
women. Chinese women with gestational diabetes have
about eight times increased risk of developing type 2
diabetes.102 The strength of association was similar in a
systematic review and meta-analysis of studies in
different populations.103 Gestational diabetes has
increased in China and across Asia over the last
decade.104,105 Data from Tianjin City, where citywide
screening for gestational diabetes in all pregnant mothers
has been done since 1998, revealed a 2·8 times increase
in the prevalence of gestational diabetes during
1999–2008, from 2·4% to 6·8%.104
Gestational diabetes is also associated with increased
risk of obesity and diabetes in the offspring, and could
play an important part in perpetuating a vicious cycle of
diabetes begetting diabetes.105,106 In a multiethnic cohort,
Chinese infants were more susceptible to the effects of
maternal hyperglycaemia on adiposity when compared
with Indian infants.107 Importantly, the risk of childhood
obesity seems to be lower in offspring of mothers with
gestational diabetes who were breastfed compared with
those not breastfed.108 Furthermore, women who breastfed
their children had lower risk of developing diabetes
themselves.109 Maternal obesity is also associated with
increased risk of diabetes in the offspring. Therefore, it
seems that both pathways initiated by maternal
undernutrition (nutrient-mediated teratogenesis) and
intrauterine over-nutrition (fuel-mediated teratogenesis),
could be important for the diabetes epidemic in rapidly
developing countries such as China.110 The contribution
of the different risk factors for diabetes across the
lifecourse is shown in figure 4.
Although the mechanisms by which the intrauterine
environment and early life events affect an individual’s
7
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Intrauterine Infancy Childhood and Adulthood
adolescence
Genetic Caesarean section Obesity Ageing
Maternal undernutrition Formula fed Unhealthy diet Obesity and central obesity
Placental insufficiency Gut microbiota Sugar-sweetened beverages Smoking
Maternal obesity Rapid weight gain PCOS Unhealthy diet
Maternal diabetes Gestational diabetes
Paternal health status Disturbed sleep
Environmental toxins
Drugs
Risk of type 2 diabetes
Figure 4: Different risk factors for type 2 diabetes across the lifecourse
The factors are listed according to the period at which they are most likely to begin becoming important. Factors
are likely to have persistent effects through later stages of the lifecourse as well. PCOS=polycystic ovary syndrome.
risk of diabetes is unclear, epigenetic changes and the
gut microbiota could be important.101,111 Deep shotgun
sequencing of 345 Chinese individuals identified a gut
microbial profile associated with type 2 diabetes, which
was associated with abundance of butyrate-producing
bacteria and enrichment of sulphate reduction and
resistance to oxidative stress.112 The gut microbiota can be
altered by caesarean section delivery compared with
spontaneous birth, which could be important for China.
In one report, as many as 46% of livebirths in rural areas
were by caesarean section, and this might be partly
driven by health insurance coverage.112 The rate might be
even higher in women who conceive through assisted
reproduction techniques, and was 85% in one study.113
The complex relation between early life events, nutrition,
and changes in the gut microbiota is an area of research
that will hopefully bring about novel insights regarding
the pathogenesis of diabetes.
Genetic factors
Type 2 diabetes is a complex disease that is determined
by genetic and environmental factors. In a recent
systematic review and meta-analysis of prevalence
studies in China, a positive family history of diabetes was
one of the strongest risk factors for type 2 diabetes in
Chinese people, with an odds ratio of 2·33 (95% CI
1·54–3·51).114 The heritability of type 2 diabetes has been
calculated as 30–70%.115 Several approaches have been
taken to identify susceptibility genes for type 2 diabetes,
and we focus here on variants identified in the Chinese
population.
TCF7L2 is considered the strongest and most consistent
signal for type 2 diabetes in Europeans. TCF7L2 encodes
transcription factor 7-like 2, an important component of
the Wnt signalling pathway. The present evidence
suggests that TCF7L2 variants are associated with insulin
secretion, and might also modulate the insulinotropic
actions of incretins.116,117 Moreover, Gaulton and
colleagues118 found that the T risk allele of rs7903146 is
located in more open chromatin than the non-risk C allele,
8 www.thelancet.com/diabetes-endocrinology Published online September 11, 2014 http://dx.doi.org/10.1016/S2213-8587(14)70145-7
suggesting that the T risk allele makes TCF7L2 DNA more
accessible, with greater enhancer activity.118 These data
suggest that genetic variation at TCF7L2 affects
susceptibility to type 2 diabetes, with the risk allele
conferring a gain-of-function effect, with the open
chromatin status in islet cells allowing increased
transcriptional activity of TCF7L2. These findings might
explain, at least in part, the association between TCF7L2
and type 2 diabetes. Importantly, due to the low frequency
of the risk allele of rs7903146 in the Chinese population,
most initial studies in Chinese people did not replicate the
association of this variant with type 2 diabetes, but other
nearby variants with evidence of association were found.119
With the advent of genome-wide association studies,
numerous loci have been identified that confer
susceptibility to type 2 diabetes. More than 70 loci have
been identified to date, with around 40 of these loci
discovered in European populations. Notably, not all of
these European loci have been replicated in east Asians
(appendix pp 1–13). For example, in a replication study in
Han Chinese of variants discovered from the earlier
studies in Europeans, only CDKN2A⁄B, HHEX,
CDKAL1, SLC30A8, FTO, IGF2BP2, and MTNR1B were
replicated.120 There are often marked differences in the
genetic architecture (appendix pp 1–13), with different
frequencies of risk alleles, emphasising the need for both
large-scale replication studies, and ethnic-specific studies
to identify the most relevant genetic variants in a
population. Most genetic variants have similar effect
sizes in different populations, but some that have higher
risk allele frequency within the Chinese population, such
as rs7756992 near CDKAL1, might have a substantially
higher population-attributable risk in Chinese than in
European people (appendix pp 1–13).
To further investigate the genetic factors for type 2
diabetes in east Asians, efforts have been made to identify
specific susceptibility loci with genome-wide association
studies. About 20 loci have been discovered in east Asian
studies as susceptibility loci for type 2 diabetes, including
variants near KCNQ1, SRR, PTPRD, UBE2E2,
C2CD4A/B, MAEA, PSMD6, ZFAND3, GCC1, KCNK16,
PEPD, HNF4A, GLIS3, GRK5, RASGRP1, PAX4,
MIR129-LEP, GPSM1, and SLC16A137,120,121 (appendix
pp 1–13). Among these loci, KCNQ1 was regarded as the
strongest locus for type 2 diabetes in populations of east
Asian ethnic origin. KCNQ1 encodes the pore-forming
subunit of the voltage-gated K+ channel, which plays an
important part in the repolarisation of action potentials
in cardiac muscles.122 This gene was first identified
through two genome-wide association studies in the
Japanese population, where several single nucleotide
polymorphisms (rs2237892, rs2237895, rs2237897,
rs2283228) were strongly associated with type 2 diabetes,
with ORs ranging from 1·26 to 1·41.123,124 The association
was later replicated in the Chinese population.123,125
KCNQ1 variants were strongly associated with insulin
secretion.123,125 However, all identified single nucleotide

polymorphisms are located in intronic regions of
KCNQ1; whether these single nucleotide polymorphisms
directly modify expression of this gene or whether they
are just in linkage disequilibrium with unknown causal
variants, still needs to be investigated. Although the
nearest gene is often used to refer to polymorphisms
identified by genome-wide association studies, a causal
relation between the gene or the variant with type 2
diabetes is often not established. Most type 2 diabetes
loci discovered so far seem to be near genes related to
β-cell dysfunction, emphasising the important role of
β-cell dysfunction in the pathogenesis of type 2 diabetes.
Despite efforts to understand the genetic cause of type
2 diabetes, loci discovered so far collectively explain less
than 10% of the overall heritability.126 Furthermore, most
identified risk variants seem to have a lower allele
frequency in Asians, and therefore do not seem to explain
ethnic differences in diabetes risk.127 Nevertheless, people
who carry the most risk variants seem most susceptible
to the effects of lifestyle factors and obesity.128 More
research, including trans-ethnic mapping and the use of
new technologies such as deep sequencing, are needed
to reveal the underlying genetic factors of type 2 diabetes
in Chinese and other populations.
Perspective on prevention
Over a short period of time, the Chinese population has
experienced a striking change in diet, exercise level,
sleep–work pattern, and other environmental factors
associated with urbanisation. Many of these changes
have contributed to the current epidemic of diabetes in
China and in Asia. The ageing population, coupled with
reduced physical activity and changes in dietary pattern
leading to increased obesity, are some of the most
important factors contributing to the epidemic. A family
history of diabetes is present in 23% of newly diagnosed
cases and 43% of previously diagnosed cases;3 it is
associated with a two to three times increased risk of
type 2 diabetes, has high population-attributable risk,
and is one of the most important risk factors for type 2
diabetes in Chinese people. Nevertheless, currently
identified genetic variants seem to explain only a very
small fraction of the risk associated with a positive
family history, which is likely to also encompass effects
from unidentified genetic variants, gene–gene
interactions, epigenetic mechanisms, effects of the
intrauterine environment, gut microbiota, shared living
environment, and similar lifestyle and behaviour among
family members.
Much effort is now focused on encouraging lifestyle
changes in adults, and the long-term follow-up data
from the Da Qing Diabetes Prevention Study—which
suggest sustained long-term benefits of a lifestyle
intervention in reducing diabetes, cardiovascular, and
all-cause mortality—are encouraging.129 Indeed, given
the high absolute risk of diabetes associated with obesity
at any level of genetic risk, a universal approach to
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Series
Search strategy and selection criteria
We searched PubMed for published aticles from Jan 1, 2000 to March 30, 2014, with the
search terms “diabetes” and “risk factors” or “epidemiology” or “dietary” or “exercise” or
“genetics” or “polymorphisms” in combination with the terms “Chinese” or “China”. We
selected publications in the past 5 years (from January, 2009), but also included
commonly referenced and highly regarded older publications. We also searched the
reference lists of articles identified by this search strategy and selected those we judged
relevant. Review articles and book chapters are cited in many instances to provide readers
with more details and more references than we had space to cite. Our reference list was
modified on the basis of comments from peer reviewers.
lifestyle intervention is important.128 Reducing smoking
will be another important public health target in China.
Insights into the role of early life factors has opened up
opportunities to intervene at different stages across the
lifecourse. In addition to encouraging a healthy dietary
pattern and physical activity, these advances emphasise
the need for efforts to improve health literacy, optimise
maternal health, promote breastfeeding, and optimise
nutrition for infants and children to reduce the risk of
diabetes and other non-communicable diseases from
early on. Public health policies to reduce the burden of
diabetes and other non-communicable diseases will
require cross-disciplinary, multi-sector, and public–
private partnerships to address this escalating epidemic
and its associated healthcare burden.10 Central and local
governments will play a key part in implementing some
of the changes needed to combat obesity and diabetes.
The Chinese Ministry of Health, together with other
ministries and state administrations, have formulated a
national plan for non-communicable disease prevention
and treatment, with emphasis on government
leadership, inter-sector cooperation, social participation,
improving accessibility, equity and effectiveness of care,
integrating prevention with treatment, and a focus on
primary health care.130 How China tackles this public
health challenge will provide important lessons for other
developing countries faced with an increasing burden of
diabetes.
Contributors
RCWM, XL, and WJ did the literature search, data collection, and
interpretation. All authors contributed equally to the writing. RCWM
was responsible for drafting the figures and tables.
Declaration of interests
We declare no competing interests.
Acknowledgments
RCWM received support from the Research Grants Council Theme-based
Research Scheme (T12-402/13N), the Research Grants Council General
Research Fund (CU471713), and the European Foundation for the Study
of Diabetes (EFSD)/Chinese Diabetes Society (CDS)/Lilly Collaborative
Research Programme. XL received support from the Ministry of Science
and Technology of China (2012CB524900), the National Natural Science
Foundation of China (30930081 and 81321062), and the Chinese Academy
of Sciences (KSCX2-EW-R-10). WJ received support from the Ministry of
Science and Technology of China (2011CB504001), the National Natural
Science Foundation of China (9131110 and 81220108006), and Ministry of
Education of China (20120073110086).
9
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