Increased circulatory levels of lipopolysaccharide (LPS) and zonulin signify novel biomarkers of proinflammation in patients with type 2 diabetes.

Emerging data indicate that gut-derived endotoxin (metabolic endotoxemia) may contribute to low-grade systemic inflammation in insulin-resistant states. Specific gut bacteria seem to serve as lipopolysaccharide (LPS) sources and several reports claim a role for increased intestinal permeability in the genesis of metabolic disorders. Therefore, we investigated the serum levels of LPS and zonulin (ZO-1, a marker of gut permeability) along with systemic levels of tumor necrosis factor-α (TNF-α) and Interleukin-6 (IL-6) in patients with type 2 diabetes mellitus (T2DM) compared to control subjects. Study subjects were recruited from the Chennai Urban Rural Epidemiology Study [CURES], Chennai, India. Study group (n = 45 each) comprised of a) subjects with normal glucose tolerance (NGT) and (b) patients with T2DM. LPS, ZO-1, TNF-α, and IL-6 levels were measured by ELISA. Serum levels of LPS [p < 0.05], LPS activity [p < 0.001], ZO-1 [p < 0.001], TNFα [p < 0.001], and IL-6 [p < 0.001] were significantly increased in patients with T2DM compared to control subjects. Pearson correlation analysis revealed that LPS activity was significantly and positively correlated with ZO-1, fasting plasma glucose, 2 h post glucose, HbA1c, serum triglycerides, TNF-α, IL-6, and negatively correlated with HDL cholesterol. Regression analysis showed that increased LPS levels were significantly associated with type 2 diabetes [odds ratio (OR) 13.43, 95 % CI 1.998-18.9; p = 0.003]. In Asian Indians who are considered highly insulin resistant, the circulatory LPS levels, LPS activity, and ZO-1 were significantly increased in patients with type 2 diabetes and showed positive correlation with inflammatory markers and poor glycemic/lipid control.

Mortality rates due to diabetes in a selected urban south Indian population--the Chennai Urban Population Study [CUPS--16].

OBJECTIVE: The aim of this study was to determine the mortality rate in diabetic and non-diabetic subjects in urban south India. METHODS: The Chennai Urban Population Study is an ongoing epidemiological study in Chennai [formerly Madras, in south India]. All individuals > or = 20 years of age living in two residential colonies in Chennai were invited to participate in the study. Of the total 1399 eligible subjects, 1262 individuals responded [90.2%] at baseline, and of these, 1140 individuals [90.3%] could be followed annually from 1997 to 2003-04. Mortality rates and causes of death were the main outcome measures. RESULTS: The median follow up period was six years. The overall mortality rate was higher in diabetic compared to non-diabetic subjects [18.9 vs.5.3 per 1000 person-years, p=0.004]. Mortality due to cardiovascular [diabetic subjects, 52.9%; non-diabetic subjects, 24.2%,p=0.042] and renal causes[diabetic subjects, 23.5%; non-diabetic subjects, 6.1%,p=0.072] was higher among diabetic subjects whereas mortality due to gastrointestinal 112.1%], respiratory [9.1%], lifestyle related [6.1%] and unnatural causes [18.2%] were observed only among non-diabetic subjects. Hazards ratio [HR] for all cause mortality for diabetes was 3.6, [95% Confidence Interval [CI]: 2.02-6.53, p<0.001] and this remained significant even after adjusting for age [HR:1.9, 95% CI:1.04-3.45, p=0.038]. Light grade physical activity was associated with higher mortality rate [p=0.008], but the significance disappeared when adjusted for age. Smoking was also associated with increased mortality. CONCLUSIONS: In urban India, mortality rates are two fold higher in people with diabetes compared to nondiabetic subjects. Cardiovascular and renal diseases are the commonest causes of death among diabetic subjects.

Secular trends in the prevalence of diabetes and impaired glucose tolerance in urban South India--the Chennai Urban Rural Epidemiology Study (CURES-17).

AIMS/HYPOTHESIS: The aim of this study was to determine the secular trends in prevalence of diabetes and IGT in urban India. MATERIALS AND METHODS: The Chennai Urban Rural Epidemiology Study (CURES) screened 26,001 individuals aged > or =20 years using the American Diabetes Association fasting capillary glucose criteria. The study population, which was representative of Chennai, was recruited by systematic random sampling. Every tenth subject from Phase 1 of CURES was invited to participate in Phase 3 for screening by World Health Organization (WHO) plasma glucose criteria. The response rate was 90.4% (2,350 responders from 2,600 potential subjects). The prevalences of diabetes and IGT in CURES were compared with three earlier studies: two conducted on a representative population of Chennai in 1989 and 1995, and the other the National Urban Diabetes Survey (NUDS) completed in 2000. RESULTS: The overall crude prevalence of diabetes using WHO criteria in CURES was 15.5% (age-standardised 14.3%), while that of IGT was 10.6% (age-standardised 10.2%). Prevalence of diabetes increased by 39.8% (8.3-11.6%) from 1989 to 1995; by 16.3% (11.6-13.5%) between 1995 and 2000; and by 6.0% (13.5-14.3%) between 2000 and 2004. Thus within a span of 14 years, the prevalence of diabetes increased by 72.3% (chi (2) trend 22.23, p < 0.0001). The prevalence of IGT increased by 9.6% from 1989 to 1995 and by 84.6% between 1995 and 2000 (chi 2 trend 52.9, p < 0.0001). However, it decreased by 39.3% between 2000 and 2004 (p < 0.0001). There was a shift in the age at diagnosis of diabetes to a younger age in CURES compared with NUDS. CONCLUSIONS/INTERPRETATION: Compared with earlier studies, the prevalence of diabetes in Chennai, representing urban India, has increased while that of IGT has decreased.

Community empowerment--a successful model for prevention of non-communicable diseases in India--the Chennai Urban Population Study (CUPS-17).

BACKGROUND AND OBJECTIVE: Randomized clinical trials have documented that lifestyle changes through physical activity can prevent diabetes. However there is no data whether such strategies are applicable at community level, that is, in a real life setting. This study demonstrates the first attempt in India, to our knowledge, of increasing physical activity through community empowerment in an attempt at primary prevention of non communicable diseases. METHODS: The Chennai Urban Population Study [CUPS] was conducted in the year 1996 in two residential areas: a middle income group the Asiad colony at Tirumangalam, and a low income group at Bharathi Nagar in T. Nagar. The Asiad colony was selected for this study. Of the 524 eligible individuals available at baseline in 1998 [age > or =20 years], 479 individuals consented for the study (response rate: 91.4%). After seven years, in 2004, the number of eligible individuals increased to 712 of whom 705 consented for the study (response rate:99%). Education regarding the benefits of physical activity was provided by mass awareness programmes like public lectures and video clippings. Both at baseline and during follow-up, details about the physical activity were collected using a validated questionnaire, which included job related and leisure time activities, and specific questions on exercise. Study individuals were then graded as having light, moderate and heavy physical activity using a scoring system. RESULTS: In response to the awareness programmes given by our research team, the colony residents constructed a unique public park with their own funds. Though the occupation grades did not change, there was a significant change in the pattern of physical activity. At baseline, only 14.2% of the residents did some form of exercise. more than three times a week, which presently increased to 58.7% [p < 0.001]. The number of subjects who walked more than three times a week increased from 13.8% at baseline to 52.1% during follow-up [p < 0.001]. CONCLUSION: This study is a demonstration of how community empowerment with increased physical activity could possibly lead to prevention of diabetes and other non communicable diseases at the community level. This study also highlights the importance of sharing the results of research studies with the community.

Association of physical inactivity with components of metabolic syndrome and coronary artery disease--the Chennai Urban Population Study (CUPS no. 15).

AIM: The aim of the study was to assess the influence of physical activity on the components of metabolic syndrome (MS) in an urban south Indian population in Chennai. METHODS: The Chennai Urban Population Study (CUPS) is an epidemiological study involving two residential areas in Chennai in South India. Of the total of 1399 eligible subjects (age > or = 20 years), 1262 individuals participated in the study. MS was diagnosed based on modified Adult Treatment Panel (ATP) III guidelines. Details about the physical activity were collected using questionnaire, which included job-related and leisure-time activities, and specific questions on exercise. Study individuals were then graded as light, moderate and heavy using a scoring system. We assessed the relationship between the grades of physical activity and the components of MS and coronary artery disease (CAD). Insulin resistance was calculated using the homeostasis assessment model (HOMA-IR). RESULTS: Prevalence of most of the components of MS (diabetes P < 0.001, obesity P = 0.003, abdominal obesity P < 0.001 and hypertension P < 0.001) and MS per se (P < 0.001) increased significantly with decrease in physical activity. Among non-diabetic subjects, HOMA-IR was significantly higher in subjects who did light-grade activity compared with heavy-grade activity (P = 0.041). Logistic regression analysis revealed physical activity to be significantly associated with MS [heavy activity: reference, moderate activity, odds ratio (OR) 1.639, (P = 0.017); light activity: OR 2.289, (P < 0.001)]. Subjects in the light-grade activity group also had higher odds of CAD (OR 2.42, 95% confidence interval 1.40, 4.24, P = 0.011), compared with the heavy-grade activity group. CONCLUSION: Physical inactivity is associated with the components of MS and CAD in this urban south-Indian population. Lifestyle changes focusing on increasing physical activity could help to prevent the exploding epidemic of MS and CAD in India.

Awareness and knowledge of diabetes in Chennai--the Chennai Urban Rural Epidemiology Study [CURES-9].

BACKGROUND AND AIM: There are virtually no epidemiological studies from India assessing the level of awareness of diabetes in a whole population. The aim of the present study was to assess the awareness of diabetes in an urban south Indian population in Chennai. METHODS: The Chennai Urban Rural Epidemiology Study (CURES) is an ongoing population based study conducted using a systematic sampling method on a representative population (aged > or = 20 years - 26001 individuals) of Chennai [formerly Madras], the largest city in Southern India. A structured questionnaire was used to obtain information related to demography, education and medical history. The questionnaire included five questions on diabetes awareness. RESULTS: Of the total 26,001 individuals, only 75.5% (19642/26001) of the whole population reported that they knew about a condition called diabetes or conversely nearly 25% of the Chennai population was unaware of a condition called diabetes. 60.2% (15656/26001) of all participants and 76.7% (1173/1529) of the self reported diabetic subjects knew that the prevalence of diabetes was increasing in India. Only 22.2% (5764/ 26001) of the whole population and 41.0% (627/1529) of the known diabetic subjects were aware that diabetes could be prevented. Knowledge of the role of obesity and physical inactivity in producing diabetes was very low, with only 11.9% (3083/26001) of study subjects reporting these as risk factors for diabetes. Only 19.0% (4951/26001) of whole population knew that diabetes could cause complications. Even among the self reported diabetic subjects, only 40.6% (621/1529) were aware that diabetes could produce some complications. CONCLUSION: Awareness and knowledge regarding diabetes is still grossly inadequate in India. Massive diabetes education programmes are urgently needed both in urban and rural India.

Association of hypertension with cluster of insulin resistance syndrome factors: the Chennai Urban Population Study (CUPS-12).

The objective of this study was to investigate the association of insulin resistance and the cluster of insulin resistance syndrome (IRS) factors with hypertension in a native urban population from southern India. The Chennai Urban Population Study (CUPS) is an epidemiological study involving two residential areas in Chennai in southern India. Of the total of 1399 eligible subjects (age >or=20 years), 1262 (90.2%) participated in the study. Subjects were classified as hypertensives if they had systolic blood pressure (SBP) >or=140 mmHg or diastolic blood pressure (DBP) >or=0 mmHg, if they were known hypertensives, or if they were receiving treatment with antihypertensive drugs. Insulin resistance was computed using the homeostasis model assessment (HOMA IR). The overall prevalence of hypertension in the population was 22.1%. Prevalence of hypertension increased with an increase in quartiles of fasting insulin levels ( p=0.035) and HOMA IR ( p=0.03). Logistic regression analysis revealed that HOMA IR was significantly associated with hypertension, which was not altered even after addition of risk factors like age, smoking habit and alcohol consumption into the model. However, inclusion of variables associated with IRS abolished the association of insulin resistance with hypertension. Factor analysis identified four factors: factor 1 had positive loading of body mass index, age, systolic and diastolic blood pressures; factor 2 had positive loading of HOMA IR, fasting plasma glucose, triglycerides and body mass index; factor 3 had positive loading of waist-hip ratio, triglycerides and smoking habit and negative loading of alcohol consumption; factor 4 was loaded with age and serum cholesterol. Factor 1, the hypertension factor loaded with systolic and diastolic blood pressures, shared a correlation with the insulin resistance cluster through body mass index. Our results suggest that the "insulin resistance cluster" is associated with hypertension in this urban population of southern India.

Glucose intolerance (diabetes and IGT) in a selected South Indian population with special reference to family history, obesity and lifestyle factors--the Chennai Urban Population Study (CUPS 14).

AIM OF THE STUDY: The aim of the study was to assess the impact of family history of diabetes, obesity and lifestyle factors particularly physical activity on glucose intolerance in a selected south Indian population. MATERIALS AND METHODS: The Chennai Urban Population Study (CUPS) is an epidemiological study involving two residential areas in Chennai in South India representing the middle and lower socio-economic group. Of the total of 1399 eligible subjects (age > or = 20 years), 1262 (90.2%) participated in the study. A detailed questionnaire was used to collect details on medical history, family history of diabetes, family income and physical activity. All the study subjects underwent a glucose tolerance test (GTT) and were categorized as having normal glucose tolerance (NGT), impaired glucose tolerance (IGT) or diabetes using WHO consulting group criteria. Obesity and abdominal obesity were defined using the new Asia Pacific guidelines. RESULTS: The overall prevalence of diabetes in the study population was 12.0%, (age-standardized -9.3%), which included 7.2% of known diabetic subjects and 4.8% undiagnosed diabetic subjects, while the prevalence of impaired glucose tolerance was 5.9% (age-standardized prevalence 5.0%). The prevalence of glucose intolerance (Diabetes + IGT) was significantly higher among subjects with both parents diabetic (55%) compared to those with one parent diabetic (22.1%, p = 0.005) and those with no family history (15.6%, p < 0.0001). Prevalence of glucose intolerance was significantly higher among subjects who had light grade physical activity (23.2%) compared to moderate (17.5%, p = 0.04) and heavy grade activity (8.1 % p < 0.00001). Subjects belonging to higher socio-economic status (SES) and who also had a positive family history of diabetes had five times greater prevalence of glucose intolerance compared to subjects from lower socioeconomic status and no family history (p < 0.0001). Regression analysis revealed age (p < 0.0001), waist circumference (p < 0.0001), body mass index (p < 0.0001), waist-hip ratio (p < 0.0001), systolic blood pressure (p < 0.0001), diastolic blood pressure (p < 0.0001), family history of diabetes (p < 0.0001), higher SES (p < 0.0001), moderate (p = 0.001) and light (p < 0.001) grade physical activity to be associated with glucose intolerance. Multiple logistic regression analysis showed that even after adjusting for variables like age and family history of diabetes, physical activity showed a significant association with glucose intolerance CONCLUSION: The prevalence of glucose intolerance is high in this selected urban south Indian population. Lifestyle factors and family history have a synergistic effect on increasing the risk for diabetes in this population.

Is the 'rule of halves' in hypertension still valid?--Evidence from the Chennai Urban Population Study.

AIM OF THE STUDY: The aim of the present study was to assess the applicability of the rule of halves in an urban population in South India. METHODS: The Chennai Urban Population Study (CUPS) is an ongoing population based study involving two residential colonies representing a middle and lower socio-economic status in Chennai city. The response rate for the study was 90.1%. Based on a glucose tolerance test (GTT), the study subjects were categorized as having normal glucose tolerance test (NGT), impaired glucose tolerance test (IGT) or diabetes. Blood pressure was measured for all the study subjects and the subjects were classified as hypertensive using the criteria, systolic blood pressure (SBP) > or = 140 mm Hg and/or diastolic blood pressure > or = 90 mmHg and/or known hypertensives and/or treatment with antihypertensive drugs. Controlled hypertension was defined as SBP < 140 mmHg and DBP < 90 mmHg. RESULTS: The overall prevalence of hypertension in this population is 22.1% (279/1262). Of these 279 individuals with hypertension, only 37.3% (104/279) were known hypertensives. Of the 104 known hypertensives, only 52 subjects (50%) were under any kind of antihypertensive therapy. Of these 52 individuals, only 21 (40%) had blood pressure under control. Prevalence of hypertension was higher in subjects with glucose intolerance. Awareness and treatment of hypertension was slightly higher among the diabetic hypertensive subjects. Analysis on the different social classes revealed that the prevalence, awareness and treatment of hypertension to be significantly higher among the middle income group compared to lower income group. CONCLUSION: The rule of halves is still valid in this urban South Indian population and thus the awareness, treatment and control measures for hypertension are still inadequate in this population.

Prevalence and risk factors of hypertension in a selected South Indian population--the Chennai Urban Population Study.

OBJECTIVE: Hypertension is a major public health problem in developing countries. There is however very little population based data particularly in South India. The aim of this study is to determine the prevalence of hypertension and its associated risk factors in an urban South Indian population at Chennai. METHODS: The Chennai Urban Population Study (CUPS) is an epidemiological study involving two residential areas in Chennai in South India. Of the total of 1399 eligible subjects (age > or = 20 years), 1262 (90.2%) participated in the study. All the study subjects underwent a glucose tolerance test (GTT) and were categorized as having normal glucose tolerance (NGT), impaired glucose tolerance (IGT) or diabetes mellitus (DM). Subjects were classified as hypertensive using the criteria, systolic blood pressure (SBP) > or = 140 mm Hg, and/or diastolic blood pressure (DBP) > or = 90 mm Hg and/or treatment with anti-hypertensive drugs. Twelve-lead resting electrocardiography (ECG) was performed in 1175 individuals and peripheral Doppler studies were done in 50% of the individuals (n=631). RESULTS: The overall crude prevalence of hypertension (HTN) in this population is 21.1% (n=266) while the age standardized prevalence is 17.0%. Body mass index (BMI) and waist-hip ratio (WHR) were significantly higher (p < 0.001) in the HTN group compared to the non-hypertensive individuals. The prevalence of diabetes (p < 0.001), obesity (p < 0.001), CAD (p = 0.001) and PVD (p = 0.0055) was higher among the hypertensive compared to normotensive group. Multiple logistic regression analysis revealed HTN to be significantly associated with age (p < 0.001), body mass index (p < 0.001) and glucose intolerance (p = 0.005). CONCLUSION: The prevalence of hypertension appears to be high in this urban South Indian population and this calls for urgent steps for its prevention and control.

Prevalence of insulin resistance syndrome in a selected south Indian population--the Chennai urban population study-7 [CUPS-7].

BACKGROUND & OBJECTIVES: Although earlier studies had shown socio-economic factors to be strongly associated with the insulin resistance syndrome (IRS) and its components, there is still a paucity of data on Indians who have increased insulin resistance. In this study, we assessed the prevalence of IRS in two socio-economic groups in an urban south Indian population. METHODS: The Chennai Urban Population Study (CUPS) is an epidemiological study involving two residential areas in Chennal in south India. Of the 1262 eligible subjects (age > or = 20 yr) who participated in the study, 1070 (76.5%) subjects who had a complete set of data were recruited for this study. Insulin resistance was calculated using the homeostasis assessment (HOMA) model. Insulin resistance syndrome was defined as the presence of insulin resistance in combination with at least 2 of the following conditions: hyperglycaemia, hypertension, dyslipidemia or central body obesity. RESULTS: The overall prevalence of IRS was 11.2 per cent (95% confidence interval: 9.4-13.3). The prevalence of the IRS in the middle-income group (18.7%) was significantly higher compared to the low income group (6.5%; P < 0.001). Multiple logistic regression analysis revealed age (P < 0.001), body mass index (P < 0.05) and socio-economic status (P = 0.014) to be associated with IRS. INTERPRETATION & CONCLUSION: The overall prevalence rate of IRS was 11.2 per cent. Age and higher socio-economic status were the risk factors for insulin resistance in this selected urban south Indian study population.