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Thr54 allele carriers of the Ala54Thr variant of FABP2 gene have associations with metabolic syndrome and hypertriglyceridemia in urban South Indians
The intestinal fatty acid–binding protein gene is proposed as a candidate gene for diabetes because the protein it codes is involved in fatty
acid absorption and metabolism. This study investigates the association of the Ala54Thr variant of the intestinal fatty acid–binding protein
gene on type 2 diabetes mellitus and other related metabolic traits in Asian Indians. Ala54Thr polymorphism was genotyped by using
polymerase chain reaction–restriction fragment length polymorphism in unrelated 773 type 2 diabetic and 899 normal glucose-tolerant
(NGT) subjects, randomly chosen from the Chennai Urban Rural Epidemiology Study, an ongoing population-based study in South India.
The Ala54Thr polymorphism was not associated with type 2 diabetes mellitus or obesity. However, genotype-phenotype study revealed that
the NGT subjects carrying the Thr54 allele had significantly higher 2-hour plasma glucose ( P = .007), glycated hemoglobin ( P = .004),
2-hour insulin ( P = .027), and fasting low-density lipoprotein cholesterol ( P = .032) levels compared with those with the Ala54 allele.
Normal glucose-tolerant subjects with Ala54Thr and Thr54Thr genotypes had significantly higher fasting serum triglyceride levels ( P = .003)
compared with those with Ala54Ala. The subjects were stratified into those with hypertriglyceridemia (serum triglyceride levels
z150 mg/dL) and those without. The odds ratio for hypertriglyceridemia for the individuals carrying the Ala54Thr genotype was 1.491 (95%
confidence interval [CI], 1.22-1.83, P b .0001), and for those carrying the Thr54Thr genotype, it was 1.888 (95% CI, 1.34-2.67; P b .0001).
Subjects were also stratified into those with metabolic syndrome (MS) and those without, according to modified Adult Treatment Panel III
guidelines. The odds ratio (adjusted for age and sex) for MS for the individuals carrying the Ala54Thr genotype was 1.240 (95% CI,
1.02-1.51; P = .03), whereas for those carrying the Thr54Thr genotype, it was 1.812 (95% CI, 1.28-2.57; P = .001). Carriers of the Thr54
allele have associations with MS and hypertriglyceridemia in this urban South Indian population
Differential gene expression of NADPH oxidase (p22phox) and hemoxygenase-1 in patients with Type 2 diabetes and microangiopathy.
AIMS: While the downstream effects of increased reactive oxygen species (ROS) in the pathogenesis of diabetes were well studied, only a few studies have explored the cellular sources of ROS. We examined whether protection against oxidative stress is altered in patients with diabetes and microangiopathy by examining changes in NADPH oxidase (p22(phox)) and hemoxygenase-1 (HO-1) levels. METHODS: NADPH oxidase (p22(phox)) and HO-1 gene expression were probed by RT-PCR using leucocytes from patients with Type 2 diabetes without (n = 19) and with microangiopathy (n = 20) and non-diabetic subjects (n = 17). Levels of lipid peroxidation as measured by thiobarbituric reactive substances (TBARS) and protein carbonyl content (PCO) were determined by fluorimetric and spectrophotometric methods, respectively. RESULTS: p22(phox) gene expression (mean +/- SE) was significantly (P < 0.05) higher in diabetic patients with (0.99 +/- 0.04) and without microangiopathy (0.86 +/- 0.05) compared with control subjects (0.66 +/- 0.05). Consistent with the mRNA data, the p22(phox) protein expression and NADPH oxidase activity was also increased in cells from diabetic patients compared with control subjects. However, HO-1 gene expression was significantly (P < 0.05) lower in patients with (0.73 +/- 0.03) and without microangiopathy (0.85 +/- 0.02) compared with control subjects (1.06 +/- 0.03). The mean (+/- SE) levels of TBARS were significantly (P < 0.05) higher in diabetic patients with (14.36 +/- 1.3 nM/ml) and without microangiopathy (12.20 +/- 1.3 nM/ml) compared with control subjects (8.58 +/- 0.7 nM/ml). The protein carbonyl content was also significantly (P < 0.05) higher in diabetic patients with (1.02 +/- 0.04 nmol/mg protein) and without microangiopathy (0.84 +/- 0.06 nmol/mg protein) compared with control subjects (0.48 +/- 0.02 nmol/mg protein). In diabetic subjects, increased p22(phox) gene expression was negatively correlated with HO-1 and positively correlated with TBARS, PCO, HbA(1c) and diabetes duration. In contrast, HO-1 gene expression was correlated negatively with p22phox, TBARS, PCO, HbA(1c) and diabetes duration. CONCLUSION: Our results indicate that increased oxidative damage is seen in Asian Indians with Type 2 diabetes and microangiopathy and is associated with increased NADPH oxidase (p22(phox)) and decreased HO-1 gene expression
Reproducibility and validity of an interviewer-administered semi-quantitative food frequency questionnaire to assess dietary intake of urban adults in southern India
We report on the reproducibility and validity of a food frequency questionnaire (FFQ)
developed for southern India. One hundred and two adult subjects aged ]/20 years drawn from
the Chennai Urban Rural Epidemiology Study participated. The FFQ was developed based on
local foods and habits, and was administered three times at 0, 6 and 12 month periods (called
FFQ1, FFQ2 and FFQ3) to assess the reproducibility. To test the validity of the FFQ, multiple
24-h recalls collected at 2-monthly intervals for a period of 1 year and the estimated energy
intake/basal metabolic rate (EI/BMR) ratio were used. The ‘EpiNu’ in-house food and nutrient
database was used to compile dietary intakes, which were analyzed for statistical analysis. The
intraclass correlation coefficient for all three FFQs ranged from 0.72 for carbohydrates to 0.45
for folate. The de-attenuated Pearson correlation for the energy adjusted nutrients between
FFQ3 and 24-h recalls ranged from 0.73 for carbohydrates to 0.35 for calcium. Bland and
Altman plots for energy intake between the two methods showed the limits of agreement ranged
from 768 to /1358 calories/day (9/2 standard deviations). Misclassification was low for most of
the nutrients. Under-reporting of the energy intake (EI/BMR ratioB/1.2) was higher in females
than males. This FFQ appears to be a robust tool to measure dietary intakes in southern India
Telomere shortening occurs in Asian Indian Type 2 diabetic patients
Aim
Telomere shortening has been reported in several diseases including atherosclerosis
and Type 1 diabetes. Asian Indians have an increased predilection for
Type 2 diabetes and premature coronary artery disease. The aim of this study was
to determine whether telomeric shortening occurs in Asian Indian Type 2 diabetic
patients.
Methods
Using Southern-blot analysis we determined mean terminal restriction
fragment (TRF) length, a measure of average telomere size, in leucocyte DNA.
Type 2 diabetic patients without any diabetes-related complications (
n
= 40)
and age- and sex-matched control non-diabetic subjects (
n
= 40) were selected
from the Chennai Urban Rural Epidemiology Study (CURES). Plasma level of
malondialdehyde (MDA), a marker of lipid peroxidation, was measured by
TBARS (thiobarbituric acid reactive substances) using a fluorescence method.
Results
Mean (
±
SE) TRF lengths of the Type 2 diabetic patients (6.01
±
0.2 kb)
were significantly shorter than those of the control subjects (9.11
±
0.6 kb) (
P =
0.0001). Among the biochemical parameters, only levels of TBARS showed a
negative correlation with shortened telomeres in the diabetic subjects (
r =
−
0.36;
P =
0.02). However, telomere lengths were negatively correlated with insulin
resistance (HOMA-IR) (
r =
−
0.4;
P =
0.01) and age (
r =
−
0.3;
P =
0.058) and
positively correlated with HDL levels (
r =
0.4;
P =
0.01) in the control subjects.
Multiple linear regression (MLR) analysis revealed diabetes to be significantly
(
P <
0.0001) associated with shortening of TRF lengths.
Conclusions
Telomere shortening occurs in Asian Indian Type 2 diabetic patients
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 Small Dense LDL with Coronary Artery Disease and Diabetes in Urban Asian Indians - The Chennai Urban Rural Epidemiology Study (CURES-8)
Objective: Earlier studies in Europeans have identified small dense LDL to be associated with coronary artery
disease and diabetes. In this study we assessed the association of small dense LDL with diabetes and CAD in
Asian Indians.
Methods: Study subjects were selected from the Chennai Urban Rural Epidemiology Study (CURES), a
population based study on representative sample of Chennai city in southern India. Group 1:non-diabetic
subjects (n=30); Group 2: diabetic subjects without CAD (n=30); Group 3:diabetic subjects with CAD (n=30).
LDL subfractions were estimated using LipoPrint LDL system. LDL subfractions 3 and above, defined as
small dense LDL was summed up to determine the overall small LDL. 75th percentile of the overall small
dense LDL in non-diabetic subjects was used as a cut-off for defining elevated levels of small dense LDL.
Results: The mean age of the study subjects was not significantly different among groups. Overall small
dense LDL was significantly higher in diabetic subjects with CAD (16.7 ± 11.1 mg/dl, p<0.05) and without
CAD (11.1 ± 8.0 mg/dl, p<0.05) compared to non-diabetic subjects without CAD (7.2 ± 6.8 mg/dl). Small
dense LDL showed a positive correlation with fasting plasma glucose (r=0.252, p=0.023), HbA1c (r=0.281,
p=0.012), total cholesterol (r=0.443, p<0.001), triglycerides(r=0.685, p<0.001), LDL(r=0.342, p=0.002), total
cholesterol/HDL ratio (r=0.660, p=<0.001) and triglycerides/HDL ratio(r=0.728, p<0.001) and a negative
correlation with HDL cholesterol (r= -0.341, p=0.002) and QUICKI values (r= -0.260, p=0.019). ROC curves
constructed to predict elevated small dense LDL ((9.0 mg/dl) revealed that triglycerides/HDL ratio and total
cholesterol/HDL ratio had higher AUC values compared to other parameters. A triglycerides/HDL ratio of
3.0 had the optimum sensitivity (80.0%) and specificity (78.0%) for detecting elevated small dense LDL.
Conclusion: This data suggests that in Asian Indians, small dense LDL is associated with both diabetes and
CAD and that a triglycerides/HDL ratio (3.0 could serve a surrogate marker of small dense LDL
Risk of noninsulin dependent diabetes mellitus conferred by obesity and central adiposity in different ethnic groups: A comparative analysis between Asian Indians, Mexican Americans and Whites
Epidemiological data from Asian Indians from Madras (AI) and Mexican Americans (MA) and non-Hispanic Whites (NHW) from San Antonio heart study were compared to determine the possible contributions by the anthropometric measurements to the varied prevalence of noninsulin dependent diabetes mellitus (NIDDM) in these ethnic groups. MA had the highest rate of obesity (mean body mass index (BMI) 28.9 ± 5.9 kg/m2) and the highest prevalence of diabetes (men 19.6%; women 11.8%, < 0.001 vs other groups). NHW although had high rates of obesity (mean BMI 26.2 ± 5.2 kg/m2) had low prevalence of diabetes (men 4.4%; women 5.7%) than the AI (men 9.9%; women 5.7%) (Mean BMI 22.3 ± 4.4 kg/m2, P < 0.001). Although AI had lower BMI than MA, the risk conferred by BMI was similarly high in AI and MA and both the ethnic groups had higher risks than NHW. Impaired glucose tolerance (IGT) was also more prevalent in MA than in AI (men, MA vs AI, 11.8 vs 7.5%, P < 0.003; women 16.1 vs 5.5%, P < 0.001). NHW had lower prevalence of IGT in men (5.7%) and women (6.3%) which were significantly lower (P < 0.001) compared to MA only. Age and BMI were predictive factors of NIDDM in all, while waist to hip ratio (WHR) was significant only in AI and MA, although NHW had high WHR. This may be an indicator of differences in genetic susceptibility. This study also highlights the similarity in risk factors between AI and MA living in urban environment and the significance of distribution of adiposity in the comparatively lean AI
Incidence of IDDM in children in urban population in Southern India
This study was carried out to estimate the incidence of childhood insulin dependent diabetes mellitus (IDDM) in an urban southern Indian population. A registry for IDDM has been set up in the city of Madras, South India. Details of newly diagnosed IDDM children, aged less than 15 years, were analysed retrospectively, for a period of 1991–1994. Primary sources were government and service hospitals, large diabetes clinics and secondary sources were diabetes camp, private diabetologists and endocrinologists. A capture-recapture method was used and the estimate of case in the population (1991 census) was calculated. Incidence (case/100 000) was calculated in the total group and then for boys and girls separately. The incidence for the 4 year period was 10.5/100 000/year (CI 5.0). The corresponding values for boys and girls were 12.6 ± 11 and 9.6 ± 4.7 respectively. The peak incidence was between 10 and 12 years. This is the first population based incidence data from India and showed that the incidence of childhood IDDM is not low in urban children
Prevalence of retinopathy in non insulin dependent diabetes mellitus at a diabetes centre in Southern India
A cohort of 6792 NIDDM patients attending a diabetes centre at Madras in South India was screened using a combination of retinal photography and clinical examination by retinal specialists. A total of 2319 patients (34.1%) had evidence of retinopathy. This included 2090 patients (30.8%) with non-proliferative diabetic retinopathy including 435 patients (6.4%) with maculopathy and 229 patients (3.4%) with proliferative diabetic retinopathy. Multiple logistic regression analyses showed that duration of diabetes, glycosylated haemoglobin, type of treatment (insulin treatment versus non-insulin treatment), systolic and diastolic blood pressures and serum creatinine, showed a positive association with retinopathy while body mass index (BMI) showed an inverse association. The prevalence rates of retinopathy in Southern Indians are comparable to those seen in Europeans. However in view of the high prevalence of diabetes in the Indian sub-continent, diabetic retinopathy could become a formidable challenge in the future