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Association of telomere shortening with impaired glucose tolerance and diabetic macroangiopathy
No full textObjective: Shortening of telomere length has been reported in several conditions including Type 2 diabetes and atherosclerosis. The aims of
this study were (1) to assess whether telomere shortening occurs at the stage of pre-diabetes, i.e., impaired glucose tolerance (IGT) and (2)
whether telomere shortening was greater in Type 2 diabetic subjects with atherosclerotic plaques.
Methods: Subjects with impaired glucose tolerance (IGT) (n = 30), non-diabetic control subjects (n = 30), Type 2 diabetic patients without
(n = 30) and with atherosclerotic plaques (n = 30) were selected from the Chennai Urban Rural Epidemiology Study (CURES), an ongoing
epidemiological population-based study. Southern-blot analysis was used to determine mean terminal restriction fragment (TRF) length, a
measure of average telomere size, in leukocyte DNA. Levels of thiobarbituric acid reactive substances (TBARS), protein carbonyl content
(PCO) and high sensitive C-reactive protein (hs-CRP) were measured by standard methodologies. Carotid intima-media thickness (IMT) was
assessed by high resolution B-mode ultrasonography.
Results: The mean (±S.E.) TRF lengths were significantly lower in IGT subjects (6.97±0.3 kb; p = 0.002) and lower still in Type 2 diabetic
subjects without plaques (6.21±0.2; p = 0.0001) and lowest in Type 2 diabetic subjects with atherosclerotic plaques (5.39±0.2; p = 0.0001)
when compared to control subjects (8.7±0.5). In IGT subjects, TRF length was positively correlated to HDL cholesterol and negatively
correlated to glycated hemoglobin (HbA1c), TBARS, PCO, HOMA-IR and IMT. In multiple linear regression analysis, presence of diabetes,
HDL cholesterol and increased TBARS levels appear as significant determinants of telomere shortening.
Conclusion: Telomere shortening is seen even at the stage of IGT. Among subjects with Type 2 diabetes, those with atherosclerotic plaques
had greater shortening of telomere length compared to those without plaques
Association of A1C with cardiovascular disease and metabolic syndrome in Asian Indians with normal glucose tolerance.
Get PDFOBJECTIVE: This study examines the association of A1C with cardiovascular disease (CVD) risk factors, coronary artery disease (CAD), and metabolic syndrome in Asian Indians with normal glucose tolerance (NGT). RESEARCH DESIGN AND METHODS: This cross-sectional study recruited subjects from phase III of the Chennai Urban Rural Epidemiology Study (CURES), an epidemiological study in a representative population of Chennai (formerly Madras) in South India, conducted between January 2003 and June 2004. Included were 1,644 subjects with NGT, i.e., fasting plasma glucose <100 mg/dl (5.6 mmol/l) and 2-h postload plasma glucose <140 mg/dl (7.8 mmol/l). A1C was measured using the Biorad Variant machine. Metabolic syndrome was defined based on modified Adult Treatment Panel III guidelines. RESULTS: The mean +/- SD A1C value in the study cohort was 5.5 +/- 0.4%. A1C showed a significant association with BMI (beta = 0.017, P < 0.001), systolic (beta = 0.002, P = 0.028) and diastolic (beta = 0.202, P = 0.017) blood pressure, waist circumference (beta = 0.007, P < 0.001), serum cholesterol (beta = 0.002, P < 0.001), triglycerides (beta = 0.001, P < 0.001), LDL cholesterol (beta = 0.002, P < 0.001), fasting insulin (beta = 0.009, P < 0.001), and homeostasis model assessment of insulin resistance (beta = 0.047, P < 0.001) after adjusting for age and sex. Regression analysis showed that A1C had a strong association with metabolic syndrome that persisted after adjusting for age and sex (odds ratio [OR] 2.9 [95% CI 2.08-4.00]; P < 0.001). A1C also had a strong association with CAD (2.6 [1.23-5.63]; P = 0.01), but the significance was lost when adjusted for age and sex. CONCLUSIONS: There is a strong association of A1C with prevalent CVD risk factors in Asian-Indian subjects with NGT
Prevalence and Risk Factors of Diabetic Nephropathy in an Urban South Indian Population: The Chennai Urban Rural Epidemiology Study (CURES 45)
Get PDFOBJECTIVE— The aim of this study was to determine the prevalence of diabetic nephropathy
among urban Asian-Indian type 2 diabetic subjects.
RESEARCH DESIGN AND METHODS— Type 2 diabetic subjects (n 1,716), inclusive
of known diabetic subjects (KD subjects) (1,363 of 1,529; response rate 89.1%) and randomly
selected newly diagnosed diabetic subjects (NDD subjects) (n 353) were selected from
the Chennai Urban Rural Epidemiology Study (CURES). Microalbuminuria was estimated by
immunoturbidometric assay and diagnosed if albumin excretion was between 30 and 299 g/mg
of creatinine, and overt nephropathy was diagnosed if albumin excretion was 300 g/mg of
creatinine in the presence of diabetic retinopathy, which was assessed by stereoscopic retinal
color photography.
RESULTS— The prevalence of overt nephropathy was 2.2% (95% CI 1.51–2.91). Microalbuminuria
was present in 26.9% (24.8 –28.9). Compared with the NDD subjects, KD subjects had
greater prevalence rates of both microalbuminuria with retinopathy and overt nephropathy (8.4
vs. 1.4%, P 0.001; and 2.6 vs. 0.8%, P 0.043, respectively). Logistic regression analysis
showed that A1C (odds ratio 1.325 [95% CI 1.256 –1.399], P 0.001), smoking (odds ratio
1.464, P0.011), duration of diabetes (1.023, P0.046), systolic blood pressure (1.020, P
0.001), and diastolic blood pressure (1.016, P0.022) were associated with microalbuminuria.
A1C (1.483, P 0.0001), duration of diabetes (1.073, P 0.003), and systolic blood pressure
(1.031, P 0.004) were associated with overt nephropathy.
CONCLUSIONS— The results of the study suggest that in urban Asian Indians, the prevalence
of overt nephropathy and microalbuminuria was 2.2 and 26.9%, respectively. Duration of
diabetes, A1C, and systolic blood pressure were the common risk factors for overt nephropathy
and microalbuminuria
‘ADOPT’ and ‘DREAM’ trials and the Indian perspective
No full textTwo recent landmark studies, the ADOPTand DREAM trials have looked at
efficacy of rosiglitazone in the treatment and prevention of type 2 diabetes. The results
of the ADOPTstudy done on recently diagnosed type 2 diabetic subjects suggested that
rosiglitazone was more effective in slowing down the progression to monotherapy
failure compared to metformin or glyburide. However, rosiglitazone was associated
with weight gain, edema, increase in the levels of LDL cholesterol and a reduction in the
haematocrit and higher rates of fractures in women. The DREAM study looked at the
efficacy of rosiglitazone in the prevention of type 2 diabetes in individuals with prediabetes.
There was a 62% reduction in risk for developing diabetes with rosiglitazone
and this effectwasmore pronounced in obese and overweight individuals. Liver function
was unaffected or improved with rosiglitazone. However, the frequency of non-fatal
heart failure was higher in the rosiglitazone, groupcompared to the placebo, group. The
prevalence of type 2 diabetes in India has been steadily increasing over the decades and
the prevalence of Impaired Glucose Tolerance (IGT) is also very high. Although the
ADPOT and DREAM have widened the horizon for the use of rosiglitazone in both
treatment and prevention of type 2 diabetes, the side-effects associated with it points
to the need for carefully choosing patients
Absence of Association of Metabolic Syndrome with PPARGC1A, PPARG and UCP1 Gene Polymorphisms in Asian Indians
No full textThe objective of this study was to evaluate the association of PPARG coactivator1 alpha
(PPARGC1A), peroxisome proliferator activated receptor gamma (PPARG), and uncoupling
protein1 (UCP1) gene polymorphisms with the metabolic syndrome (MS) in an Asian Indian
population. Nine common polymorphisms were genotyped via polymerase chain reaction restriction
fragment length polymorphism and direct sequencing in 950 normal glucose-tolerant
subjects and 550 type 2 diabetic subjects, chosen randomly from the Chennai Urban Rural
Epidemiological Study, an ongoing population based study in Southern India. Among the 9
polymorphisms examined, only the Thr394Thr variant of the PPARGC1A gene was significantly
associated with diabetes and obesity. The genotype frequency of GA of Thr394Thr variant
was 16% (138/887) in the nonMS group and 22% (136/613) in the MS group, and this genotype
frequency was significantly higher with MS both in males (p 0.01) and females (p
0.05), compared to the without-MS group. Logistic regression analysis revealed that the odds
ratio for MS for the susceptible genotype GA of Thr394Thr was 1.411 [95% CI: 1.03–1.84, p
0.012]. In the multiple logistic regression analysis, however, there was no association of this
polymorphism as an independent factor with MS. Hence, the study shows that the polymorphisms
in the PPARGC1A, PPARG and UCP1 genes are not associated with MS in Asian Indians
Prevalence of metabolic syndrome using WHO, ATPIII and IDF definitions in Asian Indians: the Chennai Urban Rural Epidemiology Study (CURES-34)
No full textAim To compare the prevalence of metabolic syndrome (MS) using the
World Health Organisation (WHO), Adult Treatment Panel III (ATPIII) and
International Diabetes Federation (IDF) criteria of MS in an urban south
Indian population, and their ability to identify coronary artery disease (CAD)
in males and females.
Methods Chennai Urban Rural Epidemiology Study (CURES) is one of the
largest epidemiological studies on diabetes carried out in India, in which
26 001 individuals aged ≥20 years were screened using systematic random
sampling method. Every tenth subject recruited in Phase 1 of CURES was
requested to participate in Phase 3, and the response rate was 90.4%.
An oral glucose tolerance test (OGTT) was performed in all individuals
except self-reported diabetic subjects. Anthropometric measurements and
lipid estimations were done in all subjects and the prevalence of MS estimated
using the three criteria. Diagnosis of CAD, made by resting 12 lead ECG, was
compared by the three criteria of MS.
Results MS was identified in 546 subjects (23.2%) by WHO criteria, 430
subjects (18.3%) by ATPIII criteria and 607 subjects (25.8%) by IDF criteria.
Only 224 of these subjects were identified by all the three criteria. There was
an increased risk of probable CAD in MS subjects diagnosed by WHO criteria
(odds ratio (OR) 3.86, 95% Confidence Interval (CI), 2.37–6.29, p < 0.001),
compared to ATPIII criteria (OR 2.19, 95% CI 1.30–3.67, p < 0.05) and IDF
criteria (OR 1.90, 95% CI 1.16–3.12, p < 0.05). The WHO criteria marked
out a much higher population for CAD risk compared to ATPIII and IDF
criteria in males, but not in females.
Conclusion In Asian Indians, the WHO, ATPIII and IDF criteria of MS
identify different individuals. The WHO criteria identify a greater number of
CAD subjects in males, but not in females. Copyright 2006 John Wiley &
Sons, Ltd
Glutamine fructose-6-phosphate amidotransferase (GFAT) gene expression and activity in patients with type 2 diabetes: inter-relationships with hyperglycaemia and oxidative stress.
No full textOBJECTIVE:: Cell culture and animal model studies have strongly suggested a role for the rate-limiting enzyme for hexosamine biosynthesis, glutamine:fructose-6-phosphate amidotransferase (GFAT) in insulin resistance. However, there are very few clinical studies and none on Asian Indians, a high-risk group for type 2 diabetes (T2DM), which examined the role of GFAT in insulin resistance and T2DM. DESIGN AND METHOD:: The study group comprised of T2DM subjects without any complications (n=25) and control non-diabetic subjects (n=23). GFAT mRNA expression and activity were measured by semi-quantitative RT-PCR and fluorimetry, respectively. Oxidative damage was assessed in plasma by the extent of lipid peroxidation [thiobarbituric acid reactive substances (TBARS)] and protein carbonyl content (PCO) using standard methods. RESULT:: The mean (+/-SE) GFAT activity was significantly higher in diabetic (30.22+/-2.40 pM/mg protein/min) compared to control subjects (20.10+/-1.12 pM/mg protein/min) (p<0.001). Plasma levels of diabetic patients also exhibited increased lipid peroxidation and protein carbonylation. GFAT activity was positively correlated (p<0.005) with GFAT mRNA, HbA(1c), insulin resistance (HOMA-IR), postprandial plasma glucose and levels of TBARS and PCO. In multiple logistic regression analysis, the association between GFAT activity and T2DM persisted even after adjusting for age, gender, BMI and HOMA-IR (OR=1.202, p=0.026). CONCLUSION:: Increased GFAT activity appears to be associated with insulin resistance, postprandial hyperglycaemia and oxidative stress in T2DM and may point towards a potential pathway amenable for therapeutic intervention
‘ADOPT’ and ‘DREAM’ trials and the Indian perspective
No full textTwo recent landmark studies, the ADOPTand DREAM trials have looked at
efficacy of rosiglitazone in the treatment and prevention of type 2 diabetes. The results
of the ADOPTstudy done on recently diagnosed type 2 diabetic subjects suggested that
rosiglitazone was more effective in slowing down the progression to monotherapy
failure compared to metformin or glyburide. However, rosiglitazone was associated
with weight gain, edema, increase in the levels of LDL cholesterol and a reduction in the
haematocrit and higher rates of fractures in women. The DREAM study looked at the
efficacy of rosiglitazone in the prevention of type 2 diabetes in individuals with prediabetes.
There was a 62% reduction in risk for developing diabetes with rosiglitazone
and this effectwasmore pronounced in obese and overweight individuals. Liver function
was unaffected or improved with rosiglitazone. However, the frequency of non-fatal
heart failure was higher in the rosiglitazone, groupcompared to the placebo, group. The
prevalence of type 2 diabetes in India has been steadily increasing over the decades and
the prevalence of Impaired Glucose Tolerance (IGT) is also very high. Although the
ADPOT and DREAM have widened the horizon for the use of rosiglitazone in both
treatment and prevention of type 2 diabetes, the side-effects associated with it points
to the need for carefully choosing patients
Lack of association between serum adiponectin levels and the Pro12Ala polymorphism in Asian Indians
No full textAims
The aim of the study was to investigate the association of serum adiponectin
levels with the Pro12Ala polymorphism of the peroxisome proliferator
activated receptor-
γ
(
PPARG
) gene in Asian Indians.
Methods
We selected 400 diabetic subjects, 200 with the Pro12Pro genotype
(100 male and 100 female) and 200 with the Pro12Ala genotype (100 male and
100 female) and 400 age- and sex-matched normal glucose tolerance subjects
with similar genotype profiles from the Chennai Urban Rural Epidemiology
Study. Fasting serum adiponection levels were measured using radioimmunoassay.
The Pro12Ala polymorphism was genotyped by PCR–restriction fragment
length polymorphism using
BstUI
.
Results
All clinical and biochemical parameters were similar in the subjects with
the Pro12Pro and Pro12Ala genotypes. There was no significant difference in serum
adiponectin values between subjects with the Pro12Pro and Pro12Ala genotypes
(males 5.4 vs. 5.8
μ
g/ml,
P
= 0.546; females 6.9 vs. 7.2
μ
g/ml,
P
= 0.748). Adiponectin
values did not differ among these two genotypes even when categorized
based on their diabetes status (normal glucose tolerance Pro12Pro 7.9 vs. Pro12Ala
7.7
μ
g/ml,
P
= 0.994; diabetes Pro12Pro 4.7 vs. Pro12Ala 5.4
μ
g/ml,
P
= 0.622).
Conclusion
The Pro12Ala polymorphism of the
PPARG
gene is not associated
with serum adiponectin levels in Asian Indians