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Cystatin C and cystatin glomerular filtration rate as markers of early renal disease in Asian Indian subjects with glucose intolerance (CURES-32).
No full textBACKGROUND: The aim of this study was to assess cystatin C (cys-C) as a marker of early diabetic nephropathy and cystatin glomerular filtration rate (cys-GFR) in Asian Indians. METHODS: Five groups of subjects were studied: Group 1, normal glucose tolerance (NGT) and normoalbuminuria (n = 43); group 2, impaired glucose tolerance (IGT) and normoalbuminuria (n = 44); group 3, type 2 diabetes (T2DM) with neither microalbuminuria nor retinopathy (n = 40); group 4, T2DM with microalbuminuria but without diabetic retinopathy (n = 40); and group 5, T2DM with microalbuminuria and any degree of diabetic retinopathy (DR) (n = 42). Subjects were recruited from the Chennai Urban Rural Epidemiology Study (CURES). Microalbumin concentration was assessed in the urine sample by immunoturbidometric assay. cys-C concentrations were measured in serum by a high-sensitivity particle-enhancing nephlometric assay. cys-GFR was calculated by the formula (86.7/cys-C) - 4.2. RESULTS: cys-C levels were highest in group 5 (1.75 +/- 0.12 mg/L) followed by group 4 (1.30 +/- 0.08 mg/L), group 3 (0.98 +/- 0.04 mg/L), group 2 (0.89 +/- 0.03 mg/L), and group 1 (0.79 +/- 0.18 mg/L, P < 0.001). cys-GFR levels were in reverse order going from highest in group 1, followed by groups 2, 3, 4, and 5. cys-C levels were correlated with age, fasting plasma glucose, glycosylated hemoglobin, microalbuminuria, and serum cholesterol. CONCLUSIONS: cys-C levels increase and cys-GFR levels decrease with increasing severity of glucose intolerance and are highest and lowest, respectively, in type 2 diabetes mellitus (T2DM) subjects with microalbuminuria and retinopathy. In T2DM subjects, cys-C and cys-GFR appear to be useful markers of early renal damage
Molecular convergence of hexosamine biosynthetic pathway and ER stress leading to insulin resistance in L6 skeletal muscle cells
No full textAugmentation of hexosamine biosynthetic
pathway (HBP) and endoplasmic reticulum (ER) stress
were independently related to be the underlying causes of
insulin resistance. We hypothesized that there might be a
molecular convergence of activated HBP and ER stress
pathways leading to insulin resistance. Augmentation of
HBP in L6 skeletal muscle cells either by pharmacological
(glucosamine) or physiological (high-glucose) means,
resulted in increased protein expression of ER chaperones
(viz., Grp78, Calreticulin, and Calnexin), UDP-GlcNAc
levels and impaired insulin-stimulated glucose uptake.
Cells silenced for O-glycosyl transferase (OGT) showed
improved insulin-stimulated glucose uptake (P\0.05) but
without any effect on ER chaperone upregulation. While
cells treated with either glucosamine or high-glucose
exhibited increased JNK activity, silencing of OGT resulted
in inhibition of JNK and normalization of glucose
uptake. Our study for the first time, demonstrates a
molecular convergence of O-glycosylation processes and
ER stress signals at the cross-road of insulin resistance in
skeletal muscle
Refined grain consumption and the metabolic syndrome in urban Asian Indians (Chennai Urban Rural Epidemiology Study 57).
No full textThe objective of the study was to evaluate the association of refined grains consumption with insulin resistance and the metabolic syndrome in an urban south Indian population. The study population comprised 2042 individuals aged > or = 20 years randomly selected from the Chennai Urban Rural Epidemiology Study (CURES), a cross-sectional study on a representative population of Chennai, southern India. The metabolic syndrome was defined according to modified Adult Treatment Panel III guidelines; and insulin resistance, by the homeostasis assessment model. The mean refined grain intake was 333 g/d (46.9% of total calories) in this population. After adjustment for age, sex, body mass index, metabolic equivalent, total energy intake, and other dietary factors, higher refined grain intake was significantly associated with higher waist circumference (8% higher for the highest vs the lowest quartile, P for trend < .0001), systolic blood pressure (2.9%, P for trend < .0001), diastolic blood pressure (1.7%, P for trend = .03), fasting blood glucose (7.9%, P for trend = .007), serum triglyceride (36.5%, P for trend < .0001), low high-density lipoprotein cholesterol (-10.1%, P for trend < .0001), and insulin resistance (13.6%, P < .001). Compared with participants in the bottom quartile, participants who were in the highest quartile of refined grain intake were significantly more likely to have the metabolic syndrome (odds ratio, 7.83; 95% confidence interval, 4.72-12.99). Higher intake of refined grains was associated with insulin resistance and the metabolic syndrome in this population of Asian Indians who habitually consume high-carbohydrate diets
Common variants of inflammatory cytokine genes are associated with risk of nephropathy in type 2 diabetes among Asian Indians.
Get PDFBACKGROUND: Inflammatory cytokine genes have been proposed as good candidate genes for conferring susceptibility to diabetic nephropathy. In the present study, we examined the combined effect of multiple alleles of pro inflammatory cytokine genes for determining the risk of nephropathy in type 2 diabetic patients. METHODOLOGY/PRINCIPAL FINDINGS: Eight single nucleotide polymorphisms (SNPs) of pro-inflammatory cytokine genes (CCL2, TGFB1, IL8, CCR5, and MMP9) were genotyped in two independently ascertained type 2 diabetic cohorts with (DN) and without nephropathy (DM); consisting of patients from North India (n = 495) and South India (n = 188). Genotyping was carried out using PCR, allele specific oligonucleotide-PCR (ASO-PCR), PCR-RFLP and TaqMan allelic discrimination assays and the gene-gene interaction among genetic variants were determined by multi dimensional reduction (MDR) software. Serum high sensitive CRP (hs-CRP) levels were measured by ELISA. The hs-CRP levels were significantly higher in DN as compared to the DM group (p<0.05). The CCL2, IL8, CCR5 and MMP9 polymorphisms were found to be associated with the risk of diabetic nephropathy. Frequency of CCL2 II, IL8 -251AA, CCR5 59029AA and MMP9 279Gln/Gln genotypes were significantly higher in DN than in DM group (p<0.05) and associated with an increased risk of nephropathy in both North and South Indian cohorts. CCR5 DD and IL8 -251AA genotypes were more prevalent in North Indian DN group only. The co-occurrence of risk associated genotypes (II, -2518GG (CCL2), DD (CCR5) and 279Gln/Gln (MMP9) conferred a tenfold increased risk of nephropathy among type 2 diabetics (p<0.0002). CONCLUSION: The present study highlights that common variants of inflammatory cytokine genes exert a modest effect on risk of DN and a combination of risk alleles confer a substantial increased risk of nephropathy in type 2 diabetes among Asian Indians
Efficacy and safety of exenatide in patients of Asian descent with type 2 diabetes inadequately controlled with metformin or metformin and a sulphonylurea☆☆☆
No full textAims: To evaluate the efficacy of exenatide in Asian patients with type 2 diabetes (T2D)
inadequately controlled with oral agents.
Methods: Patients taking metformin (MET) alone or with a sulphonylurea (SU) were randomly
assigned to exenatide 5 mg then 10 mg twice-daily for 4 and 12 weeks, respectively, or
placebo. The primary endpoint was baseline to endpoint HbA1c change.
Results: 466 patients (age 54 9 years, weight 68.7 11.2 kg, BMI 26.3 3.3 kg/m2, and HbA1c
8.3 1.1%; mean S.D.) were enrolled in the full analysis set. Endpoint HbA1c reduction
(mean [95% CI]) with exenatide was superior to placebo (1.2 [1.3, 1.1]% vs. 0.4 [0.5,
0.2]%, p < 0.001). More exenatide- than placebo-treated patients achieved HbA1c 7% (48%
vs. 17%, p < 0.001). At endpoint, weight reduction was greater with exenatide (1.2 [1.5,
0.9] kg) than placebo (0.1 [0.3, 0.2] kg), p < 0.001. Nausea, generally mild-to-moderate,
was the most common adverse event with exenatide (25% vs. 1% with placebo). The
incidence of symptomatic hypoglycaemia with exenatide and placebo were 36% and 9%,
respectively ( p < 0.001). Hypoglycaemia rates (events/patient-year) for patients taking exenatide
with MET or MET and SU were 1.8 (0.9, 3.7) and 4.7 (3.5, 6.5), respectively.
Conclusion: Exenatide treatment improved glycaemic control in Asian patients with T2D and
had a similar safety profile as in non-Asian patients
Reliability and Validity of a Modified PHQ-9 Item Inventory (PHQ-12) as a Screening Instrument for Assessing Depression in Asian Indians (CURES - 65)
Get PDFAbstract
Objectives: To evaluate the validity and reliability of the modified Patient Health Questionnaire(PHQ) 12 item
instrument as a screening tool for assessing depression compared to the PHQ -9 in a representative south
Indian urban population.
Methods: The Chennai Urban Rural Epidemiology Study [CURES] is a large cross-sectional study conducted
in Chennai, South India. In Phase 1 of CURES(urban component), 26,001 individuals aged ≥ 20 years
individuals were selected by a systematic sampling technique of whom one hundred subjects were randomly
selected, using computer-generated numbers, for this validation study. Two self-reported questionnaires
(modified PHQ-12 item and PHQ 9 item) were administered to the subjects to compare their effectiveness in
detecting depression. Reliability and validity were assessed and Receiver Operating Characteristic (ROC)
curves were plotted. Pearson’s correlation was used to compare the two questionnaires.
Results: The mean age of the study was 38.6±11.6 years and 48% were males. Pearson’s correlation coefficient
between the modified PHQ-12 and the PHQ-9 item was 0.913 [p<0.0001]. Factor Analysis revealed that the
modified PHQ 12 item scale can be used as a unidimensional scale and had excellent internal
consistency(Cronbach’s alpha:0.88). A cut point of >4 calculated using the ROC curves for the modified PHQ-
12 item had the highest sensitivity (92.0%) and specificity (90.7%) using PHQ-9 as the gold standard. The
positive predictive value was 76.7%, and the negative predictive value, 97.1% and the area under the ROC
curve, 0.979 (95% Confidence Interval: 0.929 - 0.997, p<0.0001).
Conclusion: The modified PHQ-12 item is a valid and reliable instrument for large scale population based
screening of depression in Asian Indians and a cut point score of 4 or greater gave the highest sensitivity and
specificity.
Unexpected and Abnormally Low Hdl Cholesterol Levels on Combination Hypolipidemic Therapy
Get PDFAbstract
In general, Indians have low HDL cholesterol levels. Fenofibrate, a drug widely used in the treatment of
hypertriglyceridemia, usually also increases HDL cholesterol. There have been a few reports in the literature of a
paradoxical decrease in serum HDL-cholesterol in patients treated with fenofibrate, either alone or in combination
with a statin. We report three cases of paradoxical decrease in serum HDL- cholesterol in type 2 diabetic patients
treated with a statin-fenofibrate combination
Parental history of type 2 diabetes mellitus, metabolic syndrome, and cardiometabolic risk factors in Asian Indian adolescents
No full textThe objective was to study the influence of parental history of type 2 diabetes mellitus on prevalence of the metabolic syndrome (MS)
and other cardiometabolic risk factors in Asian Indian adolescents. Adolescents aged 12 to 19 years (N = 321) were recruited from the
Chennai Urban Rural Epidemiology Study. Based on parental diabetic status, 3 groups were studied: group 1, offspring of parents with
normal glucose tolerance (n = 105); group 2, offspring of 1 diabetic parent (n = 114); and group 3, offspring of 2 diabetic parents (n = 102).
Subjects underwent blood pressure and anthropometric measurements as well as an oral glucose tolerance test and a fasting lipid profile.
Metabolic syndrome was diagnosed using the International Diabetes Federation definition. Body mass index (P b .001) and waist and hip
circumference (P b .05 for group 2 and P b .001 for group 3) were significantly higher in groups 2 and 3 compared with group 1. Highdensity
lipoprotein cholesterol was significantly lower in groups 2 and 3 compared with group 1 (P b .05). Serum triglycerides were
significantly higher in group 3 (P b .05) compared with the other 2 groups. Adolescents in group 3 (P b .001) and group 2 (P b .05) were
significantly more overweight and had more abdominal obesity compared with those in group 1. Impaired fasting glucose and impaired
glucose tolerance were also significantly higher in group 3 compared with the other 2 groups. High blood pressure showed an increasing
trend from group 1 to group 3 (P for trend b .05). Two metabolic abnormalities were present in 7.6%, 14.9%, and 22.5% of adolescents in
groups 1, 2, and 3, respectively (trend χ2: 9.04, P = .003). Prevalence of MS was higher in groups 2 and 3 compared with group 1 but did not
reach statistical significance because of small numbers. The cardiometabolic profile of the parents was similar to that of the adolescents.
Parental history of type 2 diabetes mellitus increases risk of not only glucose intolerance but also other cardiometabolic risk factors like
overweight, low high-density lipoprotein cholesterol, and high blood pressure in Asian Indian adolescents.
© 2009 Elsevier Inc. All rights reserved
Prevalence and significance of generalized and central body obesity in an urban Asian Indian population in Chennai, India (CURES: 47)
No full textObjectives: To determine the prevalence of generalized and abdominal obesity in urban Asian Indians and compare the
association of body mass index (BMI) and waist circumference (WC) with metabolic risk variables.
Methods: Subjects were recruited from the Chennai Urban Rural Epidemiology Study (CURES) carried out between 2001 and
2004 and involved 2350/2600 eligible subjects (response rate 90.4%). Anthropometric measurements, lipids and oral glucose
tolerance tests were carried out. Generalized obesity (BMIX23 kgm2) and abdominal obesity (WCX90cm in men and
X80cm in women) were defined using WHO Asia Pacific guidelines.
Results: The age standardized prevalence of generalized obesity was 45.9% (95% CI: 43.9–47.9%), (women: 47.4%; men:
43.2%, P¼0.210), while that of abdominal obesity was 46.6% (95% CI: 44.6–48.6%), (women: 56.2%4 men: 35.1%,
Po0.001). Area under the curve for identifying subjects with any three metabolic risk factors using BMI was 0.66, 95% CI: 0.63–
0.69, Po0.001, while, for WC, it was 0.70, 95% CI: 0.66–0.74, Po0.001 for men, and 0.69, 95% CI: 0.65–0.74, Po0.001 for
women. Isolated generalized obesity (normal WC, increased BMI) was present in 12.7% of men and 6.1% of women. Isolated
abdominal obesity (increased WC, normal BMI) was present in 4.7% of men and 14% of women. Combined obesity was present
in 32.6% of men and 43.3% of women.
Conclusions: In Asian Indians, the prevalence of combined obesity is high among both sexes, while isolated generalized obesity
is more common in men and isolated abdominal obesity more common in women. However, these prevalence rates vary
markedly depending on cut points used. WC is a better marker of obesity-related metabolic risk than BMI in women compared
to men in this population