Incidence of Diabetes and Pre-diabetes in a Selected Urban South Indian Population (Cups - 19)

Abstract Objectives: Several cross-sectional studies have reported on the prevalence of diabetes in India. However, there are virtually no longitudinal population-based studies on the incidence of diabetes from India. The aim of the study was to determine the incidence of diabetes and prediabetes in an urban south Indian population. Methods: The Chennai Urban Population Study [CUPS], an ongoing epidemiological study in two residential colonies in Chennai [the largest city in southern India, formerly called Madras] was launched in 1996; the baseline study was completed in 1997. Follow-up examination was performed after a mean period of 8 years. At follow-up, 501 [47.0%] subjects had moved out of this colonies and were lost to follow-up. Of the remaining 564 individuals, 513 [90.9%] provided blood samples for biochemical analysis. Regression analysis was done using incident diabetes as dependant variable to identify factors associated with development of diabetes or pre-diabetes. Results: Among subjects with normal glucose tolerance (NGT) at baseline [n=476], 64 (13.4%) developed diabetes and 48 (10.1%) developed pre-diabetes (IGT or IFG). The incidence rate of diabetes was 20.2 per 1000 person years and that of pre-diabetes was 13.1 per 1000 person years among subjects with NGT. Of the 37 individuals who were pre-diabetic at baseline, 15 (40.5%) developed diabetes [incidence rate: 64.8 per 1000 person years], 16 (43.2%) remained as pre-diabetic and 6 (16.2%) reverted to normal during the follow-up period. Regression analysis revealed obesity [Odds Ratio (OR): 2.1, p=0.001], abdominal obesity [OR: 2.23, p<0.001] and hypertension [OR: 2.57, p<0.001] to be significantly associated with incident diabetes. The Indian Diabetes Risk Score (IDRS) showed the strongest association with incident diabetes [OR: 5.14, p<0.001]. Conclusion: The study shows that the incidence of diabetes is very high among urban south Indians. While obesity, abdominal obesity and hypertension were associated with incident diabetes, IDRS was th

Prevalence, Awareness and Control of Hypertension in Chennai - The Chennai Urban Rural Epidemiology Study (CURES – 52)

Objective : To study the prevalence, awareness and control of hypertension in Chennai representing Urban South India. Methods : The Chennai Urban Rural Epidemiology Study (CURES) is one of the largest epidemiological studies on diabetes carried out in India, where 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 of CURES and the response rate was 2,350/26,001 or 90.4%. An oral glucose tolerance test was performed in all individuals except self-reported diabetic subjects. Anthropometric measurements and lipid estimations were done in all subjects. Hypertension was diagnosed in all subjects who were on drug treatment for hypertension or if the blood pressure ≥ 140/90 mmHg. Results : Hypertension was present in 20% [men:23.2% vs. women:17.1%, p<0.001] of the study population. Isolated systolic hypertension (Systolic BP ≥ 140 and Diastolic BP<90 mmHg) was present in 6.6% while isolated diastolic hypertension (DBP ≥ 90 and SBP<140 mmHg) was present in 4.2% of the population. Among the elderly population (aged ≥ 60 years), 25.2% had isolated systolic hypertension. Age, body mass index, smoking, serum cholesterol and triglycerides were found to be strongly associated with hypertension. Among the total hypertensive subjects, only 32.8% were aware of their blood pressure, of these, 70.8% were under treatment and 45.9% had their blood pressure under control. Conclusion : Hypertension was present in one-fifth of this urban south Indian population and isolated systolic hypertension was more common among elderly population. Majority of hypertensive subjects still remain undetected and the control of hypertension is also inadequate. This calls for urgent prevention and control measures for hypertensio

RNA interference screening reveals host CaMK4 as a regulator of cryptococcal uptake and pathogenesis

ABSTRACT Cryptococcus neoformans , the causative agent of cryptococcosis, is an opportunistic fungal pathogen that kills over 200,000 individuals annually. This yeast may grow freely in body fluids, but it also flourishes within host cells. Despite extensive research on cryptococcal pathogenesis, host genes involved in the initial engulfment of fungi and subsequent stages of infection are woefully understudied. To address this issue, we combined short interfering RNA silencing and a high-throughput imaging assay to identify host regulators that specifically influence cryptococcal uptake. Of 868 phosphatase and kinase genes assayed, we discovered 79 whose silencing significantly affected cryptococcal engulfment. For 25 of these, the effects were fungus specific, as opposed to general alterations in phagocytosis. Four members of this group significantly and specifically altered cryptococcal uptake; one of them encoded CaMK4, a calcium/calmodulin-dependent protein kinase. Pharmacological inhibition of CaMK4 recapitulated the observed defects in phagocytosis. Furthermore, mice deficient in CaMK4 showed increased survival compared to wild-type mice upon infection with C. neoformans . This increase in survival correlated with decreased expression of pattern recognition receptors on host phagocytes known to recognize C. neoformans . Altogether, we have identified a kinase that is involved in C. neoformans internalization by host cells and in host resistance to this deadly infection. </jats:p

Distribution-Free Tests for Two-Sample Location Problems Based on Subsamples

Nonparametric tests for location problems have received much attention in the literature. Many nonparametric tests have been proposed for one, two and several samples location problems. In this paper a class of test statistics is proposed for two sample location problem when the underlying distributions of the samples are symmetric. The class of test statistics proposed is linear combination of U-statistics whose kernel is based on subsamples extrema. The members of the new class are shown to be asymptotically normal. The performance of the proposed class of tests is evaluated using Pitman Asymptotic Relative Efficiency. It is observed that the members of the proposed class of tests are better than the existing tests in the literature

SOME CLASSES OF NONPARAMETRIC TESTS FOR SPECIAL TWO-SAMPLE LOCATION PROBLEM BASED ON SUBSAMPLE EXTREMES

The special two-sample location problem is an important problem which is useful in comparing the performance of two measuring instruments. The problem of comparing the performances of two packing machines in which one machine may underfill the packets and the other may overfill the packets on an average, fits into special twosample location setup wherein one wishes to test for the point of symmetry versus an appropriate alternative. The only test available in the literature to the best of our knowledge is the class of tests due to Shetty and Umarani [13] which is based on U-statistics. In this paper, two classes of test statistics are proposed which are based on extremes of subsamples. The performances of the proposed classes of tests ar

A Class of Nonparametric Tests for the Two-Sample Location Problem

The two-sample location problem is one of the fundamental problems encountered in Statistics. In many applications of Statistics, two-sample problems arise in such a way as to lead naturally to the formulations of the null hypothesis to the effect that the two samples come from identical populations. A class of nonparametric test statistics is proposed for two-sample location problem based on U-statistic with the kernel depending on a constant ’a’ when the underlying distribution is symmetric. The optimal choice of ’a’ for different underlying distributions is determined. An alternative expression for the class of test statistics is established. Pitman asymptotic relative efficiencies indicate that the proposed class of test statistics does well in comparison with many of the test statistics available in the literature. The small sample performance is also studied through Monte-Carlo Simulation techniqu

Regulation of the JNK pathway by TGF-beta activated kinase 1 in rheumatoid arthritis synoviocytes.

c-Jun N-terminal kinase (JNK) contributes to metalloproteinase (MMP) gene expression and joint destruction in inflammatory arthritis. It is phosphorylated by at least two upstream kinases, the mitogen-activated protein kinase kinases (MEK) MKK4 and MKK7, which are, in turn, phosphorylated by MEK kinases (MEKKs). However, the MEKKs that are most relevant to JNK activation in synoviocytes have not been determined. These studies were designed to assess the hierarchy of upstream MEKKs, MEKK1, MEKK2, MEKK3, and transforming growth factor-beta activated kinase (TAK)1, in rheumatoid arthritis (RA). Using either small interfering RNA (siRNA) knockdown or knockout fibroblast-like synoviocytes (FLSs), MEKK1, MEKK2, or MEKK3 deficiency (either alone or in combination) had no effect on IL-1beta-stimulated phospho-JNK (P-JNK) induction or MMP expression. However, TAK1 deficiency significantly decreased P-JNK, P-MKK4 and P-MKK7 induction compared with scrambled control. TAK1 knockdown did not affect p38 activation. Kinase assays showed that TAK1 siRNA significantly suppressed JNK kinase function. In addition, MKK4 and MKK7 kinase activity were significantly decreased in TAK1 deficient FLSs. Electrophoretic mobility shift assays demonstrated a significant decrease in IL-1beta induced AP-1 activation due to TAK1 knockdown. Quantitative PCR showed that TAK1 deficiency significantly decreased IL-1beta-induced MMP3 gene expression and IL-6 protein expression. These results show that TAK1 is a critical pathway for IL-1beta-induced activation of JNK and JNK-regulated gene expression in FLSs. In contrast to other cell lineages, MEKK1, MEKK2, and MEKK3 did not contribute to JNK phosphorylation in FLSs. The data identify TAK1 as a pivotal upstream kinase and potential therapeutic target to modulate synoviocyte activation in RA

Prevalence and Risk Factors of Diabetic Nephropathy in an Urban South Indian Population: The Chennai Urban Rural Epidemiology Study (CURES 45)

OBJECTIVE— 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