Search

There has been a huge increase in diabetes and its associated cardiovascular complications over the last decade, predominantly in the middle- and low-income countries. In these countries, the majority live in rural areas. The Rural Epidemiology of Diabetes in South India (REDSI) study was aimed to analyze the prevalence of diabetes, cardiovascular risk factors, and its complications in rural farming and non-farming villages in Tamil Nadu, South India. A research survey on the prevalence of self-reported diabetes, cardiovascular risk factors (age, sex, obesity, hypertension, hypercholesterolemia, alcohol and tobacco use) and agricultural occupational exposure was executed among 106,111 people from 61 villages in the state of Tamil Nadu, South India, during 2015–2018. Overall, we observed a diabetes prevalence of 11.9% in rural South India. A nearly two-fold higher prevalence of diabetes was observed among the farming community (15.0%) compared to that among the non-farming population (8.7%). Logistic regression analyses revealed a strong association with agrochemical exposure (P < 0.0001) and diabetes prevalence among rural farming people. Our survey indicates a high prevalence of diabetes in rural South India particularly among the farming community. This survey in conjunction with other epidemiological and experimental studies raises the need for understanding the etiology of diabetes and other cardiovascular risk factors in rural communities.

Liver disease is the only major chronic disease and mortality is increasing. Earlier detection of liver fibrosis can reduce progression to cirrhosis and hepatocellular carcinoma. Many studies have reported an increased prevalence in liver fibrosis among adults in urban regions but there are few data in physically active rural populations without attributable metabolic risk factors. This aim of this study is to investigate the prevalence of abnormal liver functions tests (LFTs) and liver fibrosis among adults in a rural population.This cross-sectional study included observations from KMCH-NNCD-II (2017) study (Significant liver fibrosis (F2-F4) was observed in 14.4%, and cirrhosis in 0.8%. There was an association of liver fibrosis with abnormal LFTs but no association between alcohol consumption, viral hepatitis, hepatic liver screening and liver fibrosis. Among metabolic risk factors, no association was observed for hypertension and hypercholesterolemia but diabetes [OR - 3.206 (95% CI: 1.792 - 5.736)], obesity [1.987 (1.341 - 2.944)] and metabolic syndrome [2.539 (1.680 - 3.836)] showed association with significant liver fibrosis (F2-F4) after adjustment for confounding factors.Our results suggest that the prevalence of liver fibrosis in rural population is similar to urban counterparts. The association of metabolic risk factors with liver fibrosis in physically active rural population warrants further investigations in future studies.This study is funded by KMCH Research Foundation, India.

Pseudomonas aeruginosa is a major infectious agent among Gram-negative bacteria, which causes both acute and chronic infections. Infections due to P. aeruginosa are hard to treat, as it entails various strategies like virulence factors synthesis, drug efflux systemsresistance and protein secretion systems during pathogenesis. Despite extensive research in Pseudomonas pathogenesis, novel drug targets and potential therapeutic strategies are urgently needed. In this study, we investigated the genetic requirements of P. aeruginosa PAO1 for rat cardiomyocyte (H9C2) infection by insertion sequencing (INSeq). A mutant library comprising ~70,000 mutants of PAO1 was generated and the differentiated form of H9C2 cells (d-H9C2) was infected with the library. The infected d-H9C2 cells were maintained with antibiotic-protection and without any antibiotics in the growth media for 24 h. Subsequently, DNA library for INSeq was prepared, sequenced and fitness analysis was performed. One hundred and thirteen mutants were negatively selected in the infection condition with antibiotic-protection, whereas 143 mutants were negatively selected in antibiotic-free condition. Surprisingly, a higher number of mutants showed enriched fitness than the mutants of reduced fitness during the infection. We demonstrated that the genes associated with flagella and T3SS are important for adhesion and invasion of cardiomyocytes, while pili and proteases are conditionally essential during host cell lysis. Hence, our findings highlight the essential genes for cardiomyocyte infection, particularly during the intracellular phase. The aerotaxis receptor Aer, plays a critical role during intracellular life. Genes such as flgE, flgF, flhA, flhB, fliA, fliC, fliF, motA, aotJ, aer, wbpJ, ponA, fleQ, PA5205, hmgA, trkH and pslH are essential for infection.

Aims South Asia has emerged rapidly as an epicentre of non-communicable diseases (NCDs) specifically diabetes and cardiovascular diseases. The prevalence rate, risk factors and aetiology of NCDs in different socio-demographic settings are not clearly understood. This study was performed to assess the prevalence of diabetes and atherosclerosis and their risk factors in urban, sub-urban and rural communities of South India. Methods Three communities [Nallampatti (rural), Thadagam (sub-urban) and Kalapatti (urban)] in South India were selected for participation in the KMCH-NCD Studies. Study volunteers were administered a detailed questionnaire, underwent anthropometric measurements, clinical measurements including blood pressure, glycated haemoglobin (HbA1c ), non-fasting lipid profile and serum creatinine. Carotid intima-media thickness was measured using B-mode ultrasound. Multiple logistic regression analyses were performed to understand the association of risk factors with diabetes and atherosclerosis. Results A total of 2976 native participants, ≥20 years of age were screened. The prevalence of diabetes was 16%, 26% and 23% respectively in the rural, sub-urban and urban study populations. Association of obesity with diabetes was observed in only urban population while hypertension and dyslipidaemia showed association in both urban and semi-urban populations. Association of diabetes with atherosclerosis was observed in urban and semi-urban populations. Hypertension in semi-urban and obesity and dyslipidaemia in urban population showed association with atherosclerosis. Conclusions Diabetes and atherosclerosis burden reported in the three different communities were higher than previous reports, especially in rural and sub-urban regions. No traditional risk factor is identified to be associated with prevalence of diabetes and atherosclerosis in rural population. These findings suggest an urgent need for investigation into the role of non-traditional risk factors like environmental or occupational exposures may help to better understand the aetiology of diseases in non-urbanized communities.

Background: Hypertension (HTN) is an important risk factor for cardiovascular mortality in India. HTN prevalence data are predominantly available for urban and rural populations in India but not in the mushrooming suburban areas. This study was conducted to estimate the prevalence of HTN and associated risk factors in suburban Tamil Nadu. Methods: In this Kovai Medical Center Hospital Non-Communicable Disease Study, we enrolled adults >20 years of age residing at Thadagam (suburban) in Coimbatore district, Tamil Nadu, India. All participants had a detailed questionnaire and anthropometric measurements. Blood samples were taken for glycosylated hemoglobin, nonfasting lipid profile, and serum creatinine. Prevalence of HTN (self-reported cases of HTN or systolic blood pressure ≥140 mm Hg and or diastolic blood pressure ≥90 mm Hg) was estimated. Multivariable logistic regression analysis was used to identify factors influencing HTN. Results: A total of 1030 participants were involved in this study. The prevalence of HTN was 47.1% in this area, with similar prevalence in both genders. The ratio of known HTN to newly diagnosed HTN was 1:1.3. Nearly 5% of adults between 20 and 39 years had HTN in this cohort. On multivariate logistic regression, after adjustment for age and sex, HTN was significantly associated with diabetes and atherosclerosis. Conclusions: This study identified a high prevalence of HTN in suburban region of Tamil Nadu. Aggressive screening protocols and targeted treatment are the need of the hour to reduce the burden of HTN and cardiovascular diseases in suburban India.

ObjectiveDiabetes and cardiovascular diseases are growing burdens in rural communities worldwide. We have observed a high prevalence of diabetes among rural farming communities in India and sought to evaluate the association of non-traditional risk factors, such as metals, with diabetes and other cardiometabolic risk factors in this community.MethodsAnthropometric measurements, chemistries and carotid intima-media thickness were determined in 865 participants of the Kovai Medical Center and Hospital-Nallampatti Non-Communicable Disease Study-I (KMCH-NNCD-I, 2015), a cross-sectional study conducted in a farming village in South India. Urinary metal levels were determined by inductively couped plasma-mass spectrometry analysis and corrected to urinary creatinine level. Statistical analyses were performed to study the association between urinary metal levels and clinical parameters.Results82.5% of the study population were involved in farming and high levels of toxic metals were detected in the synthetic fertilisers used in the study village. The prevalence of pre-diabetes, diabetes and atherosclerosis was 43.4%, 16.2% and 10.3%, respectively. On logistic regression analysis, no association of traditional risk factors such as body mass index, blood pressure and total cholesterol with disease conditions was observed, but urinary levels of metals such as arsenic, chromium, aluminium and zinc showed an association with diabetes, while arsenic and zinc showed an association with pre-diabetes and atherosclerosis.ConclusionsOur data suggest a probable role of metals in the aetiology of diabetes and cardiovascular diseases in rural communities. Identifying and eliminating the causes of increased levels of these environmental chemicals could have a beneficial impact on the burden of non-communicable diseases in rural population.

The physiological cardiac hypertrophy is an adaptive condition without myocyte cell death, while pathological hypertrophy is a maladaptive condition associated with myocyte cell death. This study explores the miRNome of α-2M-induced physiologically hypertrophied cardiomyocytes and the role of miRNA-99 family during cardiac hypertrophy. Physiological and pathological cardiac hypertrophy was induced in H9c2 cardiomyoblast cell lines using α-2M and isoproterenol respectively. Total RNA isolation and small RNA sequencing were executed for physiological hypertrophy model. The differentially expressed miRNAs and its target mRNAs were validated in animal models. Transcription factor binding sites were predicted in the promoter of specific miRNAs and validated by ChIP-PCR. Subsequently, the selected miRNA was functionally characterized by overexpression and silencing. The effects of silencing of upstream regulator and downstream target gene were studied. Analysis of small RNA reads revealed the differential expression of a large set of miRNAs during hypertrophy, of which miR-99 family was highly downregulated upon α-2M treatment. However, this miR-99 family expression was upregulated during pathological hypertrophy and confirmed in animal models. ChIP-PCR confirms the binding of Egr-1 transcription factor to the miR-99 promoter. Further, silencing of Egr-1 decreased the expression of miR-99. The overexpression or silencing of miR-99 diverges the physiological hypertrophy to pathological hypertrophy and vice versa by regulating Akt-1 pathway. Silencing of Akt-1 replicates the effect of overexpression of miR-99. Conclusion The results proved Egr-1 mediated regulation of miR-99 family that plays a key role in determining the fate of cardiac hypertrophy by regulating Akt-1 signaling.

The advent of industrial revolution caused a large inflow of synthetic chemicals for medical, agricultural, industrial and other purposes in the world. In general, these chemicals were subjected to toxicological risk assessment for human health and ecology before release for public use. But today we are witnessing a negative impact of some of these chemicals on human health and environment indicating an underestimation of toxic effects by current risk assessment protocol. Recent studies established gut microbiota as one of the key player in intercession of toxicity of drugs and synthetic chemicals. Hence, the need of the hour is to include the assessment for microbiota specifically gut microbiota in human toxicological risk assessment protocol. Herewith we are proposing a framework for assessment of gut microbiota upon exposure to drugs or chemicals.

Diabetes is rapidly emerging as one of the biggest health concerns worldwide, with profound implications for disability, mortality, and costs. This suddenly escalating rate of diabetes correlates with global industrialization and the production of plastics, pesticides, synthetic fertilizers, electronic waste, and food additives that release endocrine-disrupting chemicals (EDCs) into the environment and the food chain. Emerging evidence indicates an association between exposure of EDCs and diabetes. In humans, these chemicals are also metabolized by the gut microbiota and thereby their toxicodynamics are altered. In this review we highlight studies that focus on the role of gut microbiota in EDC-induced hyperglycemia and dysregulated glucose homeostasis. We also discuss the translational implications of understanding EDC-microbiota interactions for the diagnosis and treatment of diabetes.

In last few decades, the prevalence of diabetes and vascular diseases has intensified concurrently with increased use of synthetic chemicals in agriculture. This study is aimed to evaluate the association of co-accumulation of arsenic and organophosphate (OP) insecticides with diabetes and atherosclerosis prevalence in a rural Indian population.This study included observations from KMCH-NNCD-I (2015) cross-sectional study (n = 865) from an Indian farming village. The participants had assessment of clinical parameters including HbAOn multivariate regression analyses, total organophosphate level and arsenic accumulation showed association with diabetes and atherosclerosis. Higher odds ratio with significant trends were observed for the sub-quartiles formed by the combination of higher quartiles of arsenic and total organophosphates in association with diabetes and atherosclerosis.We observed evidence of possible synergism between arsenic and OPs in association with prevalence of diabetes, pre-diabetes and atherosclerosis in the study population. Our findings highlight the importance of understanding health effects of mixed exposures and raises vital questions on the role of these agrochemicals in the etiology of diabetes and vascular diseases.

Diabetes and cardiovascular disease (CVD) have evolved as the leading cause of mortality and morbidity worldwide. In addition to traditional risk factors, recent studies have established that the human microbiota, particularly gut bacteria, plays a role in the development of diabetes and CVD. Although the presence of microbes in blood has been known for centuries, mounting evidence in this metagenomic era provides new insights into the role of the blood microbiota in the pathogenesis of non-infectious diseases such as diabetes and CVD. We highlight the origin and physiology of the blood microbiota and circulating microbial metabolites in relation to the etiology and progression of diabetes and CVD. We also discuss translational perspectives targeting the blood microbiota in the diagnosis and treatment of diabetes and CVD.

Aim Our aim was to study the potential role of Cystatin C as a marker for renal function and cardiovascular disease in a rural South Indian population. Methods Local Ethics Committee approval and informed consent was obtained from all participants. Inclusion criterion was that participants had to be ≥20 and ≤85 years of age. All participants were administered a detailed questionnaire, and had their anthropometric measurements taken including height, weight, and waist circumference. Blood was drawn for determining random glucose, glycosylated hemoglobin, nonfasting lipid profile, Cystatin C, uric acid, and hemoglobin. Urine samples were collected for urine protein creatinine ratio. All participants had their carotid intima thickness determined by high-resolution B-mode carotid ultrasound. Results A total of 865 participants were screened in this study. Cystatin C value of >1 mg/l and creatinine of >1.1 mg/dl in females and 1.3 mg/dl in males were defined as “elevated levels.” Nearly a third of this population had elevated Cystatin C levels. Higher levels of Cystatin C, even within the normal creatinine range, was associated with cardiovascular risk markers like age, blood pressures, uric acid, and carotid intima thickness. Conclusions Cystatin C in a rural South Indian population correlates well with creatinine and cardiovascular markers. Long-term follow-up of this cohort stratified on the basis of Cystatin C will be extremely helpful in augmenting the utility of Cystatin C as an atherosclerotic risk marker in an Indian population.

Authors would like to correct the error in the online publication, which is mentioned below.

Caramel colours are the preferential food colouring agent globally, reaches wide age groups through eatables. Colas, a sweetened carbonated drink are most common caramel coloured beverage and its consumption is linked with diabetes, obesity, pancreatic cancer and other endocrine disorders. A major by-product produced during caramelization is 4-methylimidazole (4-MEI) that is detected in noteworthy concentrations in colas and other beverages. Previous studies revealed the neurotoxic and carcinogenic potential of 4-MEI in animals at higher doses but the effect of 4-MEI at theoretical maximum daily intake dose on glucose homeostasis is unexplored. Here, mice treated with 4-MEI (32 µg/kg bodyweight/day) for seven weeks exhibited severe hypoglycaemia and hyperinsulinemia mediated by hyperplasia of pancreatic beta cells and induces metabolic alterations. On combinatorial treatment, 4-MEI suppressed the glucogenic potential of non-artificial sweeteners and promotes lipogenesis. Furthermore, increased levels of C-peptide, LDL-cholesterol and triglycerides were observed in the humans with regular intake of 4-MEI containing beverages. In summary, 4-MEI induced pancreatic beta cell hyperplasia and leads to disruption of glucose and lipid homeostasis. This study suggests the need for further assessment and reconsideration of the wide usage of 4-MEI containing caramels as food additives.

The Akt signalling pathway is a crucial network of proteins, which plays a role in neonatal cellular proliferation, hypertrophy and cellular survival mechanism in the heart through a multifaceted system including, small non-coding RNAs (sncRNAs). Despite numerous reports on the distorted expression of these proteins in various cardiovascular diseases, this review focuses on the role of miRNA and piRNA in altering Akt signalling. Nevertheless the role of these sncRNAs in the Akt pathway needs to be studied in detail, there are evidence indicating that they can play a vital function in Akt-mediated cardiac survival. Recent reports indicate that, modification of such miRNA/piRNA causes alteration in the Akt pathway during both physiology and pathology. Therefore, understanding the antisense mediated molecular mechanisms of Akt pathway can devise a new vision towards biomarkers and therapeutic approaches to various cardiovascular diseases.

The morbidity and mortality rate of cardiovascular diseases are increasing massively worldwide. The environmental pollutants especially agrochemicals are the most unrecognized cardiovascular risk factors. Monocrotophos (MCP), an organophosphate pesticide with acetylcholine esterase inhibition activity is widely used in India and other parts of the world. The present study investigated the cardiotoxicity of prolonged intake of MCP. Wistar rats were administered 1/50th of LD50 dosage of MCP (0.36mg/kg body weight) orally via gavage daily for three weeks. MCP administered animals exhibited mild-hyperglycemia and dyslipidemia in blood. Cardiac oxidative stress was conferred by accumulation of protein carbonyls, lipid peroxidation and glutathione production. The cardiac markers (cTn-I, CK-MB and LDH) were showed elevated expression in blood plasma, which signals the cardiac tissue damage. The histopathology of the heart tissue authenticated the MCP induced tissue damage by showing signs of nonspecific inflammatory changes and oedema between muscle fibres. Thus the findings of this preliminary study illustrate the cardiotoxic effect of prolonged MCP intake in rats and suggest that MCP can be a possible independent and potent environmental cardiovascular risk factor.

The exploration of noncoding RNAs, especially microRNAs (miRNAs), in the past few decades redrafted the central dogma of molecular biology and our understanding of gene regulation. These miRNAs are small (∼21–25 nt), endogenous, evolutionarily conserved, noncoding, single-stranded RNA molecules that regulate gene expression by posttranscriptional silencing. They play a vital role in all segments of life, from embryo development to aging, physiology to pathology, and in all forms of life, from algae to angiosperms and protozoa to mammals. In this chapter, we discuss the techniques employed to study the biology of miRNAs, screening techniques, and their potential applications in various fields; in short, miRNAs are tiny but mighty.

Background Organophosphates are the most frequently and largely applied insecticide in the world due to their biodegradable nature. Gut microbes were shown to degrade organophosphates and cause intestinal dysfunction. The diabetogenic nature of organophosphates was recently reported but the underlying molecular mechanism is unclear. We aimed to understand the role of gut microbiota in organophosphate-induced hyperglycemia and to unravel the molecular mechanism behind this process. Results Here we demonstrate a high prevalence of diabetes among people directly exposed to organophosphates in rural India (n = 3080). Correlation and linear regression analysis reveal a strong association between plasma organophosphate residues and HbA1c but no association with acetylcholine esterase was noticed. Chronic treatment of mice with organophosphate for 180 days confirms the induction of glucose intolerance with no significant change in acetylcholine esterase. Further fecal transplantation and culture transplantation experiments confirm the involvement of gut microbiota in organophosphate-induced glucose intolerance. Intestinal metatranscriptomic and host metabolomic analyses reveal that gut microbial organophosphate degradation produces short chain fatty acids like acetic acid, which induces gluconeogenesis and thereby accounts for glucose intolerance. Plasma organophosphate residues are positively correlated with fecal esterase activity and acetate level of human diabetes. Conclusion Collectively, our results implicate gluconeogenesis as the key mechanism behind organophosphate-induced hyperglycemia, mediated by the organophosphate-degrading potential of gut microbiota. This study reveals the gut microbiome-mediated diabetogenic nature of organophosphates and hence that the usage of these insecticides should be reconsidered. Electronic supplementary material The online version of this article (doi:10.1186/s13059-016-1134-6) contains supplementary material, which is available to authorized users.

Background The discovery of PIWI-interacting RNAs (piRNAs) has fundamentally changed our understanding of post transcriptional regulation of transposons and other genes. Unlike miRNA and siRNA, the piRNAs are the most abundant but least studied RNA species in mammals. Although the expression of PIWI proteins and piRNAs has long been regarded as germline specific, increasing evidences suggest the expression of piRNAs in somatic cells. Methods In this study, the small RNA sequencing executed during induction of cardiac hypertrophy in both in vivo and in vitro conditions were annotated for the expression of piRNAs. The expression of piRNAs was validated by qPCR and RNA immunoprecipitation. In addition, the presence of piRNAs in circulation of myocardial infarction patients was studied by qPCR. Results We identified an abundant and altered expression of piRNAs during cardiac hypertrophy. The differentially expressed piRNAs was validated by qPCR and RNA immunoprecipitation. The significantly and differentially expressed piRNAs were predicted to target different retrotransposons and mRNAs in the rat genome. The detection of specific piRNA in serum of myocardial infarction patients suggests the potential of piRNA for diagnosis. Conclusion Overall this study is the first to provide a whole-genome analysis of the large repertoire of piRNAs in the cardiac system and this would pave a new path to understanding the molecular aetiology of piRNA and retrotransposons in the physiology and pathology of the cardiac system.

Aim: To assess the prevalence of noncommunicable diseases in a true rural farming population in South India and compare the data with the landmark contemporary Indian Council of Medical Research-India Diabetes (ICMR-INDIAB) study. Methods: Local Ethics Committee approval and informed consent was obtained from all participants. Inclusion criteria were participants, aged ≥20 and ≤85 years, from Nallampatti, a classical farming village from Tamil Nadu state, India. All participants were administered a detailed questionnaire, had anthropometric measurements including height, weight, and waist circumference. Bloods were drawn for random blood glucose, glycated hemoglobin (HbA1c), nonfasting lipid profile, Cystatin C, uric acid, and hemoglobin. All participants had carotid intima-media thickness (CIMT) done by high-resolution B-mode carotid ultrasound. Results: More than 50% of the population had either diabetes or prediabetes based on HbA1c. Nearly, 40% of the population had hypertension with suboptimal control in those with known hypertension. Nearly, a third of the population had dyslipidemia, elevated cystatin C levels, and abnormal CIMT. The burden was higher than the comparable ICMR-INDIAB study in rural Tamil Nadu. Conclusion: One-third to one-half of this rural farming population is at risk of cardiovascular disease, with poor control of preexisting cardiovascular risk factors. Current Indian data may underestimate the risk in different ethnic populations and regions of India. Long-term follow-up of this cohort for the incident cardiovascular disease will shed light on the true cardiovascular risk in a typical South Indian rural farming population.

Physiological cardiac hypertrophy is an adaptive mechanism, induced during chronic exercise. As it is reversible and not associated with cardiomyocyte death, it is considered as a natural tactic to prevent cardiac dysfunction and failure. Though, different studies revealed the importance of microRNAs (miRNAs) in pathological hypertrophy, their role during physiological hypertrophy is largely unexplored. Hence, this study is aimed at revealing the global expression profile of miRNAs during physiological cardiac hypertrophy. Chronic swimming protocol continuously for eight weeks resulted in induction of physiological hypertrophy in rats and histopathology revealed the absence of tissue damage, apoptosis or fibrosis. Subsequently, the total RNA was isolated and small RNA sequencing was executed. Analysis of small RNA reads revealed the differential expression of a large set of miRNAs during physiological hypertrophy. The expression profile of the significantly differentially expressed miRNAs was validated by qPCR. In silico prediction of target genes by miRanda, miRdB and TargetScan and subsequent qPCR analysis unraveled that miRNAs including miR-99b, miR-100, miR-19b, miR-10, miR-208a, miR-133, miR-191a, miR-22, miR-30e and miR-181a are targeting the genes that primarily regulate cell proliferation and cell death. Gene ontology and pathway mapping showed that the differentially expressed miRNAs and their target genes were mapped to apoptosis and cell death pathways principally via PI3K/Akt/mTOR and MAPK signaling. In summary, our data indicates that regulation of these miRNAs with apoptosis regulating potential can be one of the major key factors in determining pathological or physiological hypertrophy by controlling fibrosis, apoptosis and cell death mechanisms.