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Biomedical subjects

M Viswanathan

Publications and source records attributed to M Viswanathan.

At least 73 records · Page 4Linked to original sources

Prevalence of diabetes in pregnant women--a study from southern India.

This study was carried out to assess the prevalence of diabetes in southern Indian women during pregnancy. Nine hundred and fifty women having > or = 24 weeks of gestation, attending two general gynaecology centres for antenatal check-ups were screened. Initially, the screening test with 1-h plasma glucose sampling following 50 g glucose load was done and those with glucose values > or = 140 mg/dl were subjected to a 3-h oral glucose tolerance test (OGTT) with 100 g glucose load. Among the 950 women, 6 were known diabetic subjects. Of the other 944, 89 were positive on screening test and 67 of them reported for OGTT. Four were detected to have gestational diabetes mellitus (GDM) (O'Sullivan and Mahan's criteria). Therefore the prevalences of total diabetes and GDM were 1.19% and 0.56%, respectively.

Adult↗

Autoradiographic localization and characterization of angiotensin II receptor subtypes in the rat thymus.

Angiotensin II (ANG II) receptors were present in the thymus of newborn rats (179 +/- 34 fmol/mg protein). In newborns, binding was predominantly localized in the trabecula, and was selectively displaced by the AT2 ligand CGP 42112A (83-85%) and to a lower extent by the AT1 antagonist losartan (15-17%), indicating a marked predominance of AT2 receptors. Angiotensin II binding was very low in the cortical and medullary areas in the thymus of newborn rats and was no longer detected in the thymus of 4- and 8-week-old rats. No detectable binding for the ACE inhibitor [125I]351A was observed in the thymus of the rat, regardless of the age studied. Our results indicate a possible role for circulating ANG II during development of the thymus with no clear correlation to lymphocyte maturation.

Animals↗

Heterogeneous expression of angiotensin II AT1 receptors in neointima of rat carotid artery and aorta after balloon catheter injury.

We examined the expression of angiotensin II receptor subtypes and angiotensin-converting enzyme in the rat aorta and carotid artery at 1, 2, 4, 8, 15, and 30 days after balloon catheter injury or sham surgery. The AT1 receptor expression was enhanced in the neointima at 8 days in the aorta and carotid artery compared to that in intact media. Maintenance of the high expression of AT1 receptors in the neonintimal tissue at 15 and 30 days was localized to a subpopulation of neointimal cell close to the lumen of the vessel and was correlated to the distribution of smooth muscle cells immunoreactive to proliferating cell nuclear antigen. During the initial stages after injury, binding of [125I]351A to angiotensin-converting enzyme was significantly decreased in both the intima/media layers as well as adventitia in carotid artery and aorta. Binding of [125I] 351A to angiotensin-converting enzyme was significantly lower in the neointima compared to that in the intima/media of intact vessels. Our results reveal that the expression of AT1 receptors is heterogeneous in the neointima, and suggest that enhanced expression of AT1 receptors in the balloon catheter-injured carotid artery and aorta may be limited to proliferating intimal smooth muscle cells.

Angioplasty, Balloon↗

Risk of pancreatic carcinoma in tropical calcifying pancreatitis: an epidemiologic study.

To assess the risk of pancreatic cancer in subjects with tropical calcifying pancreatitis (TCP), we have followed 185 patients with TCP from the Diabetes Research Center in Madras, India for an average of 4.5 years. The diagnosis of TCP was based upon long-standing epigastric pain, laboratory tests, presence of pancreatic calculi, endoscopic retrograde cholangiopancreatography (ERCP) findings, and ultrasonography. During the follow-up period, 24 patients died from all causes, with 6 deaths (25%) from cancer of the pancreas. Three pancreatic cancers were biopsy positive. Average age at onset of pancreatic cancer was 45.6 +/- 7.3 years--considerably younger than for Western populations. When compared with the background pancreatic cancer rate, subjects with TCP appear to have a significantly increased risk of pancreatic cancer: relative risk = 100, 95% CI = 37-218. Even under the most stringent assumptions (restricting the analysis to biopsy-proven cases, assuming that the true background rate of pancreatic cancer in Madras resembles high-risk Western populations, assuming that tropical pancreatitis begins at birth) the risk is still elevated: relative risk = 5, 95% CI = 1.03-3-14.6. The exact mechanism linking various forms of pancreatitis to pancreatic cancer remains to be elucidated.

Adult↗

Apolipoprotein D gene polymorphism: a new genetic marker for type 2 diabetic subjects in Nauru and south India.

Type 2 diabetes is characterized by abnormalities in both glucose and lipoprotein metabolism and genes involved in lipid metabolism are legitimate candidates for involvement in Type 2 diabetes. We have previously reported an association in Nauruans between a Taq 1 polymorphism of the apolipoprotein D gene (apo D) and Type 2 diabetes. In this study these findings were investigated further in the Nauruan population as well as two other ethnic groups. In South Indian subjects, there was a significant difference in genotype distribution of apo D genotypes between diabetic subjects (n = 110) and controls (n = 88; p = 0.004) which was similar to that previously found in the Nauruan subjects. No such association was seen in elderly Finnish subjects (diabetic n = 69; impaired glucose tolerance n = 26 and normal glucose tolerance n = 31). Linkage between the apo D polymorphism and diabetes in 12 Nauruan families was only excluded under a highly penetrant dominant model and was unlikely under other single gene models. Since the beta cell glucose transporter gene (Glut 2) is found in a similar chromosomal location to apo D, South Indian subjects (diabetic n = 95 and controls n = 56) were typed at this locus. No association between diabetes and the Glut 2 Taq I polymorphism was found in the South Indian subjects. Furthermore, there was no evidence of linkage disequilibrium between the apo D and Glut 2 genes. In conclusion, apo D might act as a modifying gene for Type 2 diabetes in some ethnic groups.

Adolescent↗

Differences in plasma insulin responses in urban and rural Indians: a study in southern-Indians.

Fasting and 2 h post glucose plasma immunoreactive insulin (fasting IRI and 2 h IRI) responses were measured in urban (n = 149) and rural (n = 40) individuals with normal glucose tolerance during an epidemiological survey. In this survey, 900 urban and 1038 rural subjects were screened for glucose intolerance by capillary blood sampling. The respective response rates were 91% and 88%. We had planned to collect venous blood for IRI estimation, i.e. from 180 urban and 200 rural subjects. The compliance for the same was poor from the rural subjects and therefore the number available for IRI estimation was small. The mean +/- SD ages of the urban and rural groups were similar (35.3 +/- 9.9 and 38.6 +/- 13.1 years, respectively). The rural population had lower body mass index (BMI) and subscapular:triceps ratio compared to the urban group (p < 0.001). The total calorie consumption was lower and physical activity was higher in rural population. Fasting and 2 h insulin values in urban population were 16.6 +/- 9.4 mU l-1 and 60.6 +/- 42.5 mU l-1 and in rural 6.7 +/- 5.1 mU l-1 and 32.4 +/- 27.8 mU l-1, respectively; the values being significantly lower in the rural population (p < 0.001). Multiple regression analysis showed that in urban population the fasting insulin was correlated to the BMI and the 2h IRI to 2 h glucose, BMI and the subscapular:triceps ratio. In the rural population, similar results were obtained, except in that the 2 h IRI was influenced by the gender also.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Characterization of melatonin receptors and signal transduction system in rat arteries forming the circle of Willis.

The aims of this study were to characterize the melatonin receptors in rat brain arteries forming the circle of Willis. Saturation studies performed using in vitro autoradiography and [125I]iodomelatonin revealed the presence of two binding sites: one with a Kd of 13 pM, and the second characterized by a Kd of 832 pM. Coincubation with a nonhydrolyzable guanine nucleotide analog [guanosine-5'-O-(3-thiotriphosphate)] inhibited 2-[125I]iodomelatonin binding in a concentration-dependent manner, whereas adenine nucleotide adenosine-5'-O-(3-thiotriphosphate) was ineffective. In saturation studies performed in the presence of guanosine-5'-O-(3-thiotriphosphate), the high affinity site was no longer detectable, and the affinity of the receptor was decreased to the high picomolar range. Melatonin, at nanomolar concentrations, was able to inhibit forskolin-stimulated cAMP production in rat circle of Willis arteries. Preincubation with pertussis toxin counteracted the effect of melatonin. Our results demonstrate that melatonin receptors in rat cerebral arteries are linked to their second messenger through a pertussis toxin-sensitive G-protein, similar to what has been described for melatonin receptors in different areas of vertebrate brain.

Animals↗

High prevalence of NIDDM and IGT in an elderly south Indian population with low rates of obesity.

OBJECTIVE--To assess the prevalence of diabetes and impaired glucose tolerance (IGT) in the urban and rural elderly population in south India. RESEARCH DESIGN AND METHODS--Urban and rural populations > or = 60 years of age and representative of the areas (873 urban and 588 rural subjects) were screened for diabetes and IGT using fasting and 2-h postglucose capillary blood glucose measurements. RESULTS--In the urban area, 211 (23.7%) had diabetes, and 101 (12.4%) had IGT. In the rural area, 56 (9.9%) had diabetes, and 82 (14.9%) had IGT. The ratio of newly diagnosed to known diabetes was 1:3 in the urban and 1:1 in the rural areas. Positive family history of diabetes, body mass index (BMI), subscapular-to-triceps ratio, and waist-to-hip ratio were significantly associated with diabetes in the urban population. Only age and BMI showed significant association with diabetes in the elderly rural population. None of the tested parameters, except age in the urban subjects, showed association with IGT. CONCLUSIONS--This study highlights the high prevalence of glucose intolerance in elderly south Indians having low mean BMI (mean +/- SD; urban 21.7 +/- 4.6, rural 17.9 +/- 3.3 kg/m2). Although there was a twofold higher prevalence of diabetes in the urban area, the occurrence of IGT was similar in urban and rural populations.

Age Factors↗

Pancreatic beta cell function in normoglycaemic offspring of diabetic parents.

The aim of the study was to look for any time-realted fluctuation in the pancreatic beta cell function in normal offspring of diabetic parents, over a period of three years. Serum insulin (IRI) and C-peptide (CP) responses to oral glucose were reevaluated three years after the initial study in 25 normoglycaemic offspring of conjugal Type 2 diabetic parents. The mean area under the curve of IRI (AUC IRI) response was higher than normal control value in the offspring at both time points (P < 0.01) and the two values did not differ much. The 2 hr IRI was also significantly higher (P < 0.05) than the control value. CP responses at both time points in the offspring did not differ from the mean control value. Wide fluctuations in the individual IRI were noted on follow-up despite similar plasma glucose response. Follow-up IRI was higher in 6, lower in 5 (+/- 25% of the initial) and remained unaltered in the other 4 offspring. The corresponding CP showed increased values in 3, decreased values in 5 and no change in 7 offspring. The fluctuations were nonuniform in nature among the individuals studied. Disparity between the IRI and CP responses were present in 5 offspring during the follow-up. This study thus shows that wide fluctuations in insulin responses occur even in the normoglycaemic offspring of diabetic parents.

Adult↗

Prevalence of proteinuria in non-insulin dependent diabetes.

Proteinuria was estimated in 600 non-insulin dependent diabetes mellitus (NIDDM) patients in 24 hrs collection of urine. The test was repeated at least twice in a year to confirm the persistence of proteinuria. Mild proteinuria (200-500 mg/d) occurred in 94 (15.7%) and nephropathy (> 500 mg/d) in 112 (18.7%) patients. Nephropathy commonly occurred with long-standing diabetes (> 10 years). Development of proteinuria correlated directly with the duration of diabetes, diastolic and systolic blood pressure, age of the patients, serum creatinine and inversely with creatinine clearance. Retinopathy was seen in 75% of those with nephropathy. It is concluded that proteinuria occurs in one third of NIDDM patients and the risk of nephropathy increases with duration of disease.

Diabetes Mellitus, Type 2↗

Localization of angiotensin AT1 receptors in the rat heart conduction system.

We characterized angiotensin II receptor subtypes in the conduction system of the rat heart using quantitative autoradiography. In both the sinoatrial and atrioventricular nodes, binding could be totally displaced by losartan, and was insensitive to PD 123177, indicating that angiotensin II receptors in the conduction system of the rat heart belong to the AT1 subtype. Angiotensin AT1 receptors could play a direct role in the regulation of the heart chronotropic properties.

Angiotensin II↗

Positive association in the absence of linkage suggests a minor role for the glucokinase gene in the pathogenesis of type 2 (non-insulin-dependent) diabetes mellitus amongst south Indians.

Mutations of the glucokinase gene have been implicated in the development of glucose intolerance in pedigrees with maturity-onset diabetes of the young. However, the contribution of the glucokinase gene to the aetiology of common Type 2 (non-insulin-dependent) diabetes mellitus is uncertain. We have studied the role of the glucokinase gene in the pathogenesis of Type 2 diabetes in South Indians, using both population-association and linkage methodology. A pair of CA-repeat sequences (GCK(3') and GCK(5')) straddling the glucokinase gene were employed as markers, each subject being typed using the polymerase chain reaction and polyacrylamide gel electrophoresis. Comparisons of allele frequencies at these markers were made between 168 Type 2 diabetic subjects and 70 racially-matched control subjects. No differences in allele frequencies were apparent at the GCK(5') marker; however, there were significant differences in allele frequencies at the GCK(3') marker between the Type 2 diabetic subjects and control subjects (chi 2 = 11.6, df = 3, p = 0.009) with an increase of the z allele (78.0% vs 66.4%) and a decrease of the z + 2 allele (13.7% vs 25.0%) amongst the diabetic subjects. Linkage between glucose intolerance and the glucokinase gene was studied in 53 nuclear pedigrees under a variety of genetic models. Linkage was excluded (lod score < -2) at a recombination fraction of zero under five of the ten models used and highly unlikely (-2 < lod score < -1) under the others. The combination of positive association and negative linkage suggests that glucokinase acts as a minor gene influencing the development of Type 2 diabetes within this population.

Adult↗

Fasting plasma glucose in the diagnosis of diabetes mellitus: a study from southern India.

The usefulness of fasting plasma glucose (FPG) in the diagnosis of diabetes mellitus was assessed in Asian Indians in South India. Oral GTT values in 570 newly screened adults were studied. Taking the WHO criteria of 2 h plasma glucose (PG) of > or = 11.1 mmol l-1 for diagnosis of diabetes, the validity of a FPG of > or = 7.8 mmol l-1 cut off value for diabetes was assessed. Using the regression analysis, the correlations of the FPG to 2 h PG were examined. Among the 268 with 2h PG value of > or = 11.1 mmol l-1, 205 (76.5%) had FPG > or = 7.8 mmol l-1. Sensitivity of FPG was 76.5% for diagnosis of diabetes and its specificity was 99%. An exponential regression model gave the best fit for FPG vs 2 h PG and using the regression equation, the predicted FPG for a 2 h PG of 11.1 mmol l-1 was 7.05 mmol l-1. Sensitivity increased to 90.3% with FPG of 7.05 mmol l-1 while the specificity remained at 92%. It is concluded that in the south Indian subjects, the sensitivity for diagnosis of diabetes with FPG of > or = 7.8 mmol l-1 was 76.5%; and it increased to 90.3% with FPG of > or = 7.05 mmol l-1.

Adult↗

Glomerular angiotensin II receptor subtypes during development of rat kidney.

We used quantitative autoradiography to investigate distribution of angiotensin II (ANG II) receptor subtypes during development of the kidney in the rat. In fetal, newborn, and 3-day-old rats, immature glomeruli in the form of comma and S-shaped bodies, located in the nephrogenic zone of the renal cortex, expressed only the angiotensin AT2 receptor subtype. Conversely, the juxtamedullary glomeruli, in more advanced developmental stages, expressed only the AT1 subtype. Similarly, maturing and fully developed glomeruli, present in 1-, 2-, and 8-wk-old rats, expressed only AT1 receptors. In the kidney medulla, there was a similar change in ANG II receptor subtype expression, with the AT2 subtype expressed earlier and the AT1 subtype later during development. Our results demonstrate a selective expression of ANG II receptor subtypes during kidney development. We have found glomerular and medullary AT1 receptors only at developmental stages when kidney function has matured. Conversely, AT2 receptors are expressed only in immature structures, suggesting that they may have a role during kidney organogenesis.

Aging↗

Maternal age and birth order of young IDDM patients. A study from southern India.

OBJECTIVE: To assess the effects of maternal age and birth order on the risk of IDDM in Asian Indians. RESEARCH DESIGN AND METHODS: Data from a diabetes registry in Madras, India, was used to find IDDM patients diagnosed before 20 yr of age. A questionnaire was used to elicit clinical details of subjects. RESULTS: Children with mothers < or = 24 yr of age had a higher percentage of IDDM. Children with lower birth orders had a higher prevalence of IDDM. CONCLUSIONS: The risk of IDDM in children is increased in children with lower birth orders, born of younger mothers.

Adolescent↗

The islet amyloid polypeptide gene and non-insulin-dependent diabetes mellitus in south Indians.

Islet amyloid polypeptide (IAPP), otherwise called amylin, is the monomeric component of islet amyloid. Deposition of this amyloid is a characteristic feature of non-insulin-dependent diabetes mellitus in humans and may play a role in the pathogenesis of the disease. As such, abnormalities in the structure or expression of the IAPP gene might contribute to the inheritance of this condition. The IAPP gene was studied in a well-characterised population of 62 unrelated Dravidian subjects with non-insulin-dependent diabetes mellitus and 56 normal Dravidian controls, using a restriction fragment length polymorphism generated by PvuII digestion. Genotype and allele frequencies did not differ between diabetic subjects and controls. Taken together with recent findings in Europid and other racial groups, an abnormality of the IAPP gene is highly unlikely to represent a major gene for the development of non-insulin-dependent diabetes mellitus.

Alleles↗

Prevalence of childhood diabetes in an urban population in south India.

The objective of the study was to estimate the prevalence of insulin-dependent diabetes in children less than or equal to 15 years in an urban area in south India, by a population study. Three zones from the northeastern part of the city demarcated by the Directorate of Census were chosen. Ascertainment of the cases from these zones was made (a) by collecting data from the major hospitals and diabetes clinics by personal visit; (b) by questionnaire sent to medical practitioners in the area; and (c) from the chemists and druggists who sell insulin. Recommendations of the Diabetes Epidemiology Research International Registry Group were used. Thirty children with insulin-dependent diabetes with age at diagnosis less than or equal to 15 years were identified. The prevalence was 0.26/1000. The peak age at diagnosis was 12 years. This first population-based study of prevalence of insulin-dependent diabetes in south India shows that insulin-dependent diabetes is not rare. It is higher than reported from many other Asian countries.

Adolescent↗

Comparative study of the clinical profiles of alcoholic chronic pancreatitis and tropical chronic pancreatitis in Tamil Nadu, south India.

In a comparative study of tropical chronic pancreatitis (TCP) and alcoholic chronic pancreatitis (ACP) occurring in the same population, we analyzed the clinical profile of 50 patients of ACP seen over the past 3 years at our centers and compared this with the profile of our TCP patients. A majority (75%) of patients in both groups belonged to Tamil Nadu and 90% had never consumed cassava. Whereas TCP occurred in young subjects of both sexes, ACP patients were all males and presented at an older age. The frequency of pain, diabetes, and pancreatic calcification was similar in the two groups. Patients in both groups were lean, but signs of severe malnutrition were rare. Prediabetic patients had normal body mass index. There were striking differences in radiological appearance of pancreatic calculi in TCP and ACP. Malignancy of the pancreas was present in three patients with TCP. Benign bile duct stenosis was seen in three patients with ACP but not in TCP. Compared to ACP seen in the West, our ACP patients had a shorter duration of symptoms in spite of having advanced disease. TCP and ACP have distinct clinical profiles and it is possible that some environmental factors may hasten the progress of ACP in the tropics.

Abdominal Pain↗