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Biomedical subjects

A Ramachandran

Publications and source records attributed to A Ramachandran.

At least 127 records · Page 7Linked to original sources

Diabetic retinopathy at the time of diagnosis of NIDDM in south Indian subjects.

Several studies from the U.K. and the U.S. have shown that retinopathy was present at diagnosis of non-insulin dependent diabetes mellitus (NIDDM) indicating the likelihood of a latent phase of hyperglycaemia for a long period. This study looked for the prevalence of retinopathy at diagnosis of NIDDM in South Indian subjects who have a fairly high prevalence of diabetes and also a high rate of undetected diabetes. One thousand NIDDM subjects with varying duration of diabetes underwent detailed ophthalmoscopic examination for retinopathy. It was noted that the prevalence of retinopathy increased linearly with duration of diabetes. Among the 60 newly diagnosed NIDDM, 4 (6.7%) subjects had background diabetic retinopathy. Using a weighted linear regression analysis with percentage of retinopathy in relation to duration, it was estimated that hyperglycaemia could have been present 4.1 years prior to the diagnosis of NIDDM. Although the prevalence of retinopathy at diagnosis in South Indian NIDDM was lower than the other reported values, in view of the high prevalence of diabetes in Indians, a large number of patients would have the risk of microangiopathy even before diagnosis of diabetes is made.

Adult↗

An association in non-insulin-dependent diabetes mellitus subjects between susceptibility to retinopathy and tumor necrosis factor polymorphism.

In IDDM an association between diabetic retinopathy and polymorphic markers of MHC has been described. However, these associations are complicated by a primary association between the MHC and IDDM. Because the pathogenesis of retinopathy is likely to be the same in IDDM and NIDDM, NIDDM subjects with retinopathy would be the ideal population to study for an association with MHC markers. The following South Indian subjects were therefore studied: unselected NIDDM (n = 76), unselected IDDM (n = 99), non-diabetic controls (n = 96), NIDDM subjects with maculopathy (MAC), n = 55, NIDDM subjects with proliferative retinopathy (PR), n = 53, and without retinopathy (LTD), n = 46. DNA was amplified and studied using a microsatellite polymorphism located 3.5 kb upstream of TNF-beta within the MHC class III region on the short arm of chromosome 6. No differences in allelic distribution were observed between the random NIDDM subjects and controls (p = 0.17). Differences in allelic distribution were found between unselected IDDM and controls (P = 0.016) and between the NIDDM subjects with maculopathy and/or proliferative retinopathy and no retinopathy (P = 0.006). This association could be accounted for by those patients with proliferative retinopathy (MAC vs LTD, p = 0.23; MAC vs PR, p = 0.07; and PR vs LTD, p = 0.002).

Alleles↗

Incidence of IDDM in children in urban population in southern India. Madras IDDM Registry Group Madras, South India.

This study was carried out to estimate the incidence of childhood insulin dependent diabetes mellitus (IDDM) in an urban southern Indian, population. A registry for IDDM has been set up in the city of Madras. South India. Details of newly diagnosed IDDM children, aged less than 15 years, were analysed retrospectively, for a period of 1991-1994. Primary sources were government and service hospitals, large diabetes clinics and secondary sources were diabetes camp, private diabetologists and endocrinologists. A capture-recapture method was used and the estimate of case in the population (1991 census) was calculated. Incidence (case/100,000) was calculated in the total group and then for boys and girls separately. The incidence for the 4 year period was 10.5/100,000/year (CI 5.0). The corresponding values for boys and girls were 12.6 +/- 11 and 9.6 +/- 4.7 respectively. The peak incidence was between 10 and 12 years. This is the first population based incidence data from India and showed that the incidence of childhood IDDM is not low in urban children.

Adolescent↗

An association between type 1 diabetes and the interleukin-1 receptor type 1 gene. The DiMe Study Group. Childhood Diabetes in Finland.

The polygenic susceptibility to type 1 diabetes is well established and recent studies have demonstrated linkage of a further locus on chromosome 2q to disease. We have studied a polymorphism of the interleukin-1 receptor type 1 gene (IL1R1) on chromosome 2q in type 1 diabetic and control subjects from Finland, the United Kingdom, South India: three populations in which the risk of disease varies from very high to very low. In the medium-risk U.K. population we find a very strong association of IL1R1 with type 1 diabetes (p = 0.0002) but we find no overall association in either the high-risk Finnish or low-risk South-Indian populations. However, we do find heterogeneity of risk at IL1R1 amongst Finnish diabetic subjects according to the possession of HLA-DR associated susceptibility (p = 0.0001); there is an association with IL1R1 in only those Finnish diabetic subjects who do not possess high-risk HLA-DR4 or DR3 haplotypes (p = 0.006), as recently demonstrated for the insulin gene region in this population. We find no such heterogeneity of risk in either the U.K. or South-Indian populations. This study further demonstrates the genetic heterogeneity of disease susceptibility between and within populations and also supports the hypothesis of an interaction of the IL1R1 locus with genes within the HLA and insulin gene regions in the susceptibility to type 1 diabetes.

Adolescent↗

Effects of pineal indoles and parachlorophenylalanine on seasonal reproduction in the pigeon

The effect of melatonin, methoxytryptophol (ML), methoxytryptamine (MT) and parachlorophenylalanine (p-CPA) on the mass and histology of the testes and the adrenal and thyroid glands and on serum thyroid hormone levels have been studied in the recrudescent phase of the feral pigeon Columba livia. All the pineal indoles showed a common anti-gonadal effect, resulting in the arrest of spermatogenesis and the degeneration of germ cells. Treatment with melatonin resulted in adreno-cortical enlargement and medullary hypertrophy, whereas ML, MT and p-CPA induced medullary enlargement and hypertrophy without having much influence on the cortex. Treatment with melatonin and ML brought about colloid retention in the thyroid follicles, while MT and p-CPA induced colloid depletion and hypertrophy of the follicular epithelium. From the present study, it can be concluded that both pineal indoles and p-CPA induce testicular regression in the breeding phase but do so by different mechanisms.

Journal Article↗

Insulin receptor substrate-1 gene mutations in NIDDM; implications for the study of polygenic disease.

Variations in the coding regions of the insulin receptor substrate-1 (IRS-1) gene have recently been suggested to contribute to the susceptibility of non-insulin-dependent diabetes mellitus (NIDDM). The purpose of this study was to examine the role of the IRS-1 missense mutations at codons 972 (glycine to arginine) and 513 (alanine to proline) in two diverse populations from South India and Finland at high risk for NIDDM. DNA was amplified and digested with restriction enzymes BstN1 to detect the codon 972 mutation and Dra III to detect the codon 513 mutation. The codon 513 mutation was not found in the study subjects. The codon 972 mutation was present in 10.3% of 126 middle-aged NIDDM subjects and 5.3% of 95 matched control subjects in the South Indians (p = 0.17). In elderly Finnish subjects the frequency of the mutation was 7.5% in 40 NIDDM subjects and 7% in 42 matched control subjects. The frequency of codon 972 mutation in the South Indian NIDDM subjects was very similar to the two previously published studies in Danish and French subjects although each study individually fails to reach conventional levels of significance. The data from all four ethnic groups were analysed together after ascertaining that significant heterogeneity did not exist between the studies. Overall, the frequency of the codon 972 mutation is found in 10.7% NIDDM subjects and 5.8% control subjects (p = 0.02). These studies suggest that the codon 972 mutation of the IRS-1 gene might act as a susceptibility gene predisposing to NIDDM in certain ethnic groups.

Adult↗

Proteinuria in NIDDM in south India: analysis of predictive factors.

There are few data on the risk factors for diabetic nephropathy in the Asian Indian population, although several studies have shown a high prevalence of the disease in this ethnic group. This study also aimed to assess the role of hyperglycaemia and hypertension in the causation and course of nephropathy in this population, which has low rates of obesity. Retrospective analysis of two groups of non-insulin dependent diabetic (NIDDM) patients, one without proteinuria (< 100 mg/day, n = 25) and the other with proteinuria (> or = 500 mg/day, n = 25), matched for age, sex, duration of diabetes and body mass index (BMI) was done to study the factors predisposing to proteinuria and also its progression during a 2 year follow-up. Logistic regression analysis showed that the factors contributory to proteinuria were initial HbA1 and initial systolic blood pressure. The average proteinuria during the follow-up was dependent on the initial and average systolic and diastolic blood pressure values. No correlation was seen between cholesterol or triglyceride values and the change in proteinuria. Creatinine clearance deteriorated in the proteinuric group and this was related to the presence of proteinuria and initial diastolic blood pressure. This study emphasizes the importance of blood pressure in the progression of diabetic nephropathy, even in people who have low BMI. Therefore, good control of blood pressure has an important role to play in the management of this condition.

Blood Glucose↗

Family studies of non-insulin-dependent diabetes mellitus in South Indians.

Though a genetic basis for non-insulin-dependent diabetes mellitus (NIDDM) is clear, the likely mode of inheritance is not known. The segregation of NIDDM was studied in 64 nuclear South Indian pedigrees (449 individuals) ascertained through an affected proband having both parents and more than 1 sibling alive and available for oral glucose tolerance testing. A high proportion of parents were found to be of abnormal glucose tolerance [89 of 128 (70%) diabetic and 11 of 128 (9%) impaired]. Complex segregation analysis was performed using (1) POINTER which implements the mixed model and distinguishes major gene, multifactorial and non-transmitted environmental contributions to affection and (2) COMDS which implements an oligogenic model with major gene, modifier gene and environmental contributions to a) affection and b) diathesis (an ordered polychotomy amongst non-affected family members, based on 2-h plasma glucose level). Using POINTER, there was no formal support for a major gene and the most parsimonious solutions were achieved with multifactorial models. Using COMDS, we found i) significant improvements in models when information on glucose levels in nondiabetic family members (diathesis) was included, ii) support for segregation of a diallelic gene as well as background familial resemblance, and iii) under the best-supported model, this diallelic locus featured incomplete dominance (d = 0.8) and a disease-predisposing allele frequency of 14%. In South Indians, segregation of NIDDM is inadequately described by simple major gene models: more complex models provide more satisfactory descriptions. This finding, if applicable in other populations, has important implications for the search for diabetes-susceptibility genes.

Blood Glucose↗

Delayed onset of diabetes in children of low economic stratum--a study from southern India.

Influence of the socioeconomic status on the age at onset of insulin-dependent diabetes mellitus (IDDM) was analysed in 614 patients who developed diabetes < or = 20 years. The peak occurrence was seen at 11 years in girls (n = 293). The boys (n = 321) showed multiple peaks between 11 and 18 years. In the urban patients (n = 463), the peak was at 11 years in contrast to a delayed peak at 18 years in the rural group (n = 151). When analysed with respect to the family income, the higher income group (HIG) (Rs > 2000/month) showed a sharp peak at 11 years whereas the lower income group (LIG) showed a peak at 18 years (chi 2 = 7.2, P = 0.007). The median body weight of the LIG was lower compared to the HIG. Although the exact cause for the delayed age at onset of IDDM in the rural or LIG is not known, it is likely to be a consequence of the lower socioeconomic and nutritional status (indicated by low body weight) and probably indicates the influence of environmental factors in the pathogenesis of the disease.

Adolescent↗

Height at onset of insulin-dependent diabetes in children in southern India.

A total of 250 children with insulin-dependent diabetes mellitus (IDDM), having age at onset of diabetes < or = 18 years were studied. Their height at onset of diabetes was compared with that of the normal age- and sex-matched control population. No differences were observed in the heights of the two groups of children. Therefore, our results were similar to that found in Japan and differed from the reports in European children with IDDM in whom an increased growth velocity was noted before the onset of IDDM.

Adolescent↗

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↗

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↗

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↗

Ofloxacin-containing combined drug regimens in the treatment of lepromatous leprosy.

A total of 26 clinically diagnosed adult patients, with active untreated lepromatous leprosy, with a Bacteriological Index of 4+ or more, were admitted to the hospital of the Central Leprosy Teaching and Research institute, Chengalpattu, India, between 1989 and 1991. After prescribed investigations, the patients were randomly allocated in groups of 3 to 3 treatment regimens, namely: 1, clofazimine 50 mg daily and 300 mg once in 4 weeks + dapsone 100 mg daily (AA); 2, (AA)+ofloxacin 400 mg daily (BB); and 3, (AA)+ofloxacin 800 mg daily (CC). The drugs were administered for 56 days continuously under supervision. Sequential biopsy results on day 0, 7, 14, 28 and 56 in normal mouse footpad revealed no growth by day 28 and 56 in all patients treated with CC and BB regimens, respectively. Calculation of the proportion of viable Mycobacterium leprae through analysis of median infectious dose (ID50) showed significant differences on day 7 in the percentage of kill between the ofloxacin-containing regimens and the other. Moderate to marked clinical improvement has been observed in a significantly higher proportion of patients treated with ofloxacin-containing regimens. All the 3 regimens were well tolerated. No severe complications or side-effects to the drugs were noticed with any of the regimens that required any suspension of treatment or the administration of steroids. Addition of ofloxacin to the standard WHO recommended MDT regimen for multibacillary patients may reduce the present duration of therapy. Ofloxacin may also be considered as an alternative drug in rifampicin-resistant cases or where rifampicin is contraindicated.

Adult↗

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↗