Biomedical subjects

A Ramachandran

Publications and source records attributed to A Ramachandran.

At least 145 records · Page 8Linked to original sources

PubMed1993

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↗

PubMed1993

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↗

PubMed1993

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↗

PubMed1992

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↗

PubMed1992

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↗

PubMed1992

Prevalence of glucose intolerance in Asian Indians. Urban-rural difference and significance of upper body adiposity.

OBJECTIVE: To evaluate the prevalence of NIDDM and IGT in the urban and rural areas in southern India. RESEARCH DESIGN AND METHODS: Two populations of the same ethnic background, but different socioeconomic background were chosen for this study. Nine-hundred urban people and 1038 rural subjects were studied. Fasting and 2-h post-glucose capillary blood samples after a 75 g oral glucose load (WHO criteria) were obtained in these randomly selected adults (greater than or equal to 20 yr of age). RESULTS: Using the WHO criteria, the prevalence of NIDDM, adjusted to the age of the respective general population, was 8.2% in the urban and 2.4% in the rural populations. The prevalence was 8.4 and 7.9%, respectively, in urban men and women, and 2.6 and 1.6% in rural men and women. The age-adjusted prevalence of IGT was 8.7 and 7.8% in the urban and rural areas, respectively. The prevalence of IGT was 8.8% in urban men and 8.3% in women; the corresponding values for rural men and women were 8.7 and 6.4%. The prevalence of NIDDM increased with age, markedly so in the urban people. The urban-rural difference was significant for NIDDM (chi 2 = 29.4, P less than 0.001) but not for IGT. In the urban population, 65% of the NIDDM patients were known cases, whereas in the rural area, the known cases accounted for only 24%. Bivariate analysis showed an association of BMI, STR, and WHR with prevalence of NIDDM plus IGT. In the multiple logistic regression analysis, age, BMI, STR, and WHR were associated significantly with glucose intolerance in the urban population, whereas only age was significant in the rural population. The best predictors of NIDDM were age, BMI, WHR, and urbanization. CONCLUSIONS: The study showed a high prevalence of NIDDM in the urban southern Indian population. The prevalence of NIDDM in the same ethnic group in rural areas was significantly lower. The prevalence of IGT was similar in both populations. Upper body adiposity was a significant predictor of NIDDM in this population with low rates of obesity.

Adipose Tissue↗

PubMed1992

Genetic epidemiology of NIDDM among Asian Indians.

Prevalence of non-insulin-dependent diabetes (NIDDM) in India was reported to be 2.3% in the urban and 1.5% in the rural areas in the early 1970s by the Indian Council of Medical Research (ICMR). Recent studies both in the migrant Indians and in the native Indians have shown the prevalence to be much higher than the above values. Similar prevalence of NIDDM in the migrant and native Indians in affluent areas suggests that Indians as an ethnic group have a high genetic risk for diabetes. Our recent study in South India showed a high prevalence of diabetes in the urban area (8.2%) versus a low prevalence of 2.4% in the rural area. Age, urban-rural factor, body mass index (BMI) and the waist:hip ratio (WHR) were positively associated with diabetes. Interestingly, the prevalence of impaired glucose tolerance (IGT) was similar in urban and rural areas (8.7% and 7.8%, respectively) despite a four-fold lower prevalence of diabetes in the latter. The ratio of new to known diabetes was 1:2 in the urban and 3:1 in the rural areas. There was a male preponderance among Indian diabetic patients. Migration from rural to urban environment with changes in dietary habits and physical inactivity may have contributed to the increased prevalence of diabetes. A high rate of familial aggregation is noted in NIDDM in India and the genetic risk of NIDDM increases with increasing family history of diabetes. In the adult offspring of diabetic parents, hyperinsulinaemia and decreased insulin sensitivity are observed before the development of glucose intolerance.

Diabetes Mellitus, Type 2↗

PubMed1992

Glucagon response to glucose load in offspring of conjugal type 2 diabetic parents in south India.

Immunoreactive glucagon responses were measured in 21 normoglycaemic adult offspring of non-insulin dependent (Type 2) diabetic parents, in the fasting state and during an oral glucose tolerance test. In 7 of the 21 offspring, the mean fasting immunoreactive glucagon value was significantly lower than the control value (p < 0.001). In this group, glucose stimulation did not produce inhibition of immunoreactive glucagon secretion. The insulin response in this group was not significantly different from the values in the other study groups. In the other 14 offspring, the pattern of glucagon response to glucose stimulation was similar to controls. It is likely that this non-suppressive effect of glucose on immunoreactive glucagon in some of the "prediabetic" individuals is an early change in the alpha cell function during the natural history of non-insulin dependent diabetes in Asian Indian subjects.

Adult↗

PubMed1992

Insulin responses to varying hyperglycaemia in newly diagnosed non-insulin dependent diabetic patients.

The effect of varying degrees of hyperglycaemia on insulin secretion was studied in newly diagnosed non-insulin dependent diabetic patients, stratified according to the fasting plasma glucose values. Of the 116 patients studied, 62 were non-obese and 54 obese. Insulin response patterns during 2h oral glucose tolerance test were analysed in comparison with the values in weight matched control subjects and also with respect to the degree of hyperglycaemia. The effect of hyperglycaemia on beta cell secretion differed in obese and non-obese patients. In the non-obese, fasting insulin levels were within normal range even in those with severe hyperglycaemia while the corresponding values in response to glucose stimulation showed a decreasing pattern. In obese patients, even fasting immunoreactive insulin (IRI) value was decreased and with increasing hyperglycaemia the reduction in IRI response to glucose stimulation was of greater magnitude compared to non-obese patients. Thus the modulating effect of obesity on insulin secretion appears to disappear with development of hyperglycaemia. The insulinogenic index was low in all the diabetic patients.

Adult↗

PubMed1991

Nutritional profile of fibrocalculous pancreatic diabetes and primary forms of diabetes seen in southern India.

Plasma levels of retinol binding protein (RBP), prealbumin, total protein, albumin, transferrin and ferritin were estimated in three groups of diabetic patients seen at a diabetes centre in S. India. The groups consisted of patients with fibrocalculous pancreatic diabetes (FCPD), non-insulin-dependent diabetes mellitus (NIDDM) and insulin-dependent diabetes mellitus (IDDM). Mean RBP levels were lower in FCPD and IDDM patients compared to controls but this did not reach statistical significance. Prealbumin levels were normal in FCPD patients, but low in IDDM compared to controls (P less than 0.005) and NIDDM (P less than 0.05). FCPD patients had lower transferrin levels compared to controls (P less than 0.05). There were no differences in the levels of total protein, albumin and ferritin in any of the study groups. The study shows that biochemical evidence of undernutrition is seen in FCPD and IDDM patients while NIDDM patients are not significantly different from non-diabetic control subjects.

Adult↗

PubMed1991

Microalbuminuria in NIDDM patients in south India.

Urinary albumin excretion (UAE) was estimated by radioimmunoassay in 316 non-insulin dependent diabetic patients (NIDDM), with diabetes for 10 or more years and proteinuria less than 150 mg/24 h. Albuminuria was determined in 24 h collection of urine in 259 patients but in the other 57, a random sample was used. The mean UAE was 23 +/- 45.3 (SD) micrograms/mg creatinine in the patients against 4.4 +/- 2.7 micrograms/mg in the controls (30). Ninety patients (28.5%) had microalbuminuria i.e., the UAE exceeded, 20 micrograms/mg creatinine. A higher percentage (31.7%) of men had microalbuminuria than women (23.6%). The presence of microalbuminuria was similar in the insulin-treated and in oral drug-treated patients (29.6% and 26.5% respectively). Stepwise multiple regression analysis using albumin/creatinine ratio as the dependent variable showed that factors such as blood pressure, blood glucose, HbA1, body mass index, sex, age, duration of diabetes and the association of vascular complications of diabetes did not have significant correlation to microalbuminuria. Creatinine clearance showed a significant inverse correlation to the albumin/creatinine ratio. Although the prevalence of microalbuminuria in NIDDM in this study is not significantly different from those reported from other countries, the morbidity index due to kidney disease could be high due to the large absolute number involved in our country. This underscores the need for early detection of the disease and institution of preventive measures to arrest its progression.

Adult↗

PubMed1991

Pregnancy in fibrocalculous pancreatic diabetes.

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Adult↗

PubMed1990

Plasma glucagon responses in tropical fibrocalculous pancreatic diabetes.

Plasma insulin and glucagon responses to a glucose load were measured in a group of patients with fibrocalculous pancreatic diabetes (FCPD) and compared with patients with noninsulin-dependent diabetes mellitus (NIDDM) and control subjects. Both diabetic groups had markedly diminished insulin responses but the differences between FCPD and NIDDM groups were not significant. In control subjects, in response to the glucose load, plasma glucagon levels decreased while they increased in NIDDM patients. In FCPD patients there was no significant change in glucagon levels in response to the glucose load. The study shows that FCPD patients lack pancreatic alpha-cell responses to a glucose load. This may play a role in protecting these patients against ketosis.

Adult↗

PubMed1990

Fibrocalculous pancreatic diabetes and obesity.

Fibrocalculous pancreatic diabetes (FCPD) is a form of diabetes secondary to chronic pancreatitis that is found in tropical countries. Most patients with FCPD are lean and many are frankly undernourished. Four patients with FCPD who were obese are reported in this paper and this is the first report of obesity in FCPD patients.

Adult↗

PubMed1990

Development of carbohydrate intolerance in offspring of Asian Indian conjugal type 2 diabetic parents.

Sixty-four offspring of conjugal diabetic parents (OCDP) who were normoglycaemic initially were available for a retest after a period of 4-9 years. Among them 10 (15.6%) had developed diabetes, 19 (29.7%) had developed IGT and the remaining 35 (54.7%) had maintained normal GTT. The predictive value of the baseline (initial) parameters was tested. Among the non-obese OCDP (BMI less than 25 and less than 27 for women and men, respectively), the initial sum of plasma glucose (sigma PG), and the mean increment of insulin during GTT (delta IRI), and the 2-h IRI values were higher in the group that developed abnormal glucose tolerance (P less than 0.05 compared to controls and normal OCDP). They also had higher insulin:glucose ratios, indicating higher insulin output for a given glucose concentration. On the other hand, among the obese OCDP the initial parameters did not differ between those who developed abnormal glucose tolerance and those who did not. Stepwise multiple regression analysis showed that the baseline sigma plasma glucose value was significantly related to the final 2-h plasma glucose when all the OCDP were taken together (P = 0.0023) and also in the non-obese OCDP (P = 0.0002). The other parameter which showed a relation to the final 2-h plasma glucose was the baseline delta IRI, although it was not statistically significant (P = 0.08). No such relation was observed in the obese group.

Blood Glucose↗

PubMed1990

Familial aggregation in type 1 (insulin-dependent) diabetes mellitus: a study from south India.

An analysis of 617 Type 1 (insulin-dependent) diabetic patients from 587 families was made. In 33 families (5.6%) there was more than one Type 1 diabetic patient. In 98 families (16.7%) positive family history of Type 2 (non-insulin-dependent) diabetes was present. There was a linear correlation between the age at diagnosis of the proband and that of the sibling (r = 0.73, p less than 0.001) in the Type 1 multiplex families. The risk of Type 1 diabetes in relatives was found to be 2.7% by Li Mantel estimate, which is lower than that reported among Europeans. The cumulative risk was higher (p less than 0.001) in the relatives of Type 1 diabetic patients with age at diagnosis less than or equal to 10 years.

Age Factors↗

PubMed1990

Decreased insulin sensitivity in offspring whose parents both have type 2 diabetes.

Offspring of two Type 2 diabetic parents have a high prevalence of diabetes and impaired glucose tolerance. Studies in normoglycaemic offspring have shown abnormal insulin responses. Twenty-four non-obese offspring having normal oral glucose tolerance were investigated by the insulin tolerance test for abnormalities of insulin sensitivity. Plasma insulin responses were measured during an oral glucose tolerance test. Although the plasma glucose responses during the OGTT were similar to the control values, the corresponding insulin responses were higher. The mean area under the insulin curve was 121 +/- 29 (+/- SD) mU l-1 h in the control subjects and 203 +/- 73 mU l-1 h in the offspring (p less than 0.001). The mean KITT value in the offspring was 4.3 +/- 1.9 min-1 x 100 which was significantly lower (p less than 0.01) than the value of 6.2 +/- 2.0 min-1 x 100 in the control subjects. The results suggest that some offspring of two Type 2 diabetic parents have low insulin sensitivity and the presence of hyperinsulinism may be a compensatory phenomenon.

Adult↗

PubMed1990

Combination therapy of glibenclamide and insulin in NIDDM patients with secondary failure to oral drugs.

A trial of combination therapy with glibenclamide + insulin was conducted in 26 patients with non insulin dependent diabetes mellitus (NIDDM) who had secondary failure to oral hypoglycaemic agents (OHA). Patients were included in the study if they failed to respond to a dose of 15 mg of glibenclamide under strict dietary regulations. Small doses of insulin were added until satisfactory glucoregulation was achieved. On withdrawal of the OHA, in 20 patients, the post-prandial plasma glucose values (PPBS) increased again by greater than or equal to 25%; they were considered as "responders". Responders were divided into two equal groups of alternate patients; group I was treated with insulin + glibenclamide and group II with insulin + placebo. The patients were then followed up at monthly intervals for 6 months. The dose of insulin required to maintain normal plasma glucose value was significantly lower (P less than 0.05) in group I. Fewer patients in group I needed two injections of insulin per day; however this difference was not statistically significant. Normalisation of serum triglyceride and lowering of HbA1 occurred in both groups. This study shows that addition of glibenclamide to insulin treatment is advantageous in NIDDM patients showing secondary failure to OHA.

Administration, Oral↗