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Biomedical subjects

V Mohan

Publications and source records attributed to V Mohan.

At least 55 records · Page 3Linked to original sources

The genetics of non-insulin-dependent diabetes mellitus in south India: an overview.

Non-insulin-dependent diabetes mellitus affects approximately 10% of urban Indian and Indian migrant populations and as such carries major health implications for these groups. Whilst a strong genetic component to the aetiology of non-insulin-dependent diabetes mellitus is incontestable, progress in identifying the specific genetic determinants involved in its pathogenesis has been slow. In studies of South Indian pedigrees, preliminary segregation analysis indicates that non-insulin-dependent diabetes mellitus is likely to be a polygenic disease. A number of candidate genes have been studied with the aim of demonstrating either association or linkage with the disease; in South Indians the only positive results thus far have been associations between non-insulin-dependent diabetes mellitus and the genes for insulin, apolipoprotein D and complement component C4B. However, it seems likely that these genes contribute only a small proportion of the genetic susceptibility to non-insulin-dependent diabetes mellitus in this ethnic group and that the major genes underlying glucose intolerance remain to be determined.

Apolipoproteins

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

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

Modulation of alpha interferon levels by AZT treatment in HIV-seropositive patients.

The effect of AZT on serum HIV p24 antigen and endogenous serum alpha interferon levels was studied in AIDS and ARC patients. Following administration of AZT there was a rapid decline in the serum levels of both HIV p24 antigen and alpha interferon. When AZT treatment was interrupted, the levels of both HIV p24 antigen and of interferon rapidly increased. These findings suggest that HIV or some other AZT sensitive microorganism is the inducer of interferon which is characteristically found in the serum of AIDS and symptomatic HIV infected patients. They also suggest that the rapid decline in interferon levels may underlie some of the symptomatic benefit that follows administration of AZT.

HIV Antigens

A genetic study of retinopathy in south Indian type 2 (non-insulin-dependent) diabetic patients.

Genetic marker studies in diabetic retinopathy are controversial and frequently complicated by possible independent associations of Type 1 (insulin-dependent) diabetes mellitus with the markers so far analysed. We have looked for associations of candidate genes with retinopathy in South Indian Type 2 (non-insulin-dependent) diabetic patients; patients were subdivided into those with exudative maculopathy (n = 53), proliferative retinopathy (n = 40) and patients free from diabetic retinopathy with a minimum disease duration of 15 years (n = 45). DNA was extracted from blood samples and studied by Southern blot hybridisation techniques and the following probe enzyme combinations: HLA-DQB1; Taq 1, HLA-DQA1; Taq 1, HLA-DRA; Bgl II, insulin gene hypervariable region; Pvu II and the switch region of the immunoglobulin IgM heavy chain gene (S mu); Sac I. Differences in genotype distributions between the study groups were only detected with the S mu probe which detects polymorphism of both S mu and S alpha 1 (the switch region of IgA). Two alleles of S alpha 1 were detected sized 7.4 kilobase and 6.9 kilobase. The frequency of 6.9 kilobase homozygotes was lower in proliferative retinopathy (19%) compared to patients free from diabetic retinopathy (54%, p = 0.005) and exudative maculopathy (46%, p = 0.03). This data suggests that there is a genetic predisposition to proliferative retinopathy in Type 2 (non-insulin-dependent) diabetes of South Indian origin and that this is determined by polymorphism of the heavy chain immunoglobulin genes located on chromosome 14.

Aged

Clinicoradiological diagnosis of benign osteoblastoma of the spine in children.

Three cases of benign osteoblastoma of the spine in children are reported, diagnosed on the basis of clinicoradiological findings and confirmed at surgery and by histopathology. The authors feel that in all cases of painful scoliosis and painful torticollis, a careful search should be made for any suspicious area of sclerosis, especially in the posterior elements of the vertebrae, and all the positive or suspected cases should undergo nuclear bone scanning. All patients whose bone scan is positive should be subjected to computed tomography for differential diagnosis between osteoid osteoma and benign osteoblastoma.

Adolescent

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

Selenium and diabetes in the tropics.

We have examined the possibility that selenium deficiency may underlie one or more of the following peculiarities of chronic pancreatitis in tropical as compared to temperate zones: much higher prevalence, propensity for pancreatic calculi, and high frequency of diabetes. Selenium was measured by graphite furnace atomic absorption spectrometry in sera from 20 healthy volunteers, 36 patients with chronic pancreatitis (calcific 35, diabetic 32), and 23 patients with primary forms of diabetes, from Madras, South India; results were compared with data from 41 controls and 37 patients with chronic pancreatitis (calcific 13, diabetes 8) from Manchester, North West, England. We conclude that (a) bioavailability of selenium is equally high in each geographic area; (b) decrement in serum selenium (p less than 0.001) is of a similar order in Manchester and Madras patients, which denies a connection with calculi formation or pancreatic exocrine failure (since the incidence of these two problems was substantially higher in the Madras series); and (c) selenium levels do not account for accelerated course to diabetes in tropical chronic pancreatitis.

Adolescent

An analysis of amplified insulin gene products in diabetics of Indian origin.

We have previously described an increased incidence of the class 3 allele of the hypervariable region (HVR) 5' to the insulin gene in south Indian non-insulin dependent diabetics; this association is absent in Punjabi Sikhs with this disorder. Using the polymerase chain reaction we have amplified parts of the insulin gene from 130 subjects to look for mutations which may be in linkage disequilibrium with the class 3 allele and hence explain its association with non-insulin dependent diabetes (NIDDM). In 23 south Indian subjects with NIDDM, using the restriction enzyme MboII, a B chain mutant (insulin Chicago) was excluded. Two patterns (alpha and beta) were found, representing a PstI polymorphism in the 3' untranslated region of the insulin gene. In subjects homozygous for the class 1 allele, the allelic frequency for alpha was 0.94 (143/152) and for beta was 0.06, in heterozygotes (1,3) alpha 0.63 (54/86) and beta 0.37, and in homozygotes for the class 3 allele alpha 0.18 (4/22) and beta 0.82 (p less than 0.001), thus establishing linkage disequilibrium between these two loci. No differences in allelic frequency were found in the south Indians or Punjabi Sikhs between controls and the different types of non-insulin requiring diabetes (NIDDM, fibrocalculous pancreatic diabetes and maturity onset diabetes of the young) when both groups were matched for insulin genotypes. Thus, although this polymorphism in the 3' untranslated region of the insulin gene is in linkage disequilibrium with the class 3 allele, it does not appear to be any better at predicting diabetes than the class 3 allele itself.

Alleles

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

Spinal brucellosis.

Twenty-four cases of spinal brucellosis are described. We believe that it is possible to distinguish this condition from spinal tuberculosis on the basis of the clinical and radiological findings.

Adolescent

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

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

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

T-cell receptor beta-subunit gene polymorphism and autoimmune disease.

We have investigated the distribution of genotypes of a restriction fragment length polymorphism of the T-cell receptor beta-subunit gene in Caucasoid controls and patients with insulin-dependent diabetes mellitus, celiac disease, dermatitis herpetiformis, and idiopathic membranous nephropathy and also in South Indian controls and diabetics. We found no significant differences between the controls and patients with any disease in either ethnic group, a result which contrasts with previous reports of associations with both insulin-dependent diabetes mellitus and idiopathic membranous nephropathy. However, the most striking finding was a marked disparity between the genotype distribution in our Caucasoid control population and that previously reported by other investigators.

Autoimmune Diseases