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Biomedical subjects

V Mohan

Publications and source records attributed to V Mohan.

At least 109 records · Page 6Linked to original sources

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↗

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↗

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↗

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↗

Changes in peripheral insulin concentrations in non insulin dependent diabetes during treatment. Assessment by mathematical applications.

Serum immunoreactive insulin responses to meal stimulus were studied in 20 newly detected non insulin dependent diabetes mellitus patients, following one week of treatment with high carbohydrate, high fibre diet and glibenclamide. Ten patients showed "rapid glycaemic response" i.e. the glycaemic response was good within a week. The rest of them were called "slow responders". The insulin responses were heterogenous. Mathematical calculations using the glucose and insulin responses showed improved beta cell function and peripheral action of insulin in rapid responders. On the other hand, the slow responders showed only slightly improved beta cell function with no change in peripheral action of insulin. The second phase of the study constituted follow-up studies upto 6 months. The corrected insulin response (CIR) increased initially in several patients. The peripheral insulin action improved in all patients with longer duration of treatment and lower insulin concentrations were required to maintain normoglycaemia at this stage. The results of the study indicate that a) multiple factors influence glucoregulation, b) even short term effects of the drug appear to be mediated by extra pancreatic mechanisms, and c) the extrapancreatic action improves significantly on long term use of the drug.

Adult↗