Malnutrition related diabetes mellitus.
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Biomedical subjects
Publications and source records attributed to V Mohan.
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Pancreatic beta cell function was evaluated in 30 insulin treated non-insulin dependent diabetic patients, by estimating serum C-peptide after meal stimulation. C-peptide response was low (less than 0.6 pmol/ml) in 15 patients and it was significant (greater than 0.6 pmol/ml) in the other 15 patients. All the patients were then started on a high carbohydrate, high fibre diet and a combination of glibenclamide and metformin. In 18 patients, optimal regulation of hyperglycemia was achieved in one week and the others required insulin treatment. Among the 15 with low C-peptide values, 8 patients responded to oral hypoglycaemic agents and their C-peptide responses improved (from 0.17 +/- 0.16 to 0.78 +/- 0.2 pmol/ml). Among the 15 with significant C-peptide values, 10 responded well to oral drugs and their C-peptide values improved further (from 0.79 +/- 0.21 to 1.17 +/- 0.44 pmol/ml); but the others required insulin despite the good beta cell reserve. This study shows that the beta cell response in insulin treated NIDDM varies widely as it is influenced by the exogenous insulin and hyperglycaemia a random estimation of C-peptide will be of limited value in predicting the response to therapy.
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The serum immunoreactive insulin response to an oral glucose load was estimated in 15 Asian Indian and 29 European non-diabetic subjects, and in 45 Asian Indian and 72 European Type 2 (non-insulin-dependent) diabetic patients. In the non-diabetic group, basal insulin values were higher in the Asian Indians than the Europeans (16.7 +/- 3.0 vs. 6.9 +/- 0.7 mU/l, p less than 0.001), and remained higher throughout the glucose tolerance test. Total insulin response was also higher in the Asian Indians (p less than 0.001), and linear regression analysis revealed basal insulin, body mass index and race to be important predictors of insulin response. Amongst the diabetic patients, basal insulin values were again higher in the Asian Indians compared with the Europeans (18.0 +/- 5.0 vs. 11.5 +/- 0.9 mU/l, p less than 0.05). Total insulin response was also greater (p less than 0.01). Linear regression analysis revealed the basal insulin value to be the only significant predictor of insulin response. The results demonstrate higher insulin levels in Asian Indians than Europeans in both normal subjects and Type 2 diabetic subjects. The insulin response to a glucose load is also greater in the Asian Indians. In the control subjects, ethnic differences contribute to this response, whereas in the diabetic patients this is a function of the elevated basal insulin values of the Asian Indians.
A prospective study was undertaken in 107 Indians with impaired glucose tolerance (IGT) for a period ranging from 2 to 10 years. On follow-up, 32% still had an impaired glucose tolerance, 32% reverted to normal glucose tolerance and 36% developed diabetes. Careful dietary adherence and weight reduction were found to favour normalisation of glucose tolerance. Poor dietary adherence, persistent obesity and weight gain were found to precipitate diabetes. The study stresses the need for intensive diet therapy in individuals with IGT. Insulin responses were heterogeneous in IGT and non-predictive of the follow-up changes in glucose tolerance.
Pancreatic beta cell function was assessed by estimation of fasting and post prandial plasma C-peptide in 183 non-insulin dependent diabetic patients, who were treated with oral hypoglycaemic drugs, for more than 10 years. One-hundred-and-forty-one patients, continued to respond to oral hypoglycaemic agents (Group I) and in 42 the control was not satisfactory and had to be changed over to insulin (secondary failure, Group II). Significant beta cell reserve (PP CP greater than or equal to 0.6 pmol/ml) was present in 89 out of 183 patients (48%) and 83 (93%) of them responded to oral hypoglycaemic agents. Among the 94 patients with low beta cell reserve, 58 (62%) were on oral hypoglycaemic agents and the other 36 (38%) were on insulin. Of the 42 patients with secondary failure to the oral drugs, 36 (86%) had low C-peptide while 6 (14%) had significant C-peptide values. Secondary failure to oral hypoglycaemic agents can also occur in spite of good beta cell reserve. Beta cell reserve was not correlated either to the duration of diabetes or the age at diagnosis of the patients.
Pancreatic beta cell function in response to glucose was assessed in three different groups of offspring of conjugal diabetic parents (OCDP): those with normal glucose tolerance, those with impaired glucose tolerance (IGT), and those with diabetes. Serum immunoreactive insulin (IRI), C-peptide (CP), insulin/glucose (I/G) ratio, and IRI/CP ratios were estimated at fasting and 90 min after glucose load. Insulin secretion, measured as CP, was found to be low even in normal nonobese OCDP, but the change was not reflected in IRI value as the IRI/CP ratio was found to be elevated. The values decreased with increasing glucose intolerance. In obese OCDP, all the parameters were abnormal even among those with normal glucose tolerance, and further deterioration occurred with increasing glucose intolerance. The study shows that insulin secretory defects are detectable even in normal OCDP, and these changes deteriorate with increasing glucose intolerance. Differences are noted in the peripheral concentrations of IRI and CP between obese and nonobese OCDP before development of diabetes. After development of diabetes mellitus, these differences disappear, and the CP and IRI values in both groups are similar and low.
Non--insulin-dependent diabetes mellitus (NIDDM) patients, 94 in number, who were treated with insulin for various reasons for periods ranging from 2 to 10 years, were investigated to study the effect of long-term insulin therapy and also the effect of anti-insulin antibodies on the beta cell function. Insulin antibody titer and the stimulated C-peptide (CP) did not correlate with the duration of insulin therapy, dose of insulin, or the severity of hyperglycemia. The antibody titers were low in 45%, moderate in 10%, and high in 45%; no correlation was found between the antibody titers and the CP values. Satisfactory control of hyperglycemia was obtained in 54 patients after change of treatment to oral hypoglycaemic agents (OHA). The other 40 patients required continued insulin therapy. The initial CP values were similar in both the groups before initiating the new therapeutic patterns. Those who responded to OHA showed improved CP values on follow-up. The beta cell response to exogenous insulin is heterogeneous in NIDDM patients. In many patients, adequate preservation of beta cell function is present even after long-term insulin therapy. Many of them respond to OHA. Insulin antibodies do not influence the secretory status of the beta cells in NIDDM patients.
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The clinical features of large unselected groups of Asian (401) and European (491) patients attending a diabetic clinic were compared. The prevalences of symptomatic ischaemic heart disease, hypertension, retinopathy, and lens opacities were similar in the two groups, despite the shorter known duration and the relative youth of the Asian patients. Pedal pulses were more often absent in Europeans, whereas in the age-group 20-64 years, ankle and knee reflexes were more often unobtainable in Asians. The degree of adiposity was similar in the two groups, but was less in Asian males than females. A first-degree diabetic relative was reported more commonly in Asians than in Europeans. These findings are important in relation to the exceptionally high prevalence of diabetes recently described in the Southall Asian community.
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In a study of the retinopathy profile of 40 patients with tropical pancreatic diabetes, a form of secondary diabetes seen in tropical countries, diabetic retinopathy was detected in 13 patients. Ten patients had background retinopathy and three patients had proliferative retinopathy requiring laser photocoagulation. In two patients, fibrous retinitis proliferans was present. Three patients had evidence of diabetic maculopathy. To our knowledge, this is the first report of severe and sight-threatening retinopathy occurring with secondary diabetes. Retinopathy in these forms of diabetes has hitherto been considered to be rare or, if present, only of a mild background type.
Clinical and biochemical studies were carried out in 33 patients with diabetes secondary to chronic calcific, non-alcoholic pancreatitis (tropical pancreatic diabetes) and in 35 Type 2 (non-insulin-dependent) diabetic patients and 35 non-diabetic subjects. Despite lower body mass indices, only 25% of patients with tropical pancreatic diabetes had clinical evidence of malnutrition. There was no history of cassava ingestion. Mean serum cholesterol concentration was significantly lower in the tropical pancreatic diabetic patients (p less than 0.01) in comparison with the Type 2 diabetic patients or non-diabetic subjects, due to a significantly decreased concentration of LDL cholesterol (p less than 0.01) and VLDL cholesterol (p less than 0.05). Basal and post-glucose stimulated concentrations of serum C-peptide were highest in those pancreatic diabetic patients (n = 11) who responded to oral hypoglycaemic drugs, intermediate in the majority (n = 17), who were insulin dependent and ketosis resistant and negligible in a small sub-group (n = 5) who were ketosis prone. The occurrence of microangiopathy in pancreatic diabetic patients was common and similar to that in Type 2 diabetic patients. Thus, tropical pancreatic diabetes in South India appears to be heterogeneous with respect to level of nutrition, severity of glucose intolerance, B-cell function, response to therapy and the occurrence of microvascular complications.
The prevalence of Type 2 (non-insulin-dependent) diabetes among offspring of conjugal Type 2 diabetic parents in India was determined by performing oral glucose tolerance tests. Diabetes was present in 50% of offspring, and 12% had impaired glucose tolerance according to the National Diabetes Data Group criteria. Thus, 62% of all offspring had abnormal glucose tolerance tests. This is the highest prevalence rate for diabetes among offspring of conjugal diabetic parents and might represent an ethnic variation of the genetic factors operating in Indian patients with Type 2 (non-insulin-dependent) diabetes.