Somatomedin activity in diabetic patients.
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Biomedical subjects
Publications and source records attributed to I Jialal.
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Insulin binding and processing was studied in monolayer cultures of bovine aortic endothelial cells. Specific 125I-insulin binding was both time and temperature dependent. Maximum binding at 37 degrees C occurred at 90 min, and was 3.8%/mg protein and, at 15 degrees C, 7%/mg protein at 4 h. 125I-insulin was crosslinked to its receptor using disuccinimidyl suberate (DSS), and the structure of the receptor complex was identified by SDS-polyacrylamide gel electrophoresis and autoradiography; a major band with Mr = 145,000 was identified, which corresponds to the alpha-subunit of the insulin receptor reported in other tissues. Receptor-bound insulin was internalized, and both the rate and the amount of internalization were temperature dependent. The rate of internalization was slowest at 4 degrees C, and fastest at 37 degrees C, and the maximum amount of 125I-insulin internalized in 120 min was 16% at 4 degrees C, 45% at 15 degrees C, and 81% at 37 degrees C. Despite the high rate of internalization, endothelial cells do not appear to degrade insulin significantly, as determined by gel chromatography and TCA solubility (7% at 4 h) of media-associated radioactivity. In addition, the majority of internalized insulin (75%) was released by 60 min, largely as intact insulin. Chloroquine treatment at high concentration did not exert any major effect on insulin binding or degradation within the first 60 min, but thereafter produced a marked increase in cell-associated radioactivity.(ABSTRACT TRUNCATED AT 250 WORDS)
Serum and urine beta 2-microglobulin concentrations were measured in 17 primigravidas with mild pregnancy-induced hypertension and nine normotensive control patients matched for gestational age. Serum beta 2-microglobulin and creatinine clearance values were not different between the two groups but urinary excretion of beta 2-microglobulin was three times higher in the hypertensive patients. This difference disappeared within seven days of delivery. These results indicate that a reversible renal tubular lesion occurs in pregnancy-induced hypertension even in the absence of detectable proteinuria.
The responses of plasma prolactin, follicle-stimulating hormone (FSH), luteinizing hormone (LH), and thyroid-stimulating hormone were measured in ten women with Sheehan's syndrome after intravenous administration of the appropriate releasing hormones. Growth hormone and cortisol responses to insulin-induced hypoglycemia were also measured. It was found that two patients were biochemically borderline euthyroid and eight were probably hypothyroid in the face of thyroid-stimulating hormone values in the reference range; in two patients thyroid-stimulating hormone response to thyrotropin-releasing hormone was appropriate. In no patient were the minimum prolactin levels achieved, in response to thyroid-releasing hormone as established in reference subjects. Growth hormone response to hypoglycemia was inadequate in all patients and only one patient achieved reference range values of cortisol during hypoglycemia. In six patients fasting LH and FSH were in the reference range and the response to gonadotropin-releasing hormone was adequate and appropriate in eight patients. In light of these findings it is suggested that prolactin response to thyrotropin-releasing hormone administration would be a reliable and simple screening procedure for suspected Sheehan's syndrome.
Glycosylated haemoglobin (Hb A1) values were estimated immediately after delivery in 29 patients who had given birth to a large infant, in 25 who had delivered a macerated stillborn infant, and in 31 controls matched for age and parity. No difference in mean Hb A1 values was found between mothers of normal-sized and of large infants. The mean Hb A1 level for the mothers who had delivered a macerated stillborn infant was higher than that for the control group (8,26% v. 7,65%). Although this was not statistically significant, there were 5 patients with a raised Hb A1 value and a normal glucose tolerance test result; this may suggest gestational diabetes.
Beta-2-microglobulin (BMG) is physically linked to the allo-antigenic HLA chain on the cell surface and is accordingly a marker for the HLA antigens. BMG concentrations were measured in serum and cerebrospinal fluid (CSF) samples from 22 patients with choriocarcinoma, 5 with hydatidiform mole and 17 reference subjects in the first trimester of pregnancy. Serum BMG levels were elevated in the patients with choriocarcinoma, particularly when human chorionic gonadotrophin levels were higher than 50 000 U/l (less than 50 000 U/l--1,6 +/- 0,3 mg/l; greater than 50 000 U/l--2,75 +/- 0,72 mg/l; molar pregnancy--1,42 +/- 0,44 mg/l; reference subjects--1,47 +/- 0,15 mg/l) (mean +/- 1 SD). BMG levels in the serum and CSF were not increased when metastases were present in the cranium. None of the patients had evidence of abnormal renal function as determined by serum urea, electrolyte and creatinine levels and the creatinine clearance rate. These results suggest that BMG and HLA antigens are expressed on the trophoblastic cells in choriocarcinoma, or alternatively that the maternal immunocytes produce increased quantities of BMG.
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Carbohydrate metabolism was evaluated in 26 women with a twin pregnancy and 26 women with a singleton pregnancy. The groups were similar in respect of age, parity and gestational age. Each woman had an oral glucose tolerance test. No significant differences in venous blood sugar values or insulin responses were found between singleton and twin pregnancies.
Glucose tolerance and lipid levels in a random sample of 103 Indian patients (96 males and 7 females) with coronary artery disease (CAD) aged between 20 and 55 years were compared with those in a healthy Indian control group matched as regards age and sex. Previous episodes of myocardial infarction were taken as evidence of CAD. Of the patients 44% were overweight. Glucose tolerance was abnormal in 55% of the patients. Both cholesterol and triglyceride values in the patients with CAD were significantly higher than those in the control group. Serum cholesterol levels were over 6,5 mmol/l in 62% of the patients with CAD and serum triglyceride levels were over 2,0 mmol/l in .53%. Males with CAD tended to have lower plasma high-density lipoprotein (HDL) cholesterol levels than the control group (P less than 0,01). There was a significant negative correlation between body mass index and HDL cholesterol, and no correlation was demonstrated between body mass index and total cholesterol or triglyceride levels. Furthermore, when the patients were sub-grouped according to their glucose tolerances it was found that only the triglyceride levels were significantly different (values were higher in those with abnormal glucose tolerance). Our data suggest that abnormal glucose tolerance and lipid aberrations are significant risk factors in Indian patients with CAD.
The mean total serum oestradiol level was found to be significantly increased in 8 patients with carcinoma of the breast when compared with 8 healthy reference subjects matched for race, sex and age. The calculated mean free oestradiol index was also higher in these patients. There were no significant differences, however, between the levels of LH, FSH, prolactin. DHEA-S, testosterone and SHGB in the 2 groups. The patients showed a significantly increased LH response to GnRH while there was no difference in the FSH response. Only 1/7 patients had a tumour devoid of steroid hormone receptors. It may be that an increased level of circulating oestradiol-17 beta is an important factor in the aetiology of hormone-dependent male breast cancer.
Response to diet and drug therapy was assessed in a group of 85 Indian patients with non-insulin-dependent diabetes in the young (NIDDY). There was a significant decrease in fasting plasma glucose (FPG) values on therapy (pretreatment 13.3 +/- 0.5 mmol/l; post-treatment 9,7 +/- 0,4 mmol/l) (P less than 0,001). Prior to therapy the majority of patients had either moderate (40%) or severe (59%) diabetes; on therapy, the majority had either mild (21%) or moderate (62%) diabetes. Estimation of glycosylated haemoglobin (Hb A1) levels revealed that control was excellent (Hb A1 less than 10%) in 47% of patients and excellent or adequate (Hb A1 less than 12%) in 78%. Hb A1 levels correlated significantly with the FPG value (r = 0,78; P less than 0,001). In 8 patients with iron deficiency anaemia the HB a1 level did not fall within the correlation norms between Hb A1 and FPG. Treatment of the anaemia restored the correlative norms. Hb A1 levels were significantly higher in patients with microvascular complications (12,1 +/- 0,8%) than in those without any vascular complications (10,3 +/- 0,3%) (P less than 0,01).
Cortisol and growth hormone (GH) responses to a 100 g oral glucose load were measured in 85 Indian patients with non-insulin-dependent diabetes in the young (NIDDY) and 50 reference subjects; in 16 patients and 12 reference subjects the glucagon responses were also assessed. Fasting serum cortisol and plasma glucagon levels were significantly higher in the NIDDY group (P less than 0.001); in contrast, GH levels in the NIDDY patients were significantly lower (P less than 0.01). Plasma glucagon was only significantly suppressed 150 minutes after oral glucose loading in the NIDDY group, in contrast to the reference group, which showed maximum suppression at 90 minutes; at all time intervals plasma glucagon levels were significantly higher in the NIDDY patients. Obesity did not affect fasting plasma glucagon levels. In response to the oral glucose load serum cortisol levels in the NIDDY patients were suppressed in parallel with those in the reference group but remained significantly higher throughout the period of observation at all time intervals. Obese NIDDY patients had higher fasting cortisol levels, but their response to orally administered glucose was no different from that of the NIDDY group as a whole. GH suppression by oral glucose in NIDDY patients was less than that in the reference group, and the rebound rise occurred earlier. Obese NIDDY patients had higher fasting GH levels than their non-obese counterparts, but responses to the glucose load were not different.
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Of 85 Indian patients with non-insulin-dependent diabetes in the young, 16 (19%) were found to have vascular disease. Of these 16 patients 14 had diabetic retinopathy and 6 nephropathy. Five of the patients with nephropathy also had retinopathy, and the 6th had bilateral cataracts. Three patients had ischaemic heart disease associated with nephropathy and/or retinopathy. No patient had peripheral or cerebrovascular disease, and 15 (18%) were found to have hypertension; 5 (31%) of the patients with vascular disease had hypertension.
In 56 patients in whom the glomerular filtration rate (GFR) was estimated by the 51Cr-EDTA technique, serum creatinine and beta 2-microglobulin levels were also measured. In the 15 patients with a GFR of greater than or equal to 80 ml/min, both serum creatinine and beta 2-microglobulin levels were within the reference range. However, the beta 2-microglobulin level was elevated (greater than 2,3 mg/l) in all 41 patients with a GFR of less than 80 ml/min, while the serum creatinine level was increased (greater than 133 mumol/l) in only 35 patients. In the remaining 6 patients, the creatinine values ranged from 75 to 125 mumol/l. It would therefore seem that serum beta 2-microglobulin assay is a more sensitive test than creatinine assay for detecting impaired renal function.
Over a 5-year period 14 patients with acromegaly and gigantism were seen at the endocrine clinic of King Edward VIII Hospital: 9 were Blacks and 5 Indians; 8 of the patients were women. The mean age of the patients was 46 years. Surprisingly, only 2 patients complained of acral overgrowth. Symptomatology was varied and not characteristic of the condition. On examination all patients had unequivocal signs of soft-tissue and bony overgrowth, 64% had visual abnormalities and 50% hypertension. Radiologically, 88% showed an enlarged pituitary fossa. On biochemical investigation, the fasting levels of growth hormone (GH) were increased in 12 patients and during oral glucose tolerance tests, the GH levels in these 12 patients were not suppressed. One patient in whom the fasting GH level was not increased had progressed to the stage of panhypopituitarism, in the remaining patient challenge with thyrotrophin-releasing hormone (TRH) led to increased GH levels and L-dopa challenge resulted in a paradoxical decrease in GH levels. Seven patients with increased GH levels who were challenged with L-dopa showed the typical decrease in GH levels found in this condition; in 5 of these patients, challenged with TRH, GH levels increased. The findings emphasize that despite the ease of clinical diagnosis, appropriate biochemical investigations are necessary to confirm the exact status of the disease, which is rare in the population studied.
Cholesterol, triglycerides and high-density lipoprotein (HDL) cholesterol levels were measured in Indian patients with non-insulin-dependent diabetes in the young (NIDDY). Both cholesterol and triglycerides were increased as compared with reference values. The HDL cholesterol levels were lower in cases of NIDDY. Aberrations in the lipid and lipoprotein levels were more pronounced in males. Significant correlations were found between the levels of cholesterol and glycosylated haemoglobin, and triglycerides and glycosylated haemoglobin; triglycerides and HDL cholesterol were inversely correlated. No correlation was found between triglycerides and obesity. NIDDY does not differ from the more common type of non-insulin-dependent diabetes in mature patients with regard to cholesterol, triglyceride and HDL cholesterol levels.
Non-insulin-dependent diabetes with age of onset under 35 years was studied in 85 Indian patients eighty-one per cent of the group were females, the mean age of onset of diabetes was 27 years while the mean duration was 6.3 years. the mean percentage desirable mass of the patients was 112%, obesity being present in 55% of the group. Eighty-two per cent of patients gave a positive family history; closer analysis revealed that 75% of the propositi had a diabetic parent and 41% a diabetic sibling; while three-generation transmission was present in 7%. Eighty-one patients consented to a 100 g oral glucose load. The insulin and glucose response during a 3-hour period revealed fasting hyperinsulinism with a delayed and attenuated insulin response, a much lower insulin area and higher glucose ares, a lower insulin-glucose ratio and a lower modified Seltzer insulinogenic index when compared with 50 non-diabetic reference subjects. There was no difference in insulin and glucose responses in obese and non-obese diabetics. However, subdivision of the group into those with moderate and those with severe diabetes demonstrated that the latter had significantly higher plasma glucose levels and lower insulin levels at all times, except in the fasting state, during which the insulin levels were not significantly different.