Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. It has been proposed that raised erythrocyte sodium-lithium countertransport activity in type 1 diabetic patients is associated with an increased risk of developing diabetic nephropathy. Diabetic patients with established nephropathy would therefore be expected to have high activity. 2. Standard sodium-lithium countertransport activity, sodium affinity (Km) and maximum velocity (Vmax) were measured in type 1 diabetic patients at different stages of diabetic nephropathy and in appropriately matched uncomplicated diabetic patients and normal control subjects. 3. A small proportion (15%) of patients with nephropathy had standard sodium-lithium countertransport activity higher than the control range. However, mean standard sodium-lithium countertransport activity in the diabetic patients with nephropathy [mean +/- SEM, 0.26 +/- 0.12 mmol of Li+ h-1 (l of cells)-1] was not significantly higher than in the uncomplicated diabetic patients [0.27 +/- 0.03 mmol of Li+ h-1 (l of cells)-1] or in the normal control subjects [0.25 +/- 0.02 mmol of Li+ h-1 (l of cells)-1]. 4. There were marked changes in the kinetic characteristics of the sodium-lithium countertransport in the diabetic patients with nephropathy so that there were decreases in both Km and Vmax. 5. These kinetic changes could not be attributed to an effect of either renal failure per se or the duration of diabetes. 6. The characteristic kinetic changes in sodium-lithium countertransport may indicate underlying alterations in membrane function with the onset of nephropathy in type 1 diabetes.
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PMID:Changes in erythrocyte sodium-lithium countertransport kinetics in diabetic nephropathy. 131 15

1. Sialic acid moieties of erythrocyte membrane glycoproteins are the principal determinants of the negative charge on the cell surface. The resultant electrostatic repulsion between the cells reduces erythrocyte aggregation and hence the low shear rate viscosity and yield stress of blood. 2. Using g.c.-m.s., a decrease in sialic acid content has been observed in the major erythrocyte membrane glycoprotein, glycophorin A, obtained from nine diabetic patients compared with that from seven normal control subjects [median (range): 3.30 (0.01-11.90) versus 18.60 (3.20-32.60) micrograms/100 micrograms of protein, P less than 0.02]. 3. Erythrocyte aggregation, measured by viscometry as the ratio of suspension viscosity to supernatant viscosity (LS/S) in fibrinogen solution, was increased in ten diabetic patients compared with ten normal control subjects (mean +/- SEM, 37.6 +/- 1.3 versus 33.8 +/- 0.6, P less than 0.02). 4. In the patients in whom both viscometry and carbohydrate analysis were performed, the decrease in erythrocyte glycophorin sialylation and the increase in erythrocyte aggregation in fibrinogen solution were related statistically (LS/S correlated negatively with glycophorin sialic acid content, r = 0.73, P less than 0.05). 5. Decreased glycophorin sialylation provides an explanation at the molecular level for increased erythrocyte aggregation and it may be important in the pathogenesis of vascular disease in diabetes.
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PMID:Decrease in erythrocyte glycophorin sialic acid content is associated with increased erythrocyte aggregation in human diabetes. 131 16

To elucidate the mechanism of hyperkalemia in diabetic patients without renal failure, we investigated (Na(+)-K+) adenosine triphosphatase (ATPase) activity in erythrocyte membrane, erythrocyte Na+ and K+ content, and plasma endogenous digitalis-like substance in control subjects (n = 16) and non-insulin-dependent diabetes mellitus (NIDDM) patients (n = 62). NIDDM patients were divided into normokalemic patients (NKDM, n = 48) and hyperkalemic patients (HKDM, n = 14). There was no difference in plasma glucose or hemoglobin A1c (HbA1c) levels, plasma renin activity (PRA), and plasma aldosterone concentrations (PAC) between NKDM and HKDM patients. (Na(+)-K+)ATPase activities in NIDDM patients were significantly reduced compared with those in control subjects (0.336 +/- 0.016 mumol-inorganic phosphate [Pi]/mg protein/h, mean +/- SEM, P less than .05), and (Na(+)-K+)ATPase activities in HKDM patients (0.243 +/- 0.015 mumol Pi/mg protein/h) were significantly reduced compared with those in NKDM patients (0.295 +/- 0.008 mumol Pi/mg protein/h, P less than .01). Plasma K+ content had a significant negative correlation with (Na(+)-K+)ATPase activity in diabetic patients (r = -.365, P less than .01). Erythrocyte Na+ content had a significant negative correlation with (Na(+)-K+)ATPase activity in control subjects (r = -.619, P less than .05). There was no difference in plasma endogenous digitalis-like substance among the three groups. (Na(+)-K+)ATPase activity was not significantly correlated with plasma endogenous digitalis-like substance in control subjects and diabetic patients. These findings suggest that the reduction of (Na(+)-K+)ATPase activity, which was not related to plasma digitalis-like substance, may be partly responsible for hyperkalemia in diabetic patients.
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PMID:Reduction of erythrocyte (Na(+)-K+) ATPase activities in non-insulin-dependent diabetic patients with hyperkalemia. 131 28

A total of 35 pregnancies in 28 Pregestational Diabetic Patients (PDP) were followed with the goal of achieving and maintaining near normoglycemia (as many pre-postprandial glycemias as possible between 60-140 mg/dl); 13 patients (16 pregnancies) were assigned to Subcutaneous Continuous Preprogrammed Insulin Infusion (SCII) because of high risk pregnancies (HRP) (at least one of the following: former history of spontaneous abortions, stillbirths, premature deliveries and/or sterility). The remaining 12 PDP's (15 pregnancies with no past history of the above nature) were treated with Multiple Conventional Insulin Injections (MCII). Both groups were comparable regarding the following clinical parameters: age, time of onset and class of diabetes. All patients were instructed in performing 3 to 7 daily Self Capillary Blood Glucose controls (SCBG). Mean follow-up observation period was (mean +/- SEM) 28.5 +/- 2.5 weeks for SCII and 3.2 MCII and 28.8 +/- 3.2 weeks for MCII. All the 3 PDP drop out's (4 pregnancies) belonged to the CMII group. No drop out's were recorded in the SCII group. Both insulin therapy approaches were similarly effective in improving metabolic control in that comparable levels of mean blood glucose (MBG) and HbA1 were attained by SCII and MCII (Fig. 1). Compliance, as evidenced by average of daily SCBG was also similar in both groups (Fig. 2). Such satisfactory metabolic control was achieved mostly because of an increase in the percentage (65%) of "fair" glycemias (60-139 mg/dl) and not because of an increase in hypoglycemias (< 60 mg/dl) which could have canceled out an undesirable degree of hyperglycemias thus rendering "false satisfactory" MBG's and HbA1 (Fig. 1). With the above degree of metabolic control obtained there occurred no severe hypoglycemic episodes requiring medical intervention. All newborns to the PDP's who remained under treatment showed an adequate APGAR (X +/- SEM, 9.5 +/- 0.2) regardless of the modality (SCII or MCII) of insulin delivery used (Tables 1, 2). The single malformed baby found in this series was born to a patient on SCII who happened to start on the intensified insulin treatment rather late in her pregnancy (21st week) and, in addition, the patient self medicated with high doses of chlorpromazine because of recurrent vomiting episodes. Incidence of neonatal hypoglycemia (HY) or macrosomy (MS) was comparable in both groups (Tables 1, 2). It is to be pointed out, however, that PDP's who bore the babies with no HY or MS had presented a larger number of low glycemic values than mothers who bore the babies with HY and/or MS.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:[Intensified insulin therapy in the management of gestational diabetes]. 134 Sep 1

Diabetic osteopenia has been known as one of the chronic complications of diabetes mellitus, and a decrease in bone turnover has been thought to be one of the pathophysiological characteristics of this complication. In order to investigate the effect of long-term insulin therapy on low bone turnover in diabetes, pancreas transplantation was performed on streptozotocin-induced diabetic rats. Plasma levels of bone gamma-carboxyglutamic acid-containing protein(osteocalcin) in untreated diabetic rats were 0.9 +/- 0.1 (mean +/- SEM) nmol/l, significantly lower than the value of 4.2 +/- 0.6 nmol/l in control rats (p less than 0.01). Pancreas transplantation reversed this decrease to 6.3 +/- 1.1 nmol/l, which was not significantly different from the value in control rats. The circulating levels of calcitriol were significantly decreased in the untreated diabetic group (p less than 0.01), and the decrease was fully reversed by pancreas transplantation. In addition, the decreases in bone length, strength and weight were also improved by the transplantation. This evidence clearly shows that the improvement of metabolic derangements in diabetes by insulin is essential for the prevention of deterioration in diabetic osteopenia. It is possible, therefore, that insulin exerts an indirect beneficial influence through the metabolic amelioration on the decreases in bone turnover and circulating osteocalcin in diabetes mellitus, or has a direct stimulatory effect on the osteoblasts via the insulin receptor since its presence has been shown recently in osteoblastic cells.
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PMID:Effect of pancreas transplantation on decreased levels of circulating bone gamma-carboxyglutamic acid-containing protein and osteopenia in rats with streptozotocin-induced diabetes. 138 56

The aim of the study described here was to evaluate aerobic function during exercise and its determinants in middle-aged men with newly diagnosed Type 2 (non insulin-dependent) diabetes. Using breath-by-breath technique, we measured O2 uptake at anaerobic (ventilatory) threshold and at peak exercise in a group of diabetic men (n = 19; fasting blood glucose 8.6 +/- 0.7 mmol l-1, mean +/- SEM) without any disease or medication that could have had an influence on exercise performance, and compared the results to those observed in non-diabetic healthy control men (n = 18). There were no differences in physical activity or smoking habits between the groups. Oxygen uptake was lower in the diabetic men than in the control men both at anaerobic threshold (15.0 +/- 0.8 vs. 18.8 +/- 1.0 ml min-1 kg-1, P < 0.01) and at peak exercise (25.3 +/- 1.5 vs. 31.1 +/- 1.4 ml min-1 kg-1, P < 0.01). In the diabetic men peak O2 uptake showed an inverse linear correlation with age (r = -0.71, P < or = 0.001), fasting blood glucose (r = -0.49, P < 0.05) and glucose response in an oral glucose tolerance test (r = -0.43, P < 0.05). In addition, long-term smoking was associated with impaired peak O2 uptake. In a stepwise multiple regression procedure 75% of the total variance of peak O2 uptake in the diabetic men was explained by age, post-load blood glucose response and smoking history. Thus, in addition to ageing and smoking, hyperglycaemia is correlated with impaired aerobic power in men with newly diagnosed Type 2 diabetes.
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PMID:Relationship between hyperglycaemia and aerobic power in men with newly diagnosed type 2 (non insulin-dependent) diabetes. 142 84

First-degree relatives of patients with NIDDM manifest severe insulin resistance despite normal glucose tolerance test. To examine the mechanisms underlying the normal glucose tolerance, we evaluated the serum glucose/C-peptide/insulin dynamics and free fatty acid (FFA) as well as substrate oxidation rates and energy expenditure (EE) (indirect calorimetry) in nine young offspring of NIDDM patients (mean +/- SEM age 30 +/- 2.3 years, body mass index 24.2 +/- 1.2 kg/m2). Nine age-, sex- and weight-matched, normal subjects with no family history of diabetes served as the controls. Metabolic parameters were measured before, during and after a two-step glucose infusion (2 and 4 mg/kg.min) for 120 min. Mean basal serum glucose, insulin and C-peptide levels were similar in both groups. During 2 mg/kg.min glucose infusion, mean serum insulin and C-peptide rose to significantly (P less than 0.05-0.02) greater levels in the offspring vs. controls, while serum glucose levels were similar. With the 4 mg/kg.min glucose infusion, mean serum glucose, insulin and C-peptide levels were significantly (P less than 0.02-0.001) greater in the offspring at 100-120 min. Isotopically-derived (D[3-3H]glucose), basal hepatic glucose output (HGO) was not significantly different between the offspring vs. controls (1.86 +/- 0.30 vs. 1.78 +/- 0.06 mg/kg.min). During glucose infusion, basal HGO was partially suppressed by 66% at 60 min and by 100% at 120 min in the offspring. In contrast, HGO was completely (100%) suppressed at both times in the controls. Following cessation of glucose infusion, HGO rose to 1.64 +/- 0.12 mg/kg.min in the offspring and 1.46 +/- 0.05 mg/kg.min in the controls (P less than 0.05) between 200 and 240 min. These were 88% and 82% of the respective basal HGO values. At low glucose infusion (t = 0-60 min), the mean absolute, non-oxidative glucose disposal remained 1.5-fold greater in the offspring while at higher glucose infusion, nonoxidative glucose metabolism was not different in both groups. Throughout the study period, oxidative glucose disposal rate was not significantly different in both groups. The mean basal FFA was significantly greater in the offspring vs. controls (865 +/- 57 vs. 642 +/- 45 microEq/l). It was appropriately suppressed during glucose infusion to a similar nadir in both groups (395 +/- 24 vs. 375 +/- 33 microEq/l). The mean basal lipid oxidation was also significantly greater in the offspring than controls (1.06 +/- 0.05 vs. 0.75 +/- 0.04 mg/kg.min, P less than 0.05).(ABSTRACT TRUNCATED AT 400 WORDS)
Diabetes Res Clin Pract 1992 Sep
PMID:The effects of superphysiologic hyperinsulinemia on glucose and lipid metabolism in glucose-tolerant offspring of patients with non-insulin-dependent diabetes mellitus (NIDDM). 142 56

An increased lipid peroxidation, due to the altered intracellular ratio between free radicals and antioxidant systems, has been recently related to diabetes. To study the possible relationship between lipid peroxidation and metabolic control, we measured the plasma concentrations of malondialdehyde (MDA), end product of the oxidation of polyunsaturated fatty acids, in poorly and well controlled Type 2 diabetic patients. A significant increase in plasma malondialdehyde concentrations was found in poorly controlled diabetics when compared to well controlled patients (p < 0.001) and to healthy normoglycaemic subjects (p < 0.001), whereas no significant difference was observed between the two latter groups. Plasma MDA/Cholesterol and MDA/triglyceride ratios were both higher in poorly controlled diabetics than in well controlled (p < 0.005) and in normal subjects (p < 0.01 and p < 0.02 for MDA/CHOL and MDA/TG respectively). In diabetic patients a positive correlation was found between plasma MDA levels and mean daily blood glucose (p < 0.01), plasma fructosamines (p < 0.001), HbA1 (p < 0.05) and plasma triglycerides (p < 0.05), while no significant correlation was shown between plasma malondialdehyde and total cholesterol. Malondialdehyde levels were followed-up for 7 days running (T1-T7) in five poorly controlled diabetics, treated with conventional insulin therapy. This group showed normalized plasma lipid peroxide values (0.486 +/- 0.13 mumol/l, T5, M +/- SEM) 72 h after the restoration of glycaemic control (145 +/- 25 mg/dl, T2, M +/- SEM). These results confirm the increase of lipid peroxidation during Type 2 diabetes. The correlation with the degree of metabolic imbalance suggests a possible role for lipid peroxidation in the occurrence of glucose-induced macromolecular changes.
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PMID:Increased lipid peroxidation in type 2 poorly controlled diabetic patients. 145 13

We studied the natural course of disease in spontaneously diabetic rats, Long Evans Tokushima Lean (LETL) rats, to determine whether it showed similar pathogenetic heterogeneity to that of patients with insulin-dependent diabetes mellitus (IDDM) with regard to the relationships between age at onset, rapidity of disease progress, and degree of beta-cell function at the time of its manifestation. Type 1 diabetes developed in 35 rats (6.3%) between 40 and 140 days of age. Eight rats that became diabetic at age 69 days or less were more severely ketotic at the time of first detection of glycosuria and showed more rapid deterioration than seven rats that became diabetic later after birth (mean plasma 3-hydroxybutyrate levels, 4,707 +/- 1,215 pmol/L v 1,390 +/- 859 pmol/L; mean +/- SEM, P < .01). The mean plasma levels and pancreatic content of immunoreactive insulin (IRI) of the early onset rats, 47 +/- 13 pmol/L and 19 +/- 12 pmol/g tissue weight, were significantly lower (P < .01) than the corresponding values of the late-onset rats, 262 +/- 52 pmol/L and 348 +/- 87 pmol/g tissue weight, respectively. Both values were markedly lower than the mean values of 25 nondiabetic LETL rats, 976 +/- 122 pmol/L and 3,488 +/- 628 pmol/g tissue weight. Plasma immunoreactive glucagon (IRG) levels were significantly increased in the diabetic groups (early onset, 57 +/- 13 pmol/L; late-onset, 51 +/- 12 pmol/L; nondiabetic, 18 +/- 1 pmol/L; P < .01). These changes in pancreatic hormone levels of the early onset and late-onset rats were compatible with the histological features of their pancreatic islets.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Correlation between residual beta-cell function and age at onset of spontaneous diabetes in Long Evans Tokushima lean rats. 146 Nov 46

Angiotensin-converting enzyme (ACE) inhibitors decrease albuminuria in patients with diabetic nephropathy. To study the change in albuminuria in relation to changes in systemic and renal hemodynamics, nine normotensive patients with type 1 (insulin-dependent) diabetes mellitus and persistent proteinuria were given a single oral dose of 25 mg of the ACE inhibitor captopril. Blood pressure, glomerular filtration rate (GFR), effective renal plasma flow (ERPF), and albumin excretion rate (AER) were measured in two periods of 40 minutes before and in four periods of 40 minutes after administration of captopril. A constant water diuresis was maintained. Blood pressure did not decrease significantly (130/79 +/- 4/3 v 124/74 +/- 4/3 mm Hg; mean +/- SEM), median AER decreased from 403 (interquartile range [IQR], 812) micrograms/min to 333 (707) micrograms/min (P < 0.01). GFR did not change (123 +/- 13 v 117 +/- 14 mL/min), but ERPF increased significantly from 609 +/- 56 to 714 +/- 55 mL/min (P < 0.01). Consequently, the filtration fraction (FF; quotient of GFR and ERPF) decreased from 0.20 +/- 0.014 to 0.17 +/- 0.014 (P < 0.01). A strong correlation was found between the decrease of AER and the decrease of FF (rs = 0.75; P < 0.02). No correlation was found between the decrease in AER and changes in GFR or blood pressure. In the normotensive patient with diabetic nephropathy, captopril causes an acute reduction of AER, which is probably mediated by a lowering of the intraglomerular pressure.
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PMID:Captopril acutely lowers albuminuria in normotensive patients with diabetic nephropathy. 146 82


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