Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011854 (type 1 diabetes)
 20,749 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In insulin-dependent diabetes (IDDM), an overactivity of sodium-lithium countertransport (Na+/Li+ CT) has been associated with the risk of nephropathy and hypertension, two conditions of insulin resistance. We investigated the sensitivity to insulin with a hyperinsulinemic (approximately 719 pM [approximately 100 microU/ml]) euglycemic clamp in two groups of normotensive nonproteinuric IDDM patients; 12 (10 men, 2 women) had high Na+/Li+ CT activity (mean 0.47, range 0.42-0.68 mmol/L red blood cells [RBC]/h, group 1) and 12 (9 men, 3 women) had normal Na+/Li+ CT activity (mean 0.24, range 0.12-0.31 mmol/L RBC/h, group 2). The two groups were similar in age (mean +/- SE 36 +/- 2 vs. 33 +/- 1 yr), duration of diabetes (19 +/- 3 vs. 18 +/- 2 yr), body mass index (26 +/- 0.8 vs. 24 +/- 0.6 kg/m2), arterial blood pressure (systolic/diastolic 121 +/- 4/79 +/- 2 vs. 122 +/- 3/77 +/- 2 mmHg), and glycemic control (HbA1 8.5 +/- 0.4 vs. 8.0 +/- 0.4%). Albumin excretion rate (AER) ranged between 4.7 and 148 (geometric mean 14) micrograms/min in group 1 and between 2.7 and 93 (geometric mean 11) micrograms/min in group 2. There were four microalbuminuric patients (AER greater than 30 micrograms/min) in each group. Whole-body glucose uptake was significantly reduced on average in group 1 compared with group 2 (41.6 +/- 2.2 mumol.kg-1.min-1 [7.48 +/- 0.4 mg.kg-1.min-1] vs. 49.6 +/- 2.2 mumol.kg-1.min-1 [8.93 +/- 0.4 mg.kg-1.min-1, P = 0.03), but some overlap existed between the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Sodium-lithium countertransport activity and insulin resistance in normotensive IDDM patients. 153 93

Type 1 diabetes mellitus is associated with an increase in total exchangeable body sodium. To delineate a site of possible altered sodium handling, proximal tubular sodium reabsorption (PTRNa) was measured in 30 diabetic children, age 12.0 (range 7-16) yr, duration of diabetes 4.5 (range 0.2-12) yr, and compared with 10 non-diabetic children, age 10.0 (range 8.6-12.5) yr. PTRNa was calculated from the fractional clearance of lithium, which was determined from a single blood sample and a random untimed urine sample, taken between 0700 and 0830 h at home, fasting, before insulin therapy. PTRNa was significantly increased in the diabetic children compared with the non-diabetic children (81.6(SE 1.0) vs 74.2(2.6)%, p = 0.014). There was no relationship of PTRNa with age, duration of diabetes, metabolic control (glycosylated haemoglobin, plasma and urinary glucose, plasma lactate), or urinary protein excretion (albumin, N-acetyl-beta-D-glucosaminidase). Elevated sodium reabsorption in the proximal renal tubule may account for the high total exchangeable body sodium found in Type 1 diabetic patients.
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PMID:Increased proximal tubular reabsorption of sodium in childhood diabetes mellitus. 182 44

The relationship of the development of glomerular hyperfiltration in diabetes to changes in extracellular fluid volume has not been previously examined. To accomplish this task, male Wistar rats were chronically cannulated in the bladder, femoral artery and vein. Control measurements of glomerular filtration rate (GFR), renal plasma flow (RPF), extracellular fluid volume (ECF), and urinary sodium excretion were performed on two separate days prior to infusion of streptozotocin (65 mg/kg body wt i.v.). After infusion of streptozotocin, the IDDM rats were separated into two groups: untreated IDDM group of rats and IDDM rats treated with insulin at doses sufficient to normalize blood glucose (Ultralente, 2 to 8 IU/day). A third group of normal non-diabetic rats served as time controls. Measurements of renal function occurred at 1, 4, 7, 11, and 15 days after infusion of streptozotocin. Blood glucose in the non-diabetic measurement period averaged 137 +/- 30 mg/dl and increased from 412 +/- 55 after 24 hours in the untreated diabetic rats to 533 +/- 33 mg/dl after 15 days of IDDM. The time controls and the insulin-treated diabetic rats did not differ in blood glucose values at the time measurements were performed. Glomerular filtration rate increased from 1.0 +/- 0.1 to 1.7 +/- 0.1 ml/min/100 g body wt by day 15 in the untreated diabetic rats with significant increases in GFR within 24 hours. GFR of both time controls and the insulin-treated IDDM rats did not significantly vary during the time of the study. The increase in GFR in the untreated IDDM group was associated with a concomitant increase in RPF.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Disassociation between glomerular hyperfiltration and extracellular volume in diabetic rats. 189 71

The 64-kDa pancreatic beta-cell autoantigen, which is a target of autoantibodies associated with early as well as progressive stages of beta-cell destruction, resulting in insulin-dependent diabetes (IDDM) in humans, has been identified as the gamma-aminobutyric acid-synthesizing enzyme glutamic acid decarboxylase. We have identified two autoantigenic forms of this protein in rat pancreatic beta-cells, a Mr 65,000 (GAD65) hydrophilic and soluble form of pI 6.9-7.1 and a Mr 64,000 (GAD64) component of pI 6.7. GAD64 is more abundant than GAD65 and has three distinct forms with regard to cellular compartment and hydrophobicity. A major portion of GAD64 is hydrophobic and firmly membrane-anchored and can only be released from membrane fractions by detergent. A second portion is hydrophobic but soluble or of a low membrane avidity, and a third minor portion is soluble and hydrophilic. All the GAD64 forms have identical pI and mobility on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Results of pulse-chase labeling with [35S]methionine are consistent with GAD64 being synthesized as a soluble protein that is processed into a firmly membrane-anchored form in a process which involves increases in hydrophobicity but no detectable changes in size or charge. All the GAD64 forms can be resolved into two isoforms, alpha and beta, which differ by approximately 1 kDa in mobility on sodium dodecyl sulfate-polyacrylamide gel electrophoresis but are identical with regard to all other parameters analyzed in this study. GAD65 has a shorter half-life than the GAD64 forms, remains hydrophilic and soluble, and does not resolve into isomers. Comparative analysis of the brain and beta-cell forms of GAD show that GAD65 and GAD64 in pancreatic beta-cells correspond to the larger and smaller forms of GAD in brain, respectively. The expression of different forms and the flexibility in subcellular localization of the GAD autoantigen in beta-cells may have implications for both its function and autoantigenicity.
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PMID:Pancreatic beta cells express two autoantigenic forms of glutamic acid decarboxylase, a 65-kDa hydrophilic form and a 64-kDa amphiphilic form which can be both membrane-bound and soluble. 174 45

Diabetes mellitus and hypertension constitute two powerful independent risk factors for cardiovascular, renal and atherosclerotic disease. The frequent occurrence of the two diseases in the same individual doubles the risk of cardiovascular death, as well as substantially increasing the frequency of transient ischemic attacks, strokes, peripheral vascular disease with lower extremity amputations, as well as end-stage renal disease and blindness. Although hypertension usually occurs in IDDM in association with renal disease, in NIDDM the evolution of hypertension appears to be multifactorial and independent of renal disease. Obesity appears to be dissociable from hypertension and NIDDM with a common link between obesity, hypertension and NIDDM appearing to be hyperinsulinism and insulin resistance. It has been suggested that hyperinsulinism and insulin resistance may lead to hypertension through altered intracellular calcium metabolism, enhanced renal sodium reabsorption, or through an effect of insulin upon lipid and/or catecholamine metabolism. Further, insulin itself may have a direct effect upon the atherosclerotic process in the hypertensive diabetic patient. These considerations have been taken into account in the structuring of antihypertensive therapy in Type I and Type II Diabetes Mellitus.
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PMID:Diabetes and hypertension. 207 56

The responsiveness of renin-angiotensin and kallikrein-kinin systems to furosemide challenge has been investigated in forty-six diabetic patients (34 NIDDM/12 IDDM), subdivided into Group I (uncomplicated DM), Group II (DM with hypertension), Group III (DM with nephropathy), Group IV (DM with hypertension and nephropathy) and a control group of 10 healthy volunteers. Plasma renin activity (PRA) was estimated by radioimmunoassay in blood samples drawn before and 10 min after furosemide administration (0.5 mg/kg i.v.). Urinary kallikrein levels were measured by bioassay using estrogenized rat uterus preparation in 4h urine samples collected before and after the diuretic. Urinary Na+ and K+ were also measured. The basal PRA in diabetics was not significantly different from controls, whereas, urinary kallikrein levels were markedly low in all patients. Both PRA and kallikrein levels increased after furosemide in controls while in diabetics this response was severely blunted. In a subset of Group I, a paradoxical fall in PRA and kallikrein levels was noted after furosemide, an effect similar to that observed in patients with nephropathy (Group III). This response in absence of clinical and biochemical parameters of nephropathy indicates early derangement of renal hemodynamic mechanisms heralding the onset of nephropathy.
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PMID:Plasma renin activity and urinary kallikrein excretion in response to intravenous furosemide in diabetic patients. 208 34

The ability of insulin-dependent diabetic (IDDM) women to breast-feed has been documented, however, there is little information concerning milk composition or factors that influence successful breastfeeding. Placental lactogen and prolactin levels can be normalized during pregnancy with good metabolic control. These hormones affect the readiness of the mammary gland for lactation. Prolactin maintains mammary gland insulin receptors to ensure anabolism. Lactation in IDDM women may be influenced by hyper- or hypoglycemia as women balance their insulin needs. Milk from diabetic animals has decreased lactose, fat, protein and volume and these effects can be reversed with insulin administration. Mature breast milk of IDDM women has increased glucose and sodium and mammary gland lipid metabolism may be impaired. Milk lactose and citrate, markers of lactogenesis II, suggest delayed lactation occurs in diabetic women. Many factors may influence lactation success and breast milk composition of IDDM women. Some of these include: method of delivery, feeding frequency, fetal condition, gestational age, mastitis incidence, metabolic control and maternal dietary intake. Lactation management of the IDDM woman must address these factors.
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PMID:Lactation in insulin-dependent diabetes. 209 Oct 54

Leucocyte sodium influx was studied in 29 type 1 (insulin dependent) diabetic subjects and compared to 24 non diabetic controls matched for age, body mass index and blood pressure. Total sodium influx from a low external concentration ((Na+) = 10 mmol/l) was reduced in type 1 diabetes (0.23 vs 0.31 mmol/l/min, p less than 0.05) as was amiloride insensitive sodium influx (0.09 vs 0.13 mmol/l/min, p less than 0.01). No difference was found in amiloride sensitive flux. No ionic flux was correlated with plasma glucose or insulin concentrations or with HbA1 levels. Intracellular sodium accumulation in type 1 diabetes is not due to an increase in total sodium influx, as judged from an external concentration of 10 mmol/l.
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PMID:Cellular sodium influx is low in type 1 (insulin dependent) diabetes. 209 77

Aim of this study is to evaluate whether among type I diabetic adolescents (IDDM) the erythrocyte Na-Li countertransport (CNT Na-Li) is correlated with arterial pressure and tubular sodium reabsorption. We have studied 16 IDDM adolescents (age 15 +/- 0.5 year) et 15 normal subjects (age 14.5 +/- 1 year). CNT Na-Li, creatinine and lithium clearances (as markers of glomerular filtration rate and proximal tubular sodium reabsorption) have been measured in all subjects and nocturnal urinary albumin excretion rate (UAER) was measured in IDDM adolescents. CNT Na-Li was 308 +/- 26 mumol Li/l RBC/h in IDDM adolescents and 211 +/- 74 mumol Li/l RBC/h in controls (p less than 0.01). The fractional excretion of lithium (FELi) was significantly reduced in IDDM adolescents compared to normal subjects (12 +/- 2 vs 19 +/- 2%; p less than 0.01). Among the IDDM adolescents, 5 had the CNT Na-Li higher than the 95th percentile of controls (greater than 360 mumol Li/l GR/h); their systolic arterial pressure was significantly higher than in diabetics with normal CNT Na-Li (126 +/- 2 vs 116 +/- 2; p = 0.03), while there were no differences for diabetes duration, glycemic control, serum potassium, creatinine clearance, FELi and UAER. The relationship between CNT Na-Li and arterial pressure in IDDM adolescents deserves further studies.
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PMID:[Erythrocyte sodium-lithium countertransport in diabetic adolescents]. 212 63

Renal function was studied in 18 patients with Type 1 diabetes mellitus. All were participating in the Canadian-European randomized placebo-controlled cyclosporin trial in newly diagnosed Type 1 diabetic patients, nine being randomized to placebo, and nine to cyclosporin A. During treatment for 12 to 18 months, cyclosporin A caused significant reductions in the glomerular filtration rate (before drug withdrawal, cyclosporin 97 +/- 18 vs placebo 125 +/- 16 ml min-1 1.73-m-2, p less than 0.05), renal plasma flow (454 +/- 83 vs 536 +/- 70 ml min-1 1.73-m-2, p less than 0.05), and lithium clearance (17 +/- 3 vs 28 +/- 5 ml min-1 1.73-m-2, p less than 0.05). The fractional proximal reabsorption was increased (0.82 +/- 0.03 vs 0.78 +/- 0.03, p less than 0.05), and the fractional distal sodium reabsorption reduced (0.88 +/- 0.03 vs 0.94 +/- 0.02, p less than 0.05). These results are in accordance with the hypothesis that the nephrotoxic effect of cyclosporin A results from a preferential constriction of afferent glomerular vessels. One year after withdrawal of the drug, all variables were similar in the two groups, except for blood glucose control which was worse in the cyclosporin A treated group. When corrected for differences in blood glucose control it appeared that in three out of nine patients glomerular filtration rate had not completely returned to the reference range of the placebo group. We conclude that the nephrotoxic side-effects of cyclosporin A treatment for 1 year are reversible. There are, however, signs of minor and perhaps chronic renal injury.
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PMID:Nephrotoxicity of cyclosporin A in patients with newly diagnosed type 1 diabetes mellitus. 214 40


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