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Query: UMLS:C0011854 (type 1 diabetes)
 20,749 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Insulin-dependent diabetes mellitus (IDDM) is a common metabolic disease often complicated by a number of pathological conditions among which are haematological changes and alterations in blood cell function. Human and feline diabetes mellitus patients have been reported to be associated with oxidative stress that can lead to membrane alterations and to reduced erythrocyte life-span. Erythrocyte function in dogs affected by IDDM has been investigated during insulin therapy, paying attention to antioxidant status, membrane resistance, enzyme activities and 2,3-diphosphoglycerate (2,3DPG) concentration. Thirteen diabetic and 36 healthy dogs were bled and haematology and blood chemistry assays were performed to evaluate the degree of compensation. Osmotic fragility, the activities of the enzymes glucose-6-phosphate dehydrogenase (G6PD) and pyruvate-kinase (PK) and the concentrations of reduced glutathione (GSH) and 2,3DPG were evaluated in the erythrocytes. Diabetic dogs did not differ from controls in terms of haematological parameters, except for higher numbers of platelets. Higher values of fructosamine, glucose, protein, plasma potassium and calculated osmolality were detected in the plasma from diabetic dogs. No differences were detected in osmotic fragility, GSH concentration and PK activity between the two groups but 2,3DPG concentration and G6PD activity were statistically significantly higher in the diabetic group. The results indicate minimal alterations in erythrocyte functions occur in insulin-treated diabetic dogs. This contrasts with what has been reported for IDDM humans and cats.
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PMID:Some aspects of erythrocyte metabolism in insulin-treated diabetic dogs. 1200 34

We have previously demonstrated that experimental hypoglycaemia in adults with type 1 diabetes causes an abnormal electrocardiogram (ECG), with increases in QT interval and dispersion. These abnormalities in cardiac repolarisation indicate a risk of ventricular tachycardia and sudden death in other conditions, including ischemic heart disease and congenital long QT syndrome. We have hypothesised that they could contribute to the dead in bed syndrome--the recently described sudden unexpected death in young people with type 1 diabetes--which occurs around three times more frequently than in those without diabetes. It is clearly impossible to explore the causes of a rare and fatal complication by direct observation. We have therefore explored the pathophysiology in a series of experimental studies involving non-diabetic subjects and surrogate endpoints. These have demonstrated that abnormal cardiac repolarisation occurs consistently during insulin-induced hypoglycaemia and that either potassium infusion or beta-blockade prevents increased QT dispersion but only partially prevents QT lengthening. The sympathoadrenal discharge induced by hypoglycaemia alters cardiac repolarisation by both direct and indirect (by reducing extracellular potassium) mechanisms. Other factors that might contribute to the clinical risk of cardiac arrhythmias during nocturnal hypoglycaemia include autonomic neuropathy. This is associated with prolonged QT interval in the non-hypoglycaemic state and has been proposed as a cause of sudden death in those affected. We have examined cardiac repolarisation during clamped hypoglycaemia in patients with type 1 diabetes, with and without autonomic neuropathy. Our data demonstrate lengthening of QTc (QT interval corrected for heart rate) during hypoglycaemia in all groups with no significant differences between the groups, suggesting that autonomic dysfunction does not contribute to hypoglycaemia-induced QTc lengthening in type 1 diabetes. Our hypothesis would be strengthened by demonstrating similar changes during clinical hypoglycaemia. We have recently completed studies in prepubescent children and adults that show modest but significant changes in QTc during nocturnal hypoglycaemia in both populations. We have also demonstrated that pre-treatment with beta-blocking agents prevents abnormal cardiac repolarisation during experimental hypoglycaemia. This has identified a possible treatment if we can identify patients at high risk. Further work is necessary to determine whether we can reliably identify patients who could be at special risk during hypoglycaemia and who might benefit from protection with agents such as beta-blockers. Sudden death in young people with diabetes is, thankfully, rare. However its consequences are so devastating that an excess risk of 3 to 4 times the non-diabetic population seems sufficient to warrant further investigation of the mechanisms that may cause it.
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PMID:Abnormalities of the electrocardiogram during hypoglycaemia: the cause of the dead in bed syndrome? 1216 2

Maintaining glycemic and metabolic control is difficult in diabetic patients who are undergoing surgery. The preoperative evaluation of all patients with diabetes should include careful screening for asymptomatic cardiac or renal disease. Frequent self-monitoring of glucose levels is important in the week before surgery so that insulin regimens can be adjusted as needed. Oral agents and long-acting insulin are usually discontinued before surgery, although the newer long-acting insulin analog glargine may be appropriately administered for basal insulin coverage throughout the surgical period. The usual regimen of sliding scale subcutaneous insulin for perioperative glycemic control may be a less preferable method because it can have unreliable absorption and lead to erratic blood glucose levels. Intravenous insulin infusion offers advantages because of the more predictable absorption rates and ability to rapidly titrate insulin delivery up or down to maintain proper glycemic control. Insulin is typically infused at 1 to 2 U per hour and adjusted according to the results of frequent blood glucose checks. A separate infusion of dextrose prevents hypoglycemia. Potassium is usually added to the dextrose infusion at 10 to 20 mEq per L in patients with normal renal function and normal preoperative serum potassium levels. Frequent monitoring of electrolytes and acid-base status is important during the perioperative period, especially in patients with type 1 diabetes because ketoacidosis can develop at modest levels of hyperglycemia.
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PMID:Perioperative management of diabetes. 1367 27

The renaissance of glucose-insulin-potassium infusion (GIK) as a treatment of acute myocardial infarction both in diabetic and nondiabetic subjects has raised new interests to clarify the effects and mechanisms of insulin on myocardium. Although the action of insulin on substrate metabolism is quite well studied in heart, the cardiovascular effects were until recent years poorly known. Insulin induces skeletal muscle vasodilation mainly via the endothelium-dependent mechanism and appears to have an important role in normal vascular function. There is increasing amount of evidence that insulin acts as a vasodilatory hormone also in coronary arteries. Insulin enhances myocardial blood flow and decreases coronary vascular resistance in a dose-dependent manner in healthy subjects. Moreover, insulin is able to increase myocardial blood flow also in subjects who are characterized by coronary dysfunction such as subjects with obesity, type 1 diabetes and coronary artery disease. However, vasodilatory effect of insulin may be blunted in these patients. Since already very small increase in myocardial blood flow can reduce significantly myocardial ischemia, these vasodilatory actions of insulin in coronary arteries might partly contribute to beneficial effects of GIK therapy. On the other hand, in contrast to these acute beneficial effect of insulin, epidemiological studies have indentified chronic hyperinsulinemia, a common feature in subjects with insulin resistance to glucose uptake, as an independent risk factor for coronary artery disease. The present article review the physiological and pathophysiological role of insulin in cardiac vasculature and its clinical importance during myocardial ischemia and development of coronary artery disease.
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PMID:Insulin and myocardial blood flow. 1256 4

Glucose has recently been found to decrease muscle potassium content. The aim of this study was to evaluate the effect of the infusion of glucose and insulin and the effect of magnesium supplementation on serum and muscle sodium and potassium and muscle [3H]ouabain binding capacity in patients with Type 1 diabetes mellitus and in controls. Muscle potassium and sodium content, muscle [3H]ouabain binding capacity and serum potassium and sodium concentrations were determined in 10 patients with Type 1 diabetes mellitus and in 5 controls before and after an euglycaemic, hyperinsulinaemic clamp, and after an intravenous magnesium load test. Nine of the patients with Type 1 diabetes mellitus were restudied after 24 weeks of oral magnesium oxide supplementation. Basic serum and muscle sodium and potassium and muscle [3H]ouabain binding capacity did not differ between groups. The infusion of glucose and insulin reduced muscle potassium content, whereas muscle sodium content was unchanged. There were no differences between groups. Oral magnesium oxide supplementation increased muscle potassium content by 6%. Muscle [3H]ouabain binding capacity was unchanged. In patients with Type 1 diabetes mellitus, the intravenous infusion of magnesium increased serum potassium concentration before but not after oral magnesium oxide supplementation. In controls, the infusion of magnesium did not affect serum potassium concentration. It was found that intravenous infusion of glucose and insulin decreases muscle potassium content, probably by shifting potassium from the muscle cells to the splanchnic organs. Oral magnesium oxide supplementation increases muscle potassium content in patients with Type 1 diabetes mellitus. The increase in serum potassium concentration owing to the intravenous infusion of magnesium could be used in the evaluation of magnesium status in patients with Type 1 diabetes mellitus. This, however, requires further investigation.
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PMID:Effect of glucose/insulin infusion and magnesium supplementation on serum and muscle sodium and potassium and muscle [3H]ouabain binding capacity in Type 1 diabetes mellitus. 1275 90

Many clinicians are uncomfortable about using angiotensin-converting enzyme (ACE) inhibitors or angiotensin II type 1 receptor blockers (AT(1)-blockers) to treat patients with renal disease because of concerns about increasing serum creatinine levels. However, the benefits of these medications, particularly their efficacy in slowing the progression of renal disease, outweigh such concerns. ACE inhibitors are effective in patients with type 1 diabetes and renal disease, as well as in those with nondiabetic renal disease and proteinuria >0.5 g/d. AT(1)-blockers slow the progression of diabetic nephropathy in patients with type 2 diabetes. Although these classes of medications should not be used in patients with severe renal insufficiency (e.g., glomerular filtration rate <20 mL/min), they may be beneficial in patients with mild-to-moderate renal insufficiency. Nonetheless, caution should be exercised in those with a glomerular filtration rate <30 mL/min, and serum creatinine and potassium levels should be checked approximately 1 week after starting treatment. There is also evidence suggesting that these medications lead to greater reductions in blood pressure and proteinuria when used in combination than when alone. The purpose of this paper is to review the mechanisms of action of these two classes of medication, as well as the experimental and clinical evidence that they slow the progression of renal disease.
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PMID:Comparative effects of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers on blood pressure and the kidney. 1275 83

Hypertension is extremely common in patients with diabetes mellitus. In type 1 diabetes it usually signifies the onset of nephropathy. Tight control of hypertension in diabetes has shown to decrease the complications like ischaemic heart disease and renal failure thereby reducing the morbidity and mortality. Management of hypertension in diabetes include weight reduction, dietary restriction of sodium, adequate intake of potassium and calcium, regular exercise, cessation of smoking and drug therapy. Many type 2 diabetic patients require more than one drug for good blood pressure control. Even though many of the hypotensive drugs are effective in diabetic patients, ACE inhibitors have an edge over the other drugs in view of its favourable effect on the accompanying co-morbid conditions.
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PMID:Hypertension and diabetes mellitus. 1296 45

Several lines of evidence suggest that the aetio-pathogenesis of the common form of type 2 diabetes mellitus and its intrinsically related features of impaired insulin secretion and decreased insulin sensitivity (insulin resistance) includes a strong genetic component. At present, however, little is known about the nature of this genetic component although familial clustering of the disease has been described for decades. Major break-throughs in the genetic sciences of type 2 diabetes have been identifications of insulin receptor gene mutations in syndromes of severe insulin resistance and mutations in pancreatic beta-cell genes in the monogenic sub-group of type 2 diabetes: maturity-onset-diabetes-of-the-young, MODY. Pathophysiological models of insulin resistance in skeletal muscles and impaired glucose-induced insulin secretion in the beta-cells have formed a basis for selecting candidate genes with potential influence on the development of type 2 diabetes ("diabetogenes"). This process of selecting and analyzing genes for mutations that potentially associate with either type 2 diabetes mellitus, insulin resistance or impaired insulin secretion is often described as the "candidate gene approach". The studies reported in this thesis are excerpts from an extensive strategy of genetically dissecting (mutation analysis) in: 1) patients with the common form of late-onset type 2 diabetes mellitus the pathways that transduce the insulin signals from the plasma membrane to the activation of glycogen synthesis in skeletal muscle, and in 2) patients with either late-onset type diabetes or MODY the pathways involved in normal beta-cell development and beta-cell function (insulin secretion). Twelve of the genes that encode proteins in the insulin-signalling pathway from the insulin receptor through the phosphatidylinositide-regulated kinases down to the complex of phosphatases that regulate glycogen synthesis in skeletal muscle were analyzed. We could not confirm that a Val985Met variant in the insulin receptor is associated with type 2 diabetes or that the Met326Val of the p85 alpha regulatory subunit of the phosphoinositide-3 kinase is associated with insulin resistance. We found no coding mutations (missense) in the insulin signalling protein kinases but we confirmed that the 5 bp deletion (PP1ARE) in the 3'-end of the PPP1R3 gene that encodes the glycogen-associated regulatory subunit of protein phosphatase-1 (PP1G) is associated with insulin resistance estimated as insulin mediated glucose uptake. In contrast to protein kinases in skeletal muscles the genes encoding beta-cell transcription factors (IPF-1, NeuroD1/BETA2, and Neurogenin 3) are polymorphic but we could not confirm that the Asp76Asn of IPF-1 is a susceptibility gene for late-onset type 2 diabetes. On the other hand we confirmed that the Ala45Thr variant in NeuroD1/BETA2 may represent a susceptibility gene for type 1 diabetes but none of these genes revealed any MODY-specific mutations. Also the gene encoding the ATP-regulatable potassium channels of the beta-cell (Kir6.2) is polymorphic but none of these polymorphisms associated with changes in glucose-induced insulin secretion. Reviewed in context of the existing data our studies support the candidate gene approach as a feasible method for directly either identifying or excluding any gene as a diabetes-susceptibility gene ("diabetogene").
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PMID:Candidate genes and late-onset type 2 diabetes mellitus. Susceptibility genes or common polymorphisms? 1469 50

In vitro data have recently suggested that sulfonylureas (SUs) enhance GH secretion by modulating the effects of GHRH and somatostatin in pituitary cells. The present study was undertaken to explore in more detail a possible influence of a single dose of SU (glibenclamide) and a non-SU (repaglinide) insulin secretagogue on circulating GH dynamics. Ten C-peptide-negative type 1 diabetic individuals were examined on three occasions in random order. Either glibenclamide (10.5 mg), repaglinide (8 mg), or placebo was administered after overnight normalization of plasma glucose by iv insulin infusion. Subsequently, GH concentrations were measured regularly after stimulation with GHRH (bolus 0.1 micro g/kg) alone and during concomitant infusion with somatostatin (7 ng.kg(-1).min(-1)). Insulin was replaced at baseline levels (0.25 mU.kg(-1).min(-1)) and plasma glucose clamped at 5-6 mmol/liter. Overall, there were no significant statistical differences in GH responses determined as either GH peak concentrations, integrated levels of GH, or secretory burst mass of GH during the experimental protocol. In contrast, plasma glucagon concentrations were significantly increased during glibenclamide and repaglinide exposure. The present experimental design does not support the hypothesis that acute administration of pharmacological doses of the oral antihyperglycemic agents glibenclamide and repaglinide per se enhance GH release in humans. Additionally, this study shows that these potassium channel inhibitors seem to stimulate glucagon secretion in people who have severe intraislet insulin deficiency (e.g. type 1 diabetes). However, extrapolation of our findings to type 2 diabetic individuals should be done with some caution.
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PMID:The insulin secretagogues glibenclamide and repaglinide do not influence growth hormone secretion in humans but stimulate glucagon secretion during profound insulin deficiency. 1471 64

Noradrenaline and neuropeptide Y (NPY) in the hypothalamus regulate a number of important endocrine and autonomic functions. Alterations in brain neurotransmitter content have been described in type 1 diabetes but there is little understanding of whether these changes affect neurotransmitter release. This study examined for the first time, region-specific co-release of NPY and noradrenaline from the hypothalamus of male Sprague-Dawley rats treated intravenously with 48 mg/kg streptozotocin (STZ) or vehicle. Five weeks later, the release of endogenous noradrenaline and NPY was monitored by in vitro superfusion of ventral and dorsal hypothalamus slices under basal and potassium-stimulated conditions. STZ-diabetes induced significant increases in basal noradrenaline and NPY overflow from the ventral hypothalamus (P<0.05); only NPY overflow was increased in the dorsal hypothalamus (P<0.05). Noradrenaline overflow increased similarly to potassium depolarisation in vehicle and STZ-diabetic rats, whereas diabetic rats showed a significantly increased NPY overflow response to potassium depolarisation compared to vehicle rats. These region-specific increases in endogenous noradrenaline and NPY overflow from the hypothalamus in diabetes suggest increased neuronal activity at rest and enhanced responses under some conditions. Increased hypothalamic NPY and noradrenaline overflow most likely contributes to diabetic hyperphagia.
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PMID:Increased endogenous noradrenaline and neuropeptide Y release from the hypothalamus of streptozotocin diabetic rats. 1504 28


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