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

Proximal tubular dysfunction may be implicated in the pathogenesis of diabetic nephropathy. An investigation of proximal tubular function was carried out by assessing proximal tubular sodium-reabsorption and low molecular weight protein excretion in a group of patients with type 1 diabetes mellitus. Normoalbuminuric [group A, n = 6, albumin excretion rate (AER) mean (range) 4 (0-10) micrograms/min], and microalbuminuric [group B, n = 6, AER 88 (35-198) micrograms/min] patients with type 1 diabetes were compared with matched controls. Simultaneous lithium and growth hormone (GH) clearance and urinary beta 2-microglobulin excretion were assessed. Fasting plasma glucose at the start of the study was [median (range)] 13 (10.2-15.1), 9.3 (5.9-15) and 4.1 (4.0-5.0) mmol/l in groups A, B and controls, respectively, with a mean coefficient of variation during the study of 3.9% (group A) and 5.2% (group B). There was no significant difference in plasma glucose levels between patients in groups A and B. Urinary GH excretion was raised in the patients with microalbuminuria (group B; P < 0.05), although there was no difference in serum GH clearance rate between the patient groups and controls. Urinary GH correlated with B 2-microglobulin in the diabetic subjects (r = 0.665, P < 0.05) and with the degree of microalbuminuria in group B patients (r = 1, P < 0.01). Urinary GH was also greater than 10 microU, the median value observed in the controls, in 5 of 6 (83%) patients in group A. Glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) measured by constant infusion of 51Cr-ethylene diamine tetra-acetic acid (EDTA) and I125-para-amino hippuric acid (PAH), respectively, showed relative hyperfiltration in the normoalbumiruric group compared with controls (P < 0.05) and group B (P < 0.05). Absolute proximal reabsorption of sodium and of water (APRNa and APRH2O) was significantly higher in group A patients (P < 0.05). Although GFR was significantly higher in group A patients, no differences were found in fractional proximal reabsorption of sodium and water (FPRNa+H2O) or end proximal delivery between the patient groups and controls. Therefore, the measurement of protein reabsorptive capacity provides a more sensitive marker of renal tubular impairment in type 1 diabetes than sodium/fluid reabsorptive capacity. In patients with microalbuminuria, both glomerular and tubular damage may coexist. Our results stress the usefulness of markers of renal tubular function in monitoring the course of diabetic nephropathy. This study also shows that assessment of GH clearance has promise as a marker of renal tubular protein reabsorptive capacity.
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PMID:Proximal tubular reabsorption of growth hormone and sodium/fluid in normo- and microalbuminuric insulin-dependent diabetes mellitus. 913 54

In insulin-dependent (type 1) diabetes mellitus, increasing peripheral insulin sensitivity might be a useful approach in controlling the process leading to beta cell destruction by reducing insulin output and thereby reducing the antigenicity associated with its release. The aim of this study was to investigate whether the use of a biguanide, Metformin, which has been suggested to increase insulin sensitivity, was capable of modifying the natural history of diabetes in a model of type 1 diabetes, the non-obese diabetic (NOD) mouse. Using age-, sex- and litter-matched groups, three groups of 32 animals each were treated with Metformin in their drinking water at a high dose of 200 mg/kg body weight and at a low dose of 20 mg/kg body weight; the third group of mice acted as controls. Diabetes incidence at 30 weeks of age was similar in all groups. No significant differences in the calculated index of insulitis were observed in treated or control animals. We conclude that Metformin does not affect the disease process leading to clinical diabetes in this animal model.
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PMID:Metformin does not alter diabetes incidence in the NOD mouse. 923 Mar 45

Exaggerated vasoconstriction and blunted vasodilation of peripheral resistance arteries to various vasoactive agents characterize patients with IDDM. We characterized the hemodynamic effects of insulin in skeletal muscle in patients with IDDM. Muscle blood flow and blood volume were measured basally and during a high-dose insulin infusion (5 mU x kg(-1) x min[-1]) in seven normotensive patients with IDDM (age, 30 +/- 6 years; BMI, 24.5 +/- 2.0 kg/m2; blood pressure, 124 +/- 12/78 +/- 11 mmHg) and nine matched normal subjects, using [15O]H2O, [15O]CO, and positron emission tomography (PET). Whole-body insulin sensitivity was determined using the euglycemic insulin clamp technique. Insulin-stimulated whole-body glucose uptake was significantly lower in the patients with IDDM (45 +/- 15 micromol x kg(-1) x min[-1]) than in the normal subjects (62 +/- 14 micromol x kg(-1) x min[-1]) (P < 0.05). Insulin increased muscle blood flow by 111 +/- 69% above basal from 3.0 +/- 2.0 to 5.8 +/- 3.0 ml x 100 g(-1) muscle x min(-1) (P < 0.005) in the normal subjects, but only by 42 +/- 30% from 2.0 +/- 0.9 to 2.9 +/- 1.4 ml x 100 g(-1) muscle x min(-1) (P < 0.005) in patients with IDDM (P < 0.05 for change in flow in IDDM vs. normal subjects). The calculated muscle vascular resistances were comparable basally, but higher during hyperinsulinemia in the patients with IDDM (37 +/- 17 mmHg x 100 g x min x ml[-1]) than in the normal subjects (16 +/- 7 mmHg x 100 g x min x ml[-l]) (P < 0.05). Muscle blood volume increased significantly by insulin in both groups without any difference between the groups. We conclude that the ability of supraphysiological concentrations of insulin to stimulate muscle blood flow is blunted in patients with IDDM, because of the inability of insulin to stimulate linear flow velocity rather than blood volume in skeletal muscle. This defect adds yet another defect to the list of abnormalities in vascular function in IDDM, which might predispose these patients to develop hypertension.
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PMID:Effects of insulin on blood flow and volume in skeletal muscle of patients with IDDM: studies using [15O]H2O, [15O]CO, and positron emission tomography. 939 89

Proglucagon contains the sequence of two glucagon-like peptides, GLP-1 and GLP-2, secreted from enteroendocrine cells of the small and large intestine. GLP-1 lowers blood glucose in both NIDDM and IDDM patients and may be therapeutically useful for treatment of patients with diabetes. GLP-1 regulates blood glucose via stimulation of glucose-dependent insulin secretion, inhibition of gastric emptying, and inhibition of glucagon secretion. GLP-1 may also regulate glycogen synthesis in adipose tissue and muscle; however, the mechanism for these peripheral effects remains unclear. GLP-1 is produced in the brain, and intracerebroventricular GLP-1 in rodents is a potent inhibitor of food and water intake. The short duration of action of GLP-1 may be accounted for in part by the enzyme dipeptidyl peptidase 4 (DPP-IV), which cleaves GLP-1 at the NH2-terminus; hence GLP-1 analogs or the lizard peptide exendin-4 that are resistant to DPP-IV cleavage may be more potent GLP-1 molecules in vivo. GLP-2 has recently been shown to display intestinal growth factor activity in rodents, raising the possibility that GLP-2 may be therapeutically useful for enhancement of mucosal regeneration in patients with intestinal disease. This review discusses recent advances in our understanding of the biological activity of the glucagon-like peptides.
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PMID:Glucagon-like peptides. 951 8

Disturbances of coronary circulation have been reported in diabetic patients with microvascular complications but without obstructive coronary atherosclerosis. The aim of the present study was to investigate coronary flow reserve in young adult patients with IDDM but without microalbuminuria and diabetic autonomic neuropathy. Coronary flow reserve was determined in 12 nonsmoking male patients with IDDM (age 30.0 +/- 6.6 years) and 12 healthy matched volunteers. Groups were similar with respect to blood pressure and serum lipid concentrations, and no subject had a positive family history of coronary heart disease. The patients with IDDM had normal exercise echocardiography and autonomic nervous function tests. Five patients had minimal background retinopathy, and none had microalbuminuria. Positron emission tomography and [15O]H2O were used to measure myocardial blood flow at rest and after dipyridamole administration. The studies were performed during euglycemic hyperinsulinemia (serum insulin approximately 70 mU/l). The baseline myocardial blood flow was similar in patients with IDDM and in control subjects (0.84 +/- 0.18 vs. 0.88 +/- 0.25 ml x g(-1) x min(-1), NS). The myocardial blood flow during hyperemia was 29% lower in patients with IDDM (3.17 +/- 1.57) compared with the control subjects (4.45 +/- 1.37 ml x g(-1) x min(-1), P < 0.05). Consequently, coronary flow reserve (the ratio of flow during hyperemia and at rest) was lower in diabetic patients than in control subjects (3.76 +/- 1.69 vs. 5.31 +/- 1.86, P < 0.05) and the total coronary resistance during hyperemia was higher in diabetic patients (53.7 +/- 31.5) compared with the control subjects (31.4 +/- 11.6 mmHg x min x g x ml(-1), P < 0.05). The coronary flow reserve was similar in diabetic patients with and without mild background retinopathy. No association was found between the coronary flow reserve and serum lipid or HbA1c values in either group. Coronary flow reserve is impaired in young adult males with IDDM and no or minimal microvascular complications and without any evidence of coronary heart disease. This abnormality cannot be explained by standard coronary heart disease risk factors. The results imply early impairment of coronary vascular reactivity in IDDM patients, which may represent an early precursor of future coronary heart disease or may contribute to the pathogenesis of diabetic cardiomyopathy.
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PMID:Coronary flow reserve is reduced in young men with IDDM. 951 21

This study was aimed to establish TSH dependent, transplantable thyroid tumor (TT) in B6C3F1 (BCF1) mice. In addition, transplanted TT was examined for its growth in mice given 17 beta-estradiol (E2), retinoic acid (RA), tamoxifen (TAM), T3 and T4. Both sexes of BCF1 mice were observed for 12 months under IDD and distilled water (DW), starting at 4 weeks of age. Groups of mice received an i.p. injection of radioactive iodine (131I) once at a dose of 60 mu Ci/head and/or given 0.25 mg E2 pellet s.c. One piece of induced pituitary or thyroid tumor was individually dissected aseptically and s.c. grafted under the fat pad of one site of the neck in the same strain of mice at 5 weeks of age. All mice were sacrificed between 7.5 to 13.5 months after grafting the tumors depending on the experiments. The transplantability of both pituitary and thyroid tumor was 100% in IDD mice, but TT was about 50% with a combined treatment of IDD plus E2. A supplement of thyroid hormones of T3 or T4 in mice with IDD completely inhibited the growth of in situ or grafted thyroid tumors. The growth of in situ thyroid gland was significantly promoted by the oral administration of RA in both sexes, whereas the growth of transplanted TT was significantly increased by RA in the female, but not in the male. Oral administration of TAM proved inhibitory upon in in situ and transplanted TT in the male, but not in the female. Thyroid tumor induced by IDD could grow only in mice with IDD and was partially regulated of its growth by RA and TAM.
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PMID:Effect of 17 beta-estradiol, retinoic acid and tamoxifen upon primary and transplanted thyroid tumor in B6C3F1 mice fed an iodine deficient diet. 953 64

Effects of taurine supplementation on lipid peroxide formation and the activities of glutathione (GSH) dependent enzymes in diabetic model mice were investigated. Type I diabetes mellitus was induced by injecting alloxan to ICR mice while type II diabetes mellitus was produced by high calorie diet feeding to genetically hyperglycemic KK mice. Taurine was given in drinking water at the level of 5% (w/v) for seven days. The malondialdehyde (MDA) levels of liver and the islets of type I diabetes were significantly increased compared to the control group but the levels were significantly decreased by taurine supplementation. In the type II diabetic model, the concentrations of MDA were not changed by taurine treatment. The activity of hepatic and islet GSH-peroxidase (GPX) was increased in the type I diabetic group, but in type II animals it was decreased. Hepatic GPX activity of both type I and II diabetics was not altered by taurine supplementation but was increased in the islets of the type II animals. No effect on the activity of GSH S-transferase (GST) was observed in both types of diabetes (I and II) following taurine supplementation. These results suggest that taurine supplementation protects type I diabetic mice from lipid peroxide formation.
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PMID:Effect of taurine supplementation on the lipid peroxide formation and the activities of glutathione-related enzymes in the liver and islet of type I and II diabetic model mice. 963 20

Since bioelectrical characteristics correspond well to body water compartments, this study investigated bioelectrical differences between type 1 and type 2 diabetic subjects that could reflect differences in body water compartments. We investigated cross-sectionally 612 adult subjects, classified into 10 groups according to sex and disease (control, obese normal glucose tolerant, non-obese type 2 diabetes, obese type 2 diabetes, type 1 diabetes). Resistance (R), reactance (Xc) and phase angle (PA) were measured (800 microA - 50 kHz alternating current). The bioelectrical vector was obtained by plotting R and Xc normalized for height (ht), it is easily identified on the basis of the length (inversely related to the total body water, likewise R) and direction, given by the PA (inversely related to the extra-/intra-cellular water - ECW/ICW -). Results show that disease and sex had a significant (ANOVA: P<0.0001 for both F disease and F sex) and independent effect on both R/ht and Xc/ht; no difference was found between type 2 and type 1 diabetic groups. A bioelectrical vector with a lower PA characterized both type 2 and type 1 diabetic groups. An independent positive correlation between fasting plasma glucose and R/ht and a negative correlation between fasting plasma glucose and PA were observed. These findings suggest a non-different body water content and distribution between type 2 and type 1 diabetic subjects; the bioelectrical vector indicates a higher ECW/ICW in type 2 and type 1 diabetic compared to nondiabetic subjects.
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PMID:Bioelectrical characteristics of type 1 and type 2 diabetic subjects with reference to body water compartments. 993 22

It is expected that microvascular blood flow might be affected by blood glucose, blood insulin and C-peptide levels. In our investigation skin microvascular blood flow (LDF) was measured using laser doppler fluxometry at skin temperatures of 37 degrees C and 44 degrees C during a 75 g oral glucose load (OGT) or water in ten healthy volunteers (6 male, 4 female, age: 28.1+/-4.0) who had fasted overnight. The transcutaneous oxygen tension (tcPO2) was measured using a transcutaneous oxygen electrode at a temperature of 44 degrees C. The microvascular response to acetylcholine was investigated before the start of the ingestion period and after 30 minutes. In addition, the capillary blood cell velocity (CBV) was measured using dynamic capillaroscopy. During OGT an increase in LDF could be observed at 37 degrees C (180%, p < 0.005) but only a slight increase was observed at 44 degrees C (86%, n.s.). The microvascular response to acetylcholine increased by 164% (p < 0.05) and the TcPO2 values increased by 30% (p < 0.01) during the OGT investigation. No significant changes in the microvascular measurements could be observed during the water experiment. No significant changes could be observed in the CBV measurements in any phase of the investigation. Plasma C-peptide and insulin levels exhibited an association with the LDF measurements at 37 degrees C (r = 0.22, p < 0.05; r = 0.30, p < 0.05; respectively), whereas blood sugar values showed an association with the TcPO2 measurements (r = 0.39, p < 0.01). After the ingestion of glucose a sophisticated modulation of microvascular blood flow was found in healthy volunteers. Further studies are necessary to investigate the role of a disturbed postprandial blood sugar control, insulin and C-peptide secretion in the development of microvascular dysfunction, especially in IDDM.
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PMID:Microvascular skin blood flow following the ingestion of 75 g glucose in healthy individuals. 1007 23

Treatment of type 1 diabetes mellitus has made tremendous advances within the last decades. With concern to insulin delivery there are two promising new approaches. One is the intrapulmonary insulin delivery which has become feasible by the development of new inhalation devices which provide a sufficient degree of intrapulmonary drug retention. Also oral insulin delivery seems feasible when surface active substances are used to cross the mucosal membrane in the gut. Clinical research has also focussed on coatings for the insulin molecules to solve the problem raised by the proteolytic activity of the digestive system. A very new agent produced by a fungus called Pseudomassaria has been demonstrated to reverse the clinical signs of diabetes mellitus in mice. The compound diffuses through the cell membrane, binds to the inner part of the insulin receptor and activates the insulin typical biological effects. Nowadays a variety of insulin analogs are designed and tested for their clinical use. By shifting the isoelectric point towards to a slightly acidic pH, HOE 901 precipitates at physiologic pH resulting in a constant and peakless insulin delivery. NN 304 is a 14-carbon aliphatic fatty acid acylated analog that binds to serum albumin resulting in a flatter time-action profile than NPH insulin. Also rapid acting insulin analogs are or will be launched in the near future aiming to ensure an improved postprandial glucose regulation. Glucagon-like peptide-1 (GLP-1) improves metabolic control by a variety of effects, e.g. the enhancement of insulin secretion and inhibition of glucagon secretion. Moreover, GLP-1 reduces food and water intake controlled by the brain, and inhibits gastric emptying. A disadvantage of GLP-1 is its very short half-life. Novel derivatives with the beneficial effects of GLP-1 but a better resistance against degradation have been designed. In addition substances have been developed inhibiting GLP-1 degradation or augmenting GLP-1 release from its abundant endogenous pool. Finally, there is a variety of interesting approaches aiming to improve or ease blood glucose self-monitoring. One is the development of subcutaneous catheters for continuous blood glucose control. In another system reverse iontophoresis is used for sampling interstitial fluid which reflects capillary blood glucose levels. Instead of using an electric current, a brandnew system creates micropores in the skin by a laser ablation system. Through these micropores a specific device performs a mild suction to obtain intersitial fluid. Further systems which measure blood glucose by near infrared spectroscopy are still investigated in order to improve their technical function and to reduce their weight. This article intends to give an overview over the new developments in the treatment and management of type-1-diabetes mellitus.
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PMID:New developments in the treatment of type 1 diabetes mellitus. 1052 18


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