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

Altogether 54 male patients with insulin-dependent diabetes mellitus participated in the studies. The impact of insulin-induced hypoglycemia on posthypoglycemic insulin sensitivity was evaluated for up to 12 hours following nadir hypoglycemia. The effect on glucose homeostasis following transient elevation of counterregulatory hormones was studied by exogenous administration of adrenaline, adreno-corticotropic hormone and growth hormone and by suppression of the endogenous release of growth hormone in connection with hypoglycemia. The studies were performed in the fasting state preceded by a 24 hour intravenous insulin infusion in order to avoid interference of subcutaneous insulin. Insulin resistance was determined by a constant rate intravenous infusion of somatostatin, insulin and glucose. This test seemed appropriate for the evaluation of total insulin resistance, and its reproducibility was acceptable. By using this method it was demonstrated that insulin resistance occurred for at least 12 hours after a hypoglycemic event in patients with IDDM, and that adrenaline caused immediate insulin resistance which, however, faded out within four to six hours, while GH exerted no immediate effect on insulin sensitivity but caused marked and sustained insulin resistance after a lag period of about four hours. Cortisol had no apparent effect within six hours but enhanced the effect of GH. The magnitude of these diabetogenic effects of hypoglycemia and GH was less pronounced in patients who already were more insulin resistant. These results are compatible with the idea that adrenaline is of major importance for the counterregulation and restoration of blood glucose during the first few hours following hypoglycemia, while GH is responsible for the induction of a long-lasting state of insulin resistance. It is possible that such prolonged insulin resistance may cause posthypoglycemic hyperglycemia in patients with IDDM. These studies therefore indicate that the GH suppressing hormone somatostatin may be of clinical value as an adjunct to insulin in the treatment of patients with insulin-dependent diabetes mellitus and labile blood glucose control.
 ...
PMID:Studies on posthypoglycemic insulin resistance in insulin-dependent diabetes mellitus. 290 16

The use of hospital services was studied in 228 patients with known diabetes (KD) (52 insulin treated. 101 diet plus oral hypoglycaemic agents (OHAs), 66 diet treated and 9 without treatment) and 87 subjects with fasting hyperglycaemia (FH) found by screening of a well-defined population aged 60-74 years. Ninety per cent were NIDDM as evaluated by a high C-peptide response on glucagon stimulation. Information about all admissions during the year before ascertainment was obtained from the complete regional computerized hospital registration system. The overall average admission rate per year for KD males was 0.47 and for females 0.50. The average number of bed-days occupied per person-year was 6.8 for KD males and 8.2 for females. These rates are 2-3 times higher than those of the general population. Insulin treated NIDDM patients had a rate of 23.9, whereas IDDM patients had a rate of 15.2 bed-days per person-year. The corresponding figures for patients treated with OHAs were 3.5 and for patients treated with diet 4.6. FH had overall bed-day occupancy rates of 0.50 and 1.09 for males and females, respectively, which was less than half of that expected from the general population. IF discharge diagnosis (principal and/or subsidiary) had been used for identification of hospitalized patients with diabetes the bed-days used by KD patients would have been underestimated by 15.3%, most pronounced for diabetics treated with OHAs (21.1%) or diet (21.6%).
 ...
PMID:Use of hospital services by elderly diabetics: the Frederica study of diabetic and fasting hyperglycaemic patients aged 60-74 years. 295 43

The effects of insulin in vitro on perfused liver from streptozotocin-diabetic rats and their untreated littermates during gluconeogenesis from either [3-13C]alanine + ethanol or [2-13C]pyruvate + NH4Cl + ethanol were studied by 13C NMR. A 13C NMR determination of the rate of pyruvate kinase flux under steady-state conditions of active gluconeogenesis was developed; this assay includes a check on the reuse of recycled pyruvate. The preparations studied provided gradations of pyruvate kinase flux within the confines of the assay's requirement of active gluconeogenesis. By this determination, the rate of pyruvate kinase flux was 0.74 +/- 0.04 of the gluconeogenic rate in liver from 24-h-fasted controls; in liver from 12-h-fasted controls, relative pyruvate kinase flux increased to 1.0 +/- 0.2. In diabetic liver, this flux was undetectable by our NMR method. Insulin's hepatic influence in vitro was greatest in the streptozotocin model of type 1 diabetes: upon treatment of diabetic liver with 7 nM insulin in vitro, a partial reversal of many of the differences noted between diabetic and control liver was demonstrated by 13C NMR. A major effect of insulin in vitro upon diabetic liver was the induction of a large increase in the rate of pyruvate kinase flux, bringing relative and absolute fluxes up to the levels measured in 24-h-fasted controls. By way of comparison, the effects of ischemia on diabetic liver were studied by 13C NMR to test whether changes in allosteric effectors under these conditions could also increase pyruvate kinase flux. A large increase in this activity was demonstrated in ischemic diabetic liver.
 ...
PMID:Effects of insulin on perfused liver from streptozotocin-diabetic and untreated rats: 13C NMR assay of pyruvate kinase flux. 303 Apr 12

The mechanisms of sc insulin absorption are not understood, and models for interpreting in vivo data cannot be developed without gross simplification. To overcome this difficulty we developed a new approach which makes use of deconvolution analysis and does not require any model of the sc tissue. In five normal subjects and seven insulin-dependent diabetic (IDDM) patients endogenous insulin secretion was suppressed by means of a hypoglycemic glucose clamp procedure (approximately 2.8 mmol/L) sustained by a continuous insulin infusion (approximately 4 pmol/min.kg). A bolus injection of insulin (5.4 nmol) was administered iv, and plasma insulin concentrations were measured frequently for 2 h to assess iv insulin kinetics. Insulin then was injected sc in the abdominal region, and plasma insulin concentrations were measured for 8 h. Each subject was studied twice, with porcine and semisynthetic human insulin (Actrapid, Novo). The rate of insulin absorption was reconstructed by deconvolution from the plasma concentrations and iv insulin kinetic data. Linearity of the iv insulin kinetics, essential for deconvolution analysis, was confirmed by a dose-response study in the range of the measured concentrations (150-1800 pmol/L). In most instances, a two-compartment model was adequate to describe the iv response. The mean plasma insulin clearance rates were 15.5 +/- 1.9 (+/- SD) mL/min.kg (porcine) and 17.2 +/- 6.0 (human) in normal subjects and 20.7 +/- 8.8 (porcine) and 20.9 +/- 9.1 (human) in the IDDM patients. The rate of appearance of human insulin from sc tissue was faster than that of porcine insulin in both normal and IDDM subjects, but no significant differences were found in bioavailability, which was 55 +/- 12% (+/- SD; porcine) and 61 +/- 34% (human) in the normal subjects, and 84 +/- 28% (porcine) and 86 +/- 23% (human) in the IDDM patients. The rate of absorption and bioavailability were higher in the IDDM patients than in the normal subjects, a difference possibly related to increased sc blood flow in the IDDM patients. No differences were found with regard to glucose requirement values, normalized to plasma insulin concentrations, in agreement with the finding that the bioavailability of the two insulin species was similar.
 ...
PMID:Porcine and human insulin absorption from subcutaneous tissues in normal and insulin-dependent diabetic subjects: a deconvolution-based approach. 304 44

Diabetes mellitus is a heterogenous syndrome. Insulin dependent type I diabetes is characterised by progressive beta-cell-loss, resulting in a deterioration of insulin secretion. Cause of the beta-cell-destruction is a chronic autoimmune process, which starts already months to years before manifestation of the disease. New advances in the diagnosis of the autoimmune mechanisms, which are responsible for type I diabetes might help to prevent type I diabetes by immunization or immunosuppressive therapy in the near future. At the moment multiple daily insulin injections are the substitution therapy of the choice in type I diabetes mellitus. This kind of therapy is designed to imitate the physiologic dynamics of insulin secretion in healthy subjects. In non insulin dependent diabetes a defect in insulin action seems to be the primary cause of the disease although there are also defects in insulin secretion in type II diabetes mellitus. Most type II diabetics are overweight at the beginning of the disease and the primary goal of therapy in these patients is normalization of bodyweight and improvement of peripheral and hepatic insulin sensitivity. Regular exercise is seen as a cornerstone in the treatment of type I and type II diabetes. Besides the acute blood glucose lowering effect of exercise, regular exercise has beneficial effects on the circulatory system and muscle system, leads to an increase in insulin sensitivity, to a decrease of the daily insulin dosage and to a stabilization of metabolic control. Furthermore beneficial effects of exercise on plasma lipids and lipoproteins are reported. In overweight diabetics regular exercise facilitates normalization of body weight.
 ...
PMID:[Pathogenesis and therapy of type I and type II diabetes mellitus]. 306 11

To assess mechanisms leading to the 'dawn phenomenon' in type 1 diabetes mellitus, overnight insulin clearance, hepatic blood flow and insulin sensitivity of glucose metabolism were determined in 9 type 1 diabetic subjects treated with continuous subcutaneous insulin infusions. Glucose clamp studies were performed twice, once after midnight (from 24.00 to 02.00 h), and once in the early morning (from 06.00 to 08.00 h) during insulin infusion at 15 mU/m2/min. Insulin clearance was 482 +/- 57 ml/m2/min during the first, and 528 +/- 56 ml/m2/min during the second clamp (nonsignificant). Hepatic plasma flow assessed by measuring indocyanine green clearance was 984 +/- 115 and 1,040 +/- 163 ml/min, after the first and after the second clamp, respectively (nonsignificant). Glucose uptake during the two clamps was not significantly different. Since hepatic blood flow is known to influence insulin clearance and hepatic glucose metabolism, the data demonstrate that overnight changes in hepatic blood flow and insulin clearance do not contribute to the previously described early morning increase in insulin requirements in type 1 diabetic subjects (dawn phenomenon).
 ...
PMID:Alterations in insulin clearance and hepatic blood flow during the night do not contribute to the 'dawn phenomenon' in type 1 diabetes. 306 6

Recently, we demonstrated that spaghetti caused significantly lower glycaemic response than rice and potato in insulin-dependent diabetic (IDDM) subjects and that this difference was also present when spaghetti and potato were taken as part of a mixed meal. We have now compared the blood glucose and insulin responses to 50 g of carbohydrate in the form of white bread, potato and white spaghetti in 6 non-insulin-dependent diabetic (NIDDM) patients. The blood glucose response after white spaghetti observed over a 3-h period was only 60 +/- 10 per cent (P less than 0.02) of that seen in response to potato (395 +/- 116 mmol/l x 180 min vs 641 +/- 108 mmol/l x 180 min) and 47 +/- 9 per cent (P less than 0.01) of that seen in response to white bread (395 +/- 116 mmol/l x 180 min vs 805 +/- 93 mmol/l x 180 min). Insulin responses showed an identical pattern reflecting the glycaemic responses. To see if the difference in the glucose responses in NIDDM patients is preserved if these carbohydrate-rich foods are taken as part of a mixed meal we looked at the blood glucose and insulin responses to 50 g of carbohydrate in the form of potato and white spaghetti when ingested together with bolognese sauce (167 g) in 7 NIDDM patients.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Comparison of blood glucose and insulin responses in non-insulin dependent diabetic patients. Studies with spaghetti and potato taken alone and as part of a mixed meal. 307 22

A study of non-infective skin associations of diabetes mellitus was conducted on 100 consecutive outpatient diabetics over a 3-month period. 10 were insulin-dependent diabetics (IDDM), 24 insulin-requiring and 66 non-insulin dependent diabetics (NIDDM). A total skin evaluation was done for each patient with skin biopsy whenever appropriate. Twenty-three patients had diabetic dermopathy; the frequency of retinopathy in this group (39.1%) is significantly higher than that without diabetic dermopathy (6.9%) (p less than 0.001). There were 20 instances of cutaneous complications of therapy; 10 had insulin lipodystrophy (29.4% of 34 insulin users). Twelve patients, 8 of whom were overweight, had acanthosis nigricans. There were 6 Indians among them and all the patients had NIDDM. Eight had xanthelasma. Vitiligo occurred in 3.3% of those with NIDDM. Classical scleredema diabeticorum and cheiroarthropathy occurred in 2% of patients. One patient had atypical granuloma annulare. There was a higher incidence of xanthelasma in our study compared with studies done previously. Insulin lipodystrophy and acanthosis nigricans in the absence of classically described syndromes of insulin resistance seem to be fairly common phenomena and merit further investigation locally.
 ...
PMID:Non-infective skin associations of diabetes mellitus. 322 40

Sera from 80 subjects with IDDM and NIDDM, together with sera from 20 patients with miscellaneous autoimmune conditions and 20 healthy adult subjects were tested for insulin receptor antibodies by (1) inhibition of 125I-insulin binding to EBV-transformed lymphoid cells, and by (2) immunoprecipitation of solubilized insulin receptors in the presence of an excess of mono-specific anti-human IgG or IgM; this test allowed the assessment of the class of antibody activity. Anti-insulin antibodies in the sera were also measured using a double antibody technique. Anti-insulin receptor antibodies were found in 13 of 33 subjects with IDDM and six of 47 with NIDDM. These were principally in the IgM class, and in both groups of diabetics there was a good correlation between % inhibition of insulin binding to intact cells, and % of antibody precipitated by IgM (P less than 0.001), but not by IgG (P greater than 0.1). There was also a good correlation between the % inhibition of insulin binding to intact cells and the daily dose of insulin used in treatment (P less than 0.001). Insulin antibodies were found in seven of 33 subjects with IDDM and six of 12 with NIDDM, all of whom were on insulin treatment. These six subjects were the only ones with NIDDM who also had anti-insulin receptor antibody activity, suggesting that such antibodies may represent auto-anti-idiotype activity. This study shows that autoimmunity in insulin dependent (Type I) diabetes is not limited to islet cells and that such patients also develop antibodies to the insulin receptor. While three out of five patients with relative insulin resistance (requirement greater than 90 u/day) also showed evidence of insulin receptor antibody activity, the clinical significance of these antibodies has yet to be determined.
 ...
PMID:Insulin receptor antibodies in diabetes mellitus. 328 Jan 81

Effects of epinephrine (Epi) infusion on the absorption of subcutaneously injected 125I-labeled soluble human insulin (10 U) from the thigh or the abdomen were studied in 16 healthy subjects and from the thigh in 10 insulin-dependent diabetic (IDDM) patients. Epi was infused at 0.3 (high dose) or 0.1 (low dose; healthy subjects) nmol.kg-1.min-1 i.v., resulting in arterial plasma Epi levels of approximately 6 and 2 nM, respectively. Saline was infused on a control day. Insulin absorption was measured as disappearance of radioactivity from the injection site and as appearance of plasma immunoreactive insulin (IRI). Adipose tissue blood flow was measured with the 133Xe clearance technique. First-order disappearance rate constants of 125I from the thigh depot decreased approximately 40-50% during the high dose of Epi compared with control (P less than .001). The corresponding decrease from the abdominal depot was approximately 40% (P less than .001), whereas no significant change was found during the low Epi dose. IRI fell compared with control in all groups at the high Epi dose. The Epi-induced depression of insulin absorption occurred despite unaltered or even slightly increased subcutaneous blood flow. The results indicate that circulating Epi at levels seen during moderate physical stress depresses the absorption of soluble insulin from subcutaneous injection sites to an extent that might be important for glycemic control in IDDM patients. Furthermore, dissociation is found between changes in insulin absorption and subcutaneous blood flow during Epi infusion, suggesting that factors other than blood flow may also influence the absorption of subcutaneously injected insulin.
 ...
PMID:Influence of circulating epinephrine on absorption of subcutaneously injected insulin. 328 90


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>