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)

A 45-year-old man with type I diabetes mellitus of 25-yr duration and well controlled by conventional insulin therapy developed an isolated adrenocorticotropic hormone (ACTH) deficiency. He presented with a 3-month history of weight loss, weakness, anorexia and persistent tendency to hypoglycemia that he had never experienced before. Basal and dynamic endocrine testing disclosed absent cortisol secretion caused by an isolated ACTH deficiency due to a primary pituitary defect. Corticosteroid replacement therapy allowed again a good glycometabolic control. The possible causes of hypoglycemia in insulin-treated diabetes and the pathogenetic basis of the reported association are discussed.
 ...
PMID:Development of isolated ACTH deficiency in a man with type I diabetes mellitus. 284 79

The cytokine interleukin 1 beta (IL-1) has been implicated as a pathogenetic factor in the initial events leading to insulin-dependent diabetes mellitus. Previous studies investigating the impact of IL-1 on diabetes incidence in spontaneously diabetic rodent models have been conflicting. IL-1 induces anorexia and previous studies are hampered by the lack of pair-fed controls to the IL-1 treated animals. We report that daily injections of 4.0 micrograms/kg/day of recombinant human IL-1 (rhIL-1) for 13 weeks from 25-30 days of age did not alter the incidence of diabetes in the diabetes-prone (DP) BB rats (75%) when compared to pair-fed, vehicle treated controls (55%, p = 0.18), or to unhandled DP BB rats (80%, p = 0.71). However, IL-1 induced significantly higher blood glucose concentrations in the prediabetic period (p < 0.00005) and at diabetes onset (p < 0.00005) in the DP BB rats and caused episodes of blood glucose concentrations > 11 mmol/l in the prediabetic period in 11/20 DP BB rats compared to 4/27 diabetes-resistant (DR) BB rats and 4/28 Wistar Furth (WF) rats (both p < 0.004), compared to DP BB). Further, rhIL-1 induced fever in 11 weeks in the DP BB rats compared to 3 weeks in the DR BB and 6 weeks in the WF rats. Using high performance size exclusion chromatography specific anti-rhIL-1-antibodies were demonstrated in DR BB and WF, but not in DP BB rats. These antibodies neutralized the inhibitory effect of rhIL-1 on insulin secretion from isolated islets of Langerhans in vitro. The reduced pyrogenic and endocrine effect of rhIL-1 in the DR BB and WF rats compared to the DP BB rats could be explained by the impaired ability of the DP BB rats to produce anti-rhIL-1-antibodies. In conclusion, administration of rhIL-1 modulated the prediabetic period, and produced higher blood glucose concentrations at diagnosis, but did not change the diabetes incidence in DP BB rats. The results are not in conflict with the hypothesis that IL-1 is a pathogenetic factor in IDDM, caused by high local concentrations of rat IL-1 in the islets during early insulitis. The results also show the necessity of pair-feeding of the control group to the rhIL-1 group when interpreting data from experiments investigating rhIL-1 effects on diabetes development in animal models.
 ...
PMID:Interleukin-1 beta (IL-1) does not reduce the diabetes incidence in diabetes-prone BB rats. 806 Nov 61

Using a validated postal questionnaire, we investigated the frequency of 24 gastrointestinal symptoms during the previous 3 months in a cohort of 110 young adult patients (54 males and 56 females, mean age 37.2 +/- 4.7 years) with onset of Type 1 diabetes mellitus at < 16 years of age. They were compared with 210 age- and sex-matched controls (104 males and 106 females). The main difference in the frequency of various symptoms between the two groups was a significant increase among the diabetic patients in upper gastrointestinal symptoms, such as loss of appetite (17.8% vs 3.6%, p < 0.001), early satiety (26.8% vs 6.1%, p < 0.001), nausea (22.7% vs 9.1%, p < 0.01) and vomiting (12.2% vs 3.0%, p < 0.01). No difference was noted in the frequency of symptoms from the lower gastrointestinal tract, apart from a significant increase in the feeling of incomplete defaecation (28.6% vs 17.0%, p < 0.04) in the diabetic patients. Patients with levels of haemoglobin A1c in the highest quartile had significantly more gastrointestinal symptoms than other diabetic patients. Further, the prevalence of symptoms was higher in females than in males. In conclusion, long-term Type 1 diabetes is accompanied by a markedly increased frequency of upper gastrointestinal symptoms, mainly in females and patients with poor metabolic control.
 ...
PMID:Increased prevalence of upper gastrointestinal symptoms in long-term type 1 diabetes mellitus. 873 31

This study was designed to assess (by means of a diagnostic interview based on DSM-III-R criteria) the prevalence of eating disorders in 69 insulin-dependent diabetic (IDDM) out-patients, and the relationship with somatic risks. We found no cases of anorexia nervosa or bulimia nervosa, current or lifetime, in male patients with IDDM. No female patients with IDDM had anorexia, and 4.8% had current and lifetime bulimia. Eating disorders not otherwise specified (bulimic type) were significantly more frequent in women than in men (lifetime incidence 43% vs. 21%; current incidence 33% vs. 5%), and generally occurred after the onset of IDDM. Self-reports of bulimic behaviours according to the Bulimic Investigatory Test of Edinburgh (BITE) were associated with high levels of glycosylated haemoglobin. There was no association between eating disorders (current or lifetime), with somatic complications being more likely to be explained by a long duration of illness and impaired glycaemic control.
 ...
PMID:Eating disorders and insulin-dependent diabetes mellitus (IDDM): relationships with glycaemic control and somatic complications. 954 9

When aiming at preventing IDDM in man, knowledge of the molecular mechanisms leading to beta cell destruction may facilitate identification of new possible intervention modalities. A model of IDDM pathogenesis in man suggests that cytokines, and IL-1 in particular, are of major importance in the initial events (Nerup et al 1994) (Fig. 1). In vitro rat experiments demonstrated that rhIL-1 beta inhibits beta cell function and induces beta cell death both in isolated islets of Langerhans and in the isolated perfused pancreatic gland. With the long term goal of identifying new modalities capable of preventing IDDM in man, the aim af this review was to investigate the effects of rhIL-1 beta on beta-cell function and viability in normal rats. This review discussed 1) the pharmacokinetics of IL-1 beta in rats as the basis for choice of route of administration and dose of rhIL-1 beta, 2) the effects and molecular mechanisms of IL-1 beta on temperature and food intake used as control parameters for successful injection of rhIL-1 beta in rats, 3) the effects of one or more injection of IL-1 beta on rat beta cell function, 4) the molecular mechanisms leading to IL-1 beta induced beta cell inhibition in vivo, and some possible intervention modalities based on the molecular mechanisms, 5) the effects of IL-1 beta on spontaneous diabetes mellitus in DP BB rats, and 6) the effects and molecular mechanisms of IL-1 beta induced inhibition of thyroid epithelial cell function and aggravated thyroiditis in DP BB rats, compared to the effects of IL-1 beta on rat beta cell function. Finally, this review discussed the effects of IL-1 beta on human beta cells in vitro, and the clinical relevance of these experiments, with special reference to a clinical trial with the aim of preventing IDDM in man. The pharmacokinetic studies suggested that IL-1 beta is distributed according to a two-compartment model with a first-order elimination. Interleukin-1 beta reached all the investigated organs in the rats, was accumulated in kidneys and was excreted in the urine. The data suggested that IL-1 beta also accumulated in the islets of Langerhans. After injection of 4.0 micrograms/kg pathophysiologically relevant concentrations of rhIL-1 beta were reached and intact rhIL-1 beta persisted for up to 5 hrs in plasma. Peripheral injections of IL-1 beta dose-dependently induced fever and anorexia in rats, probably via induction of PGE2 in the brain or in peripheral tissues thereafter passing the blood-brain barrier. Nitric oxide produced by cNOS seems to be a molecular mediator of IL-1 beta induced fever but not of anorexia. Fever and anorexia are well described effects of IL-1 beta in rats, and are as such usefull control parameters of the absorption and biological activity of IL-1 beta after peripheral injection. Injections of rhIL-1 beta to normal, non-diabetes prone rats induced initial beta cell stimulation followed by inhibition, in accordance with in vitro data. Furthermore, induction of peripheral insulin resistance coincided with beta cell inhibition after one daily injection for 5 days, leading to a transient diabetes mellitus-like state, characterized by hyperglycemia and hypoinsulinemia. At this time point, electron-microscopy did not demonstrate beta cell destruction. However, IL-1 beta induced intercellularly edema and microvillous processes on the beta cells, which might be early evidence of apoptosis. The diabetes mellitus-like state was not aggravated if the daily injections were continued beyond 5 days. Daily injections of rhIL-1 beta for 2 to 4 weeks induced formation of blocking IL-1 beta-antibodies in normal rats. Hence, injections exceeding 2 weeks should only be performed using species homologous IL-1 beta. The molecular mechanism of IL-1 beta induced beta cell inhibition in rats in vivo as in vitro, are likely to involve binding of IL-1 beta to the IL-1RtI, since the IL-1RtII is considered to be a decoy receptor. (ABSTRACT TRUNCATED)
 ...
PMID:Interleukin-1 beta induced transient diabetes mellitus in rats. A model of the initial events in the pathogenesis of insulin-dependent diabetes mellitus? 958 1

In this study the prevalence of eating disorders in a population-based cohort of 89 female patients with type 1 diabetes, 14-18 y of age, was compared with that in age-matched healthy controls. Of all diabetic girls in the study area, 92% participated in the study. The majority were treated with multiple insulin injections and the mean HbA1c of the participants was 8.4%. On average, diabetic girls were 6.8 kg heavier than the controls. A two-stage design was used. The first consisted of a validated self-report questionnaire, the Eating Disorder Inventory (EDI). Girls who had high scores were then interviewed about eating habits and mental health using a semistructured interview, the BAB-T (Assessment of Anorexia-Bulimia - Teenager version). No cases of anorexia or bulimia nervosa were found, but 15 diabetic patients (16.9%) compared with 2 control girls (2.2%), p<0.01, had disturbed eating behaviour according to the questionnaire. In 6 of these 15 diabetic girls an eating disorder was confirmed at the interview, mainly binge eating and self-induced vomiting. None of the control girls showed an eating disorder. Overweight diabetic girls scored higher on EDI than non-overweight diabetic girls (chi2 = 4.9; p = 0.038). No relationships were found between EDI scores and metabolic control (HbA1c), dose of insulin, frequency of hypoglycaemia or diabetic ketoacidosis.
 ...
PMID:Eating disorders in adolescent girls with insulin-dependent diabetes mellitus: a population-based case-control study. 1010 40

The adipocyte hormone leptin reduces food intake in normal animals. During uncontrolled type 1 diabetes, plasma leptin levels fall, whereas food intake increases. To test the hypothesis that low leptin levels contribute to diabetic hyperphagia, we investigated the effect on food intake of replacement of leptin at basal plasma concentrations for 7 days in Long-Evans rats with uncontrolled diabetes induced by streptozotocin (STZ). One group of STZ diabetic rats received saline (STZ + Sal) (n = 11), while the other group (STZ + Lep) (n = 15) received a subcutaneous infusion of recombinant rat leptin (100 microg x kg(-1) x day(-1)) via osmotic minipumps. A nondiabetic control group (Con) (n = 11) received saline only. In the STZ + Sal group, plasma leptin levels decreased by 75% (P < 0.05) from 2.4+/-0.5 on the day before STZ/citrate buffer vehicle (Veh) injection (day 0) to 0.6+/-0.2 ng/ml on day 7. In contrast, plasma leptin levels on days 3-7 were comparable to pretreatment values in both the STZ + Lep group (day 0: 2.6+/-0.4 vs. day 7: 2.5+/-0.3 ng/ml, NS) and the Con group (day 0: 3.8+/-0.4 vs. day 7: 2.9+/-1.0 ng/ml, NS). In the STZ + Sal group, daily food intake increased gradually to values 43% above basal by day 7 (day 0: 24+/-2 to day 7: 33+/-3 g, P < 0.05), whereas food intake did not increase in either the STZ + Lep group (day 0: 24+/-1 vs. day 7: 21+/-2 g, NS), or the Con group (day 0: 23+/-1 vs. day 7: 23+/-2 g). Plasma glucose levels exceeded nondiabetic control values (7.7+/-0.2 mmol/l) in both diabetic groups, but were lower in the STZ + Lep group (17.2+/-1.8 mmol/l) than in the STZ + Sal group (24.3+/-1.1 mmol/l, P < 0.05). To determine if sensitivity to leptin-induced anorexia was affected by STZ treatment, a second experiment was performed in which the effect of intracerebroventricular leptin injection (at doses of 0.35, 1.0, or 3.5 microg) on food intake was measured 10 days after STZ or Veh treatment. Leptin suppressed both 4- and 24-h food intake in the two groups to an equal extent at every dose (by 15, 22, and 35%, respectively). These findings support the hypothesis that the effect of uncontrolled diabetes to lower leptin levels contributes to diabetic hyperphagia and that this effect is not due to altered leptin sensitivity.
 ...
PMID:Low plasma leptin levels contribute to diabetic hyperphagia in rats. 1034 16

The cultural drive to be thin can lead to eating disorders in many women and girls. In adolescent females with diabetes, the increased focus on eating and the weight gain associated with good glycemic control likely increase their susceptibility to abnormal eating. It is clear that nonspecified and subthreshold eating disorders, and possibly bulimia and anorexia, are more common in this group of patients. Good nutritional counseling to help patients avoid weight gain and family counseling to improve communication between patients and their families may help decrease this risk. Intentional insulin omission is a frequent means of preventing weight gain or increasing weight loss in adolescent females with type 1 diabetes. Eating disorders should be suspected in patients with recurrent diabetic ketoacidosis or poor glycemic control that is resistant to attempts at improvement. Treatment includes decreasing dietary restraint, promoting healthy eating, and either psychiatric counseling or psychologic intervention, or both.
 ...
PMID:Eating disorders in adolescents with type 1 diabetes. A closer look at a complicated condition. 1131 70

The incidence of the metabolic syndrome, type 2 diabetes and cardio- and cerebrovascular disease is increasing in the Western world. The adipocyte derived protein adiponectin is thought to have a protective role against these conditions. But why is it so? Is it reasonable to believe that we have adiponectin to gain protection from welfare related diseases? Humans have had a far deadlier foe throughout history than obesity and sedentariness and that is starvation. During starvation, the body is catabolic in order to provide fuel. Catabolism is also seen in patients with advanced cardiac or renal failure, type 1 diabetes and anorexia. These subjects have higher adiponectin levels than controls. In this article, I will put forward the hypothesis that the adiponectin system evolved in order to help us to survive periods of malnourishment.
 ...
PMID:Adiponectin: saving the starved and the overfed. 1750 73

The era of interferon (IFN) administration in the treatment of patients with chronic viral hepatitis creates an essential turning point for therapy of these diseases. Incessant progress of the new, more efficient and lower side effects of interferon causes decrease in treatment withdrawal. The side effects like myalgia, nausea, fatigue and loss of appetite, usually with good reaction for symptomatic treatment and intensity of the symptoms decreases during treatment continuation. Due to strong immuno-modulatory activities and long-lasting therapy, autoimmune diseases are observed in some cases. Therefore treatment process should be carefully and trifle monitored especially in autoantibodies appearance aspect. To the most common interferon mediated autoimmune diseases belong thyroiditis, autoimmune hepatitis and thrombocytopenia. Interstitial pneumonitis, systemic lupus erythematosus, type I diabetes mellitus, asthma and sarcoidosis exacerbation as well as glomerular diseases are observed rarely. In our paper we discus an issue of autoimmune diseases induction phenomena caused by interferon therapy administrated in the treatment of chronic viral hepatitis.
 ...
PMID:[Interferon therapy in chronic viral hepatitis; an autoimmunity dilemma]. 1794 66


1 2 Next >>