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 decreased insulin response, preferentially to glucose, has been considered a hallmark of non-insulin dependent diabetes mellitus (Type 2) in humans. Syndromes resembling human diabetes occur spontaneously in many animal species and can also be induced by treating animals with drugs or viruses, excising their pancreases or manipulating their diet. Among these models, rat diabetes induced by neonatal streptozotocin administration (n-STZ models) has been first recognized as an adequate tool to study the long-term consequences of a gradually reduced beta-cell mass. More recently, the GK (Goto Kakisaki) Wistar rat has become available and is now considered as a promising spontaneous rat model of non-insulin dependent diabetes. We and others have found that defects in insulin secretion and action develop in the n-STZ and the GK models, which in many ways resemble those described in human non-insulin dependent diabetes. This review is aimed to sum up with a comparative approach, the informations so far collected in the n-STZ and GK models concerning the cellular mechanisms leading to the desensitization of their beta-cells to glucose. Taken together, the data reinforce the view that the impairment of glucose-induced insulin release in n-STZ and GK rats is clearly related to a defect in oxidative glycolysis. This leads to a severe decrease in the mitochondrial oxidative catabolism of glucose-derived pyruvate. Its coincides with a lower ATP/ADP ratio in glucose-stimulated islets and a subsequent alteration of ionic events tightly coupled to the fuel function of the hexose in islet cells, i.e. the decrease in K+ conductance.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Glucose refractoriness of pancreatic beta-cells in rat models of non-insulin dependent diabetes. 780 48

Iatrogenic hypoglycemia is a major problem for patients with IDDM. The principles of glucose counterregulation, the physiological mechanisms that normally prevent or correct hypoglycemia, are now known. In concert with decrements in insulin, increments in glucagon, and in the absence of the latter increments in epinephrine, stand high in the hierarchy of redundant glucose counterregulatory factors. In IDDM, iatrogenic hypoglycemia is the result of the interplay of absolute or relative insulin excess and compromised glucose counterregulation. Syndromes of compromised glucose counterregulation include hypoglycemia unawareness (loss of the warning, neurogenic symptoms of developing hypoglycemia), defective glucose counterregulation (the result of combined deficiencies of the glucagon and epinephrine responses to falling glucose levels), and elevated glycemic thresholds (lower glucose levels required) for autonomic activation and symptoms during effective intensive therapy. These have been conceptualized as examples of hypoglycemia-associated autonomic failure. Hypoglycemia unawareness, but not defective glucose counterregulation, is reversible during scrupulous avoidance of iatrogenic hypoglycemia. Clearly, we need to learn to replace insulin in a much more physiological fashion, or to prevent, correct, or compensate for compromised glucose counterregulation, or both, if we are to eliminate hypoglycemia from the lives of people with IDDM without compromising glycemia control. In the meantime we must practice hypoglycemia risk factor reduction with our patients, continue to seek better insight into the fundamental mechanisms of compromised glucose counterregulation, and develop practical preventive clinical strategies.
 ...
PMID:Hypoglycemia-induced autonomic failure in insulin-dependent diabetes mellitus. 863 Jul 45

Glutamate decarboxylase (GAD65) is a major autoantigen in insulin-dependent diabetes (IDDM) and the neurological disorder Stiff-Man-Syndrome (SMS). We derived a human monoclonal autoantibody (MICA 2) from peripheral blood of a patient newly diagnosed with IDDM, which reacted with GAD65 in Western blots. This indicated that a linear epitope is recognized by MICA 2. Using an epitope cDNA library we mapped the MICA 2 epitope to a contiguous stretch of 26 amino acids (506-531) in the C-terminus of GAD65. Neither blocking experiments with synthetic peptides nor analysis of overlapping decapeptides expressed as fusion proteins allowed us to further narrow down the epitope to the typical size of linear epitopes of 6-8 amino acids. We suggest that a miniconformational epitope provided by amino acids 506-531 is recognized by MICA 2, which withstands SDS gel electrophoresis without destruction or partially refolds during the Western blot procedure. A sequence homology with human heat shock protein 60 (HSP60) maps to this region of GAD65 but no cross-reactivity of MICA 2 with HSP60 occurred. Our data demonstrate that reactivity of an antibody in Western blots does not necessarily define a classic linear epitope of 6-8 amino acids and describe a new autoreactive epitope in GAD65 different from those reported for sera from patients with SMS.
 ...
PMID:Mapping of an autoreactive epitope within glutamate decarboxylase using a diabetes-associated human monoclonal autoantibody and an epitope cDNA library. 874 89

We report on a 33-year-old male patient with generalized acquired lipodystrophy, insulin resistant diabetes mellitus and acanthosis nigricans (Lawrence Syndrome). First probable symptoms of lipodystrophy (weight loss, shrinkage of subcutaneous fatty tissue, and loss of muscular strength) became evident three years ago, with the onset of diabetes mellitus occurring about six months later. The patient suffered from the following clinical symptoms: IDDM with increasing insulin-requirement, extreme reduction of fatty tissue, fatty liver hepatitis with elevated liver enzymes, glomerulopathy, muscular and neuropathic pains, as well as hypertriglyceridaemia. A basal C-peptide concentration is rather high. Definitely, the endogenous insulin secretion is increased. In other words, insulin resistance is documented. In an effort to identify the pathogenetic mechanisms of lipoatrophic diabetes mellitus in this patient and to develop a therapeutic strategy, antibodies against different tissues and endocrinologic regulation were investigated. It was possible to demonstrate the presence of serum autoantibodies against lipocytes of the subcutis and other tissues, against hepatic stellate cells, together with autoantibodies against different endocrine organs. By studying the basis of diabetic abnormalities relating to the growth hormone (GH), the insulin-like growth factor (IGF) dynamics in this patient, i.e. reductions of GH, IGF-I, IGF-II, IGF-Binding protein (IGF-BP) 2 and IGF-BP 3, were detected. An immunosuppressive treatment strategy was not beneficial.
 ...
PMID:Dysregulation of insulin-like growth factors in a case of generalized acquired lipoatrophic diabetes mellitus (Lawrence Syndrome) connected with autoantibodies against adipocyte membranes. 951 65

Diabetes mellitus is a heterogeneous disorder. Evidence for heterogeneity is based on measuring endogenous insulin level since some forty years ago. Insulin is lacking at the time of diagnosis in most patients, whose disease started rapidly, with classical symptoms, and who are mainly children, adolescents or young adults. In the majority of middle-aged, obese diabetics, insulin levels are frequently high at diagnosis. Since insulin measuring from sera became a routine laboratory test these two main types were nominated as insulin-dependent, and insulin non-dependent types (IDDM and NIDDM). The aim of the recent classification was, that different diabetic subgroups should be based on etiologic evidence. (Previous classification was based mainly due to the current therapy!). To avoid confusing nominations, the recent classification recommended to abandon the acronyms, IDDM and NIDDM, and only type-1 and type-2 should be used In the third subgroup-other diabetic groups--there are selected many disorders, whose etiology is mostly clear. As fourth subgroup gestational diabetes preserved its previous place. There are some differential-diagnostic problems in between type-1 and type-2 subgroups, especially between lean body weight type-2 and-the newly discovered latent-onset diabetes in adults (LADA). Diagnostic criteria of diabetes and prediabetic states are being changed according to epidemiological data, because type-2 patients die frequently from cardio-cerebrovascular fatal disorders, and elevated blood sugar values-especially postprandially-contribute to it. Thresholds of blood sugar values for diagnosing diabetes are therefore decreasing, and a new category: impaired fasting glucose (IFG, blood sugar: 6, 1-7.0 mmol/l) was introduced. Impaired glucose tolerance (IGT) remained as prediabetic state. IGT + IFG are nominated as impaired glucoregulation. These two categories cover different populations. Oral glucose loading test in most problematic cases should be carried out. The clinical importance of postprandial hyperglycaemia (postprandial state) is discussed. As a new clinical concept, the Metabolic Syndrome seems to replace type-2 diabetes in the majority of these patients, even in the impaired glucose tolerance (IGT) state. Diabetics, carrying the features of this syndrome need holistic care.
 ...
PMID:[New diagnostic and classification system in diabetic syndrome]. 1250 59

The aim of this study was to examine the long-term effect of lung transplantation on Health Related Quality of Life by studying 28 patients who survived at least 55 months after lung transplantation. Measures included the Nottingham Health Profile, questions concerning lung-specific problems, the State-Trait Anxiety Inventory, the Self-rating Depression Scale, the Index of Well-Being, the Karnofsky performance index, and questions concerning activities of daily life. Furthermore, comorbid conditions were measured. Before transplantation patients reported restrictions on almost all quality of life measures. Until approximately 43 months after transplantation there were significant improvements on most dimensions of the Nottingham Health Profile and more patients could walk without dyspnea. Significant improvements occurred with regard to the levels of anxiety, depression, and well being, and the scores on the Karnofsky performance index improved. Activities of daily life could be performed without help by most patients. After approximately 43 months patients experienced more dyspnea, anxiety, depression, and a lower level of well being. The number of patients suffering from a decrease of kidney function, drug treated hyperlipidemia, insulin dependent diabetes mellitus and bronchiolitis obliterans syndrome increased. It may be concluded that patients experience a stable and better overall quality of life after transplantation. Long-term after lung transplantation patients experience a decline on several dimensions of quality of life, which may be explained by an increase of comorbid conditions and Bronchiolitis Obliterans Syndrome.
 ...
PMID:Long-term quality of life in patients surviving at least 55 months after lung transplantation. 1267 22

Autoimmune Polyendocrine Syndromes (APS) were initially defined as a multiple endocrine gland insufficiency associated to an autoimmune disease in a patient. Neufeld & Blizzard (1980) suggested a classification of APS, based on clinical criteria only, describing four main types. APS-1 is characterized by presence of chronic candidiasis, chronic hypoparathyroidism, Addison's disease. It is a very rare syndrome interesting young subjects correlating to different mutations of AIRE (AutoImmuneRegulator) gene on chromosome 21. APS-2 is characterized by presence of Addison's disease (always present), autoimmune thyroid diseases and/or type 1 diabetes mellitus. It is a rare syndrome interesting particularly adult females and associated to a genetic pattern of HLA DR3/DR4. Autoimmune thyroid diseases associated to other autoimmune diseases (excluding Addison's disease and/or hypoparathyroidism), are the main characteristics of APS-3. The different clinical combinations of autoimmune diseases not included in the previous groups are characteristics of APS-4. In this paper criteria for defining a disease as autoimmune are presented. Furthermore, the classification, epidemiology, pathogenesis, genetic, animal models, clinical features, laboratory's tests, imaging, therapy, recent progresses in understanding the APS and a detailed analysis of large group of our patients affected by different types of APS are proposed and discussed.
 ...
PMID:Update on autoimmune polyendocrine syndromes (APS). 1281 89

In this article the pregnancy of a woman suffering from the complete triad typical of Autoimmune Polyglandular Syndrome Type 2 (Addison's disease + type 1 diabetes + Hashimoto's thyroiditis) is reported. By using insulin pump therapy with insulin lispro, it was possible to balance diabetes control with changes of steroid replacement therapy. Pregnancy was uneventful until week 27, when signs of preeclampsia occurred. The boy was born without difficulty at gestational age 37 weeks by planned cesarean section but signs of diabetic fetopathy (macrosomia, hypoglycaemia and hypocalcaemia) were expressed. He required a short course of hydrocortisone therapy. He made a good and rapid recovery. The mother made a good post-operative recovery too, but 4 months after the delivery microalbuminuria as well as mild hyperuricemia are still present. Interdisciplinary approach and very careful observation of the mother as well as of the child enabled successful outcome of this highly risky pregnancy.
 ...
PMID:Pregnancy in a woman suffering from type 1 diabetes associated with Addison's disease and Hashimoto's thyroiditis (fully developed Autoimmune Polyglandular Syndrome Type 2). 1521 52

The objective of the study was to determine the clinical characteristics and mortality of patients with hyperglycaemic hyperosmolar syndrome (HHS) and diabetic ketoacidosis (DKA) at a Jamaican tertiary care hospital. In a retrospective study of 1560 admissions for diabetes during the period 1998-2002, 980 dockets were reviewed and 164 individuals met the ADA diagnostic criteria for DKA or HHS. Patients with HHS were older than DKA patients (64.5 years [95% CI: 60.7-68.4] versus 35.9 years [95% CI: 30.2-41.6]), but were not more likely to be non-compliant with medications, infected, or male. Overall, 24% had a mixed DKA/HHS syndrome. Most DKA patients had type 2 diabetes (62%). Only 2% of HHS and 6% of DKA/HHS patients had type 1 diabetes. Syndrome specific mortality was: DKA 6.7%, HHS 20.3%, and DKA/HHS 25% (p for trend=0.013). Mortality increased significantly with age, especially in patients > or =50 years. Significant univariate predictors of mortality were altered mental status on admission, co-existing medical disease, increasing age, older age at onset of diabetes, acute stressors, and DKA/HHS. In multivariate models, only altered mental status was significant (OR=3.59; 95% CI: 1.24-10.41). Hence, hyperglycaemic crises in a Jamaican tertiary care hospital are associated with significant mortality especially in patients who are older or with altered mental status.
 ...
PMID:Predictors of hyperglycaemic crises and their associated mortality in Jamaica. 1645 89

In select cases of type 1 diabetes mellitus (DM1) the pancreas transplantation has been shown to ameliorate the disease, to reduce the need for exogenous insulin and normalize glycosylated hemoglobin (A1c) levels. The efficacy of this therapy in Mauriac Syndrome (SM) is not yet well established. We report a patient with MS treated with intensive insulin therapy, physical activity program, nutritional and psychological assistance, with persistently elevated fast glycemia and A1c levels, inadequate lipid profile and decreased IGF-1 (insulin like growth factor) levels. Due to a poorly metabolic control, pancreas transplantation was indicated. After one year follow up, the patient had no symptoms and showed persistent insulin independence with fast glucose <110 mg/dl, normal lipid profile and IGF-1 levels and significant decrease in A1c (4.6%). The pancreas transplantation improved diabetes control and promoted better quality of life for this patient. Pancreas transplantation proved to be an effective treatment strategy in patients with MS, improving their clinical and biochemical derangements. In this report we present the first case of MS controlled by pancreas transplantation registered in the indexed medical literature, as an alternative therapy in this group of patients.
 ...
PMID:[Pancreas transplantation in Mauriac Syndrome: clinical and biochemical parameters after one year follow up]. 1654 2


1 2 Next >>