Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0011860 (type 2 diabetes)
 57,723 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Diabetes is a major health problem of increasing incidence in the United States. Diabetes research has been limited by lack of availability of good animal models, particularly for the study of comorbidities associated with diabetes. We investigated the use of cynomolgus monkeys as an animal model of both type 1 and type 2 diabetes and compared these naturally occurring diseases with streptozotocin-induced diabetes. Both type 1 diabetics and streptozotocin-induced diabetics present with sudden onset of hyperglycemia and are ketosis prone without exogenous insulin. Type 2 diabetics can have a very long period of moderate hyperglycemia and hypertriglyceridemia and only require exogenous insulin therapy if pancreatic islet reserves are depleted. Type 2 diabetes is preceded by a relatively long period of insulin resistance that is associated with obesity and dyslipidemia. As insulin resistance progresses, islet size and insulin content increases initially. However, with sustained periods of insulin resistance, islet amyloid polypeptide (IAPP) is deposited in islets and can replace normal islet architecture, resulting in an insulin-deficient state. Appearance of IAPP also occurs in human type 2 diabetics but not in conventional rodent models. Unlike type 2 diabetes, neither type 1 nor streptozotocin-induced diabetes is associated with IAPP. Rather, islets can appear normal histologically, but have decreased insulin secretion and immunostaining. Further, the amount of insulin present in the islet is correlated with plasma insulin levels following glucose challenge. Studies are ongoing to determine the pathogenic changes associated with the progression of diabetes and to find novel drug treatments for diabetics.
 ...
PMID:Naturally occurring and experimental diabetes in cynomolgus monkeys: a comparison of carbohydrate and lipid metabolism and islet pathology. 1121 78

Regular physical exercise has been known to be beneficial in the treatment of type 2 diabetes. Epidemiological studies of physical exercise: previous non-randomized studies suggested that a life-style intervention program involving diet and/or exercise reduced the progression of impaired glucose tolerance (IGT) to type 2 diabetes. Recent randomized controlled intervention trials also showed that diet and/or exercise intervention led to a significant decrease in the incidence of diabetes among those with IGT. Endocrinological and metabolic effects of exercise: in well controlled diabetic patients, physical exercise promotes utilization of blood glucose and lowers blood glucose levels. On the other hand, in poorly controlled diabetic patients with ketosis, physical exercise results in further rises in blood glucose, free fatty acids and ketone body concentrations. Long-term gentle regular jogging increases insulin action in respect of both carbohydrate and lipid metabolism despite no influence on body mass index or maximal oxygen uptake. A significant correlation was observed between deltaMCR (insulin sensitivity) and average daily steps Our recent data suggested that the improvement of insulin action by physical exercise was attributed, at least in part, to the increase in insulin-sensitive GLUT4 (glucose transporter 4) on the plasma membrane in skeletal muscle. In conclusion, as an adjunct to other forms of therapy, mild regular physical exercise will play an important role in primarily preventing type 2 diabetes.
 ...
PMID:Diabetes and life-styles: role of physical exercise for primary prevention. 1124 67

We report a 43-year-old man who presented diabetic ketoacidosis 1 year after receiving kidney transplantation. He was a recipient of renal transplantation treated with metyl-prednisolone and tacrolimus regimen. The serum level of tacrolimus was 12.4 ng/ml, and he showed hyperphagia before a month of admission. A week before admission, he was aware of polydipsia, polyuria, and general fatigue. He visited our hospital and was found to have severe hyperglycemia (925 mg/dl), significant ketosis and mild metabolic acidosis (pH 7.341), although he had not been diagnosed as diabetes mellitus. He administrated in our hospital, and was treated with insulin for 5 weeks. He was not obese (BMI = 18.2 kg/m(2)) and had no family history of type 2 diabetes. He was finally treated with diet therapy alone. The 24 h urine C-peptide secretion on the third hospital day was low (8.4 microg per day). However, no autoantibodies against pancreatic islets were positive, and his insulin secretion was recovered at discharge suggesting that he was not type 1 diabetes. Although, tacrolimus has been reported to cause or worsen diabetes mellitus, the present case suggests that it could cause severe decrease in insulin secretion which leading to diabetic ketoacidosis in lean subject without previous history of diabetes mellitus.
 ...
PMID:Sudden onset of diabetes with ketoacidosis in a patient treated with FK506/tacrolimus. 1187 16

Diabetes is an evolving disease, with changing patterns seen in both type 1 and type 2 diabetes. A wide (over 400-fold) variation exists in worldwide incidence rates of type 1 diabetes, with the highest occurring in Finland (over 45 per 100,000 under the age of 15 years) and the lowest in parts of China. In many countries (e.g. in Europe, the Middle East, Australia) the incidence of autoimmune-mediated type 1 diabetes in children <15 years of age has risen by 2-5% per annum. Type 2 diabetes is also increasing rapidly globally and is occurring at a younger age, including in adolescence and childhood. In the USA, approximately one third of newly diagnosed in the adolescent age group is type 2, with up to 20% presenting with ketosis and ketoacidosis. The management of type 2 diabetes is especially difficult in the adolescent age group. Obesity is the single most obvious risk factor for type 2 diabetes. Lifestyle modification programmes starting in childhood are urgently needed and society needs to change its attitudes to childhood nutrition, play and exercise.
 ...
PMID:Childhood diabetes: a global perspective. 1197 14

Diabetes mellitus in humans is a heterogeneous disorder classified clinically into two main types. The diagnosis of type 1 versus type 2 diabetes is made phenotypically using criteria such as age at onset, abruptness of hyperglycemic symptoms, presence of ketosis, degree of obesity and the perceived need for insulin replacement. The pathogeneses of type 1 and type 2 diabetes are believed to be different. Type 1 diabetes is an autoimmune disease mediated by cellular effector mechanisms; whereas classic type 2 diabetes is not autoimmune but results from insulin resistance and a nonautoimmune insulin secretory defect. Most type 1 diabetes patients are diagnosed in childhood or young adulthood before the age of 35 years. However, there is clearly a subgroup of patients clinically diagnosed with type 2 diabetes who are greater than 35 years of age and have evidence of autoimmunity. The disease of these autoantibody-positive type 2 diabetics is often termed latent autoimmune diabetes in adults (LADA), slowly progressive type 1 diabetes, latent type 1 diabetes, and type 1.5 diabetes. This group of patients comprises approximately 10-15% of Caucasian type 2 diabetes patients. Type 1.5 diabetes patients tend to present with islet cell autoantibodies, islet-reactive T cells, higher HbA(1c) levels, lower C peptide, and a propensity toward insulin dependency compared to autoantibody-negative classic type 2 diabetes subjects.
 ...
PMID:Beta cell rest and recovery--does it bring patients with latent autoimmune diabetes in adults to euglycemia? 1202 Oct 87

MMDM patients are typically young at onset with low body mass index, require insulin treatment for glycemic control, have insulin resistance, and do not develop ketosis on withdrawal of insulin. WHO's revised classification in 1999, based on the etiopathogenesis of the disease, identifies only two categories: type 1 diabetes and type 2 diabetes. MMDM could be considered as type 1b diabetes. Genetic and immunological studies were done on MDDM patients (n = 72) from Cuttack and healthy controls to understand and to justify its inclusion in the category of type 1b diabetes. Antibodies (Abs) to tyrosine pyrophosphatase (IA2-Abs), glutamate decarboxylase 65 (GAD65-Abs), and other minor markers like ICA12 Abs and tissue transglutaminase Abs (TTG-Abs) were studied. HLA-DR and DQ were studied for the genetic markers. Of the MMDM patients 30% were positive for either GAD65 or IA-2 antibodies, and 14% were positive for ICA12 antibodies. All three antibody markers together accounted for 39% of PDDM patients, as some patients were positive for more than one autoantibody. TTG antibodies (specific for Celiac disease) were present in 14/71 (20%) of MMDM patients compared to 3/122 (2%) controls. All four autoantibodies accounted for 53% of PDDM patients, leaving 47% of patients free of known autoantibodies. The autoantibody-negative PDDM patients were analyzed for HLA and MICA markers, showing that DR7-DQ9 and MICA allele 9 are increased in this group compared to healthy controls, which suggests an autoimmune response to an unknown dietary autoantigen. We conclude from our data that an autoimmune mechanism is involved in the etiology of MMDM. In addition, the presence of silent celiac disease seen with MMDM patients, which has not yet been reported, is significant. It is important to note that subclinical celiac disease exists with diabetes mellitus and must be considered in the diagnosis of MMDM.
 ...
PMID:Molecular mechanisms involved in the etiopathogenesis of malnutrition-modulated diabetes mellitus. 1202 Oct 93

Antibodies to tyrosine phosphatase (IA2-Ab) and glutamate decarboxylase 65 (GAD65-Ab) are major markers for IDDM in Caucasians. TTG-Ab is specific for celiac disease. Celiac disease is caused by ingestion of the protein gliadin, a component of wheat gluten, and usually resolves on its withdrawal. Ten to twenty percent of celiac disease patients also have IDDM. The aim of the study was to estimate the prevalence of TTG-Ab in MMDM (n = 71), IDDM (n = 74), and NIDDM (n = 216) and 122 controls from Cuttack in eastern India. MMDM patients are typically young at onset with low body mass index, require insulin for glycemic control, have insulin resistance, and do not develop ketosis on withdrawal of insulin. TTG-Ab was evaluated by radioimmunoassay using in vitro translated recombinant human 35S-TTG. In controls, TTG-Ab was present in 3/122 (2%); in MMDM, TTG-Ab was present in 14/71 (20%); 11/74 (15%) IDDM (P < 0.05 vs. controls) and 23/216 (11%) NIDDM (P < 0.05 vs. controls) were also positive for TTG-Ab. We conclude that MMDM, IDDM, and NIDDM patients from Cuttack have a significantly high proportion of TTG-Ab compared to healthy controls. The highest significance is seen with MMDM patients. It is important to note that subclinical celiac disease must be considered in the differential diagnosis of MMDM.
 ...
PMID:Autoantibodies to tissue transglutaminase in patients from eastern India with malnutrition-modulated diabetes mellitus, insulin-dependent diabetes mellitus, and non-insulin-dependent diabetes mellitus. 1202 Nov 13

Tropical chronic pancreatitis (TCP) is a juvenile form of chronic calcific non-alcoholic pancreatitis, seen almost exclusively in the developing countries of the tropical world. The classical triad of TCP consists of abdominal pain, steatorrhoea, and diabetes. When diabetes is present, the condition is called fibrocalculous pancreatic diabetes (FCPD) which is thus a later stage of TCP. Some of the distinctive features of TCP are younger age at onset, presence of large intraductal calculi, more aggressive course of the disease, and a high susceptibility to pancreatic cancer. Pancreatic calculi are the hallmark for the diagnosis of TCP and in non-calcific cases ductal dilation on endoscopic retrograde cholangiopancreatography, computed tomography, or ultrasound helps to identify the disease. Diabetes is usually quite severe and of the insulin requiring type, but ketosis is rare. Microvascular complications of diabetes occur as frequently as in type 2 diabetes but macrovascular complications are uncommon. Pancreatic enzyme supplements are used for relief of abdominal pain and reducing the symptoms related to steatorrhoea. Early diagnosis and better control of the endocrine and exocrine dysfunction could help to ensure better survival and improve the prognosis and quality of life of TCP patients.
 ...
PMID:Tropical chronic pancreatitis. 1465 69

Type 1 diabetes is an organ-specific autoimmune disease characterized by T cell-mediated destruction of pancreatic beta cells. In Japanese population, the incidence of type 1 diabetes in children is very low compared to European countries. However, there are more patients with type 1 diabetes in adults, including latent autoimmune diabetes in adults (LADA). The circulating autoantibodies to multiple islet autoantigens including GAD, insulin, and IA-2 are the important immunological features of type 1 diabetes. The prevalences of anti-islet autoantibodies in patients with Japanese type 1 diabetes are 60-70% for GAD autoantibodies, 45-50% for insulin autoantibodies (IAA), and 60-65% for IA-2 autoantibodies at disease onset, which are similar to those reported in Caucasian patients. With combinatorial analysis of these autoantibodies, 90% of patients express at least one of these autoantibodies and are classified as type 1A diabetes. Although the majority of patients with type 1 diabetes are young, lean, and ketosis-prone, there are a number of patients with type 1 diabetes initially diagnosed as having type 2 diabetes at disease onset called LADA. These patients with LADA often progress toward an insulin-deficient state within several years after diagnosis. High levels of GAD autoantibodies have a high predictive value for future insulin deficiency in LADA. Further, epitope analysis of GAD65 autoantibodies may be helpful to predict future insulin dependency in LADA patients. In conclusion, Japanese patients with type 1 diabetes are clinically heterogeneous and the determination of immunological features are helpful to clarify the characteristics of the Japanese type 1 diabetic syndrome.
 ...
PMID:Epitope analysis of GAD65 autoantibodies in Japanese patients with autoimmune diabetes. 1467 8

Nonautoimmune ketosis-prone diabetic syndromes are increasingly frequent in nonwhite populations. We have characterized a cohort of patients of sub-Saharan African origin who had ketosis-prone type 2 diabetes (n = 111), type 1 diabetes (n = 21), and type 2 diabetes (n = 88) and were admitted to a hospital for management of uncontrolled diabetes. We compared epidemiological, clinical, and metabolic features at diabetes onset and measured insulin secretion (glucagon-stimulated C-peptide) and insulin action (short intravenous insulin tolerance test) during a 10-year follow-up. Ketosis-prone type 2 diabetes shows a strong male predominance, stronger family history, higher age and BMI, and more severe metabolic decompensation than type 1 diabetes. In ketosis-prone type 2 diabetes, discontinuation of insulin therapy with development of remission of insulin dependence is achieved in 76% of patients (non-insulin dependent), whereas only 24% of patients remain insulin dependent. During evolution, ketosis-prone type 2 diabetes exhibit specific beta-cell dysfunction features that distinguish it from type 1 and type 2 diabetes. The clinical course of non-insulin-dependent ketosis-prone type 2 diabetes is characterized by ketotic relapses followed or not by a new remission. Progressive hyperglycemia precedes and is a strong risk factor for ketotic relapses (hazard ratio 38). The probability for non-insulin-dependent ketosis-prone type 2 diabetes to relapse is 90% within 10 years, of whom approximately 50% will become definitively insulin dependent. Insulin sensitivity is decreased in equal proportion in both ketosis-prone type 2 diabetes and type 2 diabetes, but improves significantly in non-insulin-dependent ketosis-prone type 2 diabetes, only after correction of hyperglycemia. In conclusion, ketosis-prone type 2 diabetes can be distinguished from type 1 diabetes and classical type 2 diabetes by specific features of clinical pathophysiology and also by the natural history of beta-cell dysfunction and insulin resistance reflecting a propensity to glucose toxicity.
 ...
PMID:Ketosis-prone type 2 diabetes in patients of sub-Saharan African origin: clinical pathophysiology and natural history of beta-cell dysfunction and insulin resistance. 1498 48


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