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

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.
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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.
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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

Energy for muscular exercise is derived initially from the breakdown of muscle glycogen, and later from circulating glucose released by the liver and from non-esterified fatty acids. Muscle glucose uptake may increase 20-fold. In normal subjects, insulin secretion declines and release of counter-regulatory hormones increases. In type 1 diabetes, glycaemic changes during exercise depend largely on blood insulin levels. In the young diabetic, during insulin deficiency, and therefore in a poor degree of metabolic control, i.e. hyperglycaemic and ketotic, exercise accentuates hyperglycaemia and ketosis, leading to extreme fatigue. If the insulin dosage is too high, the increase in muscular assimilation, combined with the shutdown of liver glucose production, may result in a severe hypoglycaemia. During the recovery period, the repletion of muscular and hepatic glycogen stores may also provoke an hypoglycaemia during hours after the cessation of muscular work. The recommendations for physical activity in type 1 diabetes include: 1) obtain good metabolic control; 2) in the few hours preceding the exercise, ingest complex carbohydrates; 3) in the case of unforeseen physical activity, increase glucose consumption immediately before, during, and after the activity; 4) in the case of foreseen activity, decrease the insulin dose (from 10 to 50%) acting during and even after intense muscular work; 5) do not inject the insulin at a site that will be heavily involved in the muscular activity.
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PMID:[Sports and type I diabetes: personal experience]. 1242 37

Maturity-onset diabetes of the young (MODY) is a rare form of juvenile diabetes mellitus, defined by early onset, absence of ketosis, non-insulin-dependent diabetes and autosomal dominant inheritance. Advances in molecular genetic analysis have identified mutations accounting for different MODY subtypes, all of them associated with defects of insulin secretion. We present a case of a nine year-old boy, admitted to our outpatient clinic because of mild and intermittent osmotic symptoms (polyuria, polyphagia and polydipsia) and persistently high values of fasting blood glucose in the last year. He had a family history of diabetes in three consecutive generations compatible with autossomal dominant inheritance. His height was 138.5 cm (90th centile) and his weight was 33.5 Kg (90th centile). General examination was unremarkable, in a prepubertal boy. A standard oral glucose tolerance test was performed. The fasting blood glucose was 118 mg/dl with a two hour value of 160 mg/dl. ICA, IAA and GAD autoantibodies were undetectable. He started on diet therapy, keeping his fasting blood glucose measurements on the upper limits of normal and HbA1c in the normal range. He was diagnosed as having MODY 2 on a clinical basis, as it is not possible to perform molecular analysis of this pathology in Portugal. As MODY is recently thought to account for 2-5% of all cases of type 2 Diabetes Mellitus it is important to consider it as a possible diagnosis in children who present with incidental hyperglycaemia. Molecular genetic testing is very important as it enables us to make a firm diagnosis of MODY, to define a follow up plan and to reassure patients families, once the prognosis is significantly different among the different sub-types of MODY. We emphathize the need of creating national and international reference centres where such testing can be done.
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PMID:[Mature onset diabetes of the young (MODY)]. 1268 Feb 90

Ketosis-prone diabetes is heterogeneous. Its causes could include novel beta-cell functional defects. To characterize such defects, 103 patients with diabetic ketoacidosis were evaluated for beta-cell autoimmunity and human leukocyte antigen (HLA) class II alleles, with longitudinal measurements of beta-cell function and biochemical and clinical parameters. They were classified into four A beta groups, based on the presence of glutamic acid decarboxylase (GAD)65, GAD67, or IA-2 autoantibodies (A+ or A-) and beta-cell functional reserve (beta+ or beta-). The group distribution was: 18 A+beta-, 23 A-beta-, 11 A+beta+, and 51 A-beta+. Collectively, the two beta- groups differed from the two beta+ groups in earlier onset and longer duration of diabetes, lower body mass index, less glycemic improvement, and persistent insulin requirement. HLA class II genotyping showed that the A-beta- group differed from the A+beta- group in having lower frequencies of two alleles strongly associated with autoimmune type 1 diabetes susceptibility: DQA*03 and DQB1*02. Similarly, the A-beta+ group differed from the A+beta+ group in having a lower frequency of DQB1*02. Ketosis-prone diabetes comprises at least four etiologically distinct syndromes separable by autoantibody status, HLA genotype, and beta-cell functional reserve. Novel, nonautoimmune causes of beta-cell dysfunction are likely to underlie the A-beta+ and A-beta- syndromes.
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PMID:Ketosis-prone diabetes: dissection of a heterogeneous syndrome using an immunogenetic and beta-cell functional classification, prospective analysis, and clinical outcomes. 1460 30

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.
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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.
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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

A mild increase of AST and/or ALT is sometimes observed among patients with diabetic ketosis or diabetic ketoacidosis (DKA) after initial insulin treatment, and the exact mechanism is still undefined. Therefore, we compared the clinical background between patients with and without transient elevation of liver transaminase (TELT) at the onset of type 1 diabetes mellitus with diabetic ketosis or DKA. Among 50 patients, 13 patients showed TELT. The TELT group was characterized by higher plasma glucose (P<0.05), higher HbA1c (P<0.05), and higher triglyceride (P<0.01) before insulin therapy than those without TELT. The TELT group needed significantly more insulin (P<0.05) for the treatment. In echo-histogram analysis of three patients with TELT, the increase of liver-kidney contrast after insulin treatment suggested fat deposition to the liver. The fat deposition to the liver might be one of the causes of the mild increase of AST and/or ALT after initial treatment of insulin in diabetic ketosis or DKA.
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PMID:Transient elevation of liver transaminase after starting insulin therapy for diabetic ketosis or ketoacidosis in newly diagnosed type 1 diabetes mellitus. 1503 24

Autoantibody and T cells reacting with islet proteins have been demonstrated in patients with type 1 diabetes. In recent years an increasing number of children have been clinically classified with type 2 (not ketosis prone, evidence of insulin resistance, presence of acanthosis nigricans, and obesity) or indeterminant diabetes (admixture of clinical features of types 1 and 2). In this study, we compared the islet cell autoantibody and T-cell responses to islet proteins in type 2 (n = 19) and indeterminant (n = 16) children (<18 yr of age) to classic type 1 (n = 37) diabetic patients. We observed that 37 of 37 type 1 diabetic children demonstrated autoantibody and/or T-cell reactivity to islet proteins. Fourteen of the 19 type 2 patients were positive for islet cell autoantibodies, and six of 14 were positive for T-cell responses to islet proteins. For the indeterminant patients, 11 of 16 of the patients were positive for autoantibodies, and six of 16 patients were positive for T-cell responses to islet proteins. These results demonstrate that autoimmunity to islet proteins is present in a high percentage of children classified as indeterminant or type 2 diabetes. Moreover, the presence of obesity or acanthosis nigracans does not reliably distinguish children with or without islet cell autoimmunity.
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PMID:Autoimmunity to islet proteins in children diagnosed with new-onset diabetes. 1512 45

Young onset diabetic subjects in tropical developing countries include a group of subjects who exhibits a characteristic ketosis resistance termed as Malnutrition Related Diabetes Mellitus (MRDM) by the WHO Study Group. The mechanism for this resistance to ketosis is still uncertain. To understand this mechanism we have studied the serum responses of glucose, non-esterified fatty acid (NEFA) and triglyceride (TG) to intravenous fat emulsion in newly diagnosed 8 fibrocalculous pancreatic diabetes (FCPD) and 11 low insulin secretory (LIS) subjects under 30 years of age along with 27 age-matched Non Insulin Dependent Diabetes Mellitus (NIDDM) subjects. Overnight fasting subjects were given a 90 min infusion of intralipos 10% (2.5 mg/kg body weight/min) and serum was collected at 0, 60, 90, 120 and 150 min. The fasting NEFA in the 3 groups were almost similar (micromol/l, M +/- SEM: 486 +/- 58, 564 +/- 76 and 559 +/- 34 in FCPD, LIS and NIDDM respectively). Fasting TG also showed a close similarity among 3 groups (mg/dl, M+/-SEM: 117 +/- 11, 110 +/- 22 and 123 +/- 4 in FCPD, LIS and NIDDM respectively). Intravenous fat caused a steady rise of NEFA as well as TG in all groups during the 90 minutes of infusion followed by a gradual fall. No two groups significantly differed regarding NEFA and TG at any time point. Fasting glucose was markedly higher in FCPD (22.9 +/- 2.5, mmol/l, M+/-SEM) and LIS (20.8 +/- 1.6) than NIDDM (11.0 +/- 1.0). In all the 3 groups glucose showed a slow but steady fall. Fasting C-peptide was very low in FCPD (0.42 +/- 0.08, ng/ml, M +/- SEM) and LIS (0.55 +/- 0.09) whereas it was within normal range in NIDDM patients (2.99 +/- 0.24). The results suggest the following: (a) Depleted body fat store do not lead to a decreased supply of NEFA in FCPD and LIS subjects at the fasting state; (b) Increased supply of NEFA in these subjects lead to a normal esterification response as evidenced by a parallel rise of TG; (c) Inspite of markedly low level of the antilipolytic hormone insulin, FCPD and LIS subjects are capable to maintain NEFA and TG responses similar to NIDDM subjects. This may indicate that factor (s) other than substrate and esterification is (are) probably involved in the ketosis resistance of FCPD and LIS subjects; and (d) Although FCPD and LIS differ regarding generalized pancreatic damage (which raises the possibility of involvement of glucagon producing alpha-cells in the FCPD group) the two groups do not differ regarding the ketogenic substrate and esterfication responses.
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PMID:Ketosis resistance in under thirty diabetic subjects. 1528 87


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