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

Autoantibodies to 65 kD glutamic acid decarboxylase (GADAA) and ICA512 (ICA512AA) were measured by radioimmunoassays using as antigens in vitro transcribed and translated [35S]-methionine-labeled human GAD65 and ICA512 (IA-2). The prevalence of GADAA and ICA512AA in sera from 87 patients with IDDM was 39 and 23%, respectively. The frequency and titer of ICA512AA declined sharply within 5 years after the onset of IDDM. Among patients tested within 4 years after diagnosis, the prevalence of ICA512AA was significantly higher in acute onset IDDM than in slowly progressive IDDM (37 versus 6%, P < 0.025) irrespective of age, while there was no difference in GADAA frequency between acute onset and slowly progressive subtypes (51 versus 63%). A total of two patients out of 121 patients with NIDDM were positive for GADAA, and two other NIDDM patients, who were suffering from sarcoidosis, were positive for ICA512AA. Neither of the antibodies were positive in sera from four atypical NIDDM patients, aged < 20 years, who showed ketosis at onset and required insulin followed by excellent metabolic control with diet restriction alone. These observations suggest that ICA512AA are associated with rapid progression of beta cell damage in IDDM. ICA512 radioassay, in combination with GAD assay may provide a useful diagnostic marker for IDDM especially in youth.
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PMID:Combined measurements of GAD65 and ICA512 antibodies in acute onset and slowly progressive IDDM. 917 63

As autoimmunity is an important factor in the etiopathogenesis of IDDM, 85 ketosis prone i.e. insulin dependent diabetes (IDD) were evaluated for immunological and beta cell functional status. Islet cell antibodies (ICA) against purified islet cells used in Microwell ELISA Method, were detected in 27.1% of cases (23/85). There was a prevalence of 36.4% of ICA positivity in newly diagnosed cases and its prevalence declined with duration. The highest ICA positivity was observed in fourth decade of life. 17 of the 23 ICA positive cases (73.9%) had a mean duration of 2.1 years whereas the remaining 6/23 (26.1%) had a mean duration of 9 years. Females showed a younger age of onset of diabetes. Only one female with duration of 10 years tested positive for ICA.ICA positive males had later age of onset and longer duration of diabetes as compared to ICA positive females. Ten ICA positive cases studied were showing non-significant C-peptide (CP) release (after glucose load) in comparison to negative cases (14); p < 0.05, 8 of these cases were with < 3 months duration. Significantly low delta % C-peptide response implies a low residual beta-cell function and further loss of beta cell function earlier in ICA +ve cases. Thus this study leads to understand in depth the immune mechanism of IDDM.
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PMID:Prevalence of islet cell antibodies and B cell functional status in insulin dependent diabetes. 928 5

Maturity-onset diabetes of the young (MODY) is a rare form of juvenile diabetes mellitus that presents with hyperglycaemia in the absence of ketosis. We present three cases of MODY, all of whom had pedigrees with diabetics in multiple generations. All our patients presented in adolescence with evidence of insulin resistance. Two patients were relatively overweight. All three patients were readily controlled on diet alone. None had any clinical evidence of diabetic complications in early adulthood. Recently there has been a marked increase in our understanding of MODY. Genetic linkage and mutational analyses have identified three subtypes (MODY1, 2 and 3) that are all transmitted in an autosomal dominant fashion. The pathophysiology of the MODY subtypes is variable with both increased and decreased insulin levels being seen. A failure to recognise MODY will result in a lack of appropriate therapy and the potential for diabetic complications.
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PMID:Maturity-onset diabetes of the young (MODY): three case reports and new perspectives. 936 44

Ketones can reactivate the production of fetal hemoglobin (HbF) in vitro and in vivo. A reactivation of HbF by ketones, which are generated during starvation, remains largely speculative. Therefore, we investigated HbF in 31 women with anorexia nervosa or bulimia, using both of these as models of intermittent starvation ketosis. For comparison, we also studied 42 female control subjects matched for age. beta-Hydroxybutyrate levels were higher in patients than in controls (460 +/- 90 v 110 +/- 20 mumol/L; P < .0001). We correlated beta-hydroxybutyrate, metabolic, and hematologic parameters with HbF. HbF was measured with high pressure liquid chromatography. The data were analyzed with logistic regression analysis. An elevated HbF fraction (> 0.87%) was observed four times as often in patients than in controls (29% v 7%, P = .01). After adjustment for age, we found HbF elevations associated with beta-hydroxybutyrate levels (P = .005). No other correlations between the various metabolic/ hematologic parameters and HbF were significant. In conclusion, beta-hydroxybutyrate generated in starvation is associated with increased levels of HbF. Thus, unrestrained lipolysis can produce beta-hydroxybutyrate in sufficient quantities to induce a clinically measurable amount of HbF. These findings suggest that intermittent ketosis might also explain some increases of HbF in type 1 diabetes and pregnancy.
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PMID:Fetal hemoglobin in starvation ketosis of young women. 942 27

Differentiating NIDDM-Y from IDDM in youth is a diagnostic challenge. Serum insulin levels at diagnosis may help differentiate between NIDDM-Y and IDDM if the level is elevated, but the serum insulin level is low or undetectable in 45% of patients with NIDDM-Y. Islet-specific antibodies may be present in serum at diagnosis, and ketosis or ketoacidosis may occur. For our patients, clinical features are most helpful in differentiating NIDDM-Y from IDDM and include ethnic background, age and gender at diagnosis (approximately 80% of First Nation patients from northern Manitoba are adolescent females), presence of obesity and acanthosis nigricans, lack of symptoms or weight loss, and strong family history of NIDDM.
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PMID:Diagnostic criteria for non-insulin dependent diabetes in youth (NIDDM-Y). 949 13

Forty-three cases of diabetic ketosis were analysed to determine the mode of presentation, treatment modalities and outcome. Among these cases 62.8% were non-insulin dependent diabetes mellitus (NIDDM) patients and 37.2% belonged to the insulin dependent diabetes mellitus (IDDM) group. Six patients had blood glucose levels of more than 250 mg/dl but less than 300 mg/dl who were grouped separately for analysis under the term "euglycaemic diabetic ketoacidosis (EGDK)". Infection was the commonest precipitating factor in diabetic ketosis in all groups. Abdominal pain and vomiting occurred with NIDDM and EGDK cases. Drowsiness was common and coma was rare. Acute myocardial infarction (MI) and pulmonary oedema occurred with NIDDM cases. Shock, acidosis, acquired respiratory distress syndrome (ARDS) and mucor mycosis were seen with IDDM cases. Mortality was 7 out of 43(16.3%). Saline requirement was lower in NIDDM and EGDK cases. Intensive insulin therapy with hourly intravenous doses were needed for IDDM cases while majority of NIDDM cases could be managed with 6 hourly doses of insulin given subcutaneously or intramuscularly.
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PMID:Changing profile of diabetic ketosis. 956 97

To understand latent autoimmune diabetes mellitus in adults (LADA), we compared the clinical characteristics, fasting plasma glucose and C-peptide level, genetic frequency of HLA-DQA1, -DQB1 chain in 25 patients with LADA, 57 patients with insulin-dependent diabetes mellitus (IDDM, 21 patients with children-onset IDDM, 36 patients with adult-onset IDDM with ketosis), 38 patients with NIDDM (mild and moderate 30 patients and severe 8) and 42 normal persons. The onset of age was 20-48 years old associated with obvious polyphagia, and weight loss. Body mass index (BMI) was < or = 25 and fasting plasma glucose was > or = 16.5 mmol/L (297 mg/dl). Fasting and 1, 2 hour post prandial C-peptide level showed low and flatter curve (0.4, 0.8 and 0.8 nmol/L respectively). Glutamate decarboxylase (GAD) antibody was positive. HLA-DQ beta chain substitution of aspartate molecule was at position 57 (susceptic gene). LADA could be diagnosed if a patient has the first point and any point of the second to the fourth point. Patients with LADA should take diet, exercises, especially insulin as early as possible in order to control fasting and post prandial plasma glucose, and prevent from further destroy of residue islet B cells and reduce diabetic complications of eye, kidney and nerve.
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PMID:[Clinical characteristics and main diagnostic points of latent autoimmune diabetes mellitus in adults]. 1037 7

It has been reported that excessive intake of sugar-containing soft drinks results in diabetic ketoacidosis (DKA) or ketosis (DK) in obese patients with non-insulin dependent diabetes mellitus (NIDDM). We describe the clinical characteristics and results of long-term follow-up for 24 newly-diagnosed patients with acute-onset NIDDM presenting with DKA or DK. A history of excessive intake of sugar-containing soft drinks was found in 19 (Group A); serious non-diabetic illnesses were found in 5 (Group B). The range of patient ages in Group A was 16 to 57 years while all patients in Group B were 60 years or older. In Group A, no patient was positive for autoantibodies, specific HLAs for Japanese insulin dependent diabetes mellitus, or mutation of the beta-3-adrenergic receptor gene. The body mass indices (BMIs) at onset and admission and serum C-peptide immunoreactivities at admission and discharge were significantly higher in patients in Group A than in patients Group B. In conclusion, we reconfirmed that excessive intake of sugar-containing soft drinks is one of the contributing factors in DKA or DK-onset NIDDM patients. We found no autoimmune mechanism involved in the pathogenesis and that a polymorphism in the beta-3-adrenergic receptor gene could be associated with the development of soft-drink ketosis.
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PMID:Analysis and a long-term follow up of ketosis-onset Japanese NIDDM patients. 1041 33

Recent studies have suggested that elevated cellular lipid peroxidation may play a role in the development of cellular dysfunction and other complications of diabetes. People with type 1 diabetes frequently encounter elevated levels of the ketone bodies acetoacetate (AA), beta-hydroxybutyrate (BHB), and acetone (ACE). This study was undertaken to test the hypothesis that ketosis might increase lipid peroxidation and lower glutathione (GSH) levels of red blood cells (RBCs) in diabetic patients. This study demonstrates that incubation of AA with normal RBCs in phosphate-buffered saline (37 degrees C for 24 h) resulted in marked GSH depletion, oxidized glutathione accumulation, hydroxyl radical generation, and increased membrane lipid peroxidation. Increases in oxygen radicals and lipid peroxidation and depletion of GSH in RBCs were not observed with BHB or ACE treatments. Similarly, there was a significant generation of superoxide ion radicals even in a cell-free buffer solution of AA, but not in that of BHB. The presence of BHB together with AA did not influence the capacity of AA to generate oxygen radicals in a cell-free solution or the increase in lipid peroxidation of RBCs incubated with AA. The antioxidants vitamin E and N-acetylcysteine (NAC) blocked increase in lipid peroxidation in AA-treated RBCs. To examine the effects of ketone bodies in vivo, studies were performed that showed a significant decrease in GSH and an increase in lipid peroxidation levels in RBCs of hyperketonemic diabetic patients, but not in normoketonemic type 1 diabetic patients, when compared with age-matched normal subjects. This study demonstrates that elevated levels of the ketone body AA can increase lipid peroxidation and lower GSH levels of RBCs in people with type 1 diabetes.
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PMID:Hyperketonemia can increase lipid peroxidation and lower glutathione levels in human erythrocytes in vitro and in type 1 diabetic patients. 1048 Jun 18

Maturity onset diabetes of the young is characterized by early onset diabetes inherited in an autosomal dominant pattern. Classic MODY occurs predominantly in Caucasians and presents before age 25, is nonketotic, and is generally not insulin-requiring. Less than 5% of cases of childhood diabetes in Caucasians are caused by MODY. ADM is a subtype of MODY that occurs in approximately 10% of African-Americans with youth onset diabetes. In contrast to MODY in Caucasians, ADM presents clinically as acute onset diabetes often associated with weight loss, ketosis, and even diabetic ketoacidosis. Approximately 50% of patients with ADM are obese. Therefore, based strictly on clinical grounds, at onset, ADM cannot be distinguished from type 1 diabetes. Months to years following diagnosis, a non-insulin-dependent clinical course develops in patients with ADM that is clearly different from type 1 diabetes. Mutations in five genes can cause MODY. These genes encode hepatocyte nuclear factor-4 alpha (HNF-4 alpha, MODY1), glucokinase (MODY2), hepatocyte nuclear factor-1 alpha (HNF-1 alpha, MODY3), insulin promoter factor-1 (IPF-1, MODY4), and hepatocyte nuclear factor-1 beta (HNF-1 beta, MODY5). These monogenic forms of MODY have been used as model systems to investigate the inheritance and pathophysiology of type 2 diabetes. Clinicians, should be able to diagnose MODY. Type 1 diabetes, the most common form of diabetes in Caucasians, is always insulin-requiring for control and survival, whereas patients with MODY do not usually require long-term insulin for survival. Diagnostic confusion can lead to inappropriate management and patient expectations. Primary care physicians must be alert to avoid therapeutic confusion when patients with ADM enter into the non-insulin-dependent stage. An approach to the diagnosis of childhood diabetes is offered in Table 4. The majority of youth onset diabetes remains type 1; however, the frequency of type 2 diabetes is rising in obese children and adolescents and especially in obese minority youth. The diagnosis of MODY can be made through a careful review of the patient's clinical course, severity of hyperglycemia, and family history. The identification of islet autoantibodies is confirmatory evidence of autoimmune (type 1) diabetes. Because testing for MODY mutations is expensive and is performed at a select number of research laboratories only, routine molecular genetic studies to search for the various MODY mutations should be limited to research investigations. In the future, the availability of gene chip technology may allow rapid screening of mitochondrial and MODY mutations.
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PMID:Monogenic diabetes mellitus in youth. The MODY syndromes. 1060 19


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