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Query: UMLS:C0011860 (type 2 diabetes)
 57,723 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The aim of the study was 1) to establish the prevalence of GAD antibodies (GADab) in a population-based study of type 2 diabetes in western Finland, 2) to genetically and phenotypically characterize this subgroup, and 3) to provide a definition for latent autoimmune diabetes in adults (LADA). The prevalence of GADab was 9.3% among 1,122 type 2 diabetic patients, 3.6% among 558 impaired glucose tolerance (IGT) subjects, and 4.4% among 383 nondiabetic control subjects. Islet antigen 2 antibodies (IA2ab) or islet cell antibodies were detected in only 0.5% of the GADab- patients. The GADab+ patients had lower fasting C-peptide concentrations (median [interquartile range]: 0.46 [0.45] vs. 0.62 [0.44] nmol/l, P = 0.0002) and lower insulin response to oral glucose compared with GADab- patients. With respect to features of the metabolic syndrome, the GADab+ patients had lower systolic (140 [29.1] vs. 148 [26.0] mmHg, P = 0.009) and diastolic (79.2 [17.6] vs. 81.0 [13.1] mmHg, P = 0.030) blood pressure values, as well as lower triglyceride concentrations (1.40 [1.18] vs. 1.75 [1.25] mmol/l, P = 0.003). GADab+ men had a lower waist-to-hip ratio compared with GADab- patients. Compared with GADab- patients and control subjects, the GADab+ patients had an increased frequency HLA-DQB1*0201/0302 (13 vs. 4%; P = 0.002) and other genotypes containing the *0302 allele (22 vs. 12%; P = 0.010). However, the frequency of these high-risk genotypes was significantly lower in GADab+ type 2 patients than in type 1 diabetes of young or adult onset (0201/0302 or 0302/X: 36 vs. 66 vs. 64%, P < 0.001). The GADab+ type 2 group did not differ from control subjects with respect to genotypes containing the protective DQB1-alleles *0602 or *0603, nor with respect to the type 1 high-risk genotype in the IDDM1 (Hph1 +/+). We conclude that GADab+ patients differ from both GADab- type 2 diabetic patients and type 1 diabetic patients with respect to beta-cell function, features of the metabolic syndrome, and type 1 diabetes susceptibility genes. Further, we propose that LADA be defined as GADab positivity (>5 relative units) in patients older than 35 years at onset of type 2 diabetes.
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PMID:Clinical and genetic characteristics of type 2 diabetes with and without GAD antibodies. 989 37

The disease process in classical Type 1 diabetes patients (IDDM) is believed to be autoimmune. In contrast, the disease process in classical Type 2 diabetes patients (NIDDM) is not autoimmune and a decreased sensitivity to insulin action is the main abnormality. The clinical distinction of Type 1 diabetes versus Type 2 diabetes is recognized to be imperfect and has limitations. There is a group of individuals (Type 1 1/2 diabetes), who present like typical NIDDM, but have some of the immunological and clinical features of IDDM. We review the current medical literature on Type 1 1/2 diabetes with special reference to its clinical characteristics, natural history and pathophysiology. Since the distinction between these two forms of diabetes may have important therapeutic implications especially with regards to the benefits of insulin therapy in patients with Type 1 1/2 diabetes and because of the need for uniformity in its diagnosis we recommend that both clinical plus biochemical criteria (the presence of ICA and/or GAD Ab, HLA typing and tests to quantify beta cell function) be used to make a diagnosis. Comparative studies in the area of cytokine production, T cell reactivity and autoantibody clustering between classic Type 1 diabetes and Type 1 1/2 diabetes patients are needed as are studies with the animal model of Type 1 1/2 diabetes, Psammomys obesus.
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PMID:Type 1 1/2 diabetes: myth or reality? 1005 87

Two major types of diabetes have been recognized since the late 1930s. However, in recent times there have been major changes in classification and understanding of these types, including improved knowledge of maturity-onset diabetes in the young, with the identification of mutations relating to impaired insulin secretion and the recognition of slow-onset type 1 diabetes in adults now designated as latent autoimmune diabetes in adults (LADA). A major problem area in diabetes classification concerns cases of slowly progressive forms of type 1 and type 2 diabetes, particularly in adults aged 25-50 years. This is a more contemporary problem because cases of type 2 diabetes are presenting at an increasingly younger age. In the landmark U.K. Prospective Diabetes Study of type 2 diabetes, islet cell antibodies (ICAs) and antibodies to glutamic acid decarboxylase (anti-GAD) were measured at diagnosis in 3,672 patients. The overall proportion with ICAs was 6%, and anti-GADs was 10%. These subjects clearly had type 1 diabetes or LADA by both phenotypic and genotypic features. The presence of auto antibodies correlated particularly with a younger age and phenotypic features consistent with type 1 diabetes (e.g., early age at diagnosis, lower BMI, and reduced beta-cell function). Overall, of patients requiring insulin by 6 years, 38% were anti-GAD+ at baseline compared with 5.3% of those not on insulin at 6 years. Antibodies to GAD indicate an underlying autoimmune process and have a high positive predictive value for type 1 diabetes and future insulin dependency in adults.
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PMID:Crucial points at diagnosis. Type 2 diabetes or slow type 1 diabetes. 1009 1

A prospective study over 10 years on the natural history of beta-cell function in islet cell antibody (ICA)-positive NIDDM disclosed a characteristic findings of slowly progressive IDDM distinct from those of acute onset IDDM. The characteristics includes: (1) the clinical phenotype at the onset of diabetes is non-insulin requiring, (2) the onset is late age, (3) beta-cell failure progresses slowly over several years with persistently positive low-titer ICA and high titer of GAD antibodies, (4) pathological study on autopsied pancreas demonstrated that beta-cell loss is incomplete, and exocrine pancreas is often atrophied with cell infiltration of CD8+ T lymphocytes, (5) higher family history of NIDDM, and (6) association with some genetic predisposition including HLA-DQA1*0301-DQB1*0401 and/or mitochondrial gene mutation at nucleotide pair 3243, and a lack of association with HLA-A24. These results are sharply contrast with acute onset IDDM, suggesting a presence of distinct subtype of IDDM in Japanese population. We also demonstrated that small dose of insulin therapy was effective for the suppression of immunological beta-cell failure.
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PMID:[Slowly progressive IDDM]. 1019 41

The purposes of the present study were to 1) find the prevalence of various types of diabetes; 2) determine the prevalence of glutamate decarboxylase autoantibody (anti-GAD) and 3) identify clinical characteristics which may help in predicting insulin deficiency in young Thai adults with diabetes. Subjects consisted of 93 adults with diabetes mellitus aged 15-40 years. In each subject, basal and post glucagon C-peptide levels were determined by radioimmunoassay. Anti-GAD was measured by radioimmunoassay and mitochondrial 3243 tRNA(Leu(UUR)) gene mutation was detected by PCR-RFLP. Data were expressed as mean +/- SEM. The mean age of subjects was 31.0 +/- 0.7 years with age at diagnosis of 25.6 +/- 0.9 years. Thirty nine (41.9%) were males and 54 (58.1%) were females. Pancreatic calcification was found in 7 (7.5%) of the patients while 2 (2.2%) were identified as having Wolfram syndrome. Four (4.3%) had nonketotic diabetes with affected family members in multiple generations consistent with MODY. Mitochondrial 3234 tRNA(Leu(UUR)) gene mutation was detected in only one patient. After excluding 14 subjects with pancreatic calcification, Wolfram's syndrome, MODY or mitochondrial gene mutation, 45 (57.0%) were found to be insulin-deficient and 34 (43.0%) were insulin-sufficient based on post-glucagon C-peptide levels. Using stepwise logistic regression analysis, it was found that younger age at diagnosis (p<0.001), smaller waist circumference (p<0.01), previous history of DKA (p<0.01) was significantly associated with insulin deficiency. After excluding patients with DKA, younger age at diagnosis of diabetes (p<0.05) and lower BMI (p<0.01) were related to insulin deficiency. Concerning the role of autoimmunity, it was found that 13 (28.3%) of insulin-deficient subjects were positive for anti-GAD while 4 (11.8%) of those who were insulin-sufficient had positive results. Of the 54 patients currently on insulin, 42 (77.8%) are insulin deficient and 14 (25.9%) have positive anti-GAD. There were 10 (18.5%) who were both insulin sufficient and negative for anti-GAD suggesting that insulin therapy may not be required. We concluded that about half of young Thai adults with diabetes are not insulin-deficient and treatment with insulin may be unnecessary. The prevalence of glutamate decarboxylase antibody and mitochondrial 3234 tRNA(Leu(UUR)) gene mutation is low and as yet undefined factors are accountable for insulin deficiency in a significant number of patients.
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PMID:Diabetes mellitus in young Thai adults. 1121 56

LADA or type 1.5 diabetes is a slowly progressive form of autoimmune diabetes of adults and represents a considerable proportion (about 5-10%) of all diabetic patients. Associations with high risk HLA genotypes and autoimmune phenomena (GAD, IA2, ICA) show similarities with type 1 diabetes, but phenotypical characteristics of these patients do not allow the correct identification without screening of GAD antibodies. The relatively low antibody titers against islet-cell antigens in LADA patients may be sign of a less aggressive form of autoimmune diabetes and could be responsible for the long non-insulin requirement phase of this diabetes type. Similar as in prediabetic relatives of type 1 diabetic patients the risk for beta cell failure in adult "type 2 diabetic" patients increases with the number of antibodies positive. Consequently, low titers of GAD--in particular in elderly patients--do not predict a progressive and rapid loss of beta-cell failure, when associations with high risk genotypes or other islet-cell antibodies are lacking. Patients with LADA share insulin resistance with type 2 diabetic patients, but display a more severe defect in stimulated beta-cell capacity than patients with classical type 2 diabetes. With respect to features of the metabolic syndrome, patients with LADA have lower BMI, blood pressure and triglyceride levels compared with classical type 2 diabetes patients. Early identification of LADA patients will be mandatory, when effective immune interventions are available for prevention of the beta-cell destructive process and insulin requirement of these patients.
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PMID:Progress in the characterization of slowly progressive autoimmune diabetes in adult patients (LADA or type 1.5 diabetes). 1146 May 97

This study was undertaken to determine which type 1 diabetes-associated autoantibodies and what clinical characteristics are most useful to identify patients with type 1(1/2) diabetes. We studied 125 patients, recently diagnosed clinically with type 2 diabetes for the presence of islet cell antibodies (ICA), insulin autoantibodies (IAA), antibodies to glutamic acid decarboxylase(GADAb), and IA-2a (IA-2Ab). Patients with a diagnosis of type 2 diabetes who met all of the following criteria at diagnosis were studied: age > or = 30 years, no history of ketonuria or ketoacidosis, and not requiring insulin treatment. Thirty-six patients (29%) were positive for at least 1 antibody. Thirty-two (26%) were ICA positive and 20 (16%) GADAb positive. Insulin autoantibodies and IA-2Ab occurred less frequently in 2 (1.6%) and 8 (6.4%) patients, respectively. There was no significant difference in the ages at diagnosis between the Ab(+) and Ab(-) patients, age in years (range) 47.2 (32 to 64) versus 51.2 (31 to 77), respectively, P =.06. Body mass index (BMI) was different in the 2 groups, with Ab(+) patients being less obese, BMI (range) 28.3 kg/m(2) (17.6 to 54.9) versus 32.0 kg/m(2) (19.2 to 68.8), respectively, P =.01. Clinical presentation of diabetes was more commonly symptomatic with polyuria and polydipsia in Ab(+) patients, while in Ab(-) patients, diagnosis was more often incidental, P =.002. However, more than 95% of patients overlapped in both age and BMI irrespective of antibody status. Similarly, 42% of Ab(+) patients had their diabetes diagnosed incidentally, while 29% of Ab(-) patients presented with polyuria and polydipsia. We therefore conclude that screening with antibodies, mainly ICA and GAD, but not age, BMI, or clinical presentation should be used to identify type 1(1/2) diabetes.
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PMID:Islet cell antibodies and glutamic acid decarboxylase antibodies, but not the clinical phenotype, help to identify type 1(1/2) diabetes in patients presenting with type 2 diabetes. 1155 30

The IA-2 is a major autoantigen of type 1 diabetes belonging to the protein tyrosine phosphatase family. We report on the humoral autoimmunity to an alternatively-spliced variant of IA-2 (IA-2 variant) and autoimmune-mediated diabetes age of onset association with IA-2 autoantibody epitope specificities, in 144 recent-onset patients with type 1 diabetes and 54 GAD autoantibody-positive patients with type 2 diabetes. The cytoplasmic domain of IA-2 (IA-2ic) detected a somewhat greater proportion of patients expressing autoantibodies than IA-2 variant (56%vs. 52% of patients with type 1 diabetes and 17%vs. 9% of GAD autoantibody-positive patients with type 2 diabetes). Conversely, only 1% of IA-2 variant autoantibody-positive patients failed to react to IA-2ic construct. Among 80 patients with type 1 diabetes who were positive for autoantibodies to IA-2ic, 8% recognized the juxtamembrane region (JM, representing amino acids 601-629) only, 64% bound the protein tyrosine phosphatase (PTP)-like domain of IA-2 only, and 29% bound both JM and PTP epitopes. Autoantibodies to the PTP-like domain were prevalent in children and adolescents with type 1 diabetes. The age of disease onset in patients with IA-2JM autoantibodies only, was significantly higher than those in patients reacted with the PTP-like domain of IA-2 (P< 0.02). Among GAD autoantibody-positive patients with type 2 diabetes reacted with IA-2ic, 44% bound the JM region only, and 33% bound epitopes in the PTP-like domain only; 22% had autoantibodies to both regions. The frequency of GAD autoantibody-positive patients with type 2 diabetes positive for autoantibodies to the JM region only, was significantly higher than that in patients with type 1 diabetes (P< 0.01). IA-2PTP autoantibodies were significantly associated with HLA-DR4, while the additional reactivity to IA-2JM was associated with HLA-DR9 allele. These results suggest that autoantibody recognition of IA-2 epitopes in autoimmune diabetes is associated with age of disease onset, which may reflect the intensity of the beta-cell destruction process.
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PMID:Association between IA-2 autoantibody epitope specificities and age of onset in Japanese patients with autoimmune diabetes. 1177 57

Right classification of diabetes is important clinical issue. The aim of present study was to compare clinical, biochemical and immunological features, to analyze their practical use and to establish new decision tree which make the distinction between diabetes type 1, LADA, diabetes type 2 and MODY. We studied 97 not obese (mean BMI 26.3 +/- 4.9 kg/m2) patients aged 14 to 70 years, mean age 43 +/- 11.7 years, 53 women, 44 men. Mean duration of diabetes--2.3 +/- 4.3 years. We measured basal and stimulated C-peptide (6 minutes after 1 mg i.v. glucagon) (ELISA) and antibodies titers to glutamic acid decarboxylase--antiGAD65, tyrosine phosphatase-like molecule--IA2 and insulin--IAA (RIA). Autoimmune diabetes (LADA, type 1) was diagnosed with presence of one or more islet antigen antibodies. The highest frequencies had anti-GAD antibodies 33/97 (34%). The most complicated was to sort out group of patients with LADA. Comparison between this group and patients with diabetes type 2 have shown that BMI, co-existence of autoimmune disease, autoimmune markers and basal and stimulated C-peptide level measured at entry for the classification were useful in differentiation. Moreover we observed significantly lower C-peptide basal, stimulated and over basal level in group with MODY diabetes in comparison to diabetes type 2 patients. In the studied group were 5 patients with diabetes type 2 and obesity, in relatively young age. At the end there was one case of ADM (atypical diabetes mellitus). Clinical criteria for the classification of diabetes not always correlated with diagnosis. Autoimmune markers, basal and stimulated C-peptide were useful specially in differentiation between LADA and diabetes type 2 or diabetes type 1. Autoimmune diabetes co-existe with autoimmune disease. Proposed diagnostic scheme take for consideration presence of autoantibodies as well as C-peptide criteria.
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PMID:[Clinical, biochemical and immunological characteristic of diabetes type I, LADA, diabetes type II, and MODY patients]. 1268 30

To examine the association of low-grade systemic inflammation with diabetes, as well as its heterogeneity across subgroups, we designed a case-cohort study representing the approximately 9-year experience of 10,275 Atherosclerosis Risk in Communities Study participants. Analytes were measured on stored plasma of 581 incident cases of diabetes and 572 noncases. Statistically significant hazard ratios of developing diabetes for those in the fourth (versus first) quartile of inflammation markers, adjusted for age, sex, ethnicity, study center, parental history of diabetes, and hypertension, ranged from 1.9 to 2.8 for sialic acid, orosomucoid, interleukin-6, and C-reactive protein. After additional adjustment for BMI, waist-to-hip ratio, and fasting glucose and insulin, only the interleukin-6 association remained statistically significant (HR = 1.6, 1.01-2.7). Exclusion of GAD antibody-positive individuals changed associations minimally. An overall inflammation score based on these four markers plus white cell count and fibrinogen predicted diabetes in whites but not African Americans (interaction P = 0.005) and in nonsmokers but not smokers (interaction P = 0.13). The fully adjusted hazard ratio comparing white nonsmokers with score extremes was 3.7 (P for linear trend = 0.008). In conclusion, a low-grade inflammation predicts incident type 2 diabetes. The association is absent in smokers and African-Americans.
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PMID:Low-grade systemic inflammation and the development of type 2 diabetes: the atherosclerosis risk in communities study. 1282 49


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