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Query: UMLS:C0948265 (metabolic syndrome)
 24,271 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The objective of this study was to investigate possible defects in the insulin sensitivity and/or the acute insulin response in a group of Mexican patients displaying early-onset type 2 diabetes and to evaluate the contribution of mutations in three of the genes linked to maturity-onset diabetes of the young. We studied 40 Mexican patients with an age of diagnosis between 20 and 40 yr in which the insulin sensitivity as well as the insulin secretory response were measured using the minimal model approach. A partial screening for possible mutations in 3 of the 5 genes linked to maturity-onset diabetes of the young was carried out by PCR-single strand conformation polymorphism analysis. A low insulin secretory capacity (AIRg = 68.5 +/- 5 muU/mL.min) and a near-normal insulin sensitivity (3.43 +/- 0.2 min/muU.mL x 10(4)) were found in these patients. Among this group we found two individuals carrying missense mutations in exon 4 of the hepatocyte nuclear factor-1alpha (HNF-4alpha) gene (Asp(126)-->His/Tyr and Arg(154)-->Gln, respectively) and one carrying a nonsense mutation in exon 7 of the HNF-1alpha gene (Gln(486)-->stop codon); 7.5% had positive titers for glutamic acid decarboxylase antibodies. Thirty-five percent of cases had insulin resistance; these subjects had the lipid abnormalities seen in the metabolic syndrome. A defect in insulin secretion is the hallmark in Mexican diabetic patients diagnosed between 20 and 40 yr of age. Mutations in either the HNF-1alpha or the HNF-4alpha genes are present among the individuals who develop early-onset diabetes in our population. These particular sequence changes have not been previously reported and therefore represent putative new mutations. Even in the absence of endogenous hyperinsulinemia, insulin resistance is associated with an adverse lipid profile.
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PMID:Early-onset type 2 diabetes: metabolic and genetic characterization in the mexican population. 1123 4

According to the most recent classification of diabetes mellitus the latent autoimmune diabetes in adults belongs to the group of type 1 autoimmune diabetes mellitus, as a slowly progressive form. It is not clear whether LADA is a distinct clinical entity or it is a part of the clinical spectrum of type 1 diabetes mellitus. The authors compare the antropologic (body mass index, waist to hip ratio), immunologic (occurrence of islet cell cytoplasmic autoantibodies and autoantibodies against glutamic acid decarboxylase and tyrosin phosphatase), genetic (HLA DR and DQ alleles known to be associated to type 1 diabetes mellitus) characteristics and occurrence of the features of the metabolic syndrome in the groups of type 1 and type 2 diabetes and LADA. 81 type 1 and 190 type 2 diabetics and 38 LADA patients were involved into the study. Freshly diagnosed type 1 diabetics served for controls of the autoantibody study: 48 patients manifested < or = 16 years of age and 89 type 1 diabetics manifested above 16 years of age. The three main diabetic groups differed in age: the average age in the type 1, type 2 and LADA groups were 37, 63 and 58 years respectively. There was no difference among the three groups in gender. The duration of the disease differed significantly between the type 2 and LADA groups (4.0 and 8.0 years respectively). In spite of the shorter duration of the disease in the LADA group, compared to the type 2 diabetics the frequency of insulin dependency was significantly higher in the LADA (81.6%) than in the type 2 group (46.7%). The BMI and WHR were comparable between the type 1 and LADA patients (average values were 23 and 0.83 in type 1 patients and 23.25 and 0.89 in LADA). The type 2 group differed significantly from type 1 and LADA (average values were 29.1 and 0.5). The concentration of glycated hemoglobin was comparable in the three groups. But there was a significant difference in HbA1c concentration between the freshly diagnosed subgroups of type 1 and LADA patients: 10.85% and 8% respectively. The fasting C-peptid levels were significantly higher in the sera of type 2 diabetics (0.75 pmol/l) compared to type 1 (0.2 pmol/l) and LADA patients (0.29 pmol/l). There was a significant difference in C-peptid concentrations between the type 1 and LADA groups, too. The insulin deficiency in LADA seemed to be not as severe as in type 1 diabetes. The serum total cholesterol and triglyceride levels were significantly higher and the HDL cholesterol concentration significantly lower in type 2 diabetics comparing to type 1 and LADA patients and there was no significant difference in this respect between the type 1 and LADA groups. The frequency of occurrence of hypertension differed no significantly between type 2 and LADA, but that of in type 1 diabetes was significantly lower than both type 2 and LADA. The occurrence of multiple autoantibodies (ICA + GADA + anti-IA2) was much more frequent in type 1 diabetes compared to LADA. In the sera of LADA patients the occurrence of ICA and GADA alone or ICA + GADA was characteristic (31.5% - 21.1% - 15.8% respectively). There was no difference between type 1 diabetes and LADA in the occurrence of the alleles of the MHC kown to be associated with type 1 diabetes. The occurrence of the haplotypes HLA DQ2/DR3 and/or DQ8/DR4 was observed in two thirds of type 1 diabetic and LADA patients. Chronic diabetic complications were observed in all of the groups and there was only a secondary connection of the complications with the type of the diabetes. Based on the results the authors suggest that LADA is a part of the clinical spectrum of type 1 diabetes of autoimmune origin.
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PMID:[Latent autoimmune diabetes in adults(LADA): part of the clinical spectrum of type-1 diabetes mellitus of autoimmune origin]. 1177 Jan 76

Type 1 diabetes (with predominant insulin deficiency) was until recently assumed to be the diagnosis of almost all children presenting with glucose intolerance. This requires insulin treatment via subcutaneous injections, and most patients develop microvascular and macrovascular complications in adulthood. Advances in genetics in the 1990s identified a group of genetic disorders of pancreatic beta-cell function (maturity-onset diabetes of the young) for which the outlook is better than type 1, genetic testing is available, and oral medication is the preferred treatment. In 2000, the first cases of type 2 diabetes (predominant insulin resistance) were reported in UK children, reflecting a trend seen in North America over the last 20 years. Affected children are usually overweight or obese, often female, pubertal, predominantly of ethnic minority (South Asian) origin and have a family history of type 2 diabetes. The diagnosis is aided by demonstration of insulin resistance, and may include measurement of fasting insulin and C-peptide, markers of the metabolic syndrome (fasting lipids, sex hormone binding globulin) and absence of autoantibodies against beta-cell components (e.g. glutamic acid decarboxylase). Management is aimed towards weight stabilization in the growing child, education on healthy lifestyles and the treatment of hyperglycaemia with both insulin and insulin-sensitizing agents. The underlying cause of type 2 diabetes in children is likely to be related to the epidemic of childhood obesity. There is emerging evidence of an appalling outlook for these young people in terms of miscarriages and microvascular and cardiovascular complications, which are likely to present an enormous economic and health services burden over the next 20 years.
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PMID:The emergence of type 2 diabetes in childhood. 1471 81

The Japanese Brazilian population has one of the highest prevalences of diabetes worldwide. Despite being non-obese according to standard definitions, their body fat distribution is typically central. We investigated whether a subset of these subjects had autoantibodies that would suggest a slowly progressive form of type 1 diabetes. A total of 721 Japanese Brazilians (386 men) in the 30- to 60-year age group underwent clinical examination and laboratory procedures, including a 75-g oral glucose tolerance test and determinations of serum autoantibodies. Antibodies to glutamic acid decarboxylase (GADab) were determined by radioimmunoassay and to thyroglobulin (TGab) and thyroperoxidase (TPOab) by flow-cytometry assays. Mean body mass index was 25.2 +/- 3.8 kg/m2, but waist circumference was elevated according to the Asian standards. Diabetes, impaired glucose tolerance, and impaired fasting glycemia were found in 31%, 22%, and 22%, respectively, and 53% of the subjects had metabolic syndrome. Glutamic acid decarboxylase (GADab) was positive in 4.72%, TGab in 9.6%, and TPOab in 10% of the whole sample. When participants were stratified according to the presence of thyroid antibodies, similar frequencies of GADab were found in positive and negative groups. The prevalence rates of glucose metabolism disturbances did not differ between GADab positive and negative groups. Our data did not support the view that autoimmune injury could contribute to the high prevalence of diabetes seen in Japanese Brazilians, and the presence of co-morbidities included in the spectrum of metabolic syndrome favors the classification as type 2 diabetes.
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PMID:Autoimmunity does not contribute to the highly prevalent glucose metabolism disturbances in a Japanese Brazilian population. 1727 84

Latent autoimmune diabetes in the adult (LADA) is a slowly progressive form of autoimmune diabetes, characterized by diabetes-associated autoantibody positivity. A recent hypothesis proposes that LADA consists of a heterogeneous population, wherein several subgroups can be identified based on their autoimmune status. A systematic review of the literature was carried out to appraise whether the clinical characteristics of LADA patients correlate with the titre and numbers of diabetes-associated autoantibodies. We found that the simultaneous presence of multiple autoantibodies and/or a high-titre anti-glutamic acid decarboxylase (GAD)--compared with single and low-titre autoantibody--is associated with an early age of onset, low fasting C-peptide values as a marker of reduced pancreatic B-cell function, a high predictive value for future insulin requirement, the presence of other autoimmune disorders, a low prevalence of markers of the metabolic syndrome including high body mass index, hypertension and dyslipidaemia, and a high prevalence of the genotype known to increase the risk of Type 1 diabetes. We propose a more continuous classification of diabetes mellitus, based on the finding that the clinical characteristics gradually change from classic Type 1 diabetes to LADA and finally to Type 2 diabetes. Future studies should focus on determining optimal cut-off points of anti-GAD for differentiating clinically relevant diabetes mellitus subgroups.
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PMID:The islet autoantibody titres: their clinical relevance in latent autoimmune diabetes in adults (LADA) and the classification of diabetes mellitus. 1802 40

In this paper, the islet autoimmunity status and relation to clinical characteristics, beta cell function and cardio-metabolic risk factors in young-onset Asian diabetic patients are evaluated at baseline. The study population consisted of 912 patients (from China, India, Malaysia and Singapore) with age 12-40 years and diabetes duration <12 months. Autoantibodies to glutamic acid decarboxylase (GADA) and tyrosine phosphatase (IA-2A), beta cell function and cardio-metabolic risk parameters were assessed. Among our young patient cohort, 105 (11.5%) patients were GADA and/or IA-2A positives (Ab +ve). Ab +ve patients were younger, leaner, had more severe hyperglycaemia and lower beta cell function. The frequency of metabolic syndrome was significantly lower in Ab +ve patients (27%) compared to Ab -ve patients (54%). However, a substantial proportion of patients in both groups of patients had atherogenic dyslipidaemia, hypertension and albuminuria (micro or macro). In our study cohort, only one in 10 Asian youth with new-onset diabetes had evidence of islet autoimmunity. At least 60% of Ab +ve and 50% of Ab -ve patients demonstrated classical features of type 1 and type 2 diabetes respectively. Regardless of autoimmunity status, the cardio-metabolic risk factors, in particular atherogenic dyslipidaemia, hypertension and albuminuria were common in our patients with young-onset diabetes.
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PMID:Islet autoimmunity status in Asians with young-onset diabetes (12-40 years): association with clinical characteristics, beta cell function and cardio-metabolic risk factors. 1820 2

Background. Latent autoimmune diabetes in adults (LADA) is characterized by islet beta-cell loss and absolute insulin deficiency, however, studies in recent years have shown some extent of insulin resistance in LADA patients. In view of insulin resistance being the central pathogenesis of metabolic syndrome (MS), we hypothesized that MS could be found in LADA patients. Methods. A total of 60 glutamic acid decarboxylase antibody (GAD-Ab)-positive LADA patients and 120 patients with type 2 diabetes (T2DM) were enrolled for the study. MS and its components were diagnosed according to the working definitions proposed by World Health Organization and National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III [ATP III]). Insulin resistance and high sensitive C reactive protein (hsCRP) levels were also evaluated in patients with or without MS. Serum insulin and hsCRP levels were determined with radioimmune and immunoturbidimetric assays, respectively. Results. MS was found in 50% of LADA patients by WHO criteria and in 40% by ATP III criteria. The proportions of MS and its metabolic components were all comparable between LADA and T2DM patients except that a lower proportion of hypertension was seen in LADA. LADA patients with MS had significantly higher HOMA-IR index (0.85 +/- 0.33 vs. 0.60 +/- 0.26, p = 0.001 for WHO criteria; 0.89 +/- 0.34 vs. 0.62 +/- 0.26, p = 0.000 for ATP III criteria) and hsCRP levels (0.86 vs. 0.41, p = 0.019 for WHO criteria; 0.96 vs. 0.66, p = 0.018 for ATP III criteria) than LADA without MS patients. Conclusions. Our findings indicate that MS does exist in LADA patients, suggesting that the a diagnosis of MS could not exclude one of LADA and that insulin sensitizers may be beneficial in therapeutic strategies for treating these conditions.
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PMID:Metabolic syndrome in adult-onset latent autoimmune diabetes. 1837 Jul 24