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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

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

As clinicians, we are faced to difficult situations in young diabetic patients. The prevalence of type 2 diabetes increases in these patients due to a rising incidence of obesity. We present two clinical observations which both illustrate the insufficiencies of the present classifications. Modern tools are now available for diagnosis such as anti-GAD65 and IA-2 antibodies, genetic tools to investigate for specific mutations, but quantitative means of beta cell mass are lacking. Clinical examination is still accurate to identify type 1 or type 2 diabetes, MODY and mitochondrial diabetes. Weight curve, lesions of acanthosis nigricans, criteria of metabolic syndrome, history of diabetes are critical factors. This problematic has important consequences in our daily practice: the right choice for rapid and good metabolic control.
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PMID:Classification of diabetes in young adults: new concepts for an old disease. 1635 9

Excessive secretion of adrenal hormones, such as glucocorticoid and mineralocorticoid, leads to metabolic syndrome, including insulin resistance, obesity, and hypertension. These metabolic abnormalities are ameliorated by adrenalectomy (ADX). To identify pituitary mediators for ADX-induced physiological alterations, such as weight loss and hypotension, we investigated the effect of ADX on the pituitary transcriptome using serial analysis of gene expression (SAGE). SAGE method is based on isolation of short sequence tags, which usually correspond to unique mRNA species. The SAGE libraries were constructed from pituitary gland of intact (n = 51) and ADX (n = 12) mice. Thirty-one transcripts were differentially expressed between intact and ADX. Three transcripts encoding for proopiomelanocortin and three other transcripts involved in regulation of hormone secretion (neuromedin B, proprotein convertase subtilisin/kexin type 2, and IA-2) were induced by ADX. In addition, ADX increased the expression levels of genes encoding for cation extracellular matrix (matrix gamma-carboxyglutamate protein) and transport (solute carrier family 22 member 17). Conversely, ADX downregulated two transcripts involved in mitochondrial oxidative phosphorylation (nicotinamide adenine dinucleotide (NADH) dehydrogenase 3 and cytochrome c oxidase 3). Moreover, ADX significantly modulated the expression levels of one gene with uncharacterized function and 20 novel transcripts. This study reveals alterations of pituitary gene expressions that may be associated with ADX-induced physiological changes including weight loss.
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PMID:Regulation of pituitary gene expression by adrenalectomy. 1910 26

Diabetic patients tend to show a reduced QOL because of macrovascular complications such as cerebral and myocardial infarction, as well as marked microvascular complications. It is important for the prevention and amelioration of these complications to diagnose diabetes mellitus (DM) early and effectively control glycemia, the blood pressure, lipids, and body weight. We examine fasting plasma glucose (FPG) and HbA1c for a diagnosis of diabetes at any time, but examine 75gOGTT for impaired glucose tolerance or DM. Examination to be necessary for a pathologic classification of DM is islet-associated antibody, namely, GAD antibody, IA-2 antibody and the measurement of IRI, blood/urinary C-peptide to evaluate insulin secretory ability. HOMA-R is an index of insulin resistance, and HOMA-beta is an index of insulin secretory ability which can be calculated from FPG and IRI, but we need to be aware that the insulin secretory ability of the patient may have decreased already. HbA1c is a standard index of glycemic control, but glycoalbumin measurement is suitable for disease states such as anemia and liver cirrhosis, and 1,5-anhydroglucitol is suitable for detecting changes in levels of urinary glucose. Examinations necessary for the evaluation of diabetic nephropathy are microalbumin and 24hr Ccr in the urine, but eGFR has been recently recommended instead of 24hr Ccr. We measure small dense LDL-C, RLP-C, and Lp (a) as well as conduct conventional lipid analyses for dislipidemia combined with DM for qualitative as well as quantitative data. Metabolic syndrome is caused by the life habits of overeating and lack of exercise, leading to atherosclerotic disease, because insulin resistance advances from visceral fat accumulation. TNF-alpha and leptin levels as insulin resistance advances and adiponectin levels as insulin resistance improves are measured as adipocytokines secreted by visceral fat tissue.
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PMID:[Clinical laboratory examination of diabetic patients in conjunction with metabolic syndrome]. 2003 Jan 75

The aim of our study was to establish the possible association between double or triple antibody positivity and latent autoimmune diabetes (LADA) phenotype in the context of metabolic syndrome (MS) prevalence and its individual components. This cross-sectional study population comprised 69 islet cell antibody-positive patients coming for their comprehensive annual review. They were divided into three groups according to antibody positivity. Twenty-five (36.2 %) were male, mean age of 51 years with disease duration of 8 years. Twenty-eight (40.58 %) were positive only for GAD Abs, 26 (37.68 %) were positive for ICA and GAD Abs and 15 (21.74 %) were positive for GAD, ICA, and IA2 Abs. The lowest value of waist circumference, MS, and artherial hypertension prevalence was found in the group positive for all three antibodies. In the multinomial multivariate logistic regression model, MS was negatively associated with triple Abs positivity compared to single Ab positivity and double Abs positivity. Our results highlight the importance of inverse association between simultaneous Abs positivity for ICA, GAD, and IA2 with the MS and its components present in LADA patients. This inverse relationship might implicate that LADA patients are phenotypically closer to T1DM. The contribution of IA2 Ab positivity merits is to be considered in the determination of LADA phenotypes, while its diagnostic value needs to be clarified in future follow-up studies.
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PMID:Relationship between autoantibodies combination, metabolic syndrome components and diabetic complications in autoimmune diabetes in adults. 2496 36