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  • Author: Gustavo D Frechtel x
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Mariano J Taverna, María T Martínez-Larrad, Gustavo D Frechtel and Manuel Serrano-Ríos

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Mariano J Taverna, María T Martínez-Larrad, Gustavo D Frechtel and Manuel Serrano-Ríos

Objective

The metabolic syndrome (MS) is a cluster of cardiometabolic factors, which predisposes to diabetes and cardiovascular disease (CVD). Early detection of high-risk individuals for MS using accurate measures of insulin resistance (IR) could improve detection and prevention of CVD and diabetes. The aim of this study was to explore the ability of lipid accumulation product (LAP), compared with traditional measures of IR, to identify MS.

Design

In total, 768 Spanish adults were recruited. MS was assessed using the revised criteria of National Cholesterol Education Program/Adult Treatment Panel III (NCEP/ATP III) and International Diabetes Federation (IDF). Measures of IR such as homeostasis model assessment of IR and LAP, an index of lipid accumulation based on a combination of waist circumference and serum triglycerides, were calculated. Receiver operating characteristic analysis was performed in order to detect the parameter with the best predictive capability for MS.

Results

The prevalence of MS-NCEP/ATP III and MS-IDF was 15.1 and 20.5% for men respectively, and 15.4 and 17.5% for women. LAP showed the highest diagnostic accuracy for MS-NCEP/ATP III (area under the curve 0.91 and 0.90 among males and females) and MS-IDF (0.88 for both males and females). This was confirmed by internal validation using 20 000 bootstrap samples. Among males and females, different LAP cut-off values exhibited high sensitivity (78–85%) and specificity (78–85%) for MS-NCEP/ATP III and MS-IDF identification with elevated efficiency (proportion of positives and negatives classified correctly by the test=78–85%). When the sample was stratified according to decades of life, LAP exhibited a slightly lower performance among women than men, especially for MS-IDF detection.

Conclusions

In non-diabetic adults LAP has a strong and reliable diagnostic accuracy for MS-IDF and, especially, MS-NCEP/ATP III among females and, in particular, among males from Spain.

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Natalia I Faccinetti, Luciano L Guerra, Alberto Penas Steinhardt, Ruben F Iacono, Gustavo D Frechtel, Liliana Trifone, Edgardo Poskus, Aldana Trabucchi and Silvina N Valdez

Objective

In order to gain further knowledge of the structure of zinc transporter 8 (ZnT8) epitopes, we studied the role of the amino acid at position 325 in the antigen and its dimeric conformation for autoantibodies to ZnT8 (ZnT8A) recognition.

Methods

For this purpose, several ZnT8 C-terminal domain variants were designed: monomer carrying Arg325 or Trp325, homo-dimers ZnT8-Arg–Arg325 and ZnT8-Trp–Trp325, and hetero-dimer ZnT8-Arg–Trp325. Two groups of Argentinian diabetic patients were subjected to analysis using [35S]-ZnT8 variants by radioligand binding assay (RBA): i) 100 new-onset, insulin-dependent, type 1 diabetic patients and ii) 282 slowly progressing to insulin requirement, non-obese adult-onset diabetic patients. In addition, 50 type 1 diabetic patients and 100 normal control sera provided by the American Diabetes Association (ADA) were evaluated in order to calculate the sensitivity and specificity of ZnT8A assays for each antigenic variant. Other routine β-cell autoantibodies were also tested by RBA.

Results

Of the 100 Argentinian type 1 diabetic patients, 65 were ZnT8A+. Out of them, 8 patients recognized all recombinant forms of ZnT8 and most patients (56) reacted against the heterodimer. Additionally, out of 282 non-obese adult-onset diabetic patients 46 were ZnT8A+, whereas 29 patients recognized only dimers. Besides, exclusive reactivity against ZnT8A was found in 9.0% for type 1 diabetes mellitus and 10.3% for non-obese adult-onset diabetic patients.

Conclusions

Significantly higher signal values in RBA were obtained with the heterodimeric variant. An increased detection of humoral autoimmunity was found in both groups when ZnT8A was employed in combination with the other β-cell autoantibodies. The inclusion of homodimeric immunoreactive peptides revealed the existence of quaternary structure-defined epitopes probably resembling the actual state of the autoantigen in vivo. Finally, the differential profiles of ZnT8A exhibited by type 1 and non-obese adult-onset diabetic patients suggest the different nature of autoimmune processes underlying both pathologies.