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      Levothyroxine and insulin requirement in autoimmune polyglandular type 3 syndrome: a real-life study

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          Abstract

          Purpose

          To evaluate factors influencing the insulin and levothyroxine requirement in patients with autoimmune polyglandular syndrome type 3 (APS-3) vs. patients with type 1 diabetes mellitus (T1DM) and autoimmune hypothyroidism (AH) alone, respectively.

          Methods

          Fifty patients with APS-3, 60 patients with T1DM and 40 patients with AH were included. Anthropometric, clinical and biochemical parameters were evaluated in all patients. Insulin requirement was calculated in patients with APS-3 and T1DM, while levothyroxine requirement was calculated in APS-3 and AH.

          Results

          Patients with APS-3 showed higher age ( p = 0.001), age of onset of diabetes ( p = 0.006) and TSH ( p = 0.004) and lower total insulin as U/day ( p < 0.001) and U/Kg ( p = 0.001), long-acting insulin as U/day ( p = 0.030) and U/kg ( p = 0.038) and irisin ( p = 0.002) compared to T1DM. Patients with APS-3 had higher waist circumference ( p = 0.008), duration of thyroid disease ( p = 0.020), levothyroxine total daily dose ( p = 0.025) and mcg/kg ( p = 0.006), triglycerides ( p = 0.007) and VAI ( p = 0.010) and lower age of onset of thyroid disease ( p = 0.007) than AH.

          At multivariate analysis, levothyroxine treatment and VAI were associated with insulin and levothyroxine requirement in APS-3, respectively. VAI was independently associated with insulin requirement in T1DM. Circulating irisin levels were independently associated with levothyroxine requirement in AH.

          Conclusion

          Patients with APS-3 show lower insulin requirement and higher levothyroxine requirement than T1DM and AH alone, respectively. Levothyroxine treatment and VAI affect insulin and levothyroxine requirement, respectively, in APS-3. In T1DM, adipose tissue dysfunction, indirectly expressed by high VAI, is associated with an increased insulin requirement, while circulating irisin levels influence the levothyroxine requirement in AH.

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          Most cited references45

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          2. Classification and Diagnosis of Diabetes: Standards of Medical Care in Diabetes—2020

          (2019)
          The American Diabetes Association (ADA) "Standards of Medical Care in Diabetes" includes the ADA's current clinical practice recommendations and is intended to provide the components of diabetes care, general treatment goals and guidelines, and tools to evaluate quality of care. Members of the ADA Professional Practice Committee (https://doi.org/10.2337/dc20-SPPC), a multidisciplinary expert committee, are responsible for updating the Standards of Care annually, or more frequently as warranted. For a detailed description of ADA standards, statements, and reports, as well as the evidence-grading system for ADA's clinical practice recommendations, please refer to the Standards of Care Introduction (https://doi.org/10.2337/dc20-SINT). Readers who wish to comment on the Standards of Care are invited to do so at professional.diabetes.org/SOC.
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            A PGC1α-dependent myokine that drives browning of white fat and thermogenesis

            Exercise benefits a variety of organ systems in mammals, and some of the best-recognized effects of exercise on muscle are mediated by the transcriptional coactivator PGC1α Here we show that PGC1α expression in muscle stimulates an increase in expression of Fndc5, a membrane protein that is cleaved and secreted as a new hormone, irisin. Irisin acts on white adipose cells in culture and in vivo to stimulate UCP1 expression and a broad program of brown fat-like development. Irisin is induced with exercise in mice and humans, and mildly increased irisin levels in blood cause an increase in energy expenditure in mice with no changes in movement or food intake. This results in improvements in obesity and glucose homeostasis. Irisin could be a protein therapeutic for human metabolic disease and other disorders that are improved with exercise.
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              Is Open Access

              Visceral Adiposity Index

              OBJECTIVE To individuate a novel sex-specific index, based on waist circumference, BMI, triglycerides, and HDL cholesterol, indirectly expressing visceral fat function. RESEARCH DESIGN AND METHODS Visceral adiposity index (VAI) was first modeled on 315 nonobese healthy subjects. Using two multiple logistic regression models, VAI was retrospectively validated in 1,498 primary care patients in comparison to classical cardio- and cerebrovascular risk factors. RESULTS All components of metabolic syndrome increased significantly across VAI quintiles. VAI was independently associated with both cardiovascular (odd ratio [OR] 2.45; 95% CI 1.52–3.95; P < 0.001) and cerebrovascular (1.63; 1.06–2.50; P = 0.025) events. VAI also showed significant inverse correlation with insulin sensitivity during euglycemic-hyperinsulinemic clamp in a subgroup of patients (R s = −0.721; P < 0.001). By contrast, no correlations were found for waist circumference and BMI. CONCLUSIONS Our study suggests VAI is a valuable indicator of “visceral adipose function” and insulin sensitivity, and its increase is strongly associated with cardiometabolic risk.
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                Author and article information

                Contributors
                giuseppe.pizzolanti@unipa.it
                carla.giordano@unipa.it
                Journal
                J Endocrinol Invest
                J Endocrinol Invest
                Journal of Endocrinological Investigation
                Springer International Publishing (Cham )
                0391-4097
                1720-8386
                24 October 2020
                24 October 2020
                2021
                : 44
                : 7
                : 1387-1394
                Affiliations
                GRID grid.10776.37, ISNI 0000 0004 1762 5517, Dipartimento di Promozione della Salute, Materno-Infantile, Medicina Interna e Specialistica di Eccellenza “G. d’Alessandro” (PROMISE), Sezione di Malattie Endocrine, del Ricambio e della Nutrizione, , Università di Palermo, ; Piazza delle Cliniche 2, 90127 Palermo, Italy
                Author information
                http://orcid.org/0000-0002-8088-4947
                http://orcid.org/0000-0001-6052-8438
                http://orcid.org/0000-0003-1731-9395
                Article
                1421
                10.1007/s40618-020-01421-3
                8195810
                33099763
                656d3802-b35b-451b-ad3d-ed344890058c
                © The Author(s) 2020

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 3 June 2020
                : 7 September 2020
                Funding
                Funded by: Università degli Studi di Palermo
                Categories
                Original Article
                Custom metadata
                © Italian Society of Endocrinology (SIE) 2021

                type 1 diabetes mellitus,autoimmune hypothyroidism,visceral adiposity index,irisin,cardiovascular risk

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