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      The Comparative Study on the Status of Bone Metabolism and Thyroid Function in Diabetic Patients with or without Ketosis or Ketoacidosis

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          Abstract

          Purpose

          This study aims to identify changes in bone turnover markers and thyroid function in diabetic ketosis (DK) and diabetic ketoacidosis (DKA).

          Materials and Methods

          We compared data from the Department of Endocrinology at Shanghai Pudong Hospital from 2018 to 2020 on the pancreatic status and previous glucose control, bone transformation, calcium homeostasis, and thyroid function in groups with diabetes (DM alone, n=602), DK (n=232), and DKA (n=60). Similar comparisons were made in recurrent DK (A) (n=17) and single DK (A) (n=272).

          Results

          The fasting C-peptide level decreased significantly, but hemoglobin A1c (HbA1c) levels were higher in DK or DKA (p<0.05). Blood calcium and 25-hydroxyvitamin D3 (25-OH-VitD3) levels were significantly lower in DKA (p<0.05), but parathyroid hormone (PTH) levels remained constant across all three groups. The N-terminal middle molecular fragment of osteocalcin (N-MID) and β-C terminal cross-linking telopeptide of type 1 collagen (β-CTX) showed significant inverse alterations in DKA, regardless of gender or age (p<0.05). Otherwise, DKA significantly inhibited thyroid function (p<0.05). Furthermore, Spearman correlation analyses revealed a relationship between N-MID and HbA1c in DM alone (r=−0.27, p<0.01), while total triiodothyronine (TT3, r=0.62, p<0.01) or free T3 (FT3, r=0.61, p<0.01) in DK, and DKA (TT3, r=0.45, p<0.01; FT3, r=0.43, p<0.01). Multilinear regression analyses revealed that β-CTX (β=0.564), HbA1c (β=−0.196), TT3 (β=0.183), and 25-OH-VitD3 (β=−0.120) were the only independent determinants of N-MID in DM, whereas FT3 (β=0.491), β-CTX (β=0.315) in DK, and FT3 (β=0.420), β-CTX (β=0.367), TG (β=−0.278) in DKA. Only 25-OH-VitD3 was found to be significantly lower in recurrent DK (A) than in single onset DK (A) (p<0.05), and β-CTX (β=0.745) was found to be significantly independently associated with N-MID.

          Conclusion

          Our preliminary findings show a dramatic change in bone turnover markers in DM patients with DK and DKA, and this change may be related to thyroid function.

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          Most cited references40

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          The role of vitamin D and calcium in type 2 diabetes. A systematic review and meta-analysis.

          Altered vitamin D and calcium homeostasis may play a role in the development of type 2 diabetes mellitus (type 2 DM). EVIDENCE ACQUISITION AND ANALYSES: MEDLINE review was conducted through January 2007 for observational studies and clinical trials in adults with outcomes related to glucose homeostasis. When data were available to combine, meta-analyses were performed, and summary odds ratios (OR) are presented. Observational studies show a relatively consistent association between low vitamin D status, calcium or dairy intake, and prevalent type 2 DM or metabolic syndrome [OR (95% confidence interval): type 2 DM prevalence, 0.36 (0.16-0.80) among nonblacks for highest vs. lowest 25-hydroxyvitamin D; metabolic syndrome prevalence, 0.71 (0.57-0.89) for highest vs. lowest dairy intake]. There are also inverse associations with incident type 2 DM or metabolic syndrome [OR (95% confidence interval): type 2 DM incidence, 0.82 (0.72-0.93) for highest vs. lowest combined vitamin D and calcium intake; 0.86 (0.79-0.93) for highest vs. lowest dairy intake]. Evidence from trials with vitamin D and/or calcium supplementation suggests that combined vitamin D and calcium supplementation may have a role in the prevention of type 2 DM only in populations at high risk (i.e. glucose intolerance). The available evidence is limited because most observational studies are cross-sectional and did not adjust for important confounders, whereas intervention studies were short in duration, included few subjects, used a variety of formulations of vitamin D and calcium, or did post hoc analyses. Vitamin D and calcium insufficiency may negatively influence glycemia, whereas combined supplementation with both nutrients may be beneficial in optimizing glucose metabolism.
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            Mechanisms of diabetes mellitus-induced bone fragility

            Diabetes mellitus is associated with an increased risk of fragility fractures. Here, Napoli and colleagues discuss the complex interactions between glucose homeostasis and bone fragility, the epidemiology of fractures in patients with diabetes mellitus and the effects of antidiabetic drugs on bone health.
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              New insights into the biology of osteocalcin.

              Osteocalcin is among the most abundant proteins in bone and is produced exclusively by osteoblasts. Initially believed to be an inhibitor of bone mineralization, recent studies suggest a broader role for osteocalcin that extends to the regulation of whole body metabolism, reproduction, and cognition. Circulating undercarboxylated osteocalcin, which is regulated by insulin, acts in a feed-forward loop to increase β-cell proliferation as well as insulin production and secretion, while skeletal muscle and adipose tissue respond to osteocalcin by increasing their sensitivity to insulin. Osteocalcin also acts in the brain to increase neurotransmitter production and in the testes to stimulate testosterone production. At least one putative receptor for osteocalcin, Gprc6a, is expressed by adipose, skeletal muscle, and the Leydig cells of the testes and appears to mediate osteocalcin's effects in these tissues. In this review, we summarize these new discoveries, which suggest that the ability of osteocalcin to function both locally in bone and as a hormone depends on a novel post-translational mechanism that alters osteocalcin's affinity for the bone matrix and bioavailability. This article is part of a Special Issue entitled Bone and diabetes.
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                Author and article information

                Journal
                Diabetes Metab Syndr Obes
                Diabetes Metab Syndr Obes
                dmso
                Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy
                Dove
                1178-7007
                12 March 2022
                2022
                : 15
                : 779-797
                Affiliations
                [1 ]Department of Endocrinology, Shanghai Pudong Hospital, Fudan University Pudong Medical Center , Shanghai, 201399, People’s Republic of China
                [2 ]Clinical Research OB/GYN REI Division, University of California , San Francisco, CA, USA
                [3 ]Shanghai Key Laboratory of Vascular Lesions Regulation and Remodeling, Shanghai Pudong Hospital , Shanghai, People’s Republic of China
                Author notes
                Correspondence: Ligang Zhou, Tel +8613611927616, Email zhouligang@yahoo.com
                [*]

                These authors contributed equally to this work

                Author information
                http://orcid.org/0000-0001-6173-0507
                Article
                349769
                10.2147/DMSO.S349769
                8926020
                35309734
                096866b7-cf45-43c5-9652-6ede905bc1d8
                © 2022 Xu et al.

                This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

                History
                : 23 November 2021
                : 08 March 2022
                Page count
                Figures: 11, Tables: 11, References: 40, Pages: 19
                Funding
                Funded by: Project of Key Medical Discipline of Pudong Hospital of Fudan University;
                Funded by: Project of Key Medical Specialty and Treatment Center of Pudong Hospital of Fudan University;
                Funded by: Special Department Fund of the Pudong New Area Health Planning Commission;
                Funded by: Outstanding Leaders Training Program of Pudong Health Bureau of Shanghai;
                Funded by: Pudong New Area Clinical Plateau Discipline Project;
                Funded by: the Natural Science Foundation of China;
                Funded by: National Natural Science Foundation of China, open-funder-registry 10.13039/501100001809;
                Funded by: Shanghai Natural Science Foundation, open-funder-registry 10.13039/100007219;
                This work was supported by the Project of Key Medical Discipline of Pudong Hospital of Fudan University (Zdxk2020-11), Project of Key Medical Specialty and Treatment Center of Pudong Hospital of Fudan University (Zdzk2020-24), Integrative Medicine special fund of Shanghai Municipal Health Planning Committee (ZHYY- ZXYJHZX-2-201712), Special Department Fund of the Pudong New Area Health Planning Commission (PWZzk2017-03), Outstanding Leaders Training Program of Pudong Health Bureau of Shanghai (PWR12014-06), Pudong New Area Clinical Plateau Discipline Project (PWYgy-2021-03), the Natural Science Foundation of China (21675034), National Natural Science Foundation of China (81370932), Shanghai Natural Science Foundation (19ZR1447500).
                Categories
                Original Research

                Endocrinology & Diabetes
                bone turnover marker,diabetes mellitus,thyroid function,dka
                Endocrinology & Diabetes
                bone turnover marker, diabetes mellitus, thyroid function, dka

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