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      The relationship between insulin sensitivity and serum antithrombin 3 activity in patients with type 2 diabetes

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          Abstract

          Background

          Antithrombin 3 (AT3) is a physiological inhibitor of thrombin, and serum AT3 activity was found to decrease at the status of type 2 diabetes (T2D). T2D was presented with an increased risk of thrombotic complications at the background of impaired insulin sensitivity. The aim of this study was to investigate the relationship between insulin sensitivity indices and serum AT3 activity in patients with T2D.

          Methods

          We conducted a cross-sectional study in patients with T2D who consented to participate in the study at the Endocrinology Department of Affiliated 2 Hospital of Nantong University from January 2015 to June 2018. All patients received serum AT3 activity test and 75 g oral glucose tolerance test (OGTT). Basal and systemic insulin sensitivity were assessed by homeostasis model assessment of insulin resistance (HOMA-IR) and Matsuda index (ISI Matsuda), respectively, from the OGTT. And other relevant clinical data were also collected.

          Results

          Total of 1612 patients with T2D were enrolled in the study, with a mean age of 58.67 ± 13.09 years and a median diabetes duration of 6 years (interquartile range, 1–10 years). Across ascending quartiles of serum AT3 activity, HOMA-IR progressively decreased, while ISI Matsuda progressively increased (all P for trend < 0.001). Moreover, serum AT3 activity was negatively correlated with HOMA-IR ( r = −0.189 , P < 0.001) and positively correlated with ISI Matsuda ( r = 0.221 , P < 0.001). After adjusting for other metabolic risk factors, hemostatic parameters and glucose-lowering therapies by multivariate linear regression analysis, HOMA-IR ( β = −0.185, t = −5.960 , P < 0.001) and ISI Matsuda ( β = 0.197 , t = 6.632 , P < 0.001) remained independently associated with the serum AT3 activity in patients with T2D, respectively.

          Conclusions

          Reduced basal and systemic insulin sensitivity are associated with decreased serum AT3 activity in patients with T2D.

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          Most cited references46

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          Homeostasis model assessment closely mirrors the glucose clamp technique in the assessment of insulin sensitivity: studies in subjects with various degrees of glucose tolerance and insulin sensitivity

          F Saggiani, T Monauni, M. Zenere … (2000)
          To evaluate whether the homeostasis model assessment (HOMA) is a reliable surrogate measure of in vivo insulin sensitivity in humans.
          Article 0 comments Cited 346 times – based on 0 reviews     Review now
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            Mortality from coronary heart disease in subjects with type 2 diabetes and in nondiabetic subjects with and without prior myocardial infarction.

            S. Haffner, S Lehto, T Rönnemaa … (1998)
            Type 2 (non-insulin-dependent) diabetes is associated with a marked increase in the risk of coronary heart disease. It has been debated whether patients with diabetes who have not had myocardial infarctions should be treated as aggressively for cardiovascular risk factors as patients who have had myocardial infarctions. To address this issue, we compared the seven-year incidence of myocardial infarction (fatal and nonfatal) among 1373 nondiabetic subjects with the incidence among 1059 diabetic subjects, all from a Finnish population-based study. The seven-year incidence rates of myocardial infarction in nondiabetic subjects with and without prior myocardial infarction at base line were 18.8 percent and 3.5 percent, respectively (P<0.001). The seven-year incidence rates of myocardial infarction in diabetic subjects with and without prior myocardial infarction at base line were 45.0 percent and 20.2 percent, respectively (P<0.001). The hazard ratio for death from coronary heart disease for diabetic subjects without prior myocardial infarction as compared with nondiabetic subjects with prior myocardial infarction was not significantly different from 1.0 (hazard ratio, 1.4; 95 percent confidence interval, 0.7 to 2.6) after adjustment for age and sex, suggesting similar risks of infarction in the two groups. After further adjustment for total cholesterol, hypertension, and smoking, this hazard ratio remained close to 1.0 (hazard ratio, 1.2; 95 percent confidence interval, 0.6 to 2.4). Our data suggest that diabetic patients without previous myocardial infarction have as high a risk of myocardial infarction as nondiabetic patients with previous myocardial infarction. These data provide a rationale for treating cardiovascular risk factors in diabetic patients as aggressively as in nondiabetic patients with prior myocardial infarction.
            Article 0 comments Cited 345 times – based on 0 reviews     Review now
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              Advanced glycation end products: sparking the development of diabetic vascular injury.

              Alison Goldin, Joshua A Beckman, Ann Marie Schmidt … (2006)
              Advanced glycation end products (AGEs) are proteins or lipids that become glycated after exposure to sugars. AGEs are prevalent in the diabetic vasculature and contribute to the development of atherosclerosis. The presence and accumulation of AGEs in many different cell types affect extracellular and intracellular structure and function. AGEs contribute to a variety of microvascular and macrovascular complications through the formation of cross-links between molecules in the basement membrane of the extracellular matrix and by engaging the receptor for advanced glycation end products (RAGE). Activation of RAGE by AGEs causes upregulation of the transcription factor nuclear factor-kappaB and its target genes. Soluble AGEs activate monocytes, and AGEs in the basement membrane inhibit monocyte migration. AGE-bound RAGE increases endothelial permeability to macromolecules. AGEs block nitric oxide activity in the endothelium and cause the production of reactive oxygen species. Because of the emerging evidence about the adverse effects of AGEs on the vasculature of patients with diabetes, a number of different therapies to inhibit AGEs are under investigation.
              Article 0 comments Cited 294 times – based on 0 reviews     Review now
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                Author and article information

                Journal
                Journal ID (nlm-ta): Endocr Connect
                Journal ID (iso-abbrev): Endocr Connect
                Journal ID (hwp): EC
                Title: Endocrine Connections
                Publisher: Bioscientifica Ltd (Bristol )
                ISSN (Electronic): 2049-3614
                Publication date (Electronic): 02 June 2021
                Publication date Collection: 01 July 2021
                Volume: 10
                Issue: 7
                Pages: 667-675
                Affiliations
                [1 ]Department of Endocrinology , Affiliated Hospital 2 of Nantong University and First People’s Hospital of Nantong City, Nantong, China
                [2 ]Medical Research Center , Affiliated Hospital 2 of Nantong University, and First People’s Hospital of Nantong City, Nantong, China
                Author notes
                Correspondence should be addressed to J Su or X Wang: sujbzjx@ 123456163.com or wangxueqin108@ 123456163.com

                *(H Wang and J Cao contributed equally to this work)

                Author information
                http://orcid.org/0000-0002-2138-0263
                Article
                Publisher ID: EC-21-0087
                DOI: 10.1530/EC-21-0087
                PMC ID: 8240710
                PubMed ID: 34077393
                SO-VID: 976debd4-b52a-4eff-ab67-35b0e24463a2
                Copyright © © The authors
                License:

                This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

                History
                Date received : 22 May 2021
                Date accepted : 02 June 2021
                Categories
                Subject: Research

                Keywords: antithrombin 3,diabetes,insulin sensitivity,type 2 diabetes
                Data availability:
                Keywords: antithrombin 3, diabetes, insulin sensitivity, type 2 diabetes

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