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      Impact of triglycerides and waist circumference on insulin resistance and β-cell function in non-diabetic first-degree relatives of type 2 diabetes

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          Abstract

          Background

          Although there is abundant evidence indicating the relative contribution of insulin resistance (HOMA-IR) and β-cell dysfunction (HOMA-β) among first-degree relatives (FDRs) of Type 2 DM patients, few studies reported the association between HOMA-IR and HOMA-β with metabolic syndrome. Our objective was to evaluate the impact of metabolic syndrome factors on HOMA-IR, HOMA-β and glycoproteins in non-diabetic FDRs.

          Methods

          In this study, 103 Yemeni male subjects aged 25–42 years, with BMI < 25 kg/m 2 were examined, 39 of whom were normal subjects with no family history of diabetes served as control and 64 subjects were non-diabetic FDRs of Type 2 DM patients.

          Results

          Both glycoproteins, glycated haemoglobin (HbA1c) and fructosamine as well as insulin, HOMA-IR and HOMA-β were significantly ( p = 4.9 × 10 −9; 6.0 × 10 −8; 6.6 × 10 −12; 1.3 × 10 −7; 5.5 × 10 −12, respectively) higher in non-diabetic FDRs as compared to control group. Fasting plasma glucose, though within normal range, were significantly ( p = 0.026) higher in non-diabetic FDRs. Linear regression analysis showed that both TG and WC are the main metabolic syndrome factors that significantly increased HOMA-IR (B = 0.334, p = 1.97 × 10 −6; B = 0.024, p = 1.05 × 10 −5), HOMA-β (B = 16.8, p = 6.8 × 10 −5; B = 0.95, p = 0.004), insulin (B = 16.5, p = 1.2 × 10 −6; B = 1.19, p = 8.3 × 10 −6) and HbA1c (B = 0.001, p = 0.034; B = 0.007, p = 0.037).

          Conclusion

          Triglyceride and WC are the important metabolic syndrome factors associated with insulin resistance, basal β-cell function and insulin levels in non-diabetic FDR men of Type 2 DM patients. Moreover, FDRs showed insulin resistance with compensatory β-cell function (hyperinsulinaemia) suggesting that insulin resistance precede the development of pancreatic β-cell dysfunction in individuals at risk of Type 2 DM.

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          Most cited references81

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          Pathophysiology and treatment of type 2 diabetes: perspectives on the past, present, and future.

          Glucose metabolism is normally regulated by a feedback loop including islet β cells and insulin-sensitive tissues, in which tissue sensitivity to insulin affects magnitude of β-cell response. If insulin resistance is present, β cells maintain normal glucose tolerance by increasing insulin output. Only when β cells cannot release sufficient insulin in the presence of insulin resistance do glucose concentrations rise. Although β-cell dysfunction has a clear genetic component, environmental changes play an essential part. Modern research approaches have helped to establish the important role that hexoses, aminoacids, and fatty acids have in insulin resistance and β-cell dysfunction, and the potential role of changes in the microbiome. Several new approaches for treatment have been developed, but more effective therapies to slow progressive loss of β-cell function are needed. Recent findings from clinical trials provide important information about methods to prevent and treat type 2 diabetes and some of the adverse effects of these interventions. However, additional long-term studies of drugs and bariatric surgery are needed to identify new ways to prevent and treat type 2 diabetes and thereby reduce the harmful effects of this disease. Copyright © 2014 Elsevier Ltd. All rights reserved.
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            Insulin resistance and hyperglycaemia in cardiovascular disease development.

            The prevalence of diabetes mellitus will likely increase globally from 371 million individuals in 2013 to 552 million individuals in 2030. This epidemic is mainly attributable to type 2 diabetes mellitus (T2DM), which represents about 90-95% of all cases. Cardiovascular disease is the leading cause of mortality among individuals with diabetes mellitus, and >50% of patients will die from a cardiovascular event-especially coronary artery disease, but also stroke and peripheral vascular disease. Classic risk factors such as elevated levels of LDL cholesterol and blood pressure, as well as smoking, are risk factors for adverse cardiovascular events in patients with type 1 diabetes mellitus (T1DM) and T2DM to a similar degree as they are in healthy individuals. Patients with T1DM develop insulin resistance in the months after diabetes mellitus diagnosis, and patients with T2DM typically develop insulin resistance before hyperglycaemia occurs. Insulin resistance and hyperglycaemia, in turn, further increase the risk of adverse cardiovascular events. This Review discusses the mechanisms by which T1DM and T2DM can lead to cardiovascular disease and how these relate to the risk factors for coronary artery disease.
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              The pathogenesis of insulin resistance: integrating signaling pathways and substrate flux.

              Insulin resistance arises when the nutrient storage pathways evolved to maximize efficient energy utilization are exposed to chronic energy surplus. Ectopic lipid accumulation in liver and skeletal muscle triggers pathways that impair insulin signaling, leading to reduced muscle glucose uptake and decreased hepatic glycogen synthesis. Muscle insulin resistance, due to ectopic lipid, precedes liver insulin resistance and diverts ingested glucose to the liver, resulting in increased hepatic de novo lipogenesis and hyperlipidemia. Subsequent macrophage infiltration into white adipose tissue (WAT) leads to increased lipolysis, which further increases hepatic triglyceride synthesis and hyperlipidemia due to increased fatty acid esterification. Macrophage-induced WAT lipolysis also stimulates hepatic gluconeogenesis, promoting fasting and postprandial hyperglycemia through increased fatty acid delivery to the liver, which results in increased hepatic acetyl-CoA content, a potent activator of pyruvate carboxylase, and increased glycerol conversion to glucose. These substrate-regulated processes are mostly independent of insulin signaling in the liver but are dependent on insulin signaling in WAT, which becomes defective with inflammation. Therapies that decrease ectopic lipid storage and diminish macrophage-induced WAT lipolysis will reverse the root causes of type 2 diabetes.
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                Author and article information

                Contributors
                malhabori@hotmail.com
                Journal
                BMC Endocr Disord
                BMC Endocr Disord
                BMC Endocrine Disorders
                BioMed Central (London )
                1472-6823
                16 June 2021
                16 June 2021
                2021
                : 21
                : 124
                Affiliations
                GRID grid.412413.1, ISNI 0000 0001 2299 4112, Department of Biochemistry and Molecular Biology, Faculty of Medicine and Health Sciences, , University of Sana’a, ; Sana’a, Republic of Yemen
                Article
                788
                10.1186/s12902-021-00788-5
                8207623
                33407357
                cddcf37d-64ec-46fa-9032-8bd3739c870e
                © The Author(s) 2021

                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/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

                History
                : 26 February 2021
                : 10 May 2021
                Categories
                Research
                Custom metadata
                © The Author(s) 2021

                Endocrinology & Diabetes
                first-degree relatives of type 2 dm,insulin resistance,β-cell function,metabolic syndrome,hba1c,fructosamine

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