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Agius R, Pace NP, Fava S. Anthropometric and Biochemical Correlations of Insulin Resistance in a Middle-Aged Maltese Caucasian Population. J Nutr Metab 2024; 2024:5528250. [PMID: 38420511 PMCID: PMC10901578 DOI: 10.1155/2024/5528250] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2023] [Revised: 12/20/2023] [Accepted: 01/31/2024] [Indexed: 03/02/2024] Open
Abstract
Background Insulin resistance (IR) is associated with increased cardiovascular disease risk, and with increased all-cause, cardiovascular, and cancer mortality. A number of surrogate markers are used in clinical practice to diagnose IR. The aim of this study was to investigate the discriminatory power of a number of routinely available anthropometric and biochemical variables in predicting IR and to determine their optimal cutoffs. Methods We performed a cross-sectional study in a cohort of middle-aged individuals. We used receiver operator characteristics (ROC) analyses in order to determine the discriminatory power of parameters of interest in detecting IR, which was defined as homeostatic model assessment-insulin resistance ≥2.5. Results Both the lipid accumulation product (LAP) and visceral adiposity index (VAI) exhibited good discriminatory power to detect IR in both males and females. The optimal cutoffs were 42.5 and 1.44, respectively, in males and 36.2 and 1.41, respectively, in females. Serum triglycerides (TG) and waist circumference (WC) similarly demonstrated good discriminatory power in detecting IR in both sexes. The optimal cutoffs for serum TG and WC were 1.35 mmol/L and 96.5 cm, respectively, in men and 1.33 mmol/L and 82 cm, respectively, in women. On the other hand, systolic and diastolic blood pressure, liver transaminases, high-density lipoprotein cholesterol, serum uric acid, ferritin, waist-hip ratio, "A" body shape, thigh circumference, and weight-adjusted thigh circumference all had poor discriminatory power. Conclusions Our data show that LAP, VAI, TG, and WC all have good discriminatory power in detecting IR in both men and women. The optimal cutoffs for TG and WC were lower than those currently recommended in both sexes. Replication studies are required in different subpopulations and different ethnicities in order to be able to update the current cut points to ones which reflect the contemporary population as well as to evaluate their longitudinal relationship with longer-term cardiometabolic outcomes.
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Affiliation(s)
- Rachel Agius
- Faculty of Medicine and Surgery, University of Malta, Tal-Qroqq, Msida, Malta
- Mater Dei Hospital, Triq Dun Karm, Msida MSD2090, Malta
| | - Nikolai Paul Pace
- Faculty of Medicine and Surgery, University of Malta, Tal-Qroqq, Msida, Malta
| | - Stephen Fava
- Faculty of Medicine and Surgery, University of Malta, Tal-Qroqq, Msida, Malta
- Mater Dei Hospital, Triq Dun Karm, Msida MSD2090, Malta
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Zhang S, Wu Z, Zhuang Y, Sun X, Wang J, Chen S, Guo D, Xu P, Zhang C, Yang J. The metabolic score for insulin resistance in the prediction of major adverse cardiovascular events in patients after coronary artery bypass surgery: a multicenter retrospective cohort study. Diabetol Metab Syndr 2023; 15:157. [PMID: 37461067 PMCID: PMC10351175 DOI: 10.1186/s13098-023-01133-7] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/23/2023] [Accepted: 07/05/2023] [Indexed: 07/21/2023] Open
Abstract
BACKGROUND The metabolic score for insulin resistance (METS-IR) is a simple, convenient, and reliable marker for resistance insulin (IR), which has been regarded as a predictor of cardiovascular disease (CVD) and cardiovascular events. However, few studies examined the relationship between METS-IR and prognosis after coronary artery bypass graft (CABG). This study aimed to investigate the potential value of METS-IR as a prognostic indicator for the major adverse cardiovascular events (MACE) in patients after CABG. METHOD 1100 CABG patients were enrolled in the study, including 760 men (69.1%) and 340 women (30.9%). The METS-IR was calculated as Ln [(2 × FPG (mg/dL) + fasting TG (mg/dL)] × BMI (kg/m2)/Ln [HDL-C (mg/dL)]. The primary endpoint of this study was the occurrence of major adverse cardiovascular events (MACE), including a composite of all-cause death, non-fatal myocardial infarction (MI), coronary artery revascularization, and stroke. RESULT The following-up time of this study was 49-101 months (median, 70 months; interquartile range, 62-78 months). During the follow-up period, there were 243 MACEs (22.1%). The probability of cumulative incidence of MACE increased incrementally across the quartiles of METS-IR (log-rank test, p < 0.001). Multivariate Cox regression analysis demonstrated a hazard ratio (95% CI) of 1.97 (1.36-2.86) for MACE in quartile 4 compared with participants in quartile 1. The addition of the METS-IR to the model with fully adjusting variables significantly improved its predictive value [C-statistic increased from 0.702 to 0.720, p < 0.001, continuous net reclassification improvement (NRI) = 0.305, < 0.001, integrated discrimination improvement (IDI) = 0.021, p < 0.001]. CONCLUSION METS-IR is an independent and favorable risk factor for predicting the occurrence of MACE and can be used as a simple and reliable indicator that can be used for risk stratification and early intervention in patients after CABG.
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Affiliation(s)
- Shuai Zhang
- National Key Laboratory for Innovation and Transformation of Luobing Theory, Shandong University, Jinan, 250012, China
- The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, Shandong University, Jinan, 250012, China
- Department of Cardiology, Qilu Hospital of Shandong University, Jinan, 250012, China
| | - Zhenguo Wu
- National Key Laboratory for Innovation and Transformation of Luobing Theory, Shandong University, Jinan, 250012, China
- The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, Shandong University, Jinan, 250012, China
- Department of Cardiology, Qilu Hospital of Shandong University, Jinan, 250012, China
| | - Yifan Zhuang
- National Key Laboratory for Innovation and Transformation of Luobing Theory, Shandong University, Jinan, 250012, China
- The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, Shandong University, Jinan, 250012, China
- Department of Cardiology, Qilu Hospital of Shandong University, Jinan, 250012, China
| | - Xiangfei Sun
- Department of Cardiovascular Surgery, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250021, Shandong, China
- Department of Cardiovascular Surgery, Shandong Provincial Hospital, Affiliated to Shandong First Medical University, Jinan, 250021, Shandong, China
| | - Juan Wang
- Department of Cardiology, The Second Hospital of Shandong University, Jinan, 250033, Shandong, China
| | - Sha Chen
- National Key Laboratory for Innovation and Transformation of Luobing Theory, Shandong University, Jinan, 250012, China
- The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, Shandong University, Jinan, 250012, China
- Department of Cardiology, Qilu Hospital of Shandong University, Jinan, 250012, China
| | - Dachuan Guo
- National Key Laboratory for Innovation and Transformation of Luobing Theory, Shandong University, Jinan, 250012, China
- The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, Shandong University, Jinan, 250012, China
- Department of Cardiology, Qilu Hospital of Shandong University, Jinan, 250012, China
| | - Panpan Xu
- National Key Laboratory for Innovation and Transformation of Luobing Theory, Shandong University, Jinan, 250012, China
- The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, Shandong University, Jinan, 250012, China
- Department of Cardiology, Qilu Hospital of Shandong University, Jinan, 250012, China
| | - Cheng Zhang
- National Key Laboratory for Innovation and Transformation of Luobing Theory, Shandong University, Jinan, 250012, China.
- The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, Shandong University, Jinan, 250012, China.
- Department of Cardiology, Qilu Hospital of Shandong University, Jinan, 250012, China.
| | - Jianmin Yang
- National Key Laboratory for Innovation and Transformation of Luobing Theory, Shandong University, Jinan, 250012, China.
- The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, Shandong University, Jinan, 250012, China.
- Department of Cardiology, Qilu Hospital of Shandong University, Jinan, 250012, China.
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Agius R, Fava MC, Pace NP, Fava S. Prevalence rates of metabolic health and body size phenotypes by different criteria and association with insulin resistance in a Maltese Caucasian population. BMC Endocr Disord 2022; 22:160. [PMID: 35706017 PMCID: PMC9199253 DOI: 10.1186/s12902-022-01071-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/11/2022] [Accepted: 05/26/2022] [Indexed: 11/17/2022] Open
Abstract
INTRODUCTION Hyperinsulinemia and insulin resistance are known to be associated with increased cardiovascular morbidity and mortality. A metabolically unhealthy phenotype is frequently used as a surrogate marker for insulin resistance. The aims of the current study were to compare the prevalence of the body size phenotypes using different definitions of metabolic health and to investigate which one of them is most strongly associated with insulin resistance in men and women. METHODS We conducted a cross-sectional study in a middle-aged cohort of Maltese Caucasian non-institutionalized population. Metabolic health was defined using the various currently used definitions. RESULTS There were significant differences in the prevalence of body size phenotypes according to the different definitions. We also found significant sex differences in the predictive value of the various definitions of the metabolically unhealthy phenotype to predict insulin resistance. The strongest association was for the definition of having >2 NCEP-ATPIII criteria to characterize the metabolic unhealthy phenotype in women (odds ratio of 19.7). On the other hand, the Aguilar-Salinas et al. definition had the strongest association in men (odds ratio of 18.7). CONCLUSIONS We found large differences in the prevalence of the various body size phenotypes when using different definitions, highlighting the need for having standard criteria. Our data also suggest the need for sex-specific definitions of metabolic health.
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Affiliation(s)
- Rachel Agius
- Faculty of Medicine and Surgery, University of Malta Medical School, Tal-Qroqq, Msida, Malta
- Mater Dei Hospital, Triq Dun Karm, Msida, MSD2090, Malta
| | | | - Nikolai Paul Pace
- Faculty of Medicine and Surgery, University of Malta Medical School, Tal-Qroqq, Msida, Malta
| | - Stephen Fava
- Faculty of Medicine and Surgery, University of Malta Medical School, Tal-Qroqq, Msida, Malta.
- Mater Dei Hospital, Triq Dun Karm, Msida, MSD2090, Malta.
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Farhan S, Redfors B, Maehara A, McAndrew T, Ben-Yehuda O, De Bruyne B, Mehran R, Vogel B, Giustino G, Serruys PW, Mintz GS, Stone GW. Relationship between insulin resistance, coronary plaque, and clinical outcomes in patients with acute coronary syndromes: an analysis from the PROSPECT study. Cardiovasc Diabetol 2021; 20:10. [PMID: 33413366 PMCID: PMC7791845 DOI: 10.1186/s12933-020-01207-0] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/06/2020] [Accepted: 12/26/2020] [Indexed: 02/08/2023] Open
Abstract
Background We investigated the association of insulin resistance (IR) with coronary plaque morphology and the risk of cardiovascular events in patients enrolled in the Providing Regional Observations to Study Predictors of Events in Coronary Tree (PROSPECT) study. Methods Patients with acute coronary syndromes (ACS) were divided based on DM status. Non-DM patients were further stratified according to homeostasis-model-assessment IR (HOMA-IR) index as insulin sensitive (IS; HOMA-IR ≤ 2), likely-IR (LIR; 2 < HOMA-IR < 5), or diabetic-IR (DIR; HOMA-IR ≥ 5). Coronary plaque characteristics were investigated by intravascular ultrasound. The primary endpoint was major adverse cardiac events (MACE); a composite of cardiac death, cardiac arrest, myocardial infarction, and rehospitalization for unstable/progressive angina. Results Among non-diabetic patients, 109 patients (21.5%) were categorized as LIR, and 65 patients (12.8%) as DIR. Patients with DIR or DM had significantly higher rates of echolucent plaque compared with LIR and IS. In addition, DIR and DM were independently associated with increased risk of MACE compared with IS (adjusted hazard ratio [aHR] 2.29, 95% confidence interval [CI] 1.22–4.29, p = 0.01 and aHR 2.12, 95% CI 1.19–3.75, p = 0.009, respectively). Conclusions IR is common among patients with ACS. DM and advanced but not early stages of IR are independently associated with increased risk of adverse cardiovascular events. Trial Registration ClinicalTrials.gov Identifier: NCT00180466.
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Affiliation(s)
- Serdar Farhan
- Icahn School of Medicine At Mount Sinai, The Zena and Michael A. Wiener Cardiovascular Institute, New York, NY, USA
| | - Björn Redfors
- Clinical Trials Center, Cardiovascular Research Foundation/ Columbia University Medical Center, 1700 Broadway, 9th Floor, New York, NY, 10019, USA.,NewYork-Presbyterian Hospital/Columbia University Irving Medical Center, New York, NY, USA.,Department of Cardiology, Sahlgrenska University Hospital, Gothenburg, Sweden
| | - Akiko Maehara
- Clinical Trials Center, Cardiovascular Research Foundation/ Columbia University Medical Center, 1700 Broadway, 9th Floor, New York, NY, 10019, USA. .,NewYork-Presbyterian Hospital/Columbia University Irving Medical Center, New York, NY, USA.
| | - Thomas McAndrew
- Clinical Trials Center, Cardiovascular Research Foundation/ Columbia University Medical Center, 1700 Broadway, 9th Floor, New York, NY, 10019, USA
| | - Ori Ben-Yehuda
- Clinical Trials Center, Cardiovascular Research Foundation/ Columbia University Medical Center, 1700 Broadway, 9th Floor, New York, NY, 10019, USA.,NewYork-Presbyterian Hospital/Columbia University Irving Medical Center, New York, NY, USA
| | | | - Roxana Mehran
- Icahn School of Medicine At Mount Sinai, The Zena and Michael A. Wiener Cardiovascular Institute, New York, NY, USA.,Clinical Trials Center, Cardiovascular Research Foundation/ Columbia University Medical Center, 1700 Broadway, 9th Floor, New York, NY, 10019, USA
| | - Birgit Vogel
- Icahn School of Medicine At Mount Sinai, The Zena and Michael A. Wiener Cardiovascular Institute, New York, NY, USA
| | - Gennaro Giustino
- Icahn School of Medicine At Mount Sinai, The Zena and Michael A. Wiener Cardiovascular Institute, New York, NY, USA
| | - Patrick W Serruys
- Department of Cardiology, NUIG, National University of Ireland, Galway, Ireland.,Imperial College of Science, Technology and Medicine, London, UK
| | - Gary S Mintz
- Clinical Trials Center, Cardiovascular Research Foundation/ Columbia University Medical Center, 1700 Broadway, 9th Floor, New York, NY, 10019, USA
| | - Gregg W Stone
- Icahn School of Medicine At Mount Sinai, The Zena and Michael A. Wiener Cardiovascular Institute, New York, NY, USA.,Clinical Trials Center, Cardiovascular Research Foundation/ Columbia University Medical Center, 1700 Broadway, 9th Floor, New York, NY, 10019, USA
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Glycated Hemoglobin in the Diagnosis of Diabetes Mellitus in a Semi-Urban Brazilian Population. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2019; 16:ijerph16193598. [PMID: 31561434 PMCID: PMC6801550 DOI: 10.3390/ijerph16193598] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/28/2019] [Revised: 09/16/2019] [Accepted: 09/20/2019] [Indexed: 01/10/2023]
Abstract
The study evaluated glycated hemoglobin (HbA1c) as a diagnostic tool for diabetes and pre-diabetes in the Brazilian population. Further, the homeostasis model assessment of insulin resistance (HOMA-IR) was also examined against HbA1c values to identify the most suitable cut-off points for HOMA-IR to predict the risk of diabetes. A cross-sectional study was conducted among 714 randomly selected subjects. HbA1c, fasting, and 2 h plasma glucose values were measured. Insulin resistance estimates were calculated with HOMA-IR. The receiver operating characteristic curve assessed HbA1c performance. The adjusted prevalence rate of diabetes mellitus was 14.7%, and pre-diabetes 14.2%. The optimal HbA1c cut-off value was ≥6.8% for the diagnosis of diabetes, and ≥6.0% for pre-diabetes. The area under the curve using HbA1c was 0.85 (95% CI: 0.80–0.90) for detecting diabetes and 0.61 (95% CI: 0.55–0.67) for pre-diabetes. The optimal HOMA-IR cut-off value was 2.06 for HbA1c at 6.8%. The HbA1c cut-off value of ≥6.8% may be suitable for diagnosing diabetes in the Brazilian population. Our results do not support the use of HbA1c to diagnose pre-diabetes. A HOMA-IR cut-off point of 2.06 was a sensitive marker to assess the risk of diabetes.
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Pi-Sunyer X. Changes in body composition and metabolic disease risk. Eur J Clin Nutr 2018; 73:231-235. [PMID: 30275524 DOI: 10.1038/s41430-018-0320-x] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2018] [Accepted: 09/06/2018] [Indexed: 11/09/2022]
Abstract
As individuals gain weight, they increase the amount of fat that they accrue on their body. This causes adipocytes to enlarge and increases not only subcutaneous fat but also deposits fat in other vulnerable areas of the body. This ectopic fat is deposited in the intra-abdominal visceral fat depot, in muscle, in the liver and in the beta cells. Fat in these locations initiates a dysfunctional state in these insulin-sensitive tissues leading to insulin resistance, the appearance of the Metabolic Syndrome, and an increased risk of developing both type 2 diabetes and cardiovascular disease. A loss of weight and with it a loss of fat decreases this risk.
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Affiliation(s)
- Xavier Pi-Sunyer
- Columbia University College of Physicians and Surgeons and Columbia Institute of Human Nutrition, New York, NY, USA.
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The effect of hormone therapy on bone mineral density and cardiovascular factors among Iranian female athletes with amenorrhea/oligomenorrhea: A randomized clinical trial. Med J Islam Repub Iran 2018; 32:27. [PMID: 30159278 PMCID: PMC6108246 DOI: 10.14196/mjiri.32.27] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2016] [Indexed: 12/12/2022] Open
Abstract
Background: Functional hypothalamic menstrual disorder (FHMD) has a destructive effect on the athlete's bone mineral density and cardiovascular system. Utilizing hormone replacement therapy to treat FHMD in athletes is controversial. This study was conducted to examine the effect of hormone therapy on bone density and the cardiovascular system of professional female athletes with FHMD. Methods: In this study, 18 female athletes with at least a 2- year history of FHMD were recruited in a 9-month single blind randomized clinical intervention (RCT) and randomly classified into 2 groups: the oral contraceptive pills (OCP) group, who received a lowdose combined oral contraceptive (OC) containing 30 µg ethinyl estradiol and 150 µg levonorgestrel (n= 10), and the control group (n= 8). Bone mineral densitometry (BMD) and certain cardiovascular risk factors were measured before and after the 9-month trial. The Chi square test was used to compare the quantitative and qualitative results. Results: Bone mineral density did not change significantly in either group. Very low density lipoprotein (VLDL) (p= 0.035) and Apolipoprotein B (Apo B) (p= 0.04) reduced significantly in the OCP group. An increase was observed in the serum levels of Apolipoprotein A (Apo A) (p= 0.01) in the control group. Changes in the Apo B to Apo A ratio was significant in both groups (OCP group: p= 0.018, control group: p= 0.040). No significant changes were observed in the other measured factors. Conclusion: Although the administration of estrogen did not significantly increase bone mineral density, it had positive effects on the cardiovascular system and lipid profile.
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Diamond MP, Thornton K, Connolly-Diamond M, Sherwin RS, DeFronzo RA. Reciprocal Variations in Insulin-Stimulated Glucose Uptake and Pancreatic Insulin Secretion in Women With Normal Glucose Tolerance. ACTA ACUST UNITED AC 2016. [DOI: 10.1177/107155769500200507] [Citation(s) in RCA: 29] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Affiliation(s)
- Michael P. Diamond
- Departments of Obstetrics and Gynecology and Medicine, Yale University School of Medicine, New Haven, Connecticut; Department of Obstetrics and Gynecology, Division of Reproductive Endocrinology and Infertility, Hutzel Hospital, 4707 St. Antoine Boulevard, Detroit, MI 48201
| | | | | | | | - Ralph A. DeFronzo
- Departments of Obstetrics and Gynecology and Medicine, Yale University School of Medicine, New Haven, Connecticut
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Cariou B, Fruchart JC, Staels B. Review: Vascular protective effects of peroxisome proliferator-activated receptor agonists. ACTA ACUST UNITED AC 2016. [DOI: 10.1177/14746514050050030301] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
ardiovascular disease is significantly increased in patients with the metabolic syndrome and type 2 diabetes. A clustering of risk factors, including dyslipidaemia, insulin resistance, hypertension, inflammation and coagulation disorders are acting in concert to promote cardiovascular events in these patients. Peroxisome proliferator-activated receptors (PPARs) are transcription factors that influence vascular function by altering gene expression in vascular tissue and indirectly via effects on other tissues. Indeed, PPAR activation displays beneficial effects on glucose homeostasis and lipid metabolism, and also on endothelial function and vessel wall inflammation. Clinically used PPARα agonists, such as fibrates, and PPARγ agonists, such as insulin-sensitising thiazolidinediones, may consequently alter the process of atherosclerosis, especially in subjects with the metabolic syndrome and type 2 diabetes. The present review highlights emerging evidence for beneficial effects of PPAR α and PPARγ in the prevention and treatment of atherosclerosis in such high-risk patients.
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Affiliation(s)
- Bertrand Cariou
- Département d'Athérosclérose, Institut Pasteur de Lille & Faculté de Pharmacie, Université de Lille2, Lille, France
| | - Jean-Charles Fruchart
- Département d'Athérosclérose, Institut Pasteur de Lille & Faculté de Pharmacie, Université de Lille2, Lille, France
| | - Bart Staels
- Département d'Athérosclérose, Institut Pasteur de Lille & Faculté de Pharmacie, Université de Lille2, Lille, France,
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Gumanova NG, Gavrilova NE, Chernushevich OI, Kots AY, Metelskaya VA. Ratios of leptin to insulin and adiponectin to endothelin are sex-dependently associated with extent of coronary atherosclerosis. Biomarkers 2016; 22:239-245. [PMID: 27300270 DOI: 10.1080/1354750x.2016.1201539] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/09/2023]
Abstract
OBJECTIVE Noninvasive diagnostics of early stages of coronary artery disease and discrimination between various extents of vascular lesions in patients is an important clinical problem especially considering wide spread use of cholesterol lowering drugs that affect lipid and lipoprotein profiling. The main goal of our study was to evaluate applicability of new combinations of noninvasive biomarkers such as leptin to insulin and adiponectin to endothelin ratios, for detection of early stages of coronary atherosclerosis versus later stages of the disease. PATIENTS AND METHODS A number of previously validated serum biomarkers were tested in a group of 500 patients with coronary artery disease and examined for their association with severity of coronary lesion according to Gensini score determined by coronary angiography. RESULTS Lowest extent of coronary lesions was associated with significant increase in apoA-I levels and with significantly increased ratios of adiponectin to endothelin and leptin to insulin. In male but not in female patients, adiponectin to endothelin ratio below 7.0 was associated with Gensini score representing early to high coronary lesions (p = 0.02). In female but not in male patients, leptin to insulin ratio below 3.5 was associated with Gensini score representing early to high coronary lesions (p = 0.013). CONCLUSION Leptin to insulin and adiponectin to endothelin ratios are novel derived biomarkers useful for noninvasive diagnostics of initial stages of coronary lesions in patients with coronary artery disease.
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Affiliation(s)
- Nadezhda G Gumanova
- a Department of Biochemistry , National Research Center for Preventive Medicine of Ministry of Healthcare of Russian Federation , Moscow , Russia
| | - Natalia E Gavrilova
- b Department of Medicine , National Research Center for Preventive Medicine of Ministry of Healthcare of Russian Federation , Moscow , Russia
| | | | - Alexander Y Kots
- d Department of Biochemistry and Molecular Medicine , the George Washington University, School of Medicine and Health Sciences , Washington , DC , USA
| | - Victoria A Metelskaya
- a Department of Biochemistry , National Research Center for Preventive Medicine of Ministry of Healthcare of Russian Federation , Moscow , Russia
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11
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Approach to diabetes management in patients with CVD. Trends Cardiovasc Med 2015; 26:165-79. [PMID: 26411567 DOI: 10.1016/j.tcm.2015.05.005] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/12/2015] [Revised: 05/11/2015] [Accepted: 05/11/2015] [Indexed: 11/20/2022]
Abstract
Epidemiologic analyses have established a clear association between diabetes and macrovascular disease. Vascular dysfunction caused by metabolic abnormalities in patients with diabetes is associated with accelerated atherosclerosis and increased risk of myocardial infarction (MI), stroke, and peripheral arterial disease. Patients with diabetes are at two to four fold higher CV risk as compared to non-diabetic individuals, and CVD remains the leading cause of mortality in patients with this condition. One strategy to reduce CVD burden in patients with diabetes has been to focus on controlling the major metabolic abnormality in this condition, namely hyperglycemia. However, this has not been unequivocally demonstrated to reduced CV events, in contrast to controlling other CVD risk factors linked to hyperglycemia, such as blood pressure, dyslipidemia, and platelet dysfunction. However, In contradistinction, accrued data from a number of large, randomized clinical trials in both type 1 (T1DM) and type 2 diabetes (T2DM) over the past 3 decades have proven that more intensive glycemic control retards the onset and progression of microvascular disease. In this review, we will summarize the key glucose-lowering CV outcomes trials in diabetes, provide an overview of the different drugs and their impact on the CV system, and describe our approach to management of the frequently encountered patient with T2DM and coronary artery disease (CAD) and/or heart failure (HF).
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12
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[The association of hyperinsulinemia with cardiovascular risk and cancer poses new challenges in the treatment of the insulin resistance type 2 diabetes patient]. HIPERTENSION Y RIESGO VASCULAR 2015; 32:21-6. [PMID: 26179854 DOI: 10.1016/j.hipert.2014.06.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2014] [Revised: 06/14/2014] [Accepted: 06/16/2014] [Indexed: 11/20/2022]
Abstract
Hyperinsulinemia has been associated with cardiovascular risk, both independently and by facilitating the development of other cardiovascular risk factors. It has also been associated by different routes with increased cancer risk. Thus, this makes it a priority to identify and treat the hyperinsulinemic patient early in order to delay or prevent cardiovascular risk and the development of type 2 diabetes mellitus (T2DM) and certain types of cancer. A new strategy is needed for the treatment of hyperglycemia in these patients, whose primary objective would be to achieve weight loss, reduce insulin resistance and thereby hyperinsulinemia. That is, prescribing insulin secretors and insulin should be used with caution in these patients.
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Mankal PK, Kotler DP. From wasting to obesity, changes in nutritional concerns in HIV/AIDS. Endocrinol Metab Clin North Am 2014; 43:647-63. [PMID: 25169559 DOI: 10.1016/j.ecl.2014.05.004] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/24/2022]
Abstract
Optimal nutrition is an important part of human immunodeficiency virus (HIV) care; to support the immune system, limit HIV-associated complications as well as maintain better quality of life and survival. The presentation and nature of malnutrition in patients with HIV has changed dramatically over the past 30 years from predominantly a wasting syndrome to lipodystrophy and, now, frailty. Nevertheless, we continue to see all 3 presentations in patient care today. The pathogenesis of poor nutrition in HIV-infected patients depends on caloric intake, intestinal nutrient absorption/translocation, and resting energy expenditure, which are features seen in all chronic diseases.
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Affiliation(s)
- Pavan K Mankal
- Department of Medicine, Mount Sinai St. Luke's, Mount Sinai Roosevelt Hospital, Icahn School of Medicine at Mount Sinai, Mount Sinai Health System, 1111 Amsterdam Avenue, New York, NY 10025, USA; Division of Gastroenterology, Mount Sinai St. Luke's, Mount Sinai Roosevelt Hospital, Icahn School of Medicine at Mount Sinai, Mount Sinai Health System, 1111 Amsterdam Avenue, New York, NY 10025, USA
| | - Donald P Kotler
- Department of Medicine, Mount Sinai St. Luke's, Mount Sinai Roosevelt Hospital, Icahn School of Medicine at Mount Sinai, Mount Sinai Health System, 1111 Amsterdam Avenue, New York, NY 10025, USA; Division of Gastroenterology and Hepatology, Mount Sinai St. Luke's, Mount Sinai Roosevelt Hospital, Icahn School of Medicine at Mount Sinai, Mount Sinai Health System, 1111 Amsterdam Avenue, New York, NY 10025, USA.
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14
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15
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Prashantha Kumar B, Baig NR, Sudhir S, Kar K, Kiranmai M, Pankaj M, Joghee NM. Discovery of novel glitazones incorporated with phenylalanine and tyrosine: Synthesis, antidiabetic activity and structure–activity relationships. Bioorg Chem 2012; 45:12-28. [DOI: 10.1016/j.bioorg.2012.08.002] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2012] [Revised: 07/22/2012] [Accepted: 08/03/2012] [Indexed: 10/28/2022]
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16
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Kawamoto R, Kohara K, Kusunoki T, Tabara Y, Abe M, Miki T. Alanine aminotransferase/aspartate aminotransferase ratio is the best surrogate marker for insulin resistance in non-obese Japanese adults. Cardiovasc Diabetol 2012; 11:117. [PMID: 23020992 PMCID: PMC3499385 DOI: 10.1186/1475-2840-11-117] [Citation(s) in RCA: 50] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/09/2012] [Accepted: 09/20/2012] [Indexed: 12/17/2022] Open
Abstract
Background The aim of the present study was to examine how liver markers are associated with insulin resistance in Japanese community-dwelling adults. Methods This cross-sectional study included 587 men aged 58 ± 14 (mean ± standard deviation; range, 20–89) years and 755 women aged 60 ± 12 (range, 21–88) years. The study sample consisted of 998 (74.4%) non-obese [body mass index (BMI) <25.0 kg/m2] and 344 (25.6%) overweight (BMI ≥25 kg/m2) subjects. Insulin resistance was defined by homeostasis model assessment of insulin resistance (HOMA-IR) of at least 2.5, and HOMA-IR and potential confounders were compared between the groups. Areas under the curve (AUC) of the receiver operating characteristic curves (ROC) were used to compare the power of these serum markers. Results In non-obese subjects, the best marker of insulin resistance was alanine aminotransferase (ALT)/aspartate aminotransferase (AST) ratio of 0.70 (95% confidence interval (CI), 0.63-0.77). In overweight subjects, AUC values for the ALT/AST ratio and ALT were 0.66 (0.59-0.72) and 0.66 (0.59-0.72), respectively. Multiple linear regression analyses for HOMA-IR showed that ALT/AST ratios were independently and significantly associated with HOMA-IR as well as other confounding factors in both non-obese and overweight subjects. The optimal cut-off point to identifying insulin resistance for these markers yielded the following values: ALT/AST ratio of ≥0.82 in non-obese subjects and ≥1.02 in overweight subjects. In non-obese subjects, the positive likelihood ratio was greatest for ALT/AST ratio. Conclusions In non-obese Japanese adults, ALT/AST ratio may be the best reliable marker of insulin resistance.
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Affiliation(s)
- Ryuichi Kawamoto
- Department of Community Medicine, Ehime University Graduate School of Medicine, Toon-city, Ehime, Japan.
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17
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Hawkins MA. Markers of Increased Cardiovascular Risk: Are We Measuring the Most Appropriate Parameters? ACTA ACUST UNITED AC 2012; 12 Suppl 2:107S-14S. [PMID: 15601958 DOI: 10.1038/oby.2004.275] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Abstract
The vital task of evaluating cardiovascular disease risk in individual patients is challenging in light of the ever-growing list of risk factors. Some of the traditional measures of cardiovascular risk, such as blood lipid levels, have been further refined to provide better risk assessments. Certain specific parameters, such as lipoprotein buoyancy, seem to be better predictors of cardiovascular disease than total lipoprotein levels. Furthermore, as the contribution of systemic inflammation to the pathogenesis of atherosclerosis is increasingly recognized, several inflammatory markers have become associated with disease risk. Consequently, many studies have attempted to determine the individual merits of these factors in predicting cardiovascular risk.
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Affiliation(s)
- Meredith A Hawkins
- Department of Medicine, Division of Endocrinology, Diabetes Research and Training Center, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
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18
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Khan MF, Kumar P, Pandey J, Srivastava AK, Tamrakar AK, Maurya R. Synthesis of novel imbricatolic acid analogues via insertion of N-substituted piperazine at C-15/C-19 positions, displaying glucose uptake stimulation in L6 skeletal muscle cells. Bioorg Med Chem Lett 2012; 22:4636-9. [DOI: 10.1016/j.bmcl.2012.05.097] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2012] [Accepted: 05/25/2012] [Indexed: 12/18/2022]
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19
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Kadota S, Matsuda M, Izuhara M, Baba O, Mitsuoka H, Shioji K, Uegaito T. The association between post-load low insulin level and high mortality rates in patients with no previous diagnosis of diabetes mellitus. Int J Cardiol 2011; 148:59-63. [DOI: 10.1016/j.ijcard.2009.10.024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/13/2009] [Revised: 10/05/2009] [Accepted: 10/15/2009] [Indexed: 01/08/2023]
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20
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Kumar BP, Soni M, Kumar SS, Singh K, Patil M, Baig RN, Adhikary L. Synthesis, glucose uptake activity and structure–activity relationships of some novel glitazones incorporated with glycine, aromatic and alicyclic amine moieties via two carbon acyl linker. Eur J Med Chem 2011; 46:835-44. [DOI: 10.1016/j.ejmech.2010.12.019] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2010] [Revised: 11/17/2010] [Accepted: 12/15/2010] [Indexed: 10/18/2022]
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21
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Affiliation(s)
- Aled W Roberts
- University Hospital of Wales and Wales College of Medicine.
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22
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Panunzi S, De Gaetano A, Mingrone G. Advantages of the single delay model for the assessment of insulin sensitivity from the intravenous glucose tolerance test. Theor Biol Med Model 2010; 7:9. [PMID: 20298586 PMCID: PMC2858103 DOI: 10.1186/1742-4682-7-9] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2009] [Accepted: 03/18/2010] [Indexed: 12/27/2022] Open
Abstract
Background The Minimal Model, (MM), used to assess insulin sensitivity (IS) from Intra-Venous Glucose-Tolerance Test (IVGTT) data, suffers from frequent lack of identifiability (parameter estimates with Coefficients of Variation (CV) less than 52%). The recently proposed Single Delay Model (SDM) is evaluated as a practical alternative. Methods The SDM was applied to 74 IVGTTs from lean (19), overweight (22), obese (22) and morbidly obese (11) subjects. Estimates from the SDM (KxgI) were compared with the corresponding MM (SI), 1/HOMA-IR index and Euglycemic-Hyperinsulinemic Clamp (M-EHC over 7 subjects) estimates. Results KxgI was identifiable in 73 out of 74 subjects (CV = 69% in the 74th subject) and ranged from 1.25 × 10-5 to 4.36 × 10-4min-1pM-1; SI CV was >52% in 36 subjects (up to 2.36 × 109%) and presented 18 extreme values (≤ 1.5 × 10-12 or ≥ 3.99). KxgI correlated well with 1/HOMA-IR (r = 0.56, P < 0.001), whereas the correlations KxgI-SI and 1/HOMA-IR-SI were high (r = 0.864 and 0.52 respectively) and significant (P < 0.001 in both cases) only in the non-extreme SI sub-sample (56 subjects). Correlations KxgI vs. M-EHC and SI vs. M-EHC were positive (r = 0.92, P = 0.004 and r = 0.83, P = 0.02 respectively). KxgI decreased for higher BMI's (P < 0.001), SI significantly so only over the non-extreme-SI sub-sample. The Acute Insulin Response Index was also computed and the expected inverse (hyperbolic) relationship with the KxgI observed. Conclusions Precise estimation of insulin sensitivity over a wide range of BMI, stability of all other model parameters, closer adherence to accepted physiology make the SDM a useful alternative tool for the evaluation of insulin sensitivity from the IVGTT.
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Affiliation(s)
- Simona Panunzi
- CNR-Institute of Systems Analysis and Computer Science (IASI), BioMathLab, Rome, Italy.
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23
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Kapur S, Groves MN, Zava DT, Kapur S. Postprandial insulin and triglycerides after different breakfast meal challenges: use of finger stick capillary dried blood spots to study postprandial dysmetabolism. J Diabetes Sci Technol 2010; 4:236-43. [PMID: 20307382 PMCID: PMC2864157 DOI: 10.1177/193229681000400202] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
BACKGROUND High levels of insulin and lipids following a meal are recognized risk factors for atherosclerosis. Monitoring such risk factors in the general population is hampered by the inconvenience of venipuncture blood collection, particularly for both premeal and postmeal analyses. This study examined insulin and triglyceride levels in dried blood spots (DBSs) collected after different breakfast meal challenges to assess the potential of this method for risk assessment. METHODS Glucose levels were measured using a glucose meter, and insulin and triglycerides were determined in DBS samples collected from 19 healthy volunteers before and at four time points up to 2.5 h after consuming each of five typical breakfast meals varying in nutritional composition. RESULTS At 2 h, glucose was within normal postprandial values (<140 mg/dl) for all meals; significantly lower glucose was seen after meal 2 (the lowest carbohydrate content) compared to the other meals. Insulin returned to normal fasting levels (<15 microIU/ml) in significantly more subjects (90%) after meal 2 and significantly fewer subjects (31%) after meal 4 (highest carbohydrate content) than the other meals. Triglycerides were elevated to a similar extent in all subjects, with no significant differences between meals; levels were still rising at 2.5 h. CONCLUSIONS Subjects were able to collect blood spots with minimum disruption to their normal daily activities. Relative ease of collection, analyte stability in dried blood, and the close correlation with serum levels that we have previously demonstrated makes DBS a convenient and simple tool for assessing the individual impact of different diets on postprandial dysmetabolism.
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Affiliation(s)
- Sonia Kapur
- ZRT Laboratory, LLC, Beaverton, Oregon, USA.
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Abstract
Type 2 diabetes has become an epidemic in the United States, mainly due to an increase in obesity and sedentary lifestyle. Diabetes is considered a cardiovascular risk equivalent, and cardiovascular death remains the most common cause of death in this population. The cardiovascular complications of diabetes, beginning as early as 10 years before the development of frank hyperglycemia, are strongly linked to the development of insulin resistance and the ensuing metabolic disarray often referred to as the metabolic syndrome. To provide proper therapy for cardiovascular prevention, the downstream effects of insulin resistance must be understood. The most important aspect of treating patients with the metabolic syndrome is the realization that treatment must begin before the development of frank hyperglycemia, particularly if cardiovascular events are to be avoided. Thus, in addition to managing the hyperglycemia that develops with the onset of diabetes, insulin resistance, dyslipidemia, and hypertension must also be properly addressed.
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Affiliation(s)
- Angela M Taylor
- University of Virginia, Division of Cardiovascular Medicine, 1215 Lane Street, Hospital Expansion Building C, Box 800158, Charlottesville, VA 22908, USA.
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Abstract
The normal endothelium produces a number of vasodilator substances such as nitric oxide (NO) and prostacyclin (PGI2) that regulate vasomotor tone, reduce platelet aggregation, and inhibit the recruitment and activity of inflammatory cells. The functions of vascular endothelial cells are disturbed in diabetic patients. The major cause for mortality and a great percent of morbidity in patients with diabetes mellitus is atherosclerosis. Insulin has recently been shown to stimulate NO release and the expression of NO synthase by the endothelium. Insulin is thus a vasodilator, has anti-platelet activity, and now has been shown to be anti-inflammatory and thus, potentially anti-atherogenic. Similar anti-inflammatory effects of thiazolidenediones (TZDs), troglitazone, and rosiglitazone suggest that they too may have potential anti-atherogenic effects. These effects of insulin and TZDs are of importance since the two major states of insulin resistance, obesity and type 2 diabetes, are associated with a marked increase in atherosclerosis, coronary heart disease, and stroke. These recent observations have extremely important implications for the understanding of the pathogenesis of atherosclerosis in insulin-resistant states and for a rational approach to their comprehensive treatment, including the prevention of atherosclerosis and its complications. This review challenges the previously proposed hypothesis that hyperinsulinemia represents a common pathophysiological pathway of diabetic complications and advances our hypothesis that insulin, through its effect on the endothelium, leucocytes, and platelets, has anti-inflammatory and thus potentially anti-atherogenic properties. Furthermore, through its anti-inflammatory effects, its use improves clinical outcomes in at least two clinical states characterized by profound inflammation-acute myocardial infarction and sepsis.
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Affiliation(s)
- Ahmad Aljada
- Division of Endocrinology, Diabetes and Metabolism, State University of New York at Buffalo, Buffalo, New York, USA
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26
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Akinci G, Akinci B, Coskun S, Bayindir P, Hekimsoy Z, Ozmen B. Evaluation of markers of inflammation, insulin resistance and endothelial dysfunction in children at risk for overweight. Hormones (Athens) 2008; 7:156-62. [PMID: 18477553 DOI: 10.1007/bf03401507] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/28/2022]
Abstract
OBJECTIVE Childhood obesity is associated with impaired endothelial function, insulin resistance and inflammation. Being at risk for overweight has been defined as having a body mass index (BMI) between the 85th and 94th percentile for age and sex. In this study, we looked for features linked to cardiovascular risk in children who are at risk for overweight. DESIGN Twenty-one children who were at risk for overweight (study group) and 20 children with a BMI between the 25th-74th percentiles (controls) were studied. Fasting blood levels of glucose, insulin, total cholesterol, HDL cholesterol, triglycerides, uric acid, fibrinogen and high sensitive C-reactive protein (CRP) were assessed in both groups. LDL-cholesterol, HOMA-IR and QUICKI indices were calculated. Flow-mediated Vasodilatation (FMD) was determined for the evaluation of endothelial function. RESULTS Increased HOMA-IR was observed in children who were at risk for overweight. Waist circumference was the main predictor of insulin resistance in these children. Higher levels of CRP were found in the study group compared to controls, while plasma fibrinogen did not differ in the two groups. The children who were at risk for overweight had lower FMD values and slightly elevated lipids compared to controls; however, these differences were not statistically significant. CONCLUSION Insulin resistance and inflammation indices were higher in children who were at risk for overweight as has been shown for obese children. The data suggest that appropriate treatment strategies for weight control are essential not only for obese children but also for those at risk for overweight.
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Affiliation(s)
- Gulcin Akinci
- Department of Pediatrics, Celal Bayar University Medical School, Manisa, Turkey
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27
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Naya T, Hosomi N, Ohyama H, Ichihara SI, Ban CR, Takahashi T, Taminato T, Feng A, Kohno M, Koziol JA. Smoking, fasting serum insulin, and obesity are the predictors of carotid atherosclerosis in relatively young subjects. Angiology 2008; 58:677-84. [PMID: 18216377 DOI: 10.1177/0003319707303589] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
The purpose of this study was to identify predictors of atherosclerosis in a healthy young cohort comprised of 241 subjects who underwent a regular employee medical check-up at Ohshima National Sanatorium over a 9-month period. All subjects underwent carotid ultrasound examinations to determine maximal common carotid artery intima media thickness. In addition, serum total cholesterol, triglycerides, high-density lipoprotein cholesterol, blood urea nitrogen, creatinine, glucose, and insulin were evaluated. The subjects were relatively young (mean age, 44 years; range, 18 to 62 years), with 130 females (54%) and 111 males (46%). Maximal common carotid artery intima media thickness was predicted by smoking habit, body mass index, fasting blood sugar, fasting serum insulin, and systolic blood pressure (F(5,235) = 52.8, P < 10(-5)). There was clear separation in common carotid artery intima media thickness values based on body mass index, smoking, and fasting serum insulin, and somewhat more overlap with systolic blood pressure and fasting blood sugar. These findings suggest that smoking and high values of body mass index, fasting serum insulin, systolic blood pressure, and fasting blood sugar are warning factors for early atherosclerosis development, and could conceivably serve as the basis of diagnostic screening. Smoking is particularly deleterious, as smokers with high body mass index, high fasting serum insulin, or high systolic blood pressure tend to have larger common carotid artery intima media thickness values than would have been predicted by consideration solely of the individual risk factors.
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Affiliation(s)
- Takayuki Naya
- Department of Cardiorenal and Cerebrovascular Medicine, Division of Stroke, Kagawa University School of Medicine, Kagawa, Japan
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Kim HJ, Ahn CW, Kang ES, Myoung SM, Cha BS, Won YJ, Lim SK, Kim KR, Huh KB, Lee HC. The level of 2-h post-challenge glucose is an independent risk factor of carotid intima-media thickness progression in Korean type 2 diabetic patients. J Diabetes Complications 2007; 21:7-12. [PMID: 17189868 DOI: 10.1016/j.jdiacomp.2005.11.004] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/19/2005] [Revised: 07/15/2005] [Accepted: 11/08/2005] [Indexed: 10/23/2022]
Abstract
OBJECTIVE To evaluate the relationship between the metabolic abnormalities commonly associated with diabetes and the changes in carotid intima-media thickness (IMT) in Korean type 2 diabetic patients who do not have clinically manifest cardiovascular disease (CVD). DESIGN In a prospective study, a total of 152 type 2 diabetic patients were recruited from a group of outpatients at the Yonsei University Hospital. MATERIALS AND METHODS The carotid IMTs of 152 subjects with type 2 diabetes (mean age 63.5+/-7.0 years) were determined at baseline and after a mean follow-up time of 23.7+/-3.7 months. Fasting plasma glucose, serum total cholesterol (TC), serum triglyceride, high-density lipoprotein cholesterol (HDL-C), HbA1c, oral glucose tolerance test (OGTT) results for 2-h post-challenge glucose (2hPG), and blood pressure measurements were collected every 3 months and averaged. RESULTS The highest quartiles of baseline C-peptide and homeostatic model assessment (HOMA) index showed more IMT progression than the lowest quartiles. The change in the mean IMT correlated with average values of HbA1c (r=.219, P=.007), the 2-h post-challenge glucose (r=.239, P=.003), HDL-C (r=-.228, P=.005), LDL-C (r=.175, P=.033), and non-HDL-C (r=.194, P=.016). Multiple regression analysis demonstrated that the independent risk factor for the mean IMT change in diabetic patients was the average 2hPG level (P=.004). The change in the mean IMT of those in the lowest quartile of average 2hPG (<11.1 mmol/l) was 823+/-176 to 841+/-146 microm (P=.276). In the highest quartile (2hPG >15.3 mmol/l), however, the mean IMT increased from 794+/-127 to 882+/-153 microm (P<.001). CONCLUSION The 2hPG parameter among the various metabolic parameters exerts the greatest influence upon the prevention of carotid IMT progression in type 2 diabetic subjects. The level of 2hPG is an independent risk factor for the progression of carotid IMT in Korean type 2 diabetic patients.
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Affiliation(s)
- Hyeong-Jin Kim
- Division of Endocrinology, Department of Internal Medicine, Kwandong University College of Medicine, Myongji Hospital, Koyang, Korea
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Abstract
Despite criticism regarding its clinical relevance, the concept of the metabolic syndrome improves our understanding of both the pathophysiology of insulin resistance and its associated metabolic changes and vascular consequences. Free fatty acids (FFA) and tumour necrosis factor-alpha (TNF-alpha) play prominent roles in the development of insulin resistance by impairing the intracellular insulin signalling transduction pathway. Obesity is an independent risk factor for cardiovascular disease and strongly related to insulin resistance. In case of obesity, FFAs and TNF-alpha are produced in abundance by adipocytes, whereas the production of adiponectin, an anti-inflammatory adipokine, is reduced. This imbalanced production of pro- and anti-inflammatory adipokines, as observed in adipocyte dysfunction, is thought to be the driving force behind insulin resistance. The role of several recently discovered adipokines such as resistin, visfatin and retinol-binding protein (RBP)-4 in the pathogenesis of insulin resistance is increasingly understood. Insulin resistance induces several metabolic changes, including hyperglycaemia, dyslipidaemia and hypertension, all leading to increased cardiovascular risk. In addition, the dysfunctional adipocyte, reflected largely by low adiponectin levels and a high TNF-alpha concentration, directly influences the vascular endothelium, causing endothelial dysfunction and atherosclerosis. Adipocyte dysfunction could therefore be regarded as the common antecedent of both insulin resistance and atherosclerosis and functions as the link between obesity and cardiovascular disease. Targeting the dysfunctional adipocyte may reduce the risk for both cardiovascular disease and the development of type 2 diabetes. Although lifestyle intervention remains the cornerstone of therapy in improving insulin sensitivity and its associated metabolic changes, medical treatment might prove to be important as well.
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Affiliation(s)
- A M J Wassink
- Department of Vascular Medicine, University Medical Centre Utrecht, The Netherlands
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30
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Abstract
The metabolic syndrome, also known as the dysmetabolic syndrome, syndrome X or the insulin resistance syndrome, refers to the clustering of cardiovascular disease risk factors that are present in many individuals who are at increased risk for both cardiovascular events and type 2 diabetes. Prediabetic subjects typically exhibit an atherogenic pattern of cardiovascular risks that is associated with hyperinsulinaemia. Thus, identification of components of the metabolic syndrome is important if patients are to be treated early enough to prevent cardiovascular events and other complications related to diabetes. Therapies targeted to specific components of the metabolic syndrome such as improving glycaemic control, managing dyslipidaemia and reducing the prothrombotic state should help to minimize cardiovascular risk, particularly if initiated early. Traditional pharmacologic agents used to manage the individual components of the metabolic syndrome do not typically impact the other components. The thiazolidinediones, a new class of agents that improve insulin resistance, have the ability, in addition to their glucose-lowering effects, to exert several powerful anti-atherogenic properties, including anti-inflammatory effects in the vascular endothelium, redistribution of visceral fat and reduction of insulin resistance, hyperinsulinaemia and hyperproinsulinaemia. This makes the thiazolidinediones ideal candidates for the early treatment of many components associated with the metabolic syndrome.
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Affiliation(s)
- Kathleen L Wyne
- Division of Endocrinology and Metabolism, Department of Internal Medicine, University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390-8857, USA.
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Abstract
Coronary artery disease (CAD) is a leading cause of morbidity and mortality worldwide and was responsible for 7.2 million deaths in 2003. Various studies have pointed out that South Asians have a higher prevalence of CAD as compared with other ethnicities. South Asians may have a genetic predisposition to CAD; however, environmental, nutritional, and lifestyle factors may also be responsible. South Asians have a much higher prevalence of metabolic syndrome, diabetes, insulin resistance (and resultant hyperinsulinemia), central obesity, dyslipidemias (lower high-density lipoprotein, increased lipoprotein[a], higher triglyceride levels), increased thrombotic tendency (increased plasminogen activator inhibitor-1 and decreased tissue plasminogen activator levels), decreased levels of physical activity, and low birth weights ("fetal origins hypothesis"). In addition, the dietary indiscretions and sedentary lifestyle practiced by most South Asians puts them at a higher risk. A multidisciplinary approach involving the population at risk, healthcare personnel, and the government is required to diminish the incidence. Educational programs regarding the genetic predisposition as well as risk factors for CAD, physical activity, and dietary modifications need to be encouraged. There is a need for implementation of newer guidelines as well as a lower threshold for initiating therapeutic interventions in this population. Mass media should be involved to bring about behavioral changes, and these changes should be reinforced at the physician's level.
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Affiliation(s)
- Updesh Singh Bedi
- Department of Cardiology, Chicago Medical School-Veterans Affairs Medical Center, Chicago, Illinois 60064, USA
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Lender D, Sysko SK. The Metabolic Syndrome and Cardiometabolic Risk: Scope of the Problem and Current Standard of Care. Pharmacotherapy 2006; 26:3S-12S. [PMID: 16637782 DOI: 10.1592/phco.26.5part2.3s] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/13/2023]
Abstract
The metabolic syndrome is a public health concern because its prevalence is increasing in the United States, and it is associated with cardiovascular morbidity and mortality. We discuss epidemiologic trends in and causes of the metabolic syndrome. The relationships among the cardiometabolic risk factors that contribute to the metabolic syndrome-obesity, insulin resistance, proinflammatory and prothrombotic states, atherogenic dyslipidemia, and hypertension-and between these risk factors and cardiovascular morbidity and mortality are explained. Currently available interventions to modify these risk factors and the importance of preventive strategies and early detection efforts are also addressed.
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Affiliation(s)
- Dan Lender
- Division of Endocrinology, Diabetes, and Nutrition, School of Medicine, University of Maryland, Baltimore, Maryland 21201, USA.
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33
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Westphal SA, Palumbo PJ. A case for introducing insulin early in the treatment of type 2 diabetes mellitus. ACTA ACUST UNITED AC 2006. [DOI: 10.1016/s1557-0843(06)80012-6] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/09/2023]
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Rosenberg DE, Jabbour SA, Goldstein BJ. Insulin resistance, diabetes and cardiovascular risk: approaches to treatment. Diabetes Obes Metab 2005; 7:642-53. [PMID: 16219008 DOI: 10.1111/j.1463-1326.2004.00446.x] [Citation(s) in RCA: 42] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Abstract
The prevalence of diabetes is increasing worldwide. Insulin resistance and diabetes mellitus are major predictors of cardiovascular ischaemic disease. Other risk factors for cardiovascular death including hypertension, dyslipidaemia, smoking and visceral obesity are especially lethal in diabetics. C-reactive protein, plasminogen activator inhibitor-1, matrix metalloproteinases and other emerging risk factors and their roles are continually being researched and discovered. Treatment of this syndrome must be aimed at lifestyle modification, glycaemic control and management of concomitant risk factors. Diet and exercise play a vital role in the treatment of diabetes and the metabolic syndrome. Weight reduction and increased physical activity will improve insulin resistance, hyperglycaemia, hypertension and dyslipidaemia. Hypertension management has been shown to be especially important in diabetics to prevent cardiovascular events. Likewise, multiple clinical trials show that reduction of cholesterol is even more vital in diabetics than the general population for risk reduction of coronary disease. There is a great deal of evidence that tight control of glycaemia is essential to treatment of this condition. There are a variety of available pharmacological agents available including metformin, insulin secretagogues, alpha-glucosidase inhibitors, thiazolidinediones and insulin. The mechanisms and side effects of these medications are discussed. As macrovascular disease is the major cause of morbidity and mortality, an early, aggressive, multi-factorial approach to treatment of the metabolic syndrome and diabetes is vital to prevent adverse cardiac outcomes.
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Affiliation(s)
- Daniel E Rosenberg
- Division of Endocrinology, Diabetes and Metabolic Diseases, Department of Medicine, Jefferson Medical College of Thomas Jefferson University, Philadelphia, PA 19107, USA
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35
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Oterdoom LH, de Vries APJ, van Son WJ, van der Heide JJH, Ploeg RJ, Gansevoort RT, de Jong PE, Gans ROB, Bakker SJL. Validation of insulin resistance indexes in a stable renal transplant population. Diabetes Care 2005; 28:2424-9. [PMID: 16186274 DOI: 10.2337/diacare.28.10.2424] [Citation(s) in RCA: 29] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
OBJECTIVE The purpose of this study was to investigate the validity of established insulin resistance indexes, based on fasting blood parameters, in a stable renal transplant population. RESEARCH DESIGN AND METHODS Fasting insulin, homeostasis model assessment (HOMA), the quantitative insulin sensitivity check index (QUICKI), and McAuley's index were assessed for correlation and agreement with whole-body glucose uptake (M value) divided by prevailing serum insulin concentrations (I value) assessed during a hyperinsulinemic-euglycemic clamp in 51 stable renal transplant recipients, who were at a median of 7.5 years after transplant. Multivariate linear regression analyses were used to determine independent risk factors for insulin resistance. RESULTS The M/I value correlated with fasting insulin concentration (r = -0.56), HOMA (r = -0.53), QUICKI (r = 0.52), and McAuley's index (r = 0.61) (all P < 0.01). Linear regression showed agreement between all indexes and insulin resistance. However, McAuley's index showed the strongest agreement irrespective of age, sex, renal allograft function, and obesity. In multivariate analysis, fasting insulin concentration (beta = -0.59, P = 0.002), fasting triglyceride concentration (beta = -0.33, P = 0.04), and BMI (beta = -1.22, P = 0.05) were independently associated with the M/I value. CONCLUSIONS All investigated insulin resistance indexes were valid estimates of insulin resistance in the long-term stable renal transplant population. However, correlation and agreement were strongest for McAuley's index. In addition to fasting insulin and triglyceride concentrations, of which McAuley's index is composed, only BMI seemed to be independently associated with insulin resistance in this population.
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Affiliation(s)
- Leendert H Oterdoom
- Renal Transplant Program, University of Groningen and University Medical Center Groningen, P.O. Box 30.001, 9700 RB Groningen, Netherlands
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Montalcini T, Gorgone G, Federico D, Ceravolo R, Emanuele V, Sesti G, Perticone F, Pujia A. Association of LDL cholesterol with carotid atherosclerosis in menopausal women affected by the metabolic syndrome. Nutr Metab Cardiovasc Dis 2005; 15:368-372. [PMID: 16216723 DOI: 10.1016/j.numecd.2004.10.003] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/19/2004] [Revised: 08/26/2004] [Accepted: 10/28/2004] [Indexed: 10/25/2022]
Abstract
BACKGROUND AND AIM The metabolic syndrome is a highly prevalent condition associated with cardiovascular disease. However, the contribution of LDL to cardiovascular risk is not estimated since it is not part of ATP III criteria. METHODS AND RESULTS This is an observational study evaluating the association between metabolic syndrome and carotid atherosclerosis, according to LDL cholesterol levels. Two hundred and sixty-five menopausal women were consecutively enrolled, they all underwent clinical examination, biochemical characterization and ultrasound evaluation. In particular, carotid atherosclerosis, a well known marker of cardiovascular disease, was evaluated. Women affected by cardiovascular disease were excluded from the study. The metabolic syndrome was found strongly associated with carotid atherosclerosis in our study population. In individuals with normal or near normal LDL, the incidence of carotid atherosclerosis was significantly lower than in subject with high LDL. A high plasma LDL concentration was independently associated with carotid atherosclerosis (p=0.026) among women with the metabolic syndrome. CONCLUSIONS High LDL cholesterol levels are associated with carotid atherosclerosis in menopausal women with the metabolic syndrome. Although it remains prudent to recommend an integrated control of all modifiable risk factors to prevent cardiovascular disease, decreasing LDL levels should be considered a high priority.
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Affiliation(s)
- Tiziana Montalcini
- Department of Clinical and Experimental Medicine "G. Salvatore", University of Catanzaro Magna Graecia, Via T Campanella, 88100 Catanzaro, Italy
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Nicasio J, McFarlane SI. Early insulin therapy and the risk of cardiovascular disease in Type 2 diabetes. ACTA ACUST UNITED AC 2005. [DOI: 10.2217/14750708.2.5.685] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
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Bauduceau B, Baigts F, Bordier L, Burnat P, Ceppa F, Dumenil V, Dupuy O, Le Berre JP, Mayaudon H, Paillasson S. Epidemiology of the metabolic syndrome in 2045 French military personnel (EPIMIL study). DIABETES & METABOLISM 2005; 31:353-9. [PMID: 16369197 DOI: 10.1016/s1262-3636(07)70204-5] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
Abstract
CONTEXT The Metabolic syndrome is considered to be an important public health problem, but few epidemiological studies have defined the present situation in France. EPIMIL is a prospective epidemiological study that began on February 1, 2003. SUBJECTS AND METHODS This study was designed to identify the clinical and laboratory parameters of metabolic syndrome and cardiovascular risk factors in a population of 2045 male military personnel based in the Paris region. The initial 1-year cross-sectional study will be followed by a 10-year follow-up and patient care. RESULTS The 2045 subjects included 185 (9%) presented at least 3 of the 5 NCEP ATP III criteria defining metabolic syndrome. They were significantly older (42.2 +/- 8.5 yrs) than the other subjects (37.3 +/- 8.7 yrs, P<0.001), had a higher BMI (29.5 +/- 3.4 vs 24.8 +/- 2.9 kg/m2, P<0.001) and a greater body weight at age 20 (75.4 +/- 11 vs 70.4 +/- 8.5 kg, P<0.01). Smoking, little physical activity and family histories of diabetes and arterial hypertension were more frequent in these men. While levels of the cholesterol and CRP us were higher, Lp(a) and homocysteine concentrations were normal. Plasma insulin and BMI (r = 0.456 P<0.0001) and plasma insulin and waist circumference (r = 0.446 P<0.0001) were well correlated. Lastly, plasma insulin, free fatty acids and cardiovascular risk increased steadily with the increase in the number of metabolic syndrome criteria. CONCLUSIONS These results in a large and particularly uniform population of men show the prevalence of metabolic syndrome in adult men, and demonstrate its link with insulin resistance. Men with several risk factors require specific care, particularly for hypertension and dyslipidemia; the effectiveness of this care will be evaluated during the follow-up period.
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Affiliation(s)
- B Bauduceau
- Service d'Endocrinologie, hôpital d'Instruction des Armées Bégin, 69, avenue de Paris, 94160 Saint-Mandé, France.
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Ness KK, Oakes JM, Punyko JA, Baker KS, Gurney JG. Prevalence of the metabolic syndrome in relation to self-reported cancer history. Ann Epidemiol 2005; 15:202-6. [PMID: 15723765 DOI: 10.1016/j.annepidem.2004.07.092] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2004] [Accepted: 07/22/2004] [Indexed: 12/20/2022]
Abstract
PURPOSE To estimate the prevalence of metabolic syndrome in persons with a history of cancer from a population-based sample of adults, and compare that prevalence to persons without a history of cancer. METHODS Data from the Third National Health and Nutrition Examination Survey were analyzed to compare prevalence and prevalence differences of the metabolic syndrome, as defined by Adult Treatment Panel III criteria, between 486 persons with a reported history of cancer and 12,526 persons with no reported history of cancer. RESULTS The prevalence of metabolic syndrome was 258/1000 persons for those with a cancer history and 184/1000 persons among those without, resulting in a prevalence difference of 74/1000 persons (95% CI, 38-110). Prevalence differences varied substantially by age at interview. The prevalence difference was highest among those aged 40 to 49 years (112/1000 persons) and 50 to 59 years (73/1000 persons), while those in younger (18-39 years) and older (: 60 years) age groups had a moderately higher prevalence among those without a cancer history. CONCLUSION These results add to the emerging concern that metabolic syndrome and associated risks for cardiovascular disease and type 2 diabetes may be an adverse late effect of cancer and/or its treatment.
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Affiliation(s)
- Kirsten K Ness
- Division of Epidemiology and Clinical Research, Department of Pediatrics, School of Medicine, University of Minnesota, Minneapolis, MN 55455, USA
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Hwalla N, Shaker L, Torbay N, Azar ST, Habbal Z, Adra N. Postprandial glycemic and insulinemic responses to high-carbohydrate vs high-protein meals in obese normoglycemic subjects with varied insulin sensitivity. Nutr Res 2005. [DOI: 10.1016/j.nutres.2005.05.002] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
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Abstract
Acromegaly is associated with insulin resistance and an increased incidence of cardiovascular disease. However, it remains unclear to what extent the effects of growth hormone (GH) excess on cardiovascular morbidity and mortality are mediated through insulin resistance versus through other direct or indirect effects of GH. Adequate control of GH excess by surgery or pharmacologic interventions is associated with decreased insulin resistance, reflected in decreased plasma insulin levels and fasting glucose levels or improved glucose tolerance. Despite divergent effects of both somatostatin and somatostatin analogs on GH, insulin and glucagon secretion, and glucose absorption, treatment with the somatostatin analogs octreotide and lanreotide has only limited effects on glucose metabolism. However, glucose sensitivity has only been formally examined using a hyperinsulinemic euglycemic clamp in a minority of these studies. Treatment with the GH-receptor antagonist pegvisomant ameliorates insulin sensitivity, reflected in decreased fasting plasma insulin levels and fasting glucose levels. Nonetheless, the effect of pegvisomant on glucose sensitivity has not been formally tested by hyperinsulinemic clamp conditions. In acromegaly, preliminary observations on new octreotide analogs with greater specificity for somatostatin-receptor subtypes indicate that these compounds achieve better control of GH hypersecretion than octreotide, but may also negatively influence insulin release. Assessment of insulin secretion and glucose levels in acromegalic patients during administration of these compounds is thus mandatory.
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Affiliation(s)
- Alberto M Pereira
- Department of Endocrinology & Metabolism, Leiden University Medical Center, Leiden, The Netherlands.
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El-Atat FA, Nicasio J, Clark LT, McFarlane SI. An overview of the beneficial cardiovascular effects of thiazolidinediones. ACTA ACUST UNITED AC 2005. [DOI: 10.2217/14750708.2.1.113] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
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Li L, Yang GY. Effect of hepatic glucose production on acute insulin resistance induced by lipid-infusion in awake rats. World J Gastroenterol 2004; 10:3208-11. [PMID: 15457577 PMCID: PMC4611275 DOI: 10.3748/wjg.v10.i21.3208] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
AIM: To explore the influence of hepatic glucose production on acute insulin resistance induced by a lipid infusion in awake rats.
METHODS: A hyperinsulinaemic-euglycaemic clamp was established in awake chronically catheterized rats. Two groups of rats were studied either with a 4-h intraarterial infusion of lipid/heparin or saline. Insulin-mediated peripheral and hepatic glucose metabolism was assessed by hyperinsulinaemic-euglycaemic clamp combined with [3-3H]-glucose infusion.
RESULTS: During hyperinsulinaemic-euglycaemic clamp, there was a significant increase in plasma free fatty acid (FFA, from 741.9 ± 50.6 to 2346.4 ± 238.5 μmol/L, P < 0.01) in lipid-infused group. The glucose infusion rates (GIR) in the lipid infusion rats, compared to control rats, were significantly reduced (200-240 min average: Lipid infusion; 12.6 ± 1.5 vs control; 34.0 ± 1.6 mg/kg.min, P < 0.01), declining to - 35% of the corresponding control values during the last time of the clamp (240 min: Lipid infusion; 12.0 ± 1.9 vs control; 34.7 ± 1.7 mg/kg·min, P < 0.0001). At the end of clamp study, the hepatic glucose production (HGP) in control rats was significantly suppressed (88%) from 19.0 ± 4.5 (basal) to 2.3 ± 0.9 mg/kg.min (P < 0.01). The suppressive effect of insulin on HGP was significantly blunted in the lipid-infused rats (200-240 min: From 18.7 ± 3.0 to 23.2 ± 3.1 mg/kg·min (P < 0.05). The rate of glucose disappearance (GRd) was a slight decrease in the lipid-infused rats compared with controls during the clamp.
CONCLUSION: These data suggest that lipid infusion could induces suppression of hepatic glucose production, impairs the abilities of insulin to suppress lipolysis and mediate glucose utilization in peripheral tissue. Therefore, we conclude that lipid-infusion induces an acute insulin resistance in vivo.
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Affiliation(s)
- Ling Li
- Department of Endocrinology, The Second Affiliated Hospital, Chongqing Medical University, Chongqing 400010, China
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Aminot-Gilchrist DV, Anderson HDI. Insulin resistance-associated cardiovascular disease: potential benefits of conjugated linoleic acid. Am J Clin Nutr 2004; 79:1159S-1163S. [PMID: 15159251 DOI: 10.1093/ajcn/79.6.1159s] [Citation(s) in RCA: 27] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Abstract
Type 2 diabetes and associated cardiovascular disease have reached global epidemic proportions. Recent data from the World Health Organization Multinational Study of Vascular Disease in Diabetes indicate that cardiovascular disease is the leading cause of mortality (52% of deaths) in individuals with type 2 diabetes. Although insulin resistance plays a critical role in the pathogenesis of type 2 diabetes-related cardiovascular disease, other related risk factors often cluster in a single patient; the combination of insulin resistance and these risk factors is known as the metabolic syndrome. According to the World Health Organization definition, this constellation of risk factors includes hypertension, elevated plasma triacylglycerol, reduced HDL cholesterol, central obesity, and microalbuminuria. The Multiple Risk Factor Intervention Trial showed that, although diabetes or insulin resistance is an independent risk factor for cardiovascular disease mortality, these other components of the metabolic syndrome confer additive risk. Thus, to effectively address cardiovascular disease in persons with diabetes, intervention would ideally target all these factors. Conjugated linoleic acid could represent a candidate agent. The therapeutic potential of conjugated linoleic acid against insulin resistance-associated cardiovascular disease is discussed on the basis of the reported effects of conjugated linoleic acid on individual components of the metabolic syndrome.
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Affiliation(s)
- Denise V Aminot-Gilchrist
- National Centre for Agri-Food Research in Medicine, St Boniface General Hospital Research Centre, Winnipeg, Canada
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Abstract
There is a high prevalence of type 2 diabetes mellitus and coronary artery disease among urban and migrant Asian Indians, despite the absence of traditional risk factors. Evidence exists that Asian Indians are more insulin resistant than white persons and that insulin resistance may play an important role in the pathogenesis of these diseases. Increased visceral fat in Asian Indians is associated with increased generalized obesity, which is not apparent from their nonobese body mass index. Increased visceral fat is related to dyslipidemia and increased frequency of insulin resistance and may account for the increased prevalence of diabetes mellitus and cardiovascular disease in Asian Indians. In addition, early protein energy deprivation, as indicated by low weight at birth and at 1 year of age, may induce a state of vulnerability to the development of type 2 diabetes in later life, especially if the quantitative and qualitative aspects of nutrition and altered lifestyles during adult years pose an additional challenge.
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Affiliation(s)
- Mandeep Bajaj
- Diabetes Division, Department of Medicine, University of Texas Health Science Center, 7703 Floyd Curl Drive, San Antonio, TX 78284-7886, USA.
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Dandona P, Aljada A, O'donnell A, Dhindsa S, Garg R. Insulin Is an Anti-inflammatory and Anti-atherosclerotic Hormone. Metab Syndr Relat Disord 2004; 2:137-42. [DOI: 10.1089/met.2004.2.137] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023] Open
Affiliation(s)
- Paresh Dandona
- Division of Endocrinology, Diabetes and Metabolism, State University of New York and Kaleida Health, Buffalo, New York
| | - Ahmad Aljada
- Division of Endocrinology, Diabetes and Metabolism, State University of New York and Kaleida Health, Buffalo, New York
| | - Amy O'donnell
- Division of Endocrinology, Diabetes and Metabolism, State University of New York and Kaleida Health, Buffalo, New York
| | - Sandeep Dhindsa
- Division of Endocrinology, Diabetes and Metabolism, State University of New York and Kaleida Health, Buffalo, New York
| | - Rajesh Garg
- Division of Endocrinology, Diabetes and Metabolism, State University of New York and Kaleida Health, Buffalo, New York
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Abstract
Type 2 diabetes is a rapidly growing disorder that affects millions of Americans. It usually results from a combination of insulin resistance and a beta-cell secretory defect leading to hyperglycemia and microvascular and macrovascular complications, including cardiovascular disease. With the increasing number of options available for the treatment of type 2 diabetes, it can be difficult to determine which medication to prescribe for each patient. Ideally, an agent that effectively lowers glucose concentrations while also minimizing disease progression should be chosen. The thiazolidinediones (TZDs), a relatively newer class of antidiabetic agents, have been shown to be efficacious in lowering glucose concentrations, maintaining glycemic control, and improving other cardiovascular risk factors. These include reduction of visceral adiposity, alteration of lipoprotein concentrations with a favorable distribution of cholesterol subfractions, and decreasing markers of inflammation and endothelial dysfunction. Overall, the TZDs appear to be a promising therapeutic option for consistent control of glucose levels and may slow the progression of type 2 diabetes.
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Affiliation(s)
- Shanti Serdy
- Joslin Diabetes Center and Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, USA
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Jellinger PS. Emerging concepts in management of the insulin resistance syndrome. Endocr Pract 2003; 9 Suppl 2:105-12. [PMID: 14698988 DOI: 10.4158/ep.9.s2.105] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
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Abate N, Carulli L, Cabo-Chan A, Chandalia M, Snell PG, Grundy SM. Genetic polymorphism PC-1 K121Q and ethnic susceptibility to insulin resistance. J Clin Endocrinol Metab 2003; 88:5927-5934. [PMID: 14671192 DOI: 10.1210/jc.2003-030453] [Citation(s) in RCA: 97] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Genetic susceptibility may be responsible for high prevalence of insulin resistance in Asian Indians. This study was carried out in samples of local Asian Indians and Caucasians to determine whether plasma cell membrane glycoprotein (PC)-1 K121Q and insulin receptor substrate-1 (IRS-1) G972A polymorphisms contribute significantly to susceptibility to insulin resistance in Asian Indians. The frequency of carrying at least one copy of the PC-1 121Q variant in Asian Indians was significantly higher than that in Caucasians (P = 0.01), but the frequency was similar for IRS-1 972A (6% and 7%). A significantly higher insulin area under the curve during oral glucose tolerance testing (P < 0.0001) and lower insulin sensitivity during hyperinsulinemic-euglycemic clamps (P = 0.04) were found in Asian Indians with PC-1 121Q variant compared with Asian Indians with wild-type PC-1 and with Caucasians with or without the polymorphism. IRS-1 972A was not associated with any change in insulin sensitivity. We conclude that the PC-1 K121Q polymorphism associates with primary insulin resistance in migrant Asian Indians. A relatively high frequency of this polymorphism thus may be one factor contributing to insulin resistance susceptibility in Asian Indians. This finding indicates the need for expanded studies on the association between PC-1 K121Q and insulin resistance in a representative sample of the Asian Indian population.
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Affiliation(s)
- Nicola Abate
- Center for Human Nutrition and the Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.
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