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Vashishth K, Singh SK, Jain A, Bhatia A, Sharma YP. Pathological involvement of apoptotic and inflammatory molecules in cardiovascular remodeling in rats on high fructose diet‐induced metabolic syndrome. J Food Biochem 2022; 46:e14107. [DOI: 10.1111/jfbc.14107] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2021] [Revised: 01/05/2022] [Accepted: 01/25/2022] [Indexed: 12/01/2022]
Affiliation(s)
- Kanupriya Vashishth
- Department of Cardiology Post Graduate Institute of Medical Education and Research Chandigarh India
| | - Sumit K. Singh
- University Institute of Engineering and Technology Panjab University Chandigarh India
| | - Annish Jain
- Department of Cardiology Post Graduate Institute of Medical Education and Research Chandigarh India
| | - Alka Bhatia
- Department Experimental Medicine and Biotechnology Post Graduate Institute of Medical Education and Research Chandigarh India
| | - Yash P. Sharma
- Department of Cardiology Post Graduate Institute of Medical Education and Research Chandigarh India
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Lee HA, Kim MJ, Han JS. Alleviating effects of lupeol on postprandial hyperglycemia in diabetic mice. Toxicol Res (Camb) 2021; 10:495-500. [PMID: 34141163 DOI: 10.1093/toxres/tfab019] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2020] [Revised: 11/09/2020] [Accepted: 02/16/2021] [Indexed: 11/13/2022] Open
Abstract
This study aimed to investigate the inhibition activities of lupeol on carbohydrate digesting enzymes and its ability to improve postprandial hyperglycemia in streptozotocin (STZ)-induced diabetic mice. α-Glucosidase and α-amylase inhibitory assays were executed using a chromogenic method. The effect of lupeol on hyperglycemia after a meal was measured by postprandial blood glucose in STZ-induced diabetic and normal mice. The mice were treated orally with soluble starch (2 g/kg BW) alone (control) or with lupeol (10 mg/kg BW) or acarbose (10 mg/kg BW) dissolved in water. Blood samples were taken from tail veins at 0, 30, 60, and 120 min and blood glucose was measured by a glucometer. Lupeol showed noticeable inhibitory activities on α-glucosidase and α-amylase. The half-maximal inhibitory concentrations (IC50) of lupeol on α-glucosidase and α-amylase were 46.23 ± 9.03 and 84.13 ± 6.82 μM, respectively, which were more significantly effective than those of acarbose, which is a positive control. Increase in postprandial blood glucose level was more significantly lowered in the lupeol-administered group than in the control group of both STZ-induced diabetic and normal mice. In addition, the area under the curve was significantly declined with lupeol administration in the STZ-induced diabetic mice. These findings suggest that lupeol can help lower the postprandial hyperglycemia by inhibiting carbohydrate-digesting enzymes.
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Affiliation(s)
- Hyun-Ah Lee
- Department of Food Science and Nutrition, Pusan National University, Busan 46241, Republic of Korea
| | - Min-Jung Kim
- Department of Food Science and Nutrition, Pusan National University, Busan 46241, Republic of Korea
| | - Ji-Sook Han
- Department of Food Science and Nutrition, Pusan National University, Busan 46241, Republic of Korea
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Taskinen MR, Björnson E, Matikainen N, Söderlund S, Pietiläinen KH, Ainola M, Hakkarainen A, Lundbom N, Fuchs J, Thorsell A, Andersson L, Adiels M, Packard CJ, Borén J. Effects of liraglutide on the metabolism of triglyceride-rich lipoproteins in type 2 diabetes. Diabetes Obes Metab 2021; 23:1191-1201. [PMID: 33502078 DOI: 10.1111/dom.14328] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/21/2020] [Revised: 01/08/2021] [Accepted: 01/23/2021] [Indexed: 01/07/2023]
Abstract
AIM To elucidate the impact of liraglutide on the kinetics of apolipoprotein (apo)B48- and apoB100-containing triglyceride-rich lipoproteins in subjects with type 2 diabetes (T2D) after a single fat-rich meal. MATERIALS AND METHODS Subjects with T2D were included in a study to investigate postprandial apoB48 and apoB100 metabolism before and after 16 weeks on l.8 mg/day liraglutide (n = 14) or placebo (n = 4). Stable isotope tracer and compartmental modelling techniques were used to determine the impact of liraglutide on chylomicron and very low-density lipoprotein (VLDL) production and clearance after a single fat-rich meal. RESULTS Liraglutide reduced apoB48 synthesis in chylomicrons by 60% (p < .0001) and increased the triglyceride/apoB48 ratio (i.e. the size) of chylomicrons (p < .001). Direct clearance of chylomicrons, a quantitatively significant pathway pretreatment, decreased by 90% on liraglutide (p < .001). Liraglutide also reduced VLDL1 -triglyceride secretion (p = .017) in parallel with reduced liver fat. Chylomicron-apoB48 production and particle size were related to insulin sensitivity (p = .015 and p < .001, respectively), but these associations were perturbed by liraglutide. CONCLUSIONS In a physiologically relevant setting that mirrored regular feeding in subjects with T2D, liraglutide promoted potentially beneficial changes on postprandial apoB48 metabolism. Using our data in an integrated metabolic model, we describe how the action of liraglutide in T2D on chylomicron and VLDL kinetics could lead to decreased generation of remnant lipoproteins.
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Affiliation(s)
- Marja-Riitta Taskinen
- Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland
| | - Elias Björnson
- Department of Molecular and Clinical Medicine, University of Gothenburg, Gothenburg, Sweden
| | - Niina Matikainen
- Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland
- Endocrinology, Abdominal Center, Helsinki University Hospital, Helsinki, Finland
| | - Sanni Söderlund
- Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland
- Endocrinology, Abdominal Center, Helsinki University Hospital, Helsinki, Finland
| | - Kirsi H Pietiläinen
- Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland
- Endocrinology, Abdominal Center, Helsinki University Hospital, Helsinki, Finland
| | - Mari Ainola
- Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland
| | - Antti Hakkarainen
- HUS Medical Imaging Center, Radiology, Helsinki University Hospital, University of Helsinki, Finland
- Department of Neuroscience and Biomedical Engineering, Aalto University School of Science, Espoo, Finland
| | - Nina Lundbom
- HUS Medical Imaging Center, Radiology, Helsinki University Hospital, University of Helsinki, Finland
| | - Johannes Fuchs
- Proteomics Core Facility at Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Annika Thorsell
- Proteomics Core Facility at Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Linda Andersson
- Department of Molecular and Clinical Medicine, University of Gothenburg, Gothenburg, Sweden
| | - Martin Adiels
- Department of Molecular and Clinical Medicine, University of Gothenburg, Gothenburg, Sweden
| | - Chris J Packard
- Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK
| | - Jan Borén
- Department of Molecular and Clinical Medicine, University of Gothenburg, Gothenburg, Sweden
- Wallenberg Laboratory/Cardiology, Sahlgrenska University Hospital, Gothenburg, Sweden
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Takao T, Suka M, Yanagisawa H, Iwamoto Y. Impact of postprandial hyperglycemia at clinic visits on the incidence of cardiovascular events and all-cause mortality in patients with type 2 diabetes. J Diabetes Investig 2017; 8:600-608. [PMID: 27978599 PMCID: PMC5497051 DOI: 10.1111/jdi.12610] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/31/2016] [Revised: 11/27/2016] [Accepted: 12/06/2016] [Indexed: 12/24/2022] Open
Abstract
AIMS/INTRODUCTION We evaluated the impact of postprandial hyperglycemia at clinic visits on the incidence of cardiovascular diseases (CVD) and all-cause mortality independently of mean glycosylated hemoglobin in type 2 diabetes patients in a real-world setting. MATERIALS AND METHODS The present retrospective observational cohort study included 646 type 2 diabetes patients. All of the participants had their initial consultations at the Institute for Diabetes Care and Research, Asahi Life Foundation affiliated Marunouchi Hospital, Tokyo, Japan, during the period from 1995 to 1996, visited the clinic ≥4 times, had their 2-h post-breakfast blood glucose (2h-PBBG) levels measured and were followed up for ≥1 year. The 646 patients were followed up for survival. Of the 646 patients, 618 had no history of CVD at the first visit and had measured 2h-PBBG until the first CVD onset or censorings. These two cohorts were followed up through June 2012, and subsequently questionnaires were mailed. Multivariate Cox proportional hazard models were used to evaluate the risk of CVD incidence and death. RESULTS CVD occurred in 78 patients, and 56 patients died. The median follow-up periods of the CVD cohort and the mortality cohort were 15.6 and 15.9 years, respectively. The mean 2h-PBBG is a significant predictor of the CVD incidence and all-cause mortality after adjusting for the mean glycosylated hemoglobin, the number of 2h-PBBG measurements, age, sex and classical risk factors. CONCLUSIONS Postprandial hyperglycemia represented by the mean level of 2h-PBBG at clinic visits is associated with CVD incidence and all-cause mortality independently of the mean glycosylated hemoglobin level in type 2 diabetes patients. Prospective interventional trials are warranted to confirm the present findings.
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Affiliation(s)
- Toshiko Takao
- Division of Diabetes and MetabolismThe Institute for Adult DiseasesAsahi Life FoundationTokyoJapan
| | - Machi Suka
- Department of Public Health and Environmental MedicineThe Jikei University School of MedicineTokyoJapan
| | - Hiroyuki Yanagisawa
- Department of Public Health and Environmental MedicineThe Jikei University School of MedicineTokyoJapan
| | - Yasuhiko Iwamoto
- Division of Diabetes and MetabolismThe Institute for Adult DiseasesAsahi Life FoundationTokyoJapan
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Muller CJF, Malherbe CJ, Chellan N, Yagasaki K, Miura Y, Joubert E. Potential of rooibos, its major C-glucosyl flavonoids, and Z-2-(β-D-glucopyranosyloxy)-3-phenylpropenoic acid in prevention of metabolic syndrome. Crit Rev Food Sci Nutr 2017; 58:227-246. [PMID: 27305453 DOI: 10.1080/10408398.2016.1157568] [Citation(s) in RCA: 46] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/09/2023]
Abstract
Risk factors of type 2 diabetes mellitus (T2D) and cardiovascular disease (CVD) cluster together and are termed the metabolic syndrome. Key factors driving the metabolic syndrome are inflammation, oxidative stress, insulin resistance (IR), and obesity. IR is defined as the impairment of insulin to achieve its physiological effects, resulting in glucose and lipid metabolic dysfunction in tissues such as muscle, fat, kidney, liver, and pancreatic β-cells. The potential of rooibos extract and its major C-glucosyl flavonoids, in particular aspalathin, a C-glucoside dihydrochalcone, as well as the phenolic precursor, Z-2-(β-D-glucopyranosyloxy)-3-phenylpropenoic acid, to prevent the metabolic syndrome, will be highlighted. The mechanisms whereby these phenolic compounds elicit positive effects on inflammation, cellular oxidative stress and transcription factors that regulate the expression of genes involved in glucose and lipid metabolism will be discussed in terms of their potential in ameliorating features of the metabolic syndrome and the development of serious metabolic disease. An overview of the phenolic composition of rooibos and the changes during processing will provide relevant background on this herbal tea, while a discussion of the bioavailability of the major rooibos C-glucosyl flavonoids will give insight into a key aspect of the bioefficacy of rooibos.
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Affiliation(s)
- Christo J F Muller
- a Biomedical Research and Innovation Platform , South African Medical Research Council , Tygerberg , South Africa
| | - Christiaan J Malherbe
- b Post-Harvest and Wine Technology Division , Agricultural Research Council (ARC), Infruitec-Nietvoorbij , Stellenbosch , South Africa
| | - Nireshni Chellan
- a Biomedical Research and Innovation Platform , South African Medical Research Council , Tygerberg , South Africa
| | - Kazumi Yagasaki
- c Division of Applied Biological Chemistry , Institute of Agriculture, Tokyo University of Agriculture and Technology , Fuchu , Tokyo , Japan.,d Center for Bioscience Research and Education , Utsunomiya University , Utsunomiya , Tochigi , Japan
| | - Yutaka Miura
- c Division of Applied Biological Chemistry , Institute of Agriculture, Tokyo University of Agriculture and Technology , Fuchu , Tokyo , Japan
| | - Elizabeth Joubert
- b Post-Harvest and Wine Technology Division , Agricultural Research Council (ARC), Infruitec-Nietvoorbij , Stellenbosch , South Africa.,e Department of Food Science , Stellenbosch University, Private Bag X1, Matieland Stellenbosch , South Africa
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Postprandial effects of wine consumption on Platelet Activating Factor metabolic enzymes. Prostaglandins Other Lipid Mediat 2017; 130:23-29. [PMID: 28323197 DOI: 10.1016/j.prostaglandins.2017.03.002] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2016] [Revised: 01/17/2017] [Accepted: 03/13/2017] [Indexed: 11/22/2022]
Abstract
Platelet Activating factor (PAF) is a potent inflammatory mediator that is involved in the initiation and the prolongation of atherosclerosis. The purpose of the study was to investigate the effect of wine consumption on the activity of PAF metabolic enzymes and on IL-6 levels as a cytokine inflammatory marker. Healthy men participated in 4 daily trials and consumed a standardized meal along with Robola wine (trial R), or Cabernet Sauvignon (trial CS), or ethanol solution (trial E), or water (trial W). A significant trial effect was found in the activity of lyso-PAF acetyltransferase (Lyso-PAF AT) (ptrial=0.01). In specific, R trial decreased enzyme activity compared to E trial (p=0.03) while a trend for differentiation was observed between CS trial and E one (p=0.06) as well as between R trial and W one (p=0.07). Concerning PAF-cholinephosphotransferase (PAF-CPT) activity, a significant trial effect was found (ptrial<0.00). Specifically, both R (p=0.002) and CS (p=0.001) trials decreased enzyme activity compared to E trial. Concerning lipoprotein-associated phospholipase A2 (LpPLA2) no time either trial effect was observed. Concerning IL-6 levels a significant time effect was found (ptime<0.00) while no trial effect was revealed. In conclusion, the protective effect of wine consumption could partly be explained through the modulation of PAF metabolism by wine micro-constituents that lead to lower PAF levels.
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Minato S, Takenouchi A, Uchida J, Tsuboi A, Kurata M, Fukuo K, Kazumi T. Association of Whole Blood Viscosity With Metabolic Syndrome in Type 2 Diabetic Patients: Independent Association With Post-Breakfast Triglyceridemia. J Clin Med Res 2017; 9:332-338. [PMID: 28270893 PMCID: PMC5330776 DOI: 10.14740/jocmr2885w] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/24/2016] [Indexed: 02/06/2023] Open
Abstract
Background Associations of whole blood viscosity (WBV) with metabolic syndrome (MS) have not been extensively studied in patients with type 2 diabetes. Methods Intrapersonal means of 12 measurements of waist circumference, blood pressure (BP) and high-density lipoprotein cholesterol and those of six measurements of fasting and post-breakfast triglycerides (TG) during 12 months were calculated in a cohort of 168 patients with type 2 diabetes. Based on these means, MS was diagnosed according to the modified National Cholesterol Education Program Adult Treatment Panel III criteria with the Asian definition of abdominal obesity. WBV was calculated from hematocrit and total serum protein concentrations by a validated formula. Results Diabetes patients with MS (n = 77) had higher WBV as compared to those without MS (6.38 ± 0.06 vs. 6.10 ± 0.07 cP, P = 0.004). As the number of MS components increased, WBV increased (component number 1: 6.12 ± 0.10, 2: 6.09 ± 0.10, 3: 6.37 ± 0.08, 4: 6.42 ± 0.10, 5: 6.30 ± 0.15 cP, P for trends = 0.001). Multiple regression analysis revealed that male gender, diastolic BP and post-breakfast TG were determinants of WBV independent of fasting TG, body mass index (BMI) and waist circumference (R2 = 0.258). Conclusions Both the presence of MS and the number of MS components were associated with higher WBV in patients with type 2 diabetes. Physicians need to perform a close follow-up of type 2 diabetes patients with MS on inhibitors of sodium-glucose co-transporters 2, which may increase stroke risk associated with an increase in hematocrit and therefore blood viscosity. Post-breakfast TG was an independent determinant of WBV. Elevated WBV may represent an important confounder of the relationship between MS, postprandial hyperlipidemia and elevated cardiovascular risk in this population.
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Affiliation(s)
- Satomi Minato
- Research Institute for Nutrition Sciences, Mukogawa Women's University, Nishinomiya, Hyogo, Japan; Graduate School of Human Science and Environment, University of Hyogo, Himeji, Hyogo, Japan
| | - Akiko Takenouchi
- Department of Food Sciences and Nutrition, School of Human Environmental Sciences, Mukogawa Women's University, Nishinomiya, Hyogo, Japan
| | - Junko Uchida
- Postgraduate School of Food Sciences and Nutrition, Mukogawa Women's University, Nishinomiya, Hyogo, Japan
| | - Ayaka Tsuboi
- Research Institute for Nutrition Sciences, Mukogawa Women's University, Nishinomiya, Hyogo, Japan; Department of Nutrition, Osaka City Juso Hospital, Osaka, Japan
| | - Miki Kurata
- Research Institute for Nutrition Sciences, Mukogawa Women's University, Nishinomiya, Hyogo, Japan; Department of Food Sciences and Nutrition, School of Human Environmental Sciences, Mukogawa Women's University, Nishinomiya, Hyogo, Japan; Postgraduate School of Food Sciences and Nutrition, Mukogawa Women's University, Nishinomiya, Hyogo, Japan
| | - Keisuke Fukuo
- Research Institute for Nutrition Sciences, Mukogawa Women's University, Nishinomiya, Hyogo, Japan; Department of Food Sciences and Nutrition, School of Human Environmental Sciences, Mukogawa Women's University, Nishinomiya, Hyogo, Japan; Postgraduate School of Food Sciences and Nutrition, Mukogawa Women's University, Nishinomiya, Hyogo, Japan
| | - Tsutomu Kazumi
- Research Institute for Nutrition Sciences, Mukogawa Women's University, Nishinomiya, Hyogo, Japan; Diabetes Division, Department of Medicine, Kohnan Kakogawa Hospital, Kakogawa, Hyogo, Japan
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Mottalib A, Mohd-Yusof BN, Shehabeldin M, Pober DM, Mitri J, Hamdy O. Impact of Diabetes-Specific Nutritional Formulas versus Oatmeal on Postprandial Glucose, Insulin, GLP-1 and Postprandial Lipidemia. Nutrients 2016; 8:nu8070443. [PMID: 27455318 PMCID: PMC4963919 DOI: 10.3390/nu8070443] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2016] [Revised: 06/24/2016] [Accepted: 07/19/2016] [Indexed: 12/26/2022] Open
Abstract
Diabetes-specific nutritional formulas (DSNFs) are frequently used as part of medical nutrition therapy for patients with diabetes. This study aims to evaluate postprandial (PP) effects of 2 DSNFs; Glucerna (GL) and Ultra Glucose Control (UGC) versus oatmeal (OM) on glucose, insulin, glucagon-like peptide-1 (GLP-1), free fatty acids (FFA) and triglycerides (TG). After an overnight fast, 22 overweight/obese patients with type 2 diabetes were given 200 kcal of each of the three meals on three separate days in random order. Blood samples were collected at baseline and at 30, 60, 90, 120, 180 and 240 min. Glucose area under the curve (AUC0–240) after GL and UGC was lower than OM (p < 0.001 for both). Insulin positive AUC0–120 after UGC was higher than after OM (p = 0.02). GLP-1 AUC0–120 and AUC0–240 after GL and UGC was higher than after OM (p < 0.001 for both). FFA and TG levels were not different between meals. Intake of DSNFs improves PP glucose for 4 h in comparison to oatmeal of similar caloric level. This is achieved by either direct stimulation of insulin secretion or indirectly by stimulating GLP-1 secretion. The difference between their effects is probably related to their unique blends of amino acids, carbohydrates and fat.
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Affiliation(s)
| | - Barakatun-Nisak Mohd-Yusof
- Joslin Diabetes Center, Boston, MA 02215, USA.
- Department of Nutrition and Dietetics, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Selangor 43400, Malaysia.
| | | | | | | | - Osama Hamdy
- Joslin Diabetes Center, Boston, MA 02215, USA.
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Nakamura K, Yamagishi S, Matsui T, Yoshida T, Imaizumi T, Makino T, Shimizu T, Inoue H. Acarbose, an α-Glucosidase Inhibitor, Decreases Aortic Gene Expression and Serum Levels of Monocyte Chemoattractant Protein-1 in Fructose-fed Rats. J Int Med Res 2016; 34:525-30. [PMID: 17133782 DOI: 10.1177/147323000603400510] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022] Open
Abstract
Insulin resistance is one of the determinants of post-prandial hyperglycaemia. Recently, acarbose, an α-glucosidase inhibitor that delays the absorption of carbohydrates from the small intestine, has been found to reduce the incidence of cardiovascular disease in patients with impaired glucose tolerance or diabetes. However, the molecular mechanism by which acarbose inhibits cardiovascular events remains unknown. In this study, we examined whether oral administration of acarbose could suppress expression of monocyte chemoattractant protein-1 (MCP-1) in fructose-fed rats, a widely used animal model of insulin resistance. Serum MCP-1 levels were elevated in fructose-fed rats after 4 weeks. Acarbose treatment for 4 weeks reduced the fructose-induced elevation of serum MCP-1 levels. Acarbose treatment for 8 weeks decreased MCP-1 mRNA levels in the aortae of fructose-fed rats. These results suggest that the cardioprotective effects of acarbose could be due, at least in part, to the suppression of MCP-1 expression.
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Affiliation(s)
- K Nakamura
- Department of Internal Medicine, Murume University School of Medicine, Kurume, Japan; 2Department of Dermatology, Faculty of Medicine, University of Toyama, Toyama, Japan
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Yin XF, Jeon YE, Chung HC, Choung SY, Shim JH, Kang IJ. In vitro efficacy evaluation for prevention of diabetes and diabetic complications using Aster sphathulifolius. Food Sci Biotechnol 2015. [DOI: 10.1007/s10068-015-0040-0] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022] Open
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Physical quality and in vitro starch digestibility of bread as affected by addition of extracted malva nut gum. Lebensm Wiss Technol 2014. [DOI: 10.1016/j.lwt.2014.04.046] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
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12
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Dairi S, Madani K, Aoun M, Him JLK, Bron P, Lauret C, Cristol JP, Carbonneau MA. Antioxidative properties and ability of phenolic compounds of Myrtus communis leaves to counteract in vitro LDL and phospholipid aqueous dispersion oxidation. J Food Sci 2014; 79:C1260-70. [PMID: 24962212 DOI: 10.1111/1750-3841.12517] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2013] [Accepted: 03/29/2014] [Indexed: 01/03/2023]
Abstract
UNLABELLED Antioxidant activities of Myrtus communis leaf phenolic compounds (McPCs) were investigated on 2,2'-9-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS(+) •) and oxygen radical absorbance capacity (ORAC) tests or on oxidation of biological models, human low-density lipoprotein (LDL) and phospholipid aqueous dispersion (L-α-phosphatidylcholine stabilized by bile salts). Two extraction techniques, microwave-assisted (MAE) and conventional (CE), were used to isolate McPCs, producing similar results of phenolic compound content. ABTS(+) • assay showed clearly that myrtle extracts exhibited a stronger scavenging effect than butylated hydroxyanisole and α-tocopherol, with a slight advantage for myrtle CE extract. In ORAC assay, the both McPC extracts were similarly less effective than the pure compounds as caffeic acid and myricitrin (myricetin 3-O-rhamnoside) but stronger than butylated hydroxytoluene. Moreover, myrtle CE and MAE extracts, and myricitrin were able to inhibit similarly the production of conjugated dienes and to prolong the lag phase (Tlag) during Cu(2+)-induced LDL oxidation with a dose-response effect. The cryo-electron microscopy observations on studied phospholipid dispersion stabilized by bile salts (BS) revealed the presence of bilayer vesicles and micelles. In 2,2'-azobis (2-amidinopropane) hydrochloride-induced phospholipid/BS oxidation, myrtle CE and MAE extracts gave similar effects to α-tocopherol and caffeic acid but myricitrin showed a higher protective effect than myrtle extracts. We showed also that no synergic or additive effect between α-tocopherol and myrtle extracts or caffeic acid in α-tocopherol-enriched phospholipid/BS dispersion, but myricitrin showed an additive effect and thus promoted the total antioxidant activity. These data showed that myrtle extract could be used as potential natural antioxidants, food stabilizers, or natural health products. PRACTICAL APPLICATION We show that microwave-assisted extraction could be an alternative method for plant phenolic compound recovery allowing important gain in time extraction.We report inhibition of low-density lipoprotein oxidation in vitro initiated by Cu(2+) ions. We report that myrtle extract may be a source of natural antioxidants to counteract phospholipid peroxidation as well as α-tocopherol.
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Affiliation(s)
- Sofiane Dairi
- Faculty of Nature and Life Sciences, 3BS Laboratory A. Mira Univ, Bejaia, 06000, Algeria; UMR 204 NUTRIPASS, - Univ., Inst. of Clinical Research - -641, Av. Doyen Gaston Giraud, 34093 Montpellier Cedex 5, France
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13
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Bailey DP, Locke CD. Breaking up prolonged sitting with light-intensity walking improves postprandial glycemia, but breaking up sitting with standing does not. J Sci Med Sport 2014; 18:294-8. [PMID: 24704421 DOI: 10.1016/j.jsams.2014.03.008] [Citation(s) in RCA: 228] [Impact Index Per Article: 20.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2013] [Revised: 02/21/2014] [Accepted: 03/06/2014] [Indexed: 11/25/2022]
Abstract
OBJECTIVES To explore the effects of breaking up prolonged sitting time with standing or light-intensity walking on a range of cardiometabolic risk markers. DESIGN A randomised three-period, three-treatment acute crossover trial. METHODS Ten non-obese adults took part in three trials: (1) uninterrupted sitting; (2) seated with 2-min bouts of standing every 20 min; and (3) seated with 2-min bouts of light-intensity walking every 20 min. Two standardised test drinks (total 80.3 carbohydrate, 50 g fat) were provided after an initial 1-h period of uninterrupted sitting. Plasma glucose and blood pressure were assessed hourly to calculate area under the curve. Total cholesterol, HDL, and triglycerides were assessed at baseline and 5-h. ANOVAs were used to explore between-trial differences. RESULTS Glucose area under the curve was lower in the activity-break condition compared to the uninterrupted sitting and standing-break conditions: mean area under the curve 18.5 (95% CI 17, 20), 22.0 (20.5, 23.5), and 22.2 (20.7, 23.7) mmol L/5-h, respectively, p<0.001; no difference between uninterrupted sitting and standing-break conditions (p>0.05). Systolic and diastolic blood pressure area under the curve did not differ significantly between conditions, nor did responses in lipid parameters (p>0.05). CONCLUSIONS This study suggests that interrupting sitting time with frequent brief bouts of light-intensity activity, but not standing, imparts beneficial postprandial responses that may enhance cardiometabolic health. These findings may have importance in the design of effective interventions to reduce cardiometabolic disease risk.
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Affiliation(s)
- Daniel P Bailey
- University of Bedfordshire, Institute for Sport and Physical Activity Research, Department of Sport Science and Physical Activity, UK.
| | - Christopher D Locke
- University of Bedfordshire, Institute for Sport and Physical Activity Research, Department of Sport Science and Physical Activity, UK
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Kanner J, Gorelik S, Roman S, Kohen R. Protection by polyphenols of postprandial human plasma and low-density lipoprotein modification: the stomach as a bioreactor. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2012; 60:8790-8796. [PMID: 22530973 DOI: 10.1021/jf300193g] [Citation(s) in RCA: 72] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/31/2023]
Abstract
Recent studies dramatically showed that the removal of circulating modified low-density lipoprotein (LDL) results in complete prevention of atherosclerosis. The gastrointestinal tract is constantly exposed to food, some of it containing oxidized compounds. Lipid oxidation in the stomach was demonstrated by ingesting heated red meat in rats. Red wine polyphenols added to the rats' meat diet prevented lipid peroxidation in the stomach and absorption of malondialdehyde (MDA) in rat plasma. In humans, postprandial plasma MDA levels rose by 3-fold after a meal of red meat cutlets. MDA derived from meat consumption caused postprandial plasma LDL modification in human. The levels of plasma MDA showed a 75% reduction by consumption of red wine polyphenols during the meat meal. Locating the main biological site of action of polyphenols in the stomach led to a revision in the understanding of how antioxidants work in vivo and may help to elucidate the mechanism involved in the protective effects of polyphenols in human health.
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Affiliation(s)
- Joseph Kanner
- Department of Food Science, ARO , Volcani Center, Bet Dagan, Israel.
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Miyamoto T, Fukuda K, Kimura T, Matsubara Y, Tsuda K, Moritani T. Effect of percutaneous electrical muscle stimulation on postprandial hyperglycemia in type 2 diabetes. Diabetes Res Clin Pract 2012; 96:306-12. [PMID: 22296854 DOI: 10.1016/j.diabres.2012.01.006] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/17/2011] [Revised: 10/14/2011] [Accepted: 01/03/2012] [Indexed: 10/14/2022]
Abstract
AIMS The aim of this study was to examine whether percutaneous electrical muscle stimulation (EMS) attenuates postprandial hyperglycemia in type 2 diabetes. METHODS Eleven patients with type 2 diabetes participated in two experimental sessions; one was a 30-min EMS 30 min after a breakfast (EMS trial) and the other was a complete rest after a breakfast (Control trial). In each trial, blood was sampled before and at 30, 60, 90, and 120 min after the meal. RESULTS Postprandial glucose level was significantly attenuated in EMS trial at 60, 90, and 120 min after a meal (p<0.05). The C-peptide concentration was also significantly lowered in EMS trial (p<0.01). On the other hand, there was no significant increase in creatine phosphokinase (CPK) concentration in each trial. CONCLUSIONS The present results provide first evidence indicating that EMS is a new exercise method for treating postprandial hyperglycemia in individuals with type 2 diabetes, especially who cannot perform adequate voluntary exercise because of excessive obesity, orthopedic diseases, or severe diabetic complications.
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Affiliation(s)
- Toshiaki Miyamoto
- Graduate School of Human and Environmental Studies, Kyoto University, Yoshida, Sakyo-ku, Kyoto, Japan
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Shoji K, Mizuno T, Shiiba D, Kawagoe T, Mitsui Y. Effects of a meal rich in 1,3-diacylglycerol on postprandial cardiovascular risk factors and the glucose-dependent insulinotropic polypeptide in subjects with high fasting triacylglycerol concentrations. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2012; 60:2490-2496. [PMID: 22385133 DOI: 10.1021/jf204825p] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/31/2023]
Abstract
It was previously reported that compared to triacylglycerol (TAG) oil, diacylglycerol (DAG) oil improves postprandial lipid response. However, the effects of DAG oil on postprandial hyperglycemia and incretin response have not yet been determined. In this study, the effects of DAG oil on both postprandial hyperlipidemia and hyperglycemia and the response to the glucose-dependent insulinotropic polypeptide (GIP) were studied. This randomized, double-blind, crossover study analyzed data for 41 individuals with high fasting triacylglycerol concentrations. The subjects ingested test meals (30.3 g of protein, 18.6 g of fat, and 50.1 g of carbohydrate) containing 10 g of DAG oil (DAG meal) or TAG oil (TAG meal) after fasting for at least 12 h. Blood samples were collected prior to and 0.5, 2, 3, 4, and 6 h after ingestion of the test meal. Postprandial TAG concentrations were significantly lower after the DAG meal compared with the TAG meal. Postprandial TAG, insulin, and GIP concentrations were significantly lower after the DAG meal compared with the TAG meal in 26 subjects with fasting serum TAG levels between 1.36 and 2.83 mmol/L. DAG-oil-based meals, as a replacement for TAG oil, may provide cardiovascular benefits in high-risk individuals by limiting lipid and insulin excursions.
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Affiliation(s)
- Kentaro Shoji
- Health Care Food Research Laboratories, Kao Corporation, Tokyo, Japan.
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Chu CS, Lee KT, Cheng KH, Lee MY, Kuo HF, Lin TH, Su HM, Voon WC, Sheu SH, Lai WT. Postchallenge responses of nitrotyrosine and TNF-alpha during 75-g oral glucose tolerance test are associated with the presence of coronary artery diseases in patients with prediabetes. Cardiovasc Diabetol 2012; 11:21. [PMID: 22397368 PMCID: PMC3316140 DOI: 10.1186/1475-2840-11-21] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/14/2011] [Accepted: 03/07/2012] [Indexed: 12/18/2022] Open
Abstract
BACKGROUND Meta-analysis has demonstrated an exponential relationship between 2-hr postchallenge hyperglycemia and coronary artery disease (CAD). Pulsatile hyperglycemia can acutely increase proinflammatory cytokines by oxidative stress. We hypothesized that postchallenge proinflammatory and nitrosative responses after 75 g oral glucose tolerance tests (75 g-OGTT) might be associated with CAD in patients without previously recognized type 2 diabetes mellitus (T2DM). METHODS Serial changes of plasma glucose (PG), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and nitrotyrosine levels were analyzed during 75 g-OGTT in 120 patients (81 male; age 62 ± 11 years) before coronary angiography. Patients were classified as normal (NGT; 42%), impaired (IGT; 34%) and diabetic (T2DM; 24%) glucose tolerance by 75 g-OGTT. RESULTS Postchallenge hyperglycemia elicited TNF-α, IL-6 and nitrotyrosine levels time-dependently, and 2-hr median levels of TNF-α (7.1 versus 6.4 pg/ml; P < 0.05) and nitrotyrosine (1.01 versus 0.83 μmol/l; P < 0.05), but not IL-6 or PG, were significantly higher in patients with CAD in either IGT or T2DM groups. After adjusting risk factors and glucose tolerance status, 2-hr nitrotyrosine in highest quartiles (OR: 3.1, P < 0.05) remained an independent predictor of CAD by logistic regression analysis. CONCLUSIONS These results highlight postchallenge proinflammatory and nitrosative responses by 75 g-OGTT, rather than hyperglycemia per se, are associated with CAD in patients without previous recognized diabetes.
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Affiliation(s)
- Chih-Sheng Chu
- Division of Cardiology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- Department of Internal Medicine, Faculty of Medicine, College of Medicine, Kaohsiung, Taiwan
- Department of Internal Medicine, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung, Taiwan
- Graduate Institute of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Kun-Tai Lee
- Division of Cardiology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- Department of Internal Medicine, Faculty of Medicine, College of Medicine, Kaohsiung, Taiwan
| | - Kai-Hong Cheng
- Division of Cardiology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- Department of Internal Medicine, Faculty of Medicine, College of Medicine, Kaohsiung, Taiwan
- Graduate Institute of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Min-Yi Lee
- Graduate Institute of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Hsuan-Fu Kuo
- Department of Internal Medicine, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung, Taiwan
- Graduate Institute of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Tsung-Hsien Lin
- Division of Cardiology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- Department of Internal Medicine, Faculty of Medicine, College of Medicine, Kaohsiung, Taiwan
| | - Ho-Ming Su
- Division of Cardiology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- Department of Internal Medicine, Faculty of Medicine, College of Medicine, Kaohsiung, Taiwan
| | - Wen-Chol Voon
- Division of Cardiology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- Department of Internal Medicine, Faculty of Medicine, College of Medicine, Kaohsiung, Taiwan
| | - Sheng-Hsiung Sheu
- Division of Cardiology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- Department of Internal Medicine, Faculty of Medicine, College of Medicine, Kaohsiung, Taiwan
| | - Wen-Ter Lai
- Division of Cardiology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- Department of Internal Medicine, Faculty of Medicine, College of Medicine, Kaohsiung, Taiwan
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Cacciapuoti F. Possible reduction of cardiovascular risk in the elderly: prevention of post-prandial hyperglycaemic “spikes” by acarbose. MEDITERRANEAN JOURNAL OF NUTRITION AND METABOLISM 2011. [DOI: 10.1007/s12349-010-0038-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
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In vitro retardation of glucose diffusion with gum extracted from malva nut seeds produced in Thailand. Food Chem 2011; 127:455-60. [DOI: 10.1016/j.foodchem.2010.12.153] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2010] [Revised: 11/10/2010] [Accepted: 12/31/2010] [Indexed: 11/21/2022]
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Reinforcement of the adrenergic overdrive in the metabolic syndrome complicated by obstructive sleep apnea. J Hypertens 2010; 28:1313-20. [PMID: 20164804 DOI: 10.1097/hjh.0b013e328337a9fd] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
BACKGROUND Metabolic syndrome is characterized by a marked sympathetic overactivity. It is unknown, however, whether the neuroadrenergic activation can be ascribed to obstructive sleep apnoea (OSA), OSA exerts potentiating effects on the metabolic syndrome-related sympathetic activation and reflex/metabolic variables (insulin resistance) participate at the phenomenon. METHODS AND RESULTS We conducted a cross-sectional study of healthy individuals and metabolic syndrome patients recruited in our outpatient clinic. Fifty-five middle-age men classified according to Adult Treatment Panel III criteria and apnea-hypopnea index (overnight polysomnographic evaluation) as healthy controls without OSA and metabolic syndrome patients without and with OSA were studied. Blood pressure (Finapres), heart rate (ECG) and muscle sympathetic nerve activity (MSNA; microneurography) were measured at rest and during baroreflex manipulation. Compared with controls, patients with metabolic syndrome with and without OSA displayed higher waist-hip ratio, blood pressure, triglycerides and homeostasis model assessment index values but lower high-density lipoprotein cholesterol. MSNA was significantly higher in patients with metabolic syndrome without OSA than in controls (61.9 +/- 3.9 vs. 37.7 +/- 4.1 bursts/100 heartbeats, respectively, P < 0.01), a further marked increase being detected in patients with metabolic syndrome with OSA (77.1 +/- 4.3 bursts/100 heart beats, P < 0.01). Compared with controls, baroreflex control of heart rate and MSNA was markedly impaired in patients with metabolic syndrome with OSA, a further impairment in baroreflex-heart rate modulation being detected in metabolic syndrome with OSA. In the metabolic syndrome group as a whole, at the multivariate analysis, MSNA was significantly related to the apnoea-hypopnoea index but not to other variables. CONCLUSION Thus the sympathetic activation of metabolic syndrome occurs independently on OSA. OSA, however, markedly potentiates this neuroadrenergic abnormality via a hypoxic-dependent chemoreflex activation.
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Borg R, Kuenen JC, Carstensen B, Zheng H, Nathan DM, Heine RJ, Nerup J, Borch-Johnsen K, Witte DR. Associations between features of glucose exposure and A1C: the A1C-Derived Average Glucose (ADAG) study. Diabetes 2010; 59:1585-90. [PMID: 20424232 PMCID: PMC2889756 DOI: 10.2337/db09-1774] [Citation(s) in RCA: 71] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
OBJECTIVE Various methods are used to quantify postprandial glycemia or glucose variability, but few have been compared and none are standardized. Our objective was to examine the relationship among common indexes of postprandial glycemia, overall hyperglycemia, glucose variability, and A1C using detailed glucose measures obtained during everyday life and to study which blood glucose values of the day provide the strongest prediction of A1C. RESEARCH DESIGN AND METHODS In the A1C-Derived Average Glucose (ADAG) study, glucose levels were monitored in 507 participants (268 type 1 diabetic, 159 type 2 diabetic, and 80 nondiabetic subjects) with continuous glucose monitoring (CGM) and frequent self-monitoring of blood glucose (SMBG) during 16 weeks. We calculated several indexes of glycemia and analyzed their intercorrelations. The association between glucose measurements at different times of the day (pre- and postprandial) and A1C was examined using multiple linear regression. RESULTS Indexes of glucose variability showed strong intercorrelation. Among postprandial indexes, the area under the glucose curve calculated from CGM 2 h after a meal correlated well with the 90-min SMBG postprandial measurements. Fasting blood glucose (FBG) levels were only moderately correlated with indexes of hyperglycemia and average or postprandial glucose levels. Indexes derived with SMBG strongly correlated with those from CGM. Some SMBG time points had a stronger association with A1C than others. Overall, preprandial glucose values had a stronger association with A1C than postprandial values for both diabetes types, particularly for type 2 diabetes. CONCLUSIONS Indexes of glucose variability and average and postprandial glycemia intercorrelate strongly within each category. Variability indexes are weakly correlated with the other categories, indicating that these measures convey different information. FBG is not a clear indicator of general glycemia. Preprandial glucose values have a larger impact on A1C levels than postprandial values.
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Affiliation(s)
- Rikke Borg
- Steno Diabetes Center, Copenhagen, Denmark.
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22
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Guglielmotto M, Giliberto L, Tamagno E, Tabaton M. Oxidative stress mediates the pathogenic effect of different Alzheimer's disease risk factors. Front Aging Neurosci 2010; 2:3. [PMID: 20552043 PMCID: PMC2874401 DOI: 10.3389/neuro.24.003.2010] [Citation(s) in RCA: 49] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2009] [Accepted: 01/20/2010] [Indexed: 12/19/2022] Open
Abstract
Alzheimer's disease (AD) is a progressive neurodegenerative disorder affecting the elderly population. Mechanistically, the major cause of the disease bases on the altered processing of the amyloid-β (Aβ) precursor protein (APP), resulting in the accumulation and aggregation of neurotoxic forms of Aβ. Aβ derives from the sequential proteolytic cleavage of the β- and γ-secretases on APP. The causes of Aβ accumulation in the common sporadic form of AD are not completely known, but they are likely to include oxidative stress (OS). OS and Aβ are linked to each other since Aβ aggregation induces OS in vivo and in vitro, and oxidant agents increase the production of Aβ. Moreover, OS produces several effects that may contribute to synaptic function and cell death in AD. We and others have shown that the expression and activity of β-secretase (named BACE1; β-site APP cleaving enzyme) is increased by oxidant agents and by lipid peroxidation product 4-hydroxynonenal and that there is a significant correlation between BACE1 activity and oxidative markers in sporadic AD. OS results from several cellular insults such as aging, hyperglycemia, hypoxic insults that are all well known risk factors for AD development. Thus, our data strengthen the hypothesis that OS is a basic common pathway of Aβ accumulation, common to different AD risk factors.
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Affiliation(s)
- Michela Guglielmotto
- Department of Experimental Medicine and Oncology, University of Turin Turin, Italy
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Affiliation(s)
- Antonio Ceriello
- Warwick Medical School. Clinical Science Research Institute. University of Warwick. UK
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24
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Abstract
Soft drink overconsumption is now considered to be a major public health concern with implications for cardiovascular diseases. This follows a number of studies performed in animals suggesting that chronic consumption of refined sugars can contribute to metabolic and cardiovascular dysregulation. In particular, the monosaccharide fructose has been attracting increasing attention as the more harmful sugar component in terms of weight gain and metabolic disturbances. High-fructose corn syrup is gradually replacing sucrose as the main sweetener in soft drinks and has been blamed as a potential contributor to the current high prevalence of obesity. There is also considerable evidence that fructose, rather than glucose, is the more damaging sugar component in terms of cardiovascular risk. This review focuses on the potential role of sugar drinks, particularly the fructose component, in the pathogenesis of obesity and cardiovascular diseases.
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Uto H. alpha-Glucosidase inhibitor acarbose and sequestome 1/A170/p62 deficient mice: A promising therapy and unique model for non-alcoholic fatty liver disease. Hepatol Res 2009; 39:845-6. [PMID: 19712270 DOI: 10.1111/j.1872-034x.2009.00585.x] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Affiliation(s)
- Hirofumi Uto
- Department of Digestive and Lifestyle-related Disease, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan
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26
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Edens MA, Kuipers F, Stolk RP. Non-alcoholic fatty liver disease is associated with cardiovascular disease risk markers. Obes Rev 2009; 10:412-9. [PMID: 19413701 DOI: 10.1111/j.1467-789x.2009.00594.x] [Citation(s) in RCA: 57] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Recognition of the link between non-alcoholic fatty liver disease (NAFLD) and cardiovascular disease (CVD) has boosted research in this area. The main objective of this paper is to review the literature on NAFLD in the context of CVD, focussing on underlying mechanisms and treatment. Besides excessive fatty acid influx, etiologic factors may include components of the metabolic syndrome, cytokines and mitochondrial dysfunction. NAFLD is associated with both hepatic and systemic insulin resistance. In the case of NAFLD, the liver overproduces several atherogenic factors, notably inflammatory cytokines, glucose, lipoproteins and coagulation factors, and factors increasing blood pressure. Intervention studies on diet and laparoscopic surgery revealed improvements of hepatic fat content and CVD risk profile. Pharmacological approaches with potential benefit have been developed as well, but effects are often confounded by weight change. NAFLD is associated with an increased CVD risk profile (and hepatic risk). In order to improve CVD risk profile, prevention and treatment of NAFLD seem advisable. However, well-designed intervention studies, randomized clinical trials and long-term follow-up studies are scarce.
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Affiliation(s)
- M A Edens
- Department of Epidemiology, Center for Liver, Digestive and Metabolic Diseases, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
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Xie XT, Liu Q, Wu J, Wakui M. Impact of cigarette smoking in type 2 diabetes development. Acta Pharmacol Sin 2009; 30:784-7. [PMID: 19434055 PMCID: PMC4002374 DOI: 10.1038/aps.2009.49] [Citation(s) in RCA: 75] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2009] [Accepted: 03/22/2009] [Indexed: 12/20/2022] Open
Abstract
Many patients with type 2 diabetes mellitus (DM2) are at risk for micro and macro vascular complications, which could be observed in heavy smokers. Cigarette smoking increases the risk for type 2 diabetes incidence. Nicotine, acknowledged as the major pharmacologically active chemical in tobacco, is responsible for the association between cigarette smoking and development of diabetes. This minireview summarized recent studies on nicotine effects on insulin action and insulin secretion, indicating the impact of nicotine on type 2 diabetes development.
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Affiliation(s)
- Xi-tao Xie
- Center for Metabolic Biology, Arizona State University, Tempe, AZ 85287–3704, USA
| | - Qiang Liu
- Division of Neurology, Barrow Neurological Institute, Phoenix, AZ 85013–4496, USA
| | - Jie Wu
- Division of Neurology, Barrow Neurological Institute, Phoenix, AZ 85013–4496, USA
| | - Makoto Wakui
- Division of Clinical Research, Hirosaki National Hospital, Hirosaki 036–8545, Japan
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Cho HJ, Son SM, Jin SM, Hong HS, Shin DH, Kim SJ, Huh K, Mook‐Jung I. RAGE regulates BACE1 and Aβ generation
via
NFAT1 activation in Alzheimer's disease animal model. FASEB J 2009; 23:2639-49. [DOI: 10.1096/fj.08-126383] [Citation(s) in RCA: 92] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Affiliation(s)
- H. J. Cho
- Department of Biochemistry and Biomedical SciencesSeoul National University College of MedicineSeoulKorea
| | - S. M. Son
- Department of Biochemistry and Biomedical SciencesSeoul National University College of MedicineSeoulKorea
| | - S. M. Jin
- Department of Biochemistry and Biomedical SciencesSeoul National University College of MedicineSeoulKorea
| | - H. S. Hong
- Department of Biochemistry and Biomedical SciencesSeoul National University College of MedicineSeoulKorea
| | - D. H. Shin
- Department of PhysiologySeoul National University College of MedicineSeoulKorea
- Ischemia/Hypoxia Disease InstituteSeoul National University College of MedicineSeoulKorea
| | - S. J. Kim
- Department of PhysiologySeoul National University College of MedicineSeoulKorea
- Ischemia/Hypoxia Disease InstituteSeoul National University College of MedicineSeoulKorea
| | - K. Huh
- Neuroscience Graduate ProgramAjou University School of MedicineSuwonKorea
| | - I. Mook‐Jung
- Department of Biochemistry and Biomedical SciencesSeoul National University College of MedicineSeoulKorea
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Ritt M, Ott C, Raff U, Schneider MP, Schuster I, Hilgers KF, Schlaich MP, Schmieder RE. Renal vascular endothelial function in hypertensive patients with type 2 diabetes mellitus. Am J Kidney Dis 2008; 53:281-9. [PMID: 19100670 DOI: 10.1053/j.ajkd.2008.10.041] [Citation(s) in RCA: 27] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2008] [Accepted: 10/07/2008] [Indexed: 12/15/2022]
Abstract
BACKGROUND Basal nitric oxide (NO) activity has a pivotal role in the regulation of glomerular hemodynamics, and in animal experiments, its alteration has been associated with morphological changes characteristic of diabetic nephropathy. STUDY DESIGN Prospective observational-study during a mean follow-up of 2.1 years. SETTING & PARTICIPANTS 66 hypertensive patients (aged 30 to 80 years) with type 2 diabetes and estimated glomerular filtration rate (GFR) greater than 80 mL/min/1.73 m(2) with normoalbuminuria or microalbuminuria. PREDICTOR Mean arterial pressure during follow-up during treatment with telmisartan or ramipril for 9 weeks, followed by treatment according to the discretion of the individual primary care physician. OUTCOMES & MEASUREMENTS Renal vascular resistance, renal plasma flow, GFR, and change in renal plasma flow in response to infusion of the NO synthase inhibitor N-monomethyl-L-arginine as an indicator of basal NO activity in the renal vasculature. RESULTS 50 of 66 patients could be reexamined. At follow-up, mean arterial pressure decreased from 106 +/- 9.1 to 100 +/- 11 mm Hg (P < 0.001). Body mass index and hemoglobin A(1c) levels were unaltered. Renal vascular resistance decreased (from 128 +/- 44 to 103 +/- 30 mm Hg/mL/min/1.73 m(2); P < 0.001), renal plasma flow increased (from 490 +/- 133 to 589 +/- 154 mL/min/1.73 m(2); P < 0.001), and GFR did not change (113 +/- 22 versus 116 +/- 26 mL/min/1.73 m(2); P = 0.4) during follow-up. The decrease in renal plasma flow in response to N-monomethyl-l-arginine infusion was more pronounced at follow-up (-56.7 +/- 39 versus -73.4 +/- 48 mL/min/1.73 m(2); P = 0.02), indicating improved basal NO activity. After adjustment for possible confounders, patients with a marked decrease in mean arterial pressure showed more improved basal NO activity during follow-up than those with a less pronounced decrease in mean arterial pressure (P = 0.04). LIMITATIONS Patients were treated according to the discretion of the individual primary care physician. CONCLUSIONS During follow-up, renal vascular resistance, renal plasma flow, and renal endothelial function (indicated by basal NO activity) improved. Better blood pressure control was associated with improved endothelial function of the renal vasculature, thereby potentially mediating the changes in renal hemodynamics.
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Affiliation(s)
- Martin Ritt
- Department of Nephrology and Hypertension, University of Erlangen-Nürnberg, Erlangen, Germany
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Schwartz SL, Ratner RE, Kim DD, Qu Y, Fechner LL, Lenox SM, Holcombe JH. Effect of exenatide on 24-hour blood glucose profile compared with placebo in patients with type 2 diabetes: a randomized, double-blind, two-arm, parallel-group, placebo-controlled, 2-week study. Clin Ther 2008; 30:858-67. [PMID: 18555933 DOI: 10.1016/j.clinthera.2008.05.004] [Citation(s) in RCA: 42] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/08/2008] [Indexed: 01/13/2023]
Abstract
OBJECTIVE The aim of this study was to examine the glucose-lowering effect of exenatide over 24 hours in patients with type 2 diabetes with inadequate glycemic control using metformin, with or without a thiazolidinedione (TZD). METHODS This randomized, double-blind, 2-arm, parallel-group, placebo-controlled, 2-week study was conducted in patients with type 2 diabetes with inadequate glycemic control, despite metformin with or without a TZD. Patients underwent a baseline and a week-2 (study end) 24-hour admission during which serial serum glucose measurements were taken. Preprandial and postprandial concentrations of triglycerides and free fatty acids were also measured. Meals provided for each patient were identical at the baseline and week-2 assessments. Following the baseline admission, patients were randomized to receive SC injections of either exenatide (5 microg BID for 1 week, then 10 microg BID for the next week) or placebo (volume equivalent) for 14 days. RESULTS A total of 30 patients (19 women [63%], 11 men [37%]; mean [SD] age, 52.6 [11.2] years; weight, 94.3 [23.0] kg; body mass index, 34.2 [6.1] kg/m(2); glycosylated hemoglobin value, 8.0% [0.9%]; diabetes duration, 8.7 [5.6] years; race, Hispanic 18 [60%], white 10 [33%], black 2 [7%]) were eligible. Seventeen patients (57%) were randomized to treatment with exenatide and 13 patients (43%) received placebo. Concurrent antidiabetic medications were metformin only (n = 19 [63%]) and metformin plus a TZD (n = 11 [37%]). All postbaseline values were least squares mean (SE). After 2 weeks (study end), the 24-hour time-average glucose values were 7.0 (0.2) and 8.8 (0.3) mmol/L for exenatide-treated and placebo-administered patients, respectively (P < 0.001). The glucose values for patients treated with exenatide were lower compared with those in patients who received placebo 2 hours after the morning meal (6.6 [0.4] vs 12.0 [0.5] mmol/L; P < 0.001), the midday meal (8.8 [0.5] vs 11.8 [0.6] mmol/L; P = 0.001), and the evening meal (6.8 [0.4] vs 11.3 [0.4] mmol/L; P < 0.001). The mean durations of patient exposure to glucose concentrations >7.8 and >11.1 mmol/L were significantly shorter for the exenatide group compared with the placebo group (>7.8 mmol/L: 6.8 [0.9] vs 14.1 [1.1] hours; >11.1 mmol/L: 1.0 [0.7] vs 4.7 [0.8] hours; both, P < 0.001). After 2 weeks, the postprandial triglyceride excursions after the morning and evening meals for patients treated with exenatide were significantly lower compared with those treated with placebo. There was no apparent effect on free fatty acid concentrations. CONCLUSIONS In these patients with type 2 diabetes, exenatide was associated with significantly reduced glucose concentrations at multiple time points during 24 hours, with the greatest effect seen on postprandial glucose concentrations. In addition, exenatide was associated with decreased overall hyperglycemic exposure and significantly decreased postprandial triglyceride excursions. These results are consistent with those seen in other studies that reported the effectiveness of exenatide in controlling hyperglycemia in patients with type 2 diabetes.
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Alssema M, Schindhelm RK, Dekker JM, Diamant M, Nijpels G, Teerlink T, Scheffer PG, Kostense PJ, Heine RJ. Determinants of postprandial triglyceride and glucose responses after two consecutive fat-rich or carbohydrate-rich meals in normoglycemic women and in women with type 2 diabetes mellitus: the Hoorn Prandial Study. Metabolism 2008; 57:1262-9. [PMID: 18702953 DOI: 10.1016/j.metabol.2008.04.022] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/05/2007] [Accepted: 04/22/2008] [Indexed: 11/18/2022]
Abstract
Both postprandial hyperglycemia and hypertriglyceridemia have been identified as risk markers for cardiovascular disease, but parameters associated with these postprandial responses are largely unknown. The objective was to assess whether usually measured clinical and biochemical parameters can predict postprandial glucose and triglyceride responses and whether these responses are associated with each other. Postmenopausal women, 76 with normal glucose metabolism (NGM) and 41 with type 2 diabetes mellitus (T2DM), received 2 consecutive fat-rich meals and carbohydrate-rich meals on separate occasions. Blood samples were taken before and at t = 1, 2, 4, 6, and 8 hours after breakfast; lunch was given at t = 4 hours. Regression analysis was performed with incremental area under the postprandial triglyceride curve (triglyceride-iAUC) and glucose curve (glucose-iAUC) after fat-rich and carbohydrate-rich meals, respectively. In women with NGM, fasting triglycerides, hemoglobin A(1c), total cholesterol, and, inversely, high-density lipoprotein cholesterol were independently associated with triglyceride-iAUC; and age and fasting triglycerides were independently associated with glucose-iAUC. In women with T2DM, fasting triglycerides were independently associated with triglyceride-iAUC, whereas hemoglobin A(1c) and fasting glucose were stronger than fasting triglycerides associated with glucose-iAUC. Glucose-iAUC and triglyceride-iAUC were associated with each other in women with T2DM, but not in those with NGM. The association between glucose-iAUC and triglyceride-iAUC in women with T2DM and the association of fasting triglycerides with both glucose-iAUC and triglyceride-iAUC in NGM and T2DM suggest a common underlying mechanism for postprandial increments in glucose and triglycerides, especially in T2DM. Commonly measured clinical and biochemical parameters can only partly explain postprandial glucose and triglyceride excursions.
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Affiliation(s)
- Marjan Alssema
- EMGO Institute, VU University Medical Center, 1007 MB Amsterdam, The Netherlands.
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Wajchenberg BL. Postprandial glycemia and cardiovascular disease in diabetes mellitus. ACTA ACUST UNITED AC 2008; 51:212-21. [PMID: 17505628 DOI: 10.1590/s0004-27302007000200010] [Citation(s) in RCA: 16] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2007] [Accepted: 01/11/2007] [Indexed: 11/22/2022]
Abstract
This article reviews the role of fasting and postprandial glycemia to the overall glycemic control of patients with type 2 diabetes and glucose intolerance, as well as their causal relationship upon micro and macrovascular complications. Recent studies have suggested that a third component of the glucose triad, the postprandial glucose excursions, might have a role in the overall glycemic load and might also reflect glycemic control. Epidemiological and intervention studies are presented in the article, supporting the conclusion that postprandial hyperglycemia in impaired glucose tolerance and diabetic subjects is a more powerful marker of cardiovascular disease risk than fasting hyperglycemia, then the treatment directed at specifically lowering postprandial glucose is crucial, as underlined by the American Diabetes Association.
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Affiliation(s)
- Bernardo Léo Wajchenberg
- Endocrine Service, Heart Center of The Heart Institute, Hospital das Clínicas, The University of São Paulo Medical School, São Paulo, SP, Brazil
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Signori LU, Plentz RDM, Irigoyen MC, Schaan BD. [The role of post-prandial lipids in atherogenesis: particularities of diabetes mellitus]. ACTA ACUST UNITED AC 2008; 51:222-31. [PMID: 17505629 DOI: 10.1590/s0004-27302007000200011] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2006] [Accepted: 11/20/2006] [Indexed: 01/22/2023]
Abstract
Atherosclerosis is a complex and multifactorial disease, which determines clinical events that cause significant morbidity-mortality, represented by acute myocardial infarction, angina and sudden death. It is associated with lipid disturbances, platelet activation, thrombosis, endothelial dysfunction, inflammation, oxidative stress, altered matrix metabolism, among other disturbances. All these abnormalities are usual and more pronounced in diabetic patients, as well as in the post-prandial state. Among the coronary artery disease risk factors that are not usually employed in clinical practice in the whole population, postprandial hyperlipemia plays a major role, being a possible early marker of metabolic abnormalities and vascular dysfunction not yet seen in the fasting state. Recent results showed that post-oral lipid overload changes are negatively associated with endothelial dysfunction, and vascular reactivity abnormalities are strongly related to atherosclerosis progression and cardiovascular events. These abnormalities could disclose a lipid intolerance state that can be detected in apparently healthy subjects even before fasting abnormalities are seen. This review will deal with the pathophysiology changes involved in post-prandial hyperlipemia and its relationship with atherogenesis, with particular emphasis to diabetes mellitus.
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Affiliation(s)
- Luis Ulisses Signori
- Instituto de Cardiologia do Rio Grande do Sul, Fundação Universidade de Cardiologia, Porto Alegre, RS, and Unidade de Hipertensão, InCor, Hospital das Clínicas de São Paulo, Brazil
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Rotteveel J, van Weissenbruch MM, Twisk JWR, Delemarre-Van de Waal HA. Abnormal lipid profile and hyperinsulinaemia after a mixed meal: additional cardiovascular risk factors in young adults born preterm. Diabetologia 2008; 51:1269-75. [PMID: 18496668 DOI: 10.1007/s00125-008-1029-5] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/01/2007] [Accepted: 04/04/2008] [Indexed: 11/25/2022]
Abstract
AIMS/HYPOTHESIS Low birthweight in infants born at term is related to the presence of the metabolic syndrome as an adult. Individuals born preterm invariably have low birthweights and may develop the metabolic syndrome as well. Although high BP, glucose intolerance and insulin resistance have been documented, dyslipidaemia has never been reported in individuals born preterm. METHODS In three groups of young adults [29 participants from the POPS (Project On Premature and Small for Gestational Age Infants) cohort born preterm appropriate for gestational age (POPS-AGA), 28 participants from the POPS cohort born preterm small for gestational age (POPS-SGA) and 30 individuals born at term with normal birthweight (CON)] we investigated fasting lipids as well as postprandial responses during a mixed meal test. The relationship between fasting and postprandial measurements and insulin sensitivity, measured by the hyperinsulinaemic clamp, was investigated. RESULTS Preterm participants had higher BP than CON individuals. Postprandial triacylglycerol levels were increased in POPS-SGA men. POPS-SGA individuals were hyperinsulinaemic during the mixed meal test. CONCLUSIONS/INTERPRETATION The mixed meal test provides additional information on cardiovascular risk factors. Postprandial triacylglycerol levels are increased in POPS-SGA men. Postprandial hyperinsulinaemia is found in POPS-SGA individuals.
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Affiliation(s)
- J Rotteveel
- Department of Pediatrics, VU University Medical Center, P.O. Box 7057, 1007 MB, Amsterdam, The Netherlands.
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Robinson LE, Buchholz AC, Mazurak VC. Inflammation, obesity, and fatty acid metabolism: influence of n-3 polyunsaturated fatty acids on factors contributing to metabolic syndrome. Appl Physiol Nutr Metab 2008; 32:1008-24. [PMID: 18059573 DOI: 10.1139/h07-087] [Citation(s) in RCA: 59] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Metabolic syndrome (MetS) comprises an array of metabolic risk factors including abdominal obesity, dyslipidemia, hypertension, and glucose intolerance. Individuals with MetS are at elevated risk for diabetes and cardiovascular disease. Central to the etiology of MetS is an interrelated triad comprising inflammation, abdominal obesity, and aberrations in fatty acid metabolism, coupled with the more recently recognized changes in metabolism during the postprandial period. We review herein preliminary evidence regarding the role of dietary n-3 polyunsaturated fatty acids in modulating each of the components of the triad of adiposity, inflammation, and fatty acid metabolism, with particular attention to the role of the postprandial period as a contributor to the pathophysiology of MetS.
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Affiliation(s)
- Lindsay E Robinson
- Department of Human Health and Nutritional Sciences, Room 336-B Animal Science and Nutrition Building, University of Guelph, Guelph, ON N1G 2W1, Canada
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Hanefeld M, Schaper F. Acarbose: oral anti-diabetes drug with additional cardiovascular benefits. Expert Rev Cardiovasc Ther 2008; 6:153-63. [PMID: 18248270 DOI: 10.1586/14779072.6.2.153] [Citation(s) in RCA: 50] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
Acarbose is an alpha-glucosidase inhibitor acting specifically at the level of postprandial glucose excursion. This compound lowers HbA(1c) by 0.5-1% in patients with Type 2 diabetes, either drug naive or in combination with other antidiabetic drugs. In those with impaired glucose tolerance (IGT), it reduces the incidence of newly diagnosed diabetes by 36.4%. Furthermore, it has beneficial effects on overweight, reduces blood pressure and triglycerides, and downregulates biomarkers of low-grade inflammation. In the Study To Prevent Non-Insulin-Dependent-Diabetes-Mellitus (STOP-NIDDM) trial, acarbose significantly reduced the progression of intima media thickness, incidence of cardiovascular events and of newly diagnosed hypertension. In a meta-analysis of patients with Type 2 diabetes (MERIA), acarbose intake was associated with a reduction of cardiovascular events by 35%. Acarbose is a very safe drug but in approximately 30% of patients, it can cause gastrointestinal complaints due to its mode of action, which in the majority disappear after 1-2 months. Acarbose is approved for treatment of IGT in 25 countries. It can be given alone or in combination with other oral antidiabetics and insulin. Acarbose is particularly effective in those with IGT and early diabetes and patients with comorbidities of the metabolic syndrome.
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Affiliation(s)
- Markolf Hanefeld
- Centre for Clinical Studies, Dresden, Fiedlerstrasse 34, 01307 Dresden, Germany.
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Hanefeld M, Schaper F, Koehler C. Effect of Acarbose on Vascular Disease in Patients with Abnormal Glucose Tolerance. Cardiovasc Drugs Ther 2008; 22:225-31. [DOI: 10.1007/s10557-008-6091-1] [Citation(s) in RCA: 29] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/21/2008] [Accepted: 01/24/2008] [Indexed: 01/18/2023]
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Lund SS, Tarnow L, Frandsen M, Smidt UM, Pedersen O, Parving HH, Vaag AA. Impact of metformin versus the prandial insulin secretagogue, repaglinide, on fasting and postprandial glucose and lipid responses in non-obese patients with type 2 diabetes. Eur J Endocrinol 2008; 158:35-46. [PMID: 18166815 DOI: 10.1530/eje-07-0500] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
OBJECTIVE Non-obese patients with type 2 diabetes (T2DM) are characterized by predominant defective insulin secretion. However, in non-obese T2DM patients, metformin, targeting insulin resistance, is non-inferior to the prandial insulin secretagogue, repaglinide, controlling overall glycaemia (HbA1c). Whether the same apply for postprandial glucose and lipid metabolism is unknown. Here, we compared the effect of metformin versus repaglinide on postprandial metabolism in non-obese T2DM patients. DESIGN Single-centre, double-masked, double-dummy, crossover study during 2x4 months involving 96 non-obese (body mass index < or = 27 kg/m2) insulin-naïve T2DM patients. At enrolment, patients stopped prior oral hypoglycaemic agents therapies and after a 1-month run-in period on diet-only treatment, patients were randomized to repaglinide (2 mg) thrice daily followed by metformin (1 g) twice daily or vice versa each during 4 months with 1-month washout between interventions. METHODS Postprandial metabolism was evaluated by a standard test meal (3515 kJ; 54% fat, 13% protein and 33% carbohydrate) with blood sampling 0-6 h postprandially. RESULTS Fasting levels and total area under the curve (AUC) for plasma glucose, triglycerides and free fatty acids (FFA) changed equally between treatments. In contrast, fasting levels and AUC of total cholesterol, low-density lipoprotein (LDL) cholesterol, non-high-density lipoprotein (non-HDL) cholesterol and serum insulin were lower during metformin than repaglinide (mean (95% confidence intervals), LDL cholesterol difference metformin versus repaglinide: AUC: -0.17 mmol/l (-0.26; -0.08)). AUC differences remained significant after adjusting for fasting levels. CONCLUSIONS In non-obese T2DM patients, metformin reduced postprandial levels of glycaemia, triglycerides and FFA similarly compared to the prandial insulin secretagogue, repaglinide. Furthermore, metformin reduced fasting and postprandial cholesterolaemia and insulinaemia compared with repaglinide. These data support prescription of metformin as the preferred drug in non-obese patients with T2DM targeting fasting and postprandial glucose and lipid metabolism.
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Affiliation(s)
- Søren S Lund
- Steno Diabetes Center, Niels Steensens Vej 2, 2820 Gentofte, Denmark.
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Nogi A, Yang J, Li L, Yamasaki M, Watanabe M, Watanabe M, Hashimoto M, Shiwaku K. Plasma n-3 polyunsaturated fatty acid and cardiovascular disease risk factors in Japanese, Korean and Mongolian workers. J Occup Health 2007; 49:205-16. [PMID: 17575401 DOI: 10.1539/joh.49.205] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
The favorable role of n-3 polyunsaturated fatty acid (PUFA) in cardiovascular disease (CVD) has been demonstrated in animal experiments and in humans in Western countries, but its effect remains controversial in Asian populations. An observational study of Japanese, Koreans and Mongolians with extended histories of remarkably different frequencies of fish intake was conducted to examine whether differences in plasma n-3 PUFA affects CVD risk factors. We conducted a cross-sectional study in workplace settings and determined body mass index (BMI), blood pressure, total cholesterol, LDL-cholesterol, HDL-cholesterol, triglyceride (TG), glucose, insulin, homeostasis model assessment-insulin resistance (HOMA-IR) and fatty acid composition in plasma. A total of 411 Japanese, 418 Korean and 252 Mongolian workers aged 30-60 yr participated in this study. The Japanese ate fish more frequently and had remarkably higher values of eicosapentaenoic acid, docosahexaenoic acid and n-3 PUFA, and lower values of BMI and HOMA-IR, followed by the Koreans, and then the Mongolians. In age groups, the Japanese and Koreans showed a similar tendency of increase in n-3 PUFA with increasing age. General linear measurement multivariate analysis after adjustment for gender, age, smoking, drinking, exercise habits and BMI showed n-3 PUFA was associated with HDL-C and TG in the Japanese, while it was associated with systolic blood pressure in the Koreans, and TG in the Mongolians. In conclusion, an increase in n-3 PUFA was associated with HDL-C and TG in the Japanese and Mongolians, but these beneficial effects were not constant across the three Asian ethnic groups.
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Affiliation(s)
- Akiko Nogi
- Department of Environmental and Preventive Medicine, Shimane University School of Medicine, Izumo City, Shimane, Japan
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Chappuis B, Braun M, Stettler C, Allemann S, Diem P, Lumb PJ, Wierzbicki AS, James R, Christ ER. Differential effect of pioglitazone (PGZ) and rosiglitazone (RGZ) on postprandial glucose and lipid metabolism in patients with type 2 diabetes mellitus: a prospective, randomized crossover study. Diabetes Metab Res Rev 2007; 23:392-9. [PMID: 17211855 DOI: 10.1002/dmrr.715] [Citation(s) in RCA: 48] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
BACKGROUND Postprandial metabolism is impaired in patients with type 2 diabetes (T2Dm). Two thiazolidinediones pioglitazone (PGZ) and rosiglitazone (RGZ) have similar effects on glycaemic control but differ in their effects on fasting lipids. This study investigated the effects of RGZ and PGZ on postprandial metabolism in a prospective, randomized crossover trial. METHODS Seventeen patients with T2Dm were randomized to RGZ or PGZ for 12 weeks, with an 8-week wash-out period. Fasting blood samples were taken for glucose (FPG), insulin, HbA(1c), lipids, apolipoproteins (apo), lipoprotein (LPL) and hepatic lipase (HL), and cholesterol ester transfer protein (CETP) activity. A standardized breakfast was served and postprandial glucose, insulin, and lipid subfraction profiles were determined. RESULTS RGZ and PGZ treatment resulted in a similar improvement in FPG, HbA(1c) and homeostasis model assessment. Fasting and postprandial triglyceride (TG) levels were significantly lower following PGZ therapy (fasting: -0.35 vs 0.44 mmol/L; p < 0.04; postprandial AUC-TG: -195.6 vs 127.9 mmol/L/min; p < 0.02) associated with changes in VLDL-2-TG (-0.10 vs 0.21 mmol/L; p = 0.23) and VLDL-3-TG (0.0 vs 0.34 mmol/L; p < 0.04). Fasting cholesterol increased with RGZ compared to PGZ (0.06 vs 0.59 mmol/L; p < 0.04), particularly in VLDL-2-C (-0.30 vs 0.59 mmol/L; p < 0.03) and VLDL-3-C (-0.85 vs 2.11 mmol/L; p < 0.02). Postprandial VLDL lipid and protein content increased after RGZ and decreased after PGZ. Fasting apoB, apoA-I, apoC-II/C-III-ratio, and LPL activity did not differ. CETP activity decreased after RGZ and increased after PGZ (-6.2 vs 4.2 p/mol/mL/min; p < 0.002). CONCLUSIONS Both the glitazones had similar effects on glucose metabolism. The additional beneficial effect of PGZ on lipid metabolism may be related to its effects on insulin-independent VLDL production and CETP activity.
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Affiliation(s)
- Bernard Chappuis
- Division of Endocrinology, Diabetes and Clinical Nutrition, University Hospital of Berne, Inselspital, CH-3010 Bern, Switzerland
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Schindhelm RK, Alssema M, Scheffer PG, Diamant M, Dekker JM, Barto R, Nijpels G, Kostense PJ, Heine RJ, Schalkwijk CG, Teerlink T. Fasting and postprandial glycoxidative and lipoxidative stress are increased in women with type 2 diabetes. Diabetes Care 2007; 30:1789-94. [PMID: 17468356 DOI: 10.2337/dc06-2585] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
OBJECTIVE We studied acute changes in markers of glycoxidative and lipoxidative stress, including oxidized LDL, N(epsilon)-(carboxyethyl)-lysine (CEL), N(epsilon)-(carboxymethyl)-lysine (CML), and 3-deoxyglucosone (3DG), following two consecutive meals. RESEARCH DESIGN AND METHODS Postmenopausal women (27 with normal glucose metabolism [NGM], 26 with type 2 diabetes) received two consecutive fat-rich meals and two consecutive carbohydrate-rich meals on two occasions. Glucose and triglyceride concentrations were measured at baseline and 1, 2, 4, 6, and 8 h following breakfast; lunch was given at 4 h. Oxidized LDL-to-LDL cholesterol ratio, CEL, CML, and 3DG were measured at baseline and at 8 h. RESULTS Fasting oxidized LDL-to-LDL cholesterol ratio, 3DG, and CML were higher in women with type 2 diabetes compared with women with NGM and were comparable to the postprandial values at 8 h in NGM. Postprandial rises in the oxidized LDL-to-LDL cholesterol ratio and 3DG were similar in both groups. However, the oxidized LDL-to-LDL cholesterol ratio increased more after the fat-rich meals, whereas CML and 3DG increased more after the carbohydrate-rich meals. After the fat-rich meals, the increase in the oxidized LDL-to-LDL cholesterol ratio correlated with postprandial triglycerides, whereas the increase in 3DG was correlated with postprandial glucose. CONCLUSIONS The acute changes in markers of glycoxidative and lipoxidative stress in both type 2 diabetes and NGM suggest that postabsorptive oxidative stress may partly underlie the association of postprandial derangements and cardiovascular risk.
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Affiliation(s)
- Roger K Schindhelm
- Department of Endocrinology, Vrije University Medical Center, Amsterdam, The Netherlands
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Mieszczanska H, Kaba NK, Francis CW, Gerich JE, Dodis R, Schwarz KQ, Phipps RP, Smith BH, Lee M, Messing S, Taubman MB. Effects of pioglitazone on fasting and postprandial levels of lipid and hemostatic variables in overweight non-diabetic patients with coronary artery disease. J Thromb Haemost 2007; 5:942-9. [PMID: 17461928 DOI: 10.1111/j.1538-7836.2007.02442.x] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Abstract
OBJECTIVES To evaluate the effects of pioglitazone on insulin sensitivity and levels of biomarkers associated with thrombotic risk in overweight and obese, non-diabetic subjects with coronary artery disease. BACKGROUND Little information is available regarding the effects of thiazolidinediones in the absence of diabetes. Further, although postprandial hyperlipemia is a risk factor for cardiovascular diseases, there is limited information about the postprandial effects. METHODS Twenty overweight and obese, non-diabetic patients with coronary artery disease were enrolled in a randomized, placebo-controlled, double-blind study. Subjects were on atorvastatin for the duration of the study and received either placebo or pioglitazone (45 mg day(-1)) for 12 weeks and then crossed over to the alternative therapy for an additional 12 weeks. Insulin sensitivity, fasting and postprandial levels of lipid, hemostatic, and inflammatory variables were measured, and endothelial function was assessed. RESULTS Insulin sensitivity improved from 0.03 micromol kg(-1) x min pM(-1) on placebo to 0.04 on pioglitazone (P = 0.0002), and there were decreases in fasting levels of factor (F) VII:C (102 +/- 17% to 92 +/- 18%, P = 0.001), FVII:Ag (68 +/- 12% to 60 +/- 14%, P = 0.01) and in von Willebrand factor (VWF) (174 +/- 94% to 142 +/- 69%, P = 0.01). Pioglitazone lowered postprandial levels of FVII:Ag, FVII:C, plasminogen activator inhibitor-1, VWF, and triglycerides, and increased high-density lipoproteins (+9%, P = 0.02). CONCLUSIONS Pioglitazone improves insulin sensitivity and favorably modifies fasting and postprandial lipid, hemostatic and inflammatory markers of the metabolic syndrome in overweight and obese non-diabetic patients with coronary artery disease.
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Affiliation(s)
- H Mieszczanska
- Cardiology, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA
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Manuel-Y-Keenoy B, de Vos C, van Campenhout A, Vinckx M, Abrams P, van Campenhout C. Divergent in vitro and in vivo lipid peroxidation in the postprandial phase of patients with type I diabetes mellitus. Eur J Clin Nutr 2007; 62:401-10. [PMID: 17426748 DOI: 10.1038/sj.ejcn.1602698] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Abstract
OBJECTIVE The two- to fourfold higher risk of cardiovascular disease in diabetes mellitus is more strongly predicted by the postprandial than by the fasting blood glucose and lipids. We aimed to investigate the impact of postprandial changes in serum lipoprotein fractions on lipid peroxidation in type I diabetes mellitus (T1DM). DESIGN This was a prospective observational study. SETTING The study was performed at Antwerp University Hospital, Belgium. SUBJECTS Twenty-three well-controlled T1DM patients were included. INTERVENTION Patients received a standard breakfast and lunch (>50% energy as fat). Blood was sampled at fasting (F), after the post-breakfast hyperglycemic peak (BP), just before lunch (B), after the post-lunch hyperglycemic peak (LP), after the post-lunch dale (LD) and 5 h after lunch (L) for the measurement of serum lipids, lipoprotein subfraction composition, alpha-tocopherol and lipid peroxidation in vivo and in vitro. RESULTS Serum triacylglycerols (Tgs) increased (from 1.03+/-0.40 at F to 1.60+/-0.87 mmol/l at LP, P=0.001), but cholesterol decreased by 12% in parallel with alpha-tocopherol (from 4.43+/-0.76 at F to 4.12+/-0.82 micromol/mmol total lipid at B, P=0.006). Although plasma malondialdehyde increased from 1.02+/-0.36 at F to 1.14+/-0.40 micromol/L at LP, P=0.03, copper-induced in vitro peroxidation decreased in the low-density lipoprotein and high-density lipoprotein fractions. CONCLUSIONS In well-controlled T1DM patients moderate postprandial increases in serum Tgs are accompanied by a relative deficiency in alpha-tocopherol. Lipid peroxidation in vivo increases but cannot be ascribed to changes in the susceptibility of lipoproteins to copper-induced in vitro peroxidation.
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Perkins JM, Davis SN. The Rationale for Prandial Glycemic Control in Diabetes Mellitus. ACTA ACUST UNITED AC 2007. [DOI: 10.1016/s1557-0843(07)80016-9] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/22/2022]
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Simm A, Wagner J, Gursinsky T, Nass N, Friedrich I, Schinzel R, Czeslik E, Silber RE, Scheubel RJ. Advanced glycation endproducts: a biomarker for age as an outcome predictor after cardiac surgery? Exp Gerontol 2007; 42:668-75. [PMID: 17482402 DOI: 10.1016/j.exger.2007.03.006] [Citation(s) in RCA: 68] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2006] [Revised: 03/17/2007] [Accepted: 03/20/2007] [Indexed: 11/28/2022]
Abstract
OBJECTIVE A decline in the function of all organs can be detected during ageing. Although the trend appears to be stable, deviation within the elderly population is much greater in comparison to young controls. The aim of the study was to identify a marker of senescence which correlates to heart function. Advanced glycation endproducts (AGEs) accumulate with age and are associated with degenerative diseases. METHODS Carboxymethyllysine (CML) concentrations in the pericardial fluid (as a measure of AGEs) were analysed with ELISA technique in 75 patients undergoing cardiac surgery and correlated with clinical parameters and outcome of these patients. RESULTS CML content of pericardial fluid increases significantly with age. AGEs show an inverse correlation to left ventricular ejection fraction. High CML levels correlate with poor outcome of patients as shown by adverse cardiac events, prolonged ventilation time and prolonged stay within the Intensive Care Unit. Within all parameters, AGE concentration of the pericardial fluid fits better with the outcome of the patients in comparison to age alone. Interestingly, medical treatment with nitrates correlates with increased CML content. CONCLUSION AGEs, in addition to being a marker of senescence, appear to represent a prognostic factor in cardiac surgery, which can be used as a predictor of patient outcome.
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Affiliation(s)
- A Simm
- Department of Cardiothoracic-Surgery, Martin-Luther University Halle-Wittenberg, Ernst-Grube Str 40, Halle, Germany.
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Alssema M, Schindhelm RK, Dekker JM, Diamant M, Kostense PJ, Teerlink T, Scheffer PG, Nijpels G, Heine RJ. Postprandial glucose and not triglyceride concentrations are associated with carotid intima media thickness in women with normal glucose metabolism: the Hoorn prandial study. Atherosclerosis 2007; 196:712-9. [PMID: 17275004 DOI: 10.1016/j.atherosclerosis.2006.12.021] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/09/2006] [Revised: 12/12/2006] [Accepted: 12/21/2006] [Indexed: 10/23/2022]
Abstract
The present study aimed to compare the associations of postprandial glucose (ppGL) and postprandial triglycerides (ppTG) with carotid intima media thickness (cIMT) in women with normal glucose metabolism (NGM) and type 2 diabetes (DM2). Post-menopausal women (76 with NGM, 78 with DM2), received two consecutive fat-rich and two consecutive carbohydrate-rich meals on separate occasions. Blood samples were taken before and 1, 2, 4, 6 and 8h following breakfast; lunch was given at t=4. Ultrasound imaging of the carotid artery was performed to measure cIMT. In women with NGM, an increase of 1.0 mmol/l glucose following the fat-rich meals was associated with a 50 microm cIMT increase (p=0.04), and following the carbohydrate meals, an increase of 1.8 mmol/l glucose was associated with a 50 microm larger cIMT (p=0.08). These associations were not explained by classical cardiovascular risk factors. However, no association between ppGL and cIMT was found in women with DM2 and ppTG were not associated with cIMT. The association between ppGL and cIMT in normoglycaemic women suggests that ppGL in the normal range is a marker or a risk factor for atherosclerosis. Postprandial glucose levels might be a better indicator of risk than post-OGTT glucose levels or triglyceride levels.
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Affiliation(s)
- M Alssema
- EMGO Institute, VU University Medical Center, Van der Boechorststraat 7, 1081 BT Amsterdam, The Netherlands.
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Yamagishi SI, Nakamura K, Matsui T, Ueda SI, Imaizumi T. Role of postprandial hyperglycaemia in cardiovascular disease in diabetes. Int J Clin Pract 2007; 61:83-7. [PMID: 17229182 DOI: 10.1111/j.1742-1241.2006.01168.x] [Citation(s) in RCA: 32] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
Diabetes is associated with a marked increase in the risk of atherosclerotic vascular disorders, including coronary, cerebrovascular and peripheral artery disease. Cardiovascular disease (CVD) could account for disabilities and high mortality rates in patients with diabetes. Conventional risk factors, including hyperlipidaemia, hypertension, smoking, obesity, lack of exercise and a positive family history, contribute similarly to macrovascular complications in type 2 diabetic patients and non-diabetic subjects. The levels of these factors in diabetic patients are certainly increased, but not enough to explain the exaggerated risk for macrovascular complications in diabetic population. Therefore, specific diabetes-related risk factors should be involved in the excess risk in diabetic patients. In this paper, we review the molecular mechanisms for accelerated atherosclerosis in diabetes, especially focusing on postprandial hyperglycaemia. We also discuss here the potential therapeutic strategy that specifically targets CVD in patients with diabetes.
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Affiliation(s)
- S-I Yamagishi
- Department of Medicine, Division of Cardiovascular Medicine, Kurume University School of Medicine, Kurume, Japan.
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Lucotti P, Setola E, Monti LD, Galluccio E, Costa S, Sandoli EP, Fermo I, Rabaiotti G, Gatti R, Piatti P. Beneficial effects of a long-term oral L-arginine treatment added to a hypocaloric diet and exercise training program in obese, insulin-resistant type 2 diabetic patients. Am J Physiol Endocrinol Metab 2006; 291:E906-12. [PMID: 16772327 DOI: 10.1152/ajpendo.00002.2006] [Citation(s) in RCA: 164] [Impact Index Per Article: 8.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Because chronic L-arginine supplementation improves insulin sensitivity and endothelial function in nonobese type 2 diabetic patients, the aim of this study was to evaluate the effects of a long-term oral L-arginine therapy on adipose fat mass (FM) and muscle free-fat mass (FFM) distribution, daily glucose levels, insulin sensitivity, endothelial function, oxidative stress, and adipokine release in obese type 2 diabetic patients with insulin resistance who were treated with a combined period of hypocaloric diet and exercise training. Thirty-three type 2 diabetic patients participated in a hypocaloric diet plus an exercise training program for 21 days. Furthermore, they were divided into two groups in randomized order: the first group was also treated with L-arginine (8.3 g/day), and the second group was treated with placebo. Although in the placebo group body weight, waist circumference, daily glucose profiles, fructosamine, insulin, and homeostasis model assessment index significantly decreased, L-arginine supplementation further decreased FM (P < 0.05) and waist circumference (P < 0.0001), preserving FFM (P < 0.03), and improved mean daily glucose profiles (P < 0.0001) and fructosamine (P < 0.03). Moreover, change in area under the curve of cGMP (second messenger of nitric oxide; P < 0.001), superoxide dismutase (index of antioxidant capacity; P < 0.01), and adiponectin levels (P < 0.02) increased, whereas basal endothelin-1 levels (P < 0.01) and leptin-to-adiponectin ratio (P < 0.05) decreased in the L-arginine group. Long-term oral L-arginine treatment resulted in an additive effect compared with a diet and exercise training program alone on glucose metabolism and insulin sensitivity. Furthermore, it improved endothelial function, oxidative stress, and adipokine release in obese type 2 diabetic patients with insulin resistance.
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Affiliation(s)
- Pietro Lucotti
- Diabetology, Endocrinology and Metabolic Disease Unit, Fondazione Centro San Raffaele del Monte Tabor, Milan, Italy
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Basta G, Sironi AM, Lazzerini G, Del Turco S, Buzzigoli E, Casolaro A, Natali A, Ferrannini E, Gastaldelli A. Circulating soluble receptor for advanced glycation end products is inversely associated with glycemic control and S100A12 protein. J Clin Endocrinol Metab 2006; 91:4628-34. [PMID: 16926247 DOI: 10.1210/jc.2005-2559] [Citation(s) in RCA: 160] [Impact Index Per Article: 8.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/12/2023]
Abstract
CONTEXT The interaction of advanced glycation end products, including Nepsilon-(carboxymethyl)lysine-protein adducts (CML) and S100A12 protein, with their cellular receptor (RAGE) is implicated in the pathogenesis of diabetic vascular complications. RAGE has a circulating secretory receptor form, soluble RAGE (sRAGE), which, by neutralizing the action of advanced glycation end products, might exert a protective role against the development of cardiovascular disease. OBJECTIVE The objective of the study was to investigate whether plasma sRAGE levels are associated with glycemic control, proinflammatory factors, or circulating ligands of RAGE such as plasma CML and S100A12 protein. STUDY DESIGN We studied 160 subjects, 84 subjects with type 2 diabetes (aged 60 +/- 7 yr) and 76 nondiabetic controls (aged 45 +/- 10 yr). RESULTS Plasma sRAGE was lower in diabetic patients than controls [141 (53-345) vs. 735 (519-1001) pg/ml, median (interquartile range), P < 0.0001], whereas CML levels were higher in diabetic patients than controls [67.9 (46.0-84.7) vs. 43.4 (28.0-65.0) microg/ml, P < 0.0001]. In stepwise regression analysis of the whole data set, hemoglobin A1c, insulin resistance (as homeostasis model assessment), and C-reactive protein were independently associated with plasma sRAGE, whereas age was not. In a subgroup of 26 diabetic and 24 nondiabetic subjects of similar age (54 +/- 3 yr), plasma S100A12 levels were higher in diabetic subjects [49 (39-126) vs. 28 (21-39) ng/ml]. Moreover, low sRAGE and high S100A12 were strongly associated with increased risk for cardiovascular disease (Framingham score). In this subgroup, the plasma S100A12 level was the only determinant of plasma sRAGE concentration. CONCLUSION Plasma level of sRAGE is down-regulated in chronic hyperglycemia; among its ligands, S100A12 protein, but not CML, appears to be associated with this effect.
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Affiliation(s)
- Giuseppina Basta
- Consiglio Nazionale delle Richerche Institute of Clinical Physiology, Via Moruzzi, 1, 56124 Pisa, Italy.
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Ceriello A, Davidson J, Hanefeld M, Leiter L, Monnier L, Owens D, Tajima N, Tuomilehto J. Postprandial hyperglycaemia and cardiovascular complications of diabetes: an update. Nutr Metab Cardiovasc Dis 2006; 16:453-456. [PMID: 16934443 DOI: 10.1016/j.numecd.2006.05.006] [Citation(s) in RCA: 117] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/20/2006] [Revised: 05/07/2006] [Accepted: 05/25/2006] [Indexed: 11/16/2022]
Abstract
Type 2 diabetes is characterised by a gradual decline in insulin secretion in response to nutrient loads; hence, it is primarily a disorder of postprandial glucose (PPG) regulation. However, physicians continue to rely on fasting plasma glucose (FPG) and glycosylated haemoglobin (HbA1c) levels as indicators for disease management. There is a linear relationship between the risk of cardiovascular disease (CVD) and the two-hour oral glucose tolerance test (OGTT), while a recent study confirms postprandial hyperglycaemia as an independent risk factor for CVD in type 2 diabetes. At the same time, several intervention studies have shown that treating postprandial hyperglycaemia may reduce the incidence of new cardiovascular events. Evidence supports the hypothesis that postprandial hyperglycaemia may be linked to CVD through the generation of oxidative stress. Furthermore, clinical data suggest that postprandial hyperglycaemia is a common phenomenon, even in patients who may be considered in 'good metabolic control'. Therefore, in addition to HbA1c and FPG, physicians should consider monitoring and targeting PPG in patients with type 2 diabetes.
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Affiliation(s)
- Antonio Ceriello
- Clinical Science Research Institute, Clinical Science Building, Warwick Medical School, University of Warwick, Coventry, UK.
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