title: Effects of 6-month eicosapentaenoic acid treatment on postprandial hyperglycemia, hyperlipidemia, insulin secretion ability, and concomitant endothelial dysfunction among newly-diagnosed impaired glucose metabolism patients with coronary artery disease. An open label, single blinded, prospective randomized controlled trial.
abstract: Recent experimental studies have revealed that n-3 fatty acids, such as eicosapentaenoic acid (EPA) regulate postprandial insulin secretion, and correct postprandial glucose and lipid abnormalities. However, the effects of 6-month EPA treatment on postprandial hyperglycemia and hyperlipidemia, insulin secretion, and concomitant endothelial dysfunction remain unknown in patients with impaired glucose metabolism (IGM) and coronary artery disease (CAD).
  
  
  
  We randomized 107 newly diagnosed IGM patients with CAD to receive either 1800 mg/day of EPA (EPA group, n = 53) or no EPA (n = 54). Cookie meal testing (carbohydrates: 75 g, fat: 28.5 g) and endothelial function testing using fasting-state flow-mediated dilatation (FMD) were performed before and after 6 months of treatment. The primary outcome of this study was changes in postprandial glycemic and triglyceridemic control and secondary outcomes were improvement of insulin secretion and endothelial dysfunction. After 6 months, the EPA group exhibited significant improvements in EPA/arachidonic acid, fasting triglyceride (TG), and high-density lipoprotein cholesterol (HDL-C). The EPA group also exhibited significant decreases in the incremental TG peak, area under the curve (AUC) for postprandial TG, incremental glucose peak, AUC for postprandial glucose, and improvements in glycometabolism categorization. No significant changes were observed for hemoglobin A1c and fasting plasma glucose levels. The EPA group exhibited a significant increase in AUC-immune reactive insulin/AUC-plasma glucose ratio (which indicates postprandial insulin secretory ability) and significant improvements in FMD. Multiple regression analysis revealed that decreases in the TG/HDL-C ratio and incremental TG peak were independent predictors of FMD improvement in the EPA group.
  
  
  
  EPA corrected postprandial hypertriglyceridemia, hyperglycemia and insulin secretion ability. This amelioration of several metabolic abnormalities was accompanied by recovery of concomitant endothelial dysfunction in newly diagnosed IGM patients with CAD. Clinical Trial Registration UMIN Registry number: UMIN000011265 ( https://www.upload.umin.ac.jp/cgi-open-bin/ctr/ctr.cgi?function=brows&action=brows&type=summary&recptno=R000013200&language=E ).
authors: Division of Cardiovascular Medicine, Department of Internal Medicine, Hyogo Prefectural Himeji Cardiovascular Center, 520 Saisho-Kou, Himeji, Hyogo, 670-0981, Japan. taktak319@yahoo.co.jp.
authors: Takahiro
authors: T
authors: Sawada
authors: Division of Cardiovascular Medicine, Department of Internal Medicine, Hyogo Prefectural Himeji Cardiovascular Center, 520 Saisho-Kou, Himeji, Hyogo, 670-0981, Japan.
authors: Hideo
authors: H
authors: Tsubata
authors: Division of Diabetes and Endocrinology, Hyogo Prefectural Himeji Cardiovascular Center, 520, Saisho-Kou, Himeji, Hyogo, 670-0981, Japan.
authors: Naoko
authors: N
authors: Hashimoto
authors: Division of Diabetes and Endocrinology, Hyogo Prefectural Himeji Cardiovascular Center, 520, Saisho-Kou, Himeji, Hyogo, 670-0981, Japan.
authors: Michinori
authors: M
authors: Takabe
authors: Division of Cardiovascular Medicine, Department of Internal Medicine, Hyogo Prefectural Himeji Cardiovascular Center, 520 Saisho-Kou, Himeji, Hyogo, 670-0981, Japan.
authors: Taishi
authors: T
authors: Miyata
authors: Division of Cardiovascular Medicine, Department of Internal Medicine, Hyogo Prefectural Himeji Cardiovascular Center, 520 Saisho-Kou, Himeji, Hyogo, 670-0981, Japan.
authors: Kosuke
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authors: Aoki
authors: Division of Cardiovascular Medicine, Department of Internal Medicine, Hyogo Prefectural Himeji Cardiovascular Center, 520 Saisho-Kou, Himeji, Hyogo, 670-0981, Japan.
authors: Soichiro
authors: S
authors: Yamashita
authors: Division of Cardiovascular Medicine, Department of Internal Medicine, Hyogo Prefectural Himeji Cardiovascular Center, 520 Saisho-Kou, Himeji, Hyogo, 670-0981, Japan.
authors: Shogo
authors: S
authors: Oishi
authors: Division of Cardiovascular Medicine, Department of Internal Medicine, Hyogo Prefectural Himeji Cardiovascular Center, 520 Saisho-Kou, Himeji, Hyogo, 670-0981, Japan.
authors: Tsuyoshi
authors: T
authors: Osue
authors: Division of Cardiovascular Medicine, Department of Internal Medicine, Hyogo Prefectural Himeji Cardiovascular Center, 520 Saisho-Kou, Himeji, Hyogo, 670-0981, Japan.
authors: Kiminobu
authors: K
authors: Yokoi
authors: Division of Cardiovascular Medicine, Department of Internal Medicine, Hyogo Prefectural Himeji Cardiovascular Center, 520 Saisho-Kou, Himeji, Hyogo, 670-0981, Japan.
authors: Yasue
authors: Y
authors: Tsukishiro
authors: Division of Cardiovascular Medicine, Department of Internal Medicine, Hyogo Prefectural Himeji Cardiovascular Center, 520 Saisho-Kou, Himeji, Hyogo, 670-0981, Japan.
authors: Tetsuari
authors: T
authors: Onishi
authors: Division of Cardiovascular Medicine, Department of Internal Medicine, Hyogo Prefectural Himeji Cardiovascular Center, 520 Saisho-Kou, Himeji, Hyogo, 670-0981, Japan.
authors: Akira
authors: A
authors: Shimane
authors: Division of Cardiovascular Medicine, Department of Internal Medicine, Hyogo Prefectural Himeji Cardiovascular Center, 520 Saisho-Kou, Himeji, Hyogo, 670-0981, Japan.
authors: Yasuyo
authors: Y
authors: Taniguchi
authors: Division of Cardiovascular Medicine, Department of Internal Medicine, Hyogo Prefectural Himeji Cardiovascular Center, 520 Saisho-Kou, Himeji, Hyogo, 670-0981, Japan.
authors: Yoshinori
authors: Y
authors: Yasaka
authors: Division of Diabetes and Endocrinology, Hyogo Prefectural Himeji Cardiovascular Center, 520, Saisho-Kou, Himeji, Hyogo, 670-0981, Japan.
authors: Takeshi
authors: T
authors: Ohara
authors: Division of Cardiovascular Medicine, Department of Internal Medicine, Hyogo Prefectural Himeji Cardiovascular Center, 520 Saisho-Kou, Himeji, Hyogo, 670-0981, Japan.
authors: Hiroya
authors: H
authors: Kawai
authors: Division of Cardiovascular Medicine, Department of Internal Medicine, Hyogo Prefectural Himeji Cardiovascular Center, 520 Saisho-Kou, Himeji, Hyogo, 670-0981, Japan.
authors: Mitsuhiro
authors: M
authors: Yokoyama
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D003324:Coronary Artery Disease / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D004334:Drug Administration Schedule; D015118:Eicosapentaenoic Acid / Q000008:administration & dosage* / Q000009:adverse effects; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000503:physiopathology; D005260:Female; D006801:Humans; D006943:Hyperglycemia / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D015228:Hypertriglyceridemia / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D000960:Hypolipidemic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D018836:Inflammation Mediators / Q000097:blood; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D000078790:Insulin Secretion; D007564:Japan; D008297:Male; D008875:Middle Aged; D019518:Postprandial Period; D011446:Prospective Studies; D020127:Recovery of Function; D016037:Single-Blind Method; D013997:Time Factors; D016896:Treatment Outcome; D014280:Triglycerides / Q000097:blood; D014664:Vasodilation / Q000187:drug effects
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D007004:Hypoglycemic Agents; D000960:Hypolipidemic Agents; D018836:Inflammation Mediators; D007328:Insulin; D014280:Triglycerides; D015118:Eicosapentaenoic Acid
keywords: Eicosapentaenoic acid; Endothelial dysfunction; Impaired glucose metabolism; Postprandial hyperglycemia; Postprandial hypertriglyceridemia; Postprandial insulin secretion