期刊论文详细信息
Diabetology & Metabolic Syndrome
Effects of nateglinide and rosiglitazone on pancreatic alpha- and beta-cells, GLP-1 secretion and inflammatory markers in patients with type 2 diabetes: randomized crossover clinical study
Maria Elizabeth Rossi da Silva1  Rosa Ferreira dos Santos1  Dalva Marreiro Rocha1  Márcia Regina Silva Correia1  Rosa Tsumeshiro Fukui1  Maria Rosário Cunha1  Glauce Cordeiro Ulhôa Tostes1 
[1] Laboratório de Carboidratos e Radioimunoensaios LIM-18 do Hospital das Clínicas da Faculdade de Medicina da, Universidade de São Paulo, São Paulo, Brazil
关键词: Type 2 diabetes;    Inflammatory markers;    Haemostatic factors;    GLP-1;    Rosiglitazone;    Nateglinide;   
Others  :  1235250
DOI  :  10.1186/s13098-015-0120-6
PDF
【 摘 要 】

Background

To compare the effects of nateglinide and rosiglitazone on inflammatory markers, GLP-1 levels and metabolic profile in patients with type 2 diabetes (DM2).

Methods

A prospective study was performed in 20 patients with DM2, mean age 51.82 ± 8.05 years, previously treated with dietary intervention. Participants were randomized into rosiglitazone (4–8 mg/day) or nateglinide (120 mg 3 times a day) therapy. After 4 months, the patients were crossed-over with 8 weeks washout period to the alternative treatment for an additional 4-month period on similar dosage schedule. The following variables were assessed before and after 4 months of each treatment period: (1) a test with a standardized 500 calories meal for 5 h including frequent measurements of glucose, insulin, glucagon, proinsulin, GLP-1, free fat acids (FFA), and triglycerides levels was obtained. The lipid profile and HbA1 levels were measured at fasting. (2) Haemostatic and inflammatory markers: platelet aggregation, fibrinogen, PAI-1 activity, C reactive protein (CRP), IL-6, TNF-α, leptin, sICAM and TGFβ levels.

Results

Both therapy decreased blood glucose levels under the postprandial curve but neither affected glucagon and GLP-1 levels. Nateglinide was associated with higher insulin and pro-insulin secretion, but similar pro-insulin/insulin ratio when compared with rosiglitazone. Only rosiglitazone decreased Homa β, PAI-1 activity, CRP, fibrinogen, TGFβ, FFA and triglyceride levels.

Conclusions

Nateglinide and rosiglitazone were effective in improving glucose and lipid profile and β cell function, but rosiglitazone afforded a better anti-inflammatory effect. No drug restored alpha cell sensitivity or changed GLP-1 levels. Maintenance of haemostatic factors, inflammatory factors and glucagon levels can be related to the continuously worsening of cardiovascular function and glucose control observed in DM2.

【 授权许可】

   
2016 Tostes et al.

【 预 览 】
附件列表
Files Size Format View
20160108031805835.pdf 1067KB PDF download
Fig.2. 60KB Image download
Fig.1. 86KB Image download
【 图 表 】

Fig.1.

Fig.2.

【 参考文献 】
  • [1]Stolar M: Glycemic control and complications in type 2 diabetes mellitus. Am J Med 2010, 123(Suppl 3):S3-S11.
  • [2]American Diabetes Association: Standards of medical care in diabetes 2014 Diabetes Care 2014, 37(suppl 1):S14-S80.
  • [3]Yau H, Rivera K, Lomonaco R, Cusi K: The future of thiazolidinedione therapy in the management of type 2 diabetes mellitus. Curr Diab Rep 2013, 13:329-341.
  • [4]Parulkar AA, Pendergrass ML, Granda-Ayala R, Lee TR, Fonseca VA: Nonhypoglycemic effects of thiazolidinediones. Ann Intern Med 2001, 134:61-71.
  • [5]Zou C, Hu H: Use of pioglitazone in the treatment of diabetes: effect on cardiovascular risk. Vasc Health Risk Manag 2013, 9:429-433.
  • [6]Guardado-Mendoza R, Prioletta A, Jiménez-Ceja LM, Sosale A, Folli F: The role of nateglinide and repaglinide, derivatives of meglitinide, in the treatment of type 2 diabetes mellitus. Arch Med Sci. 2013, 9:936-943.
  • [7]Hu S: Interaction of nateglinide with K (ATP) channel in beta-cells underlies its unique insulinotropic action. Eur J Pharmacol 2002, 442:163-171.
  • [8]Kitahara Y, Miura K, Yasuda R, Kawanabe H, Ogawa S, Eto Y: Nateglinide stimulates glucagon-like peptide-1 release by human intestinal L cells via a K (ATP) channel-independent mechanism. Biol Pharm Bull 2011, 34:671-676.
  • [9]Abdelmoneim AS, Hasenbank SE, Seubert JM, Brocks DR, Light PE, Simpson SH: Variations in tissue selectivity amongst insulin secretagogues: a systematic review. Diabetes Obes Metab 2012, 14:130-138.
  • [10]Mita T, Watada H, Shimizu T, Tamura Y, Sato F, Watanabe T, Choi JB, Hirose T, Tanaka Y, Kawamori R: Nateglinide reduces carotid intima-media thickening in type 2 diabetic patients under good glycemic control. Arterioscler Thromb Vasc Biol 2007, 27:2456-2462.
  • [11]Derosa G: Nateglinide does not reduce the incidence of diabetes or cardiovascular outcomes in people with impaired glucose tolerance and cardiovascular disease or risk factors. Evid Based Med. 2011, 16:7-8.
  • [12]Kato, T., et al. Postprandial endothelial dysfunction in subjects with new-onset type 2 diabetes: an acarbose and nateglinide comparative study. Cardiovasc Diabetol. 2010. doi:10.1186/1475-2840-9-12.
  • [13]The NAVIGATOR study Group: Effect of nateglinide on the incidence of diabetes and cardiovascular events N Engl J Med 2010, 362:1463-1476.
  • [14]Major-Pedersen A, et al.: Effects of acute and chronic attenuation of postprandial hyperglycemia on postglucose-load endothelial function in insulin resistant individuals: is stimulation of first phase insulin secretion beneficial for the endothelial function? Horm Metab Res 2008, 40:607-613.
  • [15]Clauss A: Rapid physiological coagulation method for determination of fibrinogen. Acta Haematol 1957, 17:237-246.
  • [16]Born GVR: Aggregation of blood platelets by adenosine diphosphate and its resersal. Nature 1962, 194:927-929.
  • [17]Singer JM, Andrade DF. Bio-environmental and public health statistics. In: Sen PK, Rao CR, editors. Analysis of longitudinal data. In Handbook of Statistics. Amsterdam: North Holland; 2000. pp. 115–60.
  • [18]Inoguchi T, et al.: Chronic sulfonylurea treatment and hyperglycemia aggravate disproportionately elevated plasma proinsulin levels in patients with type 2 diabetes. Endocr J 2000, 6:763-770.
  • [19]Pozzilli P, Strollo R, Bonora E: One size does not fit all glycemic targets for type 2 diabetes. J Diabetes Investig 2014, 5:134-141.
  • [20]Martin JH, Deacon CF, Gorrell MD, Prins JB: Incretin-based therapies—review of the physiology, pharmacology and emerging clinical experience. Intern Med J. 2011, 41:299-307.
  • [21]Duffy NA, Green BD, Irwin N, Gault VA, McKillop AM, O’Harte FP, et al.: Effects of antidiabetic drugs on dipeptidyl peptidase IV activity: nateglinide is an inhibitor of DPP IV and augments the antidiabetic activity of glucagon-like peptide-1. Eur J Pharmacol 2007, 568:278-286.
  • [22]McKillop AM, Duffy NA, Lindsay JR, Green BD, Patterson S, O’Harte FP, Bell PM, Flatt PR: Insulinotropic actions of nateglinide in type 2 diabetic patients and effects on dipeptidyl peptidase-IV activity and glucose-dependent insulinotropic polypeptide degradation. Eur J Endocrinol 2009, 161:877-885.
  文献评价指标  
  下载次数:37次 浏览次数:14次