Skip to main content
SpringerLink
Log in

Metabolic and vascular effects of silybin in hypertensive patients with high 1-h post-load plasma glucose

  • IM - ORIGINAL
  • Published:
Internal and Emergency Medicine Aims and scope Submit manuscript

Abstract

Hypertensive patients with normal glucose tolerance (NGT) but 1-h post-load plasma glucose ≥ 155 mg/dl (1-h high), during an oral glucose tolerance test (OGTT), show higher insulin resistance and multiple target organ damages. Experimental and clinical studies demonstrate that silybin presents anti-inflammatory and metabolic effects, improving insulin resistance and endothelial dysfunction. This study aims to evaluate the effects of the complex silybin–vitamin E and phospholipids on inflammatory, metabolic and vascular parameters in NGT 1-h high hypertensive patients. This is a pilot, single arm, interventional, longitudinal study enrolling 50 Caucasian NGT 1-h high hypertensive outpatients, 27 men and 23 women, age range 42–60 years (mean + SD = 52 ± 7). After 6 months of silybin intake, there is a significant improvement in metabolic profile. The glucose response during OGTT significantly improves (AUCglucose0–120 309.6 ± 63.4 at baseline vs 254.6 ± 35.5 at the follow-up, ∆ = − 55, 95% CI from − 67 to − 43, p < 0.0001), so as insulin response (AUCinsulin0–120 238.2 ± 99.1 vs 159.3 ± 44.9, ∆ = − 78.9, 95% CI from − 100.0 to − 57.8, p < 0.0001), in accordance with the increase of insulin sensitivity index Matsuda. Silybin intake is associated with a significant reduction of both clinical and central systolic blood pressure, with betterment in clinical and central pulse pressure and reduction of arterial stiffness parameters. In conclusion, this study demonstrates that silybin may improve the metabolic aspect and vascular damage in NGT 1-h high hypertensive patients who are at higher metabolic and cardiovascular risk. Thus, in these patients, silybin might strengthen the effect of antihypertensive drugs giving further cardiovascular protection.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Ferrannini E, Cushman WC (2012) Diabetes and hypertension: the bad companions. Lancet 380:601–610. https://doi.org/10.1016/S0140-6736(12)60987-8

    Article  PubMed  Google Scholar 

  2. Muniyappa R, Montagnani M, Koh KK, Quon MJ (2007) Cardiovascular actions of insulin. Endocr Rev 28:463–491. https://doi.org/10.1210/er.2007-0006

    Article  CAS  PubMed  Google Scholar 

  3. Fiorentino TV, Marini MA, Andreozzi F, Arturi F, Succurro E, Perticone M, Sciacqua A, Hribal ML, Perticone F, Sesti G (2015) One-hour post load hyperglycemia is a stronger predictor of type 2 diabetes than impaired fasting glucose. J Clin Endocrinol Metab 100:3744–3751. https://doi.org/10.1210/jc.2015-2573

    Article  CAS  PubMed  Google Scholar 

  4. Sciacqua A, Miceli S, Carullo G, Greco L, Succurro E, Arturi F, Sesti G, Perticone F (2011) One-hour post load plasma glucose levels and left ventricular mass in hypertensive patients. Diabetes Care 34:1–6. https://doi.org/10.2337/dc11-0155

    Article  CAS  Google Scholar 

  5. Sciacqua A, Miceli S, Greco L, Arturi F, Naccarato P, Mazzaferro D, Tassone EJ, Turano L, Martino F, Sesti G, Perticone F (2011) One-hour postload plasma glucose levels and diastolic function in hypertensive patients. Diabetes Care 34:2291–2296. https://doi.org/10.2337/dc11-0879

    Article  PubMed  PubMed Central  Google Scholar 

  6. Sciacqua A, Maio R, Miceli S, Pascale A, Carullo G, Grillo N, Arturi F, Sesti G, Perticone F (2012) Association between one-hour post-load plasma glucose levels and vascular stiffness in essential hypertension. PLoS One 7:e44470. https://doi.org/10.1371/journal.pone.0044470

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Perticone F, Sciacqua A, Perticone M, Miceli S, Maio R, Tassone JE, Arturi F, Sesti G (2013) Phenotypic characterization of normotolerant hypertensive patients. Int J Cardiol 165:322–326. https://doi.org/10.1016/j.ijcard.2011.08.076

    Article  PubMed  Google Scholar 

  8. Perticone F, Sciacqua A, Perticone M, Arturi F, Scarpino PE, Quero M, Sesti G (2012) Diabetes Care 35:153–157. https://doi.org/10.2337/dc11-1727

    Article  CAS  PubMed  Google Scholar 

  9. Loguercio C, Festi D (2011) Silybin and the liver: from basic research to clinical practice. World J Gastroenterol 17:2288–2301. https://doi.org/10.3748/wjg.v17.i18.2288

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Trappoliere M, Caligiuri A, Schmid M, Bertolani C, Failli P, Vizzutti F, Novo E, di Manzano C, Marra F, Loguercio C, Pinzani M (2009) Silybin, a component of silymarin, exerts anti-inflammatory and anti-fibrogenic effects on human hepatic stellate cells. J Hepatol 50:1102–1111. https://doi.org/10.1016/j.jhep.2009.02.023

    Article  CAS  PubMed  Google Scholar 

  11. Federico A, Trappoliere M, Tuccillo C, de Sio I, Di Leva A, Del Vecchio Blanco C, Loguercio C (2006) A new silybin–vitamin E–phospholipid complex improves insulin resistance and liver damage in patients with non-alcoholic fatty liver disease: preliminary observations. Gut 55:901–902. https://doi.org/10.1136/gut.2006.091967

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Loguercio C, Andreone P, Brisc C, Brisc MC, Bugianesi E, Chiaramonte M, Cursaro C, Danila M, de Sio I, Floreani A, Freni MA, Grieco A, Groppo M, Lazzari R, Lobello S, Lorefice E, Margotti M, Miele L, Milani S, Okolicsanyi L, Palasciano G, Portincasa P, Saltarelli P, Smedile A, Somalvico F, Spadaro A, Sporea I, Sorrentino P, Vecchione R, Tuccillo C, Del Vecchio Blanco C, Federico A (2012) Silybin combined with phosphatidylcholine and vitamin E in patients with nonalcoholic fatty liver disease: a randomized controlled trial. Free Radic Biol Med 52:1658–1665. https://doi.org/10.1016/j.freeradbiomed.2012.02.008

    Article  CAS  PubMed  Google Scholar 

  13. Li Volti G, Salomone S, Sorrenti V, Mangiameli A, Urso V, Siarkos I, Galvano F, Salamone F (2011) Effect of silibinin on endothelial dysfunction and ADMA levels in obese diabetic mice. Cardiovasc Diabetol. 10:62. https://doi.org/10.1186/1475-2840-10-62

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Matsuda M, DeFronzo RA (1999) Insulin sensitivity indices obtained from oral glucose tolerance testing: comparison with the euglycemic insulin clamp. Diabetes Care 22:1462–1470

    Article  CAS  PubMed  Google Scholar 

  15. Abdul-Ghani MA, Matsuda M, Balas B, DeFronzo RA (2007) Muscle and liver insulin resistance indexes derived from the oral glucose tolerance test. Diabetes Care 30:89–94. https://doi.org/10.2337/dc06-1519

    Article  CAS  PubMed  Google Scholar 

  16. Le Floch JP, Escuyer P, Baudin E, Baudon D, Perlemuter L (1990) Blood glucose area under the curve, methodological aspects. Diabetes Care 13:172–175

    Article  PubMed  Google Scholar 

  17. Levey AS, Stevens LA, Schmid CH, Zhang YL, Castro AF 3rd, Feldman HI, Kusek JW, Eggers P, Van Lente F, Greene T, Coresh J, CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) (2009) A new equation to estimate glomerular filtration rate. Ann Intern Med 150:604–612

    Article  PubMed  PubMed Central  Google Scholar 

  18. ESH/ESC guidelines for the management of arterial hypertension (2013) The task force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). Eur Heart J 34:2159–2219. https://doi.org/10.1093/eurheartj/eht151

    Article  Google Scholar 

  19. Chen CH, Ting CT, Nussbacher A, Nevo E, Kass DA, Pak P, Wang SP, Chang MS, Yin FC (1996) Validation of carotid artery tonometry as a means of estimating augmentation index of ascending aortic pressure. Hypertension 27:168–175

    Article  CAS  PubMed  Google Scholar 

  20. European Guidelines on cardiovascular disease prevention in clinical practice (2016) The sixth joint task force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice (constituted by representatives of 10 societies and by invited experts) Developed with the special contribution of the European Association for Cardiovascular Prevention & Rehabilitation (EA). Eur Heart J 37:2315–2381

    Article  Google Scholar 

  21. Bolignano D, Mattace-Raso F, Torino C, D’Arrigo G, Abd ElHafeez S, Provenzano F, Zoccali C, Tripepi G (2013) The quality of reporting in clinical research: the CONSORT and STROBE initiatives. Aging Clin Exp Res 25:9–15. https://doi.org/10.1007/s40520-013-007-z

    Article  PubMed  Google Scholar 

  22. Li HB, Yang YR, Mo ZJ, Ding Y, Jiang WJ (2015) Silibinin improves palmitate-induced insulin resistance in C2C12 myotubes by attenuating IRS-1/PI3 K/Akt pathway inhibition. Braz J Med Biol Res 48:440–446. https://doi.org/10.1590/1414-431X20144238

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Zhang Y, Hai J, Cao M, Zhang Y, Pei S, Wang J, Zhang Q (2013) Silibinin ameliorates steatosis and insulin resistance during non-alcoholic fatty liver disease development partly through targeting IRS-1/PI3K/Akt pathway. Int Immunopharmacol 17:714–720. https://doi.org/10.1016/j.intimp.2013.08.019

    Article  CAS  PubMed  Google Scholar 

  24. Ceravolo R, Maio R, Cuda G, Scozzafava A, Sciacqua A, Vatrano M, Bellieni G, D’Angelo G, Schipani FA, Sesti G, Perticone F (2003) Relation of fasting insulin related to insertion/deletion polymorphism of angiotensin-converting enzyme-gene and cardiac mass in never-treated patients with systemic hypertension. Am J Cardiol 92:1234–1237

    Article  CAS  PubMed  Google Scholar 

  25. Nerpin E, Risérus U, Ingelsson E, Sundström J, Jobs M, Larsson A, Basu S, Arnlöv J (2008) Insulin sensitivity measured with euglycemic clamp is independently associated with glomerular filtration rate in a community-based cohort. Diabetes Care 31:1550–1555. https://doi.org/10.2337/dc08-0369

    Article  PubMed  PubMed Central  Google Scholar 

  26. Sciacqua A, Scozzafava A, Pujia A, Maio R, Borrello F, Andreozzi F, Vatrano M, Cassano S, Perticone M, Sesti G, Perticone F (2005) Interaction between vascular dysfunction and cardiac mass increases the risk of cardiovascular outcomes in essential hypertension. Eur Heart J 26:921–927. https://doi.org/10.1093/eurheartj/ehi112

    Article  PubMed  Google Scholar 

  27. Avolio AP, Van Bortel LM, Boutouyrie P, Cockcroft JR, McEniery CM, Protogerou AD, Roman MJ, Safar ME, Segers P, Smulyan H (2009) Role of pulse pressure amplification in arterial hypertension: experts’ opinion and review of the data. Hypertension 54:375–383. https://doi.org/10.1161/HYPERTENSIONAHA.109.134379

    Article  CAS  PubMed  Google Scholar 

  28. Ceravolo R, Maio R, Pujia A, Sciacqua A, Ventura G, Costa MC, Sesti G, Perticone F (2003) Pulse pressure and endothelial dysfunction in never-treated hypertensive patients. J Am Coll Cardiol 41:1753–1758

    Article  CAS  PubMed  Google Scholar 

  29. Perticone F, Sciacqua A, Maio R, Perticone M, Maas R, Boger RH, Tripepi G, Sesti G, Zoccali C (2005) Asymmetric dimethylarginine, l-arginine, and endothelial dysfunction in essential hypertension. J Am Coll Cardiol 46:518–523. https://doi.org/10.1016/j.jacc.2005.04.040

    Article  CAS  PubMed  Google Scholar 

  30. Yao J, Zhi M, Minhu C (2011) Effect of silybin on high-fat-induced fatty liver in rats. Braz J Med Biol Res 44:652–659

    CAS  PubMed  Google Scholar 

  31. Ettehad D, Emdin CA, Kiran A, Anderson SG, Callender T, Emberson J, Chalmers J, Rodgers A, Rahimi K (2016) Blood pressure lowering for prevention of cardiovascular disease and death: a systematic review and meta-analysis. Lancet 387:957–967. https://doi.org/10.1016/S0140-6736(15)01225-8

    Article  PubMed  Google Scholar 

Download references

Author information

Author notes

  1. Angela Sciacqua and Maria Perticone contributed equally to the work.

Authors and Affiliations

  1. Department of Medical and Surgical Sciences, University Magna Græcia of Catanzaro, Campus Universitario di Germaneto, V.le Europa, 88100, Catanzaro, Italy

    Angela Sciacqua, Velia Cassano, Raffaele Maio, Giorgio Sesti & Francesco Perticone

  2. Department of Experimental and Clinical Medicine, University Magna Græcia of Catanzaro, Catanzaro, Italy

    Maria Perticone

  3. CNR-IFC, Istituto di Fisiologia Clinica, Clinical Epidemiology and Physiopathology of Renal Diseases and Hypertension, Reggio Calabria, Italy

    Giovanni Tripepi

  4. Internal Medicine Unit, Pugliese-Ciaccio Hospital, Catanzaro, Italy

    Desire Addesi

Authors
  1. Angela Sciacqua
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Maria Perticone
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Giovanni Tripepi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Desire Addesi
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Velia Cassano
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Raffaele Maio
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Giorgio Sesti
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Francesco Perticone
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Angela Sciacqua.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Statements on human and animal rights

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Sciacqua, A., Perticone, M., Tripepi, G. et al. Metabolic and vascular effects of silybin in hypertensive patients with high 1-h post-load plasma glucose. Intern Emerg Med 14, 77–84 (2019). https://doi.org/10.1007/s11739-018-1951-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11739-018-1951-6

Keywords

Search

Navigation