Polyherbal dietary supplementation for prediabetic adults: study protocol for a randomized controlled trial

Termeh Feinberg, L Susan Wieland, Larry E Miller, Kashif Munir, Toni I Pollin, Alan R Shuldiner, Steve Amoils, Lisa Gallagher, Mary Bahr-Robertson, Christopher R D'Adamo, Termeh Feinberg, L Susan Wieland, Larry E Miller, Kashif Munir, Toni I Pollin, Alan R Shuldiner, Steve Amoils, Lisa Gallagher, Mary Bahr-Robertson, Christopher R D'Adamo

Abstract

Background: Prediabetes describes a state of hyperglycemia outside of normal limits that does not meet the criteria for diabetes diagnosis, is generally symptomless, and affects an estimated 38% of adults in the United States. Prediabetes typically precedes the diagnosis of type 2 diabetes, which accounts for increased morbidity and mortality. Although the use of dietary and herbal supplements is popular worldwide, and a variety of single herbal medicines have been examined for glycemic management, the potential of increasingly common polyherbal formulations to return glycemic parameters to normal ranges among adults with prediabetes remains largely unexplored. The purpose of this study is to evaluate the efficacy of a commercially available, polyherbal dietary supplement on glycemic and lipid parameters in prediabetic individuals.

Methods: In this multi-site, double-blinded, randomized controlled clinical trial, 40 participants with prediabetes will be randomized to either a daily oral polyherbal dietary supplement (GlucoSupreme™ Herbal; Designs for Health®, Suffield, CT, USA; containing cinnamon bark (Cinnamomum cassia), banaba leaf (Lagerstroemia speciosa standardized to 1% corosolic acid), kudzu root (Pueraria lobata standardized to 40% isoflavones), fenugreek seed (Trigonella foenum-graceum standardized to 60% saponins), gymnema leaf (Gymnema sylvestre standardized to 25% gymnemic acid), American ginseng root (Panax quinquefolius standardized to 5% ginsenosides), and berberine HCl derived from bark (Berberis aristata)) or placebo for 12 weeks. Short-, medium-, and comparatively long-term markers of glycemic control (blood glucose and fasting insulin, fructosamine, and glycated hemoglobin/A1c, respectively), and other glycemic parameters (GlycoMark, β-cell function, and insulin sensitivity/resistance) will be obtained. Lipid profile (total cholesterol, LDL, HDL, and triglycerides), inflammation (hs-CRP), progression to type 2 diabetes mellitus, as well as safety indices (ALT, AST) will be obtained. An intention-to-treat analysis will be used to assess changes in study outcomes.

Discussion: Treatment options for adults with prediabetes are currently limited. This study aims to evaluate the safety and efficacy of a commercially available dietary supplement in the popular, but as yet insufficiently studied, category of polyherbal formulas for the management of glycemic parameters and other biomarkers associated with prediabetes.

Trial registration: ClinicalTrials.gov, ID: NCT03388762 . Retrospectively registered on 4 January 2018.

Keywords: American ginseng; Banaba; Berberine; Botanical; Cinnamon; Fenugreek; Glucose metabolism disorders; Gymnema; Kudzu; Prediabetes.

Conflict of interest statement

Ethics approval and consent to participate

The trial has been approved by the University of Maryland School of Medicine IRB (#HP-00075768) and Western IRB (#20171220).

Consent for publication

This manuscript and subsequent manuscripts will not contain any individual person’s data in any form.

Competing interests

CD has received financial compensation for service on the Scientific Advisory Board of Designs for Health®. All other authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Data collection points for a polyherbal supplementation intervention for prediabetic adults

References

    1. IDF Diabetes Atlas. Brussels: International Diabetes Federation; 2007.
    1. Overall numbers, diabetes and prediabetes. . Accessed 03 Dec 2018.
    1. Diagnosing diabetes and learning about prediabetes. . Accessed 03 Dec 2018.
    1. Bonora E. Protection of pancreatic beta-cells: is it feasible? Nutr Metab Cardiovasc Dis. 2008;18:74–83. doi: 10.1016/j.numecd.2007.05.004.
    1. National Diabetes Statistics Report, 2017. . Accessed 03 Dec 2018.
    1. Nichols GA, Hillier TA, Brown JB. Normal fasting plasma glucose and risk of type 2 diabetes diagnosis. Am J Med. 2008;121:519–524. doi: 10.1016/j.amjmed.2008.02.026.
    1. Daniele G, Abdul-Ghani M, DeFronzo RA. What are the pharmacotherapy options for treating prediabetes? Expert Opin Pharmacother. 2014;15:2003–2018. doi: 10.1517/14656566.2014.944160.
    1. Rizos CV, Elisaf MS, Mikhailidis DP, Liberopoulos EN. How safe is the use of thiazolidinediones in clinical practice? 10.1517/14740330802597821.
    1. Grant SJ, Chang DH, Liu J, Wong V, Kiat H, Bensoussan A. Chinese herbal medicine for impaired glucose tolerance: a randomized placebo controlled trial. BMC Complement Altern Med. 2013;13:104. doi: 10.1186/1472-6882-13-104.
    1. Moerman DE, Moerman DE. Native American medicinal plants: an ethnobotanical dictionary. Portland: Timber Press; 2009.
    1. Göhre A, Toto-Nienguesse ÁB, Futuro M, Neinhuis C, Lautenschläger T. Plants from disturbed savannah vegetation and their usage by Bakongo tribes in Uíge, Northern Angola. J Ethnobiol Ethnomed. 2016;12:42. doi: 10.1186/s13002-016-0116-9.
    1. Hong L, Guo Z, Huang K, Wei S, Liu B, Meng S, Long C. Ethnobotanical study on medicinal plants used by Maonan people in China. J Ethnobiol Ethnomed. 2015;11:32. doi: 10.1186/s13002-015-0019-1.
    1. Mustafa B, Hajdari A, Krasniqi F, Hoxha E, Ademi H, Quave CL, Pieroni A. Medical ethnobotany of the Albanian Alps in Kosovo. J Ethnobiol Ethnomed. 2012;8:6. doi: 10.1186/1746-4269-8-6.
    1. Bussmann RW, Glenn A, Meyer K, Kuhlman A, Townesmith A. Herbal mixtures in traditional medicine in Northern Peru. J Ethnobiol Ethnomed. 2010;6:10. doi: 10.1186/1746-4269-6-10.
    1. Raj AJ, Biswakarma S, Pala NA, Shukla G, Vineeta, Kumar M, Chakravarty S, Bussmann RW. Indigenous uses of ethnomedicinal plants among forest-dependent communities of Northern Bengal, India. J Ethnobiol Ethnomed. 2018;14:8. doi: 10.1186/s13002-018-0208-9.
    1. Lans CA. Ethnomedicines used in Trinidad and Tobago for urinary problems and diabetes mellitus. J Ethnobiol Ethnomed. 2006;2:45. doi: 10.1186/1746-4269-2-45.
    1. Ocvirk S, Kistler M, Khan S, Talukder SH, Hauner H. Traditional medicinal plants used for the treatment of diabetes in rural and urban areas of Dhaka, Bangladesh – an ethnobotanical survey. J Ethnobiol Ethnomed. 2013;9:43. doi: 10.1186/1746-4269-9-43.
    1. Gaddam A, Galla C, Thummisetti S, Marikanty RK, Palanisamy UD, Rao PV. Role of Fenugreek in the prevention of type 2 diabetes mellitus in prediabetes. J Diabetes Metab Disord. 2015;14:74. doi: 10.1186/s40200-015-0208-4.
    1. Ziegenfuss TN, Hofheins JE, Mendel RW, Landis J, Anderson RA. Effects of a water-soluble cinnamon extract on body composition and features of the metabolic syndrome in pre-diabetic men and women. J Int Soc Sports Nutr. 2006;3:45–53. doi: 10.1186/1550-2783-3-2-45.
    1. Choi MS, Ryu R, Seo YR, Jeong TS, Shin DH, Park YB, Kim SR, Jung UJ. The beneficial effect of soybean (Glycine max (L.) Merr.) leaf extracts in adults with prediabetes: a randomized placebo controlled trial. Food Funct. 2014;5:1621–1630. doi: 10.1039/c4fo00199k.
    1. Liu Y, Cotillard A, Vatier C, Bastard JP, Fellahi S, Stevant M, Allatif O, Langlois C, Bieuvelet S, Brochot A, et al. A dietary supplement containing cinnamon, chromium and carnosine decreases fasting plasma glucose and increases lean mass in overweight or obese pre-diabetic subjects: a randomized, placebo-controlled trial. PLoS One. 2015;10:e0138646. doi: 10.1371/journal.pone.0138646.
    1. Neelakantan N, Narayanan M, de Souza RJ, van Dam RM. Effect of fenugreek (Trigonella foenum-graecum L.) intake on glycemia: a meta-analysis of clinical trials. Nutr J. 2014;13:7. doi: 10.1186/1475-2891-13-7.
    1. Suksomboon N, Poolsup N, Punthanitisarn S. Effect of Aloe vera on glycaemic control in prediabetes and type 2 diabetes: a systematic review and meta-analysis. J Clin Pharm Ther. 2016;41:180–188. doi: 10.1111/jcpt.12382.
    1. Davis PA, Yokoyama W. Cinnamon intake lowers fasting blood glucose: meta-analysis. J Med Food. 2011;14:884–889. doi: 10.1089/jmf.2010.0180.
    1. Alvarado J, Schoenlau F, Leschot A, Salgad AM, Vigil Portales P. Delphinol® standardized maqui berry extract significantly lowers blood glucose and improves blood lipid profile in prediabetic individuals in three-month clinical trial. Panminerva Med. 2016;58:1–6.
    1. Alvarado JL, Leschot A, Olivera-Nappa A, Salgado AM, Rioseco H, Lyon C, Vigil P. Delphinidin-Rich Maqui Berry Extract (Delphinol®) lowers fasting and postprandial glycemia and insulinemia in prediabetic individuals during oral glucose tolerance tests. Biomed Res Int. 2016;2016:9070537. doi: 10.1155/2016/9070537.
    1. An JH, Kim DL, Lee TB, Kim KJ, Kim SH, Kim NH, Kim HY, Choi DS, Kim SG. Effect of Rubus occidentalis extract on metabolic parameters in subjects with prediabetes: a proof-of-concept, randomized, double-blind, placebo-controlled clinical trial. Phytother Res. 2016;30:1634–1640. doi: 10.1002/ptr.5664.
    1. Banuls C, Rovira-Llopis S, Lopez-Domenech S, Veses S, Victor VM, Rocha M, Hernandez-Mijares A. Effect of consumption of a carob pod inositol-enriched beverage on insulin sensitivity and inflammation in middle-aged prediabetic subjects. Food Funct. 2016;7:4379–4387. doi: 10.1039/C6FO01021K.
    1. Lee SH, Jeon YJ. Efficacy and safety of a dieckol-rich extract (AG-dieckol) of brown algae, Ecklonia cava, in pre-diabetic individuals: a double-blind, randomized, placebo-controlled clinical trial. Food Funct. 2015;6:853–858. doi: 10.1039/C4FO00940A.
    1. Choi HC, Kim SJ, Son KY, Oh BJ, Cho BL. Metabolic effects of Aloe vera gel complex in obese prediabetes and early non-treated diabetic patients: randomized controlled trial. Nutrition. 2013;29:1110–1114. doi: 10.1016/j.nut.2013.02.015.
    1. Devaraj S, Yimam M, Brownell LA, Jialal I, Singh S, Jia Q. Effects of Aloe vera supplementation in subjects with prediabetes/metabolic syndrome. Metab Syndr Relat Disord. 2013;11:35–40. doi: 10.1089/met.2012.0066.
    1. Chuengsamarn S, Rattanamongkolgul S, Luechapudiporn R, Phisalaphong C, Jirawatnotai S. Curcumin extract for prevention of type 2 diabetes. Diabetes Care. 2012;35:2121–2127. doi: 10.2337/dc12-0116.
    1. Manaf A, Tjandrawinata RR, Malinda D. Insulin sensitizer in prediabetes: a clinical study with DLBS3233, a combined bioactive fraction of Cinnamomum burmanii and Lagerstroemia speciosa. Drug Des Devel Ther. 2016;10:1279–1289.
    1. ADA (6) Glycemic targets. Diabetes Care. 2015;38 Suppl:S33–S40.
    1. Goldstein DE, Little RR, Lorenz RA, Malone JI, Nathan D, Peterson CM, Sacks DB. Tests of glycemia in diabetes. Diabetes Care. 2004;27:1761–1773. doi: 10.2337/diacare.27.7.1761.
    1. Choi JH, Gaddameedhi S, Kim SY, Hu J, Kemp MG, Sancar A. Highly specific and sensitive method for measuring nucleotide excision repair kinetics of ultraviolet photoproducts in human cells. Nucleic Acids Res. 2014;42:e29. doi: 10.1093/nar/gkt1179.
    1. Zhang Y, Li X, Zou D, Liu W, Yang J, Zhu N, Huo L, Wang M, Hong J, Wu P, et al. Treatment of type 2 diabetes and dyslipidemia with the natural plant alkaloid berberine. J Clin Endocrinol Metab. 2008;93:2559–2565. doi: 10.1210/jc.2007-2404.
    1. Yin J, Xing H, Ye J. Efficacy of berberine in patients with type 2 diabetes mellitus. Metabolism. 2008;57:712–717. doi: 10.1016/j.metabol.2008.01.013.
    1. Zhang H, Wei J, Xue R, Wu JD, Zhao W, Wang ZZ, Wang SK, Zhou ZX, Song DQ, Wang YM, et al. Berberine lowers blood glucose in type 2 diabetes mellitus patients through increasing insulin receptor expression. Metabolism. 2010;59:285–292. doi: 10.1016/j.metabol.2009.07.029.
    1. Shishtar E, Sievenpiper JL, Djedovic V, Cozma AI, Ha V, Jayalath VH, Jenkins DJ, Meija SB, de Souza RJ, Jovanovski E, Vuksan V. The effect of ginseng (the genus Panax) on glycemic control: a systematic review and meta-analysis of randomized controlled clinical trials. PLoS One. 2014;9:e107391. doi: 10.1371/journal.pone.0107391.
    1. Vuksan V, Sievenpiper JL, Koo VY, Francis T, Beljan-Zdravkovic U, Xu Z, Vidgen E. American ginseng (Panax quinquefolius L) reduces postprandial glycemia in nondiabetic subjects and subjects with type 2 diabetes mellitus. Arch Intern Med. 2000;160:1009–1013. doi: 10.1001/archinte.160.7.1009.
    1. Baskaran K, Kizar Ahamath B, Radha Shanmugasundaram K, Shanmugasundaram ER. Antidiabetic effect of a leaf extract from Gymnema sylvestre in non-insulin-dependent diabetes mellitus patients. J Ethnopharmacol. 1990;30:295–300. doi: 10.1016/0378-8741(90)90108-6.
    1. Shanmugasundaram ER, Rajeswari G, Baskaran K, Rajesh Kumar BR, Radha Shanmugasundaram K, Kizar Ahmath B. Use of Gymnema sylvestre leaf extract in the control of blood glucose in insulin-dependent diabetes mellitus. J Ethnopharmacol. 1990;30:281–294. doi: 10.1016/0378-8741(90)90107-5.
    1. Judy WV, Hari SP, Stogsdill WW, Judy JS, Naguib YM, Passwater R. Antidiabetic activity of a standardized extract (Glucosol) from Lagerstroemia speciosa leaves in type II diabetics. A dose-dependence study. J Ethnopharmacol. 2003;87:115–117. doi: 10.1016/S0378-8741(03)00122-3.
    1. Mang B, Wolters M, Schmitt B, Kelb K, Lichtinghagen R, Stichtenoth DO, Hahn A. Effects of a cinnamon extract on plasma glucose, HbA, and serum lipids in diabetes mellitus type 2. Eur J Clin Investig. 2006;36:340–344. doi: 10.1111/j.1365-2362.2006.01629.x.
    1. Gong J, Fang K, Dong H, Wang D, Hu M, Lu F. Effect of fenugreek on hyperglycaemia and hyperlipidemia in diabetes and prediabetes: a meta-analysis. J Ethnopharmacol. 2016;194:260–268. doi: 10.1016/j.jep.2016.08.003.
    1. Hou Q, Ao X, Li G, Zhang Y. Puerarin combined with avandia for diabetic nephropathy. Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2012;37:73–77.
    1. Sharma RD, Sarkar A, Hazra DK, Misra B, Singh JB, Maheshwari BB, Sharma SK. Hypolipidaemic effect of fenugreek seeds: a chronic study in non-insulin dependent diabetic patients. Phytother Res. 1996;10:332–334. doi: 10.1002/(SICI)1099-1573(199606)10:4<332::AID-PTR827>;2-J.
    1. Nagulapalli Venkata KC, Swaroop A, Bagchi D, Bishayee A. A small plant with big benefits: Fenugreek (Trigonella foenum-graecum Linn.) for disease prevention and health promotion. Mol Nutr Food Res. 2017;61. 10.1002/mnfr.201600950.
    1. Sharma RD, Raghuram TC, Rao VD. Hypolipidaemic effect of fenugreek seeds. A clinical study. Phytother Res. 1991;5:145–147. doi: 10.1002/ptr.2650050313.
    1. Takagi S, Miura T, Ishihara E, Ishida T, Chinzei Y. Effect of corosolic acid on dietary hypercholesterolemia and hepatic steatosis in KK-Ay diabetic mice. Biomed Res (Tokyo, Japan) 2010;31:213–218. doi: 10.2220/biomedres.31.213.
    1. Luo H, Kashiwagi A, Shibahara T, Yamada K. Decreased bodyweight without rebound and regulated lipoprotein metabolism by gymnemate in genetic multifactor syndrome animal. Mol Cell Biochem. 2007;299:93–98. doi: 10.1007/s11010-005-9049-7.
    1. Bishayee A, Chatterjee M. Hypolipidaemic and antiatherosclerotic effects of oral Gymnema sylvestre R. Br. leaf extract in albino rats fed on a high fat diet. Phytother Res. 1994;8:118–120. doi: 10.1002/ptr.2650080216.
    1. Wang LF, Luo H, Miyoshi M, Imoto T, Hiji Y, Sasaki T. Inhibitory effect of gymnemic acid on intestinal absorption of oleic acid in rats. Can J Physiol Pharmacol. 1998;76:1017–1023. doi: 10.1139/y98-123.
    1. Nakamura Y, Tsumura Y, Tonogai Y, Shibata T. Fecal steroid excretion is increased in rats by oral administration of gymnemic acids contained in Gymnema sylvestre leaves. J Nutr. 1999;129:1214–1222. doi: 10.1093/jn/129.6.1214.
    1. El Shafey AAM, El-Ezabi MM, Seliem MME, Ouda HHM, Ibrahim DS. Effect of Gymnema sylvestre R. Br. leaves extract on certain physiological parameters of diabetic rats. J King Saud Univ: Sci. 2013;25:135–141. doi: 10.1016/j.jksus.2012.11.001.
    1. Affuso F, Ruvolo A, Micillo F, Sacca L, Fazio S. Effects of a nutraceutical combination (berberine, red yeast rice and policosanols) on lipid levels and endothelial function randomized, double-blind, placebo-controlled study. Nutr Metab Cardiovasc Dis. 2010;20:656–661. doi: 10.1016/j.numecd.2009.05.017.
    1. Kong W, Wei J, Abidi P, Lin M, Inaba S, Li C, Wang Y, Wang Z, Si S, Pan H, et al. Berberine is a novel cholesterol-lowering drug working through a unique mechanism distinct from statins. Nat Med. 2004;10:1344–1351. doi: 10.1038/nm1135.
    1. Marazzi G, Cacciotti L, Pelliccia F, Iaia L, Volterrani M, Caminiti G, Sposato B, Massaro R, Grieco F, Rosano G. Long-term effects of nutraceuticals (berberine, red yeast rice, policosanol) in elderly hypercholesterolemic patients. Adv Ther. 2011;28:1105–1113. doi: 10.1007/s12325-011-0082-5.
    1. Pisciotta L, Bellocchio A, Bertolini S. Nutraceutical pill containing berberine versus ezetimibe on plasma lipid pattern in hypercholesterolemic subjects and its additive effect in patients with familial hypercholesterolemia on stable cholesterol-lowering treatment. Lipids Health Dis. 2012;11:123. doi: 10.1186/1476-511X-11-123.
    1. Van Wyk B-E, Wink M. Medicinal plants of the world : an illustrated scientific guide to important medicinal plants and their uses. 1. Portland: Timber Press; 2004.
    1. Hannan JM, Rokeya B, Faruque O, Nahar N, Mosihuzzaman M, Azad Khan AK, Ali L. Effect of soluble dietary fibre fraction of Trigonella foenum graecum on glycemic, insulinemic, lipidemic and platelet aggregation status of Type 2 diabetic model rats. J Ethnopharmacol. 2003;88:73–77. doi: 10.1016/S0378-8741(03)00190-9.
    1. Broca C, Manteghetti M, Gross R, Baissac Y, Jacob M, Petit P, Sauvaire Y, Ribes G. 4-hydroxyisoleucine: effects of synthetic and natural analogues on insulin secretion. Eur J Pharmacol. 2000;390:339–345. doi: 10.1016/S0014-2999(00)00030-3.
    1. Flammang AM, Cifone MA, Erexson GL, Stankowski LF., Jr Genotoxicity testing of a fenugreek extract. Food Chem Toxicol. 2004;42:1769–1775. doi: 10.1016/j.fct.2004.07.003.
    1. Gupta A, Gupta R, Lal B. Effect of Trigonella foenum-graecum (fenugreek) seeds on glycaemic control and insulin resistance in type 2 diabetes mellitus: a double blind placebo controlled study. J Assoc Physicians India. 2001;49:1057–1061.
    1. Hayashi T, Maruyama H, Kasai R, Hattori K, Takasuga S, Hazeki O, Yamasaki K, Tanaka T. Ellagitannins from Lagerstroemia speciosa as activators of glucose transport in fat cells. Planta Med. 2002;68:173–175. doi: 10.1055/s-2002-20251.
    1. Kakuda T, Sakane I, Takihara T, Ozaki Y, Takeuchi H, Kuroyanagi M. Hypoglycemic effect of extracts from Lagerstroemia speciosa L. leaves in genetically diabetic KK-AY mice. Biosci Biotechnol Biochem. 1996;60:204–208. doi: 10.1271/bbb.60.204.
    1. Hattori K, Sukenobu N, Sasaki T, Takasuga S, Hayashi T, Kasai R, Yamasaki K, Hazeki O. Activation of insulin receptors by lagerstroemin. J Pharmacol Sci. 2003;93:69–73. doi: 10.1254/jphs.93.69.
    1. Hsu FL, Liu IM, Kuo DH, Chen WC, Su HC, Cheng JT. Antihyperglycemic effect of puerarin in streptozotocin-induced diabetic rats. J Nat Prod. 2003;66:788–792. doi: 10.1021/np0203887.
    1. Hsu HH, Chang CK, Su HC, Liu IM, Cheng JT. Stimulatory effect of puerarin on alpha1A-adrenoceptor to increase glucose uptake into cultured C2C12 cells of mice. Planta Med. 2002;68:999–1003. doi: 10.1055/s-2002-35656.
    1. Murakami N, Murakami T, Kadoya M, Matsuda H, Yamahara J, Yoshikawa M. New hypoglycemic constituents in “gymnemic acid” from Gymnema sylvestre. Chem Pharm Bull. 1996;44:469–471. doi: 10.1248/cpb.44.469.
    1. Sinsheimer JE, Rao GS, McIlhenny HM. Constuents from Gymnema sylvestre leaves. V. Isolation and preliminary characterization of the gymnemic acids. J Pharm Sci. 1970;59:622–628. doi: 10.1002/jps.2600590510.
    1. Yeh GY, Eisenberg DM, Kaptchuk TJ, Phillips RS. Systematic review of herbs and dietary supplements for glycemic control in diabetes. Diabetes Care. 2003;26:1277–1294. doi: 10.2337/diacare.26.4.1277.
    1. Persaud SJ, Al-Majed H, Raman A, Jones PM. Gymnema sylvestre stimulates insulin release in vitro by increased membrane permeability. J Endocrinol. 1999;163:207–212. doi: 10.1677/joe.0.1630207.
    1. Anderson RA, Broadhurst CL, Polansky MM, Schmidt WF, Khan A, Flanagan VP, Schoene NW, Graves DJ. Isolation and characterization of polyphenol type-A polymers from cinnamon with insulin-like biological activity. J Agric Food Chem. 2004;52:65–70. doi: 10.1021/jf034916b.
    1. Imparl-Radosevich J, Deas S, Polansky MM, Baedke DA, Ingebritsen TS, Anderson RA, Graves DJ. Regulation of PTP-1 and insulin receptor kinase by fractions from cinnamon: implications for cinnamon regulation of insulin signalling. Horm Res. 1998;50:177–182.
    1. Jarvill-Taylor KJ, Anderson RA, Graves DJ. A hydroxychalcone derived from cinnamon functions as a mimetic for insulin in 3T3-L1 adipocytes. J Am Coll Nutr. 2001;20:327–336. doi: 10.1080/07315724.2001.10719053.
    1. Zhou L, Yang Y, Wang X, Liu S, Shang W, Yuan G, Li F, Tang J, Chen M, Chen J. Berberine stimulates glucose transport through a mechanism distinct from insulin. Metabolism. 2007;56:405–412. doi: 10.1016/j.metabol.2006.10.025.
    1. Lee YS, Kim WS, Kim KH, Yoon MJ, Cho HJ, Shen Y, Ye JM, Lee CH, Oh WK, Kim CT, et al. Berberine, a natural plant product, activates AMP-activated protein kinase with beneficial metabolic effects in diabetic and insulin-resistant states. Diabetes. 2006;55:2256–2264. doi: 10.2337/db06-0006.
    1. Pan GY, Huang ZJ, Wang GJ, Fawcett JP, Liu XD, Zhao XC, Sun JG, Xie YY. The antihyperglycaemic activity of berberine arises from a decrease of glucose absorption. Planta Med. 2003;69:632–636. doi: 10.1055/s-2003-41121.
    1. Ko BS, Choi SB, Park SK, Jang JS, Kim YE, Park S. Insulin sensitizing and insulinotropic action of berberine from Cortidis rhizoma. Biol Pharm Bull. 2005;28:1431–1437. doi: 10.1248/bpb.28.1431.
    1. Hoffmann D. Medical herbalism : the science and practice of herbal medicine. Rochester: Healing Arts Press; 2003.
    1. Christensen LP. Ginsenosides chemistry, biosynthesis, analysis, and potential health effects. Adv Food Nutr Res. 2009;55:1–99.
    1. Shang W, Yang Y, Jiang B, Jin H, Zhou L, Liu S, Chen M. Ginsenoside Rb1 promotes adipogenesis in 3T3-L1 cells by enhancing PPARgamma2 and C/EBPalpha gene expression. Life Sci. 2007;80:618–625. doi: 10.1016/j.lfs.2006.10.021.
    1. Desvergne B, Wahli W. Peroxisome proliferator-activated receptors: nuclear control of metabolism. Endocr Rev. 1999;20:649–688.
    1. Tobin JF, Freedman LP. Nuclear receptors as drug targets in metabolic diseases: new approaches to therapy. Trends Endocrinol Metabol. 2006;17:284–290. doi: 10.1016/j.tem.2006.07.004.
    1. Han KL, Jung MH, Sohn JH, Hwang JK. Ginsenoside 20S-protopanaxatriol (PPT) activates peroxisome proliferator-activated receptor gamma (PPARgamma) in 3T3-L1 adipocytes. Biol Pharm Bull. 2006;29:110–113. doi: 10.1248/bpb.29.110.
    1. Schupp M, Clemenz M, Gineste R, Witt H. Molecular characterization of new selective peroxisome proliferator-activated receptor gamma modulators with angiotensin receptor blocking activity. Diabetes. 2005;54:3442–52.
    1. Burgermeister E, Schnoebelen A, Flament A, Benz J, Stihle M, Gsell B, Rufer A, Ruf A, Kuhn B, Marki HP, et al. A novel partial agonist of peroxisome proliferator-activated receptor-gamma (PPARgamma) recruits PPARgamma-coactivator-1alpha, prevents triglyceride accumulation, and potentiates insulin signaling in vitro. Mol Endocrinol. 2006;20:809–830. doi: 10.1210/me.2005-0171.
    1. Barroso I, Gurnell M, Crowley VEF, Agostini M. Dominant negative mutations in human PPAR-gamma associated with severe insulin resistance, diabetes mellitus and hypertension. Nature. 1999;402(6764):880–3.
    1. Larsen TM, Toubro S, Astrup A. PPARgamma agonists in the treatment of type II diabetes: is increased fatness commensurate with long-term efficacy? Int J Obesity Relat Disord. 2003;27:147–161. doi: 10.1038/sj.ijo.802223.
    1. Pan H-J, Lin Y, Chen YE, Vance DE, Leiter EH. Adverse hepatic and cardiac responses to rosiglitazone in a new mouse model of type 2 diabetes: relation to dysregulated phosphatidylcholine metabolism. Vasc Pharmacol. 2006;45:65–71. doi: 10.1016/j.vph.2005.11.011.
    1. Lian F, Li G, Chen X, Wang X, Piao C, Wang J, Hong Y, Ba Z, Wu S, Zhou X, et al. Chinese herbal medicine Tianqi reduces progression from impaired glucose tolerance to diabetes: a double-blind, randomized, placebo-controlled, multicenter trial. J Clin Endocrinol Metab. 2014;99:648–655. doi: 10.1210/jc.2013-3276.
    1. Shin SK, Kwon JH, Jeong YJ, Jeon SM, Choi JY, Choi MS. Supplementation of cheonggukjang and red ginseng cheonggukjang can improve plasma lipid profile and fasting blood glucose concentration in subjects with impaired fasting glucose. J Med Food. 2011;14:108–113. doi: 10.1089/jmf.2009.1366.
    1. Middha P, Weinstein SJ, Mannisto S, Albanes D, Mondul AM. Beta-carotene supplementation and lung cancer incidence in the ATBC Study: the role of tar and nicotine. Nicot Tobacco Res. 2018. 10.1093/ntr/nty115.
    1. Al-Hamdani SH, Ponder DM. Evaluation and comparison of selected antioxidant concentrations in Kudzu and three common food sources. J Alabama Acad Sci. 2014;85:1–7.
    1. Menke A, Casagrande S, Geiss L, Cowie CC. Prevalence of and trends in diabetes among adults in the United States, 1988–2012. JAMA. 2015;314:1021–1029. doi: 10.1001/jama.2015.10029.
    1. Akilen R, Tsiami A, Devendra D, Robinson N. Glycated haemoglobin and blood pressure-lowering effect of cinnamon in multi-ethnic Type 2 diabetic patients in the UK: a randomized, placebo-controlled, double-blind clinical trial. Diabet Med. 2010;27:1159–1167. doi: 10.1111/j.1464-5491.2010.03079.x.
    1. Chang H-M, But PPH. Pharmacology and applications of chinese materia medica. English ed. Singapore; Philadelphia: World Scientific; 1986.
    1. Crawford P. Effectiveness of cinnamon for lowering hemoglobin A1C in patients with type 2 diabetes: a randomized, controlled trial. J Am Board Fam Med. 2009;22:507–512. doi: 10.3122/jabfm.2009.05.080093.
    1. Khan A, Safdar M, Ali Khan MM, Khattak KN, Anderson RA. Cinnamon improves glucose and lipids of people with type 2 diabetes. Diabetes Care. 2003;26:3215–3218. doi: 10.2337/diacare.26.12.3215.
    1. Lu T, Sheng H, Wu J, Cheng Y, Zhu J, Chen Y. Cinnamon extract improves fasting blood glucose and glycosylated hemoglobin level in Chinese patients with type 2 diabetes. Nutr Res. 2012;32:408–412. doi: 10.1016/j.nutres.2012.05.003.
    1. Shebek J, Rindone JP. A pilot study exploring the effect of kudzu root on the drinking habits of patients with chronic alcoholism. J Altern Complement Med. 2000;6:45–48. doi: 10.1089/acm.2000.6.45.
    1. Tsuchibe S, Kataumi S, Mori M, Mori H. An inhibitory effect on the increase in the postprandial blood glucose by Banaba extract capsule enriched corosolic acid. J Integr Stud Dietary Habits. 2006;17:255–259. doi: 10.2740/jisdh.17.255.
    1. Woo J, Lau E, Ho SC, Cheng F, Chan C, Chan AS, Haines CJ, Chan TY, Li M, Sham A. Comparison of Pueraria lobata with hormone replacement therapy in treating the adverse health consequences of menopause. Menopause. 2003;10:352–361. doi: 10.1097/01.GME.0000054764.94658.33.
    1. Reed RM, Dransfield MT, Eberlein M, Miller M, Netzer G, Pavlovich M, Pollin TI, Scharf SM, Shuldiner AR, Sin D, Mitchell BD. Gender differences in first and secondhand smoke exposure, spirometric lung function and cardiometabolic health in the old order Amish: a novel population without female smoking. PLoS One. 2017 Mar 31;12(3):e0174354. 10.1371/journal.pone.0174354. eCollection 2017.
    1. Mehta CR, Pocock SJ. Adaptive increase in sample size when interim results are promising: a practical guide with examples. Stat Med. 2011;30:3267–3284. doi: 10.1002/sim.4102.
    1. Chan AW, Tetzlaff JM, Altman DG, Laupacis A, Gotzsche PC, Krleza-Jeric K, Hrobjartsson A, Mann H, Dickersin K, Berlin JA, et al. SPIRIT 2013 statement: defining standard protocol items for clinical trials. Ann Intern Med. 2013;158:200–207. doi: 10.7326/0003-4819-158-3-201302050-00583.
    1. Wallace TMLJC, Matthews DR. Use and abuse of HOMA modeling. Diabetes Care. 2004;27(6):1487–1495. doi: 10.2337/diacare.27.6.1487.
    1. Hutchins AM, Brown BD, Cunnane SC, Domitrovich SG, Adams ER, Bobowiec CE. Daily flaxseed consumption improves glycemic control in obese men and women with pre-diabetes: a randomized study. Nutr Res. 2013;33:367–375. doi: 10.1016/j.nutres.2013.02.012.
    1. GlycoMark, editor. Diabetes treatment targets hyperglycemia…So does GlycoMark. In: Diabetes treatment targets hyperglycemia…So does GlycoMark (Editor ed.^eds.). City; 2018.
    1. Won JC, Park CY, Park HS, Kim JH, Choi ES, Rhee EJ, Lee WY, Oh KW, Kim SW, Park SW. 1,5-anhydroglucitol reflects postprandial hyperglycemia and a decreased insulinogenic index, even in subjects with prediabetes and well-controlled type 2 diabetes. Diabetes Res Clin Pract. 2009;84:51–57. doi: 10.1016/j.diabres.2009.01.002.
    1. Chan CL, Pyle L, Kelsey MM, Newnes L, Baumgartner A, Zeitler PS, Nadeau KJ. Alternate glycemic markers reflect glycemic variability in continuous glucose monitoring in youth with prediabetes and type 2 diabetes. Pediatr Diabetes. 2016; 18(7). 10.1111/pedi.12475
    1. Group IEW . ICH Harmonised Guideline. Revision of M4E Guideline on Enhancing the Format and Structure of Benefit-Risk Information in ICH Efficacy – M4E(R2) (Editor ed.^eds.) City: ICH; 2016. ICH Harmonised Guideline. Revision of M4E Guideline on Enhancing the Format and Structure of Benefit-Risk Information in ICH Efficacy – M4E(R2)
    1. Group IEW . ICH Harmonised Tripartite Guideline. Clinical Safety Data Management: Defintions and Standards for Expedited Reporting E2A (Editor ed.^eds.) City: ICH; 1994. ICH Harmonised Tripartite Guideline. Clinical Safety Data Management: Defintions and Standards for Expedited Reporting E2A.
    1. Group IEW . ICH Harmonised Tripartite Guideline. Guideline for Good Clinical Practice – E6(R1) (Editor ed.^eds.) City: ICH; 1996. ICH Harmonised Tripartite Guideline. Guideline for Good Clinical Practice – E6(R1)
    1. Goldman L, Schafer AI. Goldman-Cecil medicine. 25. Philadelphia: Elsevier/Saunders; 2016.
    1. About Chronic Kidney Disease. . Accessed 03 Dec 2018.
    1. Ferri FF. Ferri’s practical guide : fast facts for patient care. 9. Philadelphia: Elsevier; 2014.
    1. AskMayoExpert. Chronic kidney disease (adult). In: Mayo Clinic, editor. Mayo Foundation for Medical Education and Research. Rochester: Mayo Clinic.; 2015.
    1. Sun W, Zhou L, Grosser S, Kim C. A meta-analysis of missing data and non-compliance data in clinical endpoint bioequivalence studies. Stat Biopharm Res. 2016;8:334–344. doi: 10.1080/19466315.2016.1201000.
    1. Gagnier JJ, Boon H, Rochon P, et al. Reporting randomized, controlled trials of herbal interventions: an elaborated consort statement. Ann Intern Med. 2006;144:364–367. doi: 10.7326/0003-4819-144-5-200603070-00013.
    1. Kantor ED, Rehm CD, Du M, White E, Giovannucci EL. Trends in dietary supplement use among US adults from 1999–2012. JAMA. 2016;316:1464–1474. doi: 10.1001/jama.2016.14403.
    1. The Cost of Diabetes. . Accessed 03 Dec 2018.
    1. Knowler WC, Barrett-Connor E, Fowler SE, Hamman RF, Lachin JM, Walker EA, Nathan DM. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med. 2002;346:393–403. doi: 10.1056/NEJMoa012512.
    1. Group DPPR Long-term effects of lifestyle intervention or metformin on diabetes development and microvascular complications over 15-year follow-up: the Diabetes Prevention Program Outcomes Study. Lancet Diabetes Endocrinol. 2015;3:866–875. doi: 10.1016/S2213-8587(15)00291-0.
    1. Mills S, Bone K. Principles and practice of phytotherapy: modern herbal medicine. 2. Atlanta: Churchill Livingstone Elsevier; 2013.
    1. Yin J, Gao Z, Liu D, Liu Z, Ye J. Berberine improves glucose metabolism through induction of glycolysis. Am J Physiol Endocrinol Metab. 2008;294:E148–E156. doi: 10.1152/ajpendo.00211.2007.
    1. High blood cholesterol. . Accessed 03 Dec 2018.
    1. Triglycerides. . Accessed 03 Dec 2018.
    1. Wang X, Bao W, Liu J, OuYang Y-Y, Wang D, Rong S, Xiao X, Shan Z-L, Zhang Y, Yao P, Liu L-G. Inflammatory markers and risk of type 2 diabetes: a systematic review and meta-analysis. Diabetes Care. 2013;36:166–175. doi: 10.2337/dc12-0702.
    1. Rus A, Molina F, Gasso M, Camacho MV, Peinado MA, del Moral ML. Nitric oxide, inflammation, lipid profile, and cortisol in normal- and overweight women with fibromyalgia. Biol Res Nurs. 2016;18:138–146. doi: 10.1177/1099800415591035.
    1. C-reactive protein. . Accessed 03 Dec 2018.

Source: PubMed

Sponsorit ja yhteistyökumppanit

Sairaudet

Huumeiden interventiot

3
Tilaa