Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
Trials
Published in: Trials 1/2019

Open Access 01-12-2019 | Insulins | Study protocol

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

Authors: 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

Published in: Trials | Issue 1/2019

Login to get access

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.
Appendix
Available only for authorised users
Literature
1.
IDF Diabetes Atlas. Brussels: International Diabetes Federation; 2007.
2.
3.
4.
Bonora E. Protection of pancreatic beta-cells: is it feasible? Nutr Metab Cardiovasc Dis. 2008;18:74–83.PubMedCrossRef
5.
6.
Nichols GA, Hillier TA, Brown JB. Normal fasting plasma glucose and risk of type 2 diabetes diagnosis. Am J Med. 2008;121:519–24.PubMedCrossRef
7.
Daniele G, Abdul-Ghani M, DeFronzo RA. What are the pharmacotherapy options for treating prediabetes? Expert Opin Pharmacother. 2014;15:2003–18.PubMedCrossRef
8.
9.
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.PubMedPubMedCentralCrossRef
10.
Moerman DE, Moerman DE. Native American medicinal plants: an ethnobotanical dictionary. Portland: Timber Press; 2009.
11.
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.PubMedPubMedCentralCrossRef
12.
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.PubMedPubMedCentralCrossRef
13.
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.PubMedPubMedCentralCrossRef
14.
15.
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.PubMedPubMedCentralCrossRef
16.
17.
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.PubMedPubMedCentralCrossRef
18.
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.PubMedPubMedCentralCrossRef
19.
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.PubMedPubMedCentralCrossRef
20.
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;5:1621–30.PubMedCrossRef
21.
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.PubMedPubMedCentralCrossRef
22.
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.PubMedPubMedCentralCrossRef
23.
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;41:180–8.PubMedCrossRef
24.
Davis PA, Yokoyama W. Cinnamon intake lowers fasting blood glucose: meta-analysis. J Med Food. 2011;14:884–9.PubMedCrossRef
25.
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.PubMed
26.
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.PubMedPubMedCentralCrossRef
27.
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;30:1634–40.PubMedCrossRef
28.
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;7:4379–87.PubMedCrossRef
29.
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;6:853–8.PubMedCrossRef
30.
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;29:1110–4.PubMedCrossRef
31.
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.PubMedCrossRef
32.
Chuengsamarn S, Rattanamongkolgul S, Luechapudiporn R, Phisalaphong C, Jirawatnotai S. Curcumin extract for prevention of type 2 diabetes. Diabetes Care. 2012;35:2121–7.PubMedPubMedCentralCrossRef
33.
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;10:1279–89.PubMedPubMedCentral
34.
ADA. (6) Glycemic targets. Diabetes Care. 2015;38 Suppl:S33–40.
35.
Goldstein DE, Little RR, Lorenz RA, Malone JI, Nathan D, Peterson CM, Sacks DB. Tests of glycemia in diabetes. Diabetes Care. 2004;27:1761–73.PubMedCrossRef
36.
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.PubMedCrossRef
37.
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;93:2559–65.PubMedCrossRef
38.
39.
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;59:285–92.PubMedCrossRef
40.
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.PubMedPubMedCentralCrossRef
41.
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;160:1009–13.PubMedCrossRef
42.
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.PubMedCrossRef
43.
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;30:281–94.PubMedCrossRef
44.
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;87:115–7.PubMedCrossRef
45.
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;36:340–4.CrossRef
46.
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;194:260–8.PubMedCrossRef
47.
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;37:73–7.PubMed
48.
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;10:332–4.CrossRef
49.
50.
Sharma RD, Raghuram TC, Rao VD. Hypolipidaemic effect of fenugreek seeds. A clinical study. Phytother Res. 1991;5:145–7.CrossRef
51.
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;31:213–8.CrossRef
52.
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;299:93–8.PubMedCrossRef
53.
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;8:118–20.CrossRef
54.
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;76:1017–23.PubMedCrossRef
55.
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;129:1214–22.PubMedCrossRef
56.
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;25:135–41.CrossRef
57.
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;20:656–61.PubMedCrossRef
58.
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;10:1344–51.PubMedCrossRef
59.
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;28:1105–13.PubMedCrossRef
60.
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.PubMedPubMedCentralCrossRef
61.
Van Wyk B-E, Wink M. Medicinal plants of the world : an illustrated scientific guide to important medicinal plants and their uses. 1st ed. Portland: Timber Press; 2004.
62.
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;88:73–7.PubMedCrossRef
63.
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;390:339–45.PubMedCrossRef
64.
Flammang AM, Cifone MA, Erexson GL, Stankowski LF Jr. Genotoxicity testing of a fenugreek extract. Food Chem Toxicol. 2004;42:1769–75.PubMedCrossRef
65.
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;49:1057–61.PubMed
66.
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;68:173–5.PubMedCrossRef
67.
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;60:204–8.PubMedCrossRef
68.
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.PubMedCrossRef
69.
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;66:788–92.PubMedCrossRef
70.
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.PubMedCrossRef
71.
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;44:469–71.CrossRef
72.
Sinsheimer JE, Rao GS, McIlhenny HM. Constuents from Gymnema sylvestre leaves. V. Isolation and preliminary characterization of the gymnemic acids. J Pharm Sci. 1970;59:622–8.PubMedCrossRef
73.
Yeh GY, Eisenberg DM, Kaptchuk TJ, Phillips RS. Systematic review of herbs and dietary supplements for glycemic control in diabetes. Diabetes Care. 2003;26:1277–94.PubMedCrossRef
74.
Persaud SJ, Al-Majed H, Raman A, Jones PM. Gymnema sylvestre stimulates insulin release in vitro by increased membrane permeability. J Endocrinol. 1999;163:207–12.PubMedCrossRef
75.
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.PubMedCrossRef
76.
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;50:177–82.PubMed
77.
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;20:327–36.PubMedCrossRef
78.
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;56:405–12.PubMedCrossRef
79.
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;55:2256–64.PubMedCrossRef
80.
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;69:632–6.PubMedCrossRef
81.
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;28:1431–7.PubMedCrossRef
82.
Hoffmann D. Medical herbalism : the science and practice of herbal medicine. Rochester: Healing Arts Press; 2003.
83.
Christensen LP. Ginsenosides chemistry, biosynthesis, analysis, and potential health effects. Adv Food Nutr Res. 2009;55:1–99.PubMed
84.
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;80:618–25.PubMedCrossRef
85.
Desvergne B, Wahli W. Peroxisome proliferator-activated receptors: nuclear control of metabolism. Endocr Rev. 1999;20:649–88.PubMed
86.
Tobin JF, Freedman LP. Nuclear receptors as drug targets in metabolic diseases: new approaches to therapy. Trends Endocrinol Metabol. 2006;17:284–90.CrossRef
87.
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;29:110–3.PubMedCrossRef
88.
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.
89.
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;20:809–30.PubMedCrossRef
90.
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.
91.
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;27:147–61.CrossRef
92.
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.CrossRef
93.
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;99:648–55.PubMedCrossRef
94.
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;14:108–13.PubMedCrossRef
95.
96.
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.
97.
Menke A, Casagrande S, Geiss L, Cowie CC. Prevalence of and trends in diabetes among adults in the United States, 1988–2012. JAMA. 2015;314:1021–9.CrossRefPubMed
98.
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;27:1159–67.PubMedCrossRef
99.
Chang H-M, But PPH. Pharmacology and applications of chinese materia medica. English ed. Singapore; Philadelphia: World Scientific; 1986.CrossRef
100.
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;22:507–12.PubMedCrossRef
101.
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;26:3215–8.PubMedCrossRef
102.
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;32:408–12.PubMedCrossRef
103.
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;6:45–8.PubMedCrossRef
104.
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;17:255–9.CrossRef
105.
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;10:352–61.PubMedCrossRef
106.
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. https://​doi.​org/​10.​1371/​journal.​pone.​0174354. eCollection 2017.
107.
Mehta CR, Pocock SJ. Adaptive increase in sample size when interim results are promising: a practical guide with examples. Stat Med. 2011;30:3267–84.PubMedCrossRef
108.
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;158:200–7.PubMedPubMedCentralCrossRef
109.
110.
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;33:367–75.PubMedCrossRef
111.
GlycoMark, editor. Diabetes treatment targets hyperglycemia…So does GlycoMark. In: Diabetes treatment targets hyperglycemia…So does GlycoMark (Editor ed.^eds.). City; 2018.
112.
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;84:51–7.PubMedCrossRef
113.
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). https://​doi.​org/​10.​1111/​pedi.​12475
114.
Group IEW. ICH Harmonised Guideline. Revision of M4E Guideline on Enhancing the Format and Structure of Benefit-Risk Information in ICH Efficacy – M4E(R2). In: 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.
115.
Group IEW. ICH Harmonised Tripartite Guideline. Clinical Safety Data Management: Defintions and Standards for Expedited Reporting E2A. In: ICH Harmonised Tripartite Guideline. Clinical Safety Data Management: Defintions and Standards for Expedited Reporting E2A (Editor ed.^eds.). City: ICH; 1994.
116.
Group IEW. ICH Harmonised Tripartite Guideline. Guideline for Good Clinical Practice – E6(R1). In: ICH Harmonised Tripartite Guideline. Guideline for Good Clinical Practice – E6(R1) (Editor ed.^eds.). City: ICH; 1996.
117.
Goldman L, Schafer AI. Goldman-Cecil medicine. 25th ed. Philadelphia: Elsevier/Saunders; 2016.
118.
119.
Ferri FF. Ferri’s practical guide : fast facts for patient care. 9th ed. Philadelphia: Elsevier; 2014.
120.
AskMayoExpert. Chronic kidney disease (adult). In: Mayo Clinic, editor. Mayo Foundation for Medical Education and Research. Rochester: Mayo Clinic.; 2015.
121.
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;8:334–44.CrossRef
122.
Gagnier JJ, Boon H, Rochon P, et al. Reporting randomized, controlled trials of herbal interventions: an elaborated consort statement. Ann Intern Med. 2006;144:364–7.PubMedCrossRef
123.
124.
125.
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.PubMedCrossRef
126.
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;3:866–75.CrossRef
127.
Mills S, Bone K. Principles and practice of phytotherapy: modern herbal medicine. 2nd ed. Atlanta: Churchill Livingstone Elsevier; 2013.
128.
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:E148–56.PubMedCrossRef
129.
130.
131.
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;36:166–75.PubMedCrossRef
132.
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;18:138–46.PubMedCrossRef
133.
Metadata
Title
Polyherbal dietary supplementation for prediabetic adults: study protocol for a randomized controlled trial
Authors
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
Publication date
01-12-2019
Publisher
BioMed Central
Published in
Trials / Issue 1/2019
Electronic ISSN: 1745-6215
DOI
https://doi.org/10.1186/s13063-018-3032-6

Other articles of this Issue 1/2019

Trials 1/2019 Go to the issue

Update

PREDOMOS study, impact of a social intervention program for socially isolated elderly cancer patients: update to the study protocol for a randomized controlled trial

Study protocol

Is dangling of the lower leg after a free flap reconstruction necessary? Study protocol for a large multicenter randomized controlled study

Study protocol

Effects of a programme of vigorous physical activity during secondary school physical education on academic performance, fitness, cognition, mental health and the brain of adolescents (Fit to Study): study protocol for a cluster-randomised trial

Study protocol

Effect and neurophysiological mechanism of acupuncture in patients with chronic sciatica: protocol for a randomized, patient-assessor blind, sham-controlled clinical trial

Methodology

Limitations of the incidence density ratio as approximation of the hazard ratio

Study protocol

Comparison of effectiveness between warm acupuncture with local-distal points combination and local distribution points combination in breast cancer-related lymphedema patients: a study protocol for a multicenter, randomized, controlled clinical trial