Insulin resistance and serum metabolomics improvement in subjects with impaired glucose tolerance treated with Hibiscus esculentus L.

Lin  Chen; Qi  Wang; Wenjun  Sha; Cuiping  Zhang; Tian  Shen; Ming  Lu; Tao  Lei

doi:10.2298/VSP210406040C

Lin Chen Shanghai University of Traditional Chinese Medicine, Putuo Hospital, Department of Endocrinology, Shanghai, China
Qi Wang Shanghai University of Traditional Chinese Medicine, Putuo Hospital, Department of Endocrinology, Shanghai, China
Wenjun Sha Shanghai University of Traditional Chinese Medicine, Putuo Hospital, Department of Endocrinology, Shanghai, China
Cuiping Zhang Shanghai University of Traditional Chinese Medicine, Putuo Hospital, Department of Endocrinology, Shanghai, China
Tian Shen Shanghai University of Traditional Chinese Medicine, Putuo Hospital, Department of Endocrinology, Shanghai, China
Ming Lu Shanghai University of Traditional Chinese Medicine, Putuo Hospital, Department of Endocrinology, Shanghai, China
Tao Lei Shanghai University of Traditional Chinese Medicine, Putuo Hospital, Department of Endocrinology, Shanghai, China

DOI: https://doi.org/10.2298/VSP210406040C

Keywords: glucose intolerance, insulin resistance, life style, metabolomics, plants, medicinal, prediabetic state, serum

Abstract

Background/Aim. Prediabetes (PD) refers to the condition in which the blood sugar level is higher than normal but has not reached the diagnostic criteria for diabetes mellitus (DM) yet. Impaired glucose tolerance (IGT) is a major prediabetic symptom since most patients with type 2 DM have progressed from the previous PD phase. The aim of the study was to observe the changes in serum metabolomics in patients with IGT treated with Hibiscus esculentus L. (H. esculentus) combined with the change of lifestyle. Methods. Sixty patients with IGT were divided into two groups. In one group, the subjects made a lifestyle change (LC group, simple diet control), and the other group of subjects made a lifestyle change combined with H. esculentus (LCH group) treatment with daily consumption of 20 g of dried H. esculentus fruit tea. The aim was to compare the blood glucose, homeostasis model assessment-estimated insulin resistance (HOMA-IR) index, and serum metabolomics after a 60-day clinical observation period. Results. There was no statistical significance in the glucose level between the two groups by the end of the observation period. The HOMA-IR index in the LCH group was lower than in the LC group (1.7 ± 1.1 vs. 2.4 ± 1.2, p = 0.030). Serum metabolomics revealed that the levels of d-galactose, d-glucose, turanose, and uric acid in the LCH group were significantly lower than those in the LC group (16.7 ± 3.9 mmol/L vs. 21.2 ±2.9 mmol/L, 101.5 ± 40.2 mmol/L vs. 132.9 ± 36.7 mmol/L, 1.8 ± 1.6 mmol/L vs. 3.76 ± 2.46 mmol/L, 44.56 ± 15.7 μmol/L vs. 67.8 ± 23.5 μmol /L, respectively). The levels of lactic acid and conjugated linoleic acid in the LCH group were significantly higher than those in the LC group (3.3 ± 0.5 mmol/L vs. 2.3 ± 0.8 mmol/L, 6.9 ± 6.1 mmol/L vs. 2.1 ± 1.2 mmol/L, respectively). Conclusion. H. esculentus, combined with a change of lifestyle, can reduce insulin resistance and the levels of multiple monosaccharides and blood uric acid in IGT patients. Regulation of the metabolism of lactic acid and conjugated linoleic acid may be the potential mechanism of how H. esculentus reduces insulin resistance.

References

1. Cho NH, Shaw JE, Karuranga S, Huang Y, da Rocha Fernandes JD, Ohlrogge AW, et al. IDF Diabetes Atlas: Global estimates of di-abetes prevalence for 2017 and projections for 2045. Diabetes Res Clin Pract 2018; 138: 271‒81.

2. Wang L, Gao P, Zhang M, Huang Z, Zhang D, Deng Q, et al. Prevalence and Ethnic Pattern of Diabetes and Prediabetes in China in 2013. JAMA 2017; 317(24): 2515‒23.

3. Mokdad AH, Ford ES, Bowman BA, Dietz WH, Vinicor F, Bales V, et al. Prevalence of obesity, diabetes, and obesity-related health risk factors, 2001. JAMA 2003; 289(1): 76‒9.

4. Kosaka K, Noda M, Kuzuya T. Prevention of type 2 diabetes by lifestyle intervention: a Japanese trial in IGT males. Diabetes Res Clin Pract 2005; 67(2): 152‒62.

5. Roumen C, Corpeleijn E, Feskens EJ, Mensink M, Saris WH, Blaak EE. Impact of 3-year lifestyle intervention on postprandial glucose metabolism: the SLIM study. Diabet Med 2008; 25(5): 597‒605.

6. Alzeidan R, Shata Z, Hassounah MM, Baghdadi LR, Hersi A, Fayed A, et al. Effectiveness of digital health using the transtheoretical model to prevent or delay type 2 diabetes in impaired glucose tolerance patients: protocol for a ran-domized control trial. BMC Public Health 2019; 19(1): 1550.

7. Marathe PH, Gao HX, Close KL. American Diabetes Associa-tion Standards of Medical Care in Diabetes 2017. J Diabetes 2017; 9(4): 320‒4.

8. Derosa G, Maffioli P, D'Angelo A, Preti PS, Tenore G, Novellino E. Abscisic Acid Treatment in Patients with Prediabetes. Nutri-ents 2020; 12(10): 2931.

9. Huang CN, Wang CJ, Lin CL, Yen AT, Li HH, Peng CH. Abelmoschus esculentus subfractions attenuate beta amy-loid-induced neuron apoptosis by regulating DPP-4 with im-proving insulin resistance signals. PLoS One 2019; 14(6): e0217400.

10. Huang CN, Wang CJ, Lin CL, Lin HT, Peng CH. The nutraceu-tical benefits of subfractions of Abelmoschus esculentus in treating type 2 diabetes mellitus. PLoS One 2017; 12(12): e0189065.

11. Rangel-Huerta OD, Pastor-Villaescusa B, Gil A. Are we close to defining a metabolomic signature of human obesity? A sys-tematic review of metabolomics studies. Metabolomics 2019; 15(6): 93.

12. American Diabetes Association. 2. Classification and Diagno-sis of Diabetes: Standards of Medical Care in Diabetes-2020. Diabetes Care 2020; 43(Suppl 1): S14‒S31.

13. Wankhade PK, Sapkal RS, Sapkal VS. Drying characteristics of okra slices on drying in hot air dryer. Procedia Eng 2013; 51: 371‒4.

14. Chen L, Cheng CY, Choi H, Ikram MK, Sabanayagam C, Tan GS, et al. Plasma Metabonomic Profiling of Diabetic Retinopathy. Diabetes 2016; 65(4): 1099‒108.

15. Diao C, Zhao L, Guan M, Zheng Y, Chen M, Yang Y, et al. Sys-temic and characteristic metabolites in the serum of strepto-zotocin-induced diabetic rats at different stages as revealed by a (1) H-NMR based metabonomic approach. Mol Biosyst 2014; 10(3): 686‒93.

16. Rachdaoui N. Insulin: The friend and the foe in the develop-ment of type 2 diabetes mellitus. Int J Mol Sci 2020; 21(5): E1770.

17. Khatun H, Rahman A, Biswas M, Islam AU. Water-soluble Frac-tion of Abelmoschus esculentus L Interacts with Glucose and Metformin Hydrochloride and Alters Their Absorption Kinet-ics after Coadministration in Rats. ISRN Pharm 2011; 2011: 260537.

18. Sabitha V, Ramachandran S, Naveen KR, Panneerselvam K. Antidi-abetic and antihyperlipidemic potential of Abelmoschus escu-lentus (L.) Moench. in streptozotocin-induced diabetic rats. J Pharm Bioallied Sci 2011; 3(3): 397‒402.

19. Fan S, Zhang Y, Sun Q, Yu L, Li M, Zheng B, et al. Extract of okra lowers blood glucose and serum lipids in high-fat diet-induced obese C57BL/6 mice. J Nutr Biochem 2014; 25(7): 702‒9.

20. Fan S, Guo L, Zhang Y, Sun Q, Yang B, Huang C. Okra polysac-charide improves metabolic disorders in high-fat diet-induced obese C57BL/6 mice. Mol Nutr Food Res 2013; 57(11): 2075‒8.

21. Lewis AJ, Miller JJ, McCallum C, Rider OJ, Neubauer S, Heather LC, et al. Assessment of metformin-induced changes in cardi-ac and hepatic redox state using hyperpolarized pyruvate. Dia-betes 2016; 65(12): 3544‒51.

22. Gosmanova EO, Shahzad SR, Sumida K, Kovesdy CP, Gosmanov AR. Metformin is associated with increase in lactate level in elderly patients with type 2 diabetes and CKD stage 3: A case-control study. Diabetes Complications 2020; 34(1): 107474.

23. Jiang TN, Li YF, Huo LL, Zhang Q, Wang LY, Zhao CL, et al. Association between serum uric acid and large-nerve fiber dys-function in type 2 diabetes: a cross-sectional study. Chin Med J (Engl) 2019; 132(9): 1015‒22.

24. van der Schaft N, Brahimaj A, Wen KX, Franco OH, Dehghan A. The association between serum uric acid and the incidence of prediabetes and type 2 diabetes mellitus: The Rotterdam Study. PLoS One 2017; 12(6): e0179482.

25. Shimodaira M, Niwa T, Nakajima K, Kobayashi M, Hanyu N, Na-kayama T. The relationship between serum uric acid levels and β-cell functions in nondiabetic subjects. Horm Metab Res 2014; 46(13): 950‒4.

26. Zhu Y, Hu Y, Huang T, Zhang Y, Li Z, Luo C, et al. High uric acid directly inhibits insulin signaling and induces insulin re-sistance. Biochem Biophys Res Commun 2014; 447(4): 707‒14.

27. den Hartigh LJ. Conjugated linoleic acid effects on cancer, obe-sity, and atherosclerosis: a review of pre-clinical and human trials with current perspectives. Nutrients 2019; 11(2): 370.

28. Şanlier N, Gökcen BB, Sezgin AC. Health benefits of fermented foods. Crit Rev Food Sci Nutr 2019; 59(3): 506‒27.

29. Sandri EC, Camêra M, Sandri EM, Harvatine KJ, De Oliveira DE. Peroxisome proliferator-activated receptor gamma (PPARγ) agonist fails to overcome trans-10, cis-12 conjugated linoleic acid (CLA) inhibition of milk fat in dairy sheep. Animal 2018; 12(7): 1405‒12.

30. Fuke G, Nornberg JL. Systematic evaluation on the effectiveness of conjugated linoleic acid in human health. Crit Rev Food Sci Nutr 2017; 57(1): 1‒7.

31. Piras A, Carta G, Murru E, Lopes PA, Martins SV, Prates JA, et al. Effects of dietary CLA on n-3 HUFA score and N-acylethanolamides biosynthesis in the liver of obese Zucker rats. Prostaglandins Leukot Essent Fatty Acids 2015; 98: 15‒9.

32. Aloud BM, Raj P, O'Hara K, Shao Z, Yu L, Anderson HD, et al. Conjugated linoleic acid prevents high glucose-induced hyper-trophy and contractile dysfunction in adult rat cardiomyocytes. Nutr Res 2016; 36(2): 134‒42.

33. Jung D, Bucher F, Ryu S, Jeong J, Lee BY, Jeong Y, et al. An adi-ponectin receptor agonist antibody stimulates glucose uptake and fatty-acid oxidation by activating AMP-activated protein kinase. Cytokine 2020; 126: 154863.

34. Wang S, Goodspeed L, Turk KE, Houston B, den Hartigh LJ. Rosig-litazone improves insulin resistance mediated by 10,12 conju-gated linoleic acid in a male mouse model of metabolic syn-drome. Endocrinology 2017; 158(9): 2848‒59.