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Current Pharmaceutical Design


ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

Review Article

Diet and Nutritional Interventions with the Special Role of Myo-Inositol in Gestational Diabetes Mellitus Management. An Evidence-Based Critical Appraisal

Author(s): Enrique Reyes-Muñoz, Federica Di Guardo*, Michal Ciebiera , Ilker Kahramanoglu , Thozhukat Sathyapalan, Li-Te Lin, Mohsin Shah, Erbil Karaman, Shangrong Fan, Gabriella Zito and Marco Noventa

Volume 25 , Issue 22 , 2019

Page: [2467 - 2473] Pages: 7

DOI: 10.2174/1381612825666190722155512

Price: $65


Background: Gestational Diabetes Mellitus (GDM), defined as glucose intolerance with onset or first recognition during pregnancy, represents one of the most common maternal-fetal complications during pregnancy and it is associated with poor perinatal outcomes. To date, GDM is a rising condition over the last decades coinciding with the ongoing epidemic of obesity and Type 2 Diabetes Mellitus (T2DM).

Objective: The aim of this review is to discuss the role of diet and nutritional interventions in preventing GDM with the explanation of the special role of myo-inositol (MI) in this matter.

Methods: We performed an overview of the most recent literature data on the subject with particular attention to the effectiveness of diet and nutritional interventions in the prevention of GDM with the special role of MI.

Results: Nutritional intervention and physical activity before and during pregnancy are mandatory in women affected by GDM. Moreover, the availability of insulin-sensitizers such as different forms of inositol has dramatically changed the scenario, allowing the treatment of several metabolic diseases, such as those related to glucose dysbalance. Although the optimal dose, frequency, and form of MI administration need to be further investigated, diet supplementation with MI appears to be an attractive alternative for the GDM prevention as well as for the reduction of GDM-related complications.

Conclusions: More studies should be conducted to prove the most effective nutritional intervention in GDM. Regarding the potential effectiveness of MI, further evidence in multicenter, randomized controlled trials is needed to draw firm conclusions.

Keywords: Gestational diabetes mellitus, metabolic diseases, diet, nutrition, myo-inositol, prevention, management.

Casagrande SS, Linder B, Cowie CC. Prevalence of gestational diabetes and subsequent type 2 diabetes among U.S. women. Diabetes Res Clin Pract 2018; 141: 200-8.
[] [PMID: 29772286]
Ferrara A, Kahn HS, Quesenberry CP, Riley C, Hedderson MM. An increase in the incidence of gestational diabetes mellitus: Northern California, 1991-2000. Obstet Gynecol 2004; 103(3): 526-33.
[] [PMID: 14990417]
Billionnet C, Mitanchez D, Weill A, et al. Gestational diabetes and adverse perinatal outcomes from 716,152 births in France in 2012. Diabetologia 2017; 60(4): 636-44.
[] [PMID: 28197657]
Miao M, Dai M, Zhang Y, Sun F, Guo X, Sun G. Influence of maternal overweight, obesity and gestational weight gain on the perinatal outcomes in women with gestational diabetes mellitus. Sci Rep 2017; 7(1): 305.
[] [PMID: 28331199]
Bloomgarden ZT. Gestational diabetes mellitus and obesity. Diabetes Care 2010; 33(5): E60-5.
[] [PMID: 20427674]
Moll U, Olsson H, Landin-Olsson M. Impact of pregestational weight and weight gain during pregnancy on long-term risk for diseases. PLoS One 2017; 12(1)E0168543
[] [PMID: 28045917]
Hedderson MM, Gunderson EP, Ferrara A. Gestational weight gain and risk of gestational diabetes mellitus. Obstet Gynecol 2010; 115(3): 597-604.
[] [PMID: 20177292]
Zhang C, Rawal S, Chong YS. Risk factors for gestational diabetes: Is prevention possible? Diabetologia 2016; 59(7): 1385-90.
[] [PMID: 27165093]
Viana LV, Gross JL, Azevedo MJ. Dietary intervention in patients with gestational diabetes mellitus: A systematic review and meta-analysis of randomized clinical trials on maternal and newborn outcomes. Diabetes Care 2014; 37(12): 3345-55.
[] [PMID: 25414390]
Hernandez TL, Brand-Miller JC. Nutrition therapy in gestational diabetes mellitus: Time to move forward. Diabetes Care 2018; 41(7): 1343-5.
[] [PMID: 29934477]
Baz B, Riveline JP, Gautier JF. Endocrinology of pregnancy: Gestational diabetes mellitus: Definition, aetiological and clinical aspects. Eur J Endocrinol 2016; 174(2): R43-51.
[] [PMID: 26431552]
Jiwani A, Marseille E, Lohse N, Damm P, Hod M, Kahn JG. Gestational diabetes mellitus: Results from a survey of country prevalence and practices. J Matern Fetal Neonatal Med 2012; 25(6): 600-10.
[] [PMID: 21762003]
Anna V, van der Ploeg HP, Cheung NW, Huxley RR, Bauman AE. Sociodemographic correlates of the increasing trend in prevalence of gestational diabetes mellitus in a large population of women between 1995 and 2005. Diabetes Care 2008; 31(12): 2288-93.
[] [PMID: 18809630]
Lavery JA, Friedman AM, Keyes KM, Wright JD, Ananth CV. Gestational diabetes in the United States: Temporal changes in prevalence rates between 1979 and 2010. BJOG 2017; 124(5): 804-13.
[] [PMID: 27510598]
Catalano PM. Trying to understand gestational diabetes. Diabet Med 2014; 31(3): 273-81.
[] [PMID: 24341419]
Buchanan TA, Xiang A, Kjos SL, Watanabe R. What is gestational diabetes? Diabetes Care 2007; 30(Suppl. 2): S105-11.
[] [PMID: 17596457]
Buchanan TA, Xiang AH, Page KA. Gestational diabetes mellitus: Risks and management during and after pregnancy. Nat Rev Endocrinol 2012; 8(11): 639-49.
[] [PMID: 22751341]
Lambrinoudaki I, Vlachou SA, Creatsas G. Genetics in gestational diabetes mellitus: Association with incidence, severity, pregnancy outcome and response to treatment. Curr Diabetes Rev 2010; 6(6): 393-9.
[] [PMID: 20879971]
Brink HS, van der Lely AJ, van der Linden J. The potential role of biomarkers in predicting gestational diabetes. Endocr Connect 2016; 5(5): R26-34.
[] [PMID: 27492245]
Xu J, Zhao YH, Chen YP, et al. Maternal circulating concentrations of tumor necrosis factor-alpha, leptin, and adiponectin in gestational diabetes mellitus: A systematic review and meta-analysis. ScientificWorldJournal 2014; 2014926932
[] [PMID: 25202741]
Atègbo JM, Grissa O, Yessoufou A, et al. Modulation of adipokines and cytokines in gestational diabetes and macrosomia. J Clin Endocrinol Metab 2006; 91(10): 4137-43.
[] [PMID: 16849405]
Kuzmicki M, Telejko B, Szamatowicz J, et al. High resistin and interleukin-6 levels are associated with gestational diabetes mellitus. Gynecol Endocrinol 2009; 25(4): 258-63.
[] [PMID: 19408175]
Kuźmicki M, Telejko B, Lipińska D, et al. The IL-6/IL-6R/sgp130 system and Th17 associated cytokines in patients with gestational diabetes. Endokrynol Pol 2014; 65(3): 169-75.
[PMID: 24971916]
Pantham P, Aye IL, Powell TL. Inflammation in maternal obesity and gestational diabetes mellitus. Placenta 2015; 36(7): 709-15.
[] [PMID: 25972077]
Turkmen S, Johansson S, Dahmoun M. Foetal macrosomia and foetal-maternal outcomes at birth. J Pregnancy 2018; 20184790136
[] [PMID: 30174954]
Negrato CA, Mattar R, Gomes MB. Adverse pregnancy outcomes in women with diabetes. Diabetol Metab Syndr 2012; 4(1): 41.
[] [PMID: 22964143]
Garcia-Vargas L, Addison SS, Nistala R, Kurukulasuriya D, Sowers JR. Gestational diabetes and the offspring: Implications in the development of the cardiorenal metabolic syndrome in offspring. Cardiorenal Med 2012; 2(2): 134-42.
[] [PMID: 22851962]
Poola-Kella S, Steinman RA, Mesmar B, Malek R. Gestational diabetes mellitus: Post-partum risk and follow up. Rev Recent Clin Trials 2018; 13(1): 5-14.
[PMID: 28901851]
Vohr BR, Boney CM. Gestational diabetes: The forerunner for the development of maternal and childhood obesity and metabolic syndrome? J Matern Fetal Neonatal Med 2008; 21(3): 149-57.
[] [PMID: 18297569]
Zhang C, Bao W, Rong Y, et al. Genetic variants and the risk of gestational diabetes mellitus: A systematic review. Hum Reprod Update 2013; 19(4): 376-90.
[] [PMID: 23690305]
Zhang C, Ning Y. Effect of dietary and lifestyle factors on the risk of gestational diabetes: Review of epidemiologic evidence. Am J Clin Nutr 2011; 94(6)(Suppl.): 1975S-9S.
[] [PMID: 21613563]
Tobias DK, Zhang C, van Dam RM, Bowers K, Hu FB. Physical activity before and during pregnancy and risk of gestational diabetes mellitus: A meta-analysis. Diabetes Care 2011; 34(1): 223-9.
[] [PMID: 20876206]
Loy SL, Lek N, Yap F, et al. Growing Up in Singapore Towards Healthy Outcomes (GUSTO) study group. Association of maternal vitamin D status with glucose tolerance and caesarean section in a multi-ethnic asian cohort: The growing up in singapore towards healthy outcomes study. PLoS One 2015; 10(11)E0142239
[] [PMID: 26571128]
Ciebiera M, Łukaszuk K, Zgliczyńska M, Zaręba K, Rawski W, Jakiel G. The role of vitamin D in perinatology – what do we know at the beginning of 2018? An up-to-date review. Arch Med Sci 2019.
Metzger BE, Lowe LP, Dyer AR, et al. HAPO Study Cooperative Research Group. Hyperglycemia and adverse pregnancy outcomes. N Engl J Med 2008; 358(19): 1991-2002.
[] [PMID: 18463375]
Sacks DB. Diagnosis of gestational diabetes mellitus: It is time for international consensus. Clin Chem 2014; 60(1): 141-3.
[] [PMID: 24061614]
Agarwal MM, Dhatt GS, Othman Y. Gestational diabetes: Differences between the current international diagnostic criteria and implications of switching to IADPSG. J Diabetes Complications 2015; 29(4): 544-9.
[] [PMID: 25837380]
McIntyre HD, Dyer AR, Metzger BE. Odds, risks and appropriate diagnosis of gestational diabetes. Med J Aust 2015; 202(6): 309-11.
[] [PMID: 25832155]
Metzger BE, Gabbe SG, Persson B, et al. International Association of Diabetes and Pregnancy Study Groups Consensus Panel. International association of diabetes and pregnancy study groups recommendations on the diagnosis and classification of hyperglycemia in pregnancy. Diabetes Care 2010; 33(3): 676-82.
[] [PMID: 20190296]
National Institute of Health and Care Excellence UK. Diabetes in pregnancy: Management from preconception to the postnatal period 2015 [Available from:.. (online 05.02.2019).
Diabetes Poland Society. 2019 Guidelines on the management of diabetic patients. A position of Diabetes Poland. 2019 [Available from:.. (online 05.02.2019).
Kim C. Gestational diabetes: Risks, management, and treatment options. Int J Womens Health 2010; 2: 339-51.
[] [PMID: 21151681]
Goldschmidt VJ, Colletta B. The challenges of providing diabetes education in resource-limited settings to women with diabetes in pregnancy: Perspectives of an educator. Diabetes Spectr 2016; 29(2): 101-4.
[] [PMID: 27182180]
Trujillo J, Vigo A, Reichelt A, Duncan BB, Schmidt MI. Fasting plasma glucose to avoid a full OGTT in the diagnosis of gestational diabetes. Diabetes Res Clin Pract 2014; 105(3): 322-6.
[] [PMID: 25037441]
American Diabetes Association. 13. Management of diabetes in pregnancy: standards of medical care in diabetes-2018. Diabetes Care 2018; 41(Suppl. 1): S137-43.
[] [PMID: 29222384]
Ho YR, Wang P, Lu MC, Tseng ST, Yang CP, Yan YH. Associations of mid-pregnancy HbA1c with gestational diabetes and risk of adverse pregnancy outcomes in high-risk Taiwanese women. PLoS One 2017; 12(5)E0177563
[] [PMID: 28505205]
Hinkle SN, Tsai MY, Rawal S, Albert PS, Zhang C. HbA1c measured in the first trimester of pregnancy and the association with gestational diabetes. Sci Rep 2018; 8(1): 12249.
[] [PMID: 30116010]
Moses RG, Barker M, Winter M, Petocz P, Brand-Miller JC. Can a low-glycemic index diet reduce the need for insulin in gestational diabetes mellitus? A randomized trial. Diabetes Care 2009; 32(6): 996-1000.
[] [PMID: 19279301]
Diabetes UK Diet and lifestyle with gestational diabetes 2019 [Available from: (online 05.02.2019).
Padayachee C, Coombes JS. Exercise guidelines for gestational diabetes mellitus. World J Diabetes 2015; 6(8): 1033-44.
[] [PMID: 26240700]
Simmons D. Diabetes and obesity in pregnancy. Best Pract Res Clin Obstet Gynaecol 2011; 25(1): 25-36.
[] [PMID: 21247811]
Radesky JS, Oken E, Rifas-Shiman SL, Kleinman KP, Rich-Edwards JW, Gillman MW. Diet during early pregnancy and development of gestational diabetes. Paediatr Perinat Epidemiol 2008; 22(1): 47-59.
[] [PMID: 18173784]
Nohr EA, Vaeth M, Baker JL, Sørensen TIa, Olsen J, Rasmussen KM. Combined associations of prepregnancy body mass index and gestational weight gain with the outcome of pregnancy. Am J Clin Nutr 2008; 87(6): 1750-9.
[] [PMID: 18541565]
Viswanathan M, Siega-Riz AM, Moos MK, et al. Outcomes of maternal weight gain. Evid Rep Technol Assess (Full Rep) 2008; (168): 1-223.
[PMID: 18620471]
Phelps RL, Metzger BE. Caloric restriction in gestational diabetes mellitus: When and how much? J Am Coll Nutr 1992; 11(3): 259-62.
[] [PMID: 1619176]
Knopp RH, Magee MS, Raisys V, Benedetti T. Metabolic effects of hypocaloric diets in management of gestational diabetes. Diabetes 1991; 40(Suppl. 2): 165-71.
[] [PMID: 1748251]
Asbjörnsdóttir B, Rasmussen SS, Kelstrup L, Damm P, Mathiesen ER. Impact of restricted maternal weight gain on fetal growth and perinatal morbidity in obese women with type 2 diabetes. Diabetes Care 2013; 36(5): 1102-6.
[] [PMID: 23248191]
Paknahad Z, Fallah A, Moravejolahkami AR. Maternal dietary patterns and their association with pregnancy outcomes. Clin Nutr Res 2019; 8(1): 64-73.
[] [PMID: 30746349]
Bo S, Menato G, Lezo A, et al. Dietary fat and gestational hyperglycaemia. Diabetologia 2001; 44(8): 972-8.
[] [PMID: 11484073]
Qiu C, Frederick IO, Zhang C, Sorensen TK, Enquobahrie DA, Williams MA. Risk of gestational diabetes mellitus in relation to maternal egg and cholesterol intake. Am J Epidemiol 2011; 173(6): 649-58.
[] [PMID: 21324948]
Karamanos B, Thanopoulou A, Anastasiou E, et al. MGSD-GDM study group. Relation of the mediterranean diet with the incidence of gestational diabetes. Eur J Clin Nutr 2014; 68(1): 8-13.
[] [PMID: 24084515]
Lindsay RS, Loeken MR. Metformin use in pregnancy: Promises and uncertainties. Diabetologia 2017; 60(9): 1612-9.
[] [PMID: 28770325]
Bijok J, Bińkowska M, Jakiel G. [Metformin in pregnancy] Ginekol Pol 2014; 85(7): 527-31.
[PMID: 25118505]
Poomalar GK. Changing trends in management of gestational diabetes mellitus. World J Diabetes 2015; 6(2): 284-95.
[] [PMID: 25789109]
Durnwald CP. Insulin analogues in the treatment of gestational diabetes mellitus. Clin Obstet Gynecol 2013; 56(4): 816-26.
[] [PMID: 24022504]
Vitale SG, La Rosa VL, Petrosino B, Rodolico A, Mineo L, Laganà AS. The impact of lifestyle, diet, and psychological stress on female fertility. Oman Med J 2017; 32(5): 443-4.
[] [PMID: 29026481]
Phipps E, Prasanna D, Brima W, Jim B. Preeclampsia: Updates in pathogenesis, definitions, and guidelines. Clin J Am Soc Nephrol 2016; 11(6): 1102-13.
[] [PMID: 27094609]
Corrado F, D’Anna R, Laganà AS, Di Benedetto A. Abnormal glucose tolerance later in life in women affected by glucose intolerance during pregnancy. J Obstet Gynaecol 2014; 34(2): 123-6.
[] [PMID: 24456430]
Laganà AS, Vitale SG, Sapia F, et al. miRNA expression for early diagnosis of preeclampsia onset: Hope or hype? J Matern Fetal Neonatal Med 2018; 31(6): 817-21.
[] [PMID: 28282763]
Jung UJ, Choi MS. Obesity and its metabolic complications: The role of adipokines and the relationship between obesity, inflammation, insulin resistance, dyslipidemia and nonalcoholic fatty liver disease. Int J Mol Sci 2014; 15(4): 6184-223.
[] [PMID: 24733068]
Macer ML, Taylor HS. Endometriosis and infertility: A review of the pathogenesis and treatment of endometriosis-associated infertility. Obstet Gynecol Clin North Am 2012; 39(4): 535-49.
[] [PMID: 23182559]
Vitale SG, Capriglione S, Peterlunger I, et al. The role of oxidative stress and membrane transport systems during endometriosis: A fresh look at a busy corner. Oxid Med Cell Longev 2018; 20187924021
[] [PMID: 29743986]
Ciebiera M, Włodarczyk M, Zgliczyńska M, et al. The role of tumor necrosis factor α in the biology of uterine fibroids and the related symptoms. Int J Mol Sci 2018; 19(12)E3869
[] [PMID: 30518097]
Ciebiera M, Włodarczyk M, Słabuszewska-Jóźwiak A, Nowicka G, Jakiel G. Influence of vitamin D and transforming growth factor β3 serum concentrations, obesity, and family history on the risk for uterine fibroids. Fertil Steril 2016; 106(7): 1787-92.
[] [PMID: 27743697]
Laganà AS, Vergara D, Favilli A, et al. Epigenetic and genetic landscape of uterine leiomyomas: A current view over a common gynecological disease. Arch Gynecol Obstet 2017; 296(5): 855-67.
[] [PMID: 28875276]
Chern CU, Tsui KH, Vitale SG, et al. Dehydroepiandrosterone (DHEA) supplementation improves in vitro fertilization outcomes of poor ovarian responders, especially in women with low serum concentration of DHEA-S: A retrospective cohort study. Reprod Biol Endocrinol 2018; 16(1): 90.
[] [PMID: 30223902]
Fruzzetti F, Perini D, Russo M, Bucci F, Gadducci A. Comparison of two insulin sensitizers, metformin and myo-inositol, in women with Polycystic Ovary Syndrome (PCOS). Gynecol Endocrinol 2017; 33(1): 39-42.
[] [PMID: 27808588]
Lauretta R, Lanzolla G, Vici P, Mariani L, Moretti C, Appetecchia M. Insulin-sensitizers, polycystic ovary syndrome and gynaecological cancer risk. Int J Endocrinol 2016; 20168671762
[] [PMID: 27725832]
Sortino MA, Salomone S, Carruba MO, Drago F. Polycystic ovary syndrome: Insights into the therapeutic approach with inositols. Front Pharmacol 2017; 8: 341.
[] [PMID: 28642705]
Reyes-Muñoz E, Sathyapalan T, Rossetti P, et al. Polycystic ovary syndrome: Implication for drug metabolism on assisted reproductive techniques-a literature review. Adv Ther 2018; 35(11): 1805-15.
[] [PMID: 30311070]
Vitale SG, Rossetti P, Corrado F, et al. How to achieve high-quality oocytes? The key role of myo-inositol and melatonin. Int J Endocrinol 2016; 20164987436
[] [PMID: 27651794]
Zheng X, Lin D, Zhang Y, et al. Inositol supplement improves clinical pregnancy rate in infertile women undergoing ovulation induction for ICSI or IVF-ET. Medicine 2017; 96(49)E8842
[] [PMID: 29245250]
D’Anna R, Scilipoti A, Giordano D, et al. myo-Inositol supple-mentation and onset of gestational diabetes mellitus in pregnant women with a family history of type 2 diabetes: A prospective, randomized, placebo-controlled study. Diabetes Care 2013; 36(4): 854-7.
[] [PMID: 23340885]
Corrado F, D’Anna R, Di Vieste G, et al. The effect of myoinositol supplementation on insulin resistance in patients with gestational diabetes. Diabet Med 2011; 28(8): 972-5.
[] [PMID: 21414183]
Noventa M, Vitagliano A, Quaranta M, Borgato S, Abdulrahim B, Gizzo S. Preventive and therapeutic role of dietary inositol supplementation in periconceptional period and during pregnancy: A summary of evidences and future applications. Reprod Sci 2016; 23(3): 278-88.
[] [PMID: 26175275]
Croze ML, Soulage CO. Potential role and therapeutic interests of myo-inositol in metabolic diseases. Biochimie 2013; 95(10): 1811-27.
[] [PMID: 23764390]
Croze ML, Géloën A, Soulage CO. Abnormalities in myo-inositol metabolism associated with type 2 diabetes in mice fed a high-fat diet: Benefits of a dietary myo-inositol supplementation. Br J Nutr 2015; 113(12): 1862-75.
[] [PMID: 25990651]
Santamaria A, Di Benedetto A, Petrella E, et al. Myo-inositol may prevent gestational diabetes onset in overweight women: A randomized, controlled trial. J Matern Fetal Neonatal Med 2016; 29(19): 3234-7.
[] [PMID: 26698911]
Santamaria A, Alibrandi A, Di Benedetto A, et al. Clinical and metabolic outcomes in pregnant women at risk for gestational diabetes mellitus supplemented with myo-inositol: A secondary analysis from 3 RCTs. Am J Obstet Gynecol 2018; 219 300 e1-e6.
Matarrelli B, Vitacolonna E, D’Angelo M, et al. Effect of dietary myo-inositol supplementation in pregnancy on the incidence of maternal gestational diabetes mellitus and fetal outcomes: A randomized controlled trial. J Matern Fetal Neonatal Med 2013; 26(10): 967-72.
[] [PMID: 23327487]
Zheng X, Liu Z, Zhang Y, et al. Relationship between myo-inositol supplementary and gestational diabetes mellitus: A meta-analysis. Medicine 2015; 94(42)E1604
[] [PMID: 26496267]
D’Anna R, Di Benedetto V, Rizzo P, et al. Myo-inositol may prevent gestational diabetes in PCOS women. Gynecol Endocrinol 2012; 28(6): 440-2.
[] [PMID: 22122627]
Crawford TJ, Crowther CA, Alsweiler J, Brown J. Antenatal dietary supplementation with myo-inositol in women during pregnancy for preventing gestational diabetes. Cochrane Database Syst Rev 2015; (12): CD011507
[] [PMID: 26678256]
Baillargeon JP, Iuorno MJ, Apridonidze T, Nestler JE. Uncoupling between insulin and release of a D-chiro-inositol-containing inositolphosphoglycan mediator of insulin action in obese women With polycystic ovary syndrome. Metab Syndr Relat Disord 2010; 8(2): 127-36.
[] [PMID: 20156067]

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