Inositols are a group of naturally occurring polyols found in food acting as components of cell membrane phospholipids, plasma lipoproteins or phosphate forms in the nucleus, and are involved in many cellular processes.
There are nine stereoisomers: five of these (myo-, scyllo-, muco-, neo- and d-chiro-inositol) are formed naturally, while others are derived from myo-inositol, which is actively synthesised by living cells.
Myo-inositol and d-chiro-inositol have different roles in mediating the insulin signal: the former contributes to the entry of glucose into the cell as an immediately available substrate, while the latter takes part in cellular oxidative and non-oxidative metabolism leading to glycogen production in adipose tissue, muscle and liver.
Inositol therefore plays an essential role in the insulin signalling pathway, and the abundance of experimental data in the literature shows that its intracellular depletion can cause a reduced effect of insulin, and that under conditions of insulin resistance there is a deficit of d-chiro-inositol in the muscle of subjects with type 2 diabetes mellitus compared with normal subjects.
Insulin resistance is also associated with impaired renal excretion of chiro-inositol in primates, in humans with impaired glucose tolerance and type 2 diabetes mellitus, and in first-degree relatives of diabetic patients with normal glucose tolerance.
In experimental models, administration of inositol reduces hyperglycaemia in rats with diabetes and improves glucose tolerance in normal rats, but there are now several clinical studies in humans.
The first observations on inositol metabolism in gestational diabetes date back to 2007, and a case-control study was conducted in 2011 to see whether myo-inositol supplementation in women with gestational diabetes improved their metabolic profile and insulin resistance (assessed by Homa-Ir): in the inositol group, there was an improvement in insulin sensitivity, with a reduction of about 50% in insulin resistance, compared with 29% in the control group. In addition, adiponectin, a sensitive indicator of inflammation status in pregnancy, was significantly increased in the myo-inositol group compared to the control group.
In the comparison of myo-inositol and metformin on the clinical parameters of metabolic syndrome in women with polycystic ovary syndrome, both treatments were found to significantly reduce insulin response and improve insulin sensitivity in patients, but only metformin appeared to exert a beneficial effect on the endocrine and clinical features of the syndrome.
In postmenopausal women, cardiovascular risk parameters were further improved with myo-inositol supplementation with a reduction in blood pressure, c-Ld and total cholesterol, triglycerides (-34%) and improvement in Hdl cholesterol (+21%). Finally, after 6 months or one year of use, the supplement added to the diet of post-menopausal women significantly improved almost all the metabolic parameters studied compared with the placebo group and even treated the metabolic syndrome of 20% of the women in the study group (8 out of 40), while only one patient out of 40 (2.5%) no longer had a metabolic syndrome in the placebo group with diet alone.
There may be further scope for inositols in diabetes supplementation therapy, as tissues that may develop long-term microvascular complications (kidney, sciatic nerve, lens and retina) deplete myo-inositol and this intracellular deficiency may play a key role in the development and progression of these complications.
Restoring intracellular myo-inositol levels with a supplement could therefore be a suitable strategy to prevent or delay the development of neuropathy, nephropathy or diabetic retinopathy. The effect of dietary myo-inositol content (low, normal or high) was studied in patients with symptomatic distal symmetrical diabetic polyneuropathy and it was seen that a diet enriched with this inositol may have a positive effect on peripheral nerve function in symptomatic patients.
The insulin-mimetic properties of dietary inositol supplements are thought to be mainly related to the production of secondary messengers, but further research is needed to unravel the exact molecular mechanisms of action of myo-inositol, mechanisms that are still unclear.
Randomised control trials of the dietary supplement with inositol have shown positive results in women with Pcos, gestational diabetes or post-menopausal metabolic syndrome, but there is a lack of studies in men to confirm these results and to evaluate a possible application for a more generalised population of individuals who already have insulin resistance or are at risk of developing it due to genetic predisposition.
Bibliography
Potential role and therapeutic interests of myo-inositol in metabolic diseases. Biochimie, Vol. 95, Issue 10, October 2013, Pages 1811-1827;
Nuove evidenze sul ruolo della supplementazione con inositolo nel diabete gestazionale. G It Diabetol Metab 2013;33:199-203
Myo-inositol lowers the risk of developing gestational diabetic mellitus in pregnancies: A systematic review and meta-analysis of randomized controlled trials with trial sequential analysis. Journal of Diabetes and its Complications, Vol. 32, Issue 3 March 2018, Pages 342-348
Metformin vs myoinositol: which is better in obese polycystic ovary syndrome patients? A randomized controlled crossover study. Clin Endocrinol (Oxf). 2017 May;86(5):725-730.
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