A comparative study of combination of Myo-inositol and D-chiro-inositol versus Metformin in the management of polycystic ovary syndrome in obese women with infertility

Background: Polycystic ovary syndrome (PCOS) is a symptom complex associated with increased amounts of circulating androgens in females, increased insulin resistance and obesity. The drugs, Myo-inositol, D-chiro-inositol and Metformin, which are insulin sensitizers, are very helpful in taking care of one of the key components of PCOS that is insulin resistance. This study was done to compare the effects of combination of Myo-inositol and D-chiro-inositol with the use of metformin on clinical and biochemical profile in PCOS.Methods: A prospective, randomized, comparative study was conducted on 200 patients. The patients were randomly assigned into the two groups of 100 each. Group A receiving Tab. Myoinositol 550mg twice daily and Tab. D-chiro-inositol 13.8mg twice daily and Group B receiving Tab. Metformin 500mg thrice daily. The patients were assessed by menstrual cycle regulation, hirsutism score (Ferriman Gallwey), fasting and post prandial glucose and insulin levels, serum DHEA levels, serum free testosterone levels and fasting day 3 serum LH and FSH ratio.Results: In both the groups there was significant improvement in all the above mentioned parameters, however the group with Combination of Myo-inositol and D-chiro-inositol had statistically significant improvement over the Metformin group.Conclusions: Combination of Myo-inositol and D-chiro-inositol and use of metformin, significantly improved insulin sensitivity in PCOS women. But combination of Myo-inositol and D-chiro-inositol was effective in controlling the hormonal profiles (LH/FSH ration and free testosterone) when compared to Metformin.

Inhibitory Effect of D-chiro-inositol on Both Growth and Recurrence of Breast Tumor from MDA-MB-231 Cancer Cells

D-chiro-inositol (DCI) is a secondary messenger in insulin signal transduction. It is produced in vivo from myo-inositol via action of epimerase. In this study, we evaluated antitumor activity of DCI against human breast cancer both in vitro and in vivo. In order to determine the inhibitory effects of DCI on growth of human breast cancer cells (MDA-MB-231), two different assessment methods were implemented: MTT assay and mouse xenograft assay. MTT assay demonstrated downturn in cell proliferation by DCI treatment (1, 5, 10, 20 and 40 mM) groups by 18.3% (p<0.05), 17.2% (p<0.05), 17.5% (p<0.05), 18.4% (p<0.05), and 24.9% (p<0.01), respectively. Also, inhibition of tumor growth was investigated in mouse xenograft model. DCI was administered orally at the dose of 500 mg/kg and 1000 mg/kg body weight to treat nude mouse for 45 consecutive days. On the 45th day, tumor growth of DCI (500 mg/kg and 1000 mg/kg) groups was suppressed by 22.1% and 67.6% as mean tumor volumes were 9313.8 ± 474.1 mm³ and 3879.1 ± 1044.1 mm³, respectively. Furthermore, breast cancer stem cell (fCSC) phenotype (CD44⁺/CD24⁻) was measured using flow cytometry. On the 46th day, CSC ratios of DCI (500 mg/kg) and co-treatment with doxorubicin (4 mg/kg) and DCI (500 mg/kg) group decreased by 24.7% and 53.9% (p<0.01), respectively. Finally, from tumor recurrence assay, delay of 5 days in the co-treatment group compared to doxorubicin (4 mg/kg) alone group was observed. Based on these findings, we propose that DCI holds potential as an anti-cancer drug for treatment of breast cancer.

The Effects of D-Chiro-Inositol on Glucose Metabolism in 3T3-L1 Cells / 당뇨병

BACKGROUND: The target of the treatment of metabolic syndrome and diabetes is an improvement of insulin resistance. D-chiro-inositol (DCI) plays a role in a phospholipid mediating intracellular insulin action. In the previous studies, the urine level of DCI were decreased in the diabetic animal with insulin resistance. Some clinical studies showed that DCI improved a glucose level and HbA1c. Therefore we studied the relationship between DCI and glucose metabolism, especially insulin resistance. METHODS: To investigate the mechanism of DCI affecting the glucose metabolism, we examined the effects of DCI on 2-deoxyglucose uptake, gene expression of adipocytokines and AMPK pathway by using RT-PCR and western blot in 3T3-L1 cells. RESULTS: Insulin-stimulated 2-deoxyglucose uptake increased in DCI-treated cells by about 1.2-fold (relative to the control) and was inhibited by phosphoinositide 3-kinase (PI3 Kinase) inhibitors (Wortmanin, LY294002) and AMPK inhibitor (STO-609). In Western blot analysis, it didn't show the difference of phosphorylation of Akt and AMPK between DCI-treated group and control in 3T3-L1 cells. However, DCI decreased the gene expression of resistin in 3T3-L1 cells. CONCLUSION: DCI may involve other pathway of insulin signaling, but not PI3 Kinase and AMPK signaling pathways and it may be useful in managing metabolic syndrome by improving insulin resistance through increasing glucose uptake and decreasing resistin relevant to insulin resistance.

The clinical study to evaluate the safety and efficacy of D-chiro-inositol in patients with type 2 diabetes / 대한내과학회지

BACKGROUND: D-chiro-inositol (DCI) is a postreceptor signaling molecule of insulin action. Blood and urine levels of DCI were decreased in diabetic animals. Treatment of DCI improves insulin resistance and normalizes blood glucose level in diabetic animals. In diabetic patients, treatment of DCI has a effect of glucose control in some study but not in others. So we study to confirm the effect and to evaluate the safety of DCI by the use of pinitol, methyl derivates of DCI. METHODS: We performed a randomized, double-blind, placebo-controlled study in 82 patients with type 2 diabetes mellitus who visited the Eulji University Hospital from March 2005 to August 2005. We checked the change of HbA1c, FBS, and PP2 to evaluate pinitol effect of sugar control. And also we checked the effect of pinitol treatment to evaluate safety. RESULTS: We treated with either pinitol or placebo for 12 weeks in 66 patients and completed the study in 61 patients. There are no difference in the basal clinical or laboratory data between the pinotol and control groups. In the pinitol group there more decrease in the levels of HbA1c and in fasting blood glucose than in control group after 12 weeks study. When we performed subgroup analysis, in patients with a HbA1c level above 8% there was a more effectively respond to pinitol treatment. Than in less no significant side effects was occurred. There are no differences in side effects seen between the two groups. CONCLUSIONS: Treatment of pinitol was effective and safe in type 2 diabetic patients who received oral hypoglycemic agents. This is especially seen in patients with a high HbA1c level (>8%).

Determination of Urinary Myo-/Chiro-Inositol Ratios from Korean Diabetes Patients

Of two major forms (myo- and chiro-inositol) of inositols, only chiro-inositol enhances the activity of proteins involved in intracellular glucose metabolism. This study aims to determine the urinary myo-/chiro-inositol ratio in type 1 and type 2 diabetes patients and compare its ratio with the normal control group. The 24-hour urinary myo- and chiro-inositols in 71 Korean diabetes patients and 39 control subjects have been quantified using high-performance liquid chromatography, and their ratios have been evaluated as indices of insulin resistance. The level of 24-hour urinary myo-inositol was significantly higher in both type 1 and type 2 diabetes than with the control group, whereas the urinary chiro-inositol in type 1 or type 2 diabetes was lower than that in normal subjects. The myo-/chiro-inositol ratio in diabetes patients was higher than that in the control group. Twenty four-hour urinary myo-/ chiro-inositol ratios were significantly elevated in type 1 and type 2 diabetes patients compared to the control group, suggesting that a high ratio of urinary myo-/chiro- inositol in type 2 diabetes patients might be used for an index of insulin resistance.