myoinositol ( mi ) and d - chiro inositol ( dci ) are isomeric forms of inositol that were found to have insulin - like properties , acting as second messengers in the insulin intracellular pathway ; both of these molecules are involved in the increasing insulin sensitivity of different tissues to improve metabolic and ovulatory functions [ 13 ] . it is produced by the human body from d - glucose , but it is present in all living cells as membrane phospholipids and phytic acid . in food it is contained especially in pulses ( beans , grains , and nuts ) and fruits ( in particular citrus fruits ) . dci and mi have different physiological roles since the former is crucial for glycogen synthesis while the latter increases cellular glucose uptake . each tissue has its own mi / dci ratio , which is maintained through the conversion of myoinositol to d - chiro inositol occurring in tissues expressing the specific epimerase . high dci levels are present in glycogen storage tissues , such as fat , liver , and muscle , whereas very low levels of dci are typical of tissues with high glucose utilization , such as the brain and heart [ 5 , 6 ] . the inositol is mainly catabolized by the kidney , which seems to be an important regulator of plasma inositol concentrations ; however urinary excretion represents only a small fraction . indeed , deficiency or abnormalities in inositol metabolism induce a defect in glucose uptake and have been linked to insulin resistance and long term microvascular complications of diabetes . a depletion of intracellular myoinositol and an excessive urinary excretion , along with lower level of chiro inositol and lower excretion , have been frequently observed in type ii diabetic patients and in other conditions associated with insulin resistance , such as polycystic ovary syndrome , gestational diabetes , and metabolic syndrome . in general , certain data suggest that chiro inositol deficiency or imbalance is related more directly to insulin resistance itself , rather than to type ii diabetes . the chiro inositol deficiency observed in urine has also been confirmed in muscle and in blood , indicating a general defect in the body . this finding has provided the basis for initial trials of the administration of d - chiro inositol in stz diabetic rats , monkeys , and subsequently humans [ 2 , 8 ] . thus administration of myoinositol and d - chiro inositol might play a role in restoring better insulin sensitivity , as well as delaying the onset of diabetes complications . in this preliminary study obese male children have undergone an ogtt without inositol and then in association with inositol , in order to find out if the acute administration of inositol has a positive effect on insulin sensitivity . we hypothesized that there may be a direct relation between higher bmi and a greater increase of insulin after glucose administration and that the effect of inositol might be different in subjects with higher bmi . we also proposed the hypothesis that there might be a relation between fasting insulin level and degree of insulin increase after glucose intake . twenty - three consecutive obese patients , aged 11.5  2.3 ( range 715 ) , with a mean bmi of 29.8  3.1  kg / m ( mean  sd ) were recruited . exclusion criteria were delayed puberty , hypogonadism ( such as klinefelter syndrome ) , thyroid dysfunctions , and obesity - linked genetic disease . anthropometric measures , like waist - hip ratio and percent of body fat , blood pressure , and blood samples for determination of total cholesterol , ldl , hdl , and triglycerides , were assessed . all patients consumed a normocaloric diet , balanced for macronutrient distribution , in accordance with the national guidelines for the treatment of childhood obesity [ 10 , 11 ] . specifically , it is recommended that children follow , for a 6-month period , a normocaloric diet ( daily caloric intake by age and sex ) consisting of protein ( 12%15% ) , carbohydrates ( 55%60% ) , fat ( 25%30% ; < 10% saturated fatty acids , polyunsaturated fatty acids up to 10% , and monounsaturated fatty acids up to 15% ) , and fiber ( range : age ( year ) plus 5  g - age ( year ) plus 10 ) [ 11 , 12 ] . additionally , it was recommended that children engage in at least 60  min of moderate - to vigorous - intensity physical activity daily , based on walking and tailored to individual preference . after nutritional intervention patients who recorded in the first ogtt fasting insulin 15  u / ml and thus are considered as insulin - resistant were submitted to a second ogtt , which was preceded by the administration of 1 soft gel capsule of inositol [ myoinositol 1100  mg + d - chiro inositol 27.6  mg + folic acid 400  g ; inofolic combi , lo.li pharma s.r.l . , 00156 rome , italy ] . in these insulin - resistant patients , blood samples for glucose and insulin were collected before and after the ogtt and data from the first and second ogtt were compared . to assess the differences between variables over time we performed the wilcoxon signed rank sum test assuming p  0.05 as significant level . the spearman correlation coefficient was employed to identify a correlation between bmi and insulin increase after ogtt and between fasting insulin and insulin level after glucose load ( figures 1 , 2 , and 3 ) . correlation is used to assess the strength and direction of the linear relationship between two variables . figure 1 shows that the baseline correlation between bmi and insulin increase in the whole sample was statistically significant ( r = 0.2951 ; p = 0.0336 ) , confirming that higher bmi is associated with a greater insulin increase . therefore , we performed an ogtt preceded by inositol administration in a subgroup of 11 children only , where the high fasting insulin level ( 15  u / ml ) suggested increasing insulin resistance . figure 2 shows the correlation between basal insulin value and its increase after the ogtt performed without inositol and with inositol in the patients with basal insulin 15  u / ml . while correlation was strong and statistically significant in the first case ( r = 0.2281 ; p = 0.0009 ) , it lost significance when the ogtt was preceded by inositol administration ( r = 0.2447 ; p = 0.0767 ) . in this case , basal insulin level and insulin increase got close to those observed in the children who had a basal insulin level 15  u / ml ( figure 3 ) , suggesting that inositol is more effective in lowering insulin increase in children with higher basal insulin level , though this assumption is still uncertain since only a few samples have been tested . table 2 reports baseline values and variations of blood glucose and insulin after 120 minutes in the two groups of children , respectively , with insulin level  or 15  u / ml . both groups recorded a significant increase of glucose and insulin after 120 minutes : in particular , in the first group the mean glucose increase after the ogtt was 29.4  17.9  mg / dl ( p = 0.001 ) and mean insulin increase was 93.5  75.9  u / ml ( p = 0.001 ) ; in the second one mean glucose increase after the ogtt was 12.3  15.0 ( p = 0.0029 ) and mean insulin increase was 39.8  23.3 ( p = 0.0005 ) . table 3 shows the comparison between data without inositol and the ogtt performed after inositol administration in the patients with baseline insulin 15  u / ml : fasting glucose was not significantly different from the previous test ( 88.5  3.4 versus 86.9  3.9  mg / dl ) and there was a small nonsignificant reduction of glucose after 120 minutes ( 117.9  19.2 versus 106.2  18.0  mg / dl ) , while a reduction of fasting insulin ( 22.6  10.0 versus 14.7  6.7  u / ml ; p = 0.001 ) was noted , and a decrease of insulin after 120 minutes ( 116.1  81.4 versus 77.3  58.4  u / ml ; p = 0.0176 ) . in addition , in these 11 patients mean bmi after six months was not significantly different from the baseline ( 31.0  2.1 versus 31.0  2.6 in fact , they resulted to have had a bmi variation 2.5  kg / m . in particular , some children have obtained a bmi reduction ( n = 4 ) , stabilization ( n = 3 ) , or an increase ( n = 4 ) , in a similar distribution . thus bmi variation did not influence insulin variations and the results can be attributed to inositol only . the effectiveness of inositol in lowering plasma glucose concentration and postprandial blood glucose levels has been reported in several cases of mellitus diabetes in rats , monkeys , and humans . these studies showed that this effect was related to insulin - sensitizing activity [ 1518 ] . d - pinitol exerted an acute and chronic insulin - like antihyperglycaemic effect on glucose transport in stz - diabetic mice , but acute administration of d - pinitol did not significantly alter plasma glucose or insulin concentration over 6 hours in severely insulin - resistant ob / ob mice . when administered to insulin - resistant and diabetic monkeys , d - chiro inositol accelerated glucose disposal and activated glycogen synthase in muscle biopsies beyond that of maximal insulin stimulation . pinitol was administered to humans with type ii diabetes for 13 weeks and it significantly decreased mean fasting plasma glucose and insulin and improved lipid profile , while four weeks of pinitol treatment did not alter insulin - mediated glucose disposal in individuals with obesity and mild type ii diabetes [ 21 , 22 ] . it seems that body weight is not significantly affected by inositol treatment [ 19 , 21 ] while inositol has been reported to improve insulin sensitivity and ovulatory function in young women affected by polycystic ovary syndrome . when the effect of inositol has been investigated in postmenopausal women with metabolic syndrome and in pregnant women with gestational diabetes , it resulted in improvements of fasting serum insulin and blood glucose levels [ 2325 ] . in particular , in pregnant women with a family history of type 2 diabetes a supplement of myoinositol throughout the pregnancy also reduced the 1-hour glycemia at the ogtt stage and reduced the incidence of gestational diabetes . however , those studies only include women with a specific hormonal status ( gestation , menopause , or pcos ) which does not allow us to confirm a similar effect of inositol supplementation in other contexts ; therefore the true mechanism of action is still unclear . to our knowledge this is the first study to test the effect of inositol in children , even though our results are only preliminary . the main aim of this process was to determine whether an acute effect of inositol on insulin sensitivity in children exists , when administered before a glucose tolerance test . our results indicate that insulin increase after glucose intake may be attenuated when inositol is administered before the ogtt . in particular , it seems that inositol reduces insulin increase mainly in children with high basal insulin level . so patients with high fasting insulin might be the ones to benefit more from the administration of inositol . in our study the observed correlations are not high , but this may be due to the low number of units in the sample analyzed . they seem however indicative of an association between the observed insulin increase and the level of basal insulin that should be analyzed in detail with ad hoc larger studies . myoinositol and d - chiro inositol have been shown to reduce insulin increase after glucose intake in obese children . further investigations and larger studies are required to define the physiological and potential therapeutic effects of their administration , but they could be effective oral nonpharmacological agents in the prevention of type ii diabetes in children .