Article

One-year effects of myo-inositol supplementation in postmenopausal women with metabolic syndrome

Climacteric

December 2011
15(5):490-5

DOI:10.3109/13697137.2011.631063

Source
PubMed

Authors:

Angelo Santamaria

University of Messina

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Objective: To evaluate the 12-month effect of myo-inositol treatment on some biochemical parameters of women affected by metabolic syndrome. Methods: Eighty outpatient postmenopausal women, affected by metabolic syndrome, were enrolled in a 12-month study. All women were treated with a low-energy diet, and then they were randomly assigned to myo-inositol 2 g b.i.d. (n = 40) or placebo (n = 40). All the women were evaluated for serum glucose, insulin, HOMA-IR (Homeostasis Model Assessment-Insulin Resistance), triglycerides, total and high density lipoprotein cholesterol, body mass index (BMI), waist circumference and blood pressure at baseline and after 12 months of treatment. Results: With the exception of BMI and waist circumference, after 12 months of treatment, all the parameters studied showed a significant improvement in the myo-inositol group compared to the control group. At the end of the study, in the myo-inositol group, the number of women without metabolic syndrome was eight (20%) whereas, in the control group, only one woman no longer had the metabolic syndrome after 12 months of diet. Conclusions: Myo-inositol might be considered one of the insulin-sensitizing substances in the treatment of metabolic syndrome.

The effect of Inositol supplementation on blood pressure: a systematic review and meta-analysis of randomized-controlled trials

Article

Jun 2021

Background & Aims Potential effects of inositol supplementation on blood pressure (BP) have been examined in several interventional studies. Nevertheless, findings in this context are controversial. Therefore, the current systematic review and meta-analysis aimed to comprehensively assess the impact of inositol supplementation on BP. Methods Five online databases including Web of Science, Scopus, Embase, Cochrane, Google Scholar, and PubMed were systematically searched from inception to March 2020. We included all randomized clinical trials (RCTs) evaluating the effects of inositol supplementation on systolic blood pressure (SBP) and/or diastolic blood pressure (DBP) in humans. Results The random-effects meta-analysis of 7 eligible RCTs demonstrated the significant decline in both SBP (WMD − 5.69 mmHg; 95% CI − 7.35 to − 4.02, P <0.001) and DBP (WMD − 7.12 mmHg; 95% CI − 10.18 to − 4.05, P <0.001) following supplementation with inositol. Subgroup analysis showed that studies performed in individuals with metabolic syndrome with a longer duration (>8 weeks) and a dose of 4000 mg resulted in a more effective reduction in SBP and DBP with acceptable homogeneity. Conclusions The current meta-analysis, indicated that supplementation with inositol significantly decrease SBP and DBP. Further large-scale RCTs with better design are needed to confirm these findings.

From Prediabetes to Type 2 Diabetes Mellitus in Women with Polycystic Ovary Syndrome: Lifestyle and Pharmacological Management

Article

Full-text available

Jun 2020

Aims. Despite the very clear association between polycystic ovary syndrome (PCOS) and dysglycemia, few studies have explored the continuum of glycemic alterations leading from minor glucose abnormalities to overt diabetes. The purpose of this review is to trace the natural history of glycemic alteration in women with PCOS. Methods. We performed a literature review without time limit until August 2019. Inclusion criteria were studies addressing the association between impaired glucose tolerance or impaired fasting glucose or type 2 diabetes (T2D) and PCOS with at least an English abstract. The exclusion criteria were no PCOS or impaired glucose tolerance or impaired fasting glucose or T2D as outcome. The outcomes of interest were the onset of impaired glucose tolerance, impaired fasting glucose, T2D, and the progression from impaired glucose tolerance or impaired fasting glucose to T2D. Results. Healthy diet and physical activity are the first-line therapy for PCOS. Treatment with metformin was associated with significant lower 2-hour postload glucose levels and with reduction in fasting glucose when compared to placebo. Thiazolidinediones were more effective in reducing fasting glucose levels compared to placebo. Metformin and pioglitazone treatments showed similar effects on fasting glucose levels. The sodium-glucose cotransporter-2 inhibitor empagliflozin did not show differences in metabolic parameters when compared to metformin. The combination therapy with metformin plus the glucagon-like peptide-1 receptor agonist liraglutide was associated with significant improvements in basal and postload glucose levels compared with only liraglutide. Likewise, a combination therapy with the dipeptidyl peptidase-4 inhibitor saxagliptin and metformin demonstrated superiority versus metformin in fasting glucose and oral glucose tolerance test normalization. Myo-inositol supplementation was associated with lower insulin levels, glucose levels, and insulin resistance when compared with placebo, metformin, or estrogen treatments. Conclusions. The use of insulin-sensitizing agents, such as metformin and inositols, along with lifestyle interventions may improve the metabolic profile in PCOS women. 1. Introduction Diabetes mellitus is a worldwide epidemic. Its prevalence and incidence are steeply growing with an estimated 425 million of people currently having diabetes [1]. The great social burden of the disease is worsened by the huge number of people with prediabetes (i.e., impaired fasting glucose and/or impaired glucose tolerance) who are at high risk of developing it. In addition, one in two adults with diabetes (about 212 million of people) is undiagnosed. Several risk factors for the development of the disease have been well recognized. Some risk factors are gender specific, such as gestational diabetes mellitus (GDM) and polycystic ovary syndrome (PCOS). PCOS is defined by its reproductive features of hyperandrogenism, chronic oligoanovulation, and/or polycystic ovarian morphology [2]. Its prevalence is 5–15%, depending on the diagnostic criteria applied [3]. PCOS is associated with metabolic abnormalities, including insulin resistance (IR) and β-cell dysfunction [2]. The result of IR is hyperinsulinemia, which has a central role in the pathogenesis of androgen excess in PCOS. Indeed, insulin acts as a cogonadotropin to increase luteinizing hormone (LH)-induced androgen synthesis in theca cells [4] and can enhance gonadotropin-releasing hormone (GnRH)-mediated gonadotropin secretion [5]. Insulin also reduces hepatic sex hormone binding globulin (SHBG) synthesis, thereby increasing the levels of bioavailable androgens [6]. The defect of insulin action was quantified in PCOS using the euglycemic clamp [7]. Insulin action was reduced by 35–40% in both lean and obese women with PCOS compared to control women of similar age and body composition [8]. Recent studies in daughters of women affected by PCOS have found evidence for pancreatic β-cell dysfunction prior to menarche [9]. Genetic analyses showed that metabolic abnormalities such as obesity and IR contribute to the pathogenesis of PCOS [10]. Women with PCOS have a higher cardiometabolic risk compared with women without ovarian problems [11]. In women with PCOS, dysglycemia typically consists of impaired glucose tolerance [12], its prevalence being of almost 30% in both adult women [13] and affected adolescents [14]. For this reason, PCOS is associated with a two times increased risk for type 2 diabetes (T2D) [15]. Despite the very clear association between PCOS and dysglycemia, few studies have explored the continuum of glycemic alterations leading from minor glucose abnormalities to overt diabetes. The purpose of this review is to summarize the effect of lifestyle and pharmacological management on glycemic alterations of women with PCOS. 2. Materials and Methods We searched the online databases of PubMed/Medline, Scopus, Web of Science, Science Direct, Embase, CINAHL, EBSCO, and Google Scholar search engine using MeSH keywords of “impaired glucose tolerance” or “IGT,” “impaired fasting glucose” or “IFG,” “type 2 diabetes” or “T2D,” and “polycystic ovary syndrome” or “PCOS” or “PCO syndrome” without time limit until August 2019. All the reference lists of the retrieved articles were reviewed. All steps of the study were independently performed by two researchers and any disagreement between researchers was resolved by a third researcher. Inclusion criteria were studies addressing the association between impaired glucose tolerance or impaired fasting glucose or T2D and PCOS with at least an English abstract with a special focus on the available PCOS treatment. The exclusion criteria were as follows: no PCOS or impaired glucose tolerance or impaired fasting glucose or T2D as outcome, conference presentations, and letters to the editors. The outcomes of interest were the onset of impaired glucose tolerance, impaired fasting glucose, T2D, and the progression from impaired glucose tolerance or impaired fasting glucose to T2D with a special focus on the available PCOS treatment. 3. Results and Discussion 3.1. Pathogenesis of Prediabetes and Type 2 Diabetes Several risk factors have been hypothesized having a causal role in the pathogenesis of prediabetes and T2D of women with PCOS. Classical risk factors such as genetic background, obesity, and familiarity for diabetes and PCOS-specific risk factors have been described. The role of obesity does not impact independently on the onset of prediabetes and T2D because it was shown that also lean women with PCOS have a high risk of glucose alterations. However, obesity surely represents a strong additional risk factor. Among the PCOS-specific factors, IR and hyperandrogenism have been reported. Subjects with hyperandrogenism have a higher level of IR compared with those without hyperandrogenism [16]. Treatment with antiandrogens improves insulin sensitivity; therefore hyperandrogenism could contribute to the pathogenesis of prediabetes and T2D through mechanism of sustaining higher level of IR. However, hyperandrogenism in PCOS could worsen glucose tolerance by stimulating low-grade inflammation [17, 18]. Even if IR is not a feature always present in patients with PCOS, it is considered one of the key elements underlying the pathogenesis of the syndrome. It is the main factor associated with the development of T2D in those women. Reported prevalence of IR in women with PCOS varies from 44% to 70% [19] mostly because of different methods used to assess it [20]. IR is the typical condition of subjects with T2D. Women with PCOS share with people with T2D the same impaired glucose pattern consisting of a prevalent disturbance of fasting blood glucose. Higher levels of IR stress the pancreatic beta cell function, resulting in earlier functional depletion of insulin secretion capacity and higher risk of developing prediabetes and T2D. The other key element characterizing PCOS is hyperandrogenism. The relation between hyperandrogenism and IR is a chicken and egg problem. On one side, androgens may have a direct role in the inhibition of hepatic and peripheral insulin action by reducing amount and efficiency of the glucose transporter type 4 (GLUT4), especially in adipose tissue and muscles [21]. Moreover, androgens in association with increased free fatty acids (FFA) levels (a common feature in women with PCOS) reduce insulin excretion in the liver and insulin-dependent glucose uptake in skeletal muscles contributing to IR and compensatory hyperinsulinemia [22]. On the other side, it is well demonstrated that insulin has a direct role in ovarian steroidogenesis and in the ovulation control. Insulin in fact directly stimulates androgen production from ovaries, enhancing the activity of CYP17α and other steroidogenic enzymes with increased androgen production. It also inhibits the hepatic synthesis of SHBG and the secretion of the insulin-like growth factor-binding protein (IGFBP-1) resulting in elevated levels of free IGF and androgens. Furthermore, at pituitary level, insulin stimulates LH secretion, which, in association with insulin itself, acts synergistically on theca cells, increasing androgen biosynthesis [4, 23]. As shown by Dunaif et al., IR associated with PCOS, seems to be determined also by alterations at the level of the insulin receptor signalling. They observed that insulin receptors isolated from fibroblast cultured and skeletal muscle of women with PCOS presented increased insulin-independent autophosphorylation which is associated with reduced receptor activity [24, 25] and can lead to IR. However, other abnormalities have been observed also in downstream pathways, such as the serine phosphorylation of the insulin receptor substrates which inhibits its binding with PI3K and prevents the propagation of the signal downstream [26, 27]. Because of this central role of IR and compensatory hyperinsulinemia in the pathogenesis of the disease, it appears clear how insulin sensitizers represent possible therapeutic agents. Alternative mechanisms of the pathogenesis of prediabetes and T2D in subjects with PCOS are muscle mitochondrial dysfunction [28] and the gut microbiome [29]. The latter hypothesis is sustained by the presence of specific taxa of gut microorganisms that are associated with lower androgen levels. The following sections and Table 1 report existing evidence of the effect of different treatments on impaired glucose tolerance and impaired fasting glucose in women with PCOS. No treatment was effective in restoring normal glucose tolerance or reverse to impaired glucose tolerance or to impaired fasting glucose when T2D was already diagnosed. Intervention Impaired glucose tolerance (IGT) Impaired fasting glucose (IFG) Lifestyle modifications Improved (28, 29, 33, 34) Improved (28, 29, 33, 34) Metformin (i) Improvement in 2-hour glucose levels at the OGTT (46, 47) Reduction in fasting glucose levels compared to placebo (42) (ii) Reversion from IGT to normal glucose tolerance (47) Thiazolidinediones Reversion from IGT to normal glucose tolerance (60) Reduction in fasting glucose levels compared to placebo (58) SGLT2i Neutral effect (61) Neutral effect (61) GLP-1 RA Improved with the combination of liraglutide and metformin (62) Improved with the combination of liraglutide and metformin (62) DPP4i Improved with the combination of saxagliptin and metformin (63) Improved with the combination of saxagliptin and metformin (63) Inositol Improved (78) Improved (78) SGLT2i, sodium-glucose cotransporter-2 inhibitors; GLP-1 RA, glucagon-like peptide-1 receptor agonists; DPP4i, dipeptidyl peptidase-4 inhibitors; OGTT, oral glucose tolerance test.

Inositol in the MAnaGemENt of abdominal aortic aneurysm (IMAGEN): Study protocol for a randomised controlled trial

Article

Full-text available

Nov 2017
TRIALS

Background An abdominal aortic aneurysm (AAA) is a focal dilation of the abdominal aorta and is associated with a risk of fatal rupture. Experimental studies suggest that myo-inositol may exert beneficial effects on AAAs through favourable changes to biological pathways implicated in AAA pathology. The aim of the Inositol in the MAnaGemENt of abdominal aortic aneurysm (IMAGEN) trial is to assess if myo-inositol will reduce AAA growth. Methods/design IMAGEN is a multi-centre, prospective, parallel-group, randomised, double-blind, placebo-controlled trial. A total of 164 participants with an AAA measuring ≥ 30 mm will be randomised to either 2 g of myo-inositol or identical placebo twice daily for 12 months. The primary outcome measure will be AAA growth estimated by increase in total infrarenal aortic volume measured on computed tomographic scans. Secondary outcome measures will include AAA diameter assessed by computed tomography and ultrasound, AAA peak wall stress and peak wall rupture index, serum lipids, circulating AAA biomarkers, circulating RNAs and health-related quality of life. All analysis will be based on the intention-to-treat principle at the time of randomisation. All patients who meet the eligibility criteria, provide written informed consent and are enrolled in the study will be included in the primary analysis, regardless of adherence to dietary allocation. Discussion Currently, there is no known medical therapy to limit AAA progression. The IMAGEN trial will be the first randomised trial, to our knowledge, to assess the value of myo-inositol in limiting AAA growth. Trial registration Australian New Zealand Clinical Trials Registry, ACTRN12615001209583. Registered on 6 November 2015. Electronic supplementary material The online version of this article (doi:10.1186/s13063-017-2304-x) contains supplementary material, which is available to authorized users.

Plant foods, healthy plant-based diets, and type 2 diabetes: a review of the evidence

Article

Aug 2023

Mariana Del Carmen Fernández-Fígares Jiménez

Type 2 diabetes (T2D) is a metabolic chronic disease in which insulin resistance and insufficient insulin production lead to elevated blood glucose levels. The prevalence of T2D is growing worldwide, mainly due to obesity and the adoption of Western diets. Replacing animal foods with healthy plant foods is associated with a lower risk of T2D in prospective studies. In randomized controlled trials, the consumption of healthy plant foods in place of animal foods led to cardiometabolic improvements in patients with T2D or who were at high risk of the disease. Dietary patterns that limit or exclude animal foods and focus on healthy plant foods (eg, fruits, vegetables, whole grains, nuts, legumes), known as healthy, plant-based diets, are consistently associated with a lower risk of T2D in cohort studies. The aim of this review is to examine the differential effects of plant foods and animal foods on T2D risk and to describe the existing literature about the role of healthy, plant-based diets, particularly healthy vegan diets, in T2D prevention and management. The evidence from cohort studies and randomized controlled trials will be reported, in addition to the potential biological mechanisms that seem to be involved.

A review of the role of inositols in conditions of insulin dysregulation and in uncomplicated and pathological pregnancy

Article

Full-text available

Dec 2020

Inositols, a group of 6-carbon polyols, are highly bioactive molecules derived from diet and endogenous synthesis. Inositols and their derivatives are involved in glucose and lipid metabolism and participate in insulin-signaling, with perturbations in inositol processing being associated with conditions involving insulin resistance, dysglycemia and dyslipidemia such as polycystic ovary syndrome and diabetes. Pregnancy is similarly characterized by substantial and complex changes in glycemic and lipidomic regulation as part of maternal adaptation and is also associated with physiological alterations in inositol processing. Disruptions in maternal adaptation are postulated to have a critical pathophysiological role in pregnancy complications such as gestational diabetes and pre-eclampsia. Inositol supplementation has shown promise as an intervention for the alleviation of symptoms in conditions of insulin resistance and for gestational diabetes prevention. However, the mechanisms behind these affects are not fully understood. In this review, we explore the role of inositols in conditions of insulin dysregulation and in pregnancy, and identify priority areas for research. We particularly examine the role and function of inositols within the maternal-placental-fetal axis in both uncomplicated and pathological pregnancies. We also discuss how inositols may mediate maternal-placental-fetal cross-talk, and regulate fetal growth and development, and suggest that inositols play a vital role in promoting healthy pregnancy.

Effect of dietary myo-inositol supplementation on the insulin resistance and the prevention of gestational diabetes mellitus: study protocol for a randomized controlled trial

Article

Full-text available

Jul 2020
TRIALS

Background: Gestational diabetes mellitus (GDM) is defined as impaired glucose tolerance with onset or first recognition during pregnancy, which is characterized by an increased insulin resistance. Gestational diabetes mellitus is associated with pregnancy-related maternal and fetal morbidity (both antenatal and perinatal). Myo-inositol has been suggested to improve insulin resistance in women with polycystic ovary syndrome. The aim of this study is to examine the impact of myo-inositol supplementation during pregnancy on the incidence of gestational diabetes mellitus. Methods: We will conduct a single-center, open-label, randomized controlled trial. A total of 160 healthy pregnant women with singleton pregnancy at 11-13+6 weeks of gestation will be randomly allocated in two groups: intervention group (N = 80) and control group (N = 80). The intervention group will receive myo-inositol and folic acid (4000 mg myo-inositol and 400 mcg folic acid daily) from 11 to 13+6 weeks of gestation until 26-28 weeks of gestation, while the control group will receive folic acid alone (400 mcg folic acid daily) for the same period of time as intervention group. The primary outcome will be gestational diabetes incidence rate at 26-28 weeks of gestation, according to the results of a 75 g oral glucose tolerance test held at 26-28 weeks of gestation. The secondary outcomes will include fasting blood glucose levels, glycated hemoglobin levels, insulin resistance level (evaluated by homeostasis model assessment of insulin resistance and Matsuda Index), and incidence rate of diet-treated gestational diabetes and diabetes requiring insulin therapy at 26-28 weeks of gestation. Discussion: This trial will provide evidence for the effectiveness of myo-inositol supplementation during pregnancy in reducing the incidence of gestational diabetes mellitus. Trial registration: ISRCTN registry: ISRCTN16142533 . Registered on 9 March 2017.

Inositols in Insulin Signaling and Glucose Metabolism

Article

Full-text available

Nov 2018

In the past decades, both the importance of inositol for human health and the complex interaction between glucose and inositol have been the subject of increasing consideration. Glucose has been shown to interfere with cellular transmembrane transport of inositol, inhibiting, among others, its intestinal absorption. Moreover, intracellular glucose is required for de novo biosynthesis of inositol through the inositol-3-phosphate synthase 1 pathway, while a few glucose-related metabolites, like sorbitol, reduce intracellular levels of inositol. Furthermore, inositol, via its major isomers myo -inositol and D- chiro -inositol, and probably some of its phosphate intermediate metabolites and correlated enzymes (like inositol hexakisphosphate kinase) participate in both insulin signaling and glucose metabolism by influencing distinct pathways. Indeed, clinical data support the beneficial effects exerted by inositol by reducing glycaemia levels and hyperinsulinemia and buffering negative effects of sustained insulin stimulation upon the adipose tissue and the endocrine system. Due to these multiple effects, myoIns has become a reliable treatment option, as opposed to hormonal stimulation, for insulin-resistant PCOS patients.

The effects of inositol supplementation on lipid profiles among patients with metabolic diseases: A systematic review and meta-analysis of randomized controlled trials

Article

Full-text available

May 2018
LIPIDS HEALTH DIS

Background: Several studies have evaluated the effect of inositol supplementation on lipid profiles among population with metabolic diseases; however, the findings are controversial. This review of randomized controlled trials (RCTs) was performed to summarize the evidence of the effects of inositol supplementation on lipid profiles among population with metabolic diseases. Methods: Relevant RCTs studies were searched in Cochrane Library, EMBASE, MEDLINE, and Web of Science until October 2017. Two researchers assessed study eligibility, extracted data, and evaluated risk of bias of included primary studies, independently. To check for the heterogeneity among included studies Q-test and I2 statistics were used. Data were pooled by using the random-effect model and standardized mean difference (SMD) was considered as summary of the effect size. Results: Overall, 14 RCTs were included into meta-analysis. Pooled results showed that inositol supplementation among patients with metabolic diseases significantly decreased triglycerides (SMD − 1.24; 95% CI, − 1.84, − 0.64; P < 0.001), total- (SMD − 1.09; 95% CI, − 1.83, − 0.55; P < 0.001), and LDL-cholesterol levels (SMD − 1.31; 95% CI, − 2.23, − 0.39; P = 0.005). There was no effect of inositol supplementation on HDL-cholesterol levels (SMD 0.20; 95% CI, − 0.27, 0.67; P = 0.40). Conclusions: Inositol supplementation may result in reduction in triglycerides, total- and LDL-cholesterol levels, but did not affect HDL-cholesterol levels among patients with metabolic diseases. Additional prospective studies regarding the effect of inositol supplementation on lipid profiles in patients with metabolic diseases are necessary. Keywords: Inositol, Lipid profiles, Metabolic diseases, Meta-analysis

AUTHOR COPY ONLY 6:3 647-658 V Unfer A meta-analysis on myo-inositol effect in PCOS Myo-inositol effects in women with PCOS: a meta-analysis of randomized controlled trials

Article

Full-text available

Oct 2017

Myo-inositol (MI) supplementation in women with polycystic ovary syndrome (PCOS) has been evaluated over the last years. Many hormonal and reproductive impairments associated with this disorder seem relieved by the supplement. The objective of the meta-analysis was to assess the effects of MI alone or combined with d-chiro-inositol (DCI) on the endocrine and metabolic abnormalities of women with PCOS. Literature was retrieved from selected databases, MEDLINE, EMBASE, PubMed and Research Gate (up to November 2016). Only randomized controlled trials (RCTs) investigating the effects of MI alone or combined with dCI were reviewed. Nine RCTs involving 247 cases and 249 controls were included. Significant decreases in fasting insulin (SMD = −1.021 µU/mL, 95% CI: −1.791 to −0.251, P = 0.009) and homeostasis model assessment (HOMA) index (SMD = −0.585, 95% CI: −1.145 to −0.025, P = 0.041) were identified after MI supplementation. The trial sequential analysis of insulin meta-analysis illustrates that the cumulative z-curve crossed the monitoring boundary, providing firm evidence of the intervention effect. A slight trend toward a reduction of testosterone concentration by MI with respect to controls was found (SMD = −0.49, 95% CI: −1.072 to 0.092, P = 0.099), whereas androstenedione levels remained unaffected. Throughout a subgroup's meta-analysis, a significant increase in serum SHBG was observed only in those studies where MI was administered for at least 24 weeks (SMD = 0.425 nmol/L, 95% CI: 0.050-0.801, P = 0.026). These results highlight the beneficial effect of MI in improving the metabolic profile of women with PCOS, concomitantly reducing their hyperandrogenism.

Myo-inositol effects in women with PCOS: A meta-analysis of randomized controlled trials

Article

Full-text available

Nov 2017

Myo-inositol (MI) supplementation in women with polycystic ovary syndrome (PCOS) has been evaluated over the last years. Many hormonal and reproductive impairments associated with this disorder seem relieved by the supplement. The objective of the meta-analysis was to assess the effects of MI alone or combined with d-chiro-inositol (DCI) on the endocrine and metabolic abnormalities of women with PCOS. Literature was retrieved from selected databases, MEDLINE, EMBASE, PubMed and Research Gate (up to November 2016). Only randomized controlled trials (RCTs) investigating the effects of MI alone or combined with DCI were reviewed. Nine RCTs involving 247 cases and 249 controls were included. Significant decreases in fasting insulin (SMD = −1.021 µU/mL, 95% CI: −1.791 to −0.251, P = 0.009) and homeostasis model assessment (HOMA) index (SMD = −0.585, 95% CI: −1.145 to −0.025, P = 0.041) were identified after MI supplementation. The trial sequential analysis of insulin meta-analysis illustrates that the cumulative z-curve crossed the monitoring boundary, providing firm evidence of the intervention effect. A slight trend toward a reduction of testosterone concentration by MI with respect to controls was found (SMD = −0.49, 95% CI: −1.072 to 0.092, P = 0.099), whereas androstenedione levels remained unaffected. Throughout a subgroup’s meta-analysis, a significant increase in serum SHBG was observed only in those studies where MI was administered for at least 24 weeks (SMD = 0.425 nmol/L, 95% CI: 0.050–0.801, P = 0.026). These results highlight the beneficial effect of MI in improving the metabolic profile of women with PCOS, concomitantly reducing their hyperandrogenism.

ApoE2 affects insulin signaling in the hippocampus and spatial cognition of aged mice in a sex-dependent manner

Article

Full-text available

Feb 2025

Apolipoprotein E (APOE) has garnered significant attention as one of the most influential genetic risk factors for Alzheimer's disease (AD). While the pathogenic role of APOE4 in sporadic AD has been extensively studied, research on the protective effects of the APOE2 genotype and its underlying mechanisms remains limited. Additionally, the existence of sex differences in the protective effects of ApoE2 continues to be a topic of debate. In this study, we utilized humanized ApoE2- and ApoE3- target replacement mice to examine the sex-specific effects of ApoE2 on cognition. Compared with female ApoE3 mice, we found significantly lower spatial cognitive ability and impaired hippocampal synaptic ultrastructure in aged female ApoE2 mice, accompanied by reduced insulin signaling of the hippocampus. Further analyses by target metabolomics and transcriptomic analyses revealed that female ApoE2 mice exhibit an age-related decline in hippocampal inositol levels, and that alterations in inositol levels lower insulin signaling. Importantly, inositol supplementation was found to alleviate peripheral glucose intolerance, enhance insulin signaling, and ultimately improve cognitive function. Interestingly, these differences were not observed between male ApoE2 and ApoE3 mice. The research findings not only provide new insights into the impact of ApoE2 on cognition but also offer a new strategy for cognitive improvement through inositol supplementation in older women.

Myo-inositol improves developmental competence and reduces oxidative stress in porcine parthenogenetic embryos

Article

Full-text available

Dec 2024

Objective Myo-inositol (Myo-Ins), the most abundant form of inositol, is an antioxidant and plays a crucial role in the development and reproduction of mammals and humans. However, information elucidating the role of Myo-Ins in porcine embryonic development after parthenogenetic activation (PA) is still lacking. Therefore, we investigated the effect of Myo-Ins on porcine embryos and its underlying mechanisms. Methods In this study, various concentrations of Myo-Ins (0, 5, 10, and 20 mM) were added to the porcine zygotic medium (PZM3) during the in vitro culture (IVC) of porcine embryos. Several characteristics were evaluated, including cleavage rate, blastocyst formation rate, intracellular glutathione (GSH) and reactive oxygen species (ROS) levels in 4–5 cell stage embryos, total cell number, apoptotic rate in blastocysts, mitochondrial membrane potential (MMP), mitochondrial quantity, mitochondrial stress in the blastocysts, and gene expression for antioxidant and mitochondrial function markers. Additionally, the immunofluorescence of HO-1 was assessed. Results The results showed that Myo-Ins at concentrations of 10 and 20 mM significantly increased the blastocyst formation rate compared to the control group. Embryos supplemented with 20 mM Myo-Ins exhibited higher GSH levels and lower ROS levels than those in the control group. Myo-Ins supplementation also decreased the rate of apoptosis and the apoptotic index in the treatment groups. Additionally, embryos supplemented with 20 mM Myo-Ins showed increased mitochondrial membrane potential (MMP), greater mitochondrial quantity, and reduced oxidative stress in the mitochondria. Interestingly, the expression levels of genes related to mitochondrial function and the nuclear erythroid factor 2-related factor (NRF2) pathway were elevated in the Myo-Ins treated groups. Furthermore, immunofluorescence results indicated that 20 mM Myo-Ins significantly increased HO-1 expression in blastocysts compared to the control group. Conclusion In conclusion, 20 mM Myo-Ins supplementation enhanced blastocyst development and improved mitochondrial function by regulating apoptosis, reducing oxidative stress, and activating the NRF2 pathway.

Effect of dietary myo-inositol supplementation on the insulin resistance and the prevention of gestational diabetes mellitus: an open-label, randomized controlled trial

Article

Full-text available

Aug 2024
ARCH GYNECOL OBSTET

Purpose Myo-inositol (MI) is an insulin-sensitizing dietary supplement, enhancing the transfer of glucose into the cell. Gestational diabetes mellitus (GDM) is characterized by abnormal glucose tolerance, which is associated with elevated insulin resistance. The present study aimed to assess the effect of MI supplementation during pregnancy on the incidence of GDM. Methods We performed a single-center, open-label, randomized controlled trial. A cohort of 200 pregnant women at 11–13⁺⁶ weeks of gestation were randomly assigned in two groups: MI group (n = 100) and control group (n = 100). The MI group received MI and folic acid (4000 mg MI and 400 mcg folic acid daily), while the control group received folic acid alone (400 mcg folic acid daily) until 26–28 weeks of gestation, when the 75 g Oral Glucose Tolerance Test (OGTT) was performed for the diagnosis of GDM. Clinical and metabolic outcomes were assessed. Results The incidence of GDM was significantly higher in the MI group (14.9%) compared to the control group (28.5%) (P = 0.024). Women treated with MI had significantly lower OGTT glucose values, than those not treated with MI (P < 0.001). The insulin resistance as assessed by HOMA-IR was significantly lower in the MI group versus control (P = 0.045). Furthermore, MI group had significantly higher insulin sensitivity as measured by the Matsuda Index, compared to the control group (P = 0.037). Conclusion MI supplementation seems to be an effective option to improve the glycemic control of pregnant women and prevent the onset of GDM. Trial registration ISRCTN registry: ISRCTN16142533. Registered 09 March 2017.

Antidiabetic Activity, Molecular Identification and In silico Docking of Compounds in Chromatographic Fractions of Tephrosia bracteolata Guill. & Perr. (Fabaceae) Leaves

Preprint

Full-text available

Jul 2023

Background Recent efforts for the complementary treatment of diabetes have focused on medicinal plants and their bioactive compounds. Tephrosia bracteolata is one of such plants used in the management of diabetes but its anti-diabetic principles are yet to be identified. This study was aimed at identifying the compounds responsible for the antidiabetic activity of the ethylacetate fraction of Tephrosia bracteolata leaves and subsequently, carryout an in silico molecular docking of these compounds against key targets in the pathophysiology of diabetes. Methods The ethylacetate fraction (EAF) of T. bracteolata leaves was fractionated using Silica gel column chromatography to yield 100 fractions. Pooling together of fractions with similar thin layer chromatographic (TLC) mobility profile afforded seven major fractions (SF1- SF7). Preliminary phytochemical studies were carried out on the fractions using standard methods. The antidiabetic activity of the fractions was subsequently evaluated (at a dose of 200 mg/kg) against alloxan- induced diabetes in adult mice. GC-MS analysis was carried out on the fraction with the highest activity. Subsequently, some of the identified active compounds were docked against key targets in the pathology of diabetes using Auto Dock tool. Results Preliminary phytochemical analysis revealed the presence of terpenoids, saponins, steroids, glycosides, flavonoids, tannins and alkaloids in varying proportions in the fractions. The sub-fractions produced varying degrees of significant (p < 0.05) decrease in FBS at 12h and 24h- post-treatment. GC-MS analysis of the most active fraction (SF5) revealed the presence of thirty- six compounds among which are some that have been reported to possess direct or indirect antidiabetic properties. These are Mome-inositol, 2-methoxy-4-vinylphenol, 1-D-thio-glucitol, 4-Piperidinone, Hexadecanoic acid, 9- octadecanoic acid, n- hexadecanoic acid and D- allose. Molecular docking studies (Auto Dock tool) between Mome inositol, 1-D-thio-glucitol and alpha-glucosidase showed that Mome inositol (− 6.7 kcal/mol) had a stronger affinity to the enzyme. Similarly, for sodium glucose co-transporter 2 (SGLT 2), Mome inositol (− 6.5 kcal/mol) had a stronger affinity than 1-D-thio-glucitol. Conclusions The identified compounds in the fraction could be responsible for the observed antidiabetic properties of the fraction of T. bracteolata.

Gold nanoparticles enhanced molecularly imprinted poly(3-Aminophenylboronic acid) sensor for myo-inositol detection

Article

Feb 2023
MICROCHEM J

Abstract Myo-inositol (MI) is a secondary messenger that can be used to treat a variety of metabolic syndromes (MS), from diabetes to cancer, and ongoing research is reassuring a bright future for therapies. In this study, two molecular imprinting polymer (MIP) sensor matrixes were created and investigated for the determination of MI; (i) 3-aminophenylboronic acid (3-APBA) electropolymerization with MI as the template on the SPCE surface (ii) gold nanoparticles (AuNPs) initially electrodeposited on a screen-printed carbon electrode (SPCE) surface and further the molecularly imprinted poly-3-aminophenylboronic acid (PAPBA) sensor film was electropolymerized with MI on the modified AuNPs/SPCE surface. Here, the surface modification with AuNPs on SPCE better enhances the electrochemical signal compared with unmodified SPCE. The electrochemical characterization of molecularly imprinted sensors was evaluated via Cyclic Voltammetry (CV), Electrochemical Impedance Spectroscopy (EIS) and Differential Pulse Voltammetry (DPV) techniques. The morphological changes of the modified electrodes were analyzed by Scanning Electron Microscope (SEM). The performances of the imprinted sensors (such as extraction of the template, rebinding conditions, and interference study) were investigated and optimized. The overall analytical data of the MI/PAPBA/AuNPs/SPCE based imprinted sensor (linear range: 500 nM to 60 μM; limit of detection: 1.0 nM; sensitivity: 0.042 μA μM−1) was better than the MI/PAPBA/SPCE (linear range: 500 nM to 50 μM; limit of detection: 4.7 nM; sensitivity: 0.019 μA μM−1). Further, the MI/PAPBA/AuNPs/SPCE imprinted sensor was successfully validated by applying for the sensitive and selective detection of myo-inositol in human plasma samples, and the results agreed well with the HPLC literature data.

Myo-inositol supplementation for prevention of gestational diabetes mellitus in overweight and obese pregnant women: a systematic review and meta-analysis

Article

Full-text available

Jul 2022

Abstract Background The prevalence of gestational diabetes mellitus [GDM] and of its most important predisposing factor, i.e. overweight and obesity, have increased dramatically over the past 20 years. Therefore, the aim of this study was to systematically review the articles on the effect of myo-inositol supplementation on the prevention of GDM in pregnant women with overweight and obesity. Methods We conducted a systematic literature search in electronic database (MEDLINE, Cochrane Library, ClinicalTrials.gov, Embase, ProQuest, PubMed, Google scholar, Scopus, Web of science and forward and backward citations) to identify all randomized controlled trials (RCTs) published until 21 December 2021. Finally, Among the 118 identified records, four studies were eligible and were included in this systematic review. The meta-analysis results were reported in the form of odds ratio (OR) to compare the incidence of GDM and pregnancy outcomes. They were also presented in the form of mean difference (MD) to compare fasting glucose (FG), 1-h and 2-h oral glucose tolerance test (OGTT) levels between the two groups. This study was registered on PROSPERO, number CRD42021290570. Results The results showed that the incidence of GDM was significantly lower in the myo-inositol group (OR 0.32, 95% CI 0.21 to 0.48; P

The role of myo-inositol supplement in assisted reproductive techniques

Article

Jun 2022
Hum Fertil

Assisted reproductive techniques can help many infertile couples conceive. Therefore, there is a need for an effective method to overcome the widespread problems of infertile men and women. Oocyte and sperm quality can increase the chances of successful in vitro fertilisation. The maturation environment in which gametes are present can affect their competency for fer-tilisation. It is well established that myo-inositol (MI) plays a pivotal role in reproductive physiology. It participates in cell membrane formation, lipid synthesis, cell proliferation, cardiac regulation, metabolic alterations, and fertility. This molecule also acts as a direct messenger of insulin and improves glucose uptake in various reproductive tissues. Evidence suggests that MI regulates events such as gamete maturation, fertilisation, and embryo growth through intracel-lular Ca 2 þ release and various signalling pathways. In addition to the in-vivo production of MI from glucose in the reproductive organs, its synthesis by in vitro-cultured sperm and follicles has also been reported. Therefore, MI is suggested as a therapeutic approach to maintain sperm and oocyte health in men and women with reproductive disorders and individuals of reproductive age.

Myo-inositol for insulin resistance, metabolic syndrome, polycystic ovary syndrome and gestational diabetes

Article

Full-text available

Mar 2022

Role of inositol and its isomers in glucose metabolism: Огляд літератури

Article

Full-text available

Dec 2021

Despite the chemical similarities between myo-inositol and D-chiro-inositol and their synergistic effects on insulin sensitivity, they serve different functions. Insulin resistance is one of the etiological factors in the development of polycystic ovary syndrome (PCOS), diabetes mellitus, metabolic syndrome, infertility, menstrual irregularities and ovulation disorders, pregnancy complications, in particular, gestational diabetes. Myo-inositol plays an important role in the insulin transfer and hormone synthesis in the ovaries, in oocyte maturation, fertilization, implantation and post-implantation development. Many studies confirm the positive effect of inositol isomers on metabolic, hormonal and reproductive disorders, both in the form of monotherapy and in combination with other drugs to enhance the therapeutic effect and bioavailability. Myo-inositol has a favorable safety profile. Studies have shown that in patients with PCOS myo-inositol improves ovarian function and fertility, reduces the manifestations of hyperandrogenism, insulin resistance and normalizes weight. Myo-inositol and D-chiro-inositol have different mechanisms of action on insulin sensitivity and have different functions. The balance of the two isomers ensures the normal secretion of hormones and ovarian functioning, but it is currently unknown what the optimal ratio of these two isomers due to the small number of high quality studies and the difficulty of studying their isolated action. There are currently different combinations of myo- and D-chiro-inisotol, but they also have not been supported by enough high quality studies. When prescribing various isomers of inositol, it should be remembered that doses above 4000 mg are the most studied in patients with PCOS, but D-chiro-inositol concentration above 1200 mg/day has undesirable effects. Most studies indicate that D-chiro-inositol value is increased in PCOS, therefore oocytes are more sensitive to its overdose, and combination drugs require more study. Currently, there is no consensus in the literature on the advantage of combined supplements of myo- and D-chiro-inositol compared to monotherapy with myo-inositol. Today, myo-inositol monotherapy is more researched and safer.

Inositol supplementation and body mass index: A Systematic Review and meta‐analysis of randomized clinical trials

Article

Full-text available

Oct 2021

Background: Inositol is a sugar-alcohol and recognized as a key component of cell membrane phospholipids. It has crucial role in the cell signaling pathways and contribute to improving glycemic responses. Although some earlier studies have revealed the effect of inositol mediating glucose uptake by improving insulin sensitivity, the benefit of inositol supplementation in patients with overweight and obesity is not completely understood. This study aimed to assess the impact of inositol supplementation on body mass index (BMI) through a systematic review and meta-analysis of controlled clinical trials. Methods: A systematic search was performed to August 2021 in the following databases: PubMed-Medline, Embase, Web of Science and Scopus. Fifteen controlled clinical trials investigating the effect of inositol on adult's BMI were finally included in the study. A random-effects model was employed to estimate the effect size. Subgroup analysis was performed by dose, duration, age, type of inositol. Meta-regression was used to investigate presence of any linear relationship. Begg's and Egger's tests were carried out to detect small study effect. Results: The results of pooled analysis showed that inositol supplementation significantly decreased BMI scores (WMD = -0.41 kg/m2; 95% CI: -0.78, -0.04; p = 0.028). Subgroup analysis was performed to identify the source of heterogeneity among studies (I 2 = 73.9%, p < 0.001), demonstrating supplementation duration, baseline BMI, mean age of participants, type of inositol and dosage were potential sources of heterogeneity. The effect of intervention was more clinically significant in participants with polycystic ovary syndrome (PCOS) and overweight/obesity. Inositol in the form of myo-inositol (MI) had stronger effect on BMI reduction. Conclusion: The meta-analysis suggests that oral inositol supplementation has positive effect on BMI reduction. Inositol supplementation could be considered as an adjunct treatment to improve body mass index.

The feasibility of a diet which enhances inositol availability

Article

Full-text available

Jan 2021
PROG NUTR

Background: Supplementation of myo-inositol has proved effective in different pathological conditions associated with insulin-resistance, including polycystic ovary syndrome, diabetes, gestational diabetes, and metabolic syndrome. At the same time, dietary habits in developed countries tend to reduce inositol intake , due to reduced consumption of whole grain foods, legumes, and nuts, rich in phytic acid, the main source of inositol. Aim: The review aims at providing a collection of foods with high phytic acid content to be used for diets that can make available as much inositol as is obtained from nutritional supplements commonly present in the market. Methods: An extensive review concerning the phytic acid content of foods was obtained from literature; furthermore, we designed an exemplifying phytic acid rich diet in by means of a specific nutritional software. Results: Foods with high phytic acid content are: cereals (0.04-3.3% on the dry matter), legumes (0.2-2.4%), oil seeds (0.4-5.7%), and nuts (0.2-9.4%). A moderate amount of phytic acid has been found in root vegetables, tubers and fruits, while low levels are found in the leafy green vegetables. Using these data, we developed an example of weekly diet which provides a mean phytic acid content of 5 g/1660Kcal. Conclusions: This study shows that it is possible to increase phytic acid intake, and consequently inositol availability, by means of an appropriate diet as a complementary treatment to dietary supplements. In people who regularly consume fruits and vegetables, the gut microbiota efficiently degrades phytic acid to myo-inositol phosphate products, therefore this diet could be proposed to patients with increased inositol needs, such as those suffering from polycystic ovary syndrome and in insulin resistance.

D-Chiro-Inositol Regulates Insulin Signaling in Human Adipocytes

Article

Full-text available

Mar 2021

D-Chiro-Inositol (D-Chiro-Ins) is a secondary messenger in the insulin signaling pathway. D-Chiro-Ins modulates insulin secretion, the mitochondrial respiratory chain, and glycogen storage. Due to these actions D-Chiro-Ins has been proposed to correct defective insulin function in a variety of conditions characterized by metabolic dysfunction, such as polycystic ovary syndrome (PCOS), obesity, gestational diabetes and fat accumulation at menopause. Since it is unclear whether D-Chiro-Ins directly acts on adipocytes, we aimed to study D-Chiro-Ins’s actions on adipocyte viability, proliferation, differentiation, and insulin-related protein expression using a human adipocyte cell line derived from Simpson–Golabi–Behmel Syndrome (SGBS) which fully differentiates to mature adipocytes. Throughout differentiation, cells were treated with D-Chiro-Ins, 17β-estradiol (E2) or Insulin. Cell viability and proliferation were not affected by D-Chiro-Ins, then D-Chiro-Ins promoted cell differentiation only during the final days of the process, while E2 enhanced it from the first phases. D-Chiro-Ins stimulated lipid storage and the production of big lipid droplets, thus reducing the content of free fatty acids. We also found that D-Chiro-Ins, either alone or in combination with insulin and E2 increased the expression and activation of insulin receptor substrate-1 (IRS1) and glucose transporter type 4 (GLUT4). In conclusion, this work shows that D-Chiro-Ins plays a direct role in the differentiation and in the function of human adipocytes, where it synergizes with insulin and estrogen through the recruitment of signal transduction pathways involved in lipid and glucose storage. These findings give clear insights to better understand the actions of D-Chiro-Ins on fat metabolism in women in physiology and in a variety of diseases.

Identification of biomarkers for essential hypertension based on metabolomics

Article

Dec 2020
NUTR METAB CARDIOVAS

Background and aim Essential hypertension (EH) is one of the most important public health problems worldwide. However, the pathogenesis of EH is unclear and early diagnostic methods are lacking. Metabolomics demonstrates great potential for biomarker discovery and mechanistic exploration of metabolic diseases. Methods and results This review included human and animal metabolomics studies related to EH in the PubMed and Web of Science databases between February 1996 and May 2020. The study designs, EH standards and reported metabolic biomarkers were systematically examined and compared. Pathway analysis was conducted through the online software MetaboAnalyst 4.0. Twenty-two human studies and fifteen animal studies were included in this systematic review. There were many frequently reported biomarkers with consistent trends (e.g., pyruvate, lactic acid, valine, and tryptophan) in human and animal studies, and thus had potential as biomarkers of EH. In addition, several shared metabolic pathways, including alanine, aspartate and glutamate metabolism, aminoacyl-tRNA biosynthesis, arginine biosynthesis, were identified in human and animal metabolomics studies. These biomarkers and pathways, closely related to insulin resistance, the inflammatory state and impaired nitric oxide production, were demonstrated to contribute to EH development. Conclusions This study summarized valuable metabolic biomarkers and pathways that could offer opportunities for the early diagnosis or prediction of EH and the discovery of the metabolic mechanisms of EH.

The Effect of Preincubation Time and Myo-inositol Supplementation on the Quality of Mouse MII Oocytes

Article

Full-text available

Oct 2020

Background: It is demonstrated that optimal preincubation time improves oocyte quality, fertilization potential and developmental rate. This study aimed to evaluate the effect of preincubation time in the simple and myo-inositol supplemented medium on the oocyte quality regarding oxidative stress and mitochondrial alteration. Methods: Cumulus oocyte complexes (COCs) retrieved from superovulated NMRI mice were divided in groups of 0, 4 and 8 hr preincubation time in the simple and 20 mmol/L myo-inositol supplemented media. Intracellular reactive oxygen species (H2O2), glutathione (GSH), mitochondrial membrane potential (MMP), ATP content, and mitochondrial amount were measured and analyzed in experimental groups. One-way ANOVA and Kruskal-Wallis were respectively used for parametric and nonparametric variables. Statistical significance was defined as p<0.05. Results: In comparison to control group, variables including ROS, GSH, mitochondrial amount, fertilization and developmental rates were significantly changed after 4 hr of preincubation in the simple medium, while MMP decreased following 8 hr of preincubation in the simple medium (p˂0.001). Preincubation of oocytes up to 8 hr in the simple medium could not decrease ATP content. For both 4 and 8 hr preincubation times, myo-inositole could decrease H2O2 and increase GSH and MMP levels and consequently could improve fertilization rate compared to oocytes preincubated in the simple culture. Conclusion: It seems that 4 hr or more preincubation time can decrease the oocyte quality and lead to reduced oocyte fertilization and developmental potential. Howevere, myo-inositol may prevent oocyte quality reduction and improve fertilization potential in comparision to the equivalent simple groups.

Inositol and Non-Alcoholic Fatty Liver Disease: A Systematic Review on Deficiencies and Supplementation

Article

Full-text available

Nov 2020

Liver lipid accumulation is a hallmark of non-alcoholic fatty liver disease (NAFLD), broadly associated with insulin resistance. Inositols (INS) are ubiquitous polyols implied in many physiological functions. They are produced endogenously, are present in many foods and in dietary supplements. Alterations in INS metabolism seems to play a role in diseases involving insulin resistance such as diabetes and polycystic ovary syndrome. Given its role in other metabolic syndromes, the hypothesis of an INS role as a supplement in NAFLD is intriguing. We performed a systematic review of the literature to find preclinical and clinical evidence of INS supplementation efficacy in NAFLD patients. We retrieved 10 studies on animal models assessing Myoinosiol or Pinitol deficiency or supplementation and one human randomized controlled trial (RCT). Overall, INS deficiency was associated with increased fatty liver in animals. Conversely, INS supplementation in animal models of fatty liver reduced hepatic triglycerides and cholesterol accumulation and maintained a normal ultrastructural liver histopathology. In the one included RCT, Pinitol supplementation obtained similar results. Pinitol significantly reduced liver fat, post-prandial triglycerides, AST levels, lipid peroxidation increasing glutathione peroxidase activity. These results, despite being limited, indicate the need for further evaluation of INS in NAFLD in larger clinical trials.

The precursor of PI(3,4,5)P3 alleviates aging by activating daf-18(Pten) and independent of daf-16

Article

Full-text available

Sep 2020

Aging is characterized by the loss of homeostasis and the general decline of physiological functions, accompanied by various degenerative diseases and increased rates of mortality. Aging targeting small molecule screens have been performed many times, however, few have focused on endogenous metabolic intermediates-metabolites. Here, using C. elegans lifespan assays, we conducted a worm metabolite screen and identified an eukaryotes conserved metabolite, myo-inositol (MI), to extend lifespan, increase mobility and reduce fat content. Genetic analysis of enzymes in MI metabolic pathway suggest that MI alleviates aging through its derivative PI(4,5)P2. MI and PI(4,5)P2 are precursors of PI(3,4,5)P3, which is negatively related to longevity. The longevity effect of MI is dependent on the tumor suppressor gene, daf-18 (homologous to mouse Pten), independent of its classical pathway downstream genes, akt or daf-16. Furthermore, we found MI effects on aging and lifespan act through mitophagy regulator PTEN induced kinase-1 (pink-1) and mitophagy. MI's anti-aging effect is also conserved in mouse, indicating a conserved mechanism in mammals.

Quantification and characterization of Myo-inositol in locally available peanuts and pine nuts in Pakistan

Article

Full-text available

May 2020
PAK J PHARM SCI

Inositol is one of nine biologically significant isomers of hexa hydroxy-cyclohexane which plays important role for bone formation and bone mineral density. The study was conducted to quantify and characterize the myo inositol crystals isolated from the pine nuts and peanuts. High-performance liquid chromatography, UV, FTIR and XRD was utilized for the rapid, on-line detection of inositol phosphate (InsP). The absorption peaks at 382.63nm for 0.10mg peanuts and 382.68 for 0.07mg pine nuts by UV-Visible spectroscopy confirmed the presence of myoinositol. Total concentration of myoinositol obtained was 0.23 and 5.31mmol/kg. The X-ray crystallography analysis showed that the unit-cell parameters a = 6.7226 (3) Å, b = 12.1462 (5) Å, c = 18.9942 (8) Å, α= 89.00, β= 94.98, δ= 989.00. The crystal density was reported at 1.6 cm −3 while the crystal volume was recorded at 1504.7(11) Å 3. The stretching frequencies of myo-inositol crystals were observed in the region of 3800-3778 cm −1 related to alcohol O-H groups of myo-inositol. It is therefore concluded and recommended that dry fruits being the rich source of myo-inositol can be used as functional food for the treatment of polycystic ovarian syndrome.

An Evaluation of a Nutraceutical with Berberine, Curcumin, Inositol, Banaba and Chromium Picolinate in Patients with Fasting Dysglycemia

Article

Full-text available

Mar 2020

Aim To evaluate if a nutraceutical containing Berberine, Curcumin, Inositol, Banaba, and Chromium Picolinate (Reglicem®), can ameliorate glycemic status in patients with dysglycemia. Methods We enrolled 148 patients with impaired fasting plasma glucose or impaired glucose tolerance, not taking any hypoglycemic compounds. Patients were randomized to take nutraceutical or placebo for 3 months, in a randomized, double-blind, placebo-controlled design. Both nutraceutical and placebo were self-administered once a day, 1 tablet during the breakfast. Results A reduction of fasting and post-prandial plasma glucose was observed with the nutraceutical combination (p < 0.05 vs baseline and p < 0.05 vs placebo, respectively). Furthermore, a decrease of glycated hemoglobin, and fasting plasma insulin was observed with the nutraceutical combination (p < 0.05 vs baseline and p < 0.05 vs placebo, respectively). Then, there was a reduction of homeostasis model assessment index with the nutraceutical combination (p < 0.05 vs baseline and p < 0.05 vs placebo). M value was higher (p < 0.05 vs baseline and p < 0.05 vs placebo) in the nutraceutical combination group at the end of the treatment. We observed a reduction of total cholesterol (TC) (p < 0.05 vs baseline) and triglycerides (Tg) (p < 0.05 vs baseline and p < 0.05 vs placebo) with the nutraceutical combination, respectively. Finally, high sensitivity C-reactive protein was reduced after 3 months with nutraceutical combination therapy (p < 0.05 vs baseline and p < 0.05 vs placebo, respectively). Conclusion A nutraceutical containing Berberine, Curcumin, Inositol, Banaba, and Chromium Picolinate can be helpful in improving glyco-metabolic compensation, TC and Tg value, and in reducing inflammatory status in patients with dysglycemia.

Myoinositol Supplementation of Freezing Medium Improves the Quality-Related Parameters of Dog Sperm

Article

Full-text available

Nov 2019

Simple Summary The generation of free radical reactive oxygen species during freeze–thaw procedures is one of the major factors affecting the function and survival of sperm. Myoinositol is the most important natural form of inositol produced in the human body. Researchers have attempted to exploit the antioxidant nature of myoinositol to treat human infertility issues via the improvement of sperm quality traits and fertilization rates. We investigated the potential role of myoinositol neutralizing free radicals produced during the cryopreservation of dog semen. Myoinositol supplementation in the freezing medium resulted in improved quality-related parameters of dog semen including percentage motility, viability, plasma membrane integrity, and chromatin integrity. Improvement in post-thaw semen quality was confirmed by the expression of genes related to apoptosis, nuclear integrity, and reactive oxygen species generation. Abstract Oxidative stress during freeze–thaw procedures results in reduced semen fertility. A decrease in free radical levels can improve the post-thaw sperm quality. We examined the effects of myoinositol supplementation in freezing medium on the structure and function of cryopreserved dog sperm. Pooled ejaculates were diluted with buffer without or with myoinositol (1 or 2 mg/mL). Analysis of fresh semen revealed that the optimal concentration of myoinositol was 1 mg/mL, and this concentration was used in further experiments. Post-thaw semen quality in the myoinositol-supplemented group was superior (p < 0.05) compared with that in the control group in terms of motility (57.9 ± 0.4% vs. 47.8 ± 0.2%), sperm viability (57.5 ± 0.5% vs. 44.6 ± 0.6%), intact plasma membrane (56.6 ± 0.4% vs. 46.2 ± 0.6%), and acrosome membrane (59.3 ± 0.5% vs. 51.8 ± 0.5%). In addition, sperm in the myoinositol-supplemented group showed a significantly lower expression of pro-apoptotic (BAX) and mitochondrial reactive oxygen species (ROS) modulator (ROMO1) genes but higher expression of anti-apoptotic (BCL2), and protamine-related (PRM2 and PRM3) genes compared with that in the control group. Therefore, myoinositol supplementation before freezing can protect against oxidative stress and improve post-thaw dog sperm quality.

Supplementation of sperm freezing medium with myoinositol improve human sperm parameters and protects it against DNA fragmentation and apoptosis

Article

Full-text available

Mar 2019
Cell Tissue Bank

The aim of this study is to evaluate the beneficial effect of Myoinositol (MYO) supplement in freezing media on the post thaw sperm quality. Semen samples from 40 normozoospermic men were divided into two aliquots and frozen with simple or 2 mg/mL MYO supplemented freezing medium. Post thaw process including, computer-assissted sperm analysis was used to analyze sperm motility and morphology. Reactive oxygen species was evaluated by the fluorometry of DCFH-DA, as well as total antioxidant capacity and lipid peroxidation were measured based on colorimetric assay by ELISA reader. Eventually, DNA fragmentation was assessed using TUNEL staining. MYO significantly improved progressive motility and normal morphology in treated samples (p < 0.05). Lipid peroxidation (malondialdehyde level) can be diminished in samples were frozen by MYO supplemented freezing media (p < 0.05). While MYO did not affect the amount of ROS (p > 0.05), it was associated with high values of total antioxidant capacity (p < 0.05). DNA integrity was significantly affected by MYO, as in MYO treated samples, DNA fragmentation was decreased compared to control ones (p < 0.001). The findings support the use of 2 mg/mL myoinositol supplemented freezing media in sperm cryopreservation to increase sperm quality after freezing–thawing procedures.

Myo-Inositol

Article

Full-text available

Dec 2018

Christian Egarter

Myo-Inositol ist das wichtigste Isomer der Inositol-Familie und ein intrazellulärer „second messenger“. Eine orale Verabreichung führt zu positiven Effekten auf die Insulinresistenz und den Fett- und Glukosemetabolismus sowie zu einer Senkung der Androgenspiegel. Zusätzlich zu diesen Effekten konnten auch günstige Auswirkungen im Rahmen von In-vitro-Fertilisations(IVF)-Zyklen auf Eizell- und Spermienqualität in kleineren Studien gezeigt werden.

Do inositol supplements enhance phosphatidylinositol supply and thus support endoplasmic reticulum function?

Article

Full-text available

Jun 2018

Robert H Michell

This review attempts to explain why consuming extra myo inositol (Ins), an essential component of membrane phospholipids, is often beneficial for patients with conditions characterised by insulin resistance, non-alcoholic fatty liver disease and endoplasmic reticulum (ER) stress. For decades we assumed that most human diets provide an adequate Ins supply, but newer evidence suggests that increasing Ins intake ameliorates several disorders, including polycystic ovary syndrome, gestational diabetes, metabolic syndrome, poor sperm development and retinopathy of prematurity. Proposed explanations often suggest functional enhancement of minor facets of Ins Biology such as insulin signalling through putative inositol-containing ‘mediators’, but offer no explanation for this selectivity. It is more likely that eating extra Ins corrects a deficiency of an abundant Ins-containing cell constituent, probably phosphatidylinositol (PtdIns). Much of a cell’s PtdIns is in ER membranes, and an increase in ER membrane synthesis, enhancing the ER’s functional capacity, is often an important part of cell responses to ER stress. This review: (a) reinterprets historical information on Ins deficiency as describing a set of events involving a failure of cells adequately to adapt to ER stress; (b) proposes that in the conditions that respond to dietary Ins there is an overstretching of Ins reserves that limits the stressed ER’s ability to make the ‘extra’ PtdIns needed for ER membrane expansion; and (c) suggests that eating Ins supplements increases the Ins supply to Ins-deficient and ER-stressed cells, allowing them to make more PtdIns and to expand the ER membrane system and sustain ER functions.

Inositols in Midlife

Article

Full-text available

Jan 2018

This review describes the mechanistic, animal, and clinical data related to the use of inositols in midlife. It covers studies related to the mechanism of action of myo-inositol and D-chiro-inositol and randomized controlled trials conducted in postmenopausal women with metabolic syndrome and supports these data with the results of in vitro and animal studies on inositol in nephropathy and other related conditions. Recent advances related to biochemistry, pharmaceutical science, and genetics are discussed. It concludes that inositols have a potential role to play in maintaining metabolic health in postmenopausal women.

Myoinositol and Inositol Hexakisphosphate in the Treatment of Breast Cancer: Molecular Mechanisms

Chapter

Jan 2018

Nutritional and Acquired Deficiencies in Inositol Bioavailability. Correlations with Metabolic Disorders

Article

Full-text available

Oct 2017
INT J MOL SCI

Communities eating a western-like diet, rich in fat, sugar and significantly deprived of fibers, share a relevant increased risk of both metabolic and cancerous diseases. Even more remarkable is that a low-fiber diet lacks some key components—as phytates and inositols—for which a mechanistic link has been clearly established in the pathogenesis of both cancer and metabolic illness. Reduced bioavailability of inositol in living organisms could arise from reduced food supply or from metabolism deregulation. Inositol deregulation has been found in a number of conditions mechanistically and epidemiologically associated to high-glucose diets or altered glucose metabolism. Indeed, high glucose levels hinder inositol availability by increasing its degradation and by inhibiting both myo-Ins biosynthesis and absorption. These underappreciated mechanisms may likely account for acquired, metabolic deficiency in inositol bioavailability.

Modulation of both Insulin Resistance and Cancer Growth by Inositol

Article

Aug 2017
CURR PHARM DESIGN

Insulin resistance indicates a deregulated set of biochemical pathways and physiological functions involved in the pathogenesis of a number of diseases, including type 2 diabetes and cancer. Conversely, a number of synthetic and natural insulin sensitizers, including inositol, have been recognized to exert both anti-diabetic as well as anti-cancer properties. Inositol participates in insulin transduction signaling, and deregulated inositol metabolism has been ascertained in several conditions associated with insulin resistance. Two distinct inositol-phosphoglycans released upon insulin stimulation act as insulin-mimetic by counteracting hyperinsulinemia, hyperglycemia and their metabolic complications. Additionally, inositol may directly interfere with both glucose metabolism and carcinogenesis by modulating a number of critical processes downstream of insulin stimulation, including anti-oxidant defenses, oxidative glucose metabolism and endocrine modulation. A selected cluster of biochemical factors (PI3K/Akt, PDH and AMPK-related pathways), that are presently considered putative targets for anticancer treatments, are also specifically modulated by inositol or its derivatives. What is more, studies on inositol mechanism of action paved the way in understanding that both insulin resistance and cancer share a few perturbed, critical biochemical pathways. Asides from basic investigations, preliminary studies in vivo demonstrated the beneficial effect of inositol in fostering glucose homeostasis as well as in antagonizing cancer growth. Thereby, inositol fulfills the requirement to target both insulin resistance and cancer, and its clinical usefulness deserves to be adequately addressed by specific, randomized trials.

Myoinositol: from gametes to embryonic development

Article

Jan 2016

Mariangela Palmieri

DCEO Biotechnology: Tools To Design, Construct, Evaluate, and Optimize the Metabolic Pathway for Biosynthesis of Chemicals

Article

Full-text available

Apr 2017

Chemical synthesis is a well established route for producing many chemicals on a large scale, but some drawbacks still exist in this process, such as unstable intermediates, multistep reactions, complex process control, etc. Biobased production provides an attractive alternative to these challenges, but how to make cells into efficient factories is challenging. As a key enabling technology to develop efficient cell factories, design-construction-evaluation-optimization (DCEO) biotechnology, which incorporates the concepts and techniques of pathway design, pathway construction, pathway evaluation, and pathway optimization at the systems level, offers a conceptual and technological framework to exploit potential pathways, modify existing pathways and create new pathways for the optimal production of desired chemicals. Here, we summarize recent progress of DCEO biotechnology and examples of its application, and provide insights as to when, what and how different strategies should be taken. In addition, we highlight future perspectives of DCEO biotechnology for the successful establishment of biorefineries.

Myo-inositol and melatonin in the menopausal transition

Article

Full-text available

Dec 2016

Introduction: The aim of the study was to evaluate the effects on serum insulin and serum thyroid profile of a dietary supplement, myo-inositol, given alone or in combination with melatonin to women during menopausal transition. Methods: Forty women aged 45–55 years and at least 6 months of amenorrhea were enrolled in this study. They were randomly assigned to two groups of 20 each. One group took myo-inositol (myo-Ins) (2 g twice a day) and the other group took 2 g/d myo-Ins plus 3 g/d melatonin before sleeping. At the beginning of the study and after 6 months, all women were evaluated for the following indices: waist circumference, body mass index, blood pressure, endometrial thickness, as well as serum concentrations of TSH, FT3, FT4 and insulin. Results: Both at baseline and at 6 months, the two groups were statistically similar for each of the considered indices. If percent changes (Δ%, 6 months over baseline) are contrasted in the two groups, serum TSH decreased in the myo-Ins group but increased in the latter, while serum insulin decreased in both groups. Conclusions: The combination of myo-Ins plus melatonin seems to affect positively glucose metabolism, while myo-Ins only seems to improve thyroid function.

Myo-inositol supplementation in diet-induced obese lactating rats mitigates metabolic dysregulation and improves offspring health in early life

Article

Jun 2025
J NUTR BIOCHEM

Saliva, Plasma, and Multifluid Metabolomic Signatures of Periodontal Disease, Type 2 Diabetes Progression, and Markers of Glycemia and Dyslipidemia Among Puerto Rican Adults With Overweight and Obesity

Article

Jul 2024

Background Evidence from cohort studies indicates a bidirectional relationship between periodontal disease and type 2 diabetes (T2D), but the underlying mechanisms remain unknown. In this study, we aimed to (1) identify saliva, plasma, and multifluid metabolomic signatures associated with periodontal disease and (2) determine if these signatures predict T2D progression and cardiometabolic biomarkers at year 3. Methods and Results We included participants from the SOALS (San Juan Overweight Adult Longitudinal Study) (n=911). Metabolites from saliva (k=635) and plasma (k=1051) were quantified using liquid chromatography–mass spectrometry. We applied elastic net regression with 10‐fold cross‐validation to identify baseline metabolomic signatures of periodontal disease. Multivariable Cox proportional hazards regression and linear regression were used to evaluate the association with T2D progression and biomarker concentrations. Metabolomic profiles included highly weighted metabolites related to lysine and pyrimidine metabolism. Periodontal disease or its 3 metabolomic signatures were not associated with T2D progression in 3 years. Prospectively, 1‐SD increments in the multifluid and saliva metabolomic signatures were associated with higher low‐density lipoprotein (multifluid: 12.9±5.70, P =0.02; saliva: 13.3±5.11, P =0.009). A 1‐SD increment in the plasma metabolomic signature was also associated with Homeostatic Model Assessment for Insulin Resistance (2.67±1.14, P =0.02) and triglyceride (0.52±0.18, P =0.002). Conclusions Although metabolomic signatures of periodontal disease could not predict T2D progression, they were associated with low‐density lipoprotein, triglyceride, and Homeostatic Model Assessment for Insulin Resistance levels at year 3.

Early Life Programming of Adipose Tissue Remodeling and Browning Capacity by Micronutrients and Bioactive Compounds as a Potential Anti-Obesity Strategy

Article

Full-text available

May 2024

The early stages of life, especially the period from conception to two years, are crucial for shaping metabolic health and the risk of obesity in adulthood. Adipose tissue (AT) plays a crucial role in regulating energy homeostasis and metabolism, and brown AT (BAT) and the browning of white AT (WAT) are promising targets for combating weight gain. Nutritional factors during prenatal and early postnatal stages can influence the development of AT, affecting the likelihood of obesity later on. This narrative review focuses on the nutritional programming of AT features. Research conducted across various animal models with diverse interventions has provided insights into the effects of specific compounds on AT development and function, influencing the development of crucial structures and neuroendocrine circuits responsible for energy balance. The hormone leptin has been identified as an essential nutrient during lactation for healthy metabolic programming against obesity development in adults. Studies have also highlighted that maternal supplementation with polyunsaturated fatty acids (PUFAs), vitamin A, nicotinamide riboside, and polyphenols during pregnancy and lactation, as well as offspring supplementation with myo-inositol, vitamin A, nicotinamide riboside, and resveratrol during the suckling period, can impact AT features and long-term health outcomes and help understand predisposition to obesity later in life.

Dietary Supplementation of Myo-Inositol, Cocoa Polyphenols, and Soy Isoflavones Improves Vasomotor Symptoms and Metabolic Profile in Menopausal Women with Metabolic Syndrome: A Retrospective Clinical Study

Article

Full-text available

Apr 2024
MED LITH

Background and Objectives: Hormonal changes physiologically occurring in menopausal women may increase the risk of developing metabolic and vasomotor disturbances, which contribute to increase the risk of developing other concomitant pathologies, such as metabolic syndrome (MetS). Materials and Methods: Retrospective data from 200 menopausal women with MetS and vasomotor symptoms taking one sachet per day of the dietary supplement INOFOLIC® NRT (Farmares srl, Rome, Italy) were collected. Each sachet consisted of myo-Inositol (2000 mg), cocoa polyphenols (30 mg), and soy isoflavones (80 mg, of which 50 mg is genistin). Patients recorded their symptoms through a medical questionnaire at the beginning of the administration (T0) and after 6 months (T1). Results: We observed an improvement in both the frequency and the severity of hot flushes: increased percentage of 2–3 hot flushes (28 at T0 vs. 65% at T1, p value < 0.001) and decreased percentage of 4–9 hot flushes (54% at T0 vs. 18% at T1, p value < 0.001). Moreover, symptoms of depression improved after supplementation (87% at T0 vs. 56% at T1 of patients reported moderate depression symptoms, p value < 0.001). Regarding metabolic profile, women improved body mass index and waist circumference with a reduction in the percentage of overweight and obesity women (88% at T0 vs. 51% at T1, p value = 0.01; 14% at T0 vs. 9% at T1, p value = 0.04). In addition, the number of women suffering from non-insulin dependent diabetes reduced (26% at T0 vs. 16% at T1, p value = 0.04). Conclusions: These data corroborate previously observed beneficial effects of the oral administration of myo-Inositol, cocoa polyphenols, and soy isoflavones against menopausal symptoms in the study population. Considering the promising results of the present study, further prospective controlled clinical trials are needed to deeply understand and support the efficacy of these natural compounds for the management of menopausal symptoms.

Recent advances in myo-inositol recovery and purification from agricultural sources as potential dietary supplements: A review

Article

Dec 2023

Myo-inositol improves the viability of boar sperm during liquid storage

Article

Full-text available

Jul 2023

Introduction Liquid preservation of boar semen is a highly preferred method for semen preservation in pig production. However, oxidative stress is the main challenge during the liquid preservation of boar semen in a time dependent manner. Therefore, supplementation of sperm with antioxidants during storage to protect them from oxidative stress has been the focus of recent research. Myo-inositol (Myo-Ins), the most active form of inositol, which belongs to the vitamin (Vit.) (B1 group has been shown to improve semen quality) (1). This study aimed to investigate whether Myo-Ins supplementation protects boar sperm in liquid preservation against oxidative stress and determine the appropriate concentration of Myo-Ins to be used in this regard. Methods Boar sperm was diluted with a semen extender with different concentrations of Myo-Ins (2, 4, 6, and 8 mg/mL) depending on the previous studies (1, 24). Sperm motility and viability, plasma membrane and acrosome integrity, mitochondrial membrane potential (MMP), semen time survival, and gene expression were measured and analyzed on days 0, 1, 3, 5, and 7 for the different samples. Results Different concentrations of Myo-Ins exerted different protective effects on the boar sperm quality. The addition of 2 mg/mL Myo-Ins resulted in higher sperm motility and viability, plasma membrane and acrosome integrity, MMP, and effective survival time. Investigation of mRNA expression patterns via qRT-PCR suggested that the 2 mg/mL Myo-Ins sample had increased expression of antioxidative genes. Conclusion The addition of Myo-Ins to semen extender improved the boar semen quality by decreasing the effects of oxidative stress during liquid preservation at 17°C. Additionally, 2 mg/mL is the optimum inclusion concentration of Myo-Ins for semen preservation.

Therapeutic options for pre-gravidary training in women with a history of combined infertility

Article

Full-text available

Apr 2022

The objective: to substantiate and evaluate the improvement of pre-gravida preparation in women with a history of combined infertility factors. Materials and methods. We examined 102 women who were diagnosed with two factors of infertility simultaneously – infertility of tubal origin and infertility associated with anovulation caused by hyperprolactinemia and polycystic ovary syndrome. All patients were divided into groups according to the three-month pre-gravida preparation regimen: the 1st group (52 women) received basic pre-gravida preparation (dydrogesterone, folic acid, metformin) in combination with diet; the 2d group 2 (50 patients) – an improved scheme of pre-gravida preparation (dydrogesterone, methyl tetrahydrofolate, potassium iodide, vitamin D3, a complex of myo-inositol and D-chiro-inositol) in combination with diet. The reliability of relative values was evaluated by the Fisher angular transformation method. Results. In women of the 1st group the number of cases of gestational diabetes (30.8 %) was slightly higher than in patients of the 2nd group (20.0 %), the frequency of fetal macrosomia was significantly higher (19.2 % and 10.0 % persons, respectively). The incidence of early miscarriage in persons of the 2d group was significantly lower (40.0 %) than in the 1st group (69.2 %), the risk of late miscarriage was twice lower (14.0 % and 26.9 %, respectively). Conclusions. The proposed complex of pre-gravida preparation in the women with a combined form of infertility (tubal infertility and infertility associated with anovulation), which includes inositol, contributes to a greater reduction in the incidence of obstetric and perinatal complications.

Effects of inositol on glucose homeostasis: Systematic review and meta-analysis of randomized controlled trials

Article

Jun 2018
CLIN NUTR

Background & aims: The effect of inositol on glucose homeostasis is not well characterized. The aim of the present meta-analysis is to synthesize the effects of inositol on glucose homeostasis in different clinical conditions. Methods: We performed a systematic review (CRD42017057927) following PRISMA guidelines. Web of Science and Medline were searched for randomized controlled trials (RCTs) that addressed supplementation with compounds of the inositol family in humans and assessed their effects on glucose homeostasis. Results: We screened 476 abstracts and included 20 RCTs with a total of 1239 subjects. Meta-analysis showed in the treatment arm a reduction in fasting plasma glucose (Mean difference (MD) -0.44 mmol/l, 95% CI -0.65, -0.23), 2 h PG after 75 g OGTT (MD -0.69 mmol/l, 95% CI -1.14, -0.23), abnormal glucose tolerance (Relative risk (RR) 0.28, 95% CI 0.12, 0.66), fasting insulin (MD -38.49 pmol/l, 95% CI -52.63, -24.36), and HOMA-IR (MD -1.96 mmol × mUI/l, 95% CI -2.62, -1.30). No differences were observed in BMI, HbA1c and % of patients requiring insulin treatment. Sensitivity analysis did not change treatment estimates. Mention to adverse events was only present in 13 articles with no sign of seriousness. Conclusions: Inositol supplementation decreases blood glucose through an improvement in insulin sensitivity that is independent of weight. Assessment of adverse effects is scarce among published trials and should be fully addressed before considering inositol as a therapeutic agent for glucose-related outcomes. The characterization of the subjects achieving benefit from the intervention and the formulations to be used should also be known.

Effects of inositol on glucose homeostasis: systematic review and meta-analysis of randomized controlled trials

Article

May 2017

Identification of differential metabolic characteristics between tumor and normal tissue from colorectal cancer patients by gas chromatography-mass spectrometry

Article

May 2017
BIOMED CHROMATOGR

Colorectal cancer (CRC) is one of the most common human malignancies and encompasses cancers of the colon and rectum. Although the gold-standard colonoscopy screening method is effective in detecting CRC, this method is invasive and can result in severe complications for patients. The purpose of this study was to determine differences in metabolites between CRC and matched adjacent non-tumor tissues from CRC patients, to identify potential biomarkers that may be informative and developed screening methods. Metabolomic analysis was performed on clinically localized CRC tissue and matched adjacent non-tumor tissue from twenty CRC patients. Unsupervised analysis, supervised analysis, univariate analysis, and pathway analysis were used to identify potential metabolic biomarkers of CRC. The level of twenty-five metabolites in CRC tissues were significantly altered compared to the matched adjacent non-tumor tissues. Four metabolites (lactic acid, alanine, phosphate, and aspartic acid) demonstrated good area under the curve (AUC) of Receiver- Operator Characteristic (ROC) with acceptable sensitivities and specificities, indicating their potential as important biomarkers for CRC. Alterations of amino acid metabolism and enhanced glycolysis may be major factors in the development and progression of colorectal cancer. Lactic acid, alanine, phosphate, and aspartic acid could be effective diagnostic indicators for CRC.

Suplementos nutricionales como modificadores del riesgo cardiovascular en componentes del síndrome metabólico en adultos

Article

Full-text available

Dec 2016

Objetivo: analizar los suplementos nutricionales con ácidos grasos de cadena larga, micronutrientes y antioxidantes en la población adulta, como posibles modificadores del riesgo cardiovascular en pacientes con diagnóstico de síndrome metabólico, o alguno de sus componentes. Métodos: Se realizó una revisión de la literatura en las bases de datos Medline y Embase, utilizando los términos “Metabolic Syndrome” AND “Dietary supplements” y ‘Metabolic Syndrome’/exp AND ‘Dietary supplement’/exp, respectivamente, sobre el papel de los suplementos nutricionales en la modificación del riesgo cardiovascular en adultos con síndrome metabólico o alguno de sus componentes. Resultados: De 475 artículos depurados, se seleccionaron 37 que estudiaran el posible beneficio de los suplementos nutricionales en el síndrome metabólico. Algunos estudios muestran un potencial de ácidos grasos de cadena larga y antioxidantes (vitamina D, vitamina E) para reducir el riesgo cardiovascular de pacientes con síndrome metabólico, evidenciado en la reducción de parámetros como colesterol total, glucemia, índice de masa corporal y perímetro abdominal. Conclusión: El uso de suplementos nutricionales con ácidos grasos de cadena larga y antioxidante podría tener efectos benéficos en la disminución de riesgo cardiovascular en pacientes con diagnóstico de síndrome metabólico o alguno de sus componentes. El uso de suplementos con otros componentes debe estudiarse a mayor profundidad para efectuar recomendaciones.

Italian standards for diabetes mellitus 2007: Executive summary

Article

Full-text available

Jun 2008

Alberto De Micheli

Ovulatory and Metabolic Effects of d- Chiro -Inositol in the Polycystic Ovary Syndrome

Article

Full-text available

May 1999

Women with the polycystic ovary syndrome have insulin resistance and hyperinsulinemia, possibly because of a deficiency of a D-chiro-inositol-containing phosphoglycan that mediates the action of insulin. We hypothesized that the administration of D-chiro-inositol would replenish stores of the mediator and improve insulin sensitivity. We measured steroids in serum and performed oral glucose-tolerance tests before and after the oral administration of 1200 mg of D-chiro-inositol or placebo once daily for six to eight weeks in 44 obese women with the polycystic ovary syndrome. The serum progesterone concentration was measured weekly to monitor for ovulation. In the 22 women given D-chiro-inositol, the mean (+/-SD) area under the plasma insulin curve after the oral administration of glucose decreased from 13,417+/-11,572 to 5158+/-6714 microU per milliliter per minute (81+/-69 to 31+/-40 nmol per liter per minute) (P=0.007; P=0.07 for the comparison of this change with the change in the placebo group); glucose tolerance did not change significantly. The serum free testosterone concentration in these 22 women decreased from 1.1+/-0.8 to 0.5+/-0.5 ng per deciliter (38+/-7 to 17+/-3 pmol per liter) (P=0.006 for the comparison with the change in the placebo group). The women's diastolic and systolic blood pressure decreased by 4 mm Hg (P<0.001 and P=0.05, respectively, for the comparisons with the changes in the placebo group), and their plasma triglyceride concentrations decreased from 184+/-88 to 110+/-61 mg per deciliter (2.1+/-0.2 to 1.2+/-0.1 mmol per liter) (P=0.002 for the comparison with the change in the placebo group). None of these variables changed appreciably in the placebo group. Nineteen of the 22 women who received D-chiro-inositol ovulated, as compared with 6 of the 22 women in the placebo group (P<0.001). D-Chiro-inositol increases the action of insulin in patients with the polycystic ovary syndrome, thereby improving ovulatory function and decreasing serum androgen concentrations, blood pressure, and plasma triglyceride concentrations.

Hu G, Qiao Q, Tuomilehto J, Balkau B, Borch-Johnsen K, Pyorala K, for the DECODE Study Group. Prevalence of the metabolic syndrome and its relation to all-cause and cardiovascular mortality in non diabetic European men and women

Article

Full-text available

Jun 2004
ARCH INTERN MED

Few studies have evaluated the associations between the metabolic syndrome (by any definition) and mortality. This study examined the age- and sex-specific prevalence of the metabolic syndrome and its association with all-cause and cardiovascular mortality in nondiabetic European men and women. The study was based on 11 prospective European cohort studies comprising 6156 men and 5356 women without diabetes and aged from 30 to 89 years, and had a median follow-up of 8.8 years. A modification of the World Health Organization definition of the metabolic syndrome was used. The subjects were considered to have the metabolic syndrome if they had hyperinsulinemia and 2 or more of the following: obesity, hypertension, dyslipidemia, or impaired glucose regulation; however, other definitions were also studied. Hazard ratios for all-cause and cardiovascular mortality were estimated with Cox models in each cohort. Meta-analyses were performed to assess the overall association of the metabolic syndrome with mortality risk. The age-standardized prevalence of the metabolic syndrome was slightly higher in men (15.7%) than in women (14.2%). Of the 1119 deaths recorded during follow-up, 432 were caused by cardiovascular disease. The overall hazard ratios for all-cause and cardiovascular mortality in persons with the metabolic syndrome compared with persons without it were 1.44 (95% confidence interval [CI], 1.17-1.84) and 2.26 (95% CI, 1.61-3.17) in men and 1.38 (95% CI, 1.02-1.87) and 2.78 (95% CI, 1.57-4.94) in women after adjustment for age, blood cholesterol levels, and smoking. The overall prevalence of the metabolic syndrome in nondiabetic adult Europeans is 15%. Nondiabetic persons with the metabolic syndrome have an increased risk of death from all causes as well as cardiovascular disease.

Effect of Rosiglitazone on Endothelial Function and Inflammatory Markers in Patients With the Metabolic Syndrome

Article

Full-text available

Jun 2006
DIABETES CARE

The aim of this study was to assess the effect of rosiglitazone on endothelial function and inflammatory markers in patients with the metabolic syndrome. This was a randomized, double-blind, controlled clinical trial. One hundred subjects (54 men and 46 women) with the metabolic syndrome, as defined by the Adult Treatment Panel III, were followed for 12 months after random assignment to rosiglitazone (4 mg/day) or placebo. Primary end points were flow-mediated dilation and high-sensitivity C-reactive protein (hs-CRP) levels; secondary end points were lipid and glucose parameters, homeostasis model assessment (HOMA) of insulin sensitivity, endothelial function score, and circulating levels of interleukin (IL)-6, IL-18, and adiponectin. Compared with 60 control subjects matched for age and sex, patients with the metabolic syndrome had decreased endothelial function, raised concentrations of inflammatory markers, and reduced insulin sensitivity. After 12 months, subjects with the metabolic syndrome receiving rosiglitazone showed improved flow-mediated vasodilation (4.2%, P < 0.001) and reduced hs-CRP levels (-0.7 mg/dl, P = 0.04), compared with the placebo group. Moreover, HOMA (-0.8, P = 0.01) and serum concentrations of IL-6 (-0.5 pg/ml, P = 0.045) and IL-18 (-31 pg/ml, P = 0.036) were significantly reduced in subjects receiving rosiglitazone, whereas adiponectin levels showed a significant increment (2.3 microg/ml, P = 0.02). High-density lipoprotein-cholesterol levels increased more and triglyceride levels decreased more in the rosiglitazone group compared with the placebo group. At 1 year of follow-up, 30 subjects receiving rosiglitazone still had features of the metabolic syndrome, compared with 45 subjects receiving placebo (P < 0.001). Rosiglitazone might be effective in reducing the prevalence of the metabolic syndrome.

Myo-inositol administration positively affects hyperinsulinemia and hormonal parameters in overweight patients with polycystic ovary syndrome

Article

Full-text available

Apr 2008

To evaluate the effects the administration of myo-inositol (MYO) on hormonal parameters in a group of PCOS patients. Controlled clinical study. PCOS patients in a clinical research environment. 20 overweight PCOS patients were enrolled after informed consent. All patients underwent hormonal evaluations and an oral glucose tollerance test (OGTT) before and after 12 weeks of therapy (Group A (n = 10): myo-inositol 2 gr. plus folic acid 200 mug every day; Group B (n = 10): folic acid 200 mug every day). Ultrasound examinations and Ferriman-Gallwey score were also performed. Plasma LH, FSH, PRL, E2, 17OHP, A, T, glucose, insulin, C peptide concentrations, BMI, HOMA index and glucose-to-insulin ratio. After 12 weeks of MYO administration plasma LH, PRL, T, insulin levels and LH/FSH resulted significantly reduced. Insulin sensitivity, expressed as glucose-to-insulin ratio and HOMA index resulted significantly improved after 12 weeks of treatment. Menstrual cyclicity was restored in all amenorrheic and oligomenorrheic subjects. No changes occurred in the patients treated with folic acid. Myo-inositol administration improves reproductive axis functioning in PCOS patients reducing the hyperinsulinemic state that affects LH secretion.

Italian standards for diabetes mellitus 2007: executive summary: Diabete Italia, AMD Associazione Medici Diabetologi, SID Società Italiana di Diabetologia

Article

Full-text available

Apr 2008
ACTA DIABETOL

Alberto De Micheli

2ND MESSENGERS OF INSULIN ACTION

Conference Paper

Mar 1990
DIABETES CARE

AR SALTIEL

Despite significant advances in past years on the chemistry and biology of insulin and its receptor, the molecular events that couple the insulin-receptor interaction to the regulation of cellular metabolism remain uncertain. Progress in this area has been complicated by the pleiotropic nature of the actions of insulin. These most likely involve a complex network of pathways resulting in the coordination of mechanistically distinct cellular effects. Because the well-recognized mechanisms of signal transduction (i.e., cyclic nucleotides, ion channels) appear not to be central to insulin action, investigators have searched for a novel second-messenger system. A low-molecular-weight substance has been identified that mimics certain actions of insulin on metabolic enzymes. This substance has an inositol glycan structure, and is produced by the insulin-sensitive hydrolysis of a glycosylphosphatidylinositol in the plasma membrane. This hydrolysis reaction, which is catalyzed by a specific phospholipase C, also results in the production of a structurally distinct diacylglycerol that may selectively regulate one or more of the protein kinases C. The glycosyl-phosphatidylinositol precursor for the inositol glycan enzyme modulator is structurally analogous to the recently described glycosyl-phosphatidylinositol membrane protein anchor. Preliminary studies suggest that a subset of proteins anchored in this fashion may be released from cells by a similar insulin-sensitive phospholipase-catalyzed reaction. Future efforts will focus on the precise role of the metabolism of glycosyl phosphatidylinositols in insulin action.

Diabetes, hypertension, and cardiovascular disease: An update - Response

Article

Sep 2001

JR Sowers

Executive Summary of The Third Report of The National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, And Treatment of High Blood Cholesterol In Adults (Adult Treatment Panel III)

Article

May 2001

Evaluation Expert Panel on Detection and Treatment of High Blood Cholesterol in Adults

LR: 20061115; JID: 7501160; 0 (Antilipemic Agents); 0 (Cholesterol, HDL); 0 (Cholesterol, LDL); 57-88-5 (Cholesterol); CIN: JAMA. 2001 Nov 21;286(19):2401; author reply 2401-2. PMID: 11712930; CIN: JAMA. 2001 Nov 21;286(19):2400-1; author reply 2401-2. PMID: 11712929; CIN: JAMA. 2001 Nov 21;286(19):2400; author reply 2401-2. PMID: 11712928; CIN: JAMA. 2001 Nov 21;286(19):2400; author reply 2401-2. PMID: 11712927; CIN: JAMA. 2001 May 16;285(19):2508-9. PMID: 11368705; CIN: JAMA. 2003 Apr 16;289(15):1928; author reply 1929. PMID: 12697793; CIN: JAMA. 2001 Aug 1;286(5):533-5. PMID: 11476650; CIN: JAMA. 2001 Nov 21;286(19):2401-2. PMID: 11712931; ppublish

Effects of myo-inositol supplementation in postmenopausal women with metabolic syndrome: A perspective, randomized, placebo-controlled study

Article

Jan 2011

The aim of this study was to evaluate whether myo-inositol, an insulin-sensitizing substance, may improve some features of metabolic syndrome in postmenopausal women. Eighty postmenopausal women affected by the metabolic syndrome were enrolled prospectively in the study and treated with diet plus supplementation of myo-inositol (2 g BID plus diet: intervention group) or with diet plus placebo (control group) for 6 months. They were evaluated at baseline and after 6 months for insulin resistance (homeostasis model assessment ratio [HOMA] insulin resistance), lipid profile, and blood pressure. Myo-inositol plus diet improved systolic and diastolic blood pressure, HOMA index, cholesterol, and triglyceride serum levels with highly significant differences, compared with the groups treated only with diet and placebo. In the group treated with myo-inositol, a decrease in diastolic blood pressure (-11%), HOMA index (-75%), and serum triglycerides (-20%) and an improvement in high-density lipoprotein cholesterol (22%) were shown. Supplementation with myo-inositol may be considered a reliable option in the treatment of metabolic syndrome in postmenopausal women.

Uncoupling Between Insulin and Release of a d - Chiro -Inositol–Containing Inositolphosphoglycan Mediator of Insulin Action in Obese Women With Polycystic Ovary Syndrome

Article

Feb 2010

Obese women with polycystic ovary syndrome (PCOS) manifest impaired insulin-stimulated release of a d-chiro-inositol-containing inositolphosphoglycan (DCI-IPG) insulin mediator during oral glucose tolerance testing (OGTT), which appears to be restored by the administration of metformin. This suggests that either obesity or PCOS is associated with a defect in the coupling of the stimulation of the insulin receptor by insulin to the release of the DCI-IPG mediator. The objective of this study was to compare the release of bioactive DCI-IPG between normal nonobese women and obese PCOS women during stimulation with two different concentrations of insulin when glucose levels are clamped. We performed a cross-sectional case-control study at the clinical research center of an academic medical center. A two-step euglycemic-hyperinsulinemic clamp was carried out in 8 nonobese normal and 8 obese PCOS women, during which DCI-IPG bioactivity was monitored. At baseline, PCOS women were significantly more obese, hyperinsulinemic, and insulin resistant than the controls. During the clamp studies, DCI-IPG bioactivity increased significantly over the first 45 min of the low-insulin step of the clamp in normal nonobese women (P = 0.046) and then decreased to baseline levels; DCI-IPG increased again after initiation of the high-insulin step (P = 0.029). Despite higher insulin levels during the clamp in PCOS women, DCI-IPG bioactivity remained flat throughout both insulin steps and was thus significantly lower than in controls during the initial periods of both steps. The coupling between insulin action and the release of the DCI-IPG mediator is selectively impaired in obese PCOS women, which may contribute to the insulin resistance in these women.

Effects of 1-year treatment with metformin on metabolic and cardiovascular risk factors in non-diabetic upper-body obese subjects with mild glucose anomalies: A post-hoc analysis of the BIGPRO1 trial

Article

Sep 2009

Metformin has recently been considered as a possible pharmacological complement to lifestyle measures for preventing type 2 diabetes in high-risk subjects. However, little is known of its effects on metabolic and cardiovascular risk factors in non-diabetic subjects. The BIGPRO1 trial was a 1-year multicentre, randomized, double-blind, controlled clinical trial of metformin versus placebo, carried out in the early 1990s, in 457 upper-body obese non-diabetic subjects with no cardiovascular diseases or contraindications to metformin. We compared the changes (1-year minus baseline) in cardiometabolic risk factors between treatment groups in two subsets of trial subjects: those with impaired fasting glucose (IFG) or impaired glucose tolerance (IGT) (n=101); and those who fulfilled the inclusion criteria of the Diabetes Prevention Program (DPP) (n=51). Comparisons were adjusted for age and gender. In the IFG/IGT subset, significant differences in 1-year changes were observed for systolic blood pressure, which decreased markedly more in the metformin group than in the placebo group (P<0.003), and for fasting plasma glucose, and total and LDL cholesterol, which decreased slightly in the metformin group, but increased in the placebo group (P<0.04). Similar results were observed in the subset with DPP criteria. Also, there were no significant differences in 1-year changes for weight, waist-to-hip ratio, 2-h post-load blood glucose, fasting and 2-h post-load insulin, HDL cholesterol, triglycerides and fibrinolytic markers between the two treatment groups. In subjects at high risk of developing diabetes, the use of metformin showed beneficial and no untoward effects on cardiometabolic risk factors.

Pioglitazone treatment in type 2 diabetes mellitus when combined with portion control diet modifies the metabolic syndrome

Article

Apr 2009
DIABETES OBES METAB

Treatment with thiazolidinediones (TZDs) produces weight gain. To test whether a portion control diet could prevent weight gain during treatment with pioglitazone in patients with type 2 diabetes mellitus (T2DM). This 16-week randomized, open-label, parallel arm study compared three groups: (i) pioglitazone plus the American Diabetes Association diet (Pio + ADA); (ii) pioglitazone plus a portion control weight loss diet (Pio + PC); (iii) metformin plus the American Diabetes Association diet (Met + ADA). All participants received the same advice about calorie reduction, lifestyle change and exercise. Fifty-one men and women with T2DM, naive to TZDs, were randomized to a 16-week study. Pioglitazone (Pio) was titrated to a dose of 45 mg/day and metformin (Met) to a dose of 2 g/day. Fasting blood was collected for lipids, insulin and glycosylated haemoglobin A1c (HbA1c) at baseline and 16 weeks. Forty-eight of fifty-one randomized subjects completed the study. Patients treated with Pio + ADA gained 2.15 +/- 1.09 kg (mean +/- SD) compared with a weight loss of 2.59 +/- 1.25 kg (p < 0.05) in the Pio + PC group, and a weight loss of 3.21 +/- 0.7 kg (p < 0.05) in the Met + ADA group. Waist circumference and visceral adipose tissue decreased significantly more in the Pio + PC group than in the Pio + ADA group. High-density lipoprotein cholesterol levels were significantly increased in the Pio + PC group compared with the Met + ADA group. Pioglitazone reduced insulin resistance (homeostasis model assessment of insulin resistance (HOMA-IR)) more than metformin. No significant differences between groups were seen for glucose, insulin, HbA1c or low-density lipoprotein cholesterol levels. Pio + PC, prevented weight gain, reduced waist circumference and visceral fat compared with Pio + ADA diet.

Hyperinsulinemia Does Not Increase the Risk of Fatal Cardiovascular Disease in Elderly Men or Women without Diabetes: The Rancho Bernardo Study, 1984–1991

Article

Dec 1994
AM J EPIDEMIOL

The relation of fasting and 2-hour serum insulin to the risk for fatal cardiovascular disease was examined in men and women without diabetes. Between 1984 and 1987, 80% of all surviving local members of the Rancho Bernardo Study cohort had measures of insulin and glucose levels obtained before and after a 75-g oral glucose tolerance test. Over the next 5 years, there were 24 cardiovascular disease deaths among 538 men and 21 cardiovascular disease deaths among 705 women. Fasting insulin was unrelated to cardiovascular disease death in men or women; 2-hour insulin was significantly lower in men (but not in women) who died from cardiovascular disease. In men, a 1-standard deviation increase in 2-hour insulin was associated with a 36% reduction in cardiovascular disease mortality (p = 0.01). The significant inverse association of 2-hour insulin with cardiovascular disease death persisted in multiply adjusted models (relative hazard = 0.68; 95% confidence interval 0.47-0.96). Patterns were similar when the analysis was repeated, including men with non-insulin-dependent diabetes mellitus or heart disease at baseline. These findings were not explained by antihypertensive drug use or cigarette smoking. Hyperinsulinemia was not a risk factor for cardiovascular disease in these older men or women. The role of insulin as a cardiovascular disease risk factor requires further investigation.

The Homeostasis Model in the San Antonio Heart Study

Article

Aug 1997
DIABETES CARE

Both insulin resistance and decreased insulin secretion have been shown to predict the development of NIDDM. However, methods to assess insulin sensitivity and secretion are complicated and expensive to apply in epidemiological studies. The homeostasis model assessment (HOMA) has been suggested as a method to assess insulin resistance and secretion from the fasting glucose and insulin concentrations. However, this method has not been extensively evaluated, particularly in different ethnic groups. We applied the HOMA model to cross-sectional analyses of the San Antonio Heart Study (n = 2,465). HOMA insulin resistance (IR) was very strongly correlated with fasting insulin (r = 0.98) and HOMA beta-cell function (beta-cell) was moderately correlated with the 30-min increment in insulin concentration over the 30-min increment in glucose concentration (delta I30/delta G30) in an oral glucose tolerance test (OGTT) (r = 0.44). NIDDM was characterized by both high HOMA IR and low HOMA beta-cell function. In Mexican-Americans, HOMA IR in NIDDM subjects was 9.5 compared with 2.7 in normal glucose tolerance (NGT) subjects. In contrast, HOMA beta-cell function showed only small differences in Mexican-Americans (176 NIDDM; 257 NGT). However, the delta I30/delta G30 (pmol/mmol) showed much larger differences (75 NIDDM; 268 NGT). When modeled separately, impaired glucose tolerance (IGT) was characterized by high HOMA IR and high HOMA beta-cell function. However, when analyzed in the same regression model, high HOMA IR and low HOMA beta-cell function characterized subjects with IGT. These results were similar in both ethnic groups. Mexican-Americans had increased insulin resistance (as judged by both HOMA IR and fasting insulin) and insulin secretion (by HOMA beta-cell and delta I30/delta G30) relative to non-Hispanic whites. We conclude that HOMA provides a useful model to assess insulin resistance and beta-cell function in epidemiological studies in which only fasting samples are available and that, further, it is critical to take into account the degree of insulin resistance in assessing insulin secretion by the HOMA model.

Prediction of Coronary Heart Disease Using Risk Factor Categories

Article

Jun 1998

The objective of this study was to examine the association of Joint National Committee (JNC-V) blood pressure and National Cholesterol Education Program (NCEP) cholesterol categories with coronary heart disease (CHD) risk, to incorporate them into coronary prediction algorithms, and to compare the discrimination properties of this approach with other noncategorical prediction functions. This work was designed as a prospective, single-center study in the setting of a community-based cohort. The patients were 2489 men and 2856 women 30 to 74 years old at baseline with 12 years of follow-up. During the 12 years of follow-up, a total of 383 men and 227 women developed CHD, which was significantly associated with categories of blood pressure, total cholesterol, LDL cholesterol, and HDL cholesterol (all P<.001). Sex-specific prediction equations were formulated to predict CHD risk according to age, diabetes, smoking, JNC-V blood pressure categories, and NCEP total cholesterol and LDL cholesterol categories. The accuracy of this categorical approach was found to be comparable to CHD prediction when the continuous variables themselves were used. After adjustment for other factors, approximately 28% of CHD events in men and 29% in women were attributable to blood pressure levels that exceeded high normal (> or =130/85). The corresponding multivariable-adjusted attributable risk percent associated with elevated total cholesterol (> or =200 mg/dL) was 27% in men and 34% in women. Recommended guidelines of blood pressure, total cholesterol, and LDL cholesterol effectively predict CHD risk in a middle-aged white population sample. A simple coronary disease prediction algorithm was developed using categorical variables, which allows physicians to predict multivariate CHD risk in patients without overt CHD.

Diabetes, Hypertension, and Cardiovascular Disease An Update

Article

Apr 2001
Hypertension

Cardiovascular diseases (CVDs) are the major causes of mortality in persons with diabetes, and many factors, including hypertension, contribute to this high prevalence of CVD. Hypertension is approximately twice as frequent in patients with diabetes compared with patients without the disease. Conversely, recent data suggest that hypertensive persons are more predisposed to the development of diabetes than are normotensive persons. Furthermore, up to 75% of CVD in diabetes may be attributable to hypertension, leading to recommendations for more aggressive treatment (ie, reducing blood pressure to <130/85 mm Hg) in persons with coexistent diabetes and hypertension. Other important risk factors for CVD in these patients include the following: obesity, atherosclerosis, dyslipidemia, microalbuminuria, endothelial dysfunction, platelet hyperaggregability, coagulation abnormalities, and "diabetic cardiomyopathy." The cardiomyopathy associated with diabetes is a unique myopathic state that appears to be independent of macrovascular/microvascular disease and contributes significantly to CVD morbidity and mortality in diabetic patients, especially those with coexistent hypertension. This update reviews the current knowledge regarding these risk factors and their treatment, with special emphasis on the cardiometabolic syndrome, hypertension, microalbuminuria, and diabetic cardiomyopathy. This update also examines the role of the renin-angiotensin system in the increased risk for CVD in diabetic patients and the impact of interrupting this system on the development of clinical diabetes as well as CVD.

Risk factors for coronary heart disease: Implications of gender

Article

Mar 2002

It has been recognized over the past years that women form a distinct subpopulation within patients with coronary heart disease. This phenomenon should be acknowledged in the management and in the assessment of coronary heart disease. Over the past years remarkable progress has been made concerning our knowledge of cardiovascular risk factors related to gender. For instance, diabetes, high density lipoproteins and triglycerides levels have been found to have a greater impact on coronary heart disease risk in women compared to men. On the other hand, evidence showing that lipoprotein (a) is a cardiovascular risk factor seems to be stronger in men than in women. For optimal treatment and prevention of coronary heart disease it is necessary to acknowledge that it is not self-evident that women and men show similar responses to risk factors or to treatment. This review article addresses the role of cardiovascular risk factors focusing on the differential impact they might have on men and women.

High-density lipoprotein-cholesterol and risk of stroke and carotid atherosclerosis: A systematic review

Article

Mar 2008

Epidemiological studies have found no relationship between total cholesterol and stroke risk, but little attention has been paid to high-density lipoprotein-cholesterol (HDL-C). We performed a systematic PubMed literature search for epidemiological studies that examined the association between HDL-C level and stroke or carotid intima-media thickness (IMT). We identified 18 studies on the relationship between HDL-C and stroke risk and 37 on HDL-C and carotid IMT. Eight of ten prospective cohort studies (n=238,739) and three of eight case-control studies (n=3604 cases, 8220 controls) supported an association between elevated HDL-C level and decreased risk of stroke. Prospective cohort studies reporting on relative risk per unit increase in HDL-C showed an 11-15% decreased stroke risk per 10-mg/dl increase in HDL-C. Of 37 studies on carotid IMT, 31 reported cross-sectional, one longitudinal, and five both cross-sectional and longitudinal associations between HDL-C level and carotid IMT. Of 36 cross-sectional studies (n=51,288), 20 showed an inverse association between HDL-C level and carotid IMT. Of six longitudinal studies (n=20,065), three showed no association, one showed a weak association in a subgroup of white women and two showed a significant inverse relationship between HDL-C level and carotid IMT. Pooled estimates could not be calculated because of the variation in study designs and analysis. The weight of evidence in the literature supports an inverse association between HDL-C level and stroke or carotid atherosclerosis, but more data are needed to firmly establish this protective effect.

Second Messengers of Insulin Action

Article

Mar 1990
TRENDS ENDOCRIN MET

Alan R. Saltiel

The molecular events involved in coupling the insulin receptor to the regulation of cellular metabolism remain unknown. Recent studies indicate that some of insulin's actions may be mediated by a novel oligosaccharide. This molecule is generated in cells by the insulin-dependent hydrolysis of a novel membrane glycolipid, termed a glycosyl-phosphatidylinositol. This glycolipid is structurally similar to a newly described protein anchor. The evaluation of the hormonal regulation of this new glycolipid may yield information on a new mechanism of signal transduction.

The homeostasis model in the San Antonio Heart study

Sm Haffner
H Miettinem
Mp Stern

Prevalance of the metabolic syndrome and its relation to all-cause and cardiovascular mortality in nondiabetic European men and women

G Hu
Q Qiao
J Tuomilehto

Effect of rosiglitazone on endothelial function and inflammatory markers in patients with the metabolic syndrome

K Esposito
M Ciotola
D Carleo

One-year effects of myo-inositol supplementation in postmenopausal women with metabolic syndrome

Abstract

No full-text available

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