-
1.
The effect of metformin and myoinositol on metabolic outcomes in women with polycystic ovary syndrome: role of body mass and adiponectin in a randomized controlled trial.
Soldat-Stanković, V, Popović-Pejičić, S, Stanković, S, Prtina, A, Malešević, G, Bjekić-Macut, J, Livadas, S, Ognjanović, S, Mastorakos, G, Micić, D, et al
Journal of endocrinological investigation. 2022;(3):583-595
Abstract
PURPOSE To compare the effects of insulin sensitizers metformin (MET) and myo-inositol (MI) on adiponectin levels and metabolic characteristics in women with polycystic ovary syndrome (PCOS) with respect to their body mass index (BMI). METHODS In this open label, parallel randomized clinical trial, 66 women with PCOS (33 normal-weight and 33 overweight/obese) were randomized to either MI (4 g/day) or MET (1500 mg/day) for a period of 6 months. Serum concentration of adiponectin, hormonal and metabolic laboratory outcomes and clinical assessment of BMI, body composition and Ferriman-Gallwey score (FG score) were evaluated before and after treatment. RESULTS After the 6-month intervention, comparison between MET and MI in time to treatment analysis showed no significant differences between the two treatments for all analyzed parameters. Only borderline significantly lower AUC glucose was found in the MET group in comparison to the MI group (p = 0.071). The main effect of treatment was shown for glucose concentration at 120 min OGTT (p = 0.032) and testosterone (p = 0.002). The main effect of time was shown for body mass (p = 0.004), waist circumference (p < 0.001), BMI (p = 0.003), body fat mass (p = 0.001), adiponectin (p = 0.020), fasting glucose (p = 0.001), testosterone (p = 0.015), SHBG (p = 0.013), 17OH progesterone (p = 0.008), LH (p = 0.004) and estradiol (p = 0.014). CONCLUSION Our study showed similar effects of MET and MI on BMI, body composition, hormonal profile, metabolism of glucose and insulin, and adiponectin level. The two insulin sensitizers, MET and MI, were useful in reducing BMI and improving body composition without significant differences between the two treatments in PCOS women. TRIAL REGISTRATION ISRCTN13199265. Trial registration date: 14.04.2021. (ISRCTN Registry), retrospectively registered.
-
2.
Policaptil Gel Retard in adult subjects with the metabolic syndrome: Efficacy, safety, and tolerability compared to metformin.
Guarino, G, Della Corte, T, Strollo, F, Gentile, S, ,
Diabetes & metabolic syndrome. 2021;(3):901-907
Abstract
BACKGROUND Policaptil Gel Retard® (PGR), is a new macromolecule complex based on polysaccharides slowing the rate of carbohydrate and fat absorption. It proved to significantly reduce body weight, acanthosis nigricans expression, HbA1c levels, and glucose metabolism abnormalities in obese, hyper-insulinemic adolescents. No such data are available for adults. AIM: to compare the effects of PGR vs. metformin in adult subjects with the Metabolic Syndrome (MS) and T2DM on a Low Glycemic Index diet. SUBJECTS AND METHODS This spontaneous clinical, longitudinal, single-blind, randomized study based on a per-protocol analysis enrolled 100 outpatients with MS and T2DM consecutively referring to our clinic for three months, and randomly assigned to either the active treatment (Group A:, 6 tablets/day) or the comparator (Group B: Metformin tablets, 1500-2000 mg/day in two divided doses during the two main meals, to minimize side effects) to be taken 30 min before each main meal in equally divided doses. Serum lipid profile, anthropometry, HOMA-IR index, and tolerability parameters were evaluated before and after a 6-month follow-up period. RESULTS all parameters improved at a similar rate in both groups but for the lipid profile, which got even better in Group A. Group A also experienced less prominent gastrointestinal side effects than its counterpart. CONCLUSION For the first time, we showed the non-inferiority of PGR compared to metformin in obese adult subjects with the MS and T2DM as for glycemic control and a clear-cut superiority of PGR in terms of both serum lipid-lowering capacity and tolerability.
-
3.
The Effects of Vitamin D Supplementation on Metabolic and Oxidative Stress Markers in Patients With Type 2 Diabetes: A 6-Month Follow Up Randomized Controlled Study.
Cojic, M, Kocic, R, Klisic, A, Kocic, G
Frontiers in endocrinology. 2021;:610893
Abstract
Vitamin D deficiency could play an important role in the pathogenesis of type 2 diabetes mellitus (T2DM) as it may alter several crucial processes in the development of diabetes and its complications, such as pancreatic insulin secretion, peripheral insulin resistance, persistence of systemic "sterile" inflammation and immune activation. Vitamin D may also have an antioxidant effect through the inhibition of free radicals generation. The reported study was designed with eligible consecutively recruited patients with T2DM on standard metformin therapy (n=130), randomized in 1:1 ratio, considered to have undergone Vitamin D supplementation according to the guidelines proposed by the Endocrine Society, or to have continued with metformin only. The potential benefit was monitored through the influence on glycemia level, glycated haemoglobin (HbA1c), insulin resistance index (calculated as homeostatic model assessment; HOMA-IR), Castelli Risk Index I and Tryglicerides/Thiobarbituric acid-reactive substances (TG/TBARS) Index in a 6-month follow up period. Our study indicates that oral daily doses of vitamin D improve HbA1c levels over the 3-month and 6-month period, followed by a significant decrease in advanced oxidation protein products levels over the 3-month period when higher vitamin D doses are given. The effect of vitamin D on HOMA-IR index, malondialdehyde levels and TG/TBARS index was not statistically significant. Further investigation should consider defining the doses of vitamin D in patients with T2DM which may attenuate the oxidative stress risk, the risk of metabolic syndrome and the risk of related cardiovascular events.
-
4.
Impact of myoinositol with metformin and myoinositol alone in infertile PCOS women undergoing ovulation induction cycles - randomized controlled trial.
Prabhakar, P, Mahey, R, Gupta, M, Khadgawat, R, Kachhawa, G, Sharma, JB, Vanamail, P, Kumari, R, Bhatla, N
Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology. 2021;(4):332-336
Abstract
PURPOSE To evaluate the benefits of myoinositol plus metformin versus myoinositol alone in infertile polycystic ovarian syndrome (PCOS) women undergoing ovulation induction cycles. MATERIALS AND METHODS Total 116 infertile PCOS women were randomized: Group I (n = 57): metformin (1500 mg) plus myoinositol (4 g) per day; Group II (n=59): myoinositol 4 g per day. Subjects were advised to try for spontaneous conception. Those who did not conceive after three months were given three cycles of ovulation induction. Primary outcome was clinical pregnancy rate after 6 months. Secondary outcomes were improvement in metabolic and endocrine parameters, ongoing pregnancy, abortion and multiple pregnancy rate. RESULTS Baseline demographic, metabolic and hormonal parameters were comparable in two groups. After 3 months of therapy, both study groups had comparable improvement in metabolic and hormonal parameters. After 6 months, clinical pregnancy rate was 42.0% in Group I and 45.5% Group II respectively (RR 0.92(95% CI:0.60-1.43) (p > .05). Side-effects (mainly gastrointestinal) were significantly higher in Group I than group II. CONCLUSIONS Myoinositol (4 g) might be used alone as an insulin sensitizer to improve metabolic, hormonal and reproductive outcome in infertile PCOS women. Further studies with large numbers are warranted to confirm the role of myoinostiol as a sole insulin sensitizer.
-
5.
Effect of clomiphene citrate treatment on the Sertoli cells of dysmetabolic obese men with low testosterone levels.
Pelusi, C, Fanelli, F, Baccini, M, Triggiani, V, Bartolomeo, N, Carbone, MD, De Pergola, G, Di Dalmazi, G, Pagotto, U, Pasquali, R, et al
Clinical endocrinology. 2020;(1):38-45
Abstract
BACKGROUND Clomiphene citrate (CC) has been shown to restore the hypothalamic-pituitary-gonadal (HPG) axis by increasing testosterone (T) levels to physiological levels in patients with dysmetabolic conditions such as obesity, metabolic syndrome and type 2 diabetes mellitus (T2DM). However, the data are unclear regarding the effects on Sertoli cell (SC) function. AIM: To study SC function by assessing Inhibin B (IB) and anti-Mullerian hormone (AMH) levels at baseline and after 3 months of CC treatment. MATERIALS AND METHODS This is an ancillary study of a cross-over, randomised, double-blind, placebo-controlled trial performed to evaluate androgen response to CC treatment in dysmetabolic obese subjects with low T levels treated with metformin. We evaluated SC function by assessing IB and AMH levels at baseline and after 3 months of each treatment in ten dysmetabolic obese subjects with low T levels. In all subjects, the influence of the clinical characteristics, metabolic and hormonal baseline parameters on SC and Leydig (LC) function, evaluated respectively with AMH, IB, follicle-stimulating hormone (FSH) and T levels, was tested. RESULTS No significant changes were observed for IB and AMH concentrations after each treatment period. Whereas T and oestradiol (E2) levels were shown to be significantly higher in the CC plus metformin phase (CC/Met) only. No clinical, metabolic or hormonal parameters showed significant effects on serum AMH at baseline or after treatments. However, baseline T, dihydrotestosterone (DHT) and E2 positively affected IB levels during CC/Met therapy (P = .003, P = .038 and P = .049, respectively). Baseline leptin and FSH had a negative (P = 031) and positive (P = .048) respectively role on T levels during CC/Met, as they were statistically significant compared to the placebo period (Plac/Met). CONCLUSION Unlike the LC activity, CC was unable to influence SC function, as shown by the lack of IB and AMH serum modifications, thus suggesting an intrinsic nonreversible defect of SC cells in patients with dysmetabolic conditions.
-
6.
Reduced circulating levels of chemokine CXCL14 in adolescent girls with polycystic ovary syndrome: normalization after insulin sensitization.
García-Beltran, C, Cereijo, R, Quesada-López, T, Malpique, R, López-Bermejo, A, de Zegher, F, Ibáñez, L, Villarroya, F
BMJ open diabetes research & care. 2020;(1)
Abstract
OBJECTIVE CXCL14 (C-X-C motif chemokine ligand-14) is a chemokine released by active brown fat, showing protective effects against insulin resistance in experimental models. Polycystic ovary syndrome (PCOS) in adolescent girls is usually related to hepato-visceral fat excess and insulin resistance, and associates with comorbidities such as type 2 diabetes. Treatment with a low-dose combination of one antiandrogen and antimineralocorticoid drug (spironolactone) and two insulin sensitizers (pioglitazone/metformin) (SPIOMET) is particularly effective in improving these metabolic derangements. Adipose tissue may be involved in the metabolic alterations of PCOS, and it is a likely target of therapeutic action. We investigated the alterations in CXCL14 levels and the effects of drugs composing SPIOMET treatment on CXCL14 in human adipocytes. RESEARCH DESIGN AND METHODS We studied 51 adolescent patients with PCOS and 21 age-matched healthy controls. Thirty-one adolescent patients with PCOS under SPIOMET or oral contraception-based treatment were also studied. For studies in vitro, Simpson Golabi Behmel Syndrome (SGBS) adipose cells were used. Gene expression for CXCL14 and other genes was quantified using quantitative real-time PCR. The levels of CXCL14 and adipokines in serum and cell culture media were determined by ELISA. RESULTS Serum CXCL14 levels are reduced in patients with PCOS. One-year SPIOMET treatment normalized CXCL14 concentrations and improved the metabolic status of patients with PCOS. Pioglitazone induced CXCL14 expression in differentiating human SGBS adipocytes, in parallel with the induction of marker genes of brown adipogenesis. Spironolactone induced CXCL14 expression and release in differentiated human adipocytes. CONCLUSION Insulin sensitization with SPIOMET normalizes the abnormally low levels of CXCL14 in girls with PCOS. This is consistent with the effects of pioglitazone and spironolactone inducing CXCL14 expression and promoting a brown-like phenotype in adipocytes. CXCL14 may be a novel biomarker for PCOS as well as a potential mediator of the beneficial effects of the SPIOMET combination and may hold promise as a therapeutic modulator of the disorder. TRIAL REGISTRATION NUMBERS ISRCTN29234515 and ISCRCTN11062950.
-
7.
Comparing the individual effects of metformin and rosiglitazone and their combination in obese women with polycystic ovary syndrome: a randomized controlled trial.
Li, Y, Tan, J, Wang, Q, Duan, C, Hu, Y, Huang, W
Fertility and sterility. 2020;(1):197-204
Abstract
OBJECTIVE To compare the effects of metformin, rosiglitazone, and their combination in obese polycystic ovary syndrome (PCOS) patients with insulin resistance. DESIGN Prospective randomized controlled trail. SETTING Tertiary teaching hospital. PATIENT(S): Obese Chinese women (body mass index [BMI] ≥25 kg/m2) with insulin resistance who fulfilled the Rotterdam criteria of PCOS. INTERVENTION(S): In group 1, 68 patients administered metformin (1,500 mg/day); in group 2, 67 patients administered rosiglitazone (4 mg/day); in group 3, 69 patients administered metformin (1,000 mg/day) and rosiglitazone (4 mg/day) for 6 months, all with the same diet and regular exercise lifestyle recommendation. MAIN OUTCOME MEASURE(S): Average menstrual interval, anthropometric measurements, androgen-related parameters, and metabolic features of insulin, carbohydrates, and lipids, with intention-to-treat analysis. RESULT(S): The baseline parameters showed no statistically significant differences. After the 6-month treatment, most participants showed an improved menstrual pattern. There were statistically significant decreases in acne scores, weight, BMI, waist circumference, waist-to-hip ratio, and serum testosterone. The metabolic indexes of insulin, carbohydrates, and lipids were improved obviously compared with the baseline in each group. Among the three groups, the patients administered 1,500 mg/day metformin experienced greater reductions in weight. However, the rosiglitazone users (alone or combined with metformin) showed a more notable decline in total cholesterol and triglyceride levels. CONCLUSION(S): Considering the benefits of metformin on weight loss, high-dose metformin (1,500 mg/day) along with lifestyle modification should be recommended for obese, insulin-resistant women with PCOS. Rosiglitazone alone or combined with low-dosage metformin plus lifestyle modification should be considered for the women with abnormal lipid profiles. CLINICAL TRIAL REGISTRATION NUMBER ChiCTR-TRC-13003642 (Chinese Clinical Trial Registry).
-
8.
Effect of Metformin on Microvascular Endothelial Function in Polycystic Ovary Syndrome.
Heidari, B, Lerman, A, Lalia, AZ, Lerman, LO, Chang, AY
Mayo Clinic proceedings. 2019;(12):2455-2466
-
-
Free full text
-
Abstract
OBJECTIVE To investigate the factors that are associated with the effect of metformin on endothelial dysfunction in polycystic ovary syndrome (PCOS). PATIENTS AND METHODS From March 24, 2014, to November 18, 2016, 48 women with PCOS were randomly assigned to 1500 mg/d of metformin (N=29) or no treatment (N=13) for 3 months; 42 patients (29 in the initial treatment group and 13 in the no treatment group) completed the study. Study variables were measured at baseline and after 3 months. Participants who did not receive metformin initially were then treated with metformin for another 3 months, and study variables were measured again. Endothelial function was measured as reactive hyperemia-peripheral arterial tonometry (RH-PAT) from the index finger. RESULTS The age and baseline endothelial function (mean ± SD) of the participants were 32.7±6.9 years and 1.8±0.5, respectively. No notable change was observed in endothelial function after 3 months with metformin compared with no treatment. However, after stratifying participants who received metformin based on baseline endothelial function, there was a significant improvement following metformin treatment in participants with abnormal baseline endothelial function (1.3±0.3 vs 1.7±0.3; P<.001) but not in those with normal baseline endothelial function (2.1±0.4 vs 2.0±0.5; P=.11). CONCLUSION Metformin improves endothelial function in women with PCOS and endothelial dysfunction independent of changes in glucose metabolism, dyslipidemia, or presence of prediabetes. Metformin has a direct effect on endothelial function in PCOS, and measurement of endothelial function can stratify and follow response to metformin treatment in PCOS. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT02086526.
-
9.
Circulating zinc-α2-glycoprotein is reduced in women with polycystic ovary syndrome, but can be increased by exenatide or metformin treatment.
Zheng, S, Liu, E, Zhang, Y, Long, T, Liu, X, Gong, Y, Mai, T, Shen, H, Chen, H, Lin, R, et al
Endocrine journal. 2019;(6):555-562
-
-
Free full text
-
Abstract
The study was to investigate circulating zinc-α2-glycoprotein (ZAG) concentrations in women with PCOS, and changes in ZAG levels after exenatide or metformin treatment. One hundred eighty-two women with polycystic ovary syndrome (PCOS) who met the 2003 Rotterdam diagnostic criteria and 150 controls without PCOS were recruited. We partitioned women with PCOS into groups according to body mass index or blood glucose concentrations, determined serum ZAG, anthropometric parameters, metabolic and endocrine indicators, and inflammatory markers, and statistically analyzed the results. Eighty-two overweight/obese subjects of the recruited women with PCOS were then randomly assigned to groups administered either 12 weeks of exenatide injection (10 μg b.i.d.) or oral metformin (1,000 mg b.i.d.). Circulating ZAG levels were determined after 12 weeks of treatment. The results showed that circulating ZAG was significantly lower in PCOS women than in healthy women (p < 0.01). Overweight/obese women and those with higher blood glucose levels had lower circulating ZAG. After 12 weeks of exenatide or metformin treatment, there were significant increases (p < 0.01) in circulating ZAG in both treatment groups (the exenatide baseline level was 46.54 ± 2.38 ng/mL vs. 56.41 ± 2.02 ng/mL after treatment, p < 0.01; metformin baseline was 47.81 ± 2.14 ng/mL vs. 55.67 ± 2.01 ng/mL after treatment, p < 0.01), however there was no statistical difference between the 2 treatments (p > 0.05). Circulating ZAG is closely related to PCOS and could be an important adipokine involved in the occurrence and development of PCOS. ZAG might possibly be applicable as a new observational indicator in the treatment of PCOS.
-
10.
Effect of metformin combined with lifestyle modification versus lifestyle modification alone on proinflammatory-oxidative status in drug-naïve pre-diabetic and diabetic patients: A randomized controlled study.
Bulatova, N, Kasabri, V, Qotineh, A, Al-Athami, T, Yousef, AM, AbuRuz, S, Momani, M, Zayed, A
Diabetes & metabolic syndrome. 2018;(3):257-267
Abstract
BACKGROUND Targeting biomarkers of oxidative-proinflammatory stress may result in improvement of modifiable metabolic syndrome, pre-diabetes and diabetes risk factors and subsequent risk reduction. METHODS 64 newly diagnosed antihyperglycemic treatment-naïve prediabetic and type 2 diabetes mellitus (T2DM) patients were randomly assigned using block design to either metformin combined with therapeutic lifestyle changes (TLC) or TLC alone. Body mass index (BMI), waist circumference, blood pressure, fasting plasma glucose (FPG), glycated hemoglobin (HbA1c), fasting lipid profile, plasma oxidative status and tumor necrosis factor (TNF)-α were measured at baseline, after 3 months and after 6 months from baseline. RESULTS Except for HbA1c, baseline values did not differ significantly between the two groups. The post 3-months relative reductions in BMI (P=0.014) and HbA1c (P=0.037) in metformin combined with TLC intervention were significantly greater than those in TLC alone group. TNFα plasma levels were decreased significantly vs. baseline by metformin combined with TLC intervention (-22.90±46.76%, P=0.01). Conversely, TLC alone basically worsened proinflammatory status (42.40±40.82 %), P<0.001. Metformin with TLC treatment effected a therapeutic decrement of the oxidative stress (-15.44±35.32%, P=0.029 vs. baseline) unlike TLC alone (61.49±122.66%, P=0.01 vs. baseline). Both interventions' effects were sustained in the 6-month follow up periods. CONCLUSION In both intervention groups, the relative changes in plasma TNFα were significantly correlated (P<0.01) with systolic blood pressure and the relative changes in oxidative stress were markedly correlated (P<0.05) with total cholesterol.