Denosumab improves glucose parameters in patients with impaired glucose tolerance: a systematic review and meta-analysis.

OBJECTIVE: Receptor activator of NF-κß ligand (RANKL) is crucial for the development of hepatic insulin resistance and poor glucose uptake; therefore, inhibiting RANKL with Denosumab could improve fasting plasma glucose (FPG) and insulin (FPI). METHODS: A systematic review was conducted to evaluate the effects of Denosumab on glycemic parameters. PubMed, SCOPUS, EBSCO, and LILACS databases were searched for studies that investigated the effect of Denosumab on FPG, glycated hemoglobin (HbA1c), FPI, and Homeostatic Model Assessment for Insulin Resistance (HOMA1-IR). The pooled standard difference in means (SDM) and 95% confidence intervals (95%CI) were calculated. The results were stratified into (1) Normal Glucose Tolerance (NGT) and (2) Impaired Glucose Tolerance (IGT). RESULTS: Six publications (1203 participants) were included. There was a significant association between Denosumab and FPG (SDM = -0.388, 95%CI: -0.705 to -0.070, p = .017) and with HOMA1-IR (SDM = -0.223, 95%CI: -0.388 to -0.058, p = .008), but not for HbA1c and FPI. When stratified by glucose tolerance, the association between Denosumab and FPG, HbA1c, and HOMA1-IR was present for the IGT group. Lastly, Denosumab had a time-dependent effect on HbA1c (slope = -0.037, 95%CI: -0.059 to -0.015, p < .005). CONCLUSIONS: Denosumab significantly improved glycemic parameters. This outcome was more prominent for subjects with compromised glucose tolerance, positing that Denosumab can be used as a treatment to improve glucose metabolism for persons with pre-diabetes and diabetes.

The association between interleukin-6 promoter polymorphisms and rheumatoid arthritis by ethnicity: A meta-analysis of 33 studies.

OBJECTIVE: We performed a meta-analysis to determine the effect Interleukin-6 (IL-6) promoter polymorphism (-174 G>C, -572 G>C, and -597 G>A) have on the development rheumatoid arthritis (RA) by ethnicity. MATERIAL AND METHODS: PubMed, EBSCO, LILACS, and Scopus databases were searched for studies exploring the association between any IL6 polymorphisms and RA until November 2018. Genotype distributions were extracted and, depending on the level heterogeneity, determined by the ψ2-based Q test and the Inconsistency Index (I2), fixed-effects or random-effects models were used to calculate pooled odds ratios (ORs) with 95% confidence intervals (95%CIs) for the heterozygous, homozygous, dominant, recessive, and allelic genetic models. RESULTS: From 708 identified publications, 33 were used in this analysis. For the -174 polymorphism, Asians (ORheterozygous=7.57, 95%CI: 2.28-25.14, ORhomozygous=5.84, 95%CI: 2.06-16.56, ORdominant=7.21, 95%CI: 2.30-22.63, ORrecessive=5.04, 95%CI: 1.78-14.28, ORallelic=6.60, 95%CI: 2.26-19.28, p<.05) and Middle East countries (ORheterozygous=2.30, 95%CI: 1.10-4.81, ORdominant=2.27, 95%CI: 1.22-4.22, ORallelic=2.29, 95%CI: 1.24-4.23, p<.05) were associated with a significant risk of developing RA. Whereas, for Latinos, the C-allele was associated with a benefit (ORhomozygous=0.26, 95%CI: .08-.82, ORrecessive=.25, 95%CI: .08-.80, p<.05). For the -572 polymorphism, Asians demonstrated a significant association for the homozygous and recessive genetic models (8 studies, ORhomozygous=1.56, 95%CI: 1.16-2.09, ORrecessive=1.63, 95%CI: 1.08-2.45, p<.05). For the -597 polymorphism, no association was observed. CONCLUSIONS: Here, the -174 G>C polymorphism increased the risk of developing RA in Asians and Middle East populations. Interestingly, for Latinos, the polymorphism was associated with a benefit. For the -572 polymorphism, only the Asian population showed an increased risk of developing RA for the CC genotype.

The association between interleukin-6 promoter polymorphisms and rheumatoid arthritis by ethnicity: A meta-analysis of 33 studies / Asociación entre los polimorfismos del promotor de la interleucina-6 y la artritis reumatoide analizado por etnicidad: un metaanálisis de 33 estudios

Objective: We performed a meta-analysis to determine the effect Interleukin-6 (IL-6) promoter polymorphism (−174 G>C, −572 G>C, and −597 G>A) have on the development rheumatoid arthritis (RA) by ethnicity. Material and methods: PubMed, EBSCO, LILACS, and Scopus databases were searched for studies exploring the association between any IL6 polymorphisms and RA until November 2018. Genotype distributions were extracted and, depending on the level heterogeneity, determined by the ψ2-based Q test and the Inconsistency Index (I2), fixed-effects or random-effects models were used to calculate pooled odds ratios (ORs) with 95% confidence intervals (95%CIs) for the heterozygous, homozygous, dominant, recessive, and allelic genetic models. Results: From 708 identified publications, 33 were used in this analysis. For the −174 polymorphism, Asians (ORheterozygous=7.57, 95%CI: 2.28–25.14, ORhomozygous=5.84, 95%CI: 2.06–16.56, ORdominant=7.21, 95%CI: 2.30–22.63, ORrecessive=5.04, 95%CI: 1.78–14.28, ORallelic=6.60, 95%CI: 2.26–19.28, p<.05) and Middle East countries (ORheterozygous=2.30, 95%CI: 1.10–4.81, ORdominant=2.27, 95%CI: 1.22–4.22, ORallelic=2.29, 95%CI: 1.24–4.23, p<.05) were associated with a significant risk of developing RA. Whereas, for Latinos, the C-allele was associated with a benefit (ORhomozygous=0.26, 95%CI: .08–.82, ORrecessive=.25, 95%CI: .08–.80, p<.05). For the −572 polymorphism, Asians demonstrated a significant association for the homozygous and recessive genetic models (8 studies, ORhomozygous=1.56, 95%CI: 1.16–2.09, ORrecessive=1.63, 95%CI: 1.08–2.45, p<.05). For the −597 polymorphism, no association was observed. Conclusions: Here, the −174 G>C polymorphism increased the risk of developing RA in Asians and Middle East populations. Interestingly, for Latinos, the polymorphism was associated with a benefit. For the −572 polymorphism, only the Asian population showed an increased risk of developing RA for the CC genotype.(AU)

Objetivos: Realizamos un meta-análisis para determinar el efecto de los polimorfismos del promotor de interleucina-6 (IL-6) (-174 G>C, -572 G>C, y -597 G>A) sobre el desarrollo de artritis reumatoide (RA) analizado por etnicidad. Materiales y métodos: En las bases de datos PubMed, EBSCO, LILACS y Scopus se buscaron estudios con la asociación entre polimorfismo de IL-6 y RA publicados hasta noviembre 2018. se obtuvieron las distribuciones de genotipo y de acuerdo al nivel de heterogeneidad el efecto fijo o aleatorio fueron utilizados para calcular los Odds Ratio (OR) con intervalos de confianza del 95% para los modelos genéticos heterocigoto, homocigoto, dominante, recesivo y alélico. Resultados: De 708 estudios identificados, 33 fueron utilizados para este análisis. Para el polimorfismo -174, los países Asiáticos (ORheterocigoto=7,57, 95%CI: 2,28–25,14, ORhomocigoto=5,84, 95%CI: 2,06-16,56, ORdominante=7,21, 95%CI: 2,30-22,63, ORrecesivo=5,04, 95%CI: 1,78-14,28, ORalélico=6,60, 95%CI: 2,26-19,28, p<0,05) y del Medio Oriente (ORheterocigoto=2,30, 95%CI: 1,10-4,81, ORdominante=2,27, 95%CI: 1,22-4,22, ORalélico=2,29, 95%CI: 1,24-4,23, p<0,05) están asociados con el riesgo de desarrollar RA significativamente. Mientras que, para los Latinos, el alelo-C está asociado con un beneficio (ORhomocigoto=0,26, 95%CI: 0,08-0,82, ORrecesivo=0,25, 95%CI: 0,08-0,80, p<0,05). Para el polimorfismo -572, los Asiáticos están asociados significativamente con los modelos genéticos homocigoto y recesivo (8 estudios, ORhomocigoto=1,56, 95%CI: 1,16-2,09, ORrecesivo=1,63, 95%CI: 1,08-2,45, p<0,05). Para el polimorfismo -597, no se observó asociación. Conclusiones: El polimorfismo -174 G>C aumenta el riesgo de desarrollar RA en población Asiática y Medio Oriente. Curiosamente, para los Latinos el polimorfismo está asociado con un beneficio. Para el polimorfismo -572, solo la población Asiática demuestra una aumento en el riesgo de desarrollar RA con el genotipo CC.(AU)

Metformin does not improve insulin sensitivity over hypocaloric diets in women with polycystic ovary syndrome: a systematic review of 12 studies.

OBJECTIVE: To improve insulin action, most clinicians prescribe Metformin in patients with insulin resistance (IR). Women with polycystic ovary syndrome (PCOS), in which IR is an important physiopathological mechanism, treatment with Metformin and specialized diets have been suggested to reduce the patient's IR. However, numerous studies have demonstrated conflicting results with respect to supplementing a diet with Metformin. Therefore, we conducted a meta-analysis to determine if Metformin provides a benefit in conjunction with hypocaloric diets to improve insulin sensitivity in PCOS women. METHODS: PubMed, SCOPUS, LILACS, and EBSCO databases and retrieved studies' bibliographies were searched for prospective studies that investigated the effect between Metformin and hypocaloric diets in PCOS women until April 2020. Pre- and post-intervention values for fasting plasma glucose (FPG), fasting plasma insulin (FPI), and IR indices (HOMA1-IR, ISI, and QUICKI) were extracted. Using Comprehensive Meta-Analysis software, the pooled standard difference in the means (SDM) and 95%CIs were calculated. RESULTS: 11 publications (12 studies) were selected. There was not a benefit of adding Metformin to a hypocaloric diet with respect to FPG (SDM= -0.17; 95%CI: -0.48-0.14, p = .28) and FPI (SDM = 0.16; 95%CI: -0.24-0.55, p = .45). None of the IR indices also demonstrated any benefit of using Metformin when a diet intervention was implemented (HOMA1-IR: SDM = 0.28; 95%CI: -0.27-0.84, p = .315; ISI: SDM = 0.344; 95%CI: -0.17-0.85, p = .186; QUICKI: SDM= -0.01; 95%CI: -0.42-0.41, p = .968). CONCLUSION: Here, we determined that adding Metformin to hypocaloric diets did not improve serum glucose or insulin concentrations as well as IR in PCOS women.

Association between Osteoprotegerin and Charcot Neuroarthropathy: a systematic review.

AIMS: Osteoprotegerin (OPG) has been associated with Charcot Neuroarthropathy (CN); however, three studied OPG polymorphisms (1181C > G, 245A > C and 950 T > C) have yielded conflicting results. Therefore, this meta-analysis was conducted to determine the difference in serum OPG concentrations between healthy controls and diabetics with and without CN and the effect OPG polymorphisms have on CN development. METHODS: PubMed, LILAC, SCOPUS, and EBSCO databases and retrieved publications' bibliographies were searched for studies that examined for OPG and CN. Depending on the heterogeneity, fixed or random effects were used to calculate the pooled odds ratio (OR) or standard difference in means (SDM) with 95% confidence intervals (95%CI) for 5 genetic models (heterozygous, homozygous, dominant, recessive, and allelic) and serum concentrations, respectively. RESULTS: Seven publications (12 studies) demonstrated that serum OPG concentrations were more elevated in subjects with CN (SDM = 0.719, 95%CI = 0.555-0.883, p < 0.001). When CN was compared to healthy controls or diabetics, the difference was more prominent for healthy controls (SDM = 1.043, 95%CI = 0.676-1.409, p < 0.001) than diabetics (SDM = 0.639, 95%CI = 0.456-0.821, p < 0.001) and the SDM difference was significant (p = 0.013). Using 6 publications (9 studies), neither the 1181C > G or the 950 T > C polymorphisms showed any significant associations for any genetic model. For the 245A > C polymorphism, only the homozygous genetic model showed a significant association between the polymorphism and CN (OR = 2.850, 95%CI: 1.051-7.729, p = 0.040). CONCLUSIONS: Here, we determined a potential correlation between the CN and serum OPG concentrations and that only the CC genotype of the 245A > C polymorphism showed an increased risk of developing CN.

The Association Between Interleukin-6 Promoter Polymorphisms and Rheumatoid Arthritis by Ethnicity: A Meta-Analysis of 33 Studies.

OBJECTIVE: We performed a meta-analysis to determine the effect Interleukin-6 (IL-6) promoter polymorphism (-174 G>C, -572 G>C, and -597 G>A) have on the development rheumatoid arthritis (RA) by ethnicity. MATERIAL AND METHODS: PubMed, EBSCO, LILACS, and Scopus databases were searched for studies exploring the association between any IL6 polymorphisms and RA until November 2018. Genotype distributions were extracted and, depending on the level heterogeneity, determined by the ψ2-based Q test and the Inconsistency Index (I2), fixed-effects or random-effects models were used to calculate pooled odds ratios (ORs) with 95% confidence intervals (95%CIs) for the heterozygous, homozygous, dominant, recessive, and allelic genetic models. RESULTS: From 708 identified publications, 33 were used in this analysis. For the -174 polymorphism, Asians (ORheterozygous=7.57, 95%CI: 2.28-25.14, ORhomozygous=5.84, 95%CI: 2.06-16.56, ORdominant=7.21, 95%CI: 2.30-22.63, ORrecessive=5.04, 95%CI: 1.78-14.28, ORallelic=6.60, 95%CI: 2.26-19.28, p<.05) and Middle East countries (ORheterozygous=2.30, 95%CI: 1.10-4.81, ORdominant=2.27, 95%CI: 1.22-4.22, ORallelic=2.29, 95%CI: 1.24-4.23, p<.05) were associated with a significant risk of developing RA. Whereas, for Latinos, the C-allele was associated with a benefit (ORhomozygous=0.26, 95%CI: .08-.82, ORrecessive=.25, 95%CI: .08-.80, p<.05). For the -572 polymorphism, Asians demonstrated a significant association for the homozygous and recessive genetic models (8 studies, ORhomozygous=1.56, 95%CI: 1.16-2.09, ORrecessive=1.63, 95%CI: 1.08-2.45, p<.05). For the -597 polymorphism, no association was observed. CONCLUSIONS: Here, the -174 G>C polymorphism increased the risk of developing RA in Asians and Middle East populations. Interestingly, for Latinos, the polymorphism was associated with a benefit. For the -572 polymorphism, only the Asian population showed an increased risk of developing RA for the CC genotype.