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.

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.

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.

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.