1.
Adverse pregnancy outcomes in women with diabetes-related microvascular disease and risks of disease progression in pregnancy: A systematic review and meta-analysis.
Relph, S, Patel, T, Delaney, L, Sobhy, S, Thangaratinam, S
PLoS medicine. 2021;(11):e1003856
Abstract
BACKGROUND The rise in the global prevalence of diabetes, particularly among younger people, has led to an increase in the number of pregnant women with preexisting diabetes, many of whom have diabetes-related microvascular complications. We aimed to estimate the magnitude of the risks of adverse pregnancy outcomes or disease progression in this population. METHODS AND FINDINGS We undertook a systematic review and meta-analysis on maternal and perinatal complications in women with type 1 or 2 diabetic microvascular disease and the risk factors for worsening of microvascular disease in pregnancy using a prospective protocol (PROSPERO CRD42017076647). We searched major databases (January 1990 to July 2021) for relevant cohort studies. Study quality was assessed using the Newcastle-Ottawa Scale. We summarized the findings as odds ratios (ORs) with 95% confidence intervals (CIs) using random effects meta-analysis. We included 56 cohort studies involving 12,819 pregnant women with diabetes; including 40 from Europe and 9 from North America. Pregnant women with diabetic nephropathy were at greater risk of preeclampsia (OR 10.76, CI 6.43 to 17.99, p < 0.001), early (<34 weeks) (OR 6.90, 95% CI 3.38 to 14.06, p < 0.001) and any preterm birth (OR 4.48, CI 3.40 to 5.92, p < 0.001), and cesarean section (OR 3.04, CI 1.24 to 7.47, p = 0.015); their babies were at higher risk of perinatal death (OR 2.26, CI 1.07 to 4.75, p = 0.032), congenital abnormality (OR 2.71, CI 1.58 to 4.66, p < 0.001), small for gestational age (OR 16.89, CI 7.07 to 40.37, p < 0.001), and admission to neonatal unit (OR 2.59, CI 1.72 to 3.90, p < 0.001) compared to those without nephropathy. Diabetic retinopathy was associated with any preterm birth (OR 1.67, CI 1.27 to 2.20, p < 0.001) and preeclampsia (OR 2.20, CI 1.57 to 3.10, p < 0.001) but not other complications. The risks of onset or worsening of retinopathy were increased in women who were nulliparous (OR 1.75, 95% CI 1.28 to 2.40, p < 0.001), smokers (OR 2.31, 95% CI 1.25 to 4.27, p = 0.008), with existing proliferative disease (OR 2.12, 95% CI 1.11 to 4.04, p = 0.022), and longer duration of diabetes (weighted mean difference: 4.51 years, 95% CI 2.26 to 6.76, p < 0.001) compared to those without the risk factors. The main limitations of this analysis are the heterogeneity of definition of retinopathy and nephropathy and the inclusion of women both with type 1 and type 2 diabetes. CONCLUSIONS In pregnant women with diabetes, presence of nephropathy and/or retinopathy appear to further increase the risks of maternal complications.
2.
Sodium-glucose cotransporter 2 (SGLT-2) inhibitors and microvascular outcomes in patients with type 2 diabetes: systematic review and meta-analysis.
Dorsey-Treviño, EG, González-González, JG, Alvarez-Villalobos, N, González-Nava, V, Contreras-Garza, BM, Díaz González-Colmenero, A, Rodríguez-Tamez, G, Barrera-Flores, FJ, Farrell, AM, Montori, VM, et al
Journal of endocrinological investigation. 2020;(3):289-304
Abstract
PURPOSE The effect of the sodium-glucose 2 (SGLT-2) inhibitors on microvascular complications remains uncertain. We performed a systematic review to determine the efficacy of the SGLT-2 inhibitors on microvascular outcomes in patients with type 2 diabetes. METHODS A comprehensive search was performed using Ovid, MEDLINE, EMBASE, Web of Science, and Scopus from inception to May 2019. Randomized trials comparing SGLT-2 inhibitors with placebo or other medication for type 2 diabetes for ≥ 4 weeks were included. Diabetes-related microvascular complications such as nephropathy, retinopathy, neuropathy, and peripheral vascular disease were evaluated. A random-effect model using mean differences for continuous outcomes and risk ratio for dichotomous outcomes was used to synthesize data. PROSPERO (CRD 42017076460). RESULTS A total of 40 RCTs with overall moderate quality of evidence were included. SGLT-2 inhibitors reduced the risk of renal-replacement therapy (0.65; 95% CI 0.54-0.79), renal death (0.57; 95% CI 0.49-0.65), and progression of albuminuria (0.69; 95% CI 0.66-0.73). Conversely, they appeared ineffective in maintaining eGFR (0.33; 95% CI - 0.74 to 1.41) or reducing serum creatinine (- 0.07; 95% CI - 0.26 to 0.11), whereas urine albumin-creatinine ratio (- 23.4; 95% CI - 44.6 to - 2.2) was reduced. Risk of amputation was non-significant (1.30; 95% CI 0.93-1.83). No available data were found regarding neuropathy and retinopathy to perform a quantitative analysis. CONCLUSION SGLT-2 inhibitors may reduce the risk of renal patient-important outcomes but fail to improve surrogate outcomes. Apparently, no increased risk of amputations was observed with these medications. No data were available regarding other microvascular complications.
3.
The Impact of Vitamin D Receptor Gene Polymorphisms on the Susceptibility of Diabetic Vascular Complications: A Meta-Analysis.
Song, N, Yang, S, Wang, YY, Tang, SQ, Zhu, YQ, Dai, Q, Zhang, H
Genetic testing and molecular biomarkers. 2019;(8):533-556
Abstract
Background: To determine whether vitamin D receptor (VDR) gene polymorphisms are correlated with susceptibility to diabetic vascular complications. Methods: We included all eligible studies, and used Stata12.0 to calculate the pooled results. Results: Eight thousand eleven diabetic patients and 1635 normal controls from 27 studies were included. Our results showed that there was no correlation between VDR gene TaqI variants and diabetic nephropathy (DN) or diabetic retinopathy (DR) susceptibility. In comparison with diabetic patients without DN, there was a link between the VDR gene ApaI variant and DN susceptibility under allelic model (p = 0.029) in all populations. In addition, the VDR gene BsmI variant correlated with DN under both dominant (p = 0.005) and allelic (p = 0.003) models in Asian populations. The VDR gene FokI variant was also correlated with DN susceptibility under the recessive model (p = 0.027) in the Asian subgroup. In comparison with diabetic patients without DR, we identified a link between the VDR gene ApaI variant and DR susceptibility under the dominant model (p = 0.034) in all populations. Also, the VDR gene FokI variant was correlated with DR under the recessive (p = 0.016), the allelic (p = 0.001), and the dominant (p < 0.001) models in all populations. When compared with healthy controls, the VDR gene BsmI variant was associated with DR under the additive (p = 0.014), the allelic (p = 0.033), and the dominant (p < 0.001) models in Indian populations. Conclusions: The VDR gene BsmI, ApaI, and FokI gene variants are associated with DN and DR susceptibility. No association was found between the VDR gene TaqI gene variants and diabetic vascular complications.