Background: This meta-analysis aimed to pool all the available data to provide a well-powered assessment of the role of maternal Vitamin D levels in developing gestational diabetes mellitus (GDM) because already published studies evaluating this association are small in sample size and yielded conflicting findings. Material and Methods: A systematic review and meta-analysis of observational studies was performed. We searched electronic databases (PubMed and Cochrane Central) from inception to April 2021 for published and unpublished observational studies that determined the association between the reduction of Vitamin D levels and the risk of developing GDM in pregnant women. Results from studies were pooled as mean ± standard deviation (SD) and odds ratios (OR) using the random-effects model. Results: Forty-four studies, consisting of 37,838 pregnant women were included in this meta-analysis. Dichotomous studies showed a significant association between maternal Vitamin D deficiency and increased risk of GDM (OR = 1.38; 95% confidence interval [CI] = 1.21-1.57; P < 0.00001). Studies with continuous data also showed a significant association between maternal Vitamin D deficiency and the risk of developing GDM (weighted mean difference (WMD): –5.14 nmol/L, 95% CI = –6.28 to -4.00; P < 0.00001). Moderate heterogeneity was also detected. Conclusion: In conclusion, all studies demonstrated that lower levels of maternal serum Vitamin D were associated with a higher risk of developing GDM in pregnancy.

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Dear Editor, Metformin is a hypoglycemic drug of the class biguanides used as the first-line treatment for type 2 diabetes mellitus (T2DM). The drug acts by inhibiting hepatic gluconeogenesis, decreasing intestinal absorption of glucose and circulating insulin. It has also been suggested that the drug indirectly increases insulin sensitivity by increasing peripheral glucose utilization. Data from the World Health Organization (WHO) shows that breast cancer (BC) is the most prevalent cancer in women, with an incidence of 1.7 million cases in 2012 (25 % of all female cancers). It is the fifth leading cause of death from cancer overall.1 A clinical trial conducted in 2019 elaborated that metformin altered host metabolism proving to be a substitute for a fasting-like mechanism that affects cancer cells' metabolism and growth environment of cancer cells including an increase in beta-OH-butyric acid (BHBA).2 It was further corroborated by a research that found an inverse relationship between metformin and BC. This is accomplished by boosting the activity of AMP-dependent protein kinase, which suppresses the mTOR-associated oncogenic signalling pathway. This induces S phase arrest and apoptosis in triple-negative breast cancer cells. Data from 18,527 participants brought about 2,680 participants who used metformin at least three months before the diagnosis of BC. A multivariate study showed that this was negatively associated with BC risk (0.821, 0.726-0.912, p=0.002).3 A favourable response on disease-free survival and overall survival in BC patients with T2DM. The number of CD8+ tumour-infiltrating lymphocytes (TILS) has been increased with the use of metformin engendering anti-carcinogenic effects.4 In the last 15 years, we have seen a drastic change in the demographics of BC, with an estimated increase of 70.7 to 130.6% in 2020 and 2025 relative to 2015 in the 30-34 age group in Pakistan.5 There has been a significant increase in T2DM along with increased use of metformin for its treatment which thus raises a question about the efficacy of the drug in a neoadjuvant setting for BC on Pakistani society. Further research, especially clinical trials, needs to be conducted in Pakistan including but not limited to a correlation of metformin use and incidence of BC.