Triangulating evidence for the causal impact of single-intervention zinc supplement on glycaemic control for type 2 diabetes: systematic review and meta-analysis of randomised controlled trial and two-sample Mendelian randomisation

Abstract

Although previous studies suggested the protective effect of zinc for type-2 diabetes (T2D), the unitary causal effect remains inconclusive. We investigated the causal effect of zinc as a single intervention on glycemic control for T2D, using a systematic review of RCTs and two-sample Mendelian randomization (MR). Four primary outcomes were identified: fasting blood glucose/fasting glucose, HbA1c, HOMA-IR, and serum insulin/fasting insulin level. In the systematic review, four databases were searched from the establishment to June 2021. Studies, in which participants had T2D and intervention did not comprise another co-supplement, were included. Results were synthesized through the random-effects meta-analysis. In the two-sample MR, we used random allocation of single nucleotide polymorphisms (SNPs), strongly related to zinc supplements, to infer the relationship causally, but not specified T2D. SNPs were from MR-base. In the systematic review and meta-analysis, 14 trials were included with a total of 897 participants. The zinc supplement led to a significant reduction in the post-trial mean of fasting blood glucose (mean difference (MD): -26.52 mg/dL, 95%CI: -35.13, -17.91), HbA1c (MD: -0.52%, 95%CI: -0.90, -0.13), and HOMA-IR (MD: -1.65, 95%CI: -2.62, -0.68), compared to the control group. In the two-sample MR, zinc supplement with 2 SNPs reduced the fasting glucose (inverse-variance weighted coefficient: -2.04 mmol/L, 95%CI: -3.26, -0.83). From systematic review and two-sample MR analyses, zinc supplementation alone may causally improve glycemic control among T2D patients. The findings are limited by power from the small number of studies and SNPs included in the systematic review and two-sample MR analysis respectively.

Can Nutrition Contribute to a Reduction in Sarcopenia, Frailty, and Comorbidities in a Super-Aged Society?

“…Appropriate management procedure for malnutrition in diabetes mellitus patients has not still been established. Zn [130,131], vitamin E [132], folate [133], and L-arginine [134,135] supplementation and fiber-rich diets [136] have been suggested to potentially improve blood glucose control and insulin resistance. The reason why L-arginine improved glycemic control and insulin resistance is not clear in detail.…”

“…Zinc (Zn) [130,131], vitamin E [132], folate [133], and L-arginine [134,135] supplementation and fiber-rich diets [136] may improve glycemic control and insulin resistance (IR) in type 2 diabetes mellitus patients. The Mediterranean diet may improve glycemic control [137] and reduce cardiovascular diseases risk [137,138].…”

Can Nutrition Contribute to a Reduction in Sarcopenia, Frailty, and Comorbidities in a Super-Aged Society?

“…Appropriate management procedure for malnutrition in diabetes mellitus patients has not still been established. Zn [131,132], vitamin E [133], folate [134], and L-arginine [135,136] supplementation and fiber-rich diets [137] have been suggested to potentially improve blood glucose control and insulin resistance. The reason why l-arginine improved glycemic control and insulin resistance is not clear in detail.…”

“…Zinc (Zn) [131,132], vitamin E [133], folate [134], and L-arginine [135,136] supplementation and fiber-rich diets [137] may improve glycemic control and insulin resistance (IR) in type 2 diabetes mellitus patients. The Mediterranean diet may improve glycemic control [138] and reduce cardiovascular diseases risk [138,139].…”

Comparison of caffeine consumption behavior with plasma caffeine levels as exposures in drug-target Mendelian randomization and implications for interpreting effects on obesity

“…Studies like the UK Biobank (UKB) have measured participants' self-reported exposure to many pharmacological compounds (6), such as prescribed and/or over-the-counter medication use, or vitamin supplementation use. These data enable an alternative drug-target MR approach, in which genome-wide significant variants associated with the target respective behavioral proxy are used instead of cis-variants (7). Since these phenotypes are generally cheaper to measure than biomarker or protein expression data, they may allow for larger sample sizes and potentially more powerful analyses (8).…”