Burden of micronutrient deficiency among patients with type 2 diabetes: systematic review and meta-analysis

Type 2 diabetes mellitus (T2D) is a global health concern with increasing incidence and prevalence. It's a multifactorial metabolic disorder characterized by elevated blood glucose levels due to insulin resistance, impaired insulin secretion, and reduced pancreatic beta-cell mass. Genetic predisposition and environmental factors, including lifestyle, diet, and obesity, contribute significantly to its onset. Micronutrients play a vital role in glucose metabolism and insulin signaling pathways. Deficiencies in essential micronutrients can disrupt these pathways, potentially leading to the development and progression of T2D. Studies have shown the physiological implications of micronutrient deficiencies and their direct link to increased morbidity and mortality in diabetes. Approximately one-third of the global population suffers from at least one micronutrient deficiency, which may impair insulin action through oxidative stress or reduced activity of insulin-associated enzymes. The inconsistencies in the prevalence of micronutrient deficiencies reported across various studies, however, pose a challenge for healthcare professionals and policymakers in establishing nutritional recommendations for diabetes management. This systematic review and meta-analysis aimed to address these inconsistencies by comprehensively evaluating the burden of micronutrient deficiencies among T2D patients, providing crucial data for evidence-based policy and practice.

Previous research on the role of micronutrient deficiencies in T2D has been limited and yielded inconsistent results. While some studies focused on individual micronutrient deficiencies, their prevalence varied widely. For instance, some reported a high prevalence of vitamin D deficiency among T2D patients (as high as 80.4%), while others showed much lower prevalence (32.7%). This lack of consensus highlighted the need for a comprehensive systematic review and meta-analysis to synthesize available evidence and provide a more accurate estimate of the overall burden of micronutrient deficiencies in this population.

This systematic review and meta-analysis followed the PRISMA 2020 guidelines and the Cochrane Handbook. A comprehensive literature search was conducted across Embase, ProQuest, PubMed, Scopus, Cochrane Library, Google Scholar, LILACS, and grey literature. The search included keywords related to micronutrient deficiencies, T2D, and prevalence, using Boolean operators. The search strategy was peer-reviewed using the PRESS Evidence Based Checklist. The review included observational studies (cross-sectional and cohort studies) assessing the prevalence of micronutrient deficiencies (minerals/electrolytes and vitamins) in T2D patients published between 1998 and 2023, irrespective of country, language, or economy. Studies were excluded if they focused on type 1 diabetes, gestational diabetes, patients under 18 years, or those with micronutrient supplementation. A pre-piloted data extraction sheet was used to collect data on study characteristics, micronutrients, diagnostic criteria, and cut-off values for deficiency. Two independent reviewers screened titles, abstracts, and full texts, resolving any disagreements through discussion with a third reviewer. The Joanna Briggs Institute Critical Appraisal Checklist was used to assess the methodological quality of the included studies. Statistical analysis was performed using R V.4.3.2 with packages like tidyverse, meta, and metafor. Pooled prevalence was estimated using a random-effects model, with variance stabilization achieved through logit, double arcsine, and generalized linear model transformations. Heterogeneity was assessed using I² and τ², and publication bias was evaluated using Egger's regression test and funnel plots. Subgroup analyses were conducted based on sex, presence of diabetic complications, study setting (hospital-based vs. community-based), WHO region, metformin use, and publication year. Meta-regression explored trends in prevalence over time. Sensitivity analyses assessed the robustness of the pooled prevalence estimates by removing studies with high weight and outliers.

The analysis included 132 studies with 52,501 participants. The pooled prevalence of multiple micronutrient deficiency was 45.30% (95% CI 40.35% to 50.30%). Women had a higher prevalence (48.62%, 95% CI 42.55% to 54.70%) than men (42.53%, 95% CI 36.34% to 48.72%). Vitamin D deficiency was the most common (60.45%, 95% CI 55% to 65%), followed by magnesium (41.95%, 95% CI 27% to 56%). Vitamin B12 deficiency was higher among metformin users (28.72%, 95% CI 21.08% to 36.37%). Prevalence varied significantly across WHO regions, with the highest prevalence observed in the Americas (54.04%, 95% CI 35.03% to 72.48%). Hospital-based studies showed a higher prevalence (46%) than community-based studies (22%). Significant heterogeneity was observed across studies (I²=99%; p=0). Sensitivity analyses showed no substantial changes in pooled prevalence after removing studies with weights >10% or outliers. Egger's test indicated potential publication bias. Meta-regression showed no significant trend in prevalence over time for overall micronutrient deficiency or individual micronutrients, except for a slight non-significant increasing trend for vitamin D and a decreasing trend for magnesium. The certainty of evidence for overall micronutrient deficiency was moderate due to potential publication bias.

This systematic review and meta-analysis provide strong evidence for a substantial burden of micronutrient deficiencies among T2D patients globally. The high prevalence of vitamin D deficiency, in particular, highlights the importance of addressing this nutritional deficiency in diabetes management. The observed sex difference, with higher prevalence in women, warrants further investigation into potential underlying factors. The geographical variations in prevalence reflect the influence of dietary habits, lifestyle, and cultural practices. The study's limitations include the predominantly hospital-based nature of the included studies, leading to potential selection bias and limiting the generalizability of the findings to the general population. The lack of population-based studies prevented direct comparison of micronutrient deficiency prevalence between T2D patients and the general population. Future research should focus on conducting large-scale population-based studies to establish the true prevalence and determine causality between micronutrient deficiency and T2D, potentially through case-control and cohort studies. Randomized controlled trials are necessary to evaluate the effectiveness of micronutrient supplementation in improving glycemic control and reducing complications in T2D.

This systematic review and meta-analysis reveal a high prevalence of micronutrient deficiencies, especially vitamin D deficiency, among T2D patients. Women experienced a higher prevalence than men, and prevalence varied across geographical locations. The predominantly hospital-based nature of the included studies limits the generalizability of the findings. Future research should focus on large-scale, population-based studies to better understand the relationship between micronutrient deficiencies and T2D, and to guide evidence-based interventions aimed at improving the management of this prevalent chronic condition.

The primary limitation of this study is the preponderance of hospital-based, cross-sectional studies, which introduces selection bias and restricts the generalizability of findings to the broader population. The absence of community-based studies prevents a direct comparison of micronutrient deficiency prevalence between T2D patients and the general population. Although a comprehensive search strategy was employed, the possibility remains that some relevant studies were overlooked, potentially impacting the overall results. Furthermore, the heterogeneity observed across studies underscores the influence of various contextual factors, including geographic location, socio-economic factors and other lifestyle related factors.