Malnutrition and type 2 diabetes mellitus across diverse global populations: a systematic review of observational evidence.

Background: Malnutrition, encompassing undernutrition, overnutrition, and micronutrient deficiency represents a global public health challenge with substantial implications for the development and clinical progression of type 2 diabetes mellitus (T2DM). The bidirectional relationship between nutritional status and glycemic regulation remains incompletely characterized across diverse geographic and socioeconomic settings worldwide, warranting a systematic synthesis of the available observational evidence. Methods: A systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Searches were conducted across PubMed/MEDLINE, EMBASE, and the Cochrane CENTRAL register from inception through December 2024. Twenty primary studies were included from multiple high-, middle-, and low-income countries across Asia, Europe, Africa, the Americas, and the Middle East, encompassing a total of more than 25,000 participants. Methodological quality was assessed using the Critical Appraisal Skills Programme (CASP) checklist; 45% of studies were assessed as high confidence and 55% as moderate confidence, following structured qualitative domain-level appraisal. Results: Malnutrition prevalence, assessed by multiple validated instruments, ranged substantially across study populations and settings. Nutritional risk, defined by Geriatric Nutritional Risk Index criteria, was identified in 30.3% of participants in one Chinese cross-sectional study (n=551). Malnutrition prevalence, assessed using heterogeneous validated instruments across clinically and geographically diverse populations, ranged from 18.5% to 83.8% across included studies; this wide range reflects substantial variation in assessment instrument, patient acuity, clinical setting, and population demographics rather than a uniform epidemiological estimate. Indicators of undernutrition - including hypoalbuminemia, low BMI, and micronutrient deficiency - were associated with impaired glycemic regulation, greater complication burden, and elevated mortality risk. Adjusted odds ratios for diabetic retinopathy associated with malnutrition ranged from 1.67 (95% CI: 1.04-2.70) to 2.24 (95% CI: 1.07-4.69) depending on nutritional index used. Severe malnutrition was associated with 8.91-fold higher adjusted mortality odds (95% CI: 1.04-76.18) compared with moderate malnutrition among hospitalized T2DM patients. Conversely, indicators of overnutrition including elevated BMI and increasing waist circumference - were consistently associated with incident T2DM and adverse cardiometabolic profiles across multiple prospective and cross-sectional studies. Early-life famine exposure was associated with elevated adjusted odds of hyperglycemia in adulthood (aOR range: 1.34-1.57), emphasizing the relevance of developmental nutritional programming to adult T2DM risk. A dual burden of malnutrition concurrent undernutrition and overnutrition within the same populations and study samples - was observed across multiple geographic settings, consistent with patterns documented during nutritional transition. Conclusion: This systematic review identifies broadly consistent observational associations, with variability in association strength and direction by outcome domain and clinical context between malnutrition in both its under- and overnutrition forms and adverse clinical outcomes in T2DM across diverse global populations. These findings should be interpreted as associative rather than causal, given the predominance of observational cross-sectional and case-control designs, substantial heterogeneity in malnutrition definitions and outcome measures, and inherent risks of reverse causality and residual confounding. Future research should prioritize longitudinal and mechanistic study designs to clarify temporal pathways, and contextually appropriate nutritional screening should be integrated into T2DM prevention and management frameworks globally. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier, CRD42024559848.