Prediabetes in Transition: Insights from the Tehran Lipid and Glucose Study

Abstract

Context: Prediabetes (Pre-DM) is an intermediate state between normoglycemia and type 2 diabetes (T2D), encompassing heterogeneous phenotypes, including isolated impaired fasting glucose (iIFG), isolated impaired glucose tolerance (iIGT), and combined iIFG-impaired glucose tolerance (IFG-IGT). This review aimed to synthesize evidence from the Tehran Lipid and Glucose Study (TLGS) on modifiable and non-modifiable determinants of Pre-DM transition. Evidence Acquisition: Relevant TLGS publications were identified through PubMed and Scopus up to September 2025 using keywords including “prediabetes,” “impaired fasting glucose,” “impaired glucose tolerance,” “diabetes,” “regression,” “progression,” “determinants,” and “Tehran Lipid and Glucose Study.” Eligible studies included prospective analyses of Pre-DM regression and progression. Results: Evidence from the Tehran Lipid and Glucose Study indicates that both non-modifiable and modifiable factors influence the Pre-DM transition. Regression to normoglycemia (NGR) was associated with younger age, lower fasting glucose, higher physical activity, and adherence to healthy diets, whereas progression to T2D was associated with obesity, central adiposity, the combined IFG-IGT phenotype, and unhealthy dietary patterns. Specifically, high adherence to the Alternate Healthy Eating Index (AHEI), higher intakes of low-fat dairy, certain minerals, and coffee facilitate regression to NGR, while Western-style diets increase the risk of progression to T2D. Across the phenotypes, regression to NGR was most likely in individuals with IGT, particularly those with ≥ 5% weight loss and adherence to healthy dietary patterns. Combined IFG-IGT benefited from high adherence to the AHEI. The iIFG phenotype appears particularly susceptible to excessive exposure to nitrate/nitrite, zinc, and diets high in cholesterol, saturated, and trans fats, which may attenuate reversion to NGR and facilitate progression to T2D. Conclusions: Findings from the TLGS cohort show that healthy lifestyle factors favor regression to NGR, whereas obesity and poor dietary habits accelerate progression to T2D.