Dual Dietary Assault: Unraveling the Synergistic Impact of High‐Fat and High‐Sucrose Intake on Type 2 Diabetes Pathogenesis

Type 2 diabetes mellitus (T2DM) is a complex metabolic disorder with a major global impact, strongly influenced by dietary patterns. High-fat diet (HFD) and excessive sucrose intake individually contribute to metabolic disturbances; however, their combined effects in obesity-related T2DM remain less explored. This narrative review aims to elucidate how HFD and sucrose interact independently and synergistically to exacerbate T2DM progression. The underlying mechanisms will be discussed within the context of insulin resistance, β-cell dysfunction, systemic low-grade chronic inflammation, oxidative stress, dyslipidemia, adipose tissue dysfunction, gut microbiota dysbiosis, epigenetic modifications, and mitochondrial dysfunction. Evidence indicates that the co-consumption of HFD and sucrose results in more severe metabolic impairments such as increased adiposity, disrupted lipid and glucose homeostasis, heightened inflammation, and worsened glucose intolerance compared to either factor alone, thereby accelerating T2DM onset. The review will also propose preventive and therapeutic strategies emphasizing whole-food dietary patterns, reduced intake of processed and added sugars, and incorporation of physical activity. These approaches aim to mitigate inflammation, restore mitochondrial function, and rebalance gut microbiota. Ultimately, this review seeks to highlight the synergistic dietary effects contributing to T2DM pathology and promote comprehensive lifestyle interventions for its prevention and management.