Type 2 diabetes (T2D) is a metabolic disease characterized by insulin resistance, poor insulin secretion, and chronic hyperglycaemia.1 Up to 2021, there were 537 million people diagnosed with T2D and 6.7 million deaths in the same year worldwide, indicating a high prevalence and mortality.2

The increase in mortality and poor quality of life in T2D is mainly due to the development of chronic organic complications traditionally classified into macrovascular complications such as cardiomyopathy and microvascular complications that include neuropathy, kidney disease, non-alcoholic fatty liver disease (NAFLD), osteoporosis and oral cavity diseases, developed as a consequence of low-grade chronic inflammation, glucotoxicity, dyslipidaemia, oxidative stress, and the accumulation of advanced glycation end products (AGEs) caused by hyperglycemia.3., 4., 5., 6., 7.

T2D patients frequently develop more than one complication, each of which can induce or aggravate other complications.5., 6., 8., 9. However, studying the relationships and mechanisms between the different complications in T2D is complicated and invasive in clinical research, making it difficult to fully understand their pathophysiology and the development of therapeutic strategies that can improve the whole systemic health of patients with T2D.

Experiments in mice are often an accessible strategy for studying the pathophysiology of T2D, because the results obtained have been faithfully transferred to human patients by genetic homology.10 T2D mice models have been widely used to study the pathophysiology or therapeutic strategies focused on cardiovascular,11 neuronal,12 renal,13 hepatic,14 bone,7 and salivary gland15 complications in diabetes. However, there are few models that have been validated to develop multiple complications in the same individual, as seen in humans.16 The interactions between T2D and its complications are relevant and necessary to comprehensively understand the pathophysiology of T2D considering multi-organ damage.

We focus on investigating whether the T2D induction strategy based on a high-calorie diet and low doses of streptozotocin induces multi-organ damage and the development of macro- and microvascular complications in the same individual, and if the different complications are related to each other.