Pancreatic cancer (PC) records dismal survival rates, making early detection the cornerstone for improved outcomes. Diabetes is a known risk factor for pancreatic cancer and over 40% of PC patients report being diagnosed with diabetes 3-5 years prior to their cancer diagnosis. Thus, pancreatic cancer-related diabetes (PCRD), presenting a window of opportunity for early detection. However, the exact mechanisms and factors that mediate PCRD are not known. Pancreatic stellate cells (PSCs) play a key role in cancer progression and PSCs are present around earliest cancer lesions termed pancreatic intraepithelial neoplasm (PanINs) and around islets. Further, PSCs are activated by hyperglycaemia causing further cancer progression. We postulate that interaction between PSCs and PanINs/cancer cells lead to the secretion of factors carried by exosomes, to cause islet dysfunction and impaired signalling in peripheral cells, ultimately resulting in PCRD. This study aimed to investigate the role of exosomes in the development of PCRD and to examine the relationship between hyperglycaemia, insulin resistance and pancreatic cancer progression using a transgenic mouse model of pancreatic cancer bearing Kras mutations and fed a high fructose diet. Additionally, we assessed the effects of exosomes derived from pancreatic cancer and PSC co-cultures on insulin secretion by mouse beta cells and insulin signalling using mouse hepatocytes. Next, we explored the exosome cargo using proteomics, transcriptomics and lipidomics. We identified that high fructose diet-induced glucose intolerance in transgenic Kras mutation bearing mice, promotes PC progression, activation of PSCs and intrapancreatic inflammation. Exosomes derived from co-cultures of PC and PSCs impaired insulin secretion by mouse beta cells and impaired insulin signalling in mouse hepatocytes. We identified 12 candidate markers (7 proteins, 4 RNAs and 1 lipid marker) that are differentially expressed between the groups. Bioinformatic analysis demonstrated that these are linked to insulin secretion and signalling pathways, which may be involved in the pathogenesis of PCRD. In conclusion, this study identified a potential mechanism and mediators of PCRD, which may aid in early detection of pancreatic cancer.