Type 2 diabetes mellitus (T2DM) is a complex disease involving both environmental and genetic contributing factors. T2DM and metabolic syndrome are associated with decreased insulin like growth factor 1 (IGF-1) and vitamin D3. Several studies reported a positive influence of IGF-I on glucose homeostasis exerting insulin-like biological effects. In addition, vitamin D3 has been demonstrated to stimulate insulin secretion from the pancreatic β-cells and modulate β-cell growth and differentiation. Indeed, low vit D3 level has emerged as a risk factor for insulin resistance and T2DM. The relationship between vitamin D deficiency and insulin resistance could develop through inflammation. Pro-neurotensin (pro-NT) is the stable precursor of neurotensin that is secreted by intestinal neuroendocrine cells in response to food ingestion, facilitating lipid absorption with a direct influence on blood glucose control being co-secreted with other gastrointestinal hormones, such as glucagon-like peptide-1 (GLP-1). Elevated pro-NT levels were linked with an increased risk of T2DM and cardiovascular disease and have been reported to predict future development of obesity and diabetes mellitus. Therefore, IGF-I, vitamin D3 and pro-NT can be regarded as promising biomarkers for early diagnosis and treatment of T2DM and can also predict future development of diabetic complications.