The present invention relates to the unexpected discovery of an exceptionally non-conservative mutation in a very large kindred with a high prevalence of early CAD, obesity, hypertriglyceridemia and diabetes. The gene harboring the mutation is Cela2a. Characterization of the encoded protein unraveled important functions in regulation of insulin secretion and lipolysis. Thus, in various embodiments described herein, the invention encompasses a therapeutic composition comprising a Cela2a polypeptide or polynucleotide. Additionally, the invention relates to methods of altering glucose and/or lipid metabolism in a subject, methods of treating atherosclerosis, diabetes, hypertension, or hypertriglyceridemia in a subject, methods of detecting atherosclerosis and/or diabetes in a subject, and methods of identifying a subject at risk of developing atherosclerosis and/or diabetes. Further, the invention encompasses a kit for carrying out the aforementioned methods.
