Diabetes and tobacco use are two of the largest public health challenges of our time. We aim to investigate the association between the two by comparing biochemical profiles of diabetic tobacco users (TUs) and tobacco nonus-ers (TNUs) to provide insight into the joint effect of tobacco and diabetes on body systems. This case-controlled study included 265 subjects, aged 18-60 yr, from the suburban population of Delhi, India. With the help of a questionnaire, participants are interviewed regarding their history of tobacco use. Results show association of tobacco use with elevated body-mass index, blood glucose levels, and insulin resistance in otherwise healthy and diabetic TUs. Even without previous history of coronary heart disease, total cholesterol and triglycerides are significantly further increased in TUs rather than in TNUs, indicative of initiation of lipid metabolism disorders. Tobacco use is also seen as a cause of oxidant/antioxidant imbalance in the body. Low serum albumin coupled with increased markers of inflammation and globulin levels is an indicator of generalized inflammation caused by tobacco's toxic effects. Creatinine levels are significantly higher in diabetic TUs, posing a threat to nephropathy progression. Evidence sufficiently infers that tobacco activates multiple biological pathways, through which the risk of metabolic disease increases. These factors may work in conjunction to increase risk of certain microvascular and macrovascular complications.