It is a well-known fact that smoking is bad for your health. If smoking is bad for healthy people, it is even worse for people with health problems! Not only is it not good for the treatment of the disease, but it may also increase the symptoms of the disease and even induce complications. Smoking can increase insulin resistance! Diabetics need to be vigilant and should never smoke or expose themselves to second-hand smoke. The reasons why smoking can aggravate insulin resistance are as follows: a. Nicotine in tobacco can selectively activate AMPKα2 in adipocytes, AMPKα2 as a protein kinase can phosphorylate the 334-position serine of MAP kinase phosphatase 1 (MKP1) and promote the proteasomal pathway degradation process of MKP1. (1) Nicotine-dependent MKP1 decline induces abnormal activation of p38 mitogen-activated protein kinase (p38MAPK) and c-jun N-terminal kinase (JNK), leading to phosphorylation of serine at position 307 of insulin receptor substrate 1 (IRS1). (2) Phosphorylated IRS1 accelerates degradation and inhibits protein kinase B (PKB), resulting in loss of insulin-mediated inhibition of the lipolytic process in cells. (3) Ultimately, nicotine increases the lipolytic process in adipocytes, leading to weight loss, but the increased lipolytic process also increases the level of free fatty acids in the circulatory system, causing insulin resistance in insulin-sensitive tissues. Second, smoking may impair the early steps of insulin signaling, glucose transport and glucose phosphorylation, or other biochemical pathways of glucose metabolism that are initiated at the same time, resulting in reduced insulin sensitivity and insulin resistance. Third, long-term smoking can cause increased sympathetic nervous system activity, leading to increased release of catecholamines and other glucose-raising hormones and elevated levels of circulating catecholamines, which are potent antagonists of insulin action, and catecholamines at the cellular level, which reduce insulin action by impairing insulin signaling/transmission pathways and intrinsic activity, resulting in reduced synthesis of glucose transporter proteins. Numerous studies have confirmed that smoking leads to insulin resistance and accelerates the development of macrovascular and microvascular complications in diabetes and is one of the main causes of premature death in diabetic patients.