Diabetes-inducing effects of bronchial asthma

Table 1 The effect of bronchial asthma medications on blood glucose and diabetes mellitus

Drug	Effect	Mechanism
Beta-agonists	Beta2-agonists can improve insulin sensitivity[83]. Improved glucose tolerance and homeostasis[84]. No clinically significant increase in blood glucose in patients with DM[85]	Stimulating glucose uptake in the skeletal muscle, improving whole-body insulin sensitivity, and reducing hepatic lipids and glycogen[84]
Anticholinergic	There are no recorded harmful effects of inhaled anticholinergic drugs on the glucose level or insulin resistance. Oral anticholinergics can attenuate the late-phase insulin activity in varying degrees of glycemic status[86]	Insulin secretion is influenced by the cholinergic system[86]
Xanthine derivatives (phosphodiesterase inhibitors)	Aminophylline inhibits the endogenous glucose production in T2DM by stimulating insulin secretion[87]. A single dose of theophylline can improve hypoglycemia unawareness in patients with T1DM; however, prolonged theophylline use is associated with tolerance of that effect, causing a sustained effect on different responses to hypoglycemia (cardiovascular, metabolic, and symptom responses)[88]	Paracrine factors, such as adenosine, may be involved in regulating basal insulin secretion[87]
Systemic corticosteroids	High risk of developing DM and progression to insulin therapy in persons using long-term systemic steroids[90-93]. Patients with asthma without a diagnosis of DM who used corticosteroids developed hyperglycemia[94]. Risk factors for developing DM in subjects using systemic glucocorticoids include older age, higher fasting blood glucose levels and HbA1c, lower glomerular filtration rate, presence of pregnancy, visceral obesity, insulin resistance, and family history of DM[97]	Increased hepatic gluconeogenesis. The peripheral glucose uptake by the skeletal muscle, adipose tissue, liver, and bone is reduced. Insulin resistance and its effect on glycemic control. Inhibition of insulin secretion by pancreatic β cells. Steroids favor the systemic release of triglycerides and fatty acids that negatively affect β cells' function[96,97]
ICS	Systemic bioavailability of ICS increases the risk of systemic adverse effects, especially with higher doses of ICS, increasing the risk of DM and hyperglycemia. Other factors that determine ICS's potential for systemic adverse effects include the dose of the drug, the patient's age, and the presence of other co-morbidities. Newer ICS preparations have essentially zero oral bioavailability and exhibit 98%–99% binding to serum proteins, making them unable to reach the glucocorticoid receptors. Efforts to improve the delivery devices to choose the best form of the ICS are ongoing[101,102]	The same mechanisms as with systemic steroids when the drug reaches the circulation
Leukotriene receptor antagonists	No recorded evidence of their effect on DM control or insulin resistance exists. Montelukast has a protective effect against diabetic retinopathy[104]	Leukotriene receptor antagonism by montelukast resulted in a significant decrease in early, diabetes-induced retinal capillary leakage, leukocyte adherence, and superoxide generation[104]
Biologic agents	Few case reports show elevation of blood glucose following administration of omalizumab, an anti-IgE antibody. That was not noticed after administering mepolizumab, a monoclonal antibody against IL-5[105-107]	Each vial of omalizumab (150 mg) contains 145.5 mg sucrose. However, because of the infrequent use of omalizumab (every two or four weeks), sucrose included in the omalizumab vial did not seem to influence glycaemic control[105-107]

T2DM: Type 2 diabetes mellitus; T1DM: Type 1 diabetes mellitus; ICS: Inhaled corticosteroids; IL: Interleukin.