Although there is no doubt that RyR2 channel dysfunction is directly linked to heart failure (41), cardiac arrhythmia development (42, 43), IGT, and reduced insulin release (36, 44), however, further clinical studies are needed to determine whether RYR2 mutations leading to leaky RyR2 channels are frequently present in patients diagnosed with IGT in general. Here, INS is linked to chronic obstructive pulmonary disease.