Progressive deterioration of insulin secretion in Japanese type 2 diabetic patients in comparison with those who carry the S20G mutation of the islet amyloid polypeptide gene: A long‐term follow‐up study

Aims/Introduction:  In order to clarify the enhanced β‐cell dysfunction in type 2 diabetic patients carrying the S20G mutation of the islet amyloid polypeptide gene (S20G‐patients), we first estimated the decline of insulin secretion in Japanese type 2 diabetic patients without the S20G mutation (non‐S20G‐T2D‐patients) by long‐term observation, and then compared it with that of the S20G‐patients. Materials and Methods:  We followed 70 non‐S20G‐T2D‐patients (body mass index <30 kg/m 2 ) for more than 10 years and six S20G‐patients for more than 5 years. We measured fasting C‐peptide (F‐CP) every 1–2 years and carried out a glucagon test at least once during the follow‐up period. F‐CP and a 5‐min value of C‐peptide after glucagon injection (5′‐CP) were used as the indices of insulin secretion. We excluded patients who had renal dysfunction and/or anti‐insulin antibodies in the insulin‐treated patients. The individual annual declines were calculated from the slopes of the regression lines between C‐peptide levels and duration (years after diagnosis). Results:  The mean individual annual declines of both F‐CP and 5′‐CP were significantly greater in the S20G‐patients than the non‐S20G‐T2D‐patients (F‐CP; 0.047 ± 0.026 vs 0.011 ± 0.037 nmol/L/year, P  = 0.025, 5′‐CP; 0.139 ± 0.055 vs 0.022 ± 0.012 nmol/L/year, P  = 0.008). Conclusions:  We established the annual decline of insulin secretion in the Japanese type 2 diabetic patients by the long‐term observation. The results show that the decline of insulin secretion is more rapid in the S20G‐patients than the non‐S20G‐T2D‐patients. (J Diabetes Invest, doi: 10.1111/j.2040‐1124.2011.00102.x, 2011)