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

Abstract

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).

Keywords: Insulin secretion; Islet amyloid polypeptide; Type 2 diabetes.

Figure 1

The slopes obtained from the individual regression lines between fasting serum C‐peptide level (F‐CP) and duration in (a) a representative type 2 diabetic patient who lacked the S20G mutation of the islet amyloid polypeptide gene and (a–g) the six type 2 diabetes patients who carried the S20G mutation of the islet amyloid polypeptide gene (the panels from b to g are listed in the patients’ order from 1 to 6).

Figure 2

Proportion of each therapy according to duration of diabetes in the type 2 diabetic patients who lacked the S20G mutation of the islet amyloid polypeptide gene. Open bars, gray bars, black bars represent the proportion of the patients (%) in each duration of diabetes who underwent diet therapy, oral hypoglycemic therapy and insulin therapy, respectively.

Figure 3

Correlations between (a) fasting serum C‐peptide level (F‐CP) and (b) 5‐min level of serum C‐peptide level after the intravenous injection of 1 mg glucagon (5′‐CP) and duration of diabetes in the type 2 diabetic patients who lacked the S20G mutation of the islet amyloid polypeptide gene. (a) F‐CP in the non‐diabetic subjects are indicated as the arrow (0.558 ± 0.241 nmol/L; mean vales ± SD), and the dashed line indicates the virtual line extended the value horizontally.

Figure 4

(a) Annual changes of fasting serum C‐peptide level (F‐CP) in the type 2 diabetic patients without (non‐S20G‐T2D‐patients, n = 70) and those with the S20G mutation of the IAPP gene (S20G‐patients, n = 6). (b) Those who had 5‐min level of serum C‐peptide level after the intravenous injection of 1 mg glucagon (5′‐CP) in the 42 non‐S20G‐T2D‐patients and the four S20G‐patients. Individual values are shown as scatter plots and mean vales ± SD as columns, with statistical significance of the difference below columns. *P = 0.025, **P = 0.008 for the difference between the indicated groups. Individual annual decline was multiplied (−1) by the annual change.