Excessive maternal transmission of diabetes in Japanese families with young-onset type 2 diabetes and insulin secretion defect according to clinical features

The aim of the study is to identify the clinical characteristics of Japanese patients with young-onset type 2 diabetes (YT2D). Family history of diabetes and clinical data were collected for 30 unrelated males (from 11 to 20 years old at age of onset) and 20 females (from 10 to 20 years old at age of onset) with YT2D diagnosed at ≤20 years of age. Fasting C-peptide levels were measured in all, and glucagon stimulation tests were performed twice in six of them over several years. Moreover, 858 people with type 2 diabetes (T2D) diagnosed at >20 years of age were randomly recruited in order to compare the transmission pattern of them. Among the study subjects, 68% reported at least one parent with diabetes. Diabetes was more frequent among mothers than fathers of probands (P = 0.020), although this tendency was not observed in T2D diagnosed at >20 years of age. Fasting C-peptide levels of patients with diabetes duration of ≥10 years were significantly lower than for patients with diabetes duration of <10 years (0.61 ± 0.26 vs. 0.84 ± 0.43 nmol/l, P = 0.036). The fasting C-peptide levels among male patients with a family history of diabetes were also significantly lower than those without a family history (0.56 ± 0.25 vs. 0.83 ± 0.37 nmol/l, P = 0.034), while all female subjects had a family history of diabetes. Glucagon stimulation tests showed the following data; 0 min: 0.56 ± 0.31 vs. 0.39 ± 0.22 nmol/l, 3 min: 1.41 ± 0.77 vs. 0.87 ± 0.47 nmol/l, 6 min: 1.37 ± 0.80 vs. 0.79 ± 0.35 nmol/l, 10 min: 1.06 ± 0.60 vs. 0.81 ± 0.49 nmol/l, and 30 min: 0.58 ± 0.30 vs. 0.50 ± 0.19 nmol/l, respectively. These results demonstrated that YT2D among Japanese people occurring in excess with maternal transmission is associated with β-cell dysfunction at the onset of diabetes and as the disease advances.