Birthweight correlates with later metabolic abnormalities in Chinese patients with maturity-onset diabetes of the young type 2

PURPOSE: Glucokinase-maturity onset diabetes of the young (GCK-MODY), also known as MODY2, is caused by heterozygous inactivating mutations in the GCK gene. The aim of this study is to investigate the relationship of birthweight and cardiometabolic characteristics in MODY2 patients. METHODS: Genetic screening for GCK mutations from 192 classical MODY families was performed, and birthweight and clinical profiles of 76 patients from 25 families with identified GCK mutations were collected. RESULTS: Mutations in GCK were identified in 25 (13%) of the 192 families. Four novel (c.1334 G > C, c.1289_1294delTGACGC, c.584 T > C, and c.30delC) and twenty-one previously reported mutations were identified and cosegregated with the clinical phenotypes of MODY2 within the pedigrees. MODY2 patients presented a mean birthweight of 3.11 ± 0.44 kg. Additionally, birthweight was negatively correlated with 2 h-postprandial glucose (r = −0.426, P = 0.006), glycated albumin (r = −0.462, P = 0.035), glycated hemoglobin (r = −0.529, P = 0.001), total cholesterol (r = −0.430, P = 0.016), and low-density lipoprotein cholesterol (LDL-C) (r = −0.383, P = 0.033) levels after adjustment for age, gender and BMI. Importantly, among the patients who inherited mutations from their mothers, 7 patients whose mothers were treated with insulin during pregnancy had particularly lower birthweight (2.83 ± 0.39 vs. 3.37 ± 0.39 kg; P = 0.003), higher total cholesterol (6.15 ± 0.43 vs. 4.06 ± 0.16 mmol/L; P = 0.002) and LDL-C (4.05 ± 0.35 vs. 2.21 ± 0.13 mmol/L; P = 0.001) levels compared to the other 21 patients whose mothers received no treatment. CONCLUSIONS: The correlations between birthweight and cardiometabolic indexes indicated that MODY2 patients with lower birthweight (<3.1 kg) should be monitored and treated more actively to prevent metabolic abnormalities, particularly dyslipidemia. Importantly, prenatal genic diagnosis is highly recommended to avoid inappropriate treatment in pregnancy leading to lower birthweight of offspring.