Variants of ADIPOQ have been inconsistently associated with adiponectin level in diverse populations. We explored association of single nucleotide polymorphism (SNP) in the ADIPOQ (+276 G>T, rs1501299) with circulating total adiponectin and insulin resistance (IR) in Ukrainian T2DM cohort.
Materials and methods: 544 T2DM patients (M/F: 241/303, age 56.3±0.4 years, diabetes duration 7.8±1.0 years, BMI 31.7±0.2 kg/m2, HbA1c 7.6±0.2%) and 215 healthy controls (C) were genotyped. The SNP +276G>T in the ADIPOQ was detected using PCR-RELP. Plasma total adiponectin, IR and lipid profile were determined. Statistical analysis was performed with ANOVA and χ2 test.
Results: Comparing with C significant (P<0.001) increase in triglyceridaemia (2.89±0.12 vs 1.23±0.26 mM), plasma FFA levels (1.35±0.03 vs 0.34±0.07 mM), plasma insulin levels (132.47±6.11 vs 85.21±8.01 pM) and HOMA-IR (8.35±0.40 vs 1.77±0.41) as well as hypoadiponectinaemia (4.99±0.16 vs 11.80±1.45 mg/l) were observed in T2DM patients. Major allele in the studied groups was G (frequency in C: 0.691, and in diabetics: 0.601). In T2DM the T allele frequency was 0.399 and different significantly from C (0.307). In comparison with C, T2DM had more TT (16.9% vs 9.3%, P<0.05), but less GG (37.1% vs 47.4%, P<0.05) homozygotes. It was determined lower severity of dyslipidemia, i.e. total cholesterol (P<0.01), triglycerides (P<0.02) and β-lipoprotein cholesterol (P<0.05) against the background of less hypoadiponectinaemia (on 15.4%) in GG homozygotes (P<0.1) compared to TT-carriers. Higher HOMA-IR was revealed in TT compared to other genotypes with maximal difference in patients with obesity (HOMA-IR indexes in carriers of TT, GT and GG genotypes were 10.96±1.52, 8.40±0.65 and 8.96±0.74, respectively, P<0.02 for TT vs GT and GG).
Conclusions: The study demonstrates for the first time that ADIPOQ variants are associated with IR phenotype in Ukrainian T2DM patients. We suggest the predominant impact of metabolic disturbances and hyperinsulinaemia on diabetic hypoadiponectinaemia genesis.
16 - 20 May 2015
European Society of Endocrinology