Association of obesity in T2DM with differential polymorphism of ghrelin, growth hormone secretagogue receptor-1 and telomeres maintenance genes.

BACKGROUND: Although obesity and T2DM comorbidity is too frequent, the molecular basis of diabetic obesity is largely unexplained and barely investigated. MATERIALS: Cross-sectional studies were conducted in Kingdom of Saudi Arabia (KSA) in 2013 and Kuwait in 2019. Fasting blood samples were obtained from a total of 216 T2DM patients (104 from KSA) and 193 nondiabetic subjects (93 from KSA) after their consents. Eight SNPs in 5 genes known to be associated with both obesity and T2DM, ghrelin (GHRL) and growth hormone secretagogue receptor -GHSR (KSA) and telomeres maintenance genes (Kuwait) were genotyped by rtPCR. Both patients and controls were grouped into obese and non-obese and sub-grouped into 4-BMI- grades: normal, overweight (OW), obese (OBS) and severely obese (SOBS). RESULTS: Showed that the only SNP which was distinguished between all groups/subgroups in all study subjects was the ACYP2 rs6713088G/C, where the common CC genotype was under-expressed in the obese compared to non-obese diabetics (17.8% vs. 40.4%, p 0.01) and between the 4-BMI-grade (p 0.025). Interestingly the same genotype was over-expressed in obese compared to non-obese non-diabetics (50% vs. 27.6%, p 0.04). Furthermore, the GHRL (rs27647C/T), GHSR (rs509030G/C) and TERC (rs12696304G/C) MAFs were significantly low in normal BMI patients; p=0.034, 0.008 and 0.011, respectively. CONCLUSIONS: This is the first report about the molecular distinction between the obese and non-obese diabetics, it showed the association of rs6713088G/C mutant allele with diabetic obesity, while the GHRL, GHSR and TERC SNPs were differentially expressed based on the BMI-grades.

Hormonal and metabolic profiles of obese and nonobese type 2 diabetes patients: implications of plasma insulin, ghrelin, and vitamin D levels.

Type 2 diabetes (T2D) is associated with obesity whereas loss of weight is a feature of the disease; however, the two states are not mutually exclusive. Obesity is linked with changes in hormonal activity and overall body metabolism. MATERIALS AND METHODS: In this study, 408 T2D patients were recruited in three distinct studies conducted in Bahrain, Saudi Arabia, and Kuwait in three different intervals between 2001 and 2019. In addition to demographics, glycemic and lipid profiles were obtained in all studies, whereas plasma insulin and HOMA-IR, vitamin D, and ghrelin were analyzed in Saudi Arabia. Different techniques such as chemical auto-analyzer, ELISA, chemiluminescent immunoassay, radioimmunoassay were used. RESULTS: The obese (BMI ≥ 30 kg/m2) compared with nonobese (BMI 18.5 to <30) patients with diabetes were more likely to be women (P < 0.001), smaller in age (P = 0.028), and with shorter disease duration (P = 0.018). Unexpectedly, the glycemic and lipid profiles were consistently comparable between the two groups in the three sites. Furthermore, vitamin D was strikingly lower in obese patients with diabetes (P = 0.007). Finally, plasma ghrelin (P = 0.163), insulin (P = 0.063), and HOMA-IR (P = 0.166) were comparable between obese and nonobese patients with diabetes. CONCLUSION: Diabetic obesity was significantly associated with female sex, young age, short disease duration, and noticeably low vitamin D, and a trend of high insulin levels. However, the obese and nonobese patients had comparable metabolic profiles with no differences in insulin resistance and ghrelin levels. Further studies, especially at a molecular level, are needed to explore this topic which is barely investigated.