Diabetes is a quickly growing health issue in Egypt, as the prevalence of T2DM has tripled over the last two decades to affect about 15.6 percent of adults between the ages of 20–79. Several factors have been identified that affect the onset and progress of diabetes-related complications such as the age of onset or disease duration, specific genes, glycemic control, hyperlipidemia, hypertension and smoking . TCF7L2 is a highly variable transcription factor that is involved in insulin secretion and an increased rate of production of hepatic glucose. It has been reported to guard pancreatic cells against interleukin-1 as well as interferon-mediated cell apoptosis [10, 11].
In this study, blood pressure was significantly increased in diabetic patients than controls. This was in agreement with earlier studies Biadgo et al. and Bhattarai et al., who reported that blood pressure was significantly higher among those with T2DM and diabetic complications than controls [12, 13]. Microvessels are the basic functional unit in the cardiovascular system playing an important role in the maintenance of blood pressure and proper nutrient delivery. Diabetes induces pathognomonic alterations in the microvasculature that affect the capillary basement membrane leading to the progress of diabetic microangiopathy . In the current study, cholesterol and triglycerides were significantly higher in diabetic without complications than controls. However, HDL-C was significantly lower in diabetic with complications than both controls and diabetic without complications. LDL-C was significantly higher in DR group than DN group. This agreed with Biadgo et al., who found a significant increase in the levels of cholesterol and triglycerides in diabetic patients compared to controls . Also, Mukherjee et al., reported that HDL-C levels were considerably lower in patients with DM than in controls, as well as LDL-C was significantly higher in diabetic retinopathy than diabetic without retinopathy group . However, Saravani et al., stated that there was no significant difference regarding LDL-C between the diabetics and controls . In diabetic subjects, insulin resistance has been considered the reason for dyslipidemia. The causes for increased triglycerides levels in diabetic patients is an insufficient function or secretion of insulin that causes higher hepatic secretion of VLDL together with the late elimination of TG-rich lipoproteins, mostly due to greater substrate levels for TG synthesis .
Regarding genotype and allele frequencies of TCF7L2 (rs7903146), the T allele was significantly more represented in diabetic with complications than diabetic without complications, also TT and TC genotypes were significantly increased in diabetic without complications and diabetic with complications groups. This was in agreement with Nanfa et al., and Demirsoy et al., who reported that the T allele at rs7903146 was considerably related to the risk for diabetes [18, 19]. Also, Buraczynska et al., reported that T allele was highly associated with DN . Also, Assmann et al., found that T allele had been considerably related to increased risk for T2DM in a dominant inheritance model (p = 0.001) and T allele homozygosis had been associated with a greater risk for diabetes than just one copy of that allele . However, Wu et al., observed no notable associations between genotypes of TCF7L2 rs7903146 and DN . Meanwhile, Verma et al. and Mandour et al. found that the T allele was protective against diabetes [8, 22]. A study was done by Ciccacci et al. investigated TCF7L2 variants and several diabetic macro- and microvascular complications, reported that patients with T allele had an increased risk for developing DR in addition to cardiovascular disease . Also, Buraczynska et al. reported about an association between rs7903146 and nephropathy (p < 0.001) and T allele was significantly associated with DN, particularly in the early onset of diabetes . The discrepancy in the results between different studies could be attributable to the influence of many variables, like ethnic background variances, different study designs in addition to altered disease susceptibility. This could also indicate the participation of other genes in the pathogenesis of T2DM [24, 25].
The TCF7L2 gene has a vital role in the progression of T2DM by influencing pancreatic islands, adipogenesis and myogenesis. It affects the beta cells function as well as granules accountable for insulin secretion and controls the expression of proteins tangled in insulin granules exocytosis . Overexpression of TCF7L2 in human pancreatic islets was found to decrease glucose-stimulated insulin secretion. Hence, the higher risk of T2DM assembled by variants in TCF7L2 comprises the entero-insular axis, increased expression of the gene in islets cells and impaired secretion of insulin. The validation of the association of TCF7L2 with T2DM complications in other populations affords evidence for additional consideration of TCF7L2 and associated molecules and pathways as possible therapeutic targets for diabetes . In conclusion, the TCF7L2 (rs7903146) is associated with T2DM susceptibility as patients with variant TT genotype had a higher risk than the heterozygous and wild genotypes. However, there was no significant association with diabetic microvascular complications.