Genetics of diabetes-associated microvascular complications

Abstract

Diabetes is associated with excess morbidity and mortality due to both micro- and macrovascular complications, as well as a range of non-classical comorbidities. Diabetes-associated microvascular complications are those considered most closely related to hyperglycaemia in a causal manner. However, some individuals with hyperglycaemia (even those with severe hyperglycaemia) do not develop microvascular diseases, which, together with evidence of co-occurrence of microvascular diseases in families, suggests a role for genetics. While genome-wide association studies (GWASs) produced firm evidence of multiple genetic variants underlying differential susceptibility to type 1 and type 2 diabetes, genetic determinants of microvascular complications are mostly suggestive. Identified susceptibility variants of diabetic kidney disease (DKD) in type 2 diabetes mirror variants underlying chronic kidney disease (CKD) in individuals without diabetes. As for retinopathy and neuropathy, reported risk variants currently lack large-scale replication. The reported associations between type 2 diabetes risk variants and microvascular complications may be explained by hyperglycaemia. More extensive phenotyping, along with adjustments for unmeasured confounding, including both early (fetal) and late-life (hyperglycaemia, hypertension, etc.) environmental factors, are urgently needed to understand the genetics of microvascular complications. Finally, genetic variants associated with reduced glycolysis, mitochondrial dysfunction and DNA damage and sustained cell regeneration may protect against microvascular complications, illustrating the utility of studies in individuals who have escaped these complications. Graphical Abstract

The association between serum copper concentration and prevalence of diabetes among US adults with hypertension (NHANES 2011–2016)

“…The incidence of diabetes mellitus has been on the rise in recent years, and its chronic complications have a serious impact on the quality of patients 28 . The pathogenesis of diabetes mellitus mainly includes genetic, environmental and immunologic factors 29 . Studies have showed that oxidative stress causes pancreatic islet cell dysfunction and insulin resistance, which resulted in tissue cell damage 30…”

“… 28 The pathogenesis of diabetes mellitus mainly includes genetic, environmental and immunologic factors. 29 Studies have showed that oxidative stress causes pancreatic islet cell dysfunction and insulin resistance, which resulted in tissue cell damage. 30 …”

Anti-inflammatory effects of astaxanthin supplementation in the pathogenesis of diabetes mellitus and its complications: Emphasis on the role of inflammation-related microRNAs, lysophosphatidylcholine, and α-hydroxybutyrate in diabetic complications

“…In the ASX group, at baseline, serum total cholesterol, TG, and LDL were 150.98 ± 39.25, 142. 37 In Table 2, the differences in in ammation-related microRNA expression between the subjects with and without albuminuria are shown in ASX subgroups. We observed that the group of patients with albuminuria (ACR ≥ 30 mg/g) had signi cantly higher (p < 0.05) hsa-miR-21 (p = 0.003), hsa-miR-34a (p = 0.005), and hsa-miR-155 (p = 0.001) expression than the group of patients without albuminuria (ACR < 30 mg/g).…”

“…All forms of diabetes are distinguished by fasting and postprandial hyperglycemia and relative insulin de ciency (Bao et al, 2022). DM can cause microvascular complications, including retinopathy, nephropathy, and agonizing neuropathy (Lyssenko and Vaag, 2023). Diabetes is also a primary cause of macrovascular complications, which are typically related to cardiovascular diseases such as coronary artery disease, atherosclerosis, and hypertension (Maric-Bilkan, 2017).…”