Diabetes-related complications reflect longstanding damage to small and large vessels throughout the body. In addition to the duration of diabetes and poor glycemic control, genetic factors are important contributors to the variability in the development of vascular complications. Early heritability studies found strong familial clustering of both macrovascular and microvascular complications. However, they were limited by small sample sizes and large phenotypic heterogeneity, leading to less accurate estimates. We take advantage of two independent studies—UK Biobank and the Action to Control Cardiovascular Risk in Diabetes trial—to survey the single nucleotide polymorphism heritability for diabetes microvascular (diabetic kidney disease and diabetic retinopathy) and macrovascular (cardiovascular events) complications. Heritability for diabetic kidney disease was estimated at 29%. The heritability estimate for microalbuminuria ranged from 24 to 60% and was 41% for macroalbuminuria. Heritability estimates of diabetic retinopathy ranged from 6 to 33%, depending on the phenotype definition. More severe diabetes retinopathy possessed higher genetic contributions. We show, for the first time, that rare variants account for much of the heritability of diabetic retinopathy. This study suggests that a large portion of the genetic risk of diabetes complications is yet to be discovered and emphasizes the need for additional genetic studies of diabetes complications.
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Pathophysiology of mesangial expansion in diabetic nephropathy: mesangial structure, glomerular biomechanics, and biochemical signaling and regulation
Abstract Diabetic nephropathy, a kidney complication arising from diabetes, is the leading cause of death in diabetic patients. Unabated, the growing epidemic of diabetes is increasing instances of diabetic nephropathy. Although the main causes of diabetic nephropathy have been determined, the mechanisms of their combined effects on cellular and tissue function are not fully established. One of many damages of diabetic nephropathy is the development of fibrosis within the kidneys, termed mesangial expansion. Mesangial expansion is an important structural lesion that is characterized by the aberrant proliferation of mesangial cells and excess production of matrix proteins. Mesangial expansion is involved in the progression of kidney failure in diabetic nephropathy, yet its causes and mechanism of impact on kidney function are not well defined. Here, we review the literature on the causes of mesangial expansion and its impacts on cell and tissue function. We highlight the gaps that still remain and the potential areas where bioengineering studies can bring insight to mesangial expansion in diabetic nephropathy.
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- Award ID(s):
- 2133411
- NSF-PAR ID:
- 10407963
- Date Published:
- Journal Name:
- Journal of Biological Engineering
- Volume:
- 16
- Issue:
- 1
- ISSN:
- 1754-1611
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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- Free Publicly Accessible Full Text
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1186/s13036-022-00299-4
