Predisposition to essential hypertension and development of diabetic nephropathy in IDDM patients.

Fagerudd, J; Tarnow, Lise; Jacobsen, Peter Karl; Stenman, S; Nielsen, F. S.; Pettersson-Fernholm, Kim; Grönhagen‐Riska, Carola; Parving, Hans Henrik; Groop, Per Henrik

doi:10.2337/diabetes.47.3.439

Cited by 66 publications

(47 citation statements)

References 12 publications

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“…In addition, familial aggregation of renal histology is observed in siblings with diabetes, independent of diabetes duration and disease control (18); a greater prevalence of hypertensive parents among children with diabetes and nephropathy are seen (19); and ethnic differences in susceptibility to DN exist (20). Together, these observations support genetic contributions to DN.…”

Section: Familial Aggregation Of Dnsupporting

confidence: 53%

Genetic Factors in Diabetic Nephropathy

Freedman

Bostrom

Daeihagh

et al. 2007

Clinical Journal of the American Society of Nephrology

173

125

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Several genes that predispose to type 2 diabetes have recently been identified. In addition to the recognized and powerful effects of environmental factors, there is abundant evidence in support of genetic susceptibility to the microvascular complication of nephropathy in individuals with both type 1 and type 2 diabetes. Familial aggregation of phenotypes such as end-stage renal disease, albuminuria, and chronic kidney disease have routinely been reported in populations throughout the world, and heritability estimates for albuminuria and glomerular filtration rate demonstrate strong contributions of inherited factors. Recent genome-wide linkage scans have identified several chromosomal regions that likely contain diabetic nephropathy susceptibility genes, and association analyses have evaluated positional candidate genes under these linkage peaks. These complimentary approaches have demonstrated that polymorphisms in the carnosinase 1 gene on chromosome 18q, the adiponectin gene on 3q, and the engulfment and cell motility gene on 7p are likely associated with susceptibility to diabetic nephropathy. Additional genes that seem to be of importance in renal phenotypes include manganese superoxide dismutase and angiotensin 1-converting enzyme, with nitric oxide synthase implicated in albuminuria. This article reviews the inherited aspects of diabetic kidney disease with particular emphasis on recently implicated genes and pathways. It seems likely that the risk for diabetes-associated kidney disease is magnified by inheriting risk alleles at several susceptibility loci, in the presence of hyperglycemia.Clin J Am Soc Nephrol 2: 1306 -1316, 2007. doi: 10.2215/CJN.02560607 I t was previously thought that individuals who had diabetes and developed progressive diabetic nephropathy (DN) and/or ESRD were simply exposed to long durations of diabetes with relatively poor glycemic control. In other words, all individuals with diabetes were assumed to be at essentially equivalent risk for developing nephropathy, allowing for differences in their ambient serum glucose concentration. In support of the concept that exposure to a hyperglycemic environment led to DN (often with coexisting obesity, metabolic syndrome, hypertension, and hyperlipidemia), clinical trials have conclusively demonstrated that improving glycemic control delays and, in some cases, may prevent the subsequent development of albuminuria, DN, and macrovascular complications such as coronary artery disease (1,2). The concept that select individuals with diabetes were at differential risk for developing nephropathy on the basis of familial aggregation of kidney disease was initially reported in 1989 but has only recently gained broad acceptance among nephrologists and diabetologists (3). Familial Aggregation of DNThe notion that genetic factors contribute to any complex disease rests on the demonstration of familial aggregation. Familial clustering of nephropathy could result from shared genes, environmental exposures, or their combination.After repeated demonstra...

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Section: Familial Aggregation Of Dnsupporting

confidence: 53%

Genetic Factors in Diabetic Nephropathy

Freedman

Bostrom

Daeihagh

et al. 2007

Clinical Journal of the American Society of Nephrology

173

125

View full text Add to dashboard Cite

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“…The genetically determined high rate of red cell sodium-lithium counter transport is associated with the risk of essential hypertension in non-diabetic patients [40] and has been found in Type I diabetic patients with proteinuria and their parents [27,41]. Thus a familial predisposition to raised blood pressure has been suggested as a possible contributing factor to the susceptibility for diabetic nephropathy [23,24]. Furthermore, the higher prevalence of CVD in those with early microangiopathy (Group A) suggests a parallel evolution of micro-and macroangiopathy in these patients, which is supportive of the suggestion that increased urinary albumin excretion reflects a more generalized endothelial dysfunction [31,42±44].…”

Section: Discussionmentioning

confidence: 99%

Different risk factors of microangiopathy in patients with Type I diabetes mellitus of short versus long duration. The EURODIAB IDDM Complications Study

Karamanos

Porta

Songini³

et al. 2000

Diabetologia

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In diabetic patients morbidity and mortality are mainly related to the presence of late complications, namely macro-and microangiopathy. The pathogenesis of microangiopathy is being extensively studied and evidence linking the degree of glycaemic control with the development of microangiopathy has been accumulated over the last 20±30 years [1±6], while evidence is also increasing for some genetic predisposition [7±10].In Type I diabetic patients both the Stockholm Diabetes Intervention Study and the Diabetes Control and Complications Trial (DCCT) showed that glycaemic control is an important determinant of both the development and progression of diabetic microangiopathy [4,5]. The United Kingdom Prospective Diabetes Study (UKPDS) has also confirm- Diabetologia (2000) Abstract Aims/hypothesis. To identify factors associated with early development of and late protection from microvascular complications in subjects with Type I (insulin-dependent) diabetes mellitus. Methods. The frequency of microvascular complications and their relation to risk factors were studied in 300 Type I diabetic subjects with short duration of disease ( £ 5 years) compared with 1062 subjects with long duration ( ³ 14 years). Microvascular disease was defined as the presence of either retinopathy (assessed from centrally-graded retinal photographs) or urinary albumin excretion rate of more than 20 mg/min. Resu1ts. The prevalence of microvascular disease was 25 % in the short duration group. In the long duration group 18 % had no evidence of microvascular complications. In the short duration group factors associated with early development of complications were cigarette smoking and a family history of hypertension. Subjects free of microvascular complications in spite of long duration of diabetes had better glycaemic control, lower blood pressure, better lipid profile and lower von Willebrand factor levels. Conclusion/interpretation. At the early stages of Type I diabetes, cigarette smoking and genetic susceptibility to hypertension are important risk factors for microvascular complications. At a later stage, additional risk factors are poorer glycaemic control, higher blood pressure, and an unfavourable lipid profile possibly associated with endothelial dysfunction. Many of these factors are amenable to long-term intervention which should be started as soon as possible in the course of the disease. [Diabetologia (2000) 43: 348±355]

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“…45,46 It is known that agents that interrupt the renin-angiotensin system are particularly renoprotective. [47][48][49] These agents reduce systemic as well as glomerular hypertension and, by downregulating TGF-␤ 1 , 15,16,38 are likely to interrupt the TGF-␤ 1 -GLUT-1 axis.…”

Section: Discussionmentioning

confidence: 99%

GLUT-1 Overexpression

et al. 2003

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Abstract-Mesangial matrix deposition is the hallmark of hypertensive and diabetic glomerulopathy. At similar levels of systemic hypertension, Dahl salt-sensitive but not spontaneously hypertensive rats (SHR) develop glomerular hypertension, which is accompanied by upregulation of transforming growth factor ␤ 1 (TGF-␤ 1 ), mesangial matrix expansion, and sclerosis. GLUT-1 is ubiquitously expressed and is the predominant glucose transporter in mesangial cells. In mesangial cells in vitro, GLUT-1 overexpression increases basal glucose transport, resulting in excess fibronectin and collagen production.

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Predisposition to essential hypertension and development of diabetic nephropathy in IDDM patients.

Cited by 66 publications

References 12 publications

Genetic Factors in Diabetic Nephropathy

Genetic Factors in Diabetic Nephropathy

Different risk factors of microangiopathy in patients with Type I diabetes mellitus of short versus long duration. The EURODIAB IDDM Complications Study

GLUT-1 Overexpression

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