Lack of relationship between an insertion/deletion polymorphism in the angiotensin I-converting enzyme gene and diabetic nephropathy and proliferative retinopathy in IDDM patients

Tarnow, Lise; Cambien, François; Persson, Frederik; Nielsen, F. S.; Hansen, Birgitte V.; Lecerf, Laure; Poirier, Odette; Danilov, Sergei M.; Parving, Hans‐Henrik

doi:10.2337/diabetes.44.5.489

Cited by 94 publications

(96 citation statements)

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“…The prevalence of major cardiovascular events differed between patients with and without diabetic nephropathy (11% [95% CI [8][9][10][11][12][13][14] and 2% [0-4], respectively, p<0.0001). In patients with nephropathy, plasma NTproBNP at baseline was significantly elevated in patients with a history of nonfatal myocardial infarction and/or stroke (671 [34-12,418] ng l −1 , p<0.0001) as compared with patients without a history of major cardiovascular disease (97 640] ng l −1 ).…”

Section: Resultsmentioning

confidence: 99%

“…During 1993, all type 1 diabetic patients with diabetic nephropathy (n=242) attending the outpatient clinic at Steno Diabetes Center, in whom glomerular filtration rate had been measured during the same year, were invited to participate in a case-control study [10,11]. A total of 199 patients fulfilling the clinical criteria for diabetic nephropathy (persistent macroalbuminuria [>300 mg 24 h −1 ] in at least two out of three consecutive 24-h urine collections, in the presence of diabetic retinopathy and the absence of other kidney or urinary tract disease [12]) were recruited.…”

Section: Methodsmentioning

confidence: 99%

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Plasma N-terminal pro-brain natriuretic peptide as an independent predictor of mortality in diabetic nephropathy

et al. 2004

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Aims/hypothesis: Raised N-terminal pro-brain natriuretic peptide (NT-proBNP) is independently associated with an increased risk of death in chronic heart failure and acute coronary syndromes in nondiabetic populations. Diabetic nephropathy is characterised by an increased risk of cardiovascular morbidity and mortality. This study investigated the prognostic value of NT-proBNP in a large cohort of type 1 diabetic patients with and without diabetic nephropathy. Methods: In a prospective observational follow-up study, 198 type 1 diabetic patients with overt diabetic nephropathy (122 men, age [mean±SD] 41±10 years, duration of diabetes 28±8 years, GFR 74±33 ml min −1 ) and a matched control group of 188 patients with longstanding type 1 diabetes and persistent normoalbuminuria (114 men, age 43±10 years, duration of diabetes 27±9 years) were followed for 9.3 (0.0-9.5) years. Plasma NTproBNP concentration was determined by immunoassay at baseline. Results: In patients with diabetic nephropathy, plasma NT-proBNP concentration was elevated to (median [range]) 110 (5-79640) ng l −1 vs. 27 (5-455) ng l −1 in normoalbuminuric patients (p<0.0001). Among patients with nephropathy, 39 (39%) patients with plasma NTproBNP concentrations above the median and 12 (12%) with values below the median died from any cause (unadjusted hazard ratio 3.86 [95% CI 2.02-7.37], p<0.0001; covariate-adjusted hazard ratio 2.28 [1.04-4.99], p=0.04). This lower mortality rate was attributable to fewer cardiovascular deaths: 31 (31%) and 7 (7%) above and below the median NT-proBNP level respectively (unadjusted hazard ratio 5.25 [2.31-11.92], p<0.0001; covariate-adjusted hazard ratio 3.81 [1.46-9.94], p=0.006). Conclusions/interpretation: Elevated circulating NT-proBNP is a new independent predictor of the excess overall and cardiovascular mortality in diabetic nephropathy patients without symptoms of heart failure.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Plasma N-terminal pro-brain natriuretic peptide as an independent predictor of mortality in diabetic nephropathy

et al. 2004

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“…In normoalbuminuric patients, GFR was estimated on the basis of serum creatinine using the Levey formula as previously described (estimated GFR) [27]. In patients with nephropathy, GFR was measured after a single injection of radiolabelled EDTA (3.7 MBq 51 Cr-EDTA) by determination of radioactivity in venous blood samples collected 180, 200, 220 and 240 min after the injection (measured GFR) [25].…”

Section: Methodsmentioning

confidence: 99%

“…Data on the diabetic study population have been published previously [25]. In brief, approximately half of the patients (n=199) had diabetic nephropathy, which was defined on the basis of persistent albuminuria (urinary albumin excretion rate [UAE] >300 mg/24 h in at least two of three consecutive 24-h urine collections), the presence of simplex retinopathy or proliferative retinopathy, and no evidence of other kidney or renal tract disease.…”

Section: Subjectsmentioning

confidence: 99%

Increased serum adiponectin levels in type 1 diabetic patients with microvascular complications

et al. 2005

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Aims/hypothesis: Low serum adiponectin (ADPN) has been associated with increased risk of cardiovascular disease (CVD) and retinopathy in patients with type 2 diabetes mellitus. In type 1 diabetic patients, the relationship between ADPN and the presence of vascular complications is largely unknown. Methods: We investigated the relationship between serum ADPN and the presence of retinopathy, nephropathy and CVD in patients with type 1 diabetes, divided into matched groups with normoalbuminuria and no retinopathy (n=67), simplex retinopathy (n=106) or proliferative retinopathy (n=19), and nephropathy with simplex (n=62) or proliferative retinopathy (n=137). Healthy control subjects (n=25) were included. Results: Serum ADPN was increased in subjects with type 1 diabetes compared with control subjects (p<0.0001). Further, serum ADPN was higher in patients with than in those without nephropathy (p<0.0001). It was also higher in normoalbuminuric patients with than in those without proliferative retinopathy (p<0.0001). These differences remained significant after adjustment for known risk factors (p<0.03). CVD was also associated with elevated ADPN levels (p<0.05), but this difference became insignificant after risk factor adjustment. The most important predictor of serum ADPN was sex (r 2 =19%) in normoalbuminuric patients and GFR in patients with nephropathy (r 2 =18%). Conclusion/interpretation: Patients with type 1 diabetes and microvascular complications have higher serum levels of ADPN than patients without complications. It remains to be clarified whether elevated levels of ADPN are pathogenically related to the development of microvascular complications or represent a beneficial counter-regulatory response.

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“…These include the nitric oxide synthases (NOS) that mediate vasodilation and the endothelins (ETs) that are vasoconstrictors. Angiotensin-converting enzyme (ACE), which converts angiotensinogen to angiotensin, is another important mediator of vasoconstriction and homeostasis; however, studies to date on genetic markers of members [48][49][50][51][52][53][54][55][56] of this signalling pathway have not shown definitive evidence of direct genetic risk (see Table 1). …”

Section: Mhc and Immunity Markersmentioning

confidence: 99%

Molecular genetics of microvascular disease in diabetic retinopathy

Warpeha

Chakravarthy

2003

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Lack of relationship between an insertion/deletion polymorphism in the angiotensin I-converting enzyme gene and diabetic nephropathy and proliferative retinopathy in IDDM patients

Cited by 94 publications

References 0 publications

Plasma N-terminal pro-brain natriuretic peptide as an independent predictor of mortality in diabetic nephropathy

Plasma N-terminal pro-brain natriuretic peptide as an independent predictor of mortality in diabetic nephropathy

Increased serum adiponectin levels in type 1 diabetic patients with microvascular complications

Molecular genetics of microvascular disease in diabetic retinopathy

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