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P H Groop

Publications and source records attributed to P H Groop.

At least 19 recordsLinked to original sources
PubMed2007

Effect of physical activity and muscle morphology on endothelial function and arterial stiffness.

Physically active persons have a reduced risk of atherosclerotic disease. Arterial stiffness and endothelial dysfunction are important risk factors for cardiovascular disease. A high proportion of type I (slow-twitch) muscle fibers in skeletal muscle is associated with a favorable cardiovascular risk profile. We tested physical activity and muscle fiber-type distribution as determinants of endothelial function and arterial stiffness in middle-aged men. Fifty-four men (median age 58) who underwent a muscle biopsy in 1984 were re-studied in 2003. Aortic pulse wave velocity (PWV) and pulse wave reflection were assessed by applanation tonometry. Endothelial function was tested by examining the effects of salbutamol and nitroglycerin on pulse wave reflection. In multiple regression analyses aortic PWV (R2=0.51) correlated positively with age (P=0.017), BMI (P=0.001), and systolic blood pressure (P=0.004). A high augmentation index (R2=0.33) was associated with smoking (P<0.001), high LDL cholesterol (P=0.02), and elevated diastolic blood pressure (P=0.03). Impaired endothelial function (R2=0.37) was associated with high age (P=0.04), high LDL cholesterol (P=0.017), high triglycerides (P=0.027), and high physical activity (P=0.005). Muscle fiber-type distribution is not a determinant of arterial stiffness or endothelial function. Impaired endothelial function was observed in physically active men, underlining the need for further research.

Aged↗
PubMed2006

Novel sequence variants in the human xylosyltransferase I gene and their role in diabetic nephropathy.

AIMS: Decreased content of heparan sulphate proteoglycans (HSPGs) is a characteristic of the glomerular basement membrane (GBM) in diabetes and contributes to the development of diabetic nephropathy (DN). Xylosyltransferase I (XT-I) is the chain-initiating enzyme involved in the biosynthesis of HSPGs. This study investigated a possible association between XYLT-I sequence variants and susceptibility to DN. METHODS: Screening of all XYLT-I exons was performed in 74 caucasians with Type 1 diabetes (48 with and 26 without DN) and in 13 non-diabetic control subjects using denaturing high-performance liquid chromatography. RESULTS: Fifteen XYLT-I sequence variants were identified. Of these, six were previously unknown. There were significant differences in the allele frequencies of the three polymorphisms (c.343G-->T (p.A115S), IVS3+10C-->T, IVS3+30G-->C) in Type 1 diabetic patients and healthy controls. CONCLUSIONS: The occurrence of DN is independent of the XYLT-I variants detected in our study. However, three XYLT-I polymorphisms may be linked to Type 1 diabetes. Since we have previously proposed that one of these polymorphisms was not associated with Type 1 diabetes (Schön S et al. Kidney Int 2005; 68: 1483-1490), larger-scale analysis is clearly necessary to pinpoint the significance of this mutation.

Adult↗
PubMed2003

Glucose metabolism in relatives of type 1 diabetic patients with albuminuria.

OBJECTIVE: Diabetic nephropathy in type 1 diabetes is associated with familial aggregation of diabetes. In order to explore the mechanisms behind this association, we assessed glucose metabolism in glucose-intolerant relatives of type 1 diabetic patients with (ALB+) or without (ALB-) elevated urinary albumin excretion rate (UAER). METHODS: Glucose tolerance and insulin secretion were assessed using an oral glucose tolerance test (OGTT) and insulin sensitivity was measured with the short insulin tolerance test (ITT). RESULTS: One hundred and fourteen parents and siblings of 43 type 1 diabetic patients with ALB+ (UAER > or = 20 microg/min) were identified and 93 parents and siblings of 39 patients with ALB- (UAER < 20 microg/min). From this pool, a further selection was made of those (25 and 13 relatives of patients with ALB+ and ALB-, respectively) with mild abnormalities of glucose metabolism (fasting plasma glucose < 7.8 mmol/L; 2 h plasma glucose > or = 7.8 mmol/L in the OGTT). No difference in insulin sensitivity was discernible between the two groups of relatives (KITT 3.3 +/- 1.0 vs. 3.2 +/- 1.0%/min, p=NS). Although there were no significant differences in the incremental areas under glucose or insulin curves (AUC) between relatives of ALB+ and ALB- in the OGTT, the insulin secretory response to the rise in plasma glucose was impaired in relatives of patients with ALB+ (insulin AUC/glucose AUC: 7.1 [1.1-30.8] vs. 9.8 [3.6-52.2], p=0.039). CONCLUSIONS: Glucose-intolerant relatives of patients with elevated UAER seem to be characterized by impaired insulin secretion. Genetic or environmental factors related to impaired insulin secretion may be important in the development of diabetic nephropathy.

Adult↗
PubMed2001

Increased secretion of TGF-beta1 by peripheral blood mononuclear cells from patients with Type 1 diabetes mellitus with diabetic nephropathy.

AIMS: To study transforming growth factor (TGF)-beta1 secretion by peripheral blood mononuclear cells (PBMC) from Type 1 diabetic patients with and without nephropathy. METHODS: Thirty normoalbuminuric Type 1 diabetic patients (urinary albumin excretion rate (AER) < 20 microg/min), 12 microalbuminuric (AER 20-200 microg/min), 10 nephropathic (AER > 200 microg/min), and 13 non-diabetic individuals were recruited. TGF-beta1 secretion by PBMC was measured by enzyme immunoassay (EIA) after 48 h culture with and without phytohaemagglutinin (PHA) (5 microg/ml). RESULTS: After 48 h culture, the highest TGF-beta1 levels secreted by unstimulated PBMC were found in patients with nephropathy (median 6.2 (range 0.9-20.0) ng/ml) when compared to patients with normal albumin excretion (4.1 (0.2-11.3) ng/ml), microalbuminuria (1.8 (0.2-6.4) ng/ml) and healthy controls (1.0 (0.2-7.0) ng/ml); P = 0.02 for the three diabetic groups and P = 0.006 for all groups. At 48 h, the PHA-stimulated TGF-beta1 levels were 12.4 (2.9-30.0) ng/ml in nephropathic, 7.3 (0.5-21.2) ng/ml in normoalbuminuric, and 5.5 (0.5-27.6) ng/ml in microalbuminuric patients (P = 0.05). A correlation was observed between TGF-beta1 and diastolic blood pressure in the subgroup of patients with incipient and overt nephropathy (r = 0.45, P = 0.04). CONCLUSIONS: Type 1 diabetic patients with overt nephropathy show increased TGF-beta1 secretion by PBMC. Diastolic blood pressure levels correlated with TGF-beta1 secretion in diabetic patients with nephropathy. Increased TGF-beta1 secretion by PBMC may be associated with renal and vascular disease in Type 1 diabetes mellitus.

Adult↗
PubMed2000

Endothelial dysfunction in men with small LDL particles.

BACKGROUND: It is unknown whether LDL particle size is, independent of other lipids and lipoproteins, associated with endothelial dysfunction in vivo. METHODS AND RESULTS: We determined in vivo endothelial function in 34 healthy men by measuring forearm blood flow responses to intrabrachial artery infusions of acetylcholine (ACh, an endothelium-dependent vasodilator) and sodium nitroprusside (an endothelium-independent vasodilator). LDL peak particle size was measured with gradient gel electrophoresis. Men with small LDL particles (LDL diameter </=25.5 nm, n=10) had a 39% lower blood flow response to ACh than men with large LDL particles (LDL diameter >25. 5 nm, n=24, blood flow 6.9+/-3.6 versus 11.4+/-5.1 mL/dL. min, P=0. 006). The groups had comparable LDL cholesterol concentrations (3. 9+/-0.6 versus 3.7+/-1.0 mmol/L, men with small versus large LDL particles), blood pressure, glucose concentrations, and body mass indexes. LDL size (r=0.45, P=0.01) but not HDL cholesterol (r=0.31, P=0.09) or triglycerides (r=-0.19, P=0.30) was significantly correlated with endothelium-dependent vasodilation. Serum triglyceride concentrations and LDL size were inversely correlated (r=-0.44, P=0.01). In multivariate regression analysis, LDL size was the only significant determinant of the ACh-induced increase in blood flow. Sodium nitroprusside-stimulated endothelium-independent vasodilation was similar in both groups. CONCLUSIONS: Small LDL particles are associated with impaired in vivo endothelial function independent of HDL and LDL cholesterol and triglyceride concentrations. LDL size may therefore mediate adverse effects of hypertriglyceridemia on vascular function.

Acetylcholine↗
PubMed2000

Are diabetic patients in danger at renal transplantation? An invasive perioperative study.

It is assumed that diabetic patients with uraemia have more complications at renal transplantation than those who are not diabetic. We compared the preoperative ECGs, and invasive perioperative haemodynamic and oxygenation parameters in 15 diabetic and 15 non-diabetic uraemic patients undergoing renal transplantation. The number of patients with increased QT dispersion in the ECG was higher in diabetic than in non-diabetic patients (P<0.05). Before anaesthesia, heart rate and mean arterial pressure were higher (P<0.05) in the diabetic than in the non-diabetic group. After preanaesthetic volume loading all patients showed a hyperdynamic circulation, which subsided during anaesthesia. However, stroke volume index remained unchanged. Four patients in the diabetic group and six in the non-diabetic group needed additional oxygen therapy after surgery. No cardiac dysrhythmias were noted. However, the increased QT dispersion in diabetic patients calls for an adequate perioperative ECG monitoring for dysrhythmias. The diabetic and non-diabetic uraemic patients performed equally well at renal transplantation. In conclusion, renal transplantation for diabetics is justified.

Adult↗
PubMed2000

Albuminuria in nondiabetic relatives of IDDM patients with and without diabetic nephropathy.

BACKGROUND: In non-insulin-dependent diabetes mellitus (NIDDM), there is a clustering of an elevated urinary albumin excretion rate (U-AER) in nondiabetic relatives of albuminuric patients. Whether this is also the case in insulin-dependent diabetes mellitus (IDDM) is unknown. METHODS: Overnight U-AER was measured in 186 nondiabetic first-degree relatives of 80 IDDM patients with diabetic nephropathy (U-AER > 200 microg/min or 300 mg/24 hours; DN+) and in 52 relatives of 25 IDDM patients without nephropathy (U-AER < 20 microg/min; DN-). The two groups of relatives were comparable regarding gender distribution, age, obesity, blood pressure, prevalence of antihypertensive therapy, and smoking habits. RESULTS: No difference was found in overnight U-AER between relatives of patients with DN+ and DN- [median (range), 3.4 (0.1 to 372) vs. 4.0 (0.2 to 62) microg/min, respectively, P = NS]. The proportion of relatives with a U-AER = 10 microg/min was 12% in DN+ compared with 8% in DN- (P = NS). Among relatives of DN+, those with antihypertensive treatment (AHT+) had higher U-AER compared with those without [AHT+ vs. AHT-, 5.0 (0.5 to 372) vs. 3.4 (0.1 to 26.5) microg/min, P < 0.01], a phenomenon that was not seen among relatives of DN-[AHT + vs. AHT-, 3.6 (2.1 to 24.3) vs. 4.0 (0. 2 to 61.5) microg/min, P = NS]. However, this analysis was impaired by the small number of relatives of DN- with hypertension (N = 7). CONCLUSIONS: In IDDM, we found no clustering of elevated U-AER in nondiabetic relatives of patients with nephropathy. This is different from what has been reported in NIDDM, and suggests heterogeneity in the genesis of albuminuria in diabetes.

Adult↗
PubMed2000

No evidence of an exaggerated albuminuric response to physical exercise in non-diabetic siblings of type 1 diabetic patients with diabetic nephropathy.

Substantial evidence suggests a role for genetic factors in the development of diabetic nephropathy in both type 1 and type 2 diabetes. In support of this view, non-diabetic relatives of type 2 diabetic patients with nephropathy have been found to display abnormalities of urinary albumin excretion rate (AER) both when measured at rest and during physical exercise. The aim of the present study was to assess the albuminuric response to physical exercise in non-diabetic relatives of type 1 diabetic patients with nephropathy. AER was measured from urine collections performed (i) overnight, (ii) during an oral glucose tolerance test (OGTT), and (iii) during a submaximal bicycle ergometer test in 21 and 24 non-diabetic siblings of type 1 diabetic patients with (DN+; AER > 200 microg/min) and without diabetic nephropathy (DN-; AER < 20 microg/min). No difference was found in AER (median [range]) measured overnight (DN+ vs DN-: 3.8 [1.3-24.1] vs 3.5 [2.0-21.0] microg/min; P=NS), during the OGTT (DN+ vs DN-: 6.3 [3.2-26.0] vs 4.8 [1.9-15.7] microg/min; P = NS) or during the exercise test (DN+ vs DN-: 44.8 [7.0-535] vs 30.0 [3.4-1614] microg/min; P = NS). In conclusion, we found no evidence of an exaggerated albuminuric response to physical exercise in non-diabetic relatives of type 1 diabetic patients with nephropathy. This differs from previous findings in type 2 diabetes and may suggest differences in the mode of inheritance of albuminuria between type 1 and type 2 diabetes.

Adult↗
PubMed1999

The impact of a family history of Type II (non-insulin-dependent) diabetes mellitus on the risk of diabetic nephropathy in patients with Type I (insulin-dependent) diabetes mellitus.

AIMS/HYPOTHESIS: There is substantial evidence for a role of genetic factors in the development of diabetic nephropathy. In Pima Indians, a link between susceptibility to diabetic nephropathy and Type II (non-insulin-dependent) diabetes mellitus has been proposed. In this study, our aim was to examine the association between a family history of Type II diabetes and diabetic nephropathy in patients with Type I (insulin-dependent) diabetes mellitus. METHODS: In a cross-sectional case-control study, we assessed the prevalence of Type II diabetes in the parents of 137 Type I diabetic patients with diabetic nephropathy (albuminuria > 300 microg/min in two of three overnight urine collections) compared with the parents of 54 Type I diabetic patients without nephropathy (albuminuria < 20 microg/min). RESULTS: Thirty-four (25 %) of the patients with nephropathy compared with five (9 %) of the patients without nephropathy had a parental history of Type II diabetes (p = 0.019). A parental history of Type II diabetes was associated with a three-fold risk [odds ratio 2.95 (95% confidence interval: 1.03 to 8.40), p = 0.043] of diabetic nephropathy after adjustment for sex, glycaemic control and family history of hypertension. Furthermore, there was an excess of risk factors for development of Type II diabetes (higher fasting plasma glucose concentrations, higher prevalence of hypertension, higher waist-hip ratio and a tendency towards more glucose intolerance) among previously non-diabetic parents of patients with nephropathy. CONCLUSION/INTERPRETATION: Genetic or environmental factors or both related to familial Type II diabetes increase susceptibility to diabetic nephropathy in patients with Type I diabetes.

Adult↗
PubMed1999

N-acetyltransferase-2 polymorphism, smoking and type 1 diabetic nephropathy.

The N-acetyltransferase (NAT2) polymorphism has been suggested to be related to diabetic microvascular complications. To study the distribution of NAT2 genotypes in Caucasian type 1 diabetic patients with and without diabetic nephropathy, 214 adult type 1 diabetic patients and 53 healthy individuals were genotyped by polymerase chain reaction-restriction fragment length polymorphism. In addition, 75 young type 1 diabetic patients were genotyped, and 70 of them also phenotyped by caffeine. Of the adult patients, 83 had normal albumin excretion, 58 had microalbuminuria, and 73 had overt diabetic nephropathy. NAT2 allele frequencies were similarly distributed between the diabetic patients and healthy individuals: 0.29/0.2 5 (NAT2*4), 0.03/0.04 (NAT2*7B), 0.25/0.27 (NAT2*6A), and 0.43/0.44 (NAT2*5B), and within the diabetic subgroups. Because smoking is a known risk factor for diabetic nephropathy, nonsmoking and smoking patients were analysed separately. NAT2 allele frequencies differed significantly between the nonsmoking normoalbuminuric, microalbuminuric and nephropathic patients: 0.18/0.41/0.30 (NAT2*4), 0.04/0.00/0.02 (NAT2*7B), 0.35/0.18/0.17 (NAT2*6A), 0.43/0.41/0.50 (NAT2*5B), P = 0.013. In nonsmoking fast acetylators odds ratio for microalbuminuria and nephropathy was 3.1 (95% confidence interval 1.36-7.05), P = 0.007 by logistic regression. In smokers, a nonsignificant odds ratio was found [0.31 (95% confidence interval 0.08-1.2), P = 0.09]. Smoking is a strong confounding factor in relation to NAT2 analyses and diabetic nephropathy. According to our data, in nonsmoking type 1 diabetic patients fast NAT2 genotype implies an increased risk for diabetic nephropathy.

Adult↗
PubMed1999

In vivo endothelial dysfunction characterizes patients with impaired fasting glucose.

OBJECTIVE: The American Diabetes Association has recently defined a new category of abnormal glucose homeostasis called "impaired fasting glucose" (IFG), where glucose levels do not meet the criteria of diabetes but are too high to be considered normal. We determined whether endothelial dysfunction is a characteristic of subjects with IFG. RESEARCH DESIGN AND METHODS: In vivo vasodilatory responses to intra-arterial infusions of endothelium-dependent (acetylcholine [ACh]) and -independent (sodium nitroprusside [SNP]) vasoactive agents were determined in 17 IFG subjects (age 63 +/- 1 years, BMI 26.5 +/- 0.8 kg/m2, serum LDL cholesterol 3.5 +/- 0.2 mmol/l) with fasting plasma glucose levels of 117 +/- 1 mg/dl and in 12 subjects with normal fasting plasma glucose concentrations. RESULTS: The blood-flow response to the low dose of ACh was 46% (5.9 +/- 0.7 vs. 10.9 +/- 1.3 ml.dl-1.min-1, IFG vs. normal, P < 0.01) and to the high dose was 31% (9.1 +/- 1.2 vs. 13.2 +/- 1.5 ml.dl-1.min-1, P < 0.05, respectively) lower in the IFG than in the normal subjects. In contrast, blood-flow responses to both low (7.8 +/- 0.5 vs. 9.0 +/- 0.9 ml.dl-1.min-1, IFG vs. normal, NS) and high (11.6 +/- 1.2 vs. 12.3 +/- 1.3 ml.dl-1.min-1, NS, respectively) doses of SNP were comparable. The ratio of endothelium-dependent to -independent blood flow was 40% lower in the IFG (0.75 +/- 0.1) than in the normal (1.24 +/- 0.1, P < 0.001) subjects. Both fasting plasma glucose (r = -0.48, P < 0.01) and glycosylated hemoglobin (r = -0.42, P < 0.05) were inversely correlated with endothelium-dependent vasodilation but not with other parameters, such as weight, blood pressure, or lipids. CONCLUSIONS: We conclude that vascular dysfunction is associated with abnormal, although nondiabetic, glucose homeostasis.

Acetylcholine↗
PubMed1998

Risk factors for mortality in Type II (non-insulin-dependent) diabetes: evidence of a role for neuropathy and a protective effect of HLA-DR4.

To test the hypothesis that interaction between genetic, immunological, clinical and metabolic risk factors influences the outcome of Type II (non-insulin-dependent) diabetes mellitus, we examined which of the above factors present at baseline were associated with mortality in 134 Type II diabetic patients followed for 9 years. Thirty-eight patients (29%) died during the follow-up period; the majority of whom (68%) died from cardiovascular disease. At baseline, the deceased patients had higher HbA1c values (p = 0.002), higher LDL-triglycerides (p = 0.007), lower HDL-cholesterol (p = 0.007), higher non-esterified fatty acid (NEFA) concentrations (p = 0.014), and higher albumin excretion rate (p < 0.0001) than the patients who survived. In addition, the frequency of HLA-DR4 (21 vs 39%, p = 0.048) and of parietal cell antibodies (5 vs 14%, p = 0.016) were decreased in the deceased as compared to the living patients. Patients who died during follow-up also had more retinopathy (42 vs 16%, p = 0.002), neuropathy (57 vs 23%, p < 0.001), microalbuminuria (45 vs 6%, p < 0.0001), coronary heart disease (50 vs 13%, p < 0.0001), and peripheral vascular disease (27 vs 9%, p = 0.005) at baseline than patients who survived. In a multiple logistic regression analysis macroangiopathy (p = 0.004), neuropathy (p = 0.007), HbA1c (p = 0.018) and albumin excretion rate (p = 0.016) were independent risk factors for death. In patients free of cardiovascular disease at baseline, conventional risk factors such as LDL-cholesterol (p = 0.005) and age (p = 0.003) were associated with subsequent development of cardiovascular disease. In conclusion, in addition to coexisting macroangiopathy, increased albumin excretion rate, poor glycaemic control and neuropathy are risk factors for cardiovascular mortality in patients with Type II diabetes. The presence of HLA-DR4 and signs of autoimmunity may be associated with decreased risk of cardiovascular disease.

Adult↗
PubMed1998

Peritoneal dialysis access: a comparison of peritoneoscopic and surgical insertion techniques.

Prospectively collected data were analysed comparing 108 consecutive peritoneoscopically (n = 65) and surgically (n = 43) placed peritoneal dialysis catheters during a three-year period. Catheter-linked mechanical complications occurred more often in the peritoneoscopical group, and pericatheteral leakage ended in catheter loss in 13.8%. Overall probability of catheter survival in the peritoneoscopic group at 12, 24 and 36 months was 73%, 56% and 24%, and in the surgical group 87%, 87% and 66%, respectively (p < 0.05). Rates of infectious complications, peritonitis and exit site infections were similar.

Case-Control Studies↗
PubMed1998

Insulin resistance precedes microalbuminuria in patients with insulin-dependent diabetes mellitus.

BACKGROUND: Insulin resistance has been associated with hypertension and with renal complications in patients with type 1 diabetes mellitus. Causal relationships have not been fully explained. METHODS: We investigated whether insulin resistance precedes microalbuminuria by measuring insulin resistance with a euglycaemic clamp in combination with indirect calorimetry in 16 uncomplicated type 1 diabetic patients and in six healthy control subjects. The patients had over 10 year duration of diabetes, and were expected to experience either a complication-free or complicated disease course within the next few years. They have thereafter been followed for the development of microalbuminuria for 3 years. RESULTS: In a euglycaemic insulin clamp glucose disposal was lower in diabetic patients compared with control subjects (7.5 +/- 2.9 and 12.6 +/- 2.0 mg/kg LBM/min; P<0.002), mainly due to impaired glucose storage (4.3 +/- 2.3 vs 8.6 +/- 1.6 mg/kg LBM/min; P<0.001). Three years later seven IDDM patients had albumin excretion rate over 30 mg/24 h; glucose disposal (5.5 +/- 2.1 vs 9.0 +/- 2.2 mg/kg LBM/min; P<0.01) had been lower in patients who developed microalbuminuria compared with those who remained normoalbuminuric. CONCLUSIONS: Insulin resistance predicts the increment in urinary albumin excretion. Insulin resistance depends mainly on impaired glucose storage in uncomplicated IDDM.

Adolescent↗
PubMed1998

Mutations and variants of the epithelial sodium channel gene in Liddle's syndrome and primary hypertension.

Liddle's syndrome is a rare monogenic form of hypertension caused by truncating or missense mutations in the C termini of the epithelial sodium channel beta- or gamma-subunits. These mutations delete or alter a conserved proline-rich amino acid sequence referred to as the PY-motif. We report here a Liddle's syndrome family with a betaArg564X mutation with a premature stop codon deleting the PY-motif of the beta-subunit. This family shows marked phenotypic variation in blood pressure, serum potassium levels, and age of onset of hypertension. Given the similarity with primary hypertension, changes in the C termini of the beta- or gamma-subunits may contribute to the development of primary hypertension or to hypertension associated with diabetic nephropathy. Accordingly, the coding sequences for the cytoplasmic C termini of the beta- and gamma-subunits were screened for mutations with the use of polymerase chain reaction, single-strand conformation polymorphism, and direct DNA sequencing in 105 subjects with primary hypertension and 70 subjects with diabetic nephropathy. One frequent polymorphism was identified, but its frequency did not differ among subjects with primary hypertension, subjects with diabetic nephropathy, or control subjects. Two of the 175 subjects with primary hypertension or diabetic nephropathy showed variants that were not present in 186 control subjects. None of the variants changed the PY-motif sequence. In conclusion, a betaArg564X mutation is the likely cause of Liddle's syndrome in this Swedish family, but it is unlikely that mutations in the beta- and gamma-subunit genes of the epithelial sodium channel play a significant role in the pathogenesis of primary hypertension or diabetic nephropathy.

Adult↗
PubMed1998

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

Conflicting results have been reported on the relationship between familial predisposition to hypertension and development of diabetic nephropathy in IDDM. In our case-control study, we assessed the prevalence of hypertension among parents of 73 IDDM patients with diabetic nephropathy (DN+; persistent albuminuria > 200 microg/min or > 300 mg/24 h) and 73 IDDM patients without diabetic nephropathy (DN-; urinary albumin excretion < 20 microg/min or < 30 mg/24 h). Arterial hypertension, defined as antihypertensive therapy or a 24-h ambulatory blood pressure (SpaceLabs 90207) > or = 135/85 mmHg, was present in 57% of parents of DN+ patients compared with 41% of parents of DN- patients (P = 0.034; difference 16% [95% CI 1.3-29.6%]). In addition, the cumulative incidence of hypertension was higher among parents of DN+ patients (log-rank test P < 0.001), with a shift toward younger age at onset of hypertension in this group. However, the difference in prevalence of parental hypertension was not evident using office blood pressure measurements (64 vs. 57%; NS; difference 7% [-5.8-20%). Furthermore, patients with DN+ and with antihypertensive therapy in both parents were themselves more frequently treated for hypertension than were patients with DN+ and without parental treatment for hypertension (100 vs. 61%; P = 0.034; difference 39% [21-57%]). In conclusion, familial predisposition to essential hypertension increases the risk of diabetic nephropathy and may also contribute to the development of systemic hypertension in patients with IDDM and diabetic nephropathy.

Adult↗
PubMed1998

Predictors of progression from normoalbuminuria to microalbuminuria in NIDDM.

OBJECTIVE: Our objective was to establish the clinical, genetic, metabolic, and immunologic risk factors for the progression of the albumin excretion rate (AER) in normoalbuminuric NIDDM patients. RESEARCH DESIGN AND METHODS: We recruited 108 NIDDM patients with normal AER after a diabetes duration of 9 years to participate in a prospective 9-year follow-up. In addition to conventional clinical and metabolic variables, we assessed microvascular (retinopathy, nephropathy, neuropathy) and macrovascular (coronary heart disease, peripheral vascular disease) diabetic complications, genetic markers (HLA genotypes), and organ-specific autoimmune markers, including islet cell antibodies. Multiple logistic regression was used to determine independent predictors of progression of AER. RESULTS: A total of 21 patients (19%) died during the follow-up. There was an overrepresentation of men (61 vs. 39%; P = 0.044) and smokers (55 vs. 27%; P = 0.01) in patients who progressed to micro- or macroalbuminuria versus those who did not progress. In addition, progressors had higher fasting plasma glucose (P = 0.002) and HbA1 (P = 0.0002) concentrations at baseline than did nonprogressors. Neuropathy was more often seen in progressors than in nonprogressors at baseline (53 vs. 16%; P = 0.0004). Frequency of HLA genotypes and autoimmune markers did not differ between progressors and nonprogressors. In a multiple logistic regression analysis, HbA1 (P = 0.0005) and a history of smoking (P = 0.011) were independent predictors of progression of AER. CONCLUSIONS: This study reemphasizes the importance of poor glycemic control and smoking as independent risk factors for progression of AER. Furthermore, development of micro- or macroalbuminuria in NIDDM was associated with neuropathy and male sex.

Adult↗