Diabetic Nephropathy In Subjects Research Articles

Evaluation of the relationship between the prealbumin/fibrinogen ratio and diabetic nephropathy in patients with type 2 diabetes mellitus

<abstract><sec> <title>Introduction</title> <p>Our aim was to compare the prealbumin/fibrinogen ratio (PFR) of diabetic patient populations with or without diabetic nephropathy.</p> </sec><sec> <title>Materials and methods</title> <p>People with type 2 diabetes who attended the internal medicine outpatient clinic were enrolled in the study. Two groups were formed according to the proteinuria of the patients: Diabetic nephropathy and non-nephropathy group. Diabetic nephropathy was calculated using the mathematical formula of spot urine albumin/spot urine creatinine x100. Patients with proteinuria above 200 mg/g were considered to have nephropathy. PFR was simply calculated by dividing prealbumin by fibrinogen.</p> </sec><sec> <title>Results</title> <p>A total of 152 patients who attended our outpatient clinic were enrolled in the study. There were 68 patients in the diabetic nephropathy group and 84 in the non-nephropathy group. The prealbumin/fibrinogen ratios (PFR) were significantly lower in the nephropathic group [0.061 (0.02–0.16)] than the non-nephropathic group [0.0779 (0.01–0.75)] (p = 0.002).</p> </sec><sec> <title>Conclusions</title> <p>We suggest that decreased levels of PFR can indicate diabetic nephropathy in subjects with type 2 diabetes mellitus.</p> </sec></abstract>

Influence of the genetic polymorphism of haptoglobin in the occurrence of retinopathy and nephropathy in diabetics subjects

The objective of this study was to determine the frequency of haptoglobin (Hp) genotypes and their association with nephropathy and retinopathy in diabetic subjects. This is a case-control study conducted in diabetic subjects developing nephropathy and/or retinopathy. Each patient was matched to a control of the same sex and the same age ± 2 years. Hp genotyping was performed by conventional PCR without enzymatic digestion on the Proflex® System PCR (Biosystems, Spain) and the biochemical parameters were determined using enzymatic techniques with the Cobas c311 system (Roche Diagnostics, Switzerland). The study population consisted of 60 diabetic subjects with an average age of 56 years and a sex ratio of 0.43. The Hp2-2 genotype was more frequent in diabetic subjects (40%) compared to control subjects (28.3%) (p= 0.18). The distribution of Hp1-1 and Hp2-1 genotypes in diabetic subjects showed rates of 46.7 and 13.3% respectively. Multivariate analysis showed that the Hp 2-2 genotype was more associated with nephropathy (OR=1.77; p=0.8). These results showed an association between Hp polymorphism and diabetic microangiopathy. Thus, Hp2-2 genotype could be associated with a risk factor predisposing to the onset of diabetic kidney disease. Key words: Polymorphism, gene, haptoglobin, diabetes, nephropathy, retinopathy.

Experimental comparison of protective characteristics of enalapril and trimetazidine in diabetic nephropathy

Hyperglycemia, hypertension, dyslipidemia, and inflammation have been proposed to account for the development of nephropathy in diabetic subjects. The beneficial effects of enalapril on diabetic nephropathy are known. However, the effects of trimetazidine (TMZ) are still unknown. We aimed at comparing the effects of the enalapril and TMZ treatment on fibronectin expression, inducible nitric oxide synthase expression, urine proteinuria, blood glucose and glomerular, and mesangial structures of kidney in rats that take streptozotocin (STZ). In this study, 32 male Sprague–Dawley albino mature rats of 8 weeks, weighing 200–220 g were used. Diabetes was induced by intraperitoneal injection of STZ (60 mg/kg) for 24 rats. We made four groups (Group 1: control, non-diabetic rats (n = 8), Group 2: diabetes, without treatment (n = 8), Group 3: diabetes treatment with enalapril (n = 8), Group 4: diabetes treatment with TMZ (n = 8). The positive effects of renal tissue and tubules in the mesangium immunohistochemical were shown in TMZ receiving rat groups. These positive effects were in parallel with the reduction in fibronectin and I-NOS expression and reduction in the proteinuria. TMZ and enalapril treatment of diabetic rats and renal parenchyma in this study are shown to have positive effects on the different levels.

Fasting blood glucose--a missing variable for GFR-estimation in type 1 diabetes?

ObjectiveEstimation of glomerular filtration rate (eGFR) is one of the current clinical methods for identifying risk for diabetic nephropathy in subjects with type 1 diabetes (T1D). Hyperglycemia is known to influence GFR in T1D and variability in blood glucose at the time of eGFR measurement could introduce bias in eGFR. We hypothesized that simultaneously measured blood glucose would influence eGFR in adults with T1D.MethodsLongitudinal multivariable mixed-models were employed to investigate the relationships between blood glucose and eGFR by CKD-EPI eGFRCYSTATIN C over 6-years in the Coronary Artery Calcification in Type 1 diabetes (CACTI) study. All subjects with T1D and complete data including blood glucose and cystatin C for at least one of the three visits (n = 616, 554, and 521, respectively) were included in the longitudinal analyses.ResultsIn mixed-models adjusting for sex, HbA1c, ACEi/ARB, protein and sodium intake positive associations were observed between simultaneous blood glucose and eGFRCYSTATIN C (β±SE:0.14±0.04 per 10 mg/dL of blood glucose, p<0.0001), and hyperfiltration as a dichotomous outcome (OR: 1.04, 95% CI: 1.01–1.07 per 10 mg/dL of blood glucose, p = 0.02).ConclusionsIn our longitudinal data in subjects with T1D, simultaneous blood glucose has an independent positive effect on eGFRCYSTATIN C. The associations between blood glucose and eGFRCYSTATIN C may bias the accurate detection of early diabetic nephropathy, especially in people with longitudinal variability in blood glucose.

Differential effects of low-dose fenofibrate treatment in diabetic rats with early onset nephropathy and established nephropathy

We have previously shown that low-dose fenofibrate treatment has an ability to prevent diabetes-induced nephropathy in rats. We investigated here the comparative pre- and post-treatment effects of low-dose fenofibrate (30mg/kg/day p.o.) in diabetes-induced onset of nephropathy. Rats were made diabetics by single administration of streptozotocin (STZ, 55mg/kg i.p.). The development of diabetic nephropathy was assessed biochemically and histologically. Moreover, lipid profile and renal oxidative stress were assessed. Diabetic rats after 8 weeks of STZ-administration developed apparent nephropathy by elevating serum creatinine, blood urea nitrogen and microproteinuria, and inducing glomerular-capsular wall distortion, mesangial expansion and tubular damage and renal oxidative stress. Fenofibrate (30mg/kg/day p.o., 4 weeks) pretreatment (4 weeks after STZ-administration) markedly prevented diabetes-induced onset of diabetic nephropathy, while the fenofibrate (30mg/kg/day p.o., 4 weeks) post-treatment (8 weeks after STZ-administration) was less-effective. However, both pre-and post fenofibrate treatments were effective in preventing diabetes-induced renal oxidative stress and lipid alteration in diabetic rats though the pretreatment was slightly more effective. Conversely, both pre-and post fenofibrate treatments did not alter elevated glucose levels in diabetic rats. It may be concluded that diabetes-induced oxidative stress and lipid alteration, in addition to a marked glucose elevation, play a detrimental role in the onset of nephropathy in diabetic rats. The pretreatment with low-dose fenofibrate might be a potential therapeutic approach in preventing the onset of nephropathy in diabetic subjects under the risk of renal disease induction. However, low-dose fenofibrate treatment might not be effective in treating the established nephropathy in diabetic subjects.

Factors associated with diabetic nephropathy in subjects with proliferative retinopathy

The purpose was to compare the phenotype of subjects with type 2 diabetes mellitus having both retinopathy and nephropathy with that of subjects having retinopathy but no nephropathy. We recruited 196 subjects; 85 were normoalbuminuric (controls), whilst cases consisted of patients with micro- (n = 66) or macroalbuminuria (n = 45). Both groups underwent 24-h blood pressure (BP) monitoring and were analysed regarding markers of the metabolic syndrome, inflammation (erythrocyte sedimentation rate [ESR] and high-sensitivity CRP [hsCRP]) and insulin resistance (HOMA-IR). Cases had significantly higher white cell count (P = 0.02), ESR (P < 0.001), platelets (P = 0.02), triglycerides (P = 0.001), uric acid (P < 0.001), daytime and night-time systolic BP (P = 0.001 & P = 0.001, respectively), diastolic BP (P = 0.007 & P = 0.001), pulse pressure (P = 0.02 & 0.055) and mean arterial pressure (P = 0.001 & P < 0.001) in univariate analysis. Cases had a lower haemoglobin level (P = 0.01) and estimated glomerular filtration rate (eGFR) (P = 0.002) in comparison with controls. Multivariate analysis showed that night-time diastolic BP (P = 0.002, B = 1.057), platelet count (P = 0.018, B = 1.007) and eGFR (P < 0.001, B = 0.097) are independent predictors of diabetic nephropathy. Platelet count (P = 0.045, B = 1.006), night-time mean diastolic BP (P = 0.029, B = 1.042) and eGFR (P = 0.001, B = 0.975) were also found to be independent predictors of the occurrence of microalbuminuria. By analysing factors associated with diabetic nephropathy rather than microvascular disease in general, this study provides evidence that night-time diastolic BP and a relative increase in platelet count are associated with incipient diabetic nephropathy.

Prediction of Diabetic Nephropathy Using Urine Proteomic Profiling 10 Years Prior to Development of Nephropathy

We examined whether proteomic technologies identify novel urine proteins associated with subsequent development of diabetic nephropathy in subjects with type 2 diabetes before evidence of microalbuminuria. In a nested case-control study of Pima Indians with type 2 diabetes, baseline (serum creatinine <1.2 mg/dl and urine albumin excretion <30 mg/g) and 10-year urine samples were examined. Case subjects (n = 31) developed diabetic nephropathy (urinary albumin-to-creatinine ratio >300 mg/g) over 10 years. Control subjects (n = 31) were matched to case subjects (1:1) according to diabetes duration, age, sex, and BMI but remained normoalbuminuric (albumin-to-creatinine ratio <30 mg/g) over the same 10 years. Surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS) was performed on baseline urine samples, and training (14 cases:14 controls) and validation (17:17) sets were tested. At baseline, A1C levels differed between case and control subjects. SELDI-TOF MS detected 714 unique urine protein peaks. Of these, a 12-peak proteomic signature correctly predicted 89% of cases of diabetic nephropathy (93% sensitivity, 86% specificity) in the training set. Applying this same signature to the independent validation set yielded an accuracy rate of 74% (71% sensitivity, 76% specificity). In multivariate analyses, the 12-peak signature was independently associated with subsequent diabetic nephropathy when applied to the validation set (odds ratio [OR] 7.9 [95% CI 1.5-43.5], P = 0.017) and the entire dataset (14.5 [3.7-55.6], P = 0.001), and A1C levels were no longer significant. Urine proteomic profiling identifies normoalbuminuric subjects with type 2 diabetes who subsequently develop diabetic nephropathy. Further studies are needed to characterize the specific proteins involved in this early prediction.

YM440, a novel hypoglycemic agent, protects against nephropathy in Zucker fatty rats via plasma triglyceride reduction

The novel hypoglycemic agent, YM440 (( Z)-1,4-bis{4-[(3,5-dioxo-1,2,4-oxadiazolidin-2-yl) methyl] phenoxy}but-2-ene) is a ligand of the peroxisome proliferator-activated receptor, (PPAR) γ. YM440 has been shown to counteract insulin resistance in diabetic rodent models. However, it is not clear whether this compound has a significant effect on hyperlipidemia in vivo. Hyperlipidemia has been reported to be a risk factor for the early development of renal disease. The aim of this study is to examine the effects of chronic treatment with YM440 on hyperlipidemia and renal injury in obese Zucker fatty (ZF) rats. Treatment of 8-week-old ZF rats with YM440 (100 mg/kg/day) for 16 weeks decreased plasma triglyceride and cholesterol concentrations. YM440 markedly reduced the rate of progression of both albuminuria and proteinuria. YM440 normalized urinary N-acetyl-β- d-glucosaminidase (NAG) activity, which is a marker for renal proximal tubular damage, and ameliorated the rise in systolic blood pressure compared to the vehicle control. YM440 also blocked the development of nephromegaly. Histological analyses revealed that both glomerular area expansion and tubular cast accumulation gradually lessened in YM440-treated ZF rats. Regression analyses between the plasma triglyceride levels and the renal parameters (urinary protein excretion and albumin excretion) indicated that the renal parameters correlated positively with the plasma triglyceride levels. In conclusion, the hypolipidemic effects of YM440 prevent renal injury in ZF rats. YM440 might be useful for preventing the early development of diabetic nephropathy in subjects with type 2 diabetes by ameliorating metabolic control problems.

Urinary Albumin Excretion

During the past few years, a subtle increase in urinary albumin excretion (UAE) not detectable by routine methods, microalbuminuria, has become a prognostic marker for cardiovascular and/or renal risk in diabetic and nondiabetic subjects. Consequently, microalbuminuria assessment is now recommended in a risk stratification strategy not only in diabetic subjects but also for hypertension management. Microalbuminuria is defined as UAE from 30 to 300 mg/24 hours or equivalent amounts using timed overnight or spot urine samples (Table). The definition comes from studies that have established its value as a marker of risk for nephropathy in diabetic subjects. When the potential prognostic value of microalbuminuria on cardiovascular disease was being assessed in diabetic and nondiabetic populations, the threshold value pointing to an increment of risk was largely below the UAE value of 30 mg/24 hours regardless of the population studied.1 Dammsgard2 in an elderly population demonstrated that subjects with timed overnight UAE >7.5 μg/min had a higher mortality rate than those with lower values. Borch-Johnsen3 found, in a population-based cohort of 2085 consecutive subjects, the relative risk of ischemic heart disease associated with an spot urine albumin/creatinine ratio of only >0.65 mg/mmol was 2.3 when adjusted …

Microalbuminuria as a screening tool in cystic fibrosis-related diabetes

The improving longevity of cystic fibrosis (CF) subjects has resulted in an increased prevalence and duration of cystic fibrosis-related diabetes (CFRD). Microvascular complications were reported in CFRD. Microalbuminuria is well-established as a sensitive indicator of progression to diabetic nephropathy in non-CF diabetes, but confounding factors may make it less sensitive for CF subjects. We performed a cross-sectional study to look for the presence of microalbuminuria in samples from 40 CF subjects (34 without diabetes; CFND) attending the Exeter CF Clinic, compared with 43 nondiabetic, non-CF controls. The albumin-creatinine ratio (ACR) was raised in CF subjects both with (P < 0.001) and without (P < 0.0001) diabetes compared to controls. This reflected an increase in urinary albumin and a reduction in urinary creatinine in CF subjects. In single samples, microalbuminuria was present in 66.7%, 32.4%, and 15.4% of subjects in CFRD, CFND, and control groups. Repeat samples showed that 12% of CFND subjects and 17% of CFRD subjects met the criteria for a diagnosis of persistent microalbuminuria. In conclusion, CF subjects, even when not diabetic, have increased urinary albumin excretion due to chronic infection, and reduced urinary creatinine excretion due to low muscle mass. This results in subjects, who are not developing diabetic nephropathy, meeting the conventional criteria for microalbuminuria. We feel that further studies are required to clarify whether this measure is a useful tool to predict progression to diabetic nephropathy in subjects with CFRD.

Nitric oxide synthase gene polymorphisms and diabetic nephropathy.

Susceptibility to diabetic nephropathy in subjects with Type 1 diabetes is mainly genetically determined. Excess cardiovascular risk associated with diabetes is overwhelmingly concentrated in patients with nephropathy. Endothelial dysfunction is a feature of cardiovascular disease, hypertension, dyslipidaemia and smoking, all of which are associated with diabetic nephropathy. Nitric oxide regulates endothelial function and so genes encoding nitric oxide synthases could confer susceptibility to nephropathy. Recently positive associations have been reported. We examined polymorphisms within NOS3 and NOS2A, the genes encoding endothelial- and inducible nitric oxide synthase, for association with nephropathy. Large case-control studies of patients with Type 1 diabetes and overt nephropathy who had hypertension and diabetic retinopathy. The control group comprised Type 1 diabetic subjects who have been on insulin for 50 or more years and have an extremely low risk of nephropathy. Genotyping was by PCR and agarose- or automated polyacrylamide gel electrophoresis using fluorescence-labelled primers. NOS3 intron 4 genotype frequencies (n=860: 464 cases, 396 control subjects) were 2.6%, 23.3%, 74.1% and 2.3%, 22.7%, 75.0% for aa, ab and bb genotypes; p=0.935. NOS2A promoter genotype frequencies (n=715: 358 cases, 357 control subjects) were 0.3%, 16.8%, 83.0% and 0.3% 17.6% and 82.1% for +/+, +/- and -/- genotypes (p=0.952). In our cohort of Caucasian subjects with Type 1 diabetes there is no association between either of the polymorphisms studied and diabetic nephropathy. The previous suggestion from smaller studies that the intron 4 polymorphism in NOS3 could play a role in susceptibility to the disease is not confirmed.

Urinary alpha1-microglobulin as a marker of nephropathy in type 2 diabetic Asian subjects in Singapore.

This study examines urinary alpha(1)-microglobulin as a marker of early nephropathy in type 2 diabetic Chinese, Malays, and Asian Indians in Singapore. A cross-sectional study was performed on 590 consecutive type 2 diabetic patients (296 males, 294 females) who were on routine follow-up at a primary care clinic. Information was obtained from interviews, case notes, and blood and urine samples. Because the distribution of urinary alpha(1)-microglobulin levels was highly skewed, these levels were log-transformed, and geometric means were calculated. There was correction for variability in urine flow by dividing by urine creatinine levels, given as mg/mmol urine creatinine, and adjustment for confounding variables. Urinary alpha(1)-microglobulin was higher in men than in women and was directly related to age, but no ethnic differences were apparent. It was directly related to duration of diabetes, with adjusted geometric means of 1.19 and 1.43 mg/mmol urine creatinine for a duration of <10 and > or =10 years, respectively (P = 0.07). Urinary alpha(1)-microglobulin was highest in patients on insulin, followed by those on oral medication and then those on diet alone (adjusted geometric means: 1.47, 1.36, and 0.86 mg/mmol urine creatinine, respectively; P = 0.01). Levels were also higher in patients with poor glucose control, as measured by HbA(1c), fasting plasma glucose, and 2-h postprandial plasma glucose (P < 0.01 for each). Urinary alpha(1)-microglobulin was directly related to albuminuria, with adjusted geometric means for normoalbuminuria, microalbuminuria, and macroalbuminuria of 1.06, 1.47, and 4.72 mg/mmol urine creatinine, respectively (P < 0.01). However, of patients with normoalbuminuria, 33.6% had raised urinary alpha(1)-microglobulin. Likewise, of patients with normal urinary alpha(1)-microglobulin, 27.6% had albuminuria. Urinary alpha(1)-microglobulin was related to duration, severity, and control of diabetes. Urinary alpha(1)-microglobulin and albumin were directly related, but in some patients, one was present in the absence of the other. Hence, in addition to albuminuria (which measures glomerular dysfunction), urinary alpha(1)-microglobulin (which measures proximal tubular dysfunction) is useful for the early detection of nephropathy in diabetic subjects.

HOPE and MICRO-HOPE: review of the results and implications for people with diabetes

Cardiovascular disease remains the commonest cause of mortality in people with diabetes. Previous attempts to reduce the burden of heart disease in people with diabetes have tended to concentrate on the reduction of conventional cardiovascular risk factors, and less attention has been paid to wider aspects of cardiovascular disease in this group of people. The Heart Outcomes Prevention Evaluation (HOPE) study was a large, randomized trial with wide entry criteria which examined the hypothesis that ACE inhibition using ramipril would reduce cardiovascular events in patients at high risk who would not previously be treated with ACE inhibitors. Diabetes was a pre-defined subgroup, and over three thousand patients with diabetes were recruited who had evidence of vascular disease, or had diabetes and one other cardiovascular risk factor (cholesterol > 5.2, hypertension, microalbuminuria, smoking). The study was discontinued prematurely because of a significant reduction in the composite primary end-point of myocardial infarction, stroke, and death from cardiovascular disease. In the diabetic patients the primary event rate of the combination of myocardial infarction, stroke and cardiovascular death was reduced by a quarter in patients on ramipril, and this reduction was seen both in patients with and without previous cardiovascular disease. The benefit was greater than could be accounted for by the minor decrease in blood pressure, suggesting wider effects on the cardiovascular system. Ramipril also reduced the development of overt nephropathy in diabetic subjects with microalbuminuria. Ramipril should be considered for diabetic patients with existing cardiovascular disease, or who have a high risk of disease because of the presence of cardiovascular risk factors. Copyright 2001 Harcourt Publishers Ltd Copyright 2001 Harcourt Publishers Ltd doi: 10.1054/chec.2001.0111, available online at http://www.idealibrary.com on

Angiotensin II type 1 receptor gene polymorphism and the response to hyperglycemia in early type 1 diabetes.

Recent studies suggest that there is an association between the A1166-->C polymorphism of the angiotensin II type 1 receptor (AGT1R), glycemic control, and the risk of diabetic nephropathy in subjects with type 1 diabetes. Because hypertension and renal hemodynamic function are also related to the risk of diabetic nephropathy and because hyperglycemia can activate the renin angiotensin system, we sought to determine if there is an association between the AGT1R polymorphism, baseline renal and peripheral hemodynamic function, and pressor response to high glucose in subjects with early uncomplicated type 1 diabetes. There were 39 diabetic subjects genotyped for the AGT1R polymorphism by polymerase chain reaction and segregated into 2 groups: those with and those without the C1166 allele (AA and AC/CC). The average age was 27 +/- 1 years, and the mean duration of diabetes was 3.5 +/- 0.6 years. HbA(1c) values were <10% in all subjects and were similar in the 2 groups (8.2 +/- 0.3 vs. 9.1 +/- 0.4%). After a 7-day controlled diet (150 mmol sodium, 1.5-2.0 g x kg(-1) x day(-1) protein), renal hemodynamic function was assessed by inulin and para-aminohippurate clearance during clamped euglycemic conditions (4-6 mmol/l). Mean values for glomerular filtration rates did not differ between groups during euglycemia. In contrast, mean values for renal plasma flow and renal blood flow were significantly greater in the AC/CC group compared with the AA group. Values for mean arterial pressure were similar in the 2 groups, whereas renal vascular resistance was significantly reduced in the AC/CC group. In 20 subjects (10 from each genotype subgroup), hemodynamic function was assessed on a second occasion during controlled clamped hyperglycemia (9-11 mmol/l) after a similar preparatory period. In response to high glucose, plasma renin activity increased in both genotype groups to the same extent, but a pressor response was noted only in subjects with the C1166 allele. Mean arterial pressure increased significantly in the AC/CC subgroup and remained unchanged in the AA subgroup. We conclude that there is an association between the AGT1R A1166-->C polymorphism and renal hemodynamic function in early type 1 diabetes. But more importantly, the pressor response to hyperglycemia is augmented in those diabetic patients with the C1166 allele and may represent a factor that predisposes them to renal injury during periods of inadequate glucose control.

Nephropathy of type II diabetes: Evidence for hereditary factors?

Family studies point to an important genetic element in the genesis of diabetic nephropathy, but it is not known whether renal abnormalities are present prior to the onset of diabetes. To address this issue we examined all consecutive patients suffering from type II diabetes with a duration of more than 10 years who attended a diabetes outpatient clinic. Ninety-four patients had nephropathy, 307 did not. All offspring who were phenotypically normal (no hypertension, normal oral glucose tolerance, non-smoking) and agreed to participate were examined, 26 from nephropathic and 30 from non-nephropathic diabetic parents. They were compared with 30 offspring matched for age, gender and BMI from non-diabetic parents as controls. We measured urinary albumin excretion under baseline conditions and at several time points after ingestion of 300 g cooked beef and submaximal treadmill exercise, respectively. In addition, casual blood pressure, ambulatory blood pressure, urinary albumin and urinary alpha-1-microglobulin were measured. Primary renal disease was excluded by clinical examination. Under baseline conditions, median urinary albumin excretion rate (AER; microgram/min) was significantly (P < 0.005) higher in offspring of nephropathic type II diabetic patients (7.8; range 1.04 to 19.5) than in the offspring of non-nephropathic type II diabetic patients (4.8; 0.36 to 17.5) and controls (4.4; 0.16 to 18.4). Submaximal treadmill exercise caused a greater proportional increase of AER in offspring of nephropathic type II diabetics (median 16-fold) than in offspring of non-nephropathic diabetic patients (6.3-fold) or controls (4.8-fold). In offspring of nephropathic diabetic patients casual and particularly ambulatory systolic blood pressures were significantly higher, but AER was not correlated with blood pressure. In summary, higher values, albeit within the normal range, for baseline and postexercise albuminuria were noted in phenotypically normal offspring of parents with type II diabetes and nephropathy. The observation suggests that changes in transglomerular albumin traffic are demonstrable prior to the onset of diabetes and diabetic nephropathy in subjects with a potential genetic predisposition to these conditions.