Early Marker Of Diabetic Nephropathy Research Articles

Influence of snoring on microalbuminuria in diabetic patients

Obstructive sleep apnea (OSA) and snoring are known independent risk factors for insulin resistance. Microalbuminuria is an early marker of diabetic nephropathy and an independent risk factor for cardiovascular disease. The aim of our study was to search the prevalence of self-reported snoring and high-risk pre-test OSA diagnosis in diabetic patients and search the influence of snoring on microalbuminuria. A total of 237 diabetic patients (mean age, 58.6 ± 12.4 years; 126 males), were asked to complete the Berlin Questionnaire that includes questions about snoring, witnessed apnea, tiredness, history of high blood pressure and/or BMI < 30 kg/m(2). Also, their past and current medical records were reviewed for their medications, diabetic control, and complications like neuropathy, retinopathy, and microalbuminuria. According to the Berlin Questionnaire, a high pre-test probability for the diagnosis of OSA was found in 47.3% of the patients. Snoring was detected in 60.3% of the patients. The mean Epworth Sleepiness Scale score was 7.8 ± 4.6 and 31.6% of the patients reported excessive daytime sleepiness. We found that the both BMI and waist circumferences were significantly associated with snoring and high-risk pre-test OSA. There were no differences for age, gender, fasting glucose, HbA1c, and lipid panels between snorers and non-snorers, and between high-risk pre-test OSA and low-risk pre-test OSA patients. Microalbuminuria was significantly more common in patients who snore. Although snoring was independently associated with microalbuminuria, there were no differences between groups for other microvascular diabetic complications. Prevalence of OSA-related symptoms was very common in diabetic patients and further prospective studies are needed to elucidate the role of OSA's effect on diabetic control and complications.

Microalbuminuria in colorectal cancer

Background: Microalbuminuria has been found as a risk factor in many disorders. It is an early marker of diabetic nephropathy. Independent of diabetes, it means an increased risk for atherosclerosis, for cardiovascular diseases and for cardiovascular mortality. It also predicts all-cause mortality. Albuminuria has also been observed in individuals with different locations of cancers. Furthermore, it can be related to the patients' survival, to the efficacy of the treatment and in some cases to the disease extent, too. Aims: We have measured albuminuria by means of two different methodologies (immunoturbidimetry/IT/and high-performance liquid chromatography/HPLC/) to investigate whether elevated albumin-creatinine ratio (ACR) was associated with colorectal cancer (CRC) incidence, with clinical characteristics and with cancer stage. Patients and Methods: A cross-sectional study was carried out on 38 selected patients with CRC and 36 well-matched healthy volunteers, as controls. Urinary albumin excretion was measured by IT and HPLC, and ACR was calculated. Results: Patients with CRC had higher ACR compared to controls using both IT and HPLC (p&lt;0.05). ACR measured by HPLC was higher in both CRC and control groups than ACR measured by IT (p&lt;0.01). In CRC, we found a significant correlation between IT-ACR and red blood cell count (RBC) (r=–0.546; p=0.001), hematocrit (r=–0.389; p=0.030), blood urea nitrogen (r=0.368; p=0.042). We found a significant correlation between HPLC-ACR and RBC (r=–0.456; p=0.009), LDL-cholesterol (r=–0.411; p=0.022), triglyceride (r=–0.524, p=0.002), as well. IT- and HPLC-ACR did not correlate with cancer extent. Stepwise linear regression analysis was carried out in patients with CRC to find predictors of IT- and HPLC-ACR. Independent predictor of IT-ACR was RBC (β=–0.540; p=0.002) and independent predictor of HPLC-ACR was triglyceride (β=–0.466; p=0.014). Conclusions: Urinary ACR is a sensitive marker of CRC and it is not dependent on the cancer extent.

281: Urinary Excretion of Podocytes as an Early Marker of Diabetic Nephropathy

281: Urinary Excretion of Podocytes as an Early Marker of Diabetic Nephropathy

Increased Urinary Angiotensinogen Is Precedent to Increased Urinary Albumin in Patients With Type 1 Diabetes

BackgroundWe previously reported that kidney and urinary angiotensinogen levels were significantly increased before the development of diabetic nephropathy in diabetic rats. To address this system in humans, we have developed an enzyme-linked immunosorbent assay for human angiotensinogen and reported that urinary excretion of angiotensinogen levels is enhanced in patients with chronic kidney disease, including patients with type 2 diabetes. On the basis of these findings, this study was performed to demonstrate that urinary angiotensinogen levels increased before the onset of microalbuminuria and that urinary angiotensinogen can be an early biomarker of intrarenal renin-angiotensin system status in normoalbuminuric patients with type 1 diabetes compared with age- and sex-matched control subjects. MethodsThe study included 28 patients with type 1 diabetes and 21 control subjects. No subject received renin-angiotensin system blockades. Random spot urine samples as well as blood samples were obtained and analyzed. ResultsUrinary albumin:creatinine ratio or urinary protein:creatinine ratio did not increase in patients compared with control subjects, suggesting that these patients were in their premicroalbuminuric phase of diabetic nephropathy. However, the urinary angiotensinogen:creatinine ratio was significantly higher in patients than in control subjects (12.1±3.2μg/g versus 4.2±0.7μg/g). Importantly, an increase in plasma angiotensinogen levels was not observed (26.3±1.3μg/mL versus 29.5±3.3μg/mL). ConclusionsThus, in patients, an increase in urinary angiotensinogen levels is observed, and this increase is precedent to an increase in urinary albumin levels, suggesting that urinary angiotensinogen may function as an early marker of diabetic nephropathy.

Cystatin C and Cystatin Glomerular Filtration Rate as Markers of Early Renal Disease in Asian Indian Subjects With Glucose Intolerance (CURES-32)

The aim of this study was to assess cystatin C (cys-C) as a marker of early diabetic nephropathy and cystatin glomerular filtration rate (cys-GFR) in Asian Indians. Five groups of subjects were studied: Group 1, normal glucose tolerance (NGT) and normoalbuminuria (n = 43); group 2, impaired glucose tolerance (IGT) and normoalbuminuria (n = 44); group 3, type 2 diabetes (T2DM) with neither microalbuminuria nor retinopathy (n = 40); group 4, T2DM with microalbuminuria but without diabetic retinopathy (n = 40); and group 5, T2DM with microalbuminuria and any degree of diabetic retinopathy (DR) (n = 42). Subjects were recruited from the Chennai Urban Rural Epidemiology Study (CURES). Microalbumin concentration was assessed in the urine sample by immunoturbidometric assay. cys-C concentrations were measured in serum by a high-sensitivity particle-enhancing nephlometric assay. cys-GFR was calculated by the formula (86.7/cys-C) - 4.2. cys-C levels were highest in group 5 (1.75 +/- 0.12 mg/L) followed by group 4 (1.30 +/- 0.08 mg/L), group 3 (0.98 +/- 0.04 mg/L), group 2 (0.89 +/- 0.03 mg/L), and group 1 (0.79 +/- 0.18 mg/L, P < 0.001). cys-GFR levels were in reverse order going from highest in group 1, followed by groups 2, 3, 4, and 5. cys-C levels were correlated with age, fasting plasma glucose, glycosylated hemoglobin, microalbuminuria, and serum cholesterol. cys-C levels increase and cys-GFR levels decrease with increasing severity of glucose intolerance and are highest and lowest, respectively, in type 2 diabetes mellitus (T2DM) subjects with microalbuminuria and retinopathy. In T2DM subjects, cys-C and cys-GFR appear to be useful markers of early renal damage.

Albuminuria: What can we expect from the determination of nonimmunoreactive albumin?

Albuminuria is an early marker for diabetic nephropathy in patients with diabetes, and has a clear place in patient care. It also predicts cardiovascular events and mortality in diabetic patients and in the general population, and is slowly becoming accepted in population screening for cardiovascular disease and chronic kidney disease. Recently, investigators found that a considerable amount of albumin in urine is nonimmunoreactive and that classic immunochemical assays do not properly measure all albumin in urine. Assays that detect immunoreactive plus nonimmunoreactive albumin may better predict development of diabetic nephropathy, cardiovascular events, and mortality than assays that only detect immunoreactive albumin. Proof of the existence of nonimmunoreactive albumin emerged from the finding that albumin contains urine fragments. In this review, we critically appraise the presence and relevance of albumin fragments and nonimmunoreactive albumin molecules in urine, and the potential additive value of albuminuria detected by assays that assess nonimmunoreactive plus immunoreactive albumin over albuminuria detected by classic immunochemical assays in predicting end points.

C-Peptide: The Missing Link in Diabetic Nephropathy?

Proinsulin C-peptide has been found to exert beneficial effects in many tissues affected by diabetic microvascular complications, including the kidneys. Glomerular hyperfiltration and microalbuminuria are early markers of diabetic nephropathy. C-peptide at physiological concentrations effectively reduces diabetes-induced glomerular hyperfiltration via constriction of the afferent arteriole, dilation of the efferent arteriole, and inhibition of tubular reabsorption in experimental models of type 1 diabetes. The glomerular hypertrophy and mesangial matrix expansion seen in early diabetes can be reduced or prevented by C-peptide administration, possibly via interference with TGF-beta1 and TNFalpha signaling. Several of C-peptide's reno-protective effects have been confirmed in human studies; reduced glomerular hyperfiltration and diminished urinary albumin excretion have been documented in type 1 diabetes patients receiving replacement doses of C-peptide for periods of up to 3 months. In this review, we critically summarize the current state of knowledge regarding C-peptide's renal effects, and discuss possible mechanisms of its beneficial effects in diabetic nephropathy.

Microvascular Complications of Diabetes Mellitus: Renal Protection Accompanies Cardiovascular Protection

The microvascular complications of diabetes mellitus confer substantial morbidity and impair patient quality of life. Dyslipidemia and prolonged hyperglycemia promote an increase in oxidative stress, inflammation, and vascular damage, which together promote endothelial dysfunction and are associated with macrovascular and microvascular complications. Microalbuminuria is an early marker of diabetic nephropathy and an independent risk factor for cardiovascular disease. Diabetic nephropathy is the most common cause of end-stage renal disease in developed countries, and its prevalence is increasing. Preventing or limiting the progression of diabetic nephropathy, as demonstrated in the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) trial, may prevent or delay renal complications, as well as convey important cardioprotective benefits in patients with type 2 diabetes.

Urinary N-acetyl beta glucosaminidase and gamma glutamyl transferase as early markers of diabetic nephropathy.

Albumin and enzymes-N-acetyl-beta-glucosaminidase (NAG) and gamma glutamyl transferase (GGT) were estimated in the morning random urine samples of 196 albustix negative diabetic patients to evaluate the clinical utility of these urinary enzymes as early markers of diabetic nephropathy. Albumin was estimated by immunoturbidimetric method and enzymes by linetic essay within six hours of voiding of urine. The urinary albumin and urinary enzyme concentration was calculated in terms of ratio with respect to urinary creatinine. Correlation coefficient (r) bewween urinary albumin and urinary enzymes in normoalbuminuric, microalbuminuric and overall diabetic cases was 0.23, 0.32 and 0.40 respectively for NAG, and 0.08, 0.06 and 0.18 respectively for GGT. NAG excretion was found increased in 34%, 63.7% and 49.5% of normoalbuminuric, microalbuminuric and overall diabetic cases respectively while GGT in 6.4%, 24.5% and 15.8%. The correlation coefficient between urinary albumin and NAG in normoalbuminuric, microalbuminuric, and overall diabetic patients with increased NAG excretion was found only 0.31, 0.27 and 0.35 respectively. No correlation was found between duration of diabetes and enzyme excretion. The study suggests that urinary NAG or GGT or both together do not have any clinical significance as an early marker of diabetic nephropathy.

Urinary N-Acetyl B Glucosaminidase as an Earlier Marker of Diabetic Nephropathy and Influence of Low-Dose Perindopril/Indapamide Combination

Introduction. Tubulointerstitial injury is both a key feature of diabetic nephropathy and an important predictor of renal dysfunction. N-Acetyl B glucosaminidase (NAG) is derived from proximal tubular cells and is widely used to evaluate tubular renal function. Objective. The objective of this study is whether NAG can be used as an early marker of diabetic nephropathy by comparing the urinary NAG levels between healthy controls and diabetic patients and determining changes in urinary NAG excretion after treatment with low-dose combination perindopril (2 mg)/indapamide (0.625 mg)/o.d. Materials and Methods. A total of 50 patients (29 female) with type II diabetes mellitus applying to our diabetes outpatient clinics for the first time were included in our study (Group 1). Diabetic patients were classified into three subgroups on the basis of their duration of diabetes: Group 1A (n = 15) ≤3 years, Group 1B (n = 19) 3 to 5 years, and Group 1C (n = 16) >5 years. The inclusion criteria were no prior use of antihypertensive agents; blood pressure <130/85 mmHg; urinary albumin excretion <30 mg/day; and absence of renal failure, diabetietes, and hypertensive retinopathy. A total of 30 healthy individuals (16 female) (Group 2) were assessed as the control group. Systolic and diastolic blood pressures, HbA1c, body mass index, 24-h microalbuminuria (MAU), and NAG measurements in urine samples were performed by using colorimetric assay method in an analyzer (Roche Cobas Mira). The assay defined as fragmentation of 3-cresolsulfonphthaleinyl-N-acetyl-β-D-glucosaminide molecule by NAG to 3-cresolsulphonphthalein and N-acetylglucosamine molecules and serum creatinine were measured in all groups. Type II diabetic patients were administered perindopril (2 mg)/indapamide (0.625 mg) combination once daily for 4 months, and urinary NAG levels were measured at the end of treatment. Results. Statistically significant differences were observed between the groups 1 and 2 with respect to the levels of NAG and HbA1c (p < 0.05). In the treatment group, NAG levels decreased significantly (p < 0.05), whereas blood pressure and HbA1c levels did not change significantly (p > 0.05). In diabetic patients, pretreatment NAG were lowest in Group 1A and highest in Group 1C, although the difference between the treatment subgroups was not statistically significant (p > 0.05). Conclusion. Urinary NAG excretion is elevated in type II diabetic patients as compared with the healthy individuals. Perindopril/indapamide administration is effective in reducing urinary NAG excretion in these patients, and this effect seems to be independent from blood pressure and glycemia control. Presence of tubular proteinuria may be an early indicator of diabetic renal disease in patients without microalbuminuria. Perindopril (2 mg)/indapamide (0.625 mg)/o.d. treatment may have beneficial effect on the tubulointerstitial damage in diabetic kidney disease.

Fenofibrate reduces progression to microalbuminuria over 3 years in a placebo-controlled study in type 2 diabetes: Results from the Diabetes Atherosclerosis Intervention Study (DAIS)

Microalbuminuria is an early marker of diabetic nephropathy and an independent risk factor for cardiovascular disease. In the Diabetes Atherosclerosis Intervention Study (DAIS), treatment of people with type 2 diabetes with micronized fenofibrate for an average of 38 months reduced the progression of angiographically evaluated coronary artery disease and improved lipoprotein level abnormalities compared with placebo. The aim of this analysis is to study the influence of the treatment on changes in urinary albumin excretion. Microalbuminuria was measured on 2 to 3 occasions by using timed overnight samples at baseline and yearly thereafter in 314 DAIS participants (77 women, 237 men; average age, 56 years); all except 3 participants had either a normal albumin excretion rate (<20 microg/min; n = 214) or microalbuminuria (albumin, 20 to 200 microg/min; n = 97) before randomization. Tabulated shifts (between normal, microalbuminuria, and macroalbuminuria) from baseline to last observed values were compared between treatment groups by means of chi-square or Fisher's exact test. Fenofibrate significantly reduced the worsening of albumin excretion (fenofibrate, 8% versus placebo, 18%; P < 0.05). This effect was caused mostly by reduced progression from normal albumin excretion to microalbuminuria: 3 of 101 participants in the fenofibrate group versus 20 of 113 participants in the placebo group (P < 0.001). Overall, changes in albumin excretion were independent of age or changes in lipid or creatinine levels, weight, or blood pressure. Improvement in lipid profiles with fenofibrate in patients with type 2 diabetes was associated with reduced progression from normal albumin excretion to microalbuminuria.

The BErgamo NEphrologic DIabetes Complications Trial (BENEDICT): design and baseline characteristics

Microalbuminuria is an early marker of diabetic nephropathy and its prevention is considered key for the primary prevention of diabetic nephropathy. Angiotensin-converting enzyme (ACE) inhibitors and nondihydropyridine calcium channel blockers (CCBs) have specific renoprotective properties in diabetes, and preliminary evidence is available that they are more effective in combination than either of the two agents alone in limiting albuminuria either in micro- or macroalbuminuric type 2 diabetic patients. The BErgamo NEphrologic DIabetes Complications Trial (BENEDICT) is a prospective, randomized, double-blind parallel-group study primarily aimed at evaluating the possibility of preventing the progression to microalbuminuria (urinary albumin excretion [UAE] rate 20–200 μg/min, i.e., incipient nephropathy) in 1209 hypertensive, type 2 diabetic patients with a normal UAE rate (<20 μg/min). During phase A of the study, patients are randomized to a 3-year treatment with one of the following: (1) a nondihydropyridine CCB (verapamil SR 240 mg/day); (2) an ACE inhibitor (trandolapril 2 mg/day); (3) the combination of the above study drugs (verapamil SR 180 mg/day plus trandolapril 2 mg/day); or (4) placebo. Phase B of the study evaluates the progression to macroalbuminuria (UAE⩾200 μg/min) in patients who progress to microalbuminuria in phase A or are found with microalbuminuria during the screening phase; these patients are randomized to a 2-year treatment with either trandolapril (2 mg/day) alone or verapamil SR (180 mg/day) plus trandolapril (2 mg/day). BENEDICT final results are expected to be available by the end of 2003 for phase A and 2 years later for phase B. The BENEDICT study, in addition to exploring whether primary prevention of diabetic nephropathy is an achievable goal, will also offer an opportunity to study prospectively risk factors of nephropathy and other chronic complications of type 2 diabetes. Here we provide an overview of the protocol and summarize the main baseline demographic, biochemical, and clinical characteristics of randomized participants.

Dyslipidemia in patients with type 2 diabetes. relationships between lipids, kidney disease and cardiovascular disease.

Type 2 diabetes mellitus is a leading cause of morbidity and mortality. Cardiovascular disease (CVD) is the most prevalent complication and primarily accounts for the excess morbidity and mortality in diabetic patients, but microvascular complications, such as kidney disease and retinopathy, are frequent and contribute to the total disease burden. Lipid abnormalities in patients with type 2 diabetes are a major problem and associated with the increased risk of CVD. The most common pattern of dyslipidemia in these patients consists of elevated levels of triglycerides and low levels of high-density lipoprotein cholesterol. Low-density lipoprotein levels in these patients are often similar to that of the nondiabetic population, although there may be important qualitative differences in the pattern that contribute to the increased risk of CVD. Abnormal levels of urinary albumin occur in 30-40% of patients with type 2 diabetes and the presence of kidney disease enhances the mortality from CVD. Microalbuminuria, an early marker of diabetic nephropathy, is an independent risk factor for CVD. The increased levels of urinary albumin secretion may represent a more generalized vascular damage than renal microvascular injury alone. This Review focuses on the significance of diabetic dyslipidemia and microalbuminuria to CVD risk as well as to kidney complications. We also discuss the role of aggressive therapy to ameliorate vascular injury in the diabetic patient and reduce or prevent the cardiovascular and renal consequences of the disease.

Urinary N-acetyl-beta-D-glucosaminidase in children with diabetes as an early marker of diabetic nephropathy

We investigated urinary N-acetyl-beta-D-glucosaminidase [NAG] levels in children with type 1 diabetes as an early marker of tubular damage and studied its correlation with microalbuminuria and glycaemic control. The study group comprised 42 children with type 1 diabetes and 20 healthy children as control. Urinary NAG to urinary creatinine ratio, microalbuminuria, glycated haemoglobin [Hb A1c], blood urea and serum creatinine were estimated. Urinary NAG levels in the children with diabetes were significantly higher than those of controls. There were positive correlations between urinary NAG levels and microalbuminuria, Hb A1c and systolic and diastolic blood pressure values. We found that 59.5% of diabetic children were positive for urinary NAG, while 38.1% of them were positive for microalbuminuria.

Type IV collagen as an early marker for diabetic nephropathy in non-insulin-dependent diabetes mellitus

We measured urinary albumin (U-Alb) and type IV collagen (uIV·C) in spot urine collected from 82 patients with non-insulin-dependent diabetes mellitus (NIDDM) and 205 controls. Eighty-two NIDDM patients that had no increased excretion of either U-Alb or uIV·C were observed for 6 months. Prevalence of increased excretion of U-Alb and uIV·C at 6 months in these patients were 32.9%, and 62.2%, respectively. Increased excretion of uIV·C was detected in 27 patients without microalbuminuria. χ 2 analysis suggested that uIV·C was more sensitive than U-Alb, and that hypertension enhanced increased excretion of both U-Alb and uIV·C. uIV·C was significantly correlated ( P<0.01) with U-Alb but not glycosylated hemoglobin A1C (HbA1C) in NIDDM patients. Taken together, uIV·C may be a useful marker for early diabetic nephropathy.

Microalbuminuria, glomerular filtration rate, and dietary fat and protein intakes in type 1 diabetes

Dear Sir: We read with interest the cross-sectional study by Riley and Dwyer (1), who reported a positive association between microalbuminuria and dietary saturated fat intake and a negative association between microalbuminuria and dietary protein intake in people with type 1 diabetes. They also reminded us that protein intake might be involved in renal hyperfiltration preceding the loss of nephron units in type 1 diabetes (2). Glomerular hyperfiltration may be another early marker of diabetic nephropathy (3, 4). We previously studied the relation between dietary macronutrient intake and glomerular hyperfiltration in 110 patients with type 1 diabetes (5). The patients’ mean ( SD) age was 34.6 ∠ 11.2 y, their mean duration of diabetes was 13.9 ∠ 9.0 y, and their mean body mass index (in kg/m 2 ) was 22.9 ∠ 2.9. None had hypertension. Mean glycated hemoglobin was 8.3 ∠ 1.4%, or 0.083 ∠ 0.014 (normal: ≤ 5.6%, or ≤ 0.056). The glomerular filtration rate (GFR) was assessed by the plasma disappearance of 3.7 3 10 4 Bq [ 51 Cr]EDTA and corrected by 1.73 m 2 body surface area. Hyperfiltration was defined as a GFR > 137 mL · min 21 · 1.73 m 22 (mean value + 2 SDs of age-matched healthy subjects) (6). Food intake was recorded with a computer-assisted program (5). The distribution of dietary intake was similar to that observed by Riley and Dwyer (1): the percentage of energy from fat, protein, and carbohydrate, respectively, was 40.2 ∠ 7.2%, 18.2 ∠ 3.2%, and 41.6 ∠ 6.9%. Our cross-sectional study outlined a positive relation of both protein and fat intakes with GFR, indicating that subjects with type 1 diabetes with glomerular hyperfiltration ( n = 15) ingested higher amounts of protein (1.60 ∠ 37 compared with 1.38 ∠ 0.34 g · kg body wt 21 ·d 21 ; P = 0.032) and fat (1.70 ∠ 0.54 compared with 1.39 ∠ 0.44 g · kg body wt 21 ·d 21 ; P = 0.0022) than did patients with normofiltration, although total energy intake was not significantly different between the 2 groups. Saturated fat intake was significantly higher in the group with hyperfiltration ( P = 0.05), whereas no difference was found for polyunsaturated fat intake. Univariate regression analysis showed that GFR was positively related to both protein intake (r = 0.28, P = 0.003) and fat intake (r = 0.25, P = 0.007). In a stepwise multivariate regression analysis, fat intake was an independent determinant of GFR (F = 13.15, P ≤ 0.002), whereas protein intake no longer appeared to be so ( F = 1.36, P ≤ 0.08). No relation was found between dietary intakes and serum total cholesterol, HDL cholesterol, apolipoprotein A-I, apolipoprotein B, or serum triacylglycerol. Thus, we found an independent, positive relation between hyperfiltration and fat intake, suggesting that fat intake may play a role in the development of renal disease. Fifteen of the 110 patients had microalbuminuria (defined as a urinary albumin excretion rate of 30‐300 mg/24 h in ♢ 2 of 3 timed, overnight urine collections) (7). Protein (1.50 ∠ 0.45 compared with 1.40 ∠ 0.33 g · kg body wt 21 ·d 21 ; P = 0.30) and fat (1.25 ∠ 0.41 compared with 1.46 ∠ 0.47 g · kg body wt 21 ·d 21 ; P = 0.10) intakes were not significantly different between patients with microalbuminuria and patients with normoalbuminuria. However, the study was not designed as a case-control study with microalbuminuria as a selection criterion. The results from Riley and Dwyer (1) and our own study support the hypothesis that dietary fat intake may play a role in the development of nephropathy in patients with type 1 diabetes. Prospective followup studies are required to strengthen this hypothesis further.

Contribution of growth hormone and IGF-I to early diabetic nephropathy in type 1 diabetes.

In children and adolescents with type 1 diabetes, we have reported an association between duration of puberty and the prevalence of nephromegaly and microalbuminuria (MA), which are early markers of diabetic nephropathy. Growth hormone (GH), IGF-I, testosterone, and prorenin are potential mediators of this effect. This study examined the relationship of these hormonal factors to kidney volume (KV) and MA in 155 subjects (78 males, age 13.2 +/- 3.5 years [mean +/- SD]) with similar diabetes duration (6.83 +/- 1.6 years) but varying pubertal experience (0-10 years). KV (by ultrasound), plasma IGF-I, testosterone, prorenin, and NaLi countertransport, and urinary albumin, urinary GH, and urinary IGF-I from three 24-h collections were measured. Multiple regression analysis showed that BSA (P < 0.0001) and urinary IGF-I (P = 0.001) were significantly associated with KV. MA subjects (albumin excretion rate 15-200 microg/min) had higher urinary IGF-I (P = 0.005) and urinary GH (P = 0.05) compared with normoalbuminuric subjects. Only 9% of the variance in urinary IGF-I could be attributed to plasma IGF-I (r = 0.30, P < 0.0001). Testosterone and prorenin were not associated with MA, but they were associated with KV in univariate analyses. The strong association of urinary IGF-I with KV, a marker for glomerular hypertrophy, and of both urinary IGF-I and urinary GH with MA suggests a role for these growth factors in the development of human diabetic nephropathy. Together, these data support animal studies that have shown that renal GH and IGF-I may contribute significantly to the pathogenesis of early diabetic nephropathy.

Contribution of growth hormone and IGF-I to early diabetic nephropathy in type 1 diabetes

In children and adolescents with type 1 diabetes, we have reported an association between duration of puberty and the prevalence of nephromegaly and microalbuminuria (MA), which are early markers of diabetic nephropathy. Growth hormone (GH), IGF-I, testosterone, and prorenin are potential mediators of this effect. This study examined the relationship of these hormonal factors to kidney volume (KV) and MA in 155 subjects (78 males, age 13.2 ± 3.5 years [mean ± SD]) with similar diabetes duration (6.83 ± 1.6 years) but varying pubertal experience (0–10 years). KV (by ultrasound), plasma IGF-I, testosterone, prorenin, and NaLi countertransport, and urinary albumin, urinary GH, and urinary IGF-I from three 24-h collections were measured. Multiple regression analysis showed that BSA (P < 0.0001) and urinary IGF-I (P = 0.001) were significantly associated with KV. MA subjects (albumin excretion rate 15–200 μg/min) had higher urinary IGF-I (P = 0.005) and urinary GH (P = 0.05) compared with normoalbuminuric subjects. Only 9% of the variance in urinary IGF-I could be attributed to plasma IGF-I (r = 0.30, P < 0.0001). Testosterone and prorenin were not associated with MA, but they were associated with KV in univariate analyses. The strong association of urinary IGF-I with KV, a marker for glomerular hypertrophy, and of both urinary IGF-I and urinary GH with MA suggests a role for these growth factors in the development of human diabetic nephropathy. Together, these data support animal studies that have shown that renal GH and IGF-I may contribute significantly to the pathogenesis of early diabetic nephropathy.

J006 Urinary 92 kDa gelatinase excretion, a novel marker of early diabetic nephropathy in hypertensive type 2 diabetic patients : modulation by amlodipine or ACE inhibitor, captopril

J006 Urinary 92 kDa gelatinase excretion, a novel marker of early diabetic nephropathy in hypertensive type 2 diabetic patients : modulation by amlodipine or ACE inhibitor, captopril

Subtractive hybridization cloning: An efficient technique to detect overexpressed mRNAs in diabetic nephropathy Technical Note

Hyperfiltration, associated with kidney hypertrophy and hyperplasia, are early markers of diabetic nephropathy [1, 2]. Procedures for the identification of renal molecules potentially involved in this early process are of particular interest. In order to detect hyperexpression of major renal proteins in early diabetic nephropathy, we used the well-known model of streptozotocin (STZ)induced diabetes in rats [3] and a robust technique of subtracted hybridization between normal and diabetic kidneys [4 ‐ 6]. Two subtracted probes were elaborated after hydridization of diabetic rat kidney cDNA with control rat kidney mRNA. These probes were used to screen a diabetic rat kidney cDNA library. Two clones were overexpressed in diabetic rat kidneys and corresponded to the multi-drug resistance 1 (mdr 1) cDNA and to the b-amyloid protein precursor (bPP), respectively. This study describes the results of subtractive hybridization cloning in rats, as well as some data obtained in human kidney sections originating from diabetic patients.