In diabetes mellitus, thickening of basement membrane in capillaries and small vessels is a well-known finding and important in the progression of diabetic microangiopathy. We evaluated whether the plasma levels of type IV collagen and fibronectin, which are important factors of basement membrane, are related with the presence of diabetic microangiopathy. Plasma type IV collagen and fibronectin levels were measured in 40 healthy controls (Mean +/- SD, age; 50.3 +/- 5.5 yr) and 94 diabetic patients (age; 52.4 +/- 13.5 yr) with and without microvascular complications. The mean plasma levels of type IV collagen (5.3 +/- 2.9 ng/ml) and fibronectin (474.4 +/- 119.4 ug/ml) in diabetic patients were significantly higher (p < 0.01) than in healthy controls (3.7 +/- 1.3 ng/ml and 319 +/- 50.9 ug/ml). The mean plasma level of type IV collagen in diabetic patients with complications (6.6 +/- 3.7 ng/ml) was significantly higher (p < 0.01) than in those without complications (4.3 +/- 1.7 ng/ml) and became higher in more complicated patients. Furthermore, the severity of retinopathy and several indicators of nephropathy such as serum BUN, creatinine and proteinuria were closely associated with plasma type IV collagen level and a significant correlation was found between plasma type IV collagen and creatinine clearance (r = -0.31, p < 0.001). There was no significant difference in plasma fibronectin concentrations, however, between the diabetic patients with complications and those without complications.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult ; Aged ; Biological Markers/blood ; Blood Proteins/urine ; Blood Urea Nitrogen ; Collagen/*blood ; Creatinine/blood ; Diabetic Angiopathies/*blood/diagnosis ; Diabetic Nephropathies/blood/diagnosis ; Diabetic Retinopathy/blood/diagnosis ; Female ; Fibronectins/*blood ; Human ; Male ; Middle Age

Patients with diabetes mellitus (DM) are associated with an increased risk of thrombosis, and are susceptible to a series of complications including nephropathy. It has also been known that plasma tissue factor (TF) antigen levels increase significantly in certain disease states. To investigate the clinical significance of an association with the various complications in patients with type 2 non-insulin-dependent DM (NIDDM), we measured the plasma levels of TF antigen in 63 patients (35 males and 28 females, mean age 60.8 yrs) with NIDDM and in 22 normal subjects (14 males and 8 females, mean age 56.0 yrs). The mean concentrations of TF were higher for patients with NIDDM (253.7 +/- 144.9 pg/ml) than in normal subjects (187.3 +/- 108.7 pg/ml with marginal statistical significance (p= 0.0530). The TF levels were higher for patients with a nephropathy than for patients without a nephropathy (p=0.0402). There was a significant positive correlation between levels of TF and BUN (r=0.84, p < 0.0001) or creatinine (r=0.93, p < 0.0001). However, TF levels were found to be similar for both groups with and without thrombosis, neuropathy, retinopathy, or infection. These results suggest that plasma TF antigen levels may be associated with nephropathy and they may reflect a renal dysfunction in NIDDM.
Biological Markers ; Diabetes Mellitus, Type II/*blood/*diagnosis ; Diabetic Nephropathies/blood/diagnosis ; Diabetic Retinopathy/blood/diagnosis ; Female ; Human ; Infection/blood/diagnosis ; Male ; Middle Aged ; Support, Non-U.S. Gov't ; Thromboplastin/*metabolism ; Thrombosis/blood/diagnosis

PURPOSE:Urine examination for microalbuminuria during the clinical silent years can help to identify those patients most likely to progress to overt nephropathy. The normalization of the AER(Albumin Excretion Rate) by alteration of glomerular hemodynamics may be the key to preventing or delaying overt nephropathy. The prognostic and therapeutic implications have led to attempts to identify patients with microalbuminuria as early as possible.Because diagnosis of microalbuminuria has required a 12 or 24 hour urine collection,there has been interested in developing tests that might serve as a first-stage screen for microalbuminuria. Most reports have dealt with the usefulness of either the albumin concentration or the albumin/creatinine ratio in a timed or randomly collected urine specimen. Exercise induced albumin excretion is increased compared to resting and could unmask latent glomerular damage. The purpose of this study is to evaluate diagostic significance of urinary albumin measurement after exercise in children with insulin dependent diabetes. METHODS:Fifty-seven patients with IDDM collected their overnight urine from 22:00 to 6:00 in following morning. Exercised method for urine examination was 100M running and collected 2 hour urine after exercise. The AER and Albumin/ creatinine ratio(ACR) were measured in the urine and compared with before and after exercise. RESULTS:Mean ages of diabetic children was 13.7 yrs old and duration of diabetes was 4.1+/-2.7yrs, HbA1c 8.6+/-1.9%,Systolic BP 107+/-10mmHg and Diastolic BP 67+/-8mmHg. The exercise induced AER was increased compared to before exercise(10.3+/-10.5 vs 18.1+/-16.0 mg/24hr). The exercise induced ACR also increased too(1.4+/-1.5 mg/g.Cr vs 4.1+/-3.6mg/g.Cr)(P<0.01). Two(3.5%) children with IDDM was positive for microalbuminuria in terms of AER before exercise and 8 children(14%) after exercise. No one positive for microalbuminuria in terms of Alb/cr before and after exercise. The charateristics of 8 children with microalbuminuria after exercise was no specific difference between positive and negative microalbuminuria. There was specific correlation between microalbuminuria and HbA1c(P<0.05) but sex, ages, duration of diabetes & blood pressure were not correlated with incidence of microalbuminuria. CONCLUSION: The mean timed urinary albumin excretion after exercise was significantly higher than before exercise. Measurement of timed urinary albumin excretion after exercise will be helpful for detecting microalbuminuria earlier.
Blood Pressure ; Child* ; Creatinine ; Diabetes Complications ; Diabetes Mellitus, Type 1 ; Diabetic Nephropathies ; Diagnosis ; Hemodynamics ; Humans ; Incidence ; Insulin ; Running

Diabetic nephropathy is the leading cause of end-stage renal disease, and is associated with increased risk of cardiovascular disease. Optimal control of blood glucose and blood pressure based on the blockade of renin-angiotensin system is the standard of care for the prevention and treatment of diabetic nephropathy. Regardless of these therapies, the prevalence of diabetic nephropathy continues to increase, highlighting the need for additional therapies. Diabetes affects the progression of kidney disease through a variety of mechanisms; several new therapeutic agents targeting these pathways have been developed, with currently being evaluated in clinical trials.
Albuminuria ; Blood Glucose ; Blood Pressure ; Cardiovascular Diseases ; Diabetic Nephropathies* ; Diagnosis ; Kidney Diseases ; Kidney Failure, Chronic ; Prevalence ; Renal Insufficiency, Chronic ; Renin-Angiotensin System ; Standard of Care

Diabetic kidney disease is a microvascular complication of diabetes mellitus and the leading cause of end-stage renal disease resulting in renal replacement therapy. Approximately 30% to 40% of diabetic patients have diabetic kidney disease, which contributes to a significant increase in morbidity and mortality. Microalbuminuria is considered the gold standard for diabetic kidney disease diagnosis; however, its predictive value is restricted. Although blood glucose control, blood pressure control, and angiotensin converting enzyme inhibitors have been the primary treatment strategies, there are no definitive treatment modalities capable of inhibiting the progression of kidney dysfunction in these patients. This study was undertaken to answer seven questions regarding the various aspects of diabetic kidney disease. Why does it develop? what kind of factors affect its development? How is it diagnosed? What are its possible biomarkers? When is a kidney biopsy necessary? What are the preventive and therapeutic options? And what are the novel treatments?
Angiotensin-Converting Enzyme Inhibitors ; Biomarkers ; Biopsy ; Blood Glucose ; Blood Pressure ; Diabetes Mellitus ; Diabetic Nephropathies ; Diagnosis ; Humans ; Kidney ; Kidney Failure, Chronic ; Mortality ; Renal Replacement Therapy

BACKGROUND: Diabetic nephropathy is the main cause of the end-stage renal disease in Korea. This study was performed to evaluate the progression pattern and risk factors of diabetic nephropathy in type 1 diabetes patients. METHODS: Total 64 patients who were registered in Ajou University Hospital since April 1994 till April 2004 were enrolled. We retrospectively analyzed the influence of systolic and diastolic blood pressure, serum creatinine, total cholesterol, albumin, HbA1c and urine albumin excretion on the rate of decline in creatinine clearance (CCr) by Cockcroft- Gault equation. RESULTS: The patients (27 males/37 females), aged 32.8+/-9.1 (mean+/-SD) years, with a mean duration of diabetes of 9.5+/-4.9 years, were followed more than 6 months. CCr were 113.0+/-20 mL/min/1.73m2 at diagnosis and a mean decrease rate was 3.8+/-3.6 mL/ min/1.73m2/year. Doubling time of serum creatinine was 13.1+/-3.2 year in patients who developed doubling of their creatinine (26.6%). Microalbuminuria and overt proteinuria developed at 8.1+/-2.5 year and at 11.4+/-1.5 year after the diagnosis of type 1 diabetes respectively. A mean decrease rate of CCr was 6.1+/-2.9 mL/min/1.73m2/year in patients who develop ESRD after 14.2+/-2.8 years. During the follow up, systolic and diastolic blood pressure, serum total cholesterol were significantly higher and the mean serum albumin and creatinine clearance were significantly lower in chronic renal failure (CRF) group compared to non-renal failure (non-CRF) group (p< 0.05). There was no significant difference in HbA1c between CRF and non-CRF groups. CONCLUSION: The results may suggest that Korean type 1 diabetes patients with diabetic nephropathy in Ajou hospital have a rather faster decline in kidney function compared with other reports. But we need further prospective study to confirm this findings.
Blood Pressure ; Cholesterol ; Creatinine ; Diabetes Mellitus, Type 1 ; Diabetic Nephropathies* ; Diagnosis ; Follow-Up Studies ; Humans ; Kidney ; Kidney Failure, Chronic ; Korea* ; Proteinuria ; Retrospective Studies ; Risk Factors ; Serum Albumin

Diabetes is often associated with chronic kidney disease (CKD) and is the primary cause of kidney failure in half of patients who receive dialysis therapy. Given the increasing prevalence of diabetes and its high morbidity and mortality, diabetic nephropathy is a serious drawback in individual patients and a tremendous socioeconomic burden on society. Despite growing concern for the management of diabetic nephropathy, the prevalence of CKD with diabetes is the same today as it was 20 years ago. The current strategy to manage diabetic nephropathy, including the control of hyperglycemia, dyslipidemia, and blood pressure and the wide-spread use of renin-angiotensin-aldosterone system inhibitors, is well established to be beneficial in the early stages of diabetic nephropathy. However, the effects are uncertain in patients with relatively progressed CKD. Therefore, early diagnosis or risk verification is extremely important in order to reduce the individual and socioeconomic burdens associated with diabetic nephropathy by providing appropriate management to prevent the development and progression of this condition. This review focuses on recent research and guidelines regarding risk assessment, advances in medical treatment, and challenges of and future treatments for diabetic nephropathy.
Albuminuria ; Blood Pressure ; Diabetic Nephropathies* ; Dialysis ; Dyslipidemias ; Early Diagnosis* ; Glomerular Filtration Rate ; Humans ; Hyperglycemia ; Mortality ; Prevalence ; Renal Insufficiency ; Renal Insufficiency, Chronic ; Renin-Angiotensin System ; Risk Assessment

PURPOSETo review evidence-based management of nephropathy in patients with type 2 diabetes.

DATA SOURCESA literature search (MEDLINE 1966 to 2000) was performed using the key word "diabetic nephropathy". Relevant book chapters were also reviewed.

STUDY SELECTIONWell-controlled, prospective landmark studies and expert review articles on diabetic nephropathy were selected.

DATA EXTRACTIONData and conclusions from the selected articles that provide solid evidence to the optimal management of diabetic nephropathy were extracted and interpreted in light of our clinical research experience with many thousands of Hong Kong Chinese patients.

RESULTSHypertension, long diabetes duration, poor glycaemic control and central obesity are the most important risk factors. Microalbuminuria is a practical marker to predict overt nephropathy in type 2 diabetic patients. Risk factor modification, renal function monitoring and combined therapies are the current integrated approaches to manage patients with diabetic kidney disease. Optimal glycaemic control is the mainstay of treatment but effective antihypertensive therapy is also key to delaying the progression of diabetic nephropathy. Angiotensin-converting enzyme inhibitors and angiotensin II receptor antagonists have important renoprotective actions independent of their blood pressure lowering actions.

CONCLUSIONSDiabetic nephropathy is the leading cause of end-stage renal disease worldwide. Monitoring renal function and screening for microalbuminuria will allow the identification of patients with nephropathy at a very early stage for intervention. Tight glycaemic control and aggressive antihypertensive treatment as well as the use of renin-angiotensin system inhibitors should substantially delay the progression of nephropathy.

Albuminuria ; diagnosis ; therapy ; Blood Glucose ; analysis ; Diabetes Mellitus, Type 2 ; complications ; Diabetic Nephropathies ; epidemiology ; therapy ; Dietary Proteins ; administration & dosage ; Humans ; Hyperlipidemias ; therapy ; Hypertension ; therapy

OBJECTIVETo investigate the relationship of Chinese medicine syndrome pattern with urinary albumin excretion rate (UAER) and its related factors in patients with diabetic nephropathy (DN).

METHODSSixty-three early stage DN patients were subjected to the study, the Chinese medicine syndrome patterns were differentiated, and their condition of methylene tetrahydrofolate reductase (MTHFR) C677T mutation was detected (shown by gene polymorphism of 677 base pairs). Meantime, plasma levels of homocysteine (Hcy), folic acid, fasting and postprandial glucose (FG and PG), glycohemoglobin (HbA1c), blood lipids as well as UAER were measured.

RESULTSSyndrome pattern was differentiated as yin-deficiency with heat-flourishing in 17 patients, qi-yin deficiency in 24, and yin-yang deficiency in 22; while accompanied blood stasis syndrome (BSS) was found in 35. Gene polymorphism detection indicated that 19 patients were of CC-type, 17 of TT-type, and 27 of CT-type. Analysis showed that higher UAER level often revealed in patients with BSS, as compared with that in patients of non-BS pattern, the difference was statistically significant (P < 0.05). UAER levels in patients of different genotypes were insignificantly different (P > 0.05), but showed a linear regressive relation, namely positively correlated with Hcy level in patients of isogeneic type (r = 0.674, P < 0.05). No statistical significance was found between levels of UAER and other related factors (P > 0.05).

CONCLUSIONUAER level in early stage DN patients of BSS pattern is rather higher, and it shows a linear regression relationship (positive correlation) with Hcy level in patients of isogeneic type.

Adult ; Aged ; Albuminuria ; physiopathology ; Diabetic Nephropathies ; genetics ; physiopathology ; urine ; Diagnosis, Differential ; Female ; Homocysteine ; blood ; Humans ; Male ; Medicine, Chinese Traditional ; Methylenetetrahydrofolate Reductase (NADPH2) ; genetics ; Middle Aged ; Polymorphism, Genetic

BACKGROUND/AIMS: Many studies have demonstrated an association between hemoglobin levels and cardiovascular disease in diabetic patients. The aim of this study was to determine whether there is an association between hemoglobin concentrations and various clinical parameters, including metabolic factors, plasma C-peptide response after a meal tolerance test, and microvascular complications, in Korean patients with type 2 diabetes. METHODS: In total, 337 male patients with type 2 diabetes were recruited. All subjects were subjected to a meal tolerance test and underwent assessment of hemoglobin levels, fasting and postprandial beta-cell responsiveness, and microvascular complications. RESULTS: Patients with lower hemoglobin concentrations had a longer duration of diabetes, a lower body mass index, and lower concentrations of total cholesterol, triglycerides, and low-density lipoprotein cholesterol. They also had lower levels of postprandial C-peptide, Delta C-peptide, and postprandial beta-cell responsiveness. They had a higher prevalence of retinopathy and nephropathy. In multivariate analyses, there was a significant association between nephropathy and hemoglobin concentration. Also, hemoglobin concentrations were independently associated with Delta C-peptide levels and postprandial beta-cell responsiveness. CONCLUSIONS: Hemoglobin concentrations are associated with postprandial C-peptide responses and diabetic nephropathy in patients with type 2 diabetes.
Aged ; Biological Markers/blood ; Blood Glucose/metabolism ; C-Peptide/blood ; Cross-Sectional Studies ; Diabetes Mellitus, Type 2/*blood/diagnosis/epidemiology ; Diabetic Nephropathies/*blood/diagnosis/epidemiology ; Diabetic Retinopathy/*blood/diagnosis/epidemiology ; Hemoglobins/*metabolism ; Humans ; Insulin-Secreting Cells/metabolism ; Linear Models ; Lipids/blood ; Logistic Models ; Male ; Middle Aged ; Multivariate Analysis ; Odds Ratio ; Postprandial Period ; Prevalence ; Republic of Korea/epidemiology ; Risk Assessment ; Risk Factors