| Diabetes mellitus (DM) is a common disease that seriously hurts people's health. According to the data from World Health Organization (WHO) and International Diabetes Federation (IDF) in 1999, there are about 130 million patients with DM around the world. It is expected that the number of patients could reach 300 million high in 2025. It is estimated that there are 20-30 million patients with DM and 30-40 million patients with impaired glucose tolerance (IGT) in our country. Approximately 40% of patients with type 1 DM and 5%~10% of those with type 2 DM will develop diabetic nephropathy (DN) usually 15 to 20 years after the onset of diabetes. DN is one of the most serious and common complications of diabetes and the major cause of end-stage renal failure. Several important mediators of DN, such as transforming growth factor-beta (TGF- P ), accumulation of the extracellular matrix (ECM), reactive oxygen intermediates and protein kinase C (PKC), have been proposed and comprehensively reviewed. The last 20 years have brought about a lucid realization that the vascular endothelium is not a mere barrier between intravascular and interstitial compartments. In fact, the vascular endothelium has received the status of an organ, albeit a widely spread one. Endothelial dysfunction plays a key role in the pathogenesis of diabetic vascular disease. Endothelin-1 (ET-1), the most potent endothelium-derived vasoconstrictor/mitogenic peptide and nitric oxide (NO), the endotheliurn-derived vasodilator have been implicated in the pathogenesis of DN.The tubulointerstitium damage is rather common in type 2 DM besides diabetic glomerusclerosis, even earlier than glomerulus damage and may contribute in acertain extent to the reduction of renal function. Urinary p2-microglobulin (02-MG) is a sensitive tubulointerstitium marker protein in diabetes.The changes of serum NO and 24 hours urinary NO excretion amount, plasma ET-1, 24 hours urinary albumin (Alb) excretion amount and 24 hours urinary Pa-MG excretion amount were observed in patients of various stages of DN and normal individuals. The purpose of this study is to evaluate the role of NO and ET-1 in the pathogenesis of DN and the value of urinary 02-MG in the early diagnosis of DN.Subjects and Methods: All patients with DM came from the First and Second Affiliated Hospital of Zhengzhou University and the Central Hospital of Zhengzhou city. Type 2 DM was diagnosed according to the criteria of American Diabetes Association (ADA) (1997). DM group consisted of 70 cases, 42 males and 28 females, age 31-79 years, mean age is 56.41 12.64 years, duration of diabetes from 1 week to 32 years, mean duration of diabetes is 8.10 6.12 years. 24 patients with type 2 DM were complicated with hypertension, all occurring after the onset of DM. The patients with type 2 DM were divided into three groups according to 24 hours urinary Alb excretion amount: 1. nil nephropathy (DM I, normoalbuminuria < 30mg/24h), 38 cases, 24 males and 14 females. 2. Incipient nephropathy (DM II, microalbuminuria 30-300 mg/24h), 20 cases, 13 males and 7 females. 3. Clinical nephropathy (DM]H, macroalbuminuria > 300 mg/24h), 12 cases, 5 males and 7 females. The patients with type 2 DM were divided into four groups according to the number of diabetic microvascular complications they had (including diabetic retinopathy, diabetic nephropathy, diabetic neuropathy): 1. The group without microvascular complications, 23 cases, 11 males and 12 females. 2. The group with one of the microvascular complications, 27 cases, 20 males and 7 females. 3. The group with any two of the microvascular complications, 10 cases, 5 males and 5 females. 4. The group with allthree of the microvascular complications, 10 cases, 6 males and 4 females. Subjectswere excluded if they had histories of liver, renal or heart disease, urinary system infection, other endocrinopathies, diabetic ketosis and other diabetic acute complications. Normal control (NC) consisted of 24 cases, 12 males and 12 females, age 40~68 years, mean age w...
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