2型糖尿病人微量白蛋白尿的转归及其危险因素的随访研究

目的研究2型糖尿病(T2DM)微量白蛋白尿(MAU)的转归及其危险因素。方法296例T2DM患者分为正常白蛋白尿(NAU)组和MAU组,分别测定尿白蛋白排泄率(UAER),分析其临床和生化特征,随访4.1年后复查上述指标。结果在(NAU)组中,维持NAU者占73.57%,进展至MAU者占24.28%,进展至大量白蛋白尿(MaAU)者占2.15%;而MAU组的病人中,回归NAU者占53.20%,维持MAU者占43.59%,进展至MaAU者占3.21%。根据UAER转归情况将所有的NAU和MAU的病人分为进展组和无进展组,比较2组病人有关临床资料可以发现,2组病人在舒张压、sCr、UA、CCr等方面差别有显著性,提示这些因素可能为UAER进展的危险因素。Logistic回归分析结果显示,舒张压、FPG、TG、LDL、HDL为UAER进展的独立危险因素。结论MAU并不是一个很好的预测和诊断早期糖尿病肾病的指标。     

Antibody induced injury to podocytes with proteinuria and foot process swelling in a transgenic (T16) mouse

T16 mice contain a human 3' untranslated sequence of the Thy 1.1 gene. Unlike normal mice they express Thy 1.1 protein on the podocytes which was immuno-localized to podocyte apical and basal plasma membranes and filtration slit. When monoclonal anti-Thy 1.1 antibody (OX7) was injected in nonproteinuric heterozygous mice there was rapid podocyte foot process swelling and proteinuria. Immunofluorescence showed granular glomerular OX7 binding at one hour. Progressive loss of pedicels occurred with 17.9 +/- 2.5, 14.4 +/- 1.1 and 10.5 +/- 3.5 per 10 nm glomerular basement membrane (GBM) remaining 1, 6 and 24 hours, respectively, after 1 mg OX7, vs 32.2 +/- 2.0 in T16 mice given saline. Twenty-four hour proteinuria was OX7 dose-dependent, peaked at 1-3 days and reduced to near basal levels 9-11 days thereafter. Proteinuria was nonselective except at very low doses (0.1 mg OX7) where microalbuminuria was seen. F(ab')2 OX7 administration also caused proteinuria in T16 mice. One milligram F(ab')1 OX7 caused diffuse foot process swelling without manifest proteinuria in T16 mice. Anti-Thy 1.1 IgM monoclonal antibody did not produce the effects of OX7 in T16 mice. Foot process swelling was not modified by histamine or 5-hydroxytryptamine antagonists. OX7 did not cause complement activation or leucocyte infiltration, hence glomerular injury appeared to be mediated directly by the antibody.     

Blood pressure control, microalbuminuria and cardiovascular risk in Type 2 diabetes mellitus.

Type 2 (noninsulin-dependent) diabetes mellitus (DM) affects about 3% of the UK population. Diabetes often coexists with a cluster of other potent cardiovascular risk factors, including hypertension, dyslipidaemia and increased tendency for thrombosis, and increases the risk of early death from cardiovascular causes by about threefold. Microalbuminuria or proteinuria also may be present, further increasing the risk of cardiovascular mortality. Cardiovascular risk factors must be treated aggressively in patients with Type 2 diabetes and control of blood pressure at 140/85 mm Hg or lower is a priority. The management of hypertension in patients from some ethnic groups demands special consideration because they have a high incidence of diabetes and hypertensive complications. Patients must be urged to adopt appropriate lifestyle changes in the first instance but additional drug treatment for hypertension is usually required. All the major classes of antihypertensive agents lower blood pressure in Type 2 diabetic patients but have different effects on metabolic risk factors in different ways. Low-dose thiazide diuretics, beta-blockers, calcium channel blockers and angiotensin converting enzyme (ACE) inhibitors have been shown to reduce cardiovascular risk. Individually, the effects of low-dose thiazide diuretics and beta-blockers on glucose and lipid metabolism is clinically insignificant, though in combination much larger metabolic effects are seen. ACE inhibitors and calcium channel blockers have no, or small, beneficial effects on glucose and lipid metabolism, while the greater beneficial effects of alpha1-blockers on lipid profiles may render them especially useful in the Type 2 diabetic patient. Long-acting calcium-channel blockers and ACE inhibitors protect renal function and are suitable as first line therapy in patients with microalbuminuria or proteinuria. Until results from the current batch of randomized, placebo-controlled trials comparing different classes of antihypertensive agents are available, the choice of antihypertensive agent is difficult. Addressing overall cardiovascular risk factors, rather than hypertension alone, is essential in the management of the hypertensive Type 2 diabetic patient.     

Baroreflex sensitivity is depressed in microalbuminuric Type I diabetic patients at rest and during sympathetic manoeuvres

Abstract Aims/hypothesis. To evaluate baroreflex sensitivity (BRS) in microalbuminuric and normoalbuminuric Type I (insulin-dependent) diabetic patients without autonomic neuropathy and in healthy control subjects. Methods. Microalbuminuric Type I diabetic patients (n = 15) were matched for age, sex, body mass index (BMI) and smoking habits with 15 normoalbuminuric patients and with 15 healthy control subjects. All subjects had a blood pressure less than 160/95 mmHg, a BMI less than 30 kg/m² and normal autonomic function on standard tests. Blood pressure and heart rate were measured non-invasively (Finapres) at rest and during sympathetic activation (handgrip, mental stress, standing). The baroreflex sensitivity was defined as the mean gain between blood pressure variability and heart rate variability in the 0.07–0.15 Hz frequency band. Results. Resting baroreflex sensitivity was decreased in the microalbuminuric patients (3.5 ± 0.4 ms/mmHg) compared with the normoalbuminuric patients and the healthy subjects (7.6 ± 1.6 and 9.5 ± 1.1 ms/mmHg, respectively, p < 0.001). The sympathetic tests reduced baroreflex sensitivity similarly in the groups without changing the between group differences. Conclusion/interpretation. Baroreflex sensitivity is reduced in Type I diabetic patients with microalbuminuria but without autonomic neuropathy. A prospective study should indicate whether this early abnormality in cardiovascular reflex function is a risk factor of cardiovascular mortality in these patients. [Diabetologia (1999) 42: 1345–1349] Received: 20 May 1999 and in revised form: 8 July 1999     

Urinary excretion of podocytes in patients with diabetic nephropathy.

BACKGROUND: Detection of podocytes in the urinary sediments of children with glomerulonephritis has been shown to indicate severe injury to the podocytes. The aim of the present study was to determine whether podocytes are present in the urine sediments of adult patients with diabetes with and without nephropathy and whether trandolapril is effective for podocyte injury. METHODS: Fifty diabetic patients (10 with normoalbuminuria, 15 with microalbuminuria, 15 with macroalbuminuria and 10 with chronic renal failure) and 10 healthy controls were studied. Urinary podocytes were examined by immunofluorescence using monoclonal antibodies against podocalyxin, which is present on the surface of podocytes. In addition, we studied plasma metalloproteinase (MMP)-9 concentrations in all patients. RESULTS: Urinary podocytes were absent in healthy controls, diabetic patients with normoalbuminuria and diabetic patients with chronic renal failure. Podocytes were detected in the urine of eight diabetic patients with microalbuminuria (53%) and of 12 patients with macroalbuminuria (80%). The number of podocytes in the urine of patients with macroalbuminuria was significantly greater than in patients with microalbuminuria (P:<0.01). However, there was no relationship between urinary albumin excretion and urinary podocytes. In addition, plasma MMP-9 concentrations were significantly correlated with the number of urinary podocytes (P:<0.01). Twelve diabetic patients with macroalbuminuria and eight patients with microalbuminuria who had urinary podocytes were treated with the angiotensin-converting enzyme inhibitor trandolapril. Urinary albumin excretion, the number of podocytes and plasma MMP-9 concentrations were reduced by the trandolapril treatment. CONCLUSIONS: Podocytes in the urine may be a useful marker of disease activity in diabetic nephropathy. Trandolapril may be effective for podocyte injury.     

Association between triglyceride-glucose index and chronic kidney disease: A cohort study and meta-analysis

Background and aimsNowadays, the relationship between triglyceride-glucose (TyG) index and chronic kidney disease (CKD) is still controversial. We aimed to prospectively investigate the relationship between TyG index and CKD in a cohort and meta-analysis.Methods and resultsA total of 10498 participants from the China Health and Retirement Longitudinal Study (CHARLS) were included. Participants were divided into four groups based on the quartiles of the TyG index. CKD was based on self-reported physicians’ diagnosis or personal eGFR level. A cox regression model was established to analyze the correlation between TyG index and CKD. A meta-analysis was conducted to incorporate the results of the current study and previous studies on the association of TyG index with CKD. In multivariable-adjusted analyses, the adjusted hazard ratio (95% confidence interval) for the highest versus lowest quartile of TyG index was 1.30 (1.08–1.57). Each 1-SD higher TyG index was associated with an increased risk of 11% (HR 1.11, 95% CI 1.03–1.19). The meta-analysis further confirmed the significant associations between TyG and CKD and pooled relative risk for highest vs lowest TyG index quartile was 1.47 (1.32–1.63).ConclusionsHigher TyG index was associated with increased risk of CKD, independently of established risk factors. The TyG index may be a predictor of incident CKD.