依那普利和硝苯地平控释片对早期糖尿病肾病合并高血压的疗效比较

目的　观察依那普利和硝苯地平控释片对早期糖尿病肾病合并高血压患者血压及尿白蛋白排泄率 (UAER)的影响。方法　随机将 44例病人分为 2组 :依那普利组 (10 mg,2次 /d,2 2例 ) ;硝苯地平控释片组 (30 mg,1次 /d,2 2例 )。疗程 6个月 ,观察治疗前后血压及 UAER的变化。结果　两组治疗后均能明显降低血压 (P <0 .0 1)及 UAER,由 90 .2和 86 .0分别降至 6 7.4和70 .8,下降 2 9.1%和 2 3.5 % ,P值均 <0 .0 1,但两组比较差异无显著性 (P>0 .0 5 )。两组治疗后U AER下降幅度与收缩压、舒张压下降幅度之间比较无显著相关性 (P值均 >0 .0 5 )。结论　依那普利和硝苯地平控释片均能有效降低血压 ,减少尿蛋白的排泄 ,保护肾脏功能     

Comparative effects of captopril versus nifedipine on proteinuria and renal function of type 2 diabetic patients.

Our study compared the effects of an angiotensin-converting enzyme inhibitor (captopril) versus a calcium antagonist (nifedipine) on proteinuria and renal function in patients with diabetic nephropathy. A randomized follow-up study was designed. Type 2 diabetic patients, with established diabetic nephropathy (proteinuria greater than 0.5 g/24 h), were treated with nifedipine (10 patients, group A) or captopril (10 patients, group B) for 6 months. Arterial blood pressure, metabolic parameters, proteinuria and renal function were measured and compared. Mean percentage differences for glomerular filtration rate, renal plasma flow and filtration fraction between the two groups were calculated. No significant differences were observed in serum glucose, glycosylated hemoglobin (hemoglobin A1c), Na+, K+ or albumin in either group or between groups. Blood pressure decreased significantly with both treatments and mean blood pressure was significantly lower in group A compared with group B at 6 months (Mann-Whitney U-test, P = 0.03). Proteinuria was similar in both groups at randomization, but after 3 and 6 months of treatment significant reductions were observed only in the group treated with captopril (P less than 0.01). A significant decrease in filtration fraction was observed in group B with an increase in group A (Mann-Whitney U-test, P = 0.03). Multiple regression analysis identified the therapeutic agent administered as an independent variable for decrease in proteinuria. It is concluded that antihypertensive treatment with captopril, but not with nifedipine, reduced proteinuria in patients with diabetic nephropathy, although a better mean blood pressure was obtained with nifedipine.(ABSTRACT TRUNCATED AT 250 WORDS)     

Increased levels of mannan-binding lectin in type 1 diabetic patients with incipient and overt nephropathy

Aims/hypothesis Diabetic nephropathy is associated with insulin resistance, and low-grade inflammation and activation of the complement system may contribute to this cascade. Mannan-binding lectin (MBL) activates the complement system, and elevated MBL concentrations have been observed in normoalbuminuric type 1 diabetic patients. The aim of this study was to assess whether MBL is associated with diabetic nephropathy in type 1 diabetes, and whether there is an association between MBL and low-grade inflammatory markers or insulin resistance.Methods A total of 191 type 1 diabetic patients from the Finnish Diabetic Nephropathy Study were divided into three groups based upon their AER. Patients with normal AER (n=67) did not take antihypertensive medication, while patients with microalbuminuria (n=62) or macroalbuminuria (n=62) were all treated with an ACE inhibitor. As a measure of insulin sensitivity we used estimated glucose disposal rate. MBL was measured by an immunofluorometric assay, C-reactive protein by a radioimmunoassay and IL-6 by high-sensitivity enzyme immunoassay.Results Patients with normal AER (median [interquartile range]: 1,154 g/l [180–2,202 g/l]) had lower levels of MBL than patients with microalbuminuria (1,713 g/l [724–2,760 g/l]; p=0.029) or macroalbuminuria (1,648 g/l [568–3,394 g/l]; p=0.019). There was a significant correlation between MBL and estimated glucose disposal rate, but not between MBL and C-reactive protein or IL-6 levels in univariate analysis. However, in a multiple regression analysis, HbA1c was the single variable independently associated with MBL (±SEM: 0.26±0.08; p=0.003).Conclusions/interpretation MBL concentrations are increased in type 1 diabetic patients with diabetic nephropathy. MBL was not associated with low-grade inflammatory markers.     

Dissociation of hypotensive and renal hemodynamic effects of an angiotensin converting enzyme inhibitor in insulin-dependent diabetic patients with incipient nephropathy

The mechanism of action of angiotensin converting enzyme (ACE) inhibitors on urinary albumin excretion (UAE) in diabetics is controversial. In order to dissociate the hypotensive and intrarenal effects, 16 insulin-dependant diabetics with permanent microalbuminuria (30-300 mg/24 h) without hypertension were given Ramipril, a long acting ACE inhibitor, at hypotensive (treatment A 5 mg/day; N = 8) and at sub-hypotensive doses (treatment B, 1.25 mg/day; N = 8) over a 6 week period in parallel double-blind study. Blood pressure, UAE, glomerular filtration renal blood flow (continuous 125I-Iodothalamate + 131I-Hippurate infusion) and converting enzyme activity (Liebermann's method), before and after treatment. In treatment group A, the blood pressure fell from 133 +/- 5/79 +/- 4 (mean +/- SE) to 125 +/- 4/77 +/- 2 mmHg (p less than 0.05 for systolic blood pressure) whereas it remained stable in treatment group B (132 +/- 7/79 +/- 4 to 128 +/- 5/80 +/- 4 mmHg). The UAE decreased in both groups: group A from an average of 74 (40-198) to 47 (5-202) mg/24 h (p = 0.07; group B, from an average of 77 (50-136) to 19 (15-120) mg/24 h (p less than 0.005), as did ACE activity: group A from 332 +/- 44 to 163 +/- 33 iu/l (p less than 0.004), group B from 423 +/- 39 to 191 +/- 28 iu/l (p less than 10-4).(ABSTRACT TRUNCATED AT 250 WORDS)     

Contrasting effects of lisinopril and nifedipine on albuminuria and tubular transport functions in insulin dependent diabetics with nephropathy.

An open, randomized, cross-over study was undertaken to assess the effects of lisinopril and nifedipine on albumin excretion, renal haemodynamics and segmental tubular reabsorption in overt diabetic nephropathy. The study consisted of a 4-week run-in period, a 3-week active treatment period, a 4-week wash-out period and a second 3-week active treatment period. Twelve patients with type 1 diabetes with albuminuria, mild to moderate hypertension and a serum creatinine level of less than 200 mumol l-1 were included. Lisinopril reduced albumin excretion from 1343 +/- 337 micrograms min-1 to 879 +/- 299 micrograms min-1 (P less than 0.01), whereas nifedipine was without effect, 1436 +/- 336 micrograms min-1 vs. 1319 +/- 342 micrograms min-1. Glomerular filtration rate (GFR) was unchanged by either drug. Both drugs increased effective renal plasma flow (ERPF) by about 20%. No differences between the drugs were observed with regard to their effect on renal haemodynamic parameters. By contrast, nifedipine exerted an inhibitory effect on several proximal tubular transport markers, whereas lisinopril was without effect. The different actions on tubular transport mechanisms exerted by lisinopril and nifedipine may contribute to the observed effect on albumin excretion.     

Contrasting renal functional reserve in very long-term Type I diabetic patients with and without nephropathy

AIMS: This study was to determine whether renal functional reserve (RFR) is present in patients who have suffered long-lasting Type I (insulin-dependent) diabetes mellitus. METHODS: Renal functional reserve was elicited by a 3-h amino acid infusion (4.5 mg x kg(-1) x min(-1)) in 10 patients with nephropathy (DN+) and 10 patients without nephropathy (DN-) who had lived with diabetes for 24 +/- 3 and 27 +/- 3 years, respectively and in 15 healthy control subjects. Renal functional reserve was calculated as the difference between amino acid-stimulated and baseline glomerular filtration rates (GFR). RESULTS: Baseline glomerular filtration rate in DN- patients (106 +/- 8) and control subjects (112 +/- 3 ml x min(-1) x (1.73m2)(-1)) was significantly higher (p < 0.01) than in DN+ patients (79 +/- 7 ml x min(-1) x (1.73m2)(-1)). Renal functional reserve was absent in DN+ patients, whereas it represented 26 +/- 4% of the baseline in DN- patients and 23 +/- 2% in control subjects. Renal vascular resistance decreased statistically significantly during amino acid infusion in DN- patients and control subjects but not in DN+ patients. CONCLUSIONS/HYPOTHESIS: These results indicate that very long-term Type I diabetic patients without diabetic nephropathy still have a normal renal functional reserve. In contrast, this reserve is suppressed in similarly long-term macroalbuminuric and hypertensive patients with overt nephropathy in spite of their remarkably maintained glomerular filtration rate. This opposite impairment supports the interpretation that glomerular hyperfiltration is a determining mechanism in human diabetic nephropathy.     

Predominantly vegetarian diet in patients with incipient and early clinical diabetic nephropathy: effects on albumin excretion rate and nutritional status.

Several studies have suggested that dietary protein quality may be an important determinant in the natural history of renal disease. We have therefore studied the effects of a predominantly vegetarian diet in eight patients with Type 1 diabetes mellitus and an albumin excretion rate (AER) in excess of 30 micrograms min-1. The AER was measured after an 8-week run-in period on the patient's usual diet, and again after 8 weeks of a predominantly vegetarian diet in which the proportion of vegetable protein was supplemented in order to minimize the reduction in total dietary protein intake. The median fractional albumin clearance fell during the study from an initial value of 188 x 10(-+) (range 58-810 x 10(-4)) at the end of the run-in period to 87 x 10(-4) (23-829 x 10(-4)) at the end of the period on low animal protein diet (difference 79 x 10(-4) (95% Cl 9-149 x 10(-4)), p less than 0.05). The AER then returned to values similar to those obtained at the beginning of the study after a further 8 weeks in those patients returning to their usual diet. No significant changes in blood glucose control or in arterial pressure were observed. A predominantly vegetarian diet may therefore have important beneficial effects on diabetic nephropathy without the need for a heavily restricted total protein intake.     

Comparison of 3 methods of measurement of blood pressure in insulin-dependent diabetic patients with or without incipient diabetic nephropathy]

Incipient diabetic nephropathy is characterized by a urinary albumin excretion (UAE) between 30-300 mg/24 h and a slightly elevated blood pressure. We measured blood pressure in 14 insulin-dependent diabetic subjects (IDDs) with persistent microalbuminuria (group A) and 50 IDDs with persistent normoalbuminuria (group B) using 3 different methods: 1) Sphygmomanometer, by a nurse, on supine position since 10 min, on the third day of hospitalization; 2) automatic device (Dinamap), on supine position, every 5 min, during 30 min; 3) ambulatory blood pressure (Spacelab 90202 every 15 min between 8 a.m. and 8 p.m.; values obtained with this last method were compared to the mean values of healthy subjects of same age. Recorded UAE was the median value of 3 twenty-four-hours urines. Blood pressure was not different among the two groups with any of the three methods: 1) SBP/DBP A: 136 +/- 14/81 +/- 9 vs B: 131 +/- 13/78 +/- 8 mmHg; ns; 2) SBP/MBP/DBP A: 134 +/- 17/96 +/- 12/79 +/- 10 vs B: 127 +/- 13/90 +/- 10/74 +/- 10 mmHg; ns; 3) A: 132 +/- 12/97 +/- 11/84 +/- 9 vs B: 127 +/- 11/91 +/- 9/82 +/- 12 mmHg; ns. There were no concordance between microalbuminuria/normoalbuminuria and systolic or diastolic blood pressure higher/lower than the mean of the healthy subjects (X2 = 1.6; ns). However, UAE was significantly related to MBP measured with 1): r = 0.29; p = 0.027, but not with 2): r = 0.24; ns, nor with 3): r = 0.26; ns. These results suggest that: 1-blood pressure of IDDs should be measured in standardized conditions; 2-diurnal ambulatory blood pressure recording does not predict incipient nephropathy in these subjects.     

Usefulness of captopril renography to predict the benefits of renal artery revascularization or captopril treatment in hypertensive patients with diabetic nephropathy

This retrospective study aimed to use captopril renography (CR) for predicting the benefits of captopril treatment in hypertensive patients with diabetic nephropathy. CR was utilized in 60 hypertensive patients with diabetic nephropathy for detecting the probability of renovascular hypertension (RVH) and predicting the benefits of renal artery revascularization or captopril treatment. Ten of the 60 patients showed a high probability of RVH with marked changes of the renogram curve after an oral intake of 50-mg captopril compared to baseline findings. All of the 10 patients confirmed significant main renal artery stenosis in all of them, bilaterally in four patients and unilaterally in the remaining six patients by renal angiographic findings. After successful revascularization, blood pressure was well controlled and renal function was preserved in all of the 10 patients. The other 50 patients showed a low or intermediate probability of RVH with normal findings or unchanged on CR after 50-mg captopril. Then, captopril alone or combination treatment started and continued on 50 patients. After monitoring for at least 6 months, blood pressure was well controlled and renal function was preserved in all the 50 patients on captopril treatment. We conclude that CR should be considered as the standard diagnostic criteria of RVH and may be helpful in predicting the beneficial impact of captopril treatment in hypertensive patients with diabetic nephropathy.     

Identifying patients with incipient diabetic nephropathy. Should 24-hour urine collections be used?

It is not clear whether 24-hour or overnight urine collections should be used to identify patients with incipient diabetic nephropathy (defined as persistent urinary albumin excretion rate [AER] of 20 to 200 micrograms/min). We therefore studied diurnal variations in AER in type I diabetics with normal AER (n = 16) and incipient (n = 12) and clinical (defined as persistent AER greater than 200 micrograms/min) nephropathy (n = 12), and in healthy controls (n = 24). In all groups AER was lowest at night. In some patients of all groups, marked diurnal variations were observed. Twenty-four-hour urine collections classified all patients correctly. Overnight urine collections, however, misclassified patients with incipient nephropathy as having normal AER in 4 of 12, 7 of 12, or 3 of 7 cases, depending on which cutoff level was used. We conclude that 24-hour urine collections are more sensitive than overnight samples in identifying patients with incipient diabetic nephropathy.     

Renoprotective effects of low-dose valsartan in type 2 diabetic patients with diabetic nephropathy

It is unknown whether the angiotensin receptor antagonist valsartan exerts a renoprotective effect on patients with type 2 diabetes and diabetic nephropathy independent of its hypotensive effects. Forty patients with type 2 diabetes participated in this study. All patients received valsartan 40 mg, a dose with no clinical effect on blood pressure levels. Blood pressure, urinary albumin excretion (UAE), and creatinine clearance were determined at baseline and at the end of the 6-month treatment period. Antihypertensive and/or antidiabetic drugs, including insulin, were permitted throughout the study. After 6 months of valsartan therapy, mean UAE decreased from 86.8 +/- 196 to 46.9 +/- 97 microg/min (n = 37). In addition, a significant decrease was observed in the UAE of the subgroup of patients displaying diabetic nephropathy (UAE > 20 microg/min, n = 14), from 219.4 +/- 275 to 102.7 +/- 141 microg/min, (P < 0.01). Changes in UAE for valsartan correlated significantly with UAE at baseline (r = -0.935, P < 0.0001). Serum creatinine levels and creatinine clearance remained stable before and after treatment with valsartan. No significant differences were observed between pre- and post-treatment body mass index, glycosylated hemoglobin, or systolic and diastolic blood pressure. In type 2 diabetic patients with diabetic nephropathy, 6 months of treatment with low dose valsartan, an angiotensin-II receptor antagonist, thus reduced UAE with no reduction in systemic blood pressure. The drug may be safely administered in this subset of type 2 diabetic patients. The long-term benefits in terms of risk reduction must still be evaluated in further trials.     

Long-term treatment with nifedipine reduces urinary albumin excretion and glomerular filtration rate in normotensive type 1 diabetic patients with microalbuminuria

The aim of the present study was to investigate the renal effects of long-term treatment with the calcium channel blocker nifedipine in normotensive type 1 diabetic patients with microalbuminuria. In a randomized, double-blind trial, 15 type 1 diabetic patients were treated with either nifedipine (n=8; dosage 30 mg/day) or placebo (n=7) for 12 months. At baseline and after 6 and 12 months of therapy, the albumin excretion rate (UAER, radioimmunoassay), glomerular filtration rate (GFR, chromium 51 ethylenediamine tetra-acetic acid clearance) and renal plasma flow (RPF, iodine 125 hippuran clearance) were determined. Nifedipine treatment caused a significant reduction of UAER after 6 and 12 months (median, Q₁/Q₃ in mg/24 h): baseline 84 (65/163); 6 months 35 (23/90),P<0.02; 12 months 39 (15/79),P<0.05. GFR was significantly decreased by nifedipine treatment (baseline 157±15, 6 months 122±8, 12 months 111±47 ml/min;P<0.05, mean ± SEM), whereas RPF remained constant. Nifedipine treatment did not influence systolic (baseline 121±7, 12 months 124±2 mmHg, mean ± SEM) or diastolic (baseline 72±2, 12 months 74±3 mmHg) arterial blood pressure. With placebo treatment no significant alterations of UAER, GFR, RPF and arterial blood pressure were observed. Metabolic control was constant throughout the whole study period. Thus, 1 year's treatment with nifedipine reduces the UAER and GFR in normotensive type 1 diabetic patients without influencing the systemic arterial blood pressure. The data, however, do not present a recommendation for the general use of nifedipine in these patients as the exact intrarenal mechanism of calcium channel blockers in humans remains to be established.     

Beneficial effects of C-peptide on incipient nephropathy and neuropathy in patients with Type 1 diabetes mellitus.

AIMS: Recent studies have indicated that proinsulin C-peptide shows specific binding to cell membrane binding sites and may exert biological effects when administered to patients with Type 1 diabetes mellitus. This study was undertaken to determine if combined treatment with C-peptide and insulin might reduce the level of microalbuminuria in patients with Type 1 diabetes and incipient nephropathy. METHODS: Twenty-one normotensive patients with microalbuminuria were studied for 6 months in a double-blind, randomized, cross-over design. The patients received s.c. injections of either human C-peptide (600 nmol/24 h) or placebo plus their regular insulin regimen for 3 months. RESULTS: Glycaemic control improved slightly during the study and to a similar extent in both treatment groups. Blood pressure was unaltered throughout the study. During the C-peptide treatment period, urinary albumin excretion decreased progressively on average from 58 microg/min (basal) to 34 microg/min (3 months, P < 0.01) and it tended to increase, but not significantly so, during the placebo period. The difference between the two treatment periods was statistically significant (P < 0.01). In the 12 patients with signs of autonomic neuropathy prior to the study, respiratory heart rate variability increased by 21 +/- 9% (P < 0.05) during treatment with C-peptide but was unaltered during placebo. Thermal thresholds were significantly improved during C-peptide treatment in comparison to placebo (n = 6, P < 0.05). CONCLUSION: These results indicate that combined treatment with C-peptide and insulin for 3 months may improve renal function by diminishing urinary albumin excretion and ameliorate autonomic and sensory nerve dysfunction in patients with Type 1 diabetes mellitus.     

Adiponectin gene polymorphism (G276T) is not associated with incipient diabetic nephropathy in Japanese type 2 diabetic patients

A single-nucleotide polymorphism (SNP) G276T in the adiponectin gene has been associated with lower plasma adiponectin levels and insulin resistance, which are related to the prevalence of type 2 diabetes or diabetic complications of macroangiopathy. We performed a case-control study to examine whether the SNP276 of the adiponectin gene was also related to early diabetic nephropathy. SNP276 was examined with genomic DNA obtained from 108 type 2 diabetic patients with microalbuminuria (urinary albumin creatinine ratio [ACR] between 30 mg/g x Cr and 300 mg/g x Cr; case subjects), and 208 patients with normoalbuminuria (ACR < 30 mg/g x Cr; control subjects). The genotype distribution and G allele frequency of SNP276 in the case subjects (0.71) did not significantly differ from the control subjects (0.69). There were no differences among the genotypes of the adiponectin gene regarding age, duration of diabetes, body mass index (BMI), hemoglobin A(1c) (HbA(1c)), serum lipids, serum creatinine, and plasma adiponectin levels. These data suggest that SNP276 of the adiponectin gene is not an independent risk factor for incipient diabetic nephropathy in Japanese type 2 diabetic patients.     

The haemodynamic effects of intravenous nifedipine in normotensive and hypertensive subjects

The antihypertensive effects of intravenous nifedipine, given by bolus and 2 hour infusion, were studied at two dose levels in seven hypertensive (mean BP 178/114 mmHg) and five age-matched normotensive controls (mean BP 128/81 mmHg). Nifedipine significantly reduced systolic and diastolic blood pressure in the hypertensive patients by approximately 20%, but not in the normotensive controls. Similar changes in heart rate and forearm blood flow were seen after bolus injection in both groups, but these were not sustained during infusion. Intravenous nifedipine may be a useful acute treatment for hypertensive emergencies.     

同型半胱氨酸与2型糖尿病合并早期肾病的关系

目的　探讨同型半胱氨酸 (Homocysteine,Hcy)与 2型糖尿病病人合并早期糖尿病肾病的关系。方法　应用高效液相色谱分析法测定 6 7例 2型糖尿病病人和 4 7例正常人的血浆 Hcy水平 ,并同步检测可溶性血栓调节蛋白(s TM)、叶酸和维生素 B1 2 。结果　 2型糖尿病病人血浆 Hcy水平明显高于对照人群 (15 .2 7± 6 .0 4 μmol/L vs12 .10± 1.86 μmol/L;P<0 .0 1) ,而合并早期糖尿病肾病的血浆 Hcy水平又高于无糖尿病肾病患者 (17.86± 8.0 4 μmol/L vs13.83± 4 .0 0 μmol/L;P<0 .0 1) ;存在高 Hcy血症的糖尿病病人 ,其早期糖尿病肾病发生率明显高于无高 Hcy血症患者(5 2 .0 % vs2 6 .2 % ;P<0 .0 5 ) ,且前者存在着较高水平的 s TM(P<0 .0 5 )。结论　高 Hcy血症与 2型糖尿病早期肾病的发病有关 ,其机制可能是通过血管内皮损伤所致