正常血压Ⅱ型糖尿病患者尿微量白蛋白多因素分析

应用多因素逐步回归的分析方法对７０例正常血压Ⅱ型糖尿病患者有关微量尿白蛋白排泄率（ＵＡＥＲ）的危险因素，包括年龄、体重指数（ＢＭＩ）、病程、收缩压、舒张压、空腹血糖（ＦＢＧ）、糖化血红蛋白（ＨｂＡ１ｃ）、红细胞山梨醇（ＲＢＣＳ）、血脂、血浆纤维蛋白原（Ｆｇ）、血浆镁、心血管交感神经活性（ＳＡ）和副交感神经活性（ＰＡ）等作了探讨。结果显示：糖尿病患者尿ＵＡＥＲ水平明显增高；多因素分析表明，在上述１７     

Increase in serum prorenin precedes onset of microalbuminuria in patients with insulin-dependent diabetes mellitus

Abstract Aims/hypothesis. The renin-angiotensin system is possibly involved in the pathogenesis of diabetic nephropathy. The most striking change in renin-angiotensin system components in blood of patients with diabetic nephropathy is an increased prorenin concentration. We investigated prospectively serum concentrations of renin-angiotensin system components and the time course of prorenin increase in normoalbuminuric diabetic patients developing microalbuminuria. Methods. Patients (n = 199) with Type I (insulin-dependent) diabetes mellitus and normoalbuminuria at baseline were prospectively followed for 10 years. The prorenin concentrations and other variables possibly associated with the occurrence of microalbuminuria, were investigated by Cox-regression analysis. Results. Of the patients 29 developed microalbuminuria. Glycated haemoglobin values were higher at baseline in these patients. Serum prorenin was similar at baseline but rose in the 29 patients before the development of microalbuminuria and was stable in patients with stable albumin excretion. Renin, angiotensinogen and angiotensin converting enzyme serum concentrations were stable in both groups. Prorenin and glycated haemoglobin were independent prognostic factors for the development of microalbuminuria. A prognostic index, based on these variables, was constructed to estimate the relative risk of developing microalbuminuria. Conclusions/interpretation. Increase in serum prorenin precedes onset of microalbuminuria in normotensive patients with insulin-dependent diabetes mellitus. High concentrations of prorenin in combination with high values of glycated haemoglobin can be used as a predictor of development of microalbuminuria. [Diabetologia (1999) 42: 1006–1010] Received: 30 December 1998 and in revised form: 1 April 1999     

Prevalence of microalbuminuria in children with Type 1 (insulin-dependent) diabetes mellitus

Summary The prevalence of microalbuminuria was determined in children aged 7 to 18 years with Type 1 (insulin-dependent) diabetes of more than 2 years' duration. All patients (n =102) attending 2 diabetes clinics were asked to collect 2 overnight timed urine samples for albumin analysis by radioimmunoassay. Complete urine collection was obtained in 97 patients (95%). Overnight urinary albumin excretion rates were also measured in 36 healthy children matched for age and sex. Nineteen of the 97 patients (20%) had microalbuminuria, i. e. overnight urinary albumin excretion rates above the upper normal level (14 g/min) in both urine collections. Microalbuminuria was only demonstrated in patients aged 15 years, prevalence 37% (19/52 patients). Arterial blood pressure was elevated, mean 122/84±11/9mmHg, in the microalbuminuric group (19 patients) compared to the age-matched normoalbuminuric diabetic group (33 patients), mean 117/74±10/10 mm Hg,p < 0.001. The prevalence of simplex retinopathy was identical in these two groups, i. e. 25%. Glycosylated haemoglobin was slightly higher in the microalbuminuric patients,p < 0.10. Our cross-sectional study reveals a high prevalence (37%) of persistent microalbuminuria, a stage highly predictive of later development of diabetic nephropathy, in Type 1 diabetic children aged 15 years.     

Low prevalence of exocrine pancreatic insufficiency in patients with diabetes mellitus

IntroductionExocrine pancreatic insufficiency (EPI) can occur in patients with diabetes mellitus (DM). Incidence of EPI and its clinical significance remain poorly defined. The aim of our study was to determine whether exocrine pancreatic function is impaired in patients with DM.Patients and methodsOne hundred and fifty consecutive patients, mean age 59.0 (±12.0 years), with DM lasting at least 5 years were included in the study. We included 50 patients with type 1 DM (DM1), 50 insulin-treated patients DM type 2 (DM2-insulin) and 50 non-insulin treated patients with DM type 2 (DM2 no-insulin). Diagnosis of DM was established from health records, lasting 15.0 ± 9.9 years on average. EPI was diagnosed with a fecal elastase-1 concentration (FE1) of less than 200 μg/g (ELISA).ResultsFE1 was reduced in 8 (5.4%) patients: mildly reduced (100–200 μg/g) in 4 patients (2.7%) and markedly reduced (<100 μg/g) in 4 patients (2.7%). Frequency of EPI was 3 in DM1, 5 in DM2(insulin) and none in DM2 (no-insulin) groups.ConclusionsEPI in DM occurred less frequently than in previous studies, probably due to our strict exclusion criteria (age, alcohol intake).     

Psychiatric disorders in juvenile patients with insulin-dependent diabetes mellitus

The relationships of psychiatric characteristics to metabolic control and psychosocial functioning were examined in a group of 16 patients with insulin-dependent diabetes mellitus (IDDM) (mean age: 14.3+/-5.1 years, mean duration of follow-up: 5.0+/-2.3 years) and psychiatric disorders. The comparison is also made to 69 IDDM controls (mean age: 17.0+/-6.7 years) without psychiatric disorders. Metabolic control was evaluated in terms of glycosylated hemoglobin (HbA1c). Psychosocial functioning at both psychiatric treatment entry and discharge was assessed using the global assessment of functioning (GAF) scale. Subjects were divided into three subgroups - Somatoform Type (25%), Behavioral Type (50%) or Psychotic Type (25%) - according to the Diagnostic and Statistical Manual of Mental Disorders, third edition revised (DSM-III-R), based on semi-structured interviews. Four patients (25%) were diagnosed as having schizophrenia or schizoaffective disorder (Psychotic Type), which is rather rare. The mean HbA1c level in the Behavioral Type patients was significantly higher than in the other subgroups (P<0. 01). After psychiatric treatment a significant difference (P<0.0001) in the GAF Scale was observed in the Psychotic Type compared with the other subgroups. We conclude that the Behavioral Type is associated with poor metabolic control and that for the Psychotic Type, improved psychosocial functioning can be achieved through psychiatric treatment.     

Increased QT dispersion in patients with insulin-dependent diabetes mellitus

AIM: To compare the QT dispersion in unselected patients with insulin-dependent diabetes mellitus to non-diabetic control subjects and to assess the association between the QT dispersion and cardiac autonomic neuropathy, ischaemic heart disease, blood pressure level and nephropathy. METHODS: 42 patients with insulin-dependent diabetes mellitus and 80 control subjects aged 40-57 years participated. The QT interval was measured in a resting 12-lead electrocardiogram (ECG) and the QT dispersion defined as the difference between the maximum and minimum QT interval. Bazett's formula was used to correct for heart rate (QTc). The degree of cardiac autonomic neuropathy was assessed by five function tests and ischaemic heart disease was defined by a previous myocardial infarction, ECG abnormalities or a positive exercise test. RESULTS: Compared to control subjects, diabetic patients had a longer QTc interval (433 vs. 416 ms; P=0.002) and a higher QT dispersion (36 vs. 30 ms; P=0.02). In the diabetic group, the QTc interval was prolonged in patients with autonomic neuropathy (449 vs. 420 ms; P=0.007) and the QT dispersion was increased in patients with ischaemic heart disease (51 vs. 33 ms; P=0.004). No association was found to urinary albumin excretion rate or blood pressure. CONCLUSION: The QT dispersion as well as the QTc interval is increased in patients with insulin-dependent diabetes mellitus. The association between QT dispersion and ischaemic heart disease indicates that abnormalities in cardiac repolarisation may be caused by complications to diabetes rather than diabetes in itself.     

Relation of blunted dilation of the brachial artery in insulin-dependent diabetes mellitus to microalbuminuria

Endothelium-dependent vasodilation in the conduit peripheral arteries of patients with insulin-dependent diabetes mellitus is impaired and is closely related to microalbuminuria. The diabetic state does not significantly influence the vascular smooth muscle functional capability.     

Osteopenia in insulin-dependent diabetes mellitus; prevalence and aspects of pathophysiology

The objective was to evaluate the prevalence and severity of osteopenia in patients with uncomplicated insulin-dependent diabetes mellitus (IDDM) and to obtain more information on the pathophysiology of diabetic osteopenia. In 35 patients with uncomplicated IDDM (21 men and 14 women; age 37.6+/-9.9 yr; duration of disease 8.5+/-3.5 years) bone mineral density was measured by dual energy X-ray absorptiometry (DEXA). In addition, markers of bone formation [plasma insulin-like growth factor I (IGF-I), serum alkaline phosphatase (ALP), serum bone alkaline phosphatase (BAP) and serum osteocalcin] and bone resorption [urinary excretion of calcium and of the cross-linked N-telopeptide of type 1 collagen, both corrected for the excretion of creatinine] were measured in the diabetic patients and in 33 healthy controls, matched for sex, age, height, weight and body mass index (BMI). In 67% of the diabetic men and 57% of the diabetic women osteopenia of the femoral neck and/or the lumbar spine (T-value < or = -1 SD) was present. Fourteen percent of the male patients, but none of the female patients, met the criteria for osteoporosis (T-value < or = -2.5 SD). In the whole group of diabetic patients the mean plasma IGF-I level tended to be lower (p<0.10) as compared to that in the controls. In the diabetic patients with femoral neck osteopenia, the mean plasma IGF-I level was significantly lower (p<0.05) than in those without osteopenia at this site. There were no differences in the mean serum ALP, BAP and osteocalcin levels between the diabetic patients and the controls, nor between the diabetic patients with and without femoral neck osteopenia. Considering only the male diabetic patients, significantly lower mean plasma IGF-I (-26%), serum ALP (-24%) and serum osteocalcin (-38%) levels were present in the patients with femoral neck osteopenia than in those without osteopenia at this site, suggesting lowered bone formation. The bone resorption markers were similar in all (sub)groups of diabetic patients and not different between diabetic patients and controls. Bone mineral density (BMD) did not correlate with plasma levels of glycosylated hemoglobin (HbA1c). BMD values were not related to any of the bone resorption or formation markers, except for plasma IGF-I both in the femoral neck (r=+0.38, p=0.026) and the lumbar spine (r=+0.34, p=0.043). Our data demonstrate that at least in male patients with IDDM, osteopenia is the consequence of a lowered bone formation with a predominance of bone resorption over formation.     

Intracellular metabolism in patients with insulin-dependent and non-insulin-dependent diabetes mellitus

Slow infusion of neutral insulin causes in patients with insulin dependent and noninsulin dependent diabetes mellitus diverse changes in the levels of cAMP, cGMP and the cAMP/cGMP ratio in leukocytes in spite of one-type changes in the concentration of contrainsular hormones in the venous blood: in patients with noninsulin dependent DM a raised cAMP/cGMP factor was lowered whereas in patients with insulin dependent DM it was increased. The authors put forward for discussion the problem of the postreceptor mechanisms of tissue insulin resistance in noninsulin dependent DM and a possibility of the use of the above indices for differential diagnosis of DM types.     

Association of D-dimer with microalbuminuria in patients with type 2 diabetes mellitus

Background Microalbuminuria has been reported to be related to incidence of cardiovascular complications in diabetes. No consistent findings have been obtained on the relationships of microalbuminuria with blood coagulation and fibrinolysis. The purpose of this study was to determine whether microalbuminuria is associated with blood markers reflecting coagulation and fibrinolysis activities in patients with type 2 diabetes. Methods The relationships of albumin excretion rate (AER) with atherosclerosis-related variables, including blood coagulation and fibrinolysis markers, were investigated in patients with type 2 diabetes who showed normoalbuminuria (AER: less than 20 μg/min) and microalbuminuria (AER: 20 μg/min or higher and less than 200 μg/min). Results AER was significantly correlated with body mass index (BMI), maximum intima-media thickness of common carotid arteries, blood HDL cholesterol, uric acid, creatinine and D-dimer. On the other hand, AER showed no significant correlation with blood platelets, fibrinogen, thrombin–antithrombin III complex, plasmin–α2 plasmin inhibitor complex and plasminogen activator inhibitor-1. In multiple regression analysis, using age, sex, BMI, pulse pressure, hemoglobin A1c, HDL cholesterol, uric acid, creatinine, D-dimer and history of anti-thrombotic therapy as explanatory variables, only D-dimer showed a significant correlation with AER. The mean level of log-converted D-dimer after adjustment for age and sex was significantly higher in subjects with microalbuminuria than in those with normoalbuminuria. Conclusions D-dimer is associated with microalbuminuria in patients with diabetes and this suggests that glomerular dysfunction is in part mediated by hypercoagulability.     

Smoking and metabolic control in patients with insulin-dependent diabetes mellitus

Within a defined geographical area, all 192 subjects with insulin-dependent diabetes of at least 2 years duration and free of diabetic complications were identified; 60 (31%) were smokers. The prevalence of smoking increased significantly with increasing haemoglobin A1c levels (17.5% among subjects with the best metabolic control, 47.5% in those with the worst control). Smoking and non-smoking diabetic patients did not differ in attitudes towards the disease, psychological well-being, extent of tedium, frequency of self-controls of blood glucose or proportion of patients with any sick leave in the preceding 2 years. In a case referent study of 25 matched patients with good or poor metabolic control, exposure to smoking was significantly more common among those with poor control (odds ratio 6.0). Thus there are several lines of evidence that smoking is associated with impaired metabolic control in patients with diabetes.     

Kidney function and glomerulopathy over 8 years in young patients with Type I (insulin-dependent) diabetes mellitus and microalbuminuria

Aims/hypothesis: We aimed to investigate prospectively the interrelation between kidney function and glomerular morphological changes over 8 years in young patients with Type I (insulin-dependent) diabetes mellitus and microalbuminuria. Methods: Kidney biopsies were taken at baseline and after 8 years in 18 subjects who were 20 years of age (19–29 mean and range), had duration of diabetes for 11 years (7–18), and who had an albumin excretion rate of 45 μg/min (15–194). The glomerular ultrastructural parameters were analysed using stereological methods. Results: At the end of the study three patients had an increased albumin excretion rate of more than 25 % a year, two of whom developed overt nephropathy. Glomerular filtration rate declined 2.3 ml/min · 1.73 m^–2· yr^–1. Glomerular volume, volume fractions of matrix and mesangium, and basement membrane thickness showed an increase over the 8 years. Multiple regression analysis showed that mean 8-years HbA_{1 c}, matrix volume fraction_baseline and basement membrane thickness BMT_baseline accounted for 70 % of the variation in AER at the end of the study. Mesangial volume fraction_baseline, glomerular filtration fraction_baseline, and mean 8-year HbA_{1 c} accounted for 73 % of the change in glomerular filtration rate from baseline. Smoking was strongly associated with the glomerular filtration rate at baseline (r = 0.65). When glomerular filtration rate_baseline was omitted from the equation, smoking was the only significant parameter linked to the change in glomerular filtration rate from the baseline. Conclusion/interpretation: In patients who had diabetes for 20 years, long-term hyperglycaemia and glomerulopathy found 8 years prior to the study, and possibly smoking, affected renal function (i. e. albumin excretion rate and glomerular filtration rate). [Diabetologia (2002) 45: 253–261] Received: 16 July 2001 and in revised form: 18 October 2001     

Clinical characteristic of elderly patients with insulin-dependent diabetes mellitus]

The number of elderly patients with insulin-dependent diabetes mellitus (IDDM) is increasing because of the prolongation of life due to the improvement of diabetic control. For better management of elderly patients with IDDM, we investigated the clinical and genetic characteristic of older patients with IDDM in comparison with younger patients. The subjects studied consisted of 19 patients with IDDM treated at the Department of Geriatric Medicine, Osaka University Hospital. Among the 19 subjects, 7 patients (37%) were more than 50 years old, including 3 patients (16%) more than 65 years old. The clinical and genetic characteristics of these 7 patients (older patients group) were compared with those of 12 patients (younger patient group) whose age was less than 50 years old. The age at onset of IDDM was significantly higher in older patient group (46 +/- 13 years old; mean +/- SD) than in younger patient group (34 +/- 6 years old). There was no significant difference in the duration of IDDM between older and younger patients (13 +/- 6 and 12 +/- 8 years, respectively). There were no significant differences in daily insulin dose, glycemic control (fasting plasma glucose and HbA1c levels) and glycemic stability as measured by the standard deviation of 10 measured fasting plasma glucose levels between the two groups. The frequency of diabetic retinopathy and neuropathy in the older patients was slightly, but not significantly, higher than that in younger patients. The frequency of diabetic nephropathy was similar in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)     

Cross-section study of pulmonary function in patients with insulin-dependent diabetes mellitus

In this study, we attempted to establish the prevalence and nature of pulmonary dysfunction in a cross section of a diabetic population and the relationship of pulmonary dysfunction to diabetic factors and complications. Forty insulin-dependent diabetic patients, 15 to 60 yr of age, and 40 healthy reference subjects, matched for age, sex, and race, were studied. All subjects were lifelong nonsmokers and had no clinical evidence of past or present respiratory disease. Lung function was assessed from the flow-volume curve, single-breath nitrogen washout, static lung elastic recoil, and pulmonary diffusing capacity (DLCO/VA) and its components: membrane diffusing capacity (Dm/VA) and pulmonary capillary blood volume (Qc/VA). The diabetic patients had an increased value for Kst(L) and in Kst(L), the exponential shape constant of the pressure-volume curve compared with that of the reference subjects (Kst(L), 0.184 +/- 0.011 versus 0.135 +/- 0.005; p less than 0.005, mean +/- SEM). The DL/VA was lower in the diabetic subjects (4.62 = 0.12 versus 5.31 +/- 0.10 ml/min/mm Hg/L; p less than 0.001), and this was due to a lower Qc/VA (9.45 +/- 0.43 versus 11.75 +/- 0.35 ml/min; p less than 0.001). The Kst(L) and Qc/VA were correlated with the duration of diabetes. The In Kst(L) was negatively correlated with both DL/VA (r = -0.32, p less than 0.05) and Qc/VA (r = -0.36, p less than 0.05). There was no association between abnormal pulmonary function and the presence of other diabetic complications. It is concluded that there are mild, duration-related abnormalities of lung elastic recoil and pulmonary diffusing capacity and a reduction in pulmonary capillary blood volume in insulin-dependent diabetes mellitus.     

Clinical impact of reducing microalbuminuria in patients with type 2 diabetes mellitus

Diabetic nephropathy in type 2 diabetes is a leading cause of end-stage renal disease worldwide. Its early clinical sign is microalbuminuria, which is not only a predictor for progression of nephropathy but also an independent risk factor for cardiovascular disease. A few decades ago, diabetic nephropathy was believed to be progressive and irreversible. Thus, the main therapeutic objective for type 2 diabetic patients with microalbuminuria was to prevent progression to overt proteinuria. However, there is now growing evidence regarding remission/regression of diabetic nephropathy. In recent clinical trials using the renin-angiotensin system blockade drugs, a reduction in microalbuminuria by the use of these drugs has been noted. We also reported that a reduction in microalbuminuria was more frequent than progression to overt proteinuria and that multifactorial control approach was important to the reduction of microalbuminuria. These results for type 2 diabetes are similar to those previously reported for type 1 diabetes. Furthermore, our recent study showed that the 8-year cumulative incidence rate of renal and cardiovascular events was significantly lower in patients with remission than in those without it. The annual decline rate of estimated glomerular filtration rate in patients with remission was also significantly slower. These studies provide clinical evidence implying that the reduction of microalbuminuria in type 2 diabetic patients occurs frequently and brings about renal and cardiovascular risk reduction. Reducing microalbuminuria is therefore considered to be an important therapeutic objective and may be a biomeasure of therapeutic success in type 2 diabetic patients.     

2型糖尿病患者微量白蛋白尿与大血管病变的关系

近年来,尿白蛋白与糖尿病患者大血管病变的关系受到重视。我们检测了对115例2型糖尿病患者的尿白蛋白排泄率(UAER),探讨其与糖尿病大血管病变的关系。　　对象与方法1.对象:115例2型糖尿病患者,均符合WHO糖尿病诊断标准。按尿白蛋白水平分为三组。(1)DM1组38例,UAER<20μg/min,