Long-term effects of linoleic-acid-enriched diet on albuminuria and lipid levels in Type 1 (insulin-dependent) diabetic patients with elevated urinary albumin excretion

Summary We conducted a 2-year prospective randomised study to investigate the effects of a linoleic-acid-enriched diet on albuminuria and lipid levels in Type 1 (insulin-dependent) diabetic patients with elevated urinary albumin excretion (overnight urinary albumin excretion rate between 10 and 200 g/min). Thirty-eight patients were randomly assigned to increase dietary polyunsaturated: saturated fatty acids ratio to 1.0 by replacement of saturated fat with linoleic-acid-rich products (n=18, two dropouts, analysis was performed in n=16) or to continue their usual diet (n=20). The total fat and protein content of the diet was unaltered. Clinical characteristics, albuminuria, blood pressure, glomerular filtration rate, metabolic control and dietary composition were similar in the two groups at baseline. In the high linoleic acid diet group, linoleic intake rose from 7±4 to 11±2 energy % and polyunsaturated: saturated fatty acids ratio rose from 0.60±0.28 to 0.96±0.16 (p<0.001 compared to usual diet group). The median increase albuminuria was 58% (95% confidence interval, 13 to 109) during the first year (p<0.02) and 55% (95% confidence interval, 11 to 127) (p<0.01) during the second year. Glomerular filtration rate remained unaltered and filtration fraction tended to rise (p<0.05 compared to usual diet group). In the usual diet group, albuminuria did not significantly increase by 16% (95% confidence interval, -17 to 38) and glomerular filtration rate declined during the second year. Blood pressure tended to rise similarly in both groups. Multiple regression analysis showed an independent effect of the high linoleic acid diet on the progression of albuminuria as well as the lack of decrease in glomerular filtration rate. Low density lipoprotein cholesterol and apolipoprotein B levels decreased in the high linoleic acid diet group (p<0.05). High density lipoprotein cholesterol declined in both groups (p<0.05). It is concluded that a linoleic-acid-enriched diet reduces atherogenic lipoproteins but does not have a beneficial effect on and might even promote renal functional abnormalities in Type 1 diabetic patients with elevated urinary albumin excretion.     

Apolipoprotein E genotype affects the response to lipid-lowering therapy in Chinese patients with type 2 diabetes mellitus

OBJECTIVE: To evaluate the effect of apolipoprotein E (apoE) genotype on baseline lipid levels and the response to hydroxy-methyl glutaryl coenzyme A reductase inhibitors (statins) therapy in Chinese patients with type 2 diabetes mellitus (DM). RESEARCH DESIGN AND METHODS: We consecutively recruited Chinese patients with type 2 DM requiring lipid-lowering therapy according to current guidelines. Patients were started on either simvastatin 10 mg daily or given an equivalent dose of lovastatin 20 mg. After 12 weeks of statin therapy, patients had fasting lipid profiles repeated. ApoE genotyping was performed by restriction fragment length polymorphism (RFLP). RESULTS: Ninety-six patients were studied. The epsilon3/epsilon3 genotype was in 62.5%, epsilon2/epsilon3 and epsilon3/epsilon4, 16.7 and 20.8%, respectively. After adjusting for confounding variables, baseline total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels were significantly higher in those with epsilon3/epsilon4 compared with epsilon2/epsilon3 genotype (6.7 vs. 5.5 mm for TC, 4.5 vs. 3.6 mm for LDL-C; p = 0.015 and p = 0.025, respectively). With statin therapy, epsilon3/epsilon4 patients had significantly greater LDL-C lowering compared with epsilon2/epsilon3 patients (48 vs. 27.7%; p = 0.04). There was no gender difference in baseline lipid parameters or response to statin therapy. CONCLUSIONS: ApoE genotype accounts for interindividual variability of baseline cholesterol levels, and response to statin therapy in Chinese patients with type 2 DM.     

Influence of apolipoprotein E genotype on the response to caloric restriction in type 2 diabetic patients with hyperlipidaemia

Aims:  Hyperlipidaemia is a major predisposing factor to atherosclerosis in patients with type 2 diabetes. Apolipoprotein (apo) E polymorphism influences lipoprotein metabolism, and the present study was undertaken to explore the relation, in type 2 diabetics, between apo E genotype and the plasma lipid response to dietary therapy.
Methods:  The subjects were 104 patients with type 2 diabetes and hyperlipidaemia, and the difference, due to apo E genotype, in dietary response was followed for 4–6 weeks. The caloric intake was maintained in the range 20–25 kcal/kg, and the medications for diabetes were not changed during the follow-up period.
Results:  Plasma total cholesterol (TC) and triglyceride (TG) levels were significantly lowered by the dietary treatment in patients with apo E genotypes of ε3/3, ε2/3 and ε3/4; however, the lipid levels in patients with ε2/4 did not respond to the diet.
Conclusions:  apo E genotype should be taken into consideration in the treatment of hyperlipidaemia in diabetic patients.     

Abnormalities in plasmas concentrations of lipoproteins and fibrinogen in Type 1 (insulin-dependent) diabetic patients with increased urinary albumin excretion

Summary Type 1 (insulin-dependent) diabetic patients with clinical nephropathy have a more than ten-fold increase in mortality of cardiovascular diseases compared with diabetic patients without nephropathy. The risk factors for cardiovascular disease, plasma concentrations of lipoproteins and fibrinogen, were investigated in 74 long-term diabetic patients: 37 with normal urinary albumin excretion, 20 with incipient nephropathy and 17 with overt clinical nephropathy based on urinary albumin excretion. The groups were matched according to sex, age and diabetes duration. The concentration of plasma cholesterol, very low density lipoprotein cholesterol, low density lipoprotein cholesterol, triglyceride and fibrinogen rose with increasing urinary albumin excretion. The plasma concentrations of these lipoproteins and fibrinogen were 11–14% higher in the patients with incipient nephropathy and 26–87% higher in the patients with overt clinical ne phropathy compared with the patients without nephropathy. The plasma concentration of high density lipoprotein cholesterol was unaffected by albuminuria. Patients with normal urinary albumin excretion and HbA_1c>8.0% had significantly higher very low density lipoprotein- and lower high density lipoprotein cholesterol concentrations compared with patients with HbA_1c<8.0%. Simple addition of the described risk factors can only account for a minor part of the greatly increased cardiovascular mortality in patients with diabetic nephropathy. An additional and possibly more decisive factor might be a change in the arterial wall, a change which promotes lipid accumulation and/or facilitates thrombus formation.     

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.     

Acute reduction of arterial blood pressure reduces urinary albumin excretion in Type 1 (insulin-dependent) diabetic patients with incipient nephropathy

Summary The effect of an acute reduction in arterial blood pressure upon kidney function was studied in 12 patients with Type 1 (insulin-dependent) diabetes and incipient nephropathy (persistent microalbuminuria). Renal function was assessed by measurement of the glomerular filtration rate (single bolus ⁵¹Cr-EDTA technique) and by the urinary albumin excretion rate (radioimmunoassay). The study was performed twice within 2 weeks, with the patients receiving a slow intravenous injection of either clonidine (225 g) or saline (154 mmol/l) in random order. Clonidine reduced arterial blood pressure from 125/79±13/8 to 104/68±9/7 mmHg (p < 0.01), urinary albumin excretion rate from 68 (31–369) to 46 (6–200) g/min (median and range) (p<0.01), and fractional clearance of albumin in all patients (median 29%) (p < 0.01). Glomerular filtration rate was 110±11 before and 106±13 ml/min/1.73 m² after clonidine injection. The blood glucose concentration was 15±4mmol/l before and 14±5 mmol/l after clonidine injection. In agreement with findings in animal studies, our results suggest that microalbuminuria is to a large extent pressure-dependent, probably because of glomerular hypertension, and that autoregulation of glomerular filtration rate is normal in most patients with incipient diabetic nephropathy.     

Lecithin:cholesterol acyltransferase activity and high-density lipoprotein subfraction composition in type 1 diabetic patients with improving metabolic control

On initial diagnosis or when metabolic control is poor, subjects with type 1 (insulin-dependent) diabetes mellitus often exhibit decreased high density lipoprotein (HDL) cholesterol levels, which have been associated in numerous studies in non-diabetic subjects with atherosclerosis and coronary artery disease. We measured the activities of plasma lecithin:cholesterol acyltransferase (LCAT), post-heparin lipoprotein lipase, and the composition of the HDL subfractions HDL₂ and HDL₃, in ten poorly controlled type 1 diabetic patients admitted to a metabolic ward (six women and four men, aged 18–37 years). The measurements were repeated after metabolic control had been optimised and again a week after discharge. The results were compared with those of ten healthy normolipidaemic subjects matched for age, sex and body mass. LCAT activity increased significantly (P<0.05) with improved metabolic control in the diabetic patients, and showed positive within — person correlation with HDL₂ cholesterol ester (r=0.67;P<0.01), HDL₂ free cholesterol (r=0.67;P<0.01), phosphatidylcholine (r=0.49;P<0.05), total phospholipids (r=0.50;P<0.01) and apolipoprotein A-I (apo A-I:r=0.72;P<0.01). With improving metabolic control HDL₂ lipid levels increased more than twofold and the compositional changes in HDL₂ were reflected by an increased apo A-I:apo A-II ratio (P<0.05) and a decreased triglyceride:apo A-I ratio (P<0.05). Changes in HDL₃ levels and composition were minor. The results of this study indicate that an increase in LCAT activity increases the concentration and changes the composition of HDL₂ in type 1 diabetic patients with improved metabolic control.     

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.     

First morning urinary albumin concentration is a good predictor of 24-hour urinary albumin excretion in children with Type I (insulin-dependent) diabetes

Summary Twenty-four hour urinary albumin excretion was measured in 97 children with Type 1 (insulin-dependent) diabetes and found to have a geometric mean of 6 mg/day (range 1–38 mg/d). The same geometric mean of 6 mg/day (range 1–45 mg/d) was found in 120 normal children. The relationship of 24-h urinary albumin excretion to the albumin concentration (mg/1) and to the ratio of albumin: creatinine (mg: mmol) on first morning urine samples in 64 patients was highly significant (r=0.93 and r=0.62 respectively, p < 0.001). In 41 patients, the relationship between 24-h urinary albumin excretion and albumin concentration upon urine samples at various times was assessed. The correlation was highest on the first morning sample (r=0.86); 09.00h to 13.00 h, 0.51; 13.00 h to 18.00 h, 0.68; 18.00 h to 23.00 h, 0.32. High sensitivity and moderate specificity was obtained using a first morning albumin concentration of greater than 20 mg/l to detect increased albumin excretion. These results show that the measurement of albumin concentration on the first morning urine sample can be used for a screening test for micro-albuminuria in children.     

Gender differences in a Type 2 (non-insulin-dependent) diabetic population with respect to apolipoprotein E phenotype frequencies

Summary Apolipoprotein E polymorphism was examined in an Italian population of Type 2 (non-insulin-dependent) diabetic patients. There were significant differences (p < 0.05) in allele frequencies between male and female patients due to an under-representation of the E4 allele in the female group. No differences in allele frequencies were noted when non-diabetic male and female control subjects were compared. Both control groups exhibited similar allele distributions to that of male diabetic patients, but were significantly different (p < 0.05) from female diabetic patients. A closer examination of the female diabetic population revealed that under-representation of the E4 allele was principally confined to patients aged 60 years or older. This sub-group showed a significantly different (p < 0.05) allele frequency profile from control subjects (both men and women) and diabetic men, whereas this was not observed in the younger diabetic women ( 59 years). The results are consistent with the suggestion that the E4 allele may be a particular risk factor for female diabetic patients.     

Double-blind, randomised study of the effect of combined treatment with vitamin C and E on albuminuria in Type 2 diabetic patients.

AIMS: Elevated levels of urinary albumin excretion rate (AER) predict high risk for progressing to end-stage renal disease. In streptozotocin-induced diabetes, supplementation with vitamin C or E reduces albuminuria and glomerular hypertrophy. We tested the hypothesis that supplementation of both vitamin C and E in pharmacological doses lowers AER in Type 2 diabetic patients with persistent micro/macroalbuminuria. METHODS: Thirty Type 2 diabetic patients with AER 30-300 mg/24 h were included in a double-blind randomised, cross-over trial. Patients received vitamin C (1250 mg) and vitamin E (680 IU) per day or matching placebo for 4 weeks with a 3-week wash-out period between treatment periods in random order. RESULTS: Combined treatment with vitamin C and E reduced AER by 19% (95% CI 6-34%) (p = 0.04), geometric mean 197 mg/24 h (95% CI 114-341 mg/24 h) vs. 243 mg/24 h (146-404 mg/24 h). No changes were seen in serum creatinine, haemoglobin A1C or blood pressure. Fasting plasma concentrations of vitamin C and E increased in all patients during active treatment (mean vitamin C 79.4 micromol/L (SD 27.8) vs. 41.9 micromol/L (18.4) and vitamin E 47.0 micromol/L (19.8) vs. 29.5 micromol/L (15.3), P < 0.000001). Except for two patients that started additional blood pressure lowering treatment during the run-in period, no changes in medication, food and exercise habits or in the number of smokers occurred during the study. CONCLUSION: Short-term treatment with vitamin C and E in pharmacological doses lowers AER in Type 2 diabetic patients with micro/macroalbuminuria. Further long-term, large-scale studies of this albuminuria reducing treatment modality are warranted.     

Unchanged incidence of severe retinopathy in a population of Type 1 diabetic patients with marked reduction of nephropathy

The incidence of nephropathy in Type 1 diabetes mellitus has declined during the past decade, probably as a result of improved glycaemic control. We wanted to investigate whether the incidence of severe retinopathy has changed during the same time period and to evaluate the importance of glycaemic control in relation to the development of severe retinopathy and nephropathy. All 213 patients in whom Type 1 diabetes mellitus was diagnosed before the age of 15 years between 1961 and 1980 in a district in south-eastern Sweden were studied. Ninety-two per cent of the patients were followed from the onset of diabetes to 1991 or to death. The cumulative incidence of severe retinopathy was not significantly different between the patients with diabetes onset 1961–65, 1966–70, 1971–75, and 1976–80. The risk of developing severe retinopathy or nephropathy was higher in patients with very poor glycaemic control (HbA_1c ≥ 8.4 %) vs patients with poor control (HbA_1c ≥ 7.2 < 8.4 %; p < 0.001). Patients with poor control had an increased risk of developing severe retinopathy vs patients with good control (HbA_1c < 7.2 %; p < 0.008) but there was no difference in the risk of nephropathy. No patients with good control developed nephropathy and only one patient developed severe retinopathy during 25 years of diabetes. © 1998 John Wiley & Sons, Ltd.     

Relationship between urinary excretion of sodium and dopamine in type 1 diabetic patients with an without microalbuminuria

The relationship between urinary sodium and dopamine excretion was investigated in 40 normal males and in 48 normotensive, Type 1 diabetic males, 11 with microalbuminuria and 37 with normal albumin excretion. In all three groups a significant correlation was demonstrated and the regression lines were similar. Thus, no evidence was found that a defect in dopamine mobilization contributes to the early renal pathophysiological changes of Type 1 diabetes.     

Association between lipoprotein subfraction profile and the response to hepatitis C treatment in Japanese patients with genotype 1b

Summary. Pegylated interferon and ribavirin combination therapy is the standard treatment for patients with chronic hepatitis C (CHC). Some groups have reported a relation between lipid values and response while others have reported that microsomal triglyceride transfer protein, a key enzyme in the assembly and secretion of lipoproteins, was related to hepatitis C virus (HCV). The aim of this study was to investigate the association between the lipoprotein profiles, classified according to size, and hepatitis C treatment and the usefulness for predicting the outcome of treatment. Forty‐four patients with CHC (27 men and 17 women) were included in the study. The serum cholesterol and triglyceride (TG) levels in the lipoprotein subclasses were determined using high‐performance liquid chromatography with gel permeation columns, which classified lipoproteins into 20 subfractions based on particle size. According to a univariate analysis, those who achieved an sustained viral response (SVR) had a significantly higher serum total cholesterol level, higher cholesterol levels in the low‐density lipoprotein subfraction (25.5 nm in diameter) and the very low‐density lipoprotein (VLDL) subfraction (44.5 and 36.8 nm), and a higher serum TG level in the VLDL subfraction (44.5 nm), compared with the corresponding values in the non‐SVR group. Higher serum cholesterol and TG concentrations in the lipoprotein subfractions were predictive of an SVR to therapy for HCV infection with genotype 1b prior to the start of interferon treatment.     

Nephropathy, but not retinopathy, is associated with the development of heart disease in Type 1 diabetes: a 12-year observation study of 462 patients.

AIMS: To study the occurrence of heart disease and death in Type 1 diabetic patients and evaluate whether presence of microangiopathy, i.e. nephropathy and retinopathy, was associated with the outcome. METHODS: A 12-year observation study of 462 Type 1 diabetic patients without a previous history of heart disease at baseline who were treated under routine care in a hospital out-patient clinic. RESULTS: A total of 85 patients developed signs of heart disease, i.e. myocardial infarction (n = 41), angina (n = 23), and heart failure (n = 17) and 56 patients died. The mortality for patients without signs of heart disease during the observation period was 7.6% compared with 51% in patients with myocardial infarction (P < 0.001), 26% in patients with angina (P < 0.01) and 65% in patients with heart failure (P < 0.001). The relative risk for death was 9.0 (P < 0.001) and 2.5 (P < 0.05) times higher in patients with macroalbuminuria and microalbuminuria, respectively. The risk for cardiovascular death was 18.3 times (P < 0.001) higher in patients with macroalbuminuria compared with patients with normoalbuminuria. In patients with sight-threatening retinopathy, the relative risk for death was 7.0 times higher (P < 0.01) and the risk for coronary heart disease events 4.4 times higher (P < 0.05) compared with patients with no retinopathy. However, when retinopathy was adjusted for presence of macroalbuminuria, this association disappeared. CONCLUSION: This study shows a high incidence of heart disease in patients with Type 1 diabetes. The worse prognosis was seen in patients with sight-threatening retinopathy and macroalbuminuria and microalbuminuria at baseline. Macroalbuminuria and microalbuminuria were independently associated with a high risk for heart disease and death while the association with sight-threatening retinopathy only occurred in the presence of nephropathy.     

Surface binding,internalization and degradation by cultured human fibroblasts of low density lipoproteins isolated from Type 1 (insulin-dependent) diabetic patients: Changes with metabolic control

Summary A previous study of low density lipoprotein metabolism by cultured cells focused on the metabolism of normal lipoproteins in vitro by fibroblasts isolated from diabetic patients. No abnormalities were found. We have followed the opposite approach. Using normal human fibroblasts as test cells we compared the metabolism in vitro of low density lipoproteins isolated from diabetic patients before and after metabolic control. We found a significant decrease (p<0.02) in internalization and degradation of low density lipoproteins isolated from diabetic patients before metabolic control when compared with those isolated from normal control subjects or from the same patients after metabolic control. The observed changes were mainly apparent in intracellular degradation. To evaluate whether the observed differences in low density lipoprotein behaviour were correlated with lipid or apolipoprotein composition, we measured cholesterol, triglyceride, apolipoprotein B and total protein levels in the low density lipoproteins tested. A significant decrease (p<0.05) of the triglyceride/protein ratio was found in post-control low density lipoproteins suggesting that a high triglyceride content may interfere with low density lipoprotein metabolism. The present study represents the first observation that metabolic control in diabetes mellitus can alter low density lipoprotein-cell interaction and suggests a possible mechanism for the enhanced incidence of atherosclerosis in diabetic patients.     

Relationship of progressively increasing albuminuria to apoprotein(a) and blood pressure in Type 2 (non-insulin-dependent) and Type 1 (insulin-dependent) diabetic patients

Summary This study has explored the temporal relationship between apoprotein(a), blood pressure and albuminuria over a mean interval of 11 years in a cohort of 107 diabetic patients of whom 26 (14 Type 2 (non-insulin-dependent), 12 Type 1 (insulin-dependent) had progressively increasing albuminuria (‘progressors’). In Type 2 diabetic patients, no significant differences were noted for HbA₁, blood pressure, creatinine clearance or serum lipids between progressors and non-progressors. In Type 1 diabetic patients, final systolic and diastolic blood pressures were higher in progressors compared with non-progressors and progressors showed impairment of renal function in association with a rise in blood pressure at the macroalbuminuric stage. Initial apoprotein(a) levels were similar in progressors and non-progressors of either diabetes type. Apoprotein(a) levels increased exponentially with time in 12 of 14 Type 2 progressors but only in 5 of 12 Type 1 progressors (p<0.01). In Type 2 diabetic patients, the annual increase in apoprotein(a) levels was 9.1±2.4%, which was significantly greater than in non-progressors, 2.0±1.2% (p<0.01) and also exceeded the rates of increase of apoprotein(a) in progressors with Type 1 diabetes, 4.0±1.4%, (p<0.05). Apoprotein(a) levels correlated significantly with albuminuria in 8 of 14 Type 2 progressors but only in 3 of 12 Type 1 progressors (p<0.05). The rate of increase of apoprotein(a) levels was not related to mean HbA₁, creatinine or creatinine clearance levels, or to albuminuria. The rate of rise of apoprotein(a) was not influenced by initial apoprotein(a) levels, suggesting that specific apoprotein(a) isoforms do not influence albuminuria-related increases in apoprotein(a). The data are consistent with the hypothesis that apoprotein(a) levels increase in response to albuminuria and may be part of a self-perpetuating process. This study also suggests that increases in apoprotein(a) levels commence during the microalbuminuria stage in diabetic patients, which is earlier than has been documented in non-diabetic proteinuria.     

Increased transcapillary escape rate of albumin in Type 1 (insulin-dependent) diabetic patients with microalbuminuria

Summary The transcapillary escape rate, intravascular mass and outflux of albumin were measured in 75 Type 1 (insulin-dependent) diabetic patients. The groups were defined as: group 1: normal urinary albumin excretion, <30 mg/24 h (n=21); group 2: microalbuminuria, 30–300 mg/24 h (n=36); group 3: diabeticnephropathy, <300 mg/24 h (n=18). Fifteen sex- and age-matched non-diabetic persons served as control subjects. The diabetes duration was: group 1: 20±9 years, group 2: 17±5 years, group 3: 19±7 years. The transcapillary escape rate of albumin was similar in controls and group 1 (5.0±1.8 versus 5.2±1.5%) and was significantly higher in the microalbuminuric group 2 and group 3 (8.1±2.2 versus 8.1±2.3 %). The differences were not explained by differences in metabolic control or blood pressure at the time of investigation. The outflux of albumin was also higher in group 2 than in group 1 and controls (7.1 ± 2.0 versus 5.3±1.5 and 5.1±2.0 g/h × 1.73 m²). It was indistinguishable from controls in group 3 (5.8±1.5 g/h × 1.73 m²) because of a reduced intravascular mass of albumin (p<0.01) in group 3. In conclusion, a universal vascular leakage of albumin is an early event in the development of diabetic nephropathy, with the leakage of albumin being fully developed in the microalbuminuric patient. In contrast, long-term diabetic patients with normal urinary albumin excretion have a normal transcapillary escape rate of albumin.     

Long-term physical training in female Type 1 (insulin-dependent) diabetic patients: absence of significant effect on glycaemic control and lipoprotein levels

Summary No objective evidence has been presented to support the beneficial effect of physical training on glycaemic control in Type 1 (insulin-dependent) diabetic patients trained two to three times a week for several months. In the present study we examined the possibility that a daily exercise programme would be more suitable for improving glycaemic control. Thirteen patients completed a 5-month study; 6 were randomized to exercise training (20 min daily bicycle exercise) and 7 served as non-exercising controls. The training resulted in an 8% increase in maximal oxygen uptake (p < 0.05). No change in glycaemic control occurred during the study period in either group. In addition, serum lipid and lipoprotein levels were followed. Total cholesterol decreased during the study period irrespective of training. No effect was noted on the levels of LDL, VLDL, HDL and HDL₂ cholesterol. A significant training effect was obtained in the HDL₃ subfraction (−10%,p < 0.05). Total triglycerides were unchanged, but a decrease in the level of LDL triglycerides was observed with training (−12%,p < 0.01). It is concluded that, in female Type 1 diabetic patients, daily physical training for several months does not improve glycaemic control and results only in minor changes in serum lipoprotein profiles.     

血管紧张素转化酶和载脂蛋白E基因多态性对新诊2型糖尿病患者亚临床动脉粥样硬化的预测

目的 为探讨血管紧张素转化酶和载脂蛋白E基因多态性与新诊2型糖尿病多因素强化干预条件下亚临床动脉粥样硬化发生的关系。方法采用聚合酶链反应一限制性片段长度多态性方法检测湖南地区汉族新诊2型糖尿病患者及93例无糖尿病对照者血管紧张素转化酶及载脂蛋白E的基因多态性，分别比较血管紧张素转化酶和载脂蛋白E基因型间以及两基因型协同作用下体重、血糖、血压、血脂和胰岛素抵抗等代谢指标水平的差异，比较分析无动脉粥样硬化与亚临床动脉粥样硬化患者血管紧张素转化酶及载脂蛋白E基因型分布特点。采用Logistie回归模型分析血管紧张素转化酶、载脂蛋白E基因型及二者协同作用下与多因素干预条件下亚临床动脉粥样硬化发生的关系。结果157例新诊2型糖尿病患者中，载脂蛋白E基因型及等位基因频率分布与对照组比较差异无显著性（P〉0．05）；血管紧张素转化酶Ⅰ等位基因频率显著高于对照组（0．707比0．581，P〈0．05），血管紧张素转化酶DD携带者收缩压水平与Ⅱ及ID携带者比较差异无显著性（P〉0．05）。载脂蛋白E4IX基因型携带者低密度脂蛋白胆固醇水平显著高于2/X携带者（P〈0．01）；血管紧张素转化酶及载脂蛋白E基因型对收缩压及低密度脂蛋白胆固醇水平无交互作用。两基因多态性与各代谢指标干预1年达标情况和动脉内中膜厚度无相关关系（P〉0．05）。血管紧张素转化酶DD携带者无一例发生亚临床动脉粥样硬化，与非DD携带者比较差异接近显著性（P=0．059），未发现载脂蛋白E基因多态性与亚临床动脉粥样硬化发生的相关性。结论以上提示，载脂蛋白E基因多态性对新诊2型糖尿病患者多因素干预条件下亚临床动脉粥样硬化的发生无预测作用；血管紧张素转化酶DD基因型可能是新诊2型糖尿病患者多因素干预条件下亚临床动脉粥样硬化发生的负性预测因子。