Haemostatic Measures in Type 2 Diabetic Patients with Microalbuminuria

The major cause of disability and early mortality in Type 2 diabetes is cardiovascular disease. An enhanced urinary albumin excretion is strongly predictive of increased mortality, but the causal relationship behind this association is unclear. Abnormalities in the haemostatic system may be involved in the vascular pathology. We therefore studied the level of von Willebrand factor (vWf:Ag), factor VIII (VIII:Ag), fibrinogen, and fibronectin in male diabetic patients 50–70 years of age, with normal albumin excretion (n = 14), microalbuminuria (n = 14), and frank albuminuria (n = 7). Fourteen healthy age-matched males served as a reference group. There were no significant differences between normo-and micro-albuminuric patients but vWf:Ag (p < 0.01), VIII:Ag (p < 0.01), and fibrinogen (p < 0.05) were increased in those with frank albuminuria. Urinary albumin excretion rate was significantly correlated to vWf:Ag (r = 0.46, p = 0.005), VIII:Ag (r = 0.45, p = 0.007), and fibrinogen (r = 0.49, p = 0.003). The known duration of diabetes was correlated to vWf and F VIII. The increased level of vWf:Ag in Type 2 diabetes and the significant association to the urinary albumin excretion rate may suggest a linkage between albuminuria and cardiovascular disease. However, the present study demonstrated no increase in haemostatic variables in patients with microalbuminuria as compared with those with normal albumin excretion.     

Orosomucoid in urine predicts cardiovascular and over-all mortality in patients with Type II diabetes

Aims/hypothesis: Urinary orosomucoid excretion rate is increased in a substantial proportion of patients with Type II (non-insulin-dependent) diabetes mellitus and normal urinary albumin excretion rate. The aim of this study was to determine whether increased urinary orosomucoid excretion rate is predictive of increased mortality in patients with Type II diabetes. Methods: In a cohort study including 430 patients with Type II diabetes, baseline urinary samples were analysed for orosomucoid and albumin. Mean follow-up was 2.4 years. Results: We found that 188 (44 %) patients had normal and 242 (56 %) patients had increased urinary orosomucoid excretion rates. During the study period 41 patients died; out of these 23 patients died of cardiovascular diseases. Odds ratio for all-cause mortality was 2.50 (95 % CI 1.00–6.22) and odds ratio for cardiovascular mortality was 9.81 (1.31–73.6) having increased urinary orosomucoid excretion rate at baseline (odds ratios adjusted for age, sex, duration of diabetes, cardiovascular diseases, weight, medication, HbA_{1 c}, plasma creatinine and urinary albumin excretion rate). Urinary albumin excretion rate was an independent predictor of all-cause mortality when urinary orosomucoid excretion rate was not included in the analysis. Subgroup analysis revealed that 39 % of the patients with normal urinary albumin excretion rate (n = 251) had increased urinary orosomucoid excretion rates and that these patients had a higher cardiovascular mortality (p = 0.007) than patients with normal urinary albumin excretion rate and normal urinary orosomucoid excretion rates. Conclusion/interpretation: We found that urinary orosomucoid excretion rate predicted all-cause and cardiovascular mortality in patients with Type II diabetes independently from other risk factors. [Diabetologia (2002) 45: 115–120] Received: 24 July 2001 and in revised form: 17 September 2001     

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.     

Diabetic nephropathy is associated with increased albumin and fibrinogen production in patients with type 2 diabetes

Aims/hypothesis Hyperfibrinogenaemia and albuminuria are cardiovascular risk factors, often coexisting in diabetic and non-diabetic people. Albuminuria in turn is associated with a compensatory albumin overproduction in non-diabetic patients. It is not known whether the presence of albuminuria in patients with type 2 diabetes mellitus is associated with greater albumin and fibrinogen production rates than in normoalbuminuric patients.Subjects, materials, and methods Using leucine isotope methods, we measured fractional and absolute synthesis rates (FSR, ASR) of albumin and fibrinogen in post-absorptive type 2 diabetic patients with either normal (n=11) or increased (n=10) urinary albumin excretion.Results In albuminuric patients, albumin FSR (16.2±1.5%/day) and ASR (20.5±1.9 g/day) were greater (p<0.02 and p<0.05, respectively) than in normoalbuminuric patients (FSR=11.5±1.1%/day; ASR=15.7±1.2 g/day). Fibrinogen FSR was similar between patients with normal and increased albumin excretion, but concentration, the circulating pool and ASR of fibrinogen were 40 to 50% greater (p<0.035) in patients with albuminuria. Albuminuria was positively correlated with albumin ASR, with fibrinogen concentration, the fibrinogen pool and ASR, whereas albumin synthesis was inversely correlated with calculated oncotic pressure.Conclusions/interpretation Synthesis of albumin and fibrinogen is upregulated in type 2 diabetic patients with increased urinary albumin excretion. Albuminuria is associated with enhanced fibrinogen and albumin synthesis.     

Increased plasma glycated low-density lipoprotein concentrations in diabetes: a marker of atherogenic risk

Nonenzymatic glycation of apolipoprotein B in the low-density lipoprotein (LDL) complex has been considered a proatherogenic modification contributory to the increased susceptibility of patients with diabetes to atherosclerosis. We postulated that glycated LDL concentrations might be associated with other markers of cardiovascular disease. To explore this hypothesis, we measured glycated LDL concentrations by a monospecific immunoassay in 50 patients with type 1 and 100 patients with type 2 diabetes and examined relationships with the amount of albumin excretion and the serum cholesterol and triglyercide concentrations. Plasma glycated LDL showed a significant positive correlation (r = 0.325; P < 0.001) with urinary albumin excretion that was higher in type 1 (r = 0.463) than in type 2 (r = 0.245) patients. The mean glycated LDL concentration progressively increased with increasing albumin excretion when patients were subcategorized into groups of normoalbuminuria, low (相似文献   

Plasma N-terminal pro-B-type natriuretic peptide and mortality in type 2 diabetes

Aims/hypothesis Raised N-terminal pro-B-type natriuretic peptide (NT-proBNP) is associated with a poor cardiac outcome in non-diabetic populations. Elevated NT-proBNP predicts excess morbidity and mortality in diabetic patients with an elevated urinary albumin excretion rate. This study investigated the prognostic value of NT-proBNP in a cohort of type 2 diabetic patients. Subjects, materials and methods In a prospective observational follow-up study, 315 type 2 diabetic patients with normoalbuminuria (n=188), microalbuminuria (n=80) and macroalbuminuria (n=47) at baseline were followed for a median (range) of 15.5 (0.2–17.0) years. Plasma NT-proBNP concentrations were determined by immunoassay at baseline. Endpoints were overall and cardiovascular mortality. Results Of the patients, 162 died (51%), 119 of them (74%) due to cardiovascular causes. All-cause mortality was increased in patients with NT-proBNP in the second and third tertiles (hazard ratios [95% CI] compared with the first tertile, 1.70 [1.08–2.67] and 5.19 [3.43–7.88], p<0.001). These associations persisted after adjustment for urinary albumin excretion rate, glomerular filtration rate and conventional cardiovascular risk factors (covariate adjusted hazard ratios 1.46 [0.91–2.33] and 2.54 [1.56–4.14], p<0.001). This increased mortality was attributable to more cardiovascular deaths in the second and third NT-proBNP tertile (unadjusted hazard ratios 1.63 [0.96–2.77] and 4.88 [3.01–7.91], p<0.001; covariate adjusted 1.37 [0.79–2.37] and 2.26 [1.27–4.02], p=0.01). When patients with normo-, micro- and macroalbuminuria were analysed separately, NT-proBNP levels above the median (62 ng/l) were consistently associated with increased overall and cardiovascular mortality in all three groups (p<0.001). Conclusions/interpretation In patients with type 2 diabetes, elevated circulating NT-proBNP is a strong predictor of the excess overall and cardiovascular mortality, this predictor status being independent of urinary albumin excretion rate and conventional cardiovascular risk factors.     

Comparison of Platelet Aggregability in Japanese Type 2 Diabetic Patients With and Without Microalbuminuria

Microalbuminuria is associated with higher cardiovascular morbidity and mortality in Type 2 (non-insulin-dependent) diabetic patients. This study was designed to assess whether Type 2 diabetic patients with microalbuminuria (urinary albumin excretion rate (AER) 20–200 μg min^?1) is associated with alterations in platelet aggregability as compared with those with normal urinary albumin excretion (AER < 20 μg min^?1). Platelet aggregability was compared between 21 Japanese Type 2 diabetic patients with microalbuminuria and 21 individually pair-matched (for age, sex, body mass index, treatment, and HbA_1c level) patients with normoalbuminuria. The in vitro platelet aggregation induced by 1.0 and 3.0 μmol I^?1 ADP and 0.5 and 1.0 mg I^?1 collagen was measured using platelet-rich plasma. No significant differences were observed between the two groups in the values for maximum percent platelet aggregation, percent aggregation at 3 min, and aggregation velocities after adding ADP or collagen. Microalbuminuric patients had significantly higher mean values for systolic (p < 0.004) and diastolic (p < 0.02) blood pressures and plasma fibrinogen level (p < 0.03) as compared with the respective mean values in normoalbuminuric patients. The results suggest that Japanese microalbuminuric Type 2 diabetic patients do not differ in the degree of platelet aggregability as compared with normoalbuminuric patients, despite an increase in certain other coronary risk factors.     

Thrombogenic factors are related to urinary albumin excretion rate in Type 1 (insulin-dependent) and Type 2 (non-insulin-dependent) diabetic patients

Summary Parameters of haemostasis, endothelial cell markers and lipid peroxide levels were studied in 64 Type 1 (insulin-dependent) and 94 Type 2 (non-insulin-dependent) diabetic patients according to their urinary albumin excretion rate in comparison with age-matched control subjects. We determined plasma levels of fibrinogen (Clauss' method), coagulation factor VII:activity (clotting assay), factor VII antigen, protein C and S antigen, von Willebrand factor antigen,d-dimer concentration (ELISA), and lipid peroxide levels (thiobarbituric acid) in relation to urinary albumin excretion rate (RIA). Significant positive correlations were found between urinary albumin excretion rate and plasma fibrinogen (p<0.005,p<0.02), factor VII activity (p<0.0002,p<0.002), factor VII antigen (p<0.0001,p<0.001), protein C (p<0.003,p<0.05), and lipid peroxides (p<0.02,p<0.004) in Type 1 as well as in Type 2 diabetes. Von Willebrand factor (p<0.001) and protein S (p<0.0005) correlated with albuminuria only in patients with Type 1 diabetes. Although most of the haemostatic abnormalities are already found in normoalbuminuric patients, the significant positive correlations to urinary albumin excretion indicate that endothelial cell damage and coagulation disorders deteriorate with the progression of diabetic nephropathy.     

Microalbuminuria in insulin-dependent diabetes: Prevalence and practical consequences

Urinary albumin excretion in a representative sample of 679 patients with Type I (insulin-dependent) diabetes, 18 to 50 years of age, was investigated. Patients on antihypertensive therapy were excluded. Urinary albumin excretion was examined in one 24 hour urine sample using an ELISA technique. Twenty-three per cent of the patients had microalbuminuria, i.e., 30–300 mg albumin/24 h. The prevalence of microalbuminuria was independent of sex, age, insulin dose and diabetes duration. In the majority of those cases in which microalbuminuria was found during the first 10 years of diabetes, the concentrations were in the lower range, i.e., 30–50 mg/24 h. The prevalence of incipient nephropathy (urinary albumin excretion in a single urine sample of 51–300 mg/24 h) increased with diabetes duration. In patients with inciplent nephropathy hemoglobin A_1c tended to be, and blood pressure was, elevated compared with age, sex, and duration matched patients with normal urinary albumin excretion rates (p=0.08 and p<0.001, respectively). Urinary albumin excretion and blood pressure were significantly correlated in the total group (n=401, r=0.2, p<0.001). On the basis of these findings practical guidelines for the handling of patients with microalbuminuria are proposed.     

Microalbuminuria in Type 2 diabetes: an independent predictor of cardiovascular mortality

Background: Microalbuminuria has been shown to be associated with cardiovascular mortality in type 2 diabetic subjects. It is unclear to what extent this is due to the increased prevalence of other cardiac risk factors. Aims: To examine the relationship of urine albumin excretion to cardiovascular mortality and to determine its status as an independent risk factor. Methods: In a prospective longitudinal study from 1986–1999 we followed 666 type 2 diabetic subjects from a diabetes outpatient service. Cardiovascular risk factors including urine albumin concentration were measured at study entry. Cox proportional hazards regression was used to determine risk factors for mortality. The hazard ratios of microalbuminuria and macroalbuminuria for all cause, cardiovascular and coronary heart disease mortality were determined after accounting for other cardiac risk factors including blood pressure, glycated haemoglobin, total cholesterol, HDL cholesterol, triglycerides, urea, smoking, body mass index, patient age and disease duration. Results: The prevalence of urine albumin of 30–300 mg/L at study entry was 31.7%. A total of 167 deaths occurred (80 from cardiovascular disease). Mortality hazard ratios in subjects with urine albumin of 30–300 mg/L as compared to <30 mg/L, adjusted for age, sex and other cardiovascular risk factors were 1.77 (95% CI 1.22–2.57, p=0.002) for all causes, 2.34 (95% CI 1.38–3.99, p=0.002) for cardiovascular and 1.78 (95% CI 0.97–3.26, p=0.061) for coronary heart disease (CHD) mortality. Other factors significantly associated with cardiovascular mortality included diastolic blood pressure, HDL cholesterol and glycated haemoglobin. Total cholesterol and log triglyceride were significantly associated with CHD mortality. Disease duration, age at diagnosis, smoking and body mass index were not related to cardiovascular or CHD mortality. Conclusions: We confirm microalbuminuria as an independent predictor of mortality in type 2 diabetes despite its association with a number of conventional cardiovascular risk factors.     

Echocardiographic-determined Left Ventricular Wall Characteristics in Insulin-dependent Diabetic Patients

Abstract. Left ventricular wall mass, thickness and movement were investigated by echocardiography in 80 insulin-dependent diabetic patients with no signs of ischaemic heart disease and in 40 healthy controls. In diabetics with a disease duration of >30 yr, urinary albumin excretion rate >200 μg/min (clinical nephropathy), proliferative retinopathy or autonomic neuropathy, both the posterior wall thickness and the septal thickness were increased compared to controls. The posterior wall thickness and the septal thickness were positively correlated to blood pressure (p<0.001), disease duration (p<0.001), urinary albumin excretion rate (p<0.001), and negatively correlated to the heart variation during deep respiration (p<0.01). The left ventricular wall mass was correlated to both blood pressure (p<0.01) and urinary albumin excretion rate (p<0.01). By multiple regression analysis urinary albumin excretion rate, disease duration and heart rate variation during deep respiration did not add significantly to the correlation between left ventricular wall mass/wall thickness and blood pressure. The septal movement was reduced in diabetics with proliferative retinopathy or clinical nephropathy. In conclusion, left ventricular wall thickness and wall mass were closely related to blood pressure in insulin-dependent diabetics. Signs of impaired cardiac function, such as reduced septal movement, were seen only in patients with severe microvascular disease.     

Albumin excretion and vascular deaths in NIDDM

Summary Non-insulin-dependent diabetes mellitus (NIDDM) is associated with premature mortality, generally thought to be exaggerated in patients with microalbuminuria. This prospective 8-year follow-up study aimed to determine outcome, mortality and cause of death in NIDDM patients with abnormal urinary albumin excretion compared to those with normal albumin excretion. We recruited 153 NIDDM patients with abnormal urinary albumin excretion and 153 control subjects with albumin excretion within the normal non-diabetic range, matched for age, sex and duration of diabetes, from three University hospital diabetic clinics in Newcastle upon Tyne. The outcome measures were status at follow-up, mortality and cause of death. Subjects with abnormal albumin excretion had a significantly higher 8-year mortality than matched control subjects (Odds Ratio 1.47, p=0.02; 108 vs 66 per 1000 person years follow-up, p<0.001). This difference was seen at all levels of abnormal albumin excretion, from just outside the normal range (10.6–29.9 g/min: 104 vs 61 per 1000 person years follow-up, p<0.001) to more conventional definitions of microalbuminuria (30 g/min: 111 vs 71 per 1000 person years follow-up, p<0.01). Those with abnormal albumin excretion had an excess of vascular deaths compared to matched control subjects (Odds Ratio 1.70, p = 0.009), again at different levels of albumin excretion (10.6–29.9 g/min p<0.01, 30–150 g/min p<0.05). On multivariate analysis, age, initial ischaemic heart disease and initial albumin excretion rates were independent predictors of death from all causes. Even a minor elevation of albumin excretion above the normal non-diabetic range is associated with excess mortality from vascular causes in NIDDM.Abbreviations NIDDM Non-insulin-dependent diabetes mellitus - AER albumin excretion rate - SBP systolic blood pressure - DBP diastolic blood pressure - CI confidence interval - MAP mean arterial pressure     

Microalbuminuria predicts mortality in non-insulin-dependent diabetics

Forty-four non-insulin-dependent diabetics (NIDD), all with urine negative to Albustix, were studied in 1966/67. By the end of 1980, 17 had died, all but two from cardiovascular causes. All causes of mortality and time to death were significantly related in univariate analyses to age and to the overnight urinary albumin excretion rate (AER), but not to systolic and diastolic blood pressure levels or to duration of diabetes when the latter was corrected for age. Age and duration were highly correlated with each other. In multivariate analyses age and AER were independent predictors of both mortality and time to death, with AER having the greater degree of significance. Thus subclinically elevated albumin excretion rates ('microalbuminuria') indicate a substantially increased mortality risk in non-insulin-dependent diabetes.     

Alteration of oxide reductive and haemostatic factors in type 2 diabetics

Abstract. Objective. To assess any pathogenic role of radical activity and haemostatic alteration in the early cardiovascular disease of microalbuminuric type 2 diabetics (non-insulin dependent). Design. A selected cohort of type 2 diabetics was identified, divided according to urinary albumin excretion and compared with a healthy control group depending on some haemostatic factors and radical activity. Setting. All the subjects were studied as outpatients. Subjects. Eighty diabetics and 84 healthy controls were interviewed and underwent blood tests to exclude standard cardiovascular risk factors before follow up. Main outcome measures. The subjects were males, age range 43–55 years, and divided according to albumin excretion (microalbuminuria > 30–200 mg L^?1; normoalbuminuria < 15 mg L^?1). The mean duration of diabetes referred by the patients was 9.3 years in albuminuric and 11.1 years in normoalbuminuric patients with a good control of plasma glucose level. Neither the diabetics nor the control group showed clinical evidence of renal and cardiovascular diseases. Results. Microalbuminuric patients presented elevated malondialdehyde concentration, glutathione peroxidase activity, phospholipidic fatty acid levels, fibrinogen, plasminogen activator inhibitor, tissue plasminogen activator and von Willebrand factor compared with normoalbuminuric patients and controls. More collagen was required in microalbuminuric diabetics than in normoalbuminurics and controls. Conclusions. Our results confirm that both free radical activity and changes in haemostatic factors can be observed in type 2 diabetes and particularly in patients with albuminuria. Our very selected series with short duration, good control of diabetes and lack of clinical evidence of cardiovascular disease may suggest that these abnormalities develop earlier and may be associated with, and/or implicated in, the pathogenesis of microvascular complications which can be related to a higher and early cardiovascular morbidity and mortality rate in microalbuminuric diabetics.     

Lack of an association of urinary albumin excretion with interleukin-6 or C-reactive protein in patients with type 2 diabetes

The reason for the elevation of fibrinogen concentration in diabetic patients with nephropathy is not known so far. In order to elucidate the mechanism of such an increase in fibrinogen levels, we investigated haemorheological and inflammatory markers in type 2 diabetic patients in a cross-sectional design. Thirty-two non-smoking type 2 diabetic patients (13 women, 19 men; body mass index 29.1±5.4 kg/m², age 62.8±12.1 years) were investigated. Patietns with C-reactive protein levels > 1.5 mg/dl were excluded from the study. Concentration of fibrinogen was measured by immunonephelometry, C-reactive protein by immunoturbidimetry, and interleukin-6 (IL-6) by an enzyme-linked immunosorbent assay, and viscosity of plasma and of whole blood was determined by rotation viscosimetry. Concentrations of inflammatory parameters were well correlated with each other (p<0.05 for all correlations): IL-6 with C-reactive protein (r=0.48), and C-reactive protein with fibrinogen (r=0.41). While no associations were found with concentrations of C-reactive protein or IL-6, urinary albumin excretion was correlated with erythrocyte sedimentation rate (r=0.47) and with fibrinogen concentration (r=0.39; p<0.05). In patients with type 2 diabetes mellitus, urinary albumin excretion was not associated with concentrations of IL-6 or C-reactive protein. These results suggest an IL-6-independent mechanism for increased fibrinogen levels and erythrocyte sedimentation rate in type 2 diabetic patients with increased urinary albumin excretion. Received: February 2000 / Accepted in revised form: October 2001     

Urinary Infection and Albumin Excretion in Insulin-dependent Diabetes Mellitus: Implications for the Measurement of Microalbuminuria

The frequency of urinary infection was determined using quantitative microbiology in 172 insulin-dependent diabetic patients repeatedly being tested for microalbuminuria over 18 months on at least six occasions. The point prevalence of urinary infection at first screening for microalbuminuria was 3 %. Over the period of study, 20 of the patients (12 %) showed evidence of urinary infection, defined as a pure growth of a recognized pathogen >10⁷ l⁻¹. Infection was more common in women than men (20 % vs 5 %, p<0.01) and was significantly associated with the presence of peripheral neuropathy (p<0.05). Infection was not related to patient age, duration of diabetes, glycaemia, blood pressure, retinopathy or autonomic neuropathy. There were no significant within-patient differences in albumin excretion, glycaemic control or blood pressure in relation to the presence and absence of urinary infection. In only one patient (5 %) did urinary infection significantly increase the urinary albumin excretion and this was associated with pyuria. We conclude that the presence of urinary infection does not apparently affect the measurement of urinary albumin excretion unless pyuria is present. Unless diabetic patients are symptomatic, examination of the urine for infection is probably unwarranted when testing for microalbuminuria.     

The Relationship Between Plasminogen Activator Inhibitor-1 and Insulin Resistance in Newly Diagnosed Type 2 Diabetes Mellitus

It is not clear whether elevated levels of the fibrinolytic inhibitor, plasminogen activator inhibitor-1 (PAI-1) in Type 2 diabetes mellitus are the result of obesity or coexistent atherosclerosis. Therefore the relationship between PAI-1 and insulin resistance, determined by the homeostasis model assessment (HOMA) was investigated in a group of 26 insulin-resistant, normotensive newly diagnosed Type 2 diabetic patients with a low probability of atherosclerosis. Compared with a normal control group, closely matched for body mass index (BMI), fibrinolytic activity was depressed in the diabetic patients due to elevated levels of the inhibitor PAI-1, 17.6 (11.1–28) vs 8.4 (4.9–14.1) IU ml^?1, p < 0.001. PAI-1 was related to BMI, r = 0.59, p < 0.001 plasma insulin, r=0.66, p < 0.001; insulin resistance, r = 0.54, p< 0.005 and urinary albumin excretion, r=0.48, p < 0.01, but not HbA_1c or fasting glucose. PAI-1 was not related to blood pressure or plasma triglyceride levels. This study suggests that at the time of diagnosis of Type 2 diabetes mellitus, elevated PAI-1 levels are already linked to other risk factors for vascular disease including hyperinsulinaemia, insulin resistance, and urinary albumin excretion, and this is not the result of obesity or coexistent atherosclerosis.     

Levels of cardiovascular risk factors in type 2 diabetes mellitus are dependent on the stage of proteinuria.

Levels of cardiovascular risk factors were determined in 75 patients with Type 2 diabetes mellitus. The patients were divided into three groups according to their urinary protein excretion (UPE): (a) normal proteinuria (less than or equal to 70 mg d-1); (b) microproteinuria (70-500 mg d-1); and (c) macroproteinuria (greater than 500 mg d-1). A significant stepwise increase in mean systolic blood pressure, LDL-cholesterol and fibrinogen levels was observed from the first to the third investigated group of patients. Mean apoprotein B levels were significantly increased in the group with macroproteinuria compared to the other two groups. Significant linear correlations were found between UPE and LDL-cholesterol, total cholesterol, apoprotein B, creatinine, systolic blood pressure and diabetes duration. In summary, it is concluded that the levels of some cardiovascular risk factors increase with the stage of proteinuria in Type 2 diabetes mellitus.     

Alterations in serum lipids and apolipoproteins in male Type 1 (insulin-dependent) diabetic patients with microalbuminuria

Summary The relationships between serum lipid, apolipoprotein levels and urinary albumin excretion were investigated in 20 male Type 1 (insulin-dependent) diabetic patients with microalbuminuria (overnight urinary albumin excretion between 10 and 200 g/min), in 18 male Type 1 diabetic patients without microalbuminuria and in 18 male control subjects. In the microalbuminuric patients low density lipoprotein cholesterol was higher than in the control subjects (p<0.05); the high density lipoprotein/low density lipoprotein cholesterol ratio was lower than in the normoalbuminuric diabetic patients (p<0.05), and in the control subjects (p<0.01); apolipoprotein B was higher than in the normoalbuminuric patients (p<0.05); the apolipoprotein A₁/B ratio was lower than in the normoalbuminuric diabetic patients (p<0.05). Serum triglyceride was higher in the microalbuminuric diabetic patients and in the control subjects than in the normoalbuminuric diabetic patients (p<0.05, for both), but was not different between the microalbuminuric diabetic patients and the control subjects. No significant differences between the 3 groups were present with respect to serum cholesterol, high density lipoprotein cholesterol and apolipoprotein A₁. In the 2 combined Type 1 diabetic groups there were significant correlations between urinary albumin excretion and the high density lipoprotein/low density lipoprotein cholesterol ratio (R -0.40, p<0.02), apolipoprotein B (R0.35, p<0.05) and the apolipoprotein A₁/B ratio (R -0.44, p<0.01). These results indicate microalbuminuria related differences in lipid and apolipoprotein levels in male Type 1 diabetic patients, which may contribute to an increased risk of cardiovascular disease.     

Prevalence of microalbuminuria in maturity onset primarily non-insulin-requiring diabetes mellitus: Effect of disease duration,glycemic control,and mean systemic blood pressure

Because of the frequency of late cardiovascular complications in maturity onset non-insulin-dependent (Type II) diabetes mellitus, there have been few studies regarding nephropathy in this patients population. The authors have analyzed the prevalence of microalbuminuria and the nature of clinical manifestations associated with elevated albumin excretion rate (AER) in a large poputation presenting with Type II diabetes. Among 318 patients studied during 1986, pathologically elevated 24 h AERs were found in 59%. The rate of microalbuminuria among 205 Type I diabetic patients screened during the same interval was 43%. AER was found to be positively correlated with duration of disease (p<0.0008) and metabolic control as determined by measurement of glycosylated hemoglobin (HaA1_c) (p<0.002). There was only a modest agreement between AER and mean systemic blood pressure. The high prevalence of microalbuminuria in Type II diabetic patients and its known association with increased mortality emphasize the need for long-term follow up studies in order to clarify whether elevated AER in this patient populationsis predictive for overt diabetic nephropathy.