Diabetes mellitus and vascular calcification

Two types of arterial calcification are well recognized:intimal (atherosclerotic) and medial (Monckeberg type). These two calcifications are considered different in pathogenesis. Arterial calcification has recently been reported to be an organized, regulated process similar to bone formation. The relation of calcification to diabetes mellitus remains still unclear. EBCT can noninvasively and accurately detect coronary artery calcification. Diabetic patients seem to have increased prevalence of coronary calcification when compared with non-diabetic patients. Medial artery calcification is an independent predictor of cardiovascular mortality in diabetic patients.     

Elevation of urinary betaig-h3, transforming growth factor-beta-induced protein in patients with type 2 diabetes and nephropathy

Transforming growth factor-beta (TGF-beta) is a pro-sclerotic growth factor implicated in the pathogenesis of diabetic nephropathy. betaig-h3 is an extracellular matrix protein which is induced in many cells by TGF-beta. This study examined urinary betaig-h3 excretion in diabetic patients with elevated urinary albumin excretion and the clinical application of urinary betaig-h3 as a marker of diabetic nephropathy. Urinary and serum betaig-h3 levels were determined by enzyme-linked immunosorbent assay in 163 type 2 diabetic patients and 101 healthy control subjects of comparable age and weight. The ratio of urinary betaig-h3 and TGF-beta to creatinine was analyzed in patients with different degree of nephropathy. The betaig-h3 to creatinine ratio in urine was elevated in all groups of type 2 diabetics with normoalbuminuria (101.6 +/- 9.27), microalbuminuria (120.2 +/- 14.48), and overt proteinuria (146.3 +/- 16.34), when compared with control subjects (64.8 +/- 7.14) (P < 0.01). There was a positive correlation between urinary betaig-h3 and TGF-beta excretion rate and a positive correlation between urinary betaig-h3 and albumin excretion rate (AER). These data show that urinary levels of betaig-h3 are elevated in type 2 diabetic patients with nephropathy and may be used as a marker of diabetic nephropathy.     

Serum lipids and lipoproteins in insulin-dependent diabetic patients with persistent microalbuminuria

Serum lipid and lipoprotein concentrations were measured in 18 insulin-dependent diabetic patients with persistent microalbuminuria and an equal number with persistently normal albumin excretion. The groups were matched for sex, age, duration of diabetes, body mass index, insulin dose, and glycosylated haemoglobin. Diabetic patients with persistent microalbuminuria were found to have a significantly lower high density lipoprotein (HDL) cholesterol concentration (difference 0.29, 95% Cl 0.12 to 0.46, mmol l-1, p less than 0.01) and a higher low density lipoprotein (LDL) cholesterol:HDL cholesterol ratio (difference 0.97, 95% Cl 0.29 to 1.65, p less than 0.01) than patients with normal albumin excretion. No significant differences were found in total cholesterol, triglycerides, LDL cholesterol, apolipoprotein (apo) A-I and apo B concentrations. Compared to an age and sex-matched group of non-diabetic subjects with normal albumin excretion, diabetic patients with persistent microalbuminuria had significantly higher concentrations of total cholesterol (p less than 0.05), LDL cholesterol (p less than 0.05) and apo B (p less than 0.01), but a lower concentration of HDL cholesterol (p less than 0.05). No significant differences were found in serum lipids and lipoproteins between diabetic patients with normal albumin excretion and non-diabetic subjects.     

Correlations of urinary albumin excretion and atherosclerosis in Japanese type 2 diabetic patients

Microalbuminuria and aortic stiffness are associated with high mortality in type 2 diabetic patients. We tested the hypothesis that the presence of microalbuminuria correlates with aortic stiffness and insulin resistance in type 2 diabetic patients. The study consisted of 36 Japanese patients with type 2 diabetes and microalbuminuria (age: 56+/-9 years, mean+/-S.D.) and a control group of 44 age-matched patients with normoalbuminuria (56+/-7 years). Brachial-ankle pulse wave velocity (BaPWV) was measured by automatic oscillometric method. BaPWV was used as an index of atherosclerosis. The BaPWV was higher in the microalbuminuria group than in the normoalbuminuria group (p<0.005). Fasting plasma glucose (p<0.05) and insulin concentrations (p<0.005), and the homeostasis model assessment (HOMA) index (p<0.0005), were higher in the microalbuminuria group than in the normoalbuminuria group. Multiple regression analysis showed that urinary albumin excretion was independently predicted by BaPWV and HOMA index. Our results indicate that the presence of microalbuminuria in Japanese patients with type 2 diabetes is characterized by increased aortic stiffness and insulin resistance, and that the BaPWV, HOMA index are independent predictors of urine albumin excretion.     

Association of serum levels of IGF-I and IGFBP-1 with renal function in patients with type 2 diabetes mellitus.

OBJECTIVE: Our aim was to determine whether serum Insulin-like growth factor-I (IGF-I) and Insulin-like growth factor binding protein-1 (IGFBP-1) levels were different between type 2 diabetic patients and non-diabetic control group. We also aimed to establish any relationship that might exist between the serum IGF-I and IGFBP-1 levels with the urinary albumin excretion (UAE), creatinine clearance and urinary N-acetyl-beta-D-glucosaminidase (NAG) excretion (as a marker of renal tubular dysfunction) and other parameters (such as age, duration of diabetes, treatment, etc.) in patients with type 2 diabetes mellitus (DM). DESIGN: Fifty-nine type 2 diabetic patients and thirty-one non-diabetic controls were included in this study. RESULTS: Mean serum IGF-I levels in diabetic patients were lower than the non-diabetic controls (158+/-12 vs. 287+/-26microg/l), (p<0.001). Serum IGFBP-1 levels were also higher in type 2 diabetic patients compared to the control group (67+/-5 vs. 35+/-4microg/l), (p<0.001). No relationship was obtained between IGF-I and IGFBP-1 levels with neither UAE nor urinary NAG excretion. A significant negative relationship was observed between creatinine clearance and serum IGFBP-1 level (r=-0.39, p=0.004). In multiple regression analysis IGF-I was independently and negatively associated with age and insulin treatment. On the other hand, IGFBP-1 was negatively related with creatinine clearance and positively related with the duration of diabetes. CONCLUSION: These results suggest that type 2 DM leads to a decrease in the IGF-I while elevating the IGFBP-1 levels. Further studies are needed to clarify a potential role of increased levels of IGFBP-1 in decreased creatinine clearance in type 2 DM.     

Evaluation of aortic arch calcification in type 2 diabetic patients

BACKGROUND: The purpose of this study is to evaluate the severity of aortic arch calcification among type 2 diabetic patients in association with diabetes duration, diabetic complications, coronary artery disease and presence of cardiovascular risk factors. PATIENTS AND METHODS: This study included 207 type 2 diabetic patients (101 men) with a mean age of 61.5 +/- 8.1 years and a mean diabetes duration of 13.9 +/- 6.4 years. Aortic arch calcification was assessed by means of posteroanterior chest X-rays. Severity of calcification was graded as follows: grade 0 (no visible calcification), grade 1 (small spots of calcification or single thin calcification of the aortic knob), grade 2 (one or more areas of thick calcification), grade 3 (circular calcification of the aortic knob). RESULTS: Severity of calcification was grade 0 in 84 patients (40.58%), grade 1 in 64 patients (30.92%), grade 2 in 43 patients (20.77%) and grade 3 in 16 patients (7.73%). In simple regression analysis severity of aortic arch calcification was associated with age (p = 0.032), duration of diabetes (p = 0.026), insulin dependence (p = 0.042) and presence of coronary artery disease (p = 0.039), hypertension (p = 0.019), dyslipidaemia (p = 0.029), retinopathy (p = 0.012) and microalbuminuria (p = 0.01). In multiple regression analysis severity of aortic arch calcification was associated with age (p = 0.04), duration of diabetes (p = 0.032) and presence of hypertension (p = 0.024), dyslipidaemia (p = 0.031) and coronary artery disease (p = 0.04), while the association with retinopathy, microalbuminuria and insulin dependence was no longer significant. CONCLUSIONS: Severity of aortic arch calcification is associated with age, diabetes duration, diabetic complications (retinopath), microalbuminuria), coronary artery disease, insulin dependence, and presence of hypertension and dyslipidaemia.     

Urinary excretion of albumin, α-1-microglobulin,and N-acetyl-B-D-glucosaminidase in relation to smoking habits in diabetic and nondiabetic subjects

Smoking may be a risk factor for the development of diabetic nephropathy. Therefore, the urinary excretion of albumin, α-1-microglobulin, and N-acetyl-BD glucosaminidase was studied in 24 young adult diabetic patients who smoked. None of these patients had urine samples positive for albumin as determined by the Albustix method (i.e., a urinary concentration of albumin of < 0.5 g in 24 hr). Control groups were nonsmoking diabetic patients (matched for age and duration of diabetes) and nondiabetic subjects (smokers and nonsmokers). Explred breath carbon monoxide and the urinary nicotine metabolite continine were measured as objective markers of smoking load. No significant differences in concentrations of urinary proteins were found among any of the four groups. Therefore, smoking is not associated with the development of an increased urinary excretion of albumin within the “microalbuminuria” range. However, further studies are required to determine whether smoking is a risk factor for the progression of established microalbuminuria to Albustix positive proteinuria in diabetic patients.     

Plasma lipids and urinary albumin excretion rate in Type 1 diabetes mellitus: the EURODIAB IDDM Complications Study.

AIMS: To examine the relationship between increased urinary albumin excretion rate and fasting plasma lipids among male and female respondents to the EURODIAB IDDM Complications Study, and attempt to explain inconsistencies in previous reports. METHODS: A cross-sectional study of 3250 randomly selected Type 1 diabetic patients from 31 diabetes clinics in 16 European countries was carried out between 1989 and 1990. Plasma lipids and urinary albumin were measured centrally. The present analysis was confined to the subgroup of 2205 patients attending after a 10-12 h overnight fast. Mean age was 33 years (SD 10) and mean duration of Type 1 diabetes mellitus was 15 years (SD 9). RESULTS: The prevalence of microalbuminuria (24-h urinary albumin excretion rate 20-200 microg/min) was 21.7% (95% confidence interval 19.9-23.5) and macroalbuminuria (24-h urinary albumin excretion rate > 200 microg/min) 7.8% (6.6-9.0). In comparison to patients with normal urinary albumin excretion rate (< 20 microg/min), and after controlling for age, sex, glycaemic control, duration of diabetes and current smoking, macroalbuminuria was associated with significantly (P<0.01) increased fasting plasma triglycerides, cholesterol, LDL-cholesterol, cholesterol:HDL-cholesterol ratio and, in women, reduced HDL-cholesterol. In men and women with microalbuminuria, the only significant association was with increased plasma triglycerides. CONCLUSIONS: These data confirm that there is an association between fasting plasma lipids and increasing urinary albumin excretion rate in European Type 1 diabetic patients. In microalbuminuric patients, however, the association was weaker than previously reported and partly explained by confounding factors.     

The relationship between the development and progression of microalbuminuria and arterial blood pressure in type 1 (insulin-dependent) diabetes mellitus.

OBJECTIVE: to investigate the association between urinary albumin excretion and arterial blood pressure in type 1 (insulin-dependent) diabetes. RESEARCH DESIGN AND METHODS: urinary albumin excretion and blood pressures were followed prospectively for a mean period of 26 months (range 18-29 months) in 46 young type 1 (insulin-dependent) diabetic subjects without overt nephropathy. Supine blood pressures (BP) were measured by a single observer using a random zero sphygmomanometer. Albumin excretion was assessed at baseline by a timed clinic excretion rate (AER; microalbuminuria = AER greater than 33 micrograms/min), and at follow-up in at least two urine specimens by the albumin/creatinine (A/Cr) ratio (micro-albuminuria = A/Cr greater than 3.7 mg/mmol). RESULTS: 39 subjects initially had normal AERs. Seven had developed microalbuminuria at follow-up: their mean BP rose from 114 +/- 13/62 +/- 13 to 119 +/- 7/77 +/- 5 mmHg (for diastolic BP, P less than 0.05), while there was no change in the mean BP in the remaining 32 patients. A rise in diastolic BP of greater than 10 mmHg occurred in five of the seven subjects who developed microalbuminuria, and in only seven of 32 who did not (P = 0.02). In the seven patients in whom microalbuminuria persisted (n = 3) or progressed to overt proteinuria (n = 4), BP increased from 123 +/- 12/70 +/- 14 to 139 +/- 12/88 +/- 10 mmHg (P less than 0.02 for both). CONCLUSIONS: this study has shown that BP is normal before the onset of microalbuminuria, and that a rise in diastolic BP accompanies the development or progression of microalbuminuria. The rate of rise in BP may be more important than the absolute level in defining 'hypertension' in young diabetic patients with microalbuminuria.     

Urinary excretion of beta-thromboglobulin and N-acetyl-beta-D-glucosaminidase in type 1 diabetes: potential indicators of early nephropathy?

While microalbuminuria indicates the glomerular damage of early diabetic nephropathy, tubular abnormalities also occur at an early stage of diabetic renal disease. Urinary excretion of beta-thromboglobulin (BTG) and N-acetyl-beta-D-glucosaminidase (NAG) was measured in 132 normotensive Type 1 (insulin-dependent) diabetic patients with no evidence of overt renal disease, of whom 35 had microalbuminuria and the remainder had normal urinary albumin excretion. Of 21 patients in whom there was a detectable urinary BTG concentration, only 8 (38%) had a concurrently abnormal urinary albumin excretion. NAG excretion was elevated in 22 (63%) of the 35 patients with microalbuminuria; significant associations were also identified between urinary NAG excretion and smoking habit (x2 = 12.7, p less than 0.001) and glycated haemoglobin (r = 0.49, p less than 0.01). It is concluded that measurement of urinary BTG is not of sufficient sensitivity to be of value in the detection of early diabetic renal disease, but measurement of urinary NAG may be of value in the detection of diabetic nephropathy at a potentially reversible stage.     

Inducible myocardial ischaemia in asymptomatic Type 2 diabetic patients

BACKGROUND: to define the prevalence of inducible myocardial ischaemia in asymptomatic Type 2 diabetic patients and its relation to urinary albumin excretion rate (AER). METHODS: 98 Type 2 diabetic patients aged 56+/-7 years, and 20 non-diabetic volunteers were recruited. Dypiridamole plus exercise thallium-201 myocardial single photon emission computed tomography (SPECT) was performed in all participants. Exclusion criteria were: age <30 or >70 years, evidence of cardiovascular disease, anomalous ECG, autonomic neuropathy or serum creatinine level >177 micromol/l. RESULTS: 36 out of 98 diabetic patients (37%) showed abnormal thallium SPECT (considered as inducible myocardial ischaemia), versus one out of 20 (5%) in control group (odds ratio 7.3 (95% CI 1.1-50.5), P<0.005). Among diabetic patients, prevalence of inducible ischaemia was greater in those with higher urinary AER (AER <30:30-300:> 300 mg/24 h: 26: 53: 88%, and greater in the normoalbuminuric group compared to the control group (26 vs. 5%; P<0.05). An AER >30 mg/24 h was the only independent factor associated with inducible myocardial ischaemia in the multivariate analysis (P=0.009). CONCLUSIONS: raised urinary AER in asymptomatic diabetic patients is a risk factor for present myocardial ischaemia demonstrated by thallium dypiridamole tomography. The prevalence of inducible myocardial ischaemia in asymptomatic diabetic patients without known coronary disease is much higher than in non-diabetic population.     

New definition of microalbuminuria in hypertensive subjects: association with incident coronary heart disease and death

Microalbuminuria has so far been defined as urinary albumin excretion between 20 and 200 microg/min (or 15 to 150 microg/min overnight). In a recent report, an overnight urinary albumin excretion >5 microg/min was strongly predictive of coronary heart disease and death in the general population. The aim of the present study was to confirm this observation in a population of hypertensive individuals. In The Third Copenhagen City Heart Study in 1992 to 1994, 1734 men and women aged 30 to 70 years with hypertension, but no history of coronary heat disease, delivered a timed overnight urine sample. They were followed-up prospectively by registers until 2000 with respect to coronary heart disease, and until 2004 with respect to death. During follow-up, 123 incident cases of coronary heart disease and 308 deaths were traced. Incident coronary heart disease occurred in 11% of subjects with urinary albumin excretion > or =5 microg/min compared with 5% in subjects with urinary albumin excretion <5 microg/min (P<0.001). Similarly, the cumulative mortality was 28% versus 13% (P<0.001). The relative risks of coronary heart disease and death associated with urinary albumin excretion > or =5 microg/min were 2.0 (1.4 to 2.9; P<0.001) and 1.9 (1.5 to 2.3; P<0.001), respectively, after adjustment for age, sex, blood pressure level, antihypertensive drugs, diabetes, creatinine clearance, smoking, lipoproteins, and body mass index. In conclusion, our study supports the new definition of microalbuminuria as urinary albumin excretion >5 microg/min. In future risk assessment in hypertensive individuals, measurement of microalbuminuria has to be included.     

Low muscular mass and overestimation of microalbuminuria by urinary albumin/creatinine ratio

Microalbuminuria is a mild urinary albumin elevation and is associated with cardiovascular disease. Urinary albumin/creatinine ratio is recommended for microalbuminuria assessment, because it reflects urinary albumin excretion. Muscular mass could affect albumin/creatinine ratio, because urinary creatinine reflects muscular mass. The study investigated high albumin/creatinine ratio attributed to low urinary creatinine without microalbuminuria. The Gubbio Population Study for ages 45 to 64 collected data on weight, skinfold, urinary albumin, urinary creatinine, and coronary heart disease. Weight and skinfold thickness were used to calculate fat and nonfat mass and urinary creatinine as a marker of muscular mass. Microalbuminuria was defined as urinary albumin of 20 to 199 microg/min and high albumin/creatinine ratio as a ratio of 17 to 250 microg/mg in men and of 25 to 355 microg/mg in women. Persons with macroalbuminuria (urinary albumin > or =200 microg/min) were excluded to focus analyses on microalbuminuria. Coronary heart disease was defined by ECG and questionnaire. The target cohort consisted of 1623 men and women, ages 45 to 64. Prevalence was 8.5% for high albumin/creatinine ratio (n=138), 4.3% for microalbuminuria (n=69), 5.2% for high albumin/creatinine ratio without microalbuminuria (n=85), and 1.0% for nonhigh albumin/creatinine ratio with microalbuminuria (n=16). High albumin/creatinine ratio without microalbuminuria was inversely associated with nonfat mass and urinary creatinine (P<0.04). Compared with persons with a nonhigh albumin/creatinine ratio, coronary heart disease was more prevalent in persons with a high albumin/creatinine ratio and microalbuminuria (18.9% and 7.1%; P=0.002), not in persons with a high albumin/creatinine ratio without microalbuminuria (8.2% and 7.1%; P=0.706). A high albumin/creatinine ratio in persons with low muscle mass indicates low urinary creatinine more often than microalbuminuria and cardiovascular disease.     

Rationale and design of a study comparing two fixed-dose combination regimens to reduce albuminuria in patients with type II diabetes and hypertension

Diabetic nephropathy is the leading cause of end-stage renal disease (ESRD). The early stage of nephropathy is manifested by the presence of low levels of urinary albumin (microalbuminuria or urinary albumin excretion >or=30 and <299 mg/day). Albuminuria is a marker for development of nephropathy in type II diabetes and for increased cardiovascular morbidity and mortality. Recent studies have demonstrated the importance of antihypertensive agents that inhibit the renin-angiotensin-aldosterone (RAA) system to reduce the risk and slow down the progression of renal disease. A new clinical trial, GUARD (Gauging Albuminuria Reduction With Lotrel in Diabetic Patients With Hypertension), is designed to compare the change in urinary albumin to creatinine ratio after 1 year of initial treatment with either amlodipine besylate/benazepril HCl or benazepril HCl/hydrochlorothiazide. Other objectives include a comparison of the proportion of patients who progress to overt diabetic nephropathy and the safety of these two combination therapies in these high-risk patients.     

The incidence of microalbuminuria and its associated risk factors in type 2 diabetic patients in isfahan, iran

AIM: The study was carried out to determine the five-year incidence of microalbuminuria and to assess its associated risk factors for type 2 diabetic patients in Isfahan, Iran. METHODS: 505 type 2 diabetic patients (22% male, 78% female) with normal urinary albumin levels, being treated at Isfahan Endocrine and Metabolism Research Center, were consecutively selected. After the initial selection in 1999, the patients were followed for five years. Mean and standard deviation (SD) of age and duration of diabetes was 57.4 (9.5) and 10.2 (4.7) years, respectively. BMI, blood pressure, fasting plasma glucose, HbA1c, serum lipids and serum creatinine were measured and re-examined every three months. 24-h urinary albumin excretion was measured and reviewed annually. Microalbuminuria was diagnosed when at least two measurements indicated the excretion of more than 30 mg albumin in 24-h urinary samples. RESULTS: During 5-year follow up, 176 patients developed microalbuminuria, giving an incidence rate of 82.3/1000 person/year (95% CI: 78.3-86.2). Males had a higher incidence than females (104.4 vs. 66.2/1000 person/year, p < 0.001). Duration of diabetes, abnormal levels of HbA1c, hypertension and high serum creatinine were significantly associated with microalbuminuria. There was no difference in mean of age, BMI, and lipid levels between patients with and without microalbuminuria. Multivariate analysis was used to show that duration of diabetes, HbA1c, hypertension and retinopathy were the independent variables related to microalbuminuria. CONCLUSIONS: The incidence of microalbuminuria in the study population was higher than in other populations. The higher incidence and the considerable gender difference in this population may be attributed to inferior glycemic control and lack in screening for risk factors, but this needs to be explored in further studies.     

Plasma and urinary vascular endothelial growth factor and diabetic nephropathy in Type 2 diabetes mellitus.

AIMS: Vascular endothelial growth factor (VEGF) has been implicated in the pathogenesis of diabetes mellitus. We determined whether alterations of plasma and urinary VEGF levels are related to diabetic nephropathy in Type 2 diabetic patients. METHODS: One hundred and seven patients and 47 healthy controls were studied. Study subjects were divided into four groups using urinary albumin-to-creatinine ratio (ACR): a non-diabetic healthy control group (n = 47), a normoalbuminuric diabetic group (n = 37), a microalbuminuric diabetic group (n = 37) and an overt proteinuric diabetic group (n = 33). VEGF levels were measured by enzyme-linked immunosorbent assay. RESULTS: (i) Urinary VEGF concentrations were significantly higher in the diabetic groups, even at the normoalbuminuric stage (log VEGF/Cr, normoalbuminuria; 4.33 +/- 1.06 vs. control; 3.53 +/- 0.79, P = 0.009). Urinary VEGF excretions increased as diabetic nephropathy advanced. (ii) Plasma and urinary VEGF levels were higher in hypertensive diabetic patients than in the normotensive individuals with diabetes. (iii) In those with diabetes, plasma VEGF levels were found to be positively correlated with plasma urea (r = 0.398, P = 0.039) and urinary ACR (r = 0.251, P = 0.044), and urinary VEGF to be positively correlated with urinary ACR (r = 0.645, P < 0.001), and creatinine (r = 0.336, P = 0.009), and to be negatively correlated with serum albumin (r = -0.557, P < 0.001). Urinary VEGF and serum creatinine were independently correlated with urinary ACR. CONCLUSIONS: Urinary excretion of VEGF increased during the earlier stage of diabetic nephropathy and was significantly correlated with urinary albumin excretion. This suggests that urinary VEGF might be used as a sensitive marker of diabetic nephropathy and for predicting disease progression.     

Urinary Glycosaminoglycan Excretion in NIDDM Subjects: Its Relationship to Albuminura

Nephropathy is a serious microvascular complication of diabetes mellitus which is preceded by a period of microalbuminura. Increased loss of proteoglycan (PG) from glomerular basement (GBM) has been postulated to alter glomerular charge selectivity which contributes to urinary loss of albumin. In this study we measured the excretion of urinary glycosaminoglycans (GAG), the degradation products of PG, in 82 non-insulin-dependent (NIDDM) (Type 2) diabetic and 34 non-diabetic subjects. We found that diabetic subjects had a significantly higher GAG urinary excretion rate compared to non-diabetic subjects (12.54 ± 5.67 vs 8.80 ± 3.99 μg glucuronic acid min⁻¹, p = 0.0001). Categorizing for albuminuric status shows that the diabetic normo-, micro- and macroalbuminuric groups have a higher GAG excretion rate than non-diabetic subjects. Heparan sulphate (HS) GAG urinary excretion was measured in 25 samples from diabetic subjects and 18 non-diabetic subjects. Diabetic subjects excreted more HS GAG than controls both as a rate or as a percentage of total GAG (3.70 ± 1.94 vs 2.38 ± 1.48 μg glucosamine min⁻¹, p = 0.02; 31.6 % ± 12.5 vs 23.1 % ± 10.4, p = 0.02). Categorizing for albuminuric status shows that micro- and macro-albuminuric groups have a significantly higher HS GAG excretion rate than non-diabetic subjects. We conclude that, as in IDDM, excretion of GAG and HS GAG is higher in NIDDM and may precede the development of microalbuminuria.     

Urinary N-acetyl-beta-D-glucosaminidase excretion in insulin-dependent diabetes mellitus: relation to microalbuminuria, retinopathy and glycaemic control

N-Acetyl-beta-D-glucosaminidase (NAG) excretion was measured in early morning urine samples from 133 Albustix-negative, normotensive insulin-dependent diabetic patients and 89 non-diabetic controls. Urinary NAG activity was determined using a chromogenic substrate, 2 methoxy-4-(2'-nitrovinyl)-phenyl 2-acetamido-3-deoxy-beta-D-glucopyranoside, and expressed as mumol MNP released/hour/mmol of creatinine. Overall, diabetic patients were found to have a significantly elevated mean urinary NAG activity (p less than 0.01) compared to controls. Within the diabetic patients urinary NAG activity was significantly elevated in patients with either microalbuminuria (p less than 0.001) or "poor" glycaemic control (p less than 0.001), but not in those with retinopathy (p = 0.117). Three-way analysis of variance revealed that the relationship of raised urinary NAG to microalbuminuria and "poor" glycaemic control were statistically independent. Elevated urinary NAG excretion in insulin-dependent diabetes mellitus appears to be associated with early diabetic nephropathy and poor long-term glycaemic control.     

Microalbuminuria, cardiovascular autonomic dysfunction, and insulin resistance in patients with type 2 diabetes mellitus

Urinary albumin excretion/microalbuminuria and cardiovascular autonomic dysfunction are associated with high mortality in type 2 diabetic patients. We tested the hypothesis that the presence of microalbuminuria would correlate with cardiovascular autonomic dysfunction and insulin resistance in type 2 diabetic patients. The study group consisted of 15 Japanese patients with type 2 diabetes and microalbuminuria (age: 56 +/- 10 years, mean +/- SD). The control group consisted of 19 age-matched patients with normalbuminuria (56 +/- 7 years). Cardiovascular autonomic function was assessed by baroreflex sensitivity (BRS), heart rate variability, plasma norepinephrine concentration, and cardiac 123I-metaiodobenzylguanidine (MIBG) scintigraphy. BRS was lower in the microalbuminuria group than in the normalbuminuria group (P < .05). Early and delayed 123I-MIBG myocardial uptake values were lower (P < .05 and P < .005, respectively) and the percent washout rate of 123I-MIBG was higher (P < .0005) in the microalbuminuria group than in the normalbuminuria group. Fasting plasma glucose (P < .05) and insulin concentrations (P < .05), and the homeostasis model assessment (HOMA) index (P < .01) were higher in the microalbuminuria group than in the normalbuminuria group. Multiple regression analysis showed that urinary albumin excretion was independently predicted by the myocardial uptake of 123I-MIBG at delayed phase, fasting plasma insulin concentration, and the HOMA index. Our results indicate that the presence of microalbuminuria in our Japanese patients with type 2 diabetes is characterized by depressed cardiovascular autonomic function and insulin resistance, and that the myocardial uptake of 123I-MIBG at delayed phase, fasting plasma insulin, and HOMA index are independent predictors of urinary albumin excretion.     

Mean platelet volume in patients with type 2 diabetes mellitus

AIM OF THE STUDY: To evaluate mean platelet volume (MPV) in type 2 diabetic versus non-diabetic patients, as well as to investigate the associations between MPV and diabetic complications. MATERIALS AND METHODS: This study included 416 patients divided into two groups. Group A comprised 265 type 2 diabetic patients (131 men) with a mean age of 67.4 +/- 9.5 years and a mean diabetes duration of 14.5 +/- 5.7 years. Group B comprised 151 non-diabetic patients (74 men) with a mean age of 68.6 +/- 9.1 years. MPV (blood samples anticoagulated with sodium citrate) was measured in two blood cell counters (Sysmex SF 3000 and Cell-Dyn 3700). RESULTS: MPV was significantly higher (P = 0.01) in group A (14.2 +/- 2.2 fl) than in group B (7.1 +/- 1.2 fl). In group A MPV was significantly higher (P = 0.043) in patients with retinopathy (15.8 +/- 1.3 fl) than in patients without retinopathy (10.9 +/- 1.1 fl) and also significantly higher (P = 0.044) in patients with microalbuminuria (15.6 +/- 1.2 fl) than in patients without microalbuminuria (10.1 +/- 1.2 fl). No association, however, was found in group A between MPV and age, gender, duration of diabetes, insulin dependency, BMI, HbA1c, coronary artery disease or dyslipidaemia. CONCLUSIONS: MPV is higher in type 2 diabetic patients than in non-diabetic patients. Among type 2 diabetic patients MPV is higher in those who have microvascular complications (retinopathy or microalbuminuria).