Diagnostic and prognostic value of vasodilator stress echocardiography in asymptomatic Type 2 diabetic patients with positive exercise thallium scintigraphy: a pilot study.

AIM: To assess the diagnostic and prognostic value of vasodilator stress echocardiography in Type 2 diabetic patients with positive exercise perfusion scintigraphy. METHODS: Of an initial cohort of 50 asymptomatic Type 2 diabetic patients undergoing exercise single photon emission computed tomography (SPECT) thallium scintigraphy, 24 had a positive thallium scan, with a reversible perfusion defect. All these 24 underwent high dose (up to 0.84 mg/kg in 10 min) dipyridamole echocardiography and coronary angiography independently of stress echocardiography results. All patients were then followed for 61+/-22 months. RESULTS: Coronary angiography showed normal coronary arteries in 11 patients and significant (> 50% visually assessed diameter reduction in a major vessel) coronary artery disease in 13. Stress echocardiography showed 92% sensitivity and 100% specificity for non-invasive detection of coronary artery disease. During follow-up, five patients experienced cardiac events: heart failure in one, angina with subsequent revascularization in two, and myocardial infarction in two. Event-free survival was 100% in the 12 patients with negative and 58% in the 12 patients with positive stress echocardiography (P = 0.08 by Mantel-Cox test). CONCLUSIONS: In asymptomatic Type 2 diabetic patients with stress-induced perfusion defects, vasodilator stress echocardiography is an excellent diagnostic and prognostic tool proven with long-term follow-up.     

Use of dobutamine stress echocardiography in detecting silent myocardial ischaemia in asymptomatic diabetic patients: a comparison with thallium scintigraphy and exercise testing.

AIMS: Silent myocardial ischaemia is frequent in diabetic patients. The aim of this study was to compare the efficacy of thallium-201 single-photon emission computed tomography (201Tl SPECT) coupled with exercise stress testing (EST), and dobutamine stress echocardiography (DSE) in the detection of asymptomatic coronary artery disease. METHODS: Fifty-six asymptomatic diabetic patients, with a known duration of diabetes > 15 years for Type 1 and > 5 years for Type 2, having at least three added risk factors, but without rest ECG abnormalities, were enrolled in this prospective study. All of them were submitted to DSE with a maximum infusion rate of 40 microg/kg per min dobutamine +/- i.v. atropine, and to 201Tl SPECT coupled with EST. Coronary angiography was performed if at least one test was abnormal. RESULTS: Diabetic patients were 37 males and 19 females, aged mean (sd) 60 +/- 10 years, 10 Type 1 and 46 Type 2, with a known duration of disease of mean (sd) 17 +/- 9 years. Feasibility of DSE was 91%. No serious complication occurred during the test. Coronary angiography was performed in 26 patients (47%); 17 were abnormal (30% of the whole group): six patients had a one-vessel, six a two-vessel and five a three-vessel disease. Predictive positive value was 69% for DSE, 75% for 201Tl SPECT and 60% for EST. DSE was falsely negative in four cases vs. eight for 201Tl SPECT and nine for EST. CONCLUSIONS: Asymptomatic coronary disease is common in diabetes associated with other risk factors. DSE appears useful in its detection and a good alternative to 201Tl SPECT.     

Prediction of cardiac death in hemodialysis patients by myocardial fatty acid imaging.

OBJECTIVES: The aim was to evaluate the potential of single-photon emission computed tomography (SPECT) to predict cardiac death in chronic hemodialysis patients using the iodinated fatty acid analogue iodine-123 123I-beta-methyl iodophenyl-pentadecanoic acid (BMIPP). BACKGROUND: We previously reported that BMIPP SPECT could detect asymptomatic coronary artery disease with high sensitivity in hemodialysis patients. METHODS: We prospectively enrolled 375 asymptomatic hemodialysis patients who had undergone dual SPECT using 123I-BMIPP and 201thallium (Tl) chloride. Patients who had a clinical history of myocardial infarction and/or coronary revascularization were excluded from the study. Uptake on SPECT images was graded in 17 segments on a 5-point scale (0 normal, 4 absent) and assessed as summed BMIPP or Tl scores. RESULTS: During a 3.6 +/- 1.0-year follow-up, 57 patients who had undergone coronary revascularization within 60 days of SPECT were excluded from the analysis. Among the remaining 318 patients (male/female: 170/148; 64 +/- 12 years of age), 50 died of cardiac events (acute myocardial infarction 22, congestive heart failure 17, cardiac sudden death 11). Stepwise Cox hazard analysis associated cardiac death with age (> or =70 years) and with severely abnormal BMIPP SPECT images (BMIPP summed scores > or =12: hazard ratio 21.894; p < 0.0001). Kaplan-Meier analysis showed that the cardiac death-free survival rates at 3 years were 61% and 98% in patients with BMIPP summed scores of > or =12 and <12, respectively. CONCLUSIONS: Severely impaired myocardial fatty acid metabolism, which might mainly reflect repetitive myocardial ischemia, can identify a high-risk group of cardiac death among hemodialysis patients.     

Comparison of coronary calcium and stress myocardial perfusion imaging in apparently healthy siblings of individuals with premature coronary artery disease

Detection of subclinical coronary atherosclerosis is possible using exercise myocardial perfusion imaging for inducible ischemia or multidetector computed tomography for coronary artery calcium (CAC), which is used to detect subclinical coronary atherosclerosis. The extent to which these screening tests converge in an asymptomatic population that is at increased risk for coronary artery disease remains unknown. We compared the concordance of findings in 260 asymptomatic middle-age siblings of hospitalized index patients <60 years of age with documented coronary artery disease. All subjects underwent maximal exercise testing with postexercise and delayed attenuation-corrected thallium single-photon emission computed tomography and multidetector computed tomography for CAC. An abnormal exercise single-photon emission computed tomographic (SPECT) result occurred in >50% of subjects with a CAC score >100, but also in 12% with no CAC, 9% with CAC scores of 1 to 10, and 20% with CAC scores of 11 to 100. In subjects with an abnormal exercise SPECT result, 59% had CAC scores < or =100. Overall, there was only a modest agreement between an abnormal exercise SPECT result and high CAC scores. In conclusion, although moderate or severe CAC is often associated with inducible ischemia, the absence of CAC or the presence of only mild CAC by no means precludes inducible myocardial ischemia. These screening tests may reflect different aspects or stages of coronary disease in an asymptomatic middle-age population.     

Significant bacteriuria in outpatient diabetic and non-diabetic persons.

AIMS: The prevalence of significant bacteriuria (SB) in diabetes mellitus has not been clearly established. Having previously investigated SB frequency in inpatient diabetic women, we now screened for SB (both asymptomatic and symptomatic forms) in outpatients. METHODS: We examined 511 consecutive outpatients with Type 1 (T1D) or Type 2 diabetes (T2D), and 98 non-diabetic subjects. At least one uncontaminated midstream urine sample was available from 602 subjects: 64 T1D (37 female, age 49 +/- 13 years, diabetes duration 23 +/- 15 years), 441 T2D (212 female, 66 +/- 10 years, 12 +/- 10 years), and 97 healthy control subjects (39 female, 57 +/- 12 years). On the same day, we determined: blood cell count, fasting plasma glucose (FPG), glycated haemoglobin (HbA(1c)), plasma creatinine, urinary creatinine, and urinary albumin excretion (UAE; microg/mg urinary creatinine). RESULTS: The rate of SB was 14.1% in T1D, 9.3% in T2D and 6.2% in control subjects (P = NS). The 50 diabetic patients with SB differed from the 455 diabetic patients without SB in gender (43 male vs. 206 female, P < 0.001), FPG (10.2 +/- 3.6 vs. 9.2 +/- 2.9 mmol/l, P < 0.05), HbA(1c) (7.8 +/- 1.1 vs. 7.5 +/- 1.3%, P < 0.05), and UAE (median 15.6 vs. 7.6 microg/mg, P < 0.01). Eleven diabetic patients with SB had symptoms (vs. 48 without SB, P < 0.05); UAE levels were higher in the 39 asymptomatic diabetic patients with SB than in the 11 symptomatic patients. CONCLUSIONS: The prevalence of SB is similar in outpatient diabetic individuals and in non-diabetic subjects. The main risk factors for SB in diabetic patients were female gender and UAE. The likelihood of asymptomatic SB increased with UAE levels, i.e. with the presence of established microangiopathy. Poor glycaemic control is associated with bacteriuria, either as a cause or consequence of bacteriuria.     

The effects of insulin and short-term hyperglycaemia on myocardial blood flow in young men with uncomplicated Type I diabetes

AIMS/HYPOTHESIS: Insulin enhances coronary vasodilation in healthy subjects. We tested whether insulin is able to induce coronary vasodilation in Type I (insulin-dependent) diabetic mellitus patients. Additionally, the effect of short-term hyperglycaemia on myocardial perfusion was studied. METHODS: Myocardial blood flow was quantitated basally and during adenosine infusion (140 microg/kg per min i.v.) with or without simultaneous insulin infusion (1 mU/kg per min for 60 min) in nine non-smoking Type I diabetic males (HbA(1c) 7.4+/-1.0%) without diabetic complications and 10 healthy non-diabetic otherwise matched males using positron emission tomography and (15)O-water. Diabetic patients were studied on two occasions, once during normoglycaemia (plasma glucose ~6 mmol/l) and once during hyperglycaemia (approximately 10 mmol/l) induced by reducing the dose of insulin for two days. RESULTS: Resting myocardial blood flow was similar in the studied groups (NS). Hyperaemic adenosine stimulated flow was 23% lower in diabetic than in non-diabetic subjects (3.09+/-0.72 vs 4.0+/-1.13 ml x g(-1) x min(-1), p<0.05). Insulin increased significantly adenosine stimulated flow by 23% in diabetic and 17% in non-diabetic subjects (NS between the groups). Hyperglycaemia for two days had no effect on flow values when compared to the values during normoglycaemia (NS). CONCLUSION/INTERPRETATION: Insulin has similar vasodilative effects on coronary arteries in diabetic and non-diabetic subjects. Short-term hyperglycaemia does not alter myocardial blood flow or abolish insulin induced vasodilation in these patients. Insulin induced coronary vasodilation might contribute to the known beneficial effect of intensive insulin therapy on myocardial ischaemia in diabetic patients.     

Yield of stress single-photon emission computed tomography in asymptomatic patients with diabetes

Background

Patients with diabetes without clinically apparent coronary artery disease are at increased risk of cardiac death. The value of screening stress testing in these patients remains controversial. The goal of this study was to examine the yield of stress single-photon emission computed tomography (SPECT) in asymptomatic diabetic patients.

Methods

The results of stress SPECT in patients without prior myocardial infarction or coronary revascularization were compared in asymptomatic diabetics (n = 1738) versus symptomatic diabetic patients (n = 2998), asymptomatic nondiabetic patients (n = 6215), and symptomatic nondiabetic patients (n = 16,214).

Results

Abnormal scans were present in 58.6% of asymptomatic diabetic patients, approximately equal to the percentage in symptomatic diabetic (59.5%) (P = not significant) and higher than in asymptomatic nondiabetic (46.2%) (P < .001) and symptomatic nondiabetic (44.4%) (P < .001) patients. The breakdown of high-risk scans followed a similar pattern in the 4 patient subsets: asymptomatic diabetic, 19.7% versus symptomatic diabetic, 22.2% (P = .051); asymptomatic nondiabetic, 11.1% (P < .001); and symptomatic nondiabetic, 12.5% (P < .001). Patients with diabetes had more electrocardiographic and scan evidence for silent myocardial infarction versus those without diabetes.

Conclusions

Asymptomatic diabetic patients have a high prevalence of both abnormal and high-risk SPECT scans. The finding that approximately 1 in 5 of these individuals has a high-risk scan suggests a potentially more widespread application of screening stress SPECT in asymptomatic diabetic patients to identify those with severe coronary artery disease.     

Albumin excretion rate and its relation to kidney disease in non-insulin-dependent diabetes mellitus

Abstract. Objective . To estimate the occurrence of increased albumin excretion rate (AER) and its significance as a marker of diabetic kidney disease in non-insulin-dependent diabetic subjects. Design . Population-based, controlled cross-sectional study. Setting . A primary health care centre in the city of Tampere, south-west Finland. Subjects . Consecutive, recently diagnosed (n = 150) and long-term (n = 146) middle-aged non-insulin-dependent diabetic subjects. Matched non-diabetic control subjects (n = 150). Main outcome measures . Albumin excretion rate, fractional AER, microalbuminuria (AER 30–300 mg 24 h^?1), clinical nephropathy (AER exceeding 300 mg 24 h^?1) and kidney biopsy in diabetic subjects with an AER exceeding 100 mg 24 h^?1. Results . Mean (± standard deviation [SD]) 24-h AER was increased in recently diagnosed diabetic subjects, 54 (111) mg, and long-term diabetic subjects, 134 (479) mg, compared to non-diabetic control subjects, 16 (19) mg. The fractional AER was 7.5 (18.3) × 10^?6 in recent diabetic subjects, 53.1 (306.9) × 10^?6 in long-term diabetic subjects and 2.8 (3.7) × 10^?6 in non-diabetic control subjects. Microalbuminuria was found in 8% of non-diabetic subjects, in 29% of recent and in 27% of long-term diabetic subjects. The prevalence of clinical nephropathy was 7% in long-term and 4% in recent diabetic subjects, whilst no non-diabetic subject had nephropathy. In 12 of 16 eligible kidney biopsies, diabetic glomerulosclerosis was found, in four subjects the finding was normal. Conclusions . The AER is clearly increased in recent non-insulin-dependent diabetic subjects and further increased in diabetic subjects with a mean disease duration of 10 years. An increased AER in non-insulin-dependent diabetic subjects suggests diabetic kidney disease.     

Occupational Hydrocarbon Exposure and Diabetic Nephropathy

Exposure to hydrocarbons has been implicated in the pathogenesis of glomerulonephritis but its role in the development of diabetic nephropathy remains unknown. Three groups of patients with Type 1 diabetes of over 10 years duration were studied. Group 1 comprised 45 patients (23 F) with no diabetic nephropathy (urinary albumin excretion (AER) –30 mg 24 h^?1), group 2 comprised 37 patients (17 F) with incipient diabetic nephropathy (AER between 30–300 mg 24 h^?1), and group 3 comprised 31 patients (15 F) with overt diabetic nephropathy (AER >300 mg 24 h^?1). The groups were comparable for age, sex, duration of diabetes, recent glycaemic control, social class, and residential area. Patients were assessed blindly by a validated questionnaire and interview for hydrocarbon exposure, consumption of tobacco, analgesic agents, and alcohol. Exposure scores to hydrocarbons derived from the questionnaire were significantly higher in patients with incipient and overt diabetic nephropathy with smoking adjusted odds ratios of 3.6 and 5.2, respectively. The consumption of alcohol, analgesic agents, tobacco, and smoking habits were similar in the three groups. In conclusion, hydrocarbon exposure may be a key environmental factor in the development of diabetic nephropathy in patients with Type 1 diabetes.     

Prognostic relevance of symptoms versus objective evidence of coronary artery disease in diabetic patients.

AIM: Little is known about the prognostic significance of silent versus symptomatic coronary artery disease (CAD) in diabetic patients. We therefore assessed the incidence of scintigraphic evidence of CAD in diabetic patients without known CAD and the impact of symptoms and scintigraphic findings on prognosis. METHODS AND RESULTS: A consecutive series of 1737 diabetic patients without known CAD underwent dual-isotope myocardial perfusion SPECT (MPS) and 1430 were followed-up for a median of 2 (1-8.5) years. Critical events were defined as myocardial infarction or cardiac death. Objective evidence of CAD was found in 39% of 826 asymptomatic diabetic patients, in 51% of 151 diabetic patients with shortness of breath (SOB), and in 44% of 760 diabetic patients with angina. During follow-up, 98 critical events occurred. Annual critical event rates were 2.2% in asymptomatic, 3.2% in angina, and 7.7% in diabetic patients with shortness of breath ( p < 0.001 versus other groups). With MPS evidence of CAD, critical event rates increased to 3.4% (asymptomatic), 5.6% (angina), and 13.2% (SOB) ( p 相似文献   

Urinary concentration of transforming growth factor-beta-inducible gene-h3(beta ig-h3) in patients with Type 2 diabetes mellitus.

AIMS: The expression of TGF beta-inducible gene h3(beta ig-h3) has been used to assess the biological activity of TGF beta in the kidney. In this study, we investigated whether the urinary concentration of beta ig-h3 is associated with diabetic nephropathy in patients with Type 2 diabetes mellitus. We also evaluated the relationship between the urinary concentration of beta ig-3 and proteinuria and microalbuminuria (AER) in a normal healthy population and in Type 2 diabetes patients. METHODS: Four hundred and seventy-nine Type 2 diabetic patients without non-diabetic kidney diseases and 528 healthy control subjects were enrolled. The study subjects were divided into five groups: a non-diabetic healthy control group with normal ACR (n = 443), a non-diabetic healthy control group with microalbuminuria (n = 85), a normoalbuminuric diabetic group (n = 198), a microalbuminuric diabetic group (n = 155) and an overt proteinuria group (n = 126). Urinary levels of beta ig-h3 were measured by enzyme-linked immunosorbent assay. RESULTS: (i) Urinary excretion of beta ig-h3 was significantly higher in the diabetic groups than in the controls, even in the normoalbuminuric stage (25.02 +/- 8.84 vs. 18.67 +/- 6.56, P = 0.03). In diabetic patients, urinary beta ig-h3 levels increased significantly as diabetic nephropathy advanced (25.02 +/- 8.84 vs. 34.06 +/- 24.55 vs. 169.63 +/- 57.33, P < 0.001). (ii) Proteinuria was found to be significantly correlated with urinary beta ig-h3 (healthy control; r = 0.137, P = 0.019, diabetic patients; r = 0.604, P < 0.001). ACR was also found to be significantly related with urinary beta ig-h3 in diabetic patients (r = 0.383, P = 0.006). (iii) In diabetic patients, urinary beta ig-h3 was significantly related with systolic and diastolic blood pressure (systolic blood pressure: r = 0.436, P = 0.024; diastolic blood pressure, r = 0.365, P = 0.042), total cholesterol and HbA(1c) (cholesterol: r = 0.169, P = 0.03, HbA(1c); r = 0.387, P = 0.044). Logistic regression analyses showed that urinary beta ig-h3 was associated with a significant increase in the risk of microalbuminuria and proteinuria in diabetic patients. CONCLUSIONS: Longitudinal monitoring of urinary beta ig-h3 may improve the likelihood of detecting diabetic nephropathy at an earlier stage and beta ig-h3 could be a sensitive marker of diabetic kidney disease progression.     

Asymptomatic coronary artery disease in diabetes: associated with autonomic neuropaphy?

To elucidate the potential association of diabetic autonomic neuropathy with increased prevalence of silent coronary artery disease (CAD), 138 asymptomatic diabetic subjects were screened using exercise ECG. 24-h ambulatory ECG and dynamic thallium scintigraphy. Fourteen patients with exercise-induced myocardial ischaemia and angiographically confirmed CAD (50% coronary artery narrowing) were found using this protocol. Their autonomic nervous function was assessed using standard cardiovascular tests and compared with that of 23 consecutive diabetic patients catheterised because of symptomatic CAD (mean New York Heart Association class 3.0). The diabetic patients with symptomatic CAD had more severe coronary atherosclerosis than the diabetic patients with asymptomatic CAD assessed by jeopardy score (P<0.01). The groups did not, however, differ with respect to autonomic function tests. Five patients (22%) with symptomatic CAD and 3 patients (21%) with asymptomatic CAD had definite autonomic dysfunction, i.e. two or more abnormal tests. Thus, our results suggest that the frequency of autonomic neuropathy is not increased in diabetic patients with asymptomatic CAD. The contribution of diabetic autonomic neuropathy to the absence of cardiac pain needs further clinical and pathological studies.     

T wave normalization during dobutamine stress testing in patients with non-Q wave myocardial infarction. A marker of myocardial ischaemia?

Conflicting results in a heterogenous patient population havebeen described on the functional significance of stress-inducedT wave normalization in the ECG. The aim of this study was toevaluate the relationship between T wave normalization duringdobutamine stress testing and stress-induced ischaemia evaluatedby echocardiography and myocardial perfusion scintigraphy inpatients with previous non-Q wave myocardial infarction. Among520 patients who underwent dobutamine stress testing in conjunctionwith simultaneous echocardiography and 201 thallium or sestamibiSPECT for evaluation of suspected myocardial ischaemia, 36 wereselected according to the following criteria: previous non-Qwave myocardial infarction, normal QRS, negative T waves intwo or more ECG leads and no significant ST segment depressionor elevation at rest or during stress. Diagnosis of ischaemiarelied upon the occurrence of reversible perfusion defects byscintigraphy and stress-induced wall motion abnormalities byechocardiography. During the test, T wave normalization (definedas a resting negative T wave becoming upright in one or moreECG leads during stress) occurred in 20 patients (group 1),while in 16 patients the T waves remained negative (group 2).The prevalence of ischaemia was higher in group I than in group2 both by scintigraphy (85% vs 38%, p=0.004) and by echocardiography(70% vs 32%, p=0·02). The sensitivity, specificity andaccuracy of T wave normalization in the detection of ischaemiawere 74%, 77% and 75% by SPECT and 74%, 65% and 69% by echocardiographyrespectively. CONCLUSION: In patients with non-Q wave myocardial infarction and suspectedmyocardial ischaemia, T wave normalization without concomitantECG changes during dobutamine stress testing is associated witha higher prevalence of ischaemia compared to patients with persistentT wave inversion. This ECG finding should not be disregardedas a marker of ischaemia in that particular patient population.     

Prevalence of hypertension in Type 1 (insulin-dependent) diabetes mellitus

Summary The prevalence of hypertension in a representative sample (n=10202) of the Danish general population aged 16–59 years was assessed to 4.4% based on three blood pressure readings. In Type 1 (insulin-dependent) diabetic patients of similar age (n=1703) the prevalence was determined in a similar way to 14.7% (p<0.00001). The excess prevalence in Type 1 diabetic patients was due to hypertension in patients with incipient and clinical nephropathy as the prevalence of hypertension among diabetic patients with normal urinary albumin excretion (essential hypertension) was 3.9%, similar to that observed in the general population. The patients with Type 1 diabetes and essential hypertension had higher systolic (146±19 vs 133±18 mmHg, p<0.00001) and diastolic blood pressure (87±12 vs 79±7mmHg, p<0.00001), but less changes in the eye background than patients with incipient nephropathy (urinary albumin excretion 30–300 mg/24 h) (p<0.03), indicating that the two groups were also different with respect to other microangiopathic lesions. Patients with essential hypertension were defined as having a normal urinary albumin excretion before and during antihypertensive treatment (if any). They were followed-up for a 58 (6–234) month period. We confirmed that hypertension is more common among Type 1 diabetic patients than in the general population and found the prevalence of essential hypertension similar in Type 1 diabetic patients to the non-diabetic population. This supports our hypothesis that hypertension is very unlikely to be the cause of diabetic nephropathy.     

A nation-wide cross-sectional study of urinary albumin excretion rate, arterial blood pressure and blood glucose control in Danish children with type 1 diabetes mellitus. Danish Study Group of Diabetes in Childhood

Nation-wide screening for microalbuminuria in Denmark was performed in 22 paediatric departments treating children with Type 1 diabetes. Over a period of 6 months 1020 children (less than or equal to 12 years) and adolescents (greater than 12 to 19 years) were screened (81% of total). Of these, 957 (94%) performed at least two timed overnight urine collections. In 209 non-diabetic subjects the upper 95% limit for normal albumin excretion rate (AER) was 20 micrograms min-1. Mean overnight AER was significantly (p less than 0.001) elevated in diabetic (3.0 x/divided by 2.3 (SD tolerance factor) micrograms min-1) and in non-diabetic (2.5 x/divided by 2.2 micrograms min-1) adolescents compared with diabetic (1.7 x/divided by 2.1 micrograms min-1) and non-diabetic (1.3 x/divided by 2.2 micrograms min-1) children. In the diabetic patients AER was positively correlated with the body surface area and age. Among the patients with Type 1 diabetes, 4.3% (18 males and 23 females) had AER greater than 20 to 150 micrograms min-1 (persistent microalbuminuria). A further 7 adolescents (0.7%) had overt proteinuria (greater than 150 micrograms min-1). Clinical data for the 41 diabetic patients with AER greater than 20 to 150 micrograms min-1 were compared with those for 569 diabetic adolescents with AER less than or equal to 20 micrograms min-1 and duration of diabetes more than 2 years. The group with AER greater than 20 to 150 micrograms min-1 had significantly higher mean age (16.5 years) than the group with AER less than or equal to 20 micrograms min-1 (15.0 years; p less than 0.001). Females with AER greater than 20 to 150 micrograms min-1 had significantly higher mean HbA1c level (10.8 +/- 1.9%) than those with AER less than or equal to 20 micrograms min-1 (9.8 +/- 1.9%, p less than 0.003); they also had impaired linear growth (standard deviation score -0.25 vs + 0.16; p = 0.003). These associations were not found in males. Mean body mass index (BMI) was significantly increased in both females (22.2 +/- 2.9 kg m-2) and males (20.8 +/- 2.7 kg m-2) with AER greater than 20 to 150 micrograms min-1, compared with diabetic patients with AER less than or equal to 20 micrograms min-1 (females 20.8 +/- 3.0 kg m-2, p = 0.02; males 19.7 +/- 2.4 kg m-2, p less than 0.006).(ABSTRACT TRUNCATED AT 400 WORDS)     

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.     

Transcapillary escape rate of albumin in hypertensive patients with Type 1 (insulin-dependent) diabetes mellitus

Summary Diabetic patients with elevated urinary albumin excretion rate (incipient or clinical nephropathy) also have an increased transcapillary escape rate of albumin. This study was designed to clarify whether this is caused by a general vascular dysfunction or by elevated systemic blood pressure. The systemic blood pressure and the transcapillary escape rate of albumin were measured in the following groups after 4 weeks without antihypertensive treatment: Group 1 — eleven healthy control subjects. Group 2 — ten Type 1 (insulin-dependent) diabetic patients with incipient nephropathy (urinary albumin excretion rate: 30–300 mg/24 h) and normal blood pressure. Group 3 — eleven non-diabetic patients with essential hypertension. Group 4 — nine Type 1 diabetic patients with hypertension but normal urinary albumin excretion (<30 mg/24 h). Group 5 — eleven Type 1 diabetic patients with nephropathy (urinary albumin excretion rate > 300 mg/24 h) and hypertension. Systolic and diastolic blood pressure were similar in the three hypertensive groups: group 3, 148±8/95±6; group 4, 150±12/94±8 and group 5; 152±12/92±7mmHg, but significantly elevated (p<0.001) compared to control group 1,117±12/74±9 and group 2, 128±7/82±4 mm Hg. The transcapillary escape rate of albumin was similar in the control subjects (5.2±2.7%) and the subjects in the normoalbuminuric groups 3 and 4 (6.2±1.9 and 5.1±1.4 %, respectively) and significantly lower (p<0.001) than in patients with elevated urinary albumin excretion without or with hypertension group 2, 10.1±2.8 and group 5, 11.4±5.7 %. The increased transcapillary escape rate of albumin in patients with elevated urinary albumin excretion is unrelated to moderate systemic hypertension and may therefore be caused by alterations in the properties of the capillary walls.     

Screening asymptomatic diabetic patients for coronary artery disease: why not?

Given the elevated risk of cardiovascular events and the higher prevalence of silent coronary artery disease (CAD) in diabetic versus non-diabetic patients, screening asymptomatic diabetic patients for CAD is an appealing concept. However, many factors argue against implementing a broad-based screening program at the present time. Foremost is the lack of any published data demonstrating that a prospectively applied screening program improves outcome in asymptomatic diabetic patients. The true prevalence of CAD, and in particular prognostically important CAD, in this population is uncertain. Consensus documents recommend more aggressive treatment of hypertension and hyperlipidemia solely on the basis of diabetes status, without differentiation based on the presence or absence of identifiable CAD. There is no evidence that use of anti-ischemic medication can alter the natural history of CAD in these patients. Retrospectively performed studies using stress single-photon emission computed tomography (SPECT) imaging have reported that approximately 50% and 20% of patients have abnormal and high-risk images, respectively. However, the only prospectively designed study, the DIAD (Detection of Ischemia in Asymptomatic Diabetics) study, reported a much lower percentage of abnormal SPECT images (16%) and images with a very large (>/=10% of the left ventricle) defect (1%). The financial implications of screening all asymptomatic diabetic patients determined to be at intermediate and high risk by clinical scoring systems is enormous. Clearly more data are needed to address this issue. Future studies should consider possible methods to enrich the patient subset that might benefit from screening and should include carefully performed cost-effective analyses.     

Evaluation of exercise electrocardiography and thallium tomographic imaging in detecting asymptomatic coronary artery disease in diabetic patients

Thallium tomographic imaging and exercise electrocardiography were performed on 136 diabetic patients without symptoms of heart disease. Thirty three patients had post-exercise thallium defects and 19 had ST 1 mm greater than or equal to segment depression during exercise electrocardiography. Both tests were positive in 13 patients. Coronary angiography was subsequently performed on 33 patients with either scintigraphic and/or electrocardiographic evidence of myocardial ischaemia. Angiographically significant coronary artery disease (greater than or equal to 50% narrowing of the coronary artery lumen) was detected in 13 patients. Six patients had minimal coronary artery stenosis (less than 50%), and 14 had normal coronary arteries. Six patients refused cardiac catheterisation. In 14 out of 27 patients with post-exercise thallium defects coronary angiography did not show any coronary artery stenoses (positive predictive accuracy 48%). Exercise electrocardiography showed only one false positive result (positive predictive accuracy 94%) but failed to detect coronary artery disease in three patients with a positive scintigraphic result. The accuracy of a positive exercise electrocardiographic test seems to be better than that of a positive thallium tomographic scan for detecting asymptomatic coronary artery disease in diabetic patients. The high number of false positive thallium defects may be the result of technical features inherent in thallium tomography and/or the possible disease of the small intramyocardial arteries in diabetic patients.     

Evaluation of exercise electrocardiography and thallium tomographic imaging in detecting asymptomatic coronary artery disease in diabetic patients.

Thallium tomographic imaging and exercise electrocardiography were performed on 136 diabetic patients without symptoms of heart disease. Thirty three patients had post-exercise thallium defects and 19 had ST 1 mm greater than or equal to segment depression during exercise electrocardiography. Both tests were positive in 13 patients. Coronary angiography was subsequently performed on 33 patients with either scintigraphic and/or electrocardiographic evidence of myocardial ischaemia. Angiographically significant coronary artery disease (greater than or equal to 50% narrowing of the coronary artery lumen) was detected in 13 patients. Six patients had minimal coronary artery stenosis (less than 50%), and 14 had normal coronary arteries. Six patients refused cardiac catheterisation. In 14 out of 27 patients with post-exercise thallium defects coronary angiography did not show any coronary artery stenoses (positive predictive accuracy 48%). Exercise electrocardiography showed only one false positive result (positive predictive accuracy 94%) but failed to detect coronary artery disease in three patients with a positive scintigraphic result. The accuracy of a positive exercise electrocardiographic test seems to be better than that of a positive thallium tomographic scan for detecting asymptomatic coronary artery disease in diabetic patients. The high number of false positive thallium defects may be the result of technical features inherent in thallium tomography and/or the possible disease of the small intramyocardial arteries in diabetic patients.