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Biomedical subjects

K M Shaw

Publications and source records attributed to K M Shaw.

At least 19 recordsLinked to original sources
PubMed2006

Angiotensin II does not affect endothelial tone in Type 1 diabetes-results of a double-blind placebo controlled trial.

AIMS: Previously, we have demonstrated that patients with normoalbuminuric Type 1 diabetes are characterized by impaired nitric oxide bioavailability compensated for by increased vasodilatory prostanoid-mediated vasodilation. Experimental evidence suggests vascular responses to endogenous angiotensin II involve the nitric oxide and prostaglandin pathways. We examined whether selective blockade of angiotensin II influences endothelial tone with particular reference to the nitric oxide/prostaglandin pathways in patients with Type 1 diabetes free from vascular complications. METHODS: At baseline, we studied changes in forearm blood flow in response to brachial arterial infusions of acetylcholine, l-NMMA, a combination of l-NMMA and the cyclo-oxygenase inhibitor indomethacin and nitroprusside in 30 patients with normoalbuminuric Type 1 diabetes [21 male, 9 female; age 38.5 +/- 1.9 years (mean +/- sem)]. Patients were randomized to 2 weeks' treatment with placebo or the selective angiotensin II receptor blocking agent irbesartan, 300 mg, prior to forearm vasoactive responses being re-examined. RESULTS: The forearm responses to nitroprusside and acetylcholine were unchanged by both placebo (P = 0.23 and P = 0.36, respectively) and irbesartan (P = 0.41 and P = 0.36). Similarily, dose-response curves to acetylcholine in the presense of l-NMMA alone (P = 0.42) and a combination of l-NMMA and indomethacin (P = 0.44) were not altered by angiotensin II blockade. CONCLUSION: This study demonstrated that physiological blockade of endogenous angiotensin II in Type 1 diabetes does not augment agonist-evoked vasodilation or the contribution of nitric oxides and prostanoids to endothelial tone.

Acetylcholine↗
PubMed2006

Plasma homocysteine, oxidative stress and endothelial function in patients with Type 1 diabetes mellitus and microalbuminuria.

AIMS: The purpose of this study was to examine the associations between endothelial function, plasma homocysteine and oxidative stress in patients with Type 1 diabetes mellitus (DM) and microalbuminuria compared with DM patients with normoalbuminuria and non-diabetic control subjects. We wished to test the hypothesis that increased cardiovascular risk in patients with Type 1 diabetes and microalbuminuria may be in part as a result of hyperhomocysteinaemia-mediated oxidative stress leading to impaired endothelial function. METHODS: We measured forearm blood flow, total plasma homocysteine, total antioxidant status (TAOS) and whole blood glutathione in 31 DM patients, 16 with microalbuminuria and 15 with normoalbuminuria, and 15 non-diabetic control subjects. RESULTS: Plasma homocysteine levels were significantly higher in the microalbuminuric diabetic patients compared with the normoalbuminuric patients and the control subjects. TAOS was significantly lower in the micoalbuminuric and normoalbuminuric diabetic patients compared with the control subjects, although TAOS levels were similar in both groups of diabetic patients. There was no difference in forearm blood flow between the groups and no association between measured endothelial function and antioxidant defence/oxidative stress and homocysteine in each group. There was no association between plasma total homocysteine and TAOS or whole blood glutathione within the groups. CONCLUSIONS: We have found mild hyperhomocysteinaemia in microalbuminuric DM patients compared with normoalbuminuric DM patients and non-diabetic subjects and some evidence for reduced antioxidant defence in DM patients. These findings add to our understanding of the increased risk of vascular disease in patients with Type 1 diabetes.

Adult↗
PubMed2006

Flavonoid-rich grapeseed extracts: a new approach in high cardiovascular risk patients?

The management of traditional risk factors such as hypertension and dyslipidaemia has been successful in reducing the development of cardiovascular disease. However, this has not resulted in the amelioration of complications; prompting attention to be focused on novel markers of vascular risk such as endothelial dysfunction (a determinant of vascular tone), vascular inflammation, oxidative stress and insulin resistance. With an ever-growing interest in plant-derived products, agents that could have a beneficial effect on this complex web of pathophysiology have thus been a major area of research and interest. Flavonoids have been a major focus of attention since the days of the French paradox and the presence of high quantity of flavonoids in grapeseed extracts has prompted research looking at its effects on novel markers of vascular risk. This review briefly summarises mechanisms implicated in the development of vascular disease and then focuses upon the potential role of the antioxidant properties of flavonoid-rich grapeseed extracts in the reversal of these processes.

Cardiovascular Diseases↗
PubMed2006

Diabetic erectile dysfunction--an indicator of generalised endothelial function per se?

Erectile dysfunction (ED) affects up to 70% of men with diabetes. However, the pathophysiology of ED in diabetes remains uncertain with both neuronal and vascular factors cited. We examined whether ED is an indicator of generalized endothelial dysfunction. A unique group of diabetic patients free from established conventional cardiac risk factors were investigated. Forearm bloodflow responses to nitroprusside and acetylcholine on 11 diabetic men with ED and 11 potent diabetic men were measured by venous plethysmography. Patient characteristics between the impotent and potent patients were similar except for Hba1c which was higher in the group with ED (8.35% vs. 7.03%: p = 0.003). Both groups showed increases in FBF to incremental infusions of nitroprusside and acetylcholine but the area under curve (AUC) were similar in the ED and the non-ED groups (p = 0.16 and p = 0.17, respectively). We demonstrated that ED in patients with type 2 diabetes is not associated with additional generalized endothelial dysfunction.

Area Under Curve↗
PubMed2005

The contribution of nitric oxide and vasodilatory prostanoids to bradykinin-mediated vasodilation in Type 1 diabetes.

AIMS: To investigate the effect of bradykinin on endothelial tone in normoalbuminuric Type 1 diabetic patients and specifically whether any changes are mediated through nitric oxide or prostaglandins. METHODS: Forearm blood flow was measured using venous occlusion plethysmography at baseline and after brachial artery infusions of incremental doses of bradykinin (50, 100 and 200 ng/min) in 15 patients with Type 1 diabetes and 13 non-diabetic controls. Forearm blood flow at baseline and following bradykinin was then re-examined after local infusion of L-NMMA, a nitric oxide synthase inhibitor, and L-NMMA with indomethacin, a cyclo-oxygenase inhibitor. RESULTS: Baseline blood flow in the diabetic and control groups were similar (4.46 +/- 1.11 vs. 3.41 +/- 1.23 ml/min/100 ml, respectively; P = 0.07). After infusion of L-NMMA and L-NMMA with indomethacin, there was a similar reduction in blood flow responses to bradykinin in both groups. There was no significant difference between the diabetic patients and control subjects in the percentage reduction in forearm blood flow following L-NMMA (16.55 vs. 18.12%, respectively, P = 0.94) and L-NMMA with indomethacin (47.1 vs. 37.3%, respectively, P = 0.14). CONCLUSIONS: This study demonstrates that bradykinin-stimulated vasodilation is mediated by both nitric oxide and prostaglandin release from the endothelium in patients with Type 1 diabetes and normoalbuminuria, and in healthy control subjects. We have also shown that the relative contributions of nitric oxide and prostaglandin to bradykinin-mediated vasodilation are similar in these diabetic patients compared with non-diabetic subjects.

Adult↗
PubMed2005

Cardiovascular risk in women with polycystic ovarian syndrome (PCOS).

AIMS: Studies have suggested that polycystic ovary syndrome (PCOS) is associated with increased cardiovascular risk. The aim of this study was to examine cardiovascular risk profiles in women with PCOS compared with healthy age and weight matched control subjects using novel biochemical and biophysical markers. METHODS: After ethics committee approval, 11 women with PCOS and 12 controls were recruited (mean age, 32; SD, 6.5 years; mean body mass index (BMI), 33.1; SD, 5.9 kg/m2). Serum was analysed for lipid and lipoprotein profile (total and high density lipoprotein cholesterol, triglycerides, apolipoprotein B-100, apolipoprotein A1, lipoprotein (a)), and sialic acid, fibrinogen, homocysteine, and C reactive protein (CRP) concentrations. Endothelial function was also assessed by a standard venous occlusion plethysmography technique to measure reactive hyperaemic forearm blood flow (RH), and expressed as per cent increase from baseline. RESULTS: There were no significant differences in glucose, lipid, or lipoprotein concentrations between the two groups. Furthermore, sialic acid (PCOS: mean, 70.5; SD, 149 mg/litre; controls: mean, 71.3; SD, 112 mg/litre), fibrinogen (PCOS: mean, 3.1; SD, 1.0 g/litre; controls: mean, 3.3; SD, 0.7 g/litre), CRP (PCOS: mean, 4.6; SD, 4.2 mg/litre; controls: mean, 5.41 SD, 5.5 mg/litre), and RH (PCOS: mean, 158.7; SD, 135.5%; controls: mean, 200.1; SD, 114.2%) were similar. CONCLUSIONS: There were no differences in surrogate markers of the processes linked to enhanced cardiovascular risk between patients with PCOS and weight matched controls.

Adolescent↗
PubMed2004

GUIDE study: double-blind comparison of once-daily gliclazide MR and glimepiride in type 2 diabetic patients.

BACKGROUND: Progressive beta-cell failure is a characteristic feature of type 2 diabetes; consequently, beta-cell secretagogues are useful for achieving sufficient glycaemic control. The European GUIDE study is the first large-scale head-to-head comparison of two sulphonylureas designed for once-daily administration used under conditions of everyday clinical practice. DESIGN: Eight hundred and forty-five type 2 diabetic patients were randomized to either gliclazide modified release (MR) 30-120 mg daily or glimepiride 1-6 mg daily as monotherapy or in combination with their current treatment (metformin or an alpha-glucosidase inhibitor) according to a double-blind, 27-week, parallel-group design. Efficacy was evaluated by HbA1c and safety by hypoglycaemic episodes using the European Agency definition. RESULTS: HbA1c decreased similarly in both groups from 8.4% to 7.2% on gliclazide MR and from 8.2% to 7.2% on glimepiride. Approximately 50% of the patients achieved HbA1c levels less than 7%, and 25% less than 6.5%. The mean difference between groups of the final HbA1c was -0.06% (noninferiority test P < 0.0001). No hypoglycaemia requiring external assistance occurred. Hypoglycaemia with blood glucose level < 3 mmol L(-1) occurred significantly less frequently (P = 0.003) with gliclazide MR (3.7% of patients) compared with glimepiride (8.9% of patients). The distribution of the sulphonylurea doses was similar in both groups. CONCLUSIONS: This study provides new insights into therapeutic strategies using sulphonylureas. It shows that gliclazide MR is at least as effective as glimepiride, either as monotherapy or in combination. The safety of gliclazide MR was significantly better, demonstrating approximately 50% fewer confirmed hypoglycaemic episodes in comparison with glimepiride.

Diabetes Mellitus, Type 2↗
PubMed2004

Reduced forearm reactive hyperaemia in normoalbuminuric subjects with Type 1 diabetes and retinopathy.

AIM: To determine whether the forearm vasodilatory response to reactive hyperaemia (RH) is reduced in normoalbuminuric subjects with Type 1 diabetes mellitus and retinopathy compared with subjects with no retinopathy. METHODS: Forearm RH, an indicator of endothelial function, was measured, using strain-gauge plethysmography, in 39 normoalbuminuric subjects (22 with retinopathy) with long-standing Type 1 diabetes mellitus. RESULTS: were evaluated in relation to conventional risk factors for atherosclerosis, and C-reactive protein (CRP), which we have recently determined to be an independent correlate of forearm RH. RESULTS: Forearm RH was decreased in subjects with retinopathy compared with those with no retinopathy (219 +/- 182 vs. 473 +/- 355, P < 0.01). Both retinopathy and CRP proved to be independent and negative predictors, and explain 27% of the variance, in forearm RH. CONCLUSION: Retinopathy in subjects with Type 1 diabetes mellitus may reflect a generalized process of endothelial dysfunction, even in the absence of microalbuminuria.

Age Factors↗
PubMed2001

Long-term predictors of coronary artery disease and mortality in type 1 diabetes.

We assessed clinical and biochemical predictors of death and/or cardiovascular disease in 147 type 1 diabetes mellitus (DM) patients followed-up for 14 years. At follow-up, 28 of patients (19%) had died, and 25 patients (18%) had developed or died of coronary artery disease (CAD). At baseline, those who died had significantly higher serum creatinine (p=0.001) and urine albumin/creatinine ratio (p=0.016), greater prevalence of retinopathy (p=0.006), lower serum apolipoprotein A1 (p=0.046), and lower daily insulin dose (p=0.024) than those who survived. CAD patients had a longer duration of diabetes (p<0.001), were older at the onset of diabetes and at presentation (p=0.001), and had higher prevalences of retinopathy (p=0.005) and neuropathy (p=0.016). The CAD group also had higher baseline serum creatinine (p=0.02), lower HDL cholesterol (p=0.004) and apolipoprotein A1 (p=0.007) and higher LDL cholesterol (p=0.028) and apolipoprotein B concentrations (p=0.027). Under logistic regression analysis (adjusted for age and sex), baseline urine albumin/creatinine ratio (p=0.003), presence of retinopathy (p=0.004), serum creatinine (p=0.028), and serum urea (p=0.034) were the most powerful predictors of mortality, while duration of diabetes (p<0.0001), baseline HDL cholesterol (p=0.012), serum creatinine (p=0.02), apolipoprotein B (p=0.038), LDL cholesterol (p=0.039), and systolic blood pressure (p=0.055) were the strongest predictors of CAD. These findings emphasize the role of abnormal lipoprotein metabolism in the development of CAD in type 1 DM. Indicators of renal impairment and the presence of retinopathy seem to be of greater importance in predicting overall mortality.

Adult↗
PubMed2001

Mutagenesis and functional reconstitution of chlamydial major outer membrane proteins: VS4 domains are not required for pore formation but modify channel function.

Chlamidial organisms are obligate intracellular pathogens containing highly antigenic porin-like major outer membrane proteins (MOMPs). MOMP epitopes are of substantial medical interest, and they cluster within four relatively short variable (VS) domains. If MOMPs adopt a beta-barrel fold, like bacterial porins, the VS domains may form extramembranous loops and the conserved regions of the protein may correspond to predicted membrane-located beta-strands. However, molecular studies on native MOMPs have been hampered by the need to culture chlamydiae in eukaryotic host cells and purification and reconstitution remain problematic. In addition, the organisms are difficult to manipulate genetically, and it has also been difficult to functionally reconstitute recombinant MOMPs. To help overcome these problems and improve our understanding of MOMP structure and function, we cloned and expressed C. trachomatis and C. psittaci MOMPs and functionally reconstituted them at the single-channel level. We measured significant functional differences between the two proteins, and by removing and exchanging VS4, we tested the hypothesis that the largest variable domain forms an extramembranous loop that contributes to these differences. Proteins in which VS4 was deleted continued to form functional ion channels, consistent with the idea that the domain forms an extramembranous protein loop and incompatible with models in which it contributes to predicted membrane-located beta-strands. Additionally, the properties of the chimeric proteins strongly suggested that the VS4 domain interacts closely with other regions of the protein to form the channel entrance or vestibule. Our approach can be used to probe structure-function relationships in chlamydial MOMPs and may have implications for the generation of effective antichlamydial vaccines.

Amino Acid Sequence↗
PubMed2000

Comparison of vasodilator effects of substance P in human forearm vessels of normoalbuminuric Type 1 diabetic and non-diabetic subjects.

AIMS: To compare the vasodilatory responses to substance P in human forearm vessels in Type 1 normoalbuminuric diabetic and non-diabetic subjects. METHODS: Forearm blood flow (FBF) was measured using a plethysmography technique in 12 normoalbuminuric Type 1 diabetic subjects (six males, six females) (HbA(1c) 8.2 +/- 0.3% (mean +/- SEM)) and 12 non-diabetic healthy control subjects in response to the infusion of the vasodilators substance P (SP), acetylcholine (ACh) and nitroprusside. RESULTS: There was no significant difference in baseline FBF between the two groups (2.80 +/- 0.29 ml/min per 100 ml forearm tissue (diabetic group) vs. 2.85 +/- 0.37 ml/min per 100 ml (non-diabetic group), P = 0.45). Infusion of SP was associated with an incremental increase in FBF in the diabetic (0.6, 2 and 6 ng/min - 6.08 +/- 1.07, 7.82 +/- 1.08 and 9.48 +/- 1.14 ml/min per 100 ml, respectively) and the non-diabetic group (0.6, 2 and 6 ng/min - 5.41 +/- 0.80, 6.93 +/- 0.96 and 9.25 +/- 1.11 ml/min per 100 ml, respectively). Similarly, an incremental rise in FBF was observed during infusion of ACh (diabetic group: 7.5, 15 and 30 microg/min - 7.14 +/- 1.22, 8.91 +/- 1.40 and 11.67 +/- 1.93 ml/min per 100 ml, respectively; non-diabetic group: 7.5, 15 and 30 microg/min - 5.87 +/- 0.81, 7.49 +/- 0.96 and 10.74 +/- 1.29 ml/min per 100 ml, respectively). When FBF was expressed as percentage change from baseline, there was no significant difference in vasodilatory responses between the two groups for SP (0.6 ng/min, P = 0.21; 2 ng/min, P = 0.19; 6 ng/min, P = 0.19) or ACh (7.5 microg/min, P = 0.20; 15 microg/min, P = 0.20; 30 microg/min, P = 0.35). CONCLUSIONS: This study suggests that endothelium-dependent vasodilatory responses to SP (and ACh) are not impaired in Type 1 diabetic subjects with normal urinary albumin excretion.

Acetylcholine↗
PubMed2000

Effects of cyclo-oxygenase inhibition on vasodilatory response to acetylcholine in patients with type 1 diabetes and nondiabetic subjects.

OBJECTIVE: Studies examining vasodilatory responses to acetylcholine (ACh) and its derivatives have been conflicting. Enhanced activation of the cyclo-oxygenase pathway and increased availability of vasodilatory prostanoids may occur in type 1 diabetes, and this may compensate for the observed reduction in nitric oxide (NO) activity We examined the role of cyclo-oxygenase inhibition on vasodilatory responses in 12 healthy normotensive type 1 diabetic adults and 12 nondiabetic control subjects of similar age, sex, and BMI. RESEARCH DESIGN AND METHODS: Forearm blood flow was measured using a venous occlusion plethysmography technique at baseline and after brachial artery infusions of ACh (7.5, 15, and 30 microg/min). Forearm blood flow at baseline and after ACh was then reexamined after local intra-arterial infusion of indomethacin (0.3 mg/100 ml forearm volume), a cyclo-oxygenase inhibitor. RESULTS: Baseline blood flow in the diabetic and control groups were similar (2.65 +/- 0.26 vs. 2.59 +/- 0.20 ml/min per 100 ml, respectively; P = 0.4). After indomethacin infusion, the vasodilatory responses to all doses of ACh were reduced in both the diabetic (by 25.30 +/- 4.90%) and control group (by 11.23 +/- 5.45%). However, the reduction in blood flow response to ACh after indomethacin was greater in diabetic patients compared with control subjects (P = 0.03). CONCLUSIONS: Our findings suggest that vasodilatory, prostanoids are important in determining endothelial response to ACh in diabetic and nondiabetic subjects. Increased prostaglandin-mediated vasodilation may compensate for attenuated responses to NO previously reported in diabetic subjects. These findings may partly explain the conflicting reports of endothelial dysfunction in patients with type 1 diabetes.

Acetylcholine↗
PubMed1999

Endothelial dysfunction in Type 2 diabetic subjects with and without microalbuminuria.

AIMS: The primary aim of this study was to determine whether microalbuminuria is associated with endothelial dysfunction in Type 1 diabetes mellitus. The secondary aim was to determine whether any reported biochemical markers of cardiovascular risk are associated with endothelial dysfunction in this group. METHODS: Measurements were made of the vasodilatory responses of the brachial artery to post-ischaemic hyperaemia and to sublingual glyceryl trinitrate (GTN) (causing endothelium-dependent and endothelium-independent dilation, respectively) using a high-resolution ultrasound technique in 18 Type 1 diabetic patients with microalbuminuria, 18 age and sex-matched normoalbuminuric Type 1 diabetic patients and 18 non-diabetic control subjects. RESULTS: There was a significant reduction in flow-mediated dilation (FMD) in microalbuminuric and normoalbuminuric diabetic patients compared with control subjects (2.4% (95% confidence interval (CI) 1.0-3.8%) and 2.3% (95% CI 0.7-3.9%) respectively vs. 6.3% (95% CI 5.1-7.5%), P<0.0001) but no difference in GTN-mediated dilation (14.7% (95% CI 10.7-18.7%) and 15.2% (95% CI 11.2-19.2%) vs. 18.7% (95% CI 16.1-21.3%), P = 0.09). There was no significant difference in FMD, however, between the microalbuminuric group and normoalbuminuric group (P=0.45). FMD was not significantly associated with urinary albumin-creatinine ratio, glycosylated haemoglobin, plasma glucose, lipid or lipoprotein concentrations in diabetic patients. There was a positive correlation between active transforming growth factor (TGF)-beta concentration, a novel biochemical marker of macrovascular disease, and FMD in diabetic patients (r=0.36, P<0.05). GTN-mediated dilation was positively associated with HDL-cholesterol concentration (r = 0.49, P = 0.002) but not with other biochemical variables (including active TGF-beta concentration). Active TGF-beta concentration was not associated with degree of microalbuminuria or other biochemical parameters. CONCLUSIONS: These data suggest that endothelial dysfunction occurs in Type 1 diabetic patients regardless of urine albumin status. Endothelial dysfunction appears therefore to predate the development of microalbuminuria as a marker for the development of coronary artery disease. It is also concluded that low plasma levels of active TGF-beta are associated with an impaired endothelial response and this may provide a useful tool for identifying Type 1 diabetic patients at a greater risk of coronary artery disease.

Adult↗
PubMed1997

Modeling the tensile behavior of human Achilles tendon.

Uniaxial quasi-static tensile stress, sigma versus strain, epsilon, data were obtained from 29 cadaveric Achilles tendons (donor ages: 36 to 100 years), at a strain rate of either 10 or 100%/s. These results were then used in modeling the elastic component of the tensile deformational behavior of this tissue. Two approaches were taken. In the first, it was shown that the following constitutive relation provided an excellent fit to the elastic section of the sigma-epsilon curve, sigma = C epsilon exp[D epsilon + F epsilon 2], with C, D and F being material constants, whose values for the present dataset were found to be C = 2.00 +/- 0.99, D = 0.089 +/- 0.087 and F = -0.0047 +/- 0.0095. The values of these coefficients were not statistically significantly affected by either donor age or test strain rate. In the second approach, the value of the modulus of elasticity of a filamentary polymer matrix composite material was computed as a function of various combinations of values of the modulus of elasticity of the fiber, the modulus of elasticity of the matrix, and angle of orientation of the principal material axes with respect to the reference coordinate axes (theta) for a fiber volume fraction of 0.6 and a material Poisson's ratio of 0.4. By comparing these results with the experimentally-obtained values of the tangent modulus of elasticity of the tendons (defined as the slope of the linear section of the post-toe zone in the sigma-epsilon plot), and assuming that the tendon may be idealized as a filamentary polymer matrix composite material, the suggestion is made that the winding angle of the fibers (collagen fibrils) in the tendon (taken to be equal to theta) is about 6 degrees.

Achilles Tendon↗
PubMed1996

Serum sialic acid and the long-term complications of insulin-dependent diabetes mellitus.

Elevated serum sialic acid (SSA) predicts cardiovascular disease in the non-diabetic population and is also associated with the presence of microalbuminuria and clinical proteinuria in patients with insulin-dependent diabetes (IDDM). We have studied 121 patients with IDDM of long duration (mean duration 25.2 years) to investigate the relationship of SSA concentrations to the presence of retinopathy, nephropathy, and neuropathy. SSA levels were elevated in patients with retinopathy (0.578 +/- 0.161 gl-1, n = 98) when compared with those without retinopathy (0.468 +/- 0.145 gl-1, n = 23, p = 0.002). Patients with nephropathy (urinary albumin:creatinine ratio of > 3 mg mmol-1 in all of three early morning specimens of urine) also had raised SSA levels (0.625 +/- 0.169 gl-1, n = 30) compared with those without nephropathy (0.533 +/- 0.160 gl-1, n = 91, p = 0.006). There was a significant correlation of SSA with urinary albumin:creatinine ratio (correlation coefficient 0.33, p < 0.001). SSA levels were not related to the presence or absence of neuropathy (0.567 +/- 0.181 gl-1, n = 28, vs 0.533 +/- 0.160 gl-1, n = 93, p = 0.92, respectively). In conclusion, retinopathy and nephropathy but not neuropathy are associated with increased SSA levels in patients with IDDM. The significance of this is not yet clear but it is possible that sialic acid is involved in the pathophysiology of microvascular disease in IDDM.

Adult↗
PubMed1996

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 > 10(7)I-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.

Adult↗
PubMed1996

Lipids, lipoproteins, antioxidants and glomerular and tubular dysfunction in type 1 diabetes.

We aimed to examine the relationship of serum lipids, lipoproteins, apolipoproteins and antioxidants with renal dysfunction as measured by urinary excretion of albumin and of retinol binding protein (RBP) in insulin-dependent diabetes mellitus (IDDM). We studied 121 patients with IDDM. Glomerular function was assessed as the urinary albumin/creatinine ratio (UA/UC), and tubular function as the urinary retinol-binding protein/creatinine ratio (UR/UC), both measured in three early morning spot urine samples. The mean (range) UA/UC was 1.95 mg/mmol (0.3-476.5) and UR/UC was 17.5 micrograms/mmol (1.0-1853.8). 17% of the patients had a UA/UC > 3 mg/mmol and 33% had a UR/UC > 20 micrograms/mmol. Significant positive correlations were observed between both UA/UC and UR/UC and the following: serum total cholesterol (P < 0.005); triglycerides (P < 0.001); apolipoproteins A-I (P < 0.05), A-II (P < 0.02) and B (P < 0.002); glycated haemoglobin (P < 0.002). No significant associations were found with serum vitamin E, beta-carotene or total antioxidant activity. In multiple regression, only UA/UC was independently associated with serum apo B and cholesterol concentrations. In conclusion, in IDDM glomerular dysfunction, as measured by UA/UC, is associated with elevated serum cholesterol, triglycerides, apo B, apo A-I and apo A-II, but not with HDL cholesterol or antioxidant status. Tubular dysfunction tends to occur with increasing albuminuria, but it is not independently associated with serum lipid, lipoprotein, apolipoprotein or antioxidant levels.

Adult↗