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Biomedical subjects

D K Yue

Publications and source records attributed to D K Yue.

At least 19 recordsLinked to original sources
PubMed1996

Comparative effects of indapamide and captopril on blood pressure and albumin excretion rate in diabetic microalbuminuria.

Nephropathy affects about one third of diabetic patients and its onset can be predicted almost a decade in advance by detecting small quantities of albumin in the urine (microalbuminuria). Thus, detection of proteinuria or microalbuminuria in diabetic patients carries important implications and merits intervention. Strategies for delaying the relentless progression of microalbuminuria to diabetic nephropathy and ultimately end-stage renal failure are focused on improving glycemic control and reducing blood pressure. Studies with beta-blockers, calcium antagonists, diuretics, and angiotensin-converting enzyme (ACE) inhibitors in hypertensive diabetics with microalbuminuria have shown a significant reduction in urinary albumin excretion rates (AER), with effective lowering of blood pressure. In a crossover study, we compared the effects of captopril versus indapamide as monotherapy for 12 weeks on AER and blood pressure in 31 diabetic patients with established microalbuminuria. The 2 drugs were equally effective in reducing AER (average reduction 30-40%) and had comparable antihypertensive effects.

Albuminuria↗
PubMed1996

Reduction of leucocyte proteolytic enzyme activity in diabetic patients with microalbuminuria and proteinuria: its possible role in diabetic nephropathy.

Mesangium enlargement and glomerular basement membrane thickening are cardinal features of diabetic nephropathy. The reasons for these changes are uncertain but decreased degradation of extracellular matrix may play a role. Mesangium degradation can be modulated by factors intrinsic to the kidney or by factors in the circulation. In this study the capacity of leucocyte proteolytic enzymes to degrade mesangium matrix materials was investigated. Leucocytes were obtained from 57 patients with NIDDM (age 58.3 +/- 8.8 years, duration 9.4 +/- 7.3 years, body mass index (BMI) 30 +/- 6 kg m-2, HbA1c 7.7 +/- 2.0%) and 21 control subjects (age 55.1 +/- 14.6 years, BMI 25 +/- 4 kg m-2). Leucocyte lysates from control and NIDDM subjects with normal AER degraded matrix to the same extent (40.6 +/- 8.2% vs 42.9 +/- 13.5%) while lysates from patients with microalbuminuria and proteinuria were less able to degrade matrix (33.0 +/- 14.2% and 26.1 +/- 12.7%, respectively). There was a significant inverse correlation between matrix degradation and AER (r = -0.49) and multiple regression analysis showed that AER was the most important factor determining degradation rate (R2 = 0.24). Degree of metabolic control, age, and blood pressure were not significant factors. The major enzyme(s) responsible for the matrix degradation was identified as metalloproteinase(s). We conclude that leucocytes from diabetic patients with abnormal albumin excretion have a decreased proteolytic capacity to degrade extracellular matrix. This may play a role in the glomerular basement membrane thickening and mesangium expansion which occurs in diabetic nephropathy.

Albuminuria↗
PubMed1996

Why does ethnicity affect prevalence of gestational diabetes? The underwater volcano theory.

To study why gestational diabetes (GDM) is more common in some ethnic groups than others, we tested the hypothesis that GDM is more common in people who are temporally closer to developing non-insulin-dependent (Type 2) diabetes mellitus (NIDDM). The prevalence of GDM and the mean age of affected women in each major ethnic group were determined. From our database of NIDDM 6052 patients, the mean age of onset in each ethnic gorup was calculated and the mean difference between age of developing GDM and age of developing NIDDM derived (NIDDM-GDM age gap). This age gap was used to adjust for the susceptibility to GDM of each group. The overall prevalence of GDM was 6.7% (CI 6.0%-7.4%). In Anglo-Celtic women it was 3.0% (CI 2.3%-3.7%). For the other ethnic groups the prevalence and odds ratio (OR) were: Chinese (15.0% CI 11.8%-18.2% OR 5.6), Vietnamese (9.6% CI 6.6%-12.5% OR 3.6), Indian (16.7% CI 9.8%-23.5% OR 6.4), Arabic (7.3% CI 4.6%-10.1% OR 2.5) and Aborigines (10.1% CI 3.8%-16.4% OR 3.7). The OR for susceptibility to GDM did not change after adjustment for BMI and maternal age and it correlated significantly with the NIDDM-GDM age gap (r = -0.85; p = 0.03). However, it fell substantially after adjustment for NIDDM-GDM age gap. For women of different ethnic origins there is a difference in the time gap between their pregnancies and the time at which they would on average be expected to develop diabetes. This difference may be an important factor underlying the higher prevalence of GDM in some ethnic populations.

Age of Onset↗
PubMed1996

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 micrograms 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 micrograms 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.

Age Factors↗
PubMed1996

Ethnic differences in the prevalence of hypertension and proteinuria in NIDDM.

There are large ethnic differences in both the prevalence of diabetes and the pattern of clinical complications, especially diabetic nephropathy and coronary heart disease. The aim of this study was to compare ethnic differences in the prevalence of two important risk factors, hypertension and proteinuria, among 1845 consecutive patients with non-insulin-dependent diabetes mellitus (NIDDM) undergoing annual complications assessment. Using a well-established database and systematic methods of data collection, information on clinical, demographic and laboratory variables was compared among seven ethnic groups: Anglo-Celtic (n = 896), Italian (n = 246), Greek (n = 209), Arabic (n = 147), Chinese (n = 131), Indian (n = 115) and Aborigine (n = 101). The odds ratios (OR) for developing hypertension (relative to Anglo-Celtic subjects) were lower in all ethnic groups, especially Arabs (OR = 0.4), Indians (OR = 0.4) and Aborigines (OR = 0.6). By contrast, the odds ratios for proteinuria (relative to Anglo-Celts) were consistently higher in all ethnic groups, e.g. Arabs (OR = 3.0) and Aborigines (OR = 3.1), even after correction for age, duration of diabetes and glycaemic control. Thus, relative to Anglo-Celtic patients, other ethic groups are less likely to have hypertension and more likely to have proteinuria. These findings may have important implications for understanding the ethnic differences in onset and progression of diabetic nephropathy.

Arabs↗
PubMed1996

Impaired vascular reactivity in insulin-dependent diabetes mellitus is related to disease duration and low density lipoprotein cholesterol levels.

OBJECTIVES: This study sought to examine whether endothelial function is impaired in the large vessels of asymptomatic young adults with insulin-dependent diabetes and whether endothelial dysfunction is related to duration or control of diabetes, small-vessel disease or other vascular risk factors. BACKGROUND: Endothelial dysfunction is an early event in atherosclerosis, and large-vessel atherosclerotic disease is the major cause of morbidity and mortality in diabetes. METHODS: We compared 80 young adults with insulin-dependent diabetes (15 to 40 years old; mean [+/- SD] diabetes duration 13 +/- 8 years) with 80 matched nondiabetic control subjects. Using high resolution vascular ultrasound, we measured brachial artery responses to reactive hyperemia (with increased flow causing endothelium-dependent dilation) and sublingual glyceryltrinitrate (causing endothelium-independent dilation). RESULTS: Flow-mediated dilation was significantly impaired in diabetic subjects (5.0 +/- 3.7% vs. 9.3 +/- 3.8% in control subjects, p < 0.001). The ratio of flow-mediated dilation to glyceryltrinitrate-induced dilation was significantly lower in the diabetic subjects (p < 0.02), indicating that impaired dilation to increased flow was out of proportion to the impairment of the glyceryltrinitrate response in these subjects (15.6 +/- 5.6% vs. 19.7 +/- 6.6% in control subjects, p < 0.001). On multivariate analysis, flow-mediated dilation was inversely related to both duration of diabetes (r = -0.26, p < 0.05) and low density lipoprotein (LDL) cholesterol levels (r = -0.38, p < 0.005). CONCLUSIONS: Vascular reactivity is impaired in the systemic arteries of asymptomatic young adults with insulin-dependent diabetes and may represent early large-vessel disease. The degree of impairment is related to the duration of diabetes, and these patients appear particularly vulnerable to damage from LDL cholesterol, even at levels considered acceptable in nondiabetic subjects.

Adolescent↗
PubMed1996

Indapamide is as effective as captopril in the control of microalbuminuria in diabetes.

Microalbuminuria is a predictor of overt diabetic nephropathy and macrovascular disease. Thirty-one diabetic patients with persistent urinary albumin excretion rate (AER) of 20-200 mu g min-1 were randomised to receive indapamide 2.5 mg or captopril 37.5 mg daily for 12 weeks. After a 4-week washout, patients received the alternate agent for 12 weeks. Resting blood pressure (BP), AER, cholesterol, triglycerides, and HbA1c were measured at baseline, after 6 and 12 weeks of each treatment, and after a 4-week washout period following each treatment arm. Results from patients who completed at least one treatment arm were analysed by repeated-measures analysis of variance (ANOVA). AER (median value and interquartile range) decreased significantly from baseline after treatment with indapamide and captopril [60(27-106) vs. 40(14-112) and 33(17-100); p < 0.005], but there was no difference between the effects of the two agents. Mean systolic BP (SBP) was also significantly reduced with treatment, and no difference was noted between the effects of the two agents. No correlation between changes in AER and SBP was noted with either agent. Diastolic blood pressure (DBP), cholesterol, triglycerides, and HbA1c did not change during the study. These results suggest that indapamide is an effective alternative to angiotensin-converting enzyme (ACE) inhibitors in the treatment of diabetic patients with microalbuminuria.

Albuminuria↗
PubMed1996

Management of neuropathic ulceration.

Patients with diabetes who develop neuropathic foot ulcers are often managed with prolonged bed-rest or given a total contact cast. As these methods are not ideal for many patients, we examined a boot cast as an alternative approach to treating intractable neuropathic ulcers. Fourteen diabetic patients with a total of 16 neuropathic ulcers have been treated. The boot cast is a fibreglass, removable cast, tailor-made for individual patients. For treatment of neuropathic ulcers, a window is cut over the area of the ulcer site to reduce weight-bearing pressure. Despite the long pre-existing duration of the ulcers studied (mean 912 days), ulcers that reached 100% healing did so by 130 days. The mean period in which there has been no recurrence to date is 218 days. The boot cast was found to be an effective treatment in the management of diabetic foot problems. It allows patients to remain ambulant and reduces risk factors for amputation.

Casts, Surgical↗
PubMed1994

Cell-associated proteoglycans of retinal pericytes and endothelial cells: modulation by glucose and ascorbic acid.

Abnormalities of retinal pericytes and endothelial cells are prominent features of diabetic retinopathy. In this study, we used cultures of bovine retinal cells to examine the regulation of cell-associated proteoglycans, a class of highly sulfated macromolecules important in the regulation of cell growth. Bovine retinal pericytes and endothelial cells were radiolabeled with 35SO4 and cell-associated proteoglycans were removed from the cell surface, quantified, and characterized. The effects of high glucose concentration (25 mM), phorbol 12,13-dibutyrate (PDBu, 0.1 microM), and ascorbic acid (0.1 mM) on cell-associated proteoglycans and growth of these cells were studied. Our results showed that both the ionically bound and the membrane-intercalated forms of cell-associated proteoglycans are present on retinal cells. The predominant cell-associated proteoglycan of pericytes is chondroitin sulfate and for endothelial cells it is heparan sulfate. High glucose concentration and ascorbic acid increased the cell-associated proteoglycans on pericytes but reduced them on endothelial cells. In contrast to this divergent trend, high glucose concentration and ascorbic acid inhibited the growth of both pericytes and endothelial cells. The effects of high glucose on retinal cell-associated proteoglycans were mimicked by PDBu added in a manner to stimulate protein kinase C activity. We conclude that cell-associated proteoglycans are present on retinal pericytes and endothelial cells. High glucose concentration and ascorbic acid affect cell-associated proteoglycans of these two cell types in opposite directions, whereas both suppress the growth of the two cell types. Therefore, it is not likely that high glucose concentration and ascorbic acid change the rate of retinal cell growth directly by affecting cell-associated proteoglycan levels.

Animals↗
PubMed1994

Obstructive sleep apnea in obese noninsulin-dependent diabetic patients: effect of continuous positive airway pressure treatment on insulin responsiveness.

Patients with noninsulin-dependent diabetes mellitus (NIDDM) are often obese and frequently complain of tiredness. These features are also characteristically seen in patients with obstructive sleep apnea (OSA). Therefore, it was the aim of this study to assess the prevalence of OSA among a group of obese NIDDM patients who have some clinical features of OSA. The effect of reversal of OSA by nasal continuous positive airway pressure (CPAP) treatment on insulin responsiveness was also investigated. From a population of 179 NIDDM patients with a body mass index (BMI) greater than 35 kg/m2, we performed ambulatory sleep monitoring on 31 (15 males and 16 females) who admitted to either heavy snoring or excessive sleepiness. Results were reviewed by a sleep physician blinded to the clinical status of the patients, and 22 (70%) were found to have moderate or severe OSA, with mean oxygen desaturation indexes of 10.3 +/- 5.3 and 30.7 +/- 13.2 episodes/h, respectively. A subgroup of 10 patients (seven males and three females) with a mean BMI of 42.7 +/- 4.3 kg/m2 was treated with nightly CPAP for 4 months. These subjects all had significant OSA, with frequent obstructive apneas (mean, 47 +/- 31.6 episodes/h) and oxygen desaturation (mean minimum O2 saturation, 74 +/- 9.5%), as determined by polysomnography. One patient was excluded from analysis because of infrequent use of CPAP. Insulin responsiveness in terms of glucose disposal measured by hyperinsulinemic euglycemic clamps improved from 11.4 +/- 6.2 to 15.1 +/- 4.6 mumol/kg.min (P < 0.05) during CPAP treatment. These results indicate that OSA occurs commonly in obese NIDDM patients with excessive sleepiness or heavy snoring. Treatment of their OSA may improve insulin responsiveness.

Adult↗
PubMed1994

High glucose concentration causes a decrease in mesangium degradation. A factor in the pathogenesis of diabetic nephropathy.

Mesangium enlargement is a constant feature of diabetic nephropathy and is likely to be important in the pathogenesis of this diabetic complication. Whether decreased degradation of mesangium plays any role in causing the enlargement is uncertain. We developed a system of preparing radioactively labeled mesangium matrix from mesangial cell cultures to be used as substrates for studies of mesangium degradation. Degradation is commenced by growing mesangial cells on the labeled matrix and monitored by the release of radioactivity into the culture medium. High glucose concentration (30 mM), whether present 1) when the matrix is being made or 2) when the degradation is taking place, reduces the rate of mesangium degradation. The second but not the first of these two phenomena was abolished by aminoguanidine. Phorbol 12-myristate 13-acetate, added in a manner to antagonize the action of protein kinase C, inhibited mesangium degradation and was not able to nullify the effect of high glucose. Thus it appears unlikely that a high glucose concentration inhibits mesangium degradation by increasing mesangial cell protein kinase C activity. We conclude that decreased degradation of mesangium as a result of hyperglycemia may play a role in causing the mesangium enlargement that occurs in diabetic nephropathy.

Cell Division↗
PubMed1993

A single visit diabetes complication assessment service: a complement to diabetes management at the primary care level.

Modern diabetes management emphasizes the early detection and prompt treatment of diabetic complications. However it is difficult to organize comprehensive screening at the primary care level. To address this problem we established a complication assessment service whereby all the major diabetes-specific complications were assessed in a single 3 h visit. A report with results and recommendations was sent to the general practitioner (GP). Being philosophically a complication-specific service, no attempt was made to intervene with metabolic management. This paper describes our experience with the first 743 patients of whom 92% had been referred from GPs. Of the diabetes-specific complications, 22% of patients had one, 5% had two, and 1% had three major complications. Many of the patients were unaware of the presence of these complications. One hundred and three people had attended the service on more than one occasion with an average time between visits of 1.7 years. The results demonstrated that GPs were very good at following a recommendation to refer a patient for ophthalmic assessment (85% of cases) and improving hypertension but were less successful in treating hyperlipidaemia. This service has proven to be an excellent forum for the collection of data and the teaching of health professionals. It is a move away from the traditional format of hospital-based clinics providing comprehensive diabetes management.

Australia↗
PubMed1993

Low literacy: a problem in diabetes education.

Eighty-five diabetic patients who were proficient in English were studied to assess the impact of educational material of varying literacy levels on patient comprehension. Two samples of available diabetes foot care material of Grade 11 and 9 readability (measured by SMOG formula) and purposely written in-house material of Grade 6 readability were used. Patients were randomized to read information of either Grade 6 and Grade 11 or Grade 6 and Grade 9 readability. Socio-demographic data and reading habits were collected to allow for identification of literacy markers. The mean CLOZE score (a measure of comprehension) was better in patients who read the Grade 6 information than for both the Grade 11 and Grade 9 information (59.5 +/- 11.8, 46.8 +/- 22.0, 45.8 +/- 22.2 respectively, p < 0.001). When evaluated in terms of percent of patients that could independently understand the material, Grade 6 information outperformed the Grade 11 and Grade 9 information (60%, 19%, 21%, respectively, p < 0.001). For the Grade 11 and Grade 9 information, poorer comprehension was associated with a non-English speaking background, early school leaving age, infrequent reading habits, and preference for tabloids (p < 0.02). Comprehension when patients read the Grade 6 information was no longer dependent on two of the four identified literacy markers. We conclude that reducing literacy demands of health literature improves patients' comprehension. Attention to socio-demographic data and reading habits can assist educators in assessing patients' literacy status and ensuring patients are given literature of compatible readability.

Diabetes Mellitus↗
PubMed1993

Regression of microalbuminuria: results of a controlled study, indapamide versus captopril.

Our aim was to assess the effect of blood pressure treatment on albumin excretion rate (AER) in diabetic patients using two antihypertensive agents with different modes of action: indapamide and captopril. Patients with persistent microalbuminuria on two occasions (AER 20-200 micrograms/min) entered a randomized crossover study of 12 weeks of therapy with a constant dose of either indapamide 2.5 mg daily or captopril 12.5 mg three times daily, with a 4-week washout between therapy periods. Blood pressure was measured using a random-zero sphygmomanometer and AER by radioimmunoassay on a timed urine collection. Results (mean +/- standard deviation) were analyzed by repeated measures of analysis of variance after log transformation of AER data. Twelve patients [nine men; mean age 58 +/- 7.5 years (range 49-73 years), all with non-insulin-dependent diabetes mellitus (NIDDM)] were studied. Both blood pressure [initial mean systolic 144 +/- 14 mm Hg (range 124-166)/initial mean diastolic 85 +/- 6 mm Hg (range 75-96)] and AER [initial 92 +/- 36 micrograms/min (range 36-161)] were significantly reduced below basal levels (at the 0.05 level) at all study intervals by both antihypertensive agents. The results show the importance of blood pressure and its treatment on AER in patients with NIDDM. In this study, indapamide was as effective as an angiotensin-converting enzyme inhibitor in reducing both blood pressure and microalbuminuria.

Aged↗