Biomedical subjects

D K Yue

Publications and source records attributed to D K Yue.

At least 19 recordsLinked to original sources

PubMed2006

The metabolic syndrome in type 2 diabetes: When does it matter?

AIMS: Young adults with type 2 diabetes (T2Dm) present the clinician with the problem of when to start therapies for the primary prevention of vascular disease and how to identify those at most vascular risk. We examine whether the metabolic syndrome (MetS) can be a useful clinical tool to stratify vascular risk in this context. METHODS: Data were collected from 5928 subjects with T2Dm, and subjects were categorized as having MetS by World Health Organization criteria (body mass index criteria modified for Asians using >23 kg/m2). The prevalence of macrovascular disease was examined by MetS status and age. RESULTS: The overall MetS prevalence was 72.3%. MetS was associated with an increased prevalence of ischaemic heart disease (IHD) (17.2% MetS vs. 11.6% no MetS, p < 0.0001), coronary artery bypass graft (7.6 vs. 4.7%, p < 0.0003), peripheral vascular disease (PVD) (4.7 vs. 3.7%, p = 0.08) and stroke (6 vs. 3.9%, p = 0.002) across all age groups. MetS subjects had an IHD prevalence equivalent to that seen in subjects who were one decade older without MetS. The most significant impact of MetS was for the age group of 40-49 years with much lesser impact seen with progressively increasing age [odds ratio (OR) = 2.1 for IHD in MetS compared with no MetS at age 40-50 years, p < 0.05; falling progressively to OR = 1.5 at age >70 years, p > 0.05]. Similar trends were seen for coronary artery by-pass graft (CABG) and PVD. There was a strong relationship between the number of MetS risk factors and IHD prevalence (r = 0.99, p = 0.0001). CONCLUSIONS: These data suggest that MetS is particularly useful in stratifying vascular risk in younger T2Dm patients and in those with a high number of MetS components. For patients with MetS, especially those with a full house of MetS risk factors, commencing risk-lowering interventions 10 years earlier than their MetS-free counterparts could be considered.

Adult↗

PubMed2005

Which diabetic patients should receive podiatry care? An objective analysis.

INTRODUCTION: Diabetes is the leading cause of lower limb amputation in Australia. However, due to limited resources, it is not feasible for everyone with diabetes to access podiatry care, and some objective guidelines of who should receive podiatry is required. METHODS: A total of 250 patients with neuropathy (Biothesiometer; Biomedical Instruments, Newbury, Ohio, USA) ( > 30, age < 65)) but no active foot lesion, and 222 without neuropathy matched for age, type of diabetes, gender and duration, was followed prospectively for 2 years. Sensation was also tested using a 10 g Semmes Weinstein monofilament (Royal Prince Alfred Hospital Diabetes Centre). After the baseline examination, patients were contacted at 6 months and thereafter yearly to determine ulcer status. Incidence of foot ulceration across different risk categories was calculated using Kaplan-Meier survival curve. Log-rank test and Cox's proportional model were used to compare groups. The Number Needed to Treat (NNT) to prevent one ulcer per year was calculated using the standard formulae. RESULTS: During the follow-up period, 34 new ulcers occurred in the neuropathy group and three ulcers in the control group (chi2 (1df) = 21.3; P < 0.0001), equating to an annual incidence of 6.3% and 0.5%, respectively. Fifty-four per cent of the ulcers were due to trauma from footwear. Further stratification of the neuropathy group showed annual incidence of ulceration to be 4% for those with abnormal biothesiometer reading, but who could still feel the monofilament, 10% for those who cannot feel the monofilament and 26% for those with previous ulceration or amputation. Predictors of ulceration were past history of ulceration/amputation (chi2 = 27.8; P < 0.0001) and the presence of neuropathy (chi2 = 4.7; P = 0.03). Assuming a 55% relative risk reduction in ulceration from podiatry care (mean of estimates from 10 reports), the NNT to prevent one foot ulcer per year was: no neuropathy (vibration perception threshold (VPT) < 30)), NNT = 367; neuropathy (VPT > 30) alone, NNT = 45; +cannot feel monofilament, NNT = 18; +previous ulcer/amputation, NNT = 7. CONCLUSION: Provision of podiatry care to diabetic patients should not be only economically based, but should also be directed to those with reduced sensation, especially where there is a previous history of ulceration or amputation.

Age Factors↗

PubMed2005

Glargine is superior to neutral protamine Hagedorn for improving glycated haemoglobin and fasting blood glucose levels during intensive insulin therapy.

AIM: To compare glycaemic control and symptomatic hypoglycaemia rates with glargine versus neutral protamine Hagedorn (NPH) in poorly controlled type 1 diabetes patients. METHODS: Patients (n = 125) received preprandial insulin lispro and either glargine (n = 62) or NPH (n = 63) at bedtime for 30 weeks in a multicentre, randomized, single-blind (a blinded investigator made titration decisions) study. Basal insulin dosage was titrated to achieve fasting blood glucose (FBG) values < 5.5 mmol/L. RESULTS: Baseline characteristics were similar for the two groups (mean diabetes duration 17.5 +/- 10.1 years) except mean glycated haemoglobin (HbA(1c)), which was lower in the glargine versus NPH group (9.2 +/- 1.1% vs 9.7 +/- 1.3%; P < 0.02). At end-point, mean HbA(1c) was 8.3 versus 9.1% for the glargine versus NPH groups. Adjusted least-squares mean (LSM) change from baseline was -1.04 versus -0.51%, a significant treatment benefit of 0.53% for HbA(1c) in favour of glargine (P < 0.01). Mean baseline FBG were similar for the glargine and NPH groups (11.2 vs 11.4 mmol/L). The means for end-point FBG were 7.9 versus 9.0 mmol/L. Adjusted LSM change from baseline was -3.46 versus -2.34 mmol/L, with a significant difference of 1.12 mmol/L in favour of glargine (P < 0.05). There were similar total numbers of daytime mild, moderate or severe hypoglycaemia episodes in the two treatment arms. However, significantly fewer moderate or severe nocturnal hypoglycaemic episodes were observed in the glargine group (P = 0.04 and P = 0.02). CONCLUSION: Glargine is superior to NPH for improving HbA(1c) and FBG levels during intensive insulin therapy in patients with type 1 diabetes, and is associated with less severe nocturnal hypoglycaemia.

Adolescent↗

PubMed2004

Connective tissue growth factor mediates high glucose effects on matrix degradation through tissue inhibitor of matrix metalloproteinase type 1: implications for diabetic nephropathy.

High glucose concentration inhibits matrix degradation and affects the activities of the enzymes responsible, the matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs). Connective tissue growth factor (CTGF) expression is increased in diabetic nephropathy and is a downstream mediator of TGF-beta actions. However, whether CTGF regulates matrix degradation and the mechanism of effect in diabetes has not been reported. Human mesangial cells were cultured in media containing 5 or 25 mM glucose and, in some experiments, with recombinant human (rh)CTGF (0-1000 ng/ml) and/or appropriate neutralizing antibodies. Matrix degradation was inhibited by rhCTGF in a dose-dependent manner, and the decrease in matrix degradation caused by high glucose and by TGF-beta was significantly attenuated by addition of CTGF-neutralizing antibody (by 40.2 and 69.1%, respectively). Similar to 25 mM glucose, addition of rhCTGF increased MMP-2, TIMP-1, and TIMP-3 mRNA by 2.5-, 2.1-, and 1.6-fold, respectively (P < 0.05) but had no effect on membrane-type (MT)1-MMP or TIMP-2. Addition of TIMP-1 antibody to conditioned medium abolished the decrease in degradation caused by rhCTGF and partially prevented (by 79%) the glucose-induced inhibition of matrix degradation. In vivo studies of glomeruli from diabetic and control rats showed that intensive insulin treatment prevented the increase in expression of CTGF and TIMP-1 and attenuated the decreased matrix degradation seen in diabetes. In summary, CTGF inhibits matrix degradation by increasing TIMP-1 expression, and by this action it contributes to the inhibition of matrix breakdown by high glucose, implying that CTGF has a role in the reduced matrix degradation observed in diabetic nephropathy.

Animals↗

PubMed2002

Decreased matrix degradation in diabetic nephropathy: effects of ACE inhibition on the expression and activities of matrix metalloproteinases.

AIMS/HYPOTHESIS: Extracellular matrix accumulation is thought to be involved in the pathogenesis of diabetic nephropathy. Increased matrix synthesis has been well documented but the effects of diabetes on degradative pathways, particularly in the in vivo setting, have not been fully explored. Furthermore, the effect of renoprotective therapies on matrix accumulation through these pathways has not been examined. We investigated the degradative pathway of type IV collagen and the effects of ACE inhibition in experimental diabetic nephropathy. METHODS: Diabetes was induced in 16 rats by administrating streptozocin; 8 of the diabetic rats were allocated at random to receive the ACE inhibitor perindopril (2 mg/l) in their drinking water and 8 age and weight matched rats served as controls. Gene expression of matrix metalloproteinase ( MMP) and tissue inhibitor of metalloproteinase ( TIMP) was measured by RT-PCR and type IV collagen content by immunohistochemistry. MMP activities were determined by degradation of a radiolabelled substrate and by zymography. RESULTS: Six months of diabetes was associated with a decrease in mRNA and enzymatic activity of MMP-9 (21 % and 51 % respectively, p < 0.05 vs control) and a 51 % increase in TIMP-1 mRNA ( p < 0.05 vs control). By contrast, MMP-2 mRNA was increased but its activity decreased (43 % and 43 % respectively, p < 0.05 vs control). Total degradative capacity of kidney tissue from diabetic rats was also lower (Control: 48 +/- 7 %, Diabetic: 33 +/- 6 %, p < 0.05). Activation of latent MMPs with amino-phenylmercuric acetate increased matrix degradation by two-fold. However the relative decrease associated with experimental diabetes still remained. All diabetes-associated changes in MMP and TIMP mRNA and activities were attenuated by perindopril treatment in association with reduced type IV collagen accumulation. CONCLUSIONS/INTERPRETATION: These results indicate that the impairment of matrix degradation contributes to matrix accumulation in diabetic nephropathy and that the beneficial effects of ACE inhibition could in part be mediated by modulation of changes in matrix degradative pathways.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed2002

Retinopathy in a Chinese population with type 2 diabetes: factors affecting the presence of this complication at diagnosis of diabetes.

This study examined the prevalence of retinopathy in 2131 patients with type 2 diabetes attending a Beijing hospital for the first time. The median age of patients was 58 years (IQR 50-65). The overall prevalence of retinopathy was 27.3% (95% CI: 25.4-29.2) and for proliferative retinopathy 7.8% (95% CI: 6.7-8.9). When all patients were considered together, duration of diabetes (OR=1.8; P=0.001) and albumin excretion rate (OR=1.5; P=0.019) were independent risk factors for retinopathy. Blue-collar occupation (OR=1.5; P=0.047) and blood pressure (OR=1.2; P=0.021) were additional risk factors for non-proliferative and proliferative retinopathy respectively. Amongst the 773 newly diagnosed patients, 21% (95% CI: 17.8-23.6) already had retinopathy. The median age of those patients with retinopathy at diagnosis of diabetes was 3 years higher that those without retinopathy, and blue-collar workers (OR=2.2; P=0.012) as well as female gender were particularly at risk (OR=2.0; P=0.033). There was a strong correlation between duration of diabetes with the presence of retinopathy (r=0.95; P=0.01). By extrapolation, it could be estimated that some degree of hyperglycaemia might have been present for more than 20 years before diabetes was diagnosed. These findings emphasise the importance of earlier diagnosis of diabetes and its complications, especially in socially disadvantaged groups.

Age of Onset↗

PubMed2002

Effects of mesangium glycation on matrix metalloproteinase activities: possible role in diabetic nephropathy.

High glucose concentrations can decrease degradation of mesangium by reducing the activities of matrix metalloproteinases (MMPs). The aim of this study was to investigate the effects of glycation of mesangium matrix on MMP-2, the principal MMP secreted by mesangial cells to degrade type IV collagen. Also examined were membrane type 1 MMP (MT1-MMP), tissue inhibitors of MMPs (TIMP)-1 and -2, and transforming growth factor-beta (TGF-beta), which together regulate MMP-2 activities in an interacting manner. Human fetal mesangial cells were grown on mesangium matrix glycated by incubation in 500 mmol/l ribose, with or without aminoguanidine. The activities and gene expression of the abovementioned enzymes/inhibitors were measured by degradation of radiolabeled mesangium matrix, RT-PCR, and zymography. Glycation of mesangium matrix resulted in a threefold increase in advance glycation end products and reduced by 45% the matrix-degrading activity of MMPs secreted by mesangial cells. Analogous to the direct effects of high glucose concentrations, glycation of matrix increased the gene expression of MMP-2 and TIMP-1 (control 100 +/- 16.9 vs. glycated 197.3 +/- 30.6% and control 100 +/- 5.3 vs. glycated 152.1 +/- 20.1%, respectively; P < 0.05) and decreased MT1-MMP (control 100 +/- 1.17 vs. glycated 54.1 +/- 15.2%; P < 0.05). However, unlike high glucose concentrations, glycation was not associated with decreased activation of MMP-2. Similarly, glycation but not high glucose increased expression of TIMP-2 (control 100 +/- 5.9 vs. glycated 168.2 +/- 31.4%; P < 0.05), and the effects of glycation on degradation can be abolished by anti-TIMP-2 antibody. Glycation of matrix decreased TGF-beta mRNA by 38.2% and total and active TGF-beta by 35.5 and 21.5%, respectively, opposite the effects of high glucose concentrations. Our results indicate that glycation of matrix affects the balance between MMP-2 and its activator and inhibitors, but this phenomenon is not due to TGF-beta. The process of glycation may impart to the mesangium matrix a memory effect that contributes to the long-term toxicity of hyperglycemia.

Cells, Cultured↗

PubMed2001

Continuity of care in diabetes: to whom does it matter?

The Australian health care system allows patients to move around to seek medical treatment. This may impact negatively on continuity of care. To determine factors associated with continuity of care for persons with diabetes, the profiles of 479 patients attending the Diabetes Centre, Royal Prince Alfred Hospital, Sydney, Australia, were examined. The majority of patients (87.7%) attended only one general practitioner and had been under the care of the referring doctor for a median of 6.2 years. These patients were older (P=0.02), but were comparable with those attending multiple doctors in terms of their type, duration and treatment of diabetes as well as their clinical and complication profile. There was also a relationship between age and the length of time under the care of the referring doctor (P=0.0002). The HbA(1c), lipid, blood pressure and treatment profiles of patients attending the referring doctor short, medium or long-term were comparable. However, there was an upward trend in the proportion of patients with a history of cerebrovascular disease, ischaemic heart disease or any complication of diabetes with each incremental increase in length of time under the referring doctor. Appropriately, patients seek continuity of care as they age and their health needs become more complex.

Aged↗

PubMed2001

Use of Medicare services related to diabetes care: the impact of rural isolation.

This study used Medicare data for people living in New South Wales (NSW) (1993-1997) to examine the impact of rural isolation on the utilisation of diabetes health care services. The relative odds of attending a specialist was slightly higher for people in urban areas when compared to their rural counterparts but reached as high as 1.85 in regard to attendance to consultant physicians. Surveillance of diabetes parameters over the 5 year period showed greatest improvement in rural areas. The proportion of patients each year with glycaemic control assessed by quantification of glycosylated haemoglobin (HbA1c) or renal function and vascular risk by microalbuminuria estimation rose to 57.4% and 12.3%, respectively, in rural areas compared to 55.2% and 11.3% in major urban areas. This study has shown that the level of monitoring in rural areas is equal to urban areas, despite decreased access to medical care, highlighting the vital role GPs play in diabetes management in rural NSW.

Clinical Laboratory Techniques↗

PubMed2001

Augmentation of central arterial pressure in Type 2 diabetes.

AIMS: Aortic systolic blood pressure has been shown to be augmented in Type 1 diabetes, indicative of more rapid pulse wave reflection due to increased arterial stiffness. This abnormality is more pronounced in diabetic males. The aim of this study was to examine the effects of diabetes on augmentation of aortic systolic pressure in subjects with Type 2 diabetes. METHODS: Radial artery pressure waveforms were obtained non-invasively by applanation tonometry. A central aortic waveform can be derived using a transfer function obtained from previous studies during cardiac catheterization. A total of 88 subjects with Type 2 diabetes (51 men and 37 women, aged 55.8 years (interquartile range (IR) 49.7-64.1), duration of diabetes 7.5 years (IR 2.4-12.4), HbA1c 7.6% (IR 6.6-8.7)) and 85 controls subjects (40 men and 45 women, aged 55.3 years (IR 44.2-66.4)) were studied. The central aortic waveform allowed determination of the: (i) aortic augmentation index and (ii) subendocardial viability ratio. RESULTS: Similar to Type 1 diabetic subjects, patients with Type 2 diabetes had a significantly higher aortic augmentation index (136.1 +/- 18.0% vs. 128.3 +/- 19.2%, t = 2.8, P = 0.006) and lower subendocardial viability ratio (137.4 +/- 25.0% vs. 155.1 +/- 25.9%; t = 4.6, P = 0.0001) compared with controls. Multivariate analysis identified diabetes as an important determinant of aortic augmentation index (t = 4.0, P = 0.0001). The higher aortic augmentation index was due mainly to the male cohort (t = 2.6; P = 0.01) and was not apparent for females with diabetes (P = 0.2). CONCLUSIONS: Type 2 diabetes is characterized by higher augmentation of aortic systolic pressure and unfavourable ratio of myocardial perfusion to cardiac workload. These results are consistent with increased arterial stiffness. The age-related progression of arterial stiffness is similar in Type 1 and Type 2 diabetes. Anti-hypertensive agents that reduce wave reflection and augmentation may help to prevent systolic hypertension and cardiac hypertrophy in diabetes.

Aorta↗

PubMed2001

TBI or not TBI: that is the question. Is it better to measure toe pressure than ankle pressure in diabetic patients?

AIMS: Measurement of ankle blood pressure is a simple method of assessing lower limb arterial blood supply. However, its use in diabetes has been questioned due to the presence of medial artery calcification. Measurement of toe blood pressure has been advocated as an alternative but it is technically more difficult. The aim of this study was to obtain information to guide clinicians as to when pressure measurements should be taken at the toe. METHODS: Ankle brachial index (ABI) and toe brachial index (TBI) were measured by Doppler ultrasound, or photoplethysmography on 174 subjects with diabetes and 53 control subjects. The Bland and Altman method, and the Cohen's method of measuring agreement between two tests were used to compare ABI with TBI. RESULTS: The mean differences between ABI and TBI in control and diabetic subjects are 0.40 +/- 0.13 and 0.37 +/- 0.15, respectively. Nearly all diabetic patients with an ABI < 1.3 have an ABI-TBI gradient falling within the normal range established from the non-diabetic cohort. In contrast, the majority of diabetic subjects with an ABI > or = 1.3 have ABI-TBI differences outside this range. When patients are categorized according to ABI and TBI, there is also good agreement between the tests when ABI is low or normal (84% and 78% agreement, respectively), but not when ABI is elevated. CONCLUSION: In the majority of patients with diabetes, assessment of TBI conveys no advantage over ABI in determining perfusion pressure of the lower limbs. Only in those patients with overt calcification, which gives an ABI > or = 1.3, are toe pressure measurements superior. This guideline should simplify assessment and treatment of diabetic patients with disease of the lower limbs. Diabet. Med. 18, 528-532 (2001)

Adult↗

PubMed2001

Differential shared care for diabetes: does it provide the optimal partition between primary and specialist care?

AIMS: To establish whether a system of differential shared care between general practitioners and specialists is compatible with patients receiving the level of care they require. METHODS: We sought to trace 200 shared care patients whose care had been kept at the general practitioner level after initial referral and compared them with a group of patients who had been re-referred to the Royal Prince Alfred Hospital Diabetes Centre for specialist review. RESULTS: There were no significant differences in glycaemic, blood pressure and lipid levels of returned and non-returned patients at initial assessment. However, non-returned patients were less likely to have a history of macrovascular disease or risk factor (adjusted odds ratio (OR) 0.4; 95% confidence interval (CI) 0.2-0.6). Their referral letter was also more likely to emphasize their type and/or duration of diabetes (adjusted OR 4.6; 95% CI 2.5-8.4). Nearly half (47.1%) of the non-returned group changed their doctor in the years following their initial specialist review, increasing their likelihood of not being re-referred five-fold (adjusted OR 5.0; 95% CI 2.9-8.8). At initial assessment, non-returned patients were given less treatment recommendations (adjusted OR 0.5; 95% CI 0.3-0.7). Doctors registered with the Diabetes Shared Care Programme referred more patients than their non-shared care counterparts. However, a higher proportion of these doctors (52.5% vs. 21.3%; chi(2) = 16.5, 1 d.f., P = 0.00005) were selective in whom they re-referred. CONCLUSION: Differential shared care encourages appropriate referral to specialist services, without compromise to standards of care. Diabet. Med. 18, 554-557 (2001)

Australia↗

PubMed2000

Functional and structural abnormalities in the nerves of type I diabetic baboons: aminoguanidine treatment does not improve nerve function.

AIMS/HYPOTHESIS: To improve understanding of the pathophysiology of diabetic neuropathy and to establish a primate model for experimental studies, we examined nerve changes in baboons with Type I (insulin-dependent) diabetes mellitus. We also examined the effect of aminoguanidine (an inhibitor of the formation of advanced glycation end products) on nerve function. METHODS: Male baboons (Papio hamadryas) were assigned to four groups; control, diabetic, control and diabetic treated with aminoguanidine. Diabetes was induced with streptozotocin (60 mg/kg, intravenous). Insulin and aminoguanidine (10 mg/kg) were injected subcutaneously daily. Motor and sensory nerve conduction velocity was measured using standard techniques. Autonomic function was examined by measuring heart rate response to positional change. Sural nerve morphometry was analysed in the diabetic group (mean duration 5.5 years) along with their age-matched controls. RESULTS: The diabetic groups were smaller in size with a mean HbA1c of 8.9 +/- 1.2%. The nerve conduction velocity and heart rate response was reduced in the diabetic groups. Morphometric analysis of the diabetic sural nerve showed smaller axon diameter (2.99 +/- 0.06 microns vs 3.29 +/- 0.06 microns; p < 0.01) accompanied by thinner myelin (1.02 +/- 0.02 microns vs 1.15 +/- 0.02 microns, p < 0.01) with no change in the axon density. Treatment with aminoguanidine for 3 years had no effect on glycaemic control and did not restore conduction velocity or autonomic dysfunction in the diabetic animals, contrary to the studies in rats. CONCLUSIONS/INTERPRETATION: These results show that the primate is a good model to study diabetic neuropathy and suggest that the accumulation of advanced glycation end products are not an early mechanism of nerve damage in this disorder.

Aging↗

PubMed2000

Response of Charcot's arthropathy to contact casting: assessment by quantitative techniques.

AIMS/HYPOTHESIS: This study used two different methods of quantitative bone scanning to study the relation between activity of Charcot's arthropathy and clinical variables over 12 months. METHODS: Skin temperature of affected and unaffected feet was measured at baseline and every 3 months for 12 months in 17 subjects. Eight subjects underwent a three-phase quantitative bone scan at baseline and 3 monthly for 12 months. Bone isotope uptake in a standard rectangular area over the foot and tibia was analysed by the bilateral scan method (the ratio of isotope uptake of affected and unaffected feet) and the unilateral scan method (the ratio of isotope uptake of affected foot and ipsilateral tibia). The affected foot was placed in a contact cast for an average of 8 months. RESULTS: At presentation the affected foot was hotter than the unaffected foot but the temperature became progressively cooler over 12 months. Median isotope uptake in the affected foot was 2.1% of the injected dose (interquartile range, IQR 1.9-3.0). In both scanning methods the ratio of uptake decreased after casting but at 12 months the affected foot still had more isotope uptake. There was a strong correlation between temperature difference and the ratio of uptake in the bilateral scan method (r = 0.90; p < 0.0001) but when using the unilateral scan method this relation was not significant (r = 0.1;p = 0.6). A strong relation existed between perfusion of the affected foot in the dynamic phase and isotope uptake in the delayed phase of the scans (r = 0.92; p < 0.0001). CONCLUSION/INTERPRETATION: Bone activity and skin temperature of Charcot's arthropathy can be measured quantitatively and both improve over 12 months with contact casting. There is a strong relation between perfusion and disease activity in this condition.

Aged↗

PubMed2000

High glucose concentration inhibits the expression of membrane type metalloproteinase by mesangial cells: possible role in mesangium accumulation.

AIMS/HYPOTHESIS: High glucose concentration decreases the degradation of mesangium matrix, an action substantially mediated by a reduction in the activities of the matrix metalloproteinases (MMPs). Metalloproteinase-2 is unique in that it is activated on the cell surface by one of the membrane type metalloproteinases (MT1-MMP), a process involving complex interactions with tissue inhibitor of metalloproteinase-2. The aim of this study was investigate the effects of glucose concentration on mesangial cell gene expression of MT1-MMP and its ability to modulate the activation of metalloproteinase-2. METHODS: Gene expression was determined using competitive RT-PCR, protein expression of MMP-2 was measured by western blot and its activation by zymography. Concanavalin A, known to increase MT1-MMP expression was added in some experiments. RESULTS: High glucose concentration decreased MT1-MMP gene expression (11.52 +/- 1.63 and 4.84 +/- 0.72 amol/microg RNA, 5 vs 25 mmol/l glucose, respectively) and decreased activation of MMP-2 by 30% despite a twofold increase in gene expression of MMP-2. Concanavalin A increased expression of MT1-MMP and activation of MMP-2. Irrespective of whether MMP-2 was from endogenous or exogenous source there was an excellent correlation between the MT1-MMP expression and degree of MMP-2 activation, whereas the gene expression of TIMP-2 was not significantly altered by high glucose concentration or concanavalin A. CONCLUSION/INTERPRETATION: Our results indicate that in a high glucose milieu, suppression of MT1-MMP expression could explain the low MMP-2 activity in the presence of high MMP-2 expression. This process could contribute to the mesangium matrix accumulation in diabetic nephropathy.

Blotting, Western↗

PubMed2000

Effects of glucose on matrix metalloproteinase and plasmin activities in mesangial cells: possible role in diabetic nephropathy.

Diabetic nephropathy is characterized by an accumulation of mesangium matrix that correlates well with the loss of kidney function. High glucose concentration is known to increase the synthesis of many matrix components. Recently, we have shown that degradation of matrix also decreases in diabetes. The major enzymes responsible for matrix degradation are the matrix metalloproteinases. The physiology of these enzymes is complex and their activity is tightly regulated at many levels. At the transcriptional level matrix metalloproteinase (MMP) expression is increased by protein kinase C (PKC) agonists, and some growth factors. In contrast transforming growth factor (TGF)-beta can decrease MMP expression. Once synthesized, MMPs are secreted as inactive pro-enzymes that are activated by other MMPs or plasmin. To effect this, plasmin must be liberated from plasminogen in the pericellular environment. In turn, activated MMPs can be inhibited by binding to specific inhibitors known as tissue inhibitor of metalloproteinases (TIMP). Cell culture and animal studies have shown that high glucose (HG) decreases expression of MMPs and increases expression of TIMPs. HG can also affect MMP activation by decreasing plasmin availability and reducing expression of a membrane-bound MMP called MT1-MMP. How HG induces these changes remains to be fully elucidated. One possibility is that HG can increase TGF-beta. which may in turn alter MMP promoter activity: this area is currently being studied in our laboratory.

Animals↗

PubMed2000

The pattern of diabetes care in New South Wales: a five-year analysis using Medicare occasions of service data.

OBJECTIVE: To use Medicare occasions of service data to establish the pattern and standard of care received by people with diabetes. METHOD: Information about visits to medical practitioners as well as utilisation of diabetes related procedures for people living in New South Wales (NSW) for the individual years between 1993 to 1997 was retrieved using a Health Insurance Commission data file. Individuals were deemed to have diabetes if an HbA1c which can only be ordered for a person with known diabetes, had been performed over the five-year period. RESULTS: On average over the study period, persons with diabetes accounted for 3.1% of the population but they used 5.5% of general practitioner services. A large proportion of patients also received care at the specialist and consultant physician level, 51.2% and 38.6% respectively, a three to four fold increase when compared with their non-diabetic counterparts. There was also a 1.3 to 1.8 fold increase in the mean number of attendances to the various medical practitioners. Surveillance of diabetes parameters was inadequate but small improvements were seen over the 5 year study period (proportion of persons with diabetes with a HbA1c performed: 48.8% to 56.8%; Lipids: 49.4% to 52.0%; HDL cholesterol: 18.3% to 18.8%; microalbuminuria: 4.7% to 11.6%). CONCLUSION: This study has highlighted the heavy burden imposed by diabetes on our health care system. IMPLICATIONS: The use of Medicare occasions of service data represents a cost efficient way of monitoring health service utilisation.

Diabetes Mellitus↗

PubMed1999

Diabetes management: shared care or shared neglect.

Shared care is increasingly being advocated as a way of managing patients with diabetes. While this approach has been supported by clinical trials, the success of shared care in 'real life' is not well established. If health care professionals leave undone what they think is done by others, shared care can become neglected care. Follow up of 200 'shared care' patients who had been referred to the Royal Prince Alfred Diabetes Centre, Sydney, Australia on two or more occasions between October 1995 and September 1998 showed that the majority of specialist recommendations regarding metabolic control (76%), referral to an ophthalmologist (73%) and blood pressure treatment (76%) had been implemented by the primary care physician; however, they were less likely to implement recommendations regarding lipid treatment (55%). The median HbA1c (7.6% vs. 8.4%; P = 0.04), cholesterol (5.6 vs. 6.8 mmol/l; P = 0.0005) and triglyceride (2.0 vs. 2.8 mmol/l; P = 0.05) levels for patients in whom recommendations had been implemented were significantly lower at the time of second referral. Doctors registered with the Diabetes Shared Care Programme and those who wrote longer letters were more likely to implement recommendations than their counterparts (87.2%, versus 70.9%; chi2 = 4.12, 1 df; P = 0.04 and 56 words (inter-quartile range (IQR): 36-71) versus 45 words (IQR: 23-59); P = 0.02, respectively). It therefore appears that diabetes care can be well provided by a shared care approach. However, further monitoring of different shared care models is warranted.

Australia↗