Time to move from serum creatinine to eGFR.
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Biomedical subjects
Publications and source records attributed to J P New.
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BACKGROUND: Diabetes and its complications are more prevalent among South Asians than people of European origin and there is some evidence that patients of South Asian origin with diabetes receive poorer quality care. METHODS: Longitudinal study of patients with diabetes in Blackburn, UK. Processes of care indicators [measurement of blood pressure (BP), cholesterol and glycosolated haemoglobin (HbA1c)] and values of these intermediate outcomes were extracted for all patients registered on a diabetes information system for the period 1995-2001. Differences in processes of care indicators and intermediate outcomes between ethnic groups were estimated after adjusting for the potential confounding factors of sex, age and socioeconomic status (SES). Generalized estimating equations were used to model trends and to test for differences in trends over time. RESULTS: Process of care was similar in South Asian and European patients. Mean BP and cholesterol concentration fell during the study period. South Asians had a higher level of HbA1c throughout the study period. South Asians had lower levels of BP and cholesterol in 1995 but the differences diminished or were abolished over time. SES did not explain differences between ethnic groups. Analyses stratified by baseline levels of intermediate outcomes (above or within target) demonstrated improvements among above target patients were greater among European patients. CONCLUSIONS: Processes of care indicators are similar in diabetic patients of South Asian and European origin, irrespective of SES. However, there are worrying differences in improvements over time in the intermediate outcomes, and glycaemic control remained poorer among patients of South Asian origin patients throughout.
OBJECTIVE: To determine the effectiveness of specialist nurse delivered education in primary care to improve control of hypertension and hyperlipidaemia in patients with diabetes. DESIGN AND SETTING: Practice-level randomized controlled trial, Salford, England. SUBJECTS: From 44 practices, 10 303 subjects presenting in general practice with raised blood pressure (= 140/80 mmHg), raised total cholesterol (= 5.0 mmol/l) or both. INTERVENTIONS: Practices were randomized to receive either the intervention for hyperlipidaemia or for hypertension; practices acted as control for the intervention not received. Specialist nurses arranged a schedule of visits with general practitioners and general practice nurses, reminding them of diabetes protocols and clinical targets. They provided educational materials and protocols used in secondary care for nurse and doctor interventions including stepping up pharmacotherapy when necessary. Practices received a list of patients in their practice who were poorly controlled at their last annual review; new and recalled patients were targeted. OUTCOME MEASURES: At subsequent annual review, blood pressure and total cholesterol values were obtained from the Salford electronic diabetes register for patients from participating practices. RESULTS: Overall, specialist nurse-led educational outreach to primary care was associated with no improvement in patients achieving target after 1 year-odds ratio (OR): 1.03 (95% CI 0.95-1.11; P = 0.52). Similar results were achieved with hyperlipidaemia OR: 1.04 (95% CI 0.88-1.23; P = 0.62) and hypertension OR: 1.01 (95% CI 0.80-1.27; P = 0.93). CONCLUSION: This study provides evidence that the use of specialist nurses to perform educational outreach to improve target adherence to patients with diabetes in primary care is not effective.
AIMS: To assess the performance of a handheld bedside ketone sensor in the face of likely metabolic disturbances in diabetic ketoacidosis, namely: pH, glucose and acetoacetate. METHODS: The effects of pH (7.44-6.83), glucose (5-50 mmol/l) and acetoacetate (0-5 mmol/l) were examined in venous blood to investigate the accuracy of betahydroxybutyrate measurement (0-5 mmol/l) by a handheld ketone sensor. Sensor results were compared with a reference method. Linear regression models were fitted to the difference between the methods with the concentration of metabolite as the explanatory factor. RESULTS: Decreasing pH and increasing glucose had no effect on the accuracy of the handheld ketone sensor; the gradients of the fitted lines were -0.14 and -0.003, respectively. The 95% confidence intervals were -0.7-0.4 and -0.01-0.004, respectively (P = 0.59 and 0.4, respectively). In the acetoacetate study, a positive relationship between the sensor and reference method results was found, the gradient was 0.09. The 95% confidence interval was 0.05-0.14 (P < or = 0.001), indicating that high concentrations of acetoacetate interfere with the sensor performance. CONCLUSIONS: Acidosis and hyperglycaemia have minimal effects on the sensor performance. However, high concentrations of acetoacetate result in some overestimation of betahydroxybutyrate. This bedside ketone sensor provides useful data over a broad range of conditions likely to be encountered during moderate to severe diabetic ketoacidosis.
AIMS/HYPOTHESIS: Our aim was to investigate trends in provision and outcomes of care by socio-economic status among patients with diabetes in Salford, United Kingdom. METHODS: Salford is a deprived urban area in North West England. Data for people with diabetes who were younger than 20 years of age (4034 patients in the year 1993 and 5671 by the year 2000) were extracted from the Diabetes Information System. Age-standardised means, proportions and attainment of targets were calculated for: processes of care indicators, intermediate outcomes and prescribing of preventive drug treatments in 1993 to 1994 and in 2000 to 2001 by quintiles of Townsend deprivation score. We did comparisons of means and proportions using age-adjusted linear regression and of trends using generalised estimating equations. Rate ratios for first microvascular and first macrovascular complication were estimated from proportional hazards models. RESULTS: Marked improvements occurred in all indicators. For patients managed in primary care, blood pressure and cholesterol measurement increased from 53% to 64% (p<0.001) and 27% to 61% (p<0.001) respectively; whilst mean systolic blood pressure decreased from 147 to 140 mmHg (p<0.001) and cholesterol concentrations from 6.0 to 5.1 mmol/l (p<0.001). Mean HbA(1c) increased from 7.8 to 8.1% (p<0.001). Prescribing of aspirin, anti-hypertensive and lipid-lowering drugs increased greatly. Trends varied little by socio-economic status. Patients from more affluent areas generally received more frequent clinical monitoring and preventive treatments, and had a lower BMI (29.5 vs 30.2 kg/m(2); p=0.009) and HbA(1c) (7.8 vs 8.2% p=0.006), though risks of first microvascular or macrovascular complications were similar. CONCLUSION/INTERPRETATION: Improvements in process and outcomes of care are possible for patients from all socio-economic groups. Socio-economic deprivation does not preclude high quality diabetes care.
AIMS: Diabetic pregnancies have an increased risk of respiratory distress syndrome (RDS) and preterm delivery. Antenatal corticosteroids can prevent RDS but induce acute severe hyperglycaemia. We have developed a protocol which prevents hyperglycaemia and can be used easily by ward staff. METHODS: Intramuscular dexamethasone is given in two doses 12 h apart. Subcutaneous insulin and diet are continued but from the first dexamethasone dose until 12 h after the second, supplementary intravenous insulin is infused according to hourly blood glucose measurements. The protocol incorporates four graded sliding scales. The initial scale is selected according to the patient's current subcutaneous insulin dose and advanced if the blood glucose is > or = 10.1 mmol/l for 2 consecutive hours. RESULTS: In a 10-month period eight (three gestational, five pre-gestational) women received antenatal corticosteroids from a total of 37 diabetic pregnancies. The median amount of supplementary intravenous insulin required was 74 U (range 32-88 U); the median glucose values achieved were 5.8-8.9 mmol/l. Seventy-five percent of glucose measurements were within an acceptable range of 4-10 mmol/l. Only one baby developed RDS. DISCUSSION: Large amounts of supplementary intravenous insulin are needed to achieve even moderate glycaemic control. This protocol enables routine ward staff to manage this successfully.
AIMS: To examine patients' perspectives on ease of use and pain with the MediSense alternate site blood glucose testing device (Soft-Sense) compared with their current glucose testing method, and to evaluate the analytical performance of the MediSense device with the laboratory reference method. METHODS: Study participants were shown how to use the Soft-Sense glucose device and asked to perform two tests on their forearm. A capillary sample was collected from their finger and tested on the external port of the Soft-Sense meter and a laboratory method (YSI Glucose Analyser). Finally, one drop of blood was also directly tested from the finger onto the external port. Patients completed a questionnaire comparing ease of use and associated pain of their current testing method with the Soft-Sense meter. RESULTS: Patients preferred the Soft-Sense device to their own for ease of use and for less pain (93% found it easier to use and 96% less painful; P < 0.001). Glucose results correlated closely with the laboratory method (mean absolute percentage bias for the forearm 11.0%, finger 6.0%, and collected capillary sample 5.7%). Error grid analysis showed that all Soft-Sense results were clinically acceptable. CONCLUSIONS: Patients prefer the Soft-Sense alternate site testing device to their existing measuring method. The device accurately measures whole blood glucose.
AIMS: To devise a system for assessing in-patient glycaemic control and care satisfaction in diabetic patients admitted to hospital for reasons other than their diabetes. METHODS: Consecutive January to March 2001 case-notes were reviewed. Admissions with acute metabolic complications, acute myocardial infarction and pregestational or gestational diabetes were excluded. Glycaemic control, frequency of blood monitoring and management of hyperglycaemia were recorded. The diabetes treatment satisfaction questionnaire was used to assess preadmission satisfaction with care. Post-admission a 12-stem questionnaire was used to assess satisfaction with in-patient diabetes management. RESULTS: Hypoglycaemia was common. Although none developed a hyperglycaemic emergency, high blood glucose was prevalent and, frequently, persistent hyperglycaemia or recurrent hypoglycaemia was not acted on appropriately. The overall score for in-patient satisfaction with treatment was fair (4.1 +/- 1.8 on a six-point scale; 6 = very satisfied and 1 = very dissatisfied). Scores were higher among patients on surgical wards than on medical wards (P = 0.008), but satisfaction did not vary when patients were stratified according to sex, age and mode of treatment. CONCLUSION: Current systems are not achieving satisfactory in-patient glycaemic control and there is poor satisfaction with medical in-patient diabetes care. Following changes intended to produce improvements, this assessment system can be used recurrently to monitor in-patient care and satisfaction.
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AIMS/HYPOTHESIS: To examine changes in diabetes care provision after the introduction of a district diabetes information system. METHODS: All patients with diabetes registered on the system between 1993 and 1998 (n = 6544) were included in the analysis. Drop-out cohort analysis was used to handle population changes, logistic regression models with general estimating equations were used to examine changes in clinical performance over time. RESULTS: After the introduction of the system, care processes improved appreciably, in both primary and secondary care. The proportion of patients receiving a preventative care review within the calendar year rose from 56% in 1993 to 67% in 1998. The proportion of these in whom each process was completed improved in all categories from 1993 to 1998: blood pressure 96% to 98%; glycaemic check 67% to 93%; lipid check 31% to 68%; renal check 46% to 87%; fundoscopy 79% to 92%; foot screen 87% to 87%. Similarly there was an increase in the proportion of patients achieving intermediate outcome treatment targets (HbA1c < or = 9.0% from 29% to 43%; cholesterol < or = 5.5 mmol/1 5% to 19%; blood pressure < or = 160/90 37% to 46%). CONCLUSION/INTERPRETATION: Our results suggest appreciable improvements in diabetes care between 1993 and 1998. These changes apply to an entire population of patients across primary and shared care. We believe that these improvements could, in part, be attributable to the way in which the district diabetes information system has facilitated the structured cascade of diabetes care.
AIMS: The aims of this study were to examine the effects of trandolapril, a long acting angiotensin converting enzyme (ACE) inhibitor with high tissue uptake, on insulin sensitivity and lipid concentrations in hypertensive patients with Type 2 diabetes mellitus. METHODS: Insulin sensitivity was assessed after an acute dose (day 3) and 19 days continuous treatment (days 3-21) using the isoglycaemic, hyperinsulinaemic glucose clamp with D[3-3H] labelled glucose, a variable D[3-3H] priming dose and a 'hot' glucose infusion. Rates of glucose appearance (Ra) and glucose disappearance (Rd) were isotopically determined during the basal and insulin stimulated periods of the clamp. Twenty-four (5 female) hypertensive (blood pressure >75th centile for age and sex) patients with Type 2 diabetes mellitus were studied. Patients were randomized, in a double-blind manner, to either trandolapril 4 mg daily (T) or placebo (P). RESULTS: Baseline (day 1) systolic (mean +/- SD; P 164+/-14 and T 168+/-13 mm Hg) and diastolic (P 93+/-6, and T 98+/-10 mm Hg) blood pressures were comparable. On days 3 and 21, significant reductions were observed in both groups (P<0.001). In the trandolapril-treated group, serum trandolapril concentrations were >200 pg/ml on days 3 and 21, in all patients apart from one subject at a single visit, while trandolapril was undetectable in the placebo group. Body mass index (BMI) was greater in T compared with P (32.2+/-5.4 v. 28.3+/-4.6, P = 0.07). After correcting for BMI, basal hepatic glucose output (HGO) P 2.6 (95% CI 2.23-3.13) and T 1.91 (1.33-2.51) mg x kg(-1) x min(-1) and clamped HGO P 0.32 (-0.44-1.09) and T 0.87 (0.40-1.34) mg x kg(-1) x min(-1) were similar in both groups. The insulin sensitivity index was comparable in both groups on all days. Total cholesterol concentrations were similar in both groups throughout the study. Triglyceride concentrations were significantly lower in group P 1.38 (1.07-1.68); T 2.14 (1.70-2.58) mmol/l, P<0.01), no significant treatment effect being observed. CONCLUSIONS: An acute dose and 19 days' continuous treatment with trandolapril resulted in no change in insulin sensitivity or plasma lipid profiles in patients with Type 2 diabetes mellitus and hypertension. These data support the metabolic neutrality of trandolapril in patients with Type 2 diabetes mellitus and hypertension.
OBJECTIVE: To evaluate the performance of a hand-held ketone sensor that is able to measure blood beta-hydroxybutyrate (beta-HBA) concentrations within 30 s in patients with diabetic ketoacidosis (DKA) and patients who attend a weight management clinic. RESEARCH DESIGN AND METHODS: Two groups of patients were studied: 19 patients admitted with DKA and 156 patients attending a weight management clinic. Paired capillary and venous whole blood samples were measured using the ketone sensor and also using an enzymatic laboratory reference method. RESULTS: The ketone sensor accurately measured beta-HBA concentrations in patients with DKA (limits of agreement -0.9 to + 1.0 mmol/l) or starvation-induced ketonemia (limits of agreement -0.5 to +0.5 mmol/l). CONCLUSIONS: This ketone sensor accurately measures whole blood beta-HBA concentrations within 30 s.
Premenstrual exacerbation of asthma, as reflected by a reduction in peak expiratory flow rate (PEFR), has been demonstrated in 40-100% of female asthmatics. Epidemiological data demonstrate that admission to hospital with an exacerbation of asthma occurs more frequently perimenstrually. Therapeutic interventions aimed at modifying this precipitating factor, however, remain limited. We report on a 32-yr old female with asthma in whom a marked increase in symptoms and reduction in PEFR occurred premenstrually, necessitating recurrent admissions to hospital. Frequent severe exacerbations resulted in the chronic use of oral maintenance corticosteroids. In order to suppress gonadotrophin secretion and ovarian function, a long-acting gonadotrophin-releasing hormone analogue was administered with a view to inducing a reversible menopause. This resulted in improvement in respiratory symptoms, the absence of PEFR dips premenstrually, a reduction in maintenance prednisolone dosage and no further hospital admissions during a follow-up period of 14 months. The authors propose that gonadotrophin-releasing hormone-analogue therapy is a rational and innovative adjuvant treatment worthy of further study in cases of severe premenstrual asthma.
A reduction of 50% or more in diabetes-related amputations is a primary target of the St Vincent Declaration. This is thought to be achievable because both primary and secondary preventative healthcare strategies are effective in reducing the incidence of diabetic foot ulceration and progression to amputation. Unfortunately there is a group who cannot benefit from preventative health care, that is, newly diagnosed diabetic patients with already established severe complications. Using our population-based district diabetes information system we investigated, during the period 1 January 1992 to 31 December 96, the incidence and prevalence of lower extremity amputations (LEAs) and the proportion occurring in patients newly or recently diagnosed as having diabetes. Seventy-nine diabetic patients (59 male, 20 female) were recorded as having had 94 LEAs, the incidence of diabetes-related LEA being 475 per 100,000 diabetic patient-years. Of these LEAs 16 (20.2%) were performed within 1 year of diabetes being diagnosed. This study highlights an appreciable and previously unrecognized problem: patients presenting with established complications of diabetes who cannot benefit from secondary preventative healthcare. These patients pose a potential obstacle to achieving targets for reductions in diabetes-related amputations.
Abnormalities of renal autoregulation with glomerular hyperfiltration and raised intraglomerular pressure have been suggested as important factors in the initiation and development of diabetic nephropathy. Angiotensin converting enzyme (ACE) inhibition appears to have a specific reno-protective role in diabetic nephropathy, possibly by reducing intraglomerular pressure. The acute effects of ACE inhibition on renal haemodynamics in normotensive, non-insulin-dependent diabetes mellitus (NIDDM) have not been previously reported. We measured simultaneous glomerular filtration rate (GFR) and renal plasma flow (RPF) in 29 (4 female) subjects, mean age 52 years (range 27-70), using 51Cr EDTA and 125I Hippuran. Clearances were corrected to 1.73 m(-2). All patients were normotensive (blood pressure < 75th centile for age and sex), newly diagnosed (< 30 days), taking no antihypertensive or hypoglycaemic medication. Subjects were randomly allocated (double blind) to receive the ACE inhibitor trandolapril 4mg day(-1) (H) (hypotensive dose), trandolapril 0.5 mg day(-1)(L) (non-hypotensive dose) or placebo (P) for 10 days after which renal haemodynamics were remeasured. For all subjects baseline GFR, RPF and filtration fraction (FF) were 97+/-21 ml min(-1) mean+/-SD, 439+/-120 ml min(-1) and 22.3+/-2.9 % respectively. Glomerular hyperfiltration (GFR> 120 ml min[-1]) was only demonstrated in 3 subjects (10.3 %). In group H mean arterial pressure (103+/-8 vs 93+/-9 mmHg, p < 0.001) and FF (23.8+/-2.3 vs 20.0+/-4.0%, p = 0.03) fell while RPF increased (376+/-111 vs 426+/-60 ml min(-1), p = 0.02), there was no significant change in GFR. No significant change in mean arterial pressure, GFR, RPF or FF occurred in groups P and L. These studies suggest that in newly diagnosed normotensive NIDDM subjects normal renal autoregulation occurs and glomerular hyperfiltration is uncommon.
A pig model of insulin-dependent diabetes was used to examine the importance of the portal-systemic insulin gradient for whole-body metabolic control. Six pigs had jugular vein, portal vein, and carotid artery cannulae implanted before being made diabetic (150 mg kg[-1] streptozotocin). Each animal received 4 weeks of portal and 4 weeks of peripheral insulin delivery in random order. The blood glucose target range was 5-10 mmol x l(-1), and serum fructosamine and fasting and postprandial blood glucose concentrations were not different between peripheral and portal insulin infusion. Insulin requirement was not different between the 4 week infusion periods, but fasting peripheral insulin levels after peripheral delivery (124 +/- 16 (mean +/- SEM) pmol x l[-1]) were significantly higher (p < 0.05) than in portally infused (73.8 +/- 5.4 pmol x l[-1]) or pre-diabetic control animals (68.4 +/- 3.6 pmol x l[-1]). Basal hepatic glucose output was also higher (p < 0.05) in peripherally (4.2 +/- 0.4 mg x kg[-1] x min[-1]) than in portally infused animals (2.9 +/- 0.4 mg x kg[-1] x min[-1]) or controls (3.0 +/- 0.3 mg x kg[-1] x min[-1]). Clamp glucose metabolic clearance rate was, however, not different between the peripheral and portal insulin delivery routes (8.1 +/- 1.0 vs 9.0 +/- 0.7 ml x kg[-1] x min[-1]), although both were significantly lower (p < 0.05) than that measured in prediabetic control animals (11.7 +/- 1.0 ml x kg[-1] x min[-1]). Lipid profiles and subfractions were similar in all three groups. It is concluded that the portal route of delivery is superior to the peripheral in maintaining more appropriate insulin concentrations and control of hepatic glucose output, although in the absence of euglycaemia it is still associated with significant metabolic abnormalities.
The enzyme steroid 5 alpha-reductase, via NADPH, catalyses the conversion of testosterone to dihydrotestosterone, which is required for the embryonic differentiation of the external male genitalia and the prostate. An impairment of this reaction causes a form of male pseudohermaphroditism in which genetic males differentiate predominantly as phenotypic females. Molecular analysis of the 5 alpha-reductase type 2 gene in a patient with confirmed biochemical 5 alpha-reductase deficiency has resulted in the identification of a novel mutation, GAA to AAA, at codon 200. This mutation produces an amino acid change from glutamic acid to lysine, and may affect the ability of the enzyme to bind its co-factor.