R. T. Jung

The prevention of progression of arterial disease and diabetes (POPADAD) trial: factorial randomised placebo controlled trial of aspirin and antioxidants in patients with diabetes and asymptomatic peripheral arterial disease

Objective To determine whether aspirin and antioxidant therapy, combined or alone, are more effective than placebo in reducing the development of cardiovascular events in patients with diabetes mellitus and asymptomatic peripheral arterial disease. Design Multicentre, randomised, double blind, 2×2 factorial, placebo controlled trial. Setting 16 hospital centres in Scotland, supported by 188 primary care groups. Participants 1276 adults aged 40 or more with type 1 or type 2 diabetes and an ankle brachial pressure index of 0.99 or less but no symptomatic cardiovascular disease. Interventions Daily, 100 mg aspirin tablet plus antioxidant capsule (n=320), aspirin tablet plus placebo capsule (n=318), placebo tablet plus antioxidant capsule (n=320), or placebo tablet plus placebo capsule (n=318). Main outcome measures Two hierarchical composite primary end points of death from coronary heart disease or stroke, non-fatal myocardial infarction or stroke, or amputation above the ankle for critical limb ischaemia; and death from coronary heart disease or stroke. Results No evidence was found of any interaction between aspirin and antioxidant. Overall, 116 of 638 primary events occurred in the aspirin groups compared with 117 of 638 in the no aspirin groups (18.2% v 18.3%): hazard ratio 0.98 (95% confidence interval 0.76 to 1.26). Forty three deaths from coronary heart disease or stroke occurred in the aspirin groups compared with 35 in the no aspirin groups (6.7% v 5.5%): 1.23 (0.79 to 1.93). Among the antioxidant groups 117 of 640 (18.3%) primary events occurred compared with 116 of 636 (18.2%) in the no antioxidant groups (1.03, 0.79 to 1.33). Forty two (6.6%) deaths from coronary heart disease or stroke occurred in the antioxidant groups compared with 36 (5.7%) in the no antioxidant groups (1.21, 0.78 to 1.89). Conclusion This trial does not provide evidence to support the use of aspirin or antioxidants in primary prevention of cardiovascular events and mortality in the population with diabetes studied. Trial registration Current Controlled Trials ISRCTN53295293.

The diabetes audit and research in Tayside Scotland (darts) study: electronic record linkage to create a diabetes register

Abstract Objectives: To identify all patients with diabetes in a community using electronic record linkage of multiple data sources and to compare this method of case ascertainment with registers of diabetic patients derived from primary care. Design: Electronic capture-recapture linkage of records included data on all patients attending hospital diabetes clinics, all encashed prescriptions for diabetes related drugs and monitoring equipment, all patients discharged from hospital, patients attending a mobile unit for eye screening, and results for glycated haemoglobin and plasma glucose concentrations from the regional biochemistry database. Diabetes registers from primary care were from a random sample of eight Tayside general practices. A detailed manual study of relevant records for the 35 144 patients registered with these eight general practices allowed for validation of the case ascertainment. Setting: Tayside region of Scotland, population 391 274 on 1 January 1996. Main outcome measures: Prevalence of diabetes; population of patients identified by different data sources; sensitivity and positive predictive value of ascertainment methods. Results: Electronic record linkage identified 7596 diabetic patients, giving a prevalence of known diabetes of 1.94% (0.21% insulin dependent diabetes, 1.73% non-insulin dependent): 63% of patients had attended hospital diabetes clinics, 68% had encashed diabetes related prescriptions, 72% had attended the mobile eye screening unit, and 48% had biochemical results diagnostic of diabetes. A further 701 patients had isolated hyperglycaemia (plasma glucose >11.1 mmol/l) but were not considered diabetic by general practitioners. Validation against the eight general practices (636 diabetic patients) showed electronic linkage to have a sensitivity of 0.96 and a positive predictive value of 0.95 for ascertainment of known diabetes. General practice lists had a sensitivity of 0.91 and a positive predictive value of 0.98. Conclusions: Electronic record linkage was more sensitive than general practice registers in identifying diabetic subjects and identified an additional 0.18% of the population with a history of hyperglycaemia who might warrant screening for undiagnosed diabetes. Key messages It has been recommended that regional registers of patients with diabetes are established in order to facilitate effective monitoring and treatment of diabetes In Tayside we created a diabetes register by record linkage of multiple data sources: all patients attending hospital diabetes clinics, all encashed prescriptions for diabetes related drugs and monitoring equipment, all patients discharged from hospital, patients attending a mobile unit for eye screening, and results for glycated haemoglobin and plasma glucose concentrations from the regional biochemistry database This register identified 7596 patients with diabetes in Tayside, giving a prevalence of diabetes of 1.94% Record linkage was more sensitive than general practice registers in ascertaining cases of known diabetes A unique patient identifier, the community health number, was fundamental for successful record linkage

High prevalence of primary aldosteronism in the Tayside hypertension clinic population.

Primary aldosteronism (PA) was thought to be rare but recent evidence from Australia suggests that it may be more common. As this has important implications in terms of hypertension management, we undertook to screen for this treatable condition in our hypertension clinic. We obtained blood samples in sequential patients referred for assessment in our hypertension clinic in Tayside for plasma renin activity (PRA) and aldosterone. The aldosterone to PRA ratio (ARR) was used as an initial screening test to identify potential patients with PA. Those patients with an elevated ratio (⩾750) were admitted for the salt loading and fludrocortisone suppression test. These patients also underwent adrenal CT scanning, and in selected patients, adrenal scintigraphy. Between May 1995 and January 1997 (21 months), we screened a total of 495 patients. ARR was available in 465 (93.9%) patients. Out of that number, 77 (16.6%) had an elevated ratio of ⩾750, five of whom had an adrenal adenoma (one had previous adrenalectomy). Forty-five of these patients were admitted for the salt loading and fludrocortisone suppression test with 41 positive test results suggesting PA. One patient with a negative salt loading test result however had an adenoma proven on histology. A total of 43 cases of PA were identified, giving a minimum prevalence of 9.2% (43/465). Potentially the prevalence may be up to 15% assuming that the ARR has a sensitivity of 93% (42/45) in predicting PA. In conclusion, about one in 10 patients attending a hypertension clinic may have PA. This suggests that the prevalence of PA in Tayside is as high as that in the Australian hypertensive population, and this is likely to be true elsewhere, with obvious important implications for hypertension management.

Effects of weight loss in overweight/obese individuals and long-term lipid outcomes--a systematic review.

This paper aims to review the evidence for long‐term effectiveness of weight loss on cholesterol, high‐density lipoprotein (HDL), low‐density lipoprotein (LDL) and triglycerides in overweight/obese people. Current evidence is mostly based on short‐term studies. A systematic review of long‐term lipid outcomes of weight loss in studies published between 1966 and 2001, was conducted. Inclusion criteria included all cohort studies and trials carried out on participants with body mass index of greater than or equal to 28 kg m−2. Studies had at least two weight change measurements and follow‐up of more than 2 years. Thirteen long‐term studies with a follow‐up of more than 2 years were included. Cholesterol has a significant positive linear relationship with weight change (r = 0.89) where change in weight explains about 80% of the cholesterol difference variation (Adj R2 = 0.80). For every 10 kg weight loss a drop of 0.23 mmol L−1 in cholesterol may be expected for a person suffering from obesity or are grossly overweight. Weight loss has long‐term beneficial effects especially on LDL and cholesterol. Weight loss in obese patients should be encouraged and sustained.

Effects of Weight Loss in Overweight/Obese Individuals and Long-Term Hypertension Outcomes A Systematic Review

Many studies have assessed short-term effects of weight loss on blood pressure, whereas little attention has been paid to long-term effects. We conducted a systematic review to evaluate the long-term effects of weight loss on hypertension outcome measures in adults using literature published from 1966 to 2001. All prospective studies and trials, performed on participants with body mass index of ≥28 kg/m2 with a follow-up of >2 years and weight changes recorded, were included. The data from these studies were used to model the long-term effects on blood pressure. Previous reviews on shorter-term studies indicate a 1:1 drop in blood pressure (mm Hg) with weight loss (kilograms). Our findings, based on studies with follow-up of ≥2 years, demonstrate blood pressure decreases less than this after weight loss. The surgical intervention studies exhibited huge weight losses with undramatic blood pressures changes. When surgical interventions are excluded, the models suggest that for 10 kg weight loss, decreases of 4.6 mm Hg and 6.0 mm Hg in diastolic and systolic blood pressure, respectively, may be expected, about half of that predicted from the short-term trials. Initial blood pressure, the length of follow-up, medication changes, and physiological restrictions may contribute to this reduced effect in the long-term studies. Extrapolation of short-term blood pressure changes with weight loss to the longer term is potentially misleading. The weight/hypertension relationship is complex and needs well-conducted studies with long-term follow-up to examine the effects of weight loss on hypertension outcomes.

Serum thyroid-stimulating hormone concentration and morbidity from cardiovascular disease and fractures in patients on long-term thyroxine therapy.

CONTEXT For patients on T(4) replacement, the dose is guided by serum TSH concentrations, but some patients request higher doses due to adverse symptoms. OBJECTIVE The aim of the study was to determine the safety of patients having a low but not suppressed serum TSH when receiving long-term T(4) replacement. DESIGN We conducted an observational cohort study, using data linkage from regional datasets between 1993 and 2001. SETTING A population-based study of all patients in Tayside, Scotland, was performed. PATIENTS All patients taking T(4) replacement therapy (n = 17,684) were included. MAIN OUTCOME MEASURES Fatal and nonfatal endpoints were considered for cardiovascular disease, dysrhythmias, and fractures. Patients were categorized as having a suppressed TSH (<or=0.03 mU/liter), low TSH (0.04-0.4 mU/liter), normal TSH (0.4-4.0 mU/liter), or raised TSH (>4.0 mU/liter). RESULTS Cardiovascular disease, dysrhythmias, and fractures were increased in patients with a high TSH: adjusted hazards ratio, 1.95 (1.73-2.21), 1.80 (1.33-2.44), and 1.83 (1.41-2.37), respectively; and patients with a suppressed TSH: 1.37 (1.17-1.60), 1.6 (1.10-2.33), and 2.02 (1.55-2.62), respectively, when compared to patients with a TSH in the laboratory reference range. Patients with a low TSH did not have an increased risk of any of these outcomes [hazards ratio: 1.1 (0.99-1.123), 1.13 (0.88-1.47), and 1.13 (0.92-1.39), respectively]. CONCLUSIONS Patients with a high or suppressed TSH had an increased risk of cardiovascular disease, dysrhythmias, and fractures, but patients with a low but unsuppressed TSH did not. It may be safe for patients treated with T(4) to have a low but not suppressed serum TSH concentration.

QT and QTc dispersion are accurate predictors of cardiac death in newly diagnosed non-insulin dependent diabetes: cohort study

Patients with non-insulin dependent diabetes mellitus have an excess risk of dying from cardiovascular disease. One small study suggested that a prolonged QT interval could predict cardiac death in patients with diabetic nephropathy who have received insulin treatment. The question now is whether the same is true in newly diagnosed diabetes in patients who have no apparent complications. In addition, QT dispersion, a new but related electrocardiographic variable, predicts cardiac death in patients who have chronic heart failure, peripheral vascular disease, or essential hypertension.1–3 We investigated whether it also predicted cardiac death in diabetic patients. The study group of 182 patients with non-insulin dependent diabetes mellitus (103 men; mean age 52.8 (SD 8.5) years) represented the Dundee cohort of the United Kingdom prospective diabetes study, which was recruited between 1982 and 1988. Patients were followed up for a mean of 10.3 (1.7) years. …

Diabetes and Lower-Limb Amputations in the Community: A retrospective cohort study

OBJECTIVE There are few U.K. data on the incidence rates of amputation in diabetic subjects compared with the nondiabetic population. RESEARCH DESIGN AND METHODS We performed a historical cohort study of first lower-extremity amputations based in Tayside, Scotland (population 364,880) from 1 January 1993 to 31 December 1994. The Diabetes Audit and Research in Tayside Scotland (DARTS) database was used to identify a prevalence cohort of 7,079 diabetic patients on 1 January 1993. We estimated age-specific and standardized incidence rates of lower-limb amputations in the diabetic and nondiabetic cohorts. Results were compared with a previous study that evaluated lower-extremity amputations in diabetic patients in Tayside in 1980–1982. RESULTS There were 221 subjects who underwent a total of 258 nontraumatic amputations. Of the 221 subjects, 60 (27%) patients were diabetic (93% NIDDM), and 63% were first amputations. The median duration of diabetes was 6 years (range: newly diagnosed to 41 years). Nonhealing ulceration (31%) and gangrene (29%) were the two main indications for amputation in the diabetic subjects. Of the 161 nondiabetic subjects, 140 (80%) underwent first amputations. The adjusted incidences in the diabetic and nondiabetic groups were 248 and 20 per 100,000 person-years, respectively. Tayside patients with diabetes thus had a 12.3-fold risk of an amputation compared with nondiabetic residents (95% Cl 8.6–17.5). The estimated proportion of diabetic patients in the population rose from 0.81% in 1980–1982 to 1.94% in 1993–1994, whereas the absolute rate of amputation in diabetic subjects was unchanged from that in 1980–1982. CONCLUSIONS These population-based U.K. amputation data are similar to amputation rates in the U.S. Amputation rates appear to have decreased significantly since 1980–1982. The impact of diabetes education and prevention programs that target the processes leading to amputation can now be evaluated.

Morbidity in patients on l-thyroxine: a comparison of those with a normal TSH to those with a suppressed TSH

OBJECTIVE Patients on l‐thyroxine with a ‘suppressed’ TSH (< 0 05 mU/l) were compared to those in whom TSH was detectable but not elevated (0 05– 4 0 mU/l), with regard to morbidity data.

Weight loss in obese diabetic and non-diabetic individuals and long-term diabetes outcomes - a systematic review

The aim was to review the evidence for the long‐term effects of weight loss on diabetes outcomes in obese people or for those at risk of developing type 2 diabetes. Current evidence is mostly based on short‐term studies. This is a systematic review of long‐term outcomes of weight loss in studies published between 1966 and 2001. Eleven long‐term studies with a follow up of more than 2 years were included. Results show that those with diabetes who lost weight intentionally significantly reduced their mortality risks by 25%. Additionally, weight loss of 9–13 kg was most protective. Patients with the risk of developing diabetes due to either family history of diabetes or impaired glucose tolerance, saw a reduction in this risk. Those with large weight losses achievable with surgical interventions reduced their risk by at least 63%. Metabolic handling of glucose improved in 80% of those already with type 2 diabetes who lost weight. Based on one large study, intentional weight loss in obese patients appears to have a beneficial effect on mortality risk for those with type 2 diabetes. Clearly, further studies are needed to endorse this. The risk of developing diabetes being reduced by weight loss was shown in seven studies. However, the results were from studies with different analytical adjustments and outcome indices, making it difficult to make direct comparisons and should be viewed with caution. More long‐term prospective studies need to be conducted with commitment to improving the methodological quality and standardization, in order to accurately assess the long‐term effects of weight loss for obese diabetic and non‐diabetic individuals.