Prognosis following first acute myocardial infarction in Type 2 diabetes: a comparative population study.

AIMS: To estimate the incidence of death and macrovascular complications after a first myocardial infarction for patients with Type 2 diabetes. RESEARCH DESIGN: In a retrospective, incidence cohort study in the Tayside Region of Scotland we studied all patients hospitalized with a diagnosis of first acute myocardial infarction from 1 April 1993 to 31 December 1994. The primary endpoint was time to death. Secondary endpoints were 2-year incidence of hospital admission for angina, myocardial infarction, stroke, heart failure, coronary angiography, coronary artery bypass graft (CABG) and percutaneous transluminal coronary angioplasty (PTCA). RESULTS: The 147 patients with Type 2 diabetes had significantly worse survival with an increase in relative hazard of 67% compared with non-diabetic patients. After adjustment for age, sex, smoking status, prior heart failure, prior angina, delay to hospitalization, site of infarction, drug therapy with aspirin, beta-blockers, streptokinase and hyperlipidaemia and treated hypertension, Type 2 diabetes was still associated with a 40% higher death rate compared with people without diabetes (P < 0.05) There was no significant difference in death rates in those aged over 70 years, but an indication of a trend in younger individuals with a four-fold increase in death rate in those with diabetes aged < 60 years, compared with a rate ratio of 2.6 in those with diabetes aged 61-70 years. CONCLUSIONS: Among hospitalized patients with first acute myocardial infarction, Type 2 diabetes mellitus is consistently associated with increased mortality and increased hospital admission for heart failure. The estimated 4-year survival rate is only 50%. Our results indicate that younger subjects with Type 2 diabetes and acute myocardial infarction are a high-risk group deserving of special study, and support the argument for aggressive targeting of coronary risk factors among patients with Type 2 diabetes.

Contraindications to metformin therapy in patients with Type 2 diabetes--a population-based study of adherence to prescribing guidelines.

AIMS: To define the number of people in Tayside, Scotland (population 349 303) with Type 2 diabetes who use metformin, the incidence of contraindications to its continued use in these people and the proportion that discontinued metformin treatment following the development of a contraindication. METHODS: Retrospective cohort study of the incidence of contraindications to metformin in all patients with Type 2 diabetes using metformin from January 1993 to June 1995. The contraindications of acute myocardial infarction, cardiac failure, renal impairment and chronic liver disease were identified by: the regional diabetes information system, biochemistry database and hospital admissions database and a database of all encashed community prescriptions. RESULTS: One thousand eight hundred and forty seven subjects (26.3% of those with Type 2 diabetes) redeemed prescriptions for metformin. Of these, 3.5% were admitted with an acute myocardial infarction (71 episodes); 4.2% were admitted with cardiac failure (114 episodes); 21.0% received metformin and loop diuretics for cardiac failure concurrently; 4.8% developed renal impairment; and 2.8% developed chronic liver disease. The development of contraindications rarely resulted in discontinuation of metformin, for example only 17.5% and 25% stopped metformin after admission with acute myocardial infarction and development of renal impairment, respectively. In total, 24.5% of subjects receiving metformin, 6.4% of all people with Type 2 diabetes, had contraindications to its use. There was one episode of lactic acidosis in 4600 patient years. CONCLUSIONS: This population-based study shows that 24.5% of patients prescribed metformin have contraindications to its use. Development of contraindications rarely results in discontinuation of metformin therapy. Despite this, lactic acidosis remains rare. Diabet. Med. 18, 483-488 (2001)

Diabetes and lower-limb amputations in the community. A retrospective cohort study. DARTS/MEMO Collaboration. Diabetes Audit and Research in Tayside Scotland/Medicines Monitoring Unit.

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% CI 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.

Adherence to insulin treatment, glycaemic control, and ketoacidosis in insulin-dependent diabetes mellitus. The DARTS/MEMO Collaboration. Diabetes Audit and Research in Tayside Scotland. Medicines Monitoring Unit.

BACKGROUND: Intensive insulin treatment effectively delays the onset and slows the progression of microvascular complications in insulin-dependent diabetes mellitus (IDDM). Variable adherence to insulin treatment is thought to contribute to poor glycaemic control, diabetic ketoacidosis, and brittle diabetes in adolescents and young adults with IDDM. We assessed the association between the prescribed insulin dose and the amount dispensed from all community pharmacies with the Diabetes Audit and Research in Tayside Scotland (DARTS) database. METHODS: We studied 89 patients, mean age 16 (SD 7) years, diabetes duration 8 (4) years, and glycosylated haemoglobin (HbA1c) 8.4 (1.9)%, who attended a teaching hospital paediatric or young-adult diabetes clinic in 1993 and 1994. The medically recommended insulin dose and cumulative volume of insulin prescriptions supplied were used to calculate the days of maximum possible insulin coverage per annum, expressed as the adherence index. Associations between glycaemic control (HbA1c), episodes of diabetic ketoacidosis, and all hospital admissions for acute complications and the adherence index were modelled. FINDINGS: Insulin was prescribed at 48 (19) IU/day and mean insulin collected from pharmacies was 58 (25) IU/day, 25 (28%) of the 89 patients obtained less insulin than their prescribed dose (mean deficit 115 (68; range 9-246] insulin days/annum). There was a significant inverse association between HbA1c and the adherence index (R2 = 0.39; p < 0.001). In the top quartile (HbA1c > 10%), 14 (64%) of individuals had an adherence index suggestive of a missed dose of insulin (mean deficit 55 insulin days/annum). There were 36 admissions for complications related to diabetes. The adherence index was inversely related to hospital admissions for diabetic ketoacidosis (p < 0.001) and all hospital admissions related to acute diabetes complications (p = 0.008). The deterioration in glycaemic control observed in patients aged 10-20 years was associated with a significant reduction (p = 0.01) in the adherence index. INTERPRETATION: We found direct evidence of poor compliance with insulin therapy in young patients with IDDM. We suggest that poor adherence to insulin treatment is the major factor that contributes to long-term poor glycaemic control and diabetic ketoacidosis in this age group.

ACE inhibitor use is associated with hospitalization for severe hypoglycemia in patients with diabetes. DARTS/MEMO Collaboration. Diabetes Audit and Research in Tayside, Scotland. Medicines Monitoring Unit.

OBJECTIVE: To evaluate the association between the use of ACE inhibitors and hospital admission for severe hypoglycemia and to explore the effects of potential confounding variables on this relationship. RESEARCH DESIGN AND METHODS: The association between the use of ACE inhibitors and the incidence of hypoglycemia is controversial. A recent study reported that 14% of all hospital admissions for hypoglycemia might be attributable to ACE inhibitors. We performed a nested case-control study, using a cohort of 6,649 diabetic patients taking insulin or oral antidiabetic drugs, on the Diabetes Audit and Research in Tayside, Scotland (DARTS) database. From 1 January 1993 to 30 April 1994, we identified 64 patients who had been admitted to Tayside hospitals with hypoglycemia and selected 440 control patients from the same cohort. RESULTS: Hypoglycemia was associated with the use of ACE inhibitors (odds ratio [OR] 3.2, 95% CI 1.2-8.3, P = 0.023), whereas use of beta-blockers and calcium antagonists was not associated with an increased risk of hospitalization for hypoglycemia with ORs of 0.9 (95% CI 0.3-3.3) and 1.7 (95% CI 0.2-2.1), respectively. There were significant differences between case and control patients in type of diabetes treatment, diabetes duration, place of routine diabetes care, and congestive cardiac failure. These differences did not confound the relationship between ACE inhibitors and hypoglycemia (adjusted OR 4.3, 95% CI 1.2-16.0). CONCLUSIONS: The results show that the association between ACE inhibitor therapy and hospital admission for severe hypoglycemia is not explained by these confounding factors. Although ACE inhibitors have distinct advantages over other antihypertensive drugs in diabetes, the risk of hypoglycemia should be considered.

The diabetes audit and research in Tayside Scotland (DARTS) study: electronic record linkage to create a diabetes register. DARTS/MEMO Collaboration.

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.