Criteria for previously undiagnosed diabetes and risk of mortality: 15-year follow-up of the Edinburgh Artery Study cohort.

AIMS: To compare risk of all-cause and cardiovascular mortality associated with different criteria for undiagnosed diabetes and glucose tolerance. METHODS: A population-based cohort of 758 men and 738 women of 55-74 years of age who had an oral glucose tolerance test or known diabetes at baseline were followed up until death or for 15 years. Mortality outcomes were compared by baseline diabetes status using people with normal glucose tolerance (i.e. those without diabetes, impaired fasting glucose or impaired glucose tolerance) as the reference group. RESULTS: Prevalence of undiagnosed diabetes using World Health Organization (WHO) criteria (fasting glucose of > or = 7.0 mmol/l and/or a 2-h post-challenge glucose of > or = 11.1 mmol/l) was 6.6%, of which 81% was associated with fasting glucose > or = 7.0 mmol/l and 19% was associated with isolated post-challenge hyperglycaemia. Hazard ratios (95% CI) for all-cause mortality adjusted for age and sex were 1.51 (1.09-2.08) for new diabetes by the American Diabetes Association (ADA) criterion (fasting glucose of > or = 7.0 mmol/l regardless of post-challenge glucose), 1.60 (1.20-2.13) for new diabetes by WHO criteria and 1.98 (1.14-3.44) for isolated post-challenge hyperglycaemia. Hazard ratios (95% CI) for cardiovascular mortality adjusted for age and sex were 1.89 (1.17-3.00), 1.73 (1.12-2.66) and 1.08 (0.34-3.40) for new diabetes by ADA and WHO criteria and for isolated post-challenge hyperglycaemia, respectively. CONCLUSIONS: Undiagnosed diabetes was associated with increased risk of all-cause mortality by any criteria but significantly increased cardiovascular disease mortality was only associated with diabetes diagnosed using the fasting glucose criterion. Mortality risks were similar in this population using either ADA or WHO criteria for diagnosis of diabetes.     

Serum uric acid, mortality and glucose control in patients with Type 2 diabetes mellitus: a PreCIS database study.

AIMS: To determine the association of serum uric acid with all-cause mortality and hyperglycaemia in patients with Type 2 diabetes. METHODS: Retrospective cohort analysis of 535 consecutive patients who had uric acid determinations between 1998 and 2004 and whose subsequent vital status was determined at a median of 4.5 years. The association with mortality was analysed with Cox proportional hazards models. The incremental predictive value of uric acid was examined with concordance indexes. The proportional risk of mortality was represented with the Kaplan-Meier survival curves by uric acid quartiles. RESULTS: We studied 370 men and 165 women aged 59.3 +/- 11.5 years. Mean uric acid was 371.7 +/- 106.2 micromol/l. Patients with glycated haemoglobin (HbA(1c)) > or = 9% had lower uric acid vs. the rest (342.2 +/- 112.1 vs. 383.5 +/- 106.2, P = 0.002). Overall mortality was 10.8%. For each 59 micromol/l increase in uric acid there was a 41% increase in risk of death (unadjusted analysis). The association of uric acid with mortality remained after adjustment for covariates (hazard ratio = 1.21, 95% confidence interval 1.07-1.45) and after gender subanalyses. Uric acid increased the accuracy of prediction when added to a model including Framingham risk factors, components of metabolic syndrome and fibrinogen (P = 0.03). Mortality was higher in patients taking diuretics vs. the rest (15.9 vs. 7.3%), but uric acid predicted mortality in both subgroups. CONCLUSIONS: Serum uric acid predicts mortality in Type 2 diabetic patients regardless of gender, HbA(1c), renal function and diuretic use. Intervention studies should determine whether uric acid is a potential therapeutic target or only a marker of mortality risk.     

Renal damage in patients with Type 2 diabetes: a strong predictor of mortality.

AIMS: (i) To compare mortality rates in a cohort of Type 2 diabetic patients with those of the general population; (ii) to assess the prognostic role of pre-existing chronic conditions; (iii) to evaluate the impact of different severity of renal damage on mortality. METHODS: All 3892 patients with Type 2 diabetes attending our Diabetic Clinic during 1995 and alive on 1 January 1996 were identified and followed for 4.5 years. Information on vital status (100% complete) and causes of death (98.5% complete) for 599 deceased subjects was derived from death certificates. RESULTS: In comparison with the general population, standardized mortality ratios (x 100) were: 125 (95% confidence interval 104-148) in patients aged < 75 and 85 (75-95) in patients > or = 75 years. Cardiovascular diseases and diabetes were responsible for most of the excess deaths. In a Cox-proportional hazard model, renal damage was a powerful predictor of death (hazard ratio = 2.39; 95% confidence intervals = 2.00-2.85). The severity of renal damage was associated with increasing hazard ratios for death from all-cause mortality and from specific causes (especially coronary artery disease, other cardiovascular causes and diabetes) after multiple adjustments. Other significant predictors of death were: greater age, glycated haemoglobin, smoking, lower body mass index, pre-existing coronary and peripheral artery disease and known co-morbidity (cirrhosis and cancer). CONCLUSIONS: Renal damage of any severity is significantly associated with subsequent mortality from all causes and from cardiovascular diseases. These associations are not confounded by pre-existing co-morbidity or coronary diseases.     

Changing aspirin use in patients with Type 2 diabetes in the UKPDS.

AIMS: To examine the proportion of UK Prospective Diabetes Study (UKPDS) patients with Type 2 diabetes taking aspirin regularly for the primary and secondary prevention of cardiovascular disease (CVD) before and after publication of the 1997 American Diabetes Association (ADA) Clinical Practice Recommendations and the 1998 Joint British Recommendations on the Prevention of Coronary Disease in Clinical Practice. METHODS: UKPDS annual review data from 1996/7 (n = 3190) and 2000/1 (n = 2467) were used to determine the prevalence of patients taking aspirin regularly in relation to known CVD risk factors and pre-existing CVD. RESULTS: Patients taking aspirin regularly were more often male than female (24 vs. 20%, P = 0.0033), older (66 +/- 8 vs. 62 +/- 9 years, P < 0.0001) and less often Afro-Caribbean than White Caucasian or Indian Asian (11 vs. 23 vs. 22%, respectively, P < 0.0001). Between 1996/7 and 2000/1 aspirin use in patients without pre-existing CVD increased from 17 to 31% (P < 0.0001) and for those with pre-existing CVD from 76 to 82% (P = 0.032). CONCLUSION: The majority of patients with pre-existing CVD were taking aspirin regularly. Although aspirin use in those without pre-existing CVD approximately doubled after publication of the ADA and Joint British Recommendations, less than two-thirds of these high-risk patients were being treated according to guidelines. This may relate to a lack of convincing evidence for primary CVD prevention or failure to adhere to guidelines. It may be that more trial data is needed to convince clinicians of the value of aspirin therapy in Type 2 diabetes.     

Effects of a structured health education programme by a diabetic education nurse on cardiovascular risk factors in Chinese Type 2 diabetic patients: a 1-year prospective randomized study.

AIMS: To assess the effect of regular diabetic health education on cardiovascular risk factors in Chinese Type 2 diabetic patients. METHODS: This was a 1-year prospective randomized study. One hundred and eighty Type 2 diabetic subjects were recruited from three regional diabetic centres in Hong Kong. Ninety received additional structured reinforcement of diabetic health education by a trained nurse after the doctors' consultations every 3 months (intervention group). The others received the same medical care except no nursing reinforcement (control group). Outcome measures included fasting plasma glucose, HbA(1c), body mass index, waist circumference, blood pressure and lipid profiles, which were assessed before the study and after 1 year. RESULTS: Two of the controls defaulted follow-up. The intervention group and controls had similar age and sex distribution. At the end of study, the intervention group had reducted their waist circumference, diastolic blood pressure, HbA(1c), total cholesterol and low-density lipoprotein cholesterol levels. The controls had reduced their total cholesterol and low-density lipoprotein cholesterol levels. Other cardiovascular risk factors were not significantly changed in the controls. Addition of drugs and/or dosage increment of anti-diabetic drugs, lipid-lowering agents and anti-hypertensive agents were similar between the two groups. CONCLUSIONS: Regular structured reinforcement with diabetic health education is useful. It helps to control more successfully some of the cardiovascular risk factors in Chinese Type 2 diabetic patients.     

The comparison of venous plasma glucose and whole blood capillary glucose in diagnoses of Type 2 diabetes: a population-based screening study.

AIM: To evaluate the degree of concordance between venous plasma glucose (PG) and capillary whole blood glucose (BG) in diagnosing Type 2 diabetes and to compare the prevalence of confirmed and unconfirmed Type 2 diabetes. METHODS: All 40- to 69-year olds without known diabetes listed with five general practices were invited for screening (2051 persons). People identified by screening as being at high risk for having diabetes (random BG (rBG) > or = 4.5 mmol/l or HbA1c > or = 5.9%) were examined using BG and PG. The main outcome measures were confirmed diabetes cases (one diabetic glucose value plus symptoms or two diabetic glucose values on two different days) and unconfirmed diabetes (one diabetic glucose value on the first day of testing). RESULTS: One thousand and twenty-eight (50%) accepted screening. Diabetes was confirmed by BG or PG in 22 patients (1.8%), and in 14 of these by both BG and PG. Four patients in whom diabetes was confirmed only by BG had unconfirmed diabetes by PG. Three of four people in whom diabetes was confirmed only by PG had unconfirmed diabetes according to BG. The prevalence of unconfirmed diabetes was 3.3% and the prevalence of confirmed diabetes 2.1%. CONCLUSION: Confirmed diabetes can be diagnosed by either BG or PG. BG seems more convenient than PG for use in general practice. The prevalence of confirmed diabetes was lower than the prevalence of unconfirmed diabetes.     

IRIS II study: the IRIS II score--assessment of a new clinical algorithm for the classification of insulin resistance in patients with Type 2 diabetes.

AIMS: With the increasing availability of new drugs for the treatment of insulin resistance in patients with Type 2 diabetes, simple methods for their identification is an important challenge. The aim of our study was to compute a new algorithm for estimating insulin resistance in a routine clinical setting. METHODS: Clinical data and blood samples were collected from 4265 Type 2 diabetic patients from 149 clinical sites. A clinical algorithm to estimate insulin resistance was developed by stepwise multiple regression analysis. The new generated score was compared with the HOMAIR-score, calculated from fasting insulin and glucose levels measured in a central laboratory. In a subgroup of 48 patients, the score was verified against a frequently sampled intravenous glucose tolerance test with subsequent modified minimal model analysis according to Bergman. RESULTS: Multiple regression analysis revealed fasting blood glucose, BMI, triglycerides and HDL as the most powerful predictors of insulin resistance which were used for further computation of the IRIS II score. A significant overall correlation was found between the HOMAIR-score and the new clinical IRIS II score (r = 0.42; P < 0.0001). Compared with HOMAIR, the new score revealed a specificity of 0.95, a sensitivity of 0.34 and a positive predictive value of 0.95. This was in good agreement with the subset analysis of the intravenous glucose tolerance test, where a sensitivity of 0.37 and a specificity of 0.85 of the IRIS II score was calculated. Patients with insulin resistance according to the IRIS II score revealed an increased odds ratio for overall vascular complications (1.28; 1.11-1.46; P < 0.001). CONCLUSIONS: The new IRIS II score can identify insulin resistance in Type 2 diabetic patients with high predictive value and high specificity.     

A prospective study of Type 2 diabetes and depressive symptoms in the elderly: the Rancho Bernardo Study.

AIMS: The association between Type 2 diabetes and depressive symptoms was examined prospectively to assess possible causal relationships between the two diseases. METHODS: A cohort of 971 men and women aged 50 and older from the adult population of Rancho Bernardo, California had an oral glucose tolerance test and completed the Beck Depression Inventory (BDI) at two clinic visits, 1984-87 and 1992-96. RESULTS: Depressive symptoms at baseline were associated with higher follow-up levels of non-fasting plasma glucose (P = 0.001) and an increased risk of developing Type 2 diabetes [odds ratio (OR) = 2.50; 95% confidence interval (CI) = 1.29-4.87], independent of sex, age, exercise and body mass index. Conversely, baseline non-fasting plasma glucose was not significantly associated with follow-up depressive symptoms and Type 2 diabetes at baseline was not significantly associated with the onset of BDI scores > or = 11 by the second visit (OR = 0.73; 95% CI = 0.41-1.30). CONCLUSIONS: Depressed mood is more likely to be a risk factor for Type 2 diabetes in older adults than the reverse.     

GAD antibodies in probands and their relatives in a cohort clinically selected for Type 2 diabetes.

AIMS: A subset of patients who present as if they have Type 2 diabetes have positive pancreatic autoantibodies, and have been referred to as having latent autoimmune diabetes in adults (LADA). We assessed the prevalence and clinical characteristics of patients with glutamic acid decarboxylase antibodies (GADA) in a cohort clinically selected for Type 2 diabetes and determined the presence of diabetes and GADA in their first-degree relatives. METHODS: GADA were measured in 2059 subjects, not known to be related, and clinically selected as having Type 2 diabetes for genetic studies. Clinical characteristics were compared in GADA positive and GADA negative subjects. Diabetes and GAD antibody status were compared in 208 first-degree relatives of GADA positive and GADA negative probands. RESULTS: Of the subjects, 136 (7%) were GADA positive. Compared with the GADA negative subjects, they were slimmer (P < 0.001), diagnosed at a younger age (P = 0.011) and progressed to insulin faster (P < 0.001). Thirty-three per cent of GADA positive subjects had a first-degree relative with diabetes compared with 42% of GADA negative subjects (P = 0.034). The overall prevalence of GADA was similar in the first-degree relatives of GADA positive and GADA negative probands (4 v 5%), and 19 of 22 (86%) diabetic relatives of GADA positive probands were GADA negative. CONCLUSION: Despite clinically selecting a Type 2 diabetes cohort, 7% were GADA positive with an altered phenotype. These GADA positive patients had a strong family history of non-autoimmune diabetes. This suggests that, in this subgroup of patients, autoimmune pancreatic beta-cell destruction occurs on a background of Type 2 diabetes genetic susceptibility.     

Effects of alcohol consumption on mortality in patients with Type 2 diabetes mellitus

Aims/hypothesis Moderate alcohol intake has been associated with increased life expectancy due to reduced mortality from cardiovascular disease. We prospectively examined the effects of alcohol consumption on mortality in Type 2 diabetic patients in Switzerland.Methods A total of 287 patients with Type 2 diabetes mellitus (125 women, 162 men), recruited in Switzerland for the WHO Multinational Study of Vascular Disease in Diabetes, were included in this study. After a follow-up period of 12.6±0.6 years (means ± SD), mortality from CHD and from all causes was assessed.Results During the follow-up, 70 deaths occurred (21 from CHD, 49 from other causes). Compared with non-drinkers, alcohol consumers who drank alcohol 1 to 15 g, 16 to 30 g and 30 g or more per day had the following risk rates of death from CHD: 0.87 (95% CI: 0.25 to 2.51, NS), 0.00 (95% CI: 0.00 to 0.92, p less than 0.05) and 0.37 (95% CI, 0.01 to 2.42, NS), respectively. The corresponding risk rates of death from all causes were 1.27 (95% CI: 0.68 to 2.28, NS), 0.36 (95% CI: 0.09 to 0.99, p less than 0.05) and 1.66 (95% CI: 0.76 to 3.33, NS).Conclusions/interpretation In Swiss Type 2 diabetic patients moderate alcohol consumption of 16 to 30 g per day was associated with reduced mortality from CHD and from all causes. Alcohol intake above 30 g per day was associated with a tendency towards increased all-cause mortality.Abbreviations HR Hazard ratio - ICD-9 International Classification of Disease 9 - RR risk rate     

Microalbuminuria in Type 2 diabetes: an independent predictor of cardiovascular mortality

Background: Microalbuminuria has been shown to be associated with cardiovascular mortality in type 2 diabetic subjects. It is unclear to what extent this is due to the increased prevalence of other cardiac risk factors. Aims: To examine the relationship of urine albumin excretion to cardiovascular mortality and to determine its status as an independent risk factor. Methods: In a prospective longitudinal study from 1986–1999 we followed 666 type 2 diabetic subjects from a diabetes outpatient service. Cardiovascular risk factors including urine albumin concentration were measured at study entry. Cox proportional hazards regression was used to determine risk factors for mortality. The hazard ratios of microalbuminuria and macroalbuminuria for all cause, cardiovascular and coronary heart disease mortality were determined after accounting for other cardiac risk factors including blood pressure, glycated haemoglobin, total cholesterol, HDL cholesterol, triglycerides, urea, smoking, body mass index, patient age and disease duration. Results: The prevalence of urine albumin of 30–300 mg/L at study entry was 31.7%. A total of 167 deaths occurred (80 from cardiovascular disease). Mortality hazard ratios in subjects with urine albumin of 30–300 mg/L as compared to <30 mg/L, adjusted for age, sex and other cardiovascular risk factors were 1.77 (95% CI 1.22–2.57, p=0.002) for all causes, 2.34 (95% CI 1.38–3.99, p=0.002) for cardiovascular and 1.78 (95% CI 0.97–3.26, p=0.061) for coronary heart disease (CHD) mortality. Other factors significantly associated with cardiovascular mortality included diastolic blood pressure, HDL cholesterol and glycated haemoglobin. Total cholesterol and log triglyceride were significantly associated with CHD mortality. Disease duration, age at diagnosis, smoking and body mass index were not related to cardiovascular or CHD mortality. Conclusions: We confirm microalbuminuria as an independent predictor of mortality in type 2 diabetes despite its association with a number of conventional cardiovascular risk factors.     

Insulin use and increased risk of mortality in type 2 diabetes: a cohort study

Aim: To compare population‐based rates of all‐cause and cardiovascular (CV) mortality in newly treated patients with type 2 diabetes according to levels of insulin exposure. Methods: Using the administrative databases of Saskatchewan Health, 12272 new users of oral antidiabetic therapy were identified between 1991 and 1996 and grouped according to cumulative insulin exposure based on total insulin dispensations per year: no exposure (reference group); low exposure (0 to <3); moderate exposure (3 to <12) and high exposure (≥12). Time‐varying multivariable Cox proportional hazards models were used to examine the relationship between insulin exposure and all‐cause, CV‐related and non‐vascular mortality after adjustment for demographics, medications and comorbidities. Results: Average age was 65 (s.d. 13.9) years, 45% were female, and mean follow‐up was 5.1 (s.d. 2.2) years. In total, 1443 (12%) subjects started insulin, and 2681 (22%) deaths occurred. The highest mortality rates were in the high exposure group; 95 deaths/1000 person‐years compared with 40 deaths/1000 person‐years in the no exposure group [unadjusted hazard ratio (HR): 2.32; 95% confidence interval (CI): 1.96–2.73]. After adjustment, we observed a graded risk of mortality associated with increasing exposure to insulin: low exposure [adjusted HR (aHR): 1.75; 95% CI: 1.24–2.47], moderate exposure (aHR: 2.18; 1.82–2.60) and high exposure (aHR: 2.79; 2.36–3.30); p = 0.005 for trend. Analyses restricted to CV‐related (p = 0.042 for trend) and non‐vascular (p = 0.004 for trend) mortality showed virtually identical results. Conclusions: We observed a significant and graded association between mortality risk and insulin exposure level in an inception cohort of patients with type 2 diabetes that persisted despite multivariable adjustment.     

Muscle-strengthening activities and risk of cardiovascular disease,type 2 diabetes,cancer and mortality: A review of prospective cohort studies

The benefits of aerobic moderate-to-vigorous physical activity (MVPA) on major non-communicable diseases (NCDs) are well established. However, much less is known whether muscle-strengthening activities (i.e., resistance/weight/strength training) confer similar benefits. Herein, we conducted a narrative literature review and summarized the existing evidence from large prospective cohort studies on muscle strengthening activities and risk of major chronic diseases and mortality in adults generally free of major NCDs at baseline. Current epidemiologic evidence suggests that engagement in muscle-strengthening activities over 1–2 sessions (or approximately 60–150 min) per week was associated with reduced risk of cardiovascular disease (seven studies; approximately 20%–25% reduction), type 2 diabetes (four studies; approximately 30% reduction), cancer mortality (four studies; approximately 15%–20% reduction) as well as all-cause mortality (six studies; approximately 20%–25% reduction). For diabetes, the risk appears to lower further with even higher levels of muscle-strengthening activities, but some studies for cardiovascular and all-cause mortality suggest a reversal whereby higher levels (≥2.5 h/week) have less benefit, or are even harmful, relative to lower levels of activity. The likely mechanisms contributing to a benefit include improvement in body composition, lipid profile, insulin resistance and inflammation. The evidence supports engaging in 1–2 sessions (up to 2.5 h) per week, preferably performed complementary to the recommended levels of aerobic MVPA. Although data are limited, caution is suggested for training exceeding 2.5 h per week. Further studies are required to better understand the influence of frequency, duration and intensity of muscle-strengthening activities on major NCDs and mortality in diverse populations.     

Perinatal mortality in Type 2 diabetes mellitus.

AIMS: In many parts of the world the number of pregnancies in women with Type 2 diabetes mellitus (DM) now exceeds that in women with Type 1 DM, but there are few data published on perinatal mortality in Type 2 DM. This study reports observational data on perinatal mortality in Type 2 DM from a population with a high background rate of this disorder. METHODS: Over a 12-year period (1985-1997) at the Diabetes Clinic at National Women's Hospital, Auckland, there were 434 pregnancies in women with Type 2 DM (256 known and 178 diagnosed with gestational diabetes mellitus (GDM), but confirmed to have Type 2 DM early post-partum), 160 pregnancies in women with Type 1 DM and 932 in women with GDM. Perinatal mortality was classified as either intermediate fetal death (20-28 weeks' gestation), late fetal death (28 weeks' gestation to term) or early neonatal death (up to 1 month post-partum). RESULTS: The perinatal mortality in Type 2DM was 46.1/1,000, significantly higher than the rates for the general population (12.5), Type 1 DM (12.5) and GDM (8.9) (P < 0.0001). Congenital malformations accounted for only 10% of the perinatal mortality. There was a seven-fold increase in the rate of late fetal death and 2.5-fold increase in the rates of intermediate fetal and late neonatal death. Subjects with Type 2 DM were significantly older and more obese than subjects with Type 1 DM, and presented later to the diabetes service. CONCLUSIONS: Perinatal mortality in Type 2 DM is significantly increased, mainly owing to an excess of late fetal death. Maternal factors such as obesity may be important contributors to the high perinatal mortality. Women diagnosed with GDM who have unrecognized Type 2 DM are also at high risk, but perinatal mortality is low in women with milder degrees of glucose intolerance in pregnancy.     

Interactive effect of retinopathy and macroalbuminuria on all-cause mortality, cardiovascular and renal end points in Chinese patients with Type 2 diabetes mellitus.

AIMS: To examine the effect of albuminuria and retinopathy on the risk of cardiovascular and renal events, and all-cause mortality in patients with Type 2 diabetes. METHODS: A post-hoc analysis of 4416 Chinese patients without macrovascular complications at baseline (age 57.6 +/- 13.3 years). Glomerular filtration rate (eGFR) was estimated by the abbreviated Modification of Diet in Renal Disease Study Group Formula, further adjusted for Chinese ethnicity. Clinical end points were all-cause mortality, cardiovascular events (heart failure or angina, myocardial infarction, lower limb amputation, re-vascularization procedures and stroke) and renal end points (reduction in eGFR by more than 50% or eGFR < 15 ml/min/1.73 m2 or death as a result of renal causes or need for dialysis). RESULTS: Compared with individuals without complications, subjects with retinopathy and macroalbuminuria had higher rates of cardiovascular events (14.1 vs. 2.4%), renal events (40.0 vs. 0.8%) and death (9.3 vs. 1.7%, P < 0.001). For composite event of death, cardiovascular and renal events, the presence of retinopathy, microalbuminuria alone, macroalbuminuria alone, retinopathy with microalbuminuria or retinopathy with macroalbuminuria increased the risk [hazard ratio (95% CI)] by 1.61 (1.05 to 2.47; P = 0.04), 1.93 (1.38 to 2.69; P < 0.001), 4.34 (3.02 to 6.22; P < 0.001), 2.59 [1.76 to 3.81; P < 0.001) and 6.83 (4.89 to 9.55; P < 0.001) fold, respectively. The relative excess risk as a result of interaction between retinopathy and macroalbuminuria was 15.31, implying biological interaction in the development of renal events. CONCLUSIONS: In Chinese patients with Type 2 diabetes, retinopathy interacts with macroalbuminuria to increase the risk of composite cardio-renal events.     

PROactive 06: cost-effectiveness of pioglitazone in Type 2 diabetes in the UK.

AIMS: To determine the cost-effectiveness of adding pioglitazone to existing treatment regimens in patients with Type 2 diabetes with a history of macrovascular disease who are at high risk of further cardiovascular events. METHODS: We conducted two analyses. A within-trial cost-effectiveness analysis (CEA) based on data from the PROspective pioglitAzone Clinical Trial In macroVascular Events (PROactive) Study was performed to estimate the impact of additional pioglitazone treatment on life expectancy, quality-adjusted life expectancy (QALE) and macrovascular events. PROactive data was then used as a basis for a lifetime modelling analysis using a modified version of the validated CORE diabetes model that simulated the same outcomes over a 35-year time horizon. We accounted for direct medical costs from a health-care payer perspective and related these to the clinical outcomes from the study. Costs and benefits were discounted at 3.5% per annum and extensive sensitivity analyses were performed to account for uncertainty in input parameters. RESULTS: (i) Within-trial CEA: compared with placebo, pioglitazone was associated with improved life expectancy (undiscounted 0.0109 years), increased QALE [0.0190 quality-adjusted life years (QALYs)] and slightly higher costs ( pounds 102 per patient). After a mean treatment period of 3 years, the incremental cost-effectiveness ratio (ICER) of pioglitazone vs. placebo was pounds 5396 per QALY gained. The ICERs were relatively insensitive to cost and utility values and were most sensitive to event rates in the pioglitazone arm. (ii) Long-term CEA: pioglitazone was associated with improvements in clinical outcomes based on model projections beyond the PROactive Study. Patients treated with pioglitazone could expect improved life expectancy (undiscounted 0.406 years), increased QALE (0.152 QALYs) and higher costs of care ( pounds 619 per patient) compared with those on existing treatment alone. The base case analysis indicated that the ICER of pioglitazone vs. placebo was pounds 4060 per QALY gained. The cost-effectiveness acceptability curve showed there was an 84.3% likelihood that pioglitazone would be considered cost-effective in the UK using a willingness-to-pay threshold of pounds 30 000 per QALY gained. These long-term results were most sensitive to variation in the time horizon, the duration of cardiovascular benefit of pioglitazone, and changes in mortality rates. CONCLUSIONS: The addition of pioglitazone to existing therapy in patients with Type 2 diabetes at high risk of further cardiovascular events is cost-effective and represents good value for money by currently accepted standards in the UK.     

Excess mortality in Black compared with White patients with Type 1 diabetes: an examination of underlying causes.

AIMS: Excess mortality in Type 1 diabetes has previously been found among Black individuals. The aim of the present study was therefore to determine underlying causes. METHODS: A longitudinal study of 1261 [1184 White (93.9%) and 76 Black (6.0%)] individuals diagnosed with Type 1 diabetes between 1965 and 1979, at age<17 years from the Allegheny County, Pennsylvania and Children's Hospital of Pittsburgh registries. Subjects were contacted in 1999 to determine living status and, where appropriate, cause of death. Living status was determined in 1183 participants (93.8%). RESULTS: Of the 200 deaths overall, cause of death was determined in 157 subjects (79%); 31 dying from acute and 101 from chronic complications, and 25 from non-diabetes related causes. Seven deaths were investigated but no cause determined. Black participants had a significantly higher mortality rate compared with White participants for acute complications (hazard ratio=4.9, 95% confidence interval: 2.0, 11.6), but not for any other cause. There was a temporal decline in the 20-year mortality rates in both racial groups across the three cohorts diagnosed in 1965-69, 1970-74 and 1975-79. CONCLUSIONS: These results show that the excess mortality in Black people was attributed to acute complications which therefore should be a focus for prevention.