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Aims: To study the effect of age at death, sex, ethnic group, date of death, underlying cause of death and social class on the frequency of reporting diabetes on death certificates in known cases of diabetes., Methods: Data were extracted from certificates recording 981 deaths which occurred between 1985 and 1999 in people aged 45 years or more who participated in the UK Prospective Diabetes Study, to which 23 English, Scottish and Northern Ireland centres contributed. Diabetes (9th revision of the International Classification of Diseases; ICD-9 250) entered on parts 1A-1C or 2A-2C of the death certificate was considered as reporting diabetes. Logistic regression analyses were used to determine independent factors associated with the reporting of diabetes., Results: Diabetes was reported on 42% (419/981) of all death certificates and on 46% (249/546) of those with underlying cardiovascular disease causes. Reporting of diabetes was independently associated on all death certificates with per year of age increase (OR 1.02; 95% CI 1.001-1.04, P = 0.037), underlying cause of death (non-cardiovascular causes OR 0.76; 95% CI 0.59-0.98, P = 0.035) and social class (classes I-II OR 1.00; class III OR 1.35; 95% CI 0.96-1.89, P = 0.084, classes IV-V OR 1.48; 95% CI 1.05-2.10, P = 0.027). Stratification by age, sex, and underlying cause of death also revealed significant differences in the frequency of reporting diabetes over time., Conclusions: The rate of reporting of diabetes on cardiovascular disease death certificates remains poor. This may indicate a lack of awareness of the importance of diabetes as a risk factor for cardiovascular disease.

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.

Aims: The autoantigen SOX-13 of the SRY-related high mobility group box is a low-frequency reactant in sera from patients with Type 1 diabetes. We further investigated the potential diagnostic role of anti-SOX-13, and in particular its ability to distinguish Type 1 from Type 2 diabetes, in two large, well-characterized cohorts., Methods: SOX-13 autoantibody status was ascertained using a radioimmunoprecipitation assay in (i) a random sample of 546 participants in an Australian community-based study (the Fremantle Diabetes Study; FDS) of whom 119 had Type 1 and 427 Type 2 diabetes, and (ii) a sample of 333 subjects with Type 2 diabetes from the United Kingdom Prospective Diabetes Study (UKPDS) stratified by age, anti-glutamic acid decarboxylase (GAD) and islet cell antibody (ICA) status, and requirement for insulin therapy within 6 years of diagnosis., Results: The frequencies of anti-SOX-13 in the FDS subjects were 16.0% and 14.8% for Type 1 and Type 2 patients, respectively, and levels were similar. In the UKPDS subjects, the frequency was 4.5%. In a logistic regression model involving demographic, anthropometric and metabolic variables, only diabetes duration was significantly associated with anti-SOX-13 positivity, especially for duration > 5 years (P < 0.002). When the coexistence of autoantibodies was assessed in the two study samples, there were no significant associations between anti-SOX-13 and ICA, anti-GAD or ICA512/IA-2., Conclusions: Whilst the frequency of anti-SOX-13 may be increased in some populations of diabetic patients, this reactivity does not usefully distinguish Type 1 from Type 2 diabetes. However, the association with diabetes duration suggests that anti-SOX-13 may be a non-specific marker of tissue damage associated with chronic hyperglycaemia.

Aims: To assess the effect of diet on fasting plasma lipids and lipoproteins in patients with newly diagnosed Type 2 diabetes., Methods: A total of 2,906 patients each underwent 3 months' diet therapy before allocation to therapy in a randomized controlled clinical trial. Lipids and lipoproteins were measured at diagnosis and after 3 months' diet., Results: The mean body weight at diagnosis was 83 kg. Weight decreased after diet by a mean of 4.5 kg; body mass index (BMI) decreased by 1.51 kg/m2; plasma glucose fell by 3 mmol/l from 11 mmol/l; and HbA1c by 2% from 9%. Triglyceride concentrations were reduced in men by -0.41 (95% confidence interval (CI) -0.47 to - 0.35) mmol/l from a geometric mean 1.8 (1 SD interval 1.0-3.0) mmol/l, and in women by -0.23 (-0.28 to -0.18) mmol/l from a similar level. Cholesterol decreased in men by -0.28 (-0.33 to -0.24) mmol/l from 5.5 (1.1) mmol/l, and in women by -0.09 (-0.14 to -0.04) mmol/l from 5.8 (1.2) mmol/l with corresponding changes in LDL cholesterol. HDL cholesterol increased in men by 0.02 (0.01 to 0.04) mmol/l and in women by 0.01 (0 to 0.02) mmol/l. Triglyceride concentration in the top tertile was reduced by 37% in men (> 2.1 mmol/l) and by 23% in women (> 2.2 mmol/l) with regression to mean accounting for 13% and 6%, respectively. Similarly cholesterol in the top tertile was reduced by 12% in men (> 5.8 mmol/l) and 7% in women (> 6.2 mmol/l) with 6% of the decrease in both men and women accounted for by regression to the mean., Conclusions: Initial dietary therapy in patients with newly diagnosed Type 2 diabetes substantially reduced plasma triglyceride, marginally improved total cholesterol and subfractions, and resulted in a potentially less atherogenic profile, although this did not eliminate the excess cardiovascular risk in patients with Type 2 diabetes.

Patients with Type 2 (non-insulin-dependent) diabetes mellitus (DM) on sulphonylurea therapy convert to insulin progressively as the sulphonylureas 'fail'. The rate of failure and the features of those who fail have been poorly described. To assess secondary failure rates of sulphonylureas, we report on the responses in 1305 patients with newly diagnosed Type 2 DM randomly allocated to therapy with either chlorpropamide or glibenclamide in the UK Prospective Diabetes Study (UKPDS). These patients were initially treated by diet for 3 months and had a fasting plasma glucose > 6 mmol l(-1); mean age 53 (SD 9) years; BMI 26.8 (SD 5.0) kg m(-2); and median fasting plasma glucose 9.1 (7.6-12.5 quartiles) mmol l(-1). If their fasting plasma glucose subsequently rose above 15.0 mmol l(-1), or they developed hyperglycaemic symptoms, additional hypoglycaemic therapy was given: metformin, ultratard insulin, and soluble insulin as required. By 6 years, 44% had required additional therapy. Of those randomized to glibenclamide, 48% required additional therapy by 6 years, compared with 40% of those allocated to chlorpropamide (p < 0.01). Sixty-one per cent, 39%, and 23%, respectively, of patients with fasting plasma glucose > or = 10.0 mmol l(-1), > or = 7.8 mmol l(-1) to < 10.0 mmol l(-1) and < 7.8 mmol l(-1) at randomization required additional therapy (p < 0.001). In the initial 3 years, non-obese subjects (BMI < 30 kg m(-2)) were more likely to require additional therapy than obese patients (BMI > or = 30 kg m(-2)) (43% vs 53% at 6 years; p < 0.001). Modelled beta-cell function showed that those with lower function were more likely to fail (p < 0.0001). Thus sulphonylureas fail as a therapeutic agent at rates which are dependent both on the phenotype at presentation and perhaps on the agent used initially. Higher failure rates were found in those with higher glucose concentrations, those who were younger, those with lower beta-cell reserve and those randomized to glibenclamide compared with chlorpropamide.