Cancer incidence and mortality in 23 000 patients with type 1 diabetes in the UK: Long-term follow-up.

Type 2 diabetes is associated with raised risk of several cancers, but for type 1 diabetes risk data are fewer and inconsistent We assembled a cohort of 23 473 UK patients with insulin-treated diabetes diagnosed at ages <30, almost all of whom will have had type 1 diabetes, and for comparison 5058 diagnosed at ages 30 to 49, of whom we estimate two-thirds will have had type 2, and followed them for an average of 30 years for cancer incidence and mortality compared with general population rates. Patients aged <30 at diabetes diagnosis had significantly raised risks only for ovarian (standardised incidence ratio = 1.58; 95% confidence interval 1.16-2.11; P < .01) and vulval (3.55; 1.94-5.96; P < .001) cancers, with greatest risk when diabetes was diagnosed at ages 10-14. Risks of cancer overall (0.89; 0.84-0.95; P < .001) and sites including lung and larynx were significantly diminished. Patients diagnosed with diabetes at ages 30 to 49 had significantly raised risks of liver (1.76;1.08-2.72) and kidney (1.46;1.03-2.00) cancers, and reduced risk of cancer overall (0.89; 0.84-0.95). The raised ovarian and vulval cancer risks in patients with type 1 diabetes, especially with diabetes diagnosed around pubertal ages, suggest possible susceptibility of these organs at puberty to metabolic disruption at diabetes onset. Reduced risk of cancer overall, particularly smoking and alcohol-related sites, might reflect adoption of a healthy lifestyle.

Glucagon-like peptide analogues for type 2 diabetes mellitus: systematic review and meta-analysis.

BACKGROUND: Glucagon-like peptide (GLP-1) analogues are a new class of drugs used in the treatment of type 2 diabetes. They are given by injection, and regulate glucose levels by stimulating glucose-dependent insulin secretion and biosynthesis, suppressing glucagon secretion, and delaying gastric emptying and promoting satiety. This systematic review aims to provide evidence on the clinical effectiveness of the GLP-1 agonists in patients not achieving satisfactory glycaemic control with one or more oral glucose lowering drugs. METHODS: MEDLINE, EMBASE, the Cochrane Library and Web of Science were searched to find the relevant papers. We identified 28 randomised controlled trials comparing GLP-1 analogues with placebo, other glucose-lowering agents, or another GLP-1 analogue, in patients with type 2 diabetes with inadequate control on a single oral agent, or on dual therapy. Primary outcomes included HbA1c, weight change and adverse events. RESULTS: Studies were mostly of short duration, usually 26 weeks. All GLP-1 agonists reduced HbA1c by about 1% compared to placebo. Exenatide twice daily and insulin gave similar reductions in HbA1c, but exenatide 2 mg once weekly and liraglutide 1.8 mg daily reduced it by 0.20% and 0.30% respectively more than glargine. Liraglutide 1.2 mg daily reduced HbA1c by 0.34% more than sitagliptin 100 mg daily. Exenatide and liraglutide gave similar improvements in HbA1c to sulphonylureas. Exenatide 2 mg weekly and liraglutide 1.8 mg daily reduced HbA1c by more than exenatide 10 µg twice daily and sitagliptin 100 mg daily. Exenatide 2 mg weekly reduced HbA1c by 0.3% more than pioglitazone 45 mg daily.Exenatide and liraglutide resulted in greater weight loss (from 2.3 to 5.5 kg) than active comparators. This was not due simply to nausea. Hypoglycaemia was uncommon, except when combined with a sulphonylurea. The commonest adverse events with all GLP-1 agonists were initial nausea and vomiting. The GLP-1 agonists have some effect on beta-cell function, but this is not sustained after the drug is stopped. CONCLUSIONS: GLP-1 agonists are effective in improving glycaemic control and promoting weight loss.

Treatment effects may remain the same even when trial participants differed from the target population.

OBJECTIVES: Randomized controlled trials (RCTs) have been criticized for lacking external validity. We assessed whether a trial in people with type I diabetes mellitus mirrored the wider population and applied sample-weighting methods to assess the impact of differences on our trial's findings. STUDY DESIGN AND SETTING: The Relative Effectiveness of Pumps over MDI and Structured Education trial was nested within a large UK cohort capturing demographic, clinical, and quality of life data for people with type I diabetes mellitus undergoing structured diabetes-specific education. We first assessed whether our RCT participants were comparable with this cohort using propensity score modeling. After this, we reweighted the trial population to better match the wider cohort and re-estimated the treatment effect. RESULTS: Trial participants differed from the cohort in regard to sex, weight, HbA1c, and also quality of life and satisfaction with current treatment. Nevertheless, the treatment effects derived from alternative model weightings were similar to that of the original RCT. CONCLUSION: Our RCT participants differed in composition to the wider population, but the original findings were unaffected by sampling adjustments. We encourage investigators take steps to address criticisms of generalizability but doing so is problematic; external data, even if available, may contain limited information and analyses can be susceptible to model misspecification.

Mortality from cerebrovascular disease in a cohort of 23 000 patients with insulin-treated diabetes.

BACKGROUND AND PURPOSE: Disease of the cardiovascular system is the main cause of long-term complications and mortality in patients with type I (insulin-dependent) and type II (non-insulin-dependent) diabetes. Cerebrovascular mortality rates have been shown to be raised in patients with type II diabetes but have not previously been reported by age and sex in patients with type I diabetes. METHODS: A cohort of 23 751 patients with insulin-treated diabetes, diagnosed under the age of 30 years from throughout the United Kingdom, was identified during 1972 to 1993 and followed up for mortality until the end of December 2000. Age- and sex-specific mortality rates and standardized mortality ratios (SMRs) were calculated. RESULTS: There were 1437 deaths during the follow-up, 80 due to cerebrovascular disease. Overall, the cerebrovascular mortality rates in the cohort were higher than the corresponding rates in the general population, and the SMRs were 3.1 (95% CI, 2.2 to 4.3) for men and 4.4 (95% CI, 3.1 to 6.0) for women. When stratified by age, the SMRs were highest in the 20- to 39-year age group. After subdivision of cause of death into hemorrhagic and nonhemorrhagic origins, there remained a significant increase in mortality from stroke of nonhemorrhagic origin. CONCLUSIONS: Analyses of mortality from this cohort, essentially one of patients with type I diabetes, has shown for the first time that cerebrovascular mortality is raised at all ages in these patients. Type I diabetes is at least as great a risk factor for cerebrovascular mortality as type II diabetes.

Self monitoring of blood glucose - a survey of diabetes UK members with type 2 diabetes who use SMBG.

BACKGROUND: Aim - to survey members of Diabetes UK who had Type 2 diabetes and who used self monitoring of blood glucose (SMBG), to elicit their views on its usefulness in the management of their diabetes, and how they used the results. A questionnaire was developed for the Diabetes UK website. The questionnaire was posted on the Diabetes UK website until over 500 people had responded. Questions asked users to specify the benefits gained from SMBG, and how these benefits were achieved. We carried out both quantitative analysis and a thematic analysis for the open ended free-text questions. FINDINGS: 554 participants completed the survey, of whom 289 (52.2%) were male. 20% of respondents were recently diagnosed (< 6 months). Frequency of SMBG varied, with 43% of participants testing between once and four times a day and 22% testing less than once a month or for occasional periods.80% of respondents reported high satisfaction with SMBG, and reported feeling more 'in control' of their diabetes management using it. The most frequently reported use of SMBG was to make adjustments to food intake or confirm a hyperglycaemic episode.Women were significantly more likely to report feelings of guilt or self-chastisement associated with out of range readings (p = < .001). CONCLUSION: SMBG was clearly of benefit to this group of confirmed users, who used the results to adjust diet, physical activity or medications. However many individuals (particularly women) reported feelings of anxiety and depression associated with its use.

United Kingdom cervical cancer screening and the costs of time and travel.

OBJECTIVES: The aim of this study was to estimate the time and travel costs generated by women when attending for Papanicolaou (Pap) smear tests or colposcopy appointments in the United Kingdom, both absolutely and relative to the health service cost of the national cervical cancer screening programs. METHODS: Data were obtained from questionnaires completed by two samples of women participating in a three-center trial of management of low-grade abnormalities detected by screening (n = 1,106 for Pap smears and n = 1,203 for colposcopy appointments). Women were 20 to 59 years of age and resident in Grampian or Tayside, Scotland, or Nottingham, England. Questionnaire data were supplemented with sociodemographic information previously collected at the time of recruitment to the trial. RESULTS: The mean total time and travel costs per attendance at a smear test and at a colposcopy appointment were estimated to be 9.2 pounds and 27.4 pounds, respectively, averaged across the three trial areas (valued at 2002 prices). Statistically significant intercenter disparities in time and travel costs were identified, particularly with respect to colposcopy appointments. For these, time and travel costs in Nottingham were substantially less than those in Grampian and Tayside (22.9 pounds, 30.2 pounds, and 32.1 pounds, respectively). Time and travel costs amount to 26 and 33 percent, approximately, over and above the direct health service costs of the English and Scottish screening programs, respectively. CONCLUSIONS: The time and travel costs associated with participation in the UK cervical cancer screening programs are substantial and are not spatially uniform across the country.

Clinical- and cost-effectiveness of pegylated interferon alfa in the treatment of chronic hepatitis C: a systematic review and economic evaluation.

OBJECTIVES: To assess the clinical-effectiveness and cost-effectiveness of pegylated interferon alfa (2a and 2b) combined with ribavirin in previously untreated patients with moderate to severe chronic hepatitis C, compared with the current standard treatment, which is nonpegylated interferon alfa combined with ribavirin. METHODS: Systematic review and economic evaluation. A sensitive search strategy was applied to several electronic bibliographic databases. Relevant studies were critically appraised and meta-analyzed. A hypothetical cohort of 1,000 patients entered a Markov model and were followed up for a more than 30-year period to predict natural history, duration spent in each health state, and treatment costs. RESULTS: Two fully published Phase III randomized controlled trials were included. Methodological quality was generally good. Dual therapy with pegylated interferon was significantly more effective than nonpegylated dual therapy with a pooled sustained virological response rate (SVR) of 55 percent (95 percent confidence interval [CI], 52-58 percent) compared with 46 percent (95 percent CI, 43-49 percent). The pooled relative risk of remaining infected was 0.83 (95 percent CI, 0.76-0.91 percent). Genotype was the strongest predictor of outcome, with SVRs in patients with the more responsive genotypes 2 and 3 reaching up to 80 percent. The incremental cost per quality-adjusted life year (QALY) for pegylated dual therapy compared with nonpegylated dual therapy was 12,123 pounds sterling. The cost per QALY remained under 30,000 pounds sterling for most patient subgroups and in sensitivity analyses. CONCLUSIONS: Pegylated interferon is clinically effective, represents good value for the money, and is a significant advance in the treatment of this insidious disease.