OBJECTIVEType 2 diabetes is associated with an increased risk of several types of cancer and with reduced survival after cancer diagnosis. We examined the hypotheses that survival after a diagnosis of solid-tumor cancer is reduced in those with diabetes when compared with those without diabetes, and that treatment with metformin influences survival after cancer diagnosis.RESEARCH DESIGN AND METHODSData were obtained from >350 U.K. primary care practices in a retrospective cohort study. All individuals with or without diabetes who developed a first tumor after January 1990 were identified and records were followed to December 2009. Diabetes was further stratified by treatment regimen. Cox proportional hazards models were used to compare all-cause mortality from all cancers and from specific cancers.RESULTSOf 112,408 eligible individuals, 8,392 (7.5%) had type 2 diabetes. Cancer mortality was increased in those with diabetes, compared with those without (hazard ratio 1.09 [95% CI 1.06–1.13]). Mortality was increased in those with breast (1.32 [1.17–1.49]) and prostate cancer (1.19 [1.08–1.31]) but decreased in lung cancer (0.84 [0.77–0.92]). When analyzed by diabetes therapy, mortality was increased relative to nondiabetes in those on monotherapy with sulfonylureas (1.13 [1.05–1.21]) or insulin (1.13 [1.01–1.27]) but reduced in those on metformin monotherapy (0.85 [0.78–0.93]).CONCLUSIONSThis study confirmed that type 2 diabetes was associated with poorer prognosis after incident cancer, but that the association varied according to diabetes therapy and cancer site. Metformin was associated with survival benefit both in comparison with other treatments for diabetes and in comparison with a nondiabetic population.

While controlling for other factors, the fear of hypoglycaemia was an important determinant of health-related utility. The magnitude of fear of hypoglycaemia was associated with the severity and frequency of hypoglycaemia. Hypoglycaemia was associated with a considerable decrement in health-related utility as a function of increased fear. Measures should be taken to minimise the severity and frequency of hypoglycaemia.

Patients with type 2 diabetes initiated with metformin monotherapy had longer survival than did matched, non-diabetic controls. Those treated with sulphonylurea had markedly reduced survival compared with both matched controls and those receiving metformin monotherapy. This supports the position of metformin as first-line therapy and implies that metformin may confer benefit in non-diabetes. Sulphonylurea remains a concern.

Context:The safety of insulin in the treatment of type 2 diabetes mellitus (T2DM) has recently undergone scrutiny.Objective:The objective of the study was to characterize the risk of adverse events associated with glucose-lowering therapies in people with T2DM.Design and Setting:This was a retrospective cohort study using data from the UK General Practice Research Database, 2000–2010.Patients:Patients comprised 84 622 primary care patients with T2DM treated with one of five glucose-lowering regimens: metformin monotherapy, sulfonylurea monotherapy, insulin monotherapy, metformin plus sulfonylurea combination therapy, and insulin plus metformin combination therapy. There were 105 123 exposure periods.Main Outcome Measures:The risk of the first major adverse cardiac event, first cancer, or mortality was measured. Secondary outcomes included these individual constituents and microvascular complications.Results:In the same model, and using metformin monotherapy as the referent, the adjusted hazard ratio (aHR) for the primary end point was significantly increased for sulfonylurea monotherapy (1.436, 95% confidence interval [CI] 1.354–1.523), insulin monotherapy (1.808, 95% CI 1.630–2.005), and insulin plus metformin (1.309, 95% CI 1.150–1.491). In glycosylated hemoglobin/morbidity subgroups, patients treated with insulin monotherapy had aHRs for the primary outcome ranging from 1.469 (95% CI 0.978–2.206) to 2.644 (95% CI 1.896–3.687). For all secondary outcomes, insulin monotherapy had increased aHRs: myocardial infarction (1.954, 95% CI 1.479–2.583), major adverse cardiac events (1.736, 95% CI 1.441–2.092), stroke (1.432, 95% CI 1.159–1.771), renal complications (3.504, 95% CI 2.718–4.518), neuropathy (2.146, 95% CI 1.832–2.514), eye complications (1.171, 95% CI 1.057–1.298), cancer (1.437, 95% CI 1.234–1.674), or all-cause mortality (2.197, 95% CI 1.983–2.434). When compared directly, aHRs were higher for insulin monotherapy vs all other regimens for the primary end point and all-cause mortality.Conclusions:In people with T2DM, exogenous insulin therapy was associated with an increased risk of diabetes-related complications, cancer, and all-cause mortality. Differences in baseline characteristics between treatment groups should be considered when interpreting these results.

OBJECTIVETo assess the association of compliance with treatment (medication and clinic appointments) and all-cause mortality in people with insulin-treated type 2 diabetes.RESEARCH DESIGN AND METHODSData were extracted from U.K. general practice records and included patients (N = 15,984) who had diagnostic codes indicative of type 2 diabetes or who had received a prescription for an oral antidiabetic agent and were treated with insulin. Records in the 30 months before the index date were inspected for clinical codes (recorded at consultation) indicating medication noncompliance or medical appointment nonattendance. Noncompliance was defined as missing more than one scheduled visit or having at least one provider code for not taking medications as prescribed. Relative survival postindex date was compared by determining progression to all-cause mortality using Cox proportional hazards models.RESULTSThose identified as clinic nonattenders were more likely to be smokers, younger, have higher HbA1c, and have more prior primary care contacts and greater morbidity (P < 0.001). Those identified as medication noncompliers were more likely to be women (P = 0.001), smokers (P = 0.014), and have higher HbA1c, more prior primary care contacts, and greater morbidity (all P < 0.001). After adjustment for confounding factors, medication noncompliance (hazard ratio 1.579 [95% CI 1.167–2.135]), clinic nonattendance of one or two missed appointments (1.163 [1.042–1.299]), and clinic nonattendance of greater than two missed appointments (1.605 [1.356–1.900]) were independent risk factors for all-cause mortality.CONCLUSIONSMedication noncompliance and clinic nonattendance, assessed during routine care by primary care physicians or their staff, were independently associated with increased all-cause mortality in patients with type 2 diabetes receiving insulin.

Diabetes is confirmed as a significant risk factor for peripheral vascular disease, infection, neuropathy, and ulceration. The severity of these disorders in terms of increased risk of hospital mortality, length of stay, and risk of surgical procedure is also demonstrated for those patients with diabetes.

There was a significant increase in the incidence of diagnosed type 2 diabetes between 1991 and 2010 and the proportion of people diagnosed at a relatively early age has increased markedly.

During this follow-up period, women with PCOS were not at increased risk of LVD, cancer, or death, but they had increased risk of type 2 diabetes.