J. A. Johnson

Mortality After Incident Cancer in People With and Without Type 2 Diabetes: Impact of metformin on survival

OBJECTIVE Type 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 METHODS Data 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. RESULTS Of 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]). CONCLUSIONS This 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.

Diabetes and cancer (1): evaluating the temporal relationship between type 2 diabetes and cancer incidence

Substantial evidence suggests that people with type 2 diabetes have an increased risk of developing several types of cancers. These associations may be due to a number of direct and indirect mechanisms. Observational studies of these associations, including the potential role for glucose-lowering therapy, are being increasingly reported, but face a number of methodological challenges. This paper is the first of two review papers addressing methodological aspects underpinning the interpretations of links between diabetes and cancer, and suggests potential approaches to study designs to be considered in observational studies. This paper reviews factors related to cancer incidence in the diabetic population; the second paper relates to studies of cancer mortality.

Reduced cardiovascular morbidity and mortality associated with metformin use in subjects with Type 2 diabetes

Aim  Metformin therapy reduces microvascular complications in Type 2 diabetes; questions remain, however, regarding its impact on macrovascular events. This study examined metformin use in relation to risk of cardiovascular‐related hospitalization and mortality.

Intensive glycaemic control and cancer risk in type 2 diabetes: a meta-analysis of major trials

Aims/hypothesisThe purpose of this study was to explore the relationship between hyperglycaemia in type 2 diabetes and risk of cancer incidence or cancer mortality. We were interested to determine if data from major randomised controlled trials would support a hypothesis that improving glycaemic control may reduce the risk of cancer outcomes.MethodsWe included major randomised controlled trials conducted with an overall aim of intensified glycaemic control in type 2 diabetes. We abstracted data from published papers and supplemental material and conducted separate meta-analyses of cancer mortality and cancer incidence.ResultsFour trials reported cancer mortality for the intensive (222 events in 53,892 person-years) and standard control (155 events in 38,743 person-years) arms (UK Prospective Diabetes Study [UKPDS] 33, UKPDS 34, Action to Control Cardiovascular Risk in Diabetes [ACCORD] and Veterans Affairs Diabetes Trial [VADT]); the summary risk ratio for cancer mortality was 1.00 (95% CI 0.81–1.24; I2 = 0%). Excluding the UKPDS metformin trial resulted in a pooled risk estimate of 1.03 (95% CI 0.83–1.29; I2 = 0%). Three trials reported cancer incidence for the study arms (Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation [ADVANCE], PROspective pioglitAzone Clinical Trial In macroVascular Events [PROactive], Rosiglitazone Evaluated for Cardiac Outcomes and Regulation of Glycaemia in Diabetes [RECORD]) with 357 events in 47,974 person-years with improved glycaemic control and 380 events in 45,009 person-years in the control arms; the pooled risk ratio for cancer incidence was 0.91 (95% CI 0.79–1.05; I2 = 0%).Conclusions/interpretationData from large randomised controlled trials of intensified glycaemic control suggest that cancer risk is not reduced by improving glycaemic control in type 2 diabetes. These data therefore do not support the hypothesis that hyperglycaemia is causally linked to increased cancer risk.

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.

The safety profile of exogenous insulin in people with type 2 diabetes: justification for concern

There is no doubt about the value of exogenous insulin for people with type 1 diabetes. The purpose of this commentary is to discuss emerging evidence that this may not be the case for the majority of people with type 2 diabetes.

Impact of gestational diabetes mellitus and high maternal weight on the development of diabetes, hypertension and cardiovascular disease: a population-level analysis

To examine the association between gestational diabetes mellitus (GDM) and high maternal weight and the risk of development of chronic disease.

Statin use in Type 2 diabetes mellitus is associated with a delay in starting insulin

Aims  It has been suggested that HMG Co‐A reductase inhibitors (‘statins’) may reduce the risk of developing Type 2 diabetes mellitus. This study was designed to evaluate whether use of statins would also delay progression to insulin therapy.

Self-monitoring in Type 2 diabetes : a randomized trial of reimbursement policy

Aim  Self‐monitoring of blood glucose is often considered a cornerstone of self‐care for patients with diabetes. We assessed whether provision of free testing strips would improve glycaemic control in non‐insulin‐treated Type 2 diabetic patients.

Validation of diabetes case definitions using administrative claims data

Diabet. Med. 28, 424–427 (2011)