MD Conference Express ADA 2012 - (Page 12)
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The Cancer-Insulin Link: Where We Stand Today
Written by Phil Vinall
John Buse, MD, PhD, University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA, presented an overview of what is known about insulin and cancer. A MEDLINE search for insulin and cancer on May 22, 2012, found 25,543 articles. Hemkens et al. [Hemkens LG et al. Diabetologia 2009] were the first investigators to report that patients who used higher doses of glargine had an increased risk of cancer of all forms. However, results from other studies have been inconsistent. A combined analysis of 31 randomized controlled trials (mostly of 6-month duration) found no difference in cancer occurrence between insulin glargine and comparative groups (mostly neutral protamine Hagedorn, or NPH, insulin) [Home PD, Lagarenne P. Diabetologia 2009]. Data from a long-term randomized trial in patients with type 2 diabetes [Rosenstock J et al. Diabetologia 2009] also found no evidence of any difference in the rate of benign or malignant tumor development with insulin glargine versus NPH insulin. Chang et al. [Chang C-H et al. PLoS One 2011] found a dose-dependent increase in cancer risk for treatment with glargine compared with human insulin (p<0.0001): the adjusted HR was 1.09 (95% CI, 1.00 to 1.19) for a daily dose of 10 IU, 1.19 (95% CI, 1.10 to 1.30) for a daily dose of 30 IU, and 1.31 (95% CI, 1.20 to 1.42) for a daily dose of 50 IU. The researchers found no increased risk for aspart (p=0.30) or lispro (p=0.96) compared with human insulin. Studies in Sweden and Scotland suggest that women who used insulin glargine alone had a significantly higher risk of breast cancer compared with users of other types of insulin, whereas this increased risk was not observed among those who received insulin glargine in combination with other insulin [Jonasson JM et al. Diabetologia 2009; Colhoun HM et al. Diabetologia 2009]. More recent reports have found no increased cancer risk from glargine exposure (eg, the Northern European Study of Insulin and Cancer and the Kaiser Permanente California Cohort Study). Common risk factors for diabetes and cancer include age, glycemia, obesity, physical activity, gender, smoking, diet, and alcohol use [Giovannuci E et al. Diabetes Care 2010] (Figure 1). However, it has yet to be determined which of these factors is associated with cancer and what potential mechanisms might mediate these associations. Clayton et al. investigated the potential involvement of growth hormone (GH), insulin-like growth factor (IGF-1),
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and insulin on tumor promotion and progression. The authors endorsed long-term surveillance for cancer incidence in all populations that have been exposed to increased levels of GH [Clayton PE et al. Nat Rev Endocrinol 2011]. Figure 1. Common Risk Factors for Diabetes and Cancer.
Age Glycemia Increased diabetes risk Obesity Physical Activity Increased cancer risk
Gender
Diet
Smoking
Alcohol
Reproduced with permission from the American Diabetes Association. Giovannuci E et al. Diabetes Care 2010.
Agin et al. [Agin A et al. Diabetes Metab 2007] assessed in vitro glargine blood biotransformation and its inter-individual variability. Outcomes showed that inter-individual variability of glargine biotransformation is noteworthy. However, the bioactivity of glargine metabolites must be assessed before clinical observations of glargine interindividual variability and its metabolism can be correlated. The pharmacological bioactivity of glargine metabolites has been suggested by Kuerzel et al. [Kuerzel GU et al. Curr Med Res Opin 2003] but is not yet clearly demonstrated. Sommerfeld et al. [Sommerfeld MR et al. PloS One 2010] characterized the glargine metabolites in vitro with regard to their insulin receptor (IR) and IGF-1 receptor (IGF1R) binding and signaling properties, as well as their metabolic and mitogenic activities. Findings strongly supported the idea that insulin glargine metabolites contribute with the same potency as insulin glargine to blood glucose control but lead to significantly reduced growth-promoting activity. The Northern European Database Study Peter Boyle, DSc, FRCP, FRCPS, FMedSci, International Prevention Research Institute, Lyon, France, discussed the results and context of the Northern European Database Study of Insulin and Cancer Risk [Abstract CTSY13. American Diabetes Association 2012]. Because administrative databases were used in the report, it shares
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Table of Contents for the Digital Edition of MD Conference Express ADA 2012
MD Conference Express ADA 2012
Contents
ORIGIN Trial Results
New Lessons in Hypertension and Diabetes
Closed-Loop Insulin Therapy in Young Children
The Precocious “AGE’ing” Effect of Type 1 Diabetes in Children
Abatacept in Patients with New-Onset Type 1 Diabetes: One-Year Follow-Up
Explaining the UKPDS Legacy Effect
Insulin and Cancer
Insulin Analogs
Dyslipidemia
Insulin Therapy
Incretin Therapies
Diabetes and Chronic Kidney Disease Guidelines Update
Managing Hyperglycemia in Hospitalized Patients
CVD Prevention and Treatment in Women With Diabetes
China Da Qing Study: Lifestyle Change in Women With IGT Extends Life
Markers of Macrovascular Complications in Pediatric Diabetes
Nonoperative Management of the Infected Diabetic Foot
Diabetic Retinopathy: Changing Prevalence and Severity Require Flexible Interventions
New ADA/EASD Position Statement Endorses a Patient-Centered Approach
MD Conference Express ADA 2012
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