Prevalence of Insulin Resistance, Metabolic Syndrome, and Type 2 Diabetes in Canadian Women at High Risk for Breast Cancer

Abstract

There is considerable literature on the surveillance and management of women at high risk for developing breast cancer (BC) due to genetic mutations, family history, and mantle radiotherapy at a young age or a high score on risk calculation models (1). These women may benefit from more effective risk management interventions and heightened screening (1). Many of the afore-mentioned BC risk factors are nonmodifiable and it is therefore desirable to identify potential modifiable risk factors and related prevention strategies in high-risk women.There have been observations of an increased risk of BC associated with markers of insulin resistance (IR) such as hyperglycemia and hyperinsulinemia (2,3) and in patients with type 2 diabetes (T2D) (4). IR is believed to be a core component of the metabolic syndrome (MetS), which is a cluster of suboptimal physiological conditions, including abdominal obesity, dyslipidemia, high blood pressure, hyperglycemia, or receiving drug treatment for these conditions (5). MetS has shown to be associated with an increased risk of BC among postmenopausal women (6). Despite the evidence showing an association between IR, MetS, T2D, and BC (2-6), the prevalence of these conditions has never been reported in women at high risk for BC. To study this further, we undertook the study described below.Of the 368 identified eligible women engaged in follow-up at the High Risk Clinic of the Women's Breast Health Centre (WBHC) in Ottawa (ON, Canada), 100 women consented to participate in this study approved by the research ethics boards of the Ottawa Hospital Research Institute.Eligible women had to be ≥35 years old and Caucasian (because the Gail model that we used to assess risk had been validated in this subgroup of women) (7) and had to have any of the following criterion: 5-year Gail score ≥1.7; BC Gene (BRCA) mutation; biopsy-proven lobular carcinoma in-situ; atypical ductal hyperplasia; or previous mantle radiation. Participants could be pre-or postmenopausal but women with surgically/medically induced menopause were excluded.Participants completed a questionnaire and had anthropometric measurements (height, weight, and waist circumference) and blood pressure taken at the WBHC. Fasting blood samples were drawn at a Gamma-Dynacare Medical Laboratory (Ottawa, ON) for measurements of glucose, insulin, HDL-cholesterol and triglycerides. IR was established using the Homeostasis model assessment of IR (HOMA-IR) with a cut-point of 2.29 for Caucasians (8). MetS was based on having three out of five criteria defined by the AHA/NHLBI (9). T2D was diagnosed using the 2008 Canadian Diabetes Association guidelines. Due to blood work requisition or laboratory errors, we derived MetS in 88 participants, 96 for IR, and 97 for T2D. Characteristics between pre-and postmenopausal women were compared using independent t-tests (continuous variables) or Fisher's exact test (categorical variables).On average, women were in their late fifties (58.2 AE 0.8), nonsmokers (98%), moderate alcohol consumers (≤5 drinks/w...

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