Metabolic syndrome and diabetes for the urologist Neil E. Fleshner, MD, MPH, FRCSC;' Bimal Bhindi, MDt ‘ Professor of Surgery and Martin Barkin Chair of Urology, University of Toronto, Head, Division of Urology, University Health Network, Love Chair in Prostate Concer Prevention, Princess Margaret Hospital, Toronto, ON; Resident in Urology, University of Toronto, Toronto, ON

Cite as: Can Urol Assoc J 2014;8(7-8):Sl 59-61. http://dx.doi.org/10.5489/cuoj.2314 Published online August 11,2014.

Type 2 diabetes can result in a number of urological con­ sequences. Renal consequences may include kidney stones, pyelonephritis/inflam m ation or chronic renal failure. In the Abstract bladder, urinary tract infections or cystopathy/retention may develop. Infertility, andropause and erectile dysfunction are also Type 2 diabetes has a number of know urological consequences. known urological consequences of type 2 diabetes.9 Epidemiologic and clinical data suggest a link between metabolic Recent e p id e m io lo g ic and c lin ic a l data suggest a lin k syndrome and prostatic diseases, such as benign prostatic hyperplasia between m etabolic syndrome and prostatic diseases, such (BPH) and prostate cancer. Recent studies have identified metformin as as benign prostatic hyperplasia (BPH) and prostate cancer.10 a viable treatment for patients with type 2 diabetes and prostate cancer. Many of the hormones, growth factors, cytokines and other mediators associated with obesity and the metabolic syndrome e ta b o lic syndrom e com prises a co n ste lla tio n of enable crosstalk between macrophages, adipocytes, endothelial metabolic abnormalities that are associated with an cells and epithelial cells, which is implicated in carcinogenesis increased risk of cardiovascular (CV) disease, type 2 (including growth signaling, inflammation, and vascular altera­ diabetes, CV-specific mortality, and all-cause m ortality.1-2 The 1 A recent study at the University of Toronto found that tions).1 definition of metabolic syndrome varies according to different men w ith 3 or more components of the metabolic syndrome sources, but generally comprises a series of factors involving had a 38% higher odds of being diagnosed with prostate can­ insulin resistance, increased body weight, increased lipid levels, cer than men w ith no risk factors.12 These men also had a high blood pressure and impaired glucose levels (Table 1).3'7 52% higher odds of being diagnosed with clinically significant The prevalence of metabolic syndrome in Canada is estimat­ prostate cancer and a 43% higher odds of being diagnosed ed at 19%.8 Dietary excess and a sedentary lifestyle are thought with high-grade prostate cancer (Gleason 7 or higher). These to contribute to the development of m etabolic syndrome in findings suggest a biologic gradient with increasing number of genetically susceptible individuals. metabolic risk factors. As well, androgen deprivation therapy, The development of diabetes follows a series of stages, begin­ used in the treatment of prostate cancer, can induce alterations ning w ith insulin resistance in peripheral tissues, resulting in similar to those of metabolic syndrome, including increased glucose intolerance. At this stage, a postprandial rise in glucose obesity, decreased insulin sensitivity and altered lipid profiles.13 may be the only sign of metabolic disturbance. W ith increased Recent data suggest that men with type 2 diabetes and prostate insulin resistance, the patient reaches a state of hyperinsulinemia cancer have improved survival when treated with the biguanide combined with hyperglycemia - a stage that is often referred to oral hypoglycemic agent metformin. Among men with diabetes as "pre-diabetes," during which the cells become increasingly in a population-based, retrospective cohort of 3837 patients, starved for energy. During the hyperinsulinémie phase of type ! cumulative duration of treatment with the antidiabetic metformin 2 diabetes, glucose levels rise above safe levels. Finally, during follow ing a diagnosis of prostate cancer was associated with the burnout phase, beta-cells are no longer able to produce ! declines in both all-cause mortality and prostate cancer-specific insulin. Insulin resistance occurs years before the onset of type 2 mortality.14 However, despite these findings of improved survival diabetes, due to genetic factors as well as environmental factors, j in men with an existing diagnosis of prostate cancer, metformin such as sedentary lifestyle, pregnancy, nutrient intake (quan- ■ does not seem to prevent the development of prostate cancer tity and quality), puberty and aging. The net result is adiposity, in men with type 2 diabetes. A retrospective review of 5306 impaired B-cell function, and impaired insulin action. diabetic men with prostate cancer and 26 530 matched controls

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Fleshner and Bhindi

Table 1. Indications fo r bone m ineral density testin g 5 Clinical measure Insulin resistance

Body weight

Lipid -High TG -Low HDL

Blood pressure

Glucose Other

WHO (1998)3

ATP III (2001 )4

IDF (2005)5

AHA/NHLBI (2005)6

IDF & AHA/NHLBI Joint interim (2009)7

Mandatory IGT, IFG, T2DM, or lowered insulin sensitivity* plus any 2 of the following

None, but any 3 o f the follow ing 5 features

None

None, but any 3 of the following 5 features

Men: waist-to-hip ratio >0.90; women: waist-to-hip ratio >0.85 and/or BMI >30 kg/m 2

WC 2102 cm in men or 288 cm in w o m en t

Mandatory Increased WC (population specific) plus any 2 of the following

WC 2102 cm in men or 28 8 cm in w o m e n t

Ethnicity/pop-specific WC

TG 2150 mg/dL and/or HDL-C