Clinical Gems

Obesity is a global epidemic that has far-reaching economic and public health implications. Excess body weight is associated with multiple comorbidities including type 2 diabetes (T2DM), hypertension, obstructive sleep apnea (OSA), and cardiovascular disease (CVD). Dysglycemia andOSA share common risk factors such as age and obesity; hence it is not surprising that OSA and glycemic abnormalities often coexist.

Dyslipidemia: The relationship between cholesterol and cancer risk has been difficult to discern from epidemiologic studies. Individuals with the metabolic syndrome and T2DM frequently have a dyslipidemic profile with elevated triglycerides and decreased high-density lipoprotein cholesterol (HDL-C). In the Metabolic Syndrome Cancer (Me-Can) European cohort elevated triglyceride levels were associated with colon, respiratory, kidney, thyroid cancers, and melanoma in men and respiratory, cervical, and nonmelanoma skin cancers in women.

Links between diabetes and cancer: common risk factors

Epidemiologic studies demonstrate that those with diabetes are more likely to develop cancer, but the mechanisms through which this may occur are incompletely understood. The American Diabetes Association and the American Cancer Society published a consensus report in 2010, with the aim of examining the knowledge regarding the association between diabetes and cancer, exploring the risk factors for both conditions, to examine their possible biologic links and to determine whether certain treatments for diabetes modify cancer risk.

Introduction: An association between hyperglycemia, diabetes, and cancer has been recognized for many years. Epidemiologists first noted the association between diabetes and cancer in the early part of the twentieth century, while the association between hyperglycemia and cancer was reported in 1885. At that time, in Europe and North America life expectancy was improving, rates of over-nutrition and under-exercise were increasing, there was a rise in the percentage of people that were overweight, and the incidence of diabetes began to climb.

Glucose-lowering agents: Metformin is a biguanide that has been used worldwide for more than 50 years for the treatment of T2DM although its exact mechanism of action remains incompletely understood. It decreases hepatic glucose production and improves insulin sensitivity at the level of the liver, and to a lesser extent, muscle. Metformin has been reported to reduce plasma aminotransferase levels in patients with NAFLD. Early small studies suggested that metformin improved hepatic steatosis, necro-inflammation and/or fibrosis in patients with NASH, but not in more recent and better controlled clinical trials.

The role of statins in the primary and secondary prevention of CVD has been well established. Patients with NAFLD are believed to have increased cardiovascular risk and are logical candidates for their long-term use. In accordance with their higher cardiovascular risk, the use of statins should be encouraged in patients with NAFLD but their use has remained controversial in such patients, particularly in the setting of elevated liver enzymes. Recent practice guidelines on statin use in patients with NAFLD have clearly established that they are overall safe and that they do not carry a higher risk of liver toxicity.

Combined dietary intervention and exercise: The available information on the role of combined lifestyle interventions (hypocaloric diets plus exercise) in patients with NAFLD is much more extensive, with several randomized, controlled trials showing significant benefit with this comprehensive approach. Again, the overall reduction in liver fat reported in most of these trials has been strongly correlated with the amount of weight loss.

The effect of dietary intervention alone for the management of NAFLD and NASH has been evaluated extensively over the past 2–3 decades. These studies can be divided into two main types: those that have focused on weight reduction only, and clinical trials that have assessed the role of a particular dietary composition on hepatic steatosis.

Nonalcoholic fatty liver disease (NAFLD) encompasses a spectrum of liver disease ranging from simple liver fat accumulation to severe hepatic necro-inflammation (nonalcoholic steatohepatitis or NASH), and eventually cirrhosis.

Hypertriglyceridemia and low HDL cholesterol, increased risk of type 2 diabetes: Under fasting conditions, the liver of subjects with NAFLD overproduces triglyceride-enriched VLDL particles despite hyperinsulinemia when compared to equally obese subjects without NAFLD. Insulin normally decreases production of VLDL by inhibiting adipose tissue lipolysis, and by directly suppressing hepatic production of VLDL.