Hepatocellular carcinoma is a common cancer worldwide. The incidence in the East is very much higher due to endemic chronic hepatitis B virus (HBV) infection in the population. The incidence of HCC has been increasing steadily in USA and the major risk factor for HCC in US is chronic hepatitis C virus (HCV) infection. In 1975, the total incidence of HCC was approximately 1.59 per 100,000 person-years. By 2006, this had reached 4.82 per 100,000 person-years and this increase has been attributed to the increasing numbers of Asian immigrants in the United States. However, a presentation at the recent 101^st Annual Meeting of the American Association for Cancer Research (AACR) has come up with a surprising culprit (Abstract 1816, presented Arpil 19, 2010).

Researchers from the National Cancer Institute (NCI) reviewed data from the NCI SEER database. The case population studied consisted of 5607 people diagnosed with HCC. They examined the odds ratio of an individual developing HCC with the risk factors of HCV infection, HBV infection, alcohol-related disease, rare metabolic disease, diabetes and obesity. (Odds ratio tells you how much more likely it is that you are going to develop the condition compared with someone without the risk factor.) HCV infection has the highest odds ratio of 44.26 (ie 44 x more likely than a non HCV infected person). The odds ratios for HBV infection, alcohol-related disease, rare metabolic disorder, diabetes and obesity were 13.37, 4.43, 3.51, 2.37 and 1.53, respectively. However, the researchers found that diabetes was associated with the greatest percentage of cases (33.5%). The other associations were alcohol-related disorders (23.9%), HCV infection (20.7%), HBV infection (5.7%), rare metabolic disorders (3.1%) and obesity (2.7%).

The incidence of obesity and diabetes mellitus is increasing worldwide and the Asian population has not been spared. While chronic HBV infection is the most important risk factor for HCC in Asia, the general population and clinicians need to be aware that diabetes and obesity are also associated with HCC. The above study found that 67.9% of Asians with HCC had one or more of the identified risk factors. Both obesity and diabetes can be helped by adopting a prudent life style - maintaining a healthy body starts with you!

There are 2 types of diabetes mellitus – Type I and Type II. Type I diabetes occurs when the pancreatic islets, which produce insulin, are destroyed by an auto-immune process. It affects young children and they are dependent on insulin injections for life. Type II diabetes occurs when the body tissue becomes less sensitive to the action of insulin, thus, more insulin has to be produced by the body in order to keep the glucose level normal. Type II diabetes usually affects adults who are overweight / obese and older. As one gets fatter, one develops insulin resistance and this leads to an impaired glucose level. Eventually a proportion of overweight / obese people develop persistently elevated glucose levels and the condition is termed Type II diabetes.

Researcher in Umea University, Sweden, studied the association between blood glucose and cancer risk in 274,126 men and 275,818 women from Norway, Austria and Sweden (PLoS Med 2009; 6(12): e1000201). The study found that impaired glucose level was associated with increased incident and fatal cancer risk. In men, the risk per 1 mmol/L glucose increment for incident cancer and fatal cancer was increased by 5% and 15%, respectively. Significant increase in the risk of incident and fatal site-specific cancer was observed for cancer of the liver, gallbladder and the respiratory tract. Incident risk of cancer of the thyroid and multiple myeloma were increased. Men with the highest impaired glucose level also had significant increased risk of fatal colon cancer. In women, the risk for incident cancer and fatal cancer was increased by 11% and 21% respectively. Significant increase in the risk of incident and fatal site-specific cancer was observed for cancer of the pancreas and stomach. Incident risk of urinary bladder cancer was increased. Women with the most amount of impaired glucose level also had significant increased risk of incident endometrial cancer.

The result from this European study corroborates the findings of a Korean study published in 2005. Impaired glucose levels are associated with increased risk of cancer. For those who are overweight, this bit of information is another reason for you to lose weight. Achieving it depends on what you eat, how much exercise you do and how determined you are.

Obesity is reaching an epidemic proportion worldwide. Being obese is associated with increased risk of developing type II diabetes mellitus (DM) and cardiovascular disease (CVD). Previous studies of obesity have shown that individuals who have a selective excess of intra-abdominal (visceral) fat will be at a substantially higher risk of being insulin resistant and have a cardiovascular risk profile. In the body, fat tissue is a store for excess energy. The theory is that when extra energy is deposited as visceral fat and in ectopic depots such as the liver and skeletal muscle, this leads to an increased risk of DM and CVD. If the extra energy is deposited in subcutaneous depots and / or burned within the mitochondria in the liver and skeletal muscle, the individual, though obese, will be protected from these diseases. So can we find these people with metabolically benign obesity?

A study from University of Tubingen, Germany, examined a total of 314 individuals who underwent magnetic resonance (MR) tomography to measure total, visceral and subcutaneous fat, and proton MR spectroscopy to measure fat in the liver and skeletal muscle. The insulin sensitivity was estimated from oral glucose tolerance test. The intima-media thickness [IMT, it is used as an early marker of atherosclerosis (hardening of the artery)] of the common carotid artery (artery to the brain) was measured with ultrasound (Arch Intern Med 2008; 168: 1609 – 1616). There were 4 groups of individuals identified and assessed: normal weight [body mass index (BMI) < 25.0], overweight (BMI 25.0 – 29.9), obese insulin sensitive (OIS) (BMI ≥30, placement in the upper quartile of insulin sensitivity) and obese insulin resistant (OIR) (BMI ≥30, placement in the lower 3 quartiles of insulin sensitivity). Compared with the normal weight group, the overweight and obese groups have higher total body and visceral fat. Within the obese group of individuals, ectopic fat in the skeletal muscle and especially the liver and IMT values were lower in the OIS group when compared to the OIR group. The OIS group has higher insulin sensitivity than the OIR group. Interestingly, the insulin sensitivity and IMT values between the OIS group and normal weight group were not statistically different.

So is there a simpler way of identifying the metabolically benign obese people? Has no one made this observation until now because the MR machine was only invented recently? In 1956, a French clinician with a large obesity practice, published his clinical observations. In his practice, Dr Jean Vague observed that there were 2 predominant types of obese people: an upper-body, central abdominal obesity type which he called android and a lower-body, gluteal-femoral (buttocks and thighs) type which he called gynoid. He reported that patients with the upper-body, central abdominal form of obesity were prone to cardiovascular and metabolic complications such as hypertension, coronary artery disease and diabetes when compared to those having the lower-body, gluteal-femoral type. The designations android and gynoid applies to both men and women. These observations by Dr Vague seems to have gone unnoticed until the 1980s when large Scandinavian epidemiologic studies showed that CVD and death were related to the central body fat phenotype, as assessed by a high waist to hip ratio.

If you do not have an MR machine and do not know how to perform the oral glucose tolerance test, get a tape and measure your waist and hip circumference. Perform a simple mathematical calculation and you will have a rough idea if you have an android type or a gynoid type of habitus.

Even if you are a metabolically benign obese person, it would be wise not to think that you are in the clear and continue to eat as much as you want. In medicine, we are dealing with probabilities. We do not deal with absolute certainty like in rocket science. Thus, it is still a good idea for you to be normal weight rather than overweight or obese!