Transcription:
Latest Treatments and Research for Metabolic Disease

Melanie Cole (Host):  City of Hope has one of the most influential metabolic disease research programs in the world.  Our scientists’ work has revolutionized the understanding and treatment of these diseases and continues today with exciting developments.  My guest today is Dr. Sanjay Awasthi.  He’s a professor in the Department of Diabetes and Metabolic Disease Research and a professor in the Department of Medical Oncology and Therapeutics Research at City of Hope.  Welcome to the show, Dr. Awasthi.  Tell us a little bit about metabolism and the metabolic disorders in general. 

Dr. Sanjay Awasthi (Guest):  Well, the condition metabolic syndrome is a very common condition across the world.  It has increased in incidence very significantly as our population here and across the world, really, has grown more obese.  It is characterized by elevated blood pressure and insulin resistance.  Insulin resistance is a condition where insulin doesn’t have as good an effect on the liver or muscles or the fat as it should.  As a result, multiple abnormalities occur.  These include either an elevated blood sugar or abnormal glucose tolerance tests and it’s very frequently associated with hypercholesterolemia that is elevated cholesterol, elevated triglycerides, high levels of LDL—the bad levels of cholesterol--and low levels of HDL, which is the good cholesterol and a variety of other things that we can measure.  People with metabolic syndrome often have increase in size of their abdominal girth.  They have high levels of fat in the abdomen that surrounds their intestines, which is one of the best ways of knowing that the patient may have metabolic syndrome.  They have high levels of fat sometimes in the liver.  Often we find patient’s who have had a CAT scan for another reason that have a fatty liver.  These are pretty good markers of patients having insulin resistance.  Probably an underlying cause, if you will, is the presence of excess inflammation.  It’s not clear whether the inflammation is a cause or the result of the metabolic syndrome but it’s certainly associated with it.  Metabolic syndrome often transitions into type-2 diabetes.  The reason why it’s important is it increases your risk of cardiovascular death very significantly and probably also increases your risk for certain kinds of cancers. It often is associated with a variety of other inflammatory disorders like joint inflammation, or tendon or muscle inflammation and a variety of other inflammatory conditions that either are caused by or a cause of the metabolic syndrome.

Melanie:  So, with the obesity epidemic that we’ve got going on in this country, Dr. Awasthi, who is most at risk?  What do you want them to know about metabolic diseases, such as diabetes and thyroid disorders and things?  Is any prevention available or lifestyle modification behaviors?  What are things you want them to know?

Dr. Awasthi:  The most important this is control of caloric intake.  Eating too much is probably the most important and modifiable variable.  The second is, of course, exercise.  Many studies have shown that eating less and doing more exercise causes improvement in overall condition of metabolic syndrome.  It can lower your blood pressure; it can lower your total cholesterol; it can increase your HDL cholesterol and lower your LDL cholesterol.  There are other lifestyle modifications that are less important but can play a role in many people.  Things such as eating while you’re stressed, eating while you’re standing, eating excessive amounts of omega-6 fatty acid containing foods, having a large amount of fat in the diet, these are also factors that patients can modify.   Certainly one of the most important, really, is stopping smoking. Smoking is associated with something called “oxidative stress,” which is an underlying factor in insulin resistance and the inflammation that occurs in metabolic syndrome. 

Melanie:  So, when we are talking about metabolic diseases, can they lead to cancer?  Is there a link between metabolic diseases and cancer?

Dr. Awasthi:  Well, epidemiologically across populations, yes.  The cancers such as breast cancer, colon cancer and prostate cancer have been clearly linked to the presence of metabolic syndrome.  Again, it’s not exactly clear whether tendency to malignancy caused by, let’s say smoking, leads to metabolic disease or whether a metabolic disease or metabolic syndrome actually increases the risk of cancer.  One thing is quite clear and that is that many of the same factors that predispose metabolic syndrome are also things the predispose cancer.

Melanie:  So, they do tend to go together.  So, tell us a little bit about thyroid disorders and how they can lead to obesity and what can be done about those?  Is this a lifestyle thing or does this generally need treatment? 

Dr. Awasthi:  Thyroid disorders can affect the entire metabolism.  It can increase or decrease metabolism and may be a contributor, although probably relatively minor in terms of the sort of etiology of metabolic syndrome.  Recently, there’s been a lot of interest in a variety of small proteins called “peptides” that control your appetite and control satiety, the feeling of being full after eating.  These are revolutionary findings over the last couple of decades that have implicated the brain or the hypothalamus and the connection between the intestines. The hypothalamus and intestine connection is particularly important, and is going to be increasingly important, as we realize how certain bacteria that live in your intestines are a cause of inflammation that can lead to metabolic syndrome.  Thyroid disease itself is likely not a direct cause of metabolic syndrome.   

Melanie:  In just the last few minutes, Dr. Awasthi, if you would, please give us one of your horizon picture.  Tell us what’s going on in the world of metabolic disease and what do you see happening for the future?  What kind of research are you doing at City of Hope? 

Dr. Awasthi:  My research is involving metabolic pathways that metabolize poisons or toxins, particularly those that generate from omega-6 fatty acids.  I’ve been working on this for the last 30 years and have worked on a variety of enzymes in these pathways and discovered a few years ago that one of the proteins of this pathway that’s present on the cell membrane, on the outside of the cell, has a crucial role in both cancer as well as conditions such as obesity and metabolic syndrome.  So, the protein I work on is called RALBP-1 and we have shown that blocking this protein has beneficial effects in metabolic syndrome and blocking it actually causes a regression or disappearance of cancers in a variety of animal models of cancer.  I made some mice, they’re called “knock out mice” that don’t have the gene and they are very resistant to diabetes and metabolic syndrome and are extremely resistant to cancer and so we have seen in recent studies that we can have beneficial effects on both cancer and metabolic syndrome, simultaneously that are involved in this as well. 

Melanie:  That is so exciting.  What exciting research you’re doing.  Thank you so much, Dr. Awasthi.  You are listening to City of Hope Radio.  For more information you can go to cityofhope.org.  That’s cityofhope.org.  This is Melanie Cole.  Thank you so much for listening.