The underpinning for much of the death and disability from arterial vascular disease in this country is the metabolic syndrome. One of the real authorities on metabolic syndrome is Dr. Ralph DeFronzo. I particularly like his description of this collection of disorders as a “complex metabolic web”.

The patients who have this diagnosis are burdened with multiple chronic conditions: hypertension, high LDL or bad cholesterol, high triglycerides, low HDL or good cholesterol, and high blood sugar ultimately resulting in type 2 diabetes. These patients routinely have vascular systems where the vessels are inflamed and the blood more likely to clot.

Early in the condition, the arteries are thicker and less distensible than in people without the syndrome; progression of the arterial disease is the norm. Many of affected individuals also have gout. More recently, the metabolic syndrome has been called the cardiometabolic syndrome because this name underscores the impact of these conditions on the heart and the rest of the vascular system. Metabolic syndrome patients have an increased risk of coronary artery disease, cardiac enlargement, and congestive heart failure. Type 2 diabetes is the late stage of the syndrome.

Dr. DeFronzo highlights a very important clinical reality in describing the cardiometabolic syndrome as a complex metabolic web. “Job one” of the clinicians who treat these patients is to unravel that complex web using every medical and lifestyle tool in the medical toolbox.

Only 7% of these patients have all of their risk factors (hypertension, blood sugar, and cholesterol) simultaneously controlled to the most conservative goals. For each risk factor that is controlled, using the proper interventions, the risk of all adverse outcomes is reduced by roughly 50%. So, the task of the clinician is not just to control hypertension or diabetes, but rather to control all risk factors to goal at the same time.

That is where the focus, skill, and training of your provider come into play. The particular medical choices that are made are critical for success. For three decades now, I have heard physicians blame patients for not being “compliant”:

 “Mrs. Brown is diabetic and she does not listen to a thing I tell her. She just stuffs herself with anything she wants and she continues to gain weight.”

Here is the reality. Every medication commonly used for the treatment of type 2 diabetes causes weight gain with the exception of metformin (Glucophage) and the Byetta-type medications. The new drug Januvia is weight neutral. Most patients do not have their sugar controlled to goal using a single medication. Most patients require multiple drugs and even then, progressive loss of glucose control is the norm. Weight gain not only makes the control of sugar more difficult, the metabolic syndrome is itself worsened by increased abdominal weight—weight gain also makes controlling pressure, cholesterol, triglycerides, and gout more difficult.

The patient that receives a prescription for two shots of NPH insulin a day will gain 10 pounds in a year. The patient that uses glyburide plus a single shot of NPH gains 9 pounds. The regimen combining glyburide, metformin, and a single shot of NPH, produces a similar weight gain. Metformin added to a single injection of NPH at bedtime produces no weight gain, the best control of the blood sugar, and the least number of hypoglycemic attacks. The doctor with the prescription pad is producing this result—not the patient. These are impressive weight changes and they make a big difference over time. I have treated 450 type 2 diabetics for nearly 10 years with a regimen based on metformin and a long-acting insulin injection with durable control in most patients.

The treatment of high blood pressure hides the same kind of traps. Until very recently, beta blockers like propranolol (Inderal), metoprolol (Toprol), and atenolol (Tenormin) were recommended as first-line therapies for the treatment of hypertension. Many patients continue to be on these medications for the one purpose of treating high blood pressure. These medications have important metabolic effects:

  • Propranolol increases triglycerides by 25%, decreases HDL by 10%, increases total cholesterol by 9%, and increases insulin resistance by 33%.
  • Metoprolol increases triglycerides by 30%, decreases HDL by 7%, decreases total cholesterol by 1%, and increases insulin resistance by 21%.

Tricor (fenofibrate) is prescribed to treat the lipid or cholesterol abnormalities that go with metabolic syndrome; it decreases triglycerides by 29%, increases HDL by 11%, and decreases total cholesterol by 18%. When we prescribe propranolol and fenofibrate simultaneously, we have simply canceled the lipid effect of two drugs.

The prescription of propranolol makes it 28% more likely that the patient will develop diabetes. Choosing an ACE inhibitor makes it 33% less likely that a patient will develop diabetes. These are critical metabolic issues. There is a newer beta blocker carvedilol, with dramatically improved metabolic effects relative to the older drugs.

The point of all this is that treatment of these patients is very complex if it is done properly. Ninety-five percent of type 2 diabetes care is provided by primary care doctors who are under tremendous pressure to see patients at the rate of 5-6 per hour. They are required to be experts in the whole massive knowledge base of medical practice. We need focused clinics of the type described by the Institute of Medicine to treat metabolic syndrome patients. The providers in these clinics will need to be very expert in the coordinated, integrated management of metabolic syndrome patients and the resulting complications. Until that happens, we will continue to produce the same poor levels of risk factor control and pay a terrible price in lives, disability, and treasure.


  1. As someone with this syndrome, I am still left with a lot of questions.Diabetes is considered to be a chronic and progressive disease, and this post considers diabetes to be a later stage form of the syndrome. Is the syndrome itself just the same – chronic and progressive. If so, is management just a matter of life extension? That is, the consequences will come, and all we are talking about is timing.

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