James R. Gavin III, MD, PhD, the symposium moderator, introduced this “typical patient” with newly diagnosed type 2 diabetes mellitus (T2DM) during his opening remarks:
The patient described here does present the challenge of multiple “cardiometabolic” risks. The patient does have four of the five criteria for metabolic syndrome described by the Adult Treatment Panel (ATP) III
1:
This patient's HDL-C level is barely acceptable for a male (>40 mg/dL). If the patient in the case study were instead a female, she would have all five criteria of metabolic syndrome since an HDL-C level less than 50 mg/dL is considered low for a female.
Of note is that the criteria for metabolic syndrome do not include an elevated LDL-C level. Many patients with diabetes will present with near-normal LDL-C levels but are still at considerable cardiac risk because of their metabolic dyslipidemia, which
includes an elevated triglyceride concentration, depressed HDL-C, and smaller, dense LDL particles (pattern B). However, this patient is clinically diabetic, and therefore is considered a coronary heart disease risk equivalent. Thus, this patient's LDL-C level of 129 mg/dL is well above goal, and he certainly would be a candidate for statin therapy as outlined by Dr Spratt in her article beginning on
page S2. Once the LDL-C goal is achieved, the patient may be a candidate for further combination therapy to address the residual risk of elevated triglyceride concentrations and depressed HDL-C.
The ATP III guidelines
1 introduced the concept of “non-HDL cholesterol” to address the residual risk beyond LDL-C in metabolic patients such as in our case study. Non-HDL cholesterol is simply the total cholesterol minus the HDL-C cholesterol. It represents
all atherogenic and potentially atherogenic particles (including but beyond LDL-C).
The non-HDL cholesterol is actually much more predictive of cardiovascular events than LDL-C and is a reasonable surrogate marker of apolipoprotein B, which some think is the best marker of risk. The non-HDL cholesterol is easy to compute without a calculator and does not involve more complicated ratios. The goal of non-HDL cholesterol is simply 30 mg/dL higher than the patient's LDL-C goal. If one wishes to drive the LDL-C to less than 70 mg/dL in a patient with diabetes, then the non-HDL cholesterol goal would be less than 100 mg/dL.
In our case study, the patient's non-HDL cholesterol level is 192 mg/dL (234 mg/dL minus 42 mg/dL). If the patient does not respond to statin therapy alone to achieve both the LDL-C goal and non-HDL cholesterol goal, then the addition of combination therapy with a fibrate or niacin should be considered, particularly if the triglyceride concentration remains greater than 200 mg/dL. Dr Spratt's article provides a nice summary of the evidence supporting either approach. Additional studies are ongoing, and will provide the clinician with additional guidance in the near future.
Although the foregoing discussion regarding the pharmacologic approach to metabolic dyslipidemia is important, the physician cannot forget that diet and exercise always remains the cornerstone of diabetes management because it reduces insulin resistance. Diet and exercise with a focusing on 5% to 10% weight loss is recommended for all patients with impaired fasting glucose or impaired glucose tolerance. Craig W. Spellman, DO, PhD, in his article (beginning on
page S14) suggests prescribing metformin as an option for our case study patient since his HbA
1cvalue is greater than 6% and other risk factors such as hypertension and low HDL-C level are present. However, prescribing a thiazolidinedione (TZD) could also be considered since that class of drugs may also prove to have a beneficial effect on metabolic dyslipidemia.
The patient in our case study also has hypertension, and most guidelines suggest even tighter control of blood pressure in patients with diabetes to reduce the possibility of end-organ damage. Dr Haffey in his article (beginning on page S14) suggests an angiotensin-converting enzyme inhibitor (ACE-I) or angiotensin receptor blocker (ARB) as a cornerstone of therapy in patients with diabetes and hypertension. However, as Dr Haffey also points out, it is not uncommon for such patients to require three or more agents to adequately control their blood pressure to goal.
Our case study patient also complains of fatigue, and a screen for sleep apnea would also seem reasonable as it frequently can contribute to a patient's hypertension and cardiovascular risk. The patient's complaint of a degree of sexual dysfunction might also alert the physician that there may be an element of vascular dysfunction or even clinical atherosclerosis that might require further investigation.
The treatment of patients for cardiometabolic risk requires a holistic approach, which is consistent with the osteopathic physician's philosophy. Our “typical” metabolic patient described here is at considerable risk for a future cardiac event, since more than 85% of our patients who have diabetes will die from some form of atherosclerosis. Thus, it is imperative that we screen and treat our patients to established goals with evidence-based approaches that clearly can improve the quality of life and save lives.