Pre-Diabetes, Non-HDL Cholesterol, and Cardiovascular Risk

Jose is 47-year-old Hispanic man who comes to your office for a “check up.” His only symptom is that he notices he does not have the energy he once had but thinks “it’s because of his weight.” He has worked at a desk for 3 years and has gained 12 pounds. He has several paternal aunts and uncles with type 2 diabetes mellitus, and his father died at age 49 of an MI. His BMI is 29; blood pressure, 143/88 mm Hg; and waist circumference, 42 inches.

Lab values: fasting blood sugar, 132 mg/dL; HbA_1c, 6.2%; total cholesterol, 180 mg/dL; triglycerides, 250 mg/dL; LDL (calculated), 100 mg/dL; HDL, 30 mg/dL; non-HDL, 150 mg/dL.

Do you consider an LDL level of 100 mg/dL and a non-HDL level of 150 mg/dL significant? What is your diagnosis? Would you consider medication in addition to recommending lifestyle changes?

This case was recently featured as a "quiz of the week." Readers were invited to submit their answers to these questions. (Their answers appear at the bottom of the quiz.) I have summarized the responses here and offer strategic guidance on this case.

Readers posted several excellent responses to these questions. Most agreed that Jose is at significant risk for cardiovascular disease because of his lipid numbers. His HDL of 30 is particularly worrisome, as is his non-HDL (total cholesterol minus HDL, or 180-30) combined with his father’s history of a fatal MI at age 49. The LDL is 100-but it is a calculated LDL. Recall that when LDL is calculated, the higher the triglyceride value, the lower the LDL (LDL= total cholesterol minus HDL minus triglycerides divided by 5, or 180-30-250/5 =100). If the triglyceride value was 100, the LDL would have been 130.

The National Cholesterol Education Program¹ recommends that we use non-HDL as an additional risk predictor when triglyceride levels are over 200. The goal for non-HDL is LDL goal plus 30. With Jose, the goal would most likely be 100-130 because of his significant cardiovascular risk.

Metabolic syndrome was noted as the likely diagnosis and diabetes/pre-diabetes was mentioned by several readers. Jose has all 5 criteria for the metabolic syndrome: increased waist circumference, hypertension, hypertriglyceridemia, hyperglycemia, and decreased HDL level). The HbA_1c is in the pre-diabetes range (5.7 to 6.4) and blood sugar level of greater than 125 fasting fits the diagnosis of diabetes according to the 2012 American Diabetes Association (ADA) standards of care (www.diabetes.org). It is not unusual to be faced with this dilemma of not having a clear-cut diagnosis of diabetes. Both tests could be repeated, as some readers suggested.

A few readers suggested that a 2-hour post glucose load blood sugar be obtained. I think this would be helpful because postprandial blood sugar is usually higher than fasting in pre-diabetes and with HbA_1c levels that are lower.² Jose's 2-hour post-load glucose was 170.

Readers had a mixed reaction on how to treat Jose. All agreed that lifestyle changes should be recommended. A few were willing to only use lifestyle for a period of time. Many recommended the use of metformin and some suggested using a statin; one reader suggested starting niacin because of the low HDL level.

I would not be comfortable with lifestyle-only treatment. Jose's low HDL level, significant family history, and other lipid values are worrisome. His beta cell function will be improved some with lifestyle changes, but the addition of metformin may provide even more functional improvement^2,3 and improve the lipid values. A consensus statement published by the ADA³ suggests using metformin when blood sugar levels are in the pre-diabetes range (FBS, 100-125; 2-HR PP, 140-199) and one additional risk factor is present (low HDL, high triglycerides, BMI greater than 35, age less than 60, family history of cardiovascular disease, hypertension, and HbA_1c >6 ).

Jose has several of these risk factors. With his significant cardiovascular risk, I would use a low-dose statin. I would reserve niacin to see what happens to the HDL with the above treatment. Statins will increase HDL levels about 10% and exercise and diet an additional 10% or more. I might even suggest a glass of wine, which could gain Jose an additional 10% increase.

An ACE inhibitor or an ARB should also be considered. Most diabetic patients have hypertension and the risk of cardiovascular disease is much higher in diabetic patients with hypertension.

The key to all of this is motivating the patient to change. But for Jose, the sudden death of his father may be very motivating. But it also takes a motivated clinician who believes that all the above preventative strategies are of benefit.

References:

References:
1. Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. JAMA. 2001;285:2486-2497.
2. Nathan DM. Initial Management of glycemia in type 2 diabetes mellitus. N Engl J Med. 2002;347:1342-1349.
3. Nathan DM, Davidson MB, DeFronzo RA, et al. Impaired fasting glucose and impaired glucose tolerance: implications for care. Diabetes Care. 2007;30:753-759. Abstract