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Question: "I have a 45-year-old male patient with severe dyslipidemia, a glycated hemoglobin (A1C) of 8.2%, triglycerides 550, high-density lipoprotein (HDL) 38, and total cholesterol 160. [Low-density lipoprotein (LDL) can't be measured if triglycerides are above 400.] He is already taking gemfibrozil 600 mg twice daily and niacin 2 grams daily in addition to twice-daily NPH insulin. How can I proceed at this point?"
Answer: This patient presents a difficult clinical problem—a persistent and significant triglyceride elevation in spite of aggressive medication. Given the high level of triglycerides despite therapy, and the relatively low total cholesterol level of 160, I suspect he has familial hypertriglyceridemia, and that his pre-treatment triglyceride level may have been well above 1,000. Lowering his triglyceride level further is certainly desirable, as it will further raise his HDL level and lower his cardiac risk, but it will require a multifaceted approach. I would propose three areas for your consideration: 1) dietary modification; 2) improvement of his glycemic control; and 3) the possible addition of a statin.
Have a dietitian evaluate his current diet with respect to both total caloric content and the amount and type of carbohydrates he is consuming. If he is overweight, a reduction in the amount of total calories would be helpful. Whether or not he is overweight, a reduction in the amount of carbohydrate would immediately help to lower his triglyceride level. Very-low-carbohydrate diets have been shown to lower triglycerides without substantially increasing LDL levels.1,2
With an A1C level of 8.2%, his diabetic control is suboptimal. Poor control, particularly in type 2 diabetes, directly increases triglyceride levels.3 Apparently, his only diabetic therapy at this point is insulin. I would suggest starting him on metformin, increasing the dose gradually over a couple of weeks to 1,000 mg twice daily. This may help to reduce his appetite and will not facilitate further weight gain.
You may wish to consider eliminating his niacin therapy, as this may well be increasing his insulin resistance and worsening his glycemic control. The disadvantage of potential worsening of diabetic control would clearly outweigh the advantage.
I also would recommend intensifying his insulin management by having him monitor glucose 4 times daily— preprandially and at bedtime—to identify when his glucose levels are worst. NPH given twice a day will not provide much insulin coverage for either breakfast or supper, so he likely will have high blood glucose at noon and bedtime. Simply increasing the doses may increase the risk of nighttime hypoglycemia. I suspect your patient will benefit from the addition of rapid-acting insulin, such as aspart (Novolog, Novo Nordisk) or lispro (Humalog, Eli Lilly) at breakfast and supper, and I probably would eliminate the morning NPH and replace it with rapid-acting insulin at lunch as well. Sometimes meal coverage with rapid-acting insulin alone will provide excellent glucose control and long-lasting insulin for night is not required at all. If blood glucose does rise between bedtime and breakfast, this can be managed effectively with either NPH or glargine (Lantus, Sanofi-Aventis) given at bedtime.
Adding atorvastatin also may be useful, as this statin has more effective triglyceride reduction than other drugs in this category.4 If you decide on this approach, I would suggest switching from gemfibrozil to fenofibrate, as this is less likely to produce rhabdomyolysis when given in combination with statins.
Footnotes
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Do you have a clinical question? Send it to docnews{at}diabetes.org.
References
2. Foster GD, Wyatt HR, Hill JO, McGuckin BG, Brill C, Mohammed BS,
Szapary PO, Rader DJD, Edman JS, Klein S: A randomized trial of
low-carbohydrate diet for obesity. N Engl J Med 348: 2082–2090, 2003.
3. O'Brien T, Nguyen TT, Zimmerman BR: Hyperlipidemia and diabetes mellitus. Mayo Clin Proc 73:969–976, 1998.[Medline]
4. Diabetes Atorvastin Lipid Intervention (DALI) Study Group: The
effect of aggressive versus standard lipid lowering by atorvastatin on
diabetic dyslipidemia: the DALI study: a double-blind, randomized,
placebo-controlled trial in patients with type 2 diabetes and diabetic
dyslipidemia. Diabetes Care 24:1335–1341, 2001.
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