Clinical Briefs

By Louis Kuritsky, MD

Toenail Chromium in Men With Diabetes and Cardiovascular Disease

At one time in the nutrition literature, chromium (CRM) was known as glucose tolerance factor. The role of CRM in glucose homeostasis was further corroborated by studies of Asians with diets high in polished rice (and hence, low in chromium) whose abnormal glucose metabolism was restored by CRM repletion. Because CRM intake is difficult to quantify, alternative metrics for CRM nutriture status include toenail chromium levels (T-CRM). Previous case-control data indicates that a low T-CRM is associated with increased risk of cardiovascular disease in the general population.

A group of participants in the Health Professionals Follow-up Study (n = 37,737) provided toenail clippings which were stored for analysis of trace elements. A cross-sectional analysis divided subjects into men with diabetes, diabetes and established cardiovascular disease, and healthy controls at baseline. Subjects were followed over approximately 10 years to assess incident cardiovascular disease.

At baseline, healthy men had the highest T-CRM, followed by diabetics, and then diabetics with evident cardiovascular disease. Additionally, incident cardiovascular disease was greater in men with the lowest levels of T-CRM.

In persons with frank CRM insufficiency (which is generally not seen in the United States except for recipients of total parenteral nutrition inadequately balanced with chromium) CRM supplementation is clearly beneficial.

Whether CRM intake should be increased in any other group remains unknown.

Rajpathak M, et al. Diabetes. Care. 2004;27(9):2211-2216.

Combination of Fenofibrate and Rosiglitazone and HDL Cholesterol

The primary focus of lipid control, even amongst diabetics, remains the LDL level, since most accumulated data provides good support for improvement in cardiovascular outcomes subsequent and proportional to LDL reduction. HDL levels may be an even more potent predictor of cardiovascular outcomes, but have generally remained a secondary target, perhaps to some degree since pharmacotherapy specifically designed to and indicated for enhancement of HDL are lacking.

Thiazolidinediones (TZD), like rosiglitazone and pioglitazone are usually associated with favorable changes in HDL. Fibrates (eg, fenofibrate, gemfibrozil) are also often associated with favorable HDL changes, especially in the face of high triglycerides. It was anticipated then, that the combination would be equally, if not more, favorable for HDL levels.

Patients on combination TZD + fibrate were compared with controls on fenofibrate alone. Whereas fibrate alone produced a mean change of 19% increase in HDL, combination therapy produced a 20-33% decrease in HDL!

The finding of unfavorable effects upon HDL when fibrate is combined with TZD is both unexpected and inexplicable. This small study (n = 33) will require further confirmation in a larger population, but suggests a perspicacious eye by clinicians in monitoring HDL levels in persons on combination therapy with TZD and fibrate.

Normen L, et al Diabetes Care. 2004;27(9):2241-2242.

Outcomes for Patients with Diet-Controlled Diabetes

The United Kingdom Prospective Diabetes Study (UKPDS) is the landmark clinical trial which forms the foundation for treatment of persons with type 2 diabetes (DM2). UKPDS showed that treatment with metformin, a sulonylurea, or insulin reduced microvascular complications of DM2. According to this communication by Hippisley-Cox and Pringle, some clinicians in the United Kingdom identify a group of DM2 patients with mild diabetes who are felt to require only a minimum of interventions, such as diet alone.

To study this phenomenon, a cross-sectional study of 253,000 UK patients was performed which included 8,626 diabetics. Amongst this population of diabetics, 31.3% (2,700) had DM2 treated with no pharmacologic agents, hence identified as diet only.’ Only a minority of all DM2 patients had had microalbuminuria testing (14.5%), retinal screening (9%), or screening for neuropathy (4.9%). For DM2 patients registered as diet only,’ diabetic monitoring procedures were performed even less frequently than for those on pharmacotherapy. For instance, likelihood of A1c monitoring was 71% less amongst diet only’ DM2.

This UK population survey revealed that almost one-third of DM2 is managed by diet alone, accompanied by much less frequent monitoring of nephropathy, neuropathy, and retinopathy than is optimal.

Hippisley-Cox J, Pringle M. Lancet. 2004;363:423-428.

Dr. Kuritzky, Clinical Assistant Professor, University of Florida, Gainesville, is Associate Editor of Internal Medicine Alert.