Clinical Briefs

By Louis Kuritzky, MD, Clinical Assistant Professor, University of Florida, Gainesville. Dr. Kuritzky is a consultant for GlaxoSmithKline and is on the speaker's bureau of GlaxoSmithKline, 3M, Wyeth-Ayerst, Pfizer, Novartis, Bristol-Myers Squibb, AstraZeneca, Jones Pharma, and Boehringer Ingelheim.

Aspirin for all? Not so fast....

Source: Ogawa H, et al. Low dose aspirin for primary prevention of atherosclerotic events in patients with Type 2 diabetes. JAMA 2008;300:2134-2141.

The syllogistic process that led us all to accept the utility of ASA in prevention of CVD in diabetics seemed innocent enough: a) ASA reduces CV events in persons with CVD, and b) diabetes is considered a CV risk equivalent; therefore, c) ASA must reduce CV events in persons with diabetes.

Things might not be as simple as they appear. First, despite the quite consistent advocacy for ASA to reduce CV events in persons without known CVD (i.e., primary prevention), such primary prevention has never been shown to reduce mortality. Second, although adult diabetics older than age 40 have similar or even greater risk of sustaining a myocardial infarction than a non-diabetic who has already had an MI, the mechanisms inducing MI might be different in diabetics than non-diabetics; we cannot assume that just because aspirin benefits one population, it will indeed benefit another population whose background risk factors differ (for instance, diabetics typically have smaller, more dense, more atherogenic LDL than non-diabetics).

Ogawa et al published a multicenter prospective randomized trial of ASA (81-100 mg/d) vs placebo in adult, Japanese Type 2 diabetics (n = 2539). None of the subjects had sustained a known CV event, and all were free of clinically manifest PAD at baseline. The primary endpoint of the trial was a composite of fatal and nonfatal CVD events, ACS, new angina, and TIA.

After a follow-up of 4.37 years (median), although there was a trend towards reduced atherosclerotic events in the ASA group, the results were not statistically significant. The conclusion of the authors: "....low-dose ASA as primary prevention did not reduce the risk of CV events."

White coat hypertension: Not so innocent in Type 2 diabetes

Source: Kramer CK, et al. Impact of white coat hypertension on microvascular complications in Type 2 diabetes. Diabetes Care 2008;31:2233-2237.

The preponderance of evidence about the impact of hypertension (HTN) on CV and renal (CV&R) endpoints is based upon measurement of BP in the office: so-called casual or office BP. For more than 3 decades, HTN specialists have recognized that office BP is only one way to view the burden of HTN. Indeed, either 24-hr ambulatory BP monitoring or even home BP self-monitoring correlates better with CV&R endpoints than office BP. One explanation for the inaccuracy of office BP is that some patients' BP rises when in the medical setting, yet remains essentially normal at other times. This phenomenon has been called white coat hypertension (WCH), and although some examiners have pointed out that WCH portends enhanced proclivity to develop frank hypertension, and ought to be considered of greater importance when target organ damage is present, others have opined that WCH exists, but if BP is otherwise normal, no intervention (save enhanced vigilance for the development of frank HTN) is necessary.

Kramer et al studied a population of Type 2 diabetics (DM2) comparing the prevalence of nephropathy and retino-pathy in persons with WCH (n = 46) as compared to normotensives (n = 117).

DM2 subjects with WCH had a 2 times greater prevalence of nephropathy and 2.7 times greater prevalence of retinopathy (adjusted for confounders). Although the pathogenetic role played by WCH remains controversial, the associations discerned in this observational study merit concern.

Relationship between vitamin K and insulin resistance

Source: Yoshida M, et al. Effect of vitamin K supplementation on insulin resistance in older men and women. Diabetes Care 2008;31:2092-2096.

Clinicians traditionally associate vitamin K (VitK) with the coagulation system, especially as it relates to antithrombotic therapy with agents like coumadin. Although a biologically plausible mechanism remains to be identified, a recent observational study indicated a positive linear relationship between VitK and insulin sensitivity: Higher amounts of either dietary or supplemental VitK was associated with higher insulin sensitivity. Similarly, one small study indicated better glucose disposal (through better insulin sensitivity) after VitK supplementation in healthy men.

To investigate this phenomenon further, Yoshida et al studied healthy, non-diabetic adults (age 60-70; n = 355) by comparing levels of insulin resistance before and 36 months after VitK supplementation or placebo.

At the trial end, no changes were seen in levels of insulin resistance among female subjects. On the other hand, male subjects evidenced a statistically significant improvement in insulin resistance. Whether VitK supplementation might have a salutary effect in diabetics or others with overt insulin resistance syndromes (e.g., impaired glucose tolerance, obesity, polycystic ovary syndrome) remains to be clarified.