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.

I've Heard of TIA, But What The Heck is a TNA?

The formal classification of cerebrovascular disorders as we know it today is only a few decades old. One of the categories named in the original 1975 classification system was "transient attacks of neurological dysfunction," comprised of transient ischemic attacks (TIA) and transient non-localizing or mixed neurologic syndromes, generally considered to be more benign. The authors have suggested that transient neurologic attacks (TNA) be subdivided into focal TNA (= TIA, usually of ischemic vascular origin) and non-focal or mixed TNA (nf/m-TNA), of diverse etiology (including, but not limited to, vascular origin). It has been observed that in clinical practice nf/m-TNA and TIA are often grouped together by primary care clinicians and neurologists alike, attesting to the sometimes "fuzzy borders" distinguishing these entities. At the same time, nf/m-TNA has generally been regarded as more "benign," and less likely to be associated with subsequent increased stroke risk.

To better study TNA, adults aged 55 years or older (n = 6,062) were followed for 60,535 person years (about 10 years each, on average). During that time a TNA occurred on 548 individuals; the incidence of nf/m-TNA (4.4/1000 person-years) and TIA (4.7/1000 person-years) was very similar. Prognostically, the hazard ratio for subsequent stroke was increased both for victims of TIA (HR = 2.4) and nf/m-TNA (HR = 1.56-2.48). TNA that are non-focal or mixed have a less benign future than has been widely appreciated.

Bos MJ, et al. JAMA. 2007;298:2877-2885.

Advancing Insulin Therapy in Type 2 Diabetes Previously Treated with Glargine Plus Oral Agents

When oral agents alone fail to attain glycemic goals, clinicians have numerous therapeutic options for advancing glucose control, the most common of which (currently) is addition of basal insulin (eg, insulin glargine, NPH, insulin detemir), followed by targeted prandial insulin for specific excessive post-meal glucose excursions (basal/prandial treatment). Rather than adding prandial insulin to glargine (in addition to oral agents), substituting multi-dose premix for basal/prandial insulin has some advocates, and has not yet been studied in a comparative trial.

Type 2 diabetics (n=374) unable to attain satisfactory control with oral agents plus basal insulin alone were randomly assigned to thrice daily premix insulin (Humalog Mix 50/50 or Humalog Mix 75/25) or glargine/lispro. At 24 weeks, the A1C attained was superior in the basal/prandial group to the premix group (6.78% vs 6.95%, p = 0.021). Since the trial was designed to test the non-inferiority of premix compared to basal/prandial with a prespecified margin of 0.3%, premix was NOT confirmed as non-inferior to basal/prandial. Similarly, the percent of patients achieving goal A1C < 7.0 was greater for basal/prandial than premix (69% vs 54%, p = 0.009); if the A1C target was the more strict <6.5%, basal/prandial still maintained advantage (50% achieved vs 35% on premix).

Rosenstock J, et al. Diabetes Care 2008;31:20-25.

A Relationship Between Linolenic Acid and Neuropathy in Diabetics

Over 25% of mid-life diabetics have peripheral neuropathy (DPN), which is categorized as one of the microvascular consequences of diabetes based upon its putative origin in dysfunction of the vasonervorum. Good glycemic control has been found to forestall and prevent progression of neuropathy, but not reverse it. The search for etiologic factors in development of DPN has come to consider linolenic acid because of an identified relationship between high dietary linolenic acid intake and lesser macrovascular disease.

The NHANES (National Health and Nutrition Examination Survey) has periodically provided diverse US population data since 1971. In their most recent data set (1999-2004), an analysis of dietary linolenic acid in relation to DPN was examined.

Mean daily intake of linolenic acid (based upon 24-hour dietary recall report) was remarkably lower in persons with DPN (1.25 g/d) than diabetics without DPN (16.82 g/d).

This is the first investigation to characterize the inverse association between linolenic acid and DPN, and as such requires replication and further elucidation of mechanisms by which linolenic acid might be protective.

Tao M, et al. Diabetes Care 2008;31(1):93-95.