Erectile Dysfunction is a CVD Predictor
Schouten BWV, et al. Int J Impotence Research. 2008;20:92-99.
Erectile dysfunction (ED) most commonly reflects endothelial dysfunction of the corpora cavernosa. Because the risk factors for ED have been determined to be the same as those for cardiovascular disease (CVD), the concept that ED might actually be a predictor for CVD has garnered some support.
The Krimpen Study is a prospective observational study of men (n=3,924) between the ages of 50-75 residing in Krimpen, the Netherlands. From this population, all men aged 50-70 years responded to a question about erectile function. Men who were free of CVD at baseline (n=1,248) were followed for a mean of 6.3 years to compare the rate of CVD events in men reporting ED vs those without. Framingham risk scores were calculated at enrollment. Because this study sought to identify the relationship between ED and CVD, men with incident urologic disorders commonly associated with ED (eg, prostatectomy) were excluded.
After 7,945 person-years of follow up, the hazard ratio for CVD events among men with ED was 1.6 compared to men without ED at baseline. Men with the most severe ED had an even greater risk for CVD (hazard ratio = 2.6). The risk for CVD in this population was independent of Framingham risk score. This study confirms previous observations that ED is a predictor of CVD risk. Clinicians should address the CVD risk profile of men presenting with ED, even in the absence of other manifest vascular disease.
Does Traditional Thyroid Replacement (Levothyroxine) Adequately Restore T3?
Jonklaas J, et al. JAMA. 2008;299(7):769-777.
Most circulating triiodothy-ronine (T3) is created by peripheral conversion of levothyroxine (T4), although the thyroid gland does directly produce 15-20% of plasma T3. Hypothyroidism is generally treated solely with T4 replacement, providing sufficient substrate for conversion to T3 and to consistently restore the euthyroid state as measured by TSH normalization. Previous trials of "dual thyroid replacement" (combinations of T3 and T4) have not been convincingly advantageous. With post-thyroidectomy, even though TSH is normalized with levothyroxine monotherapy, the question remains whether T3 restoration is truly adequate, given that the thyroid gland is no longer present to create its typical 15% of total T3. One way to assess this is to compare the T3 levels in subjects pre-and-post thyroidectomy who receive levothyroxine replacement.
Prior to thyroidectomy, 50 euthyroid subjects had measurement of T3 and T4. After sufficient levothyroxine replacement to restore euthyroidism (as assessed by TSH < 4.5 mIU/L), serum T3 and T4 were compared to pre-surgical levels.
Compared to pre-surgery baseline, levothyroxine replacement resulted in essentially unchanged T3 levels. However, the T4 levels attained, while still normal, were 33% higher than pretreatment.
T3 levels provided by traditional levothyroxine treatment are comparable to those seen in the euthyroid state; the authors reflect that the higher (albeit still therapeutic) T4 levels seen with levothyroxine replacement may be necessary to ensure adequate T3.
Accuracy of Modern Glucose Meters
Bergenstal RM. Insulin. 2008;3:4-14.
Both the AAFP and the ADA recommend self-monitoring of blood glucose (SMBG) as an integral component of overall diabetes disease management. Accuracy of SMBG must be assured in order to confidently modulate interventions effectively.
Because capillary blood (eg, fingerstick) glucose is 10-15% lower than venous plasma glucose, most monitors present their results corrected to venous glucose levels. The ADA criteria for accuracy suggest that future systems should provide results within 10% of reference standard within the glucose range of 30-400 mg/dL, although currently available devices are subject to a slightly more tolerant 15% variability.
A metric called the Clarke Error Grid (CEG) segments SMBG results as compared to a reference laboratory into multiple zones: Zone A includes clinically accurate results which should lead to clinically correct treatment; Zone B includes results that deviate by 20% or more from reference standards, but results so-obtained would result in no treatment change or benign treatment changes. Zones C, D, and E are misreadings of sufficient inaccuracy that they could result in meaningful inappropriate treatment.
Detailed results from 172 patients tested with the OneTouch Ultra 2 show that SMBG results fall within Zone A 99% of the time, and no results were in Zone C, D, or E. Similar findings have been determined for the Ascensia Confirm, the Liberty, the EasyTouch, and OneTouch Ultra.
The authors further explain the most common source of SMBG errors: user error. Fortunately, with improved patient education, most user error can be obviated. Clinicians should be reassured that when used properly, currently available SMBG devices are remarkably accurate and unlikely to lead to inappropriate treatment.
Nonpolypoid Colorectal Neoplasms
Soetikno RM, et al. JAMA. 2008;299(9):1027-1035.
The adenomatous polyp (ADP) is recognized as the primary predecessor of colon cancer (CCA), prompting management strategies to identify and remove ADP. Recently, it has been recognized that nonpolypoid neoplasms (NPN) can also evolve to CCA. Because of their nonpolypoid configuration (flat, slightly raised, or even slightly depressed), NPN are more difficult to identify by either traditional colonoscopy or CT methodology; hence, they are easily missed. Soetikno, et al assessed the prevalence of NPN in a cohort from the Veterans Administration Hospital in California who underwent elective colonoscopy (n=1,819).
Facility in the identification of NPN has not been part of the armamentarium of most traditionally-trained endoscopists in America. Hence, the investigators underwent training specifically directed towards NPN identification by Japanese endoscopists who are expert in this particular area (NPN has previously been described particularly in Japan).
From 1,819 colonoscopies, 42% of individuals had 1 or more neoplasms, of which 170 were NPN (9.35%). Although a minority of lesions, the NPN lesions were responsible for over half of the superficial carcinomas found. Recognition of the important pathologic contribution of NPN mandates enhanced skills by endoscopists for their identification.
Predictors of Disease Progression in Type 2 Diabetes
Pani LN, et al. Diabetes Care. 2008;31:386-390.
Although type 2 diabetes (2-DM) is generally a progressive disorder, there is great variation in rate of disease progression, allowing some patients to be managed with diet and exercise whereas others quickly require intensive lifestyle and pharmacotherapeutic regimens. There has been scant investigation into predictors of diabetes progression. To that end, patient data collected from 12 outpatient practices in eastern Massachusetts was utilized to study the factors associated with 2-DM progression. To be included in the data set (n=705), patients had to be diagnosed with 2-DM, but not yet using glucose-lowering medication. Progression was defined as either having to start pharmacotherapy or developing an A1c >7%.
At one year follow up, slightly over one-fourth of patients experienced disease progression. Age, weight, and baseline A1c were determined to be predictors after multivariate analysis.
For each 1-lb increase in weight, there was a 2% increase in risk of progression. Perhaps counterintuitively, for each decade of increased age, risk of progression was reduced 15%; this result supports recent observations that younger 2-DM patients tend to be more insulin deficient, compared to older individuals who are more often insulin resistant.
This information suggests that diabetic patients who are younger and tend to gain weight are at greatest risk of disease progression, and may merit more intense lifestyle management.
A Relationship Between Antidepressants and Diabetes
Rubin RR, et al. Diabetes Care. 2008;31:420-426.
In addition to the incidence of depression being 1.5-2 fold higher in diabetics than the general population, its morbid and mortal consequences are measurably greater. Data from the recently published Diabetes Prevention Program (DPP) allows investigation of the relationship between depression, antidepressant medications, or both, and diabetes.
A Beck Depression Inventory (BDI) was administered to 3,187 of the participants in the DPP at baseline and at each annual visit. All DPP enrollees also had impaired fasting glucose and impaired glucose tolerance but did not meet diagnostic criteria for type 2 diabetes.
Risk of progressing to diabetes was not associated with depression but was associated with use of antidepressants (greater than 2-fold increased hazard ratio). Analysis for specific types of antidepressant (eg, SSRI vs SNRI) did not provide insight that any one class of antidepressant was more (or less) likely to be associated with progression to diabetes. The mechanism by which antidepressants induced this greater risk is unclear.
These data suggest that at the stage of prediabetes, since antidepressant use has been associated with disease progression, maximization of non-pharmacotherapeutic intervention merits strong consideration.
Erectile Dysfunction is a CVD Predictor; Does Traditional Thyroid Replacement (Levothyroxine) Adequately Restore T3?; Accuracy of Modern Glucose Meters; Nonpolypoid Colorectal Neoplasms; Predictors of Disease Progression in Type 2 Diabetes; A Relationship Between Antidepressants and DiabetesYou have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
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