Clinical Briefs in Primary Care
The relationship of FPG and A1c to diabetic retinopathy
Source: Cheng YJ, et al. Association of A1C and fasting plasma glucose levels with diabetic retinopathy prevalence in the U.S. population. Diabetes Care 2009;32:2027-2032.
The idea that A1c might be a reasonable metric to make the diagnosis of diabetes has been kicking around for more than a decade. Only very recently has there been advocacy from the ADA that A1c may be an acceptable method for diagnosis of diabetes (A1c ≥ 6.2%); a primary reason for this shift in perception is the widespread adoption of a nationally standardized A1c testing method. Ultimately, diagnosis is intended to go beyond simply categorizing an individual as diabetic or non-diabetic; rather, it is intended to predict risk for important complications of diabetes like retinopathy.
The NHANES (National Health and Nutrition Examination Survey) is a cross-sectional sampling of non-institutionalized civilian adults. From the NHANES 2005-2006 study population, a group of adults age ≥ 40 years had assessment of retinopathy, A1c, and fasting plasma glucose (FPG).
There was a steep increase in frequency of retinopathy at an A1c ≥ 5.5%. Although a similar increased risk was seen at a FPG of 126 mg/dL, overall, the A1c was a better predictor than FPG. Since A1c may be obtained whether or not the subject has fasted, it may become a more convenient (as well as more sensitive) method than FPG for identifying risk of retinopathy.
Getting the most bang for your buck with lipid measurement
Source: The Emerging Risk Factors Collaboration. Major lipids, apolipoproteins, and risk of vascular disease. JAMA 2009;302:1993-2000.
The emerging risk factors collaboration collected data from prospective observational studies of persons without CV disease at baseline (n = 69 studies, with 302,430 participants). Lipid fractions measured in these studies included LDL, HDL, apo B, and apo A1. Risk for incurring CV endpoints was stratified for each lipid fraction.
Triglycerides have always been the lipid fraction demonstrating the weakest association to CVD endpoints. In this data set, although the unadjusted hazard ratio for triglycerides demonstrated increased hazard, adjusted hazard ratios were not convincing. In contrast, subjects with the lowest HDL levels showed an almost 3-fold greater hazard ratio for CV events than those in the highest third. The ratio of apo B:apo A1 was also an important CV risk predictor.
Interestingly, measurement of total cholesterol, HDL, apo B, and apo A1 in the non-fasting state did not appear to appreciably alter their predictive value. Sufficient information for risk prediction, according to these data, is obtained by simply measuring cholesterol levels (total and HDL). Additionally, the authors were not able to identify any significant additional CV risk prediction by adding triglyceride levels to their calculations.
The simplicity of focusing upon total and HDL cholesterol, and being able to use non-fasting results, may enable clinicians to more readily gather predictive information on a wider population of patients.
Nortriptyline, gabapentin, or both for neuropathic pain
Source: Gilron I, et al. Nortriptyline and gabapentin, alone and in combination for neuropathic pain: A double-blind, randomised controlled crossover trial. Lancet 2009;374:1252-1261.
Neuropathic pain (NPN), such as post-herpetic neuralgia or diabetic peripheral neuropathic pain, often requires what has been described as rational polypharmacy: the combination of multiple agents in an attempt to gain maximum therapeutic advantage while minimizing adverse effects. Both nortriptyline and gabapentin have achieved some success in modulation of NPN as monotherapy. Since the mechanism of action of these agents is complementary, a trial of their combination has intellectual appeal. When choosing among antidepressants for analgesic effects, norepinephrine re-uptake inhibition appears to be a critical component. Hence, SSRIs have minimal effect, but tricyclics (e.g, amitriptyline, nortriptyline), SNRIs (e.g., duloxetine, venlafaxine), and highly selective norepinephrine re-uptake inhibitors (e.g., milnacipran) effectively reduce pain.
Combination nortriptyline and gabapentin provided significantly greater pain reduction than either agent alone. No serious adverse effects were seen in either mono- or combination therapy. Clinicians are already commonly applying combination therapies to neuropathic pain syndromes; it is gratifying to encounter sound evidence supporting this practice.
Which insulin regimen for type 2 diabetes
Source: Holman RR, et al. Three-year efficacy of complex insulin regimens in type 2 diabetes. N Engl J Med 2009;361:1736-1747.
The most recently published ADA/EASD consensus algorithm for management of type 2 diabetes (DM2) suggests that when the combination of metformin and lifestyle is insufficient to control diabetes, either sulfonylurea (if close to goal) or insulin is the most well-validated next step. Because there are many different insulins to choose from, the clinician may be uncertain whether basal insulin (i.e., detemir, glargine, NPH), prandial insulin (i.e., regular insulin or rapid-acting insulin analog), or biphasic insulin (a combination containing a basal as well as prandial insulin) should be preferred.
Holman et al performed a 3-year trial in DM2 subjects (n = 708) not at A1c goal with the combination of metformin and a sulfonylurea. Subjects were randomized to biphasic insulin aspart (BIA) bid, prandial insulin aspart (PIA) tid, or insulin detemir (DET) qd (some received detemir bid).
At 3 years, there was no statistically significant between-group difference in A1c attained. Hypoglycemia was least frequent in the DET group, and most common in the PIA cohort. Weight gain was least in the DET group, and greatest in the PIA group.
All regimens were successful in attaining goal A1c. Because hypoglycemia and/or weight gain are often deal breakers for our patients, basal insulin regimens may be preferred.
Cardioprotective effects of ACE inhibitors in African American men
Source: Papademetriou V, et al. Protective effects of angiotensin-converting enzyme inhibitors in high-risk African American men with coronary heart disease. J Clin Hypertens 2009;11:621-626.
The hope trial convinced many experts that midlife adults (age ≥ 55 years) with existing vasculopathy (history of CAD, CVD, diabetes and CV risk factors) will have improved outcomes on an ACE inhibitor (ramipril, to be specific). There is controversy about whether African Americans achieve similar risk reduction as other ethnicities; for instance, in the SOLVD CHF trial, retrospective analysis suggested less benefit for some endpoints in African Americans.
Papademetriou reviewed electronic records from the Washington, DC, VA Medical Center to study African American study subjects who had CAD documented by catheterization (n = 810). Subjects were parsed into those who had vs had not been treated with an ACE inhibitor.
Over a study period of 3-10 years (mean, 6.8 years), the relative risk reduction for CAD mortality was more than 30% in those treated with ACE inhibitors. All-cause mortality was 80% higher in African American patients who had not been treated with ACE inhibitors. Because many African American patients have relatively low renin levels, some clinicians have doubted whether CV benefits would be readily achieved with ACE inhibitors. This data analysis suggests substantial benefit from ACE inhibitor treatment in African Americans with CAD.
Missed opportunity: Aldosterone antagonists in heart failure
Source: Albert NM, et al. Use of aldosterone antagonists in heart failure. JAMA 2009;302:1658-1665.
The seminal rales trial (randomized Aldactone Evaluation Study), in which patients with NYHA Class III-IV systolic heart failure received either aldactone or placebo in addition to standard-of-care treatment (e.g., ACE inhibitors, beta blockers, digoxin) indicated that the utilization of this well tolerated, inexpensive treatment could reduce mortality by as much as 30%.
One might anticipate that such benefits would result in widespread utilization of aldosterone antagonists in heart failure.
Albert et al reviewed data from more than 200 U.S. hospitals, encompassing 43,625 patient admissions for heart failure over the 2005-2007 time period. By this time, the RALES data were more than 5 years old. Contraindications to this life-saving treatment are few, with hyperkalemia being the most common.
According to their analysis, less than 33% of patients with heart failure who were eligible for treatment with an aldosterone antagonist (i.e., without contraindications) received one. With proper monitoring, aldosterone antagonist therapy reduces risk, is safe, and is well tolerated. Although aldosterone antagonist use improved over time (from a baseline rate of 28% to an end-of-study rate of 34%), much opportunity of reduction of mortality was missed.
The relationship of FPG and A1c to diabetic retinopathy; Getting the most bang for your buck with lipid measurement; Nortriptyline, gabapentin, or both for neuropathic pain; Which insulin regimen for type 2 diabetes; Cardioprotective effects of ACE inhibitors in African American men; Missed opportunity: Aldosterone antagonists in heart failureSubscribe Now for Access
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