Clinical Briefs
By Louis Kuritzky, MD, Clinical Assistant Professor, University of Florida, Gainesville
Dr. Kuritzky is a retained consultant for Boehringer Ingelheim, Daiichi Sankyo, Forest Pharmaceuticals,
Janssen, Lilly, Novo Nordisk, Pfizer, and Sanofi.
GERD Medications and B12 Deficiency
Source: Lam JR, et al. JAMA 2014;310: 2435-2442.
The consequences of vitamin b12 (B12) deficiency most commonly include neurologic (CNS and peripheral nervous system) and hematologic (megaloblastic anemia). Because the progression of symptoms and signs related to B12 deficiency can be subtle, yet extremely burdensome to patients, clinicians must maintain a high level of vigilance for circumstances in which B12 deficiency can predictably occur, such as alcoholism and malnutrition.
Use of proton pump inhibitors (PPIs) and histamine-type 2-receptor antagonists (H2RA) is widespread in the United States. In 2012, more than 150 million prescriptions were written for PPIs alone. These numbers underestimate use since OTC versions of PPIs are also available.
Absorption of B12 requires that it first be cleaved from its food protein source on entering the GI tract. Gastric acid is required to release B12 from food. Since PPIs and H2RAs reduce gastric acidity, it should come as no surprise that they might be associated with greater risk for B12 deficiency.
A case-control study using the population of the Kaiser Permanente Northern California Healthcare system provided the opportunity to compare PPI/H2RA use among persons confirmed to have B12 deficiency (n = 25,956) vs controls (n = 184,199).
Receiving a PPI prescription for ≥ 2 years was associated with a 65% increased odds ratio of B12 deficiency. Similarly, receipt of H2RA treatment for that same interval was associated with a 25% increased risk.
The benefits of PPI and H2RA treatment are often substantial. That B12 deficiency is more likely to occur when using long-term GERD treatments should not discourage their use, but rather, increase clinician vigilance for the possibility of B12 insufficiency, especially when potentially appropriate symptoms or signs appear.
Dietary Fish Intake and New Onset Diabetes
Source: Virtanen JK, et al. Diabetes Care 2014;37:189-196.
The cornerstones of diabetes prevention are healthy diet and maintenance of desirable weight. The most focus of diet has been the role of caloric restriction to improve glycemia in overweight and obese individuals. The Kuopio Ischemic Heart Disease Risk Factor Study (KIHD) provides an opportunity to evaluate the potential role of diet and new onset diabetes in Finnish men.
The observational data from KIHD included measurement of omega-3 polyunsaturated fatty acids (PUFAs) by dietary history. Long-chain omega-3 PUFA levels are considered to be a reliable indicator of the level of fish consumption in the diet.
Over an interval of almost 20 years, there was a linear inverse relationship between omega-3 PUFAs and incident type 2 diabetes. Men in the highest quartile of omega-3 PUFA enjoyed a 33% lesser likelihood of incident diabetes, adjusted for other risk factors. The mechanisms by which omega-3 PUFAs exert a protective effect on incident diabetes are not fully understood, especially since studies that examine fish (or fish oil supplements) have not detected any direct impact on glucose metabolism. On the other hand, because higher fish intake is associated with lesser adiposity, avoiding the diabetogenic effects of obesity may be an important contributor.
The Metabolic Impact of Low-Dose Thiazide Diuretics
Source: Mukete BN, Rosendorff C.
J Am Soc Hypertens 2013;7:454-466.
Hyperglycemia and hypokalemia are well-recognized consequences of thiazide diuretic (TZD) therapy. Both adversities appear to be dose-related, and since we currently generally use low-dose TZD for treatment of hypertension (the most common indication for TZD therapy), it is useful to identify its impact on metabolic parameters.
Mukete and Rosendorff performed a meta-analysis on clinical trial data of 17,947 subjects in whom potassium (K+) and glucose measurements were taken. Overall, the mean changes in both parameters compared to other treatments were modest: an increase of glucose of only 1.4 mg/dL and a decrease in K+ of 0.27 mEq/L.
The largest hypertension trial ever performed was the ALLHAT trial, which found that compared to the calcium channel blocker amlodipine or the ACE inhibitor lisinopril, diuretic therapy was associated with a small but statistically significant increased risk for new onset diabetes (8.1% vs 9.8% vs 11.6%, respectively). Although looking at mean changes of metabolic parameters, especially restricting the view to only low-dose thiazides, looks relatively reassuring, the fact that some outliers will still experience clinically relevant hypokalemia or hyperglycemia mandates our continued vigilance for both consequences during the course of long-term treatment.
