Clinical Briefs in Primary Care

Immunochemical FOBT and low-dose aspirin

Source: Brenner H, et al. Low-dose aspirin use and performance of immunochemical fecal occult blood tests. JAMA 2010;304:2513-2520.

Immunochemical Fecal Occult Blood testing (i-FOBT) is becoming increasingly popular as a screening tool for colorectal cancer (CRC). At the same time, the number of persons taking long-term low-dose aspirin (ASA) for CV disease risk reduction is also increasing. Concern has been expressed that the predictable increase in GI bleeding associated with ASA would decrease the specificity of i-FOBT by increasing false positives. At the same time, it has been suggested that consequences of i-FOBT to detect upper GI bleeding may have been overestimated, since the globin chains detected by i-FOBT typically are degraded progressively during passage through the GI tract, and are hence less available for i-FOBT identification than bleeding more distal in the GI tract. Finally, utilization of ASA might also increase the risk of bleeding of CRC, thus enhancing likelihood of detection.

To assess the relationship between ASA, i-FOBT, and results of CRC screening, Brenner et al reported on almost 2000 adults who underwent CRC screening, 12% of whom were regular ASA users.

Sensitivity (the number of positive tests in persons confirmed to have advanced GI neoplasms) of i-FOBT was greater in ASA users than non-users. i-FOBT specificity (the number of negative tests in persons without advanced GI neoplasms) was minimally reduced.

Chronic low-dose ASA does not appear to compromise the ability of i-FOBT to detect advanced GI neoplasia, with a modest decrease in specificity.

Aerobic vs resistance exercise for type 2 diabetes

Source: Church T, et al. Effects of aerobic and resistance training on hemoglobin A1c in patients with type 2 diabetes. JAMA 2010;304:2253-2262.

Most persons with type 2 diabetes (DM2) are overweight or obese. Exercise is routinely advised for DM2, although whether a particular method of exercise has an advantage for optimization of glycemic control is not well defined.

Church et al compared the effects of aerobic exercise (AER), resistance training (RES), or the combination (AER + RES) vs placebo in previously sedentary mid-life DM2 adults (mean age = 56 years). Participants engaged in the prescribed activities for 9 months. The primary outcome was change in A1c from baseline.

At the conclusion of the trial, only the AER + RES provided statistically significant reduction in A1c compared to placebo; AER alone or RES alone did not.

It would be unfortunate if clinicians were to interpret this trial as indicating a lack of value of either AER or RES alone. All exercise groups had favorable changes in anthropomorphic metrics, and exercise has been shown to be associated with a favorable impact upon cardiovascular risk in large population studies, an effect that may be independent of glycemic effects.

Atrial fibrillation risk: Choose your parents wisely

Source: Lubitz SA, et al. Association between familial atrial fibrillation and risk of new-onset atrial fibrillation. JAMA 2010;304:2263-2269.

A familial component contributes to atrial fibrillation (a-FIB) risk, such that independent of other risk factors (e.g., hypertension), having a first-degree relative with a-FIB increases risk.

Using data from participants (n = 11,971) in the Framingham Heart Study, Lubitz et al examined the relationship between having a first-degree relative (sibling or parent) with a-FIB and subsequent development of a-FIB during an 8-year window of observation.

Subjects with a positive family history had an increased risk of a-FIB compared to those without a family history (5.8% vs 3.1% over 8 years). Risk increased further with the number of family members affected by a-FIB. The younger the age of a-FIB onset in a family member, the greater the increase in a-FIB risk.

Overall, having a positive family history for a-FIB increased risk of new-onset a-FIB by 40%. Of all risk factors for a-FIB, hypertension is responsible for the largest population-attributable risk; whether treatment of hypertension in persons with demonstrated increased risk for a-FIB because of family history might provide reduction in a-FIB risk remains to be determined.

The effects of obesity upon activity of short-acting insulin analogs

Source: Gagnon-Auger M, et al. Dose-dependent delay of the hypoglycemic effect of short-acting insulin analogs in obese subjects with type 2 diabetes: A pharmacokinetic and pharmacodynamic study. Diabetes Care 2010;33:2502-2507.

The most recent ADA/EASD algorithm for management of type 2 diabetes (DM2) indicates basal insulin as an appropriate next step if glycemic goals are not attained with metformin and lifestyle interventions. After fasting glucose levels are controlled on basal insulin regimens, it is common to use prandial bolus insulin (especially short-acting insulin analogs) if A1c goals have not been reached. The activity profile of short-acting insulin analogs has been established by trials in either lean healthy subjects or type 1 diabetics; neither population may be pharmacokinetically or pharmacodynamically concordant with DM2, and most are overweight or obese. To examine these issues, obese DM2 subjects (n = 7) received lispro insulin and were monitored for time to peak insulin concentration, maximal attained insulin concentration, and efficacy for reducing glucose.

Absorption of low-dose lispro (10 units) was similar in DM2 and controls, but its hypoglycemic effect was less in obese persons. At higher doses (30 units and 50 units), however, both absorption and efficacy were diminished in obese DM2 subjects. The authors challenge the current perceptions of the utility of short-acting insulin analogs in DM2, reminding us that the purpose of prandial insulin is to provide rapid rise and rapid glucose-lowering effects, both of which appear to be diminished in obese individuals. In any case, these data confirm that clinicians might anticipate proportionately less "bang-for-the-buck" as they up-titrate short-acting insulin analog doses in obese DM2.

Capitalizing on the second-meal effect in type 2 diabetes

Source: Chen JM, et al. Utilizing the second-meal effect in type 2 diabetes: Practical use of a soya-yogurt snack. Diabetes Care 2010;33:2552-2554.

It is probably not widely known that Mom was right — at least as it pertains to diabetes — that you should NOT skip breakfast. Why? Because of the "second-meal effect," a little-recognized physiologic response that can have a potentially favorable effect on glucose.

The way the "second-meal effect" works is like this: When breakfast is eaten, the degree of hyperglycemia seen after lunch is less than if the same amount of calories are given without having eaten breakfast. It has been suggested that the improved glucose level is related to a reduction in preprandial free fatty acids, which allows for greater storage of muscle glycogen during a second meal (and hence a greater disappearance of glucose from the plasma). This phenomenon occurs in both diabetic and non-diabetic individuals. Based upon this observation, Chen at al hypothesized that perhaps providing a pre-breakfast snack would reduce post-breakfast hyperglycemia.

Diabetic subjects (n = 10) were administered a snack of soya beans and yogurt 2 hours before breakfast. For scheduling convenience, the snack was administered at 8 am, and breakfast at 10 am.

Plasma glucose 2 hours after breakfast was significantly lower in the group who received the snack. Since postprandial glucose levels have been associated with adverse cardiovascular outcomes in diabetics, it might be both desirable and possible to manipulate post-meal hyperglycemia without using medications.

Seeking the best diet for weight-loss maintenance

Source: Larsen TM, et al. Diets with high or low protein content and glycemic index for weight loss maintenance. N Engl J Med 2010;363:2102-2013.

Identifying the "best" diet to achieve and maintain weight loss in overweight persons has been an elusive task. Even if a person is successful at reducing weight using a highly calorie-restricted diet over the short term, the choice of a preferred maintenance diet over the long term is ill-defined.

Larsen et al enrolled overweight adults who had successfully lost at least 8% of their initial body weight, and randomized them into diets based upon protein content and glycemic index. Five subgroups were thus defined based upon high or low protein (PRO) and glycemic index (GIN): high GIN + high PRO, high GIN + low PRO, low GIN + high PRO, low GIN + low PRO, and control). All subjects followed their respective diets for 26 weeks.

Both high PRO and low GIN were independently associated with lesser weight regain. Overall, adherence to diet and maintenance of weight loss was best with the high PRO + low GIN diet. It is possible that even greater benefit could have been achieved in relation to protein, because the actual separation of protein content between high PRO and low PRO of 5.4% was substantially less than the intended 12%.