Clinical Briefs

By Louis Kuritzky, MD, Clinical Assistant Professor, University of Florida, Gainesville. Dr. Kuritzky is a consultant for Abbott, AstraZeneca, Boehringer Ingelheim, Daiichi, Sankyo, Forest Pharmaceuticals, Lilly, Novo Nordisk, Takeda.

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.

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 and colleagues 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.

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%.