Managing Diabetes: First Things First, or Vice Versa

SOURCE: Abdul-Ghani M, DeFronzo RA. Is it time to change the type 2 diabetes treatment paradigm? Yes! GLP-1 RAs should replace metformin in the type 2 diabetes algorithm. Diabetes Care 2017;40:1121-1127.

In the absence of contraindications or medication intolerance, metformin has been recommended as the initial treatment choice for patients with type 2 diabetes mellitus (T2DM) for more than a decade. This advice arose from a combination of favorable metformin attributes, including cost, tolerability, safety, and (albeit limited) a relatively favorable cardiovascular profile. But the winds of change are suggesting a potential reconsideration.

Although reduction of microvascular adverse events in T2DM is well-established with “older” antidiabetic agents (e.g., sulfonylureas, metformin, insulin), the authors of this publication argue that our scope of focus for choosing optimum medications should include both efficacy in correcting hyperglycemia as well as the ability of pharmacologic intervention to address the currently recognized basic pathophysiologic defects of T2DM.

Accordingly, glucagon-like peptide-1 (GLP-1) receptor agonists (albiglutide, dulaglutide, exenatide, liraglutide, lixisenatide) demonstrate an attractive “better fit.” That is, the four cardinal activities of GLP-1 receptor agonists: glucose-dependent insulin secretion, which minimizes the risk of hypoglycemia; glucose-dependent glucagon inhibition, which blocks excess glucagon while maintaining responsiveness of glucagon to hypoglycemia; improved satiety, potentially empowering more effective adherence to healthful dietary restrictions; and delayed gastric emptying, reducing postprandial glucose excursions. These provide complementary activities that address more of the basic pathophysiologic defects of T2DM than most other agents. Finally, members of the class of GLP-1 receptor agonists recently have been shown to reduce cardiovascular events. Together, these attributes suggest GLP-1 receptor agonists might be an appropriate initial treatment for T2DM, supplanting metformin.


Considering Routine Preoperative Lab Tests for Elective Surgery

SOURCE: Martin SK, Cifu AS. Routine preoperative laboratory tests for elective surgery. JAMA 2017;318:567-568.

Many U.S. clinicians may be unfamiliar with the U.K.’s National Institute for Health and Care Excellence (NICE) agency. Since 1999, NICE has been a world-recognized leader in the development of guidelines for management of disorders such as hypertension, dyslipidemia, and other epidemiologically important topics. Recently, NICE provided recommendations about which laboratory tests (if any) might be considered routinely appropriate preoperatively for elective surgery. The rationale for providing this guidance stems from the observation that, historically, there have been an excessive number of pre-op tests performed that not only provide no benefit for patient outcomes, but actually may cause harm because of unnecessary expense as well as need for follow-up of incidental (usually irrelevant) abnormal findings.

For example, recommendations pertinent to “intermediate surgery” (i.e., inguinal hernia repair, tonsillectomy and adenoidectomy, knee arthroscopy) in essentially healthy individuals are to eliminate preoperative testing entirely. Less healthy individuals, such as those with a severe systemic disease (American Society of Anesthesiologists Grade 3 or Grade 4), should undergo pre-op renal function testing only.

For patients with symptomatic cardiovascular or renal disease, the guidelines call for a complete blood count. Space limitations preclude a comprehensive review of the full contents of this document, which may be accessed readily online.

The authors of the guideline acknowledged a very limited literature from which to draw evidence-based conclusions, and encourage further definitive research on this topic.


Measuring Urine Calcium in Nephrolithiasis Patients

SOURCE: Song L, Maalouf NM. 24-hour urine calcium in the evaluation and management of nephrolithiasis. JAMA 2017;318:474-475.

Most kidney stones contain calcium, often comprised of calcium oxalate (responsible for up to 80% of cases). Prevention of stone recurrence focuses on dietary interventions, pharmacologic interventions, and hydration. Since stone recurrence is related linearly to the level of calcium in the urine, with no “floor” to this relationship (that is, progressively lower urinary calcium is associated with proportionately lower risk for recurrence), it is valuable to identify the level of urinary calcium excretion in patients with nephrolithiasis and provide interventions to reduce urinary calcium.

Currently, the threshold of urinary calcium defined as “hypercalciuria” is > 300 mg/day in men or > 250 mg/day in women. A more gender-agnostic metric is based on body weight: > 4 mg/kg/day for either gender is considered hypercalciuric. Since studies using so-called “spot urine” measurements have indicated poor correlation with 24-hour specimens, the only accurate way to determine urinary calcium excretion is to perform the 24-hour urine measurement.

High sodium content in the diet increases calcium excretion in the urine, so sodium restriction may be beneficial. Thiazide diuretics reduce urinary calcium excretion and are useful when dietary and hydration steps are insufficient.