Glucose Variability in T2DM: Ready for Prime Time?

SOURCE: Kovatchev B, Cobelli C. Glucose variability: Timing, risk analysis, and relationship to hypoglycemia in diabetes. Diabetes Care 2016;39:502-510.

The benefits of glycemic control in type 2 diabetes (T2DM) include improved microvascular status (retinopathy, neuropathy, nephropathy) and better quality of life. Striving for progressively better control of hyperglycemia is typically associated with an increased incidence of hypoglycemia, consequences of which can range from transient unpleasant central nervous system dysfunctions and signs of autonomic activation to coma and death.

While A1c is an accurate measure of mean glucose levels, two individuals with the same A1c level can present markedly different excursions of glucose above and below the mean, which generates A1c. Typically, higher glucose variability above and below the mean reflects more episodes of greater hyperglycemia as well as hypoglycemia, which may not be readily discerned through just examining A1c. Continuous glucose monitoring, as well as frequent self-monitoring of blood glucose, have created a window of observation to detect glucose variability.

What’s the practical yield of attending to glucose variability? There is still some disagreement about the best way to measure variability, since hyperglycemic excursions typically are much less concerning than similar excursions toward hypoglycemia, so it may be necessary to use separate metrics for hypo- vs. hyperglycemic variability. Additionally, computations to assess glucose variability are not paper-and-pencil simple — they require computational tools. However, it has been shown that, as an example, at the same A1c level, glucose variability was substantially less in patients taking oral agents who added a GLP1-RA (e.g., exenatide) vs. those who added insulin glargine. While not yet a tool for routine practice, analysis of glucose variability appears to hold promise for the future.

Improvements in Pain and Physical Function After Bariatric Surgery

SOURCE: King WC, Chen JY, Belle SH, et al. Change in pain and physical function following bariatric surgery for severe obesity. JAMA 2016;315:1362-1371.

The metabolic benefits of bariatric surgery are prompt, significant, and — for the most part — durable. Many patients who suffer from severe obesity also experience joint pain (especially knee and hip) and limited mobility. What kind of effect does bariatric surgery have on those endpoints?

King et al reported on outcomes among patients with severe obesity (median body mass index = 49.5 kg/m2) who underwent bariatric surgery (n = 2,221). The outcomes of interest were bodily pain and physical function, as measured by SF-36. To be considered “improved,” patients had to meet the threshold for minimal meaningful increment of change, rather than just achieve statistical significance alone.

At one year, the majority of surgical subjects demonstrated clinically meaningful improvements in pain and physical function. Specifically addressing those already experiencing disability due to knee (n = 633) or hip (n = 500) pain at baseline, more than 75% of each group reported symptomatic improvement at one year, which was durable through three years of observation.

In addition to the favorable metabolic changes (e.g., remission of diabetes, prevention of diabetes) associated with bariatric surgery, meaningful improvements in physical function and disability due to joint pain occur promptly and are durable through at least three years of follow-up.

Two Thumbs Down for COPD Screening

SOURCE: U.S. Preventive Services Task Force. Screening for chronic obstructive pulmonary disease: US Preventive Services Task Force recommendation statement. JAMA 2016;315:1372-1377.

Since none of the currently available pharmacologic treatments for COPD can be considered disease modifying (that is, alters the course of progression or reduces mortality), even if we were to identify COPD early, why would we have any confidence that treatment would be beneficial? Despite numerous clinical trials demonstrating improvements in lung function, activity, frequency of exacerbations, and symptoms in COPD patients, none of the medications have been able to achieve the lofty threshold of disease modifying. Only smoking cessation and oxygen at late-stage disease have been found to be disease modifying.

Upon review of the currently available evidence, the U.S. Preventive Services Task Force (USPSTF) assigned a level “D” recommendation to the issue of screening asymptomatic adults for COPD, which means, “the USPSTF recommends against the service. There is moderate or high certainty that the service has no net benefit or that the harms outweigh the benefits.”

Within its Recommendation Statement, the USPSTF included recognition of one potentially valuable role of screening with spirometry: enhancing quit rates among smokers. But even then, results of clinical trials are mixed. Only one study that presented pulmonary status using the technique of lung age had an effect on smoking cessation rates; other studies presenting spirometry results in traditional methodology did not improve smoking cessation outcomes.

These USPSTF recommendations should not be misconstrued to reflect on the utility of spirometry for symptomatic individuals.