Diabetes Core Update – May 2014 (Released April 21, 2014)

Hosts: Dr. Neil Skolnik, Dr. John Russell
Focus: Review and discussion of six recent articles from ADA journals impacting diabetes care

Episode Overview

In this episode, Dr. Neil Skolnik and Dr. John Russell present and discuss six clinically relevant articles from the ADA’s journals, offering physicians and healthcare professionals nuanced insight into current trends in diabetes treatment, metabolic health in obesity, cardiovascular risk, and emerging research into the microbiome. The discussion is practical, evidence-driven, and oriented toward making these findings actionable in daily clinical practice.

Key Discussion Points & Insights

1. Trends in Antidiabetic Drug Use in the U.S. (2003–2012)

Source: Diabetes Care (March 2014)
Segment: [01:49–03:04]

• Metformin Use: Nearly doubled during the period, with 60.4 million prescriptions dispensed in 2012.
• DPP-4 Inhibitors and GLP-1 Agonists: Sitagliptin saw the largest uptake among new drugs, while use of rosiglitazone dropped precipitously due to safety concerns.
• Combination Therapy Patterns: Up to half of secondary agents were prescribed without concurrent metformin.
• Sulfonylurea Use: Remains strong due to affordability, despite higher risk for hypoglycemia.

Quote:
"Point number two is that use of metformin doubled over that almost 10 year period. That's important because metformin clearly is the recommended first line agent by the American Diabetes Association." — Dr. Neil Skolnik [03:04]

Clinical Relevance: Reminds providers to prioritize metformin as first-line therapy and underlines the medical community's rapid response to drug safety alerts.

2. Second-Line Agents for Glycemic Control: Are Newer Agents Better?

Source: Diabetes Care
Segment: [03:04–07:05]

• Study Model: Compared sulfonylureas, DPP-4 inhibitors, GLP-1 agonists, and insulin following metformin monotherapy for type 2 diabetes, focusing on life years, QALYs, and costs.
• Findings: All approaches yielded similar life expectancy and QALYs. Sulfonylureas had significantly lower cost per QALY and slightly delayed insulin dependence.
• Practical Considerations: Newer agents have potential safety advantages (lower hypoglycemia risk), but overall benefit difference is modest.

Quote:
"If you look at the quality adjusted life years between sulfonylurea and the most expensive regimen, it was probably about $150 a year which doesn't seem like kind of a night and day difference in dollars." — Dr. John Russell [07:05]

Clinical Relevance: Reinforces individualized treatment decisions, weighing cost, risk, and patient factors.

3. Predictors of Metabolically Healthy Obesity in Children

Source: Diabetes Care (Feb. 2014)
Segment: [07:05–10:05]

• Study Overview: Examined children (8–17 years, ≥85th BMI percentile) in a weight management clinic, classifying them based on insulin resistance or cardiometabolic risk factors.
• Prevalence: About 31% were metabolically healthy by insulin resistance, 21% by other risk factors.
• Predictors: Lower dietary fat intake was linked to healthier insulin profiles, while physical activity predicted better cardiometabolic health.

Quote:
"About a third of children fall into the metabolically healthy category. Interestingly, who falls into that category depends how you define it." — Dr. Neil Skolnik [10:05]

Clinical Relevance: Introduces and contextualizes the concept of metabolically healthy obesity in pediatrics, highlighting modifiable lifestyle factors.

4. Hypoglycemia and Risk of Cardiac Arrhythmias in Type 2 Diabetes

Source: Diabetes
Segment: [10:05–13:56]

• Research Design: 25 insulin-treated type 2 diabetics (with CVD or risk factors) monitored via continuous glucose sensors and ambulatory ECGs.
• Key Findings: Noted significant increases in arrhythmias during nocturnal hypoglycemia, including bradycardia, ectopy, and QTc prolongation (over 500 ms), often in asymptomatic episodes.
• Clinical Concern: Heightened risk in older adults and those with autonomic neuropathy, particularly during nighttime.

Quote:
"If an older diabetic patient has a cardiac dysrhythmia and dies in the night, no one really knows why...this would be another thing to me to say, maybe I need to be a little bit more careful in putting our older patients who are at risk for arrhythmias...in situations where they're going to have hypoglycemia." — Dr. John Russell [13:56]

Clinical Relevance: Urges careful individualization of glycemic targets in high-risk populations to minimize hypoglycemia-related cardiac risk.

5. Obesity and Gut Microbiota – Experimental Transfer Study

Source: Diabetes (Jan. 2014)
Segment: [13:56–17:03]

• Experiment: Transferred gut flora from obese-prone rats to germ-free mice; recipients developed increased weight gain, hyperphagia, and metabolic dysregulation.
• Pathways: Observed changes in satiation signaling, adiposity, gut permeability, and inflammation.
• Significance: Provides “Koch’s postulate”-like evidence for the role of microbiota in obesity pathogenesis.

Quote:
"What this study is essentially doing is using Koch's postulate...and does that with regard to obesity." — Dr. Neil Skolnik [17:03]

Clinical Relevance: Offers groundbreaking support for considering gut microbiome interventions in future obesity and metabolic disease management.

6. Alcohol Consumption, Vascular Complications, and Mortality in Type 2 Diabetes

Source: Diabetes Care
Segment: [17:03–21:44]

• Data from ADVANCE Trial: Moderate drinkers saw reduced cardiovascular events (17%), microvascular complications (15%), and all-cause mortality (13%) versus abstainers; effect stronger for wine.
• Heavy Drinking: Associated with dose-dependent increases in both cardiovascular events and mortality.
• Mechanisms: Benefits may relate to moderate consumption's anti-inflammatory effects or slight HDL increase; mechanisms not fully understood.

Quote:
"Certainly people having one or two drinks a day for a man or one drink a day for a woman certainly could have some cardiovascular benefits. This particular study said that wine did so much better...but certainly wine has been around for as long as people have been around, and it makes people happy. ...So drink up." — Dr. John Russell [21:44]

Clinical Relevance: Suggests potential benefits of moderate alcohol intake for T2DM patients, but emphasizes the need for individualized recommendations given alcohol’s risks.

Memorable Quotes & Moments

• On rapid changes in drug safety:
  "...the medical community really does respond importantly and quickly to safety concerns." — Dr. Neil Skolnik [03:04]

• On practical drug selection:
  "...coming back to what the ADA says is we really should individualize our care for our patients." — Dr. John Russell [07:05]

• On groundbreaking microbiome research:
  "What these authors did that is truly unique is looked at whether there can be a relationship between gut flora and ... cause weight gain." — Dr. Neil Skolnik [17:03]

• On nuanced alcohol advice:
  "...it becomes very hard for us to recommend alcohol to patients because certainly we see the amount of mortality and morbidity that alcohol causes in many, many patients lives." — Dr. John Russell [20:03]

Timestamps for Key Segments

• [01:49] U.S. Antidiabetic Drug Use Trends
• [03:04] New vs. Old Second-Line Agents for T2DM
• [07:05] Metabolically Healthy Obesity in Kids
• [10:05] Hypoglycemia & Arrhythmia Risk
• [13:56] Gut Microbiota and Obesity Transmission
• [17:03] Alcohol, Vascular Risk, and Mortality

Final Takeaways

• Metformin remains the backbone of type 2 diabetes therapy, but real-world prescribing often includes older agents for cost reasons and newer agents for improved safety profiles.
• Individualization remains the cornerstone of diabetes care, incorporating patient risk, tolerability, and cost.
• Advances in understanding metabolic health, arrhythmia risk, and the gut microbiome may shape future clinical strategies.
• Moderate alcohol consumption may offer benefit in type 2 diabetes but is complicated by broader public health risks.