Diabetes Core Update – July 2016

Podcast Date: June 24, 2016
Hosts: Dr. Neil Skolnik & Dr. John J. Russell
Main Theme:
A concise review of the latest clinically relevant diabetes articles published in the ADA’s journals, focusing on research with implications for practice. The hosts discuss six recently published studies spanning bariatric surgery outcomes, novel medications, tech innovations in type 1 diabetes, risk of disability, neurobiological effects of sugar, and the long-term benefits of intensive glycemic control.

1. Bariatric Surgery & Diabetes Remission

Article: Type 2 Diabetes Remission Rates Following Laparoscopic Gastric Bypass and Gastric Banding (Diabetes Care)
Segment: [00:55 – 03:44]

• Study Design: Observational cohort comparing Roux-en-Y gastric bypass and laparoscopic gastric banding in obese patients with type 2 diabetes over 3 years.
• Key Findings:
  • After 3 years, ~66% of Roux-en-Y patients vs. ~33% of gastric banding patients achieved diabetes remission.
  • Greater post-surgical weight loss predicted higher remission rates for both procedures.
  • Even after controlling for weight loss, Roux-en-Y yielded nearly double the remission rate of banding.
  • Additional baseline predictors: lower initial weight, greater fasting C-peptide, lower leptin/fat mass ratio, and lower baseline hemoglobin A1c without insulin use.
• Clinical Insight:
  • Dr. Russell (03:44):
    "If it was some other type of surgical procedure, I think more and more people would be going towards it. ... Having a Roux-en-Y procedure translated to a larger percentage of people being cured of their diabetes than a band procedure with the same amount of weight loss."
• Takeaway: Roux-en-Y bypass is more effective for diabetes remission than banding, independent of weight loss; vital info for patient counseling regarding surgical options.

2. Glucagon Receptor Antagonist for Type 2 Diabetes

Article: Randomized, Double-Blind, Placebo-Controlled Phase 2 Trial of LY2409021 (Diabetes Care)
Segment: [03:44 – 06:49]

• Background: LY2409021 (GRA) is a new oral glucagon receptor antagonist designed to lower glucose.
• Study Design: Adults with type 2 diabetes were randomized to three doses of GRA or placebo for 12 weeks.
• Results:
  • All GRA groups showed significant A1c reduction compared to placebo (up to –0.83%).
  • Mild, reversible elevations in serum transaminases (liver enzymes) were seen.
  • Low risk of hypoglycemia; adverse events were similar to placebo.
• Clinical Insight:
  • Dr. Skolnik (06:49):
    "Glucagon is like the quiet cousin of insulin… So it really fits in as an important part of the ominous octet." "This really seems like an exciting potential area of a class of medicines. It has good effect on A1c. It doesn't have a lot of hypoglycemia.”
• Takeaway: GRA shows promise as an addition to diabetes therapy, especially for patients needing oral medications with low hypoglycemia risk; further studies needed on safety, especially liver effects.

3. Outpatient Artificial Pancreas in Young Children

Article: Wearable Artificial Pancreas in Five–Nine Year Olds (Diabetes)
Segment: [06:49 – 09:29]

• Study Design: Outpatient, open-label, randomized, crossover trial of artificial pancreas vs patient-managed sensor-augmented pump (SAP) in 5–9-year-olds.
• Findings:
  • Artificial pancreas cut overnight hypoglycemia risk to zero (vs 2.2% of time in SAP).
  • Slightly less time in target glucose (57% vs 63%).
  • Higher mean overnight glucose (169 mg/dL vs 147 mg/dL).
• Clinical Insight:
  • Dr. Russell (09:29):
    "Hypoglycemia is a huge issue … This product seems superior to the insulin pump technology, especially overnight. … This would certainly be something that would kind of ease the minds of parents."
• Takeaway: Wearable artificial pancreas offers major safety benefit overnight for young children, with a tradeoff in slightly higher glucose levels; represents major technology advancement with significant future potential.

4. Diabetes and Years of Disability

Article: Lifetime Lost to Disability in Adults ≥50 With/Without Diabetes (Diabetes Care)
Segment: [09:29 – 12:12]

• Study Design: Prospective national survey (Health and Retirement Study), 20,000+ adults.
• Key Stats:
  • From age 50, those with diabetes died 4.6 years earlier and developed disability 6-7 years earlier than non-diabetics.
  • People with diabetes spent 1–2 more years disabled.
  • Men with diabetes were disabled for ~20–24% of remaining life vs 12–16% without diabetes.
• Clinical Insight:
  • Dr. Skolnik (12:12): "People with diabetes have an incredibly higher rate of disability after middle age … disability earlier and for a much longer period of time."
    • Control of micro/macrovascular risks and intensive lifestyle modification (as shown in Look AHEAD trial) can reduce disability years.
• Takeaway: Diabetes greatly accelerates and prolongs disability in aging adults; emphasizes the importance of risk factor control and behavioral interventions.

5. Brain Response to Glucose/Fructose in Obese Adolescents

Article: fMRI Brain Response After Sugary Drink in Obese vs Lean Youth (Diabetes)
Segment: [12:12 – 15:12]

• Study Design: fMRI assessment of brain perfusion after glucose/fructose ingestion in obese vs lean adolescents.
• Major Findings:
  • Obese adolescents had decreased activation in prefrontal cortex (executive function) and increased activation in hypothalamus (appetite center) compared to lean controls after glucose.
  • In lean adolescents, glucose increased prefrontal cortex activity with no change in hypothalamus.
  • Obese adolescents had blunted satiety hormone suppression and higher insulin after glucose.
• Clinical Insight:
  • Dr. Russell (15:12): “The adolescent young adult brain is still … developing until we're 25. … If this is something very dangerous to young people, we're not going to be as interested in allowing our kids to start soda at an earlier age."
    • Discussion of soda consumption trends and public health interventions (taxes, restrictions).
• Takeaway: Neurobiological responses to sugar differ by weight status in youth, potentially influencing lifelong sugar cravings and obesity risk; could impact public health policies on sugary drinks.

6. Lasting Impact of Intensive Glycemic Control (ACCORD Eye Study)

Article: Persistent Effects on Retinopathy of Intensive Glycemic Control (Diabetes Care)
Segment: [15:12 – 18:40]

• Context: Follow-up of ACCORD trial, comparing standard vs intensive glycemic control, BP, and lipid interventions on diabetic retinopathy progression.
• Results:
  • Retinopathy progression: 5.8% (intensive) vs 12.7% (standard) for glycemic control; no benefit for BP or lipid arms.
  • The “legacy effect” confirmed—the benefit of early intensive control persists years after treatment groups stop differing.
• Clinical Insight:
  • Dr. Skolnik (18:40): "Early treatment, early intensive treatment, has an effect on both macro and microvascular outcomes for years to come even after the groups are no longer … separated with regard to effect."
• Takeaway: Intensive early glucose management has durable benefits in reducing retinopathy progression—“legacy effect”—highlighting importance of early, aggressive control.

Notable Quotes & Memorable Moments

• On Bariatric Surgery:
  • "Having a Roux-en-Y procedure translated to a larger percentage of people being cured of their diabetes than a band procedure with the same amount of weight loss." – Dr. John Russell [03:44]
• On Glucagon Antagonists:
  • "Glucagon is like the quiet cousin of insulin … an important part of the family but no one is really familiar with." – Dr. Neil Skolnik [06:49]
• On Artificial Pancreas for Kids:
  • "This would certainly be something that would kind of ease the minds of parents." – Dr. John Russell [09:29]
• On Disability Risk:
  • "People with diabetes have an incredibly higher rate of disability after middle age." – Dr. Neil Skolnik [12:12]
• On Brain and Soda Policy:
  • "Our brain is still developing for 25. … Perhaps if this is something very, very dangerous to young people, we’re not going to be as interested in allowing our kids to start soda at an earlier age." – Dr. John Russell [15:12]
• On Legacy Effect:
  • "Early intensive treatment has an important effect for years to come." – Dr. Neil Skolnik [18:40]

Summary Table of Articles

| Article Topic | Journal | Main Takeaway | Segment | |---------------------------------------------|--------------|---------------------------------------------------------------------|----------| | Bariatric surgery for diabetes remission | Diabetes Care| Roux-en-Y superior to banding (remission, independent of weight) | 00:55 | | Glucagon receptor antagonist (GRA) | Diabetes Care| Promising oral med, lowers A1c, little hypoglycemia | 03:44 | | Artificial pancreas in young children | Diabetes | Reduces hypoglycemia overnight, promising for parents/kids | 06:49 | | Diabetes and years of disability | Diabetes Care| Diabetes shortens disability-free years, increases time disabled | 09:29 | | Brain response to sugar in obese youth | Diabetes | Obese youth's brains react differently to sugar; policy implications| 12:12 | | Lasting effect of intensive glycemic control| Diabetes Care| Legacy effect reduces retinopathy years later | 15:12 |

For more details and links to each article, visit www.diabetesjournals.org

Podcast Take-Home Message:
Ongoing clinical research continues to evolve the management of diabetes: from surgical strategies with metabolic benefits surpassing weight loss, to emerging therapeutics and technologies that target glucose with less hypoglycemia, to public health and lifestyle interventions with durable impacts on patient outcomes and quality of life. Early and aggressive intervention matters—for both individual and population health.