Diabetes Core Update – August 10, 2013

Podcast: Diabetes Core Update
Date: August 15, 2013
Hosts: Dr. Neil Skolnik & Dr. John J. Russell
Episode Focus: Latest research and clinical insights from ADA journals, with emphasis on incretin therapy’s effects and exercise training’s impact on quality of life in type 2 diabetes.

Main Theme and Purpose

This episode reviews significant new studies published in American Diabetes Association journals, focusing on:

• The impact of incretin-based therapies on pancreatic structure and safety (with highlights from both research and expert commentary)
• A debate on the risks and benefits of incretin therapies, including cancer and pancreatitis concerns
• The effect of exercise interventions on quality of life in people with type 2 diabetes

Targeted toward clinicians, the discussion aims to unpack the real-world relevance of these findings for diabetes management.

Key Discussion Points & Insights

1. Incretin Therapy and Pancreatic Expansion (00:56–06:22)

Study Reviewed:

• Source: Diabetes, July 2013
• Objective: Evaluate changes in the pancreas (exocrine and endocrine compartments) with incretin therapy in humans.

Findings:

• In diabetics treated with incretin therapy, there was a 40% increase in pancreatic mass (02:14).
• Observed increases in exocrine cell proliferation and dysplasia.
• Marked alpha cell hyperplasia, glucagon-expressing microadenomas, and in some, a neuroendocrine tumor.
• Beta cell mass: Decreased by 60% in diabetic subjects, but a sixfold increase seen in incretin-treated subjects—with continuing diabetes.
• Immunohistochemical changes indicated more cells co-staining for insulin and glucagon, especially with incretin therapy.

Expert Commentary:

“On the one hand, there's a bit of excitement...that incretin therapy may increase pancreatic mass...Early information about that made people think it could actually reverse diabetes. The problem is that increased pancreatic mass doesn't necessarily mean it’s functional mass.”
— Dr. Neil Skolnik [03:11]

Safety Concerns:

• Increased alpha cell mass and ductal hyperplasia may underlie the higher reported risk for pancreatitis.
• Presence of microadenomas and microscopic dysplasia is potentially a warning signal; unclear if these progress to cancer.
• No definitive answer on incretin therapy as carcinogenic—compared to estrogen's effect on breast cancer: may increase risk in predisposed individuals.

“We don't know whether these microadenomas simply are there or whether they will progress to cancer...this adds to the current state of the art and it raises some concerns for which currently there isn't a clear conclusion.”
— Dr. Neil Skolnik [05:50]

2. Point–Counterpoint: Safety of Incretin-Based Therapies (06:22–13:17)

A. Risks and Concerns (Dr. John Russell):

• GLP-1 effects: Increases insulin secretion, inhibits glucagon release, slows gastric emptying.
• Receptors found in pancreas, thyroid, bone, kidneys.
• Proposed mechanism: Exocrine proliferation may cause ductal occlusion → increased pancreatitis risk.
• Epidemiological studies: Some show increased acute pancreatitis in users, especially in first year with agents like exenatide.
• Core question: Are low-level, undetected cases of pancreatitis leading to dysplasia and neoplasia?
• Raises issue of diabetic drugs moving quickly to market, with safety concerns surfacing later.

“Even when safety concerns are being initially raised, they are being discounted and not taken seriously as they should be.”
— Dr. John Russell [08:02]

B. Benefits Outweigh Risks? (Summary of Dr. Michael Nauck's Argument):

• Pancreatitis: Data signals increased risk, but may be confounded by reporting bias and unclear diagnostic clarity (e.g. mild amylase/lipase elevations misread as pancreatitis).
• Cancer Risks: Early evidence of dysplasia/microadenomas—no proven patient-level risk yet.
• Thyroid cancer: Animal studies show increased risk, but no direct human evidence.
• Cardiovascular profile: Possible, though not statistically significant, improvements in BP (2–5 mmHg), body weight.
• Therapeutic benefits: Lower hypoglycemia risk, weight loss, durable A1C lowering, generally well tolerated with appropriate renal dosing.

“While the benefits expected or proven from using incretin-based medications seem to be substantial...the potential harms and risks typically refer to rare events and are discussed in a controversial manner.”
— Dr. Neil Skolnik, quoting Dr. Nauck [13:07]

3. Clinical Perspective: Practical Pros & Cons of Incretin Therapies (13:17–14:58)

Benefits:

• No hypoglycemia
• Weight loss
• Comparable or improved blood pressure lowering
• Good compatibility with other antidiabetic agents
• 1–2% drop in A1C
• Weekly dosing possible (e.g. exenatide)

Drawbacks:

• GI side effects (withdrawal rate 3–8%)
• Ongoing concern about pancreatitis and cancer risks
• Requires renal dose adjustments
• Slight heart rate increase

“Every one of the medicines we’re going to give people for diabetes carries its own bag of hammers. And suddenly I think we’re finding some new things from these classes of medicine that at least we need to be cognizant of as data comes in.”
— Dr. John Russell [14:39]

4. Exercise Training and Quality of Life in Type 2 Diabetes (14:58–16:48)

Study Reviewed:

• Source: Diabetes Care, July 2013 (HEART-D trial)
• Type: 9-month RCT comparing aerobic, resistance, combined exercise versus control in adults with T2D

Key Results:

• All exercise modalities improved physical quality of life versus control.
• Resistance training: Best improvement in sense of bodily pain.
• Aerobic/combined: Most improvement in physical functioning.
• Combined exercise: Greater boosts in mental health, vitality compared to control.

“It’s nice now to see clarity that [exercise] has a generalized good effect on quality of life in patients with diabetes. What do we really care about? We care about how we feel day to day.”
— Dr. Neil Skolnik [16:48]

Practical Takeaway:

• Encourage both aerobic and resistance training for optimal quality-of-life outcomes in T2D.

Notable Quotes & Memorable Moments

• On clinical uncertainty:

  “Does this class of medicine suddenly increase the progression of microadenomas onto cancer? We don’t know at this point.”
  — Dr. Neil Skolnik [05:36]

• On rapid drug adoption:

  “Is this another diabetic medicine that was rushed through market that had safety concerns that emerged post hoc...?”
  — Dr. John Russell [07:57]

• On patient-centered outcomes:

  “If you’re going to start an exercise program, it probably makes sense to do some aerobic exercise and some resistance exercises in order to yield the greatest benefit...”
  — Dr. Neil Skolnik [17:19]

Timestamps for Important Segments

| Topic | Start | |-------------------------------------------------------------------------|----------| | Introduction and Article Overview | 00:56 | | Incretin Therapy and Pancreatic Changes | 00:56 | | Clinical Implications & Discussion of Pancreatitis/Cancer Risks | 03:11 | | Point–Counterpoint: Risks of Incretin Therapies | 06:22 | | Point–Counterpoint: Benefits of Incretin Therapies | 08:12 | | Synthesis of Risk–Benefit Profile of Incretin Therapies | 13:17 | | Exercise, Quality of Life, and Clinical Takeaways | 14:58 | | Wrap-Up on Exercise Recommendations | 16:48 |

Summary

This episode synthesizes cutting-edge findings about incretin-based therapies—balancing promising benefits (hypoglycemia avoidance, weight loss, A1C reduction) against evolving concerns (pancreatitis, dysplasia, possible cancer risk). The hosts urge vigilance but not alarm, emphasizing ongoing research and careful, individualized patient management. The episode closes by affirming robust evidence for the physical and mental quality-of-life benefits of both aerobic and resistance exercise in type 2 diabetes, encouraging clinicians to promote comprehensive lifestyle interventions alongside medication.