Diabetes Core Update – June 2015

American Diabetes Association Podcast
Released: May 24, 2015
Hosts: Dr. Neal Skolnik & Dr. John Russell

Episode Overview

This episode discusses five recently published research articles relevant to clinicians treating diabetes, focusing on cardiorespiratory fitness and incident diabetes, the relationship between incretin-based therapies and pancreatitis, the impact of macronutrients on insulin needs, and genetic responses to exercise. Dr. Neal Skolnik and Dr. John Russell guide listeners through these studies, offering both clinical interpretation and practical applications for patient care.

Key Discussion Points and Insights

1. Cardiorespiratory Fitness and Incident Diabetes

[01:39–02:52]

• Study:

  • 46,000+ patients without diabetes at baseline; followed after treadmill stress testing (FIT Project).
  • Mean age: 53; 52% men; 27% African American.
  • Median follow-up: 5.2 years; 6,851 new diabetes cases (14%).

• Findings:

  • Achieving >12 METs reduced risk of incident diabetes by 54% compared to those with <6 METs.
  • This protective effect was consistent across all ages, sexes, races, obesity statuses, hypertension, and hyperlipidemia.

• Clinical Insight:

  • Dr. Skolnik emphasized:

    "If you're going to pick one intervention in life to prevent anything, including diabetes, it's going to be exercise."
    (Dr. Neal Skolnik, 02:52)

  • Fit individuals, even if obese, had lower diabetes risk than unfit non-obese individuals.
  • Reinforces the critical role of exercise irrespective of demographic or health backgrounds.

2. Incretin-based Therapies and Pancreatitis: Liraglutide Review

[02:52–07:07]

• Study:

  • Data pooled from Novo Nordisk liraglutide clinical trials (Phase 2/3, up to April 2013).
  • Total exposure: 5,000 patient-years for liraglutide; 1,300 for comparators.
  • 8 cases of acute pancreatitis with liraglutide (1.6 per 1,000 PY); 1 case with comparator (0.7 per 1,000 PY).
  • Most liraglutide cases had other risk factors for pancreatitis or occurred >6 months after drug initiation.

• Clinical Insight:

  • Dr. Russell advised caution but not alarm:

    "I probably wouldn't pick incretin-based therapies to start with [for someone with chronic pancreatitis], but...I probably would not have a super high worry about pancreatitis."
    (Dr. John Russell, 08:31)

  • Emphasized the need to consider GI side effects, but not necessarily avoid liraglutide due to pancreatitis concern alone.

3. Incretin-based Therapies and Acute Pancreatitis: Danish Population Study

[08:31–10:23]

• Study:

  • Nationwide case-control (Denmark; 2005–2012).
  • 12,000+ acute pancreatitis cases; 120,000+ controls.
  • Looked at use of GLP-1 agonists, DPP-4 inhibitors, and other antidiabetics.
  • Crude odds ratio of pancreatitis for incretin users: 1.36 (not significant); after adjustment, no increased risk.

• Clinical Insight:

  • Dr. Russell noted:

    "They didn't find that folks were any more likely to be on incretin-based therapy than other things..."
    (Dr. John Russell, 10:23)

  • Early-stage antidiabetic use (any class) somewhat linked with pancreatitis, but not attributable just to incretin drugs.
  • Conclusion: No clear elevated risk of pancreatitis with incretin therapies.

4. Macronutrients and Postprandial Glucose in Type 1 Diabetes

[10:23–12:54]

• Study:

  • Systematic review of 7 studies each on fat and protein, plus data on glycemic index.
  • Sought to determine effects of meal composition on postprandial glucose and insulin dosing.

• Findings:

  • Fat: Late postprandial hyperglycemia seen; early reduction in glucose post-eating (<3 hrs).
  • Protein: Protein-rich meals with same carb content as low-protein meals required more insulin.
  • Key takeaway: High-fat/protein meals increase insulin requirements despite equal carbohydrate count.

• Clinical Insight:

  • Dr. Skolnik summarized:

    "It questions our carb-centric model...both carbohydrates, proteins and fats in aggregate come together to determine both glucose response and insulin needs."
    (Dr. Neal Skolnik, 12:54)

  • Noted practical impact:

    "...that big rib eye I had the other night can increase insulin requirements by more than two fold."
    (Dr. Neal Skolnik, 12:54)

  • Stressed complexity of true insulin-diet matching and value of educators/dietitians in care teams.

5. Genetic Response to Low-Intensity Exercise

[12:54–16:19]

• Study:

  • 14 overweight, glucose-intolerant adults in a 4-month, unsupervised walking program.
  • Outcomes: Changes in glucose tolerance, waist circumference, work capacity, mRNA expression of mitochondrial markers.

• Findings:

  • Only those whose glucose tolerance normalized showed improved waist/work capacity and meaningful gene expression changes.
  • Non-responders showed no such improvements.

• Clinical Insight:

  • Dr. Russell related:

    "If you can change and go from being a diabetic to a non-diabetic at a cellular level, we can show changes that hopefully will make a long term outcome in our patients."
    (Dr. John Russell, 17:32)

  • Compared to neuroplasticity and asthma remodeling; changes occurred at a cellular (molecular) level with behavioral intervention.

Notable Quotes and Memorable Moments

• On the impact of exercise:

  "If you're going to pick one intervention in life to prevent anything, including diabetes, it's going to be exercise."
  (Dr. Neal Skolnik, 02:52)

• On choosing therapy in pancreatic risk:

  "I probably wouldn't pick incretin-based therapies to start with [in patients with pancreatitis] but ... I probably would not have a super high worry about pancreatitis."
  (Dr. John Russell, 08:31)

• On insulin dosing and macronutrients:

  "...that big rib eye I had the other night can increase insulin requirements by more than two fold."
  (Dr. Neal Skolnik, 12:54)

• On cellular changes with exercise:

  "If you can change and go from being a diabetic to a non diabetic at a cellular level, we can show changes that hopefully will make a long term outcome in our patients."
  (Dr. John Russell, 17:32)

Timestamps for Important Segments

• Cardiorespiratory fitness & diabetes incidence – 01:39–02:52
• Liraglutide & pancreatitis risk (clinical trials) – 02:52–07:07
• Incretin therapies & pancreatitis (Danish population study) – 08:31–10:23
• Macronutrients & insulin needs in type 1 diabetes – 10:23–12:54
• Gene expression & exercise response – 12:54–16:19

For Further Reading

Visit www.diabetesjournals.org for more information and links to the articles discussed in this episode.