Podcast Summary: Diabetes Core Update – September 2016

Date: August 25, 2016
Hosts: Dr. Neil Skolnik & Dr. John Russell

Overview

In this September 2016 edition of the Diabetes Core Update, Drs. Neil Skolnik and John Russell review and analyze six recent articles published in ADA journals. Their discussion centers on clinically relevant research, focusing on hypoglycemia, gastric bypass, insulin absorption issues, new therapeutic options, and the timely intensification of diabetes therapy. The episode delivers practical insights for diabetes care providers by breaking down the latest evidence and implications for real-world patient management.

Key Discussion Points & Insights

1. Gastric Bypass and Hypoglycemia

Reference: Diabetes Care
Timestamp: 00:56–03:22

• Study Focus: Explores how gastric bypass alters symptoms and hormonal responses during hypoglycemia in obese, non-diabetic patients.
• Key Results:
  • Post-surgical patients had fewer hypoglycemic symptoms (symptom delta score dropped from 10 to 5).
  • There were notable reductions in glucagon, cortisol, catecholamine, and sympathetic responses to low blood sugar.
  • Incretin responses (GLP-1, GIP) were also muted post-surgery.
• Clinical Implications:
  • Post-gastric bypass patients may be at increased risk for asymptomatic hypoglycemia.
  • Medication choices should be carefully considered, particularly avoiding agents like sulfonylureas that increase hypoglycemia risk.
  • Practitioners need heightened awareness when treating these patients, especially regarding symptom monitoring and public safety (e.g., driving).
• Notable Quote:
  • “If we have had someone who has had a gastric bypass, I think we need to be smarter about the medicines that induce hypoglycemia...especially if people are having asymptomatic hypoglycemia who are doing things like driving, climbing ladders, etc.”
    —Dr. John Russell [03:10]

2. Lipohypertrophy’s Effect on Insulin Absorption

Reference: Diabetes Care
Timestamp: 03:22–06:16

• Study Focus: Examined insulin absorption and action when injected into lipohypertrophic tissue (LT) versus normal adipose tissue among type 1 diabetics.
• Key Results:
  • Insulin injected into LT absorbed less effectively, with greater variability.
  • Blood glucose spikes were higher and more delayed postprandially after LT injections.
  • Severe hyperglycemia and hypoglycemia were reported, depending on the injection site.
• Clinical Implications:
  • Large day-to-day glucose fluctuations in chronic insulin users may be due to injections into LT.
  • Education on site rotation and examination for LT is crucial.
  • Diabetic educators play an important role in helping patients avoid LT complications.
• Notable Quote:
  • “When you have a patient who doesn’t seem to be responding at all to increasing doses of insulin, we ought to think about lipohypertrophy…”
    —Dr. Neil Skolnik [06:45]

3. Hypoglycemia’s Association with Mortality and CVD in Type 1 Diabetes

Reference: Diabetes Care
Timestamp: 06:16–09:51

• Study Focus: Large, population-based analysis from Taiwan examining prior severe hypoglycemia as a risk factor for all-cause mortality and cardiovascular disease (CVD).
• Key Results:
  • Severe hypoglycemia within the past year doubled the risk for death and CVD (adjusted ORs: 2.7, 2.0).
  • Even distant hypoglycemic events (3–5 years prior) increased future risk.
• Clinical Implications:
  • Vigilance regarding hypoglycemia is needed even in young patients with type 1 diabetes.
  • Past hypoglycemic episodes, regardless of recency, identify higher-risk individuals.
  • Lack of A1c data is a limitation, but comorbidities (retinopathy, CVD) were predictive.
• Notable Quote:
  • “Prior episodes of hypoglycemia, even if it was four or five years ago, did put you at an increased risk going forward.”
    —Dr. John Russell [10:30]

4. Fixed-Ratio Combination Therapy: Lixilan (Lixisenatide + Insulin Glargine)

Reference: Diabetes Care
Timestamp: 09:51–13:42

• Study Focus: Assessed efficacy and safety of a titratable fixed-ratio combo (lixisenatide/insulin glargine) versus glargine alone in type 2 diabetics uncontrolled on metformin.
• Key Results:
  • Combination therapy was superior to insulin alone in reducing A1c (6.3% vs. 6.5%).
  • Benefits: improved postprandial glucose, weight loss (–1 kg vs. +0.5 kg), low hypoglycemia rates, mild GI side effects.
• Clinical Implications:
  • Offers potent glycemic efficacy while mitigating major side effects of monotherapy (weight gain with insulin, GI issues with GLP-1RAs).
  • Expands therapeutic options for patients failing oral therapies.
• Notable Quote:
  • “It really offers a very effective, very potent option that mitigates some of the most difficult side effects of either medicine alone.”
    —Dr. Neil Skolnik [14:04]

5. Roux-en-Y Gastric Bypass vs. Lifestyle/Medical Management in Mild–Moderate Obesity

Reference: Diabetes Care
Timestamp: 13:42–18:12

• Study Focus: Compared 3-year attainment of composite ADA goals (A1c, LDL, systolic BP) and diabetes remission between intensive lifestyle/medical therapy and added gastric bypass.
• Key Results:
  • Triple goal achieved in 28% of bypass group vs. 9% of lifestyle at 3 years.
  • Significant A1c reduction (to 6.7% in surgery vs. 8.6% in lifestyle/medical).
  • More sustained diabetes remission (17% full, 19% partial) in bypass group.
  • Weight loss greater with surgery (21% vs. 6%), but adverse events were more frequent.
• Clinical Implications:
  • Gastric bypass offers potent metabolic benefits, including in patients with BMI 30–35 and longstanding, harder-to-control diabetes.
  • Careful selection and attention to ongoing need for lipid/blood pressure management is important even after surgery.
• Notable Quote:
  • “For our diabetics who have higher A1Cs despite being on maximal medications whose BMIs are under 35, we really should consider [gastric bypass] in the future as a therapeutic option.”
    —Dr. John Russell [19:23]

6. Therapeutic Inertia After Metformin Failure

Reference: Diabetes Care
Timestamp: 18:12–22:50

• Study Focus: Examined time to therapy intensification and A1c target attainment in newly diagnosed type 2 diabetics failing metformin within the Cleveland Clinic health system.
• Key Results:
  • Early intensification (within 6 months) after metformin failure led to faster achievement of A1c goals (7, 7.5, 8).
  • Many patients still experienced significant delays.
• Clinical Implications:
  • “Clinical inertia”—delayed intensification—is common and suboptimal for glycemic management.
  • Early, proactive adjustment of medications, increased metformin dose, and education correlate with better glycemic outcomes.
  • Providers and patients alike can contribute to therapeutic inertia but must strive to overcome these barriers.
• Notable Quote:
  • “If you intensify therapy early…patients tend to do better. This is not a rocket science conclusion but is rocket science in the process of taking care of patients.”
    —Dr. Neil Skolnik [23:13]

Notable Quotes & Memorable Moments

• “I think we need to be mindful…maybe take our foot off the gas a little bit in achieving glycemic control in these patients [after gastric bypass].” —Dr. John Russell [03:15]
• “Lipohypertrophy are those nodules that can be felt under the skin in patients who have injected insulin for a long period of time…less absorption, as shown in this study.” —Dr. Neil Skolnik [06:28]
• “Our type 1 diabetics, we need to be mindful of hypoglycemia, even if we have not figured out the mechanism that leads to people dying.” —Dr. John Russell [11:30]
• “By combining the two agents…they were able to mitigate many of the difficulties with each one of the injectables alone.” —Dr. Neil Skolnik [13:54]
• “Perhaps we are going to look at our patients who have lower BMIs for being quicker to have them have a gastric bypass.” —Dr. John Russell [21:10]
• “Therapeutic inertia occurs both on patients point of view…[and] on our end as physicians.” —Dr. Neil Skolnik [24:32]

Episode Timestamps

• 00:56: Gastric bypass and hypoglycemia study
• 03:22: Lipohypertrophy and insulin absorption
• 06:16: Hypoglycemia, mortality, and CVD in type 1 diabetes
• 09:51: Lixilan fixed-ratio combination therapy
• 13:42: Gastric bypass vs. lifestyle/medical management outcomes
• 18:12: Intensification of therapy and clinical inertia
• 22:50: Take-home message on early therapy intensification

Summary Takeaways

• Increased surveillance is necessary for hypoglycemia—before and after gastric bypass, and in type 1 diabetes of all ages.
• Proper technique and site rotation are key for insulin users to avoid complications like lipohypertrophy.
• Fixed-ratio injectable therapies (GLP-1 + basal insulin) offer effective, patient-friendly alternatives.
• Early, decisive medication changes after metformin failure translate to faster goal achievement in type 2 diabetes.
• Providers should stay vigilant against clinical inertia and educate patients proactively.

For further reading and detailed study links, visit www.diabetesjournals.org.