Diabetes Core Update – August 2016

Podcast Date: July 25, 2016
Hosts: Dr. Neil Skolnik and Dr. John Russell
Main Theme:
This episode reviews the latest clinically relevant articles from the American Diabetes Association’s journals, focusing on genetics and “healthy” obesity, dietary fat composition in diabetes, advances in insulin therapy, technology-assisted weight loss, predictors of hypoglycemia, and the impact of weight loss (and regain) on cardiovascular risk.

Key Discussion Points & Insights

1. Genetic Evidence for “Healthy” Obesity

Timestamps: 01:41–02:44
Discussion:

• Study from the journal Diabetes explores the link between favorable adiposity genetic variants and reduced risk of type 2 diabetes, hypertension, and heart disease.
• Sample: Over 164,000 individuals from UK Biobank and other studies.
• Findings:
  • Individuals with the most favorable alleles had higher BMI/body fat but lower risk for diabetes (OR 0.83), hypertension (OR 0.935), and heart disease (OR 0.921).
  • Introduces genetic nuance to the “obesity paradox”—the observation that overweight individuals often have better mortality outcomes except at the highest BMIs.

Notable Quote:

“This study begins to explain some of that [obesity paradox]... People with well-defined genetic tendencies to accumulate fat in a healthy manner have a lower risk of mortality... This really suggests the difference between individualized medicine versus aggregate data...”
— Dr. Neil Skolnik (02:44)

2. Metabolic Effects of Monounsaturated Fats vs. High-Carbohydrate Diet

Timestamps: 02:44–06:10
Discussion:

• Diabetes Care meta-analysis compares how monounsaturated fatty acid (MUFA)-enriched diets fare against high-carb and polyunsaturated fatty acid diets in type 2 diabetes.
• Findings:
  • MUFA diets vs. high-carb: Lower fasting glucose, triglycerides, body weight (minus 3 lbs), systolic BP, higher HDL.
  • Mediterranean-style diets (high in MUFAs like olive oil, nuts, fish) consistently show benefit over typical Western low-fat/high-carb diets.

Notable Quote:

“A low-fat diet … does not do as well as a Mediterranean diet which is going to emphasize certain fatty acids... The Mediterranean diet really shows some prudence, probably for all of our patients.”
— Dr. John Russell (06:10)

3. Advancing Basal Insulin Therapy: Lixisenatide vs. Basal Plus/Basal-Bolus

Timestamps: 06:10–09:10
Discussion:

• The GetGoal Duo 2 trial compared adding lixisenatide (GLP-1 agonist) or insulin glulisine (bolus insulin) to basal insulin glargine.
• Findings:
  • A1C reduction was similarly significant in both strategies.
  • Lixisenatide resulted in less hypoglycemia, less weight gain, but more GI side effects.
  • Supports GLP-1 agonists as a preferable next step when basal insulin alone is insufficient.

Notable Quote:

“GLP1s are emerging as the option of choice for patients who are not controlled to goal on basal insulin alone, providing equal A1C decrease with less hypoglycemia and without the weight gain.”
— Dr. Neil Skolnik (09:10)

4. Text Messaging to Augment Lifestyle Modification for Weight Loss

Timestamps: 09:10–12:35
Discussion:

• Randomized controlled trial: English- and Spanish-speaking patients with prediabetes received either standard invitations to Diabetes Prevention Classes or the same, plus supportive text messages.
• Outcomes:
  • Modest but greater weight loss in text message group (2.6 lbs vs. 0.6 lbs in control).
  • 38% of intervention group reached 3% weight loss vs. 21% with usual care.

Notable Quote:

“We are really faced with a crossroads here in medicine… in medicine we are going to have to think about being more and more creative and using this amazing technology to get patients information that is going to change their behaviors...”
— Dr. John Russell (12:35)

5. Saxagliptin and Hypoglycemia Risk—SAVOR-TIMI 53 Trial Analysis

Timestamps: 12:35–15:56
Discussion:

• Large trial (16,000+ patients): Saxagliptin vs. placebo studied for hypoglycemia incidence.
• Key Risks for Any or Major Hypoglycemia: Saxagliptin use, long diabetes duration, baseline A1C<7, renal impairment, sulfonylurea/insulin use, advanced age, black race, lower BMI.
• Practice Implication: Even DPP-4 inhibitors (like saxagliptin), generally considered “safer”, can contribute to hypoglycemia, especially combined with sulfonylureas or in certain populations.

Notable Quote:

“Hypoglycemia has emerged over the last five years as a critical issue... severe hypoglycemia is related to both decreased cognition… and even increased… cardiovascular death.”
— Dr. Neil Skolnik (15:56)

6. Weight Loss, Weight Regain & Cardiovascular Risk—Look AHEAD Data

Timestamps: 15:56–20:02
Discussion:

• Analysis of weight patterns over 4 years in the Look AHEAD trial and their association with cardiovascular risk factors.
• Key Result:
  • Larger initial weight losses lead to more improvement in A1C, BP, HDL, and triglycerides at both years 1 and 4.
  • Even full weight regain does not negate all benefits—those with large early loss and regain still had improved A1C vs. non-losers.
  • Early interventions make a difference, supporting the idea that “front loading” benefits may be long-lasting.

Notable Quote:

“Even if it is a fleeting period of time when people have lost weight and are doing better, it does resonate down the line... It’s better to have loved and lost than never to have loved at all.”
— Dr. John Russell (20:02)

Memorable Quotes & Moments

| Quote | Speaker | Timestamp | |-------|---------|-----------| | “This really suggests the difference between individualized medicine or personalized medicine... versus the use of aggregate data...” | Dr. Neil Skolnik | 02:44 | | “The Mediterranean diet really shows some prudence, probably for all of our patients.” | Dr. John Russell | 06:10 | | “GLP1s are emerging as the option of choice for patients who are not controlled to goal on basal insulin alone...” | Dr. Neil Skolnik | 09:10 | | “We are going to have to think about being more and more creative and using this amazing technology to get patients information...” | Dr. John Russell | 12:35 | | “Severe hypoglycemia is related to both decreased cognition over time...and even increased... cardiovascular death.” | Dr. Neil Skolnik | 15:56 | | “It’s better to have loved and lost than never to have loved at all.” | Dr. John Russell (citing Tennyson) | 20:02 |

Timestamps for Key Segments

• 01:41 – Genetics of obesity and cardiovascular/diabetes risk
• 02:44 – Monounsaturated fats vs. carbs in diabetes diets
• 06:10 – Lixisenatide vs. bolus insulin with basal insulin in T2DM
• 09:10 – Text messaging and weight loss
• 12:35 – Saxagliptin (SAVOR-TIMI 53) and hypoglycemia risks
• 15:56 – Weight loss, regain, and long-term cardiovascular impact (Look AHEAD)

Takeaways for Clinical Practice

• Genetic factors may distinguish “healthy” vs. “unhealthy” obesity; precision medicine is key.
• Mediterranean diets, high in monounsaturated fats, offer clear benefits for T2D patients.
• GLP-1 agonists represent an effective, lower-risk next step after basal insulin failure.
• Technology—simple interventions like text messaging—can increase the effectiveness of lifestyle programs.
• Always be vigilant for hypoglycemia, even with agents considered low-risk, especially when combined with sulfonylureas or in vulnerable patients.
• Early, even temporary, weight loss produces lasting metabolic and cardiovascular benefits in T2D.

For full articles and more, visit: www.diabetesjournals.org