Diabetes Core Update – May 2016
American Diabetes Association Podcast
Date: April 25, 2016
Presented by Dr. Neil Skolnik and Dr. John Russell

Episode Overview

This episode of Diabetes Core Update reviews and discusses newly published, clinically relevant articles from ADA journals, focusing on their implications for everyday diabetes management. Drs. Neil Skolnik and John Russell analyze key studies on:

• Long-term effects of intensive glucose control in both type 1 and type 2 diabetes
• Prevention of end-stage kidney disease
• Cardiovascular implications of different diabetes therapies
• The role of metabolic syndrome in neuropathy
• The potential for very low-calorie diets to reverse type 2 diabetes

The discussion emphasizes practical take-home points for clinicians, encouraging reflection on therapeutic strategies and the persistent impact of early interventions.

Key Articles and Discussion Points

1. Long-term Impact of Intensive Diabetes Treatment on Cardiovascular Outcomes

Study: DCCT/EDIC 30-Year Follow-up in Type 1 Diabetes
[01:58–02:55]

• Findings:

  • Intensive therapy (mean 6.5 years) vs. conventional therapy: 30% reduction in cardiovascular events, 32% reduction in major cardiovascular events after 30 years.
  • Despite similar glucose control post-trial, the reduction in events persisted.

• "Legacy Effect":
  Dr. Skolnik:

  “Six and a half years of intensive treatment versus standard of care, 30 years later has a substantial effect on hard outcomes...” [02:55]

  • Early control leads to long-lasting benefits; the “legacy effect” alters vascular trajectories years down the line.

• Clinical Relevance:

  • Delays in treatment intensification (therapeutic inertia) can have lasting negative outcomes.
  • Providers should act to overcome inertia and intensify therapy appropriately.
  • The evidence supports prioritizing early glycemic control to influence long-term macro- and microvascular outcomes.

2. Intensive Glucose Control & End-Stage Kidney Disease in Type 2 Diabetes

Study: ADVANCE Trial Long-Term Follow-Up
[05:45–06:14]

• Findings:

  • Persistent reduction in risk of end-stage kidney disease (ESKD) even ~10 years after the trial; hazard ratio 0.54 (29 vs. 53 events).

• Population Details:

  • Majority of subjects over age 65.

• Clinical Nuance:
  Dr. Russell:

  “Maybe our targets need to be higher... but we shouldn’t completely throw the baby out with the bathwater..." [06:14]

  • Tight control must be balanced against hypoglycemia risk, especially in seniors.
  • Avoid excessive risk from aggressive therapy, but do not abandon glycemic goals altogether: long-term kidney health remains at stake.

3. DPP4 Inhibitors and Heart Failure Risk in Type 2 Diabetes

Study: Retrospective Observational Study Using US Insurance Data
[08:03–09:00]

• Findings:

  • No statistically significant association between DPP4 inhibitors and increased risk of heart failure compared to sulfonylureas.
  • No major differences between specific agents (saxagliptin vs. sitagliptin).

• Contrasting Evidence:
  Dr. Skolnik:

  “...In early April, the FDA issued a Drug Safety Communication warning about the risk of heart failure with two DPP4 inhibitors...” [09:00]

  • FDA warning based on RCTs (SAVOR-TIMI and EXAMINE) showing increased heart failure hospitalizations with saxagliptin and alogliptin.

• Clinical Takeaway:

  • Caution warranted for patients with heart or kidney disease.
  • Providers must synthesize evidence from both observational data and RCTs before making definitive clinical decisions.

4. Achieving Cardiovascular Risk Factor Targets in Diabetes Care

Study: Cohort Analysis of 2,000+ Patients; Focus on BP, Lipid, A1C Goals
[11:28–13:27]

• Findings:

  • Patients reaching 1, 2, or all 3 targets showed a 36%, 52%, and 62% lower risk of CVD events, respectively.
  • Targets: BP <130/80 mmHg, LDL <100 mg/dL, A1C <7% (not all current standards).

• Clinical Relevance:
  Dr. Russell:

  “...kind of more control in more different areas does better...we can’t singularly focus on one thing.” [13:27]

  • Multimodal risk reduction (BP, lipid, glycemia) is crucial.
  • Guidelines evolve, but comprehensive management remains important.

5. Metabolic Syndrome Components Linked to Symptomatic Polyneuropathy

Study: Health, Aging, and Body Composition (Health ABC) Study
[13:28–15:51]

• Findings:

  • Increasing metabolic syndrome components correlated with higher prevalence of distal symmetric polyneuropathy (DSP), independent of glycemic status.
  • DSP prevalence increases with each added MS component; prediabetes and waist circumference particularly impactful.

• Clinical Insight:
  Dr. Skolnik:

  “...there’s a relationship between metabolic syndrome and peripheral neuropathy that might explain some of those patients who otherwise have unexplained peripheral neuropathies...” [15:51]

  • Supports clinical impressions that neuropathy can have origins beyond overt diabetes.
  • Highlights importance of metabolic syndrome assessment in neuropathy workup.

6. Very Low Calorie Diets (VLCD) for Possible Type 2 Diabetes Remission

Study: Response to 8-week VLCD and 6-Month Maintenance
[17:48–19:07]

• Findings:

  • 30 patients: 8 weeks of ~600 kcal/day led to significant weight loss (average 15 kg) and diabetes remission (fasting glucose <7 mmol/L) in 12 patients; improvements maintained for 6 months.
  • Responders had shorter diabetes duration and higher baseline insulin levels.
  • A1C in responders improved from 7.1% to 5.8%.

• Historical Context:
  Dr. Russell:

  “Egyptians knew 3500 years ago...before insulin...patients lived longer on low calorie diets...” [19:07]

  • Diet-induced remission is not a new concept; echoes historical pre-insulin treatments and bariatric surgery outcomes.

• Clinical Takeaway:

  • Aggressive early intervention, particularly via weight loss and caloric restriction, may achieve remission, especially in newly diagnosed patients.
  • Not all patients will respond; adherence to VLCD is a challenge, but early message about modifiable course is crucial.

Notable Quotes & Memorable Moments

• Dr. Skolnik on “legacy effect”:

  “...Control now matters far into the future. Really should affect the way we think about things and our decisions every day in the office.” [03:48]

• Dr. Russell reflects on balancing risk in older patients:

  “I don't think we need to necessarily say that someone is 66 years old and we're going to forego all type of diabetes care...” [06:22]

• Dr. Skolnik on evidence and safety alerts:

  “We should never use the results of any single trial as the sole indicator of how to make clinical decisions...” [09:55]

• Dr. Russell on multi-modal risk factor management:

  “Fighting this front on many different levels is going to lead for the best outcome for our patients.” [13:48]

Timestamps for Key Segments

• [01:58] DCCT/EDIC 30-Year Type 1 Diabetes Cardiovascular Outcomes
• [05:45] ADVANCE Trial and Long-Term Kidney Outcomes
• [08:03] DPP4 Inhibitors and Heart Failure Risk
• [11:28] Multi-Factorial CV Risk Target Attainment
• [13:28] Metabolic Syndrome & Polyneuropathy Prevalence
• [17:48] VLCD and Type 2 Diabetes Remission Study

Practical Clinical Pearls

• Early, intensive glycemic control can impart decades-long cardiovascular and renal protection ("legacy effect")
• Therapeutic inertia has real long-term negative consequences—act decisively in diabetes management
• Multi-modal management (BP, lipids, glycemia) yields additive cardiovascular risk reduction
• Some DPP4 agents may carry heart failure risk, particularly in at-risk populations; interpret evidence carefully
• Metabolic syndrome components, especially prediabetes and central obesity, may explain neuropathy in non-diabetics
• Profound dietary interventions can induce remission in type 2 diabetes, especially if applied early

For further information and links to these studies, visit www.diabetesjournals.org.