The Curbsiders Internal Medicine Podcast – REBOOT: #481 Prediabetes and Diabetes Prevention with Dr. Scott Isaacs

Release Date: March 9, 2026
Guest: Dr. Scott Isaacs, Endocrinologist & President, American Association of Clinical Endocrinology
Host Panel: Dr. Matthew Watto, Dr. Paul Williams, Dr. Malini Gandhi

Episode Overview

In this deep-dive "Curbsiders classic," Dr. Scott Isaacs discusses the essentials of prediabetes and diabetes prevention, focusing on clinical identification, evidence-based screening, personalized management, and an updated approach to risk framed around cardiometabolic complications rather than mere glucose thresholds. The episode is rich with practical tips, clinical pearls, and an emphasis on tailoring interventions to the individual patient.

Key Discussion Points & Clinical Insights

1. Why Screen for Prediabetes & Diabetes?

• Scope: Over 800 million adults globally have diabetes—15% of U.S. adults (~38 million), with 9 million undiagnosed. Prediabetes is even more common (100 million U.S. adults, ~38% of population). Most are unaware.
  Quote – Dr. Isaacs (07:55):
  “The vast majority of people with prediabetes don't know they have it. So that's why it's so important to do screening.”
• Metabolic Syndrome: Emphasis on recognizing metabolic syndrome (at least 3 features: hypertension, elevated glucose, high waist circumference, triglycerides/low HDL).
  Timestamp: [07:55]-[09:35]

2. Who & How to Screen

• Guidelines:
  • USPSTF: Adults 35–70 with overweight/obesity.
  • ADA: Everyone >35; <35 with additional risk factors (family history, race/ethnicity, hypertension, dyslipidemia, PCOS, inactivity, etc.)
    Quote – Dr. Isaacs (10:24):
    “The ADA recommends screening all adults over 35, and adults under 35 if they have risk factors...” Timestamp: [10:24]-[11:42]
• Practicality: Guidelines include almost everyone, but tailored risk factor assessment is key.

3. Screening Methods & Test Pitfalls

• Tests Used: Fasting plasma glucose, A1C, 2-hour oral glucose tolerance test (OGTT). Dr. Isaacs recommends using both fasting glucose and A1C for efficiency and diagnostic clarity.
  Quote – Dr. Isaacs (14:21):
  “If you do simultaneous testing of fasting plasma glucose and the A1C, it may facilitate a diagnosis because then you don’t have to have a second patient visit...” Timestamp: [14:21]-[15:24]
• Cut-offs (ADA):
  • A1C 5.7–6.4%: Prediabetes
  • FPG 100–125 mg/dL: Prediabetes
  • 2-hr OGTT 140–199 mg/dL: Prediabetes
• OGTT: Stronger predictor of future diabetes and CV complications but less practical; mainly used when results are ambiguous.
• A1C Limitations: Hemolytic anemias, hemoglobinopathies, severe CKD, transfusions, and nutritional deficiencies can skew results. Quote – Dr. Isaacs (28:18):
  “Anything that affects hemoglobin is going to affect the accuracy of the hemoglobin A1C.” Timestamp: [28:18]-[29:26]

4. Pathophysiology: Types & Progression

• Continuous Spectrum: Risk is continuous—not a hard threshold at any one value. Quote – Dr. Isaacs (19:24):
  “The cut points are really, they're arbitrary... It's not like if you have a glucose of 99, you're safe, and 100, you're at risk.” Timestamp: [19:24]-[20:17]
• Complications Beyond Glucose: Focus on total cardiometabolic risk, not just hyperglycemia: CVD, fatty liver (MASLD), CKD, heart failure, etc.
• Risk of Progression: ~5–10%/year convert from prediabetes to diabetes without intervention.

5. Physical Exam Pearls in Insulin Resistance

• Key Features:
  • Abdominal obesity (apple shape, high waist circumference)
  • Acanthosis nigricans—"dark, velvety patches" (neck, knuckles, axillae)
  • Skin tags (acrochordons)
  • PCOS signs in women (acne, hirsutism) Quote – Dr. Isaacs (34:20):
    “You can kind of look at them as they walk in the room and sometimes make that diagnosis.” Timestamp: [34:20]-[38:01]

6. Communication with Patients: Framing and Counseling

• Continuous Risk: Explain prediabetes as a spectrum, progression is influenced by lifestyle/genetics.
• Complication-Centric Approach: Set goals beyond sugar—prevent diabetes, reduce CV risk, improve liver/kidney function, sustain weight loss, and enhance quality of life. Quote – Dr. Isaacs (39:13):
  “I try to explain that the progression... is a process influenced by many factors including their lifestyle, their genetics, and their overall metabolic health.” Timestamp: [39:13]-[43:45]

7. Atypical & Secondary Prediabetes: When to Think Beyond Type 2

• Pre-type 1 Diabetes (Stage 2/"LADA"):

  • Consider in patients with autoimmune disease, young onset/preferential low body weight, family history.
  • Order autoantibodies (GAD65 most common, others: IA-2A, insulin autoantibody, ZNT8).
    Quote – Dr. Isaacs (47:44):
    “Ideally it'd be good to get multiple antibodies ... if you can only get one, it's going to be the GAD 65.” Timestamp: [47:44]-[50:49]

• Pancreatogenic/Secondary Diabetes:

  • Pancreatitis, exocrine insufficiency, sudden diabetes in lean patients.
  • 80% of new pancreatic cancer cases have prediabetes/diabetes, but rare for it to be the cause.

• Endocrine Causes:

  • Cushing's & MAX (Mild Autonomous Cortisol Secretion): Consider in resistant diabetes, adrenal incidentaloma.
  • Acromegaly: Subtle findings/hand/foot enlargement, facial changes, increased space between teeth; ask about ring/shoe size change. Quote – Dr. Isaacs (53:06):
    “As internal medicine doctors, ... you do not want to miss are Cushing's and acromegaly, especially the obvious cases.” Timestamp: [53:06]-[61:41]

8. Treatment & Prevention Strategies

Lifestyle Changes

• Key Message: 7% weight loss reduces diabetes risk by ~58% (DPP study, [63:07]-[64:22]).
• Diet: No "best" macronutrient ratio—caloric deficit trumps type of diet. Emphasize sustainable, individualized choices.
• Physical Activity: Core component of prevention. Quote – Dr. Isaacs (64:49):
  “Do what works for you… avoid obviously unhealthy foods and the extremes ... the exact percentage of macronutrients ... can be customized.”

Pharmacologic Options

Metformin

• 1st-line, especially with BMI >35 or gestational diabetes history; reduces onset risk by ~30%.
• Dosing: Start 500mg, titrate up to 2000mg/day (extended release preferred for better GI tolerance, “ghost” tablets in stool are benign).
  Timestamp: [68:23]-[73:04]

Pioglitazone

• Strong evidence (IRIS and ACT NOW trials) for diabetes prevention (reducing risk by 52% and 70% respectively).
• Only drug that directly lowers insulin resistance.
• Benefits: Reduces CV risk, inflammation, liver fat.
• Concerns: Modest weight gain (1–2% on 15mg, more on higher doses), fluid retention (avoid in advanced HF), possible bone loss, not conclusively linked to bladder CA. Quote – Dr. Isaacs (74:05): “It does ... people complain about the risks, like weight gain, but really the weight gain is minimal ... And if you combine it with metformin or SGLT2 or GLP1s, there's no weight gain.” Timestamp: [74:05]-[77:18]

Acarbose

• Reduces diabetes risk by ~25%. Poor GI tolerability limits use.
  Timestamp: [79:30]-[79:59]

Phentermine/Topiramate

• Significant weight loss, also reduces diabetes risk; practical to combine generic versions for cost.

GLP-1 Agonists & Tirzepatide

• Highly effective: 75–95% relative risk reduction.
• Key trials: SCALE (liraglutide), STEP (semaglutide 2.4mg), SELECT (CV, semaglutide), SURMOUNT-1 (tirzepatide; NNT=9).
• Benefits mostly weight-loss mediated, but some direct glycemic impact.
• Combining with metformin is common, despite little specific prediabetes trial evidence. Quote – Dr. Isaacs (81:44):
  “GLP medications reduce the risk of diabetes by 75–95% ... and with tirzepatide ... risk of type 2 diabetes reduced by about 94%.” Timestamp: [81:44]-[84:02]

9. Monitoring and Follow-Up

• Screening Frequency: If no prediabetes, every 3 years minimum; Dr. Isaacs prefers annually.
• Patients with prediabetes: A1C at least annually, often more frequently for feedback and motivation. Quote – Dr. Isaacs (87:58):
  “For patients that already have prediabetes ... I’m going to recheck their A1C at least once a year. And usually more than once a year, they want that feedback.”

Notable & Memorable Quotes

• "All patients, they have either one of two focuses, they're either minimalist or maximalist ... it's your job as their doctor to figure that out..." – Dr. Isaacs [05:03]
• "Not all prediabetes is from insulin resistance ... think about atypical prediabetes: pre type 1 (LADA), pancreatic diabetes, Cushing's syndrome, acromegaly..." – Dr. Isaacs [89:29]
• "My final take home point...not to have a purely glucocentric view of prediabetes and to focus on a complication-centric view looking at total cardiometabolic risk." – Dr. Isaacs [90:42]
• "I try to explain that the progression from normal blood sugars to prediabetes and eventually diabetes is a process influenced by many factors including their lifestyle, their genetics and their overall metabolic health." – Dr. Isaacs [39:13]

Important Timestamps

• Screening Rationale and Stats: [07:55]-[09:35]
• Guideline Differences: [10:24]-[11:42]
• Practical Screening Methods: [14:21]-[15:24]
• A1C Limitations: [28:18]-[29:26]
• Insulin Resistance Exam Pearls: [34:20]-[38:01]
• Patient Communication/Complication-Centric Approach: [39:13]-[43:45]
• Atypical Prediabetes Workup: [47:44]-[50:49]
• Endocrine Mimics (Cushing’s/Acromegaly): [53:06]-[61:41]
• Lifestyle Evidence (DPP): [63:07]-[64:22]
• Metformin Practicalities: [68:23]-[73:04]
• Pioglitazone Rationale: [74:05]-[77:18]
• GLP1/Tirzepatide Evidence: [81:44]-[84:02]
• Monitoring/Frequency: [87:58]-[89:17]
• Take Home Points: [89:29]-[90:52]

Take Home Points (from Dr. Scott Isaacs)

1. Prevalence is High: 1 in 3 US adults has prediabetes—most don’t know it.
2. Think Beyond Type 2: Not all prediabetes is insulin resistance—consider autoimmune (LADA), pancreatic, Cushing’s, and acromegaly when atypical.
3. Interventions Work:
   • Lifestyle: 7% weight loss → ~60% reduction in progression
   • Metformin: Most effective with BMI >35/family history gestational diabetes
   • GLP1/Tirzepatide: Reduce risk by 75–95%
4. Target Complications, Not Just Sugar: Focus on holistic risk—CV, liver, kidney—rather than solely A1C or glucose.

Resources & Plugs

• American Association of Clinical Endocrinology (AACE):
  "We changed our name to be more inclusive... inviting primary care, family medicine, APPs... check out our meeting in Orlando, May 15–17 and our web resources."
  AACE website
• DPP Study: Major reference for lifestyle impact.

For CME and show notes: curbsiders.vcuhealth.org

Summary by The Curbsiders Team. Listen for more clinical pearls and paul-esque witticisms!