Diabetes Remission (NOT Diabetes Reversal)

Created/Updated: #jan2025

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Corresponding notes for patients: Can Diabetes be reversed ? The truth about Diabetes remission (not Reversal)

Video Lecture

Q. Why is the term "remission" preferred over "cure" or "reversal" in type 2 diabetes?
- A cure implies:
  - Complete normalization of all aspects of diabetes, which is not the case
  - No need for further clinical follow-up, care, or management
- Current Evidence:
  - There is no known cure for type 2 diabetes
- Remission differs from reversal:
  - Implies the need for ongoing support to prevent relapse
  - Requires continued lifestyle changes and monitoring
- Corollaries for understanding remission:
  - Similar to states of matter (solid, liquid, gas)
  - Comparable to cancer remission
Q. What is the complete ADA 2021 consensus definition of diabetes remission?
- Definition requires:
  - HbA1c: < 6.5% (< 48 mmol/mol)
  - Duration: Maintained for at least 3 months
  - Medication Status: Achieved in the absence of glucose-lowering pharmacotherapy
- Key Components:
  - Glycemic Threshold:
    - Primary: HbA1c < 6.5%
    - Alternative: Fasting blood glucose < 126 mg/dL
  - Duration: Minimum 3 months
  - Medication Status: No glucose-lowering medications
- Additional Requirements:
  - Ongoing monitoring at least yearly
  - Continued complication screening
Q. What are the different types of diabetes that can and cannot achieve remission?
- Naturally remitting forms:
  - Glucocorticoid-induced diabetes / Drug-induced diabetes
  - Gestational diabetes
  - Hospital hyperglycemia
  - These serve as natural stress tests for the pancreas
- Others that can undergo remission:
  - Type 2 diabetes
  - Endocrine disorder-induced diabetes:
    - Cushing syndrome
    - Acromegaly
    - Thyrotoxicosis
    - Pheochromocytoma
- Cannot achieve remission:
  - Type 1 diabetes
  - Pancreatic diabetes
  - MODY / Monogenic diabetes
Q. Who are the best candidates with Type 2 diabetes for achieving remission?
- Young patients with residual beta-cell function
- Flatbush / ketosis-prone type 2 diabetes
- Obese type 2 diabetes
- Those with associated NAFLD and Fatty Pancreas
Q. What are all the alternative definitions for remission of Type 2 Diabetes Mellitus?
- Metabolic Remission:
  - Reversal of insulin secretory defect or insulin resistance
- Clinical or Partial Remission:
  - Achieving HbA1c below individual's set target
- Biochemical or Complete Remission:
  - Reaching HbA1c below threshold for diabetes diagnosis
- Pharmacological Remission:
  - Absence of requirement for any drug therapy
Q. How is remission classified based on duration?
- Duration-Based Categories:
  - Transient Remission: 3-6 months
  - Short-term Remission: 6 months to 1 year
  - Long-term Remission: 1-5 years
  - Prolonged Remission: More than 5 years
Q. What are the different modes of achieving remission?
- All modes fundamentally require weight loss:
  - Weight loss by lifestyle measures
  - Weight loss by meal replacement
  - Weight loss with GLP1 RA / other drugs
  - Weight loss with bariatric surgery
  - Early intensive insulin therapy and remission
Q. What are the findings regarding weight loss and remission across different metabolic disorders?
- PCOS:
  - Modest weight loss (2-5%) improves menstrual irregularities and fertility
  - Final BMI below 26 kg/m²: 78% complete remission rate after bariatric surgery
- NAFLD:
  - 5% or greater weight loss: 75% remission rate within 7-year follow-up
  - High-protein, low glycemic index diet led to improvement with mean weight loss of 6.52 kg
- Type 2 Diabetes:
  - 8-10% weight loss normalized fasting glucose
  - Weight loss was strongest predictor in DiRECT trial
- General Targets:
  - 5-10% improves blood pressure and HDL
  - 10-15% needed for sleep apnea and NASH improvement
- Individual Variations based on:
  - Severity and duration
  - Age, sex, and other characteristics

Clinical Trials for Diabetes Remission

Q. What were the complete findings of the DiRECT (Diabetes Remission Clinical Trial)?
- Study Design:
  - Cluster-randomized controlled trial in primary care practices (Scotland and England)
  - Intervention: Intensive weight management program (Counterweight-Plus)
  - Duration: 2 years
- Key Findings:
  - At 12 months: 46% of intervention group achieved remission
  - At 24 months: 36% maintained remission
- Remission Definition: HbA1c <48 mmol/mol (<6.5%) without antidiabetes medications for at least 2 months
- Notable Outcomes: Weight loss was the strongest predictor of remission
Q. What factors were associated with remission success in the DiRECT trial?
- Weight Loss (Strongest Predictor):
  - Most significant factor at 12 and 24 months
  - Greater weight loss led to higher remission rates in stepwise pattern
  - At 24 months: 86% of participants who lost ≥15 kg achieved remission
- Baseline Characteristics:
  - Fewer antidiabetes medications prescribed at baseline
  - Lower triglyceride and gamma-glutamyl transferase (GGT) levels
  - Better quality of life and less anxiety/depression
  - Lower baseline HbA1c (at 12 months)
  - Older age and male sex (at 24 months)
- Other Positive Factors:
  - Early weight loss (as early as 4 weeks) predicted remission
  - Higher program attendance
- Negative Predictors:
  - Use of antidepressants
  - Higher anxiety and depression scores
  - Higher triglyceride and GGT concentrations
  - Weight regain after initial weight loss
Q. What did the NHS T2DR Programme reveal about diabetes remission?
- Study Design:
  - National prospective service evaluation in England
  - Intervention: 12-month behavioral program with 3-month total diet replacement
- Key Findings:
  - 27% of participants with complete data achieved remission
  - 32% of program completers achieved remission
- Remission Definition: Two HbA1c measurements <48 mmol/mol, at least 3 months apart, without medications
- Notable Outcome: Demonstrated feasibility in real-world settings
Q. What were the findings of the SEED Trial?
- Study Design: 52-week study
- Intervention: Glucokinase activator (dorzagliatin)
- Key Findings:
  - 65.2% remission probability at week 52
  - 52.0% remission probability at week 12 (ADA definition)
- Notable Outcomes: Improvements in β-cell function and Time in Range
Q. What were the findings of the Digital Twin Technology studies in India?
- Digital Twin Intervention Study:
  - Design: Retrospective observational study (1 year)
  - Participants: 1853 individuals across multiple centers
  - Key Findings:
    - Mean HbA1c decreased from 8.1% to 6.3%
    - 74% reduction in antidiabetic medication use
    - Improved metabolic parameters
- Extraglycemic Parameters Study:
  - Duration: 18 months
  - Participants: 218 completers
  - Significant improvements in:
    - Systolic and diastolic blood pressure
    - hs-CRP
    - TG/HDL ratio
    - NAFLD Fibrosis Score
    - NAFLD Liver Fat Score
Q. What are the outcomes of bariatric surgery for type 2 diabetes remission?
- Nationwide Swedish Study:
  - 76.6% medication-free at 2 years
  - 69.9% at 5 years
- Swedish Obese Subjects (SOS) Study:
  - 72.3% remission at 2 years
  - 30.4% at 15 years post-surgery
  - Control group: 16.4% at 2 years, 6.5% at 15 years
- Other Studies: 50% remission within 2-4 months
- Long-term Outcomes:
  - Microvascular Complications:
    - Surgery: 20.6 per 1000 person-years
    - Control: 41.8 per 1000 person-years
  - Macrovascular Complications:
    - Surgery: 31.7 per 1000 person-years
    - Control: 44.2 per 1000 person-years
Q. What is Early Intensive Insulin Therapy (IIT) and its complete outcomes?
- Definition and Goal:
  - Short-term intensive insulin therapy (2-3 weeks)
  - Aims to improve glycemic control and preserve β-cell function
- Remission Rates from Large Chinese Trial:
  - Continuous subcutaneous insulin: 51.1%
  - Multiple daily injections: 44.9%
  - Oral hypoglycemic agents: 26.7%
- Meta-Analysis Results (7 studies, 839 participants):
  - 3 months: 66.2% remission
  - 6 months: 58.9% remission
  - 12 months: 46.3% remission
  - 24 months: 42.1% remission
- Mechanisms of Action:
  - Improved β-cell function (increased HOMA-B)
  - Reduced insulin resistance
  - Restoration of first-phase insulin secretion
  - Reduction in glucagon levels
- Predictors of Success:
  - Shorter diabetes duration (<2 years)
  - Lower baseline fasting glucose
  - Higher BMI
  - Better early-phase insulin secretion
  - Lower insulin requirements during IIT
Q. What are the Good, Bad, and Ugly aspects of diabetes remission?
- The Good:
  - Motivates patient towards healthy goal
  - Reduces cost burden and improves quality of life
  - More focus on core pathophysiology (fat reduction)
- The Bad:
  - Gets away from basic goal of metabolic therapy (reducing micro and macrovascular complications)
- The Ugly:
  - False promises from companies promoting quick fixes

Mini-App / Tool

Diabetes remission tool - Helps to find suitable patients with type 2 diabetes who could be potential candidates for diabetes remission

Presentation

Diabetes Remission presentation

Notes for Patients

Can Diabetes be reversed ? The truth about Diabetes remission (not Reversal)

Updates

27-January-25: Using Dapagliflozin for Diabetes Remission