Diabetes Remission (NOT Diabetes Reversal)

Author: Dr. Om J Lakhani

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• 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

Section Name

• 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