Predictors of type 2 diabetes in the Diabetes Remission Clinical Trial (DiRECT)

AIM:To identify predictors of type 2 diabetes remission in the intervention arm of DiRECT (Diabetes Remission Clinical Trial). METHODS:Participants were aged 20-65 years, with type 2 diabetes duration of <6 years and BMI 27-45 kg/m2 , and were not receiving insulin. Weight loss was initiated by total diet replacement (825-853 kcal/day, 3-5 months, shakes/soups), and weight loss maintenance support was provided for 2 years. Remissions [HbA1c <48 mmol/mol (<6.5%), without antidiabetes medications] in the intervention group (n = 149, mean age 53 years, BMI 35 kg/m2 ) were achieved by 68/149 participants (46%) at 12 months and by 53/149 participants (36%) at 24 months. Potential predictors were examined by logistic regression analyses, with adjustments for weight loss and effects independent of weight loss. RESULTS:Baseline predictors of remission at 12 and 24 months included being prescribed fewer antidiabetes medications, having lower triglyceride and gamma-glutamyl transferase levels, and reporting better quality of life with less anxiety/depression. Lower baseline HbA1c was a predictor at 12 months, and older age and male sex were predictors at 24 months. Being prescribed antidepressants predicted non-remission. Some, but not all effects were explained by weight loss. Weight loss was the strongest predictor of remission at 12 months (adjusted odds ratio per kg weight loss 1.24, 95% CI 1.14, 1.34; P < 0.0001) and 24 months (adjusted odds ratio 1.23, 95% CI 1.13, 1.35; P <0.0001). Weight loss in kilograms and percentage weight loss were equally good predictors. Early weight loss and higher programme attendance predicted more remissions. Baseline BMI, fasting insulin, fasting C-peptide and diabetes duration did not predict remission. CONCLUSIONS:Other than weight loss, most predictors were modest, and not sufficient to identify subgroups for which remission was not a worthwhile target

Hepatic Lipoprotein Export and Remission of Human Type 2 Diabetes after Weight Loss

This dataset was used to present data in the following paper: Hepatic Lipoprotein Export and Remission of Human Type 2 Diabetes after Weight Loss Al-Mrabeh et al. (2020), Cell Metabolism 31, 1–17. https://doi.org/10.1016/j.cmet.2019.11.01

Hepatic Lipoprotein Export and Remission of Human Type 2 Diabetes after Weight Loss

This dataset was used to present data in the following paper: Hepatic Lipoprotein Export and Remission of Human Type 2 Diabetes after Weight Loss Al-Mrabeh et al. (2020), Cell Metabolism 31, 1–17. https://doi.org/10.1016/j.cmet.2019.11.01

Remission of human type 2 diabetes requires decrease in liver and pancreas fat content but is dependent upon capacity for beta cell recovery. Taylor et al. (2018)

This dataset contains data used to present results in the following paper: Remission of human type 2 diabetes requires decrease in liver and pancreas fat content but is dependent upon capacity for beta cell recovery Taylor et al. (2018), Cell Metabolism 28, 1-10. https://doi.org/10.1016/j.cmet.2018.07.00

Understanding the mechanisms of reversal of type 2 diabetes

Clinical and pathophysiological studies have shown type 2 diabetes to be a condition mainly caused by excess, yetreversible, fat accumulation in the liver and pancreas. Within the liver, excess fat worsens hepatic responsiveness toinsulin, leading to increased glucose production. Within the pancreas, the β cell seems to enter a survival mode andfails to function because of the fat-induced metabolic stress. Removal of excess fat from these organs via substantialweight loss can normalise hepatic insulin responsiveness and, in the early years post-diagnosis, is associated withβ-cell recovery of acute insulin secretion in many individuals, possibly by redifferentiation. Collectively, these changescan normalise blood glucose levels. Importantly, the primary care-based Diabetes Remission Clinical Trial (DiRECT)showed that 46% of people with type 2 diabetes could achieve remission at 12 months, and 36% at 24 months,mediated by weight loss. This major change in our understanding of the underlying mechanisms of disease permitsa reassessment of advice for people with type 2 diabetes