It is common knowledge that type 2 diabetes mellitus is a complex, multifactorial, metabolic disease associated with genetic predisposition, obesity, sedentary lifestyle and overindulgence in high calorie foods. As a developing nation, we should be more concerned about this global pandemic as it has been predicted that by 2030, it is expected that there will be a 69% increase in number of adults with diabetes in the developing world compared to a 20% increase in the developed world.
Diabetes Mellitus exacts an expensive toll on healthcare systems worldwide and it is especially burdensome for middle and lower-income countries like ours. Successful reversal of diabetes would relieve health-care systems and societies around the world from a substantial and increasingly unsustainable socio-economic burden.
Diabetes reversal is defined as a return to below the World Health Organization (WHO)/American Diabetes Association (ADA) original diagnostic thresholds for diabetes and this return should be maintained for 3 months without any glucose-lowering pharmacotherapy.
Can Diabetes be really reversed?
Contrary to the traditional narrative that type 2 diabetes is a chronic irreversible process requiring a continuous titration of add on pharmacotherapy inexorably leading to dependence on insulin for more than 50% patients in 9-10 years, new studies highlight newer approaches to managing diabetes that emphasize reversal and remission. As per Diabetes UK website, four approaches have been suggested: low carbohydrate diets, very low-calorie diets, exercise and bariatric surgery. Systematic reviews showed that bariatric surgery could initially reverse T2DM for 58% to 95% of patients. Initial data suggested that gastric bypass is the most effective at inducing diabetes remission in T2DM patients, followed by sleeve gastrectomy, and then gastric banding. Longer term data (5-year) reveal that remission rates for T2DM patients after sleeve gastrectomy are nearly as good as those for gastric bypass.
Visceral fat accumulation, especially in liver and pancreas, has shown to be an important pathophysiological factor for type 2 diabetes mellitus. Excess fat in liver worsens hepatic responsiveness to insulin leading to increased glucose production and in the pancreas excess fat induces metabolic stress to β cells leading them to enter into survival mode. Removal of excess fat from these organs via substantial weight loss can normalize hepatic insulin responsiveness and β cell recovery possibly by redifferentiation. 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. Substantial weight loss may be achieved through Medical Nutritional Therapy (MNT) involving Low Carbohydrate Diet (LCD), Very Low-Energy Diet (VLED), behavioral changes as part of lifestyle changes recommended by American Heart Association (AHA) and exercise, namely high intensity interval training.
Exercise, high intensity interval training, in particular, has been suggested as an important key in the reversal of type 2 diabetes. The Nutrition Practice Guideline (NPC) suggests aiming for more than 150 min\week of moderate intensity aerobic physical activity, divided between 3 days per week, and with no gap of more than two consecutive days without exercise. Daily physical activity is known to be an essential component of long-term weight control. The types of exercise that appears most beneficial for reducing post-prandial glycemia and insulin resistance appear to be pre-prandial resistance training and high-intensity interval exercise.
Pharmacotherapy with Calorie Restriction Mimetic (CRM) drugs like glucagon like peptide-1 receptor agonists (GLP1RAs), calorie wasting drugs like sodium glucose co- transporter 2 inhibitors (SGLT2i) and anti-obesity drug like orlistat have been proposed to render diabetes from a progressive disease to the disease which can be put into remission. Weight loss has been postulated as a cornerstone of diabetes remission whereas widespread use of hyperphagic drugs that promote weight gain like insulin and sulphonylureas is a contradiction to this conundrum.
CRM drug like orlistat has been shown to be effective at improving glycemic profile comparable to improvement seen with antidiabetic medications. Orlistat also improves glycemic control and reduces insulin requirements when it is added to insulin monotherapy in T2 diabetes. Jennings et al found a triple therapy of metformin, pioglitazone and repaglinide to be effective for reversing newly diagnosed T2DM patients. The drugs were given at maximum tolerated doses and then tapered according to results. Remission rates are higher in newly diagnosed type 2 diabetes patients and in those patients who have not yet developed complications. American College of Lifestyle Medicine (ACLM) suggests that Whole Food Plant Based (WFPB) diet coupled with moderate intensity physical exercise may induce partial and complete diabetes remission though concrete results are yet to be obtained and necessitate further studies.
Conclusion
In conclusion, type 2 diabetes mellitus is a complex multifactorial disease with genetic predisposition. As it is complex in pathophysiology equally complex is its remission and reversal. A multitude of approaches like dietary modification with LCD or VLED, exercise, lifestyle modification, bariatric surgery, pharmacotherapy, mostly with CRM drugs, behavioral changes and a combination of plant based whole food diet coupled with moderate intensity physical exercise has been suggested as potential measure for type 2 diabetes reversal. We can unanimously conclude that greater scientific and medical community believes type 2 diabetes reversal is not a myth but a very achievable reality.
Dr. Sabin Chaulagain
Consultant Physician & Endocrinologist
Scheer Memorial Adventist Hospital, Banepa