Is there a cure for type 2 diabetes?

Type 2 diabetes mellitus (T2DM) is a chronic disease of high blood glucose due to insulin resistance and insufficient insulin production.^1-5 

Studies show that T2DM is primarily caused by excess fat stored in the pancreas and liver.^6-9 Significant weight loss from a low-calorie diet, and in some cases bariatric surgery, can result in reversal of this problem and a return to prediabetic hemoglobin A1C (HbA1C) levels.^8,10 This also lowers the person’s heart disease risk. Remission may be possible in patients who are able to lose at least 15 kg of weight and maintain that weight loss for at least one year.^5,8  

One study of dietary weight loss and its effect on T2DM remission (defined as HbA1C <6.5% for at least two months while off diabetes medication) compared an intervention group (n=137) to a control group (n=148).⁵ Overall, remission occurred in 68 (48%) participants in the diet group and 6 (4%) in the control group (odds ratio 19.7, 95% confidence interval [CI][7.8-49.8], p<0.0001). Remission was found to be dependent on the amount of weight lost. Study participants were studied up to 6 years after initial diagnoses, so the study found that remission could occur up to 6 years after initial diagnosis, but further research is necessary to examine whether remission is possible past this timeframe. Remission occurred in 31 (86%) of the people who maintained 15 kg or more weight loss at 12 months, 16 (57%) of the 28 with 10-15 kg loss, 19 (34%) of the 56 with a 5-10 kg loss, and 6 (7%) of the 89 with a 0-5 kg weight loss. No one who gained weight had remission. 

A systematic review and meta-analysis of 23 randomized clinical trials of moderate to low-quality evidence evaluated the effect of low-calorie and very-low-calorie diets on people with T2DM with the primary outcome of remission (defined as HbA1C <6.5% or fasting blood glucose <7.0 mmol/L with or without use of antidiabetic medication).¹¹ Analysis of eight low-calorie diet trials (n=264) found that people on the diet for six months had a higher rate of remission compared to controls (76/133 [57%] vs 41/131 [31%]; risk difference 0.32, 95% CI [0.17-0.47], I2=58%). Very-low-calorie diets were less successful than low-calorie diets, mainly due to poorer diet adherence. Again, the degree of weight loss was likely the chief reason for remission.  

 Although people can maintain remission, studies show that T2DM eventually recurs in about 35-50% of people who achieved remission after bariatric surgery.⁸ In people who achieved remission through weight loss, diabetes recurs in most people if weight loss is not maintained. One study examined 393 patients with A1C values ≥7% pre-intervention.¹² After participating in an intensive outpatient intervention, all participants achieved adequate glycemic control, defined as an A1C of <7%. The study found the probability of glycemic relapse was 45% 1-year post-intervention and 76% 3 years post-intervention. Patients receiving insulin therapy were particularly at risk of glycemic relapse. A shorter duration of diabetes and weight loss were significantly associated with decreased risk of relapse.  

 Without treatment, people with diabetes have a much higher risk of diabetes-related complications such as:^13-15 

• Hyperglycemic and hypoglycemic crises requiring emergency help or hospital treatment 
• Cardiovascular disease (heart attack, stroke, ischemic heart disease) 
• Kidney disease and failure 
• Vision loss and blindness 
• Neurological disease 
• Sexual dysfunction 
• Dental problems 
• Foot ulcers and amputations  

References 

1. Beck-Nielsen H, Groop LC. Metabolic and genetic characterization of prediabetic states. Sequence of events leading to non-insulin-dependent diabetes mellitus. The Journal of clinical investigation. Nov 1994;94(5):1714-21. doi:10.1172/jci117518
2. Kahn CR. Banting Lecture. Insulin action, diabetogenes, and the cause of type II diabetes. Diabetes. Aug 1994;43(8):1066-84. doi:10.2337/diab.43.8.1066
3. Robertson RP. Antagonist: diabetes and insulin resistance--philosophy, science, and the multiplier hypothesis. The Journal of laboratory and clinical medicine. May 1995;125(5):560-4; discussion 565.
4. 2. Classification and diagnosis of diabetes: standards of medical care in diabetes-2021. Diabetes Care. Jan 2021;44(Suppl 1):S15-s33. doi:10.2337/dc21-S002
5. Lean ME, Leslie WS, Barnes AC, et al. Primary care-led weight management for remission of type 2 diabetes (DiRECT): an open-label, cluster-randomised trial. Lancet. Feb 10 2018;391(10120):541-551. doi:10.1016/s0140-6736(17)33102-1
6. Taylor R, Al-Mrabeh A, Sattar N. Understanding the mechanisms of reversal of type 2 diabetes. Lancet Diabetes Endocrinol. Sep 2019;7(9):726-736. doi:10.1016/s2213-8587(19)30076-2
7. Taylor R. Type 2 diabetes and remission: practical management guided by pathophysiology. J Intern Med. Jun 2021;289(6):754-770. doi:10.1111/joim.13214
8. Obesity management for the treatment of type 2 diabetes: standards of medical care in diabetes-2021. Diabetes Care. Jan 2021;44(Suppl 1):S100-s110. doi:10.2337/dc21-S008
9. Taylor R. Calorie restriction and reversal of type 2 diabetes. Expert Rev Endocrinol Metab. Nov 2016;11(6):521-528. doi:10.1080/17446651.2016.1239525
10. Shahrad Taheri HZ, Odette Chagoury, Sarah ElHadad, Salma Hayder Ahmed, Neda El Khatib, Rasha Abou Amona, Katie El Nahas, Nour Suleiman, Abdulla Alnaama, Abdulla Al-Hamaq, Mary Charlson, Martin T Wells, Samya Al-Abdulla, Abdoul Badi Abou-Samra. Effect of intensive lifestyle intervention on bodyweight and glycaemia in early type 2 diabetes (DIADEM-I): an open-label, parallel-group, randomised controlled trial. The Lancet. 2020;8(6)doi:https://doi.org/10.1016/S2213-8587(20)30117-0
11. Goldenberg JZ, Day A, Brinkworth GD, et al. Efficacy and safety of low and very low carbohydrate diets for type 2 diabetes remission: systematic review and meta-analysis of published and unpublished randomized trial data. BMJ. Jan 13 2021;372:m4743. doi:10.1136/bmj.m4743
12. Graber AL, Shintani AK, Wolff K, Brown A, Elasy TA. Glycemic Relapse in Type 2 Diabetes. AACE Endocrine Practice. Mar 1 2006;12(2):145-151.
13. Vijan S. Type 2 diabetes. Ann Intern Med. Nov 5 2019;171(9):Itc65-itc80. doi:10.7326/aitc201911050
14. National Diabetes Statistics Report (Centers for Disease Control and Prevention, U.S. Dept of Health and Human Services) (2020).
15. National Institute of Diabetes and Digestive and Kidney Diseases. What is diabetes? NIH. Accessed January 16, 2020. https://www.niddk.nih.gov/health-information/diabetes/overview/what-is-diabetes