Type 2 diabetes (T2D) has long been thought of as a progressive, incurable chronic disease, largely because traditional means of treatment have had limited potential to reverse the disease. But newer research exists that suggests reversal is possible through three methods: bariatric surgery, low calorie diets (LCDs), very low calorie diets (VLCDs) and carbohydrate restriction.
I recently published a narrative review of 99 original articles examining the evidence for type 2 diabetes reversal using each of the three reversal methods. We have included the advantages and limitations of each summarized below.
Defining diabetes reversal
We have defined reversal as maintaining an HbA1c below 6.5% without the use of glycemic control medications. We’ve excluded metformin from this criteria because it is not specific to diabetes—many people choose to remain on metformin for reasons other than blood glucose control.
Diabetes reversal is not commonly encouraged by the healthcare system, and reversal is not a goal in the ADA guidelines. The interventions we’ll outline below are generally not the first-line standard of care, and the evidence shows that the standard of care almost never leads to diabetes reversal (1). This raises the question of whether the standard of care is the best practice, and whether reversal methods should be incorporated into the first-line standard of care.
Diabetes reversal intervention 1: Bariatric surgery
The most commonly performed bariatric surgeries in the U.S. include laparoscopic and robotic Roux-en-Y Gastric Bypass (RYGB) or Sleeve Gastrectomy (SG). Anatomically, they both decrease the size of the stomach with RYGB also diverting the small intestine. Bariatric surgery has also been shown to cause alterations in GI hormone releases that may impact eating, hunger, and satiety (2) as well as affect gut microbiota populations (3-9).
Advantages of bariatric surgery:
- Unilateral improvement in glycemia following operation (10)
- High rates of T2D remission compared to the non-surgical groups (13)
- Three-year remission rates of up to 68.7% after RYGB (14)
- Rapid blood glucose improvements (within hours to days) which likely represents the enteroendocrine responses to altered flow of intestinal contents (i.e., bile acid signaling and changes in microbiota and their metabolome) (15).
Disadvantages of bariatric surgery:
- Surgery of any type can be associated with complications leading to morbidity or mortality. Complication rates have been stated to be as high as 13% and 21% for SG and RYGB, respectively (16).
- Significant financial costs for the patient, health system, and insurance companies (U.S. average of $14,389). This cost may be outweighed by medication cost savings—prior to surgery, patients spend over $10,000 per year on diabetes medications, and that cost falls to less than $2,000 per year after surgery. Other analyses show that surgery is likely cost-effective, especially in patients who are obese (17-20).
- Increased likelihood of long term adverse events. Major adverse events included medication intolerance, need for reoperation, infection, anastomotic leakage, and venous and thromboembolic events (21-25).
Diabetes reversal intervention 2: Low calorie diets (LCDs)
Several studies have reported successful weight loss with decreased insulin resistance and medication use following a LCD or a VLCD. Total calories per day in studies for VLCDs range from 400-800kcal. LCDs range from 825-1800 kcal per day and the higher range has been shown to be significantly less effective. Research suggests that LCDs are effective in reversing diabetes in the short term (up to two years), especially in patients with a more recent diabetes diagnosis.
Advantages of LCDs:
- Quick improvements in glycemic control. A low-calorie diet of 900 kcal, including 115 g of protein, led to significant improvement in glycemic control attributed to improvements in insulin sensitivity (26).
- Effective in the short term. A VLCD and gastric bypass surgery were equally effective in achieving weight loss and improving glucose and HbA1c levels in obese patients with T2D in the short term (27). DiRECT (Diabetes Remission Clinical Trial), a community-based cluster-randomized clinical trial with 306 relatively healthy participants with T2D (given an 825 kcal/day formula for 3-5 months) found that at one year, 46% of patients met the study criteria of diabetes remission (HbA1c <6.5% without antiglycemic medications). This dropped to 36% at two-years (28,29).
Disadvantages of LCDs and VLCDs:
- Overall difficult to sustain. In one study, weight loss persisted in the diet-treated patients only for the first three months, indicating difficulties with long-term maintenance (30). Other studies also reported similar pattern of early blood glucose normalization without medication use, but the improvements were not sustained long-term (31-33). One study showed that while a VLCD normalized glucose levels within a week; however at 12 weeks over a quarter of the patients had an early recurrence of diabetes with an average weight regain of 20% (34).
- Requires substantial caloric restriction. A substantial level of calorie restriction is needed to generate enough weight loss to reverse diabetes. Short-term interventions with moderate energy restriction with metformin (which led to modest weight loss) were less effective in reversing diabetes than standard diabetes care (35).
- Severe energy restriction may have negative long-term effects. Studies have suggested that the body undergoes physiological and metabolic adaptation in response to caloric restriction, and this may shift one’s energy balance and hormonal regulation of weight toward weight regain after weight loss (36).
Diabetes reversal intervention 3: Carbohydrate restriction
Before insulin was discovered in 1921, low carbohydrate (LC) diets were the standard of care for diabetes (37). With the emergence of exogenous insulin, the goal became to maintain blood sugar control through the use of medications instead of preventing elevations in blood glucose by restricting carbohydrates in the diet. In response to recent studies, the idea of preventing blood sugar elevations with carbohydrate restriction has found its way back into the mainstream standard of care. Low carbohydrate diets have been endorsed by the ADA, the European Association for the Study of Diabetes (EASD), and the Veterans Affairs/ Department of Defense (38-40).
A low carbohydrate diet typically restricts carbs to less than 130 grams per day, and a ketogenic diet to 20-50 grams per day.
Advantages of carbohydrate restriction:
- Highly effective. In our published trial providing significant support through the use of a continuous care intervention (CCI), we examined using a low carbohydrate diet in patients with T2D (n=262), compared with usual care T2D patients (n=87) (41). At one year, the HbA1c decreased by 1.3% in the CCI, with 60% of completers achieving a HbA1c below 6.5% without hypoglycemic medication (excluding metformin). Insulin was reduced or eliminated in 94% of users. Most cardiovascular risk factors showed significant improvement (41). Improvements were not observed in the usual care patients. Another 34-week trial (43) found that a ketogenic diet intervention (20–50 g net carbs per day) resulted in HbA1c below the threshold for diabetes in 55% of the patients, compared to 0% of patients in the low-fat arm.
- Does not require calorie restriction. Patients are instructed to carefully restrict dietary carbohydrates, eat protein in moderation, and consume dietary fats to satiety.
- Sustainable with support. The one-year retention rate in our continuous care intervention was 83%, indicating that a non-calorie-restricted, low carbohydrate intervention can be sustained (41).
- More cost-effective than bariatric surgery.
- More effective than restricting overall calories. A study comparing an ad libitum (non-calorie restricted) very low carbohydrate (<20g total) diet to an energy-restricted low-glycemic diet in patients with T2D found a greater reduction in HbA1c, weight, and insulin levels in the low carbohydrate arm (44). 95% of participants in the low carbohydrate arm reduced or eliminated glycemic control medications, compared to 62% in the low glycemic index arm at 24 weeks. A small (34 participants) one-year study of an ad libitum, very low carbohydrate diet compared to a calorie-restricted moderate carbohydrate diet found a significant reduction in HbA1c between groups, favoring the low carbohydrate arm (45).
Disadvantages of carbohydrate restriction:
- Often requires support. Many of these trials included an educational component, and determining the appropriate method of support may be key to the overall success with disease reversal.
- Results are promising, but longer-term follow-up studies are needed. Follow up studies have shown sustainability at two years, so longer-term studies are needed to determine the sustainability beyond that.
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