It’s well-established that very low-carb and ketogenic diets over the short-term usually do a good job for folks with type 2 diabetes: better blood sugar levels, fewer diabetes drugs needed, improved lipids, lower blood pressure, etc. Many people—from patients to dietitians to physicians—question whether the diet and associated improvements can be sustained for more than a few months. The study at hand looked at results two years out, and found definite clinical benefit and sustainability.
First, a quick point to get out of the way. In the U.S., HgbA1c is reported as a percentage. But other countries often report HgbA1c in mmol/mol. It’s not easy to convert one to the other accurately, so when you see values in mmol/mol below, be aware they’re only my approximations, not the researchers’.
Here’s how the researchers did their study, published in the summer of 2019.
262 adults with type 2 diabetes (average age 54) were enrolled in the intervention group, called CCI (digitally-monitored continuous care intervention via a web-based app). 87 were assigned to “usual care.” For all participants at baseline, body mass index averaged 37-40, HgbA1c averaged 7.6% (60 mmol/mol), and they had diabetes for an average of eight years. The CCI group monitored beta-hydroxybutyrate (a ketone) levels, glucoses, body weight, etc, and uploaded results via the web-based app. The app also facilitated an online peer community for social support. For those who preferred in-person education (about half of the total), clinic-based group meetings were held weekly for 12 weeks, bi-weekly for 12 weeks, monthly for six months, and then quarterly in the second year. Continuous Care Intervention included individual support with telemedicine, customized nutritional guidance (emphasis on sustained nutritional ketosis), and health coaching.
The 87 Usual Care folks were recruited from the same geographic area and healthcare system. The received care from their primary care physician or endocrinologist and were counseled by a dietitian (ADA recommendations) as part of their diabetes education. Medical care was not modified for the study. This group had less intense clinical measurements than the CCI cohort.
Of the 262 participants who started with the CCI group, 218 remained after one year. So 44 drop-outs. Of these 262 pioneers, 194 remained for the entire second year (so 24 more drop-outs). If those drop-out numbers seem high to you, be aware that they are NOT. Even the Usual Care group of 87 had 19 drop-outs over the two years.
So what happened?
Reductions from baseline to two years in the CCI group included: fasting insulin, weight (down about 10% or 11.9 kg), blood pressure (systolic and diastolic), HgbA1c, and triglycerides. Those are all going in the right direction.
Other findings for the CCI group: HDL-cholesterol (“good cholesterol”) went up. Excluding metformin, the use of diabetes control drugs in the CCI group dropped from 56% of participants to 27%. Some dietitians fear the ketogenic diets are bad for bones, causing calcium to leak out of bones, weakening them since calcium is the main mineral in bones. But spine bone mineral density in the CCI group was unchanged over the two years.
The “usual care” group had no changes in those measurements or diabetes medication use.
Now, to understand some of the investigators results, you need to know their definitions. Diabetes remission = glycemic control without medication use. Partial remission is “sub-diabetic hyperglycemia of at least 1 year duration, HgbA1c level between 5.7-6.5% (39 to 48 mmol/mol), without any medications (two HbgA1c measurements).” Complete remission is “normoglycemia of at least 1 year duration, HgbA1c below 5.7% [39 mmol/mol], without any medications (two HgbA1c measurements).” Diabetes reversal per Supplementary Table 2: Sub-diabetic hyperglycemia and normoglycemia (HgbA1c below 6.5% or 48 mmol/mol), without medications except metformin.
The CCI group had resolution of diabetes (partial or complete remission in 18%, reversal in 53%), which was not seen in the usual care group. Complete remission was achieved in 17 (6.7%) of the CCI group. HgbA1c in the CCI group at two years dropped from average of 7.6% (60 mmol/mol) to 6.7% (50 mmol/mol).
“CCI diabetes reversal exceeds remission as prescriptions for metformin were usually continued given its role in preventing disease progression, preserving beta-cell function and in the treatment of pre-diabetes per guidelines.”
The average dose of insulin in CCI folks who were using insulin at baseline decreased by 81% at two years. (Have you noticed the price of insulin lately?)
Beta-hydroxybutyrate is a ketone, and at a certain level in the blood, indicates the presence of ketosis on a ketogenic diet. “The 2 year beta-hydroxybutryate (BHB) increase above baseline demonstrated sustained dietary modification.” “…the encouraged range of nutritional ketosis (> or = 0.5 mM) was observed in only a minority (14.1%) of participants at 2 years. On average, patient-measured BHB was > or = 0.5mM for 32.8% of measurement over the 2 years.”
In summary, the CCI group—eating ketogenic and/or very low-carb—showed sustained beneficial effects even two years after start of the study. I suspect the Virta app, clinic-based group meetings, and individual support and coaching contributed significantly to the participants’ success.
Steve Parker, M.D.
PS: By the way, many of the study authors are affiliated with Virta Health Corp., which I assume is a for-profit company. Virta provided funding for the study. Could that funding have unduly influenced the results? It’s always possible but I have no evidence that it did. If not already available, I expect a commercial version of the program will be within 12–24 months.
Reference: Athinarayanan, S.J., et al (including Sarah Hallberg, Jeff Volek, and Stephen Phinney). Long-Term Effects of a Novel Continuous Remote Care Intervention Including Nutritional Ketosis for the Management of Type 2 Diabetes: A 2-year Non-randomized Clinical Trial. Frontiers in Endocrinology, Vol. 10, article 348, June 19, 2019.