Adherence to Low-Carbohydrate Diets in Patients with Diabetes: A Narrative Review

Figures & data

Table 1 Summary of Trials on Adherence to LCKD in Patients with Type 2 Diabetes

Study	Year	Trial Design	Study Duration	Arm	Goal Macronutrient Intake	Dietary Records	Actual Reported Macronutrient Intake at Study Conclusion	Educational Sessions	Attendance at Counseling Session	Attrition	Biomarker Results
Guldbrand	2012	Randomized trial	2 years	VLCKD (n=30)	1800kcal for men; 1600 kcal for women with 50% of energy from fat, 20% energy from carbohydrates and 30% energy from protein.	Obtained at baseline, 2, 3, 6, and 12 months. Records conducted during three consecutive days including one weekend day and the participants were provided with dedicated scales and notebooks to weigh and record all food items consumed during these periods (no food frequency questionnaires)	1251 ± 425 kcal; 31% from carbohydrates; 44% from fat; 24% from protein	Group meetings about which food items to choose given at baseline, at 2, 6 and 12 months by physicians; no individual sessions with nutritionist		4 did not attend sessions and expressed difficulty with adherence; 10 did not complete study	significant reduction in A1c from baseline at 6 months but not at study conclusion
				Low-fat diet (n=31)	1800kcal for men; 1600 kcal for women with 30% energy from fat (< 10% from saturated fat), 55–60% of energy from carbohydrates and 10–15% energy from protein.		1458±451 kcal; 47% from carbohydrates; 31% from fat; 20% from protein			3 did not attend sessions and expressed difficulty with adherence; 4 did not complete study
Iqbal	2010	Randomized trial	2 years	VLCKD (n=70)	<30g carbohydrates per day	24 hour self reported dietary intake at baseline and 6, 12, and 24 months	Self-reported caloric intake did not differ significantly between groups at any time. At month 24, participants in the low-carbohydrate and low-fat groups reduced their caloric intake over time by 397 and 571 cal, respectively. Macronutrient intake did not differ significantly between groups at any point.	Both diet groups were invited to attend separate weekly 2h nutrition classes for the first month then every 4 weeks for the study duration. Sessions included up to 10 participants and were led by a registered dietitian with expertise in weight-loss counseling. Information was presented by lecture and handouts during the first 30min of the session, followed by reinforcement of concepts using interactive games and quizzes.	Participants attended a mean (s.d.) of 9.9 (9.5) sessions, with a mode of three sessions and a median of six sessions (interquartile range 4–12).	60% did not complete study	At month 6, the low-carbohydrate group had a clinically significant reduction in HbA1c of −0.5% (compared to −0.1% in the low-fat condition), but this was not sustained over time
				Low-fat diet (n=74)	(≤30% of calories from fat with a deficit of 500 kcal/day)					46% did not complete study
Tay	2017	Randomized trial	2 years	VLCKD (n=58)	Diet plans were individualized and energy-matched, with moderate (~30%) (500–1000 kcal/day deficit). 14% energy as carbohydrate (< 50 g per day), 28% as protein, 58% as fat (<10% saturated fat)	Foods were listed in a semi-quantitative food record that participants completed daily	1707 kcal/day with a mean of 19% daily energy from carbohydrates; 25% from protein; 50% from fat	During the first 12 weeks, participants were provided with 30% of total energy requirement in key foods. Participants met individually with a dietitian for diet instruction and support every 2 weeks for 12 weeks and monthly thereafter	Exercise session attendance was similar between the two groups	44% did not complete the study	initial 3 fold increase in plasma beta hydroxybutyrate with levels decreasing back to baseline over time. VLCKD group also had greater increases in 24 hour urinary urea/creatinine excretion ratio throughout the study period
				Low-fat, high-carbohydrate, low-glycaemic index diet (n = 57)	Diet plans were individualized and energy-matched, with moderate (~30%) (500–1000kcal/day deficit) 53% as CHO, 17% as protein, 30% as fat (<10% saturated fat); (processed carbohydrates and high glycaemic index foods were discouraged.		1757 kcal/day with a mean of 48% from carbohydrates; 18% from protein; 27% from fat			51% did not complete the study
Yancy	2004	Randomized trial	6 months	VLCKD (n=59)	<20g carbohydrates per day	24-hour recall of food intake at baseline and take-home food records (5 consecutive days + weekend) twice monthly for 3 months, then monthly for 3 months	1461.0 ± 325.7 kcal; 8% from carbohydrates (8% of daily intake), 68% from fat; 26% from protein	Group meetings took place at an outpatient research clinic twice monthly for 3 months, then monthly for 3 months. These 1hr meetings consisted of diet instruction, supportive counseling, questionnaires, and biomedical measurements		24% did not complete the study	86% of VLCKD had trace or greater urinary ketones at 2 weeks and decreased to 42% at 24 weeks.64% of VLCKD had moderate or greater ketones and decreased to 18% at 24 weeks. VLCKD had statistically greater changes in TG, HDL, and ratio of TG to HDL.
				Low-fat diet (n=60)	<30% energy from fat, <200 mg of cholesterol daily, and deficit of 500–1000 kcal/d		1502.0 ± 162.1 kcal; 52% from carbohydrates, 29% from fat, 19% from protein			43% did not complete the study
Westman	2008	Randomized trial	6 months	VLCKD (n=48)	<20g carbohydrates per day	Food records (5 consecutive days, including a weekend) at baseline and weeks 4, 12, and 24	1550 ± 440 kcal; 13% from carbohydrates, 59% from fat, 28% from protein	Group meetings took place every week for 3 months, then every other week for 3 months. These consisted of physician review of BP and BG medications if applicable.		56% did not complete the study	Mean change in HbA1c for LCKD group was −1.5%, significantly more than LGID with HbA1c change of −0.5%.
				Low glycemic index diet (n=49)	55% of daily energy intake from carbohydrate with −500 kcal less than calculated energy intake for weight maintenance		1335 ± 372 kcal per day; 44% from carbohydrates, 36% from fat, 20% from protein			37% did not complete the study
Hu	2016	Randomized trial	12 months	VLCKD (n=75)	<40g carbohydrates per day	Two 24h dietary recalls, one on a week day and thet other on a weekend day, were obtained from each participant by a certified dietician at 0, 3, 6, and 12 months	73.9%, 59.7%, and 44.8% met carbohydrate goals at 3, 6, and 12 months. Those who did not had mean deviations of 145% (representing a carbohydrate intake of approximately 98 g d−1), 104% (82 g d−1) and 198% (119 g d−1), respectively	20 regular dietary counselling sessions including four weekly individual sessions for the first month followed by 10 group sessions every other week for 5 months and 6 monthly group sessions after.	There was no significant difference in attendance between groups. 56.7% of VLCKD and 52.3% of low-fat diet group attended counselling sessions.	21% did not complete the study	VLCKD group had higher cumulative percentage urine ketones at 3, 6, and 12 months compared to low-fat diet group. This was associated with greater reductions in body weight and percent fat mass and increase in percent lean mass. No associations were identified in the low-fat group.
				Low-fat diet (n=73)	Total fat <30% of daily energy and saturated fat <7% of daily energy		59.4% and 42.2% of individuals met total and saturated fat goals at 3 months, 64.8% and 33.3% did at 6 months and 55.6% and 27.8% did at 12 months, respectively. Those who consumed more than the goal had mean deviations of 19.1% (representing an intake of about 35.7% of daily energy from total fat) and 40.6% (9.8% saturated fat) at 3 months, 17.4% (35.2% total fat) and 39.8% (9.8% saturated fat) at 6 months and 23.3% (37.0% total fat) and 46.2% (10.2% saturated fat) at 12 months, respectively			18% did not complete the study
Saslow	2017	Randomized trial	12 months	VLCKD (n=16)	Carbohydrate intake reduced over 7–10 days to between 20–50 grams of carbohydrates a day, not including fiber, with the goal of achieving nutritional ketosis as measured by blood beta-hydroxybutyrate level 0.5–3 mM twice a week at home. Protein intake prior to the study was maintained and the rest of the calories were derived from fat.	Food intake was assessed with an online 24- hour food recall questionnaire. Timing of questionnaire administration not reported.	1693.7 kcal; 57.8g from carbohydrates; 24.2% of daily calorie intake from protein; 58.0% of dietary intake from fat	Participants attended 19 classes over 12 months including twelve 2-hour classes that met weekly initially and gradually tapered to 1.5-h every 2 months. One hour was devoted to instruction on the assigned diet, with three classes also discussing the importance of sleep and exercise. Each class session included a break with snacks appropriate to the assigned diet. Participants were encouraged to change their diet gradually; ideally, by the fourth class, participants were to have changed all of their meals to be in alignment with the new recommendations. Those on VLCKD were given a goal of B-OH between 0.5 and 3 mmol measured twice weekly at home. Half of each two-hour class in both groups was focused on learning skills to support behavior change and diet maintenance.	Not reported	14/16 (87.5%); similar between groups	HbA1c in VLCKD group improved from baseline 6.6% to 6.0% and 6.1% at 6 and 12 months, respectively. HbA1c in MCCR group improved from 6.9% at baseline to 6.7% at 6 and 12m. Body weight (kg) decreased 7 kg (from 99.9 kg to 92.0 kg) in VLCKD group compared to a decrease of 2 kg (from 97.5 to 95.8 kg) in MCCR group at 12m. With regards to lipids, TG improved from 102.6 to 92.7 mg/dL in VLCKD vs an increase from 158.9 to 173.4 mg/dL in MCCR group. Changes in HDL were not significant.
				Medium carbohydrate, low fat, calorie restricted, carbohydrate counting diet (n=18)	45–50% of calories from carbohydrates; carbohydrates counted using 15 grams as a unit. Most participants were asked to eat 3 carbohydrate units per meal and 1 per snack, or 165 grams of carbohydrates a day. Protein intake was kept the same as before the study and fat consumption was lowered. Participants ate 500 fewer kilocalories (kcal) per day than their calculated maintenance needs based on their age, weight, height, and physical activity level, using the formula from the Institute of Medicine Dietary Reference Guidelines		1380.8 kcal per day; 138.5 g carbohydrates; 20.5% from protein; 35.1% from fat			15/18 (83.3%); similar between groups	There was no statistically significant change in blood glucose.
Mayer	2014	Randomized trial	48 weeks	VLCKD (n=22)	Daily carbohydrate intake limited to less than 20 g, but calories were not restricted. Carbohydrate intake was slowly liberalized if participants approached their goal weight or cravings threatened adherence.	Diet adherence was measured using 4-day food records (including 2 weekend days) at baseline and weeks 2, 12, 24, 36, and 48	Mean daily carbohydrate intake was 75.9 g, total fat 103.2 g, and energy 1707.9 kcal/day	Small group meetings (6 to 12 participants) every 2 weeks for 24 weeks, then every 4 weeks for 24 weeks. Meetings lasted 1 to 2 hours and consisted of study measurements followed by group counseling that were parallel between the 2 interventions but specific to diet.	Not reported	50% of patients did not have food records at the end of the study period	Fasting glucose declined from mean 152.6 to 133.7 (p=0.2)
				Low Fat Diet + Orlistat (n=24)	Daily intake of fat limited to <30% energy, saturated fat to <10% energy, cholesterol to <300mg, and calories (500–1000 kcal deficit). Orlistat 120mg was taken three times per day.		Mean daily carbohydrate intake was 155.8 g, total fat 55.5 g, and energy 1419.6 kcal/day			50% of patients did not have food records at the end of the study period	Fasting glucose declined from mean 149.0 to 146.8
Davis	2009	Randomized trial	12 months	VLCKD (n=55)	Initially 20–25 g of carbohydrate x 2 weeks. As weight reduced, carbohydrate intake was increased at 5 g per week.	Single-day 24h recall by in-person interviews were obtained at baseline, 6, and 12 months. At 3 months, food diaries were reviewed for the day prior.	1642 ± 600 kcal; 33% of calories from carbohydrates; 44% from fat, 23% from protein	All received 45 min dietary instruction of registered dietician and were given a specific gram allowance of carbohydrates or fat to achieve a 1-pound weight loss each week. They also had a total of six scheduled, 30-min visits with the dietician for additional counseling over 12 months. Participants also had study visits 1–2x weekly for the 1st month followed by every 6 weeks in addition to this to review dietary adherence and adjust medications.	Not reported	No difference between arms. 8 withdrew.	Decreased adherence noted based on macronutrient intake over 12 months. Weight reduction was the same in both groups at 1 year. There was no significant differences in A1c or lipids at 1 year.
				Low-fat diet (n=50)	Fat intake <25% of energy needs, based on baseline weight.		1810 ± 590 kcal; 50% of calories from carbohydrates; 31% from fat, 19% from protein		Not reported	6 withdrew.
Yancy	2020	Randomized trial	48 weeks	VLCKD weight management (n= 127)	<20–30 g of carbohydrate/d initially followed by an increase in carbohydrates based on individual	Food records were collected at baseline and every 16 weeks by 3-day food records.	Not reported.	Every 2 weeks x 16 weeks followed by every 8 weeks thereafter. More comprehensive classes including low-carbohydrate nutrition, physical activity, and weight management counseling, as well as dietician-led nutritional counseling.	60.6% of VLCKD weight management group and 55.2% of medication intensification arm attended at least 75% of counseling sessions.	14.2% did not complete HbA1c measurements at study conclusion.	VLCKD group was noninferior but not superior compared to medication intensification group. VLCKD group had greater mean reduction in A1c at 16 weeks but not at 48 weeks.
				Medication intensification arm (n=136)	Not specified.		Not reported.	Every 4 weeks x 16 weeks followed by every 8 weeks thereafter. Nurse-led classes focused on DM management.		14% did not complete HbA1c measurements at study conclusion.
Goldstein	2011	Randomized trial	52 weeks	VLCKD weight management (n= 26)	25gm of carbohydrate/d for first 6 weeks followed by max 40gm of carbohydrate/d	3-day records obtained at 1.5, 3, 6, and 12 months.	1725 ± 600 kcal; 85 gm ± 35 from carbohydrates; 111 gm ± 45 from fat; 102 gm ± 37 from protein	Weekly nutritional counseling during initial 12 weeks followed by monthly for a total of 25 sessions.	There was a small non-significant advantage in the ATK group with regards to keeping dietician appointments over the first 3 months (p=0.27).	20 participants in each group persisted for 6 months in their respective diets. 46% of VLCKD did not complete 1 year f/u.	Poor adherence in the VLCKD was observed after the initial 6 weeks, with mean carbohydrate intake more than double the goal at 3, 6, and 12 months. Only 7% of participants in VLCKD group had ketogenic effect of diet apparent at 12 months, from 61% at 6 weeks. There was no statistically significant difference in weight loss between the trial groups over the 12 month period. There was a statistically significant decrease in HbA1c level in both groups at 1 year, with no significant between-group differences.
				American Diabetes Assn (ADA) diet (n=26)	Calorie-restricted with 10–20% of daily energy intake from protein and the other 80% divided between fats, carbohydrates, and 35 gm of fiber. Men were allowed up to 1500 kcal/day and women 1200 kcal/day.		1937 ± 376 kcal; 208 gm ± 61 from carbohydrates; 85 gm ±24 from fat; 90 gm ±12 from protein			38% did not complete the 1 year follow up