A Novel Multiphase Modified Ketogenic Diet: An Effective and Safe Tool for Weight Loss in Chinese Obese Patients

Figures & data

Figure 1 Study design.

Abbreviations: LM, lifestyle modification; MMKD, multiphase modified ketogenic diet; T, titration of beinaglutide within 2 weeks.

Figure 2 Flow-chart of participant enrollment process.

Abbreviations: LM, lifestyle modification; MMKD, multiphase modified ketogenic diet.

Table 1 Baseline Characteristics of the Study Participants After the 4-Week Run-in

Variables	LM	MMKD	Beinaglutide	P value
	(n=57)	(n=22)	(n=25)
Demographic Variables
Age (years)	34±9	31±9	30±4	0.116
Sex (no.%)				0.005
Male	40(70.2)	13(59.1)	8(32.0)
Female	17(29.8)	9(40.9)	17(68.0)
Marital status (no.%)				0.663
Not married	15(26.3)	7(31.8)	5(20.0)
Married	42(73.7)	15(68.2)	20(80.0)
Education (no.%)				0.590
High school or below	14(24.6)	4(18.2)	8(32.0)
College or above	43(75.4)	18(81.8)	17(68.0)
Smoking (no.%)	10(17.5)	4(18.2)	3(12.0)	0.825
Drinking (no.%)	11(19.3)	6(27.3)	1(4.0)	0.070
Medications (no.%)
Antihypertensive therapy	15(26.3)	2(9.1)	2(8.0)	0.084
Lipid-lowering therapy	2(3.5)	2(9.1)	1(4.0)	0.603
Uric acid-lowering therapy	0	2(9.1)	1(4.0)	0.053
Liver protection therapy	2(3.5)	0	0	1.000
Anthropometric variables
Body weight (kg)	89.7±14.4	90.9±18.2	90.6±18.7	0.948
BMI (kg/m^2)	31.4±3.5	32.2±4.2	33.3±4.3	0.136
WC (cm)	101.3±9.8	101.8±11.6	102.8±14.4	0.865
HC (cm)	105.9±7.0	108.8±8.5	109.0±10.4	0.180
WHR	0.96±0.06	0.93±0.06	0.94±0.08	0.358
Muscle mass (kg)	55.0±9.3	53.5±12.3	50.1±10.0	0.131
SMM (kg)	32.4±6.5	32.0±7.9	29.6±6.3	0.232
Fat mass (kg)	31.3±8.3	34.1±6.9	37.4±10.2*	0.012
BFP (%)	34.8±6.2	37.8±4.7*	41.1±5.2^*#	<0.001
VFA (cm^2)	136.1±39.9	151.7±32.1	169.5±44.3*	0.003
Water (kg)	42.8±7.3	41.5±9.5	39.0±7.8	0.133
Metabolic Variables
Blood pressure (mmHg)
Systolic	131±13	132±14	136±16	0.252
Diastolic	76±10	77±11	80±11	0.286
Resting heart rate (beats/min)	70±11	71±10	75±10	0.254
Lipid profile
TC (mmol/L)	4.85±0.89	5.20±1.02	5.20±1.07	0.189
LDL-C (mmol/L)	2.98±0.82	3.26±0.87	3.46±1.04	0.069
HDL-C (mmol/L)	0.96±0.19	1.09±0.28	1.04±0.22	0.065
TG (mmol/l)	1.94±1.17	1.88±1.68	1.73±0.75	0.768
HBA1c (%)	5.2±0.4	5.4±0.5	5.3±0.4	0.136
FBG (mmol/L)	5.18±0.59	5.03±0.61	5.03±0.69	0.458
P2hBG (mmol/L)	7.07±1.83	7.27±1.90	7.52±1.69	0.585
LnFINS (mU/L)	2.68±0.51	2.75±0.52	3.04±0.41^*#	0.012
LnP2hINS (mU/L)	4.39±0.68	4.49±0.96	4.81±0.62	0.066
LnHOMA-IR	1.21±0.56	1.25±0.56	1.53±0.44*	0.038

Notes: *P < 0.05 compared with the LM arm; ^#P < 0.05 compared with the MMKD arm.

Abbreviations: BMI, body mass index; WC, waist circumference; HC, hip circumference; WHR, waist-to-hip ratio; SMM, skeletal muscle mass; BFP, body fat percentage; VFA, visceral fat area; TC, total cholesterol; LDL-C, low-density lipoprotein-cholesterol; HDL-C, high-density lipoprotein-cholesterol; TG, triacylglycerol; HbA1c, glycosylated hemoglobin; FBG, fasting blood glucose; P2hBG, 2h postprandial blood glucose, FINS, fasting plasma insulin, P2hINS, 2h postprandial insulin; HOMA-IR, homeostatic model assessment for insulin resistance.

Figure 3 Changes in body weight and composition. (A) Change in body weight over time during the study. (B) Change in body weight from week 0 to 12. (C) Change in skeletal muscle mass from week 0 to 12. (D) Change in fat mass from week 0 to 12. (E) Change in body fat percentage from week 0 to 12. (F) Change in visceral fat area from week 0 to 12. (G) Percentage of participants in each intervention group who had a total weight loss of at least 5% or10% of the initial body weight at week 0. (H) Mean weight loss percentage in each group after the 12-week intervention.

Notes: (B), (D), (E) and (F) Marked numbers are the estimated mean differences with 95% CI. LM (black), 12 weeks of HBD with aerobic and resistance exercise; MMKD (blue), two cycles of 2 weeks of KD, 2 weeks of transition diet and 2 weeks of HBD with aerobic and resistance exercise; Beinaglutide (orange), 12 weeks of HBD plus daily injections of beinaglutide (0.4 mg per day) with aerobic and resistance exercise.

Abbreviations: LM, lifestyle modification; MMKD, multiphase modified ketogenic diet; HBD, hypocaloric balanced diet.

Table 2 Treatment Effects for Metabolic Variables Before and After the 12 Weeks of Intervention

Variables	LM (n=50)			MMKD (n=19)			Beinaglutide (n=21)			Difference Among Groups
	Week 0	Week 12	P value	Week 0	Week 12	P value	Week 0	Week 12	P value	P value
Blood pressure (mmHg)
Systolic	129±12	125±12	0.006	132±14	125±16	0.015	139±16	134±13	0.036	0.326
Diastolic	75±10	72±9	0.008	77±11	72±10	0.042	82±11	79±8	0.073	0.072
Resting heart rate (beats/min)	71±12	70±10	0.534	70±10	70±10	0.810	77±9	74±10	0.255	0.816
Lipid profile
TC (mmol/L)	4.81±0.89	4.89±0.90	0.369	5.19±0.88	5.12±0.96	0.689	5.21±1.06	5.46±1.28	0.128	0.235
LDL-C (mmol/L)	2.97±0.84	2.90±0.75	0.287	3.33±0.77	3.27±0.89	0.684	3.58±1.06	3.78±1.21*	0.142	0.036
HDL-C (mmol/L)	0.96±0.19	1.05±0.22	<0.001	1.06±0.24	1.13±0.20	0.066	1.00±0.21	1.00±0.15*	0.966	0.039
TG (mmol/L)	1.89±1.14	1.86±1.10	0.846	1.94±1.80	1.29±0.65*	0.058	1.83±0.76	1.48±0.58	0.004	0.007
HBA1c (%)	5.1±0.4	5.2±0.4	0.299	5.4±0.5	5.1±0.4	0.069	5.4±0.3	5.2±0.3	0.012	0.192
FBG (mmol/L)	5.20±0.60	5.01±0.51	0.004	5.10±0.62	4.86±0.47	0.147	5.10±0.73	5.01±0.54	0.567	0.460
P2hBG (mmol/L)	7.10±1.91	6.84±1.61	0.313	7.07±1.98	7.01±1.63	0.886	7.45±1.75	6.91±1.99	0.250	0.850
LnFINS (mU/L)	2.68±0.53	2.54±0.61	0.061	2.77±0.40	2.30±0.55	0.002	3.10±0.38	2.90±0.49	0.023	0.079
LnP2hINS (mU/L)	4.37±0.68	4.23±0.70	0.093	4.38±0.96	4.11±0.56	0.107	4.93±0.58	4.33±0.94	0.004	0.390
LnHOMA-IR	1.21±0.58	1.04±0.65	0.025	1.27±0.45	0.77±0.61	0.003	1.60±0.41	1.40±0.50^#	0.027	0.029

Notes: *P < 0.05 compared with the LM arm; # P < 0.05 compared with the MMKD arm.

Abbreviations: TC, total cholesterol; LDL-C, low-density lipoprotein-cholesterol; HDL-C, high-density lipoprotein-cholesterol; TG, triacylglycerol; HbA1c, glycosylated hemoglobin; FBG, fasting blood glucose; P2hBG, 2h postprandial blood glucose; FINS, fasting plasma insulin; P2hINS, 2h postprandial insulin; HOMA-IR, homeostatic model assessment for Insulin resistance.

Table 3 Adverse Events During the Study

Event	All Participants	LM	MMKD	Beinaglutide
	(n=104)	(n=57)	(n=22)	(n=25)
	Number of Participants (Percent)
All adverse events	31(29.8)	10(17.5)	2(9.1)	19(76.0)
Serious adverse event	3(2.9)	1(1.8)	0	2(8.0)
Upper respiratory tract infection	7(6.7)	3(5.3)	0	4(16.0)
Nausea	16(15.4)	0	0	16(64.0)
Vomiting	4(3.8)	0	0	4(16.0)
Abdominal pain	1(1.0)	0	0	1(4.0)
Dizziness	9(8.7)	1(1.8)	2(9.1)	6(24.0)
Fatigue	2(1.9)	0	0	2(8.0)
Joint injury (recurrence of old injury or trauma)	10(9.6)	5(8.8)	0	5(20.0)
Hypoglycemic symptoms	3(2.9)	0	0	3(12.0)

Notes: serious adverse events: in the LM group, autoimmune hepatitis (in one); in the benaglutide group, haemorrhoid surgery (in one) and accidental pregnancy (in one).