Journal of Diabetes Research

Journal of Diabetes Research / 2020 / Article
Special Issue

Nontraditional Therapy of Diabetes and Its Complications

View this Special Issue

Review Article | Open Access

Volume 2020 |Article ID 4851671 | 21 pages | https://doi.org/10.1155/2020/4851671

Efficacy of Intermittent or Continuous Very Low-Energy Diets in Overweight and Obese Individuals with Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analyses

Academic Editor: Ruozhi Zhao
Received08 Sep 2019
Accepted07 Jan 2020
Published29 Jan 2020

Abstract

Objective. This study is aimed at investigating the efficacy of a very low-energy diet (VLED) in overweight and obese individuals with type 2 diabetes mellitus (T2DM). Methods. We thoroughly searched eight electronic resource databases of controlled studies concerning the efficacy and acceptability of intermittent or continuous VLEDs in patients with T2DM compared with other energy restriction interventions. Results. Eighteen studies (11 randomized and seven nonrandomized controlled trials) with 911 participants were included. The meta-analyses showed that compared with a low-energy diet (LED) and mild energy restriction (MER), VLED is superior in the reduction of body weight (mean difference (MD) , 95% confidence interval (CI) , ; , , ), blood glucose (, , ; , , ), and triglyceride (TG) (, , ; , , ) levels at the end of the intervention. After the follow-up (1–5 years), no obvious difference in weight loss (, , , ) and TG level (, , , ) between VLEDs and LEDs was evident, but VLED is more effective in glycemic control (, , ). Compared to bariatric surgery, VLEDs offered comparable effects on weight loss (, , ), glycemic control (, , ), TG (, , ), and insulin resistance improvement (, , ). Conclusion. Dietary intervention through VLEDs is an effective therapy for rapid weight loss, glycemic control, and improved lipid metabolism in overweight and obese individuals with T2DM. Thus, VLEDs should be encouraged in overweight and obese individuals with T2DM who urgently need weight loss and are unsuitable or unwilling to undergo surgery. As all outcome indicators have low or extremely low quality after GRADE evaluation, further clinical trials that focus on the remission effect of VLEDs on T2DM are needed.

1. Introduction

It is well known that obesity is a major risk factor for type 2 diabetes mellitus (T2DM) [1] and the majority of patients with T2DM are overweight or obese [2]. Obesity management is confirmed as an effective strategy in the prevention and remission of T2DM [3].

Multiple strategies including diet, physical activity, behavioural therapy, pharmacologic therapy, and bariatric surgery are recommended for obesity management [3]. In previous evidence-based clinical guidelines, dietary modification is recommended as a fundamental aspect of diabetes care, based on its benefits on glycemia and HbA1c levels [4]. Recently, several studies suggest that short-term and more extreme dietary energy restriction aiming on intensive weight loss can even reverse some cases of T2DM [57]. Very low-energy diet (VLED) has been confirmed as an effective and safe option for weight loss in obese individuals [8]. There is no standard definition of a VLED programme across different countries and continents [911]. However, a VLED is generally defined as a very low total energy intake (≤800 kcal/day) [8, 10]. Recently, a growing body of studies focus on the efficacy and acceptability of VLEDs in patients with T2DM who are overweight or obese [1214] and propose that VLEDs may be an underutilized therapy for patients with T2DM. Intermittent VLED is an alternative strategy of continuous VLEDs for T2DM, which typically involves periods of VLEDs interchanged by periods of ad libitum energy intake or mild energy restriction (MER, a slight diet intervention method which provides energy less than ad libitum energy intake but more than 1600 kcal/day) [15, 16]. The efficacy of both intermittent and continuous VLED should be considered.

A low-energy diet (LED) containing 800–1600 kcal/day is also considered an option of clinical obesity management of patients with T2DM [17, 18], but the difference in efficacy and safety between VLEDs and LEDs is rarely discussed. Bariatric surgery is recommended for obese patients (body mass index (BMI), 35.0–39.9 kg/m2) with T2DM who did not achieve durable weight loss and improvement in comorbidities with reasonable surgical methods [3]. For example, Roux-en-Y gastric bypass (RYGB), as currently one of the most effective types of bariatric surgery, achieves energy limitation by reducing stomach capacity and reducing dietary intake. However, bariatric surgeries have more adverse effects and complications compared with energy restriction strategy. Moreover, VLEDs may produce a similar effect on glycemic control, β-cell function, and insulin sensitivity as bariatric surgeries. Thus, it is necessary to evaluate the efficacy of VLEDs compared with other methods of energy restriction in overweight and obese individuals with T2DM.

A previous systematic review among overweight and obesity individuals with T2DM found that VLED has benefits of weight loss and glycemic control [19]. However, the systematic review included a small number of participants, and the long-term effect of VLEDs is unclear. Another recently published systematic review found that VLED programmes in children and adolescents with obesity induce short- to medium-term weight loss and also demonstrated significant improvements in diabetic outcomes, such as HbA1c and glucose levels [10]. Recently, several clinical studies have been conducted to compare VLEDs with other energy restriction methods. Thus, it is necessary to investigate the efficacy of VLEDs in overweight and obese adult individuals with T2DM. Our systematic review and meta-analyses are aimed at clarifying the effect of VLEDs on weight loss, glycemic control, and blood lipid levels in overweight and obese individuals with T2DM and further exploring the long-term efficacy of VLEDs to provide more substantial evidence in the clinical application of VLEDs.

2. Materials and Methods

2.1. Search Strategy

We comprehensively searched PubMed, EMBASE, Cochrane Library, Web of Science, SINOMED, China National Knowledge Infrastructure, WanFang, and Chongqing VIP Information databases from inception until July 2019 for clinical trials investigating intermittent or continuous VLEDs for overweight and obese adults with T2DM. Additional studies were searched in the reference lists of all identified publications, including relevant meta-analyses and systematic reviews.

2.2. Inclusion Criteria

Published and unpublished randomized controlled trials (RCTs) and non-RCTs, which are clinical controlled studies evaluating the efficacy of intermittent or continuous VLEDs and qualitative studies exploring the acceptability of, barriers to, and facilitators of VLEDs, were considered for inclusion in this review.

We included clinical studies that satisfied the following criteria: (1) participants in the included studies were overweight or obese (mean or ≥10% above the ideal body weight based on the Metropolitan Life Insurance Company’s tables); (2) adults (aged ≥18 years) had T2DM in older studies using a different measure of obesity; (3) studies used intermittent or continuous VLEDs comprising ≤800 kcal/day in at least one intervention arm; and (4) studies also had to include a control arm receiving other energy control methods, including LEDs (800-1600 kcal/day), bariatric surgery, and MER. We excluded clinical studies with the following features: (1) both the intervention and comparator arms received VLED treatment (except VLEDs after surgical treatment) and (2) the intervention is VLED combined with other weight loss drugs. If a study compared three or more arms, VLED arms were considered to be the intervention and other energy control methods the comparators.

The outcome indicators of this study include the following: (1) weight loss (kg), (2) fasting plasma glucose levels (mmol/l) and change in medication, (3) triglyceride (TG) level (mmol/l), (4) homeostatic model assessment of insulin resistance (HOMA-IR) level, (5) dropout, (6) side effects, and (7) rebound.

2.3. Data Extraction

Two reviewers (YS Huang and XW Fu) independently extracted data from original trial reports using a standardized form. Data extracted included study characteristics (first author, publication year, single center or multicenter, sample size, intervention and control, period of treatment, and follow-up duration), characteristics of patients (inclusion criteria, background treatments, mean age, proportion of men, baseline weight, and baseline glucose levels), reported outcomes (weight, fasting plasma glucose levels, and adverse events), and information on methodology. We contacted the study authors when we needed to obtain additional information that was unavailable in the online publications or supplementary materials.

2.4. Quality Assessment

Risk of bias of RCTs was assessed using the Cochrane Collaboration’s tool [20]. We evaluated non-RCTs according to the Risk Of Bias In Non-randomised Studies of Interventions (ROBINS-I) tool [21]. Two investigators independently completed the assessments, and discrepancies were discussed with a third party and resolved by consensus.

Additionally, the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) framework was used to assess the quality of evidence contributing to each network estimate, which characterizes the quality of a body of evidence on the basis of the study limitations, imprecision, inconsistency, indirectness, and publication bias for the primary outcomes [22].

2.5. Statistical Analyses

The data entry and analysis were conducted using Microsoft Excel 2016 and Review Manager software version 5.3, respectively. Risk ratio and standard mean difference with 95% confidence interval (CI) of the outcomes were calculated as effect measure. The -statistic was calculated for heterogeneity, as a measure of the proportion of the overall variation that is attributable to between-study heterogeneity. A fixed-effects (FE) model was used if ; otherwise, the random-effects model was used.

To assess whether the results were influenced by study characteristics (effect modifiers), a subgroup analysis was conducted according to the study duration (<12 or ≥12 months). Additionally, sensitivity analyses were performed before combining RCTs and non-RCTs in the meta-analyses to determine possible additional sources of heterogeneity and changes in effect sizes.

Publication bias was tested by visual inspection of the funnel plots. When few studies are included in the analysis, the power of the tests is too low; therefore, publication bias was only examined if >10 study comparisons were included in the analysis [23].

3. Results

3.1. Study Characteristics

The search identified 6746 studies, of which 2157 were duplicates. Then, 4589 titles and abstracts were screened, with 145 studies for full-text screening. Finally, 18 eligible studies (911 participants) [2441] evaluated the effects of intermittent or continuous VLEDs on overweight or obese patients with T2DM compared with other energy control methods, and specifically, 7 studies (583 participants) [2531] compared VLEDs with LEDs, 6 studies (204 participants) [3641] with MER, and 5 studies (124 participants) [24, 3235] with bariatric surgery. Particularly, among the five studies involving surgical treatment, four studies (Jackness et al. [24], Lips et al. [32], Plum et al. [33], and Steven et al. [35]) used gastric bypass and 1 study (Cinkajzlova et al. [34]) used a variety of surgical approaches, including gastric plication (10 participants), gastric banding (2 participants), and gastric bypass (1 participant). Seven of the 18 included studies were non-RCTs. All of them were observational studies, four of them (Jackness et al. [24], Lips et al. [32], Plum et al. [33], and Cinkajzlova et al. [34]) compared VLEDs with bariatric surgery, and 3 of them (Paisey et al. [3638]) compared VLEDs with MER. Figure 1 shows the screening process. Table 1 shows the main characteristics of included trials.


Study IDStudy typeInterventions (kcal/day)Comparator (kcal/day)Use of hypoglycemic drugsStudy duration
VLEDControlTreatmentFollow-up

Anderson 1994RCTVLED (800): at least five liquid supplements/day which provide 800 kcal with 80 g of high-quality protein+two vitamin/mineral tabletsLED (approximately 820): at least three supplements/day which provide 320 kcal and 32 g of high-quality protein, one vitamin/mineral tablet, recommended evening meal of approximately 500 kcal and 50 g of high-quality proteinUnclearUnclear3 months1 year

Carter 2016RCTIntermittent VLED (400-598): 1670-2500 kJ/day for 2 days each week, with the remaining 5 days as habitual eatingLED (1196-1555): continuous energy restriction diet of 5000-6500 kJ/dayMedications adjusted according to blood glucose level12 weeksNone

Carter 2018RCTVLED (500-600): an intermittent energy restriction diet (500-600 kcal/d) followed for 2 nonconsecutive days per week (participants followed their usual diet for the other 5 days)LED (1200-1500): a continuous energy restriction diet (1200-1500 kcal/d) followed for 7 days per weekMedications could be reduced depending on glucose12 months2 years

Carter 2019RCTVLED (500-600): an intermittent energy restriction diet (500-600 kcal/d) followed for 2 nonconsecutive days per week (participants followed their usual diet for the other 5 days)LED (1200-1500): a continuous energy restriction diet (1200-1500 kcal/d) followed for 7 days per weekMedications could be reduced depending on glucose12 months2 years

Harvey 1993RCTVLED (400-500): during weeks 1-12, consumed a 400-500 kcal/day. This was followed by a 6-week refeeding period, which required slow reintroduction of calories, carbohydrate, and fat. By the end of the 6 weeks of refeeding, subjects in the VLED were prescribed a self-selected balanced, low-calorie diet (1000-1200 kcal/day)LED (1000-1200): a self-selected balanced diet of 1000-1200 kcal per day for 6 months15 of the subjects were treated with diet only, 54 with oral medication, and 23 with insulin.24 weekNone

Wing 1991RCTVLED (400-500): weeks 0–4: 1000–1500 kcal/day; weeks 5–12: 400–500 kcal/day; weeks 13–20: 1000 kcal/day; weeks 21–72 : 1000–1500 kcal/day (weight maintenance). Included a 20-week behavioural treatment programme with weekly group meetings including instructions on behavioural modification, exercise, and dietLED (1000–1500): weeks 0-20: 1000–1500 kcal/day (intervention period); weeks 21-72: 1000–1500 kcal/day (weight maintenance). Included a 20-week behavioural treatment programme with weekly group meetings including instructions on behavioural modification, exercise, and dietUnclearUnclear20 weeks1 year

Wing 1994RCTVLED (400-500): weeks 0–12 and 24-36: 400–500 kcal/d+vitamins and supplements, otherwise 1000-1200 kcal/d. Included a 50-week behavioural treatment programme with weekly group meetings including instructions on behavioural modification, exercise, and dietLED (1000-1200): weeks 0-48: 1000-1200 kcal/d (intervention period); subjects were encouraged to keep their fat intake below 30% of the daily calorie intake. Included a 50-week behavioural treatment programme with weekly group meetings including instructions on behavioural modification, exercise, and dietUnclearUnclear1 year2 years

Jackness 2013NRCTVLED (300-500): day 1: 360 kcal/day; days 2–24: 500 kcal/dayRYGB (500): postoperative VLED is assumed of approximately 500 kcal/day until the end of week 3UnclearUnclearMean study period of 21 daysNone

Lips 2013NRCTVLED: weeks 0–3: 600 kcal/day (intervention period); weeks 3–8: 800–1000 kcal/day; after 2 months: 1200 kcal/dayRYGB (<800): first 5 days after RYGB operation: <600 kcal/day; weeks 1–3: gradual increase to 700–800 kcal/day; week 3–month 3: 1200 kcal/dayUnclearUnclear3 monthsNone

Plum 2011NRCTVLED (800): the diet divided into five servings of 160 kcal (800 kcal/day) in 237 ml per servingRYGB: postintervention, subjects followed dietary instructions provided by the surgical team55% reduction in the number of medications after LCDAntidiabetic medications were discontinued after RYGBVLED: 8.1 (0.5) weeks
RYGB: 3.4 (0.3) weeks
None

Cinkajzlova 2018NRCTVLED (595): total energy content of 2500 kJ/day for 3 weeksSurgery: the procedures included gastric plication (10 subjects), gastric banding (2 subjects), and gastric bypass (1 subject)UnclearUnclearVLCD 3 weeks; control 1 m, 3 m, and 1 yNone

Steven 2016RCTVLED (700): the VLED provided an average of 700 kcal/dayRYGB (~800): the postoperative (RYGB) diet was water only on day 1 then a semisolid diet (~800 kcal/day) for the rest of the first week.Participants were asked to stop medications prior to the first study: metformin and/or sulphonylureas for at least 72 h, dipeptidyl peptidase-4 inhibitors for 1 month, and insulin for at least 24 h7 daysNone

Paisey 1995NRCTVLED (400-670): 400-470 kcal/d for women, 540–670 kcal/d for men for 3-5 months and repeated in the course of the study if appropriate. Once an agreed target weight had been reached, patients were seen intensively to wean them back onto a low-fat diet. A standardized programme of low-fat, low-refined carbohydrate foods was introduced over a 6-week period as patients transferred from VLED to normal eating patterns. They were advised to continue low-fat nutrition in the long term with three main meals dailyMER: low-fat, low-sugar, and high-fibre intake advised; 5-day self-report food records were collected and discussed individually, repeated every 6-8 weeks. Aerobic exercises with encouragement performed at each visit followed by a group discussion on nutritionAll antidiabetic medication was stopped on day one, and insulin dosage halved. Hypotensive and hypolipidemic agents were stopped if appropriate at one monthUnclear6 monthsNone

Paisey 1998NRCTSame as “Paisey 1995”Same as “Paisey 1995”Subjects were advised to stop all antidiabetic medication and diuretics from day 1 of treatmentUnclear12 monthsNone

Paisey 2002NRCTSame as “Paisey 1995”Same as “Paisey 1995”Antidiabetic and antihypertensive medications were stopped during the first week of treatmentUnclearAt least 6 weeks5 years

Li 2017RCTVLED (300): days 1~2: low-calorie diet (1200 kcal/day); from the evening of study day 3 to the evening of study day 11: 300 kcal/day; followed by 3 low-calorie diet days (1200 kcal/day), followed by advice about a Mediterranean diet. Fasting took place only once in the 4-month periodMER: follow the principles of a Mediterranean dietSubjects were advised to abstain from other new treatments against diabetes during the study period4 monthsNone

Williams 1998RCTVLED (400-600): 1500-1800 kcal/day diet, except for a total of 20 study days during which they consumed a 400-600 kcal/day VLED.
(1-day): a VLED for 5 consecutive days during week 2 of the study and then 1 day a week for 15 weeks, subjects used diaries to record daily caloric intake
MER (1500-1800): a 1500-1800 kcal/day diet throughout the 20 weeks of the treatment programme. Included a 20-week behavioural treatment programme with weekly group meetings including instructions on behavioural modification, exercise, and diet. Subjects used diaries to record daily caloric intakeUnclearUnclear20 weeksNone

Williams 1998aRCTVLED (400-600): 1500-1800 kcal/day diet, except for a total of 20 study days during which they consumed a 400-600 kcal/day VLED.
(5-day): a VLED for 5 consecutive days during weeks 2, 7, 12, and 17+a 20-week behavioural treatment programme with weekly group meetings including instructions on behavioural modification, exercise, and diet. Subjects used diaries to record daily caloric intake
MER (1500-1800): a 1500-1800 kcal/day diet throughout the 20 weeks of the treatment programme. Included a 20-week behavioural treatment programme with weekly group meetings including instructions on behavioural modification, exercise, and diet. Subjects used diaries to record daily caloric intakeUnclearUnclear20 weeksNone

Laakso 1988RCTVLED (500-800): day 1-day 3: 30 kcal/kg/d; day 4-day 15: 500 kcal/d; day 15-day 17: 800 kcal/dMER (30 kcal/kg/d): the diet was as previously described (30 kcal/kg/d) consisting of 50% carbohydrates, 30% fat, and 20% protein divided into three main mealsAll medications for diabetes were discontinuedInsulin was started using intermediate-acting insulin as one single injection at 7 AM. The mean dosage of insulin (±SEM) was 2 weeksNone

VLED: very low-energy diet; LED: low-energy diet; MER: mild energy restriction; RYGB: Roux-en-Y gastric bypass; RCT: randomized controlled trial; NRCT: nonrandomized controlled trial.
3.2. Evaluation of the Risk of Bias of the Selected Studies

The risk of bias for the included RCTs was assessed using the Cochrane risk of bias tool. None of the RCTs had an overall low risk of bias. Most RCTs had unclear risk of bias for sequence generation, allocation concealment, blinding of participants, blinding of outcome, and selective reporting because no detailed information was provided. However, three studies had high risk of bias for blinding of participants and blinding of outcome assessment, and one study had high risk of bias for allocation concealment because it could not be performed. Moreover, there is incomplete outcome data that most studies had a low risk of bias. Risk of bias assessment of included trials is shown in Figure 2.

The risk of bias for the included non-RCTs according to the ROBINS-I tool is presented in Figure 3. None of the studies had a low or moderate risk of bias, six (Jackness et al. [24], Lips et al. [32], Plum et al. [33], and Paisey et al. [3638]) had signs of serious bias, and one (Cinkajzlova et al. [34]) had critical bias. The domain “bias due to confounding” was a main source of critical or serious risk of bias. The domain “bias in selection of participants into the study” had moderate or serious risk of bias in all studies. Risk of bias assessment is shown in Figure 3.

3.3. Meta-Analysis
3.3.1. Weight Loss

(1) VLEDs versus LEDs. Seven studies [2531] analyzed weight loss when a VLED () was compared with a LED (). Five of the studies provided data at the end of the intervention, and three provided data in the long-term follow-up (≥1 year). Subgroup analyses did result in differences in various time points. When the intervention is completed, the VLED group lost significantly more weight than the comparator arms (; ; , <0.05; ). However, when follow-up is ≥1 year, the observed difference in weight loss compared with controls was not significant (; ; ; ) (Figure 4).

(2) VLEDs versus Bariatric Surgery. Four studies [24, 32, 33, 35] analyzed the weight loss between the VLED and surgery groups, including 84 participants. Moreover, the surgical methods used in these four studies were RYGB as comparator arms. The merged data with no evidence of interstudy heterogeneity (), according to the DerSimonian-Laird FE model, revealed that the VLEDs and RYGB have similar effects on weight loss, and there is no significant difference between them (; ; , >0.05) (Figure 5).

(3) VLEDs versus MER. Four studies [3740] analyzed the weight loss when a VLED () was compared with MER (). Three studies provided data at the end of the intervention, and one provided data for long-term follow-up (5 years). In particular, the study of Williams et al. [40] contains two types of VLED interventions, and that of Paisey et al. [38] contains data for two endpoints. According to the results of the subgroup analysis, the data at the end of the intervention showed that VLED was significantly better than MER in weight loss (; ; ), with evidence of moderate heterogeneity (; ). Sensitivity analysis showed that the heterogeneity was 0% when “Paisey et al. [38]” was removed, and the effect of VLEDs on weight loss was still significantly better than that of the control (; ; ). However, when followed up for 5 years, similar to the result of the “Paisey et al. [37]” study, MER was better maintained than VLEDs (; ; ) (Figure 6).

3.3.2. Blood Glucose and Changes in Medication

(1) VLEDs versus LEDs. Four studies [25, 28, 30, 31] analyzed the blood glucose levels between the VLED and LED groups, and all of them provided data at the end of the intervention. Simultaneously, two provided data for long-term follow-up (≥1 year). A significant difference in weight change in favor of the intervention arm was noted at both the end of the intervention (; ; , <0.05) and follow-up (; ; , <0.05), and both of them had no evidence of interstudy heterogeneity (). Regarding the use of hypoglycemic drugs, Carter et al. reported that although medication dose decreased with time, all participants using medication at baseline were also using medication at the end of the study. At 2 years, one study (Wing et al. [31]) reported that fewer participants in the VLED group required medication (45% vs. 69% in the VLED and LED groups, respectively) (Figure 7).

(2) VLEDs versus Bariatric Surgery. Five studies [24, 3235] analyzed the blood glucose levels between the VLED () and bariatric surgery groups (). The merged data with no evidence of interstudy heterogeneity (), according to the DerSimonian-Laird FE model, revealed that VLEDs and surgery have similar effects on weight loss, and there is no significant difference between them (; ; , >0.05) (Figure 8). In the use of hypoglycemic drugs, one study [33] showed that all hypoglycemic drugs were discontinued in the RYGB arm and decreased by 55% in the VLED arm after the intervention. In another study [32], metformin was reintroduced in 4/15 participants in the RYGB arm and 2/12 participants in the VLED arm after the intervention, and the difference was not significant.

(3) VLEDs versus MER. Five studies [36, 37, 3941] analyzed the blood glucose levels between the VLED () and MER groups (). Results from the subgroup analyses showed that VLED was significantly better than MER in lowering blood glucose levels (; ; ) at the end of the intervention, with evidence of low heterogeneity (; ). However, at the 5-year follow-up, only one study by “Paisey et al. [37]” reported that the difference in blood glucose levels compared with controls was not significant (; ; ). In the use of hypoglycemic drugs at the end of the intervention, the study of Paisey et al. showed that, at 6 months (all patients who underwent VLEDs had reverted to normal food for at least two weeks), the patients in the VLED group discontinued insulin, sulphonylureas, or hypolipidemic agents, while patients in the MER group were not able to discontinue their antidiabetic or hypolipidemic therapies. At 1 year, 14 of 15 patients in the VLED group, but none in the conventional diet group, had discontinued insulin and any oral hypoglycemic medication (Figure 9).

3.3.3. TG

(1) VLEDs versus LEDs. Four studies [25, 28, 30, 31] analyzed the TG level between the VLED () and LED groups (). All studies provided data at the end of the intervention, and two provided data in the long-term follow-up (≥1 year). Results from subgroup analyses showed that the VLED group had significantly lower TG level than the comparator arms at the end of the intervention (; ; , <0.05; ). However, when the follow-up duration is ≥1 year, the observed difference in the TG level compared with controls was not significant (; ; , >0.05; ) (Figure 10).

(2) VLEDs versus Bariatric Surgery. Four studies [24, 3335] analyzed the TG levels between the VLED () and bariatric surgery groups (). The merged data, which had no evidence of interstudy heterogeneity (), according to the DerSimonian-Laird FE model, revealed that VLEDs and surgery have similar effects on weight loss, and there is no significant difference between them (; ; , >0.05) (Figure 11).

(3) VLEDs versus MER. Four studies [3740] analyzed the TG levels between the VLED () and MER groups (). Results from subgroup analyses showed that a VLED was significantly better than MER in lowering TG levels (; ; , <0.05) at the end of the intervention, with no evidence of interstudy heterogeneity ( ). However, at the 5-year follow-up, similar to the result of the “Paisey et al. [37]” study, the difference in lowering TG level compared with controls was not significant (; ; ) (Figure 12).

3.3.4. HOMA-IR

Four studies [24, 3234] analyzed the change in HOMA-IR between the VLED () and bariatric surgery groups (), and one study analyzed the change in HOMA-IR between the VLED () and MER groups (). The meta-analysis showed that there was no significant difference between VLEDs and surgery in increasing HOMA-IR (; ; , >0.05) (Figure 13). Additionally, one study (Li et al. [39]) reported that nonsignificant improvements in HOMA-IR were also observed between the VLED and MER groups.

3.3.5. Dropout

Comparing the VLED and bariatric surgery groups, no loss of patients was reported. However, most studies on VLEDs compared with those on LEDs or MER reported increased dropout rate.

(1) VLEDs versus LEDs. Six studies [2528, 30, 31] reported the difference in dropout rate between the VLED () and LED groups (). The meta-analyses showed that the VLED group had a similar dropout rate with the comparator arms (; ; , >0.05; ) (Figure 14).

(2) VLEDs versus MER. Five studies [36, 37, 3941] reported the difference in dropout rates between the VLED () and MER groups (). Results from the meta-analyses showed that the VLED group had a similar dropout rate with the MER group (; ; , >0.05) with no evidence of interstudy heterogeneity (; ) (Figure 15).

3.3.6. Side Effects

Nine of 18 studies involved reports of adverse reactions. Adverse reactions reported by Carter et al. [26, 27] were mainly hypoglycemia, hyperglycemia, and headache. Paisey et al. [3638] reported adverse reactions such as hypoglycemia. myocardial infarction, and telogen effluvium. Wing et al. [30, 31] mainly reported adverse reactions such as cold intolerance, constipation, and hair loss. Andorson’s study showed that frequently reported side effects during the weight loss phase included constipation, diarrhea, dizziness, and fatigue. The adverse reactions reported in Li et al.’s study were slight headache and dizziness during energy restriction. None of these studies reported significant differences in side effects between the VLED and control groups (see Table 2 for details).


Study IDVLEDControl

Carter 2016Hypoglycemia (<4 mmol/l) only occurred in insulin-controlled participants (), with no difference between treatment groups
Carter 2018Hypoglycemia ()
Hyperglycemia ()
Headache ()
Hypoglycemia ()
Hyperglycemia ()
Paisey 1995Severe hypoglycemic attack ()Myocardial infarction ()
Paisey 1998Nonfatal myocardial infarction ()
Severe hypoglycemic attack ()
Nonfatal myocardial infarction ()
Paisey 2002Nonfatal myocardial infarction ()
Telogen effluvium (, which recovered within 2 years of stopping VLEDs in five)
Primary biliary cirrhosis ()
Nonfatal myocardial infarction ()
Wing 1991Coldness, constipation, dry skin, diarrhea, dizziness, vomiting, or weakness—commonly reported side effects of VLEDs. There were no significant differences over time in any of these symptoms and no significant difference between subjects in the LED and VLED groups. However, uric acid increased significantly in the VLED group
Wing 1994Common side effects included cold intolerance, constipation, and hair loss, which all resolved when the VLED was terminatedUnclear
Andorson 1994Frequently reported side effects during the weight loss phase included constipation (56% of subjects), diarrhea (31%), dizziness (31%), fatigue (31%), flu/sore throat (13%), headache (10%), vomiting (10%), blurred vision (10%), muscle cramps (8%), and syncope (5%). None of these side effects required treatment alteration.
Li 2017No serious adverse effects: slight headache (); slight dizziness ()No serious adverse effects

VLED: very low-energy diet; LED: low-energy diet.
3.3.7. Rebound

Only three studies mentioned a rebound in body weight, blood glucose level, and other indicators after energy restriction therapy. One study [28] reported that at 24 months, in the completer analysis of 84 participants at follow-up, 44 (52%) regained weight (>1 kg weight gain) and participants regained 33% of their weight losses between 12 and 24 months. In this follow-up study, HbA1c level had increased by 0.3% (3.3 mmol/mol) from baseline at 24 months. Paisey et al. [37] found that weight loss was slower in the intensive conventional diet group than in the VLED group but better maintained at 5 years: group 1, , and group 2, . Wing et al. [30, 31] reported that, although initial weight losses were greater in the VLED group, these participants regained significantly more weight than those in the behavioural therapy group in 1 year of follow-up. Moreover, at one-year assessment, the measures of glycemic control had returned to baseline, and no differences were observed between treatment groups.

3.4. Publication Bias

All outcome indicators were analyzed in <10 studies, so publication bias was not examined.

3.5. GRADE for the Outcomes

We evaluated all outcome indicators by GRADEprofiler 3.6 from the following aspects: (1) downgrade quality of evidence, risk of bias, inconsistency, indirectness, imprecision, and publication bias and (2) upgrade quality of evidence, large effect, plausible confounding changing the effect, and dose-response gradient.

After a comprehensive analysis, the evidentiary body was formed and found that all outcome indicators had low quality or extremely low quality (see Tables 35 for details).


Quality assessmentNo. of patientsEffectQualityImportance
No. of studiesDesignRisk of biasInconsistencyIndirectnessImprecisionOther considerationsVLEDLEDRelative (95% CI)Absolute

Weight (better indicated by lower values)
 8Randomized trialsSerious1No serious inconsistencySerious2No serious imprecisionNone246241MD -1.86 lower (-3.34 to -0.37 lower)Low9
Weight: end of the intervention (better indicated by lower values)
 5Randomized trialsSerious1No serious inconsistencySerious2No serious imprecisionNone151146MD -2.77 lower (-4.81 to -0.72 lower)Low9
Weight: (better indicated by lower values)
 3Randomized trialsSerious1No serious inconsistencySerious2Serious3None9595MD -0.84 lower (-3.01 lower to 1.32 higher)Very low9
Glucose (better indicated by lower values)
 6Randomized trialsSerious1No serious inconsistencySerious2No serious imprecisionNone187180MD -1.26 lower (-1.97 to -0.55 lower)Low8
Glucose: end of the intervention (better indicated by lower values)
 3Randomized trialsSerious1No serious inconsistencySerious2No serious imprecisionNone7576MD -1.18 lower (-2.05 to -0.3 lower)Low8
Glucose: (better indicated by lower values)
 3Randomized trialsSerious1No serious inconsistencySerious2Serious4None112104MD -1.43 lower (-2.65 to -0.2 lower)Very low8
TG (better indicated by lower values)
 6Randomized trialsSerious1No serious inconsistencySerious2No serious imprecisionNone185179MD 0.31 lower (-0.5 to -0.13 lower)Low7
TG: end of the intervention (better indicated by lower values)
 3Randomized trialsSerious1No serious inconsistencySerious2No serious imprecisionNone7576MD -0.35 lower (-0.58 to -0.12 lower)Low7
TG: (better indicated by lower values)
 3Randomized trialsSerious1No serious inconsistencySerious2Serious4None110103MD -0.25 lower (-0.55 lower to 0.06 higher)Very low7
Dropout
 6Randomized trialsSerious1No serious inconsistencySerious2No serious imprecisionNone57/253
(22.5%)
69/253
(27.3%)
OR 0.74 (0.49 to 1.13)56 fewer per 1000 (from 118 fewer to 25 more)Low6
 21.4%46 fewer per 1000 (from 96 fewer to 21 more)

CI: confidence interval; OR: odds ratio. GRADE Working Group grades of evidence: high quality: further research is very unlikely to change our confidence in the estimate of effect; moderate quality: further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate; low quality: further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate; very low quality: we are very uncertain about the estimate. 1There are studies that do not account for specific stochastic methods, so they are reduced by one level. 2Interventions include continuous VLEDs and intermittent VLEDs, which differ to some extent, so they are reduced by one level. 3No explanation was provided. 4The ratio of 95% CI to the effect is more than 50%. 95% CI is wider and its accuracy is poor, so it decreases one level.

Quality assessmentNo. of patientsEffectQualityImportance
No. of studiesDesignRisk of biasInconsistencyIndirectnessImprecisionOther considerationsVLEDBariatric surgeryRelative (95% CI)Absolute

Weight
 4Randomized trialsSerious1No serious inconsistencyNo serious indirectnessSerious2None4242MD -3.14 lower (-10.04 lower to 3.67 higher)Low9
Glucose (better indicated by lower values)
 5Randomized trialsSerious1No serious inconsistencyNo serious indirectnessSerious2None6955MD 0.37 higher (-0.22 lower to 0.96 higher)Low8
TG (better indicated by lower values)
 4Randomized trialsSerious1No serious inconsistencyNo serious indirectnessSerious2None5740MD -0.04 lower (-0.25 lower to 0.17 higher)Low7
HOMA-IR (better indicated by lower values)
 4Observational studies3No serious risk of biasSerious4No serious indirectnessSerious2None60Very low6
 46MD -1 lower (-2.7 lower to 0.7 higher)

CI: confidence interval; OR: odds ratio. GRADE Working Group grades of evidence: high quality: further research is very unlikely to change our confidence in the estimate of effect; moderate quality: further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate; low quality: further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate; very low quality: we are very uncertain about the estimate. 1Some studies were nonrandomized controlled trials. 2The ratio of 95% CI to the effect is more than 50%. 95% CI is wider and its accuracy is poor, so it decreases one level. 3Case-control. 4The value of the combined results is larger, and there is statistical heterogeneity, so it falls by one grade.

Quality assessmentNo. of patientsEffectQualityImportance
No. of studiesDesignRisk of biasInconsistencyIndirectnessImprecisionOther considerationsVLEDMild energy restrictionRelative (95% CI)Absolute

Weight (better indicated by lower values)
 6Randomized trialsVery serious1,2Serious3Serious4No serious imprecisionNone8888MD -4.57 lower (-9.44 lower to 0.3 higher)Very low9
Weight: end of the intervention (better indicated by lower values)
 5Randomized trialsVery serious1,2Serious3Serious4No serious imprecisionStrong association57576MD -6.72 lower (-10.05 to -3.39 lower)Very low9
Weight: follow-up 5 years (better indicated by lower values)
 1Observational studiesSerious6No serious inconsistencyNo serious indirectnessSerious7None1312MD 4.1 higher (0.13 to 8.07 higher)Very low9
Glucose (better indicated by lower values)
 6Randomized trialsVery serious1,2No serious inconsistencySerious4No serious imprecisionNone8684MD -0.75 lower (-1.44 to -0.06 lower)Very low8
Glucose: end of the intervention (better indicated by lower values)
 5Randomized trialsVery serious1,2No serious inconsistencySerious4No serious imprecisionNone7472MD -0.74 lower (-1.44 to -0.04 lower)Very low8
Glucose: follow-up 5 years (better indicated by lower values)
 1Observational studiesSerious6No serious inconsistencyNo serious indirectnessSerious7None1212MD -1 lower (-4.62 lower to 2.62 higher)Very low8
TG (better indicated by lower values)
 6Randomized trialsVery serious1,2No serious inconsistencySerious4No serious imprecisionNone8884MD -0.49 lower (-0.86 to -0.12 lower)Very low7
TG: end of the intervention (better indicated by lower values)
 5Randomized trialsVery serious1,2No serious inconsistencySerious4No serious imprecisionNone7572MD -0.55 lower (-0.93 to -0.17 lower)Very low7
TG: follow-up 5 years (better indicated by lower values)
 1Observational studies8Serious6No serious inconsistencyNo serious indirectnessNo serious imprecisionNone13Very low7
12MD 0.4 higher (-1.11 lower to 1.91 higher)
Dropout
 6Randomized trialsVery serious1,2No serious inconsistencyNo serious indirectnessNo serious imprecisionNone14/97 (14.4%)19/97 (19.6%)OR 0.68 (0.32 to 1.48)54 fewer per 1000 (from 124 fewer to 69 more)Low6
21.1%57 fewer per 1000 (from 132 fewer to 73 more)

CI: confidence interval; OR: odds ratio. GRADE Working Group grades of evidence: high quality: further research is very unlikely to change our confidence in the estimate of effect; moderate quality: further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate; low quality: further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate; very low quality: we are very uncertain about the estimate. 1Some studies were nonrandomized controlled trials. 2There are studies that do not account for specific stochastic methods, so they are reduced by one level. 3The value of the combined results is larger and there is statistical heterogeneity, so it falls by one grade. 4Interventions include continuous VLEDs and intermittent VLEDs, which differ to some extent, so they are reduced by one level. 5After merger, the effect is large and the accuracy is high, so it goes up one level. 6Failure to adequately control confounding factors. 7The ratio of 95% CI to the effect is more than 50%. 95% CI is wider and its accuracy is poor, so it decreases one level. 8Case-control.

4. Discussion

Our systematic review provides evidence based on current clinical trials on the efficacy of continuous and intermittent VLEDs in overweight and obese individuals with T2DM by comparison to other methods of energy restriction. First, during the intervention period, a VLED is superior in the reduction of body weight and blood glucose and TG levels to LEDs and MER. After long-term follow-up, there is no obvious difference in weight loss between VLEDs and LEDs, but glycemic control is still more effective in VLEDs. Second, VLEDs offer beneficial effects on weight loss, glycemic control, and improvement of insulin resistance comparable to bariatric surgery.

Increasing evidence suggested that modest and sustained weight loss improved glycemic control in overweight and obese individuals with T2DM [3]. Furthermore, recent studies reported that intentional weight losses by low-calorie diets, usually >15 kg, could reverse T2DM into a nondiabetic state [5, 42]. Based on the current studies, our study concluded that more extreme dietary energy restriction with VLEDs is an effective method to achieve intensive weight loss in a short term and improve glycemic control more effectively compared with LEDs and MER. This conclusion supported the recommendation of the American Diabetes Association (ADA) Standards of Medical Care in Diabetes that high-intensity diet intervention, physical activity, and behavioural therapies to achieve a 500–750 kcal/day energy deficit and maintain >5% weight loss should be prescribed for patients with type 2 diabetes who are overweight or obese and ready to achieve weight loss. Furthermore, previous studies showed that rapid weight loss by VLEDs is inevitably followed by weight regain [42], but recent studies with at least 1-year follow-up found that VLEDs might present a longer effect on weight maintenance [5, 43]. Another study showed that even though weight was regained, the short-term weight loss had long-lasting benefits on glycemic control and prevention of cardiovascular effects in T2DM [44]. Our results are in line with this study. After further analysis of the effects of long-term follow-up (1–5 years), we found no obvious difference in weight loss between VLEDs and LEDs, but VLEDs still maintained better glycemic control. The lasting effects of VLEDs may be attributed to improved insulin sensitivity remaining from weight loss [45], “metabolic memory” from the treatment period [46], and “legacy effect” by lifestyle intervention [47].

It is reported that dyslipidemia, especially hypertriglyceridemia, is an independent risk factor in predicting the development of diabetes, which is partially mediated by insulin resistance and obesity [48]. Several prospective studies have demonstrated that weight loss induced decreases in pancreatic and liver TG levels in T2DM, which was associated with the recovery of insulin secretory function [6, 49]. However, the effect of weight loss by VLEDs on the plasma TG level is rarely discussed. Our meta-analyses found that VLEDs reduced the plasma TG level in T2DM more effectively compared to LEDs and MER and had an equivalent effect with bariatric surgery, which may have potential effect on preventing the development of T2DM.

Bariatric surgery is confirmed to have superior effect in T2DM [50] and has been proposed as a first-line therapy for obese patients with T2DM [3]. Bariatric surgery can restore normal liver insulin sensitivity within days and decrease plasma glucose and TG levels within weeks [51]. In this context, some studies determined whether the effects of bariatric surgery are primarily due to negative energy balance or unique to the surgical procedure [24, 51]. Our study shows that VLEDs are as effective as bariatric surgery (mainly RYGB) in terms of weight loss, glycemic control, insulin resistance improvement, and plasma TG level reduction. Additionally, VLEDs have lower costs and lesser adverse effects compared with bariatric surgery. Thus, VLEDs may be a considerable therapy when patients could not or would not wish to undergo surgical treatments.

VLEDs were found to be acceptable as indicated by the low dropout rate in both this and a previous study. The main reason may be that rapid weight loss increases patient’s confidence, and hunger of patients after VLED intervention is more inhibited. A study shows that attrition was lower when weight loss was undertaken rapidly rather than gradually, because rapid weight loss might motivate participants [52]. Moreover, ketosis suppresses appetite and increases the satiety hormone cholecystokinin, which increases the possibility that participants with rapid weight loss might have been less hungry during the weight loss phase than those following the gradual diet [5356]. Of note, the experience of healthcare professionals involved in the trial in obesity treatment also had a significant impact on attrition.

While the short-term efficacy of VLEDs is evident and patient compliance is acceptable according to our analysis, the reports of adverse reactions in the studies are incomplete, limiting the use of this method.

In a previous systematic review, Rehackova et al. [19] revealed that VLEDs led to considerable weight loss and blood glucose control via small sample or qualitative studies. However, evidence on the long-term efficacy of VLEDs with regard to weight loss in individuals with T2DM is lacking. Our study has expanded the sample size and further analyzed the follow-up results between VLEDs and LEDs. After the follow-up (1–5 years), VLEDs present a more effective glycemic control effect, but there is no obvious difference in weight loss between VLEDs and LEDs. Some included studies [28, 30, 31, 37] also showed that, at the end of VLED intervention, the decrease in body weight, blood glucose level, and other indicators would rebound to varying degrees. This shows that adherence to a VLED regimen is crucial in maximizing intervention effects. It has been shown that greater initial weight loss facilitates weight maintenance if followed by an effective weight loss maintenance programme [57]. Further exploring a strategy to suppress hunger after rapid weight loss and prevent weight regain of VLEDs is greatly important in the popularization of this method.

This meta-analysis provides some objective evidence for the application of VLEDs in obese individuals with T2DM, but there are still many limitations in the study. First, both non-RCTs and RCTs were combined in the meta-analyses, which increased the heterogeneity and risk of bias. Therefore, the results of this study still need to be confirmed by higher-quality research. Second, some high-quality research in this field has been conducted by a small number of research groups, resulting in insufficient representation of data. Thus, more extensive studies are needed to clarify the practicability of VLEDs in different ethnic groups. Third, most included studies did not mention the use of hypoglycemic drugs in participants. When VLEDs are used to intervene with obese patients with T2DM, determination of hypoglycemic drugs is difficult. In the future, the standardized research of this area should be strengthened. Lastly, only a few included studies that recorded follow-up results, which led to insufficient convincing evidence. Moreover, the longest follow-up duration in the included studies was only 5 years, so the long-term effect of VLEDs needs further study.

5. Conclusions

Dietary intervention through VLEDs is more effective in rapid weight loss and glycemic control and improved lipid metabolism in overweight and obese individuals with T2DM than LEDs and MER, although they have similar long-term effects. Moreover, VLEDs have similar efficacy and acceptability with bariatric surgery, which shows that VLEDs have considerable curative effect for remission of T2DM. However, after GRADE, it was found that all outcome indicators had low quality or base quality, so the results of this study still need to be further confirmed by high-quality research.

Abbreviations

DM:Diabetes mellitus
VLED:Very low-energy diet
LED:Low-energy diet
MER:Mild energy restriction
RYGB:Roux-en-Y gastric bypass
CI:Confidence interval
MD:Mean difference.

Conflicts of Interest

The authors declare that they have no competing interests.

Authors’ Contributions

All authors take responsibility for the integrity of the data and the accuracy of data analysis. WJ. Liu and YN. Liu contributed to the study concept and design. YS. Huang and QY. Zheng developed the protocol design. YS. Huang, XW Fu, XQ. Zheng, CH. Xia, ZB. Zhu, and QY. Zheng carried out literature retrieval and data extraction. HS. Yang and QY. Zheng performed the statistical analysis. QY. Zheng, XQ. Zhang, and WJ. Liu performed the interpretation of data. YS. Huang and QY. Zheng are responsible for the drafting of the manuscript. HS. Yang, QY. Zheng, XQ. Zhang, WJ. Liu, and YN. Liu carried out quality assessment. WJ. Liu and YN. Liu contributed to critical revision of the manuscript. HS. Yang, WJ. Liu, and YN. Liu are responsible for technical support. All authors have read and agreed to the submission to this journal of the manuscript. Yi Shan Huang and Qiyan Zheng contributed equally to this work.

Acknowledgments

This study was supported by the National Natural Science Foundation of China (Grant Nos. 81570656 and 81774278) and the Initial Scientific Research Fund of Talent Introduction in Dongzhimen Hospital Affiliated to Beijing University of Chinese Medicine (2016TSRC).

References

  1. M. Bluher, “Obesity: global epidemiology and pathogenesis,” Nature Reviews Endocrinology, vol. 15, no. 5, article 176, pp. 288–298, 2019. View at: Publisher Site | Google Scholar
  2. C. Daousi, I. F. Casson, G. V. Gill, I. A. MacFarlane, J. P. Wilding, and J. H. Pinkney, “Prevalence of obesity in type 2 diabetes in secondary care: association with cardiovascular risk factors,” Postgraduate Medical Journal, vol. 82, no. 966, pp. 280–284, 2006. View at: Publisher Site | Google Scholar
  3. American Diabetes Association, “8. Obesity management for the treatment of type 2 Diabetes:Standards of medical care in diabetes-2019,” Diabetes Care, vol. 42, Supplement 1, pp. S81–S89, 2019. View at: Publisher Site | Google Scholar
  4. American Diabetes Association, “4. Lifestyle Management:Standards of medical care in diabetes-2018,” Diabetes Care, vol. 41, Supplement 1, pp. S38–S50, 2018. View at: Publisher Site | Google Scholar
  5. M. E. Lean, W. S. Leslie, A. C. Barnes et al., “Primary care-led weight management for remission of type 2 diabetes (DiRECT): an open-label, cluster-randomised trial,” Lancet, vol. 391, no. 10120, pp. 541–551, 2018. View at: Publisher Site | Google Scholar
  6. E. L. Lim, K. G. Hollingsworth, B. S. Aribisala, M. J. Chen, J. C. Mathers, and R. Taylor, “Reversal of type 2 diabetes: normalisation of beta cell function in association with decreased pancreas and liver triacylglycerol,” Diabetologia, vol. 54, no. 10, pp. 2506–2514, 2011. View at: Publisher Site | Google Scholar
  7. M. L. Gow, L. A. Baur, N. A. Johnson, C. T. Cowell, and S. P. Garnett, “Reversal of type 2 diabetes in youth who adhere to a very-low-energy diet: a pilot study,” Diabetologia, vol. 60, no. 3, pp. 406–415, 2017. View at: Publisher Site | Google Scholar
  8. H. M. Parretti, S. A. Jebb, D. J. Johns, A. L. Lewis, A. M. Christian-Brown, and P. Aveyard, “Clinical effectiveness of very-low-energy diets in the management of weight loss: a systematic review and meta-analysis of randomized controlled trials,” Obesity Reviews, vol. 17, no. 3, pp. 225–234, 2016. View at: Publisher Site | Google Scholar
  9. R. L. Atkinson, W. H. Dietz, J. P. Foreyt et al., “Very low-calorie diets. National Task Force on the Prevention and Treatment of Obesity, National Institutes of Health,” JAMA, vol. 270, no. 8, pp. 967–974, 1993. View at: Publisher Site | Google Scholar
  10. S. Andela, T. L. Burrows, L. A. Baur, D. H. Coyle, C. E. Collins, and M. L. Gow, “Efficacy of very low-energy diet programs for weight loss: a systematic review with meta-analysis of intervention studies in children and adolescents with obesity,” Obesity Reviews, vol. 20, no. 6, pp. 871–882, 2019. View at: Publisher Site | Google Scholar
  11. P. Sumithran, L. A. Prendergast, E. Delbridge et al., “Long-term persistence of hormonal adaptations to weight loss,” New England Journal of Medicine, vol. 365, no. 17, pp. 1597–1604, 2011. View at: Publisher Site | Google Scholar
  12. A. E. Rothberg, L. N. McEwen, A. T. Kraftson, C. E. Fowler, and W. H. Herman, “Very-low-energy diet for type 2 diabetes: an underutilized therapy?” Journal of Diabetes and its Complications, vol. 28, no. 4, pp. 506–510, 2014. View at: Publisher Site | Google Scholar
  13. L. Rehackova, V. Araujo-Soares, A. J. Adamson, S. Steven, R. Taylor, and F. F. Sniehotta, “Acceptability of a very-low-energy diet in type 2 diabetes: patient experiences and behaviour regulation,” Diabetic Medicine, vol. 34, no. 11, pp. 1554–1567, 2017. View at: Publisher Site | Google Scholar
  14. L. Rehackova, V. Araujo-Soares, S. Steven, A. J. Adamson, R. Taylor, and F. F. Sniehotta, “Behaviour change during dietary type 2 diabetes remission: a longitudinal qualitative evaluation of an intervention using a very low energy diet,” Diabetic Medicine, pp. 1–10, 2019. View at: Publisher Site | Google Scholar
  15. L. Harris, A. McGarty, L. Hutchison, L. Ells, and C. Hankey, “Short-term intermittent energy restriction interventions for weight management: a systematic review and meta-analysis,” Obesity Reviews, vol. 19, no. 1, pp. 1–13, 2018. View at: Publisher Site | Google Scholar
  16. A. R. Barnosky, K. K. Hoddy, T. G. Unterman, and K. A. Varady, “Intermittent fasting vs daily calorie restriction for type 2 diabetes prevention: a review of human findings,” Translational Research, vol. 164, no. 4, pp. 302–311, 2014. View at: Publisher Site | Google Scholar
  17. N. M. Astbury, P. Aveyard, A. Nickless et al., “Doctor Referral of Overweight People to Low Energy total diet replacement Treatment (DROPLET): pragmatic randomised controlled trial,” BMJ, vol. 362, article k3760, 2018. View at: Publisher Site | Google Scholar
  18. D. E. Kloecker, F. Zaccardi, E. Baldry, M. J. Davies, K. Khunti, and D. R. Webb, “Efficacy of low- and very-low-energy diets in people with type 2 diabetes mellitus: a systematic review and meta-analysis of interventional studies,” Diabetes Obesity and Metabolism, vol. 21, no. 7, pp. 1695–1705, 2019. View at: Publisher Site | Google Scholar
  19. L. Rehackova, B. Arnott, V. Araujo-Soares, A. A. Adamson, R. Taylor, and F. F. Sniehotta, “Efficacy and acceptability of very low energy diets in overweight and obese people with type 2 diabetes mellitus: a systematic review with meta-analyses,” Diabetic Medicine, vol. 33, no. 5, pp. 580–591, 2016. View at: Publisher Site | Google Scholar
  20. J. P. Higgins and S. Green, Cochrane Handbook for Systematic Reviews of Interventions, John Wiley & Sons, Chichester (UK), 2011.
  21. J. A. C. Sterne, M. A. Hernán, B. C. Reeves et al., “ROBINS-I: a tool for assessing risk of bias in non-randomised studies of interventions,” BMJ, vol. 355, article i4919, 2016. View at: Publisher Site | Google Scholar
  22. G. H. Guyatt, A. D. Oxman, G. E. Vist et al., “GRADE: an emerging consensus on rating quality of evidence and strength of recommendations,” BMJ, vol. 336, no. 7650, pp. 924–926, 2008. View at: Publisher Site | Google Scholar
  23. S. Green, Cochrane Handbook for Systematic Reviews of Interventions. Version 5.1.0, The Cochrane Collaboration, United Kingdom, 2011.
  24. C. Jackness, W. Karmally, G. Febres et al., “Very low-calorie diet mimics the early beneficial effect of Roux-en-Y gastric bypass on insulin sensitivity and β-Cell function in type 2 diabetic patients,” Diabetes, vol. 62, no. 9, pp. 3027–3032, 2013. View at: Publisher Site | Google Scholar
  25. J. W. Anderson, V. Brinkman-Kaplan, C. C. Hamilton, J. E. B. Logan, R. W. Collins, and N. J. Gustafson, “Food-containing hypocaloric diets are as effective as liquid-supplement diets for obese individuals with NIDDM,” Diabetes Care, vol. 17, no. 6, pp. 602–604, 1994. View at: Publisher Site | Google Scholar
  26. S. Carter, P. M. Clifton, and J. B. Keogh, “The effects of intermittent compared to continuous energy restriction on glycaemic control in type 2 diabetes; a pragmatic pilot trial,” Diabetes Research and Clinical Practice, vol. 122, pp. 106–112, 2016. View at: Publisher Site | Google Scholar
  27. S. Carter, P. M. Clifton, and J. B. Keogh, “Effect of intermittent compared with continuous energy restricted diet on glycemic control in patients with type 2 diabetes: a randomized noninferiority trial,” JAMA Network Open, vol. 1, no. 3, article e180756, 2018. View at: Publisher Site | Google Scholar
  28. S. Carter, P. M. Clifton, and J. B. Keogh, “The effect of intermittent compared with continuous energy restriction on glycaemic control in patients with type 2 diabetes: 24-month follow-up of a randomised noninferiority trial,” Diabetes Research and Clinical Practice, vol. 151, pp. 11–19, 2019. View at: Publisher Site | Google Scholar
  29. J. Harvey, R. R. Wing, and M. Mullen, “Effects on food cravings of a very low calorie diet or a balanced, low calorie diet,” Appetite, vol. 21, no. 2, pp. 105–115, 1993. View at: Publisher Site | Google Scholar
  30. R. R. Wing, M. D. Marcus, R. Salata, L. H. Epstein, S. Miaskiewicz, and E. H. Blair, “Effects of a very-low-calorie diet on long-term glycemic control in obese type 2 diabetic subjects,” Archives of Internal Medicine, vol. 151, no. 7, pp. 1334–1340, 1991. View at: Publisher Site | Google Scholar
  31. R. R. Wing, E. Blair, M. Marcus, L. H. Epstein, and J. Harvey, “Year-long weight loss treatment for obese patients with type II diabetes: does including an intermittent very-low-calorie diet improve outcome?” American Journal of Medicine, vol. 97, no. 4, pp. 354–362, 1994. View at: Publisher Site | Google Scholar
  32. M. A. Lips, H. Pijl, J. B. van Klinken et al., “Roux-en-Y gastric bypass and calorie restriction induce comparable time-dependent effects on thyroid hormone function tests in obese female subjects,” European Journal of Endocrinology, vol. 169, no. 3, pp. 339–347, 2013. View at: Publisher Site | Google Scholar
  33. L. Plum, L. Ahmed, G. Febres et al., “Comparison of glucostatic parameters after hypocaloric diet or bariatric surgery and equivalent weight loss,” Obesity, vol. 19, no. 11, pp. 2149–2157, 2011. View at: Publisher Site | Google Scholar
  34. A. Cinkajzlová, M. Mráz, Z. Lacinová et al., “Angiopoietin-like protein 3 and 4 in obesity, type 2 diabetes mellitus, and malnutrition: the effect of weight reduction and realimentation,” Nutrition & Diabetes, vol. 8, no. 1, p. 21, 2018. View at: Publisher Site | Google Scholar
  35. S. Steven, K. G. Hollingsworth, P. K. Small et al., “Calorie restriction and not glucagon-like peptide-1 explains the acute improvement in glucose control after gastric bypass in type 2 diabetes,” Diabetic Medicine, vol. 33, no. 12, pp. 1723–1731, 2016. View at: Publisher Site | Google Scholar
  36. R. B. Paisey, P. Harvey, S. Rice et al., “An intensive weight loss programme in established type 2 diabetes and controls: effects on weight and atherosclerosis risk factors at 1 year,” Diabetic Medicine, vol. 15, no. 1, pp. 73–79, 1998. View at: Publisher Site | Google Scholar
  37. R. B. Paisey, J. Frost, P. Harvey et al., “Five year results of a prospective very low calorie diet or conventional weight loss programme in type 2 diabetes,” Journal of Human Nutrition and Dietetics, vol. 15, no. 2, pp. 121–127, 2002. View at: Publisher Site | Google Scholar
  38. R. Paisey, P. Harvey, S. Rice et al., “Short-term results of an open trial of very low calorie diet or intensive conventional diet in Type 2 diabetes,” Practical Diabetes International, vol. 12, no. 6, pp. 263–267, 1995. View at: Publisher Site | Google Scholar
  39. C. Li, B. Sadraie, N. Steckhan et al., “Effects of a one-week fasting therapy in patients with type-2 diabetes mellitus and metabolic syndrome - a randomized controlled explorative study,” Experimental and Clinical Endocrinology & Diabetes, vol. 125, no. 9, pp. 618–624, 2017. View at: Publisher Site | Google Scholar
  40. K. V. Williams, M. L. Mullen, D. E. Kelley, and R. R. Wing, “The effect of short periods of caloric restriction on weight loss and glycemic control in type 2 diabetes,” Diabetes Care, vol. 21, no. 1, pp. 2–8, 1998. View at: Publisher Site | Google Scholar
  41. M. Laakso, M. Uusitupa, J. Takala, H. Majander, T. Reijonen, and I. Penttila, “Effects of hypocaloric diet and insulin therapy on metabolic control and mechanisms of hyperglycemia in obese non-insulin-dependent diabetic subjects,” Metabolism, vol. 37, no. 11, pp. 1092–1100, 1988. View at: Publisher Site | Google Scholar
  42. M. E. J. Lean, “Low-calorie diets in the management of type 2 diabetes mellitus,” Nature Reviews Endocrinology, vol. 15, no. 5, article 186, pp. 251-252, 2019. View at: Publisher Site | Google Scholar
  43. M. J. Franz, J. J. VanWormer, A. L. Crain et al., “Weight-Loss Outcomes: A Systematic Review and Meta-Analysis of Weight-Loss Clinical Trials with a Minimum 1-Year Follow-Up,” Journal of the American Dietetic Association, vol. 107, no. 10, pp. 1755–1767, 2007. View at: Publisher Site | Google Scholar
  44. A. C. Feldstein, G. A. Nichols, D. H. Smith et al., “Weight change in diabetes and glycemic and blood pressure control,” Diabetes Care, vol. 31, no. 10, pp. 1960–1965, 2008. View at: Publisher Site | Google Scholar
  45. L. Aucott, A. Poobalan, W. C. S. Smith et al., “Weight loss in obese diabetic and non-diabetic individuals and long-term diabetes outcomes-a systematic review,” Diabetes Obesity and Metabolism, vol. 6, no. 2, pp. 85–94, 2004. View at: Publisher Site | Google Scholar
  46. D. LeRoith, V. Fonseca, and A. Vinik, “Metabolic memory in diabetes-focus on insulin,” Diabetes/Metabolism Research and Reviews, vol. 21, no. 2, pp. 85–90, 2005. View at: Publisher Site | Google Scholar
  47. J. Tuomilehto, P. Schwarz, and J. Lindstrom, “Long-term benefits from lifestyle interventions for type 2 diabetes prevention: time to expand the efforts,” Diabetes Care, vol. 34, Supplement 2, pp. S210–S214, 2011. View at: Publisher Site | Google Scholar
  48. R. B. D’Agostino Jr., R. F. Hamman, A. J. Karter, L. Mykkanen, L. E. Wagenknecht, and S. M. Haffner, “Cardiovascular disease risk factors predict the development of type 2 diabetes: the insulin resistance atherosclerosis study,” Diabetes Care, vol. 27, no. 9, pp. 2234–2240, 2004. View at: Publisher Site | Google Scholar
  49. S. Steven, K. G. Hollingsworth, P. K. Small et al., “Weight loss decreases excess pancreatic triacylglycerol specifically in type 2 diabetes,” Diabetes Care, vol. 39, no. 1, pp. 158–165, 2016. View at: Publisher Site | Google Scholar
  50. F. Rubino, D. M. Nathan, R. H. Eckel et al., “Metabolic surgery in the treatment algorithm for type 2 diabetes: a joint statement by International Diabetes Organizations,” Obesity Surgery, vol. 27, no. 1, pp. 2–21, 2017. View at: Publisher Site | Google Scholar
  51. R. Taylor, “Pathogenesis of type 2 diabetes: tracing the reverse route from cure to cause,” Diabetologia, vol. 51, no. 10, pp. 1781–1789, 2008. View at: Publisher Site | Google Scholar
  52. K. Purcell, P. Sumithran, L. A. Prendergast, C. J. Bouniu, E. Delbridge, and J. Proietto, “The effect of rate of weight loss on long-term weight management: a randomised controlled trial,” The Lancet Diabetes & Endocrinology, vol. 2, no. 12, pp. 954–962, 2014. View at: Publisher Site | Google Scholar
  53. G. L. Pawan and S. J. Semple, “Effect of 3-hydroxybutyrate in obese subjects on very-low-energy diets and during therapeutic starvation,” Lancet, vol. 1, no. 8314-5, pp. 15–17, 1983. View at: Publisher Site | Google Scholar
  54. F. J. McClernon, W. S. Yancy, J. A. Eberstein, R. C. Atkins, and E. C. Westman, “The effects of a low-carbohydrate ketogenic diet and a low-fat diet on mood, hunger, and other self-reported symptoms,” Obesity, vol. 15, no. 1, pp. 182–187, 2007. View at: Publisher Site | Google Scholar
  55. A. M. Johnstone, G. W. Horgan, S. D. Murison, D. M. Bremner, and G. E. Lobley, “Effects of a high-protein ketogenic diet on hunger, appetite, and weight loss in obese men feeding ad libitum,” American Journal of Clinical Nutrition, vol. 87, no. 1, pp. 44–55, 2008. View at: Publisher Site | Google Scholar
  56. S. Chearskul, E. Delbridge, A. Shulkes, J. Proietto, and A. Kriketos, “Effect of weight loss and ketosis on postprandial cholecystokinin and free fatty acid concentrations,” American Journal of Clinical Nutrition, vol. 87, no. 5, pp. 1238–1246, 2008. View at: Publisher Site | Google Scholar
  57. A. Astrup and S. Rossner, “Lessons from obesity management programmes: greater initial weight loss improves long-term maintenance,” Obesity Reviews, vol. 1, no. 1, pp. 17–19, 2000. View at: Publisher Site | Google Scholar

Copyright © 2020 Yi Shan Huang et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

287 Views | 358 Downloads | 0 Citations
 PDF  Download Citation  Citation
 Download other formatsMore
 Order printed copiesOrder

We are committed to sharing findings related to COVID-19 as quickly and safely as possible. Any author submitting a COVID-19 paper should notify us at help@hindawi.com to ensure their research is fast-tracked and made available on a preprint server as soon as possible. We will be providing unlimited waivers of publication charges for accepted articles related to COVID-19. Sign up here as a reviewer to help fast-track new submissions.