Highlights
- •A very low carbohydrate diet that limits saturated fat level (LowCHO) does not impair flow mediated dilatation (FMD).
- •A high carbohydrate, low fat (HighCHO) diet and a LowCHO diet produce similar improvements in HbA1c.
- •A HighCHO diet and a LowCHO diet produce similar weight loss.
Abstract
Background and aims
Very-low carbohydrate diets can improve glycaemic control in patients with type 2 diabetes (T2DM). However, compared to traditional higher carbohydrate, low fat (HighCHO) diets, they have been associated with impaired endothelial function (measured by flow mediated dilatation [FMD]) that is possibly related to saturated fat.
This study aimed to examine the effects of a 12-month hypocaloric very-low carbohydrate, low saturated fat (LowCHO) diet compared to an isocaloric HighCHO diet.
Methods
One hundred and fifteen obese patients with T2DM (age:58.4 ± 0.7 [SEM] yr, BMI:34.6 ± 0.4 kg/m2, HbA1c:7.33 [56.3 mmol/mol] ± 0.10%) were randomised to consume an energy restricted LowCHO diet (Carb:Pro:Fat:Sat-Fat 14:28:58: < 10% energy; n = 58) or isocaloric HighCHO diet (53:17:30: < 10%; n = 57) whilst undertaking exercise (60 min, 3/wk). Bodyweight, HbA1c and FMD were assessed.
Results
Seventy eight participants completed the intervention (LowCHO = 41, HighCHO = 37). Both groups experienced similar reductions in weight and HbA1c (−10.6 ± 0.7 kg, −1.05 ± 0.10%; p < 0.001 time, p ≥ 0.48 time × diet). FMD did not change (p = 0.11 time, p = 0.20 time × diet).
Conclusions
In patients with obesity and T2DM, HighCHO diet and LowCHO diet have similar effects on endothelial function.
Keywords
1. Introduction
Type 2 diabetes (T2DM) is a major global health problem. Weight loss via diet and regular physical activity represents the cornerstone of T2DM management. Very-low carbohydrate, high fat diets have become a popular diet strategy with enhanced benefits for glycaemic control in patients with T2DM compared to a traditional high carbohydrate low fat (HighCHO) diet [
1
, 2
]. However, very-low carbohydrate diets have also been shown to impair brachial artery flow mediated dilatation (FMD; a non-invasive measure of endothelial function and established prognostic marker for cardiovascular events [3
, 4
]) [5
, 6
, 7
]. This may limit the applicability of very-low carbohydrate diets as a diabetes management strategy and could be due, at least in part, to the high saturated fat content that is typical of the usually promoted very-low carbohydrate diets [[8]
]. This raises the suggestion that compared to a HighCHO diet, a very-low carbohydrate diet with a modified fatty acid profile that limits saturated fat level may not exert the detrimental effects on FMD observed previously. This research directly supports the recent recommendation of the necessity to identify diet patterns that improve the management of T2DM and benefit vascular function [[7]
]. It was hypothesised that a very-low carbohydrate, high fat, low saturated fat diet (LowCHO) would not affect FMD relative to a traditional HighCHO diet. The aim of this study was to examine the long-term effects of a hypocaloric, LowCHO diet compared to an isocaloric HighCHO diet on FMD in patients with T2DM.2. Materials and methods
The study was conducted at the Commonwealth Scientific and Industrial Research Organisation Clinical Research Unit (Adelaide, Australia) between May 2012 and September 2013. Detailed information on participant eligibility criteria, intervention components, and the study's primary outcomes including glycaemic control and traditional cardio-metabolic risk markers have been previously reported [
1
, 2
]. This study was approved by the Human Research Ethics Committee of the Commonwealth Scientific an Industrial Research Organisation; all participants signed written informed consent prior to participation. This paper reports on an isolated secondary study outcome examining endothelial function assessed by FMD. In brief, in a 52-week parallel design study, 115 participants who were overweight or obese (age 58 ± 0.7 years; body mass index 34.6 ± 0.4 kg/m2; 66 males/49 females) with T2DM (HbA1c 7–10% [53–86 mmol/mol] or previously diagnosed and controlled with medication) were initially block matched for age, gender, BMI, HbA1c and diabetes medication before being randomised by computer generated assignment to participate in a supervised exercise program (60 min × 3 d/wk) and to follow one of two isocaloric, energy reduced diets (females ∼6 MJ/d, males ∼7 MJ/d) for 52 weeks: LowCHO Diet (n = 58): 14% of energy as carbohydrate, 28% protein, 58% fat (<10% saturated); HighCHO Diet (n = 57): 53% carbohydrate, 17% protein, 30% fat (<10% saturated), in a 1:1 ratio. Diets were prescribed as specific whole food quantities. Randomisation procedures (sequence generation and allocation concealment) were performed by a research associate not involved in outcome assessment and intervention delivery [[2]
].Outcomes were assessed at Week 0 (baseline) and 52 after an overnight fast. Height and body mass were assessed and a venous blood sample was taken to determine HbA1c [
1
, 2
]. FMD of the brachial artery was evaluated by an experienced technician under recommended conditions [[9]
], using 2 dimensional B-mode ultrasound with a 5–13 MHz linear array transducer (Logiq e, GE Healthcare, Wauwatosa, USA); to induce ischemia a sphygmomanometer cuff was placed around the right forearm and inflated to 250 mmHg for 5 min. Snapshots (2 cardiac cycle length videos) of the brachial artery were recorded 30 s before cuff deflation (baseline) and every 15 s for 3 min after deflation. End-diastole brachial artery diameter for each snapshot was determined using the measurement function of the ultrasound instrument. Peak diameter was defined as the highest value obtained following cuff deflation. FMD was expressed as the percentage change from baseline in brachial artery diameter following cuff deflation (peak diameter – baseline). FMD measurements and images were analysed by the same technician in a blinded manner. The reproducibility of FMD in our hands, performed by a single operator on repeated occasions, was 10.6%.The sample size of the study was determined based on the primary outcome of HbA1c that have been previously reported [
[2]
]. Statistical analysis was conducted using IBM SPSS for Windows (version 21.0, Armonk, NY, USA). Data were examined for normality prior to analysis, non-normally distributed data (FMD) were log-transformed for analysis with reported values back-transformed. Univariate analysis of variance (ANOVA) was used to assess differences in baseline characteristics. Changes over time were examined using an intention-to-treat maximal likelihood fixed effect mixed models analysis. Baseline HbA1c (for weight and FMD only), age, gender were included as covariates in the model. Data are reported as means ± standard error of the mean unless otherwise specified.3. Results
Participant flow of the study has been reported elsewhere [
[2]
]. Seventy-eight participants completed the intervention and had outcomes assessed at Week 52 (LowCHO = 41, HighCHO = 37). One participant had their Week 0 FMD result excluded from the analysis due to outlying. Withdrawals and exercise session attendance were similar between groups [[2]
]. Reported dietary intakes were consistent with prescription [[2]
]. After 52 weeks, both groups experienced similar overall reductions in weight (−10.6 ± 0.7 kg; p < 0.001) and HbA1c (−1.05 ± 0.10%; p < 0.001) with no differential effect of diet (p ≥ 0.67; Table 1) [[2]
]. FMD was similar at baseline (p = 0.82) and did not change significantly in either diet group (p = 0.11 time, p = 0.48 time × diet; Table 1).Table 1Age, body weight, glycosylated haemoglobin and flow mediated dilatation before and after a 52 week energy restricted very low carbohydrate, high fat diet, low saturated fat or an isocaloric higher carbohydrate, low fat diet.
| LowCHO diet n = 58 (male 37, female 21) | HighCHO diet n = 57 (male 29, female 28) | p-value | |||||
|---|---|---|---|---|---|---|---|
| Week 0 | Week 52 | Week 0 | Week 52 | Baseline | Time | Time × Diet | |
| Age (years) | 58.5 ± 1.0 | – | 58.4 ± 0.9 | – | 0.95 | – | – |
| Body weight (kg) | 100.8 ± 1.8 | 90.4 ± 1.9 | 102.0 ± 1.8 | 91.1 ± 2.0 | 0.95 | <0.001 | 0.70 |
| HbA1c (%) | 7.26 ± 0.14 | 6.26 ± 0.12 | 7.42 ± 0.15 | 6.33 ± 0.13 | 0.47 | <0.001 | 0.67 |
| Flow mediated dilatation (%) | 5.31 ± 0.40 | 5.03 ± 0.43 | 4.83 ± 0.39 | 4.19 ± 0.42 | 0.82 | 0.11 | 0.48 |
Data are means ± SEM. LowCHO, very-low carbohydrate, high fat, low saturated fat; HighCHO, high carbohydrate, low fat.
4. Discussion
The study showed that in overweight and obese patients with T2DM who participated in a one-year lifestyle modification program, compared to a traditional HighCHO diet, a LowCHO diet did not affect FMD. Conversely, previous studies [
5
, 7
] and a meta-analysis [[6]
] have reported compared to a HighCHO diet, a very-low carbohydrate diet exerts detrimental effects on FMD. The exact reason for this discrepancy is not entirely clear, but unlike the present study, the very-low carbohydrate diets used previously have been high in saturated fat, which has been previously shown to adversely alter FMD [[8]
]. It is therefore possible that maintaining a relatively low level of saturated fat as part of the LowCHO diet prescribed in the present study may have mitigated potential impairments in FMD observed previously and the associated increased cardiovascular disease risk (CVD). Despite this, a large meta-analysis concluded there remains no decisive evidence that saturated fat is associated with an increased incidence of coronary heart disease or CVD [[10]
]. Hence, further research is required to directly compare the long-term effects of very-low carbohydrate diets that are high and low in saturated fat on CVD risk.Other than saturated fat, there are several dietary mediators of FMD that may have contributed to the [lack of] effects observed in the present study. For example, fibre intake has been positively associated with FMD [
[11]
] and prescribed levels were similar between the LowCHO and HighCHO diets examined in this study, compared to traditional very-low carbohydrate diets that are typically associated with reduced fibre levels [[12]
]. Additionally, in contrast to previous studies, the effects of the HighCHO and LowCHO diets were prescribed in combination with regular exercise training that has well documented positive effects on FMD [[13]
]. This may have also assisted to offset any impairment in FMD reported previously following consumption of a LowCHO diet.Irrespective of the lack of any differential response between the diets examined, a recent meta-analysis determined that for each 10 kg decrease in weight, FMD increased by 1.11% [
[14]
]. Hence, it is interesting that no overall improvement in FMD was observed in the present study, despite considerable weight loss (−10.6 kg). Nevertheless, within the meta-analysis there was considerable heterogeneity between individual studies. The present findings are consistent with the largest and longest study reported to date [[15]
] that also showed no change in FMD after diet and exercise induced weight loss after 2 years. It is possible the lack of effect observed in the current study may have been within the constraints of the operator CV and/or due to the specific characteristics of our study participants. It has been suggested that individuals with T2DM experience several pathophysiological changes such as an impaired endothelial-mediated and neurogenic capacity for vascular smooth muscle to relax, accumulation of advanced glycaemic end-products, and dysregulated ability to synthesise nitric oxide [[16]
]. Hence, the lack of change in vascular function reflects the possibility that participants examined had pre-existing endothelial dysfunction that may have limited potential for reversibility. Assessment of endothelial function in the current study was isolated to FMD and further studies should assess a comprehensive array of functional measures of endothelial function to gain a more comprehensive assessment of effects of these diets on atherosclerosis.Although the overall study was powered based on the primary outcome of HbA1c, A non-inferiority power calculation for FMD based on a minimally important change of 1% [
17
, 18
] indicates that a sample size of 109 participants per group is required to be 80% sure that there is no difference between treatment groups. Nevertheless, although the study had insufficient sample size to show statistical non-inferiority, the mean observed changes from baseline after 12 months were ≤0.7%, with the difference in the changes between groups 0.4%. These changes are well below the 1% change in FMD that could be considered to represent the smallest clinically relevant change. Moreover, the differential changes observed between the two groups are substantially smaller than the 1.7% difference in FMD previously observed between a low carbohydrate, high saturated fat diet and a high carbohydrate, low fat diet [[5]
]. It is therefore considered unlikely that an increase in sample size would have revealed different results.This manuscript represents the first study to examine the long-term effects of a very-low carbohydrate diet with a modified fatty acid profile that increases unsaturated fat and restricts saturated fat intake on the important prognostic marker of FMD. These current data assist in understanding the effects of very-low carbohydrate diet patterns on cardiovascular disease risk and their potential role as a diabetes management strategy.
In conclusion, in overweight and obese adults with T2DM both an energy-reduced LowCHO and HighCHO diet administered as part of a holistic lifestyle modification program incorporating exercise training had similar FMD response. This suggests a very-low carbohydrate diet high in unsaturated fat and low in saturated fat does not adversely affect endothelial function.
Conflict of interest
The funding source had no role in the design or conduct of the study; collection, management, analysis, or interpretation of the data; or preparation, review, or approval of the manuscript.
Financial support
This work was supported by a National Health and Medical Research Council project grant (103415).
Acknowledgements
The authors wish to thank the volunteers for their participation and gratefully acknowledge Anne McGuffin, Julia Weaver and Vanessa Courage for coordinating the trial; Pennie Taylor, Janna Lutze, Hannah Gilbert, Paul Foster, Gemma Williams and Fiona Barr for assisting in designing and implementing the dietary intervention; Lindy Lawson and Theresa Mckinnon for nursing expertise; Julie Syrette for assisting with the data management; Luke Johnston and Annie Hastwell (Fit for Success, Adelaide, Australia), Kelly French, Jason Delfos, Kristi Lacey-Powell, Marilyn Woods, John Perrin, Simon Pane and Annette Beckette (SA Aquatic Centre & Leisure Centre, Adelaide, Australia), and Angie Mondello and Josh Gniadek (Boot Camp Plus, Adelaide, Australia) for conducting the exercise sessions.
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Article info
Publication history
Published online: July 21, 2016
Accepted:
July 20,
2016
Received in revised form:
July 20,
2016
Received:
February 5,
2016
Footnotes
☆The study was registered with the Australian New Zealand Clinical Trials Registry (http://www.anzctr.org.au) Registry Number: ACTRN12612000369820.
Identification
Copyright
© 2016 Elsevier Ireland Ltd. All rights reserved.
