Effects on cardiovascular risk factors of a low- vs high-Glycemic Index Mediterranean Diet in high cardiometabolic risk individuals: The MEDGI-Carb Study

doi:10.21203/rs.3.rs-2957023/v1

Background

The role of dietary Glycemic Index (GI), independently of fiber intake, in modulating cardiovascular disease (CVD) risk among non-diabetic individuals has not been fully elucidated.

Objective

To evaluate the effects of a low- versus a high-GI diet, based on a Mediterranean dietary pattern, on cardiometabolic risk factors in individuals at high CVD risk, participating in the MEDGI-Carb intervention study.

Subjects and methods

: 160 individuals, aged 30–69 years, BMI 25–37 kg/m², with a waist circumference > 102 cm (males) or > 88 cm (females) and one feature of the metabolic syndrome, participated in a multi-national (Italy, Sweden, USA) randomized controlled parallel group trial. Participants were assigned to a low GI (< 55) or high-GI MedDiet (> 70) for 12 weeks. The diets were isoenergetic and similar for available carbohydrate (270g/d) and fiber (35g/d) content. Fasting metabolic parameters were evaluated in the whole cohort, while an 8-hour postprandial triglyceride profile was evaluated only in the Italian cohort.

Results

Blood pressure and most fasting metabolic parameters improved at the end of MedDiet intervention (time effect, p < 0.05 for all); however, no differences were observed between the low- and the high-GI MedDiet groups (time x group effect; p > 0.05 for all). Conversely, the low-GI diet, compared with high-GI diet, significantly reduced postprandial triglycerides (iAUC) after lunch (-80%; p = 0.013).

Conclusions

Consuming a low-GI in comparison with a high-GI MedDiet does not differentially affect any of the cardiometabolic risk factors at fasting in individuals at increased cardiometabolic risk. Conversely, the low-GI diet reduces the postprandial plasma triglyceride profile.

Clinical Trial Registry Number: NCT03410719, (https://clinicaltrials.gov).

Health sciences/Risk factors

Biological sciences/Biochemistry

Glycemic Index

Mediterranean diet

cardiometabolic risk factors

metabolic syndrome

postprandial triglycerides.

Abdominal obesity, insulin resistance, glucose abnormalities, hypertension and dyslipidemia are key components of the metabolic syndrome and are all independently associated with cardiovascular disease (1–2), the leading cause of mortality in western countries (3, 4). Diet as a modifiable risk factor and first-line therapy has a major impact on cardiometabolic conditions. The Mediterranean Diet (MedDiet) is a dietary pattern associated with favorable health outcomes (5) and, in particular, with a lower risk of type 2 diabetes (T2D) and cardiovascular diseases (CVD) (6–7). Accumulating evidence has shown that major components of the MedDiet, such as unsaturated fatty acids, dietary fiber and bioactive compounds play an important role in the prevention of CVD and other chronic degenerative conditions (8). However, the possible role of Glycemic Index (GI), independently of dietary fiber intake, in modulating CVD risk factors among non-diabetic individuals so far has not been fully elucidated. The MedDiet is characterized by the consumption of foods rich in dietary fiber with low GI such as whole grains, fruit, vegetables, and legumes but also some cereal foods with comparably low dietary fiber content but with low/medium GI due to structural/physiochemical features of the foods such as pasta, parboiled rice, sourdough bread, corn tortillas, flat bread. Thus, low GI could be another important dimension of carbohydrate quality that could significantly contribute to the beneficial effects of the traditional Mediterranean eating pattern on CVD prevention.

Data from prospective observational cohort studies have provided strong evidence that a high glycemic index (GI) and glycemic load (GL) of the diet increases the risk of developing hypertension and CVD (9–11). Conversely, the evidence provided by nutritional intervention studies aiming at evaluating the impact of dietary GI on cardio-metabolic risk factors is rather inconsistent evidence; in fact in some but not in all studies diets with a low GI were able to improve hyperlipidemia and insulin sensitivity in overweight and hyperlipidemic patients without diabetes (12–15). Even greater uncertainties exist about the potential impact of low GI diet on CVD risk factors in healthy people, particularly if the background diet has an appropriate nutrient distribution. In this context, the Shikany's study (16) showed that 4 weeks of treatment with low GI foods as part of a healthy diet, based on the recommendations of the National Cholesterol Education Program, did not show additional beneficial effects of the low GI diet on inflammatory markers, coagulation factors, and lipoprotein/lipid parameters in a group of overweight/obese men (16). Similarly, the OmniCarb trial, a study aiming at evaluating the effects of a low vs high GI diet, in the framework of a DASH-type diet, showed that after five weeks of intervention the low GI did not induce any improvements in insulin sensitivity, fasting lipid levels, or systolic blood pressure (17).

Against this background, we hypothesize that a low GI diet, compared with a high GI diet, will not substantially influence fasting cardiometabolic parameters in subjects at high risk for CVD while it may play a more important role on postprandial metabolism.

Therefore, the aim of this study is to evaluate the effects of a low- versus a high-GI healthy diet, based on the traditional Mediterranean dietary pattern, on fasting cardiometabolic risk factors in individuals at high cardiometabolic risk utilizing data obtained in the multi-national (Italy, Sweden, USA) MEDGI-Carb intervention trial (18). An additional aim is the evaluation of the postprandial triglyceride response which, for feasibility reasons, could only be performed in a subgroup of participants.

Subjects and study design

Full details of the study design and participant characteristics have been published elsewhere (18, 19). Briefly, according to a randomized, controlled, parallel group study design, 160 individuals of both genders, aged 30–69 years, BMI 25–37 kg/m², with components of the metabolic syndrome, were enrolled in the MEDGI-Carb study, an international multi-center trial conducted at three centers: i) Federico II University, Naples, Italy; ii) Chalmers University of Technology, Gothenburg, Sweden; iii) Purdue University, West Lafayette, IN, USA. The study protocol was approved by the institutional review boards at Purdue University and Federico II University and by the Swedish Ethical Review Authority. This study was registered in the public trial registry Clinicaltrials.gov (accessed on 7 December 2021) as NCT03410719. The primary endpoint of this study was the evaluation of the effects of high- versus low-GI Mediterranean diets (MedDiet) on postprandial glucose metabolism.

As previously detailed, participants were randomly assigned to a low- or high-GI MedDiet for 12 weeks. The two experimental diets were isoenergetic and designed to have the same amount of available carbohydrate (270 g/d) and fiber (35 g/d). Higher or lower energy content was achieved through the modulation of dietary unsaturated fat and protein. The overall GI of the two diets was < 55 or > 70, respectively, obtained by consuming half of the daily carbohydrates intake (135 g) from foods with low-GI (< 55), such as pasta, brown rice, corn tortillas, flatbread, all bran, and wheat bread plus rye and seeds, in the low-GI MedDiet; or from foods with high-GI (> 70), such as jasmine rice, potato, couscous, wholegrain bread, and rusks, in the high-GI MedDiet (19).

At baseline and at the end of the 12-week intervention, participants' anthropometric and clinical characteristics were assessed. Blood pressure was taken in duplicate after 15 min of rest with an

automatic sphygmomanometer. If blood pressure measurements differed by more than 5 mmHg, a third measurement was taken. The blood pressure measurements were then averaged.

In addition, plasma glucose and insulin profiles were evaluated in the study participants at baseline and at the end of intervention for 8 hours during the day, while a standard breakfast and a standard lunch were consumed with low or high GI according to the dietary treatment assigned, as reported elsewhere (18, 19). Only in the Italian branch, measurements of the eight hours triglyceride profile were also evaluated. Complete descriptions of the experimental diets, dietary administration and compliance can be found elsewhere (18, 19).

Laboratory methods

The details of blood sample collection and analysis have already been described (18). Briefly, in the three study centers, plasma glucose, total cholesterol, HDL cholesterol, and triglyceride concentrations were assayed by enzymatic colorimetric methods (ABX Diagnostics, Montpellier, France; Roche Diagnostic, USA, Indianapolis, IN) on automatic analyzers (ABX Pentra 400, HORIBA Medical, Montpellier, France; COBAS Integra 400 analyzer, Roche Diagnostic Systems, USA, Indianapolis, IN).

Plasma insulin concentrations were measured by ELISA (DIA-source ImmunoAssay S.A., Nivelles, Belgium) on a Triturus analyzer (Diagnostic Grifols S.A., Barcelona Spain) in the Italian center, while they were measured by electrochemiluminescence immunoassay method on the Elecsys 2010 analyzer (Roche Diagnotic Systems USA, Indianapolis, IN) in the Sweden and USA centers. Plasma concentrations of HbA1c were measured by high performance liquid chromatography. LDL cholesterol was calculated using the Friedewald formula. The homeostatic model assessment of insulin resistance (HOMA-IR) was calculated using the following formula: fasting glucose (mg/dL) × fasting insulin (µU/mL)/405 (20).

Statistical Analysis

Data are expressed as means ± SD unless otherwise stated. Within-group differences (12-week vs. baseline) were evaluated by paired samples t-test. Differences between groups on time changes of fasting metabolic parameters were assessed by ANOVA-repeated measures analysis and expressed as “time x group" effect. The main effect of time was also evaluated using data combined from both experimental groups. A subgroup analysis was performed in individuals with high values for the cardiovascular risk factors choosing widely accepted cut-offs according to NCEP-APTT III (2001) and modified in 2004 in accordance with the American Diabetes Associations: waist circumference > 102 cm in male and 88 cm in female, systolic blood pressure (SBP) ≥ 130 mmHg, diastolic blood pressure (DBP) ≥ 85 mmHg, fasting blood glucose ≥ 100mg/dl, triglycerides ≥ 150 mg/dl, HDL-Cholesterol < 40 mg/dl in male and < 50 mg/dl in female; HOMA Index ≥ 2.5, according to the European Group for the Study of Insulin Resistance (EGIR 1991); HbA1c value between 5.7% and 6.4%, according to the American Association of Clinical Endocrinology (AACE) Clinical Practice Guideline for prediabetes screening 2022 (21–23). Data on postprandial triglyceride response were available only for the fifty-four individuals from the Italian center. Postprandial triglycerides were expressed as absolute increments above fasting, calculated in each participant by subtracting the fasting value from that at each time point of the curve. Differences between postprandial triglyceride responses during the entire postprandial profile, at baseline and after 12- weeks of dietary treatments, were evaluated by ANOVA-repeated measures analysis, to examine the effects of dietary intervention, time, and dietary intervention × time interaction effect. In this analysis, plasma triglyceride increments above fasting measured every hour over 8 hours were included as levels of the within-subject “time” factor, and “low-GI MedDiet” and “high-GI MedDiet” were included as levels of the between-subject “dietary intervention” factors. Postprandial incremental areas of plasma triglycerides under the curve (iAUC) were calculated using the trapezoidal rule. Between-group differences in triglyceride iAUC were assessed by independent sample t test. For all analyses, the level of statistical significance was set at p < 0.05 (two tails). Statistical analysis was performed according to standard methods using the Statistical Package for Social Sciences software version 28.0 (SPSS, IBM, USA).

Fasting CVD risk factors

As previously reported (18), one hundred and sixty individuals completed the study, of whom 156 with available data on fasting plasma lipids were included, 82 randomly allocated in the low-GI MedDiet and 74 in the high-GI MedDiet. At baseline, participants in the two groups had a similar distribution of gender (44 females and 38 males in the low-GI MedDiet; 38 females and 36 males in the high-GI MedDiet), age (55.6 ± 10.5 vs. 55.8 ± 9.9 years, respectively), and BMI (30.6 ± 3.0 vs. 30.6 ± 4.2 kg/m², respectively) (Table 1). The two groups were also similar for systolic and diastolic blood pressure, fasting plasma glucose, insulin, HbA1C, lipids concentrations, and HOMA index (Table 1).

Table 1. Anthropometrics and cardiometabolic risk factors levels at baseline and after 12-week of dietary intervention
	Low-GI MedDiet			High-GI MedDiet
	(n=82)			(n=74)
	Baseline	12-week	Δ	Baseline	12-week	Δ	time x group effect°	time effect°
BMI (kg/m²)	30.6±3.0	30.4±3.4	-0.13	30.6±3.0	30.6±4.2	-0.06	0.921	0.780
Systolic blood pressure (mmHg)	128±13	124±14*	-4.6±10.7	124±12	120±12*	-4.4±11	0.915	0.0001
Diastolic blood pressure (mmHg)	81±8	78±10*	-3.6±7.5	81±9	78±8*	-3.0±7.8	0.307	0.0001
Glucose (mg/dl)	103±10	102±10	-1.2±7.0	105±10	104±9	-1.5±8.5	0.757	0.036
Insulin (μU/ml)	14.9±9.0	13.7±8.6	-1.2±7.3	16.0±8.6	15.4±10.9	-0.6±10	0.690	0.205
HbA1C (%)	5.4±0.4	5.4±0.3	-0.02±0.2	5.5±0.3	5.4±0.3	-0.1±0.3	0.275	0.028
HOMA-IR	3.9±2.6	3.5±2.4	-0.4±2.2	4.3±2.6	3.9±2.8	-0.4±2.8	0.856	0.052
Triglycerides (mg/dl)	122±69	115±63*	-7.6±40	116±44	109±54	-6.7±49.6	0.903	0.049
Total Cholesterol (mg/dl)	192±33	186±32*	-6.2±18	189±30	187±33	-2.1±21.7	0.206	0.011
LDL-Cholesterol (mg/dl)	120±26	116±25	-4.1±14.8	116±28	117±29	1.0±18.2	0.169	0.352
HDL-Cholesterol (mg/dl)	48±12	46±10*	-2.0±6.0	48±12	47±11	-1.3±6.7	0.521	0.002
All values are means ± SDs; HOMA-IR, homeostasis model assessment of insulin resistance. *p<0.05 vs. baseline according to paired sample t-test. °according to repeated measures ANOVA

No significant differences in blood pressure and metabolic parameters changes were observed between the low- and high-GI MedDiet groups (time x group effect; Table 1).

After the 12-week of dietary intervention, systolic and diastolic blood pressure (SBP and DBP) significantly decreased in both groups, as compared to baseline: -4.6 ± 10.7 and − 4.4 ± 11 mmHg for SBP and − 3.6 ± 7.5 and − 3.0 ± 7.8 mmHg for DBP after the low- and high-GI diet, respectively, p < 0.05 for all (Table 1).

A significant decrease after 12-weeks of intervention – as compared to baseline – was observed for fasting plasma triglycerides (-7.6 ± 40 mg/dl), total cholesterol (-6.2 ± 18 mg/dl) and HDL cholesterol (-2.0 ± 6.0 mg/dl) concentrations only in the low-GI MedDiet group (p < 0.05 for all) (Table 1). No other differences within each group were observed for the other metabolic parameters. In addition, when the data of the two intervention groups were combined and comparisons were performed between values recorded at the end of the intervention versus those at baseline, significant changes were detected for systolic and diastolic blood pressure, blood glucose, glycated hemoglobin, triglycerides, total cholesterol, and HDL cholesterol (time effect, p < 0.05 for all) (Table 1).

The same analyses were performed in individuals with an “abnormal” value for each CVD risk factor at baseline; accordingly, the comparison between the low- and the high-GI diet did not show any significant differences (time x group, p > 0.05 for all) (Table 2).

Table 2. Cardiovascular risk factors after the low and high-GI MedDiet in individuals with abnormal values of cardiometabolic risk factors at baseline.

	Low-GI MedDiet			High-GI MedDiet
	Baseline (n)	12-week (n)	Δ	Baseline (n)	12-week (n)	Δ	time x group effect°	time effect°
Systolic blood pressure ≥ 130 mmHg	139±8 (38)	133±12* (38)	-6±12	139±7 (22)	129±12* (22)	-10±13	0.331	0.0001
Diastolic blood pressure ≥ 85 mmHg	90±4 (26)	84±9* (26)	-6±9	90±4 (24)	85±6* (24)	-5±7	0.544	0.0001
Glucose ≥ 100 mg/dl	109±7 (53)	106±8* (53)	-2.0±7.0	109±9 (54)	106±8*I (54)	-3.0±8	0.839	0.001
HbA1C ≥ 5.7 %	5. 9±0.2 (19)	5.7±0.2* (19)	-0.2±0.2	5.9±0.1 (17)	5.7±0.4* (17)	-0.2±0.3	0.438	0.001
HOMA-IR ≥ 2.5	4.8±2.5 (59)	4.2±2.4 (59)	-0.6±2.5	5.0±2.6 (55)	4.4±3.0 (55)	-0.6±3.1	0.948	0.022
Triglycerides ≥ 150 mg/dl	219±78 (19)	188±76* (19)	-31±58	189±40 (12)	150±72 (12)	-38±68	0.748	0.005
Total Cholesterol ≥ 200 mg/dl	224±20 (33)	210±16* (33)	-14±20	221±12 (23)	217±22 (23)	-4±23	0.102	0.006
LDL-Cholesterol ≥ 100 mg/dl	129±18 (66)	124±19 (66)	-5±14	129±18 (53)	127±24 (53)	-2±19	0.336	0.023
HDL-Cholesterol < 40 mg/dl (male) < 50 mg/dl (female)	35±3 (15) 39±5 (17)	35±4 (15) 39±6 (17)	0.4±3 0.4±5	35±2 (20) 44±4 (10)	38±6 (20) 42±7 (10)	3±7 -2±5	0.317 0.264	0.155 0.458

All values are means ± SDs; (n), number of individuals with abnormal levels of the Risk Factors at baseline; HOMA-IR, homeostasis model assessment of insulin resistance.*p<0.05 vs. baseline according to paired sample t test; °according to repeated measures ANOVA

The within-group difference between values after the intervention versus baseline in the low GI- MedDiet group disappeared for HDL cholesterol, while HbA1c levels were significantly lower after the intervention in both the high- and low-GI MedDiet groups (-0.2 ± 0.2% and − 0.2 ± 0.3%, respectively, with p < 0, 05 for both); similar findings were observed for fasting plasma glucose (-2.0 ± 7.0 mg/dl and − 3.0 ± 8 mg/dl, respectively, p < 0.05 for both). In addition, when the data of the two intervention groups were combined and comparisons were performed between values recorded at the end of the intervention versus those at baseline, significant changes were detected for systolic and diastolic blood pressure, blood glucose, glycated hemoglobin, HOMA-IR, triglycerides, total cholesterol and LDL cholesterol (time effect, p < 0.05 for all) (Table 2).

Postprandial triglycerides response

As mentioned above, data on the postprandial triglyceride response were available only for fifty-four participants (n = 29 in the low-GI MedDiet and n = 25 in the high-GI MedDiet) from the Italian cohort, of which the clinical characteristics at baseline and after 12 weeks of dietary intervention are reported in the Supplementary Table 1.

At baseline, the 8-hour profile of plasma triglyceride increments above fasting was lower in the low-GI MedDiet group as compared with the high-GI MedDiet group (the GI of breakfast and lunch resembled that of the assigned diet) and the difference was at the borderline of statistical significance (time*group; p = 0.062). After 12-weeks of dietary intervention, the 8-hour profile of plasma triglyceride increments above fasting was significantly lower in the low-GI MedDiet group as compared with the high-GI MedDiet one (time x group, p = 0.042) (Fig. 1, panel A).

The postprandial triglyceride response after breakfast – calculated as iAUC for 4 hours – was not significantly different between the groups at baseline (122 ± 72 vs. 96 ± 86 mg/dL·hours, low-GI MedDiet vs. high-GI MedDiet, respectively, p = 0.243) and at the end of the intervention (92 ± 118 vs. 93 ± 90 mg/dL·hours, respectively, p = 0.971) (Fig. 1, panel B).

Conversely, the postprandial triglyceride response after lunch – calculated as iAUC for 4 hours – was significantly lower in the low-GI MedDiet as compared to the high-GI MedDiet, both at baseline (13 ± 42 vs. 94 ± 58 mg/dL·hours, respectively, p = 0.017), and at the end of the intervention (14 ± 39 vs. 56 ± 73 mg/dL·hours, respectively, p = 0.013) (Fig. 1, panel B).

In addition, the comparison between the two dietary groups at the end of the intervention for the risk factors measured at fasting showed statistically significant lower LDL cholesterol values in the low-GI MedDiet as compared with the high-GI MedDiet (p = 0.027); this was due to a significant decrease in plasma LDL- cholesterol concentrations in the low-GI MedDiet group at the end of the intervention as compared to baseline (118 ± 22 vs. 126 ± 22 mg/dL, respectively, p = 0.008), while no changes were observed in the high-GI MedDiet group (120 ± 28 vs. 117 ± 21 mg/dL) (Supplementary Table 1).

The present study shows that during a 12-week observation a low-GI diet resembling dietary habits of the traditional Mediterranean Diet has no major impact on cardiovascular risk factors in the fasting state as compared with a similar diet with a high-GI. Conversely, it is able to reduce markedly and significantly the daily postprandial triglyceride levels. The reduction of the postprandial triglyceride levels observed in this study is relevant from a clinical point of view since postprandial hypertriglyceridemia represents an independent CVD risk factor (24, 25) and the extent of the observed decrease may induce a significant reduction in the incidence of CVD risk according to predictions derived from observational longitudinal studies (24, 25).

In addition, this study shows that consuming a MedDiet for 12 weeks, irrespectively of its GI, improves the CVD risk factor profile; in fact, both systolic and diastolic blood pressure levels were reduced with both diets at the end of the intervention while markers of blood glucose metabolism, such as plasma glucose and glycosylated hemoglobin, were also reduced with both diets but only in the subgroups with higher baseline values. The beneficial effects of the MedDiet were amplified when the two dietary groups were combined, showing a significant improvement in most CVD risk factors both in the whole population and in individuals with abnormal cardiometabolic risk factor values at baseline. However, we cannot exclude that these improvements were, at least in part, due to a trial effect.

Our study is the first one that has evaluated the impact of dietary GI, independently on other dietary features, on postprandial triglycerides in the setting of a randomized controlled intervention; we were able to demonstrate that the low-GI diet reduced the postprandial triglyceride response after lunch by 75 to 80% in comparison with the high GI diet. This effect was already observed on the first day of intervention and was confirmed when the diet had been followed for 12 weeks. The reduction of plasma postprandial triglycerides was only observed after lunch; in fact, at breakfast there was no significant differences between the two diets both at baseline and after 12 weeks of dietary treatment. These results parallel those observed in relation to the postprandial glycemic and insulin responses (reported in our previous publication) since also the improvements of these parameters with the low, as compared with the high GI diet, were statistically significant only after lunch (18). This different meal effect is probably attributable to the amount of carbohydrates which was lower at breakfast (72 g) than at lunch (103 g) (19). However, it is also possible that the postprandial triglyceride response after lunch was the consequence not only of the metabolic impact of the carbohydrate present in that meal but was also modulated by the late effects of the carbohydrates present in the previous meal (as indicated by the profile of plasma triglyceride levels being still on a continuous rise when lunch was started) (Fig. 1); in other words, plasma triglyceride levels after lunch depend on the additive effects of the quality and quantity of carbohydrates both at breakfast and lunch and, therefore, the difference in the postprandial triglyceride response between the two diets is amplified after lunch (second meal effect).

The improvement of postprandial triglyceride levels observed in our study with the low-GI diet cannot be attributed to differences in dietary features other than the GI as the two diets had a very similar nutrient composition (18).

The reduction of plasma postprandial triglycerides induced by the low-GI diet, in comparison with the high GI one, could be probably mediated by postprandial blood glucose levels, significantly lower with the former diet (18). In fact, glucose and lipid metabolism are linked to each other in many ways; among the various pathways it is worth mentioning the ability of increased plasma glucose levels to promote de novo lipogenesis through concomitant upregulation of both SREBP-1c and ChREBP; the synergistic action of these enzymes directs the conversion of glucose to fatty acids and enhances esterification but attenuates fatty acid oxidation (26, 27). Accordingly, it might be speculated that this mechanism could link the reduction of the dietary GI to a lower fat accumulation in the liver, thus reducing the risk of NAFLD (28).

A main strength of our study was its randomized controlled design and its duration which was sufficient for the evaluation of the effects of a dietary intervention on glucose and lipid metabolism. Other strengths of the study were: 1) the very accurate diet prescription with emphasis on keeping the nutrient composition, including dietary fiber, very similar in the two intervention groups while markedly differentiating the diets for their GI, and 2) the stringent control of dietary compliance throughout frequent patient interviews and dietary diaries. A limitation of our study is that the assessment of the impact of GI on plasma triglyceride levels was performed in only one of the three participating centers; nevertheless, the sample size was sufficient to depict significant differences in this parameter between the two dietary treatments.

In conclusion, our study indicates that in people at high cardiometabolic risk the consumption of a low-GI diet has no relevant beneficial effect on blood pressure levels and on markers of blood glucose and insulin metabolism at fasting in comparison with a high GI diet. Conversely, this type of diet is able to markedly reduce the postprandial plasma triglyceride profile in comparison with a diet with similar characteristics but based on high GI foods. These improvements of the plasma lipid profile are paralleled by those observed in relation to blood glucose metabolism (18). The beneficial effects of the low-GI diet on postprandial glucose and triglyceride metabolism may contribute to the inverse relationship between dietary GI and CVD incidence observed in epidemiological studies (10, 11) and are additive to the improvement of the overall cardiovascular risk factor profile induced by the other features of the traditional Mediterranean dietary pattern on which both intervention diets were based. Therefore, our study reinforces dietary recommendations issued by many authoritativebodies proposing the Mediterranean diet as a dietary model apt to contribute to CVD prevention, emphasizing the choice of carbohydrate foods with a low GI.

Data Availability Statement

Additional data are available from the corresponding author on reasonable request.

Acknowledgements: W.W.C., G.R. and R.L. served as co-principal investigators. The study authors would like to thank all study participants who volunteered their valuable time and attention. We thank Barilla G&R F.lli. SpA, Parma, Italy for providing some of the cereal products for the study participants.

Author contribution Statement: Conceptualization, R.G., G.R., R.L. and W.W.C.; methodology, G.C., R.E.B., W.W.C., R.L. and G.R.; formal analysis, G.C.; investigation, R.G., G.C., R.E.B. and M.V.; resources, W.W.C., R.L. and G.R.; data curation, G.C., M.V., R.E.B. and R.G.; writing—original draft preparation, G.C. and R.G.; writing—review and editing, G.C., R.G., R.E.B., R.L. and G.R.; supervision, G.R., R.L. and W.W.C.; project administration, R.E.B., R.G., G.C. and M.V.; funding acquisition, G.R., R.L. and W.W.C. All authors have read and agreed to the published version of the manuscript.

Funding: This research was funded by Barilla International and Barilla USA. The funding sources had no role in the collection, analysis, and interpretation of data; in writing of this and any reports. and in the decision to submit the article for publication.

Informed Consent Statement: Informed consent was obtained from all subjects involved in the study.

Conflicts of Interest: Gabriele Riccardi is member of the Health and Wellbeing Advisory Board of the Barilla company; remuneration for this activity goes to his University Department. All other authors declare no conflict of interest.

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There is NO conflict of interest to disclose.

Supplementarytable1.docx
Supplementary Table 1. Anthropometric and fasting plasma metabolic parameters at baseline and after 12-week dietary intervention in the Naples cohort (n=54)

Effects on cardiovascular risk factors of a low- vs high-Glycemic Index Mediterranean Diet in high cardiometabolic risk individuals: The MEDGI-Carb Study

Status:

Journal Publication

Version 1

Abstract

Figures

Introduction

SUBJECTS AND METHODS

Subjects and study design

Laboratory methods

Statistical Analysis

Results

Fasting CVD risk factors

Postprandial triglycerides response

Discussion

Declarations

References

Additional Declarations

Supplementary Files

Status:

Journal Publication

Version 1