J Life Sci Res 2014; 12: 3-7Ⓒ 2014 Osaka Prefecture University

Journal of Life Science Research
Online ISSN 2186-5809

Review

What to eat first and how to eat to reduce amplitude of glycemic excursions
Saeko IMAI†１ and Shizuo KAJIYAMA２,３
School of Comprehensive Rehabilitation, Osaka Prefecture University, 3-7-30 Habikino, Habikino-shi, Osaka 583-8555, Japan１

２Department of Endocrinology and Metabolism, Kyoto Prefectural University of Medicine, Graduate School of Medical Science, 465

Kajii-cho, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan
３Kajiyama Clinic, 25-1-136 Oiwake-cho, Saiin, Ukyo-ku, Kyoto 615-0035, Japan

Received 10 August 2014; accepted 20 September 2014
Key words : diabetes; diet; CGM; glycemic excursions

1 Introduction
Large glucose excursions are reported to promote themacro-vascular complications associated with type 2 diabetes (T2D).1−3 Postprandial hyperglycemia and glycemic
spikes are more strongly associated with atherosclerosis
than fasting plasma glucose or HbA1c level.4 Hyperglycemia
is associated with increased risk for atherosclerosis by suppressing endothelium-dependent vasodilation, activating
thrombosis, and increasing oxidative stress in people with
T2D,5, 6 with impaired glucose tolerance (IGT), 7 and evenin subjects with normal glucose tolerance (NGT).8 A reduction in postprandial hyperglycemia by an α-glucosidase inhibitor delayed progression of carotid intima-media
thickening in subjects with T2D.9
A significant number of patients with diabetes remain
poorly controlled, mainly as a result of poor diet compliance.10−12 Patients with diabetes are advised to adopt an appropriate diet to affect blood glucose control by patientsthemselves, not by their physicians or other medical professionals on a lifelong basis. Traditionally, diets of T2D
aim to restrict energy intake and provide macronutrient balance. However, some diabetic patients may have difficulty
understanding diets based on a restrict energy intake, as
well as changing their daily food habits. Therefore, easy
and effective diets are needed to reduce glycemic fluctuations and minimize hypoglycemic events in addition to improving mean blood glucose.
In this article we reviewed our recent studies about theeffects of consuming “vegetables before carbohydrates” on
the reduction in glucose fluctuations.

Corresponding author, Email: poooch@rehab.osakafu-u.ac.jp†

2 Evaluation of efficacy of consuming vegetables before
carbohydrates on glucose excursions
A continuous glucose monitoring system (CGMS) is
capable of detecting hypoglycemia and hyperglycemia that
may be undetectable by self-monitoring blood glucose andHbA1c.13 Particularly, the mean amplitude of glycemic excursions (MAGE) is a significant determinant of overall
metabolic control, as well as increased risk of diabetes complications.1−3, 14 We examined whether consuming vegetables
before carbohydrates could reduce the daily postprandial
glucose excursions assessed by CGMS in Japanese patientswith T2D and subjects with NGT.
All participants were assigned to CGMS (Medtronic
Minimed Gold, Northridge, CA) for 72-h by consuming test
meals of vegetables before carbohydrates and carbohydrates

Fig. 1 The test meals of the study. The subjects ate the firstdishes of vegetables for 5 min, then the main dish for 5min, and consumed rice or bread for 5 min successively
within a 15 to 20 min total eating time for each meal, andvice versa.

4Fig. 2The mean of the daily glucose values was plotted to show the reduction in glucose excursions
by consuming vegetables before carbohydrates compared to the reverse regimen in both subjects
with type 2 diabetes (T2D, n = 19) and normal glucose tolerance (NGT, n = 21).

before vegetables on the 2nd and the 3rd day in a randomized
crossover design. The test meals consisted of rice/bread,meat/fish, 500 g of vegetables (tomato, spinach, broccoli,
and radish, etc), and contained 21 g of dietary fiber and125.6 kJ kg−1 per day. The energy ratio of protein, fat, andcarbohydrates was 17%, 25%, and 58%, respectively. The
subjects ate the first dishes of vegetables for 5 min, then themain dish for 5 min, and consumed rice or bread for 5 min
successively within a 15 to 20 min total eating time for eachmeal, and vice versa (Fig. 1).
Nineteen outpatients with T2D (male/female; 6/13,
age; 65.5 ± 9.4 yrs, duration of diabetes; 16.4 ± 10.2 yrs ,BMI; 22.5 ± 3.1 kg/m2, HbA1c; 7.2 ± 1.0%, FPG; 145 ± 48
mg/dl, diet/oral hypoglycemic agents/insulin treatment;
3/3/13: mean ± SD or n) and 21 subjects with NGT(male/female; 2/19, age; 29.8 ± 11.3 yrs, BMI; 20.8 ± 3.0
kg/m2, HbA1c; 5.4 ± 0.6%, FPG; 88 ± 9 mg/dl) were enrolled in the study. Glycemic parameters between the dayof consuming vegetables before carbohydrates and the dayof consuming carbohydrates before vegetables were examined.
The mean of the daily glucose values was plotted toshow the reduction in glucose excursions of consuming
vegetables before carbohydrates compared to the reverse
regimen in subjects with T2D and NGT (Fig. 2).15 The levels of standard deviation, MAGE, large amplitude ofglycemic excursions, mean 1-h postprandial glucose, mean
incremental area under the glucose curve 0-3h, and mean

incremental glucose peak were all significantly reduced
when the participants ate vegetables before carbohydrates
compared to the reverse regimen in both subjects with T2D
and NGT.16
3 The effect of consuming vegetables before carbohydrates on postprandial glucose and insulin
We reviewed the effect of eating vegetables before carbohydrates on postprandial plasma glucose and insulin inpatients with T2D. We conducted a randomized crossoverstudy in 15 outpatients with T2D controlled by diet(male/female; 7/8, age; 61.7 ± 11.6 yrs, duration of diabetes;
5.3 ± 8.8 yrs , BMI; 24.7 ± 4.3 kg/m2, HbA1c; 6.4 ± 0.6%,
FPG; 113 ± 20 mg/dl). Patients ate test meals consisting of
150 g white rice and vegetable salad (sliced tomato and cabbage with olive oil dressing), eating either vegetables before
carbohydrates or vice versa. Plasma glucose and serum insulin levels were evaluated at 0, 30, 60, 120 min after consuming each test meal. Plasma glucose and serum insulinlevels between consuming vegetables before carbohydrates
and the reverse regimen were examined.
Postprandial plasma glucose levels in those following
the vegetables before carbohydrates regimen were reduced
at 30 and 60 min compared to the reverse regimen (217 to
172 mg/dl, p < 0.01, 208 to 186 mg/dl, respectively). Postprandial serum insulin decreased significantly about 30%
at 30 and 60 min in the vegetables before carbohydrates regimen (32.9 to 22.3 μU/ml, p < 0.01, 35.4 to 24.9 μU/ml, p

5< 0.05, respectively).17
4 The effect of consuming vegetables before carbohydrates on long-term glycemic control
In addition to lowering daily glycemic excursions, westudied whether educating diabetic patients to eat vegetables before carbohydrates was effective on long-term
glycemic control. To test this hypothesis, we carried out aretrospective study in patients with T2D that comparedchanges in HbA1c as the primary outcome and changes inweight, serum lipids, and blood pressure as the secondary
outcomes. A total of 333 outpatients were divided into twogroups to receive instructions about consuming vegetables
before carbohydrates (educational group, n = 196) or a control group (n = 137) who underwent a medical examination
by a doctor. All patients were scheduled for return visits
every 4 weeks with a physical examination and they were
given general information about lifestyle and diabetes risk

Fig. 3The educational brochure about consuming vegetables
before carbohydrates for the patients with type 2 diabetes.

Table 1by either the doctor or nurses at every visit. The patients inthe educational group were routinely scheduled to see registered dietitians at every visit. Depending on the patient’s
current dietary intake, intervention aimed to encourage increased consumption of vegetables, including seaweed andmushrooms, and consuming them first for 5 min, then themain dishes (meat, fish, soybeans etc.) for 5 min, and riceor bread, including potatoes, pumpkin, corn etc, successively within a 15 to 20 min eating time using an original
educational brochure in the educational group (Fig. 3).
Improvements in glycemic control were observed inpatients in the educational group after the intervention andthe levels of blood pressure, total cholesterol, and LDL cholesterol decreased significantly in both groups after 12 and30 months (Table 1). After the intervention, dietary energy
intake, protein, fat, and carbohydrates decreased in the educational group. These reductions in dietary nutrients were
due to a decrease in the consumption of grain (rice), fruits,oil, sweets, and beverages, while the consumption of vegetables increased after intervention in the educationalgroups.18
5 What to eat first and how to eat to reduce amplitudeof glucose excursions
This evidence supports the effectiveness of consuming
vegetables before carbohydrates on daily glucose excursions and glycemic control in the long-term in patients with
T2D. Dietary carbohydrates consumed after vegetables
were digested slowly and required less insulin for subsequent metabolic disposal by the dietary fiber in the vegetables.19−22 Other factors may influence the glycemic responseand digestion of carbohydrates in the small intestine, including the rate of digestion, cooking method, transit time,

Clinical parameters of patients in the two study groups

6

and the rate of intestinal absorption.23−25 Horowitz et al. reported that whey protein and olive oil consumed before
meals resulted in a substantial reduction in postprandial glycaemia in patients with diabetes.26, 27 Protein and oil consumed before carbohydrates stimulate glucagon-like
peptide 1 (GLP-1) secretion, and delay gastric emptying
which leads to a reduction in glycemic excursions. However, in contrast to the reduced insulin secretion observed
after eating vegetables, whey protein augmented insulin secretion, possibly by a combination of the incretin effect andthe direct stimulation of β-cells by absorbed amino acids.28
Effects of consuming vegetables before carbohydrates areprobably similar to the gut peptide-based therapies for diabetes which may act predominantly by slowing gastric emptying when consuming oil and protein before thecarbohydrates.
The approach of consuming vegetables before carbohydrates supports the concept of emphasizing food choices,
what to eat first, how to eat, and not just to concentrate onenergy intake. The most important point was that themethod made it easy to make the appropriate behavioral
changes, to increase the consumption of vegetables and to
reduce the consumption of rice and sweets for patients with
T2D. As one aspect of nutritional education, consuming
vegetables before carbohydrates should be advised to patients with T2D and IGT,29 and this advice could even be
applicable to healthy people in order to prevent future cardiovascular events.
Acknowledgements
This study was supported in part by a Grant-in Aid for
Scientific Research from the Ministry of Education, Science
and Culture (23500809) and Osaka Prefecture University.
Conflict of Interest
The authors declare no potential conflicts of interest.
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