1. Journal Club 埼玉医科大学 総合医療センター 内分泌・糖尿病内科 Department of Endocrinology and Diabetes, Saitama Medical Center, Saitama Medical University 松田 昌文 Matsuda, Masafumi 2016 年 3 月 31 日 8:30-8:55 ８階 医局 Bozzetto L, Alderisio A, Giorgini M, Barone F, Giacco A, Riccardi G, Rivellese AA, Annuzzi G. Extra-Virgin Olive Oil Reduces Glycemic Response to a High-Glycemic Index Meal in Patients With Type 1 Diabetes: A Randomized Controlled Trial. Diabetes Care. 2016 Feb 9. pii: dc152189. [Epub ahead of print]

2. Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples, Italy Diabetes Care. 2016 Feb 9. pii: dc152189. フェデリコ 2 世・ナポリ大学 エキストラバージンオリーブオイ ルとはオリーブの果実を搾ってろ 過しただけの、一切化学的処理を 行わないバージンオイルで、酸度 （遊離脂肪酸の割合）が 100 ｇ当 たり 0.8 ｇを越えないものを指しま す。

3. OBJECTIVE To evaluate whether fat quality, in the context of meals with high– (HGI) or low– glycemic index (LGI), influences postprandial blood glucose (PPG) response in patients with type 1 diabetes.

4. RESEARCH DESIGN AND METHODS According to a randomized crossover design, 13 patients with type 1 diabetes on insulin pump consumed two series (HGI or LGI) of meals with the same carbohydrate quantity while differing for amount and quality of fat: 1) low in fat (“low fat”), 2) high in saturated fat (butter), or 3) high in monounsaturated fat (extra-virgin olive oil) (EVOO). Premeal insulin doses were based on insulin– to–glycemic load ratios. Continuous glucose monitoring was performed and 6-h PPG evaluated.

5. Inclusion criteria were treatment with continuous subcutaneous insulin infusion, use of fast-acting insulin analogs (aspart, lispro, glulisine) for at least 6 months, and an HbA1c <8.0% (64 mmol/mol).

6. The intervention was preceded by a 1-week run-in period during which participants underwent continuous glucose monitoring (CGM) and filled in a 7-day dietary record to optimize basal infusion rate and insulin–to–glycemic load ratio. Then, according to a randomized crossover design, participants were assigned by coin toss to a 1-week period wherein they consumed either three meals with high–glycemic index (HGI) or three meals with low– glycemic index (LGI), thereafter crossing over to the alternate series for one additional week. For each series, the sequence of meals was randomly assigned by card drawing.

7. In each series (HGI or LGI), meals were similar for total carbohydrate content but were different for amount and type of fat: 1) lowin fat (“low fat”), 2) high in saturated fat (butter), or 3) high in monounsaturated fat (extravirgin olive oil) (EVOO) (Table 1). Over the two experimental weeks, participants underwent CGM, wearing their sensors 7 days/week. They were instructed to calibrate three times per day using premeal blood glucose capillary tests. The test meals were performed between the 2nd and the 7th day of sensor life. The participants also checked capillary blood glucose 2, 4, and 6 h after test meals.

8. The participants consumed the test meals at lunchtime. According to the randomized crossover design, the 3 days per week were chosen on the basis of the subjects’ work and recreational activities in order to keep these activities reproducible and compatible with the study design. The same procedures were followed on both experimental weeks, the HGI week and the LGI week, respectively. In case of premeal blood glucose levels outside the 5–8 mmol/L range or a rapid decrease/ increase (3.3 mmol/L) of glucose levels during the last 60 min according to CGM measurement, the test meal was postponed. In the mornings preceding the test meals, patients consumed the same light breakfast in order to avoid a second-meal effect bias; moreover, they were asked to avoid strenuous physical activity on the day before and on the morning of the test meal and to refrain from any light/moderate physical activity or stressful unusual situations over 6 h after the meal. For improvement of protocol compliance, the participants received frequent call phones from study investigators, in particular before and over the 6 h after meal ingestion. Premeal insulin doses, injected just before eating, were based on the individual insulin– to–glycemic load ratio determined during patients’ educational sessions with the study team. Therefore, for each patient, insulin doses were the same for each series, i.e., before the butter, EVOO, or low-fat meals, but differed between the two series, i.e., before the HGI and LGI meals.

9. The meals with a HGI were composed of white rice (60 g), white bread (75 g), beef minced meat (90 g), and banana (180 g), plus butter (43 g) or EVOO (37 g), with 8 g EVOO in the lowfat test meal. The meals with a LGI were composed of pasta (50 g), lentils (100 g), whole-meal bread (30 g), ham (15 g), and apple (185 g), plus butter (45 g) or EVOO (37 g), with 8 g EVOO in the low-fat test meal. The whole content of butter and EVOO was added to the meals before freezing. Apples and bananas were given fresh to the participants, who were instructed to weigh the recommended portion after peeling the fruit.

10. Figure 1— Postprandial blood glucose profiles after the EVOO, butter, and low-fat meals within the context of LGI or HGI meals. ○Empty circles, EVOO; □empty squares, butter; ●full circles, low fat. *P = 0.005 for time × glycemic index interaction by repeated- measures ANOVA; †P<0.0001 for time × meal interaction by repeated-measures ANOVA.

11. Figure 2— Postprandial blood glucose iAUCs after the EVOO, butter, and low-fat meals within the context of LGI or HGI meals. Empty bars: blood glucose iAUC 0– 180 min. Full bars: blood glucose iAUC 180– 360 min. *P <0.05 vs. butter and low-fat meals by post hoc analysis of repeated- measures ANOVA. Blood glucose iAUC 0–180 min after all combined LGI vs. all combined HGI meals: P = 0.006 by repeated- measures ANOVA.

13. RESULTS PPG was significantly different between HGI and LGI meals (P = 0.005 for time 3 glycemic index interaction by repeated-measures analysis [RMA]), being significantly higher during the first 3 h after the HGI meals with a later tendency to an opposite pattern. In the context of HGI meals, PPG was significantly lower after EVOO than after low fat or butter (P < 0.0001 for time3meal interaction by RMA), with a marked difference in the 0- to 3-h glucose incremental area under the curve between EVOO (mean ± SD 198 ± 274 mmol/L × 180 min) and either low fat (416 ± 329) or butter (398 ± 355) (P < 0.05). No significant differences were observed in PPG between the three LGI meals.

14. CONCLUSIONS Carbohydrate quality of a mixed meal influences shape and extent of PPG. Besides, using EVOO in a HGI meal attenuates the early postprandial glucose response observed when this meal is consumed with either low fat or butter. Therefore, an optimal prandial insulin administration would require considering, in addition to the quantity of carbohydrates, the quality of both carbohydrate and fat.

15. Message イタリアのナポリからのオリーブオイルについての発表。 EVOO がこれだけ糖の吸収を遅らせるとは！！！ → αGI よりよいと感じるが GLP-1 など測定していないが、グルカゴン抑制かも EVOO はどこの産だろうか？ １食 37g のオリーブオイル入れる ??? 普通の OGTT や食事負荷と違ってインスリンを入れてい る！