Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Carbohydrates, glycemic index and diabetes mellitus

Short-term low carbohydrate/high-fat diet intake increases postprandial plasma glucose and glucagon-like peptide-1 levels during an oral glucose tolerance test in healthy men

Abstract

Background/Objectives:

Postprandial hyperglycemia increases the risks of development of type 2 diabetes and cardiovascular diseases. The purpose of this study was to determine whether a 3-day low-carbohydrate/high-fat diet (LC/HFD) alters postprandial plasma glucose and incretin levels during oral glucose tolerance test (OGTT) in healthy men.

Subjects/Methods:

Nine healthy young men (age (mean±s.e.), 27±1 years; body mass index, 22±1 kg/m2) consumed either a normal diet (ND: energy from 22% fat) or a LC/HFD (energy from 69% fat) for 3 days each. The total energy intake from each diet was similar. An OGTT was performed after each 3-day dietary intervention. Postprandial plasma glucose, insulin, free fatty acid and glucagon-like peptide-1 (GLP-1) levels were determined at rest and during the OGTT.

Results:

Plasma glucose levels and incremental area under the curve during the OGTT were significantly higher in the LC/HFD trial than in the ND trial (P=0.024). In addition, increase in GLP-1 levels was significantly higher in the LC/HFD trial than in the ND trial (P=0.025). The first-phase insulin secretion indexes were significantly lower in the LC/HFD trial than in the ND trial (P<0.041).

Conclusions:

These results demonstrate that even short-term LC/HFD increased postprandial plasma glucose and GLP-1 levels in healthy young men. A decrease in first-phase insulin secretion may partially contribute to the short-term LC/HFD-induced increase in postprandial plasma glucose levels.

Introduction

Postprandial hyperglycemia is a condition of high blood glucose level after eating a meal, and is an effective predictor of mortality from all causes and cardiovascular diseases (CVD) as well as the risk of developing type 2 diabetes.1, 2, 3 Furthermore, decreasing postprandial hyperglycemia with medications reduces the risks of developing CVD and type 2 diabetes.4, 5, 6 One of the factors explaining the association between postprandial hyperglycemia and the development of CVD and type 2 diabetes is the resulting acute fluctuation in blood glucose levels. Interestingly, acute fluctuation in blood glucose levels suppresses endothelium-dependent vasodilation,7 and increases levels of interleukin-6, tumor necrosis factor-α8 and platelet hyperaggregability9 in healthy men; all these parameters have been associated with the development of CVD. Therefore, it is important to elucidate the factors that elicit postprandial hyperglycemia for the prevention of both CVD and type 2 diabetes.

A low-carbohydrate/high-fat diet (LC/HFD) has a key role in the development of postprandial hyperglycemia. Short-term exposure (1–11 days) to LC/HFD decreases carbohydrate oxidation10, 11, 12, 13, 14, 15, 16 and increases endogenous glucose production.10, 17 In addition, short-term LC/HFD (3–5 days) decreases insulin sensitivity, as measured using the hyperinsulinemic–euglycemic glucose clamp18, 19 and the intravenous glucose tolerance test.20 However, little is known about the effect of LC/HFD on postprandial hyperglycemia. Although the hyperinsulinemic–euglycemic glucose clamp and intravenous glucose tolerance test are widely accepted as the gold standard for quantifying insulin resistance, they may not accurately reflect insulin action and glucose dynamics under postprandial physiological conditions, owing to the fact that insulin secretion and incretins21 contribute to postprandial glucose metabolism. Thus, an oral ingestion test would be more effective to estimate postprandial glucose metabolism. The oral glucose tolerance test (OGTT), which is used as the representative oral ingestion test, can effectively assess the response of postprandial glucose, insulin and incretins (glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP)) levels under physiological conditions.

To the best of our knowledge, few reports have investigated the effects of short-term LC/HFD on postprandial glucose metabolism using oral ingestion tests. Some studies have shown that LC/HFD for 1–5 days decreased glucose disposal during OGTT in healthy22, 23, 24 and aerobically active subjects.25 However, none of the previous studies investigated the effects of short-term LC/HFD on both postprandial glucose and incretin levels. Because incretin can stimulate insulin secretion during the postprandial period,21 a decrease in incretin secretion may indirectly contribute to the increase in postprandial glucose levels in these conditions.

The purpose of this study was to examine the effects of short-term LC/HFD on postprandial glucose, insulin and incretin levels measured using the OGTT in healthy young men.

Methods

Participants

Nine healthy young men participated in this study (age (mean±s.e.), 27±1 years; height, 176±1 cm; peak oxygen consumption (VO2 peak), 40.5±2.3 ml/kg/min). The participants had a sedentary lifestyle, that is they did not exercise on a regular basis. The participants had no history of any metabolic diseases or CVD. None of the participants were smokers, and all refrained from taking any medications or supplements known to affect their metabolism. The participant’s body mass (BM) had been stable (<3 kg change) for at least 2 months. The purpose, design and risks of this study were explained to each participant, and written informed consent was obtained. The study conformed the principles outlined in the Helsinki Declaration and was approved by the ethics committees on human research of Waseda University.

Experimental protocol

All participants performed two experimental trials lasting 4 days each. The trials consisted of consumption of (a) a normal diet (ND) and (b) LC/HFD for 3 consecutive days each. The trial order for each participant was randomized. The two trials were separated by at least 1 week and were performed within 1 month. The day before starting each trial, participants had the same diet and could eat their evening meal at any time up to 2100 h. After this meal, they refrained from consuming any food but could drink water. On the morning of day 1, the participants arrived at the laboratory at 0900 h after an overnight fast (>12 h). After they had rested in a supine position for 30 min, a blood sample was collected to measure baseline metabolite and hormone levels. In addition, BM, fat mass, and fat-free mass were measured by impedance (InnerScan BC-520; Tanita, Tokyo, Japan). After these measurements, the participants consumed ND or LC/HFD in accordance with the allocated trial for 3 days. On day 4 (after 3 days of dietary intervention), the participants arrived at the laboratory at 0900 h after an overnight fast. BM, fat mass and fat-free mass were then measured by impedance (InnerScan BC-520). After the participants had rested in a supine position for 30 min, an intravenous catheter was inserted into the antecubital vein and a baseline blood sample was collected. After the participants ingested 75 g liquid glucose (TRELAN-G75; Ajinomoto, Tokyo, Japan), 2-h OGTT was started. During OGTT, the participants rested in supine position on a bed, and blood samples were withdrawn at 15, 30, 45, 60, 90 and 120 min after ingestion of the liquid glucose.

Diet and physical activity

The food was supplied by the investigators. Each participant received ND or LC/HFD for 3 consecutive days each. Total energy intake per day was similar between ND and LC/HFD, but the percentage of carbohydrate, fat and protein to total energy intake varied. The ND contained 67% carbohydrate, 22% fat and 11% protein, whereas the LC/HFD contained 20% carbohydrate, 69% fat and 11% protein. The total energy intake per day for each participant was estimated using the Dietary Reference Intakes for Japanese equation (basal metabolic rate (reference basal metabolic rate × reference BM) × physical activity level (normal physical activity level: 1.75)).26 These diets did not vary from day to day and were designed to be as common and regular as possible. The menu of both diets was designed using a dietary analysis program (Eiyoukun, version 4.0; Kenpakusya, Tokyo, Japan) by a nutritionist. Participants were instructed to adhere to the provided menus and to check the food intake record. Food records were confirmed at the end of the dietary intervention by the investigators.

Participants were instructed to maintain their usual lifestyle throughout the experiment. The amount of physical activity during the experiment was assessed via interview.

Blood sampling and metabolite and hormone levels

Blood samples were collected in a 8.5-ml tube, containing thrombin for analyzing insulin, c-peptide, free fatty acid (FFA), β-hydroxybutyric acid (β-HBA), triglycerides (TG), total cholesterol, high-density lipoprotein cholesterol, alanine aminotransferase and aspartate aminotransferase levels, and in another 2-ml tube, containing 2.5 mg EDTA, 1000 KIU aprotinin, and 20 μl dipeptidyl peptidase-4 inhibitor (Millipore, Billerica, MA, USA) for analyzing GLP-1 and GIP levels. The blood samples in the 8.5-ml tube were centrifuged (3000 g for 10 min at 4 °C) 30 min after collection, whereas those in the 2-ml tube were kept in ice and centrifuged (3000 g for 10 min at 4 °C) within 30 min of collection. After centrifugation, the serum and plasma from each sample were transferred into a plastic tube and immediately stored at −80 °C until further analysis.

The plasma glucose level was immediately analyzed using a glucose autoanalyzer (Niporo; FreeStyle Freedom, Osaka, Japan). The serum insulin level was measured using an electrochemiluminescence immunoassay kit (Roche Diagnostics; Tokyo, Japan). The serum c-peptide level was measured using a chemiluminescent immunoassay kit (Roche Diagnostics). The serum FFA level was measured by an enzymatic colorimetric method (Wako Pure Chemical Industries; Osaka, Japan). The serum β-HBA level was measured by an enzymatic cycling method (Kainos Laboratories; Tokyo, Japan). The serum TG level was measured by an enzymatic colorimetric method (Kyowa Medex; Tokyo, Japan). Total cholesterol and high-density lipoprotein cholesterol level were measured by an enzymatic method (Kyowa Medex). Low-density lipoprotein cholesterol (LDLC) level was calculated according to the equation of Friedewald et al.27 The alanine aminotransferase and aspartate aminotransferase level were determined by the Japan Society of Clinical Chemistry transferable method (Wako Pure Chemical Industries). Plasma GLP-1 (7–36 amide and 7–37) and GIP levels were measured using the ELISA kit (Millipore).

Calculations

Homeostasis model assessment ratio (HOMA-R) was calculated according to Matthews et al.28 The incremental area under the curves (iAUC) for glucose, insulin, FFA, β-HBA, TG, GLP-1 and GIP levels during the 2-h OGTT were obtained using the trapezoidal rule. Oral glucose insulin sensitivity was calculated from plasma glucose and insulin levels before and during the OGTT to assess insulin sensitivity according to Mari et al.29 The insulinogenic index and Stumvoll first-phase insulin release index30 were used to estimate first-phase insulin release.

Statistical analysis

All data are shown as mean±s.e. Statistical analyses were performed using SPSS software (version 18; IBM, Tokyo, Japan). A two-way analysis of variance for repeated measures (trial × time) with Bonferroni post hoc analysis was used to compare changes in characteristics and metabolite levels between two trials over time. Paired t-test was used to analyze differences in iAUC of metabolites and hormones, and insulinogenic index and Stumvoll first-phase insulin release index between the two trials. Pearson’s product–moment correlation coefficient was used to determine the relationship among glucose, incremental area under the curves insulinogenic index and Stumvoll first-phase insulin release index during OGTT. The sample size was determined by a statistical power analysis (β=0.2, α=0.05) of an expected difference in metabolite variables based on our preliminary data. To interpret the magnitude of difference and correlation coefficient, effect size (ES) on the basis of Cohen31 was calculated. ES was classified as small (paired t-test: <0.20, Pearson’s product–moment correlation coefficient: <0.10), as moderate (paired t-test: 0.20–0.79, Pearson’s product–moment correlation coefficient: 0.10–0.49) and as large (paired t-test: >0.80, Pearson’s product–moment correlation coefficient: >0.50). Statistical significance was set at <0.05.

Results

Energy intake

Total energy intake per day was not significantly different between the ND and LC/HFD trials (ND, 11694±218 kJ/day; LC/HFD, 11823±260 kJ/day). Moreover, these values were not different from the energy intake per day estimated by the Dietary Reference Intakes for Japanese 2010 (11627±285 kJ/day). The percentages of carbohydrate and fat intakes were significantly different between two trials (P<0.05), but the intake of protein to total energy intake was similar (ND: carbohydrate, 66±0.1%; fat, 22±0.4%; protein, 11±0.1%; LC/HFD: carbohydrate, 20±0.3%; fat, 69±0.3%; protein, 11±0.1%).

Characteristics

Percentage of fat and fat mass remained unchanged with both the ND and LC/HFD trials (Table 1). BM and fat-free mass slightly decreased after both trials (P<0.05), but the changes were similar (BM: ND, −1.1±0.3%; LC/HFD, −1.3±0.3%; fat-free mass: ND, −0.9±0.2%; LC/HFD, −0.8±0.6%; Table 1).

Table 1 Subject characteristics and fasting blood metabolite levels before (pre) and after (post) 3-day ND and LC/HFD

Fasting metabolite and hormone levels

Fasting plasma glucose (P<0.01), serum insulin (P<0.01), HOMA-R (P<0.01) and c-peptide levels (P<0.05) significantly decreased with both the ND and LC/HFD trials, but the changes were similar in both trials (P>0.05; Table 1). Contrary to this, the FFA levels significantly increased with both the ND and LC/HFD trial (P<0.05), but with no differences between two trials (P>0.05; Table 1). The GLP-1 levels remained unchanged before and after both trials (P>0.05), but the GIP level increased after only the LC/HFD trial (P<0.05; Table 1). β-HBA remained unchanged in the ND trial (P>0.05), but it significantly increased after LC/HFD trial (P<0.05; Table 1). The TG level before both trials was identical, but it significantly decreased after the LC/HFD trial (P<0.05). Total cholesterol (P>0.05) and high-density lipoprotein cholesterol levels (P>0.05) remained unchanged before and after the ND and LC/HFD trial. The LDLC level before the ND and LC/HFD trial was lower than that after both trials (P<0.05). Alanine aminotransferase (P>0.05) and aspartate aminotransferase levels (P>0.05) remained unchanged before and after both trials.

Metabolite and hormone levels during oral glucose tolerance test

Plasma glucose levels during OGTT were significantly higher in the LC/HFD trial than in the ND trial (P<0.05; Figure 1a). Glucose iAUC was significantly greater in the LC/HFD trial than in the ND trial (P<0.05; ES, 0.91, Figure 1a). Serum insulin levels during OGTT did not differ between the ND and LC/HFD trials (Figure 1b). The GLP-1 levels during OGTT were significantly higher in the LC/HFD than in the ND trial (P<0.05; Figure 2a), and GLP-1 iAUC was significantly greater in the LC/HFD trial than in the ND trial (P<0.05, ES, 0.92; Figure 2a). The GIP levels during OGTT were similar between the ND and LC/HFD trials, and GIP iAUC did not differ between the two trials (Figure 2b). The response of FFA levels during OGTT did not differ between the ND and LC/HFD trials (Table 2). β-HBA levels during OGTT were significantly higher in the LC/HFD trial than in the ND trial (P<0.05; ES, 0.90; Table 2), and β-HBA iAUC was also significantly greater in the LC/HFD trial than in the ND trial (P<0.05; Table 2). TG levels during OGTT were significantly lower in the LC/HFD trial than in the ND trial (P<0.05; Table 2).

Figure 1
figure1

The levels and iAUC of plasma glucose (a), and serum insulin (b) during the OGTT. *Significantly different from ND value at each time point (P<0.05). Significantly different between the ND and LC/HFD values (P<0.05).

Figure 2
figure2

The levels and iAUC of plasma GLP-1(a), and GIP (b) during the OGTT. *Significantly different from the ND value at each time point (P<0.05). Significantly different between the ND and LC/HFD values (P<0.05).

Table 2 Serum FFA, β-HBA and TG levels during 2-h OGTT after 3-day ND and LC/HFD

Insulin sensitivity and insulin first-phase release

Oral glucose insulin sensitivity was not significantly different between the ND and LC/HFD trial (Figure 3a). The insulinogenic index and Stumvoll first-phase insulin release index were significantly lower in LC/HFD than in ND trial (insulinogenic index: P<0.05, ES, 0.81; Stumvoll first-phase insulin release index: P<0.05, ES, 0.82; Figures 3b and c).

Figure 3
figure3

The values of OGIS (a), insulinogenic index (b) and Stumvoll first-phase insulin release index (c). *Significantly different between the ND and LC/HFD values (P<0.05).

Relationship between glucose incremental area under the curve and first-phase insulin release

Glucose iAUC for the ND and LC/HFD trials were negatively correlated with the insulinogenic index (r=−0.71; P=0.001; ES, 0.70) and the Stumvoll first-phase insulin release index (r=−0.54; P=0.02; ES, 0.54).

Discussion

The primary purpose of this study was to compare the effects of a short-term ND and LC/HFD on postprandial glucose, insulin and incretin responses. Our findings demonstrated that short-term LC/HFD increased postprandial plasma glucose and GLP-1 levels and decreased first-phase insulin release in healthy young men.

Plasma glucose levels and iAUC during OGTT increased after 3 days of LC/HFD. This result is in agreement with some short-term dietary intervention studies.22, 23, 24, 25 Increase in postprandial glucose level would be determined by the amount of carbohydrate22 or fat23 in diet. However, it is difficult to isolate the effect of the amount of carbohydrate or fat on postprandial glucose metabolism from the current study.

Three-day LC/HFD led to increase in postprandial glucose level. One possible mechanism may be the loss of first-phase insulin release, which leads to a decrease in postprandial glucose disposal due to the reduction of peripheral glucose uptake, hepatic glucose uptake and suppression of hepatic glucose production.32 In support of this hypothesis, the insulinogenic index and the Stumvoll first-phase insulin release index were significantly lower in LC/HFD than in ND trial with no difference in the oral glucose insulin sensitivity between two trials. Moreover, the negative relationships between plasma glucose iAUC and the first-phase insulin release indexes were observed. These data are supported by the results of Swinburn et al.33 They reported that a high-fat modern diet decreased glucose tolerance and β-cell sensitivity to glucose without change in insulin sensitivity in both Pima Indians and Caucasians. Nevertheless, the reasons for the reduction in the first-phase insulin release are unclear. Although the effects of elevated plasma FFA on insulin secretion are controversial, prolonged elevation of FFA levels impaires insulin secretion.34 In the current study, the increase in fasting FFA levels was similar between ND and LC/HFD, but they negatively correlated with first-phase insulin release indexes. Therefore, it is likely that FFA levels are a contributing factor in the regulation of first-phase insulin release.

The fasting GIP levels increased only with the LC/HFD trial. Similarly, the increased GLP-1 level during OGTT was higher in the LC/HFD trial than in the ND trial. A previous study reported an increase in fasting GIP levels after high-fat overfeeding.17 However, to our knowledge, the finding that GLP-1 levels are increased in response to short-term LC/HFD is novel. The greater increase in postprandial GLP-1 levels could be explained by the change in the rate of gastric emptying. Although this parameter was not measured in the present study, the rate of gastric emptying influences the release of GLP-1. In fact, when the rate of gastric emptying increased and the rate of glucose entry into small intestine enhanced, increases in plasma GLP-1 level were promoted in healthy men.35 Moreover, the rate of gastric emptying was accelerated after a 3-day high-fat diet intake.36 Therefore, our data suggest that a LC/HFD could partly contribute to promoting the release of GLP-1 by affecting the rate of gastric empting.

GLP-1 and GIP are gut hormones that stimulate postprandial insulin secretion.21 The greater increase in GIP and GLP-1 level after LC/HFD appears to facilitate postprandial endogenous insulin secretion. However, there was no difference in the response of serum insulin levels between ND and LC/HFD. The reasons for this remain unclear. Nevertheless, it is believed that the increase in postprandial GLP-1 levels represents an adaptive response to promote declined insulin secretion for the replenishment of glycogen levels depleted in the liver and muscles.

The decrease in the fasting TG levels, which was maintained during the OGTT, was only observed with the LC/HFD. Because a LC/HFD contains little carbohydrate, it reduces blood glucose availability and glucose oxidation gradually decreases. In contrast, fat oxidation gradually increases12, 13, 16 and the contribution of TG-derived fatty acid oxidation to total fat oxidation increases with a LC/HFD.37 The increased contribution of TG-derived fatty acid oxidation is involved in the increase in lipoprotein lipase (LPL) activity in the muscle capillary bed with high-fat diet.38 LPL facilitates the release of fatty acid from TG within the muscle and very low-density lipoprotein, and increases fat oxidation.38 Considering that fasting TG is mainly delivered along with very low-density lipoprotein, although the contribution of TG in the muscle and very low-density lipoprotein to total fat oxidation is unclear, the increase in oxidation of fatty acid released from TG may decrease the fasting TG level after 3-day LC/HFD.

In conclusion, short-term LC/HFD increased postprandial glucose and GLP-1 levels in healthy young men. Impaired glucose tolerance was partly explained by reduction in insulin release. These findings demonstrated that even a short-term (3 days) excess fat intake could cause postprandial hyperglycemia in healthy young men under physiological conditions.

References

  1. 1

    DECODE group. Glucose tolerance and mortality: comparison of WHO and American Diabetes Association diagnostic criteria. The DECODE study group. European Diabetes Epidemiology Group. Diabetes Epidemiology: Collaborative analysis Of Diagnostic criteria in Europe. Lancet 1999; 354: 617–621.

    Article  Google Scholar 

  2. 2

    DECODE group. Glucose tolerance and cardiovascular mortality: comparison of fasting and 2-hour diagnostic criteria. Arch Intern Med 2001; 161: 397–405.

    Article  Google Scholar 

  3. 3

    Nakagami T . Hyperglycaemia and mortality from all causes and from cardiovascular disease in five populations of Asian origin. Diabetologia 2004; 47: 385–394.

    CAS  Article  Google Scholar 

  4. 4

    Chiasson JL, Josse RG, Gomis R, Hanefeld M, Karasik A, Laakso M . Acarbose for prevention of type 2 diabetes mellitus: the STOP-NIDDM randomised trial. Lancet 2002; 359: 2072–2077.

    CAS  Article  Google Scholar 

  5. 5

    Chiasson JL, Josse RG, Gomis R, Hanefeld M, Karasik A, Laakso M . Acarbose treatment and the risk of cardiovascular disease and hypertension in patients with impaired glucose tolerance: the STOP-NIDDM trial. JAMA 2003; 290: 486–494.

    CAS  Article  Google Scholar 

  6. 6

    Kawamori R, Tajima N, Iwamoto Y, Kashiwagi A, Shimamoto K, Kaku K . Voglibose for prevention of type 2 diabetes mellitus: a randomised, double-blind trial in Japanese individuals with impaired glucose tolerance. Lancet 2009; 373: 1607–1614.

    CAS  Article  Google Scholar 

  7. 7

    Kawano H, Motoyama T, Hirashima O, Hirai N, Miyao Y, Sakamoto T et al. Hyperglycemia rapidly suppresses flow-mediated endothelium-dependent vasodilation of brachial artery. J Am Coll Cardiol 1999; 34: 146–154.

    CAS  Article  Google Scholar 

  8. 8

    Esposito K, Nappo F, Marfella R, Giugliano G, Giugliano F, Ciotola M et al. Inflammatory cytokine concentrations are acutely increased by hyperglycemia in humans: role of oxidative stress. Circulation 2002; 106: 2067–2072.

    CAS  Article  Google Scholar 

  9. 9

    Sakamoto T, Ogawa H, Kawano H, Hirai N, Miyamoto S, Takazoe K et al. Rapid change of platelet aggregability in acute hyperglycemia. Detection by a novel laser-light scattering method. Thromb Haemost 2000; 83: 475–479.

    CAS  Article  Google Scholar 

  10. 10

    Bisschop PH, de Metz J, Ackermans MT, Endert E, Pijl H, Kuipers F et al. Dietary fat content alters insulin-mediated glucose metabolism in healthy men. Am J Clin Nutr 2001; 73: 554–559.

    CAS  Article  Google Scholar 

  11. 11

    Chokkalingam K, Jewell K, Norton L, Littlewood J, van Loon LJ, Mansell P et al. High-fat/low-carbohydrate diet reduces insulin-stimulated carbohydrate oxidation but stimulates nonoxidative glucose disposal in humans: an important role for skeletal muscle pyruvate dehydrogenase kinase 4. J Clin Endocrinol Metab 2007; 92: 284–292.

    CAS  Article  Google Scholar 

  12. 12

    Cooper JA, Watras AC, Shriver T, Adams AK, Schoeller DA . Influence of dietary fatty acid composition and exercise on changes in fat oxidation from a high-fat diet. J Appl Physiol 2010; 109: 1011–1018.

    CAS  Article  Google Scholar 

  13. 13

    Hansen KC, Zhang Z, Gomez T, Adams AK, Schoeller DA . Exercise increases the proportion of fat utilization during short-term consumption of a high-fat diet. Am J Clin Nutr 2007; 85: 109–116.

    CAS  Article  Google Scholar 

  14. 14

    Harber MP, Schenk S, Barkan AL, Horowitz JF . Alterations in carbohydrate metabolism in response to short-term dietary carbohydrate restriction. Am J Physiol Endocrinol Metab 2005; 289: E306–E312.

    CAS  Article  Google Scholar 

  15. 15

    Peters SJ, Harris RA, Wu P, Pehleman TL, Heigenhauser GJ, Spriet LL . Human skeletal muscle PDH kinase activity and isoform expression during a 3-day high-fat/low-carbohydrate diet. Am J Physiol Endocrinol Metab 2001; 281: E1151–E1158.

    CAS  Article  Google Scholar 

  16. 16

    Schrauwen P, van Marken Lichtenbelt WD, Westerterp KR . Changes in fat oxidation in response to a high-fat diet. Am J Clin Nutr 1997; 66: 276–282.

    CAS  Article  Google Scholar 

  17. 17

    Brons C, Jensen CB, Storgaard H, Hiscock NJ, White A, Appel JS et al. Impact of short-term high-fat feeding on glucose and insulin metabolism in young healthy men. J Physiol 2009; 587: 2387–2397.

    Article  Google Scholar 

  18. 18

    Bachmann OP, Dahl DB, Brechtel K, Machann J, Haap M, Maier T et al. Effects of intravenous and dietary lipid challenge on intramyocellular lipid content and the relation with insulin sensitivity in humans. Diabetes 2001; 50: 2579–2584.

    CAS  Article  Google Scholar 

  19. 19

    Stettler R, Ith M, Acheson KJ, Decombaz J, Boesch C, Tappy L et al. Interaction between dietary lipids and physical inactivity on insulin sensitivity and on intramyocellular lipids in healthy men. Diabetes Care 2005; 28: 1404–1409.

    CAS  Article  Google Scholar 

  20. 20

    Johnson NA, Stannard SR, Rowlands DS, Chapman PG, Thompson CH, O'Connor H et al. Effect of short-term starvation versus high-fat diet on intramyocellular triglyceride accumulation and insulin resistance in physically fit men. Exp Physiol 2006; 91: 693–703.

    CAS  Article  Google Scholar 

  21. 21

    Drucker DJ, Nauck MA . The incretin system: glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors in type 2 diabetes. Lancet 2006; 368: 1696–1705.

    CAS  Article  Google Scholar 

  22. 22

    Hirmsworth HP . The dietetic factor determining the glucose tolerance and sensitivity to insulin of healthy men. Clin Sci 1935; 2: 67–94.

    Google Scholar 

  23. 23

    Anderson JW, Herman RH . Effects of carbohydrate restriction on glucose tolerance of normal men and reactive hypoglycemic patients. Am J Clin Nutr 1975; 28: 748–755.

    CAS  Article  Google Scholar 

  24. 24

    Sparti A, Decombaz J . Effect of diet on glucose tolerance 36 h after glycogen-depleting exercise. Eur J Clin Nutr 1992; 46: 377–385.

    CAS  PubMed  Google Scholar 

  25. 25

    Pehleman TL, Peters SJ, Heigenhauser GJ, Spriet LL . Enzymatic regulation of glucose disposal in human skeletal muscle after a high-fat, low-carbohydrate diet. J Appl Physiol 2005; 98: 100–107.

    CAS  Article  Google Scholar 

  26. 26

    Ministry of Health Labour Welfare of Japan. Dietary reference intakes for Japanese, 2010. Daiichi Shuppan: Tokyo, Japan, 2010; in Japanese.

  27. 27

    Friedewald WT, Levy RI, Fredrickson DS . Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem 1972; 18: 499–502.

    CAS  PubMed  Google Scholar 

  28. 28

    Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC . Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 1985; 28: 412–419.

    CAS  Article  Google Scholar 

  29. 29

    Mari A, Pacini G, Murphy E, Ludvik B, Nolan JJ . A model-based method for assessing insulin sensitivity from the oral glucose tolerance test. Diabetes Care 2001; 24: 539–548.

    CAS  Article  Google Scholar 

  30. 30

    Stumvoll M, Mitrakou A, Pimenta W, Jenssen T, Yki-Jarvinen H, Van Haeften T et al. Use of the oral glucose tolerance test to assess insulin release and insulin sensitivity. Diabetes Care 2000; 23: 295–301.

    CAS  Article  Google Scholar 

  31. 31

    Cohen J . Statistical Power Analysis for the Behavioral Sciences. 2nd edn. Routledge Academic: UK, 1988.

    Google Scholar 

  32. 32

    Ferrannini E, Bjorkman O, Reichard GA, DeFronzo RA . The disposal of an oral glucose load in healthy subjects. A quantitative study. Diabetes 1985; 34: 580–588.

    CAS  Article  Google Scholar 

  33. 33

    Swinburn BA, Boyce VL, Bergman RN, Howard BV, Bogardus C . Deterioration in carbohydrate metabolism and lipoprotein changes induced by modern, high fat diet in Pima Indians and Caucasians. J Clin Endocrinol Metab 1991; 73: 156–165.

    CAS  Article  Google Scholar 

  34. 34

    Oprescu AI, Bikopoulos G, Naassan A, Allister EM, Tang C, Park E et al. Free fatty acid-induced reduction in glucose-stimulated insulin secretion: evidence for a role of oxidative stress in vitro and in vivo. Diabetes 2007; 56: 2927–2937.

    CAS  Article  Google Scholar 

  35. 35

    Chaikomin R, Doran S, Jones KL, Feinle-Bisset C, O'Donovan D, Rayner CK et al. Initially more rapid small intestinal glucose delivery increases plasma insulin, GIP, and GLP-1 but does not improve overall glycemia in healthy subjects. Am J Physiol Endocrinol Metab 2005; 289: E504–E507.

    CAS  Article  Google Scholar 

  36. 36

    Clegg ME, McKenna P, McClean C, Davison GW, Trinick T, Duly E et al. Gastrointestinal transit, post-prandial lipaemia and satiety following 3 days high-fat diet in men. Eur J Clin Nutr 2011; 65: 240–246.

    CAS  Article  Google Scholar 

  37. 37

    Schrauwen P, Wagenmakers AJ, van Marken Lichtenbelt WD, Saris WH, Westerterp KR et al. Increase in fat oxidation on a high-fat diet is accompanied by an increase in triglyceride-derived fatty acid oxidation. Diabetes 2000; 49: 640–646.

    CAS  Article  Google Scholar 

  38. 38

    Kiens B, Essen-Gustavsson B, Gad P, Lithell H . Lipoprotein lipase activity and intramuscular triglyceride stores after long-term high-fat and high-carbohydrate diets in physically trained men. Clin Physiol 1987; 7: 1–9.

    CAS  Article  Google Scholar 

Download references

Acknowledgements

This work was supported in part by a Grant-in-Aid for the Young Scientists (B) (22700703) and for the Global COE program ‘Sport Sciences for the promotion of Active Life’ (2010–2011) awarded by Ministry of Education, Culture, Sports Science and Technology of Japan.

Author information

Affiliations

Authors

Corresponding author

Correspondence to S Numao.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Numao, S., Kawano, H., Endo, N. et al. Short-term low carbohydrate/high-fat diet intake increases postprandial plasma glucose and glucagon-like peptide-1 levels during an oral glucose tolerance test in healthy men. Eur J Clin Nutr 66, 926–931 (2012). https://doi.org/10.1038/ejcn.2012.58

Download citation

Keywords

  • postprandial hyperglycemia
  • incretin
  • impaired glucose tolerance
  • glucose-dependent insulinotropic polypeptide

Further reading

Search

Quick links