A Randomized Controlled Trial

The Effect of Inulin on Weight Management and Ectopic Fat in Subjects With Prediabetes

Nicola D. Guess; Anne Dornhorst; Nick Oliver; Jimmy D. Bell; E. Louise Thomas; Gary S. Frost

Disclosures

Nutr Metab. 2015;12(36) 

In This Article

Results

Subject Characteristics

The baseline characteristics of the subjects are shown in Table 1. There were no differences between the inulin and cellulose groups in any of the baseline characteristics. A total of 44 subjects were recruited and randomised of whom five withdrew from the study before week nine, including one taking inulin and one taking cellulose who dropped out due to side-effects. An additional subject withdrew following the week nine visit. See CONSORT diagram (Additional file 1 http://static-content.springer.com/esm/art%3A10.1186%2Fs12986-015-0033-2/MediaObjects/12986_2015_33_MOESM1_ESM.docx). Furthermore, due to a drop-out (n = 1) scheduling difficulties (n = 2), withdrawal of consent for MRI (n = 1) and no longer being eligible for MRI (n = 1) five subjects who underwent baseline and week nine MRI scans did not have a scan at 18 weeks. Therefore 19 subjects completed a follow-up MRI at 9-weeks (inulin group: three females and seven males; cellulose group: four females and five males), and 14 subjects completed a follow-up MRI at 18 weeks insulin group: three females, six males; cellulose group: three females and two males).

Compliance

On average, ten out of 189 sachets (5 %) were returned at week 18. The breath hydrogen levels increased by 15.0 ± 6.3 ppm (n = 20) in the inulin group vs 2.3 ± 1.6 ppm (n = 19) in the cellulose group at week nine (p = 0.07), a difference which reached significance at week 18 (14.8 ± 3.7 ppm, n = 20 vs 0.19 ± 0.8 ppm, n = 18, p < 0.001).

Anthropological Outcomes

Weight. As intended by the study design, both groups lost similar amounts of weight during the weight loss phase (−5.3 ± 0.1 %, n = 20 vs −4.3 ± 0.4 %, n = 19, p = 0.13). Measured as absolute weight loss: −4.6 kg ± 0.6 kg vs −3.61 ± 0.3 kg. However, during the weight maintenance phase (weeks 9–18), the inulin group lost significantly more weight compared to the control (−2.3 ± 0.5 %, n = 20 vs −0.6 ± 0.4 %, n = 18, p = 0.012). Measured as absolute weight loss: −1.8 ± 0.4 kg vs −0.5 ± 0.3 kg (Fig. 2).

Figure 2.

Percentage weight loss and body fat loss measured by BIA at week nine and week 18 in inulin and cellulose groups. Analysis was done by ANCOVA with baseline weight as a covariate. Weight loss at week nine was not significantly different between inulin and cellulose groups (−5.3 ± 0.1 %, n = 20 vs −4.3 ± 0.4 %, n = 19, p = 0.13). Between weeks 9–18 the inulin group lost significantly more than the cellulose group (−2.3 ± 0.5 %, n = 20 vs −0.6 ± 0.4 %, n = 18, p = 0.012). Analysis for body loss was done by ANCOVA with baseline weight as a covariate. The inulin group lost a greater percentage of body fat as measured by BIA at 9 (−2.8 ± 0.4 %, n = 20 vs −1.2 ± 0.4 %, n = 19, p < 0.01) and 18 weeks (−3.7 ± 0.6 %, n = 20 vs −1.1 ± 0.6 %, n = 18, p = 0.01). ANCOVA: analysis of covariance; BIA: bioelectrical impedance

Body Composition. Body fat percent as analysed by BIA at week 9 and 18 showed a greater reduction in the inulin group compared to the cellulose group (−2.8 ± 0.4 %, n = 20 vs −1.2 ± 0.4 %, n = 19, p < 0.01) and (−3.7 ± 0.6 %, n = 20 vs −1.1 ± 0.6 %, n = 18, p = 0.01) respectively (Fig. 2). In the sub-group of subjects who underwent MRI, the percentage body fat measurements at 9-weeks showed a similar trend towards a reduction in body fat (−1.7 ± 0.6 %, n = 10 vs −0.1 ± 0.6 %, n = 9, p = 0.08) although this did not reach statistical significance. The delta change was not different at 18 weeks (−2.4 ± 1.2 %, n = 9 vs −2.2 ± 3.1 %, n = 5, p = 0.93). The delta change in other fat depots was not different at 9 or 18 weeks (Additional file 1 http://static-content.springer.com/esm/art%3A10.1186%2Fs12986-015-0033-2/MediaObjects/12986_2015_33_MOESM1_ESM.docx).

Intrahepato- and Intramyocellular Lipid

Intrahepatocellular lipid was reduced in the inulin group, and the delta change was significant when compared to the cellulose group at 9 and 18 weeks even after controlling for weight loss (9 weeks: −9.6 ± 2.8 %, n = 10 vs −0.5 ± 2.7 %, n = 9, p < 0.04); (18 weeks: −10.0 ± 2.6 %, n = 9 vs −2.3 ± 2.5 %, n = 5, p = 0.02) (Fig. 3). The fat content of the soleus muscle was also significantly reduced at 9 and 18 weeks (9 weeks: −0.7 ± 0.3 %, n = 10 vs 0.8 ± 0.3 %, n = 9, p < 0.005); (18 weeks: −1.3 ± 1.4 %, n = 9 vs 4.8 ± 3.0 %, n = 5, p < 0.05) (Fig. 4) but not the tibialis muscle (9 weeks: −1.4 ± 1.0 % n = 10 vs −1.0 ± 1.4 %, n = 9, p = 0.82); (18 weeks: −2.2 ± 0.8 %, n = 9 vs −2.5 ± 2.7 %, n = 5, p = 0.93).

Figure 3.

Change in intrahepatocellular lipid (IHCL) at weeks 9 and 18 in inulin and cellulose groups. Analysis was done by ANCOVA with change in body weight as a covariate. IHCL was significantly reduced in subjects randomised to the inulin supplement compared to the cellulose at 9 (−9.6 ± 2.8 %, n = 10 vs −0.5 ± 2.7 %, n = 9, p < 0.04) and 18 weeks (−10.0 ± 2.6 %, n = 9 vs −2.3 ± 2.5 %, n = 5, p = 0.02). ANCOVA: analysis of covariance; IHCL: intrahepatocellular lipid

Figure 4.

Change in intramyocellular lipid in the soleus muscle (IMCL-S) at weeks 9 and 18 in inulin and cellulose groups. Analysis was done by ANCOVA with change in body weight as a covariate. IMCL-S was significantly reduced at 9 and 18 weeks in the inulin group compared to cellulose: (9 weeks: −0.7 ± 0.3 %, n = 10 vs 0.8 ± 0.3 %, n = 9, p < 0.005); (18 weeks: −1.3 ± 1.4 %, n = 9 vs 4.8 ± 3.0 %, n = 5, p < 0.05). ANCOVA: analysis of covariance; IHCL: intrahepatocellular lipid

Measures of Appetite

Visual Analogue Scales. Subjective appetite assessment showed no differences in tAUC hunger, desire to eat, or fullness at 9 and 18 weeks between the inulin and cellulose groups (Additional file 1 http://static-content.springer.com/esm/art%3A10.1186%2Fs12986-015-0033-2/MediaObjects/12986_2015_33_MOESM1_ESM.docx). There was no difference in tAUC for the question "How much do you think you could eat right now?" (prospective food consumption) at week nine (−62.9 ± 58.2, n = 20 vs −117.8 ± 44.2, n = 19, p = 0.46) but subjects in the cellulose reported significantly greater tAUC for the prospective food consumption question than the inulin group at week 18 (4.5 ± 37.9, n = 20 vs 774.5 ± 86.97, n = 18) p = <0.0001).

Food Intake From Ad Libitum Meal. Subjects in the inulin group ate significantly less than the cellulose group at week nine compared to the baseline visit (−127.0 ± 45.4 g, n = 20 vs −0.47 ± 22.5 g, n = 19, p = 0.027). There were no differences in food intake between baseline and week 18 between the inulin and cellulose groups (−87.3 ± 51.3 g, n = 20, vs −1.2 ± 23.7 g, n = 18, p = 0.18) (Additional file 1 http://static-content.springer.com/esm/art%3A10.1186%2Fs12986-015-0033-2/MediaObjects/12986_2015_33_MOESM1_ESM.docx).

Biochemical Outcomes

Glucose. There was a significant reduction in fasting plasma glucose (FPG) in the inulin group compared to control at week nine (−0.23 ± 0.17 mmol/L, n = 20 vs 0.44 ± 0.24 mmol/L, n = 19, p = 0.005) after controlling for weight loss but the change at week 18 was no longer significant (−0.40 ± 0.19 mmol/L, n = 20 vs 0.16 ± 0.23 mmol/L, n = 18, p = 0.08) (Fig. 5i and ii). Although glucose tAUC decreased in both groups, there was no between group difference at week nine (p = 0.37) or at week 18 (p = 0.37) once controlled for weight loss (Fig. 5iii).

Figure 5.

Time course data for plasma glucose at baseline, 9-weeks and 18 weeks for inulin (i) and cellulose supplementation (ii). Black line = baseline; dark grey line = 9-week visit; light grey line = 18-week visit. tAUC was calculated using the trapezoid method. ANCOVA using weight change as a covariate was used to analyse delta change between the inulin and cellulose groups. Glucose tAUC delta change at week nine(135 ± 134, n = 17 vs 87 ± 42, n = 17, p = 0.37) or at week 18 (−267 ± 104, n = 17 vs −38 ± 21, n = 17, p = 0.37) did not differ between groups once controlled for weight loss. There was a significant difference in the FPG delta change between groups at week nine once controlled for weight loss (−0.23 ± 0.17 mmol/L, n = 20 vs 0.44 ± 0.24 mmol/L, n = 19, p = 0.005) while the change at week 18 was no longer significant (−0.40 ± 0.19 mmol/L, n = 20 vs 0.16 ± 0.23 mmol/L, n = 18, p = 0.08) (iii). ANCOVA: analysis of covariance; FPG; fasting plasma glucose; tAUC: total area under the curve

Insulin. As expected following weight loss, the insulin tAUC decreased in both inulin and cellulose groups (Fig. 6i and ii), but there were no between-group differences at week nine (p = 0.66) or week 18 (p = 0.27). The delta change in fasting insulin was also similar between inulin and cellulose at week nine (−23.3 ± 15.4 pmol/L, n = 18 vs −30.5 ± 17.6 pmol/L, n = 17, p = 0.82) and week 18 (−35.5 ± 17.8 pmol/L, n = 18 vs −14.7 ± 18.7 pmol/L, n = 17, p = 0.53). Note, due to haemolysis it was not possible to analyse all samples.

Figure 6.

Time course data for plasma insulin at baseline, 9 weeks and 18 weeks for inulin (i) and cellulose supplementation (ii). Black line = baseline; dark grey line = 9-week visit; light grey line. tAUC was calculated using the trapezoid method. ANCOVA using weight change as a covariate was used to analyse delta change between the inulin and cellulose groups. After controlling for weight lost the delta change in insulin tAUC following inulin supplementation was similar to the cellulose group at week nine (−2366 ± 575, n = 17 vs −1566 ± 1724, n = 17, p = 0.66) and week 18 (−2643 ± 671, n = 17 vs −1264 ± 1045, n = 17, p = 0.27). The delta change in fasting insulin was also similar between inulin and cellulose at week nine (−23.3 ± 15.4 pmol/L, n = 18 vs −30.5 ± 17.6 pmol/L, n = 17, p = 0.82) and week 18 (−35.5 ± 17.8 pmol/L, n = 18 vs −14.7 ± 18.7 pmol/L, n = 17, p = 0.53). ANCOVA: analysis of covariance; tAUC: total area under the curve

Insulin Sensitivity. There were no differences in delta change of HOMA-IR at week nine (−0.6 ± 0.3, n = 18 vs −0.4 ± 0.3, n = 17, p = 0.65) and week 18 (−0.7 ± 0.3, n = 18 vs −0.2 ± 0.4, n = 17, p = 0.23) or Matsuda Index at week nine (0.5 ± 0.5, n = 17 vs 0.01 ± 0.2, n = 17, p = 0.56) or week 18 (0.4 ± 0.7 n = 17, vs 0.1 ± 0.3, n = 17, p = 0.75) between the inulin and cellulose groups after adjusting for weight lost.

GLP-1

At 9 and 18 weeks the GLP-1 tAUC decreased following inulin supplementation and increased in the cellulose group and the delta changes between the groups were significantly different (−1005 ± 457, n = 17 vs 614 ± 399, n = 16, p < 0.03) and 18 weeks (−525 ± 315, n = 17 vs 4500 ± 710.4 n = 16, p < 0.0001), respectively.

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