Indices from the modelling of the data from the IVGTT.

<p>All values are mean (SEM), N = 12. Comparisons made with paired t-tests.</p

Insulin concentrations from FSIVGTT after 4 weeks daily supplementation with 40 g HAM-RS2 or placebo.

<p>N = 12, mean ± SEM. Significantly higher concentrations following HAM-RS2 compared with placebo (<i>p</i> = 0.009). Comparisons made with repeated measures ANOVA. Black circles  =  HAM-RS2; white circles  =  placebo.</p

Glucose concentrations from FSIVGTT after 4 weeks daily supplementation with 40 g HAM-RS2 or placebo.

<p>N = 12, mean ± SEM. No significant difference between the HAM-RS2 and placebo. Comparisons made with repeated measures ANOVA. Black circles  =  HAM-RS2; white circles  =  placebo; dashed line  =  baseline glucose concentrations.</p

C-peptide concentrations from FSIVGTT after 4 weeks daily supplementation with 40 g HAM-RS2 or placebo.

<p>N = 12, mean ± SEM. Significantly higher concentrations following HAM-RS2 compared with placebo (<i>p</i> = 0.016). Comparisons made with repeated measures ANOVA. Black circles  =  HAM-RS2; white circles  =  placebo.</p

Anthropometric measurements and fasting plasma concentrations taken after 4 weeks daily supplementation with either 40 g/day of HAM-RS2 or placebo.

<p>All values are mean (SEM), N = 12. Comparisons made with paired t-tests.</p>1<p>Measured by bioimpedance (Tanita, Arlington Heights, IL, USA). N = 11.</p>2<p>Mean of 3 readings taken with the subject in a sitting position, measured by an automatic blood pressure cuff (Omron MX3 Plus, Omron Healthcare Europe, Milton Keynes, United Kingdom).</p

Diurnal rhythms of plasma leptin concentrations.

<p>(a) Analysis of absolute concentration revealed a significant effect of group (<i>p</i><0.001; 2-way repeated measures ANOVA) but not of time or time x group interaction. *<i>p</i><0.05 lean vs type 2 diabetic subjects. (b–c) Following normalisation of each individual’s raw data to their own mean concentration, the group values were calculated and fitted with a cosinor curve. Normalised data are expressed relative to (b) external time of day and (c) endogenous circadian time, estimated using DLMO where 360°  =  time of DLMO. The DLMO of two participants in the type 2 diabetic participant group could not be calculated due to the absence of a peak in the melatonin profile; their data were thus excluded. Statistical analysis showed a significant effect of time (<i>p</i><0.001; 2-way repeated measures ANOVA) but not for group or interaction in both (b) and (c). (a–b) The light-dark conditions are indicated by the bars below the x-axes. In all panels, diamonds, solid red line  =  lean subjects (n = 8); square, dashed blue line  =  obese non-diabetic subjects (n = 10); triangle, dotted black line  =  type 2 diabetic subjects (n = 7).</p

Pre-screen participant data.

*<p><i>P</i><0.05 compared to lean participants; ⁺<i>P</i><0.05 compared to obese non-diabetic participants (1-way ANOVA with Bonferroni post-hoc test).</p

Acrophase (peak time) and amplitude of the leptin rhythms determined by cosinor analysis.

<p>A cosine wave was fitted to each individual leptin profile. There was no significant (<i>p</i>>0.05; 1-way ANOVA) effect of group on either the acrophase (peak time) or amplitude of the rhythms. The acrophase of the leptin rhythm was also corrected to the dim light melatonin onset (DLMO).</p

Expression of leptin mRNA in white adipose biopsies.

<p>(a) Data represent mean ± SEM of leptin mRNA in 6-hourly serial biopsies. There was a significant effect of group (<i>p</i><0.05; 2-way repeated measures ANOVA), but not of time or time x group interaction. There were no significant (<i>p</i>>0.05; Bonferroni post-hoc test) pair wise differences in leptin mRNA expression between the subject groups. The light-dark conditions are indicated by the bars below the x-axis. Diamonds, solid red line  =  lean subjects (n = 8); squares, dashed blue line  =  obese non-diabetic subjects (n = 10); triangles, dotted black line  =  type 2 diabetic group (n = 7). The average leptin mRNA expression for each subject was significantly (<i>p</i><0.05) correlated with both (b) average plasma leptin concentrations and (c) subjects’ BMI. (d) The average plasma leptin concentration for each subject was significantly (<i>p</i><0.001) correlated with subjects’ BMI.</p

Differences in amplitude, but not onset time, of nocturnal plasma melatonin concentration.

<p>(a) Data in the top panel represent mean ± SEM of plasma melatonin concentrations over 25 hours. Diamonds, solid red line  =  lean subjects (n = 8); squares, dashed blue line  =  obese non-diabetic subjects (n = 10); triangles, dotted black lines  =  type 2 diabetic subjects (n = 7). The light-dark conditions are indicated by the bar below the x-axis. There was a significant (<i>p</i>0.001; 2-way repeated measures ANOVA) effect of time, group and time x group interaction. Nocturnal melatonin concentrations were significantly higher in the obese non-diabetic group (⁺<i>p</i><0.05, vs lean, **<i>p</i><0.01 vs type 2 diabetic subjects). (b) Data in the bottom panel represent mean ± SEM of the dim light melatonin onset (DLMO) in each group. There was no significant (<i>p</i>>0.05, 1-way ANOVA) difference between the group averages. Lean  =  lean healthy participant group; ow  =  obese non-diabetic group; T2DM  =  type 2 diabetic group.</p