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Conceptualization, M.W., E.A.R., M.T.C. and V.C.M.; methodology, M.W. and M.T.C.; software, I.M.R.S.; validation, M.W., E.A.R., M.T.C. and V.C.M.; formal analysis, I.M.R.S., M.B. and M.T.C.; investigation, M.T.C., M.B., M.W. and I.M.R.S.; resources, M.T.C.; data curation, M.B. and I.M.R.S.; writing—original draft preparation, I.M.R.S.; writing—review and editing, I.M.R.S., M.T.C. and V.C.M.; visualization, I.M.R.S.; supervision, M.T.C.; project administration, M.T.C. and M.W.; funding acquisition, M.T.C. and V.C.M. All authors have read and agreed to the published version of the manuscript.
Figure 1. General Scheme for ganglioside biosynthesis. G indicates ganglioside; M indicates monosialo; D indicates disialo; T indicates trisialo; numbers indicate carbohydrate synthesis. The reactions of sialyl-transferases transfer sialic acid units. The reactions of neuramidases remove sialic acid units.
Figure 1. General Scheme for ganglioside biosynthesis. G indicates ganglioside; M indicates monosialo; D indicates disialo; T indicates trisialo; numbers indicate carbohydrate synthesis. The reactions of sialyl-transferases transfer sialic acid units. The reactions of neuramidases remove sialic acid units.
Figure 2. Gangliosides present in plasma at fasted and 4 h postprandial. (A) Percentage of mono-, poly-unsaturated GD1 ganglioside species in plasma found at fasting (baseline) and 4 h postprandial in control and diabetic subjects. (B) Percentage of mono-, poly-unsaturated and saturated GD3 species in plasma found at fasting baseline and 4 h postprandial timepoint in control and diabetic subjects. (C) Percentage of mono-, poly-unsaturated and saturated GM3 ganglioside species in plasma observed at fasting baseline and the postprandial in control and diabetic subjects. Low and high fat diet treatments were combined in subsequent analysis since no significant difference was detected in these groups. Data represent mean ± SD. Letters (a,b) indicate significant difference at p < 0.05 when individual ganglioside species are compared between control and T2DM subjects and symbol (*) indicate significant difference at p < 0.05 when individual ganglioside species are compared at 0 and 4 h time periods in the same group. Monounsaturated GD3 species (p < 0.01) and polyunsaturated GM3 (p = 0.01).
Figure 2. Gangliosides present in plasma at fasted and 4 h postprandial. (A) Percentage of mono-, poly-unsaturated GD1 ganglioside species in plasma found at fasting (baseline) and 4 h postprandial in control and diabetic subjects. (B) Percentage of mono-, poly-unsaturated and saturated GD3 species in plasma found at fasting baseline and 4 h postprandial timepoint in control and diabetic subjects. (C) Percentage of mono-, poly-unsaturated and saturated GM3 ganglioside species in plasma observed at fasting baseline and the postprandial in control and diabetic subjects. Low and high fat diet treatments were combined in subsequent analysis since no significant difference was detected in these groups. Data represent mean ± SD. Letters (a,b) indicate significant difference at p < 0.05 when individual ganglioside species are compared between control and T2DM subjects and symbol (*) indicate significant difference at p < 0.05 when individual ganglioside species are compared at 0 and 4 h time periods in the same group. Monounsaturated GD3 species (p < 0.01) and polyunsaturated GM3 (p = 0.01).
Figure 3. Gangliosides present in chylomicrons at fasted and 4 h postprandial. (A) Relative percent of total GD1 in chylomicron fraction at fasting and 4 h postprandial in control and T2DM groups (p = 0.01). (B) Relative percent of total GD3 in chylomicrons at fasting and 4 h postprandial in control and T2DM groups. (C) Relative percent of total GM3 in chylomicrons at fasting and 4 h postprandial in control and T2DM groups. Low and high fat diet treatments were combined in subsequent analysis since no significant difference was detected in these groups. Total GD1 = monounsaturated GD1 species. Total GD3 = saturated and monounsaturated GD3 species. Total GM3 = saturated, monounsaturated and polyunsaturated GM3 species. Data represent mean ± SD. Letters (a,b) indicate significant difference at p < 0.05 when individual ganglioside species are compared between control and T2DM subjects and symbol (*) indicate significant difference at p < 0.05 when individual ganglioside species are compared at 0 and 4 h time periods in the same group.
Figure 3. Gangliosides present in chylomicrons at fasted and 4 h postprandial. (A) Relative percent of total GD1 in chylomicron fraction at fasting and 4 h postprandial in control and T2DM groups (p = 0.01). (B) Relative percent of total GD3 in chylomicrons at fasting and 4 h postprandial in control and T2DM groups. (C) Relative percent of total GM3 in chylomicrons at fasting and 4 h postprandial in control and T2DM groups. Low and high fat diet treatments were combined in subsequent analysis since no significant difference was detected in these groups. Total GD1 = monounsaturated GD1 species. Total GD3 = saturated and monounsaturated GD3 species. Total GM3 = saturated, monounsaturated and polyunsaturated GM3 species. Data represent mean ± SD. Letters (a,b) indicate significant difference at p < 0.05 when individual ganglioside species are compared between control and T2DM subjects and symbol (*) indicate significant difference at p < 0.05 when individual ganglioside species are compared at 0 and 4 h time periods in the same group.
Table 1. Baseline characteristics of participants.
Table 1. Baseline characteristics of participants.
GroupControlT2DMGender (M/F)3M/4F3M/4FAge (year)51.4 ± 9.250.0 ± 8.8BMI (kg/m2)33.5 ± 8.333.2 ± 7.5Weight (kg)93.4 ± 24.191.9 ± 15.4Waist (cm)105.6 ± 15.8105.6 ± 13.5Glucose (mmol/L)5.0 ± 0.46.2 ± 1.1 *HBAlc (%)5.3 ± 0.45.9 ± 0.5 *Insulin (pmol/L)69.0 ± 53.095.0 ± 55.0HOMA-IR2.2 ± 1.73.9 ± 2.4FFAs (mmol/L)0.9 ± 0.40.7 ± 0.3Triglycerides (mmol/L)1.3 ± 0.42.0 ± 0.8TC (mmol/L)5.4 ± 0.84.8 ± 0.6HDL-C (mmol/L)1.3 ± 0.21.2 ± 0.2LDL-C (mmol/L)3.5 ± 0.72.7 ± 0.6 *C-reactive protein (mg/L)0.6 ± 0.31.6 ± 1.2Table 2. Total GM3, GD3, GD1 content in plasma and chylomicrons after consuming a low and high fat diet.
Table 2. Total GM3, GD3, GD1 content in plasma and chylomicrons after consuming a low and high fat diet.
GangliosideTable 3. Concentration (ng/mL) of GM3, GD3, GD1 and total ganglioside at fasting and in postprandial plasma samples.
Table 3. Concentration (ng/mL) of GM3, GD3, GD1 and total ganglioside at fasting and in postprandial plasma samples.
Ganglioside SpeciesTime (h)Control (ng/mL)T2DM (ng/mL)GM30681.7 ± 89.0641.7 ± 67.0 4648.9 ± 59.0667.5 ± 76.5GD3026.8 ± 7.920.9 ± 3.1 423.7 ± 3.127.6 ± 5.5GD1011.2 ± 2.89.7 ± 3.2 414.8 ± 2.612.8 ± 4.3Total0719.7 ± 97.6672.3 ± 72.1 4679.4 ± 63.2707.9 ± 58.0Table 4. Relative percent of individual ganglioside species in chylomicrons at 0 and 4 h postprandial in control and T2DM patients.
Table 4. Relative percent of individual ganglioside species in chylomicrons at 0 and 4 h postprandial in control and T2DM patients.
Individual
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