Abstract
BackgroundRecently, an integrated network analysis has revealed dysregulation in the metabolism of mannose, a glucose epimer, in severely obese individuals without diabetes. In addition, fasting plasma mannose levels (M0) are associated with insulin resistance independent of BMI. Since the association between mannose and insulin sensitivity (IS) in those with impaired glucose tolerance remains unknown, we aimed to investigate this association in individuals without severe obesity but with varying degrees of glucose tolerance.MethodsBased on 75 g OGTT data in Japanese individuals without diabetic medication, individuals were classified as having normal glucose tolerance (NGT), impaired glucose metabolism (IGM), or diabetes (DM). In each group, 25 individuals were consecutively recruited [total 75 individuals, age: 65 ± 11 (mean ± SD); BMI: 24.9 ± 3.8 kg/m2]. QUICKI and Matsuda index (MI) were calculated as IS indices. M0 was assayed using HPLC. Normally-distributed loge-transformed (ln-) values were used for MI and leptin.ResultsIn the simple regression analysis, ln-MI was negatively correlated with BMI (NGT: r = − 0.639, IGM: r = − 0.466, DM: r = − 0.613) and ln-leptin (NGT: r = − 0.480, IGT: r = − 0.447, DM: r = − 0.593) in all 3 groups. Ln-MI was not significantly correlated with M0 in NGT (r = 0.241, P = 0.245) and IGT (r = − 0.296, P = 0.152) groups, it was moderately and negatively correlated in the DM group (r = − 0.626, P < 0.001). Similar results were obtained, when QUICKI was used instead of MI as an index of IS. In multiple regression analysis in the DM group, QUICKI (Q) and ln-MI (M) were independently predicted by BMI (Q: β = − 0.413; M: β = − 0.400) and M0 (Q: β = − 0.413, M: β = − 0.426), accounting for 51.2% (P = 0.0004) and 51.2% (P = 0.0004) of the variability, respectively, which was larger than the prediction for BMI alone (Q: 38.4%, M: 37.6%).ConclusionFasting plasma mannose was associated with IS independent of BMI in Japanese individuals with DM.
Highlights
An integrated network analysis has revealed dysregulation in the metabolism of mannose, a glucose epimer, in severely obese individuals without diabetes
Laboratory examinations and anthropometric data Based on 75 g oral glucose tolerance test (OGTT) data, individuals were either classified as normal glucose tolerance (NGT), impaired glucose metabolism (IGM), or diabetes (DM) according to 2006 World Health Organization (WHO) criteria [8] [negatively correlated with body mass index (BMI) (NGT), fasting plasma glucose (FPG) < 6.1 mmol/L and 2-h plasma glucose (2-h PG) < 7.8 mmol/L; IGM, either impaired fasting glucose (IFG, FPG ≥ 6.1 and < 7.0 mmol/L) and/or impaired glucose tolerance (IGT, 2-h PG ≥ 7.8 and < 11.1 mmol/L); DM, FPG ≥ 7.0 mmol/L and/or 2-h PG ≥ 11.1 mmol/L]
quantitative insulin sensitivity check index (QUICKI) was negatively correlated with BMI (NGT: r = − 0.654, IGM: r = − 0.538, DM: r = − 0.620) and ln-leptin (NGT: r = − 0.581, IGM: r = − 0.486, DM: r = − 0.606) in all 3 groups
Summary
An integrated network analysis has revealed dysregulation in the metabolism of mannose, a glucose epimer, in severely obese individuals without diabetes. Since the association between mannose and insulin sensitivity (IS) in those with impaired glucose tolerance remains unknown, we aimed to investigate this association in individuals without severe obesity but with varying degrees of glucose tolerance. The association between mannose and insulin sensitivity in those with diabetes remains unknown, insulin resistance plays an important role in the pathogenesis of type 2 diabetes [1] and dysregulation of plasma mannose levels has been reported in type 2 diabetes [6, 7]. This study aimed to investigate the association between mannose and insulin sensitivity in individuals with varying degrees of glucose tolerance
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