1-2-linoleoylphosphatidylcholine and Insulin-Resistance

Dysglycemia and adiposity have been related to disability in patients with multiple sclerosis. The objective of this work was to determine the prevalence and characteristics of insulin resistance in patients with multiple sclerosis using the metabolomics Quantose score.. A total of 64 patients were accrued in the study. A blood sample was drawn to estimate the Quantose score, which is derived from fasting measurements of insulin, α-hydroxybutyrate, linoleoyl-glycerophosphocholine, and oleate, three nonglucose metabolites shown to correlate with insulin-stimulated glucose disposal.. Insulin resistance was documented in 33 out of 64 patients and it was found in association with the degree of disability and the time from diagnosis. Patients with the secondary progressive form of the disease showed the highest prevalence.. Insulin resistance is frequent in patients with multiple sclerosis and might contribute to metabolic complications and general disability. Early markers of dysglycemia should be sought for in these patients to avoid additional deterioration of their quality of life.

Topics: Adult; Aged; Blood Glucose; Body Mass Index; Butyrates; Disability Evaluation; Fasting; Female; Humans; Hydroxybutyrates; Insulin; Insulin Resistance; Male; Metabolomics; Middle Aged; Multiple Sclerosis; Phosphatidylcholines; Regression Analysis; Young Adult

Topics: Animals; Diabetes Mellitus, Type 2; Female; Glucose Metabolism Disorders; Humans; Hydroxybutyrates; Insulin Resistance; Male; Phosphatidylcholines

Metabolomic screening of fasting plasma from nondiabetic subjects identified α-hydroxybutyrate (α-HB) and linoleoyl-glycerophosphocholine (L-GPC) as joint markers of insulin resistance (IR) and glucose intolerance. To test the predictivity of α-HB and L-GPC for incident dysglycemia, α-HB and L-GPC measurements were obtained in two observational cohorts, comprising 1,261 nondiabetic participants from the Relationship between Insulin Sensitivity and Cardiovascular Disease (RISC) study and 2,580 from the Botnia Prospective Study, with 3-year and 9.5-year follow-up data, respectively. In both cohorts, α-HB was a positive correlate and L-GPC a negative correlate of insulin sensitivity, with α-HB reciprocally related to indices of β-cell function derived from the oral glucose tolerance test (OGTT). In follow-up, α-HB was a positive predictor (adjusted odds ratios 1.25 [95% CI 1.00-1.60] and 1.26 [1.07-1.48], respectively, for each standard deviation of predictor), and L-GPC was a negative predictor (0.64 [0.48-0.85] and 0.67 [0.54-0.84]) of dysglycemia (RISC) or type 2 diabetes (Botnia), independent of familial diabetes, sex, age, BMI, and fasting glucose. Corresponding areas under the receiver operating characteristic curve were 0.791 (RISC) and 0.783 (Botnia), similar in accuracy when substituting α-HB and L-GPC with 2-h OGTT glucose concentrations. When their activity was examined, α-HB inhibited and L-GPC stimulated glucose-induced insulin release in INS-1e cells. α-HB and L-GPC are independent predictors of worsening glucose tolerance, physiologically consistent with a joint signature of IR and β-cell dysfunction.

Topics: Adult; Animals; Biomarkers; Cell Line; Cohort Studies; Diabetes Mellitus, Type 2; Early Diagnosis; Female; Follow-Up Studies; Glucose Metabolism Disorders; Humans; Hydroxybutyrates; Insulin; Insulin Resistance; Insulin Secretion; Insulin-Secreting Cells; Male; Middle Aged; Phosphatidylcholines; Prospective Studies; Rats; ROC Curve