Changes in triglycerides and high-density lipoprotein cholesterol may precede peripheral insulin resistance, with 2-h insulin partially mediating this unidirectional relationship: a prospective cohort study.
Results of longitudinal researches regarding the temporal relationship between dyslipidemia and insulin resistance (IR) are inconsistent. This study assessed temporal relationships of blood lipids with IR and determined whether there are any mediating effects existed in these temporal relationships.



This study examined a longitudinal cohort of 3325 subjects aged 20-74 years from China with an average of 4.2 years follow-up. Measurements of fasting blood lipids, as well as fasting and 2-h serum glucose and insulin, were obtained at two time points. The Gutt index and HOMA-IR were calculated as indicators of peripheral IR and hepatic IR. A cross-lagged path analysis was performed to examine the temporal relationships between blood lipids and IR. A mediation analysis was used to examine mediating effect.



After adjusting for covariates, the cross-lagged path coefficients from baseline TG and HDL-C to follow-up Gutt index were significantly greater than those from baseline Gutt index to follow-up TG and HDL-C (β1= -0.131 vs β2= -0.047, P < 0.001 for TG; β1= 0.134 vs β2= 0.023, P < 0.001 for HDL-C). The path coefficients from baseline TG and HDL-C to follow-up 2-h insulin were significantly greater than those from baseline 2-h insulin to follow-up TG and HDL-C (β1= 0.125 vs β2= 0.040, P < 0.001 for TG; β1= -0.112 vs β2= -0.026, P < 0.001 for HDL-C). 2-h insulin partially mediated the effect of TG/HDL-C on Gutt index with a 59.3% mediating effect for TG and 61.0% for HDL-C.



These findings provide strong evidence that dyslipidemia probably precede peripheral IR and that 2-h insulin partially mediates this unidirectional temporal relationship.
National Key Discipline, Department of Nutrition and Food Hygiene, School of Public Health, Harbin Medical University, 157 Baojian Road, Harbin, 150081, People's Republic of China.
Tianshu
T
Han
National Key Discipline, Department of Nutrition and Food Hygiene, School of Public Health, Harbin Medical University, 157 Baojian Road, Harbin, 150081, People's Republic of China.
Yu
Y
Cheng
National Key Discipline, Department of Nutrition and Food Hygiene, School of Public Health, Harbin Medical University, 157 Baojian Road, Harbin, 150081, People's Republic of China.
Shuang
S
Tian
National Key Discipline, Department of Nutrition and Food Hygiene, School of Public Health, Harbin Medical University, 157 Baojian Road, Harbin, 150081, People's Republic of China.
Li
L
Wang
National Key Discipline, Department of Nutrition and Food Hygiene, School of Public Health, Harbin Medical University, 157 Baojian Road, Harbin, 150081, People's Republic of China.
Xi
X
Liang
National Key Discipline, Department of Nutrition and Food Hygiene, School of Public Health, Harbin Medical University, 157 Baojian Road, Harbin, 150081, People's Republic of China.
Wei
W
Duan
National Key Discipline, Department of Nutrition and Food Hygiene, School of Public Health, Harbin Medical University, 157 Baojian Road, Harbin, 150081, People's Republic of China. nalixin2003@163.com.
Lixin
L
Na
National Key Discipline, Department of Nutrition and Food Hygiene, School of Public Health, Harbin Medical University, 157 Baojian Road, Harbin, 150081, People's Republic of China. changhaosun2002@163.com.
Changhao
C
Sun
D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism*; D002681:China; D008076:Cholesterol, HDL / Q000097:blood*; D018450:Disease Progression; D050171:Dyslipidemias / Q000097:blood* / Q000175:diagnosis; D005260:Female; D006801:Humans; D007328:Insulin / Q000097:blood*; D007333:Insulin Resistance; D016014:Linear Models; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011379:Prognosis; D011446:Prospective Studies; D013997:Time Factors; D014280:Triglycerides / Q000097:blood*; D055815:Young Adult
D015415:Biomarkers; D001786:Blood Glucose; D008076:Cholesterol, HDL; D007328:Insulin; D014280:Triglycerides
2-h insulin; Blood lipids; Insulin resistance; Mediating effect; Temporal relationship