Clinical correlates of insulin sensitivity and its association with mortality among men with CKD stages 3 and 4.
OBJECTIVE
Insulin resistance participates in the pathogenesis of multiple metabolic and cardiovascular diseases. CKD patients have impaired insulin sensitivity, but the clinical correlates and outcome associations of impaired insulin sensitivity in this vulnerable population are not well defined.


METHODS
The prospective cohort study was from the third examination cycle of the Uppsala Longitudinal Study of Adult Men, a population-based survey of elderly men ages 70-71 years; insulin sensitivity was assessed by glucose disposal rate as measured with euglycemic clamps. Inclusion criterion was eGFR<60 ml/min per 1.73 m(2) (n=543). Exclusion criteria were incomplete data on euglycemic clamp and diabetes (n=97), leaving 446 men with CKD stages 3 and 4 (eGFR median=51.9 ml/min per 1.73 m(2); range=20.2-59.5 ml/min per 1.73 m(2)).


RESULTS
The mean of glucose disposal rate was 5.4 ± 1.9 mg/kg per minute. In multivariable analysis, the independent clinical correlates of glucose disposal rate were eGFR (slope, 0.02; 95% confidence interval, 0.01 to 0.04), hypertension (-0.48; 95% confidence interval, -0.86 to -0.11), hyperlipidemia (-0.51; 95% confidence interval, -0.84 to -0.18), and body mass index (-0.32; 95% confidence interval, -0.37 to -0.27). During follow-up (median=10.0 years; interquartile range=8.7-11.0 years), 149 participants died. In Cox regression models, glucose disposal rate was not associated with all-cause or cardiovascular mortality. Multiplicative interactions (P<0.05) were observed between glucose disposal rate and physical activity or smoking in total mortality association. After subsequent stratification, glucose disposal rate was an independent correlate of all-cause mortality in smokers (adjusted hazard ratio, 0.72; 95% confidence interval, 0.54 to 0.96 per 1 mg/kg per minute glucose disposal rate increase) and physically inactive individuals (hazard ratio, 0.77; 95% confidence interval, 0.61 to 0.97) but not their counterparts.


CONCLUSIONS
eGFR, together with various components of the metabolic syndrome, contributed to explain the variance of insulin sensitivity in men with CKD stages 3 and 4. Insulin sensitivity was associated with a lower mortality risk in individuals who smoked and individuals who were physically inactive.
Divisions of Renal Medicine and Baxter Novum, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden;, †Department of Nephrology, Peking Union Medical College Hospital, Chinese Academy of Medical Science, Beijing, China;, ‡Division of Nephrology, Peking University Shenzhen Hospital, Peking University, Shenzhen, China;, §Department of Public Health and Caring Sciences, Section of Geriatrics, and, ¶Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism, Uppsala University, Uppsala, Sweden;, ‖School of Health and Social Studies, Dalarna University, Falun, Sweden, *Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden.
Hong
H
Xu
Xiaoyan
X
Huang
Johan
J
Arnlöv
Tommy
T
Cederholm
Peter
P
Stenvinkel
Bengt
B
Lindholm
Ulf
U
Risérus
Juan Jesús
JJ
Carrero
D000367:Age Factors; D000368:Aged; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism; D005919:Glomerular Filtration Rate; D006801:Humans; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D007668:Kidney / Q000503:physiopathology; D008297:Male; D024821:Metabolic Syndrome / Q000175:diagnosis / Q000401:mortality; D015999:Multivariate Analysis; D016017:Odds Ratio; D011379:Prognosis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D051436:Renal Insufficiency, Chronic / Q000097:blood / Q000175:diagnosis / Q000401:mortality* / Q000503:physiopathology; D018570:Risk Assessment; D012307:Risk Factors; D057185:Sedentary Behavior; D012737:Sex Factors; D012907:Smoking / Q000009:adverse effects / Q000401:mortality; D013548:Sweden / Q000453:epidemiology; D013997:Time Factors
D015415:Biomarkers; D001786:Blood Glucose; D007328:Insulin