Insulin sensitivity measured with euglycemic clamp is independently associated with glomerular filtration rate in a community-based cohort.
OBJECTIVE
To investigate the association between insulin sensitivity and glomerular filtration rate (GFR) in the community, with prespecified subgroup analyses in normoglycemic individuals with normal GFR.


METHODS
We investigated the cross-sectional association between insulin sensitivity (M/I, assessed using euglycemic clamp) and cystatin C-based GFR in a community-based cohort of elderly men (Uppsala Longitudinal Study of Adult Men [ULSAM], n = 1,070). We also investigated whether insulin sensitivity predicted the incidence of renal dysfunction at a follow-up examination after 7 years.


RESULTS
Insulin sensitivity was directly related to GFR (multivariable-adjusted regression coefficient for 1-unit higher M/I 1.19 [95% CI 0.69-1.68]; P < 0.001) after adjusting for age, glucometabolic variables (fasting plasma glucose, fasting plasma insulin, and 2-h glucose after an oral glucose tolerance test), cardiovascular risk factors (hypertension, dyslipidemia, and smoking), and lifestyle factors (BMI, physical activity, and consumption of tea, coffee, and alcohol). The positive multivariable-adjusted association between insulin sensitivity and GFR also remained statistically significant in participants with normal fasting plasma glucose, normal glucose tolerance, and normal GFR (n = 443; P < 0.02). In longitudinal analyses, higher insulin sensitivity at baseline was associated with lower risk of impaired renal function (GFR <50 ml/min per 1.73 m(2)) during follow-up independently of glucometabolic variables (multivariable-adjusted odds ratio for 1-unit higher of M/I 0.58 [95% CI 0.40-0.84]; P < 0.004).


CONCLUSIONS
Our data suggest that impaired insulin sensitivity may be involved in the development of renal dysfunction at an early stage, before the onset of diabetes or prediabetic glucose elevations. Further studies are needed in order to establish causality.
Department of Health and Social Sciences, Högskolan Dalarna, Falun, Sweden.
Elisabet
E
Nerpin
Ulf
U
Risérus
Erik
E
Ingelsson
Johan
J
Sundström
Magnus
M
Jobs
Anders
A
Larsson
Samar
S
Basu
Johan
J
Arnlöv
D000328:Adult; D000368:Aged; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D055316:Cystatin C; D015891:Cystatins / Q000097:blood; D003928:Diabetic Nephropathies / Q000453:epidemiology; D005500:Follow-Up Studies; D005919:Glomerular Filtration Rate; D015309:Glucose Clamp Technique; D005951:Glucose Tolerance Test; D006801:Humans; D007328:Insulin / Q000627:therapeutic use*; D007333:Insulin Resistance / Q000502:physiology*; D008297:Male; D051437:Renal Insufficiency / Q000453:epidemiology / Q000503:physiopathology
C525030:CST3 protein, human; D055316:Cystatin C; D015891:Cystatins; D007328:Insulin