Glomerular hyperfiltration has been associated with obesity, insulin resistance, and systolic blood pressure (SBP), and has been shown to predict incidence of type 2 diabetes and faster progression to nephropathy. However, previous studies have been limited by confounders such as pre-existing diabetes or hypertension, or have used indirect measures of adiposity and insulin sensitivity (IS). Therefore, we examined the relationship between estimated glomerular filtration rate (eGFR) and IS using hyperinsulinaemic euglycaemic clamp, in a relatively young, healthy non-diabetic population. We performed 75g oral glucose tolerance test (OGTT) and measured % body fat (DEXA), body mass index (BMI), blood pressure (BP) and insulin sensitivity (M from hyperinsulinaemic euglycaemic clamp) in 104 individuals (44 females and 60 males, aged 18 to 57 years). The majority of the study population (n=89, 85.6%) was classified on their BMI as overweight or obese (38.5% overweight and 47.1% obese). eGFR was related to age, BMI, insulin sensitivity, 2 hour glucose level post OGTT and white blood cell count (all p<0.05) but not % body fat (p=0.3), systolic BP (p=0.1) or fasting glucose level (p=0.2). After adjustment for age, gender, SBP, BMI, and WBC, the inverse association between eGFR and 2 hour glucose post OGTT persisted (P<0.001).

In conclusion, markers of glucose metabolism (insulin sensitivity and 2 hour glucose post OGTT) are more closely related to eGFR in a healthy population compared to BMI and SBP which play important roles in the pathophysiology of hypertension and diabetes related nephropathy. Causal relationships and clinical implications of this finding need to be investigated by intervention studies.