The world-wide diabetes pandemic has heightened the need for early screening and prevention. Type 2 diabetes develops slowly and insidiously, and the early stages are often undetected. Here we describe how NMR relaxometry using small table-top devices can be used for the early detection of insulin resistance and metabolic syndrome. These conditions affect nearly one half of US adults and confer a two-to-five-fold increased risk for developing type 2 diabetes.
Water T2, measured using a small volume of unmodified human plasma, serum or whole blood, is exquisitely sensitive to early metabolic dysregulation. In a discovery cohort of asymptomatic non-diabetic human subjects, plasma and serum water T2 showed strong bivariate correlations with markers of insulin, glucose and lipid metabolism, as well as markers of the pro-inflammatory, pro-coagulation state. After correcting for confounding variables using multiple regression, low water T2 values were independently and additively associated with hyperinsulinemia, subclinical inflammation and dyslipidemia, even in subjects with normal glucose levels.
A fingerstick drop of settled whole blood yields two T2 values: one for the plasma supernatant (T2S) and another for the cell pellet (T2P). The T2S value revealed a sixth-power dependence on hematocrit. This sixth-power relaxation enhancement results from a susceptibility gradient from the paramagnetic pellet into the diamagnetic supernatant. Paradoxically, the cell pellet T2P correlated with metabolic markers like those observed with isolated plasma. Here, T2P is sensing modifications in red blood cells resulting from changes in whole body metabolism.
In addition to isolated blood samples, NMR relaxometry measurements can be made non-invasively in living tissues. We will discuss early results obtained using a prototype compact NMR device designed for measuring T2 in the distal segment of the human finger. Compact NMR strategies for monitoring metabolic health are sufficiently practical for translation into point-of-care clinics and community settings.