Postmortem 1H-MRS—Detection of Ketone Bodies and Glucose in Diabetic Ketoacidosis

Abstract

Diabetic ketoacidosis (DKA) is a metabolic complication of diabetes mellitus that takes a lethal course if untreated. In this way relevant to forensic medicine, secure diagnosis of DKA usually involves the evidence of elevated levels of glucose and the ketone bodies acetone, acetoacetate, and β-hydroxybutyrate in corpse fluids. We conducted a postmortem hydrogen proton magnetic resonance spectroscopy (H-MRS) in a case of lethal DKA. Distinctive resonances of all three ketone bodies as well as glucose were visible in spectra of cerebrospinal fluid, vitreous humor, and white matter. Estimated concentrations of ketone bodies and glucose supported the findings both of autopsy and biochemical analysis. Advantages of human postmortem H-MRS are the lack of movement and flow artifacts as well as lesser limitations of scan duration. PostmortemH-MRS is able to non-invasively measure concentrations of glucose and ketone bodies in small volumes of various regions of the brain. It may thus become a diagnostic tool for forensic investigations by quick determination of pathological metabolite concentrations in addition to conventional autopsy.

Postmortem Determination of Short-Term Markers of Hyperglycemia for the Purposes of Medicolegal Opinions

“…Serum collected postmortem is in most cases hemolyzed; consequently, the suggested value of total hemoglobin is exceeded, causing determination errors. Perhaps a more suitable and alternative method for determining these parameters in postmortem material is hydrogen proton magnetic resonance spectroscopy ( 1 H-MRS) [19]. Another difficulty is the lack of control materials dedicated to determining both markers in VH, although according to some researchers, it is the matrix of choice to avoid postmortem blood glycolysis [20].…”

Empagliflozin Induced Ketosis, Upregulated IGF-1/Insulin Receptors and the Canonical Insulin Signaling Pathway in Neurons, and Decreased the Excitatory Neurotransmitter Glutamate in the Brain of Non-Diabetics

“…A 25 × 18 × 20 mm 3 MRS voxel was placed within the posteromedial cortex, centered to ensure maximal coverage of bilateral precuneus, as previously undertaken [ 22 ]. Point-Resolved Spectroscopy (PRESS) with non-suppressed water reference was used to acquire metabolite concentrations, including standard water-scaled metabolites Ala, Asp, Cr, PCr, GABA, Glc, Gln, Glu, GPC, GSH, Ins, Lac, NAA, NAAG Scy, Tau, Pch, as well as the combined signals for Glu & Gln (Glx), GPC & PCh, and NAA & NAAG [ 23 , 24 ]. The ketone-related metabolites BHB, AcAc, and Acetone (Ace) were detected via a modified basis set provided in July of 2019 by LCModel’s developer, Dr. Stephen Provencher.…”

The ketogenic diet in disease and development

“…Post‐exercise and fasting levels of ketone bodies vary considerably between individuals depending on fitness level and diet, ranging from baseline levels to 1.75 mM in the hours after exercise and fasting (Koeslag et al, 1980). Levels may elevate significantly and rapidly in diabetic ketoacidosis, an often fatal hyperglycemic emergency in diabetic patients (Heimer et al, 2018). At the blood brain barrier, ketone body uptake occurs through MCT proteins, principally MCT1 and MCT2, which are distinct from the glucose transporters (GLUTs) (Dwyer et al, 2002; Morris, 2005; Pierre and Pellerin, 2005).…”