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ORIGINAL ARTICLE

Utility of a Handheld Blood Ketone Meter as a Postmortem


Indicator of Diabetic Ketoacidosis
Caris Mitchell, MD* and Brandi McCleskey, MD*†

presentation includes polyuria, polydipsia, weight loss, abdominal


Abstract: When investigating a death potentially due to diabetic ketoac- pain, vomiting, increased respiration, and symptoms of dehydra-
idosis (DKA), it is challenging to assess the glucose level in the blood, but tion.4 More severely, DKA can lead to seizures, coma, and, ulti-
β-hydroxybutyrate, the most prevalent ketone body in the blood, is rela- mately, death, occurring within hours to days.5
tively stable after death. The aim of this project is to prove that a commer- According to the American Diabetes Association, in 2019,
cially available ketone meter can be used on postmortem blood samples to DM was listed as the underlying cause of death on 87,647 death
aid the diagnosis of DKA in a novel setting (during coroner/medical exam- certificates and mentioned on 282,801 death certificates as either
iner examination). Samples with acetone detected via gas chromatography the cause or contributing cause of death, but data suggest that DM
were chosen retrospectively to determine whether the meter could detect could be underreported as a cause of death, likely due to the unre-
ketones in postmortem blood (proof-of-concept). In all of the thawed sam- liability of postmortem blood glucose concentration.2,6 Most of-
ples, the meter detected an elevated ketone level. Samples were then obtained ten, in clinical practice, hyperglycemia is diagnosed via HbA1c
in a prospective manner to include those with a possible cause of death from (glycosylated hemoglobin) or blood glucose concentration. How-
DKA along with controls. We correctly identified 16 cases in which death ever, the task presents much differently and with great difficulty in
was due to DKA with use of the ketone manner. The ketone levels ranged the postmortem setting because of the fluctuations in blood glu-
from 2.6 to 5.4 mmol/L in those cases. The diagnosis was confirmed with cose concentrations. While normal physiological functions such
a greatly elevated vitreous glucose concentration or glycated hemoglobin as cardiac and respiratory functions cease postmortem, there exists
concentration. Detecting the presence of ketones while in the autopsy suite surviving cells that thrive for a period of time and continue to me-
allowed for more accurate preliminary diagnoses and utilization of resources. tabolize glucose. Glycolysis is instinctively maintained, which fur-
Key Words: ketone meter, forensic pathology, β-hydroxybutyrate thers blood glucose decline. Nonetheless, a solution to the hurdle
of postmortem blood glucose reliability presents with the use of vit-
(Am J Forensic Med Pathol 2023;44: 17–20)
reous humor, a transparent gelatinous substance located within the
globe of the eyeball in the posterior chamber. It is described as an
D iabetes mellitus (DM) is complicated yet prevalent chronic
disease that affects millions of individuals across the country.
The Centers for Disease Control and Prevention reports an esti-
acellular, colorless, viscous substance, composed primarily of water
with glucose, ascorbic acid, collagen, and hyaluronic acid. Because
of its relative isolation in space and lack of widespread exposure to
mate of 37.3 million people, or 11.3% of the US population, living
the blood stream, both situations which are prone to postmortem
with diabetes, which included 28.7 million officially diagnosed
changes related to redistribution and hemoconcentration, vitreous
and 8.5 million, or 23%, undiagnosed.1 The pathogenesis of this
humor is considered to be an ideal substrate to analyze for postmor-
disease correlates with a lack of insulin production by the pan-
tem diagnoses.7 Although glucose in vitreous humor also declines
creas due to autoimmune β-cell destruction (type I DM) or the
postmortem, it stabilizes after 24 hours, allowing levels to be accu-
body's ineffective response to insulin (type 2 DM).2 Insulin is a
rately measured to make the proper diagnosis of DKA.8–10 This
hormone produced by the pancreas that is used to adequately bal-
process is tedious and expensive, thus leading to investigation of
ance glucose. Although a variety of complications can arise from
an alternative and novel solution using handheld ketone meters
DM, such as kidney failure, blindness, and vascular disease, one
(can also be considered point-of-care testing). These meters are fi-
of the most severe and potentially fatal complications is diabetic
nancially more accessible, detect the main ketone body, BHB, and
ketoacidosis (DKA). Historically, DKA arose as a complication
can be potentially used to determine whether one's cause of death
of type I DM; however, there are occasions in which it arises from
is due to DKA. Therefore, the aims of this project are to prove that
poorly controlled type 2 DM. Hyperglycemia in DKA is caused
commercially available handheld ketone meters can be used on
by depleted insulin, in which the body responds by increasing
postmortem blood samples and to demonstrate the ease of use
counterregulatory hormones that accelerate gluconeogenesis, gly-
for the general medicolegal death investigation community to im-
cogenolysis, and lipolysis. Accelerated lipolysis creates free fatty
prove vital statistics on deaths related to diabetes.
acids that are ultimately transformed through ketogenesis in the
liver, into ketone bodies, such as acetone, acetoacetate, and β-
hydroxybutyrate (BHB).3 β-Hydroxybutyrate is the most preva- MATERIALS AND METHODS
lent ketone body in DKA.2 With this increase in ketones, which
To determine the ability of a commercially available ketone
are considered strong acids, the body undergoes bicarbonate re-
meter to detect a ketone level in postmortem samples, the case
duction and ultimately metabolic acidosis. The classic clinical
management database of the Jefferson County Coroner/Medical
Examiner's Office was searched for decedents with acetone detected
Manuscript received May 10, 2022; accepted August 10, 2022.
From the *University of Alabama at Birmingham; and †Jefferson County
in their blood using gas chromatography/mass spectrometry (GC/
Coroner/Medical Examiner's Office, Birmingham, AL. MS) (head-space analysis). Given the retrospective nature of the
The authors report no conflict of interest. ketone meter testing, cases were limited based on blood sample
Reprints: Brandi McCleskey, MD. 1515 6th Ave S, Room 220, Birmingham, availability because of retention of original samples. The available
AL 35233. E-mail: bmccleskey@uabmc.edu.
Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.
samples spanned a 6-month period. Exclusion criteria included
ISSN: 0195-7910/23/4401–0017 decedents described as decomposed, given the potential for im-
DOI: 10.1097/PAF.0000000000000794 pact on specimen integrity. In addition, decedents younger than

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Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.


Mitchell and McCleskey Am J Forensic Med Pathol • Volume 44, Number 1, March 2023

18 years were also excluded primarily because of the paucity of It should be noted though that half of the decedents (n = 7)
cases with available specimen and/or acetone detected. A total were originally diagnosed with DKA as a cause of death by the at-
of 14 postmortem blood samples were thawed and agitated for tending forensic pathologist. Data available to the certifying foren-
use on the ketone meter. sic pathologist included medical history, circumstances surround-
The gas chromatography results and causes of death for each ing the death, gas chromatography results, and vitreous glucose
of the cases (n = 15) included in the retrospective analysis were concentrations (Table 1). Of those diagnosed with DKA, the ke-
collected. In addition, those with glucose concentrations, detected tone meter results were higher, although not significantly (mean
in vitreous humor, were also recorded. This testing was done dur- of 5.8 vs 4.9 mmol/L), and the specific concentrations should be
ing the initial case workup, and some results were not available for interpreted with caution.
all cases used during the retrospective arm.
The prospective arm of this study included 77 decedents that Prospective Cases
were examined over a nearly 4-year period. Cases were selected Over the course of nearly 4 years, 77 blood samples were
based on preference of the attending forensic pathologist. In gen- tested with the ketone meter during the examination. The ketone
eral, if diabetes was considered in the differential diagnosis, a pe- meter indicated a significantly greater level of ketones present in
ripherally obtained blood sample was used for testing via the ketone the 16 cases who were ultimately diagnosed as having a cause of
meter. Individuals younger than 18 years were also excluded from death related to DKA (P < 0.00001E-10). Vitreous humor was col-
the prospective arm to align with the retrospective arm. In cases in- lected from each of the decedents and used for glucose testing. The
volving the sudden unexpected deaths in young people, the ketone results, circumstances surrounding the death, gas chromatography re-
meter was used during the examination and a glucose level was re- sults (if available), and vitreous glucose concentrations (if available)
quested to be performed on the vitreous humor. However, in many were recorded (Table 2). Half of the individuals who were reported
of these cases, toxicological analysis detected drugs in the blood, to have a history of alcoholism and a cause of death related to chronic
and ultimately, these decedents became part of the control group. alcohol use also had a ketone concentration outside of that typically
Data were analyzed using the Student t test. stated as normal (Table 3).
RESULTS
DISCUSSION
Retrospective Cases Identifying tools to assist coroners and/or medical examiners
Fourteen samples were retrieved, thawed, and agitated before in determining the cause of death accurately, with ease, and while
being placed on the testing strip. All of the available samples had in the setting of limited resources is often challenging. This study
acetone detected in the blood sample at the time of the initial case demonstrated that a relatively inexpensive handheld ketone meter
workup, but not all cases certified were DKA. The ketone meter could be used to detect ketones in postmortem blood samples and
was able to detect ketones in all of the samples indicating that presents novel data to support the use of the meter to assist with
the meter could be used on postmortem samples and generate data triage of cases during day-to-day operations either in the field or
that correlated with the acetone originally detected by GC/MS. Ac- in the morgue during the examination. It could assist coroners with
cording to the package insert, a ketone level of greater than utilization of limited resources for cases involving natural diseases
1.5 mmol/L is highly indicative of associated increased glucose (DM) where more accurate death certification may be supported
concentration in the blood and DKA. However, each of the thawed with a point-of-care device when additional autopsy workup and
samples generated ketone levels far in excess of that typically stated ancillary testing, such as vitreous humor analysis, are cost prohibitive.
as normal (less than 1.4 mmol/L); therefore, interpretation of the Although this represents the unique use of ketone meter, a study
concentrations in thawed postmortem samples is limited and calls by Walta et al11 in 2016 also highlighted the use of point-of-care
into question the stability of BHB in postmortem samples. testing for glucose and BHB in vitreous humor.

TABLE 1. Retrospective Cases

Acetone Vitreous Glucose Ketone Level


Case Number Cause of Death Concentration, g/dL Concentration, mg/dL Detected, mmol/L
1 DKA 0.01 364 5.2
2 DKA 0.04 561 4.2
3 Hypertension 0.02 <20 5.6
4 Cardiovascular disease <0.01 N/A 4.4
5 Hypertension 0.01 N/A 6.2
6 DKA 0.06 781 8
7 DKA 0.02 622 7.2
8 DKA 0.03 N/A 5.5
9 DKA 0.01 340 5.6
10 Cardiovascular disease Trace N/A 3
11 Blunt force trauma Trace N/A 3.3
12 DKA 0.04 494 4.8
13 Chronic alcoholism 0.02 N/A 5.6
14 Hypertension 0.02 <20 6
N/A, not available/not obtained.

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Am J Forensic Med Pathol • Volume 44, Number 1, March 2023 Utility of a Handheld Blood Ketone Meter

Using the meter was particularly useful in a few of the pro-


spective cases of young persons who died suddenly and unexpect- TABLE 3. Deaths Related to Chronic Alcohol Use
edly. In the midst of the current opioid epidemic, a number of
Ethanol Acetone Vitreous Glucose Ketones
these cases were presumed overdoses; however, with the use of
Detected, Detected, Concentration, Detected,
the ketone meter, they were accurately worked up as undiagnosed
Case Number g/dL mmol/L mg/dL mmol/L
diabetes and their death was documented as complications sec-
ondary to DKA. Specifically, 24 cases were presumed as possible 5 N/A N/A N/A 0.4
drug overdoses (secondary to opioids) after a full autopsy exami- 9 0.09 N/A <20 1
nation. Of the 24 potential overdoses, 16 were confirmed with tox- 26 0.05 N/A N/A 0.6
icological testing and 6 deaths were ultimately due to DKA. This 33 N/A 0.04 8 4.9
diagnosis was accomplished using ketone meter data, vitreous
35 N/A N/A <20 2.4
glucose concentration, and histologic examination.
The diagnosis of DKA was supported by elevated glucose 37 0.05 N/A N/A 0.7
concentrations within the vitreous humor, although this matrix is 48 0.1 N/A 10 4.7
not easy to work with given its viscosity. Furthermore, the sophis- 53 0.02 N/A N/A 0.6
ticated testing platforms needed to test vitreous humor are often 65 0.09 0.01 42 2.7
not available to the general coroner or medical examiner office. 79 0.07 0.01 <20 2.3
The ketone meter will allow said coroner or medical examiner of-
fices to release accurate death certificates without significant fi-
nancial burden. determination. Because of the difficulty associated with postmor-
Death certification data are generally used for many public tem diagnosis of a diabetes related death, DM is often not accu-
health policies, public health initiatives, and research support rately listed on the death certificate as either a cause or contribut-
ing factor in death. Assisting the coroner and/or medical examiner
with gathering relevant data can support their addition of diabetes
TABLE 2. Prospective Cases on the death certificate effectively improving vital statistics data
and the accuracy of mortality data associated with diabetes.
Ketone Level The use of the handheld ketone meter not only assists corners
Detected, Average or medical examiners with limited resources but also assists those
n (Range), mmol/L needing alternatives to improve management of overwhelming
case burden despite resource availability. Using the meter will al-
Causes of death low death investigators, coroners, and medical examiners to be
Heart disease 23 0.8 (0.1–2.9) more time efficient with determining causes of death in a subset
(cardiomegaly, MI) of cases. In addition, individuals can better triage and organize
Substance (drug and 28 1.4 (0.3–4.9) based on ancillary tests that need to be ordered. For instance, at a
alcohol) related death investigation scene, the ketone meter can be used to quickly
DKA 16 3.6 (2.6–5.4) test a blood sample. If the meter reads at a certain level, the next step
Other natural causes PTE, T2DM, obesity, 0.53 (0.2–1.7) could be to collect a sample for a basic metabolic panel on vitreous
of death natural causes, humor as a supportive test or a HbA1c if resources allow.
probable natural
cause (10)
Limitations
Sex
Although there is an abundance of benefits of handheld ke-
Male 55 1.5 (0.5–5.4)
tone meters, there also exist limitations. The meter not only iden-
Female 22 1.7 (0.4–4.9) tifies BHB associated with DKA but also identifies acetoacetate,
Age ranges which can be present in many ketoacidotic states including that as-
19–30 9 1.5 (0.3–3.8) sociated with alcohol consumption. Therefore, potential cases list-
30–39 13 2 (0.3–4.3) ing DKA as the cause of death could be misidentified in patients
40–50 21 1.6 (0.2–4.6) who might have died because of alcohol use and/or abuse due to
50–60 14 1.2 (0.2–5.4) the crossover of ketone bodies in these conditions. Of note, in
>60 20 1.6 (0.1–4.9) the prospective study, 21 of the 78 decedents had a history of alco-
Race holism. Of those, 2 had DKA listed as the cause of death, and 10
White 33 1.4 (0.2–4.7)
had alcohol-related cause of death.
Black 44 1.7 (0.1–5.4)
Vitreous glucose concentration (n = 45)
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Mitchell and McCleskey Am J Forensic Med Pathol • Volume 44, Number 1, March 2023

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