Diagnosing diabetes mellitus in patients with porphyria
Anne L. Christiansen
, Anette Bygum
, Ole Hother-Nielsen
Lars M. Rasmussen
Department of Clinical Biochemistry and
Pharmacology, Odense University Hospital,
Odense C, Denmark,
Dermatology and Allergy Centre, Odense
University Hospital, Odense C, Denmark,
Department of Endocrinology, Odense
University Hospital, Odense C, Denmark
Anne Lindegaard Christiansen,
Department of Clinical Biochemistry and
Odense University Hospital
Kloevervaenget 47, Indgang 40
5000 Odense C
Conﬂicts of interest: None of the authors
have any conﬂicts of interest to declare.
The prevalence of diabetes mellitus is increased in patients with porphyria cutanea tarda.
Different tests are available for diagnosing and screening for type II diabetes mellitus,
however choosing the most suitable test is challenging. The pitfalls in the different tests
along with the interfering comorbidities and treatments concerning patients with porphyria
cutanea tarda complicate diagnosing these patients with diabetes mellitus. HbA1c, fasting
glucose, or oral glucose tolerance are the current available tests, with HbA1c as ﬁrst
choice. Measuring HbA1c requires no fasting, however HbA1c can be false low if the
patient is treated with phlebotomy or has liver cirrhosis or chronic hepatitis. Instead fasting
glucose and oral glucose tolerance tests can be used if the patient is not acutely ill. If
either of the tests give a result in the diagnostic range, the test should be repeated if the
patient has no clinical symptoms of diabetes. Diagnosing diabetes mellitus is important for
the purpose of early intervention, and this review provides the knowledge needed to
diagnose this special patient group properly.
Porphyria cutanea tarda (PCT) is a hepatocutaneous disease
arising when a speciﬁc enzyme in the hem synthesis, uropor-
phyrinogen decarboxylase, displays decreased activity. The
handling of PCT patients is often challenging because of their
competing comorbidities and the rarity of the disease.
Besides increased risk of developing hepatocellular carci-
noma, these patients also have an augmented risk of devel-
oping diabetes mellitus (DM).
PCT patients are primarily
diagnosed and treated by dermatologists, who may not be
aware of the association with and the pitfalls in testing for
DM in these patients.
There are several different tests available to diagnose DM.
However, owing to comorbidities in patients with PCT and
treatment regimens, for example, phlebotomy, the diagnostic
process is not always straightforward. Clinicians need to know
the pros and cons for each test to be able to properly diag-
nose PCT patients with possible DM. This article provides an
update on the knowledge of DM in PCT patients and the rel-
evant available tests and recommendations for a diagnostic
Porphyria Cutanea Tarda – Clinical, Genetic,
and Biochemical Aspects
Porphyria cutanea tarda is the most prevalent porphyria disease
with a prevalence around 1 : 10,000.
The decreased enzyme
activity of uroporphyrinogen decarboxylase results in accumula-
tion of hem intermediates and porphyrins, especially in skin and
the liver. Porphyrins accumulated in the skin are excited by
light, leading to fragile skin, vesicles, sores, miliae, hyperpig-
mentation, and hypertrichosis on sun-exposed areas.
25–50% of PCT patients, a genetic mutation can be found in
the gene coding for UROD, and these patients typically develop
PCT at a younger age.
The exact mechanism behind
decreased UROD activity in PCT has not been clariﬁed; how-
ever, several risk factors, which often occur in combination,
have been identiﬁed: High intake of alcohol, smoking, iron over-
load (hemochromatosis), hepatitis C or HIV infection, and intake
Even though the mean age at diagnosis var-
ies in different studies, it is mostly a disease occurring in the
elderly with an age at diagnosis around 41–64 years.
Overall, PCT is a heterogeneous and complex disease, and
most patients have some degree of liver involvement and/or
Patients have an increased risk of developing
ª 2018 The International Society of Dermatology International Journal of Dermatology 2018, 57, 763–769