Clinical Gastroenterology and Hepatology 2017;15:927–933

Clinical, Biochemical, and Histopathology Features of Patients

With Glycogenic Hepatopathy
Saurabh Mukewar,*,a Ayush Sharma,*,a Kandace A. Lackore,‡ Felicity T. Enders,‡
Michael S. Torbenson,§ Patrick S. Kamath,* Lewis R. Roberts,* and Yogish C. Kudvak

*Division of Gastroenterology and Hepatology, ‡Division of Biomedical Statistics and Informatics, §Department of Laboratory
Medicine and Pathology, and kDivision of Endocrinology, Mayo Clinic, Rochester, Minnesota

BACKGROUND & AIMS: Glycogenic hepatopathy, a syndrome characterized by hepatomegaly and increased liver
transaminases in patients with type 1 diabetes, has not been well characterized in adults. We
describe the clinical, biochemical, and histopathology profile of a cohort of patients with
glycogenic hepatopathy. We also examined differences between patients with type 1 diabetes
with versus without glycogenic hepatopathy.

METHODS: We performed a case–control study of patients with type 1 diabetes diagnosed with glycogenic
hepatopathy and patients with type 1 diabetes without glycogenic hepatopathy (control
subjects). Cases were identified in the database of electronic medical records at Mayo Clinic,
Rochester from January 1, 1998, through January 1, 2014. Age- and sex-matched control
subjects were identified from a Mayo Clinic registry of patients with type 1 diabetes who had
normal levels of liver enzymes. Demographic, clinical, laboratory, and histopathology data were
collected and compared between cases and control subjects. The primary outcome was
difference in frequency of diabetic ketoacidosis episodes and hemoglobin (Hb) A1c levels
between cases and control subjects.

RESULTS: Among the 36 patients diagnosed with glycogenic hepatopathy, 20 had undergone liver biopsy
analysis. Most cases were female (n [ 28; 77.8%). Abdominal pain was the most common
symptom (n [ 23; 63.9%); 28 patients (77.8%) had hepatomegaly. All patients had poor control
of diabetes (mean HbA1c level, 11.2 – 2.4%). A higher proportion of cases had recurrent
episodes of diabetic ketoacidosis (61%) than control subjects (9%) (P [ .009), and cases had a
higher mean level of HbA1c (11.2 – 2.4% vs 9.0 – 2.2% in control subjects; P [ .0004). Adult
cases had higher levels of aspartate transaminase (312.5 IU/L; range, 245.5–775 IU/L) than
pediatric cases (157; range, 104–267 IU/L; P [ .02) and lower serum levels of albumin (3.7 –
0.5 g/dL vs 4.3 – 0.4 g/dL for pediatric cases; P [ .008). Only 16.7% of pediatric patients with
glycogenic hepatopathy had growth retardation. Levels of liver transaminases were normalized
at follow-up examinations of 18 of 21 adult or pediatric patients with glycogenic hepatopathy.

CONCLUSIONS: More than half of patients with glycogenic hepatopathy and type 1 diabetes have recurrent
episodes of diabetic ketoacidosis, and these patients have higher levels of HbA1c than patients
with type 1 diabetes without glycogenic hepatopathy. We observed growth retardation in only
about 17% of pediatric patients with glycogenic hepatopathy.

Keywords: DKA; AST; Mauriac Syndrome; Glycogen Deposition.

auriac syndrome or glycogenic hepatopathy although there are conflicting observations.1 GH seems
M (GH) is characterized by elevated serum trans-
aminases in patients with type 1 diabetes (T1D) sec-
to be most prevalent in patients with poorly controlled

ondary to glycogen deposition in the liver.1 In the classic a

description by Mauriac, the patients were children with
poorly controlled T1D in the pre-long-term-acting insulin
era who presented with growth retardation and cushin-
goid features.2
Some recent studies have suggested that the pheno-
type of patients presenting today may be milder,3,4
Authors share co-first authorship.
Abbreviations used in this paper: AST, aspartate transaminase; BMI, body
mass index; DKA, diabetic ketoacidosis; GH, glycogenic hepatopathy;
HbA1c, hemoglobin A1c; T1D, type 1 diabetes.
Most current article
© 2017 by the AGA Institute
1542-3565/$36.00
http://dx.doi.org/10.1016/j.cgh.2016.11.038
928 Mukewar et al
T1D, but there have been no comparative studies
confirming worse glucose control in these patients
compared with T1D without GH. The aim of the current
study was to describe the clinical, biochemical, and
histopathologic profile of patients with GH and to
conduct a matched case-control study to determine
whether T1D with GH had more frequent diabetic
ketoacidosis (DKA) episodes and elevated hemoglobin
A1c (HbA1c) concentrations compared with those
without.
Materials and Methods
Study Design
This was a case-control study. Cases were patients
with T1D diagnosed with GH and control subjects were
patients with T1D without GH. Cases were identified by
searching the terms “glycogenic hepatopathy” and
“Mauriac syndrome” in electronic medical records at
Mayo Clinic, Rochester from January 1, 1998 to January
1, 2014. Age and gender matched control subjects were
identified from a Mayo Clinic registry of patients with
T1D who had normal liver enzymes. The study was
approved by the Mayo Foundation Institutional Review
Board.
“Cases” of GH were identified as patients with T1D
and a liver biopsy suggestive of glycogenic GH (patho-
logic overloading of hepatocytes with glycogen); or a
clinical diagnosis of GH based on hepatomegaly on clin-
ical examination or hepatic imaging and transaminases
elevation >2 times the upper limit of normal. Patients
with known chronic liver disease or patients in whom
elevated transaminases could be attributed to other
causes were excluded.
Study Variables
Demographic, clinical, laboratory, and histopathology
variables were abstracted including age at presentation
with GH (for cases), age when transaminases were
normal (for control subjects), sex, height (cm), weight
(kg), body mass index (BMI), percentile height for age,
percentile weight for age, and BMI for age. Clinical
features comprised history of recurrent episodes of
DKA, duration of T1D, age at diagnosis of T1D, symp-
toms at presentation (abdominal pain, abdominal
distention, vomiting), and findings of hepatomegaly
and/or splenomegaly on physical examination and/or
abdominal imaging. Laboratory findings included HbA1c
(percentage), aspartate transaminase (AST; IU/L),
alanine transaminase (IU/L), alkaline phosphatase (IU/
L), g-glutamyltransferase (IU/L), total bilirubin (mg/
dL), direct bilirubin (mg/dL), serum albumin (g/dL),
total cholesterol (mg/dL), low-density lipoprotein
cholesterol (mg/dL), high-density lipoprotein choles-
terol (mg/dL), and triglycerides (mg/dL). Liver biopsy
Clinical Gastroenterology and Hepatology Vol. 15, No. 6
findings including presence of inflammation, mega
mitochondria, and fibrosis were also noted. Follow-up
transaminase levels were also recorded and were clas-
sified as “resolved liver enzymes” or “resolving liver
enzymes.”
Outcomes
The primary outcome was to compare frequency of
recurrent DKA episodes and HbA1c levels between cases
(T1D þ GH) and control subjects (T1D þ normal liver
enzymes). Secondary outcomes were to assess differ-
ences in clinical presentation, imaging findings, and
laboratory investigations between adult (>18 years) and
pediatric (18 years) patients diagnosed with GH.
Statistical Analysis
Descriptive statistics were calculated using fre-
quencies and percentages for categorical variables and
either mean and standard deviation or median and
interquartile range for continuous variables. P values
were generated using Fisher exact tests for categorical
variables and Kruskal-Wallis tests for continuous vari-
ables. All statistical analyses were performed using SAS
version 9.3 (SAS Institute Inc, Cary, NC).
Results
Thirty-six patients were diagnosed with GH; 20 had
liver biopsy and 16 were clinically diagnosed. Hepato-
megaly was present in 32 of the 36 patients (88.9%), in
18 (50%) on both clinical examination and imaging, in 10
(27.8%) on imaging only, and in 4 (11.1%) on clinical
examination only. Most of the cases were female (28 of
36; 77.8%). Abdominal pain was the most common
symptom (23; 63.9%). All patients had poor diabetes
control (HbA1c, 11.2  2.4).
Patients With Type 1 Diabetes With and Without
Glycogenic Hepatopathy
Table 1 shows the comparison between patients
with T1D with and without GH. In the GH group, a
greater frequency of patients had history of recurrent
DKA episodes (61% vs 32%; P ¼ .02) and the GH group
had higher HbA1c levels (11.2  2.4 vs 9.0  2.2;
P ¼ .003). In pediatric patients with GH, median
percentile height for age was 30.5 (range, 1–79) and
median percentile weight for age was 64.5 (range,
1–91). In those without GH, median percentile height for
age was 54 (range, 4–86) and median percentile weight
for age was 77.5 (range, 3–96). There was no difference
in the frequency of pediatric patients with low (<5)
percentile height and weight for age between the 2
groups (16.7% vs 18.2%; P ¼ 1.00). Cases had higher
total cholesterol (266.4  95.3 vs 175.0  39.4;
June 2017 Glycogenic Hepatopathy 929

Table 1. Comparison Between Type 1 Diabetics With Glycogenic Hepatopathy and Type 1 Diabetes With Normal Liver
Enzymes

Type 1 diabetes with glycogenic Type 1 diabetes with normal liver

hepatopathy (cases) enzymes (control subjects) P valuea

Male, n (%) 8 (22.0) 7 (20.6) 1.00

BMIb 23.5  3.5 24.0  5.3 .97
Percentile height for agec 30 (8–52) 47 (36–67) .18
Percentile weight for agec 77 (58–81.5) 71 (48–76) .36
Clinical features, n (%)
Abdominal pain 23 (63.9) 13 (38.2) .055
Vomiting 6 (16.7) 5 (14.7) 1.00
Abdominal distention 6 (16.7) 0 (0) .025
Splenomegaly 2 (5.6) 0 (0) .49
Hepatomegaly 22 (61.1) 1 (2.9) < .0001
Age at diagnosis of DM, yc 8.5 (5–12) 8 (5–12) .75
Episodes of recurrent DKA, n (%) 22 (61.1) 10 (29.4) .009
Imaging findings, n (%)
Splenomegaly 0 (0) 0 (0) —
Hepatomegaly 28 (84.8) 0 (0) < .0001
Laboratory studies
HbA1c, %b 11.2  2.4 9.0  2.2 .0004
AST, U/Lc 289 (135–604) 23.5 (18–30) < .0001
ALT, U/Lc 245 (123–386) 18 (15–27.5) < .0001
Alkaline phosphatase, U/Lc 196.5 (142–289) 113 (78–145) .0003
GGT, U/Lc 97 (66–426) 11 (11–20) .0006
Total bilirubin, mg/dLb 0.5  0.3 0.5  0.3 .80
Direct bilirubin, mg/dLb 0.2  0.3 0.1  0.0 .33
Serum albumin, g/dLb 3.9  0.6 4.2  0.6 .22
INRb 0.9  0.1 1.0  0.0 .022
Total cholesterol, mg/dLb 266.4  95.3 175.0  39.4 < .0001
LDL cholesterol, mg/dLb 112.5  37.7 95.2  42.0 .072
HDL cholesterol, mg/dLb 51.5  23.7 61.3  18.7 .21
Triglycerides, mg/dLc 291.5 (180–509) 88.0 (58–126) < .0001

ALT, alanine transaminase; DM, diabetes mellitus; GGT, g-glutamyl transferase; HDL, high-density lipoprotein cholesterol; INR, international normalized ratio; LDL,
low-density lipoprotein cholesterol.
a
Kruskal-Wallis for continuous, Fisher exact for categorical.
b
Mean  standard deviation.
c
Median (interquartile range).

P < .0001) and triglyceride levels (291.5 [range,
180–509] vs 88.0 [range, 58–126]; P < .0001)
compared with control subjects. There were no
differences in BMI, abdominal pain, abdominal disten-
tion, vomiting, splenomegaly, total bilirubin, albumin,
high-density lipoprotein cholesterol, or low-density
lipoprotein cholesterol between the 2 groups.
Adult and Pediatric Patients With
Glycogenic Hepatopathy
There were 24 adult and 12 pediatric patients with
GH (Table 2). Adults had longer duration of diabetes
(13.3  5.8 vs 8.7  3.6; P ¼ .02), higher AST levels
(312.5 [range, 245.5–775] vs 157 [range, 104–267];
P ¼ .02), and lower serum albumin levels (3.7  0.5
vs 4.3  0.4; P ¼ .008) than pediatric patients. There
was no difference in sex, BMI, abdominal pain, abdominal
distention, vomiting, splenomegaly, hepatomegaly,
history of recurrent DKA, HbA1c, alanine transaminase,
alkaline phosphatase, g-glutamyltransferase, total
bilirubin, total cholesterol, high-density lipoprotein
cholesterol, low-density lipoprotein cholesterol, or tri-
glycerides between the 2 groups.
Clinical Versus Histopathologic Diagnosis of
Glycogenic Hepatopathy
The only difference found in the clinical versus
histopathologically diagnosed GH cases was in AST
levels, which were greater in biopsy proven than in
clinically diagnosed cases (301 [range, 245.5–775] vs
150 [range, 69–465.5]; P ¼ .02) (Table 3). Among those
with biopsy-confirmed GH, 3 (15%) patients had mega
mitochondria observed on histopathology.
Follow-up
Median duration of follow-up was 8 months (range,
1–72) with data available for 21 of the 36 patients. For
18 of the patients the transaminases eventually
normalized; in the other 3 patients they were trending
930 Mukewar et al Clinical Gastroenterology and Hepatology Vol. 15, No. 6

Table 2. Comparison Between Adult and Pediatric Patients With Glycogenic Hepatopathy

Adults (n ¼ 24) Pediatric (n ¼ 12) P valuea

Male, n (%) 5 (20.8) 3 (25.0) 1.00

Age at presentation, yb 23.2  5.6 16.1  2.0 < .0001
Clinical features, n (%)
Abdominal pain 14 (58.3) 9 (75.0) .47
Vomiting 6 (25.0) 0 (0) .08
Abdominal distention 2 (8.3) 4 (33.3) .15
Splenomegaly 0 (0) 2 (16.7) .10
Hepatomegaly 12 (50.0) 10 (83.3) .08
Age at diagnosis of DM, yc 9.5 (5–13) 7.5 (5–9.5) .21
Duration of DM, yb 13.3  5.8 8.7  3.6 .02
Requires insulin, n (%) 23 (95.8) 12 (100) 1.00
Episodes of recurrent DKA, n (%) 13 (54.2) 9 (75.0) .29
Imaging findings, n (%)
Splenomegaly 0 (0) 0 (0)
Hepatomegaly 19 (86.4) 9 (81.8) 1.00
Laboratory studies
HbA1c, %b 11.5  2.6 10.7  2.1 .48
AST, U/Lc 312.5 (245.5–775) 157 (104–267) .02
ALT, U/Lc 315 (188–386) 144.5 (76.5–349) .10
Alkaline phosphatase, U/Lc 193 (142–297) 243 (131–289) .77
GGT, U/Lc 181 (66–552) 77 (66–426) .56
Total bilirubin, mg/dLb 0.5  0.4 0.5  0.2 1.00
Direct bilirubin, mg/dLb 0.2  0.3 0.2  0.1 .81
Serum albumin, g/dLb 3.7  0.5 4.3  0.4 .008
INRb 0.9  0.1 0.8  0.0 .04
Total cholesterol, mg/dLb 281.7  112.0 242.0  56.3 .40
LDL cholesterol, mg/dLb 116.6  38.7 106.9  38.2 .56
HDL cholesterol, mg/dLb 52.1  24.3 50.5  23.9 .72
Triglycerides, mg/dLc 318 (180–593) 259.5 (173.5–407.5) .35

ALT, alanine transaminase; DM, diabetes mellitus; GGT, g-glutamyl transferase; HDL, high-density lipoprotein cholesterol; INR, international normalized ratio; LDL,
low-density lipoprotein cholesterol.
a
Kruskal-Wallis for continuous, Fisher exact for categorical.
b
Mean  standard deviation.
c
Median (interquartile range).

down on follow-up. The decrease in transaminases was
associated with improvement in glycemic control. None
of the patients developed any apparent long-term
adverse liver outcomes.
Discussion
This study constitutes the largest series of patients
with T1D and GH. The typical clinical presentation was
abdominal pain, hepatomegaly, recurrent DKA, elevated
HbA1c levels, and hypercholesterolemia. Growth retar-
dation was infrequently seen in pediatric patients with
GH. When compared with patients with T1D with normal
liver enzymes, patients with GH more frequently had
recurrent DKA and elevated HbA1c levels. Adult patients
with GH had higher AST levels and lower albumin levels
compared with pediatric patients. On follow-up, patients
had fluctuating liver enzymes, which eventually
normalized in most cases.
GH, or Mauriac syndrome, was described by Pierre
Mauriac in patients with T1D as hepatomegaly
and elevated liver function tests caused by glycogen
accumulation in hepatocytes.2,5 The term “glycogenic
hepatopathy” was recently coined by Torbenson et al4 to
describe this condition. Hepatic glycogenosis occurs
secondary to a combination of 2 main factors: elevated
glucose levels and elevated insulin levels. Glucose diffuses
into hepatocytes and is converted to glucose-6-phosphate
by the enzyme glucokinase. Glucose-6-phosphate is
converted to glycogen by the enzyme glycogen synthase.
Glycogen synthase exists in an active dephosphorylated
form and an inactive phosphorylated form. The active
dephosphorylated form of glycogen synthase is produced
by the action of a phosphatase enzyme, which is stimu-
lated by elevated glucose and insulin levels. Glycogen is
mobilized by glycogen phosphorylase typically in the
postabsorptive state. Thus, mechanistically, elevated
glucose and insulin levels and decreased glycogen
phosphorylase activity in the hepatocyte could lead to
deposition of glycogen in hepatocytes (Figure 1).
DKA can be considered as a surrogate marker for
poor glycemic control with elevated insulin and glucose
levels in T1D. Thus, patients with a history of DKA can be
expected to have a higher risk of developing GH. An
autopsy study evaluating the glycogen content in the
liver of patients dying from DKA showed significantly
more glycogen deposition in the liver compared with the
June 2017 Glycogenic Hepatopathy 931

Table 3. Comparison Between Biopsy Proven and Clinically Diagnosed Cases of Glycogenic Hepatopathy

Biopsy-proven glycogenic Clinically diagnosed glycogenic

hepatopathy (n ¼ 20) hepatopathy (n ¼ 16) P valuea

Male, n (%) 4 (20) 4 (25) 1.00

Age at presentation, yb 20.4 (18.6–23.8) 18.4 (16.7–21.5) .13
BMIc 23.1  2.3 24.0  4.6 .23
Percentile height for ageb 46 (26.5–52) 12.5 (5–55.5) .50
Percentile weight for ageb 77.5 (71.5–79.5) 77 (25–86) .93
BMI for ageb 77.5 (71.5–87.5) 82.5 (37–90.5) .93
Clinical features, n (%)
Abdominal pain 14 (70.0) 9 (56.3) .49
Vomiting 5 (25.0) 1 (6.3) .20
Abdominal distention 2 (10.0) 4 (25.0) .37
Splenomegaly 1 (5.0) 1 (6.3) 1.00
Hepatomegaly 12 (60.0) 10 (62.5) 1.00
Age at diagnosis of DMb 9.5 (7–13) 7 (5–11) .16
Duration of DMc 11.9  6.1 11.4  5.1 .80
Episodes of recurrent DKA, n (%) 11 (55.0) 11 (68.8) .50
Imaging findings, n (%)
Splenomegaly 0 (0) 0 (0) —
Hepatomegaly 16 (88.9) 12 (80.0) .64
Laboratory studies
HbA1c, %c 11.4  2.6 10.9  2.2 .54
AST, U/Lb 301 (245.5–775) 150 (69–465.5) .02
ALT, U/Lb 308 (191–386) 166 (76–446) .11
Alkaline phosphatase, U/Lb 170 (127–248) 243 (142–306) .28
GGT, U/Lb 66 (63–552) 117 (66–26) .42
Total bilirubin, mg/dLc 0.5  0.4 0.5  0.3 1.00
Direct bilirubin, mg/dLc 0.2  0.3 0.2  0.1 .56
Serum albuminc 3.9  0.4 4.1  0.7 .20
INRc 0.9  0.1 0.9  0.1 .77
Total cholesterol, mg/dLc 294.5  114.2 239.9  66.7 .28
LDL cholesterol, mg/dLc 111.4  21.6 113.4  47.3 .93
HDL cholesterol, mg/dLc 49.5  27.7 53.5  19.8 .55
Triglycerides, mg/dLb 315 (250–593) 231 (102–500) .11

ALT, alanine transaminase; DM, diabetes mellitus; GGT, g-glutamyl transferase; HDL, high-density lipoprotein cholesterol; INR, international normalized ratio; LDL,
low-density lipoprotein cholesterol.
a
Kruskal-Wallis for continuous, Fisher exact for categorical.
b
Median (interquartile range).
c
Mean  standard deviation.

livers of persons dying from natural causes.6 In one of
the largest series of GH published by Marble5 in 1938,
nearly 70% of patients with suspected GH had a history
of severe DKA. In comparison, a more recent study
showed lower rates of frequent DKA of about 30%.4
However, none of the previous studies compared the
rate of DKA with that in T1D without GH. Our current
study showed a higher frequency of DKA episodes in
patients with GH compared with T1D with normal
transaminases. In addition, patients with GH also had
greater HbA1c levels than control subjects. This suggests
that poor glycemic control may be associated with the
glycogen accumulation seen in GH.
There has been a change in clinical presentation of GH
over the last century. In the classic description by
Mauriac in 1931, the patient was a 10 year old with
poorly controlled T1D with protuberant abdomen, liver
enlargement, dwarfism, delayed puberty, cushingoid
features, and hypercholesterolemia.2 In a subsequent
large series by Marble,5 60 children with diabetes and
hepatomegaly were reported of whom nearly half were
dwarfs. Cushingoid features were frequently seen in
earlier reports of GH in the era before the availability of
long-acting insulin, purportedly secondary to prolonged
hypercortisolism during periods of hypoglycemia.2,7 Such
findings are infrequently observed today because of use
of long-acting insulin and probably the decreased fre-
quency of hypoglycemic events in this patient cohort. As
described in a more recent study by Torbenson et al,4
only 1 of the 5 pediatric patients with GH exhibited
classic features of Mauriac syndrome. In another study,
none of the 3 patients with GH had such features.8 In
contrast, a recent large study from the United Kingdom
showed that overall these patients appeared to be lighter
and shorter than UK reference data.1 However, the
authors did not describe what percentage of patients
presented with “classic Mauriac” features. Our findings
are similar to those of Torbenson et al4 and Olsson et al,3
because only 2 of the 12 pediatric patients had growth
retardation and cushingoid features. Thus, it seems that
932 Mukewar et al
Figure 1. High power view of slide showing classic features
of glycogenic hepatopathy with diffuse pale, swelling of the
hepatocytes.
currently pediatric patients appear to present with a
milder phenotype compared with the initial descriptions
of this syndrome.
More recently, GH has been described in young adults
with T1D.3,4,9 Interestingly, two-thirds of the patients in
our study were T1D adults presenting with transaminase
elevations. Chatila and West9 compared 8 adults with GH
with 3 pediatric patients and found no differences in
presentation. By contrast, adult patients with GH in our
study had higher AST and lower albumin levels than
pediatric cases. In all patients with elevated amino-
transferase levels, tests for chronic liver disease were
negative. Therefore, high index of suspicion for GH and
negative testing for chronic liver disease were criteria for
GH for our cohort of patients. Interestingly, we observed
higher levels of AST than alanine transaminase in our
study; this has not been reported in prior studies. Further
studies are warranted to investigate the relevance if any
and the mechanistic basis for this observation.
In people with diabetes, hepatomegaly can occur
secondary to fat or glycogen deposition. Although, fatty
liver is generally seen in obese adults with type 2 dia-
betes, it is infrequently reported in liver biopsies from
T1D with GH. In a study by Chatila and West,9 moderate
steatosis was seen in 25% of biopsies with GH, but none
had steatohepatitis. Torbenson et al4 noted mild steatosis
in 14%, mild steatohepatitis in 7%, and mild fibrosis in
14% of cases with GH. In contrast, Fitzpatrick et al1
observed steatohepatitis in 42% and fibrosis in 74% of
these patients. Interestingly, 6% of cases in that study
had bridging fibrosis. By comparison, in our study 15%
of GH cases had mild inflammation and 10% had mild
fibrosis. None of the patients had bridging fibrosis. On
follow-up, most patients had fluctuation of the liver
enzymes, which eventually normalized in most of the
patients as glycemic control improved. None of the
patients developed long-term sequelae of liver disease
secondary to glycogen accumulation.
Clinical Gastroenterology and Hepatology Vol. 15, No. 6
In a previous study by Taskinen,10 glycemic control
improved lipid values, with the cholesterol concentration
decreasing by 0.1 mM (3.87 mg/dL; 2.2%) and the
plasma triglyceride level decreasing by 0.08 mM
(7.1 mg/dL; 8%) for each percentage-point decrease in
the glycohemoglobin in a randomly selected insulin-
dependent diabetes mellitus population.11 As in our
series, patients with T1D with GH had significantly higher
values of HbA1c than patients with T1D without GH; this
could have contributed to higher triglycerides and
cholesterol levels. Furthermore, the higher risk of DKA in
GH may indicate unique alterations in lipolysis that may
account for changes in the lipid tests. Visceral white ad-
ipose tissue secretes adipokines that mediate the
inflammatory response associated with central obesity
and its complications, including nonalcoholic fatty liver
disease and steatohepatitis.12 It is possible that patients
with GH have defects in fat biology and adipokines that
may mediate the unique metabolic state and cause liver
injury similar to nonalcoholic liver disease. However, this
needs to be investigated further to better understand the
pathophysiologic mechanisms in patients with GH.
This study confirms the association of recurrent DKA
with GH. GH could be considered a surrogate marker of
poor glycemic control. Fortunately, GH does not lead to
adverse long-term outcomes and the liver enzymes
eventually normalize in most patients on follow-up. None
of the patients had advanced hepatic fibrosis. It is
important to note that GH can be seen in young adults
with T1D and most patients do not present with the
classic Mauriac syndrome features, such as dwarfism and
cushingoid features. The presentation of adults is quite
similar to that of children except for higher AST and
lower albumin levels. The study describes one of the
largest single-center series of GH, with a significant
proportion of young adult patients.
The limitations of the study are its retrospective
nature and the loss to follow-up of nearly 40% of the
patients. Also information on some laboratory tests, such
as lactose dehydrogenase and glutamate dehydrogenase,
was not available in all the patients. Glycogen storage
disorders, such as von Gierke disease, may have similar
biopsy findings. However, the age of presentation,
clinical history of T1D, lack of developmental delay, or
severe lactic acidosis made the diagnosis of von Gierke
disease unlikely.
In conclusion, patients with T1D with GH frequently
had a history of recurrent DKA and elevated HbA1c levels.
Growth retardation was uncommon in GH. Compared
with pediatric patients with GH, adult patients had
similar clinical imaging and laboratory features, except
for higher AST and lower albumin levels. On follow-up,
liver enzymes normalized in most patients.
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Reprint requests
Address requests for reprints to: Lewis R. Roberts, MD, Mayo Clinic, 200 First
Street SW, Rochester, Minnesota 55905. e-mail: roberts.lewis@mayo.edu; fax:
(507) 284–0762; and Yogish C. Kudva, MBBS, Mayo Clinic, 200 First Street
SW, Rochester, Minnesota 55905. e-mail: kudva.yogish@mayo.edu; fax: (507)
284–5745.
Conflicts of interest
The authors disclose no conflicts.