Case Study
Acute Pancreatitis in Association with Diabetic Ketoacidosis in a Newly
Diagnosed Type 1 Diabetes Mellitus Patient; Case Based Review
1
Sunil Kumar Kota, 2Sruti Jammula,
5
Kirtikumar D Modi
3
Siva Krishna Kota, 4 Lalit Kumar Meher
1
Resident, Department of Endocrinology, Medwin Hospital,Hyderabad, India. 2 PhD
Scholar, Department of Pharmaceutics, Roland Institute of Pharmaceutical Sciences,
Behrampur, India,3Registrar, Department of Anaesthesia, Central Security Hospital,
Riyadh, Saudi Arabia, 4 Head, Department of Medicine, MKCG Medical College,
Behrampur, India, 5Head, Department of Endocrinology, Medwin Hospital,
Hyderabad, India. E-mail: hidocsunil@ibibo.com
International Journal of Clinical Cases and Investigations 2012. Volume 4
(Issue 1), 54:60, 1st April, 2012
Key Words: Type 1 diabetes mellitus, diabetic ketoacidosis, acute pancreatitis,
hypertriglyceridemia
Abstract
Patients with newly detected type 1 diabetes mellitus come to the fore with initial
presentation of diabetic ketoacidosis (DKA). Among the several risk factors, acute
pancreatitis (AP) is an uncommon cause. DKA may mask coexisting AP, which occurs
in at least 10-15% cases. AP is more likely to be associated with a severe episode of
DKA with marked acidosis and hyperglycemia. Here we present the clinical and
biochemical profile of a 12 year old type 1 diabetes girl presenting with DKA
complicated by AP. Prompt diagnosis of AP in DKA or vice versa is important for
proper management. The management requires diligent correction of dehydration
and hyperglycemia, while monitoring neurological status and blood chemistry. It is
imperative to monitor and avoid potentially fatal complications of the combined
entity, including cerebral edema, thromboembolism, acute respiratory distress
syndrome and rhabdomyolysis. Exclusion of acute pancreatitis in cases with
persistent abdominal pain in this scenario is vital.
54
Introduction:
Diabetic ketoacidosis is an acute metabolic complication reflective of extremes of
abnormal insulin homeostasis mainly in type 1 diabetes mellitus (T1DM)1 It has an
estimated mortality of 2- 10%2. Acute pancreatitis (AP) coexisting with diabetic
ketoacidosis (DKA) as a cause or result has been reported previously3– 6. In these
reports, the diagnosis of AP was based solely on clinical features and associated
elevations in serum pancreatic enzymes without any confirmatory radiographic (CT
scan) findings3– 6. Several case reports emphasizing the development of diabetic
coma as a rare complication of severe AP also noted that some of these patients had
no preexisting diabetes4,7. Other reports documented an association of AP with
hyperosmolar nonketotic diabetic coma6,7.
During severe episodes of DKA, insulin deficiency increases free fatty acid(FFA) and
amino acids release from adipose tissue and muscle respectively and increased
counter-regulatory hormones causes increased gluconeogenesis and glycogenolysis
in the liver8,9. Elevated FFA taken up by liver leads to increased production of very
low density lipoprotein (VLDL) cholesterol, which causes hypertriglyceridemia.
Hypertriglyceridemia is an uncommon cause of acute pancreatitis accounting for 14% cases, especially when the serum triglyceride (TG) level exceeds 1000 mg/ dl9.
These transiently elevated levels of serum triglyceride are believed to precipitate
acute pancreatitis12. DKA is known to mask the clinical features of acute pancreatitis,
with acute pancreatitis reported in 10–15% of patients12.
We report a case of newly diagnosed T1DM presenting with DKA and AP. We also
hereby review the pathogenesis and clinical implications of such an uncommon
association
Case Report:
A 12 year old girl presented to emergency department with 6- 8 episodes of non
bloody, non bilious vomiting over past 2 days, associated with severe, continuous
non radiating epigastric pain and lethargy of 24 hours duration. She had 2 bouts of
loose motion on the day of presentation. Upon admission, the patient weighed 55 kg
with height of 161 cm and body mass index 21.2 kg/ m2. She was drowsy with heart
rate of 100/ minute, blood pressure- 100/ 60 mm hg in right arm supine position,
respiratory rate of 26/ minute with kussmaul’s acidotic breathing and body
temperature of 100.40F. Physical examination revealed dehydrated tongue with
decreased skin turgor without any evidence of eruptive or tuberous xanthoma and
xanthelesma. There was soft, tender epigastrium with sluggish bowel sounds without
any mass or skin discoloration. Neurologically she was drowsy, pupils equal in size
and normally reactive with no focal neurologic deficit.
Initial laboratory parameters included neutrophilic leucocytosis, random blood
glucose 320 mg/ dl, HbA1C 13.8%, sodium- 138 meq/ l, potassium- 4.5 meq/ l,
chloride- 95 meq/ l, cholesterol- 320 mg/dl, low density cholesterol- 156 mg/ dl
(estimated by homogenous enzymatic colorimetry method), triglyceride- 1020 mg/
dl, normal renal and liver function tests with urine strongly positive for ketones (4+).
Arterial blood gas (ABG) analysis revealed pH- 7.2, pCO2- 13 mm Hg, HCO3- 9 meq/
l
55
With a provisional diagnosis of T1DM with DKA, patient was aggressively hydrated
and treated with intravenous insulin. On the second day she had normalization of
ABG, but there was no improvement in neurological status with aggravated
abdominal pain. Follow up laboratory analysis revealed amylase levels of 440 U/ l,
lipase- 560 U/ l. Contrast tomography (CT) of abdomen revealed diffusely inflamed
and swollen pancreas without any fluid collection confirming the diagnosis of AP. This
was AP grade C, according to Balthazar CT severity index (Figure 1). Patient was
managed conservatively measures like nil by mouth, nasogastric aspiration,
intravenous fluid, insulin and monitoring of her vital clinical and laboratory
parameters.
On 3rd day, she was conscious with laboratory parameters revealing fasting blood
sugar of 124 mg/ dl, triglyceride- 340 mg/ dl, cholesterol- 181 mg/ dl, LDL- 101 mg/
dl. The patient commensed oral intake and multiple subcutaneous insulin injections.
At this stage her fasting C-peptide was 0.2 ng/ ml (N- 1.1- 4.4 ng/ ml), anti GAD
antibody titer- 1.5 U/ml (N- 0-0.9) and anti IA-2 antibody titer- 0.8 U/ ml(N- 0-0.4
U/ml), confirming the diagnosis of T1DM. On 6th day the child was asymptomatic
with a normal abdominal examination and normalization of serum amaylase and lipse
levels( 50 & 35 U/ L respectively). Repeat CT abdomen at this point showed
significant improvement. Follow up clinical examination at 2 months revealed body
weight of 63 kg with BMI 24.3 kg/ m2, good glycemic control (FBS- 102 mg/ dl,
PPBS- 135 mg/ dl, serum triglyceride- 225 mg/dl) and normal pancreatic
ultrasonography
Discussion:
Our patient presented with an episode of DKA complicated by AP. Although transient
hyperglycemia (50-70%) and glycosutria (30%) are not uncommon in AP,
permanent diabetes mellitus13 is exceedingly rare in children (14) and is relatively
infrequent in adults occurring in 1-15% of affected adults14. Pancreatic diabetes
accounts for less than 1% of all cases of diabetes mellitus.
Serum levels of pancreatic enzymes are dependent on the rate of entry of these
enzymes into circulation from pancreatic acini and clearance or metabolism by the
kidneys15,16. Because the pancreas accounts for 95% of serum lipase, in contrast to
40% to 50% for amylase, serum lipase is considered a more specific marker for
pancreatitis than amylase15. Nair et al12 observed that the specificity of elevated
amylase (at three times the normal level) was 97% for diagnosing acute
pancreatitis; while the specificity of elevated lipase (at the same level) was only
91%, indicating high amylase as a critical marker of acute pancreatitis. The
magnitude of lipase elevation appears to correlate with degree of acidosis, where as
hyperamylasemia is nonspecific. A normal serum amylase level does not rule the
possibility of a coexisting acute pancreatitis12,17. Noticeably, normoamylasemia is
possible in about 50% of patients with hypertriglyceridemia induced pancreatitis. The
mechanism is believed to be the interference with in vitro determination of the actual
amylase level by disturbance of the calorimetric methods. Serial dilutions of the
sample could reduce interference of light transmission by hyperlipidemia serum 18.In
our patient both lipase and amylase levels were elevated.
56
Acute pancreatitis can induce hyperglycemia and ketosis in a patient with diabetes
mellitus and hence may be a primary event rather than a sequel to DKA19-21.
Nonspecific elevations of amylase and/ or lipase without clinical evidence of
pancreatitis have been reported in 24.7%- 79% of DKA cases18.At least in those
patients with continuous abdominal pain, it is prudent not to ignore it as a clinical
component of DKA but to proceed further with amylase, lipase, and triglyceride
estimations, and when one of these is markedly raised (>3 times amylase and lipase
or > 1000 mg of triglyceride), a CT scan of the abdomen should be performed12.
In DKA, insulin deficiency activates lipolysis in adipose tissue releasing increased free
fatty acids, which accelerates formation of VLDL in the liver. In addition, reduced
activity of lipoprotein lipase in peripheral tissue decreases removal of VLDL from the
plasma, resulting in hypertriglyceridemia22. Moderate hypertriglyceridemia is
common during episodes of DKA (23). However, severe hypertriglyceridemia, defined
as TG level > 2000 mg/ dl is rare. Hypertriglyceridemia can cause AP by generation
of cytotoxic free fatty acids in the pancreatic circulation12,24,25. This results in
vascular endothelial cell damage, sludging of red cells, pancreatic ischemic injury
and inflammation.
Although no convincing clinical data exist, few possible explanations for
hyperlipasemia in DKA can be offered. One explanation is that lipase with a
molecular mass of 46–52 kD is removed from circulation by glomerular filtration and
then subsequently reabsorbed to be metabolized by renal tubules26,27. In DKA there
is moderate hypovolemia with a reduced glomerular filtration rate28, 29. Therefore,
less efficient handling of lipase by the kidney is conceivable, which leads to
elevations in serum levels even without overt renal failure. Another possibility is the
release of nonpancreatic lipolytic enzymes into the circulation30. Two potential
nonpancreatic sources for lipase in DKA are the stomach and liver, organs involved in
DKA6,31,32. The currently used lipase assays is 1-oleolyl-2,3-diacetylglycerol, a
substrate more readily metabolized by nonpancreatic lipolytic enzymes27,30. Another
possibility is that in recent onset diabetics immunological destruction of β cells might
spill over and cause damage to the pancreatic acini, releasing lipase into
circulation30,33.
Prompt diagnosis of AP in DKA or vice versa has several clinical implications12. Firstly
AP can aggravate the severity of ketoacidosis by worsening the depletion of
intravascular volume thus necessitating more aggressive fluid replacement.
Secondly, AP can also alter glucose homeostasis, thus making control of
hyperglycemia more difficult. Thirdly, once the ketoscidosis is controlled, oral feeding
may be resumed, which may be detrimental in some patients with AP. Patients with
DKA may experience abdominal pain even in absence of acute pancreatitis as a
result of gastritis, gastric atony or hepatomegaly and distension of liver capsule34-36.
Abdominal pain is a common feature of both these conditions. AP, therefore needs to
considered in a child with DKA and severe abdominal pain failing to resolve rapidly
with the correction of acidosis and dehydration14,37
57
Abdominal ultrasound is a particularly useful tool in supporting the diagnosis AP.
Pancreatic enlargement and hypoechogenicity on ultrasound is virtually diagnostic of
AP34. Abdominal CT, particularly contrast enhanced is an excellent tool for identifying
AP and its complications38,39. CT is the imaging modality of choice in patients with
unconfirmed AP, in those who fail to respond to conservative therapy or have
suspected complications. Nevertheless, 20% of children with a mild clinical form of
pancreatitis have a normal CT scan and is not a sensitive method for detecting gall
stones, unless they are calcified40. Ranson’s prognostic criteria are not applicable to
assess the severity of AP in DKA because they overestimate the severity12. Severity
index based on CT findings proposed by Balthazar et al appears to better correlate
with outcome (A- Normal Pancreas, B- Enlargement, C- Inflammation of pancreas
and fat, D- Single fluid collection, E- ≥ 2 fluid collection)41.
Conclusion:
Diabetes mellitus secondary to AP is extremely rare in children. It is important to
consider AP in the differential diagnosis of any child with severe prolonged abdominal
pain, particularly in association with DKA. AP is more likely to be associated with a
severe episode of DKA with marked acidosis and hyperglycemia. Elevation of serum
lipase and amylase occur in DKA, and elevation of lipase levels appears to be less
specific than amylase levels for the diagnosis of AP in the diagnosis of DKA. The
concurrent diagnosis of these 2 conditions has several important clinical implications.
Early imaging of the pancreas is recommended
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