SUCCESFULL MANAGEMENT OF SEVERE METABOLIC

ACIDOSIS IN A PREECLAMPSIA PATIENT WITH DIABETIC

KETOACIDOSIS AND ACUTE PANCREATITIS: A CASE
REPORT

Christian Poerniawan1, Candra Christian Soekamto1 Libriansyah2

Division of Endocrinology, Diabetes, and Metabolism
Department of Internal Medicine and Department of Psychiatry
Dr Ramelan Naval Hospital, Surabaya 60244, Indonesia

1
Intern Doctor at Division of Endocrinology, Department of Internal Medicine in Dr
Ramelan Naval Hospital Surabaya
2
Internist-Endocrinologist, Division of Endocrinology, Department of Internal Medicine at
Dr Ramelan Naval Hospital Surabaya

Corresponding Author :
Christian Poerniawan
Dr. Ramelan Naval Hospital, Gadung Street No. 1, Surabaya
60244, Indonesia
Call : +6281131-08878
Email : christian.poerniawan@gmail.com
Abstract
Diabetic ketoacidosis (DKA) is an acute, major, life-threatening complication of
diabetes that requires immediate treatment. Diabetic ketoacidosis in pregnancy is
an emergency that significantly causes maternal and fetal morbidity and mortality. A
33-year-old woman, gravida 2, housewife was admitted at 32 weeks of gestation to
the emergency department on February 2/2023 with multigravida, shortness of
breath and two-day history of nausea and vomiting. She had a history of diabetes
mellitus four years earlier. She missed her medication one day due to traveling to
the village for greeting her family. She presented with a two-day history of nausea
and vomiting, and a one-day history of shortness of breath, abdominal tenderness,
hypertension, elevated heart rate, increased respiratory rate, and fatigue. The
presenting blood sugar level was 713 mg/dl. Ketone testing done using her
urine sample showed ketonuria of 3+. Amylase and Lipase enzymes increased at
1004,8 and 899,4. CT Abdominal revealed acute pancreatitis. Her breath odor
revealed acetone-smelling breathing. Upon admission, she was treated with insulin
infusion for 48 hours and antibiotics for her pancreatitis. Following successful
treatment of acute pancreatitis and hyperglycemia with fluid and insulin,
his serum glucose and pancreatic enzyme level decreased to normal range.
The patient and her baby recovered and was discharged in stable condition

Keywords: diabetic ketoacidosis, acute pancreatitis, medication omission,

pregnancy
Introduction
Diabetic ketoacidosis is a life-threatening condition caused by either absolute insulin
deficiency, commonly in type-1 diabetes mellitus and complete insulin sensitivity, or
occasionally in type-2 diabetes mellitus.1 Diabetic ketoacidosis in pregnancy is an
emergency that significantly causes maternal and fetal morbidity and
mortality.2 Physiological changes that occur during pregnancy elevate the risk of
ketosis and subsequent acidosis.3 Pregnancy is a diabetogenic state with increased
insulin resistance, enhanced lipolysis, elevated free fatty acids and increased
ketogenesis.1 There are three pivotal pathophysiology of hyperglycemia in diabetic
ketoacidosis: elevation of gluconeogenesis, the elevation of glycogenolysis, and
lower peripheral glucose uptake due to a decrease in insulin action in the receptors
or a decrease in insulin levels.4 The goal of diabetic ketoacidosis management in
pregnancy comprises restoring circulation, reversing progressive acidosis; reversing
proteolysis and lipolysis, normalizing blood glucose concentration, and replacing
electrolyte losses.5,6 For treatment of diabetic ketoacidosis in pregnancy, insulin is
frequently given via intravenous route, starting with a bolus of regular insulin at a
dose of 0.1 unit/kg body weight, and then, within five minutes followed by a
continuous infusion of regular insulin of 0.1 unit/kg/hour.7-9 Normal saline (0.9%
NaCl) is recommended as the initial intravenous fluid replacement in diabetic
ketoacidosis occurred during pregnancy.10 Pancreatitis, both acute and chronic, has
a reciprocal relationship with hyperglycemia. Pancreatitis can cause a hyperglycemia
crisis or diabetes mellitus and some studies suggest that diabetes can also trigger
pancreatitis. This case illustrates that the trigger for DKA is acute pancreatitis, it
could be the other way around. But there are also several other precipitating factors
such as infection, drugs, non-compliance with medication, undiagnosed diabetes,
substance abuse, and other co-morbidities. Infections such as pneumonia,
gastroenteritis, and urinary tract infections are the most common triggers.11 This
case report demonstrates diabetic ketoacidosis with acute pancreatitis occurred
during pregnancy due to medication omission, in a pregnant woman.
Case Report
A 33-year-old woman, gravida 2, housewife was admitted at 32 weeks of gestation
to the emergency department on February 2/2023 with a two-day history of nausea
and vomiting. She had a history of diabetes mellitus four years earlier and was
treated with 2 mg of glimepiride. She had no history of stroke, trauma, pancreatitis,
alcohol use, obesity, abused drug use, car accident, underlying infection, or no
family history of diabetes mellitus. She missed her medication one day due to
traveling to the village for greeting her family. The patient also complained of
abdominal pain that penetrated to the back which appeared suddenly and had been
aching since last night. Pain is not affected by position and is not affected when the
patient eats.
She presented with multigravida, shortness of breath, two-day history of nausea and
vomiting, abdominal tenderness, hypertension, elevated heart rate, increased
respiratory rate, and fatigue. The general state was discovered to be extremely
unwell with vital signs of consciousness from the physical examination, Glasgow
Coma Scale of E3V4M5, mean arterial blood pressure of 175/98 mmHg, pulse rate of
138 beats/minute, a body temperature of 36,8°C, a height of 1.51 m, a body weight
of 63 kg, and respiratory rate of 44 breaths/minute. Her body mass index showed
27.6 kg/m2 (normal value: 18.5–24.9 kg/m2). On head inspection, there were no
nodules or swollen lymph nodes, and the eyes seemed black. Her breath odor
revealed acetone-smelling breathing. She had also lowered skin turgor and dry
tongue, drowsy, Kussmaul breathing, sunken eyes, decreased conscious level. There
were also no anaemic or icteric conjunctiva or sclera, and there was no increase in
jugular venous pressure from the neck examination. When the chest was examined,
there were no cardiac abnormalities, vesicular breath sounds could be heard in the
lungs. When the abdomen was examined, the epigastric area was sensitive, the
bowel sounds were normal, and neither the Cullen's sign nor the Grey-sign Turner's
were present. Fetal heart rate of 138 beats/minute There is no edema, no injuries,
and the extremities are still warm.
Her laboratory investigations revealed: serum glucose level of 713 mg/dL (normal
value: <200 mg/dL), pH arterial blood of 6.944 (normal value: 7.35–7.45), partial
pressure of carbon dioxide of 9.3 mmHg (normal value: 35–45 mmHg), serum
bicarbonate level of 5.5 mEq/L (normal value: 22–26 mEq/L), white blood cell count
of 22,670 cells/mm3 (normal value: 4000–10,000 cells/mm3), serum sodium level
of 132.7 mEq/L (normal value: 135–147 mEq/L), serum potassium level of 5.89
mEq/L (3.0–5.0 mEq/L), amylase level of 1004.8 U/L (normal value: 28-100 U/L),
lipase level of 899.4 U/L (normal value: 0-160 U/L); and serum ketone level of 3.8
mmol/L (normal value: 0.6–1.5 mmol/L).
Ketone testing done using her urine sample showed ketonuria of 3+. Her chest X-
ray revealed normal examination. Her breath odor revealed acetone-smelling
breathing. She had also lowered skin turgor and dry tongue, drowsy, Kussmaul
breathing, abdominal tenderness, sunken eyes, decreased conscious level, pale
peripheries on examination. CT Abdominal revealed acute pancreatitis.
From the results of the anamnesis, physical examination and supporting
examinations, it was concluded that the patient had an observation diagnosis of
preeclampsia with severe metabolic acidosis, diabetes melitus with ketoacidosis
complication and acute pancreatitis.
Upon admission, she received fluid therapy with loading NaCl 0.9% 500 cc in 1 hour,
followed by 1000 cc in 24 hours, then with maintenance 20 drops/minute, then
given antibiotics Ampicilin Sulbactam 4x1.5 gram intravenously, insulin Aspart drip 6
units/hour intravenously, Sodium bicarbonate 50 meq intravenously slowly, followed
by 50 meq in NaCl 100 cc in 4 hours. The patient is fasted. The obstetrician
colleague planned to delivered the baby immediately. she was treated with insulin
infusion for 48 hours and antibiotics 4 times daily for her pancreatitis. Her blood
glucose level was checked five times a day.
The patient was treated for four days in the intensive care unit before being moved
to the ward for seven days. After 14 days of therapy, the patient was released with
improved clinical and laboratory results as well as stable blood sugar levels. The
patient showed marked improvement (fasting blood sugar level lowered to 115
mg/dL) and then, the attending internist switched intravenous insulin to
subcutaneous insulin (neutral protamine Hagedorn insulin at 18 and 18 international
unit), vildagliptin 100 mg once daily and discharged her back to her home. She was
recommended to carry on follow-up monthly at the endocrinology clinic.
Discussion
Complex diabetic ketoacidosis is present in this case, along with acute pancreatitis
and multigravida. According to the anamnesis and the patient's history of nausea,
vomiting, and abdominal pain that spread to her back and had been aching since
previous night, she has pancreatitis and diabetic ketoacidosis. During the physical
examination, it was discovered that the patient appeared to be in a serious state of
illness overall, had decreased consciousness as measured by the GCS E3V4M5, but
had no focal neurological deficit. Her breath odor revealed acetone-smelling
breathing. She had also lowered skin turgor and dry tongue, drowsy, Kussmaul
breathing, sunken eyes, decreased conscious level on examination. When the
abdomen was examined, it was discovered that the epigastric area was sensitive
and that the bowel sounds were normal. Her laboratory investigations revealed:
serum glucose level of 713 mg/dL, pH arterial blood of 6.944, partial pressure of
carbon dioxide of 9.3 mmHg, serum bicarbonate level of 5.5 mEq/L, white blood cell
count of 22,670 cells/mm3, amylase level of 1004.8 U/L, lipase level of 899.4 U/L,
and serum ketone level of 3.8 mmol/L. Ketone testing done using her urine sample
showed ketonuria of 3+.
According to recommendations from the American College of Gastroenterology
Guidelines, the patient also had acute pancreatitis, which was diagnosed based on
abdominal pain in the left upper quadrant or epigastrium. Constant, non-specific
pain that may radiate to the back, chest, or waist. Pain is typically very intense,
though it can vary. Also, the patient had elevated amylase and lipase levels that
were over eight times the upper limit of normal, which was confirmed by CT
Abdomen pictures.12
According to the 2013 revision of the Atlanta criteria, severe acute pancreatitis is
defined as persistent organ failure lasting more than 48 hours, as opposed to
moderately severe conditions, which are characterized by local complications (such
as peripancreatic fluid, necrosis of the pancreas, or peripancreas) and/or temporary
organ failure. This patient's prognosis was evaluated using the Ranson scale, which
was measured at the time of admission and over the first 48 hours of treatment.
This patient had a Ranson scale of 3 when they were admitted to the hospital.12
The most common etiologies of acute pancreatitis are gallstones (40-70%) and
alcohol (25-35%). If there is no history of gallstones and alcohol consumption,
medications, infectious agents, and metabolic causes such as hypercalcemia and
hyperparathyroidism can be considered. Serum triglycerides must be above 1000
mg/dl to be considered as a cause of acute pancreatitis if no other etiology is
found.9 In this patient, no gallstones were found on ultrasonography, history of
alcohol was denied, and triglyceride level was 164 mg/dl.
In this case, the patient was treated with the fluid treatment, bicarbonate and
insulin recommended by the ADA consensus protocol for managing ketoacidosis
diabetic condition. Fluid therapy starts with assessing hydration status. If
hypovolemia is severe, provide 0.9% NaCl 1 liter per hour. If there is mild
dehydration, check corrected serum sodium levels. If there is cardiogenic shock, use
vasopressors and keep an eye on your hemodynamics. 0.45% NaCl is administered
(250–500 ml/hour depending on hydration status) if the blood sodium level is high
or normal, and 0.9% NaCl is administered (250–500 ml/hour depending on
hydration status) if the serum sodium level is low. Fluids can be adjusted to 5%
dextrose with 0.45% NaCl 150-250 ml/hour when blood sugar exceeds 300 mg/dl.
Although the pH in this situation is still higher than 6.9, bicarbonate therapy is not
prescribed. Bicarbonate therapy is required at pH levels below 6.9. An intravenous
insulin bolus of 0.1 units/kgBW followed by 0.1 units/kgBW/hour continuously or
0.14 units/kgBW/hour continuously can be administered in a hyperglycemic
emergency. Provide a 0.14 unit/kg bolus and continue the prior insulin titration if
the blood sugar level does not decrease by at least 10% in one hour. If blood sugar
levels approach 300 mg/dl, titrate the insulin dose down by 0.02 to 0.05
units/kg/hour and keep them there until the patient's level of consciousness returns
to normal. While potassium levels in this patient were still within the range of 3.3-
5.2 mEq/L, potassium treatment was not administered. Electrolyte, renal, pH, and
glucose monitoring must be done every 2-4 hours in cases of hyperglycemia crisis
until the patient is stable. A subcutaneous multidose insulin regimen can be started
once DKA has resolved and the patient is able to eat. To switch from insulin titration
by intravenous to subcutaneous delivery, continuous insulin infusions should be
continued 1-2 hours after subcutaneous insulin is started to maintain adequate
plasma insulin levels. In patients who have just received insulin therapy, give insulin
doses of 0.5-0.8 units/kg BW per day and adjusted as needed.13,14
Moreover, this patient has acute pancreatitis, which calls for intensive hydration in
the first 12 to 24 hours. Reassessing hydration status should be done within the first
six hours, then every 12 to 24 hours after that with the aim of lowering blood urea
nitrogen. Enteral nutrition is more effective than parenteral nutrition for nutritional
treatment in patients of severe acute pancreatitis. Parenteral nutrition can be
explored if there is no enteral route, enteral nutrition cannot be tolerated, or if
meeting caloric needs by enteral route is challenging.12
If left untreated, diabetes mellitus, a common condition brought on by insulin
resistance or deficiency, can result in severe hyperglycemia and organ damage. The
pancreas is inflamed in acute pancreatitis, which significantly increases morbidity
and death. Rapid or unexpected death is substantially influenced by acute
pancreatitis and diabetes mellitus, conditions that are rarely both present in the
same person. Uncertain interrelationships exist between the two diseases in a
complex manner. Acute pancreatitis has been linked to diabetes mellitus in several
case reports.15
According to some experts, factors associated with insulin resistance and high
glucose levels can cause oxidative stress in pancreatic cells, which can lead to acute
pancreatitis and raise the chance of developing diabetes mellitus. The connection
between hyperglycemia crisis, severe pancreatitis, and hypertriglyceridemia
(particularly triglycerides that surpass 1000 mg/dL), also known as the perplexing
triangle, is discussed in numerous other publications. Lack of insulin results in
lipolysis, which releases free fatty acids (FFA) from adipose tissue. FFA will be
absorbed by the liver, starting the synthesis of very low-density lipoprotein and the
development of hypertriglyceridemia. Blood-circulating triglycerides trigger
proteolytic enzymes, which start pancreatic auto-digestion and cause pancreatitis.15
Studies have also suggested that diabetes is brought on by pancreatitis. The
connection between acute pancreatitis and newly diagnosed hyperglycemia and/or
diabetes mellitus was recently examined in a meta-analysis. Hyperglycemia alone
(or prediabetes) is more common in patients with acute pancreatitis (16%), whereas
diabetes mellitus is more common (23%). It should be emphasized that 70% of
individuals with pancreatitis-related diabetes mellitus require ongoing insulin
therapy.15
According to some experts, the proteolytic enzymes involved in the pathophysiology
of pancreatitis can also damage and lead to necrosis of the islet cells that make
insulin, which lowers blood levels of insulin and raises blood glucose. Data showing
that acute pancreatitis can cause hyperglycemia both momentarily and permanently
support the expert theory that it may cause a reaction in people who are
predisposed to diabetes.15
Acute pancreatitis has also been cited as a cause of diabetes mellitus, which is
currently classified as type 3c diabetes. Although it is said that loss of pancreatic β-
cells due to necrosis is the cause of diabetes mellitus (after acute pancreatitis),
more than 70% of patients do not have necrosis, or only less than 30% do, and
78% of patients are managed conservatively. So it is thought that there is another
mechanism besides necrosis. Glutamic acid decarboxylase and insulinoma antigen 2
(IA2) antibodies have been found in patients with latent autoimmune DM and type 1
DM. It is believed that those who are genetically prone to developing diabetes
mellitus respond to acute pancreatitis. The chance of acquiring acute pancreatitis,
also known as acute metabolic pancreatitis, as well as the risk of developing
diabetes mellitus after experiencing acute pancreatitis are both increased by specific
metabolic variables, such as obesity and hypertriglyceridemia.16
There is a two-way causative link between pancreatitis and hyperglycemia, with
pancreatitis causing diabetes mellitus and diabetes likewise causing pancreatitis,
according to a number of papers. For instance, patients with acute pancreatitis may
be more susceptible to systemic organ failure due to hyperglycemia, while diabetic
patients are more likely to acquire pancreatitis. Even blood sugar levels are an
important predictor for determining the prognosis of acute pancreatitis based on the
Ranson score.17,18,19
In addition to insulin resistance, rapid starvation, and respiratory alkalosis, the
pathophysiology of diabetic ketoacidosis in pregnancy is also defined by these
factors, generating a state that is ketosis-prone. Cortisol, a hormone that
encourages hyperglycemia, is produced during pregnancy, and the placenta also
secretes chemicals that counteract insulin's effects. When a woman is pregnant,
glucose can freely flow from the maternal to the fetal circulation, hyperglycemia in
the mother will prompt the fetal body to secrete insulin. The goal of treating diabetic
ketoacidosis during pregnancy is to restore electrolyte balance, return
hyperglycemia and acidity to normal.20 So that in this case still requires further
studies to determine the relationship between these two diseases. However, the
management of this case is very challenging because these two conditions
exacerbate each other, and if this case is not treated quickly and appropriately then
the risk of death is very high.
Conclusion
Diabetic ketoacidosis is a severe manifestation of absolute insulin deficiency and is
characterized by hyperglycemia, secretion of ketoacids, hemoconcentration,
acidosis, and eventually coma. Diabetic ketoacidosis is a rare but major risk during
pregnancy among women with diabetes and endangers the life of the mother and
fetus. However, acute pancreatitis is rarely mentioned as a source of triggering
diabetic ketoacidosis, thus adding to the complexity of treating this patient. She
presented with a two-day history of nausea and vomiting, and a one-day history of
shortness of breath, abdominal tenderness, multigravida, hypertension, elevated
heart rate, increased respiratory rate, and fatigue. Upon admission, she was treated
with insulin infusion for 48 hours and antibiotics for her pancreatitis.

Ethical
In order to submit this case in a scientific journal without revealing the patient's
identify, the author has gotten informed consent and the patient's consent.

Acknowledgements
We would like to thank the patient for her consent to this case report publication

Funding
There is no funding to report.

Conflict of Interest
The author stated there is no conflict of interest
References
1. American Diabetes Association. Diagnosis and classification of diabetes
mellitus. Diabetes Care. 2014;37(Supplement_1):S81–90. doi:10.2337/dc14-
S081
2. Pikovsky M, Tan MY, Ahmed A, Sykes L, Agha-Jaffar R, Yu CK. Euglycaemic
ketoacidosis in pregnant women with COVID-19: two case reports. BMC
Pregnancy Childbirth. 2021;21(1):1–7. doi:10.1186/s12884-021-03928-w
3. Bonora BM, Avogaro A, Fadini GP. Euglycemic ketoacidosis. Curr Diab Rep.
2020;20(7):1–7. doi:10.1007/s11892-020-01307-x
4. Petersen MC, Shulman GI. Mechanisms of insulin action and insulin
resistance. Physiol Rev. 2018;98(4):2133–2223.
doi:10.1152/physrev.00063.2017
5. Rosenbloom AL. The management of diabetic ketoacidosis in children. Diabetes
Ther. 2010;1(2):103–120. doi:10.1007/s13300-010-0008-2
6. Wolfsdorf J, Craig ME, Daneman D, et al. Diabetic ketoacidosis in children and
adolescents with diabetes. Pediatr Diabetes. 2009;10(Suppl 12):118–133.
doi:10.1111/j.1399-5448.2009.00569.x
7. Rameshkumar R, Satheesh P, Jain P, et al. Low-dose (0.05 Unit/kg/hour) vs
standard-dose (0.1 Unit/kg/hour) insulin in the management of pediatric
diabetic ketoacidosis: a randomized double-blind controlled trial. Indian Pediatr.
2021;58(7):617–623. doi:10.1007/s13312-021-2255-x
8. Wolfsdorf JI, Glaser N, Agus M, et al. ISPAD clinical practice consensus
guidelines 2018: diabetic ketoacidosis and the hyperglycemic hyperosmolar
state. Pediatr Diabetes. 2018;19 Suppl 27:155–177. doi:10.1111/pedi.12701
9. Calimag AP, Chlebek S, Lerma EV, Chaiban JT. Diabetic ketoacidosis. Dis Mon.
2022;14:101418. doi:10.1016/j.disamonth.2022.101418
10. Thawabi M, Studyvin S. Euglycemic diabetic ketoacidosis, a misleading
presentation of diabetic ketoacidosis. N Am J Med Sci. 2015;7(6):291.
doi:10.4103/1947-2714.157490
11. Quinlan, JD. Acute Pancreatitis. Am Fam Physician. 2014; 90(9):632-639
12. Chou W, Chung M, Wang H, Chen J, Chen W, Guo H, et al. Clinical
characteristics of hyperglycemic crises in patients without a history of diabetes.
J Diabetes Invest. 2014;5:657-662
13. Tenner S, Baillie J, DeWitt J, Vege SS. ACG Clinical Guideline:
Management of Acute Pancreatitis. Am J Gastroenterol. 2013;108:1400-
1415
14. Fayman M, Pasquel FJ. Management of hyperglycemic crises. Med Clin N
Am. 2017;101:587-606.
15. Kitabchi AE, Fisher JN. Hyperglycemic crises diabetic ketoacidosis (DKA)
and hyperglycemic hyperosmolar state (HHS). Dalam: Berghe GV,
ed. Contemporary Endocrinology: Acute Cause to Consequence. Edisi ke-23.
New York. 2013:119-147
16. Butler DC, Emanuel AJ, Self SE, Batalis NI. The interplay between
diabetes and pancreatitis: two case reports of sudden, natural deaths and
a review of the literature. J Forensic Sci. 2016;1-6.
17. Das SLM, Singh PP, Phillips ARJ, Murphy R, Windson JA, Petrov MS. Newly
diagnosed diabetes mellitus after acute pancreatitis: a systematic review
and meta-analysis. Gut. 2014;63:818-831
18. Xue Y, Sheng Y, Dai H, Cao H, Liu Z. Risk of development of acute pancreatitis
with pre-existing diabetes: a meta-analysis. Eur J Gastroenterol Hepatol.
2012;24:1092-1098.
19. Zechner D, Sempert K, Genz B. Impact of hyperglycemia and acute
pancreatitis on the receptor for advanced glycation endproducts. Int J
Clin Exp Pathol. 2013;6:2021-2039.
20. Rewers A, Kuppermann N, Stoner MJ, et al. Effects of fluid rehydration strategy
on correction of acidosis and electrolyte abnormalities in children with diabetic
ketoacidosis. Diabetes Care. 2021;44(9):2061–2068.