Endocrinol Metab 27(1):89-92, March 2012 http://dx.doi.org/10.3803/EnM.2012.27.1.89
CASE REPORT
Ketoacidosis with Hypertriglyceridemia-Induced Pancreatitis in a Patient with Gestational Diabetes: A Case Report Hyun Hee Chung, Sang Hyun Park, Ji Sung Yoon, Kyu Chang Won, Hyoung Woo Lee Department of Internal Medicine, Yeungnam University College of Medicine, Daegu, Korea
Hypertriglyceridemia-induced acute pancreatitis in pregnancy is not a common complication. Moreover, ketoacidosis in gestational diabetes occurs rarely. Here we report a case of ketoacidosis with hypertriglyceridemia-induced pancreatitis in a patient with gestational diabetes that was successfully treated with insulin and supportive care. In this case, a 36-year-old woman (at 32 weeks’ gestation) was diagnosed with gestational diabetes 4 weeks prior, but did not have well controlled blood sugar. She complained of severe epigastric pain concomitant with nausea and vomiting. Radiology and laboratory tests found hypertriglyceridemia (1,996 mg/dL), acute pancreatitis, and ketoacidosis with absence of fetal deceleration on a non-stress test. The patient’s condition improved with insulin therapy and fluid replacement. To our knowledge, this is the first report of a case of ketoacidosis with hypertriglyceridemia-induced pancreatitis in a patient with gestational diabetes. (Endocrinol Metab 27:89-92, 2012) Key Words: Acute pancreatitis, Gestational diabetes, Hypertriglyceridemia
INTRODUCTION
CASE REPORT
Hypertriglyceridemia is an uncommon but well recognized cause
A 36-year-old multigravida (gravida 7, spontaneous abortion 1,
of acute pancreatitis; other recognized causes are next alcohol abuse
and induced abortion 5) was at 32 weeks of gestation when she
and gallstone-induced disorders [1,2]. Chang et al. [3] reported that
visited an outpatient clinic to control her blood glucose. She had
hypertriglyceridemia causes 56% of all gestational pancreatitis. Dur-
been diagnosed with gestational diabetes by an oral glucose toler-
ing pregnancy there is a physiologic rise in plasma lipid levels, how-
ance test (50 g) showing 438 mg/dL 4 weeks prior. However, the
ever these increases are usually not enough to cause pancreatitis.
patient had not undergone further evaluation or treatment. The pa-
In a diabetic pregnancy, hypertriglyceridemia has been found to
tient did not have a history of alcohol drinking, drug abuse, gall-
be more exaggerated compared to the rise in plasma lipid levels
stones, signs of infection, or a family history of diabetes. However,
during normal pregnancy; this may be the root cause of a higher
she stated that she had been eating a high carbohydrate and caloric
prevalence of hypertriglyceridemia in acute pancreatitis. Diabetic
diet, which included instant noodles and had no diet control even
ketoacidosis (DKA) is a serious metabolic complication especially
after having received her diagnosis of gestational diabetes. Upon
in pregnancy. Its occurrence is not common, moreover in gesta-
hospitalization to control her blood glucose, her vital signs were
tional diabetes. As in any other disease associated with pregnancy,
stable and there was no abdominal pain or tenderness on exami-
acute pancreatitis and ketoacidosis lead to greater concerns as they
nation. Furthermore, there were no stigmas of hyperlipidemia, such
pose instant serious threat to the life of mother, fetus, or both. There
as xanthelasma, xanthoma, or eruptive xanthoma. A random blood
are some reports of hypertriglyceridemia-induced acute pancreati-
glucose test was 294 mg/dL and HbA1c was 8.6%. Initial biochemi-
tis in pregnancy [4-7] and DKA in gestational diabetes [8-10]. How-
cal analysis revealed WBC 6,100 K/µL (PMN 74.1%), hemoglobin
ever, the case described here is ketoacidosis with hypertriglyceri-
14.3 g/dL, hematocrit 30.4%, sodium 120 mEq/L, potassium 3.5 mEq/
demia-induced pancreatitis in patient with gestational diabetes.
L, chloride 91 mEq/L, BUN 5.2 mg/dL, total bilirubin 1.77 mg/dL,
Received: 3 August 2011, Accepted: 30 September 2011 Corresponding author: Ji Sung Yoon Department of Internal Medicine, Yeungnam University Medical Center, Yeungnam University College of Medicine, 170 Hyeonchung-ro, Nam-gu, Daegu 705-717, Korea Tel: +82-53-620-4049, Fax: +82-53-654-8386, E-mail:
[email protected]
Copyright © 2012 Korean Endocrine Society This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
http://www.enm-kes.org
Chung HH, et al.
90 direct bilirubin 0.88 mg/dL, and urine glucose (++++). Urine and
lyzed the patient’s lipid profile, which revealed total cholesterol (TC)
serum ketone bodies were negative. The fetal condition was satis-
level of 700 mg/dL, triglyceride (TG) 1,996 mg/dL, and low density
factory on a fetal non-stress test. While the patient was receiving
lipoprotein cholesterol (LDL-C) 117 mg/dL. The fetal status was mon-
multiple subcutaneous insulin injections with human insulin for
itored via non-stress testing, which demonstrated no variability at
blood sugar control, severe epigastric pain with nausea and vomit-
that time. We could diagnose ketoacidosis associated with hyper-
ing was developed on the 2nd hospital day. The nature of the pain
triglyceridemia-induced acute pancreatitis with fetal distress state.
was deep, continuous, and was improved by knee-chest position.
The patient fasted and was administered insulin therapy along with
At that time, the vital signs were stable, but there were epigastric
fluid therapy. Her symptoms and laboratory findings improved grad-
tenderness and decreased bowel sounds. Laboratory tests showed
ually (Table 1, Fig. 1B) with recovering of fetal stress status. On the
-
12th hospital day, the patient was discharged and provided with self-
a blood glucose of 277 mg/dL, pH 7.236, PCO2 25.8 mmHg, HCO3
10.6 mmol/L, base excess -15.4 mmol/L, sodium 124 mEq/L, total
injection insulin (MSII regimen) without fibrates. At 38 weeks of
bilirubin 2.04 mg/dL, direct bilirubin 0.33 mg/dL, hs-CRP 27.054
gestation, the patient delivered a healthy baby (birth weight 3,125 g)
mg/dL, amylase 385 IU/L, lipase 395 IU/L, and serum ketone bod-
by cesarean section. After 4 weeks of delivery, laboratory test showed
ies 3.6 mmol/L. On hepatobiliary ultrasonography, the pancreas
that fasting/2 hour postprandial blood glucose 219/531 mg/dL and
showed edematous changes with fatty infiltration, which suggested
C-peptide 2.07/8.20 ng/mL, TC 322 mg/dL, TG 322 mg/dL and
acute pancreatitis (Fig. 1A); there was no evidence of a biliary prob-
LDL-C 147 mg/ dL. Based on these levels, the patient’s medications
lem. In order to determine the cause of acute pancreatitis, we ana-
were switched to glimepiride/metformin, fibrate, and a statin medi-
Table 1. Patient’s laboratory result pH Base excess (mmol/L) HCO3- (mmol/L) Ketone body (mmol/L) Amylase (IU/L) Lipase (IU/L) ESR (mm/H) CRP (mg/dL) TC (mg/dL) TG (mg/dL) HDL-C (mg/dL) LDL-C (mg/dL)
2nd HD
3rd HD
4th HD
5th HD
6th HD
7th HD
7.236 -15.4 10.6 3.6 385 395 27.054 700 1996 117
7.272 -13.8 11.6 1.1 328 108 572 896 57.8 308
7.345 -12.7 11.5 0 65 68 120 15.718 551 578 53 382
7.344 -11 13.4 0 39 43 120 9.36 334 -
7.367 -10.5 13.4 504 391 33.9 384
7.374 -8 15.8 0 -
CRP, C-reactive protein; ESR, erythrocyte sedimentation rate; HD, hospital day; HDL-C, high density lipoprotein cholesterol; LDL-C, low density lipoprotein cholesterol; TC, total cholesterol; TG, triglyceride.
A
http://www.enm-kes.org
B
Fig. 1. A. Ultrasonographic finding in abdomen. Visible pancreas showed edematous change with surrounding fat infiltration; this is suggestive of acute pancreatitis. B. This shows a mildly improved state of acute pancreatitis. http://dx.doi.org/10.3803/EnM.2012.27.1.89
Ketaoacidosis with Hypertriglyceridemia-induced Pancreatititis in a Patient with GDM
cation. Without additional problems, the patient could be observed out of hospital.
91
Mild-to-moderate hypertriglyceridemia (usually < 400 mg/dL) can be found in any cause of acute pancreatitis, in which TG is not the primary cause of pancreatitis and should not be confused with
DISCUSSION
the marked hypertriglyceridemia that causes acute pancreatitis [18]. In general, a serum TG level of more than 1,000 mg/dL is required
During pregnancy, there is a physiologic increase in cholesterol
to precipitate acute pancreatitis, based on research reports [2]. DKA
and triglyceride plasma levels. In the diabetic pregnancy, hypertri-
itself may also pose a risk for hypertriglyceridemia at mild-to-mod-
glyceridemia has been found to be more exaggerated compared to
erate levels [19] and nonspecific elevations of amylase without clini-
the rise in TGs observed during normal pregnancy; however, there
cal evidence of pancreatitis in 24.7-79.0% of dyskeratosis congenita
are contradictory studies showing no additional increase in plasma
cases [20]. In our case, the level of serum TG was 1,996 mg/dL, which
TG levels for diabetic pregnant women [11,12]. Several mechanisms
could be enough to cause acute pancreatitis; this patient had spe-
have been suggested; all are related to augmentation of the insulin-
cific symptoms and sonographic findings consistent with acute pan-
resistant state and adipose tissue lipoprotein lipase (LPL) activity,
creatitis. The severity and complication rates with hypertriglyceri-
and in an increase in plasma estrogen concentrations [13]. However,
demic pancreatitis have been reported as higher than acute pan-
it has been suggested that this increase is not sufficient to cause pan-
creatitis from other etiologies, but mortality rates have had similar
creatitis, and preexisting genetic abnormalities in the lipid metabo-
findings.
lism are required. In this case, all of above factors except genetic
The incidence of DKA in pregnancy has been reported as 1-3%,
abnormalities, which we were not able to evaluate, were considered
with fetal loss rate of 9%. Although DKA occurs more common in
causes of hypertriglyceridemia with additional dietary factors, such
patients with type 1 diabetes, it has been recognized in patients
as the excessive intake of a high carbohydrate and high caloric diet.
with type 2 diabetes, as well as in patients with gestational diabe-
Hypertriglyceridemia can alter sodium levels leading to pseudo-
tes [8-10]. The majority (78-90%) occur in the second and third tri-
hyponatremia, since excess TG in serum can displace water-con-
mesters of pregnancy due to increased insulin resistance contrib-
taining sodium [14]. On initial observation, our patient’s case showed
uted by insulin antagonistic hormones like human placental lacto-
hyponatremia, which had recovered spontaneously with the low-
gen, prolactin, and cortisol. Other ordinary contributing factors may
ering of the TG level without additional treatments for the sodium
be cessation of insulin therapy (40%) and infection (20%), pregnancy-
level. Therefore, in the case of hyponatremia with severe hypertri-
related factors may be relative state of starvation by itself, lowered
glyceridemia, clinicians should consider the possibility of pseudo-
buffering capacity and the effect of emesis.
hyponatremia and avoid overtreatment with hypertonic saline.
In addition, the fetus may suffer from acidosis that crosses the
Acute pancreatitis is uncommon in pregnancy. Its incidence has
placenta, resulting from academia that decreases uterine blood flow,
been reported 1/1,000-1/10,000 births [15], and pancreatitis secondary
tissue perfusion, and oxygenation. Because the fetus is not directly
to hyperlipidemia has an estimated incidence of 1 in 25,000 births.
accessible, external fetal heart rate tracings may be useful in show-
However, it has been reported that hypertriglyceridemia caused
ing decreased or absent variability, absent accelerations, and late
56% of gestational pancreatitis [3]. The mechanism of how hyper-
decelerations. In this case, the fetal status was also monitored with
triglyceridemia precipitates acute pancreatitis remains unknown.
non-stress test that did not experience variability based on mater-
One possible theory is that pancreatic lipase hydrolyses excess TG
nal ketoacidosis, and any negative signs were reversed after treat-
by releasing free fatty acids into the vascular bed of the pancreas,
ment of maternal DKA. Several retrospective studies have reported
thereby causing pancreatic acinar cell and capillary injury, with re-
a perinatal mortality rate of 9-35% in cases of maternal DKA. Early
sultant ischemia. Another possible theory is that hyperviscosity,
recognition and proper treatment of maternal DKA may avoid ad-
due to elevated levels of chylomicrons in these pancreatic capillar-
verse fetal outcomes.
ies, leads to ischemia and acidosis in the pancreas [16]. It has been
Formal treatment guidelines for hypertriglyceridemia in pregnancy
postulated that genetic abnormalities in lipid metabolism may be
do not exist, nor are there guidelines for treatment of hyperlipid-
exacerbated during pregnancy and may cause gestational hyper-
emic pancreatitis, which consists primarily of supportive care. Sev-
lipidemic pancreatitis [17].
eral reports of effective management have included a low fat diet,
http://dx.doi.org/10.3803/EnM.2012.27.1.89
http://www.enm-kes.org
Chung HH, et al.
92
REFERENCES
detailed fluid administration, insulin injection to increase LPL activity, antihyperlipidemia therapy (e.g., fenofibrate), heparin injection to increase LPL activity, and plasmapheresis [16]. In our present case, hypertriglyceridemia was controlled simply with insulin and fluid without lipid lowering agents. To our knowledge, the present case is the first published case of ketoacidosis with hypertriglyceridemia-induced pancreatitis in a patient with gestational diabetes. By increasing awareness of hypertriglyceridemia as a cause of acute pancreatitis especially in gestational diabetes, pregnant women with any type of diabetes require follow-up for lipid abnormalities, in cases of screening or during
19:783-791, 1990 3. Chang CC, Hsieh YY, Tsai HD, Yang TC, Yeh LS, Hsu TY: Acute pancre-
atitis in pregnancy. Zhonghua Yi Xue Za Zhi (Taipei) 61:85-92, 1998 4. Crisan LS, Steidl ET, Rivera-Alsina ME: Acute hyperlipidemic pancreatitis
in pregnancy. Am J Obstet Gynecol 198:e57-e59, 2008 5. Roberts IM: Hyperlipidemic gestational pancreatitis. Gastroenterology
104:1560-1562, 1993 6. De Chalain TM, Michell WL, Berger GM: Hyperlipidemia, pregnancy 7. Sanderson SL, Iverius PH, Wilson DE: Successful hyperlipemic pregnancy.
요 약 고중성지방혈성 췌장염은 매우 드물어 급성 췌장염의 1-4%정도 이나, 임신 중 발생률은 54%정도로 보고되고 있다. 임신 중 발생하 는 케톤산증은 연간 임산부 1,000명당 4.6-8건 발생하는 것으로 알 려져 있으나, 임신성 당뇨병에서는 드물고, 기저 당뇨병을 가진 산모 의 감염이나, 인슐린 펌프의 오작동 등에 의해 발생하는 경우가 대부 분이다. 저자 등은 임신성 당뇨병 환자에서 고중성지방혈성 췌장염에 병발된 당뇨병성 케톤산증 1예를 경험하였기에 보고하는 바이다. 증례: 36세 산모(임신 32주)가 내원 4주 전 시행한 50 g 포도당 선 별검사에서 438 mg/dL로 임신성 당뇨병을 진단 받았으나, 치료 없이 지내다가 내과에서 시행한 추적검사상 무작위 혈당검사 294 mg/dL, 당화혈색소 8.6%로 혈당조절을 위해 입원하였다. 다회 피하 인슐린 주사로 혈당을 조절하던 중 입원 2일째 오심, 구토를 동반한 심한 상 복부 통증을 호소하여 시행한 동맥혈검사상 pH 7.213, PCO2 17.9 mmHg, PO2 53 mmHg, BE -19.6 mmol/L, HCO3 7 mmol/L, 음이온
차 17.6 mEq/L, 혈중 케톤체 3.6 mmol/L, 혈당 277 mg/dL, 아밀라제 385 U/L, 리파아제 395 IU/L였으며 간담도 초음파상 급성 췌장염 소
견을 보이고, triglyceride (TG)/total cholesterol (TC) low density lipoprotein cholesterol (LDL-C) 1996/700/117 mg/dL로 측정되었다.
비자극검사로 태아 상태 관찰하며 gabexate mesylate, 인슐린 정맥 투여로 임상증상 및 혈액검사상 호전을 보였다. 임신 38주에 제왕절 개술 시행하여 3,125 gm 남아를 출산하였고, 4주 후 공복 및 식후 2시간 혈당 219/531 mg/dL, TC/TG/LDL-C 227/322/147 mg/dL로 측정
되어 glimepiride/ metformin, fibrate, statin 복용하면서 외래 경과
http://www.enm-kes.org
perlipidemic pancreatitis. Am J Gastroenterol 90:2134-2139, 1995 2. Toskes PP: Hyperlipidemic pancreatitis. Gastroenterol Clin North Am
and pancreatitis. Surg Gynecol Obstet 167:469-473, 1988
an acute pancreatitis episode.
관찰 중이다.
1. Fortson MR, Freedman SN, Webster PD 3rd: Clinical assessment of hy-
JAMA 265:1858-1860, 1991 8. Bedalov A, Balasubramanyam A: Glucocorticoid-induced ketoacidosis in
gestational diabetes: sequela of the acute treatment of preterm labor. A case report. Diabetes Care 20:922-924, 1997 9. Maislos M, Harman-Bohem I, Weitzman S: Diabetic ketoacidosis. A rare complication of gestational diabetes. Diabetes Care 15:968-970, 1992 10. Bernstein IM, Catalano PM: Ketoacidosis in pregnancy associated with the parenteral administration of terbutaline and betamethasone. A case report. J Reprod Med 35:818-820, 1990 11. Montelongo A, Lasunción MA, Pallardo LF, Herrera E: Longitudinal study of plasma lipoproteins and hormones during pregnancy in normal and diabetic women. Diabetes 41:1651-1659, 1992 12. Rizzo M, Berneis K, Altinova AE, Toruner FB, Akturk M, Ayvaz G, Rini GB, Spinas GA, Arslan M: Atherogenic lipoprotein phenotype and LDL size and subclasses in women with gestational diabetes. Diabet Med 25: 1406-1411, 2008 13. Herrera E, Amusquivar E, López-Soldado I, Ortega H: Maternal lipid metabolism and placental lipid transfer. Horm Res 65 (Suppl 3):59-64, 2006 14. Howard JM, Reed J: Pseudohyponatremia in acute hyperlipemic pancreatitis. A potential pitfall in therapy. Arch Surg 120:1053-1055, 1985 15. McKay AJ, O’Neill J, Imrie CW: Pancreatitis, pregnancy and gallstones. Br J Obstet Gynaecol 87:47-50, 1980 16. Havel RJ: Pathogenesis, differentiation and management of hypertriglyceridemia. Adv Intern Med 15:117-154, 1969 17. Chang YT, Chang MC, Su TC, Liang PC, Su YN, Kuo CH, Wei SC, Wong JM: Association of cystic fibrosis transmembrane conductance regulator (CFTR) mutation/variant/haplotype and tumor necrosis factor (TNF) promoter polymorphism in hyperlipidemic pancreatitis. Clin Chem 54:131138, 2008 18. Nair S, Yadav D, Pitchumoni CS: Association of diabetic ketoacidosis and acute pancreatitis: observations in 100 consecutive episodes of DKA. Am J Gastroenterol 95:2795-2800, 2000 19. Fulop M, Eder HA: Plasma triglycerides and cholesterol in diabetic ketosis. Arch Intern Med 149:1997-2002, 1989 20. Yadav D, Nair S, Norkus EP, Pitchumoni CS: Nonspecific hyperamylasemia and hyperlipasemia in diabetic ketoacidosis: incidence and correlation with biochemical abnormalities. Am J Gastroenterol 95:3123-3128, 2000
http://dx.doi.org/10.3803/EnM.2012.27.1.89
