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A 36-year-old G5 P2AB2 woman was admitted to our hospital due to nausea, vomiting and severe epigastric pain for one day at 24 weeks gestation. She had a history of diabetes for one year, but was not receiving any medical treatment. The patient also denied any other drug history or alcohol drinking. Physical examination revealed a blood pressure of 150/100 mmHg, body temperature 37°C, weight 60 kg, and height 159 cm. Cutaneous eruptions or xanthomas were not seen. The epigastric tenderness was severe, but without rebounding pain or muscle rigidity. Pelvic examination was unremarkable. Fundus height was 22 cm and foetal heart rate 140 beats/min. Laboratory studies showed a serum amylase level of 457 U/l (normal range <180 U/l) and lipase 1056 U/l (<190 U/l). Plasma sugar was 12.9 mmol/l, triglycerides 81.8 mmol/l and total cholesterol 20.7 mmol/l. HbA1c was 10.2% (4–6%), and postprandial serum C-peptide 0.2 nmol/l. Arterial blood gasses were pHa 7.23, paO2 113 mmHg at room air, paCO2 21 mmHg, base deficit 15 mmol/l. Blood ketone reaction was strong with 1:4 dilution. Abdominal sonography disclosed a swelling pancreas, but no evident biliary tract disease. Under a provisional diagnosis of acute pancreatitis, parenteral dextrose (2000 kcal/day by 50% glucose water and 0.9% glucose saline) and intravenous insulin were administered. Ketoacidosis was promptly corrected in one day and serum triglyceride was decreased to 13.5 mol/l by the seventh day. Thereafter a low fat diet was resumed and plasma sugar was well controlled by daily subcutaneous insulin. The serum triglyceride was further lowered to 3.3 mol/l after 2 weeks. The patient had a weight gain of 3 kg within 3 weeks of hospitalisation and finally gave birth to a healthy baby of 2600 g by caesarean section at the 38th week of pregnancy.
Questions
- 1
- What is the most likely cause of acute pancreatitis in this pregnant woman ?
- 2
- What are the possible mechanisms of her extreme gestational hypertriglyceridaemia ?
- 3
- How should her hypertriglyceridaemia be managed ?
Answers
QUESTION 1
Gestational pancreatitis is a rare complication with a high mortality for mother and foetus, the most common cause being biliary tract disease.1 However, in women with an underlying disorder of lipid metabolism, the possibility of gestational hypertriglyceridaemic pancreatitis should never be overlooked.2 Pregnancy is normally associated with a hyperlipoproteinaemia, and may be associated with as much as a 2.5-fold increase of very low density lipoprotein triglycerides (VLDL-TG) over pre-gestational levels in the middle of third trimester.3In the presence of a pre-existing lipid disorder such as familial hypertriglyceridaemia, a marked gestational hypertriglyceridaemia may occur.2 In view of the negative sonographic study of the hepatobiliary tract, denial of alcohol drinking and an extremely high plasma triglyceride level, our patient probably suffered from an acute attack of hypertriglyceridaemic pancreatitis.
QUESTION 2
Diabetes is known as a common cause of secondary lipid metabolism disorder and is often associated with increased plasma VLDL-TG levels and a marked hypertriglyceridaemia, over 2000 mg/dl, may even occur in some patients.4 5 Recently, some authors have stated that oestrogen therapy in diabetic women may lead to an extreme hypertriglyceridaemia, particularly in an uncontrolled glycaemic state, and then possibly induce acute pancreatitis.6 However, gestational hypertriglyceridaemic pancreatitis complicating uncontrolled diabetes has rarely been reported.
It had been shown that diabetic pregnancies are associated with higher plasma triglycerides than normal ones.3 7 Moreover, the increased levels of plasma triglycerides has been shown to be related to diabetic control.7 The accentuated hypertriglyceridaemia may be produced by a synergistic effect of diabetes and pregnancy on VLDL synthesis.7 In our patient, who had an uncontrolled diabetes before pregnancy, this is the most probable explanation for her extreme hypertriglyceridaemia. Nevertheless, we did not perform any other investigation of genetic lipid abnormalities on our patient or her family and could not exclude the possibility of an endogenous lipid disorder, in spite of the good recovery of hypertriglyceridaemia after insulin infusion.5Diabetic ketoacidosis, another acute metabolic complication noted in our patient, could also be associated with hypertriglyceridaemia.8 However, in the reported cases, hypertriglyceridaemia over 7000 mg/dl has rarely been found and our patient's hypertriglyceridaemia could not be attributed to diabetic ketoacidosis alone.8
QUESTION 3
Management of gestational hypertriglyceridaemic pancreatitis lies in correction of lipoprotein metabolism disturbances, and maintenance of nutritional support.9 Dietary fat restriction, lipid-free parenteral nutrition or plasma exchange have all been used to achieve this.9 10 However, antihypertriglyceridaemic drugs, such as fibric acid derivatives should not be considered, due to the possibility of teratogenic effects. Strict glycaemic control would provide another rational therapy.7 11 In our patient, diabetic VLDL-TG metabolism was normalised by intensive insulin therapy, possibly mediated by decreased hepatic VLDL synthesis and enhanced lipoprotein lipase due to the effects of insulin.12 13
Conclusion
A moderate hypertriglyceridaemia due to uncontrolled diabetes may have existed in our patient before pregnancy and was markedly exacerbated by the gestation. In consequence, acute hypertriglyceridaemic pancreatitis occurred, complicated by diabetic ketoacidosis.
Learning points
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pre-existing hypertriglyceridaemia may be exacerbated by pregnancy and thus induce a risk of acute hypertriglyceridaemic pancreatitis
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uncontrolled diabetes may exacerbate gestational hypertriglyceridaemia
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strict glycaemic control is effective in managing gestational diabetic hypertriglyceridaemia
Pancreatitis is a rare but serious event during pregnancy. Pregnant women with inadequately controlled diabetes may be at risk of hypertriglyceridaemia. Strict diabetic control during pregnancy is warranted to prevent hypertriglyceridaemic pancreatitis and achieve an optimal outcome for mother and foetus.
Final diagnosis
Gestational hypertriglyceridaemic pancreatitis and diabetic ketoacidosis, due to uncontrolled diabetes mellitus.