Diabetes Case 3

Patient Background:

A 52 year-old woman presents to the emergency department reporting severe abdominal pain. She describes the pain as a 10, with 10 being the worst pain, and points to the epigastric area, stating that the pain sometimes feels as though it is moving towards her back. Her pain is associated with nausea, but no vomiting. She reports no known medical history other than being told that she might have “borderline” or “prediabetes” eight to ten years ago, but she has not followed up regularly with her doctor. She does not smoke or drink alcohol. In the emergency department, she is found to have a blood glucose level of 718 mg/dL (normal random, <140 mg/dL) and a glycated hemoglobin (HbA1c) of 15.8% (normal, <5.7%). Biochemical evaluation is significant for slight lactic acidosis and a markedly elevated serum lipase, but no evidence of ketosis. Because her blood sample appeared lipemic, her triglycerides are measured and found to be over 2000 mg/dL (desirable, <150 mg/dL).

The patient receives fluid resuscitation and is started on intravenous insulin in normal saline. Her blood glucose and triglyceride levels improve while her pain resolves and her appetite returns. After recovery, she understands that she is being discharged on insulin therapy and asks how diabetes mellitus may have contributed to her high triglyceride levels.

Question 1

Which of the following best explains the relationship between type 2 diabetes mellitus and hypertriglyceridemia-induced pancreatitis?

Insulin resistance is associated with suppression of low-density lipoprotein (LDL)
Insulin excess causes an increase in lipolysis and circulating levels of free fatty acids (FTAs)
Glucotoxicity results in insulin release
Insufficient insulin can lead to diminished lipoprotein lipase expression.
Incorrect!
Correct!
Correct Answer
Insufficient insulin can lead to diminished lipoprotein lipase expression.

Insulin promotes glucose uptake in the fat cell through the translocation of GLUT4 storage vesicles similar to that found in muscle cells. However, the glucose that adipocytes take up is not stored as glycogen, but rather partially metabolized down the glycolytic pathway to form glycerol-3-phosphate. This key metabolic intermediary serves as a backbone to which three FFAs are esterified to form triglyceride, which is then stored in the lipid droplet occupying most of the fat cell. Lipids are delivered to the fat cell through the circulation. Lipoprotein lipase located on the outside of the fat cell cleaves triglycerides to FFAs; these free fatty acids are taken up by adipocytes where they are re-esterified. Insulin enhances adipose tissue lipoprotein lipase expression. Insufficient insulin can contribute to excess levels of circulating FFAs and triglycerides.

Insulin promotes glucose uptake in the fat cell through the translocation of GLUT4 storage vesicles similar to that found in muscle cells. However, the glucose that adipocytes take up is not stored as glycogen, but rather partially metabolized down the glycolytic pathway to form glycerol-3-phosphate. This key metabolic intermediary serves as a backbone to which three FFAs are esterified to form triglyceride, which is then stored in the lipid droplet occupying most of the fat cell. Lipids are delivered to the fat cell through the circulation. Lipoprotein lipase located on the outside of the fat cell cleaves triglycerides to FFAs; these free fatty acids are taken up by adipocytes where they are re-esterified. Insulin enhances adipose tissue lipoprotein lipase expression. Insufficient insulin can contribute to excess levels of circulating FFAs and triglycerides.