CLINICAL DIABETES
VOL. 17 NO. 4 1999


CASE STUDIES


Case Study: A 55-Year-Old Man With Obesity, Hypertriglyceridemia, and Newly Diagnosed Type 2 Diabetes Who Collapsed and Died

Deborah Thomas-Dobersen, RD, MS, CDE, and Michael J. Dobersen, MD, PhD


Presentation
A 55-year-old Caucasian man presented with polyuria, polydipsia, and "feeling dry" during the past 2 months. His medical history was remarkable for a 3-year history of poorly controlled hypertriglyceridemia. His initial fasting serum cholesterol was 299 mg/dl, triglycerides were 928 mg/dl, and high-density lipoprotein (HDL) cholesterol was 30 mg/dl before treatment.

He was treated with gemfibrozil (Lopid) 600 mg twice daily and told to watch his diet and exercise. No referral was made to a registered dietitian.

Two years later, a fasting triglyceride level of 570 mg/dl prompted further increase of gemfibrozil to 600 mg three times daily (this exceeds usual recommended dosing). The patient took no other medications and denied drinking alcohol and smoking.

Physical examination revealed a height of 5'11", weight of 240 lb (body mass index [BMI] of 34.4 kg/m2), blood pressure of 150/88 mm Hg, and pulse of 80/min. There was no abdominal tenderness or organomegally. Laboratory evaluation showed a serum glucose of 397 mg/dl. Urinalysis revealed 3+ glucose and negative ketones.

The patient was started on 5 mg glyburide [Micronase] daily. He was also given a referral to a dietitian. That evening, the patient complained of abdominal pain, nausea, vomiting and flu-like symptoms. He collapsed at home and died a short time later. At autopsy, it was found that he died of acute hemorrhagic pancreatitis. The patient was also found to have severe arteriosclerotic cardiovascular disease with severe two-vessel coronary artery atherosclerosis.

Questions
1. What is a normal level of serum triglyerides?
2. What is the medical nutrition therapy for hypertriglyeridemia?
3. What are current recommendations for screening for diabetes?
4. What effect did the onset of diabetes have on this patient's hypertriglyc- eridemia?

Commentary
The National Cholesterol Education Program (NCEP) Adult Treatment Panel II1 gives the following classification for triglyerides:

normal                         200 mg/dl
borderline high             200–400 mg/dl
high                             400–1,000 mg/dl
very high                      >1,000 mg/dl

Hypertriglyceridemia can be primary (associated with familial hypertriglyceridemia) or secondary (due to diabetes mellitus, hypothyroidism, kidney disease, or medication). Important exacerbating factors are obesity and excess alcohol intake.

Hypertriglyceridemia and low HDL cholesterol (<35 mg/dl) are commonly seen in the insulin resistance syndrome, or Syndrome X. In fact, an increase in plasma triglyceride is the most common metabolic characteristic of Syndrome X. Although all insulin-resistant patients do not develop type 2 diabetes, many do. Insulin resistance is involved in the pathogenesis and clinical course of type 2 diabetes as well as hypertension and coronary heart disease.2

In type 2 diabetes, a common abnormal lipid pattern is an elevation of very-low-density lipoprotein (VLDL) cholesterol, a reduction in HDL, and a low-density lipoprotein (LDL) cholesterol that contains a greater proportion of small, dense atherogenic LDL particles.3 Diabetes, as a possible cause of the hypertriglyceridemia, should be evaluated and treated if found, as several studies have shown that this pattern of dyslipidemia precedes the onset of type 2 diabetes mellitus.4

The goals for medical nutrition therapy, the first line of treatment1 for borderline to high triglyceride values, are:

1. weight loss if indicated
2. restriction of alcohol intake
3. increased physical activity
4. the American Heart Association (AHA) Step 1 progressing to Step 2 diets, individualized for the patient

A weight loss of only 5% of total body weight effectively lowers triglycerides. Exercise can lower triglycerides by approximately 10%. If triglycerides increase on the AHA Step 2 meal plan, the amount of carbohydrate should be decreased and the amount of mono-unsaturated fats increased. At present, it is still controversial whether this has a long-term or a short-term benefit.

The NCEP Adult Treatment Panel noted that the expertise of a registered dietitian is very helpful in achieving adherence with these protocols.1 When referring a patient to a dietitian, include laboratory data on hyperlipidemia.

People with triglycerides >500 mg/dl are at risk of pancreatitis. This risk increases as triglycerides increase, becoming very high when serum triglycerides approach 2,000 mg/dl.5 Special immediate attention to lower triglycerides to <400 mg/dl is recommended. Severe dietary fat restriction (<10% of calories) in addition to pharmacological therapy is needed to reduce the risk of pancreatitis,3 as gemfibrozil will not be able to decrease serum triglycerides when they are extremely high (>1,500 mg/dl). This severe diet can decrease serum triglycerides by 20–25%. Further reduction to Adult Treatment Panel II goals of <200 mg/dl may be beneficial.

This patient's triglyceride level was inadequately treated. The patient did not make some follow-up appointments, and the dyslipidemia may have been refractory to treatment.

The onset of type 2 diabetes in this patient may have deleteriously raised the serum triglyceride levels in two ways: by directly increasing VLDL production and by decreasing catabolism due to decreased lipoprotein lipase activity. Several assumptions must be made at this point to understand the onset of acute hemorrhagic pancreatitis. It is reasonable to assume that the triglyceride level soared to >1,000 mg/dl sometime during the onset of the type 2 diabetes. It is also reasonable to assume that the actual onset of diabetes predated the onset of symptoms by several months, possibly a year. If diabetes had been detected, improved glycemic control would have been very effective in reducing serum triglycerides.

The exact mechanism whereby hypertriglyceridemia causes pancreatitis is unknown. Presumably, the extremely high level of serum triglycerides causes "sludging" in the pancreatic vasculature, resulting in ischemia and necrosis. Alternatively, pancreatic lipase breaks down triglycerides to free fatty acids, which at high levels can also cause pancreatitis by direct toxicity (personal communication, Robert H. Eckel, MD, Lipid Research Clinic, University of Colorado Health Sciences Center, Denver, Colo.).

Diabetes occurs more frequently in individuals with hypertriglyceridemia (>250 mg/dl) and/or an HDL level of <35 mg/dl, in patients who are obese (BMI >27 kg/m), and in people over the age of 45.6 The American Diabetes Association has recommended that screening for diabetes may be appropriate for individuals with one or more risk factors.6 This patient had three risk factors. The recommended screening interval is 3 years.

More aggressive treatment of hypertriglyceridemia and earlier detection of diabetes may have lessened the impact of the onset of diabetes on triglyceridemia, thereby preventing the premature death of this patient. A referral to a lipid specialist may have helped in treating this severe, complex, or refractory disorder. An inadequate understanding of the importance of weight loss, exercise, and diet changes may have prevented a satisfactory lowering of serum triglycerides.

Clinical Pearls
1. 
Hypertriglyceridemia should be carefully monitored and aggressively treated by weight loss, diet, exercise, alcohol restriction, and pharmacological means to keep serum levels <400 mg/dl to prevent possible pancreatitis and <200 mg/dl to prevent coronary heart disease.

2.  Patients presenting with lipid patterns similar to those found in type 2 diabetes (high triglycerides and low HDL) should be screened for diabetes.

3.  Medical nutrition therapy is the cornerstone of treatment for hyperlipidemia. Referral to a registered dietitian and a lipid specialist is recommended to help with such severe dyslipidemia.


REFERENCES

1National Cholesterol Education Program (NCEP) Expert Panel: Summary of the second report of the NCEP expert panel on detection, evaluation, and treatment of high blood cholesterol (Adult Treatment Panel II). JAMA 269:3015-23, 1993.

2Reaven GM: Role of insulin resistance in human disease. Diabetes 37:1595-1607, 1988.

3American Diabetes Association: Position statement: Management of dyslipidemia in adults with diabetes. Diabetes Care 22:S56-59, 1999.

4Haffner SM: Management of dyslipidemia in adults with diabetes: Technical review. Diabetes Care 22:160-78, 1998.

5Grundy SM, Vega GL: Two different views of the relationship of hypertriglyeridemia to coronary heart disease. Arch Intern Med 152:28-34, 1992.

6American Diabetes Association: Position statement: Screening for type 2 diabetes. Diabetes Care 22:S20-23, 1999.


Deborah Thomas-Dobersen, RD, MS, CDE, is in private practice, and Michael J. Dobersen, MD, PhD, is a forensic pathologist at the Arapahoe County Coroner's Office, in Littleton, Colo.


Copyright 1999 American Diabetes Association
Updated 11/99
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