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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
1
National 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.
2
Reaven GM: Role of insulin resistance in human disease. Diabetes 37:1595-1607, 1988.
3
American Diabetes Association: Position statement: Management of dyslipidemia in adults
with diabetes. Diabetes Care 22:S56-59, 1999.
4
Haffner SM: Management of dyslipidemia in adults with diabetes: Technical review.
Diabetes Care 22:160-78, 1998.
5
Grundy SM, Vega GL: Two different views of the relationship of hypertriglyeridemia to
coronary heart disease. Arch Intern Med 152:28-34, 1992.
6
American 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.

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