Case Study:
Mr. Rodriguez & Cardiovascular Disease

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What is the relationship between diabetes and cardiovascular disease?

Fast Fact The Adult Treatment Panel III (ATP III) made diabetes a coronary heart disease equivalent, elevating it to the highest risk category.1

Patients with diabetes are at increased risk for cardiovascular disease. In one study, for example, patients with type 2 diabetes without a prior myocardial infarction were at the same risk for myocardial infarction and cardiac mortality at seven years as patients without diabetes who had had a prior myocardial infarction (20% and 19%, respectively).

What do Mr. Rodriguez's lab results show?

Fast Fact Serum lipid abnormalities differ in patients with type 1 and type 2 diabetes.2

Laboratory findings 24 hours later:

• Total Cholesterol = 195 mg/dL
• Triglycerides = 280 mg/dL
• HDL-C = 31 mg/dL
• LDL-C = 108 mg/dL
• Plasma glucose = 134 mg/dL

What does his lipid profile show?

The lipid pattern in patients with type 1 diabetes is largely related to glycemic control. The Diabetes Control and Complications Trial (DCCT) found that patients with type 1 diabetes who were in reasonable glycemic control had similar serum lipid values to normal subjects, except for young women, who had somewhat higher serum total cholesterol and lower high-density-lipoprotein (HDL) cholesterol concentrations. In comparison, poor glycemic control is associated with hypertriglyceridemia and, in some patients, high serum low-density-lipoprotein (LDL) cholesterol and low HDL cholesterol concentrations.

Among patients with type 2 diabetes, insulin resistance, relative insulin deficiency, and obesity are associated with hypertriglyceridemia, low serum HDL cholesterol concentrations, and occasionally, high serum LDL cholesterol and lipoprotein(a) {Lp(a)} values. This pattern of lipid abnormalities can be detected before the onset of overt hyperglycemia and is thought to be due in part to hyperinsulinemia.

For any serum lipoprotein concentration, patients with diabetes have more coronary disease than patients without diabetes. This increase in risk may be due in part to qualitative differences in the lipoprotein fractions or to the presence of other proatherosclerotic metabolic changes. Two such changes are high serum concentrations of small dense LDL particles and elevated Lp(a) levels.

In addition, the oxidation of lipoproteins, particularly LDL, seems to be increased in patients with diabetes, especially those with poor glucose control, hypertriglyceridemia, and microvascular and macrovascular disease. Oxidation of LDL results in a moiety that is cytotoxic to vascular endothelial and smooth muscle cells, probably contributing to atherogenesis.

It has also been proposed that glycation of apolipoprotein B (apoB) is increased in diabetic individuals and may contribute to the development of atherosclerosis. According to this theory, glycation causes impaired recognition of LDL by its receptor on hepatocytes, thereby increasing its half-life. The glycated LDL is then taken up preferentially by macrophages via a separate receptor, promoting the formation of foam cells.³

With these lab results, what are your diagnoses?

Additional Laboratory Values

• EKG = sinus rhythm 3 mm ST depression in the inferior leads
• CPK = 348 mg/dL with positive MB fraction 15%
• Troponin = positive
• Blood glucose = 289 mg/dL
• A1C = 12.2%
• Lipids = pending
• Chemistry panel = normal
• Admission medications = 25mg/dL hydrochlorothiazide (HCTZ)

Diagnoses:

• Acute myocardial infarction
• Type 2 Diabetes

How can Mr. Rodriguez attain glycemic control?

Fast Fact Patients with diabetes have unfavorable prognoses after acute myocardial infarction.4

In the Diabetes Mellitus Insulin-Glucose Infusion in Acute Myocardial Infarctions (DIGAMI) study, intensive insulin-based glucose management improved survival in patients with type 2 diabetes who had had an acute myocardial infarction.⁵

As persuasive as the data was, a follow-up study (DIGAMI 2), compared three treatment strategies:

• Group 1 - acute insulin-glucose infusion followed by insulin-based long-term glucose control;
• Group 2 - insulin-glucose infusion followed by standard glucose control;
• Group 3 - routine metabolic management according to local practice.

In this new study, A1C did not differ significantly among groups 1-3 (approx 6.8%) after two years of follow-up. Mortality between Groups 1 (23.4%) and 2 (22.6%) did not differ significantly (HR 1.03; 95% CI 0.79-1.34; P=0.831), nor did mortality between Groups 2 (22.6%) and 3 (19.3%, HR 1.23; CI 0.89-1.69; P=0.203).⁷

Thus, DIGAMI 2 did not support the fact that acutely introduced, long-term insulin treatment improves survival in patients with type 2 diabetes following myocardial infarction when compared with a conventional management at similar levels of glucose control or that insulin-based treatment lowers the number of nonfatal myocardial re-infarctions and strokes.

However, epidemiological analysis confirms that glucose level is a strong, independent predictor of long-term mortality in this patient category, underlining that glucose control seems to be a critical element of their management. It seems that the specifics of how to achieve good control are not so important as the achievement "per se" of the best possible control.

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