Protocol

(This was used in the Swedish DIGAMI-1 study).

• Prepare a solution with 80 units rapid-acting insulin in 500 ml 5 percent dextrose in water (D5W).

• Measure blood glucose every 1-2 hours.

We adjust the solution infusion according to Table 16.3. The intravenous infusion of insulin is continued for 2-3 days. When the patient starts feeding, subcutaneous administration of insulin is initiated. Based on the DIGAMI-1 results, some authors propose insulin

Table 16.3. Insulin infusion rate in diabetic persons with acute myocardial infarction (AMI)

Glucose mg/dl (mmol/L)

Adjustment

200-270 (11.1-15.0) 120-200 (6.7-11.1) 70-120 (3.9-6.7) < 70 (3.9)

Increase the rate by 6 ml/h and inject 8 units rapid-acting insulin bolus iv. Increase the rate by 3 ml/h Stable infusion rate Decrease the rate by 6 ml/h Discontinue infusion rate until blood glucose is > 120 mg/dl (6.7 mmol/L). If symptomatic hypoglycaemia ensues, infuse 20 ml glucose solution 30 percent (about 2 amps Dextrose 35 percent). Readministration of the solution is performed at a lower rate by 6 ml/h.

administration to all diabetic patients after an acute MI, for at least a few months to a year. If receiving insulin prior to the ischaemic event, and as long as he or she was well controlled, the patient returns to the previous regimen. If insulin is to be started for the first time after this event, we follow the same insulin therapy rules that are followed for Type 2 diabetic patients started on insulin, mentioned elsewhere in the book (see Chapter 28).

If the patient is obese (BMI > 30 kg/m2) or overweight but with a waist circumference > 102 cm (40 in) for men or > 88 cm (34 in) for women, and as long as he or she has a normal renal function (serum creatinine < 1.5 mg/dl [132.6 mmol/L] for men and < 1.4 mg/dl [123.8 mmol/L] for women) and a relatively normal ejection fraction (> 40-45 percent), then metformin administration is necessary as well.

If metformin is not adequate for glycaemic control, a glitazone can also be given provided there is no heart failure or intense diastolic dysfunction (i.e., pioglitazone or rosiglitazone - not yet approved for coadministration with insulin in Europe). There is significant evidence from recent studies that the administration of medicines that potentiate insulin action on the tissues of diabetics is associated with fewer cardiovascular complications in Type 2 diabetic patients with acute MI compared with medicines that potentiate insulin secretion from the pancreas. If an insulin secretagogue is needed, glibenclamide is avoided (it theoretically acts on the myocardium as well and there is fear it might deteriorate ischeamia). Glimepiride 1-6mg/day or gliclazide 80240 mg/day are preferred. One of the rapidly acting insulin secretagogues can also be administered, such as nateglinide (60, 120, 180 mg tablets) or repaglinide (0.5, 1, 2 mg tablets) three times a day (immediately before main meals - if a meal is omitted, the medicine is omitted as well).

CASE STUDY 3

A 52 year old man presents to his family physician for a regular follow-up. He is suffering from Type 2 DM and brings in the results of some laboratory tests. His lipid profile is as follows: total cholesterol 218 mg/dl (5.64 mmol/L); HDL-cholesterol 37 mg/dl (0.96 mmol/L); triglycerides 180 mg/dl (2.03 mmol/L); and LDL-cholesterol 145 mg/dl (3.75 mmol/L). The doctor is worried and recommends initiation of hypolipidaemic treatment with a statin. The patient is wondering why a friend of his, with similar lipid profile results, was only given dietary advice and no medications.

The characteristic lipid abnormalities in patients with Type 2 DM are:

1. hypertriglyceridaemia;

2. low HDL-cholesterol;

3. increased concentration of small-dense LDL particles.

Hypertriglyceridaemia is the most common lipid abnormality (see Chapter 23). Nevertheless, the role of hypertriglyceridaemia as a CVD risk factor is partly due to the coexistent low HDL-cholesterol (HDL-C) levels. Most studies have shown a decline in HDL-C levels in diabetic patients. In many studies a reverse association between HDL-C levels and cardiovascular events was observed.

Total- and LDL-cholesterol levels may be normal or mildly increased in diabetic persons compared to non-diabetic ones. It should be noted, however, that the LDL particles have undergone structural changes. The most important is the predominance of 'small and dense particles', which have been associated with increased CVD risk since they are more easily oxidized and are more atherogenic. Thus, for the same LDL-cholesterol levels, diabetic persons have a higher cardiovascular risk.

Presence of qualitative, apart from quantitative, abnormalities is one of the reasons for the differential evaluation of the blood values in a diabetic compared to a non-diabetic person.

Results of large studies, both recent and in the past (such as the Heart Protection Study [HPS] and CARDS), have proven that statin administra tion aimed at achieving especially low LDL-C levels decreases CVD events in diabetic persons substantially.

CASE STUDY 4

A 47 year old woman has the following blood test results: fasting plasma glucose 117 mg/dl [6.5 mmol/L); triglycerides 140 mg/dl (1.58 mmol/L); total cholesterol 234 mg/dl (6.05 mmol/L); HDL-C 42 mg/dl (1.09 mmol/L); LDL-C 164 mg/dl (4.24 mmol/L). She is receiving antihypertensive medicines and her blood pressure is 140/90 mmHg. Her weight is 78 kg (172 lb) and her height 164 cm (5 ft, 5 in). Waist circumference is 93 cm (36.6 in). Her doctor tells her she is suffering from 'the metabolic syndrome'. What is the metabolic syndrome and to what is it due?

It is a clinical syndrome, characterized by the clustering/coexistence of a series of metabolic disturbances, associated with insulin resistance and promoting atherosclerosis.

Therefore, diagnosis of the metabolic syndrome identifies persons at high risk of CVD occurrence and should be performed with simple means.

It was described for the first time by Reaven in 1988. He used the term metabolic syndrome X for the congregation of certain abnormal manifestations, the common base of which is insulin resistance and subse-quent hyperinsulinaemia. (Note: insulin resistance is a central point of the metabolic syndrome disturbances and is associated with it aetiologically.)

The following manifestations are included in the classical description of the syndrome:

• impaired glucose tolerance;

• hypertension;

• high triglycerides;

The presence of the metabolic syndrome has been associated with an increased frequency of coronary heart disease and other forms of macroangiopathy.

During the following years, the concept of the metabolic syndrome was enriched by other metabolic disturbances as well, such as obesity (especially central obesity or android type), microalbuminuria, as well as coagulation and fibrinolysis abnormalities.

Diagnosis of the metabolic syndrome is based on criteria set by international medical organizations. There are mild differences among them. Out of the four groups of diagnostic criteria mentioned below, the first one (NCEP ATP-III) was considered practically more useful, whereas the last one (IDF) was only recently proposed, in April 2005.

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