The metabolic response of trauma patients in critical condition includes the dysfunction of the carbohydrate metabolism, leading to the increase in blood glucose level. The response is exacerbated by the release of the counterregulatory hormones (1). Metabolic changes in critically ill patients lead to lower immunity and increased morbidity and mortality (2). Glucose blood level measurements and glycemia control, as well as choosing appropriate nutritional therapy, can improve the metabolism and decrease the risk of infection (3). Early nutritional therapy in critically ill patients is the standard care in ICUs (intensive care units) around the world. Critical condition is characterized by metabolic disorders, which result in increased muscle catabolism, reduced lean body mass, and hyperglycemia. Nutritional therapy in critically ill ICU patients should prevent both negative protein balance and overfeeding. Doing so improves nutritional outcomes. The indications for parenteral nutritional treatment should be narrowed. It is indicated when enteral nutrition is contraindicated or inadequate. Blood glucose fluctuations are an independent risk factor for infections and increased mortality in ICU patients (4, 5). Therefore, it is suggested that standard enteral formulas should be modified in order to achieve stable glucose levels. In order to avoid dangerous consequences of hyperglycemia, many ICUs lowered the acceptable lower limit of blood glucose (6, 7). The optimal blood glucose range, however, is not specified (8, 9). The prevention of hyperglycemia in ICU patients during nutritional treatment consists of applying special dietetic formulas, and the treatment of hyperglycemia – by insulin administration (10). Standard enteral formulas that are high in carbohydrates and low in fat may hinder glycemic control (11, 12). The modification of carbohydrate content and the addition of monounsaturated fats and fiber enables better glycemia control when compared with standard enteral diets (13-15).

The American Association of Clinical Endocrinologists (AACE) and the American Diabetes Association recommend blood glucose range between 140 and 180 mg/dl in critically ill patients (16). In the majority of patients that are not in life-threatening condition, preprandial blood glucose level of 100-140 mg/dl and random blood glucose level under 180 mg/dl is recommended, under the condition that this range is safely achievable. It is recommended to maintain a higher glycemia in patients prone to hypoglycemia. However, it is advised that patients with severe medical conditions have a narrower glycemia range. Despite the lack of prospective randomized controlled trials that would justify the benefits of intensive glycemic control in nutritionally treated patients, several observational and interventional studies in ICU patients suggest that maintaining blood glucose level under 150 mg/dl improves the outcomes of the patients (17).

The relationship between hyperglycemia during parenteral treatment and worse treatment outcomes is known. The patients with hyperglycemia during total parenteral nutrition (TPN) are more likely to be admitted to ICU and to die, and their stay in the hospital is longer. It is not clear whether diabetes is an additional risk factor for complications in patients on nutritional treatment. In one study, patients with diabetes had higher risk of death, cardiac complications and systemic infections when compared with non-diabetic subjects (18). Other papers did not confirm the increased risk of complications and mortality in patients with diabetes, concluding that diabetes could even have a protective effects in spite of the higher glycemia (19). The analysis of two prospective studies on a high number of patients on TPN revealed that diabetes does not increase the risk for complications of hyperglycemia in ICU patients (20). Nutritional guidelines recommend that early nutritional treatment should be considered in every patients who will be unable to eat for three or more days in ICU and 5-10 days in other department (21). Parenteral nutrition, if indicated, should be initiated within the first 24-48 hours after the admission to the ICU, because it has been proven that it does not increase mortality when compared with enteral nutrition (22). The metabolic demand of most patients can be met with the supply of 25-35 kcal/kg body weight/day depending on the severity of the disease (23), whereas some patients in critical condition may require 15-25 kcal/kg body weight/day (24). This diet requires providing about 200 grams of carbohydrates per day. Carbohydrates are the main source of calories in most TPN formulas. Glucose is the major metabolic fuel for the human body. Brain and peripheral nerves, renal medulla, leukocytes, erythrocytes, and bone marrow use glucose as their main source of oxidative energy. The minimal glucose intake per day that allows to meet the demand of the brain is estimated to be 100-120 grams. In stress conditions, such as disease or trauma, if the glucose is not provided with exogenous nutrition, the glucose will be generated in gluconeogenesis from the aminoacidic precursors obtained from proteolytic processes of skeletal muscle. During starvation, providing glucose intravenously helps to spare body protein, as it reduces the need for the proteolytic energy substrates for gluconeogenesis. In a patient exposed to stress, the maximum rate of glucose oxidation is 4-7 mg/kg body weight/min (i.e. 400-700 g/day for a patient weighing 70 kg). Both enteral and parenteral nutritional treatment is effective in preventing the complications of starvation and malnutrition in hospital patients. In clinical practice, enteral nutrition is preferred due to higher risk of hyperglycemia and infection during TPN. The strategy of hyperglycemia treatment in patients requiring nutritional treatment should include diet modification, as well as effective and safe pharmacological treatment. Unfortunately, the fear of inducing hypoglycemia and the complexity of treatment of critical patients frequently excludes the introduction of such treatment. In order to prevent dangerous hypoglycemia, interdisciplinary training programs are conducted (25).

A few prospective randomized trials have evaluated the efficacy of strategies of prevention and treatment of hyperglycemia in patients fed enterally (26-32). The strategy of hyperglycemia control during enteral nutrition should include an assessment of caloric intake as well as pharmacological treatment with insulin. Enteral treatment is administered via a nasogastric tube, or rarer, a gastrostomy. A standard formula contains 1-2 kcal/ml and consists of protein, fat in the form of long-chain triglycerides, and carbohydrates. In contrast to the standard diet, in which carbohydrates provide 55-60% of total energy content, new formulas for diabetic patients provide more calories from nonsaturated fatty acids, with 35% of total energy provided from fat (33). Moreover, they contain more fiber (10-15 g/l) and fructose (33). Research on patients with diabetes indicated that lowering the carbohydrate intake in enteral diet decreased hyperglycemia and levels of HbA1c, as well as decreased insulin demand when compared to standard diet (34). However, there are no randomized trials on critical diabetic patients comparing standard enteral diets and diabetic enteral diets (35). Enteral nutritional treatment may lead to complications, such as bacterial colonization of the stomach and gastric retention, which may lead to aspiration of the gastric content into the lungs, as well as diarrhea. Additionally, an unexpected removal of the nasogastric tube and periodic cessation of enteral nutrition due to nausea or diagnostic process of gastrointestinal tract may increase the risk of hypoglycemia in patients treated with insulin (36).