1. Introduction

Diabetes mellitus is one of the most common metabolic disorders in the industrialized countries. The disease has been diagnosed in approx. five million people in Germany alone. This figure corresponds to about 6% of the total population (Bruns & Findler, 2001). It is estimated that 25% of all critically ill patients dependent on enteral or parenteral nutrition have a diabetic metabolism (Wright, 2000).

The disease diabetes mellitus is characterized by a total deficiency of insulin (type 1) or a progressive insulin resistance (type 2). Since insulin is one of the central hormones in human metabolism, numerous metabolic processes are impaired in patients suffering from diabetes. Insulin deficiency or insulin resistance have an especially marked effect on carbohydrate and lipid metabolism. The direct results are periods of hyperglycemia (i.e. elevated blood sugar) and altered blood lipid values which are the cause, over the long term, of the increased morbidity and mortality exhibited by these patients. Typical diabetic complications include kidney damage (nephropathy), blindness (retinopathy) and a heightened risk of developing cardiovascular disease.

Precise monitoring of the metabolic status of diabetic patients is vital in order to improve their life quality and life expectancy. Blood sugar values should be kept within narrow limits; blood lipid and blood pressure values have to be brought into line with normal values. In addition, a reduction of overweight is advisable, especially in patients with type 2 diabetes mellitus. Since the discovery of insulin in 1921, the pharmacological treatment of diabetes has met with increasing success. Besides insulin, there are numerous oral medications available today which permit better metabolic management of patients with type 2 diabetes mellitus.

Next to pharmacological treatment, a balanced diet adapted to the specific metabolic requirements of the diabetic patient plays an outstanding role in the treatment of diabetes mellitus. Within the context of clinical nutrition, in particular, the successful combination of selective diabetic nutrition and pharmacological therapy has made a major contribution toward improving metabolic control and clinical outcome.

[Table of contents]

2. Definitions

The intestinal microflora represents a complex ecosystem affected by various environmental factors. It can be altered, for example, by several constituents of the human diet as well as by bacteria contained in our food. The following definitions will provide a survey of the nutrient groups involved.

Abnormal glucose tolerance

The measurement of HbA1c, a subgroup of hemoglobin altered by glycosylation, is very important for the long-term evaluation of the glucose concentration. HbA1c is created by a chemical reaction between glucose and the primary amino group of hemoglobin. This glycosylated form of hemoglobin remains stable over the entire lifetime of the erythrocytes; for this reason, it provides valuable information on the mean blood sugar value during the last 6-8 weeks. Whereas HbA1c values equal to < 6.0% of total hemoglobin are considered normal values > 7.5% point to a permanently elevated plasma glucose concentration. A change in the HbA1c value of 1% corresponds roughly to a change in the mean plasma glucose concentration of 36 mg/dl or 2.0 mmol/l (Landgraf & Haslbeck, 1999; Schumacher, 1999).

[Table of contents]

2.1 Classification & clinical picture

Diabetes mellitus is a heterogeneous disease; the term is used to describe all forms of acute and chronic hyperglycemia (elevated blood sugar) accompanied by additional disorders of carbohydrate and lipid metabolism (Badenhoop & Usadel, 1999). The complex diabetic syndrome is broken down into several types. The most recent concept for the classification and diagnosis of diabetes mellitus was presented by the American Diabetes Association (ADA) in 1997. It is based primarily on etiological and pathogenetic criteria and recognizes four different classes of diabetes mellitus (Table 3).

III

[Table of contents]

2.1.1 Diabetes mellitus type 1

Diabetes mellitus type I usually has an onset during childhood or adolescence; however, it can also appear for the first time in later life. Patients with type 1a have a genetic predisposition causing increased antibody formation against the endogenous ß-cells of the pancreas. This leads first to a reduction of insulin production and finally to total insulin deficiency. The causes of the autoimmune reaction have not yet been fully elucidated; it is suspected that viral infections, various toxic substances and nutritional factors play a role (Kasper, 2000).

In the Federal Republic of Germany diabetes mellitus type 1a accounts for approx. 5% of all cases of diabetes. So far no plausible explanation exists for the pathogenesis of subtype 1b, or idiopathic diabetes mellitus; this form of the disease is practically unknown in Europe (Kerner, 1998).

With the onset of total insulin deficiency, type 1 diabetics require an external supply of insulin (Cf. 3.2). For this reasons, this form of the disease was long referred to as "insulin-dependent diabetes mellitusö (IDDM). In this form of the disease, the intake of food and the administration of insulin must be coordinated carefully to prevent excessive fluctuations in their blood sugar concentration and the concomitant complications (Cf. 2.3 and 2.4).

[Table of contents]

2.1.2 Diabetes mellitus type 2

Diabetes mellitus type 2 usually has an onset in adulthood. It is characterized by pronounced insulin resistance – usually in combination with inadequate insulin secretion. The main causes of diabetes mellitus type 2 are sustained hyperalimentation, possibly in connection with hepatic and muscular insulin resistance of genetic origin. To stimulate the insulin-resistant tissue sufficiently, the body initially produces more insulin – a condition referred to as compensatory hyperinsulinemia. The organism reacts to this oversupply by reducing the number of insulin receptors – a mechanism known as "down regulationö. A hypercaloric diet worsens this vicious cycle, since the above-average increase in blood sugar augments insulin production; this again leads to intensified down regulation (Kasper, 2000).

Owing to the permanent over-stimulation of the ß-cells in the pancreas, the patient experiences phases of insulin deficiency; these are initially noticeable during the phases of maximum insulin secretion, i.e.

• during the postprandial rise in blood sugar
• in particular stress situations
• during the morning hours when an increased amount of insulin antagonists is secreted into the blood as a result of the circadian rhythm.

This leads to phases of hyperglycemia or glucose intolerance (Bruns & Findler, 2001).

During the hyperinsulinemic phases, the diabetes can still be managed by dietary measures and physical exercise since a reduced supply of energy leads to "up regulationö (i.e. an increase) of the insulin receptors. Only after the ß-cells of the pancreas start to secrete less insulin is the administration of insulinotropic substances, or insulin, indicated (Kasper, 2000).

Type 2 diabetes mellitus accounts for approx. 92% of all cases of diabetes. The incidence is cumulative and affects over 20% of the total population after age 60. Diabetes mellitus type 2 occurs frequently in combination with obesity, hyperlipoproteinemia and hypertension. The simultaneous occurrence of these conditions is referred to as the "metabolic syndromeö and characterizes a group of people at risk of developing premature arteriosclerosis (Bruns & Findler, 2001).

[Table of contents]

2.1.3 Other forms of diabetes mellitus

In the ADA classification system, class III comprises all other types of diabetes; these are broken down in the subgroups A to H. Group A includes the so-called MODY types (MODY = maturity onset diabetes in young people), which have previously been classified as diabetes mellitus type 2 because they are non-insulin-dependent. This form of the disease generally appears before the age of 25 and is characterized by genetic defects of ß-cell function. Groups B to H represent types of diabetes caused by a number of primary diseases or are induced by drugs and/or toxic substances (Table 3). The diabetic syndromes classified as Group III account for 3% of all cases of diabetes (Badenhoop & Usadel, 1999; Bruns & Findler, 2001).

The defining feature of gestational diabetes (Class IV) is hyperglycemia diagnosed for the first time during pregnancy. Class IV is a heterogeneous group; it includes both women who have developed a short-term disturbance of glucose tolerance caused by the metabolic changes occurring during pregnancy and women with diabetes mellitus type 1 or 2 which has manifested itself for the first time during pregnancy. The incidence of class IV diabetes is 2-4% of all pregnant women (Sauer & Rath, 2001).

[Table of contents]

2.2. Metabolism

Diabetes mellitus is caused by deficient insulin production by the ß-cells of the pancreas and/or insulin resistance of the insulin-sensitive tissue. Because insulin is a hormone which plays a central role in human metabolism, diabetes is inevitably accompanied with numerous other metabolic disturbances; these can cause both short-term and long-term damage to the organism (Cf. 2.3 and 2.4).

Insulin performs vital functions in carbohydrate, lipid and protein metabolism; in addition, it stimulates the transport of sugars and amino acids across membranes (Table 4):

[Table of contents]

2.2.1 Effects on carbohydrate metabolism

In the healthy organism the rise in the blood glucose concentration following food intake causes increased insulin secretion by the ß-cells of the pancreas. This reaction takes place in two phases; whereas the first phase is triggered by the rapid change in the glucose concentration, the second depends on the level of glucose concentration. This biphasic insulin secretion ensures precise regulation allowing the organism to maintain the postprandial blood glucose concentration within the narrow range of 60-160 mg/dl (Fig. 1). Insulin causes the uptake of blood glucose by fat tissue and muscle. In the liver (which can take up glucose independently of insulin), as well as in other tissue, insulin stimulates the process of glycogenesis, i.e. the formation of glycogen, a glucose-storage substance.

The average carbohydrate uptake of an adult is approx. 240 g per day; of this total, about 170 g is broken down into glucose – and absorbed – in the intestines. Apart from dietary glucose, a person weighing 70 kg produces approx. 240 g of endogenous glucose in the liver (gluconeogenesis). This endogenous glucose ensures that, even during periods of fasting, there will be an adequate supply of glucose to tissues which exclusively require glucose as energy substrate (i.e. erythrocytes, renal medulla, parts of the brain). Insulin regulates the process of gluconeogenesis in order to prevent overproduction of glucose and the resulting elevated fasting blood sugar values. A fasting blood glucose value of 100 mg/dl is associated with a balanced production of glucose (Chanteleau, 1995).

Besides insulin, there are other hormones (e.g. glucagon, catecholamine, growth hormone, somatostatin, etc.) which have effects on carbohydrate metabolism. The exact mechanism of action of these hormones will not be dealt with in detail here.

The type of food intake has a substantial effect on the rise in blood glucose and can reduce the amount of insulin required for blood glucose regulation. Already at the end of the last century it was abserved , that different types of foods with the same carbohydrate content cause blood glucose to rise to different levels after meals. A Glycemic Index was set down on the basis of these this finding showing the rise in blood glucose measured after a carbohydrate-containing meal expressed as a percent of the increase in blood glucose after the ingestion of the same amount of pure glucose (Fig. 2).

The glycemic index of a food is specific for a particular substrate and person. Numerous factors contribute to the value of the index: the percentage of dietary fiber which is effective in reducing blood sugar (Cf. 4.2), the manner in which the carbohydrate food was prepared, the water content of the food (liquid dietary components are absorbed faster), temperature, physical consistency, size of the meal, and individual variation. It is evident, from this broad spectrum of contributing factors, that precise determination of the glycemic index is virtually impossible. Nevertheless, it makes sense for the diabetic – and in particular the type 2 diabetic – to choose foods with a low glycemic index (Table 5) since these result in lower postprandial in blood sugar levels while leading to other beneficial effects, such as weight-reduction, by virtue of the large amount of dietary fiber they usually contain (Laube & Mehnert, 1999; Cf. 4.2).

The blood glucose concentration is also affected by physical exercise. Owing to the consumption of glucose by the muscles, muscular activity forces a non-insulin-dependent outflow of blood glucose into the muscle cells. As a consequence, carbohydrates ingested during muscular activity are utilized without the necessity of a burst of insulin production by the ß-cells (Fig. 3).

The insulin deficiency or insulin resistance exhibited by diabetic patients results in abnormal blood sugar levels, either in the form of hyperglycemic phases (in untreated individuals) or hypoglycemic phases (in individuals with poor diabetes management resulting, for example, in the admission of overly high doses of exogenous insulin. These hyperglycemic and hypoglycemic phases can lead to diabetic coma and a bevy of long term complications (Cf. 2.4).

[Table of contents]

2.2.2 Effects on lipid metabolism

In patients with the clinical picture of diabetes, the regulation of blood sugar is generally the main goal of the treatment. However, the changes of lipid metabolism due to insulin deficiency deserve at least equal attention. As shown in Table 4, insulin is responsible, under normal metabolic conditions, for inhibition of lipolysis as well as for stimulation of triglyceride and fatty acid synthesis.

In the presence of an adequate glucose supply, a balance is struck in fat tissue between lipolysis and the re-esterification of free fatty acids. When the inflow of glucose into the tissue is reduced, as in individuals who have diabetic metabolism or are fasting, the triglycerides (stored fat) are increasingly broken down into free fatty acids and glycerol. These free fatty acids are discharged into the blood and transported to the muscles and liver. Since the liver cannot utilize all of the free fatty acids for energy production, some of the free fatty acids are converted to ketone bodies or, via re-esterification, to triglycerides.. The ketone bodies serve as energy carriers which can be freely transported in the blood and can serve as an energy substrate in the muscles.

In persons with absolute insulin deficiency (diabetes mellitus type 1), too many ketone bodies may enter the blood, leading to metabolic acidosis (Cf. 2.3). The triglycerides synthesized in the liver are discharged into the bloodstream again so that they do not accumulate in the liver. In the blood they are transported by lipoproteins. The release of an increased amount of lipoproteins into the blood frequently results in hyperlipoproteinemia, especially in diabetics who are already obese. These elevated blood lipid values heighten the risk of aortosclerosis immensely (Hepp & Haring, 1999, Koolmann & Röhm, 1998). The typical clinical picture of hyperlipoproteinemia comprises elevated VLDL (very low density lipoprotein) values, elevated total cholesterol and LDL (low density lipoprotein-cholesterol) values and reduced HDL (high density lipoprotein) - cholesterol concentrations (McCargar et al, 1998).

[Table of contents]

2.2.3 Effects on protein metabolism

Protein metabolism is also impaired in patients with diabetes mellitus. The deficiency of insulin or the lack of effect of the insulin present results in a decreased intake of amino acids by the muscles simultaneous with a reduction of protein synthesis and enhanced proteolysis. The result is catabolism of the muscles with huge depletion of protein stores despite the large supply of other fuels. The degraded amino acids are primarily transported to the liver in the form of alanine; here they are used either for gluconeogenesis (further increase in blood sugar) or the production of urea (Hepp & Haring, 1999).

[Table of contents]

2.3 Direct consequences of diabetic metabolism

As described in 2.2, insulin deficiency leads to an increase in blood sugar via several routes and, in addition, to intensified degradation of lipids and proteins. If the blood sugar level remains above 160 mg/dl – 180 mg/dl for longer periods, the excess glucose will be excreted via the kidneys. This sugar can be demonstrated in the urine once the borderline kidney threshold value, i.e. the ability of the kidney to re-absorb glucose, is exceeded. Owing to the high osmotic pressure exerted by the sugar, urine production also rises (polyuria) to up to 10-15 L/day. This enormous loss of liquids and electrolytes can hardly be offset by drinking even enormous amounts of liquid. The consequences are weakness, tiredness, lack of drive. The increasing imbalance between fluid loss and fluid intake leads to exsiccosis and culminates in a hyperosmolar diabetic coma.

The intensified lipid degradation and the resulting overproduction of ketone bodies can cause complications. Acetone and the organic acid cations acetoacetate and hydroxybutate, result in over-acidification of the blood (acidosis) which causes deeper respiration (Kussmaul respiration and acetone breath) and vomiting. These developments accelerate the loss of fluids and electrolytes. Furthermore, the concomitant ketoacidosis precipitates and earlier onset of hyperosmolar coma (Fig. 4).

In addition to hyperglycemia, hypoglycemia is an additional risk in patients with diabetes mellitus. Plasma glucose values below 50 mg/dl lead to hypoglycemic shock. The symptoms of hypoglycemic shock are unconsciousness, breaking out in sweats and tremor. Frequent hypoglycemia results in cognitive dysfunction and an impaired sense of equilibrium; in older patients, in particular, this can have fatal consequences. Many different factors can trigger a drop in blood sugar: the most common are the improper use of hypoglycemic medication, vomiting after the injection of insulin, diabetic gastroparesis (Cf. 2.4.3), and stress situations (Schrezenmeir, 1998; Kasper, 2000).

[Table of contents]

2.4 Long term complications

Over the long term poor blood sugar management – especially if accompanied by frequent hyperglycemic phases – can cause a host of long term complications. These affect both small vessels (microangiopathies) and major arteries (macroangiopathies). Angiopathies are responsible for more than 75% of deaths among diabetic and are thus the most common cause of death in this group (Janka & Standl, 1999: Gonzáles Barranco 1998).

The "advanced glycosylation end productsö (AGE) also make a major contribution to the development of numerous long term complications of diabetes. These products consist of glycosylated cellular constituents. They are created by the reaction of reducing sugars with free amino acid groups of proteins. The accumulation of altered cellular constituents due to poorly controlled blood glucose can cause irreversible damage to various cellular structures (Kasper, 2000).

It is now assumed that oxidative stress also plays an important role in the pathogenesis of diabetic complications. The term "oxidative stressö describes a lack of balance between the production of free radicals and presence of antioxidant defense mechanisms. Antioxidant systems include substances such as flavonoids, vitamin E and C, carotinoids and endogenous enzymes such as catalase, superoxide dismutase and glutathione peroxidase, which convert free radicals into compounds which are less toxic to the cells. In patients with diabetes, both the overproduction of free radicals (via hyperglycemia) and a smaller reserve of antioxidant substances or enzymes have been demonstrated (Rösen et al, 2001; Cf. 4.5).

[Table of contents]

2.4.1 Macroangiopathies

Macroangiopathies occur in diabetics at an earlier age than in non-diabetics and exhibit a rapid course. In particular, the cerebral and coronary vessels and the vessels of the extremities are affected. The pathogenesis of the artherosclerotic changes takes a similar course in diabetics and in other patients; however, it is greatly accelerated by factors such as increased oxidative stress and a heightened metabolic imbalance (Janka & Standl, 1999). Type 2 diabetics – a group with a high incidence of the trio of high blood pressure, hyperlipoproteinemia and obesity known as the "metabolic syndromeö – are especially prone to heart attacks and stroke; in fact, these events occur two to six times more frequently in this group than in the rest of the population (Gonzáles Barranco, 1998). Amputations of the lower extremities have to be performed more frequently in patients with diabetes mellitus than in the population as a whole. These conditions affect men more frequently (i.e. 1.18 times as often) than women. Although doctors have succeeded in lowering this incidence in recent years, this success story is confined to the group of patients with insulin-dependent diabetes mellitus (IDDM). Patients with non-insulin-dependent diabetes mellitus (NIDDM), in contrast, have not benefited from this development (Ebskov & Ebskov 1996). According to general estimates, improved control of blood sugar values could reduce the number of amputations in diabetic patients by 50% and significantly reduce the incidence of cardiovascular events (Risse, 1999).

[Table of contents]

2.4.2 Microangiopathies

Microangiopathies are changes in the epithelia of smaller vessels such as arterioles and capillaries. The duration of manifest diabetes and the quality of blood sugar management are the most important factors in the pathogenesis of this condition. Microvascular changes occur in both types of diabetes and frequently culminate in renal insufficiency (nephropathy) and blindness (retinopathy) (Gonzáles Barranco, 1998). Approximately 30% of all new cases of blindness are due to diabetes (Janka & Standl, 1999).

After a diabetic history of 10 to 15 years, approx. 20-40% of diabetics patients will develop renal damage (nephropathy). The percentage of type 2 diabetics with renal failure is somewhat lower (10-20%): the late onset of the disease is given the credit for this lower incidence. Consistent control of blood sugar and blood pressure values, and a moderately reduced intake of protein in patients who already exhibit renal insufficiency, are two measures proven effective in preventing nephropathy (Floege, 2001).

[Table of contents]

2.4.3 Polyneuropathy

Autonomous polyneuropathy is another long term complications of diabetes. Unlike other complications experienced by diabetics, polyneuropathy is in itself not life-threatening. Nevertheless, it can be very unpleasant for the diabetic. The symptoms range from cardiovascular disorders over diarrhea, gastroparesis, abnormal sweat regulation straight through to urogenital dysfunction and impotence (Schumacher, 2000).

In patients with gastroparesis, stomach motility is impaired. This leads to delays in postprandial gastric emptying. This complication can lead to unaccustomed metabolic fluctuations accompanied by hypoglycemic phases following the intake of food. The most frequent symptoms are persistent sensation of bloating, abdominal pain, nausea and vomiting (Schumacher, 2000).

In the diabetic patient, the motility of the small intestine and colon may also be compromised by autonomous polyneuropathy. The lessened motility of the small intestine can result in excessive bacterial growth and diarrhea. Similarly, constipation occurs far more frequently in diabetics (22%) than in control individuals (7%) as a result of their impaired colon motility (Vogt et al, 1999). Dietetic treatment concepts can mitigate the gastrointestinal symptoms listed above (Schumacher, 2000; Cf. 4.2).

[Table of contents]

3. Treatment of diabetes mellitus

Diabetes mellitus is one of the frequent metabolic diseases in the western world. The numerous complications and long term complications of diabetes are the cause of the higher morbidity and mortality seen in this group of patients. In the 1990s two large long-term epidemiological studies were performed in the USA (Diabetes Control and Complications Trial) and Great Britain (United Kingdom Prospective Diabetes Study), respectively. The results of both studies showed that good blood sugar management is the best prerequisite for a reduction of diabetic complications in both type 1 and type 2 diabetics. There are various approaches, some of which can be combined, to attaining the desired state of euglycemia. In type 2 diabetics, in particular, dietary modification undertaken at an early stage can have a positive impact on its later course. Both type 1 diabetics and type 2 diabetics require pharmacological treatment adapted to their diet (Gonzáles-Barranco, 1998).

[Table of contents]

3.1 Nutritional therapy

The main objectives of nutritional therapy in patients are:

• the maintenance of normal blood glucose concentrations
• the attainment of normal serum lipid concentrations
• an adequate caloric intake and, if necessary, weight reduction
• the prevention and treatment of complications such as autonomous polyneuropathy, high blood pressure and cardiovascular diseases.

To prevent extreme blood sugar fluctuations, the diabetic should eat several small meals distributed over the course of the day. The timing of the meals and the amount of food eaten (especially the amount of carbohydrates) have to be coordinated with the insulin dosage. This strategy results in enhanced insulin sensitivity; in type 2 diabetics, it contributes to weight reduction.

The recommendations issued for the food intake of patients with diabetes mellitus have changed repeatedly since the beginning of the last century. In the 1920s diabetics were advised to meet up to 70% of their total energy requirements from fats in order to burden the metabolism with as little carbohydrate as possible. Since the dietary regimen was associated with an increased incidence of disorders of lipid metabolism, however, and better control of postprandial blood glucose levels was available with the advent of insulin therapy, it fell gradually into disfavor. In the 1980s the recommendations of the German Diabetes Association (GDA) were liberalized and brought into line for the most part with the guidelines of the German Nutrition Society.

In 1994 the ADA and the European Association of the Study of Diabetes (ESD) revamped the general principles of diabetic nutrition. The most recent recommendations of the German Diabetes Association are based on these guidelines and have been revised to take account of recent scientific data. The following survey of general dietary recommendations for diabetics corresponds to the recommendations of the GDA (GDA, 2000).

Total energy intake

The energy requirements of diabetics are no different from those of their healthy counterparts. Since approx. 80% of type 2 diabetics are obese (Hoffmann, 1998), however, many diabetics are advised to curtail their energy intake in order to achieve weight reduction. Furthermore, their goal should be to lessen their intake of foods with a high energy density, especially foods of this kind with a high fat content. The intake of simple unsaturated fatty acids has been largely liberalized.

Proteins

Diabetics, like healthy persons, are advised a total energy intake from protein of 10-20 %. A higher protein intake increases the risk of developing nephropathy. In patients with incipient or advanced nephropathy, the daily protein intake should not exceed 0.8 g/kg of body weight.

Carbohydrates and fats

Some 80-90% of total calories should be obtained from carbohydrates and fats. Less than 10% of this energy should come from saturated fatty acids and less than 10% from polyunsaturated fatty acids. It follows that the rest of the energy requirements must be supplied by carbohydrates and simple unsaturated fatty acids. The optimal ratio of these two food groups depends on the extent the patient´s obesity, his or her LDL and triglyceride concentrations in serum, and the behavior of the blood glucose concentration or insulin requirements. Trans-fatty acids, which are contained in solidified fats and in deep fried foods, should be avoided if it at all possible since they have an especially negative effect on blood lipid values. The daily intake of cholesterol should not be more than 300 mg/day.

When choosing carbohydrates, the diabetic should display a distinct preference for foods with a low glycemic index in order to counteract overly large postprandial blood sugar fluctuations. In general this means an increased intake of starch-rich foods containing a high percentage of dietary fiber. A moderate amount of sugar (e.g. fructose) can be included in the diet of both type 1 and type 2 diabetics. However, the sugar consumption should not account for more than 10% of total energy consumption and should preferably be eaten together with other foods.

According to the GDA recommendations, carbohydrate consumption should be reduced to approx. 45% of total energy intake only in patients with poorly managed diabetes; in other diabetic patients, it can account for up to 55% of total energy intake. However, the total fat consumption should not account for more than 35% of energy intake; up to 20% of daily energy requirements can be met with simple unsaturated fats can accounts (GDA, 2000).

Vitamins and antioxidant foods

An adequate intake of both fat- and water-soluble vitamins is vital for diabetics and healthy individuals. In patients with diabetes mellitus, however, a sufficient supply of antioxidant nutrients such as tocopherols, carotinoids, vitamin C and flavonoids is especially important since these substances are able to lessen oxidative stress (Cf. 2.4) (4.5 and 4.6).

Minerals

Like the members of the general population, diabetic are urged to limit their intake of table salt to less than 6 g per day. This is especially important for patients with a metabolic syndrome, i.e. who also suffer from elevated blood pressure, in order to lower their risk of developing cardiovascular disease. With respect to other minerals, the recommendations of the GDA do not deviate from the dietary recommendations for the general public. Nevertheless, there is evidence that chromium, a trace element, can exert a positive effect on diabetic metabolism (Cf. 4.7).

[Table of contents]

3.2 Pharmacological therapy

Whereas type 1 diabetics have a categorical dependence on insulin, patients with the type 2 variant of the disease have several therapeutic options open to them.

Pharmacological therapy is instituted in type 2 diabetics after dietary modification and regular physical exercise are no longer sufficient to bring the patient´s blood sugar levels close to normal values. Initially, oral anti-diabetic preparations are preferred; these drugs to not increase the secretion of insulin (i.e. belong to the group of non-insulinotropic diabetes agents); instead, they lower blood sugar via other pharmacological mechanisms. At later stages of the disease, the patient may have to take oral diabetes drugs which increase the endogenous secretion of insulin, i.e. insulinotropic diabetes agents.

If the type 2 diabetes progresses further, endogenous insulin production may break down completely, causing an absolute deficiency of insulin similar to that experienced by the type 1 diabetic. Type 2 diabetics who have reached this stage may have to receive exogenous insulin.

a-glycosidase inhibitors

These preparations (acarbose and miglitol) act in the intestine to inhibit the activity of ß-glycosidase responsible for the breakdown of oligo- and polysaccharides into glucose. As a result, carbohydrate metabolism is slowed down while glucose absorption and the rise in blood sugar are delayed. Acarbose and metformin can be administered in combination with sulfonylurea and insulin, respectively.

Biguainide

Biguanide (metformin) affects blood sugar regulation at several levels. It causes a delay in enteral glucose absorption, an increase in hepatic gluconeogenesis due to the enhanced insulin sensitivity of the cells, and an increase in glucose uptake by the muscles. Since it does not have any direct effect on insulin production or secretion, however, its action is dependent on the presence of insulin for its effect. Apart from its blood-sugar-lowering action, metformin also has a positive effect on blood lipid values; in particular, it lowers the VLDL concentration in plasma (Lohmann, 1993).

Sulfonylurea

The preparations in this class of substances stimulate the ß-cells of the pancreas to secrete larger amounts of insulin. They are administered to patients in whom dietary measures alone are not sufficient to guarantee satisfactory metabolic management but who are as a rule still able to produce sufficient amounts of insulin. Patients who have been taking sulfonylurea for several years frequently develop " secondary failureö; this means that they no longer respond optimally to the therapy and have greater difficulty keeping their blood sugar levels under control. Secondary failure is due to a decrease in the population of functioning ß-cells and the patient´s failure to adhere to the prescribed diet (Haupt et al, 1999).

Postprandial blood glucose regulators

This group of active substances consists of rapid-acting oral diabetes agents which are taken shortly before meals to reduce postprandial hypoglycemia. Like sulfonylurea, they stimulate the secretion of insulin by the pancreas; however, they take effect faster but also shorter. Postprandial glucose regulators effectively regulate both postprandial and fasting blood sugar and cause periods of postprandial hypoglycemia (due to the overproduction of insulin) to a far lesser extent than sulfonylurea. They can be administered in the form of a monotherapy or in combination with metformin (Van Gaal et al, 2001).

Insulin sensitizers (thiazolidindione, glitazone)

Since type 2 diabetes frequently occurs in combination with the metabolic syndrome, scientists had long been searching for a medication that could provide comprehensive treatment of all elements of the metabolic syndrome. The glitazones have been on the market in Germany since 2000; these substances simultaneously act on the blood sugar level and inhibit the degradation of lipids in fatty tissue. They reduce the release of free fatty acids and reduce VLDL synthesis in the liver. An anti-hypertensive effect has also been demonstrated. The glitazones act at the level of gene expression and decrease insulin resistance by improving the insulin sensitivity of the liver, skeletal muscle cells and fat cells (Klinikarzt, 2000).

Insulin therapy

In patients with an absolute insulin deficiency (type 1) or declining insulin secretion (type 2), insulin must be administered to keep the patient´s metabolism under control. Insulin therapy has been employed since the discovery of insulin in 1922; during this period it has been improved continuously by the development of new insulin preparations.

Whereas diabetics had to rely on insufficiently purified swine and bovine insulin during the early decades of insulin therapy, insulin of animal origin has now been largely replaced by highly purified semisynthetic and recombinant insulins.

The numerous products on the market fall into three main groups: products with a rapid onset of action and short duration of action (normal insulin, regular insulin), suspensions of human insulin with a delayed onset and extended duration of action (depot or delayed action insulin) and mixtures of the two (combination insulin). In addition, so-called insulin analogues have been introduced in recent years; changes in the amino acid sequence distinguish these insulins from human insulins. Moreover, insulin analogues exhibit altered pharmacokinetics.

The goal of insulin therapy is to imitate the physiological secretion of insulin by the pancreas as closely as possible in order to postpone diabetic complications such as nephropathy, retinopathy and peripheral neuropathy. This goal is best achieved with the intensified insulin therapy which is now the treatment of choice for diabetics. This therapy consists of a flexible therapeutic regimen geared to the patient´s normal meals; in contrast to the rigid traditional therapy which has been largely abandoned, it dispenses with a rigid diabetic diet. However, the intensified insulin therapy places high demands on patient cooperation. This includes measuring the blood glucose concentration three or more times a day in order to determine the required insulin dose.

[Table of contents]

4. Optimized Nutritional Therapy within the Framework of Enteral Nutrition

About 10% of all hospitalized patients have diabetes; of this total, approx. 85% have type 2 (Coulson, 2000). It has been estimated that 25% of all critically ill patients who are dependent on enteral or parenteral nutrition have a diabetic metabolism (Wright, 2000).

Despite many years of intense research, the life expectancy of diabetics is limited because of the occurrence of serious sequelae and acute complications (Cf. 2.3 and 2.4). More than 50% of diabetics die of coronary heart disease and 25% of strokes. Together microangiopathy and macroangiopathy account for 80% of all deaths in diabetics (Karsten, 1999). A retrospective study carried out in Brazil came to the conclusion that diabetics receiving enteral nutrition had a significantly higher mortality than tube-fed non-diabetics. The metabolic complications that frequently occurred in diabetics receiving enteral nutrition included hyperglycemia and hypoglycemia, ketoacidosis and hyperlipoproteinemia (Borges & Dudha, 1998).

The therapeutic objectives of any enteral nutrition regimen targeted at diabetic patients are:
• to attain or maintain an optimal nutritional state
• to prevent acute and chronic complications by optimal management of the patient´s metabolism.

[Table of contents]

4.1 Special features of an enteral nutrition regimen for patients with diabetes mellitus

Enteral nutrition is indicated on the basis of certain primary diagnoses (e.g. dysphagia, resection procedures); however, the concomitant diagnosis of diabetes mellitus has far-reaching implications for the selection of the dietary components, the access route and form of application as well as for the coordination of diet and medication.

Gastroparesis, gastric emptying disorders

Gastroparesis is a symptom of autonomous neuropathy; its incidence and severity are closely linked to the previous duration of the patient´s diabetes mellitus an the quality of his or her blood sugar management.

In view of the above, it is important to assess the extent of diabetics complications in any diabetic patient requiring enteral nutrition. The combination of gastroparesis and enteral nutrition, for example, presents the following risks:
• The intake of foods through gastric tubes can trigger vomiting, which poses the risk of aspiration.
• In patients receiving enteral nutrition, it is more difficult to coordinate the patient´s medication with his or her carbohydrate absorption; as a result, both hyperglycemia and hypoglycemia are possible.
• In post-aggression metabolic states, e.g. following surgery, metabolic changes occur which can promote or intensify hyperglycemia. This acute metabolic disturbance can in turn acutely exacerbate a pre-existing gastric emptying disorder.
• In a diabetic patient suffering from gastroparesis, the gastric emptying difficulties normally encountered after surgery can be prolonged.
• In patients with renal insufficiency as well, the resulting uremia can further exacerbate the gastroparesis.
• In patients with extremely severe gastroparesis, it may prove impossible to bring the patient´s blood sugar levels under control. In such cases, the gastroparesis alone may constitute an indication for the duodenal or jejeunal application of enteral nutrition formulas.

Therapeutic options

• Enteral feeding via gastric tubes should be employed only in stable patients with no signs of a gastric emptying disorder.
• In patients with acute clinical states, supplemental enteral nutrition formulas should be administered through a jejeunal tube; in such cases, pump-controlled application is indispensable.
• Continuous food intake even in patients on a long-term enteral nutrition regimen (e.g. stroke and diabetic patients)
• Regular management of gastric emptying during the administration of supplemental enteral nutrition formulas as well as during the further clinical course (documentation)
• Close monitoring of blood sugar to prevent an acute worsening of the gastroparesis and hyperglycemia or hypoglycemia.
• If required, medication with a propulsive effect – such as metoclopramide or domperidone – should also be administered.
(Charney, 1998; McMahon & Rizza, 1996; Nonpleggi et al, 1989)

Blood sugar management and monitoring in patients receiving enteral nutrition

In all tube-fed patients, exact monitoring of blood sugar and blood lipid values is extremely important. In addition to close monitoring, the use of a suitable balanced diet is decisive (Gallagher-Allred & O´Doriso, 1998; see below).

A special feature of the use of enteral nutrition in diabetics is the effect of liquid nourishment on blood sugar levels. Liquids and liquid dietary components pass through the stomach faster than solid dietary components (Fig. 5). Speeder gastric emptying results in a faster breakdown and absorption of dietary constituents in the small intestine and thus to more rapid absorption of glucose.

Cashmere et al (1981) compared the rise in blood sugar and insulin following the ingestion of a portion (500 kcal) of enteral nutrition formula via a gastric tube and after the ingestion of a solid meal containing the same number of calories and amount of carbohydrate. The highest blood glucose concentration was measured after 30 minutes in both cases; however, the curve was relatively flat following the ingestion of solid food. Furthermore, the amount of insulin in the blood was higher after the administration of enteral nutrition formulas via a tube. From these observations, the conclusion can be drawn that dietary constituents are absorbed more quickly from liquid formulas than from solid foods and result in greater fluctuations in blood sugar than do solid foods (Campbell & Schiller, 1991).

The coordination of medication and the administration of enteral nutrition should take account of the following factors:
• amount of carbohydrate
• form of enteral application
- administration of a bolus
- intermittent feeding or
- continuous feeding
• choice of medication: insulin (normal insulin or delayed-action insulin) and possibly oral diabetes agents
• clinical course and impact of therapy
- acute phase of the disease, stable condition
- dietary supplementation, transitional forms
(parenteral ? enteral ?oral nutrition)
- long-term enteral nutrition

To manage blood sugar values during the administration of enteral nutrition in acute disease phases, normal insulin should be used. Since enteral nutrition formulas are generally fed continuously via pumps, insulin can be administered via a perfusor. Insulin should not be added to the enteral nutrition formula under any circumstances.

During the phase of enteral nutritional supplementation, the patient´s medication should be continuously adjusted to the amount of nutrients administered; during transitions from parenteral or oral nutrition to enteral nutrition, the total quantity of nutrients administered by all routes should be taken into account. Over-feeding should be avoided.

In patients whose total energy requirements are met by tube-feeding and patients receiving continuous long-term enteral nutrition, a switch from normal insulin to delayed-action insulin (or analog insulins) is indicated. If the enteral nutrition therapy is administered intermittently over a long period (e.g. in the form of a bolus, short-action insulin (normal insulin or insulin analogue) should be used. The time span between injection and food intake should be shortened since carbohydrates ingested in liquid form (see above) are absorbed more rapidly.

Patients with stable type 2 diabetes can be treated with oral diabetes agents; in this case the type of tube used (i.e. gastric or jejeunal) determines the choice of medication (galenic form) and route of application. (Charney, 1998; McMahon & Rizza, 1996; Nompleggi et al, 1989).

To prevent long term complications, optimal blood sugar control should be ensured, especially in patients on a long-term enteral nutrition regimen, by a sufficient number of blood sugar readings and therapy adapted to the requirements of the individual patient. Blood sugar and HbA1c should be monitored regularly

Hygiene and risk of infection

The frequent occurrence of hyperglycemia or hyperinsulinemia in diabetic patients causes direct complications and long term complications. Numerous in vitro studies have demonstrated that hyperglycemia can trigger abnormal immunological defense mechanisms. In addition, frequent periods of hyperglycemia have been identified as an independent risk factor predisposing to the development of infections (McMahon, 1996). Conversely, an acute abnormal blood sugar level may be a sign of infection. Optimal blood sugar management helps to lower the risk of infection.

In all patients receiving enteral nutrition, in addition, special attention must be paid to hygienic handling of the enteral nutrition formula, regular replacement of the administration sets, and meticulous care of the enteral access.

A comprehensive diabetic treatment concept

In 1998 an international committee of experts issued a Consensus Statement on the use of enteral nutrition in diabetics (Consensus Statement, 1998). The main objectives of therapeutic planning cited by the statement were: optimal blood sugar management and general metabolic monitoring in order to achieve both short-term and long-term therapeutic goals and to prevent long term complication of diabetes. To achieve the overall goal of optimal treatment, a systematic approach to history-taking, therapeutic planning and therapeutic monitoring are necessary. This sort of approach should take account of:

• the nutritional and metabolic status of the patient
• gastrointestinal dysfunction, e.g. gastroparesis
• selection of a suitable enteral access
• selection of a suitable application form for the enteral nutrition
• coordination of pharmacological therapy and enteral nutrition
• the setting-down of parameters to be monitored and the frequency of monitoring
• selection of a suitable enteral nutrition formula (composition).

[Table of contents]

4.2 Composition of balanced diets for patients with diabetes mellitus

Standard diets contain relatively large amounts of easy-to-absorb carbohydrates; some of them contain a low percentage of dietary fiber and a fat composition which is not optimal for diabetic patients with abnormal lipid metabolism. The first enteral nutrition formulas designed especially for diabetics were put on the market in the 1990s; these are not totally in line with the most recent recommendations for diabetics (Cf. 3.1) (Coulston, 1998). For this reason, special liquid formulas and formulas for tube feeding are required which satisfy the current nutritional recommendations for diabetics and promote optimal metabolic management (Table 8).

In accordance with current dietary recommendations, the latest generation of balanced diets for diabetics derive 60-70% of the nutrition energy from carbohydrate with a low glycemic effect and from mono-unsaturated fatty acids. Saturated fatty acids and polyunsaturated fatty acids each account of < 10% of the energy intake. A high percentage of dietary fiber, a dose of antioxidant vitamins in line with requirements, and the addition of phytochemicals as well as chromium add up to an optimal diet for diabetics, one that has numerous positive effects on their particular metabolic situation (Table 9).

[Table of contents]

4.3 Carbohydrates

The carbohydrate intake of diabetics was a matter of controversy for many years (Cf. 3.1). Today large organizations such as ADA or EASD are in agreement that optimal carbohydrate intake is an individual matter: however, carbohydrates and simple unsaturated fatty acids should account for 60-70% of total energy intake. The GDA recommends that diabetics meet up to 55% of their total energy requirements with carbohydrates.

The composition of the carbohydrates given to a patient is at least as important as the amount. Carbohydrates with a low glycemic index (Cf. 2.2.1) and high percentage of dietary fiber should be chosen in order to keep the rise in blood sugar as small as possible.

Balanced diets based on the requirements of diabetic patients should not contain any easy-to-absorb carbohydrates. What is recommended instead is a high percentage of complex carbohydrates in the form of starches and a high percentage of dietary fiber. The inclusion of moderate amounts of fructose and prebiotic oligosaccharides can exert an additional positive effect on the diabetic´s metabolism.

[Table of contents]

4.3.1 Starches

Starch serves as the storage carbohydrate in many plants and is the most important food carbohydrate. It consists of numerous glucose molecules linked to form either unbranched molecules (e.g. amylose) or branched molecules (e.g. amylopectin) (Franzke, 1996). In the small intestine the largest part of the ingested starch is broken down by the digestive enzymes into individual glucose molecules which are then absorbed by the body. A significant portion of the ingested starch manages to avoid enzymatic degradation in the small intestine, however, and reaches the large intestine; here it is fermented by the intestinal flora (Cf. dietary fiber). The starch fraction which passes through the small intestine without being digested is referred to as "resistant starchö (Concepts for Modulating the Intestinal Flora, Special Issue, Practical Application of Clinical Nutrition, B. BRAUN).

Starch exerts a positive effect on the glycemic control of the diabetic patient. The underlying mechanism has not been fully elucidated. It is suspected, however, that the ingested starches and lipids interact to form complexes which slow down the hydrolysis of amylose and thus the absorption of glucose (Stürmer, 1984).

Stiller et al. (1993) investigated the metabolic effects of a balanced diet for type 2 diabetics with a modified carbohydrate component. This team was able to verify that the inclusion of starches and fructose instead of easily digestible carbohydrate in enteral nutrition formulas exerted a positive effect on postprandial blood glucose and serum insulin concentrations. A comparison of the group receiving the test diet and the control group showed no differences in triglyceride and cholesterol levels.

[Table of contents]

4.3.2 Fructose

Fructose is a simple sugar found in the normal human diet primarily in the form of sucrose (one molecule of sucrose consists of one molecule of glucose plus one molecule of fructose). Small amounts of free fructose can be found in fruit. Fructose is absorbed in the intestines, owing to its easier diffusion, and is transported directly to the liver, where it is taken up by the hepatocytes. This uptake of fructose by the hepatocytes is dependent on insulin. As a result, fructose does not accumulate in the blood of diabetics or healthy subjects. In the liver fructose can be metabolized without prior conversion; in other tissues, however, it is converted first to glucose (Rehner and Daniel, 1999).

Fructose may be utilized in the enteral nutrition of diabetics because it triggers a lower rise in blood sugar and a weaker insulin response than, for example, glucose or maltodextrin (Schrezenmeir, 1998). The same conclusion was reached by Koivisto & Yki-Jarvinen (1993) in a placebo-controlled double-blind study on the effect of fructose on glycemic control, blood lipid values and insulin secretion in type 2 diabetics. This group of researchers administered 45-65 kg of fructose a day to the test subjects for a total of four weeks. During the fructose diet the HbA1c value and insulin sensitivity of the subjects rose by 34%. No effects on blood lipid values were observed.

The intake of large amounts of fructose can have detrimental effects on blood triglyceride levels and can cause diarrhea or elevated uric acid concentrations. A diet containing moderate amounts of fructose, i.e. amounts accounting for less than 20% of total energy intake, is not expected to produce side effects of this kind (Schrezenmeir, 1998; Stürmer et al, 1994).

[Table of contents]

4.3.3 Dietary fiber

Experts in nutritional physiology define dietary fiber as food ingredients derived from plants which are not degraded (or degraded to only a slight extent) by human digestive enzymes in the small intestine and are therefore not absorbed (or absorbed to only a slight extent). These substances reach the large intestine, where they undergo bacterial fermentation for the most part. Today we know that there is a direct correlation between a diet low in fiber and numerous civilization-related diseases such as overweight, disorders of lipid metabolism, aortosclerosis, type 2 diabetes and gastrointestinal problems such as constipation, intestinal cancer or diverticulosis (Elmadfa and Leitzmann, 1998).

A distinction is made between water-soluble and water-insoluble fiber-containing substances. Water-soluble dietary fiber is broken down rapidly and almost completely by the anaerobic intestinal flora (intestinal bacteria). During this process short chain fatty acids are released which exert a wide variety of positive effects on the organism. The water-soluble fiber-containing substances include pectin, various plant gums, mucin and prebiotic carbohydrates such as inulin and oligofructose (see below). The water-insoluble fiber-containing substances, in contrast, are hardly fermented at all. Owing to their high water-binding capacity, they increase stool volume; this stimulates peristalsis and shortens transit time in the large intestine. These substances consist mainly of cellulose and hemicellulose (Kasper, 2000; Elmadfa and Leitzmann, 1998).

It is especially important for the diet of diabetics to include a high percentage of soluble fiber-containing substances since this dietary fiber fraction can lower cholesterol values and, in addition, exert positive effects on the blood glucose level. Chandalia et al (2000) investigated the effect of the ingestion of an increased percentage of dietary fiber in 13 type 2 diabetics. They compared the impact of two different diets on the blood glucose concentrations and cholesterol values of these patients. Whereas Diet 1 contained only 8 g of soluble dietary fiber, Diet 2 contained 25 g. It was discovered that Diet 2 lowered the postprandial blood glucose concentration, the areas under the curve of the 24-hour glucose and insulin concentration and plasma levels of total cholesterol, triglyceride and LDL cholesterol. In particular, the researchers attributed this effect to the larger dietary fiber fraction. The lowering of the pH in the colon lumen as a result of the increased production of short chain fatty acids is presumed to constitute the mechanism responsible for this cholesterol-lowering effect. At low pH values the bile acids (formed from cholesterol) become non-soluble and are secreted in the stool. Cholesterol is removed from the enterohepatic cycle in this fashion. The impact on blood sugar concentration is attributed to the increased viscosity and the slowing down of starch digestion (D.I.E.T., 2001).

The non-soluble types of dietary fiber also exhibit effects in the gastrointestinal tract from which diabetics can profit, especially during long periods of tube-feeding. In particular, older patients being tube-fed for longer periods of time frequently develop unpleasant complications such as diarrhea and digestive problems (Shankardass et al, 1990). Numerous studies have shown that increasing the percentage of dietary fiber in enteral nutrition formulas can both decrease the average incidence and duration of diarrhea in tube-feed patients (Guenter et al, 1991; Bass, 1996) and in general improve the patients´ health (Khali et al, 1998).

According to these studies, dietary fiber exerts a multifaceted positive effect on the metabolism and gut health of diabetics. Supplementing the formulas used for tube feeding with dietary fiber can decrease the risk of diabetic long term complications such as cardiovascular disease and microangiopathies by lowering blood sugar and blood lipid values. Moreover, the positive effect on intestinal motility is beneficial, especially for patients who already display complications in the form of polyneuropathies (e.g. gastroparesis) (Cf. 2.4.3).

[Table of contents]

4.3.4 Prebiotic carbohydrates

Prebiotics are by definition non-digestible dietary constituents which can benefit the host organism (i.e. the human being) by stimulating the growth and/or activity of one or several colon bacteria and thus the promote the health of the host (Gibson & Collins, 1999). The group of prebiotic carbohydrate includes a number of oligosaccharides, of which inulin and oligofructose are most frequently employed.

The human intestinal flora consists of billions of individual intestinal bacteria which exert beneficial and less beneficial effects on the health of the human being who is their host. One group of intestinal microflora with an especially beneficial effect are the lactic acid bacteria (Gibson & Roberfroid, 1995). The prebiotic carbohydrates inulin and oligofructose stimulate primarily the growth of bifidobacteria. This phenomenon, referred to as the "bifidogenic effectö, causes a number of effects which promote the host´s health:

Two effects of particular interest to diabetics receiving enteral nutrition, in addition to the general positive effects on intestinal motility, are the lowering of postprandial glucose and insulin concentrations and the reduction of cholesterol and triglyceride levels. Although the exact mechanisms impacting lipid and glucose metabolism have not yet been fully clarified, the results have been confirmed in numerous studies on animals and human beings (Delzenne & Kok, 2001).

Detailed information on prebiotic carbohydrates and their mechanism of action can be found in the publication "Concepts for Modulating the Intestinal Floraö (B. BRAUN, 2001).

[Table of contents]

4.4 Lipids

The recommendation given diabetics at the end of the 19th century, namely to maintain a high fat intake, was abandoned in the wake of further research on diabetes (Cf. 3.1). Over 100 years later, however, a higher fat intake has been correlated with improved glycemic control and better blood triglyceride and blood lipid values. In particular, an increased percentage of simple unsaturated fatty acids is now advocated since these have been shown to promote better management of blood glucose and blood lipid values. Moreover, the regular intake of polyunsaturated omega-3-fatty acids in the form of fish oils has been shown to exert beneficial effects on the metabolism of diabetic patients. Saturated fatty acids which have a negative effect on the diabetic´s triglyceride and lipid profile should be eaten in only small amounts, i.e. should account for < 10% of total energy intake, and trans-fatty acids should be avoided completely. This kind of fatty acids, which occur especially in solidified fats, raises the concentration of LDL cholesterol and Lp(a) lipoproteins and lowers the HDL cholesterol level. This constellation increases the risk of cardiovascular disk immensely (Katsilambros, 2001).

Whereas the diabetic who can eat normally often finds it difficult to include a precisely defined fatty acid combination in his or her diet, the lipid constituents of a enteral nutrition formula can be tailored exactly to the requirements of the diabetic patient (Schrezenmeir, 1998).

[Table of contents]

4.4.1 Monounsaturated fatty acids

The majority of type 2 diabetic patients display hyperlipoproteinemia in addition to elevated blood sugar values. Characteristic of this condition are elevated total cholesterol and LDL cholesterol levels, an elevated triglyceride concentration and a comparatively low HDL cholesterol concentration in plasma. An altered plasma lipid profile increases the risk of microvascular changes (Cf. 4.3) in diabetic patients many times over (Schrezenmeir, 1998).

Numerous studies performed in recent years have shown that the partial replacement of carbohydrates by mono-unsaturated fatty acids in balanced diets for diabetics can have a positive effect on blood lipid levels. With respect to lipid metabolism, an increased intake of mono-unsaturated fatty acids is corelated with:

• a lowering of the total cholesterol level
• a lowering of the LDL cholesterol level
• a lowering of the plasma triglyceride concentration
• a moderate increase in HDL cholesterol
• the production of forms of LDL having a lesser atherogenic effect (Katsilambros, 2001).

Apart from the positive effects on blood lipids, enteral nutrition formulas containing a comparatively high percentage of fat, in particular a higher concentration of mono-unsaturated fatty acids, ensures a better glycemic control in diabetics (Schrezenmeir, 1998). Furthermore, there is evidence that mono-unsaturated fatty acids possess antioxidant potential and, in particular, can change the decrease the oleic acid oxidation reaction in the body. Further studies will have to be carried out to explore the long-term effects of a diet rich in mono-unsaturated fatty acids on oxidative stress in diabetics (Berry, 1997).

In a placebo-controlled double-blind study lasting for three months, Craig et al (1998) demonstrated that patients on a fat-modified diet containing a high percentage of mono-unsaturated fatty acids exhibited markedly fewer infections and decubitus ulcers during the observation period. These results point to the possibility of improving the clinical outcome and life quality in these patients via modified enteral nutrition.

A diet with an increased fat fraction is generally associated with a higher caloric intake and thus weight gain. A cohort study performed by Shah and Garg (1996) showed that moderately increasing the proportion of fat in the diet of overweight diabetics by adding mono-unsaturated fatty acids did not result in weight gain unless the energy intake was increased at the same time. Interventional studies on weight loss failed to demonstrate that hypocaloric carbohydrate-rich diet resulted in higher weight loss than hypocaloric fat-rich diets. In view of these results, balanced diets rich in unsaturated fatty acids can be recommended for obese type 2 diabetics with impunity provided that the patients´ energy intake is monitored at the same time.

In patients receiving enteral nutrition, however, the recommended fat fraction of 35% and a total energy fraction of up to 20% consisting of simple unsaturated fatty acids should not be exceeded despite the positive effects this type of fatty acid exerts (GDA, 2000). In patients being treated with sulfonylurea (Cf. 3.2), in particular, an extremely elevated fat intake (> 50%) can lead to complications as a result of the increased ketone body production (Sanz-Paris, 1998).

[Table of contents]

4.4.2 Polyunsaturated fatty acids

The regular inclusion of fish in the diet, or the use of fish oil dietary supplements, is associated with a decreased incidence of coronary heart disease. This is attributed to the positive effect of omega-3-fatty acids on lipid metabolism (Prince & Deeg, 1997).

Several studies performed with diabetic patients have demonstrated that omega-3 fatty acids reduce the concentrations of total triglycerides, VLDL triglycerides and VLDL cholesterol. Several possible mechanisms have been postulated, including the suppression of VLDL production in the liver and heightened activity of lipoprotein lipase (degradation of triglyceride-rich lipoproteins) by fish oils (Prince & Deeg, 1997).

The question of whether omega-3 fatty acids exert a negative effect on blood sugar management in diabetics was long a matter of controversy. A meta-analysis of 18 randomized placebo-controlled studies carried out with 823 type 2 diabetics (Montori et al, 2000) showed that supplementing the diet with 3-18 g of fish oil for 12 weeks caused an average drop of 49 mg/dl in serum triglycerides; the increase was even greater, i.e. 64 mg/dl, in patients with hypertriglyceridemia. Fasting blood sugar and HbA1c were not significantly affected by the ingestion of fish oil. The conclusion to be drawn from these results is that the addition of fish oil to the diet of type 2 diabetics can improve the dyslipemia frequently found in this group of patients without having a detrimental effect on blood sugar.

An anti-arteriosclerotic effect is ascribed to the omega-3 fatty acids in addition to their ability to lower blood lipids. Owing to the increased intake of eicosapentanoic acid (omega-3 fatty acid), the production of "series 3ö prostaglandins and thromboxanes can be stepped up; these are substances which modulate signal transduction (Rehner & Daniel, 1999), dilate blood vessels, prevent platelet aggregation, etc. As a result, blood pressure is lowered and blood viscosity reduced (Mutanen & Freese 1996; Brown & Hu, 2001).

Because of the ease with which omega-3 fatty acids can be oxidized, diabetics should consume only moderate amounts (i.e. < 10% of total energy intake) of this type of fatty acid. If antioxidants such as vitamin E (see below) are taken together with omega-3 fatty acids, peroxidation reactions can be largely prevented (Saito, 2000).

[Table of contents]

4.5 Protein

Proteins are essential nutrients in the human diet. The quality of a protein source depends on the amount of essential amino acids (amino acids which cannot be synthesized by the organism itself) it contains and their digestibility. The availability of amino acids varies according to the protein source, degree of processing and interaction with other dietary constituents. In general animal proteins display a higher availability than plant proteins for the human organism (Elmadfa & Leitzmann, 1998); a high biological value can be achieved by a combination of animal and plant proteins.

In enteral nutrition formulas, soy protein is frequently employed as an additional protein source. Besides having a relatively high biological value, soy protein is nutritionally valuable because of its high isoflavonoid content. Consequently, the inclusion of soy protein in enteral nutrition formulas for diabetics is highly recommended (Cf. 4.6).

[Table of contents]

4.6 Vitamins

There is abundant evidence to suggest that oxidative stress plays a decisive role in the pathogenesis of diabetes and the development of diabetics long term complications (e.g. arteriosclerosis, microangiopathy, etc.). Diabetes mellitus leads to a weakening of the body´s antioxidant defense mechanisms and the increased production of free radicals (Rösen et al, 2001). The effects of supplementing the diet with substances possessing a known antioxidant effect – such as vitamin E, vitamin C, vitamin A and betacarotin – on the oxidative equilibrium of diabetics and on the clinical outcome of their treatment have been explored in numerous studies.

Investigating the susceptibility of lipoproteins (LDL) to oxidation in type 2 diabetics in comparison with health subjects, Anderson et al (1999) found an increased susceptibility. Subsequently, the diabetics were given a placebo for eight weeks, a vitamin supplement containing a-tocopherol, ß-carotene and vitamin C for 12 weeks, and then a placebo again for 8 weeks. During the period in which vitamin supplements with an antioxidant effect were administered, the susceptibility for LDL oxidation dropped significantly.

In a randomized placebo-controlled double-blind study performed by Preiser et al (2000), 51 patients were tube-fed for seven days with either an enteral nutrition formula supplemented with vitamins A, C and E or with an isocaloric formula without the vitamin supplements. The patients receiving vitamin supplements displayed a distinctly improved resistance to LDL oxidation than the control group. Since oxidized LDL constitutes an important risk factor for the development of aortosclerosis, we can conclude that supplementing the diet with antioxidant substances such as vitamins A, C and E and ß-carotene significantly lessens the risk of coronary heart disease.

[Table of contents]

4.7 Phytochemicals

Phytochemicals are substances which serve as building blocks of organic substances in the plant and as substrates for energy metabolism in humans. They include carbohydrate (including dietary fiber), fats and proteins. Phytochemicals, in contrast, are non-nutritive substances which serve as defense substances, growth regulators or pigments in plants. In contrast to the primary plant substance, they occur in only very small amounts. Of the approx. 30,000 known phytochemicals, approx. 5,000 – 10,000 occur in the human diet. As part of the human diet they can exert either health-promoting effects or effects which are detrimental to health (like the toxic substance solanine found in the green spots in potatoes). In recent years, the magnitude of the health-promoting effects, in particular, has been recognized and investigated (Nutrition Report 1996).

The most important groups of substances with health-promoting effects are:

• carotinoids
• phytosterines
• flavonoids (polyphenols)
• phytoestrogens (isoflavonoids, lignanes)

It is assumed that these phytochemicals have a very broad spectrum of action ranging from anti-carcinogenic, anti-microbial, antioxidant, anti-inflammatory, immunomodulatory and cholesterol-lowering to blood-glucose-regulating and blood-pressure-regulating (Table 9). A person eating a normal healthy diet takes in phytochemicals every day. These substances are present in fluctuating amounts in fruit, vegetables, legumes and tea (especially in unfermented green tea). Even though an absence of phytochemicals does not lead to any acute deficiency symptoms (e.g. malnutrition or vitamin deficiency), it presumably increases the long-term risk of developing various diseases, e.g. cardiovascular disease, cancer and arteriosclerosis (German Nutrition Report 1996).

Phytochemicals
Carotinoids
Phytosterines
Polyphenols
Phytoestrogens

These substances can be added to enteral nutrition formulas so that tube-fed patients do not have do without their positive effects.

Flavonoids

Flavonoids make up the largest group of plant phenols. All of the flavonoids have a basic structure with three ring systems derived from flavane or flavene. The vast majority of these substances are yellow (Latin: flavus = yellow) compounds (Franzke, 1996). In situations where flavonoids temporarily cannot be obtained from everyday foods such as fruits, vegetables and grains, the diet can be supplemented with extracts of green tea, grape seeds, citrus fruits or other plants.

There is evidence that the proanthocyanidine, a group of polyphenolic bioflavonoids obtained from grape seed extract, exhibit a strong antioxidant effect. After performing an in vitro study comparing the antioxidant action of vitamins C and E and grape seed flavonoids, Bagchi et al (1997) concluded that the flavonoids can trap free radicals far more effectively than vitamins C and E. Another study, conducted by Bouhamidi et al (1998), points to a sharp decrease in the oxidation of polyunsaturated fatty acids by small amounts of flavonoids from grape seed extract. A lessening of oxidation reactions involving lipoproteins (LDL) was also observed during an in vitro study using green tea extract (Yokozawa, 1997). During in vivo trials performed with diabetic rats, moreover, citrus flavonoids demonstrated an ability to reduce antioxidant stress (Miyake et al, 1998).

Furthermore, numerous studies carried out with human subjects attest to the positive effect of an increased intake of flavonoids. Working with a study population consisting of ten type 2 diabetics, Lean et al (1999) administered first a low-flavonoid diet and then a flavonoid-rich diet (e.g. by adding larger amounts of tea) for two consecutive weeks each. During both two-week periods, the researchers investigated the extent to which the DNA of the test subjects was damaged in vitro by free radicals. The results showed that the DNA suffered significantly less oxidative damage during the administration of the flavonoid-rich diet than during the period without dietary supplementation with flavonoids. In another study carried out with type 1 diabetics, the addition of flavonoids resulted in a reduction of the HbA1c value (Manuel y Keenoy, 1999).

Isoflavonoids

It has already been known for some time know that a diet rich in soy protein helps to improve blood lipid values, i.e. to lower LDL and total cholesterol. The mechanism responsible for this effect has not yet been fully elucidated. It is assumed that the isoflavonoids present in soy protein, in particular, have a positive effect on lipid metabolism (Friedman & Brandon, 2001).

Potter et al (1998) and Washburn et al (1999) explored the role played by soy isoflavonoids in lowering the risk of cardiovascular disease in women with a diet rich in soy protein. They noted a significant improvement in blood lipid values and blood pressure. The addition of isoflavonoids to the diet of type 2 diabetics in the form of soy protein also had several beneficial effects, including a significant reduction of LDL cholesterol and triglyceride concentration in plasma (Hermansen et al, 2001).

[Table of contents]

4.8 Chromium

It has been known for almost 40 years that chromium plays a role in glucose regulation and lipid metabolism. In patients dependent on total parenteral nutrition who suffered from chromium deficiency and were in danger of developing insulin resistance, replacement therapy with chromium III resulted in a normalization of the blood glucose concentration. Chromium was credited with acting as a "glucose tolerance factorö (Anderson, 1999).

Studies have shown that plasma chromium concentrations are about one-third lower on the average in diabetics than in healthy subjects and that chromium excretion is increased by as much as 100%. It has been postulated that the chromium deficiency building up in type 2 diabetics over a period of years contributes to the development of the insulin resistance characteristic of this group (Morris et al, 1999).

Chromium appears to play the role of a co-factor in the action of insulin. It is a constituent of a chromium-binding substance known as "low-molecular-weight chromium-binding substanceö (LMWCr) which, in combination with insulin, performs a decisive function in the activation of the insulin receptor. If not enough chromium is available to bind to the LMWCr, the activation mechanism of the insulin receptor is impaired and insulin resistance a possible consequence (Anderson, 1999; Vincent, 2000).

A study conducted by Anderson et al (1997) with 180 type 2 diabetics provided impressive confirmation of the positive effect of chromium. The subjects were given either a placebo (1), a dietary supplement containing 200 µg of chromium per day (2) or a dietary supplement containing 1,000 µg of chromium per day (3). In both groups receiving supplemental chromium, the following quantities improved – in some cases significantly – within two to four months: the HbA1c value, the glucose concentration and the insulin value. In group (3), a decrease in the cholesterol level was also observed after four months.

The chromium uptake of the general population is generally less than 50 µg daily; in diabetics, the amount lost daily (60-300 µg) is distinctly greater than the intake (Müller, 2001). For this reason, it is advisable to add extra chromium to any enteral nutrition formula designed for diabetics. Nevertheless, the intake of chromium should not exceed the currently recommended 200 µg per day (Jeejeebhoy, 1999).

[Table of contents]

5. Summary

In diabetes, optimized therapy is the basis for a good quality of life and a longer life expectancy. In addition to pharmacological therapy, nutritional therapy can bring about an additional improvement in the metabolic status of the diabetic patient.

In diabetic patients on an enteral nutrition regimen involving liquid formulas, meticulous monitoring of metabolic status is essential. The nutrient composition of balanced diets should be tailored especially to the requirements of the diabetic patient.

The carbohydrate components of enteral nutrition formulas for diabetics should not contain any easily absorbed carbohydrates. Instead, starch should be chosen as the main carbohydrate source. In combination with fructose and dietary fiber, starch guarantees slower absorption of glucose in the intestines, which makes it relatively easier to manage the patient´s glycemic status. To improve the changed blood lipid values (hyperlipoproteinemia) which occur in type 2 diabetics, in particular, it is advisable to increase the percentage of mono-unsaturated fatty acids, add a moderate amount of omega-3 fatty acids in the form of fish oil to the diet, and sharply reduce the amount of saturated fatty acids in the enteral nutrition formula used for tube feeding. A fat intake which is slightly increased in comparison with standard diets also results in improved blood sugar management.

In addition to the main nutrients, a number of other nutrients – e.g. phytochemicals, vitamins and minerals – play a role in improving the metabolic status of the diabetics. An increased intake of vitamins with an antioxidant effect can exert beneficial effects on oxidative stress and its sequelae. A group of phytochemicals called flavonoids also exert an impact on oxidative equilibrium and lessen injurious oxidation reactions in the body. Furthermore, a group of phytochemicals derived from soy protein called "isoflavonoidsö are able to improve blood lipid values such as LDL and total cholesterol. An increased intake chromium, one of the trace elements, also has a positive effect on the management of the glycemic status of diabetic patients.

A balanced diet reflecting the latest scientific findings and recommendations supports the management of the metabolic situation in diabetics patients and can make a contribution to improving the clinical outcome.

[Table of contents]

6. Literature

ADA
Nutrition Recommendations and Principles for People With Diabetes Mellitus – Position Statement.
Tenn Med 93,11 (200) 430-433

Anderson JW, Gowri MS, Turner J, Nichols L, Diwadkar VA, Chow CK, Oeltgen PR
Antioxidant supplementation effects on low-density lipoprotein oxidation for individuals with type 2 diabetes mellitus
Journal of the American College of Nutrition 18, 5 (1999) 451-461

Anderson RA
Chromium and diabetes
Nutrition 15,9 (1999) 720-722

Anderson RA, Cheng N, Bryden NA, Polansky MM, Cheng N, Chi J, Feng J
Elevated intakes of supplemental chromium improve glucose and insulin variables in individuals with type 2 diabetes
Diabetes 46, 11 (1997) 1786-1791

Badenhoop K, Usadel K-H
Klassifikation und Genetik.
In: Mehnert H, Standl E, Usadel K-H (Ed) Diabetologie in Klinik und Praxis 4. Auflage
Thieme, Stuttgart (1999)

Bagchi D, Garg A, Krohn RL, Bagchi M, Tran MX, Stohs SJ
Oxigen free radical scavenging abilities of vitamin C and E, and a grape seed proanthocyanidin extract in vitro.
Res Commun Mol Pathol Pharmacol 95, 2 (1997) 179-189

Bass DJ, Forman LP, Abrams SE, Hsueh AM
The effect of dietary fiber in the tube-fed elderly patients.
J Gerontol Nurs 22, 10 (1996) 37-44

B. Braun
Konzepte zur Modulation der Darmflora.
Klinische Ernährung in der Anwendung, Sonderausgabe (2001)

Berger M
Diabetes Mellitus
Urban & Schwarzenberg, München (1995)

Berry E
Dietary fatty acids in the management of diabetes mellitus.
Am J Clin Nutr 66, suppl (1997) 991S-997S

Borges VC, Dudha A
The dietitian´s perspective: nutrition care of patients with diabetes requiring nutrition support.
Clinical Nutrition 17, suppl (1998) 57-59

Bouhamadi R, Prevost V, Nouvelot A
High protection by grape seed proanthocyanidin (GSPC) of polyunsaturated fatty acids against UV-induced peroxidation.
C R Acad Sci 321, 1 (1998) 31-38

Brown AA, Hu FB
Dietary modulation of endothelial function: implications for cardiovascular disease.
Am J Clin Nutr 73 (2001) 673-686

Bruns W, Fiedler H
Diabetes mellitus: Klassifikation und Diagnostik nach Kriterien der WHO 1985 und der American Diabetes Association 1997.
VitaMinSpur 16 (2001) 83-90

Campbell SM, Schiller MR
Considerations for enteral nutrition support of patients with diabetes.
Top Clin Nutr 7, 1 (1991) 23-32

Chandalia M, Garg A, Lutjohann D, Bergmann K, Grundy SM, Brinkley LJ
Beneficial effects of high dietary fiber intake in patients with type 2 diabetes mellitus.
N Engl J Med 342, 19 (2000) 1392-1398

Chantelau E
Diät bei Diabetes mellitus.
In: Berger M (Ed). Diabetes mellitus.
Urban & Schwarzenberg, München (1995)

Consensus Statement
Consensus rountable on nutrition support of tube-fed patients with diabetes.
Clinical Nutrition 17, suppl (1998) 63-65

Coulston AM
Clinical experience with modified enteral formulas for patients with diabetes.
Clinical Nutrition 17, suppl (1998) 46-56

Coulston AM
Enteral nutrition in the patient with diabetes.
Current Opinion in Clinical Nutrition and Metabolic Care 3 (2000) 11-15

CraigL, Nicholson S, Silverstone F, Kennedy R
Use of a reduced-carbohydrate, modified-fat enteral formula for improving metabolic control and clinical outcomes in long-term care residents with type 2 diabetes: results of a pilot trial.
Nutrition 14 (1998) 529-534

DDG (2000) Deutsche Diabetes-Gesellschaft
Ernährungsempfehlungen für Diabetiker 2000: Stellungnahme der Diabetes and Nutrition Study Group (DNSG) of the European Association for the Study of Diabetes (EASD) und des Ausschusses Ernährung der Deutschen Diabetes Gesellschaft.
http://www.deutsche-diabetes-gesellschaft.de/statement/empf2000.htm

D.I.E.T.
Ernährungsmedizin und Diätetik aktuell – Im Fokus: Ballaststoffe in unserer Ernährung – status quo. Deutsches Institut für Ernährungsmedizin und Diätetik.
Februar (2001) 1-10

Delzenne NM, Kok N
Effects of fructan-type prebiotics on lipid metabolism.
Am J Clin Nutr 73, suppl 2 (2001) 456S-458S

Demetriades H, Botsios D, Kazantzidou D, Sakkas L, Tsalis K, Manos K, Dadoukis I
Effect of early postoperative enteral feeding on the healing of colocnic anastromoses in rats. Comparison of three different enteral diets.
Eur Surg Res 31, 1 (1999) 57-63

Ebskov B, Ebsbov L.
Major lower limb amputation in diabetic patients: development during 1982 to 1993.
Diabetologia 39 (1996) 1607-10

Elmadfa I, Leitzmann C
Ernährung des Menschen.
Verlag Eugen Ulmer, Stuttgart (1998)

Ernährungsbericht
Gesundheitliche Bedeutung sekundärer Pflanzenstoffe.
Deutsche Gesellschaft für Ernährung (Ed), Frankfurt a. M. (1996)
217-232

Floege J
Diabetische Nephropathie und Hypertonie bei Diabetes mellitus – Prophylaxe und Therapie.
VitaMinSpur 1 (2001) 35-37

Franzke C
Pflanzenphenole.
In: Franzke C (Ed) Allgemeines Lehrbuch der Lebensmittelchemie.
B. Behrs Verlag, Hamburg (1996) 231-243

Friedmann M, Brandon DL
Nutritional and health benefits of soy proteins.
Journal of Agricultural and Food Chemistry 49,3 (2001) 1069-1086

Gallagher-Allred C, O´Dorisio TM
Quality of life in tube-fed patients with diabetes mellitus.
Clinical Nutrition 17, suppl 2 (1998) 60-62

Gibson GR, Collins MD
Concept of balanced colonic microbiota, prebiotics and synbiotics.
In: Hanson

Gibson GR, Roberfroid MB
Dietary modulation of the human colonic microbiota: introducing the concept of prebiotics.
American Institute of Nutrition (1995) 1401-1413

Gonzáles-Barranco J
Glucose control guidelines: current concepts.
Clinical Nutrition 17, suppl 2 (1998) 7-17

Guenter PA, Settle RG, Perlmutter S, Marino PL, DeSimone GA, Rolandelli RH
Tube feeding-related diarrhea in acutely ill patients.
J Parenter Enter Nutr 15,3 (1991) 277-80

Haupt E, Standl E, Mehnert H
Behandlung mit insulinotropen oralen Antidiabetika (Sulfonylharstoffen).
In: Mehnert H, Standl E, Usadel K-H (Ed). Diabetologie in Klinik und Praxis.
4. Auflage, Thieme, Stuttgart (1999)

Hepp K-D, Häring H-U
Einführung in die Biochemie und Pathophysiologie des Stoffwechsels.
In: Mehnert H, Standl E, Usadel K-H (Ed). Diabetologie in Klinik und Praxis.
4. Auflage, Thieme, Stuttgart (1999)

Hermansen K, Søndergaard M, Høie L, Carstensen M, Brock B
Beneficial effects of a soy-based dietary supplement on lipid levels and cardiovascular risk markers in type 2 diabetic subjects.
Diabetes Care 24, 2 (2001) 228-233

Hoffmann L
Neue Empfehlungen bei Diabetes mellitus.
Verbraucherdienst 43,7 (1998) 515-519

Internationale Diabetes Federation
Leitfaden zu Typ-1-Diabetes mellitus.
Diabetes und Stoffwechsel 9, 3 (2000) 173-198

Janka H-U, Standl E, Standl R
Allgemeiner Überblick über die Angiopathien.
In: Mehnert H, Standl E, Usadel K-H (Ed). Diabetologie in Klinik und Praxis.
4. Auflage, Thieme, Stuttgart (1999)

Jeejeebhoy KN (1999)
The role of chromium in nutrition and therapeutics and as a potential toxin.
Nutrition Reviews 57, 11 (1999) 329-335

Jenkins DJA, Kendall CWC, Vuksan V
Inulin, oligofructose and intestinal function.
American society for Nutritional Sciences (1999) 1431S-33S

Karsten S
Neue Empfehlungen zur enteralen Ernährung von Diabetikern.
Ernährungs-Umschau 46 (1999) 90-94

Kasper H
Ernährungsmedizin und Diätetik. 9. Auflage
Urban & Fischer, München (2000)

Katsilambros NL
Nutrition in diabetes mellitus.
Exp Clin Endocrinol Diabetes 109, suppl 2 (2001) S250-S258

Kerner W
Klassifikation und Diagnose des Diabetes mellitus.
Deutsches Ärzteblatt 95, 49 (1998) A3144-A3148

Khalil L, Ho KH, Png D, Ong CL
The effect of enteral fibre-containing feeds on stool parameters in the post-surgical period.
Singapore Med J 39, 4 (1998) 156-159

Klinikarzt
Insulinsesitizer: Wende in der Therapie des Typ-2-Diabetes.
Klinikarzt 29, 2 (2000) VII

Koivisto VA, Yki-Jarvinen H
Fructose and insulinsensitivity in patients with type 2 diabetes.
J Intern Med 233, 2 (1993) 145-153

Koolman J, Röhm K.-H.
Taschenatlas der Biochemie.
2. Auflage Thieme, Stuttgart (1998)

Landgraf R, Halsbeck M
Diagnose und Differentialdiagnose.
In: Mehnert H, Standl E, Usadel K-H (Ed).
Diabetologie in Klinik und Praxis. 4. Auflage
Thieme, Stuttgart (1999)

Laube H, Mehnert H
Ernährungstherapie
In: Mehnert H, Standl E, Usadel K-H (Ed)
Diabetologie in Klinik und Praxis. 4. Auflage
Thieme, Stuttgart (1999)

Lean ME, Noroozi M, Kelly I, Burns J, Talwar D, Sattar N, Crozier A
Dietary flavonols protect diabetic human lymphocytes against oxidative damage to DNA.
Diabetes 48, 1 (1999) 176-181

Lohmann D
Diabetes mellitus Typ II.
Klinik der Gegenwart XV, 2 (1993) 1-27

Manuel y Keenoy B, Vertomemen J, De Leeuw I
The effect of flavonoid treatment on the glycation and antioxant status in Type 1 diabetic patients.
Diabetes Nutr Metab 12, 4 (1999) 256-263

McCargar LJ, Innis SM, Bowron E, Leichter J, Dawson K, Toth E, Wall K
Effect of enteral nutritional products differing in carbohydrate and fat on indices of carbohydrate and lipid metabolism in patients with NIDDM.
Molecular and Cellular Biochemistry 188 (1998) 81-89

McMahon MM, Rizza RA
Nutrition support in hospitalized patients with diabetes mellitus.
Mayo Clin Proc 71 (1996) 587-594

Miyake Y, Yamamoto K, Tsujihara N, Osawa T
Protective effects of lemon flavonoids on oxidative stress in diabetic rats.
Lipids 33, 7 (1998) 689-695

Monitori VM, Farmer A, Wollan PC, Dinneen SF
Fish oil supplementation in type 2 diabetes: a quantitative systematic review.
Diabetes Care 23 (2000) 1407-1415

Morris BW, Mac Neil S, Hardisty CA, Heller S, Burgin C, Gray TA
Chromium homeostasis in patients with type II (NIDDM) diabetes.
J Trace Elem Med Biol 13, 1-2 (1999) 57-61

Müller SD
Chrom und Zink in der Diabetestherapie.
VitaMinSpur 16, S1 (2001) 79-81

Mutanen M, Freesse R
Polyunsaturated fatty acids and peatelet aggregation.
Current Opinion in Lipidology 7 (1996) 14-19

Over M
Krankheitsbild des Diabetes mellitus (1. Folge).
Pflegen Ambulant 3 (1992) 19-22

Potter SM, Baum JA, Stillman RJ, Shay NF, Erdman JW
Soy protein Isoflavones: their effects on blood lipids and bone density in postmenopausal women.
Am J Clin Nutr 68 (1998) 137S-1379S

Preiser JC, Van Gonsum A, Berre J, Vincent JL, Carpentier Y
Enteral feeding with a solution enriched with antioxidant vitamins A, C and E enhances the resistance to oxidative stress.
Crit Care Med 28, 12 (2000) 3828-32

Prince MJ, Deeg MA
Do n-3 fatty acids improve glucose tolerance and oliemia in diabetics?
Current Opinion in Lipidology 8 (1997) 7-11

Rehner G, Daniel H
Biochemie der Ernährung.
Spektrum Akademischer Verlag, Heidelberg-Berlin (1999)

Risse A
Typ-II-Diabetiker in Deutschland: Zu viele Amputationen – jede zweite vermeidbar.
Ärztliche Praxis – Jubiläumsausgabe 1 (1999)

Rosak C, Böhm BO
Behandlung mit Insulin.
In: Mehnert H, Standl E, Usadel K-H (Ed). Diabetologie in Klinik und Praxis. 4. Auflage
Thieme, Stuttgart (1999)

Rösen P, Nawroth PP, King G, Möller W, Tritschler H-J, Packer L
The role of oxidative stress in the onset and progression of diabetes and its complications: a summery of a congress series sponsored byUNESCO-MCBN, the American Diabetes Association and the German Diabetes Society.
Diabetes Metab Res Rev 17 (2001) 15-24

Saito M
Dietary docosahexaenoic acid does not promote tissue lipid peroxide formation to the extent expected from the peroxidizability index of the lipids.
Biofactors 13, 1-4 (2000) 15-24

Sanz-Paris A, Cavo L, Guallard A, Salazar I, Albero R
High-fat versus high-carbohydrate enteral formulae: effect on blood glucose, c-peptide, and ketones in patients with type 2 diabetes treated with insulin or sulfonylurea.
Nutrition 14 (1998) 840-845

Sauer I, Rath W
Gestationsdiabetes-
VitaMinSpur S1 (2001) 114-117

Schrezenmeir J
Rationale for specialized nutrition support for Hyperglycemic patients.
Clinical Nutrition 17, suppl 2 (199() 26-34

Schumacher B
Neue europäische Ernährungsempfehlungen für Diabetiker.
VitaMinSpur 14 (1999) 86

Schumacher B
Diabetische Polyneuropathie II.
VitaMinSpur 15 (2000) 36-37

Shah M, Garg A
High-fat and high-carbohydrate diets and energy balance.
Diabetes Care 19 (1996) 1142-1152

Shankardass K, Chuchmach S, Chelswick K, Stefanovich C, Spurr S, Brooks J, Tsai M, Saibil FG, Cohes LB, Edington JD
Bowel function of long-term tube-fed patients consuming formulae with and without dietary fiber.
J Parenter Enter Nutr 14,5 (1990) 508-512

Standl E, Janka HU, Mehnert H
Behandlung mit nichtinsulinotopen oralen Antidiabetika.
In: Mehnert H, Standl E, Usadel K-H (Ed). Diabetologie in Klinik und Praxis. 4. Auflage
Thieme, Stuttgart (1999)

Stiller P, Huber H, Bögl M, Friedrich M, Haslbeck M
Metabolische Wirkungen einer kohlenhydratmodifizierten bilanzierten Diät bei Typ-II-Diabetes.
Akt Ernähr-Med 18 (1993) 70

Stürmer W, Kramer E, Kaper H, Schrezenmeir J
Favourable glycaemic effects of a new balanced liquid diet for enteral nutrition – Results of a short-term study in 30 Type II diabetic patients.
Clinical Nutrition 13 (1994) 221-227

Van Gaal LF, Van Acker KL, DeLeeuw IH
Repaglanide improves blood glucose control in sulphonylurea-naive type 2 diabetes.
Diabetes Res Clin Pract 53 ,3 (2001) 141-148

Vincent JB
Quest for the molecur mechanism of chromium action and its relationship to diabetes.
Nutrition Reviews 58,3 (2000) 67-72

Vogt M, Adamek H-E, Arnold J-C, Schilling D, Schleiffer T, Riemann J-F
Gastrointestinale Komplikationen des Diabetes mellitus.
Med Klin 94 (1999) 329-337

Washburn S, Burke GL, Morgan T, Anthony M
Effect of soy protein supplementation on serum lipoproteins, blood pressure, and menopausal symptoms in perimenopausal women.
Menopause 6 (1999) 7-13

Wright J
Total parenteral nutrition and enteral nutrition in diabetes.
Current Opinion in Clinical Nutrition and Metabolic Care 3 (2000) 5-10

Yokozawa T, Dong E
Influence of green tea and its three major components upon low-density lipoprotein oxidation.
Exp Toxicol Pathol 49, 5 (1997) 329-335

[Table of contents]

7. List of Abbreviations

[Table of contents]