Diet and Modification of Nutrient Absorption

S. Iannello Institute of Internal Medicine, University of Catania, Ospedale Garibaldi,

Catania, Italy

Diet

Introduction In the treatment of diabetes mellitus, changes in lifestyle play a major

role, in addition to treatment with insulin or oral glucose-lowering drugs. For most patients with type 2 diabetes, the changes in lifestyle (concerning diet and exercise) are the cornerstone of treatment whereas the pharmacologic intervention represents a supplementary treatment for those patients who do not respond adequately to lifestyle changes.

Dietary caloric restriction ameliorates hyperinsulinemia and hyperglycemia in obese type 2 diabetics (and improves other metabolic parameters; see table 1) and reduces the incidence of type 2 diabetes in subjects at risk or with impaired glucose tolerance (IGT). Glucose tolerance and insulin sensitivity improve when normal body weight is achieved or approached. Indeed, even

a 7–10% of weight loss is enough to improve insulin resistance in all obese type 2 diabetics. Nutritional needs are different in type 1 (lean) or type 2

(overweight or obese) diabetic patients. Diet education is crucial and requires the participation of the patient and its family in the planning-diet process and in the implementation of the adequate strategies to promote adherence to dietary intervention.

Goals of dietary therapy in diabetes are to reach and maintain ideal body weight (IBW), to maintain fasting and postprandial glycemic levels as close as possible to normal and to achieve optimal blood lipid values, while providing adequate caloric intake as required for the various metabolic needs.

Table 1. Effects of weight loss on altered parameters in obese type 2 diabetics

Insulin resistance B Hyperglycemia B Hypertriglyceridemia B Total hypercholesterolemia B

LDL cholesterol B HDL cholesterol C

Hypertension B

Modern recommended diet for diabetes is relatively high in complex carbohydrates (55–60% of total calories) and fibers, low in fats (25–30%) especially saturated (=10%, to reduce dyslipidemia and atherosclerosis associated to diabetes) and limited, but adequate, in proteins (15%).

Body Weight and Fat Distribution Increase in body weight (related to height) or frank obesity are highly

relevant to the pathogenesis of type 2 diabetes. The ‘ideal’ body weight (actually the weight associated with the lowest mortality) for each inch of height can

be derived from the 1983 Metropolitan Life Insurance Weights for Heights tables, referring to 4.2 million subjects aged 20–59. For people over 55, the tables of median weights derived from the data of the National Health and Nutrition Examination Surveys (NHANES) may also be used. A commonly used parameter relating weight to height is the body mass index (BMI), which

is calculated as follows: BMI>weight (kg)/height (m) 2 . In the clinical setting,

a BMI from 20 to 25 can be regarded as ‘normal’ while a BMI ?27 can be regarded as indicative of overweight. In some studies, the following values have been suggested for the BMI: =23.9>normal value for women; =25> normal value for men; 23.9–28.6 (female) and 25–30 (male)>overweight; ?

28.6 (female) or ?30 (male)>obesity. In 1995, the WHO established the following BMI values: normal>18.5–24.9; overweight, 1st degree>25.0–29.9; overweight, 2nd degree (or obesity)>30.0–39.9; overweight, 3rd degree (or severe obesity) q40. It should be noted that the BMI associated with the lowest mortality increases with age, ranging from =20 at age 20 to about 28 at age 70.

It should be noted that from the above values of BMI it is possible to calculate the corresponding weight values through the formula: weight (kg)>BMI¶height (m) 2 . Assessment of adipose tissue distribution is of para- mount importance to distinguish between visceral (or central or abdominal It should be noted that from the above values of BMI it is possible to calculate the corresponding weight values through the formula: weight (kg)>BMI¶height (m) 2 . Assessment of adipose tissue distribution is of para- mount importance to distinguish between visceral (or central or abdominal

be used to indicate increased risk of cardiovascular disease in women. Other recent data suggest an upward shift in the critical threshold for WHR to q

0.90, at which point there is an elevation in cardiovascular disease risk factors. It has also been shown that the simple waist circumference is a good index of central (visceral) obesity, as is also the sagittal diameter. The values of waist circumference indicating increased visceral fat and cardiovascular risk were found to be ?94 cm in men and ?80 cm in women. Recently, it has been reported that, while a waist circumference q96.5 cm is associated with high cardiovascular risk, even a waist circumference q76.2 cm entails significant risk. Interestingly, threshold values of waist girth corresponding to critical amounts of visceral adipose tissue do not appear to be influenced by sex or by the degree of obesity. It has also been estimated that a waist girth of approximately 95 cm in both sexes, WHR values of 0.94 in men and of 0.88 in women, and sagittal diameters of 22.8 cm in men and 25.2 cm in women correspond to a critical amount of visceral adipose tissue, equal to a fat area

of 130 cm 2 . The amount of intra-abdominal (visceral) fat may be precisely measured with computed tomography (CT), which however is an expensive procedure. Echography is also being used to quantify the fat tissue and its distribution.

Total Caloric Requirement The caloric requirement of diabetic patients is similar to that of normal

subjects and changes with age, sex and occupational daily work or physical activity (i.e. patients engaged in a heavy activity require a larger caloric intake). Other factors may influence dietary regimen, as the type of diabetes and the associated diseases. In lean adult diabetic patients, caloric intake should maintain a normal weight, while in obese diabetic patients (especially with upper body fat distribution) a caloric restriction is required to achieve a desirable weight. Noticeably, dietary restriction may improve metabolic control even before weight loss is attained.

Sedentary normal patients need approximately 30 cal/kg IBW/day while active normal patients need approximately 35–40 cal/kg/day. Overweight sedentary patients need 20–25 cal/kg/day and active obese patients need 30–35 cal/kg/day, while underweight patients need 35 cal/kg/day if sedentary and 40–50 cal/kg/day if active. In elderly sedentary diabetic patients, 20 cal/kg/day are usually required (after 50 years of age approximately 10% less calories for each decade is required).

A more accurate assessment of the caloric needs may be achieved by using appropriate formulas to calculate the rest metabolic rate (RMR), such as those of Harris & Benedict which are based on weight, height, age and sex. Since subjects of the same weight but of different height have similar RMR, formulas may be simplified by considering only weight, age and sex. RMR should be increased by 30, 50 or 70% for low, medium or high levels of physical activity. Table 2 shows the caloric requirement according sex and age for selected weights and activity levels, based on similar formulas.

In diabetic children the caloric needs depend on the rate of growth and activity pattern. Children 4–6 years old require 90 cal/kg/day and children 7–10 years old require 80 cal/kg/day. It is important to allow an adequate caloric intake in juvenile diabetes. Caloric requirement in children may also

be calculated by adding to the baseline value of 1,000 cal/day the amount of 100–125 cal for every year of age up to 12 years. Youngsters should consume

3 meals daily with 2 or 3 snacks (eaten at the same time each day) to minimize glycemic fluctuations and the risk of hypoglycemic episodes. After the caloric content and the composition of the diet are established, the prescription of a diet was in the past made by utilizing the data in the Exchange Lists for Meal Planning published by the American Diabetes Association. A more useful approach might be to use the precalculated diets (of various caloric content) prepared by several diabetes associations or other authoritative sources. How- ever, it is now recognized that the diet should be individualized and prepared by taking into account the eating habits and other lifestyle factors.

It is clinically relevant that 7–35% of adolescent females with type 1 diabetes may have an eating disorder, such as anorexia or bulima nervosa.

Dietary Components Dietary Carbohydrate

Carbohydrates are the most important source of energy and provide about

4 cal/g. The carbohydrate intake of diabetic patients should be equal to that of nondiabetic subjects. A dietary carbohydrate content of about 50–60% of total energy intake seems adequate in diabetic patients.

Table 2. Caloric needs according to age, sex, weight 1 and physical activity Sex and

Weight Physical activity age group

medium medium high high

kcal/day kcal/kg kcal/day Men

kcal/kg kcal/day kcal/kg kcal/day kcal/kg

18–30 years old

36.8 2,721 41.7 3,084 31–60 years old

18–30 years old

34.2 2,119 38.8 2,401 31–60 years old

33.0 2,037 37.4 2,309 1 Caloric needs at rest (RMR) per day were calculated according to the following formulas (as reported

by G. Bray): for 18- to 30-year-old men: (0.0630¶kg weight+2.8957)¶240; for 31- to 60-year-old men: (0.0484¶kg weight+3.6534)¶240; for 18- to 30-year-old women: (0.0621¶kg weight+2.0357)¶240; for 31- to 60-year-old women: (0.0342¶kg weight+3.5377)¶240. RMR was then multiplied by 1.3, 1.5 or 1.7 for low, medium or high physical activity, respectively.

Carbohydrates are available as complex or simple sugars. In diabetic patients, complex carbohydrates or polysaccharides should be preferred. Com- plex carbohydrates include: starches (present in large amounts in rice, cereals, potatoes, pulses and vegetable roots), dextrins (derived from hydrolyzed starch), glycogen (contained in liver and muscle), cellulose or pectins (indigest-

Table 3. Glycemic index of some foods

ible complex carbohydrates contained in plant foods). In diabetics, simple carbohydrates should be restricted. They include monosaccharides (glucose present in oranges and carrots, fructose present in honey and ripe fruits, and galactose derived from hydrolyzed lactose) and disaccharides (sucrose present in beetroot and sugar cane, lactose present in milk, and maltose derived from hydrolyzed starch). The formerly claimed diabetogenic effect of sucrose overconsumption has not been confirmed by epidemiological or experimental studies. However, in diabetic patients, sucrose-rich foods cause a rapid rise in glycemic values, which can be prevented by consuming these foods as part of

a mixed meal. The recommended disaccharide (sucrose plus other glucose- containing disaccharides) consumption by diabetic people should not exceed 5–10% of the total caloric intake. Sucrose addition as sweetener should not exceed 20 g/day. Fructose is a natural monosaccharide, used as a sweetener. It is converted to glucose (and stored as glycogen) or triglyceride in liver. In diabetics with insulin deficiency and impaired hepatic glycogen synthesis, fructose-derived glucose contributes to the hyperglycemia. Thus, the safety of fructose use in diabetes is a debated topic. Starches are hydrolyzed to dextrins, then to maltose and finally to glucose (through the effect of gastric acid and intestinal enzymes). They are useful in the diabetic diet because they are slowly digested and absorbed, inducing lower increments of the glycemic and insulinemic values than equivalent amounts of glucose or simple sugars.

It is well established that equimolar amounts of carbohydrate in different foods induce different glycemic postprandial excursions. Jenkins et al. [1981] have elaborated a ‘glycemic index’, representing the incremental area under

2 h glycemic curve of food divided by the corresponding area under 2 h glycemic curve after ingestion of a portion of white bread containing equivalent amounts of carbohydrates, multiplied by 100 (table 3). Reference can also be made to the glycemic response after glucose ingestion, in which instance the glycemic index for glucose is 100. Foods containing simple sugars have a high glycemic index, raising glycemia and insulinemia faster and to a greater extent, and therefore are contraindicated in diabetic patients. However, several factors can influence the food glycemic response, including: (a) type of diabetes, age, 2 h glycemic curve of food divided by the corresponding area under 2 h glycemic curve after ingestion of a portion of white bread containing equivalent amounts of carbohydrates, multiplied by 100 (table 3). Reference can also be made to the glycemic response after glucose ingestion, in which instance the glycemic index for glucose is 100. Foods containing simple sugars have a high glycemic index, raising glycemia and insulinemia faster and to a greater extent, and therefore are contraindicated in diabetic patients. However, several factors can influence the food glycemic response, including: (a) type of diabetes, age,

Dietary Fat Fats are an important source of energy, providing about 9 cal/g, and

difference in the amount and type of dietary fat can have relevant metabolic effects. In patients with IGT or type 2 diabetes or decompensated type 1 diabetes, elevated plasma levels of triglycerides and cholesterol frequently occur. Both hypertriglyceridemia and hypercholesterolemia respond in part to diet alterations. The recommended fat intake is p30% of total calories (=10% of saturated fats, 6–8% of polyunsaturated fats and 14–12% of monounsaturated fats given as olive oil). Low-fat diets are often high in carbohydrate (being the proportion of proteins relatively constant), which may favor hypertriglyceridemia. This effect may be attenuated by supplementation with fibers.

Saturated fats (which are solid at room temperature) are most often from animal source (milk, butter, cheese, bacon fat, fatty meat, etc.), but they are also contained in high concentrations in coconut and palm oils. Diets high in saturated fat are atherogenic (increasing total and LDL cholesterol levels) and favor insulin resistance; thus, a diet restricted in saturated fats is recommended. Unsaturated fats (which are liquid at room temperature) derive from vegetable source and include monounsaturated and polyunsaturated fats. A diet high in monounsaturated fatty acids or MUFA (most often assumed as olive oil, as it occurs with the Mediterranean diet) does not increase LDL levels, may improve insulin sensitivity, glycemic control and HDL cholesterol levels, and decreases plasma triglycerides. For this reason, the American Diabetes Associ- ation (ADA) and the European Association for the Study of Diabetes (EASD) set free the intake of monounsaturated fat in diabetic patients. On the contrary,

a diet high in polyunsaturated fatty acids or PUFA (such as corn, sunflower and safflower oils) reduces total and LDL cholesterol but decreases HDL

cholesterol as well; moreover, some data from the literature would suggest that they may promote carcinogenesis in experimental animals.

The intake of cholesterol should be restricted to =300 mg daily, avoiding cholesterol-rich foods (table 4), which can produce a 15–20% reduction of plasma cholesterol level. Excessive cholesterol intake causes increase in total plasma cholesterol and LDL cholesterol, which can be reduced by increasing the polyunsaturated/saturated fat ratio (which should be kept at ?0.8).

The polyunsaturated fatty acids of the omega-3 class (eicosapentaenoic and docosahexaenoic acids), which can be formed from a-linolenic acid

Table 4. Cholesterol content of some foods (mg/100 g) Brain

Egg yolk 1,480

Lobster

Lamb kidney 804

Cream

Chicken liver 746

Cheese, cheddar

Whole milk

Butter 250

Egg white

(through elongation and desaturation), are contained in fish oils and are useful to reduce the coronary risk of diabetic patients (decreasing VLDL production, lowering arterial blood pressure, reducing platelet aggregation and prolonging bleeding time). This explains the low prevalence of coronary heart disease in the Greenland Eskimos (consuming 5–10 g of fish oil fatty acids daily for a lifetime) and in the Japanese fish eaters of coastal villages. A dietary supplementation with fish or fish oil should, therefore, be recommended. It would be advisable to replace in 2–3 meals a week the red meat with fish. However, three considerations speak against an excessive intake of fish or fish oil: (a) fishes of coastal waters and lakes accumulate a large quantity of mercury and chlori- nated hydrocarbons; (b) in some type 2 diabetic patients, 3-omega fatty acids may deteriorate glycemia (both increasing hepatic glucose production and impairing insulin secretion), and (c) in patients with hypercholesterolemia but without hypertriglyceridemia the metabolic effects of fish oil are uncertain.

Recently, new fat substitutes were proposed for use in the diet of diabetic patients. One of these products is named Olestra and is made from sucrose and long-chain fatty acids, is heat-stable, tastes like vegetable oil, promotes cholesterol excretion and is calorie-free being not metabolized or absorbed. Another fat substitute is named Simpless and is made from egg white or whey protein of milk (using a process of microparticulation which confers a taste of fat), has a low-calorie content, and is useful to make ice-cream, yogurt, margarine, cheeses, etc.

Dietary Protein Proteins are formed by amino acids and provide about 4 cal/g of energy.

Some amino acids cannot be synthesized by humans and must be introduced with diet (essential amino acids). The animal proteins (contained in meat, chicken, fish, egg, milk, etc.) are of high biological value, containing adequate amount of essential amino acids, while vegetable proteins (peas, beans, dry fruits, cereals, etc.) are of low biological value, laking some essential amino acids. Leucine and arginine have important biologic effects, stimulating insulin Some amino acids cannot be synthesized by humans and must be introduced with diet (essential amino acids). The animal proteins (contained in meat, chicken, fish, egg, milk, etc.) are of high biological value, containing adequate amount of essential amino acids, while vegetable proteins (peas, beans, dry fruits, cereals, etc.) are of low biological value, laking some essential amino acids. Leucine and arginine have important biologic effects, stimulating insulin

The role of dietary protein in the development and progression of diabetic nephropathy is debated while it is clearly defined that a moderately low protein diet is the best approach for treating renal disease of diabetic patients (see chapter on Diabetic Nephropathy). The recommended amount of proteins in diabetic diet is of 12–20% of total calories. In diabetic subjects a high-protein diet can increase renal blood flow, glomerular filtration rate and intra- glomerular pressure, accelerating glomerulosclerosis to end-stage renal failure (Brenner’s hypothesis). It is useful to substitute, at least in part, vegetable proteins for animal proteins, even if proteins from animal source do not seem to significantly increase kidney workload. In subclinical or incipient stages of diabetic nephropathy, glycemic control and low protein intake (0.8 g/kg IBW/ day) may reduce renal blood flow, restore normal glomerular hemodynamics, decrease proteinuria and delay the progression of nephropathy. In overt diabetic nephropathy with albumin excretion, the recommended protein restriction should be from 0.6 to 0.8 g/kg/day. In cases of protein restriction, essential amino acids should be supplemented. To maintain energy balance, a low protein diet must be high in carbohydrates and fats and may exacerbate hyperglycemia, hypertriglyceridemia or hyperinsulinemia, increasing total and LDL cholesterol and decreasing HDL cholesterol. Moreover, in diabetic patients a low protein dietary content may favor a negative nitrogen balance and muscle wasting.

Dietary Fibers In normal subjects and type 2 diabetic patients, several studies demon-

strated an improvement of glucose tolerance and a reduction of insulin secretion when a diet high in fiber was consumed. In type 1 diabetics, high-fiber diet was found to decrease glycosuria, as well as basal and postprandial glycemic levels. Moreover, high-fıber intake may improve other metabolic parameters, and may also exert a preventive effect on cancer of bowel and diverticular disease (diseases favored by the modern tendency to consume low- fiber, refined foods). Dietary fibers are heterogeneous and consist of several complex polysaccharides resistant to gastrointestinal digestive enzymes (even if certain fibers are metabolized in the colon). Fibers can be water soluble or insoluble and their effects are variable according to the different biochemical- physiological characteristics. Celluloses, hemicelluloses and lignins bind water and cations and are insoluble (wheat products and bran) whereas pectins,

Table 5. Foods naturally rich in fibers Legumes

Beans, peas, chickpeas, lentils Vegetables

Broccoli, artichokes, zucchini, carrots, eggplants, string beans, squash, potatoes, tomatoes, celery, cabbage, onions, beets, fennels, turnips, radishes, asparagus, cucumbers, cauliflower, mushrooms

Fruits Apples, blackberries, pears, strawberries, oranges, plums, bananas, grapefruit, pineapples, peaches, cherries, apricots, kiwis, mandarins

Cereals Bran (100%), bread (rye), bread (whole-grain wheat), rice, wheat flour (whole grain)

gums and mucilages form gels and are soluble (oats, fruits and legumes). The foods naturally rich in fibers are legumes, roots, tubers, whole-grain cereals, fruits and green leafy vegetables (table 5).

Usually, the soluble fibers (especially those with high viscosity) exert useful metabolic effects, whereas insoluble fibers contribute to increase fecal bulk,

promote movements of intestinal content, being useful in constipation (which may also result from autonomic diabetic neuropathy). The physiological effects of fibers are influenced by osmolality or pH, mixture of fibers and foods, water retention, fermentation by bacteria, etc. Soluble fibers would exert their beneficial effects on carbohydrate and lipid metabolism through several mecha- nisms, which include: (a) satiating effect; (b) delayed gastric emptying time;

(c) decreased release of gut hormones, including intestinal insulin secretagogues (as GIP); (d) delayed small intestine transit time and altered colonic emptying time; (e) binding of bile acids, with impaired intestinal absorption of cholesterol; (f ) formation of gels that sequester or hide nutrients (carbohydrates, fats, cholesterol, etc.), providing a physical barrier that separates complex carbohydrates from digestive enzymes, with reduced digestion and absorption in small intestine; (g) increase of fecal bulk with accelerated intestinal transit, which may reduce absorption of nutrients; (h) fermentation by the bacteria in the colon to gases and short-chain fatty acids, which would suppress neoglu- cogenesis, and (i) improved peripheral insulin sensitivity and increased insulin receptor binding.

It is interesting that fibers have the best effects when naturally contained in aliments while they have poorer effects when added as pharmaceutical products to dietary foods. Diets useful to improve both fasting and postprandial hyperglycemia in diabetic patients have been suggested, which are rich in fibers naturally contained in foods. These diets are very rich in carbohydrates (up to 70%) and fibers (up to 35 g/day/1,000 kcal, both in soluble It is interesting that fibers have the best effects when naturally contained in aliments while they have poorer effects when added as pharmaceutical products to dietary foods. Diets useful to improve both fasting and postprandial hyperglycemia in diabetic patients have been suggested, which are rich in fibers naturally contained in foods. These diets are very rich in carbohydrates (up to 70%) and fibers (up to 35 g/day/1,000 kcal, both in soluble

and would reduce total or LDL cholesterol and triglycerides (only in diabetics), while lowering blood pressure and favoring weight loss in obese patients. In hypocaloric diets, the usually recommended fiber supplementation is in the amount of 25 g/1,000 kcal (associated with high water assumption to induce fiber swelling).

High-fiber diets can cause (especially in the first 7–10 days) cramping, abdominal discomfort, flatulence and diarrhea. These diets may also impair absorption of minerals and vitamins if used for a long time (in which instance, supplementation of calcium, trace elements and vitamins may be required). They may also increase the risk of bezoar formation, especially when a diet high in fibers is contraindicated (patients with gastrointestinal dysfunction, gastroparesis or altered absorption from pancreatic enzyme deficiency). Large amounts of dietary fibers may not be well tolerated by children, pregnant diabetic women and elderly subjects.

Alcohol and Other Nutrients Alcohol provides about 7 cal/g, is not a food but is another source of

energy that should be considered in a dietary plan. Interestingly, in women a decreased risk (50%) of developing diabetes with increasing alcohol intake was found and this effect was probably related to lower BMI linked with alcohol consumption. Allowed intake should not exceed 10 g/day. Excessive alcohol intake should be avoided in diabetic patients, because it inhibits glu- coneogenesis and can favor hypoglycemic episodes in subjects treated with insulin or drugs. In hypertriglyceridemic patients, alcohol may exacerbate dyslipidemia and liver steatosis.

Diabetic patients may also suffer from associated diseases which require special modified diets. In the presence of congestive heart failure, hypertension

and kidney disease, dietary sodium should be restricted. The sodium restriction may range from 500 to 1,000 mg/day (maximum intake =3 g/day), although the use of diuretics may reduce the need for a severe sodium restriction, which makes foods less palatable and may provocate hypotension and fluid or electrolyte disorders.

Sweeteners Sweeteners can be distinguished into caloric (or natural) sweeteners and

noncaloric (or artificial) sweeteners (table 6). In both type 1 and 2 diabetic patients, the classical sweetener, sucrose, can be allowed in the maximum amount of 20 g/day, especially if associated to a mixed meal, because it does not deteriorate metabolic control. An excessive sucrose intake should be avoided,

Table 6. Sweeteners for diabetic patients Caloric or natural sweeteners

Sucrose Fructose Sugar alcohols (sorbitol, mannitol, xylitol)

Noncaloric or artificial sweeteners

Saccharin Cyclamates Aspartame

especially in hypertriglyceridemic or obese or severely decompensated diabetic subjects. Sucrose is the most cariogenic of the nutritive sweeteners, and caries is a problem in people with diabetes.

Alternative sweeteners have been proposed (sometimes as combinations of caloric and noncaloric sweeteners). An ideal sucrose substitute for diabetic patients should taste good and not induce hyperglycemia or elevation of plasma lipids; it should also contain few calories, have an adequate stability and consistency and be of low cost. Fructose is naturally found in honey and fruits and is 1–1.8 times as sweet as sucrose. Its caloric content is about 4 cal/g (equal to that of sucrose) but fewer calories are required to provide the same sweetness. The ingested fructose is phosphorylated to fructose-1-P in the liver, independently by insulin, and after splitting by aldolase it enters the glycolytic pathway and may be converted into glucose or triglyceride. The fructose intake does not cause side effects unless it exceeds 75 g (0.5 g/kg/day in children). Large oral amounts (?50 g) may cause diarrhea. In doses up to 30–35 g it does not impair glycemic control in well-compensated diabetics while in decompensated patients it may aggravate hyperglycemia and hypertriglyceridemia. Xylitol is a sugar alcohol derived from xylose, which is naturally present in fruits and vegetables. It has a sweetness equivalent to that of fructose, produces about 4 cal/g, is slowly absorbed and does not exacerbate glycemia or triglyceridemia (although it may induce a transient increase of uric acid synthesis). In excessive doses it may cause osmotic diarrhea. Sorbitol (as well as mannitol) is a sugar alcohol, obtained by reduction of glucose or fructose, which contains about 4 cal/g. It is slowly absorbed, yet it may increase glycemia in poorly compensated diabetic patients. Large amounts (30–50 g/day) may induce osmotic diarrhea.

Saccharin is the most used artificial sweetener with no caloric content. It is not metabolized and is excreted unchanged in urine. In high doses, saccharin was reported to induce malignancy of the urinary bladder in experimental animals, but studies in diabetic subjects indicate no relationship between sac- Saccharin is the most used artificial sweetener with no caloric content. It is not metabolized and is excreted unchanged in urine. In high doses, saccharin was reported to induce malignancy of the urinary bladder in experimental animals, but studies in diabetic subjects indicate no relationship between sac-

Cyclamates are 30 times as sweet as sucrose and have no caloric value; in very high doses (2,500 mg/kg/day) they are reported to induce tumors of the urinary bladder in rats. Although no evidence of malignancy exists in humans, cyclamates were banned from the US market; however, they are still available outside the USA. Aspartame is a nutritive sweetener consisting of a synthetic dipeptide. Compared to sucrose, it has the same caloric content (about 4 cal/g) but is 180–200 times more sweet, so that negligible calories are required to provide the same sweetness. It has a good taste, but it is instable in liquid solution and during heating, and is 4–5 times as expensive as saccharin. Some side effects were reported such as phenylketonuria in predisposed subjects, neuroendocrine disorders and brain tumors. These data were not confirmed by FDA, that has set 50 lg/kg/day as a safe daily aspartame intake. The alternative sweeteners with no or low caloric value are certainly useful in the management of diabetic and obese patients that find pleasantness in sweet foods.

Hypocaloric Diet in Overweight Type 2 Diabetes In type 2 diabetes, caloric restriction should be correlated with the degree

of overweight or obesity, and the calculation of appropriate calories depends upon the body weight and the physical activity of the patient. In slightly overweight patients, a 1,600–1,800 kcal/day diet may be appropriate. In the cases with more marked overweight, a hypocaloric diet of about 1,000–1,500 kcal/day should be prescribed. In these diets, the protein content should not

be =0.8 g/kg IBW. With weight loss, in most obese diabetic patients the carbohydrate metabolism will improve, so that insulin or hypoglycemic drugs may be reduced or withdrawn. Even a modest weight loss may be associated with significant metabolic improvement, although marked individual vari- ations occur. This improvement primarily involves fasting glycemia and is correlated with decreased hepatic glucose output. These favorable effects may have a positive impact on the overweight diabetic patient with regard to the compliance to the hypocaloric diet.

The very low calorie diet (VLCD: 800–500 kcal/day, mostly derived from high-quality proteins, with vitamin and mineral supplementation) should be avoided in diabetic patients for the risk of severe arrhythmias or coronary symptoms. Moreover, a long-term evaluation of VLCD (compared to conven- tional diets) has demonstrated no significant difference on weight loss. A VLCD should be limited to type 2 diabetic patients who are 50% or more The very low calorie diet (VLCD: 800–500 kcal/day, mostly derived from high-quality proteins, with vitamin and mineral supplementation) should be avoided in diabetic patients for the risk of severe arrhythmias or coronary symptoms. Moreover, a long-term evaluation of VLCD (compared to conven- tional diets) has demonstrated no significant difference on weight loss. A VLCD should be limited to type 2 diabetic patients who are 50% or more

Diet and Exercise Exercise is a relevant component in a program of weight loss in diabetic

patients. It improves glucose tolerance, lowers glycemia, increases peripheral insulin sensitivity and reduces risk factors for coronary heart disease (amelio- rating hypertension and blood lipid profile). The combination of diet plus exercise is more effective than diet alone or exercise alone in producing long- term weight loss, in maintaining the weight loss over time and in reducing the dose of hypoglycemic drugs. The recommended exercise (walking or stationary bicycle riding) should be of low or moderate intensity but of long duration, and is especially useful in adult or older obese type 2 diabetic subjects. The exercise should be performed at least every 2–3 days for optimum effect (ex- amples: stationary bicycle riding or brisk walking for 30 min/day, or active swimming for 1 h 3 times/week). Because exercise may increase the risk of acute or delayed hypoglycemia, a prospective reduction in insulin dose for regular exercise should be used as well as a supplementary snack of about 40 g of carbohydrates. In decompensated diabetic patients with insulin deficiency, exercise is contraindicated (especially if prolonged, severe or unusual) raising glycemia and ketone levels. Alcohol may exacerbate the risk of hypoglycemia after exercise. Diabetic patients should be encouraged to increase their physical activity gradually, with increments of the activities within their daily lives (walking to work, using stairs rather than elevators, etc.). However, the effects of exercise on the caloric balance (and therefore on weight loss) may be less than expected for several reasons. In fact, from the energy lost during exercise, those calories should be subtracted that the patient would have lost with his usual activity. Moreover, often the exercise stimulates the appetite, leading to enhanced caloric assumption. Finally, in some tense individuals, exercise may induce muscular relaxation, which means decreased isometric muscular work.

Conclusion In conclusion, the reduction of the caloric intake in obese people may

have a relevant effect on the frequency of type 2 diabetes. On the other hand, a proper nutritional management of obese diabetic patients is the most have a relevant effect on the frequency of type 2 diabetes. On the other hand, a proper nutritional management of obese diabetic patients is the most

Modification of Nutrient Absorption Agents capable of modifying the absorption of complex carbohydrates

or lipids, such as a-glucosidase inhibitors and Orlistat, will be discussed in Chapter VI (Overview of Diabetes Management).

Diet and Modification of Nutrient Absorption