MXPA01008016A - Composition and process for controlling glucose metabolism in companion animals by dietary starch - Google Patents

Composition and process for controlling glucose metabolism in companion animals by dietary starch

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Publication number
MXPA01008016A
MXPA01008016A MXPA/A/2001/008016A MXPA01008016A MXPA01008016A MX PA01008016 A MXPA01008016 A MX PA01008016A MX PA01008016 A MXPA01008016 A MX PA01008016A MX PA01008016 A MXPA01008016 A MX PA01008016A
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corn
sorghum
glucose
source
diet
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MXPA/A/2001/008016A
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Spanish (es)
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Gregory Dean Sunvold
Michael Griffin Hayek
Stefan Patrick Massimino
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The Iams Company
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Abstract

A composition and process are provided for controlling postprandial glycemic and/or insulinemic response in companion animals such as dogs. The pet food composition includes a source of protein, a source of fat, and a source of carbohydrates from a grain source which excludes rice. Use of the preferred carbohydrate sources including a blend of corn and sorghum;a blend of corn, sorghum, and barley;a blend of corn, sorghum, and oats;and a blend of oats and barley tends to modulate the animal's glycemic and insulinemic responses after a meal. This effect is even more marked when the composition is fed to geriatric companion animals such as dogs.

Description

- i - COMPOSITION AND PROCESS FOR CONTROLLING GLUCOSE METABOLISM IN COMPANY ANIMALS BY STARCH IN THE DIET DESCRIPTION OF THE INVENTION The present invention relates to a composition and process for using it to alter and improve glucose metabolism in companion animals, particularly old pet animals such as dogs. Different diverse conditions are associated with a damaged glucose metabolism in companion animals such as the dog and the cat. These include diabetes (both of the insulin-dependent type and of the type that starts at maturity, which does not depend on insulin), obesity, geriatric condition and gestation (pregnancy). Another metabolic disorder associated with obesity and with diabetes is hyperinsulinemia. Hyperinsulinemia is the presence of insulin at abnormally high concentrations in the blood. The counteracting effects of hyperinsulinemia to lower blood insulin concentrations may help to slow the progression of obesity and diabetes. Aging has been associated with a loss of glycemic control not only in humans but also in dogs. Old dogs have been reported to have attenuated glycemic responses compared to their younger counterparts. The reported cause for this dysfunction in glucose metabolism in aging populations includes: increased insulin resistance of receptors and subsequent receptor alterations, decreased glucose sensitivity by pancreatic islet B cells, and impaired peripheral utilization of the glucose. The increases associated with age in the deposition of body fat may also play a role. In both dogs and cats, glucose tolerance is impaired with obesity. Several studies have examined the effect of age and glucose metabolism using the same model approach. The minimal Bergman model (Bergman et al., Am. J. Physiol, vol.236 (6), pp. E-667-77 (1979) and Bergman et al., J. Clin. Invest., Vol. (6), pp. 1456-67 (1981)) quantifies both insulin sensitivity and pancreatic responsiveness in an intact organism. The minimal model approach uses computer modeling to analyze plasma glucose and insulin dynamics during an intravenous glucose tolerance test. Using this model, it has been suggested that aging is associated with a lower rate of glucose disappearance, decreased insulin sensitivity to glucose and a second phase suppressed B-cell response to glucose stimulation. Starch has suggested as a component of the main diet the most responsible for the increase in blood glucose immediately after a meal (Milla et al., JPEN, vol, 20. p.182-86 (1996) .The term "glycemic index" it is defined as a way of comparatively classifying foods based on their glycemic response.The glycemic index and carbohydrate content in the diet have been used to explain approximately 90 percent of the ratio for differences in glucose and insulin responses. However, such studies have focused on altering the amount of starch in a diet.In a recent study, using young mongrel dogs, the source of starch in the diet is reported to influence the postprandial response to food (Sunvold et al., Recent Advances in Canine and Feline Nutriotion, pp. 123-34 (1998)). In another study, the presence of rice as a source of carbohydrates in the diet exacerbates the s glycemic and insulinemic responses in old dogs (Massimino et al. FASEB Journal, v. 13 (1999) page a375). See also, Sunvold, U.S. Patent No. 5,932,258 and WO 99/51108, wherein compositions and processes are described for improving glucose metabolism in companion animals which include, as sources of carbohydrates, combinations of sorghum and barley, corn and barley, corn and sorghum, and corn, sorghum and barley. Accordingly, there still remains a need in the art for a composition in the diet which can alter and improve glucose metabolism in companion animals, particularly the glucose metabolism of an old pet animal. The present invention satisfies the need to provide a composition and process for using the composition to alter and improve glucose metabolism in companion animals such as dogs. In accordance with one aspect of the present invention, there is provided a pet food composition that includes a source of protein, a source of fat and a source of carbohydrates from a source of grain which excludes rice. It has been found that the pet food composition which uses as a source of carbohydrate 3 a combination of corn and sorghum; a combination of corn, sorghum and barley; a combination of corn, sorghum and oats; or a combination of oats or barley, tends to modulate the animal's glycemic and insulinemic responses after a meal. This effect is even more marked when the composition is supplied as food to geriatric pets such as dogs. By "geriatric dog" one wants to supply any dog of 7 years of age or older and less than 40 kg (90 pounds) of body weight, or any dog 5 years of age or older of more than 40 kg (90 pounds) of body weight (large or giant breed). When the carbohydrate source is a combination of corn and sorghum, or a combination of oats and barley, it is preferred that these starch sources are present in the composition in a weight ratio of between 1: 5 to 5: 1, so more preferable between 1: 3 to 3: 1, and more preferably 1: 1. When the carbohydrate source is a combination of corn, sorghum and barley, or corn, sorghum and oats, it is preferred that these starch sources are present in the composition in a weight ratio of between 1: 1: 5 to 1: 5. : 1 to 5: 1: 1, more preferably from 1: 1: 3 to 1: 3: 1 to 3: 1: 1, and most preferably 1: 1: 1, respectively. Preferably, the composition comprises 20 to 40 percent crude protein, 4 to 30 percent fat, 2 to 20 percent total fiber in the diet, and a source of starch which excludes rice, but which includes a combination of other sources of grain such as corn and sorghum; corn, sorghum and barley; corn, sorghum and oats; or oats and barley. Typically, the carbohydrate sources in the composition of the present invention constitute 35 to 60 weight percent of the composition. The pet food composition may optionally include chromium tripolyolinate and water soluble cellulose ether. Additionally, the pet food composition may further include 1 to 11 weight percent fiber in the total supplemental diet or fermentable fibers which have a disappearance of organic matter from 15 to 60 weight percent when fermented by fecal bacteria during a period of 24 hours.
The invention also includes a process for controlling postprandial glycemic and insulinemic responses in a companion animal comprising the step of feeding the companion animal with a pet food composition comprising a protein source, a source of fat and a source of carbohydrates which excludes rice. Preferably, the carbohydrate source includes a grain source such as a combination of corn and sorghum; a combination of corn, sorghum and barley, a combination of corn, sorghum and oats; or a combination of oats and barley. Accordingly, it is a feature of the present invention to provide a composition and process for using it to improve glucose or insulin metabolism in companion animals, particularly old companion animals by controlling postprandial glycemic or insulinemic responses in these animals. These and other features and advantages of the present invention will become apparent from the following detailed description, the accompanying drawings and the accompanying claims. Figure 1 is a graph illustrating the effect of diet on the plasma glucose curve (A) and the corresponding statistical differences (B) in dogs after a meal; Figure 2 is a graph of the effect of diet on the plasma insulin curve (A) and the corresponding statistical differences (B) in dogs after a meal; Figure 3 is a graph of the effect of age on the plasma glucose curve (A) and the corresponding statistical differences (B) in dogs after a meal; Figure 4 is a graph of the effect of age on the plasma insulin curve (A) and the corresponding statistical differences (B) in dogs after a meal; Figure 5 is a graph of the effect of the age-diet interaction on the plasma glucose curve (A) and the corresponding statistical differences (B) in dogs after a meal; Figure 6 is a graph of the interaction of age / diet on the plasma insulin curve (A) and the corresponding statistical differences (B) in dogs after a meal, - Figure 7 is a graph of the effect of age and diet (A) and age / diet interactions (B) on the fractional rate of glucose turnover (k) and half-life (T1 / 2) in dogs after a meal; Figure 8 is a graph of the effect of breeding on plasma glucose levels (A) and the corresponding statistical differences (B) in dogs after a meal; Figure 9 is a graph of the effect of breeding on plasma insulin concentrations (A) and the corresponding statistical differences (B) in dogs after a meal; Figure 10 is a graph of the effect of age / aging on plasma glucose concentrations (A) and the corresponding statistical differences (B) in dogs after a meal; Figure 11 is a graph of the effect of age / aging on plasma insulin (A) and the corresponding statistical differences (B) in dogs after a meal; Figure 12 is a graph of the effect of age, aging and diet on postprandial glucose in dogs of the fox terriers race; Figure 13 is a graph of the effect of age, rearing and diet on postprandial insulin in dogs of the fox terriers race, Figure 14 is a graph of the effect of age, rearing and diet on postprandial glucose in dogs of the breed. hunter labrador race; Figure 15 is a graph of the effect of age, aging and diet of postprandial insulin in dogs of the labrador hunter breed, - Figure 16 is a graph illustrating glucose response curves for dogs consuming diets containing different starches in the diet; Figure 17 is a graph of the area of increase below the glucose curve for dogs consuming diets containing different starches in the diet; Figure 18 is a graph illustrating insulin response curves for dogs consuming diets containing different starches in the diet, - Figure 19 is a graph of the area of increase under the insulin curve for dogs consuming diets containing different starches in the diet; The present invention utilizes a pet food composition which excludes rice but which includes a source of granule in which it helps regulate glycemic or insulinemic responses, or both, in companion animals such as a combination of corn and sorghum, - a combination of corn, sorghum and barley; a combination of corn, sorghum and oats, - or a combination of oats and barley. In healthy but old companion animals (geriatric), the presence of rice as a source of starch in the diet exacerbates the glycemic and insulinemic responses in a food, independent of body composition, glucose clearance or half-life. Healthy geriatric animals benefit especially from feeding on the composition of the present invention. For example, geriatric dogs of large breeds that suffer from insulinemia benefit especially from feeding on the composition of the present invention. The pet food composition can be any suitable pet food formula which also provides adequate nutrition for the animal. For example, a typical dog diet for use in the present invention may contain 20 to 40 percent crude protein (and preferably 25 to 35 percent), 4 to 30 percent fat. (and preferably 10 to 18 percent) and 2 to 20 percent fiber in the total diet, along with the source of starch, all percentages by weight. Typically, the carbohydrate sources in the composition of the present invention constitute 35 to 60 weight percent, and preferably 40 to 55 weight percent of the composition. A preferred source of corn is ground corn flour. The composition also optionally contains other ingredients which also have the effect of minimizing the postprandial glycemic or insulinemic response in an animal. The composition may include chromium tripolyolinate in an amount within about 10 and about 500 micrograms of chromos per day. Chromium tripicolinate occurs in brewer's yeast, and yeast can be added to the pet food composition. Alternatively, chromium tripolyolinate can be added to the composition in a substantially pure form. The composition may also contain water soluble cellulose ether such as, for example, carboxymethylcellulose or hydroxypropylmethylcellulose ether (HPMC). If carboxymethylcellulose is used, a high viscosity composition in the range of about 5,000 to about 65,000 cps is preferable and is added to the composition in an amount of about 1 weight percent. If HPMC is used, preferably it is also a high viscosity composition in the range of about 10,000 to about 2,000,000 cps and is added to the composition in an amount of about 1-2 weight percent. An adequate grade of HPMC is available from the Dow Chemical Company under the designation METHOCELMRK-100M. It has been found that water-soluble cellulose ethers have the effect of retarding the postprandial increase in blood glucose concentrations in animals. The pet food composition of the present invention may also optionally contain a source of fermentable fibers which shows certain percentages of disappearance of organic matter. The fermentable fibers which can be used have a disappearance of organic matter (OMD) of 15 to 60 percent when fermented by fecal bacteria in vitro for a period of 24 hours. That is, 15 to 60 percent of the total organic matter present originally is fermented and converted by fecal bacteria. The disappearance of organic matter from the fibers is preferably from 20 to 50 percent, and more preferably from 30 to 40 percent. Therefore, the percentage of OMD in vitro can be calculated as follows:. { l - [(residual 0M - white OM) / initial OM]} x 100, Where residual OM is the organic matter recovered after 24 hours of fermentation, white OM is the organic matter recovered in corresponding blank tubes (ie tubes containing medium and diluted feces, but not substrates) and initial OM It is the organic matter placed in the tube before fermentation. Additional details of the procedure are found in Sunvold et al, J. Anim. Sel. 1995, vol. 73: 1099-1109. The fermentable fibers can be any fiber source with intestinal bacteria present that the animal can ferment to produce significant amounts of SCFA. For purposes of this invention, the term "Significant Quantities" of SCFA is amounts greater than 0.5 mmoles of total SCFA / gram of substrate in a 24-hour period. Preferred fibers include beet pulp, gum arabic (which includes gum felling), silium, rice bran, locust bean gum, citrus pulp, pectin, fructooligosaccharides and insulin, mannanoligosaccharides and mixtures of these fibers. The fermentable fibers are used in the pet food composition in amounts of 1 to 11 weight percent fiber of the total supplemental diet, preferably 2 to 9 weight percent, more preferably 3 to 7 weight percent. percent by weight, and much more preferably from 4 to 7 weight percent. A definition of "supplemental total diet fiber" first requires an explanation of "total fiber of the diet". The term "total fiber of the diet" is defined as the residue of vegetable food which is resistant to hydrolysis by animal digestive enzymes. The main components of the total fiber of the diet are cellulose, emicelulose, pectin, lignin and gums (as opposed to "crude fiber", which only contains some forms of cellulose and lignin). The "total fiber of the supplementary diet" is the fiber of the diet which is added to a food product above and surpassing any fiber of the diet naturally present in other components of the food product. In addition, a "fiber source" is considered to be one that consists predominantly of fiber.
In order that the invention is more easily understood, reference is made to the following examples, which are designed to illustrate the invention.
Example 1 They are divided equally to 18 young dogs (0.7 + 0.2 years old) and old dogs (9.6 + 0.2 years old) of the Labrador Cazador (LR) and Fox Terriers (FT) in age and breeding and then randomly assigned to one of two diets. nutritionally complete (n = 18 / diet) for 90 days. The first diet contains 18.2% (w / w) of ground corn, 18.2% (w / w) of brewer rice and 18.2% (w / w) of sorghum grain (CRS diet) as in starch sources; the second diet contains 28.5% (w / w) of ground corn and 28.5% (w / w) sorghum grain (CS diet) as the starch sources. See tables 1 and 2 below. Both diets are isoenergetic, providing approximately 19.3 and 19.4 kJ / g, in the CS and CRS diets, respectively, and do not differ from the total starch content.
Table 1 - Composition of Dietary Ingredients Diet CS1 Diet CRS1 (g / kg) (g / kg) Ground corn 285 182 sorghum grain 285 182 brewing rice 0 182 poultry by-product food 251 277 poultry fat 61 60 beet pip 40 40 chicken digestion 20 20 dicalcium phosphate 12 8 brewing dry yeast 10 10 dry whole egg 10 10 carbonate calcium 8 8 monosodium phosphate 4 5 potassium chloride 3 5 mineral premix2 3 3 vitamin3 premix 2 2 colin chloride 2 2 sodium chloride 2 1 DL-methionine 2 2 1 CS = corn / grain sorghum, CRS = corn / rice / sorghum grain. 2 The mineral premix provides the following per kg of diet: 41 mg of manganese, 217 mg of zinc, 168 mg of iron, 47 mg of copper, 4 mg of iodine, 80 μg of magnesium, 4.8 mg of sulfur, 620 μg of selenium 3 The vitamin premix provides the following per kg of diet: 25 KUI of vitamin A, 124 IU of vitamin E, 1561 IU of vitamin D3, 14 mg of thiamin, 59 mg of riboflavin, 90 mg of niacin, 32 mg of d-pantothenic acid, 10 mg of pirodoxin, 600 μg of biotin, 1.9 mg of folic acid, 2067 mg of choline, 23 mg of inositol, 0.31 IU of vitamin B12.
Table 2 - Nutritional Composition of the Diet1 Diet SC2 Diet CRS2 Dietary starch 43.1 43.2 Protein 25.5 27.0 Fat 12.8 13.2 Ashes 6.5 6.5 Humidity 7.0 6.8 Calcium 1.3 1.3 Phosphorus 1.1 1.1 General Energy (kJ / g) 19.2 19.4 1 All values, except moisture, are expressed on a dry matter basis. 2 CS = corn / sorghum grain, CRS = corn / rice / sorghum grain.
After 60 days with the CRS diet (which was fed as the basal diet), all animals underwent a glycemic response (GR) test followed by a glucose tolerance test (GTT, described later). After a 90-day consumption period in the experimental diets, the animals underwent the same tests that included a total body double energy X-ray absorptiometry (DEXA) scan to determine body fat, lean body mass and mineral composition . Animals were weighed daily and feed intakes recorded and adjusted to minimize weight fluctuations during the study. One animal was removed from the study for health reasons. The research protocol was approved by the Institutional Animal Care and Use Committee. The GR test is carried out on all animals before and after the 90-day feeding period. The animals were fasted for 24 hours before the test. On the morning of the test, the animals were fed half of their daily food dose. All meals were consumed in the next 10 minutes of presentation. An internal catheter (14 cm 14 gauge in the LR, 3.2 cm 22 gauge in the FT) was placed by suture using the 3-0 Dexon equipment (Butler, Columbus, OH) either in the left or right jugular vein and washed by discharge with heparinized saline. Blood samples are collected for glucose and 5-insulin analysis at -10, 0, 10, 20, 30, 45, 60, 120, 180 and 240 minutes. The time points -10 and 0 min were averaged to provide a single baseline time point. The data was plotted and analyzed as an area of increase under the curve (IAUC) determined by the trapezoidal method. It defines IAUC as the area under the response curve, but above the baseline. GTT was also carried out one week after GR. The animals were fasted for 24 hours before the GTT. Prior to administration, an internal catheter is placed 14 cm, 14 gauge, in both left or right jugular veins in the LR and a smaller 22 gauge 3.2 cm catheter is used in the FT. Haparinized saline is discharged through the catheters which are then sutured into place using Dexon 3-0 (Butler, Columbus, OH). They are collected blood samples for glucose and insulin analysis at -20, -10, 0, 2, 4, 6, 8, 10, 12, 14, 16, 19, 22, 25, 30, 40, 50, 60, 70, 80, 90, 100, 120, 140, 160 and 180 minutes. Infusion glucose (50% solution, Butler, Columbus, OH) is administered at time 0 (0.3 g glucose / kg body weight) as described by Bergman et al. (1981) and Duysinx et al., Diabete Metab, vol. , p. 425-32 (1994). It is administered by infusion at 20 minutes insulin (Human Insulin Novolin R, Novo Nordisk, Denmark). Blood samples for glucose and insulin analysis are collected in heparinized Vacutainer ™ tubes (Becton Dickinson, Sunnyvale, CA) and samples for hematological analysis are collected in Vacutainer ™ SST tubes (Becton-Dickinson, Sunnyvale, CA). The plasma for glucose and insulin determinations is obtained by centrifuging blood (1850 x g) for 8 minutes at room temperature. Glucose is analyzed immediately by glucose oxidase and a Cobas Mira Analyzer device (Roche Diagnostics Systems, Somerville NJ) and insulin is stored at -20 ° C and sent to Indiana Veterinary Diagnostics Labs (Evansville, IN) where it is analyzed using RIA-coated insulin tube DPC (Indiana Veterinary Diagnostics Labs, Evansville, IN). The data is graphed and analyzed by Bergman's minimal model program (version 3.0, Los Angeles, CA) to determine insulin sensitivity (Si), glucose effectiveness (Sg), acute insulin response to glucose ( AIRg) and the glucose concentration at t = 0 estimated by extrapolating the prediction of the glucose kinetics model at the time of injection (therefore cardiovascular mixing is not included, G (0)). The rate of glucose fractional turnover (k) and the half-life (T12) of glucose are calculated by linear regression of logarithm base 10 of glucose concentrations between 4 and 30 minutes. Double-energy X-ray absorptiometry is performed after intravenous sedation with 7 mg / kg of propofol (Rapinovet, Mallinckrodt Veterinary, Inc.) at a concentration of 10 mg / ml. The animals are maintained in an appropriate anesthetic plane via isoflurane and oxygen supplied by an anesthetic machine Matrix (Butler, Columbus, OH). If necessary, a supplemental dose of propofol at 3.3 mg / kg is administered to facilitate the induction of anesthesia. The animals are scanned with external recumbency and with the front legs parallel to their sides and their hind legs in a straight line with the rest of their body. After the scans are completed, the animals are allowed to recover from the anesthesia. Total body composition scans are performed using a Hologic QDR 4500 X-ray bone densitometer (Waltham, MA). The explorations are analyzed using Hologic programming elements (Version 9.03, Waltham, MA). All statistical analyzes are performed using the Statistical Analysis System (SAS) statistical package (version 6.12, SAS Institute, Cary, NC). All the data generated for GTT and DEXA are analyzed using GLM proc and important differences are identified by one-way ANOVA. The model includes diet, age and parenting in all interaction effects. The differences within individual time points were determined for the glucose and insulin curves using the least squares means. The correlation coefficients between body composition and k and T1 / 2 were analyzed using the Pearson correlation coefficients. All data are presented as means + SEM (standard error mean) except for the correlation coefficients. Significant differences are identified when p < 0.05.
RESULTS The individual weights of the animals did not vary during the study period (data not shown), by diet (19.5 + 0.9 kg and 20.8 + 0.9 kg, CS and CRS, respectively, p = 0.31) or by age (20.3 + 0.9 kg and 20.1 + 0.9 kg, young and old animals, respectively, p = 0.86). However, there are significant differences between the races (31.9 + 0.9 kg and 8.5 + 0.9 kg, LR and FT, respectively, p <0.0001). When dietary intake is expressed as g / kg of body weight, no significant differences are observed between diets (19.3 + 0.7 g / kg body weight and 20.2 + 0.7 g / kg body weight, CS and CRS, respectively; p = NS). As expected, the age and the. race affected the amounts of daily ingestion (22.2 + 0.7 g / kg of body weight and 17.3 + 0.7 g / kg of body weight, young and old animals, respectively, p <0.001, 15.6 + 0.7 g / kg of body weight and 23.9 + 0.7 g / kg of body weight, LR and FT, respectively, p <0.001).
Glycemic response test: The effects of diet on glucose (figure 1) and insulin (figure 2) were analyzed. No significant differences were observed due to the diet alone for plasma glucose and a weak tendency was observed for the difference and the insulin response (p = 0.21) with the CRS diet that induces a higher insulin response compared to the CS diet. However, age affected glucose responses (figure 3, p <0.001) and insulin responses (figure 4, p = 0.05). In addition the concentrations. of fasting plasma glucose significantly higher (4.9 + 0.1 mmol / 1 and 5.3 + 0.1 mmol / 1, older and younger animals, respectively, p <0.05, figure 3) younger animals- show a faster increase in glucose Plasma followed rapidly by a pronounced decline in exposure to food, compared with its older counterparts, which showed a steady increase in plasma glucose after 240 minutes. In the postprandial period, the older animals showed an exaggerated insulin secretion after 30 minutes. Figure 5 shows the effect of age / diet interaction on glucose, and Figure 6 illustrates insulin responses. The plasma glucose responses in the young animals to the CS and CRS diets were similar; however, older animals fed CS had significantly lower peak plasma glucose concentrations at 60 minutes compared to older animals fed CRS (5.3 + 0.2 mmol / 1 and 5.8 ± 0.2 mmol / 1, older dogs fed CS) and old dogs fed CRS, respectively, p <0.05). Similarly, older animals fed SC had significantly lower insulin responses compared to older animals fed CRS (p < 0.001). Race seems to play a significant role with respect to both glycemic and insulinemic responses. FT tends to show a faster increase in plasma glucose followed by a marked decrease, whereas LR shows a gradual and sustained increase in plasma glucose concentrations with values significantly higher at 120, 180 and 240 min (p < 0.05, figure 8). FT shows a faster increase in plasma insulin concentrations with significantly higher values at 30 and 45 minutes, compared to LR (p <0.05, figure 9). The values for both FT and LR do not reach baseline concentrations after 240 minutes. When age / race interaction effects are noted, large differences are observed between FT, where old FT have higher plasma glucose concentrations at 0, 10, 20, 30 and 45 minutes (p <0.05; ) compared to the young FT. Old FTs have blood glucose concentrations that increase faster, reach a higher peak, and decrease markedly when compared to young FTs, which show a sustained and gradual increase in plasma glucose concentrations (figure 10). LR shows similar glycemic responses between young and old animals. Both show a gradual increase in blood glucose concentrations without significant differences at any point in time (Figure 10). The age-related differences in insulin responses are larger among older and younger LRs (Figure 11). Although young and old LRs show a continuous increase over time in plasma insulin, old LRs have significantly higher insulin at 45, 60, 120, 180 and 240 minutes compared to young LRs (p <; 0.05; figure 11). Both young and old FT show similar gradual increases in plasma insulin; no significant differences are observed at any point in time. The effects of age and race are illustrated by the results shown in figures 12-15. Figure 12 shows the glucose response curve only in the race Fox Terriers, divided between age and diet effects. These data show little effect. However, Figure 13 shows the insulin responses for the same dog. As it is observed, the old dogs (geriatric) under the diet with CS (white squares) or the diet CRS (black triangle), show that the absence of friction in the diet (CS) produces a markedly lower insulin response in these dogs old breed Fox Terriers compared to the CRS diet. Figures 14 and 15 illustrate the same data, only in Labrador Cazador breed. Again, there is little difference in the glucose response curve (Figure 14). However, the insulin response curve (Figure 15) shows a remarkable effect. Older hunter Labrador retriever dogs that consume the CRS (rice) feed (black triangles) have a significantly elevated insulin response compared to dogs of the Labrador breed. Old hunters who consume the CS diet (white squares). Figure 15 also illustrates that, regardless of diet, older Labrador Hunter dogs (white squares and black triangles) have elevated insulin levels compared to young Labrador Hunter dogs (black squares and white triangles) . Summarizing what is shown in Figures 12-15, the presence of rice in the diet is harmful to old dogs (geriatric) with respect to their postprandial insulin response. The data shows that rice is even more harmful to the larger breed of Labrador Hunter. By removing rice as the source of starch from the diet, these hyperinsulinemic responses are reduced. Although it has not been demonstrated, prolonged hyperinsulinemia in old dogs can result in further deterioration of glucose metabolism by producing a final resistance to insulin which can lead to hyperglycemia. Therefore, the long-term presence of rice in dog diets can be harmful.
Increased area under the curves (IUAC): The IAUC is divided into three sections: acute phase (0-30 minutes), second phase (30-240 minutes) and finally total IAUC (sum of the acute phase and the second phase). The values for the IAUC are presented in Table 3 below.
Table 3 - area of increase under the curve for plasma glucose and insulin in dogs1 Glucose to Glucose to Total Glucose Glucose to Insulin to Total Insulin 0-30 min 30-240 min mmol * h | l 0-30 min 30-240 min pmol * h | l mmoPhiol mmol * h | l pmol * h / l pmol * h | l Diet CS2 45+ 12 940 + 280 990 + 290 538 + 108 19781 +2683 0320 +2676 Diet CRS 48 + 12 850 + 290 890 + 300 653 + 115 23584 + 2805 4266 +2791 Old dogs 30+ 12a3 1530 +290 '1560 +3003 596+ 115 23699 + 2805 24287 + 2791 Young dogs 63+ 12"250 + 280" 310 + 290"596 + 108 9667 +2683 20291 +2676 Old-CS 18+ 17"1440 + 400" "1450 + 410" "438 ± 158 19057 ± 3796 1948 + 3781 Old-CRS 42 ± 18"b 1630 + 43" 1670 + 440"753 + 172 28334. + 4133 29087 + 41 18 Youth-CS 73 + 17"440 + 40bc 520 + 410" "639 + 158 20506 + 3796 21 145 +3781 Juniors-CRS 53+ 17" "64¿40c 110 + 410" 552 ± 158 18834 + 3796 19444 + 3781 1 The values expressed are x ± SEM; n = 18 / treatment (young dogs, CS) and n = 17 / treatment (old dogs, CRS), except the interaction where n = 9 / treatment (n = 8 for the old treatment group-CRS). 2 CS = corn diet / sorghum grain, CRS = corn / rice / sorghum grain. 3 Values with different superscripts in the variable * treatment column are significantly different (p < 0.05). Diet alone has no effect on IAUC for plasma glucose (99 + 29 mmol * h / l and 89 + 30 mmol / h of CS and CRS, respectively, p = NS). Older animals had a significantly elevated total IAUC for plasma glucose compared to young animals (31 + 29 mmoles * h / l and 156 + 30 mmoles * h / l for young and old animals, respectively, p <0.01), whereas the young animals had a significantly higher acute phase IAUC for plasma glucose (6.3 + 1.2 mmoles * h / l 3.0 + 1.2 mmoles * h / l, young and old animals, respectively; p < 0.05). Older animals fed CRS have the highest IAUC of glucose; however, the old animals fed CS had a total glucose IAUC which is not significantly different from that of the youngsters fed CS (p <0.05). Although not significant, older animals fed CRS tend (p = 0.09) to have a higher total insulin IAUC compared to the other groups.
Speed of fractional glucose replacement and half-life: As would be expected, older animals have a significantly lower fractional rate of glucose turnover (k) (5.9 + 0% / minute and 4.4 + 0.3% / minutes, young and old animals, respectively; p <0.01), which results in a significantly longer T1 / 2 glucose (12.9 + 1.1 minute and 10.0 + 1.1 minute, young and old animals, respectively, p <0.01). The diet does not affect the k or T1 / 2 glucose (p = NS). Old animals fed CS or old animals fed CRS do not differ significantly in k (4.3 + 0.5% / minute and 4.5 + 0.5% / minute of old animals fed CS and older animals fed CRS, respectively; p = NS, figure 7) or T1 / 2 (16.9 + 1.6 minutes and 17.2 + 1.6 min, old animals fed CS and old animals fed CRS, respectively, p = NS, figure 7).
Body composition: Age is the only variable that significantly affects body fat percentage (16.8 + 1.1% and 30.4 + 1.2%, young and old animals, respectively, p <0.0001). Diet and race had no effect (p = NS). Body fat correlates significantly with k in FT, LR and CS-fed animals, is significantly correlated to T1 / 2 in animals fed CS and CRS, as well as FT, and there is a strong positive association for LR. See table 4 below.
Table 4 - Effect of age, diet and race on body composition and correlation with body fat in dogs % body fat1 Correlation Value p Correlation with T1'2 Value p with k2 Young dogs 16.8 + _1.1a --00..0044 pp-- NNSS --00..1100 p = NS Old dogs 30.4 + _1.2b --00..1166 pp == ll \\ IISS 00..1166 p = l \ IS CS 23.9+ .1 -0.48 p < 0.05 0.34 p < 0.2 CRS 23.2 + 1.1 -0.45 p < 0.1 0.40 p < 0.1 FT 23.6 + .1.1 -0.48 p < 0.05 0.53 p < 0.05 LR 23.6 + .1.1 -0.53 p < 0.05 0.42 p < 0.1 1 Values for% body fat are expressed as x + SEM; n = 18 / treatment (young dogs, CS, FT) and n = 17 / treatment (old dogs, CRS, LR). 2 Correlation data are represented by Pearson correlation coefficients. Values with different subscripts are significantly different (p <0.05) within a treatment. k = the fractional rate of glucose turnover, T1 / 2 = glucose half-life, CS = corn / grain sorghum, CRS corn / rice / sorghum grain, FT Fox Terrier, LR = Labrador Hunter, NS = not significant.
It has been reported that dietary modification increases longevity, improves insulin sensitivity and glucose tolerance, suggesting that diet may be at least partially related to glucose intolerance in older animals and may play a role in the aging process. It has been shown that high-carbohydrate diets improve the sensitivity of insulin to glucose, increase the rate of disappearance of glucose and improve the response of second-sentence β cells to glucose stimulation. Although most studies to date focus on the amount of carbohydrate alteration in the diet, experimental results suggest that the source, particularly starch, may be equally important. The source of starch regulates the glycemic response in older dogs, regardless of body fat percent and glucose kinetics. Although diet does not affect glucose tolerance, the absence of rice as a source of starch in the diet decreases postprandial insulin secretion. Removing or not including rice (a highly glycemic starch) from the diet provides a beneficial preventive nutritional strategy. The source of starch may even be more important with age compared to older dogs fed CRS in the experiments which is shown to be elevated, although not significantly, the IAUC for plasma glucose and the insulin IAUC significantly higher compared to the old dogs fed CS. These responses may be due to an as yet unidentified effect independently of body composition and glucose kinetics. The importance of glucose kinetics data is twofold. In the first place, it confirms that this population of dogs is healthy without the influence that generates confusion of diseases such as diabetes mellitus. Second, it confirms that the effect of diet on glucose and insulin in older animals is an independent effect. The experimental results show a decreased glucose IAUC for young CRS dogs compared to CS young dogs. However, there is a high number of negative IAUCs for the group of young CRS dogs. When all the negative values of the analysis are excluded, the IAUC values of glucose clearly become more representative than would be expected in young dogs based on the previous literature (732 + 394 mmoles * h / l and 1099 + 607 mmoles * h / l for young dogs fed CS and young dogs fed CRS, respectively; p = NS). When considering nutritional therapy for different stages in life and physiological states, the absorption and utilization of nutrients should be considered. However, an altered potential for digestion or absorption of nutrients between young and old dogs does not explain the differences associated with age in the glycemic responses that are. observe. The effect of age on the intestinal absorption of nutrients has previously been examined in the dog, - the experiments of nutrient balance in young and old mestizos do not find observable differences related to age in the absorption of protein, fat, starch, vitamins. . a and minerals, suggesting that the gastrointestinal tract can compensate in small decreases in absorption capacity. In fact, gastrointestinal adaptation, such as small bowel syndrome, has previously been demonstrated in other conditions. Because absorption has not been shown to be a major factor in glucose tolerance during aging, the GR protocol was chosen that uses half of the daily feed intake of each animal. Some studies use a standard glucose load, while in others the food is offered. But due to the interest in evaluating the glycemic response with the total dietary matrix instead of the independent effects of the starch sources, the food protocol was chosen. The animals are fed equal amounts within the diet treatment groups on a basis of grams of feed per kg of body weight. Although the total amounts vary on an individual basis, when they are expressed in grams of food per kg of body weight, all animals receive similar amounts. Variations of age-related species are also presented with baseline glucose values. Younger dogs show higher baseline glucose values compared to their older counterparts, an observation previously observed for this particular colony of dogs. Although these data disagree with the previous literature, other researchers have reported that there is no difference between young and old subjects and baseline glucose. In fact, when working with an old population, it is difficult to avoid confounding factors such as disease states (for example, diabetes mellitus). It is known that glucose metabolism decreases with age, and that it finally manifests itself as hyperglycemia and hyperinsulinemia. With respect to time, hyperinsulinemia can lead to insulin resistance and, ultimately, dysfunction in glucose metabolism. Hyperglycemia interconnects two theories of aging, free radical theories and glycosylation, both of which can regulate changes in the expression of genes that result in the emergence of phenotypic changes of age. These two cell-based theories work with the concept of "using and tearing" aging, where senescence is the result of the wear of some somatic cells after continuous use and operation. Other theories are based on the population (life speed, that is, development and maturation, which determines longevity) or based on organs (damage to certain organs in the body, that is, endocrine and immune organs, which affect the age) . Glycosylation and the free radical theories of aging are especially important. The theory of stable aging glycosylation is that hyperglycemia can accelerate the aging process by increasing the amount of glucose available to bind proteins. The adduction of glucose to lysine residues followed by the Maillard reaction results in a significant post-translational modification of the proteins, the formation of products with advanced glycation end (AGE). The consequences of glycosylation of the protein include a reduction in the capacity of protein digestion and replacement, cross-linked resulting in increased tissue rigidity, reduced enzyme activity (such as Na + K + ATPase), altered protein antigenicity and altered receptor-ligand interactions. Protein glycosylation secondary to hyperglycemia has been linked to many complications including accelerated atherogenesis in people with diabetes, skin / joint changes and retinopathy. Accumulations of AGE have been related to an altered speed of nerve conduction and increased secretion of various cytokines (necrosis factor ß and interleukin I-a). An additional potential mechanism for tissue damage associated with glycosylation in the generation of free radicals. Glucose, in the presence of CuS04, undergoes autooxidation and generates free radicals in vitro. Also, the glycosylation of protein itself results in the production of free radicals and partial protein degradation. The theory of free radicals of aging involves free radicals in the pathogenesis of the aging process as well as chronic human diseases associated with aging including inflammatory diseases, cataracts, diabetes mellitus and cardiovascular diseases. Certain free radicals attack vital cellular components, damage cell membranes, inactivate enzymes and damage genetic material in the nucleus of cells. Antioxidants cuiro free radicals, and it has been reported that treatment with antioxidants extends the life span of mice, although other researchers can not confirm this and have suggested that the study may have been confused by the restriction of calories. The normalization of glycemic control is currently the technique used to prevent protein glycosylation and production of free radicals induced by hyperglycemia. An adequate selection of starch sources helps to normalize glycemic control by decreasing the prostprandial glucose and insulin secretion in an older population. Therefore, adequate selection of a source of starch is necessary when trying to regulate post-hyperglycemia and hyperinsulinemia in postprandials through nutrition in groups with increased risk, such as the old population.
Example 2 The same animals and diets were used as described in Example 1; see tables 1 and 2. The test procedures were as indicated in the example. In this experiment we study the effects of age on glucose metabolism. As in Example 1, animals were fed to maintain ideal body weight. Individual animals do not fluctuate significantly in body weight. The animal weight does not differ by diet (19.5 + 0.9 kg vs. 20.8 + 0.9 kg, CS and CRS, respectively, p = NS) or age (20.1 + 0.9 kg vs. 20.3 + 0.9 kg, old and young animals, respectively, p = NS). However, the breed significantly affects the weight (31.9 + 0.9 kg vs. 8.5 + 0.9 kg, LR and FT, respectively, p <0.0001) when the dietary intake is expressed on a basis of grams of feed per kg of feed. body weight, no effect of the diet was observed (19.3 + 0.7 g / kg of body weight vs 20.2 + 0.7 g / kg of body weight, CS and CRS, respectively, p = NS) As would be expected, both age (22.2 + 0.7 g / kg of body weight vs 17.3 + 0.7 g / kg of body weight, in young and old animals, respectively, p <0.001) and the breed (15.6 + 0.7 g / kg of body weight vs. 23.9 + 0.7 g / kg body weight, LR and FT, respectively, p <0.001) significantly affects dietary intakes Age is the only variable which significantly alters% body fat (30.4 + 1.2% vs 16.8 + 1.2%, old and young animals, respectively, (p <0.0001, see Table 5.) There are no significant differences within diet and race (p = NS). Total body fat (%, - Table 5) is negatively correlated with insulin sensitivity (-0.21, p = NS), glucose effectiveness (-0.39, p <0.05) and glucose effectiveness at zero insulin (0.39, p <0.05), but it correlates positively with the insulin response to acute glucose (0.37, p <0.05). Significant effects of age / diet and age / race are also observed as shown in Table 5. Using the Bergman minimum model method, insulin sensitivity (Si), glucose effectiveness (Sg) are measured using a mathematical model. ), acute insulin response to glucose (AIRg) and the rate of disappearance of glucose (G (O)). Sg is defined as the efficiency by which glucose can restore its own concentration independently of any dynamic insulin response. These insulin-dependent, glucose-restoring mechanisms involve the effect of the mass action of glucose on peripheral utilization. This parameter represents the fractional turnover of glucose in basal insulin. Or, a quantitative improvement of the disappearance of glucose due to an increase in the concentration of plasma glucose. G (0) is defined as the glucose concentration at t = 0 estimated by extrapolation from the prediction of the glucose kinetic model with respect to the moment of injection. AIRg is defined as the acute insulin response to glucose. Is defined as the increase in the disappearance of fractional glucose by an increase in the concentration of insulin unit. In healthy individuals, there is a balance between insulin secretion and sensitivity so that secretion x sensitivity = constant. For the oral glucose tolerance test (OGTT), after the consumption of a meal, plasma glucose and insulin concentrations are measured at -10, 0, 10, 20, 30, 45, 60, 120, 180 and 240 minutes For the intravenous glucose tolerance test (IVGTT), a catheter is placed in the animal's jugular vein and samples of 2 ml of blood are drawn at the previous time points. An advantage of IVGTT versus OGTT is that IVGTT is not complicated by different rates of intestinal glucose absorption. At time 0, glucose is infused (0.5 g / kg body weight, 30% solution). At 20 minutes, human insulin is administered by infusion (0.02 units / kg of body weight). Plasma glucose and insulin concentrations are measured at all points in time, and the data in are analyzed by Bergman's mathematical model for Sg, G (0), AIRg and Si. Diet or race does not significantly affect any parameter of the minimum model; see Table 6. However, there is a tendency for CSR fed animals to have high G (0) (324 + "25 mg / dl vs. 391 + 25 mg / dl CS and CSR diets, respectively, p = 0.09) .FT tends to have a higher Sg than compared to LR (0.09 + 0.01 min "1 vs. 0.07 + 0.01 min" 1, diet FT and LR, respectively, p = 0.10) Age significantly affects Sg. Old dogs have a significantly lower Sg compared to young animals (0.07 + 0.01 min "1 vs 0.09 + 0.01 min" 1, old and young dogs, respectively, p <0.05) and tend to have a higher AIRg ( 253 + 25 μUI / ml vs. 198 + 23 μUI / ml, old and young dogs, respectively, p = 0.10) and g (0) lower (326 + 26 mg / dl vs. 389 + 24 mg / dl, old dogs and young, respectively, p = 0.09) Young dogs fed CSR show Sg significantly higher than older dogs fed CS (0.11 + 0.01 min "1 vs 0.06 + 0.01 min" 1, young dogs ali mentioned with CSR and old CS-fed, respectively, p < 0.05) and G (0) (431 + 34 mg / dl vs. 301 ± 37 mg / dl, diet of CS and CSR, respectively, p <0.05). FT animals fed CSR have significantly higher Sg compared to LR fed CS (0.10 + 0.01 min "1 vs 0.06 + 0.01 min" 1, Ft dogs fed CSR and LR fed CS, respectively, p <0.05 ). The young LR dogs showed a slight higher Si compared to old LR (11.5 + 2.3 x 10"4 min / μUI / ml vs. 3.29 + 2.3 x 104 min / μUI / ml, young LR dogs and Old LR, respectively, p < 0.05) and have a higher G (0) (408 + 34 mg / dL vs. 304 + 37 mg / dL, young LR dogs and old LR, respectively, p <0.05). The young FT dogs have Sg significantly higher compared to the old LR dogs (0.10 + 0.01 min "1 vs 0.05 + 0.01 min" 1, young FT dogs and old LR, respectively, p <0.05).
Table 5 - Correlation analysis between different treatments and complete body fat (%) in dogs Correlation with respect to body fat% Parameter% of Si Sg AIRg G (0) body fat Total 23.6 + 1.4 0.21 0.39 * 0.37 * 0.39 * CS 23.9 + 1.1 -0.39 0.42 0.33 -0.39 CSR 23.2 + 1.1 -0.04 • 0.40 0.42 0.43 Young dogs 16.8 + l.l 0.13 -0.46 0.23 0.33 Old dogs 30.4 + 1.2a -0.11 -0.03 0.18 -0.30 FT 23.6 + 1.1 0.15 • 0.28 0.23 -0.28 LR 23.6 + 1.1 -0.49 0.52 0.54 -0.47 Youth-CS 16.6 + 1.5 ° 0.06 0.01 0.30 -0.07 Youth-CSR 16.9 + 1.5 ° -0.03 -0.58 0.30 -0.39 Old-CS 31.2 + 1.7a -0.58 -0.18 0.40 -0.15 Old CSR 29.5 + 1.7a 0.16 -0.86 * -0.02 -0.58 Young-FT 15.9 + 1.5 ° 0.27 0.16 0.21 0.06 Juniors-LR 17.6 + 1.5b -0.38 -0.79 * 0.71 -0.68 * Old-FT 31.2 + 1.7a 0.10 -0.57 0.06 -0.71 * Old-LR 29.6 + 1.7a -0.72 * -0.69 * 0.51 -0.57 CS-FT 23.5 + 1.7 0.20 0.27 -0.04 0.05 CS-LR 24.4 + 1.5 -0.92 ** -0.67 * 0.59 -0.64 * CSR-FT 23.7 + 1.5 0.18 -0.51 -0.08 0.04 CSR-LR 22.8 + 1.7 -0.13 -0.73 * 0.45 -0.65 The data for body fat are expressed as mean + SEM (n = 36 total, n = 18 / single treatment groups and n = 9 / interaction treatment groups, however, an old LR dog fed with CSR was removed from the study earlier in the + 37/17/8 for the respective treatment groups), and the data for the correlations are expressed as Pearson correlation coefficients. In the body fat data group, the values which do not share similar subscripts are significantly different (p <0.05). For the correlation data set, * indicates (p < 0.05) and ** indicates (p < 0.01). Yes = insulin sensitivity, Sg = glucose effectiveness, AIRg = acute insulin response to glucose, G (0) = glucose concentration at = 0 estimated by extrapolation from the prediction of the glucose kinetics model at the time of injection ( therefore cardiovascular mixing is not included), CS = corn diet / sorghum grain, CSR = corn diet / sorghum grain / rice, FT = Fox Terriers breed, LR Labrador Hunter.
Table 6 - Bergman minimum model data in dogs Variable Yes Sg AIRg G (0) min "1 μUl / ml mg / dl 104 min / μUI / ml CS 7.8 + 1.7 0.07 + 0.01 224 + 24 324 + 25 * CSR 8.1 + 1.7 0.09 + 0.01 227 + 24 391 + 25 FT 8.1 + 1.7 0.09 + 0.01 * 210 + 24 360 + 25 LR 7.7 + 1.7 0.07 + 0.01 241 + 24 356 + 25 Old 6.2 + 1.8 0.07 + 0.01 a 253 + 25 * 326 + 26 * Young people 9.6 + 1.6 0.09 + 0.01 ° 198 + 23 389 + 24 CS-old 5.0 + 2.5 0.06 + 0.01 ° 247 + 35 301 + 37 ° CS- young 10.5 + 2.3 0.08 ± 0.01ab 202 + 32 347 + 34ab CSR-old 7.4 + 2.5 0.07 + 0.01ab 260 + 35 351 + 37ab CSR- young 8.8 + 2.3 0.11 + 0.01a 194 + 32 431 + 34a CS-FT 7.8 ± 2.5 0.08 + 0.01ab 205 + 35 321 + 37 CS-LR 7.7 + 2.3 0.06 + 0.01b 243 + 32 328 + 34 CSR-FT 8.5 ± 2.3 0.10 + 0.01a 214 + 32 399 + 34 CSR- LR 7.7 + 2.5 0.08 + 0.01ab 240 + 35 384 + 37 Old-FT 8.5 + 2.5ab 0.09 ± 0.01ab 230 + 35 349 + 37ab Old-LR 3.9 + 2.5b 0.05 + 0.01b 277 + 35 304 + 37b Young-FT 7.8 + 2.3ab 0.10 ± 0.01a 190 + 32 371 + 34ab Young-LR 11.5 + 2.3a 0.09 + 0.01ab 206 + 32 408 + 34a Values are means + SEM (n = 18 / single treatment group and n = 9 / interaction treatment group, however, an old dog was removed -CSR-LR of the study and therefore n = 35/17/8 for the respective treatment groups), the values with different superscripts are significantly different (p <0.05) within a treatment. Values with * indicate a trend (p <0.l) within a treatment. Yes = insulin sensitivity, Sg = glucose effectiveness, AIRg = acute insulin response to glucose, G (0) = glucose concentration at = 0 estimated by extrapolating the prediction of the glucose kinetic model at the time of injection (so so much cardiovascular mixing is not included), CS = corn diet / sorghum grain, CSR = corn diet / sorghum grain / rice, FT = Fox Terriers, LR = Labrador Hunter. Similar to the human population, the segment of older pet animals is substantial as demonstrated by recent demographic research conducted in the United States and the United Kingdom. In accordance with human studies, geriatric pets require a daily requirement of decreased total energy. Inactivity alone can cause a decrease of up to 20% of the total daily energy requirement of pets. This decrease, together with a natural decrease in basal metabolic rate, can result in a reduction in total energy that constitutes up to 30-40%.
Although many factors contribute to impaired glucose tolerance, two have been recognized which play a major role: pancreatic responsiveness and insulin sensitivity. The first is related to the ability of pancreatic ß cells to secrete insulin in response to glucose stimuli, while the latter depends on the ability of insulin to increase glucose uptake in muscles, liver and adipose tissue. Defects in either or both of these factors can lead to impaired tolerance to glucose, or, if large enough, to diabetes mellitus. Therefore, maintaining or improving these factors is the main objective when improving tolerance - glucose and avoiding diabetes mellitus, especially in those groups with increased risk. Age is associated with impaired glucose tolerance which has been reported as secondary to obesity and decreased physical activity. These differences in age are suppressed by feeding a diet high in carbohydrates. However, in the veterinary spectrum, feeding pet animals with a high-carbohydrate diet is not practical. In order for the animal to maintain the weight, the caloric and nutritional needs must be derived from proteins, carbohydrates and fats. If one component is increased, the other two must be reduced in order to compensate, so the essential nutrients derived from these dietary sources are reduced. This experiment demonstrates the effects of age and race on glucose tolerance. Since body fat remains unchanged between diets and races, it has been reported that carbohydrate absorption does not change with increasing age, and unidentified adiposity independent of the effect should be responsible for changes in body tolerance. glucose that are observed in this experiment. The differences between races are observed for the response to glucose and insulin during a glycemic response test. In this experiment, differences were found between the races for Sg.
Example 3 Twenty-one geriatric mongrel dogs were studied to evaluate the glycemic response to three different diets. The study consists of four periods (baseline and three experimental periods). The dogs received a standard diet during the baseline period. After the baseline period, the dogs were randomly assigned to three groups of seven dogs each. The groups remain consistent during the experimental periods. Three test diets are evaluated during the perioperative periods in a cross-group design. Each diet contains corn, sorghum (also called sorghum and milo grain) and one of the following starches: barley, oats or rice. All animals received each of the three test diets. Each period consists of a two-week stabilization period where the baseline diet or one of the test diets was administered. A glycemic response test (a general term describing the response of glucose and insulin to a meal) was performed during the third week. Tests of the resulting samples were performed to detect insulin and glucose. The characteristics of the feces were also observed during each period. Dogs are weighed weekly and the glycemic response is performed at the end of each period. Glucose and insulin levels were determined at baseline and at 10, 20, 30, 45, 60, 120, 180 and 240 postprandial minutes. Stool characteristics are obtained during a week during the second week of each period. Breeding of domestic animals - in this experiment 21 healthy geriatric mongrel dogs were used (Covance, Cumberland, VA) of which 19 are females and two males. The dogs were treated humanely and ethically throughout the study period. All the animals were up-to-date in their vaccination and parasite prevention program. The dogs were housed individually in larger tanks and identified by a unique tattoo on the ear. Fresh water was provided ad libi tum throughout the study period. The average body weight of the dogs was 12.83 kg (range: 9.93 to 18.85 kg) and the average age was 9.44 years (range: 6.86 to 13.10 years) at the beginning of the study. The dogs were fed ad libi tum for 30 minutes every day during each experimental period. Dogs seem to fit very well to the limited time of feeding presentation. One of the dogs was sacrificed due to a problem in the cervical disc. Another dog became ill and no data were collected during the last two study periods. Another dog was diagnosed with diabetes and the data generated from this dog was discarded. No other animal became ill or required medical attention during the study period. The experiment consisted of a baseline period and a treatment period of three duplicates that evaluated three diet treatments in a cross-over design. During the three-week baseline period, all of the 21 geriatric dogs received a standard diet and the dogs were trained gradually to consume their food in approximately 30 minutes. At the end of the baseline period, the dogs were randomly distributed based on their body weight into three diet treatment groups of seven dogs. Each duplicate lasts three weeks and groups of dogs are assigned to a different diet treatment during each duplicate, and therefore each dog receives each of the three diet treatments during the experimental period. A glycemic response test is performed at the end of each duplicate and at the end of the baseline period. Animals are weighed each week during the study. Stool is collected for one week (the second week) of the baseline period and the second week of each duplicate. Food intake is monitored daily throughout the study and the difference in grams between the food offered and the food that is left as the amount t consumed in the day for each dog is recorded. During the baseline period, dogs are fed to maintain body weight and are gradually trained to consume their food ad libi tum within the 30 minute period in preparation for glycemic exposures. During the experimental period, the same diet is maintained and the dogs are fed approximately at the same time each day. The body weights of the dogs are measured every week before feeding them in the morning. Scales with dynamic weighing mode (Mettier Toledo KB60s platform with a multiple interval indicator lDls [60,000g x lg] or a Mettier Toledo SM34-K scale [32,000g x 1.Og], Toledo Ohio) are used to measure body weights. The characteristic stools of the dogs are observed during seven consecutive days, during the second week of the baseline period and each duplicate of the experimental period. Faecal ratings are assigned according to Table 7.
Table 7 - definition of the faecal rating system The glycemic response tests were performed at the end of the baseline period and at the end of each duplicate. Dogs are fasted for at least 12 hours before the start of the glycemic response test. Two baseline samples are collected with a difference of approximately 10 minutes from the jugular vein directly in heparinized sodium vacuum tubes (Vacutainer ™, Becton Dickinson, Sunnyvale, CA). Immediately after the last baseline sample is collected, each dog is fed a previously calculated, individual amount of feed (ie, half of the daily average of the previous four days before exposure to the line of feed). base) and a maximum of 30 minutes is allowed for them to eat the experimental diets. Dogs that do not consume the experimental diet in the next 30 minutes are excluded from the glycemic test for that day and are retested the next day. The time 0 corresponds to the end of the food intake. Once the food consumption ends, a catheter is placed aseptically in the cephalic vein. Additional blood samples are collected at 10, 20, 30, 45, 60, 120, 180 and 240 minutes after the food has been consumed. Blood samples are collected in syringes and transferred to vacuum tubes heparinized with sodium. The blood samples are centrifuged at approximately 3000 x g for 20 minutes and two aliquots of plasma are frozen from each point in time. Plasma glucose concentrations (mg / dl) are determined by the hexokinase enzyme method (Cobas Mira, Roche Diagnostic System, Somerville, NJ) and insulin concentrations (μlU / ml) are determined by the standard radioimmunoassay method using RIA equipment (DPC Diagnostic Products Corp., Los Angeles, CA). The ingredient compositions of the experimental diets are presented in Table 8 with the nutrient composition presented in Table 9. During the study periods three experimental diets are evaluated.
Table 8 - composition of ingredients of the experimental diets Provides the following on a dry-matter basis of 92.5% 15.6 KUI / kg of vitamin A, 937 IU / kg of vitamin D, 75.4 IU / kg of vitamin E, 128.7 mg / kg of ascorbic acid, 11 mg / kg of thiamin, 34.3 mg (kg of riboflavin, 21.5 mg / kg of pantothenic acid, 58.5 pig / kg of niacin, 7.4 mg / kg of pyrodoxin, 1.2 mg / kg of folic acid, 0.4 mg / kg of biotin, 0.15 mg / kg of vitamin B12.2 Provides the following on a dry matter basis of 92.5%: 213 mg / kg of magnesium, 412 mg / kg of iron, 34.5 mg / kg of copper, 61.6 mg / kg of manganese, 227.8 mg / kg of zinc, 3.48 mg / kg of iodine, 0.27 mg / kg of selenium.
Table 9 - nutrient composition of the experimental diets The data is analyzed as follows: glucose and insulin are measured at nine different time points, as shown in Figures 16 and 18. The time point "0" is considered as the baseline and is considered the average of both baseline samples. The area under the curve (Figures 17 and 19), the area above the baseline, peak time and peak amplitude are calculated for both insulin and glucose. These variables are analyzed using the analysis of variance of a randomized block design (SAS user guide: statistics, Cary, NC, SAS Institute Inc., 1989). The classification includes sources for: treatment, replication and error. All tests F use a = 0.10 and LSD uses a = 0.05. Time-dependent responses are studied using a repeated measurement variance analysis and glucose or insulin observations by time. The classification includes sources for: time, treatment x time, duplicate within the treatment-time and error combinations. The effects of treatment are tested using duplicate, treatment, duplicate x treatment for the term error. All the F and LSD tests used were a = 0.05. Results: there are no differences between the diets for body weight or weekly food consumption amounts (data not shown). There are no detected differences between individual time points and among other evaluated variables (P> 0.05). As shown in Figure 16, the RICE diet results in a slightly higher glucose peak and a slightly elevated glucose response compared to the BARLEY and AVENA diets. Several dogs did not return to baseline glucose levels at the end of the glycemic response test indicating a reduced ability of geriatric dogs to respond to elevated glucose. The increasing area under the glucose curve (Figure 17) for those dogs that consume the RICE diet tend to be higher (P <0.12) compared to dogs that consume the BARLEY diet and that are only marginally superior in comparison with dogs that consume the diet of AVENA. The insulin response data (Figures 18 and 19) show that the 45-minute time point in the AVENA diet has a significantly lower insulin concentration (P <0.05) compared to the diet with BARLEY but is not different (P> 0.05) from the RICE diet. The insulinemic response for the RICE and BARLEY diets have two distinct insulin peaks in approximately 45 to 60 min and 180 min, and RICE induces the highest peak at both points in time. The AVENA diet results in a flatter response with a single peak. The insulin response of several dogs does not return to baseline glucose levels by the 240 min time point. This delay may indicate a reduced capacity for older dogs to respond to elevation to glucose. In fact, one of the geriatric dogs was removed from the study because it has an extremely high baseline and a poorly compensated glucose peak which is compatible with diabetes. The extremely variable glycemic response observed in these geriatric dogs in combination with large variations between duplicates conceals the effect of diet and demonstrates that geriatric dogs have an erratic glycemic response. Dogs which consume the RICE diet tend to have an increased area under the insulin curve (P <0.08) when compared to dogs fed the AVENA diet and have only a marginally increased area under the curve of insulin when compared to dogs fed the BARLEY diet. The stool scores remained normal for all dogs throughout the study and there were no differences (P> 0.05) between the treatment groups (data not shown). The RICE diet produces exaggerated glucose and insulin curves in response to a glycemic tolerance test in dogs when compared to dogs fed on BARLEY and AVENA diets. This effect can be quantified over the entire 240-min test as an increased area under the curve. Although these effects are not significantly different from a 95% confidence interval, these exaggerated responses with respect to time may be the first stage in developing insulin resistance and glucose intolerance. Currently, most of the dog diets in the commercial market contain rice as the source of starch. This may be harmful to the animal in the long term, or the animal may show signs of impaired glucose tolerance when initiating and maintaining superior glucose-to-insulin responses to a food. In this experiment, the AVENA diet was more effective in reducing the insulin response to food, while the BARLEY diet was the most effective in reducing the glucose response to a food. A combination of these two sources of starch may be beneficial in helping to control glucose response in dogs showing signs of impaired glucose tolerance or as a preventive measure for long-term feeding by decreasing both glucose and blood glucose responses. insulin before food.

Claims (23)

1. A pet food composition for controlling the postprandial glycemic and insulinemic response in a companion animal comprising a protein source, a source of fat and a carbohydrate source from a grain source, consisting of a combination of corn and sorghum, a combination of corn, sorghum and oats, and a combination of oats and barley. £
2. The pet food composition, as described in claim 1, wherein the grain source is a combination of corn and sorghum.
3. The pet food composition, as described in claim 2, wherein the ratio of corn to sorghum is from 1: 5 to 5: 1.
4. The pet food composition, as described in claim 1, wherein the grain source is a combination of corn, sorghum and oats.
5. The pet food composition, as described in claim 4, wherein the ratio of corn to sorghum to oats is from 1: 1: 5 to 1: 5: 1. to 5: 1: 1.
6. A pet food composition, as described in claim 1, wherein the grain source is a combination of oats and barley.
7. The pet food composition, as described in claim 6, wherein the ratio of oats to barley is from 1: 5 to 5: 1.
8. The pet food composition, as described in claim 1, comprising 20 to 40% of crude protein, 4 to 30% of fat and 2 to 20% of total fiber of the diet.
9. The pet food composition, as described in claim 1, which further includes chromium tripicolinate.
10. The pet food composition, as described in claim 1, further including a water soluble cellulose ether.
11. The pet food composition, as described in claim 1, which further includes 1 to 11 weight percent fiber of the total supplemental diet of fermentable fibers which have a disappearance of organic matter from 15 to 60 percent in weight when fermented by faecal bacteria during a period of 24 hours.
12. The use of a pet food composition containing a source of protein, a source of fat and a source of carbohydrates from a grain source, consisting of a combination of corn and sorghum, - a combination of corn, sorghum and oats, - and a combination of oats and barley in the manufacture of a pet food product for use in the control of the postprandial glycemic and insulinemic response. in a pet.
13. The use as described in claim 12, wherein the grain source is a combination of corn and sorghum.
14. The use as described in claim 13, wherein the ratio of corn to sorghum is from 1: 5 to 5: 1.
15. The use as described in claim 12, wherein the grain source is a combination of corn, sorghum and oats.
16. The use as described in claim 5, wherein the ratio of corn to sorghum to oats is 1: 1: 5 to 1: 5: 1 to 5: 1: 1.
17. The use as claimed in claim 12, wherein the grain source is a combination of oats and barley.
18. The use as described in claim 17, wherein the ratio of oats to barley is from 1: 5 to £ 5: 1 .
19. The use as described in claim 12, comprising 20 to 40% of crude protein, 4 to 40% of fat and 2 to 20% of total fiber of the diet.
20. The use as described in claim 12, wherein the composition further includes chromium tripolyolinate.
. 21. The use as described in claim 12, wherein the composition further includes water soluble cellulose ether.
22. The use as described in claim 12, wherein the composition further includes 1 to 11 weight percent of total fiber of the supplementary diet of fermentable fibers which have a disappearance of organic matter of 15 to 60 weight percent when they are fragmented by fecal bacteria during a period of 24 hours.
23. The use as described in claim 12, wherein the companion animal is a geriatric dog. EXTRACT OF THE INVENTION A composition and process is provided for controlling the postprandial glycemic or insulinemic response, or both, in companion animals such as dogs. The pet food composition includes a source of protein, a source of fat and a source of carbohydrates from a source of grain that excludes rice. The use of the preferred sources of carbohydrates include a combination of corn and sorghum; a combination of corn, sorghum and barley; a combination of corn, sorghum and oats; and a combination of oats and barley that tends to regulate the animal's glycemic and insulinemic responses after food. This effect is even more marked when the composition is supplied as food to geriatric pets such as dogs.
MXPA/A/2001/008016A 1999-02-23 2001-08-08 Composition and process for controlling glucose metabolism in companion animals by dietary starch MXPA01008016A (en)

Applications Claiming Priority (2)

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US60/121,087 1999-02-23
US09507066 2000-02-18

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MXPA01008016A true MXPA01008016A (en) 2002-05-09

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