CN101427134A - Method of diagnosing a body weight condition or predisposition in an animal - Google Patents

Abstract

A method for diagnosing a body weight condition or predisposition to a body weight condition in an animal by determining observed level(s) of at least one biomarker in a tissue or biofluid sample from the animal, and comparing the observed level(s) to reference level(s) for the biomarker; wherein the observed level(s) relative to the reference level(s) are individually or collectively indicative of the body weight condition or predisposition.

Description

The method of diagnosis the weight of animals situation or tendency

Background of invention

Invention field

[0001] the present invention relates to diagnose the body weight situation (condition) of animal or the method for tendency (predisposition).The invention still further relates to the method for the body condition scoring (bodycondition score) of calculating animal.

Prior art

[0002] the popular of obesity all has increase in people and inhuman colony.Human obesity rates has reached the epidemic disease ratio.In addition, studies show that in all American family pets has 25%-40% overweight or fat, and this trend is just causing growing steadily of overweight correlativity pet disease and ever-increasing animal doctor's cost.

[0003] overweight meeting becomes the hazards of development multiple imbalance (disorder) or disease.For example illnesss such as obesity and heart disease, degenerative joint disease, diabetes and cancer are associated.In addition, overweight animal may be experienced problems because of the decline of the minimizing of activity and total quality of life.The prevention of overweight condition can have lifelong effect, and the hazards of understanding about this situation of development can cause producing improved prevention and the therapeutic scheme that can optimize general health.

[0004] will comprise that for example the various biological markers (biomarker) of blood plasma leptin associate with food intake and body fat.Shiiya et al. (2002) J.Clin.Endocrinol.Metab.87 (1): 240-244 reports that the blood plasma ghrelin concentration among the obese people is lower than the body lath.

[0005] although people know overweight condition to health affected, treat this situation and be still a difficult problem, there is one to be that the inherent physiological mechanism or the variation that occur in the physiological system of keeping this situation are known little about it in its reason.It is useful measuring body weight by conventional art, but the information that obtains like this is coarse, may not too help to understand inherent physiology or the biochemical process relevant with body weight situation such as obesity.In addition, aspect the tendency of obesity or other body weight situations, the value of this conventional art is limited in detection or the normal animal of diagnosis body weight.For example, animal " body condition scoring " (BCS) conventionally be used as the health of animal formed the means of classifying.The mensuration of the BCS of animal is based on vision and the sense of touch analysis of animal health care professional to body size and the shape of animal.For example, according to this method, the animal of BCS " 1 " expression very lean (emaciated), the animal of " 2 " expression slight of statures (thin), the best body condition (optimal body condition) of " 3 " expression animal, the animal of " 4 " expression grossness (fat), the animal of " 5 " expression fat (obese).The mensuration of the BCS of animal is that those skilled in the art are familiar with; It is known to the technician that several method is arranged, for example at United States Patent (USP) the 6th, 691, and No. 639 and be disclosed method in the reference book (ISBN0-945837-05-4, the 4th edition, the 13rd chapter) of " Small Animal Clinical Nutrition " at title.Though BCS measures and used widely, this method is not ideal enough, because it is the analysis of suitable subjectivity, different personnel may determine diverse BCS to identical animal, and such result is much.Therefore, still need effective method to diagnose body weight situation or the tendency and the body condition scoring of measuring this animal exactly of animal.

[0006] we find and come based on the biomarker data that obtains from animal at this report the method for the body condition scoring of quantitative animal unexpectedly.This biomarker data also can be used to diagnose body weight situation and/or the tendency of animal, and the obesity correlativity health disorders that is used for the diagnosing animal tendency of this imbalance maybe.

Summary of the invention

[0007] the invention provides the body weight situation of diagnosis animal or the method for its tendency.Described method comprises the observation level of mensuration from tissue or at least a biological marker in the biologicfluid sample of this animal, and should the observation level and the reference levels of this biological marker compare, wherein with respect to the observation level of reference levels individually or jointly indication body weight condition or tendency.

[0008] the present invention also provides the method for the body condition scoring of quantitative animal, and described method comprises that (a) analyzes the body weight of described animal and the serum levels of at least a biological marker; (b) step (a) is acquired described data and be applied among the algorithm I-IV of the present invention described herein any one.

[0009] the present invention also is provided as the method that animal is selected health scheme (regimen).Described method comprises (a) by measuring the observation level from tissue or at least a biological marker in the biologicfluid sample of this animal, and should the observation level and the reference levels of this biological marker compare, diagnose body weight situation or its tendency; Wherein with respect to the observation level of reference levels individually or jointly indication body weight condition or tendency; (b) determine this body weight situation that is suitable for being diagnosed out or the health scheme of tendency.

[00010] the present invention also provides the method for initial (onset) of the body weight situation that detects animal or tendency in addition.Described method is included at least a biological marker of this animal of monitoring in a period of time, way is to get a plurality of time points all to measure observation level from tissue or this biological marker in the biologicfluid sample of this animal in this time period when each time point, and should the observation level and the reference levels of this biological marker compare; If wherein, then detect initial at any time with respect to the observation level of reference levels individually or jointly indication body weight condition or tendency.

[00011] the present invention also provides the method for the effect of the assessment body weight situation of certain health project management animal or tendency in addition.This method is included at least a biological marker of this animal of interior monitoring of time period of this health scheme of execution, way is to get a plurality of time points all to measure observation level from tissue or this biological marker in the biologicfluid sample of this animal in this time period when each time point, and should the observation level and the reference levels of this biological marker compare; Wherein indicate the effect of this health project management body weight situation or tendency individually or jointly with respect to the observation level of reference levels.

[0010] the present invention also provides kit in addition, and this kit comprises:

(a) one or more are in order to detect the reagent from the observation level of the tissue of animal or at least a biological marker in the biologicfluid sample; With

(b) one or more users that carry information can use media (user-accessiblemedia), and described information comprises the reference levels of (i) this biological marker; (ii) should the observation level and the algorithm that compares of this reference levels; Wherein indicate body weight situation or the tendency of this animal individually or jointly with respect to the observation level of reference levels.

[0011] the present invention also provides the obesity correlativity health status of diagnosis animal or the method for its tendency in addition, described method comprises the observation level of mensuration from tissue or at least a biological marker in the biologicfluid sample of this animal, and should the observation level and the reference levels of this biological marker compare; Wherein with respect to the observation level of reference levels individually or jointly indication body weight condition or tendency.Specifically, this method can be used for diagnosing osteoarthritis, wherein this biological marker be that alkaline phosphatase, osteocalcin, amino-terminal end cross-linked side peptide, II type cartilage are synthetic, cartilage oligo-substrate protein or carboxyl terminal cross-linked side peptide.Preferably, this biological marker is that alkaline phosphatase or II type cartilage are synthetic.

[0012] other target of the present invention, feature and advantage will be conspicuous for a person skilled in the art.

Detailed Description Of The Invention

[0013] finds according to the present invention, can effectively be used for calculating the body condition scoring of animal from the level of the tissue of animal or some biological marker in the biologicfluid sample unexpectedly.In addition, biomarker data also can be used for diagnosing in the method for body weight situation of this animal.The level of this biological marker can be from state before the meal to state fluctuation after the meal.But, the individual animals that the body weight situation is different, for example body thin (lean) and fat animal all show difference aspect the biological marker abswolute level aspect the form of this fluctuation and/or the degree and at fasting state the time.Therefore, the spectral pattern of one or more biological markers (profile) can the indication body weight condition.In addition, the tendency of this spectral pattern energy indication body weight condition, even in the situation that this situation does not obtain expressing as yet, also can indicate, and also can be used to diagnose obesity correlativity health disorders or its tendency of animal.Therefore, this spectral pattern can be used for managing body weight and the health consequences of animal, and this health consequences may be relevant with body weight situation that exist or that this animal tendency takes place in this animal.

[0014] purpose biological marker of the present invention is such biological marker, horizontal indication body weight condition of its observation with respect to reference levels or tendency.According to some embodiments, reference levels can be set up from the sample available from the healthy animal of normal type, perhaps can be the numerical value of announcing.Usually, reference levels are that the animal with same species is that object is set up, and are that object is set up if any the animal with same breed or variety type if possible.In addition, usually preferred reference levels are to be that object is set up with the animal with the similar age group of this animal.

Determining of this reference levels comprises " normally " body weight of determining animal, can be that those skilled in the art are familiar with.In this situation, difference can indication body weight condition or tendency in the observation level of (for example being higher or lower than) reference levels in fact.This species diversity can be but be unnecessary to be significant on the statistics.

[0015] or, the animal that reference levels can knownly have specific body weight situation or a tendency is that object is set up; The observation level that is similar to reference levels in this case can be indicated this situation or tendency.

[0016] level of biological marker can provide the information about inherent heredity, biochemistry or physiologic factor, mechanism or the approach relevant with specific existing body weight situation (for example normal type, overweight, obesity), but may not provide enough information like this.In some cases, the statistics correlativity between the level of biological marker and the body weight situation that observes or the tendency can enough be used for enforcement of the present invention.But in biological marker provided situation about the information of heredity, biochemistry or physiological correlations, with respect to the classic method that only relies on the physical measurement relevant with body weight, advantage can be king-sized.

[0017] animal can be people or inhuman.In each embodiment, animal is a vertebrate, for example fish, bird, Reptilia or mammal.In the middle of mammal, exemplary animal can be the member of Carnivora (Camivora), includes but not limited to Canidae and cats species.In one embodiment, animal is ox, horse, pig or other forms of domestic animal, and body condition scoring and/or body weight Determination on condition are important for these domestic animals.

[0018] in one embodiment, animal is a companion animals.What " companion animals " in this article referred to any species is come the domesticated animal individuality by caregiver as pet, the perhaps animal individual of generally being raised and train into pet of a plurality of species, comprise dog (domesticated dog, Canis familiaris) and cat (domestic cat, Felis domesticus), and no matter whether this animal individual only is or part on be in order to be raised as the companion.Therefore, " companion animals " herein comprises the work dog, raises and to control rodentine field cat etc. and pet dog and cat.In some embodiments, animal is a canid.In other embodiments, animal is a cats.

[0019] this paper also is susceptible to, and method of the present invention may be used on the people, and for example in order to quantitative people " body condition scoring ", this body condition scoring more generally is called " body mass index " or BMI.Because the body weight (kilogram) that BMI typically refers to animal may need algorithm disclosed herein is changed with calculating BMI divided by its height (rice) square.Those skilled in the art can easily finish this point.

[0020], can be that to determine animal be underweight, normal type, overweight or fat according to the present invention is based on " the body weight situation " that biological marker analysis of control reference sample is diagnosed out.Body weight is not only the problem of body weight only usually, but often relevant with the quantity or the percentage of body fat.Referring to for example Burkholder ﹠amp; Toll (2000) is at Hand et al. (eds.), Small Animal Clinical Nutrition, and 4th Edition, Chapter 13, the content among the pp402-430.

[0021] " body weight tendency " used herein is meant that animal increases, loses or keeps body weight and/or in the taxis (proneness) (being tendentiousness (propensity)) of the variation of following aspect healthy or other physiological situations.Therefore, the example of body weight tendency comprises the tendentiousness of putting on weight or the tendency of this tendentious shortage and obesity.

[0022] animal used herein " body condition scoring " (BCS) be meant the health of animal formed the means of classifying.The determining of the BCS of animal is based on vision and the sense of touch analysis of animal health care professional to body size and the shape of animal traditionally.According to this classic method, the animal that BCS " 1 " expression is very lean, the animal of " 2 " expression slight of stature, the best body condition of " 3 " expression animal, the animal of " 4 " expression grossness, the fat animal of " 5 " expression.The conventional determining of the BCS of animal is that those skilled in the art are familiar with; It is known to the technician that several method is arranged, for example at United States Patent (USP) the 6th, 691, and No. 639 and be disclosed method in the reference book (ISBN 0-945837-05-4, the 4th edition, the 13rd chapter) of " Small AnimalClinical Nutrition " at title.

[0023] according to an embodiment, body weight tendency is when animal is young, for example in the situation of canid or cats about 1 years old at most, diagnoses by method of the present invention.

[0024] the overweight or fat situation relevance reason that may be multiple disease and imbalance or worsen sexual factor.This obesity is diseases related to comprise for example metabolism change, endocrine disease, function change, degeneration joint and plastic surgery disease, angiocardiopathy, cancer, sleep-disorder, dysgenesia and their combination with health disorders.Overweight condition also can be because of the decline of the minimizing of activity or quality of life and is caused problems.Therefore, in one embodiment, body weight situation or the tendency diagnosed out by implementing the present invention are to increase body weight situation or the tendency that the off the hinges risk of obesity correlativity takes place animal.

[0025] this overweight or obesity correlativity health disorders for example comprises hyperlipidemia, dyslipidemia, insulin resistance, glucose does not tolerate, liver lipidosis, complication of anesthesia, adrenal cortex function is hyperfunction, hypothyroidism, diabetes, insulinoma, chromophobe adenoma of pituitary, hypopituitarism, damage of hypothalamus, joint compressing (joint stress), musculoskeletal pain, expiratory dyspnea, hypertension (hypertension), difficult labour, motion does not tolerate, heat does not tolerate, immunologic function descends, degeneration joint and plastic surgery disease (for example osteoarthritis), angiocardiopathy, overstretched (hypertension), respiratory distress, change in renal function, pancreatitis, transitional cell carcinoma, tired, sleep-disorder, dysgenesia and their combination.

[0026] term " biological marker " refers to quantitatively to identify in tissue or biologicfluid sample and material with the correlativity of particular phenotype or physiological situation can be provided.For example, biological marker can be cell factor, for example inflammatory cytokine; Peptide or protein, for example peptide YY, neuropeptide tyrosine, glucagon-like peptide 1 (GLP-I), alkaline phosphatase, ghrelin; Nucleic acid is for example corresponding to mRNA transcript, biochemical metabolite such as the glucose of peptide or protein biological marker; Neurotransmitter; Activator; Antagonist; Perhaps other biological sign such as thyroxine, thyroid-stimulating hormone (TSH), insulin-like growth factor-i, leptin, angiotensin I and II, c-proteins C reactive, HDL1 and 2, low-density lipoprotein, very low density lipoprotein (VLDL), chylomicron, testosterone, estradiol, cortisol, osteocalcin, amino terminal crosslinking protein, II type cartilage synthesize or cartilage oligo-substrate protein.In each embodiment, the level of at least a following biological marker is measured: glucose, GLP-1, ghrelin, leptin, adiponectin, resistance protein (resistin), resistance protein sample molecule, c-proteins C reactive, thyroid-stimulating hormone (TSH) and insulin.Useful especially biological marker comprises glucose, GLP-1, c-proteins C reactive, thyroid-stimulating hormone (TSH) and ghrelin.

[0027] term " obesity biological marker " in this article refers to and can quantitatively identify and can provide material with the correlativity of obesity in tissue or biologicfluid sample.The example of obesity biological marker includes but not limited to cholesterol, triglyceride, glucagon albumen-1, insulin-like growth factor-i, ghrelin, leptin, GLP-1, angiotensin I and II, high-density lipoprotein (HDL)-1, high-density lipoprotein (HDL)-2, low-density lipoprotein and very low density lipoprotein (VLDL).

[0028] term used herein " arthritis biological marker " is meant and can quantitatively identifies in tissue or biologicfluid sample and can provide and be the material of correlativity of the illness (for example arthritis or osteoarthritis) of feature with the body joints infringement.The example of arthritis biological marker includes but not limited to osteocalcin, amino terminal cross-linked side peptide, alkaline phosphatase, carboxyl terminal cross-linked side peptide, II type cartilage is synthetic and cartilage oligo-substrate protein.

[0029] term used herein " thyroid gland biological marker " is meant and can quantitatively identifies and can provide material with the correlativity of thyroid disease or imbalance in tissue or biologicfluid sample.The example of thyroid gland biological marker includes but not limited to thyroid-stimulating hormone (TSH) and thyroxine.

[0030] can relate to the mensuration of more than one biological marker to the diagnosis of body weight situation or tendency by the inventive method.In some cases, single biological marker is with regard to energy indication body weight condition or tendency; In other cases, the biological marker spectral pattern that comprises the level of two or more biological markers is jointly indicated this situation or tendency.In other cases, the spectral pattern that comprises the level of at least a biological marker and other blood chemistry materials such as sodium, potassium, chloride, phosphorus, cholerythrin, kreatinin or serum urea nitrogen is jointly indicated this situation or tendency.

[0031] any tissue or biologicfluid sample can be the sources of purpose biological marker.But, in most applications, the biologicfluid sample that can obtain with the invasive of minimum preferably.Biofluid for example comprises liquid, nose juice and saliva in whole blood, serum, blood plasma, celiolymph, level in gingival sulcus fluid, urine, lymph liquid, the muscle.

[0032] the available determination method well known in the art of the level of biological marker is measured.Determination method can be but be unnecessary to be the determination method that is commercially available.Usually, select determination method according to the type of biological marker and the type of sample.For example, can use commercially available immunoassay (it adopts has reactive monoclonal antibody to one or more epi-positions on the polypeptide) or competitive binding assay method, measure the serum levels of protein biological marker such as GLP-1 or ghrelin based on monoclonal antibody; Can use determination method, measure the serum levels of glucose based on the ferricyanide, hexokinase or method of cracking.

[0033] in some embodiments, the flat and/or reference levels of observation water are independently to be selected from following determination method with one or more to measure: enzyme immunoassay (EIA) (EIA), enzyme linked immunosorbent assay (ELISA) (ELISA), immunofluorescence assay (IFA), radiommunoassay (RIA), Western blotting mensuration, biochemical measurement, enzymatic determination and colorimetric estimation.It is well known to a person skilled in the art that multiple mark (label) and conjugation techniques are arranged, and they can be used in various biochemistry, nucleic acid and the determined amino acid.

[0034] tissue or biologicfluid sample can for example be collected for assessing and diagnosing in the place of nursing facility, and this place is exactly the place that animal capable obtains health care personnel's (for example doctor, animal doctor, Doctor's Assistant, internist assistant, nurse etc.) nurse.The limiting examples in the place of nursing facility comprises hospital, internist or animal doctor's office and veterinary clinic.Perhaps, can collect sample at animal residence, farm, matting canopy or the shed of letting animals feed.

[0035] to the analysis of one or more purpose biological samples in the sample, can for example carry out in the place of nursing facility in the place of collected specimens.Kit as herein described can be used for this analysis.Perhaps, sample can be delivered to second facility.The laboratory such as the commercial test laboratory of the assessment of term " second facility " fingering row clinical sample, it can be the place (promptly in other position) beyond the place of nursing facility.

[0036] in some embodiments, the observation level of one or more biological markers and the comparison of reference levels are to carry out in the place of the nursing facility or second facility.

[0037] be in the situation that single time point is gathered at sample, this can carry out in any stage of the breeding cycle of animal, for example face when having meal (before the meal) or after dining the suitable time interval (after the meal) carry out.Gather but usually preferably, when diagnosis will be based on simple sample, this sample will be when animal be in fasting state (for example time point) before the meal.

[0038] randomly, a plurality of time point collections of sample in breeding cycle.In this case, can gather at least one (being exactly one usually) sample and at least one (usually above one) sample after the meal before the meal.Proper time point for example is 0 minute (before the meal), 10,30,60,120 and 360 minutes after the meal.

[0039] sample for example the biological marker level in the blood serum sample can not adjust, perhaps can adjust by the body weight of animal.The level of not adjusting can be represented as mg/L, μ g/L or ng/L or molar concentration units such as μ mol/L, mmol/L or pmol/L with concentration unit.The available similar unit representation of the level of adjusting, but with body weight (BW) as divisor, for example mg/L/kg BW, pmol/L/kg BW etc.

[0040] in one embodiment, animal is a canid, and biological marker comprises the glucose in the serum.According to this embodiment, the reference levels that the serum level of glucose that the observation body weight in the fasting animal is adjusted is adjusted than the body weight of the canid of normal type are low at least about 10%, indicate this animal that the tendency of putting on weight is arranged.

[0041] in another embodiment, animal is a canid, and biological marker comprises the GLP-1 in the serum.According to this embodiment, the reference levels that the serum GLP-1 level that the observation body weight in the fasting animal is adjusted is adjusted than the body weight of the animal of normal type are low at least about 20%, indicate this animal that the tendency of putting on weight is arranged.

[0042] in another embodiment, animal is a canid, and biological marker comprises the ghrelin in the serum.According to this embodiment, the reference levels that the serum ghrelin level that the observation body weight in the fasting animal is adjusted is adjusted than the body weight of the canid of normal type are low at least about 20%, indicate this animal that the tendency of putting on weight is arranged.

[0043] in another embodiment, the present invention relates to the method for the body condition scoring of quantitative animal, described method comprises that (a) analyzes the body weight of described animal and the serum levels of glucose, sodium, chloride, c-proteins C reactive and thyroid-stimulating hormone (TSH); (b) data that step (a) is obtained are applied to following algorithm:

Body condition scoring=3.62352+ (0.17443 x body weight (kg))+(0.01621 x glucose (mg/dL))+(0.06496 x sodium (mmol/L))-(0.12439 x chloride (mmol/L))-(0.05575 x c-proteins C reactive (ng/mL))+(1.7239 2 x thyroid-stimulating hormone (TSH) (ng/mL)).In specific embodiment, animal is a canid.

[0044] in another embodiment, the present invention relates to the method for the body condition scoring of quantitative animal, described method comprises that (a) analyzes body weight and urea nitrogen, sodium and the muriatic serum levels of described animal; (b) data that step (a) is obtained are applied to following algorithm:

Body condition scoring=3.64120+ (0.18614 x body weight (kg))-(0.05289 x serum urea nitrogen (mg/dL))+(0.08935 x sodium (mmol/L))-(0.14088 x chloride (mmol/L)).

In specific embodiment, animal is a canid.

[0045] in another embodiment, the present invention relates to the method for the body condition scoring of quantitative animal, described method comprises that (a) analyzes the body weight of described animal and the serum levels of sodium, potassium, chloride, phosphorus, cholerythrin and ghrelin; (b) data that step (a) is obtained are applied to following algorithm:

The body condition scoring=-3.20078+ (0.4259 x body weight (kg))-(0.05508 x sodium (mmol/L))+(0.69884 x potassium (mmol/L))+(0.09472 x chloride (mmol/L))-(0.15372 x phosphorus (mg/dL))+(1.31580 x total bilirubin (mg/dL))-(0.35136 x ghrelin (ng/mL)).

In specific embodiment, animal is a cats.

[0046] in another embodiment, the present invention relates to the method for the body condition scoring of quantitative animal, described method comprises that (a) analyzes body weight and the blood urea nitrogen of described animal: the serum levels of kreatinin ratio, potassium, chloride, phosphorus and total bilirubin; (b) data that step (a) is obtained are applied to following algorithm:

The body condition scoring=-7.34191+ (0.48335 x body weight (kg))+(0.03578 x blood urea nitrogen: the kreatinin ratio)+(0.58860 x potassium (mmol/L))+(0.04683 x chloride (mmol/L))-(0.16894 x phosphorus (mg/dL))+(0.86613 x total bilirubin (mg/dL)).

In specific embodiment, animal is a cats.

[0047] diagnose out body condition scoring, body weight situation or tendency as mentioned above after, can select the health scheme that is suitable for this body weight situation or tendency.This health scheme can perhaps can be stipulated by health care professional by the care-giver of animal or animal according to selecting by any suitable reception and registration instrument (communication means) information conveyed.This health scheme can comprise one or more in meals, exercise and the drug therapy.

[0048] in some embodiments, the health scheme comprises the composition for this animal consumption.This composition for example can be alimentation composition such as food composition, fill-in, reward food (treat) or toy, it is to be noted some but not every fill-in, reward food and toy itself are food compositions.Food composition can be for example absorbed by animal or by feed to animal.This animal is in the situation of companion animals, the normally such food composition of food composition that can be used for the inventive method, it nutritionally is suitable for the body weight situation or the tendency of feeding this animal (this paper is called " pet food ") and being suitable for being diagnosed out.Pet food can more specifically be suitable for the special dietary demand of canid or cats, perhaps is suitable for some subpopulation of canid or cats such as big kind dog, doggie (puppy) or kitten (kitten), pup or cat, adult dog or cat, old dog or cat and old and feeble dog or cat.

[0049] food composition of the part of formation health scheme can be the food composition of the complete meals of nutrition basically (substantially nutritionally complete diet) is provided can for this animal." the complete meals of nutrition " are such meals, and it comprises enough nutrients of the normal health that is enough to keep the healthy animal of accepting these meals.

[0050] or, composition can be a fill-in, promptly uses to improve the meals nutrient balance generally or the composition of performance with another food composition.This fill-in comprises such food composition, its fill-in as other foods does not add dilutedly feeds, make and to select freely that other can supply with the part of animal separately in the animal grain ration (ration) that perhaps it is diluted and mixes with the usual food of animal and produce the complete meals of nutrition basically.Fill-in or can be the form outside the food composition is the formulation of medicine sample for example, comprises for example powder, liquid agent, syrup, pill etc.

[0051] composition can be the reward food.The reward food comprises for example as award or in order to lure that animal gives the composition of animal at non-meal time food into.This dog reward food as the food composition with at least some nutritive values comprises for example dog biscuit.Reward food also can be a non-nutritive basically.The composition that constitutes the part of health scheme can itself constitute the reward food, be coated in that existing reward food is gone up or above-mentioned two kinds of situations take place simultaneously.

[0052] composition can be to be suitable for the toy that the animal oral area uses.Toy comprises for example masticable toy, uses artificial bone as dog.Can be used for composition of the present invention can form coating on the surface of toy or on the surface at toy assembly, can partially or completely be incorporated in the middle of the toy, and perhaps above-mentioned two kinds of situations take place simultaneously.A variety of suitable toy sales are arranged in the market, comprise consumable toy of part (toy that for example comprises plastic assembly) and complete consumable toy (for example greenhide and various artifical bone).Toy not only can supply human but also can supply non-human, uses for companion animals, farm-animals and zoo animal specifically, uses for dog, cat or bird in particular.

[0053] in other embodiments, the health scheme comprises the exercise of certain form.Exercise can be taked any this animal and the body weight situation that is suitable for being diagnosed out or form of tendency of being fit to.For example, training can include but not limited to walking, jog or run.

[0054] health scheme can continue with such frequency to carry out or can continue carrying out such a period of time, and this frequency or time are essential or suitable for this body weight situation or tendency.For example, the health scheme can continue to carry out at least about 1 month, at least about 2 months, at least about 6 months, at least about 1 year, perhaps continue to carry out some other time, these other time is to be defined as essential or reasonable time by for example animal doctor or other health care professional.

[0055] the present invention also provides the body weight situation of detection animal or the initial method of tendency.According to this method, at least a biological marker of this animal of monitoring in a period of time, if with respect to the observation level of the reference levels of this biological marker individually or jointly indication body weight condition or tendency, then detect initial at any time point of this section in the time.

[0056] the optional at least a portion that also is included in this section period of this method is monitored the body weight of this animal in the time.Can use any technology of measuring body weight that is applicable to, include but not limited to weigh, the assessment of relative body weight (RBW), assessment, morphometry art and their combination of body condition scoring (BCS).The useful in addition information relevant with body weight can be chosen wantonly by obtaining such as following technology: magnetic resonance imaging (MRI), computerized tomography (CT), neutron activation, total body fluids of weight method (hydrodensitometry), isotope dilution method (totalbody water by isotope dilution), total health potassium, ultrasonic, bio-electrical impedance, radiograph, sound spectrograph, dual-energy x-ray absorption process (DEXA) or their combination under water.

[0057] monitoring of the monitoring of biological marker and optional body weight and/or other correlation parameters, can carry out with any time interval easily, for example with approximately per hour once, twice of every day, once a day, twice weekly, weekly, every month once, two months once, annual twice or the annual time interval.

[0058] monitoring of biological marker also can provide the process useful in order to the effect of the body weight situation of assessing certain health project management animal or tendency.According to this method, biological marker and optional body weight and/or other correlation parameters are monitored carrying out in the time of this health scheme.Can be individually with respect to the observation level of the reference levels of this biological marker or jointly indicate the effect of this health project management body weight situation or tendency.

[0059] in another embodiment of the invention, provides the kit that is fit to according to any method use described herein.This kit comprises that one or more are in order to detect the reagent from the observation level of the tissue of animal or at least a biological marker in the biologicfluid sample; Can use media with one or more users that carry information, described information comprises the reference levels of (i) this biological marker; (ii) should the observation level and the algorithm that compares of this reference levels.As in previous embodiments, indicate body weight situation or the tendency of this animal individually or jointly with respect to the observation level of reference levels.

[0060] " user can use " as herein described media comprises all media, as newspaper, disk, storage chip, card, computing machine or network, instruction on these media, information, algorithm and/or data can retrieve ground (retrievably) hold or store.Algorithm is software algorithm normally.An example of " user can use media " is SAS/STAT

Software, it uses homing method to be identified for predicting the algorithm of body condition scoring.The example of this algorithm is the algorithm I-IV that provides among the following embodiment, for example:

Algorithm I:

Body condition scoring=3.62352+ (0.17443 x body weight (kg))+(0.01621 x glucose (mg/dL))+(0.06496 x sodium (mmol/L))-(0.12439 x chloride (mmol/L))-(0.05575 x c-proteins C reactive (ng/mL))+(1.72392 x thyroid-stimulating hormone (TSH) (ng/mL))

Algorithm II:

Body condition scoring=3.64120+ (0.18614 x body weight (kg))-(0.05289 x serum urea nitrogen (mg/dL))+(0.08935 x sodium (mmol/L))-(0.14088 x chloride (mmol/L))

Algorithm III:

The body condition scoring=-3.20078+ (0.4259x body weight (kg))-(0.05508x sodium (mmol/L))+(0.69884 x potassium (mmol/L))+(0.09472 x chloride (mmol/L))-(0.15372 x phosphorus (mg/dL))+(1.31580 x total bilirubin (mg/dL))-(0.35136 x ghrelin (ng/mL))

Algorithm IV:

The body condition scoring=-7.34191+ (0.48335 x body weight (kg))+(0.03578 x serum urea nitrogen: kreatinin)+(0.58860 x potassium (mmol/L))+(0.04683 x chloride (mmol/L))-(0.16894 x phosphorus (mg/dL))+(0.86613 x total bilirubin (mg/dL)).

[0061] kit is optional is independent complete, thereby does not need laboratory equipment.Randomly, kit also comprises tissue or biologicfluid sample gathering-device.Kit can adopt various in order in the determination method (comprising above-listed determination method) of the level of measuring biological marker one or more.Can comprise standard items and standard additive (standard additions), use technique known to calibrate during in order to the level of the biological marker in quantitative sample.

[0062] in some embodiments, one or more reagent in the kit comprise report part (moiety) or mark.Report part or mark for example can comprise biotin, colour former, luminous agent or chemiluminescence agent, co-factor, enzyme, fluorescer, inhibitor, metal or magnetic-particle, radioactive nuclide, substrate or their combination, and available method well known in the art detects.For example, this method includes but not limited in order to detect the spectroscopic method of dyestuff (comprising for example colorimetric detection of enzyme reaction product), luminophore and fluorophor; Substrate carries out spectroscopy analysis, spectrophotometric analysis to reaction product then or other analyze the detection of the enzyme reporter group that carries out by adding; Scintillation counting or radioautograph method at the radioactivity group; With Raman scattering technology at metal nanoparticle (for example gold nano grain).

[0063] one or more reagent in the kit can comprise at least a antibody, for example polyclonal antibody or monoclonal antibody.Antibody can be immobilized on the solid phase carrier.For example, can adopt ELISA to come the level of the biological marker in the working sample.ELISA can relate to antibody coupling on solid phase carrier such as polymkeric substance.The sample that comprises biological marker can be introduced, allow this biological marker and this antibody interact, so can carry out signal (for example color development signal) production process to produce detectable signal on the optics.

[0064] in one embodiment, kit comprise can specificity in conjunction with the second antibody of the first antibody of this biological marker in the sample and the compound that can specificity be produced in conjunction with this first antibody and this biological marker.But the second antibody immobilization is to solid phase carrier.For example, at second antibody and first antibody/when the biological marker compound combines, second antibody can initiation reaction and for example be caused producing detectable change color.

[0065] it is conventionally known to one of skill in the art multiple mark and conjugation techniques being arranged.In order to produce, comprise the pcr amplification of few mark (oligo-labeling), nick translation, end mark and usage flag nucleotide for nucleotide sequence detection and the hybridization of the mark of quantitative usefulness or the technology of PCR probe.Perhaps, coded sequence or its any part of biological marker can be cloned in order in the carrier that produces the mRNA probe.This carrier is well known in the art, is commercially available, and can be used to come the vitro synthesized RNA probe by adding suitable RNA polymerase such as T7, T3 or SP6 and labeled nucleotide.

[0066] the optional instrument that also comprises in order to convey a message of kit, described information comprise following one or more: (a) by with respect to the indicated body weight situation of the observation level of the reference levels of this biological marker or the diagnostic result of tendency; (b) the health scheme that is fit to this diagnostic result of suggestion or regulation.

[0067] the reception and registration instrument can be attached to or the packing of other elements (element) that contain kit of packing in.The reception and registration instrument of any suitable form all can adopt, and for example document such as label, pamphlet, advertisement or package insert, computer readable digital or optical medium such as disk or CD, audio frequency show that (for example on audio tape or the CD) or video show (for example on video-tape or DVD).The reception and registration instrument can refer to be positioned at the other places more information of (as on the website).

[0068] this reception and registration instrument, comprising that document for example such as label, pamphlet, advertisement or package insert, computer readable digital or optical medium such as disk or CD, audio frequency show that (for example on audio tape or the CD), video show the one or more pages on (for example on video-tape or the DVD) and/or the website, itself is another embodiment of the present invention.

[0069] the present invention is not limited to concrete grammar described herein, scheme and reagent, because they can change.In addition, term purpose used herein only is to describe specific embodiment, and is not intended to and limits the scope of the invention.The singulative noun that this paper and appended claims use comprises plural implication, unless that context clearlys show is really not so.Similarly, word " comprises " and will do to comprise that connotation explains rather than make exclusive connotation and explain.

[0070] unless otherwise defined, otherwise technology that all this paper use and scientific terminology and any acronym, the those of ordinary skill common sense in its implication and the technology of the present invention field is identical.Though those methods any and as herein described and materials similar or the method that is equal to and material all can be used for implementing the present invention, preferable methods, device and material are those methods as herein described, device and material.

[0071] all patents mentioned in this article, patented claim and publication are attached to herein by reference, the degree of quoting is the degree that law allowed, and the purpose of quoting is to describe and openly wherein disclosedly may can be used for compound of the present invention, technology, skill, program, technology, article and other composition and method.But all the elements of this paper can not be interpreted as all admitting that the present invention does not have right as invention formerly and prior to these disclosures.

Embodiment

[0072] the present invention can be further described by the embodiment of its following preferred embodiment, but it should be understood that and add these embodiment only for purposes of illustration, and is not intended to and limits the scope of the invention, unless specifically indicate in addition.

Embodiment 1

Biological marker in the fat animal of body lean and fat

[0073] the present embodiment explanation is with respect to body weight situation or the tendency of the level energy indicator animal of some biological marker of reference levels.

[0074] in research in four days, used 20 dogs (10 bodies are thin, 10 obesities), tended to the thin dog of body and tend to the difference of blood serum metabolic thing between the fat dog with mensuration.Be included into thin group of body or be included into fat group, decide: (a) when arbitrarily feeding, put on weight (tending to obesity) or keep the tendentiousness of body weight (it is thin to tend to body) by following feature; (b) with the body condition scoring of the numeral of 1-5 (tend to the average body condition of the thin dog of body and mark approximately 3, mark about 4.1) and tend to the fat average body condition of dog; (c) participate in loss of weight research (before the fat dog participation is arranged, and the thin dog of body not having) before.

[0075] average weight of tending to the thin dog of body is 12.06kg, is 16.59kg and tend to fat dog.

[0076] continue to feed for each dog in four days once a day and keep food (maintenancefood), this keeps food is to be mixed with to satisfy or surpass for keeping the required nutritional requirement of body weight (BW).At the 4th day, before feeding (time 0 before the meal) and gather blood serum sample in the back (after the meal) 10,60,120 and 360 minutes of feeding.Insulin, triglyceride, glucose, GLP-1 and ghrelin concentration with the methods analyst sample of standard, the method of described standard sees for example laboratory manual, as Sambrook et al. (2001) Molecular Cloning:A LaboratoryManual, 3rd ed.Cold Spring Harbor Laboratory Press, Cold SpringHarbor, NY; Spector et al. (1998) Cells:A Laboratory Manual, ColdSpring Harbor Laboratory Press, Cold Spring Harbor, NY and Hampton etal. (1990) Serological Methods:A Laboratory Manual, APS Press, St Paul, MN.The serum-concentration of biological marker is adjusted by BW.The result shows in table 1-5.

[0077] tends to the thin dog of body and tend to do not having essence difference (table 1) on the serum insulin concentration after the meal between the fat dog.

Table 1

Serum insulin level

[0078] same, tending to the thin dog of body and tending to does not have essence difference (table 2) between the fat dog on serum triglyceride concentration.

Table 2

Serum triglyceride level

[0079] great majority in six sampling times or whole, tending to the thin dog of body and tending to has essence difference between the fat dog on the serum level of glucose (table 3), GLP-1 (table 4) and ghrelin (table 5).

Table 3

Serum level of glucose

Table 4

Serum GLP-1 level

Table 5

Serum ghrelin level

[0080] referring to each table, data presentation biological marker particularly serum glucose, GLP-1 and ghrelin level have utility aspect the animal of the fat tendency of body lean and fat in differentiation.

Embodiment 2

The prediction of the body weight tendency of dog

[0081] determined that thin and 30 the overweight dogs of 30 bodies carry out this research.For the purpose of this research, to be that 4 or 5 dog is classified as overweight (scoring yardstick is 1-5, and wherein 1 equals slight of stature, and 5 equal obesity/overweight) with body condition scoring (BCS).It is thin that BCS is classified as body less than 3 dog.Scheme according to the Hill mechanism animal care and the use council (Hill ' s Institutional Animal Care andUse Committee) is taken care of dog.50% dog is female (15 bodies is thin, and 15 overweight), and 50% dog is male (15 bodies is thin, and 15 overweight) in addition, to determine whether sex is playing effect aspect any sign difference.All animals are spay or castrating all, because the animal of these groups is more prone to take place obesity.Animal is weighed, provide the body condition scoring, extract blood sample.Results serum is deposited under-20 ° of C with the 1mL aliquot.

[0082] serum is carried out the analysis of chemistry screening, obesity mark, thyroid gland sign and arthritis sign.(Hill ' s Pet Nutrition Center, Topeka KS) carries out at Hill pet nutrition center in the chemistry screening.(Michigan StateUniversity, Lansing MI) carries out insulin analysis by the Michigan State University.Thyroxine, thyroid-stimulating hormone (TSH), glucagon albumen-1, insulin-like growth factor-i, ghrelin, leptin, angiotensin I and II, c-proteins C reactive, HDL1 and 2, low-density lipoprotein, very low density lipoprotein (VLDL), chylomicron, testosterone, estradiol, cortisol, osteocalcin, amino terminal crosslinking protein, II type cartilage is synthetic and the cartilage oligomeric analysis of protein by MD Biosciences, Inc. (St.Paul MN) carries out.

[0083] data are analyzed with general linear model (the General Linear Models) method (1989) of SAS, to determine to handle mean value.Experimental unit is a dog.Significant difference is then thought in P＜0.05 o'clock, and P＜0.10 o'clock then defines trend.

Table 2-1

The average measurement value of the thin and overweight dog of body

^*The not remarkable and P of NS=〉0.10

Table 2-2

The average measurement value of the thin and overweight dog of female gonosome

^*The not remarkable and P of NS=〉0.10

Table 2-3

The average measurement value of the thin and overweight dog of male body

^*The not remarkable and P of NS=〉0.10

[0084] the average body condition of thin group of overweight group and body is respectively 4.7 and 2.5.The average weight of thin group of body and overweight group is respectively 11.2 and 17.3kg.Serum has been carried out the analysis of chemical screening, obesity mark, thyroid gland sign and arthritis sign.Than thin group of body, overweight group of alkaline phosphatase (P=0.04), cholesterol (P=0.04), triglyceride (P=0.06), gross protein (P＜0.01), albumin (P＜0.01), thyroxine (P=0.05), calcium (P＜0.01), phosphorus (P=0.04), glucose (P＜0.01), insulin (P＜0.01), insulin-like growth factor-i (P＜0.01), low-density lipoprotein (P＜0.01), leptin (P＜0.01) and 2 type cartilages synthetic (P＜0.01) with higher level.Than thin group of body, overweight group of kreatinin (P=0.01), serum urea nitrogen (P＜0.01), chloride (P＜0.01), and overweight male testosterone (P=0.04) with reduced levels with reduced levels.

[0085] by progressively returning the analysis showed that these detailed biomarker datas carry out, body weight, glucose, sodium, chloride, c-proteins C reactive and thyroid-stimulating hormone (TSH) are the parameters of useful especially definite body condition scoring.For example, the body condition scoring can adopt following equation to carry out quantitatively: body condition scoring=3.62352+ (0.17443 x body weight (kg))+(0.01621 x glucose (mg/dL))+(0.06496 x sodium (mmol/L))-(0.12439 x chloride (mmol/L))-(0.05575 x c-proteins C reactive (ng/mL))+(1.72392 x thyroid-stimulating hormone (TSH) (ng/mL)).

[0086] in addition, the also available biomarker data that can obtain in routine veterinary is measured of body condition scoring carries out quantitatively.For example, by progressively returning the analysis showed that the level of biological marker is carried out, body weight of animal and urea nitrogen, sodium and muriatic serum levels are specially adapted to determine the body condition scoring.Therefore, the body condition scoring can be determined by described data are applied to following algorithm: body condition scoring=3.64120+ (0.18614 x body weight (kg))-(0.05289 x serum urea nitrogen (mg/dL))+(0.08935 x sodium (mmol/L))-(0.14088 x chloride (mmol/L)).

Embodiment 3

The biological marker level of dog in the loss of weight research

[0087] carries out loss of weight research with 20 dogs.Scheme according to the Hill mechanism animal care and the council of use is taken care of dog.All dogs have when beginning one's study greater than 37% body fat (accounting for TBW number percent), and continue to carry out loss of weight research 3 months.Each dog is assigned to (table 3-1) in two processed group.Every kind of food is all roughly ground (kibbled), dog nutrients guide preparation according to American feed control officials (Association of American Feed Control Officials), and make its equilibrium (balanced), keep demand to satisfy adult dog.All dogs all carry out dual intensity X line absorption determination method (DXA; DXA-QDR-4500, Hologic, Inc., Waltham, MA) scanning.The 0th, 1,2 with gathered blood sample in 3 months.Results serum is deposited under-20 ° of C with the 1mL aliquot.In addition, dog also obtains the toy (enrichment toy) that enriches one's life, accepts conventional reason hair, has an opportunity every day and other dogs and people are associated.

[0088] serum is carried out the analysis of chemistry screening, obesity mark, thyroid gland sign and arthritis sign.(Hill ' s Pet Nutrition Center, Topeka KS) carries out at Hill pet nutrition center in the chemistry screening.(Michigan StateUniversity, Lansing MI) carries out insulin analysis by the Michigan State University.Thyroxine, thyroid-stimulating hormone (TSH), glucagon albumen-1, insulin-like growth factor-i, ghrelin, leptin, angiotensin I and II, c-proteins C reactive, HDL1 and 2, low-density lipoprotein, very low density lipoprotein (VLDL), chylomicron, testosterone, estradiol, cortisol, osteocalcin, amino terminal crosslinking protein, 2 type cartilages are synthetic and the cartilage oligo-substrate protein analysis by MDBiosciences, Inc. (St.Paul MN) carries out.

Table 3-1

The nutrients of the dog food in the loss of weight research is formed

Nutrients is based on 100% dry food A ^*Food B ^*

Crude protein, % 25.6 24.9

Crude fat, % 8.6 7.9

Robust fibre, % 21.4 21.1

Ash content, % 5.6 5.1

Calcium, % 0.67 0.91

Phosphorus, % 0.54 0.64

Lysine, % 1.41 1.43

Methionine+cystine, % 0.73 0.79

Tryptophane, % 0.29 0.24

Threonine, % 0.91 0.90

Arginine, % 1.43 1.53

Isoleucine, % 0.83 1.05

Valine, % 1.23 1.26

Leucine, % 1.81 2.03

Histidine, % 0.72 0.57

Phenylalanine+tyrosine, % 1.70 1.64

Carnitine, ppm 300 300

But metabolisable energy, kcal/kg 2,992 2966

^*Food A=

Canid prescription meals ( Canine Prescription

), canned.Composition: water; the pork secondary product; the bean powder leftover bits and pieces; rice; pork liver; powdered cellulose; soy meal; chicken gizzard spices; vegetable oil; iron oxide; taurine; the L-carnitine; mineral matter (lime carbonate; Dicalcium Phosphate; salt; zinc paste; ferrous sulphate; copper sulphate; manganous oxide; calcium iodate; sodium selenite); beta carotene; vitamin (Choline Chloride; the cholecalciferol fill-in; the vitamin E fill-in; ascorbic acid; thiamine mononitrate; nicotinic acid; calcium pantothenate; pyridoxine hydrochloride; lactochrome; folic acid; biotin; the cobalamin fill-in).

^*Food Canid prescription meals (

Canine Prescription

), drying.Composition: corn flour; peanut shell 28.2% (fiber source); chicken secondary product powder; soy meal; the bean powder leftover bits and pieces; chicken gizzard spices; dry egg product; vegetable oil; taurine; the L-carnitine (is used BHT; BHA and ethoxyquin are anticorrosion); mineral matter (salt; ferrous sulphate; zinc paste; copper sulphate; manganous oxide; calcium iodate; sodium selenite); beta carotene; vitamin (Choline Chloride; the vitamin A fill-in; the cholecalciferol fill-in; the vitamin E fill-in; L-ascorbic acid-2-polyphosphate (vitamin C source); nicotinic acid; thiamine mononitrate; calcium pantothenate; pyridoxine hydrochloride; lactochrome; folic acid; biotin; the cobalamin fill-in).

[0089] result shows, the dog of fed food A was compared during with the 0th day in the time of the 90th day, and significant loss of weight (4924g is arranged; P＜0.01), the thin loss of body (lean loss) (721g; P＜0.01) and fat loss (4167g; P＜0.01).The dog of fed food B was compared during with the 0th day in the time of the 90th day, and significant loss of weight (3466g is arranged; P＜0.01) and fat loss (3363g; P＜0.01).The dog of fed food B does not observe in the difference of body aspect thin.Referring to table 3-2.

[0090] serum chemistry screening and electrolyte provide in table 3-3.The dog of fed food A is at globulin (P＜0.01), gross protein (P＜0.01), alkaline phosphatase (P=0.03), alanine aminotransferase (P=0.02), albumin (P＜0.01), cholesterol (P＜0.01), triglyceride (P＜0.01), phosphorus (P＜0.01), sodium (P＜0.01), sodium: descend increase aspect calcium (P=0.02), potassium (P=0.05) and chloride (P＜0.01) aspect the potassium (P=0.02).The dog of fed food B is at albumin (P＜0.01), gross protein (P＜0.01), cholesterol (P＜0.01), sodium (P＜0.01), sodium: descend increase aspect calcium (P＜0.01), chloride (P＜0.01), potassium (P＜0.01), magnesium (P＜0.01) and serum urea nitrogen (P=0.03) aspect the potassium (P＜0.01).See table 3-2 and 3-3.

Health after the table 3-2. dog consumption loss of weight food is formed

The body parameter food A food B that measures

Body weight the 0th day, g 17,569 17257

Body weight the 30th day, g 15,394 15798

Body weight the 60th day, g 13,970 14715

Body weight the 90th day, g 12,645 13791

Body weight change 0-30 days, g-2304-1459

Body weight change 0-60 days, g-3728-2542

Body weight change 0-90 days, g-4924-3466

Compared with the 30th day in the 0th day ^*＜0.01＜0.01

Compared with the 60th day in the 0th day ^*＜0.01＜0.01

Compared with the 90th day in the 0th day ^*＜0.01＜0.01

Thin the 0th day of body, g 9,678 9434

Thin the 30th day of body, g 9,093 9295

Thin the 60th day of body, g 9,059 9303

Thin the 90th day of body, g 8,961 9367

The thin variation of body 0-30 days, g-585-139

The thin variation of body 0-60 days, g-619-131

The thin variation of body 0-90 days, g-721-67

Compared with the 30th day in the 0th day ^*＜0.01 NS

Compared with the 60th day in the 0th day ^*＜0.01 NS

Compared with the 90th day in the 0th day ^*＜0.01 NS

Fat the 0th day, g 7,411 7343

Fat the 30th day, g 5,830 6028

Fat the 60th day, g 4,455 4952

Fat the 90th day, g 3,244 3979

Fat variation 0-30 days, g-1705-1314

Fat variation 0-60 days, g-3081-2390

Fat variation 0-90 days, g-4167-3363

Compared with the 30th day in the 0th day ^*＜0.01＜0.01

Compared with the 60th day in the 0th day ^*＜0.01＜0.01

Compared with the 90th day in the 0th day ^*＜0.01＜0.01

^*The probability of bigger F value

Blood chemistry screening and the sign of table 3-3. dog consumption loss of weight food after 90 days

[0091] research disclosed herein purpose is to determine that dog that body is thin and overweight dog are variant on what biological marker.Be tested and appraised the biological marker difference between body lean animals and the overweight animal, animal doctors' quantitatively body condition analysis clearly, and can also diagnose body weight situation or its tendency and diagnosis obesity correlativity health disorders or its tendency.Animal doctors can utilize these signs by blood analysis and lose weight and manage loss of weight health scheme.

[0092] as described in the embodiment 2, overweight group glucose, insulin, insulin-like growth factor-i and glucagon albumen-1 level raise, the sign of this hint insulin resistance.These results are not unexpected, because diabetes and insulin resistance usually follow obesity to occur.The dog that the data presentation of embodiment 3 has experienced loss of weight is being reduced aspect glucose and the insulin, and this shows that loss of weight can correct obesity correlativity glucose imbalance.

[0093] level of overweight its triglyceride of dog, cholesterol, low-density lipoprotein, chylomicron raises, and the level of high-density lipoprotein (HDL)-1 descends, and these indexs are common signs of dyslipidemia.With studies have shown that dog carries out, dyslipidemia is often relevant with insulin resistance.Insulin resistance plays an important role in the development of hyperlipidemia.The increase of blood triglyceride concentration is by due to the minimizing of the increase of the generation of the lipoprotein that is rich in triglyceride and their metabolism.Insulin action unusually can be by due to the increase of lipolysis in the adipocyte, lipolysis can cause fatty acid discharge to increase and fatty acid is refilled at liver and is made into triglyceride.

[0094] in embodiment 3, its cholesterol of dog and the triglyceride that carry out the loss of weight scheme descend, and this sign that shows dyslipidemia can be corrected by food and loss of weight.This canid loss of weight research with other announcements is consistent.Die etc., " Evolution of blood parametersduring weight loss in experimental obese beagle dogs (testing the differentiation of blood parameters in the fat beagle loss of weight process) " J.Anim.Physiol, a.Anim.Nutr.2004; 88:166-171 in the loss of weight scheme of overweight beagle to them feed high protein (47.5% protein and 10.9% robust fibre) or high fiber (23.8% protein and 23.3% robust fibre) meals.Any dog that they observe the two kinds of loss of weight foods of feeding has all reduced triglyceride and cholesterol, and these variation and meals that show that these observe are uncorrelated, but directly related with loss of weight.Being reduced with triglyceride that observes that loss of weight caused Diez etc. and cholesterol by this research, is the thing that can be measured in daily chemistry screening by the animal doctor.Measuring cholesterol and triglyceride and monitoring loss of weight situation for the obesity problem, may be a way the key of obesity being discussed and don't offending pet owners.What emphatically point out is, in the research and this research of Diez etc., the triglyceride of rising and cholesterol are all in the dog value range of normal announcement.Therefore, seeking unusual high triglyceride and cholesterol value may not be the good index of obesity, should keep a close eye on the elevated levels in the normal range more.

[0095] surpasses also raising on the level that is binned in the arthritis sign, although they do not show any arthritis sign (promptly walking lamely).Though arthritis signs all in overweight group all raise, it is significant on the statistics having only alkaline phosphatase and II type cartilage synthetic.The synthetic increase of alkaline phosphatase and II type cartilage can be used as the early stage index of osteoarthritis in the overweight dog.When dog suffered from bone, bile duct and/or liver diseases, alkaline phosphatase can raise usually.The alkaline phosphatase that raises in this research is relevant with bone probably, because there is not difference between two groups on alanine aminotransferase, and overweight group albumin is higher, has therefore got rid of any potential liver diseases.

[0096] when the cartilage infringement occurring, II type cartilage is synthetic can be increased usually.Cartilage matrix is made up of II type cartilage and these two kinds of principal ingredients of aggrecan (aggrecan, a kind of proteoglycans).The chondrigen fiber provides the pulling strengrth that helps keep tissue integrity.Aggrecan and chondrigen fiber interweaving are made contributions to cartilage matrix compression stiffness together.The infringement of II type cartilage and the loss of aggrecan are the essential characteristics of cartilage lesion in the osteoarthritis.Proteolytic enzyme with this infringement and cartilage cell and synovial cell's secretion associates.Matrix metalloproteinase family (being MMP-13) is responsible for the one-level cutting of the triple helix of II type cartilage.In embodiment 3, its alkaline phosphatase of dog of experience loss of weight reduces, and this shows that the management obesity can help/prevent arthritic initial.Because these foods do not add the thing in useful joint and reduce/treatment of arthritis (being n-3 fatty acid, aminoglucose and/or chondroitin), obviously are that loss of weight has reduced the alkaline phosphatase enzyme level separately.This may be because just reduced the result who is applied to the load on the joint when animal reduces body weight.Therefore, this paper also is susceptible to, and the level that arthritis biological marker such as alkaline phosphatase and II type cartilage are synthetic can be used as the tendency that biological marker is predicted animal generation osteoarthritis.

[0097] in embodiment 2 and 3, also measured leptin, ghrelin and GLP-1 concentration because known they appetite suppressed and stimulate influential.Overweight group leptin level raises, and the ghrelin level is lower simultaneously.These results and Jeusette et al., " Influence of obesity on plasma lipid and lipoprotein concentrations indogs (obesity is to the influence of dog plasma lipid and lipoprotein concentration) " Am.J.Vet.Res.2005; 66:81-86 and Sagawa et al., " Correlation between plasma leptinconcentration and body fat content in dogs (correlativity between dog plasma leptin concentration and the body fat content) " Am.J.Vet.Res.2002; 63 (1): 7-10 is consistent.In these two researchs, the leptin concentration of overweight beagle is directly related with the body fat quality.In this research, leptin concentration reduces along with the minimizing of fat mass in the loss of weight process.Jeusette etc. also observe ghrelin density loss in overweight dog, and think because the result that the excess energy storage causes ghrelin to be reduced.As disclosed herein, as if when dog is fed dry food the ghrelin level be not subjected to the influence of loss of weight.But ghrelin has increased really when dog is fed the canned foods that loss of weight uses.This may be because take in the result that more canned products causes enteron aisle plumpness (gut fill) to increase.GLP-1 flows to from stomach and also plays effect aspect the small intestine controlling nutrients the inhibiting effect of stomach and intestine transmission and gastric emptying by it.This GLP-1 mechanism it is believed that and can apply its effect to appetite.Overweight dog is compared the GLP-1 level to be increased with the thin dog of body.These results show that these hormones may be in the absorption of attempting to reduce overweight dog group; But they are not initiated the effect of taking in.

[0098] result of these researchs shows, obesity is directly related with the other diseases state of dog.The sign of embodiment 2 shows that overweight dog has shown the early stage sign of dyslipidemia, arthritis and diabetes.Many these differences of embodiment 3 proofs can alleviate by loss of weight.

Embodiment 4

The prediction of cat body weight situation

[0099] determined that thin and 30 the overweight cats of 30 bodies carry out this researchs.For the purpose of this research, be that 4 or 5 cat is classified as obesity/overweight (scoring yardstick is 1-5, and wherein 1 equals slight of stature, and 5 equal obesity) with body condition scoring (BCS).It is thin that BCS is classified as body less than 3 cat.Animal is weighed, provide the body condition scoring, extract blood sample.Results serum is deposited under-20 ℃ with the 1mL aliquot.

[00100] serum is carried out the analysis of chemistry screening, obesity mark, thyroid gland sign and arthritis sign.(Hill ' s Pet NutritionCenter, Topeka KS) carries out at Hill pet nutrition center in the chemistry screening.(MichiganState University, Lansing MI) carries out insulin analysis by the Michigan State University.Thyroxine, thyroid-stimulating hormone (TSH), ghrelin, leptin, angiotensin I and II, osteocalcin, amino terminal crosslinking protein, bone specificity alkaline phosphatase and carboxyl terminal cross-linked side peptide analysis are by MD Biosciences, Inc. (St.Paul MN) carries out.

[00101] data are analyzed with general linear model (the General Linear Models) method (1989) of SAS, to determine to handle mean value.Experimental unit is a cat.Significant difference is then thought in P＜0.05 o'clock, and P＜0.10 o'clock then defines trend.

Table 4-1

The average measurement value of the cat that the body lean and fat is fat

^*The not remarkable and P of NS=〉0.10

[00102] the average body condition of thin group of overweight group and body is respectively 4.2 and 2.5.The average weight that overweight group and body are thin group is respectively 5.8 ± 0.2 and 3.2 ± 0.2kg.Serum has been carried out the analysis of chemical screening, obesity mark, thyroid gland sign and arthritis sign.Overweight group of alkaline phosphatase (P=0.07), triglyceride (P=0.05), gross protein (P＜0.01), albumin (P＜0.01), potassium (P=0.03), magnesium (P＜0.01), sodium: potassium (P=0.02), glucose (P=0.02), leptin (P＜0.01) and thyroxine (P=0.02) with higher level.Overweight group of thyroid-stimulating hormone (TSH) (P=0.02) and ghrelin (P=0.06) with reduced levels.

[00103] by progressively returning the analysis showed that these detailed biomarker datas carry out, the serum levels of body weight and sodium, potassium, chloride, phosphorus, cholerythrin and ghrelin is the parameter of the body condition scoring (being the body weight situation) of useful especially quantitative cat.For example, the body condition scoring can adopt following equation to carry out quantitatively:

The body condition scoring=-3.20078+ (0.4259 x body weight (kg))-(0.05508 x sodium (mmol/L))+(0.69884 x potassium (mmol/L))+(0.09472 x chloride (mmol/L))-(0.15372 x phosphorus (mg/dL))+(1.31580 x total bilirubin (mg/dX))-(0.35136 x ghrelin (ng/mL)).

[00104] in addition, obtainable biomarker data carried out quantitatively during the also available routine veterinary of body condition scoring was measured.For example, by progressively returning to the analysis showed that the level of biological marker is carried out body weight and blood urea nitrogen (BUN): kreatinin, potassium, chloride, phosphorus and bilirubinic serum levels are specially adapted to determine the body condition scoring of cat.Therefore, the body condition scoring can be determined by described data are applied to following algorithm:

The body condition scoring=-7.34191+ (0.48335 x body weight (kg))+(0.03578 x blood urea nitrogen: kreatinin)+(0.58860 x potassium (mmol/L))+(0.04683 x chloride (mmol/L))-(0.16894 x phosphorus (mg/dL))+(0.86613 x total bilirubin (mg/dL)).

[00105] disclosed in this manual is the typical preferred embodiment of the present invention, though adopted specific term, but they are just with general using with unrestriced meaning rather than using for the restriction purpose, so scope of the present invention is illustrated by following claims.Obviously, according to above instruction, might make many modifications and variations of the present invention.Therefore it should be understood that the present invention except that can implementing by concrete description, can also otherwise implement within the scope of the appended claims.

Claims (38)

1. the method for the tendency of the body weight situation of diagnosing animal or body weight situation, described method comprises the observation level of mensuration from tissue or at least a biological marker in the biologicfluid sample of this animal, and should the observation level and the reference levels of this biological marker compare; Wherein with respect to the observation level of reference levels individually or jointly indication body weight condition or tendency.

2. the process of claim 1 wherein that described animal is canid or cats.

3. the process of claim 1 wherein that described animal is the most about one-year-old, indicate the tendency of the body weight situation of this animal in the life-span afterwards with respect to the observation level of reference levels individually or jointly.

4. the process of claim 1 wherein that described situation or tendency are the obesity or the tendentiousness of putting on weight.

5. the process of claim 1 wherein that described situation or tendency increase the off the hinges risk of obesity correlativity of this animal.

6. the method for claim 5, wherein said obesity correlativity health disorders is selected from hyperlipidemia, dyslipidemia, insulin resistance, glucose does not tolerate, liver lipidosis, complication of anesthesia, adrenal cortex function is hyperfunction, hypothyroidism, diabetes, insulinoma, chromophobe adenoma of pituitary, hypopituitarism, damage of hypothalamus, the joint compressing, musculoskeletal pain, expiratory dyspnea, hypertension, difficult labour, motion does not tolerate, heat does not tolerate, immunologic function descends, degeneration joint and plastic surgery disease, angiocardiopathy, overstretched, respiratory distress, change in renal function, pancreatitis, transitional cell carcinoma, tired, sleep-disorder, dysgenesia and their combination.

7. the process of claim 1 wherein that described biological marker is selected from glucose, GLP-1, ghrelin, c-proteins C reactive, thyroid-stimulating hormone (TSH) and their combination.

8. the process of claim 1 wherein the mensuration of at least two biological markers being observed level.

9. the process of claim 1 wherein that described tissue or biologicfluid sample obtain under animal is in fasting state.

10. the process of claim 1 wherein that described tissue or biologicfluid sample are that a plurality of time points in the cycle of feeding obtain, comprise at least one time point and at least one time point after the meal before the meal.

11. the process of claim 1 wherein that described tissue or biofluid are whole blood, blood plasma or serum.

12. the process of claim 1 wherein that the gentle reference levels of described observation water are independently to be selected from following determination method with one or more to measure: enzyme immunoassay (EIA), enzyme linked immunosorbent assay (ELISA), immunofluorescence assay, radiommunoassay, Western blotting mensuration, biochemical measurement, enzymatic determination and colorimetric estimation.

13. the method for claim 1, wherein (a) described animal is a canid, (b) described biological marker comprises the glucose in the serum, (c) to adjust reference levels than the body weight of the canid of normal type low at least about 10% the time when the observation body weight in the fasting animal is adjusted serum level of glucose, then diagnoses this animal that the tendency of putting on weight is arranged.

14. the method for claim 1, wherein (a) described animal is a canid, (b) described biological marker comprises the GLP-1 in the serum, (c) to adjust reference levels than the body weight of the canid of normal type low at least about 20% the time when the observation body weight in the fasting animal is adjusted serum GLP-1 level, then diagnoses this animal that the tendency of putting on weight is arranged.

15. the method for claim 1, wherein (a) described animal is a canid, (b) described biological marker comprises the ghrelin in the serum, (c) to adjust reference levels than the body weight of the canid of normal type low at least about 20% the time when the observation body weight in the fasting animal is adjusted serum ghrelin level, then diagnoses this animal that the tendency of putting on weight is arranged.

16. method of selecting the health scheme for animal, described method comprises that (a) is by measuring the observation level from tissue or at least a biological marker in the biologicfluid sample of this animal, and should the observation level and the reference levels of this biological marker compare, diagnose body weight situation or tendency; Wherein with respect to the observation level of reference levels individually or jointly indication body weight condition or tendency; (b) determine this body weight situation that is suitable for being diagnosed out or the health scheme of tendency.

17. the method for claim 16, wherein said health scheme comprise the composition for this animal consumption.

18. the method for claim 16, wherein said health scheme comprises the exercising pattern at this animal.

19. one kind is detected the body weight situation of animal or the initial method of tendency, described method is included at least a biological marker of this animal of monitoring in a period of time, way is to get a plurality of time points all to measure observation level from tissue or this biological marker in the biologicfluid sample of this animal in this time period when each time point, and should the observation level and the reference levels of this biological marker compare; If wherein, then detect initial at any time with respect to the observation level of reference levels individually or jointly indication body weight condition or tendency.

20. the method for claim 19, described method also comprise by being selected from the body weight of following technical monitoring animal: weigh, assessment, morphometry art and their combination of the assessment of relative body weight, body condition scoring.

21. the method for the effect of the body weight situation of assessing health project management animal or tendency, described method is included at least a biological marker of this animal of interior monitoring of time period of this health scheme of execution, way is to get a plurality of time points all to measure observation level from tissue or this biological marker in the biologicfluid sample of this animal in this time period when each time point, and should the observation level and the reference levels of this biological marker compare; Wherein indicate the effect of this health project management body weight situation or tendency individually or jointly with respect to the observation level of reference levels.

22. a kit, described kit comprises:

(a) one or more are in order to detect the reagent from the observation level of the tissue of animal or at least a biological marker in the biologicfluid sample; With

(b) one or more users that carry information can use media, and described information comprises the reference levels of (i) this biological marker; (ii) should the observation level and the algorithm that compares of this reference levels; Wherein indicate body weight situation or the tendency of this animal individually or jointly with respect to the observation level of reference levels.

23. the kit of claim 22, wherein said one or more reagent comprise at least a report part or mark.

24. the kit of claim 22, wherein said one or more reagent comprise at least a antibody.

25. the kit of claim 22, described kit also comprise in order to the instrument that conveys a message, described information comprise following one or more: (a) by with respect to the indicated body weight situation of the observation level of reference levels or the diagnosis of tendency; (b) the health scheme that is fit to this diagnosis of suggestion or regulation.

26. method of diagnosing the off the hinges tendency of obesity correlativity of animal, described method comprises the observation level of mensuration from tissue or at least a biological marker in the biologicfluid sample of this animal, and should the observation level and the reference levels of this biological marker compare; Wherein indicate described tendency individually or jointly with respect to the observation level of reference levels.

27. the method for claim 26, wherein said animal are canid or cats.

28. the method for claim 26, wherein said animal is the most about one-year-old, indicates the tendency of the body weight situation of this animal in the life-span afterwards individually or jointly with respect to the observation level of reference levels.

29. the method for claim 26, wherein said obesity correlativity health disorders is selected from hyperlipidemia, dyslipidemia, insulin resistance, glucose does not tolerate, liver lipidosis, complication of anesthesia, adrenal cortex function is hyperfunction, hypothyroidism, diabetes, insulinoma, chromophobe adenoma of pituitary, hypopituitarism, damage of hypothalamus, the joint compressing, musculoskeletal pain, expiratory dyspnea, hypertension, difficult labour, motion does not tolerate, heat does not tolerate, immunologic function descends, degeneration joint and plastic surgery disease, angiocardiopathy, overstretched, respiratory distress, change in renal function, pancreatitis, transitional cell carcinoma, tired, sleep-disorder, dysgenesia and their combination.

30. the method for claim 26, wherein said biological marker are selected from glucose, GLP-1, ghrelin, c-proteins C reactive, thyroid-stimulating hormone (TSH) and their combination.

31. the method for claim 26 is wherein observed the mensuration of level at least two biological markers.

32. the method for claim 26, wherein said tissue or biologicfluid sample obtain under animal is in fasting state.

Obtain 33. the method for claim 26, wherein said tissue or biologicfluid sample are a plurality of time points in the cycle of feeding, comprise at least one time point and at least one time point after the meal before the meal.

34. the method for claim 26, wherein said tissue or biofluid are whole blood, blood plasma or serum.

35. the method for claim 26, the gentle reference levels of wherein said observation water are independently to be selected from following determination method with one or more to measure: enzyme immunoassay (EIA), enzyme linked immunosorbent assay (ELISA), immunofluorescence assay, radiommunoassay, Western blotting mensuration, biochemical measurement, enzymatic determination and colorimetric estimation.

36. the method for claim 26, wherein said overweight correlativity health disorders is an osteoarthritis.

37. the method for claim 26, wherein said biological marker is an alkaline phosphatase.

38. the method for the body condition of a quantitative animal scoring, described method comprise that (a) analyzes the body weight of described animal and the serum levels of at least a biological marker; (b) the described data that step (a) is obtained are applied to any one among the algorithm I-IV of the present invention.