Diagnostic approach to polydipsia and polyuria

A variety of metabolic disturbances account for the majority of cases of polydipsia and polyuria. This chapter presents guides to differential diagnosis as well as a discussion of the etiology and clinical features of the primary causes--central diabetes insipidus, nephrogenic diabetes insipidus, and psychogenic polydipsia.     

Evaluation of a modified water-deprivation test for diagnosis of polyuric disorders in dogs.

A modified water-deprivation test was performed on 12 polyuric and 4 clinically normal dogs. Immediately after maximal urine osmolality had been achieved with water deprivation, antidiuretic hormone was injected to test further renal concentrating ability. The test provided accurate diagnosis of severe hypothalamic-neurohypophyseal diabetes insipidus in 3 dogs, partial diabetes insipidus in 2 dogs, and primary (psychogenic) polydipsia in 2 dogs. Five polyuric dogs with hyperadreno corticism had a response to the modified water-deprivation test similar to that of dogs with partial diabetes indipidus.     

Serum fructosamine measurement: a new diagnostic approach to renal glucosuria in dogs

Measurement of serum fructosamine, 1-amino-1-deoxyfructose, is commonly used in diagnosing and monitoring hyperglycaemic disorders, such as diabetes mellitus in dogs. Serum fructosamine indicates long-term serum glucose concentrations and replaces serial serum glucose measurements. This study investigates the clinical usefulness of serum fructosamine in differentiating conditions other than diabetes mellitus characterised by glucosuria. Four dogs presented with glucosuria all had serum fructosamine concentrations within or close to the reference range (313 micromol 1(-1), 291 micromol 1(-1), 348 micromol 1(-1), 262 micromol 1(-1) reference range: 250 to 320 micromol 1(-1) indicating that a single serum fructosamine measurement is a simple and efficient way of verifying concurrent persistent normoglycaemia. Therefore, serum fructosamine is a useful parameter not only in diabetic patients, bu also in differentiating conditions in dogs characterised by glucosuria without hyperglycaemia, such as primary renal glucosuria and the Fanconi syndrome. To distinguish between primary renal glucosuria and the Fanconi syndrome, measurement of the amino acid concentration in urine was performed.     

Dysautonomia and autonomic neuropathies.

The autonomic nervous system can be affected as part of a more diffuse peripheral nerve disease such as inflammatory polyneuropathy or diabetes, or as a primary disease, such as dysautonomia. Dysautonomia is being diagnosed with increasing frequency in dogs and other species in the Midwest. Affected animals present with absence of parasympathetic and autonomic ganglia and brainstem nuclei degenerate with minimal inflammation. The cause is unknown and treatment symptomatic.     

The role of vasopressin in dogs with polyuria

Polyuria and polydipsia (PUPD) occur frequently in dogs and may be caused by a variety of endocrine, metabolic, and renal disturbances. The studies described in this PhD Thesis, which was defended in January 2004 in Utrecht, investigated the role of the antidiuretic hormone vasopressin (VP) in the pathogenesis of different forms of canine polyuria. Experiments in healthy dogs demonstrated that the ranges of urine specific gravity and urine osmolality are much larger than previously thought. A water deprivation test is not required in all polyuric dogs, because serial measurements of urine osmolality may already lead to the diagnosis of primary polydipsia, in some cases. In dogs with primary polydipsia a wide variation in VP responses to hypertonic stimulation can be found, including a hyperresponse, a hyporesponse, and a non-linear response. The significance of the VP response to hypertonic saline infusion as the 'gold standard' for a diagnosis of canine polyuria is discussed. In the dog, VP is secreted in a pulsatile fashion with a wide variation in the number of VP pulses, VP pulse duration, and VP pulse amplitude and height. The occurrence of spontaneous VP pulses may severely hamper the interpretation of the curve describing the relationship between plasma osmolality and plasma VP concentration during osmotic stimulation. A radioimmunoassay to measure the VP-dependent water channel aquaporin-2 (AQP2) in urine was developed in dogs. In healthy dogs, urinary AQP2 excretion closely reflects changes in collecting duct exposure to VP. Measurement of urinary AQP2 excretion in polyuric dogs may be helpful to distinguish between central diabetes insipidus, nephrogenic diabetes insipidus, and primary polydipsia.     

Stress hyperglycemia in cats

It may be difficult to differentiate the possible causes of hyperglycemia in the cat. The following investigation was on transient hyperglycemia in 320 cats. The frequency and degree of stress-hyperglycemia and its relation to different types of primary diseases was proven. Animals with overt diabetes mellitus or pancreatic diseases were not included in this study. Plasma glucose was analyzed with the o-Toluidine- or with the glucose oxidase-method. Plasma immune-reactive insulin (IRI) was estimated by RIA. A glucose concentration of greater than or equal to 140 mg/dl (7.77 mmol/l) in the fasted animal was defined as hyperglycemia. The results of the retrospective investigation show in cats transient hyperglycemia occurs more often (3.2%) than permanent hyperglycemia (0.57%). Contrary to overt diabetes mellitus there is no sex- or age-related predisposition. Glucose values above 300 mg/dl (16.65 mmol/l) with maximal values up to 620 mg/dl (34.42 mmol/l) were estimated in 12% of the animals. In 12 from 19 hyperglycemic animals the basal IRI values were between 4 and 14 microU/ml, 11 animals had a lowered I/G ratio. In the following order of frequency the primary diseases found in combination with transient hyperglycemia were: dys- and stranguria, viral and bacterial infections, gastrointestinal diseases, neoplasia, renal insufficiency, cardiopathies etc. With improvement of the underlying disturbance the stress-related hyperglycemia normalized without insulin therapy within a few days. In conclusion, it is necessary to initially identify basic diseases that may trigger the onset of stress-hyperglycemia in the cat. Neither the extent of the glucose level nor a single plasma-insulin-value are valid indicators of confirming the diagnosis of diabetes mellitus.(ABSTRACT TRUNCATED AT 250 WORDS)     

Vasopressin response to osmotic stimulation in 18 young dogs with polyuria and polydipsia

Common disorders of water homeostasis leading to polyuria include a variety of endocrine, metabolic, and renal disturbances. After exclusion of most of these conditions, the diagnostic dilemma of differentiating between central diabetes insipidus, primary polydipsia, and nephrogenic diabetes insipidus may remain. Here, we report on 18 young dogs with polyuria that had been present in most cases since the dogs were puppies. The conditions were categorized according to the plasma vasopressin (VP) response to hypertonicity. The VP response to osmotic stimulation was tested by IV infusion of 20% NaCl for 2 hours. The VP response in all dogs was abnormal. Three categories could be distinguished: an exaggerated response (n = 3), a subnormal response (n = 4), and a nonlinear response with high plasma VP concentrations unrelated to increases in plasma osmolality (n = 11). The VP response to hypertonicity did not consistently distinguish among different clinical entities. In the 9 dogs with variations in urine osmolality compatible with primary polydipsia, exaggerated, subnormal, and nonlinear responses were observed. Examination of the present data questions the generally accepted notion that VP measurements during hypertonic saline infusion are the "gold standard" for the diagnostic interpretation of causes of polydipsia and polyuria. Studies of the peripheral reflection in plasma of the pulsatile VP release in healthy and polyuric individuals, with and without osmotic provocation, should be performed.     

Presumed primary immune-mediated thrombocytopenia in four cats

Feline primary immune-mediated thrombocytopenia (pIMT) is a rare hematological disorder. Platelet-bound antibody assays for cats have variable specificity and sensitivity and are not widely available. Diagnosis of pIMT is made on the basis of exclusion of other identifiable causes of thrombocytopenia and the response to immunosuppressive therapy. This report describes four cats with severe thrombocytopenia and no detectable underlying disease. One cat was euthanased because of pulmonary hemorrhage, while the other cats had frequent relapses, two of these cats developed diabetes mellitus due to long-term corticosteroid therapy. In these cats IMT had a chronic course and responded poorly to therapy with prednisolone. Alternative immunomodulatory drugs may be considered in the treatment of feline IMT.     

内质网应激偶联炎性反应研究进展

内质网是真核细胞蛋白合成和折叠的主要细胞器,当内质网内蛋白合成或折叠负担增加,引起未折叠或错误折叠蛋白增多时,可激活内质网几条特定信号通路,启动未折叠蛋白反应,这对维持细胞稳态有重要意义。越来越多研究表明,多种炎性反应疾病与内质网应激有密切联系。一方面,内质网应激引起的未折叠蛋白反应可以诱发或者抑制炎症,另一方面,炎性反应也能影响蛋白折叠,从而促进或缓解内质网应激。2型糖尿病、肿瘤和动脉粥样硬化等多种重大疾病的病理机制都涉及内质网应激与炎性反应的相互作用,对该问题的深入研究不仅能加深人们对这些疾病发病机制的理解,也有助于相关药物的研发。     

Water transport in the kidney and nephrogenic diabetes insipidus

Nephrogenic diabetes insipidus is caused by an inability of the kidney to concentrate urine despite adequate concentration of vasopressin in blood and is characterized by polyuria, polydipsia, and hyposthenuria in the presence of plasma hyperosmolality. Nephrogenic diabetes insipidus is the result of defects in water homeostasis in the kidney. Nephrogenic diabetes insipidus occurs when the kidneys cannot or do not respond to vasopressin. There are 2 categories of nephrogenic diabetes insipidus. Congenital nephrogenic diabetes insipidus is a rare, inherited, irreversible cause of polyuria and polydipsia in humans that is even rarer in animals. Acquired nephrogenic diabetes insipidus is more common and is often secondary to illness or medication that interferes with the action of vasopressin in the renal tubules. Unlike congenital nephrogenic diabetes insipidus, acquired or secondary nephrogenic diabetes insipidus is often reversible with correction of the associated or causative problem.     

Novel diabetes mellitus treatment: mature canine insulin production by canine striated muscle through gene therapy

Muscle-targeted gene therapy using insulin genes has the potential to provide an inexpensive, low maintenance alternative or adjunctive treatment method for canine diabetes mellitus. A canine skeletal muscle cell line was established through primary culture, as well as through transdifferentiation of canine fibroblasts after infection with a myo-differentiation gene containing adenovirus vector. A novel mutant furin-cleavable canine preproinsulin gene insert (cppI4) was designed and created through de novo gene synthesis. Various cell lines, including the generated canine muscle cell line, were transfected with nonviral plasmids containing cppI4. Insulin and desmin immunostaining were used to prove insulin production by muscle cells and specific canine insulin ELISA to prove mature insulin secretion into the medium. The canine myoblast cultures proved positive on desmin immunostaining. All cells tolerated transfection with cppI4-containing plasmid, and double immunostaining for insulin and desmin proved present in the canine cells. Canine insulin ELISA assessment of medium of cppI4-transfected murine myoblasts and canine myoblast and fibroblast mixture proved presence of mature fully processed canine insulin, 24 and 48 h after transfection. The present study provides proof of principle that canine muscle cells can be induced to produce and secrete canine insulin on transfection with nonviral plasmid DNA containing a novel mutant canine preproinsulin gene that produces furin-cleavable canine preproinsulin. This technology could be developed to provide an alternative canine diabetes mellitus treatment option or to provide a constant source for background insulin, as well as C-peptide, alongside current treatment options.     

Immunofluorescence studies of renal basement membranes in dogs with spontaneous diabetes

Renal tissue from 12 dogs with spontaneous diabetes and 16 control dogs were studied by light, immunofluorescence, and electron microscopies. Significant linear staining for immunoglobulin G and albumin were observed in the glomerular and tubular basement membranes of dogs with spontaneous diabetes--similar to that observed in human diabetes. On immunohistochemical grounds, it would appear that the dog with spontaneous diabetes is an appropriate model of diabetes in persons.     

Autoantibodies to pancreatic islet cells in canine diabetes mellitus

Indirect immunofluorescence on normal canine pancreatic tissue fixed in Bouin's solution was used to detect islet cell antibodies in dogs with diabetes mellitus, other endocrine diseases, and pancreatitis. 18 of 25 dogs with diabetes mellitus alone, 2 of 8 dogs with diabetes mellitus and concurrent pancreatitis, and 2 of 2 dogs with diabetes mellitus and concurrent pancreatic exocrine insufficiency were positive for autoantibody. 2 of 12 dogs with hypoadrenocorticism, 3 of 6 dogs with hyperadrenocorticism, 6 of 28 dogs with hypothyroidism and one of 19 dogs with pancreatitis alone were also antibody positive. None of 20 healthy dogs or 20 dogs with disorders other than those of the pancreas or endocrine organs were antibody positive. Islet cell antibodies were demonstrated in dogs with diabetes mellitus and other endocrine disorders. The possibility of autoimmune involvement in the development of diabetes mellitus in the dog should be considered.     

Current understanding of feline diabetes: part 1, pathogenesis

Type-1 diabetes, resulting from immune-mediated destruction of beta cells, appears to be rare in cats. Type-2 diabetes, characterised by inadequate insulin secretion and impaired insulin action, is the most common form of diabetes in cats. Other specific forms of diabetes constitute a substantial minority of cases. The most common is pancreatic destruction from pancreatic adenocarcinoma. Less frequent causes are insulin resistance from other endocrinopathies including acromegaly. Diabetes in cats is characterised by variable loss of insulin secretory capacity and insulin resistance. Glucose toxicity, islet amyloid-deposition, and pancreatitis contribute to further loss of beta cells and failure of insulin secretion. A significant number of cats undergo remission of their diabetes, usually 1-3 months after good glycaemic control is instituted. Obesity, old age, and Burmese breed are recognised risk factors for the development of diabetes in cats.     

蜂产品抗氧化糖尿病治本新证

以中医平衡医学的理论为指导,以蜂蜜、蜂皇浆、蜂胶、蜂花粉等蜂产品配制的“蜂宝康”对糖尿病患者进行治疗和调理,取得了意想不到的效果。近十年来,太泉蜂疗保健康复中心,在治疗、调理数百计的糖尿病患者的过程中,细心观察病情,反复探索病因,不断研究用“药”效果,终于积累了详实可靠的资料,找到了攻克糖尿病的途径,并提出了糖尿病治本新证,糖尿病并不是永远无法痊愈的终身病,天然、绿色的蜂产品完全可以对糖尿病进行有效的标本兼治,以期收到理想的效果,特提出以下理论供同道们参鉴。、     

Diabetes mellitus in elkhounds is associated with diestrus and pregnancy

Background: Female Elkhounds are shown to be at increased risk for diabetes mellitus, and occurrence of diabetes during pregnancy has been described in several cases. Hypothesis: Onset of diabetes mellitus in Elkhounds is associated with diestrus. Animals: Sixty‐three Elkhounds with diabetes mellitus and 26 healthy controls. Methods: Medical records from 63 Elkhounds with diabetes were reviewed and owners were contacted for follow‐up information. Blood samples from the day of diagnosis were available for 26 dogs. Glucose, fructosamine, C‐peptide, growth hormone (GH), insulin‐like growth factor‐1, progesterone, and glutamate decarboxylase isoform 65‐autoantibodies were analyzed and compared with 26 healthy dogs. Logistic models were used to evaluate the association of clinical variables with the probability of diabetes and with permanent diabetes mellitus after ovariohysterectomy (OHE). Results: All dogs in the study were intact females and 7 dogs (11%) were pregnant at diagnosis. The 1st clinical signs of diabetes mellitus occurred at a median of 30 days (interquartile range [IQR], 3–45) after estrus, and diagnosis was made at a median of 46 days (IQR, 27–62) after estrus. Diabetes was associated with higher concentrations of GH and lower concentrations of progesterone compared with controls matched for time after estrus. Forty‐six percent of dogs that underwent OHE recovered from diabetes with a lower probability of remission in dogs with higher glucose concentrations (odds ratio [OR], 1.2; P= .03) at diagnosis and longer time (weeks) from diagnosis to surgery (OR, 1.5; P= .05). Conclusions: Diabetes mellitus in Elkhounds develops mainly during diestrus and pregnancy. Immediate OHE improves the prognosis for remission of diabetes.     

Nephrogenic diabetes insipidus in a dog with intestinal leiomyosarcoma

Nephrogenic diabetes insipidus was diagnosed in a dog with an intestinal leiomyosarcoma. The diagnosis of nephrogenic diabetes insipidus was made on the basis of results of serum biochemical tests, urinalyses, and a water-deprivation test, along with a lack of response to exogenous administration of vasopressin following the water-deprivation test. The temporal association between resection of the intestinal mass and resolution of clinical signs of diabetes insipidus (i.e., polyuria and polydipsia) and between recurrence of clinical signs and detection of metastatic disease suggests that there may have been a causal relationship, and nephrogenic diabetes insipidus may have developed as a paraneoplastic syndrome in this dog.     

益生菌防治糖尿病的研究进展

肠道菌群与糖尿病之间的关系正被研究者们所揭示.作为肠道中一类特殊的菌群,益生菌在延缓或治疗糖尿病方面有着独特的优势.本文从机理和优势的角度总结了益生菌防治糖尿病的研究进展,并对其发展趋势进行了展望.     

Renal abscess in a dog with transient diabetes mellitus

A nine-year-old, intact female dalmatian with diabetes mellitus and a renal abscess is described. The renal abscess was treated surgically by nephrectomy, and the diabetes mellitus resolved with ovariohysterectomy. Abdominal ultrasound and ultrasound-guided aspiration of the abscess were helpful in establishing a diagnosis. To the authors' knowledge, this is the first report of a renal abscess in a dog with diabetes mellitus.