Fructosamine

Fructosamines are glycated serum proteins that, depending on their life span, reflect glycemic control over the previous 2 to 3 weeks. The nitroblue tetrazolium reduction method adapted to autoanalysis appeared to be a practical means to assay fructosamine quickly, economically, and accurately. The upper limit of the reference range is 374 μmol/L in dogs (95% percentile) and 340 μmol/L in cats (95% percentile). Newly diagnosed diabetic dogs and cats that had not undergone previous insulin therapy had significantly higher fructosamine concentrations than nondiabetic animals. In diabetic dogs that were receiving insulin therapy, the fructosamine test reflected the glycemic state far more accurately than did individual blood glucose measurements. Animals with satisfactory metabolic control revealed fructosamine concentrations within the reference range, whereas fructosamine concentrations above 400 μmol/L indicated insufficient metabolic control. On the basis of fructosamine concentrations, cats with a transitory hyperglycemia and cats with diabetes mellitus were differentiated. The fructosamine test is a valuable parameter for the diagnosis and metabolic control of diabetes mellitus in dogs and cats.     

Comparison of time-action profiles of insulin Glargine and NPH insulin in normal and diabetic dogs

Intermediate insulin injections are commonly used for glycemic control in insulin dependent diabetic dogs acting as a replacement for natural insulin. Neutral Protamin Hagedorn (NPH) insulin and insulin glargine are two types of injectable insulin preparations commonly used in humans. In our study, we investigated the time-action profiles of both aforementioned insulin preparations in normal dogs in order to determine whether co-administration of NPH and glargine would be of benefit to insulin dependent diabetic dogs as it is for humans suffering from insulin dependent diabetes. Time-action profiles of NPH insulin and insulin glargine in normal dogs demonstrated a clear difference between both insulin preparations confirming that NPH insulin is an intermediate-acting preparation whereas insulin glargine is a long-lasting preparation. In addition, co-administration of NPH insulin and insulin glargine resulted in tight glycemic control as compared to NPH insulin alone in insulin dependent diabetic dogs. However, co-administration result in hypoglycemia at the dosages tested.     

Dietary management of diabetes mellitus

Dietary therapy should be designed to enhance insulin therapy and improve glycaemic regulation of the diabetic dog and cat. Dietary therapy will not alleviate the necessity for insulin therapy in dogs and cats with insulin-dependent diabetes mellitus. Preliminary work suggests that dietary therapy may ultimately be the only therapy necessary to maintain glycaemic control in cats with suspected non-insulin-dependent diabetes mellitus. Currently, the feeding of a high fibre, high complex carbohydrate diet is recommended at a caloric intake designed to correct obesity and maintain ideal bodyweight. Several small meals should be fed during the period of insulin activity, to help minimise post prandial fluctuations in the blood glucose concentration.     

Effects of insoluble and soluble dietary fiber on glycemic control in dogs with naturally occurring insulin-dependent diabetes mellitus

OBJECTIVE: To evaluate the effects of diets differing in type and quantity of fiber on glycemic control in dogs with naturally occurring insulin-dependent diabetes mellitus. DESIGN: Prospective randomized crossover controlled trial. ANIMALS: 7 dogs with well-regulated naturally occurring insulin-dependent diabetes mellitus. PROCEDURE: Dogs were fed 1 of 3 diets for 1 month each in 1 of 6 randomized diet sequences. Diets included a low-fiber diet (LF) and 2 high-fiber diets; 1 contained only insoluble fiber (HIF), and 1 contained soluble fiber in addition to insoluble fiber (HSF). Caloric intake was unchanged throughout the study. Glycemic control was assessed after each feeding trial by measuring serum fructosamine concentration and performing 5 serial measurements of blood glucose concentration every 2 hours after the morning feeding and insulin injection. RESULTS: Significant differences were not detected in body weight, required insulin dosage, or albumin concentration among dogs fed the HIF, HSF, and LF diets. Mean and maximum blood glucose concentrations and area under the blood glucose curve were significantly lower in dogs fed the HIF diet, compared with values in the same dogs fed the HSF or LF diet. Fructosamine concentration was significantly lower in dogs fed the HIF or HSF diet, compared with values in the same dogs fed the LF diet. CONCLUSIONS AND CLINICAL RELEVANCE: In dogs with naturally occurring insulin-dependent diabetes mellitus, a dry, high insoluble-fiber diet may aid in glycemic control.     

Feline diabetes mellitus: low carbohydrates versus high fiber?

Treatment of diabetes mellitus (DM) in the cat relies primarily on the adequate insulin therapy and controlled dietary intake. The goals of managing DM in the cat have changed from attaining glycemic control to achieving diabetic remission (transient diabetes) in a large proportion of cases. Remission rates of up to 68% have been published. The used of low-carbohydrate foods for cats improves the odds of achieving diabetic remission by fourfold. Nonetheless, some cats show an improved response to high-fiber food. Clinical judgement, trial, and personal preference to currently dictate which diet to offer an individual animal.     

Dietary fibre and post prandial hyperglycaemia in normal and diabetic dogs

Blood glucose responses to three different diets were measured in six normal dogs and in five diabetic dogs stabilised on insulin replacement therapy. In all animals a control canned diet was compared with the same diet containing 20 g wheat bran, and with the same diet containing 20 g guar granules. Reductions in hyper-glycaemia were demonstrated for 240 minutes following the test meal containing guar in comparison with the control diet in all but one dog, and moderate reductions were demonstrated following the test meal containing bran. These findings suggest that, as in man, feeding restricted carbohydrate diets to diabetics is an outdated concept. As in human medicine, high fibre diets or dietary supplementation with soluble fibre, such as guar, reduces post prandial hypergly-caemia and may help to improve gylcaemic control in diabetes mellitus.     

Effect of the alpha-glucosidase inhibitor acarbose on control of glycemia in dogs with naturally acquired diabetes mellitus

OBJECTIVE: To evaluate effect of acarbose on control of glycemia in dogs with diabetes mellitus. DESIGN: Prospective randomized crossover controlled trial. ANIMALS: 5 dogs with naturally acquired diabetes mellitus. PROCEDURE: Dogs were treated with acarbose and placebo for 2 months each: in 1 of 2 randomly assigned treatment sequences. Dogs that weighed < or = 10 kg (22 lb; n = 3) or > 10 kg (2) were given 25 or 50 mg of acarbose, respectively, at each meal for 2 weeks, then 50 or 100 mg of acarbose, respectively, at each meal for 6 weeks, with a 1-month interval between treatments. Caloric intake, type of insulin, and frequency of insulin administration were kept constant, and insulin dosage was adjusted as needed to maintain control of glycemia. Serum glucose concentrations, blood glycosylated hemoglobin concentration, and serum fructosamine concentration were determined. RESULTS: Significant differences in mean body weight and daily insulin dosage among dogs treated with acarbose and placebo were not found. Mean preprandial serum glucose concentration, 8-hour mean serum glucose concentration, and blood glycosylated hemoglobin concentration were significantly lower in dogs treated with insulin and acarbose, compared with insulin and placebo. Semisoft to watery feces developed in 3 dogs treated with acarbose. CONCLUSIONS AND CLINICAL RELEVANCE: Acarbose may be useful as an adjunctive treatment in diabetic dogs in which cause for poor glycemic control cannot be identified, and insulin treatment alone is ineffective.     

Supplementing transglucosidase with a high-fiber diet for prevention of postprandial hyperglycemia in streptozotocin-induced diabetic dogs

Indigestible oligosaccharides have been shown to normalize blood glucose and insulin concentration thereby promoting good health and preventing diseases, such as diabetes. Transglucosidase (TG, α-glucosidase, enzyme code (EC) 3.2.1.20) is an enzyme capable of converting starch to oligosaccharides, such as iso-malto-oligosaccharides from maltose, via the action of amylase. The aim of this study was to evaluate whether oral administration of TG with maltose or dextrin is capable of reducing post-prandial serum glucose concentration in experimentally streptozotocin (STZ)-induced diabetic dogs fed on a high-fiber diet. Five healthy and five STZ-induced diabetic dogs were employed in this study. TG supplementation with dextrin or maltose had no detrimental effect in healthy dogs. In fact, TG and dextrin exhibited a flatlined serum glucose pattern, while reducing mean post-prandial serum insulin and glucose concentration as compared to control diet alone. When TG supplementation was tested in STZ-induced diabetic dogs under the context of a high fiber diet, a 13.8% and 23.9% reduction in mean glucose concentration for TG with maltose and dextrin, respectively was observed. Moreover, TG with dextrin resulted in a 13% lower mean post-prandial glucose concentration than TG with maltose, suggesting that dextrin may be a more efficient substrate than maltose when used at the same concentration (1 g/kg). Our results indicate that TG supplementation with diet can lead to lower postprandial glucose levels versus diet alone. However, the efficacy of TG supplementation may depend on the type of diet it is supplemented with. As such, TG administration may be useful for preventing the progression of diabetes mellitus and in its management in dogs.     

Diagnostic significance of serum glycated albumin in diabetic dogs

Measurements of serum fructosamine, glycated hemoglobin, and glycated albumin (GA) are increasingly used to complement serum glucose concentration for better management of diabetes mellitus. Fructosamine tests are currently not performed in veterinary medicine in Japan. As such, the measurement of GA may serve as a replacement test. Therefore, in the current study, serum GA and fructosamine were evaluated for a positive correlation in dogs, and, depending on the correlation, a reference range of GA percentage would also be determined from healthy control dogs. The degree of glycemic control in diabetic dogs was determined by fructosamine concentration. A positive correlation between GA and fructosamine was observed with both normal and diabetic animals. In addition, the reference interval of serum GA percentage in control dogs was determined to be 11.4-11.9% (95% confidence interval). Interestingly, no significant difference in serum GA percentages was observed between samples from diabetic dogs with excellent glycemic control and control dogs. However, good, fair, and poor glycemic control diabetic dogs resulted in a significant increase in serum GA percentages in comparison with control dogs. These results suggest that serum GA may be a useful diagnostic indicator, substituting for fructosamine, to monitor glycemic control in diabetic dogs.     

Corneal sensitivity in dogs with diabetes mellitus

OBJECTIVE: To compare aesthesiometer-determined corneal sensitivity between diabetic and nondiabetic dogs and to investigate the correlation between corneal sensitivity and duration of diabetes or status of glycemic control, as estimated by use of glycated blood protein concentrations. ANIMALS: 23 diabetic and 29 nondiabetic normoglycemic dogs. PROCEDURE: A Cochet-Bonnet aesthesiometer was used to measure corneal touch threshold (CTT) in 5 corneal regions of each dog. At the time of ocular examination, duration of diabetes mellitus was estimated from the history, and blood was drawn for assessment of blood glycosylated hemoglobin and serum fructosamine concentrations. RESULTS: Median CTT for central, nasal, dorsal, temporal, and ventral corneal regions in nondiabetic dogs (1.6, 2.3, 2.8, 2.8, and 5.1 g/mm2, respectively) was significantly lower than in diabetic dogs (2.8, 4.0, 5.1, 5.1, and 6.6 g/mm2, respectively). Median regional CTT in diabetic dogs was not significantly correlated with estimated duration of diabetes mellitus or blood glycated protein concentrations. No significant difference was found in regional CTT between eyes of normoglycemic dogs with unilateral cataracts. CONCLUSIONS AND CLINICAL RELEVANCE: Diabetic dogs have significantly reduced corneal sensitivity in all regions, compared with nondiabetic normoglycemic dogs. Regional variation in corneal sensitivity is similar in diabetic and normoglycemic dogs. Neither glycemic control nor duration of diabetes, as estimated, is significantly correlated with corneal hyposensitivity. Corneal nerve dysfunction may be associated with recurrent or nonhealing ulcers in diabetic dogs for which no other underlying cause can be found.     

Treatment of feline diabetes mellitus using an alpha-glucosidase inhibitor and a low-carbohydrate diet

The purpose of this study was to determine the effect of an alpha-glucosidase inhibitor (acarbose), combined with a low-carbohydrate diet on the treatment of naturally occurring diabetes mellitus in cats. Eighteen client-owned cats with naturally occurring diabetes mellitus were entered into the study. Dual-energy X-ray absorptiometry (DEXA) was performed prior to and 4 months after feeding the diet to determine total body composition, including lean body mass (LBM) and percent body fat. Each cat was fed a commercially available low-carbohydrate canned feline diet and received 12.5mg/cat acarbose orally every 12h with meals. All cats received subcutaneous insulin therapy except one cat in the study group that received glipizide (5mg BID PO). Monthly serum glucose and fructosamine concentrations were obtained, and were used to adjust insulin doses based on individual cat's requirements. Patients were later classified as responders (insulin was discontinued, n=11) and non-responders (continued to require insulin or glipizide, n=7). Responders were initially obese (>28% body fat) and non-responders had significantly less body fat than responders (<28% body fat). Serum fructosamine and glucose concentrations decreased significantly in both responder and non-responder groups over the course of 4 months of therapy. Better results were observed in responder cats, for which exogenous insulin therapy was discontinued, glycemic parameters improved, and body fat decreased. In non-responders, median insulin requirements decreased and glycemic parameters improved significantly, despite continued insulin dependence. The use of a low-carbohydrate diet with acarbose was an effective means of decreasing exogenous insulin dependence and improving glycemic control in a series of client-owned cats with naturally occurring diabetes mellitus.     

Changes in activities of enzymes related to energy metabolism in peripheral leukocytes of diabetic dogs with glycemic control by intensive insulin treatment

Changes in plasma glucose, immunoreactive insulin (IRI), and free fatty acids (FFA) concentrations and activities of enzymes related to energy metabolism in peripheral leukocytes were measured in type 1 diabetic dogs induced by streptozotocin administration before and after intensive insulin treatments. Before the insulin treatment, the plasma glucose concentrations were over 16.7 mmol/L and the activities of enzymes remarkably decreased in leukocytes of the diabetic dogs. In particular, malate dehydrogenase (MDH) activities decreased significantly. After glycemic control was achieved by insulin treatment, the plasma glucose concentrations were maintained between 6.8 and 7.7 mmol/L and the activities of enzymes restored to those in the control dogs. The changes in ML ratio (cytosolic MDH/lactate dehydrogenase specific activity ratio) reflected faithfully to metabolic conditions of animals and were considered to be a useful parameter to evaluate glycemic control and the effect of injected insulin in the diabetic dogs.     

Diabetes mellitus in cats.

Feline diabetes is a multifactorial disease with genetic and environmental factors, including diet, excess body weight, and physical inactivity, involved in its pathogenesis. Although type 2 diabetes is most common in cats, most cats are insulin-dependent at the time of diagnosis. If good glycemic control can be achieved early after diagnosis, a substantial proportion of diabetic cats go into clinical remission. Diabetic remission may be facilitated by using a low-carbohydrate-high-protein diet combined with a long-acting insulin, such as glargine, administered twice daily. Rather than just controlling clinical signs, these new treatment modalities make curing feline diabetes a realistic goal for practitioners.     

Funduscopic findings following cataract extraction by means of phacoemulsification in diabetic dogs: 52 cases (1993-2003)

OBJECTIVE: To determine prevalence of retinal hemorrhages and microaneurysms in dogs with diabetes mellitus following cataract extraction by means of phacoemulsification and identify potential risk factors. DESIGN: Retrospective study. PROCEDURE: Medical records of dogs undergoing phacoemulsification between 1993 and 2003 were reviewed, and information was recorded on signalment, history, physical examination findings, ophthalmic examination findings, results of laboratory testing, electroretinographic findings, and surgical findings. Glycemic control was classified as poor, intermediate, or good on the basis of baseline blood glucose concentration, perioperative body weight loss, daily insulin dosage, and presence of glucosuria and ketonuria. Data from diabetic and nondiabetic dogs were analyzed to determine prevalence and risk factors for development of retinal hemorrhages or microaneurysms following phacoemulsification. RESULTS: 11 of the 52 (21%) dogs with diabetes mellitus developed ophthalmoscopic signs of retinal hemorrhages or microaneurysms, compared with 1 of the 174 (0.6%) nondiabetic dogs. Median time from onset of diabetes mellitus to diagnosis of retinopathy was 1.4 years (range, 0.5 to 3.2 years). No risk factors for development of retinopathy were identified. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that retinal hemorrhages and microaneurysms may be more common and develop earlier in diabetic dogs than previously reported. This may affect treatment, as diabetic dogs survive longer with improved glycemic control.     

Effect of insulin dosage on glycemic response in dogs with diabetes mellitus: 221 cases (1993-1998)

OBJECTIVE: To evaluate glycemic response to insulin treatment in dogs with diabetes mellitus. DESIGN: Retrospective study. ANIMALS: 221 dogs with diabetes mellitus. PROCEDURE: Type and dosage of insulin used, minimum and maximum blood glucose concentrations, time of blood glucose concentration nadir, and optimal duration of action of insulin were determined on the basis of data obtained prior to initial examination at the teaching hospital (127 dogs), at the time of initial examination (212 dogs), at the time a second follow-up blood glucose curve was performed (59 dogs), and at the time of clinical control of diabetes mellitus (83 dogs). RESULTS: Prior to examination, 69 of 127 dogs (54%) received 1 s.c. insulin injection daily. Thirty-one dogs (24%) received a high dose of insulin (i.e., > 1.5 U/kg [0.7 U/lb] of body weight); 27 of these dogs (87%) received 1 injection/d. Eleven of 16 dogs (69%) that were hypoglycemic (blood glucose concentration < 80 mg/dl) also received 1 injection/d. However, optimal duration of action of insulin was > 12 hours in only 5 of 83 dogs (6%) evaluated at the time diabetes mellitus was clinically controlled. At that time, only 1 dog (1%) received a high dose of insulin, and the dog received 2 injections/d. Moreover, 8 of 10 dogs (80%) with hypoglycemia received 1 injection/d. CONCLUSIONS AND CLINICAL RELEVANCE: Most dogs with diabetes mellitus are clinically regulated with 2 daily insulin injections. Administration of a high dose of insulin or development of hypoglycemia may be more common in diabetic dogs that receive insulin once daily, compared with dogs that receive insulin twice daily.     

Time-action profiles of insulin detemir in normal and diabetic dogs

Insulin detemir is the first member of a new class of long-acting soluble insulin analogues capable of maintaining the basal level of insulin in humans. In this preliminary study, we investigated the time-action profiles of insulin detemir in normal and diabetic dogs since the use of insulin detemir in canines has yet to be determined. Eight animals were used in our study (three normal and five insulin dependent diabetic dogs). Time-action profiles of insulin detemir were monitored in normal dogs using an artificial pancreas apparatus under euglycemic condition. Blood sampling was performed at 2 h intervals post feeding, with insulin administration, in insulin dependent diabetic dogs. Time-action profiles of insulin detemir, in normal dogs, demonstrated that insulin detemir is a long-lasting preparation similar to what has been observed in humans. A pronounced peak was detected at 8–10 h while the glucose-lowering effect lasted for over 24 h after insulin injection, thus illustrating its longer prolonged peak activity time. Furthermore, intensive glycemic control was achieved with insulin detemir in insulin dependent diabetic dogs, using a lower dosage than NPH insulin and insulin glargine therapeutic doses. Our results indicate that insulin detemir has a greater effect than either NPH insulin or insulin glargine in canines, requiring a lower dose than either insulin preparation. However, using insulin detemir also carries a higher risk of inducing hypoglycemia as compared to either NPH insulin or insulin glargine.     

Pregnancy-related diabetes mellitus in two dogs

CASE SUMMARIES: Two cases of diabetes mellitus occurring in bitches in association with pregnancy are reported. In the first case, a bitch with suspected acromegaly developed diabetes mellitus within 2 weeks of the due date. Despite insulin therapy, euglycaemia was not achieved. Tw o live, small pups were delivered by elective Caesarean section but died within 2 days. Signs consistent with acromegaly resolved but diabetes mellitus was permanent in the bitch. In the second case, diabetic ketosis with severe gastrointestinal disease was diagnosed 2 days after Caesarean section was performed due to dystocia. The pups delivered all died within 5 days. The bitch recovered fully from diabetes mellitus within 2 weeks and has remained euglycaemic without insulin for a period of at least 18 months.

CLINICAL RELEVANCE: These two cases demonstrate that diabetes mellitus can occur in association with pregnancy in dogs, that diabetic ketosis can occur during transient diabetes mellitus in dogs, and suggest that acromegaly may occur during pregnancy-related dioestrus in dogs. The scarcity of previous reports of this nature, however, suggests that such cases are unusual.

Lack of prompt resolution of hyperglycaemia may result in secondary diabetes mellitus becoming permanent. Management should focus on immediate insulin therapy or ovariohysterectomy to minimise this risk. Even mild hyperglycaemia should not be ignored during pregnancy. The insulin antagonistic effects of pregnancy, stressful illness, surgery and dystocia can be enough to result in diabetic ketosis in the absence of permanent insulin deficiency. Maternal hyperglycaemia may contribute to adverse fetal outcomes in dogs but further study is required regarding the nature of the risk.     

Pregnancy-related diabetes mellitus in two dogs

CASE SUMMARIES: Two cases of diabetes mellitus occurring in bitches in association with pregnancy are reported. In the first case, a bitch with suspected acromegaly developed diabetes mellitus within 2 weeks of the due date. Despite insulin therapy, euglycaemia was not achieved. Two live, small pups were delivered by elective Caesarean section but died within 2 days. Signs consistent with acromegaly resolved but diabetes mellitus was permanent in the bitch. In the second case, diabetic ketosis with severe gastrointestinal disease was diagnosed 2 days after Caesarean section was performed due to dystocia. The pups delivered all died within 5 days. The bitch recovered fully from diabetes mellitus within 2 weeks and has remained euglycaemic without insulin for a period of at least 18 months. CLINICAL RELEVANCE: These two cases demonstrate that diabetes mellitus can occur in association with pregnancy in dogs, that diabetic ketosis can occur during transient diabetes mellitus in dogs, and suggest that acromegaly may occur during pregnancy-related dioestrus in dogs. The scarcity of previous reports of this nature, however, suggests that such cases are unusual. Lack of prompt resolution of hyperglycaemia may result in secondary diabetes mellitus becoming permanent. Management should focus on immediate insulin therapy or ovariohysterectomy to minimise this risk. Even mild hyperglycaemia should not be ignored during pregnancy. The insulin antagonistic effects of pregnancy, stressful illness, surgery and dystocia can be enough to result in diabetic ketosis in the absence of permanent insulin deficiency. Maternal hyperglycaemia may contribute to adverse fetal outcomes in dogs but further study is required regarding the nature of the risk.     

Effects of diet on glucose control in cats with diabetes mellitus treated with twice daily insulin glargine

The purpose of this study was to evaluate the effects of dietary modification in addition to twice daily insulin glargine. Cats were treated with insulin glargine twice daily and randomized to receive either a low carbohydrate, high protein (LCHP) diet (n=6) or a control diet (n=6) for 10 weeks. Re-evaluations of clinical signs, blood glucose curves, and serum fructosamine concentrations were performed at weeks 1, 2, 4, 6, and 10. Two of 12 cats achieved complete remission by the end of the study but remission rate was not different between diet groups. Using twice daily insulin glargine and frequent monitoring, all cats in both diet groups achieved successful glycemic control. Frequent monitoring is key to achieving glycemic control in diabetic cats; potential benefits of dietary modification require further evaluation.     

Clinical peripheral neuropathy associated with diabetes mellitus in 3 dogs

Clinical and electrodiagnostic findings in 3 spontaneously diabetic dogs with clinical peripheral neuropathy (PN) are reported. Clinical signs of a PN may develop in diabetic dogs with adequate glycemic control. In addition, laryngeal paralysis may develop in association with diabetes mellitus in dogs with clinical PN.