A survey of southeastern United States veterinarians’ preferences for managing cats with diabetes mellitus

Abstract

This study evaluated primary practitioners’ perceptions of managing feline diabetics. Surveys distributed during local continuing education events achieved a response rate of 46% (90/195). A mean of 74% feline diabetics required chronic insulin; 26% were transient diabetics. Choice of insulin was most influenced by duration of action: human recombinant protamine zinc insulin was ranked first (42%) and glargine second (27%). Dietary management was always/usually recommended by 97% respondents, with prescription or proprietary low-carbohydrate, high-protein diets recommended in 93% responses. More recent graduates (P = 0.0419), those who worked in larger practices (P = 0.0315), and those who saw more transient diabetics (P = 0.0288) were more likely to recommend dietary change. In-house blood glucose curves (BGCs) were the most popular method of assessing glycemic control, while at-home BGCs were least popular, although their use correlated positively with annual diabetic caseload (r = 0.43, P = 0.0239). Owners mishandling insulin was cited as the most common cause of poor glycemic control, while clinical signs of acromegaly were rarely recognized.

Introduction

Diabetes mellitus (DM) is the second most common endocrinopathy affecting cats, estimated to affect one in 400 cats in the USA. ¹ Cats have a form of diabetes resembling human type 2 diabetes; however, most require insulin for treatment at the time of diagnosis. Historically, they have been treated with exogenous insulin, oral anti-hyperglycemic drugs, and high fiber diets. Changes in the approach to human insulin therapy have led to the discontinuation of most of the historically-preferred ultralente and lente insulins, subsequently limiting their availability for veterinary use. Commonly used veterinary-licensed insulins (PZI Vet; Vetsulin) have also been withdrawn recently from the USA.^2,4

Revision in the dietary management of human diabetes has also influenced changes in the recommended feeding regimes for diabetic cats. The combined use of new insulins and low-carbohydrate, high-protein (LCHP) diets in cats has been suggested to increase the likelihood of achieving diabetic remission or reversion to a non-insulin-dependent state. Other factors, including the duration of diabetes mellitus and intensity of glucose monitoring may also have an influence. ⁵ Transient diabetes was defined by us as reversion to normoglycemia without exogenous insulin administration for more than 2 weeks. Reported rates of transient diabetes have increased from 10–25% of feline diabetics to greater than 50–70% of affected cats. ⁶

Given the logistical issues affecting veterinarians’ treatment of diabetic cats and the recent recommended changes in the therapeutic strategy, we sought to evaluate practitioners’ perceptions of managing feline diabetics. Specific objectives were to determine the types of insulin used and why they were selected, how veterinarians assessed glycemic control, and which factors they thought most affected their ability to manage diabetic cats successfully in primary practice. We were also interested in whether the type of veterinary practice and amount of clinical experience correlated with these decisions. We hypothesized that the majority of practitioners would report primary use of PZI insulin [either PZI Vet or the replacement product, human recombinant PZI (ProZinc)] because of familiarity with the product, and that the majority of practitioners would monitor diabetic cats by glucose curves. We further hypothesized that more recent graduates and clinicians from small animal (SA)-exclusive practices would be more likely to report both the use of glargine insulin, and the recommendation of LCHP diets.

Materials and methods

Survey questions were developed by one of the authors (JRS), and were reviewed by the other authors to ensure clarity. Additional colleagues in the field of internal medicine also reviewed the questions as content experts. Finally, the methodology was reviewed by a survey expert from the University of Georgia’s Survey Research Center. The survey and study protocols were approved by the University of Georgia’s (UGA) Institutional Review Board for Human Subjects Research (2011-10371-0). No signature was required for consent, and an informational letter was provided with each survey.

The anonymous survey was distributed in hard copy at two separate, two-day continuing education (CE) events held at the UGA College of Veterinary Medicine in the autumn of 2010. During the opening remarks, attendees were invited to participate in the survey, and several reminders were made between sessions throughout the weekend. Respondents could submit surveys at any time during the CE event. Demographic information was collected to distinguish the educational background and practice experiences of respondents.

Respondents were then asked a series of multiple-choice questions regarding management of cats with DM. The survey is provided as supplementary data. Paper survey responses, including hand-written comments, were entered into a commercial software program spreadsheet (Excel®; Microsoft Corp). Initial analysis was performed in this program, with subsequent analysis performed using commercial statistical software (SAS V 9.2, SAS Institute Inc). For questions where the respondents were asked to rank their responses and instead checked responses, the checked responses were given the average rank of the number of selections made (eg, if a respondent checked three responses, then each response was assigned a rank of 2).

Statistical analysis

Association between nominal factors was tested by the χ² test. Association between nominal factors and either scaled or ranked data was tested by a Kruskal-Wallis test. Association between numerical and nominal data was tested by an analysis of variance for nominal factors with greater than two factors or a Student’s t-test when the nominal factor had two levels only. The folded form F statistic was used to test if variances were equal between groups. If unequal, then Satterwaithe’s approximation for degrees of freedom for the Student’s t-test was used. Association of ordinal data with scaled and ranked data was performed by Spearman correlation. The ranking of each factor that influences choice of insulin was compared between respondents with different first choices of insulin using a Kruskal-Wallis test. All hypothesis tests were two-sided and the significance level was α = 0.05.

Results

A total of 195 veterinarians attended the two CE events, including 77 at the first event and 118 at the second event. Ninety-four surveys were returned. Respondents to four surveys only provided answers to the demographic questions, so these surveys were excluded from analysis, giving an overall response rate of 46% (90/195).

The mean number of years since graduation of the attending veterinarians was 19.3 ± 10.1 (range 2–53). Thirty of 90 veterinarians (33%) were employed in north or northeast Georgia; 20/90 (22%) came from Atlanta and surrounding areas; 19/90 (21%) came from other regions of Georgia, and 21/90 (23%) were based in other states. Eighty-four of 90 (93%) of the respondents worked in exclusively (or predominantly) SA practices and one was in an evenly mixed large animal and SA practice. The mean number of SA veterinarians in each practice was 2.9 ± 2.3 (range 0–15). Five respondents classified their employment as ‘other’; three were employed in academia, one was in industry and one was currently unemployed.

When questioned about the annual number of cats diagnosed with DM at their clinics, 31/90 (34%) veterinarians reported that they diagnosed DM in fewer than five cats per year, 42/90 (47%) diagnosed between five and 12, and 17/90 (19%) diagnosed more than 12 cats per year. When asked to characterize the type of feline diabetics that respondents diagnosed, the mean proportion of cats estimated to have permanent DM was 74% ± 21% (range 5–100%), with a corresponding 26% ± 21% (0–100%) identified as transient diabetics.

The most popular insulin reportedly used to manage feline diabetics was recombinant protamine zinc insulin (ProZinc; Boehringer Ingelheim) ranked first in 39/93 (42%) responses (three veterinarians selected two first choice insulins, so the total responses exceeded 90), followed by glargine (Lantus; Sanofi) selected in 25/93 (27%) responses, then neutral protamine Hagedorn (NPH)/Humulin N (Nordisk/Lilly) chosen in 16/93 (17%), and porcine zinc insulin (Vetsulin; Intervet/Schering-Plough Animal Health) in 13/93 (14%) responses. When asked to rank the factors that influenced choice of insulin, the most important factor was duration of insulin action, followed by expert opinion, experience with the type of insulin, reliability of insulin availability, cost of insulin and needles, and, finally, the species origin of insulin. There was no association between the first choice of insulin and the ranking of factors that influenced this decision.

Sixty-seven of 90 (74%) respondents reported that they always recommended a diet change as a component of diabetic management in cats, while 20/90 (22%) reported that they usually did so, and 3/90 (3%) sometimes did so. Veterinarians who had graduated more recently were more likely to recommend a diet change (mean of 18.5 years for those who did versus 24.5 years for those who did not, P = 0.0419), as were those who worked in larger practices (average number of SA practitioners was three for those who did versus two for those who did not, P = 0.0315). Over 40% (51/124) of responses (responses exceed the number of respondents when more than one ranked response is possible) selected Purina DM diet as the most commonly recommended diet followed by: Hill’s m/d (40, 32%); Royal Canin Diabetic DS 44 (13, 11%); LCHP non-prescription foods (11, 9%); and Hill’s w/d (5, 4%). An additional recommended diet was canned kitten food. Most veterinarians recommended feeding twice daily (61/90, 68%), while 15/90 (17%) recommended no change in the feeding schedule and 14/90 (15%) advocated free-choice feeding. No respondent recommended once-daily feeding. There was a significant association between percentage of transient DM cases and recommending a change in feeding schedule (P = 0.0288). The mean proportion of transient cases was 30% in the change group and 18% in the no change group.

The method ranked most commonly by the surveyed veterinarians to evaluate feline diabetic control was a blood glucose curve (BGC) performed in the clinic (mean rank = 1.7 of 76 responses; the lowest rank available was 7). This was followed by assessment of fructosamine concentration (mean rank = 2.5 of 67 responses), then a decrease in observed clinical signs (mean rank = 2.7 of 62 responses), a spot-check blood glucose concentration (mean rank = 2.9 of 55 responses), the cat’s physical examination and body weight (mean rank = 3.6 of 44 responses), and the pattern of glucosuria at home (mean rank = 4.0 of 25 responses), with BGC performed at home (mean rank 4.2 of 21 responses) as the least utilized method. However, there was a significant positive correlation between the annual number of diabetic cats seen and the use of a home BGC to assess glycemic control (r = 0.43, P = 0.0239).

The top ranked explanation by veterinarians for poor glycemic control was owner mishandling of insulin (mean rank 1.8 of 66 responses; the lowest rank available was 6), followed by concurrent pancreatitis (mean rank 2.0 of 84 responses), presence of a urinary tract infection (mean rank = 2.1 of 51 responses), and hyperthyroidism (mean rank = 3.3 of 19 responses). Acromegaly was ranked the lowest (mean rank = 3.5 of 6 responses). An additional explanation proposed by 18 attendees who selected the ‘other’ response was poor owner compliance, with half of those citing compliance with type of insulin or follow-up testing and half suggesting poor dietary compliance. Based on the number of veterinarians who wrote this option, it would have ranked the fifth most common factor thought to contribute to poor glycemic control, after hyperthyroidism.

Finally, 86/89 (97%) veterinarians said that they had never used an insulin pen for feline diabetics; three veterinarians responded that they had. There was a significant association between annual feline diabetic caseload and use of a human insulin pen (P = 0.0085). The more diabetic cats seen per year in a practice, the more likely the respondent was to have used a human insulin pen. For those veterinarians who had not used an insulin pen before, the most commonly identified reason was a lack of experience (71/122, 58% of responses), followed by an uncertainty of when they would be beneficial (23/122, 19% of responses), a lack of awareness that these devices existed (16/122, 13% of responses) and cost (9/122, 7% of responses). Owner disinterest was the least common reason cited.

Discussion

This study provides information on how a sample of US veterinarians manage feline diabetic patients. As with all retrospective surveys, the accuracy of the answers is subject to recall bias. Georgia state veterinary licensure requires a minimum CE attendance to be completed every 2 years, therefore those attending this local CE event could be considered representative of Georgian veterinarians in general. ⁷ Given that these veterinarians attended SA-focused CE events, it not surprising that the proportion in SA predominant or exclusive practice (93%) exceeded the proportion of US veterinarians in similar practices (77%). ⁸ The mean number of practitioners in each practice slightly exceeded the national average of 2; this may have reflected bias of veterinarians from larger, urban practices near Atlanta who comprised 25% of the attendees. ⁹

At least half of the respondents diagnosed up to one diabetic cat per month, and the clinical impression was that 74% of these were permanent diabetics whilst 26% were transient diabetics, although these proportions are obviously subject to recall bias. Although most cats have type 2 DM, characterized by high levels of insulin secretion and peripheral insulin resistance, the impression is that significant rates of diabetic remission have been increasing recently with the advent of longer-acting insulins in combination with LCHP diets. ¹⁰ Some advocate that the type of insulin is more important in achieving diabetic remission; ¹¹ others suggest that diet is the key component; ⁶ whilst yet others suggest that simply the intensive monitoring and early glycemic control are key factors in achieving remission. ⁵ Certainly, diabetic remission seems easier to achieve in cats with newly diagnosed DM, presumably because early reversal of glucose toxicity permits recovery of residual pancreatic cell function. ¹² Remission rates of 33–61% have been achieved in studies performed in conjunction with referral institutions, ⁵ but the rate of diabetic remission achieved by primary practitioners using long-acting insulins and LCHP diets has not been previously documented.

Protamine zinc insulin derived from 90% bovine and 10% porcine insulin (PZI Vet; Idexx Pharmaceuticals) was historically the insulin most commonly used to manage diabetic cats in the USA. ¹³ However, owing to problems inherent in using animal-derived insulins and concerns about bovine spongiform encephalopathy, this product was replaced with a recombinant human insulin formulated as a protamine zinc product (ProZinc) in late 2009. ¹⁴ The insulin action time allows for twice-daily use in most cats, and the concentration of 40 IU/ml permits easier administration of small insulin doses. Therefore, it is unsurprising that it has replaced its predecessor as the first-choice insulin. The second most popular choice was glargine, which has likely increased in popularity because of the high rates of diabetic remission achieved in cats treated with this insulin. ¹¹ This recombinant human insulin has a slightly altered amino acid structure such that it microprecipitates in subcutaneous tissue and thus has a steady action relatively free from peaks and troughs in humans. In healthy cats it has a peak activity at 14 h and a minimum duration of action of 22 h. ¹⁵ This long duration of action means glargine may be efficacious in some cats when administered only once daily at the owner’s convenience, although it is recommended that twice-daily administration is optimal for glycemic control. ¹¹ Despite the short duration of action (4–12 h) of NPH in some cats, ¹⁶ it was the first choice insulin of almost 1/5 of the respondents. Although no specific factor was associated with selection of one type of insulin, we speculate that the consistent availability of NPH and subsequent personal experience with this insulin favored its use. The least popular insulin was Vetsulin, an intermediate-acting, porcine lente insulin formulated at a concentration of 40 U/ml. This was a relatively new introduction in the USA at the time that this survey was performed, although it has been used in Europe, Canada and Australasia, as Caninsulin, to treat feline and canine diabetics for more than 10 years.^17,18 Unfortunately, problems with stability led to variable availability in late 2010; further quality control problems led to its withdrawal from the US market in early 2011.

That veterinarians who graduated more recently were more likely to recommend a change in feeding regime may reflect that these practitioners were more likely to adapt their practice habits to recent recommendations derived from the growing understanding of the prominent role of diet in feline diabetic management. There was also an association between veterinarians’ recollection of the frequency with which transient diabetics were seen and the likelihood of recommending a change in feeding schedule. Whether a cause-and-effect relationship exists between these variables could not be determined within the design of current study. Dietary influence on the management of feline diabetes has been an area of much recent research, using healthy lean or obese cats.^6,19–22 Findings on the relative merits of reduced carbohydrate content, increased protein content, or a combination of the two have been inconsistent.^5,6,20,22 Studies of commercially-available LCHP diets have been shown to increase the reversion rate of clinical diabetes to a non-insulin-dependent state compared with feeding high fiber food; ²² however, it is possible that veterinarians who are aware of this influence may also be more likely to recognize a transient diabetic state. Regardless, the recognized importance of feeding an appropriate diet in the management of feline DM was evidenced by over 97% of the veterinarians reporting that they ‘always’ or ‘usually’ recommended a diet change. LCHP prescription or proprietary diets were recommended 93% of the time, signaling a transition away from the previously recommended high-fiber diets. ²³ However, it should be remembered that cats treated with chronic insulin therapy may be equally well controlled on low carbohydrate or high fiber diets, and that concurrent conditions (eg, chronic renal disease) may be a contraindication to feeding high protein diets. ²⁴ The design of this survey did not directly permit investigation of concurrent disease in the population of cats managed by these veterinarians.

The most popular method of monitoring glycemic control in feline diabetics chosen by the respondents was a BGC performed in the hospital. A BGC can assess the time and duration of insulin effects, determine the nadir and degree of fluctuation in blood glucose concentration, and identify the Somogyi effect. While a fructosamine concentration, the second most common choice, needs only a single blood draw and minimizes the influence of stress hyperglycemia, it only identifies poor glycemic control. However, a fructosamine concentration cannot provide any further information regarding whether such poor control is a function of insulin performance. Blood glucose curves performed in the home may reduce the incidence of stress hyperglycemia whilst providing more nuanced information than can be gleaned by a simple fructosamine concentration.^25–27 Interestingly, this was the least popular option selected by the veterinarians, although more likely to be selected by those who saw the most diabetic cats. Home monitoring does not decrease the frequency of re-evaluation at the veterinary hospital; however, it is generally well tolerated by owners and allows them to actively participate in their cats’ medical care; the latter is an important factor in owner perception of quality of life for diabetic cats.^25,28,29 A recent study comparing sequential BGC performed at home showed as much variability as did a comparison of in-hospital and home BGC, and suggested that stress hyperglycemia may not be completely eliminated in the home environment. ³⁰ Nevertheless, home BGCs are less expensive for the owner and thus facilitate frequent assessments of glycemic control — a key component to the success of protocols aiming for early glycemic control or using intensive blood glucose control to promote diabetic remission in cats. ³¹ Glucosuria can also be monitored in the home environment and was only slightly more popular than home BGC among our sample of veterinarians. Whilst glucosuria is easy to detect, it can be caused by chronic hyperglycemia or by the rebound hyperglycemia following a hypoglycemic episode (Somogyi phenomenon), thus development of glucosuria alone does not provide sufficient information to dictate the direction of change (increase or decrease) in the insulin dose. ³² The combination of history, physical examination, and changes in body weight (similar to a combination of the third and fifth most popular monitoring choices in this present study), has been used to assess glycemic control in diabetic patients, but is considered less reliable in cats. ³³ Nonetheless, a recent study comparing various clinical and biochemical parameters for monitoring diabetic cats treated with porcine lente insulin concluded that the measurements most closely correlated with perfect clinical control were a combination of water intake, maximum blood glucose, mean blood glucose, and urine glucose. ³⁴

When questioned about potential causes of poor glycemic control, surveyed veterinarians ranked owners’ mishandling of insulin first. The question did not specify whether this terminology related to administration or storage of insulin. Another owner-related factor — poor owner compliance — ranked fifth. This option was not included in the original survey but was suggested by 20% of respondents; had this answer been provided as an option, it may have been ranked even more highly. Half of the owner-compliance comments related to diet, emphasizing the need to communicate the importance of both insulin and nutritional therapy in the management of feline diabetics to owners. Although susceptible to recall bias, the top ranked patient factor leading to poor glycemic control was pancreatitis, followed (in order) by urinary tract infection, hyperthyroidism, hyperlipidemia, and acromegaly. This is in agreement with previous work suggesting pancreatitis and bacterial infection are the most common causes of insulin resistance in diabetic cats. ³³ Within our study design, it was not possible to determine whether this low ranking for acromegaly among our sample of veterinarians was a result of negative testing or lack of awareness of a need to test. Although feline acromegaly has been considered a rare disorder in the past, recent work in Europe suggests that it is not always accompanied by classic phenotypical changes and therefore may be a more common cause of insulin resistance in diabetic cats than was recognized previously.^35–37 It would be interesting to monitor US veterinarians’ perception of the prevalence of feline acromegaly with wider promotion of this relatively new finding.

The final survey question related to the use of insulin dosing pens. These devices are designed to make measuring and administering insulin doses easier, less painful, and more accurate and precise. ³⁸ Most insulin pens allow administration of insulin doses in 1 U increments, although some pediatric pens permit 0.5 U increments. Although 0.5 U increments can be achieved using 0.3 ml U-100 syringes, work with pediatric nurses has shown more variability with syringe dosing compared with using insulin pens. Most syringe-measured doses exceeded the intended dose, thus increasing the risk of hypoglycemia in patients that receive small doses of insulin. ³⁹ Use of insulin pens was not very common among the surveyed veterinarians. Interestingly, lack of awareness and inexperience were cited as more common reasons not to use them, rather than device cost or owner disinterest. Investigations into the utility of insulin pens might prove a salient topic of future research.

This survey of predominantly SA practitioners at a regional CE event confirmed the frequency of use of recombinant protamine zinc insulin and LCHP dietary management in diabetic cats, in agreement with our hypothesis. Transient diabetes was recognized in a minority of cases seen by respondents, and our hypothesis that in-clinic BGCs appear to remain the mainstay of monitoring of glycemic control was correct. Based on the results of this survey, future CE events held at this location could discuss the use of home monitoring, consideration of acromegaly as a cause of poor glycemic control, and the potential utility and benefit of insulin pens in managing feline diabetics.

Supplemental Material

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The survey questionnaire