Method Validation and Establishment of Reference Intervals for an Insulin-like Growth Factor-1 Chemiluminescent Immunoassay in Cats.

Previously, radioimmunoassay (RIA) has been the only assay to measure insulin-like growth factor-1 (IGF-1) to diagnose hypersomatotropism (HS). Due to radiation concerns, availability, and the cost of IGF-1 RIA, validation of assays for automated analysers such as a chemiluminescent immunoassay (CLIA) is needed. The aim of this study was to validate a CLIA for measurement of feline IGF-1 (IMMULITE 2000® XPi, Siemens Medical Solutions Diagnostics, Malvern, PA, USA) compared to IGF1 RIA, establish reference interval (RI), and determine a cut-off value for diagnosis of HS in diabetic cats. Validation of assay performance included precision, linearity, and recovery studies. Right-sided RI was determined using surplus serum of 50 healthy adult cats. Surplus serum samples of diabetic cats with known IGF-1 concentration with (n = 32/68) and without HS (n = 36/68) were used for method comparison with RIA. The cut-off for diagnosis of HS was established using receiver operating characteristic (ROC) analysis. The intra-assay coefficient of variation (CV) was ≤4.7%, and the inter-assay CV was ≤5.6% for samples with low, medium, and high IGF-1 concentration. Linearity was excellent (R2 > 0.99). The correlation between CLIA and RIA was very high (rs = 0.97), with a mean negative bias for CLIA of 24.5%. The upper limit of RI was 670 ng/mL. ROC analysis showed an area under the curve of 0.94, with best cut-off for diagnosis of HS at 746 ng/mL (sensitivity, 84.4%; specificity, 97.2%). The performance of CLIA was good, and the RI and cut-off for HS diagnosis established in this study allow for CLIA to be used in routine work-up of diabetic cats.

Pathophysiology of Prediabetes, Diabetes, and Diabetic Remission in Cats.

Diabetes mellitus (DM) has a heterogenous cause, and the exact pathogenesis differs between patients. Most diabetic cats have a cause similar to human type 2 DM but, in some, DM is associated with underlying conditions, such as hypersomatotropism, hyperadrenocorticism, or administration of diabetogenic drugs. Predisposing factors for feline DM include obesity, reduced physical activity, male sex, and increasing age. Gluco(lipo)toxicity and genetic predisposition also likely play roles in pathogenesis. Prediabetes cannot be accurately diagnosed in cats at the current time. Diabetic cats can enter remission, but relapses are common, as these cats might have ongoing, abnormal glucose homeostasis.

Efficacy of hypophysectomy for the treatment of hypersomatotropism-induced diabetes mellitus in 68 cats.

BACKGROUND: Hypersomatotropism (HST) is an increasingly recognized endocrinopathy in cats and is mostly described associated with diabetes mellitus (DM). OBJECTIVES: To evaluate the efficacy and safety of transsphenoidal hypophysectomy in treating HST and DM in cats. ANIMALS: Sixty-eight client-owned cats with HST and DM treated by transsphenoidal hypophysectomy. METHODS: Retrospective cohort study. Medical records were reviewed for glycemic control and serum insulin-like growth factor-1 (IGF-1) concentrations. Postoperative complications, death within 4 weeks, and proportion achieving diabetic remission were recorded. Survival times and DM-free intervals were calculated. RESULTS: Fifty-eight cats (85.3%) were alive 4 weeks postoperatively with 10 (15%) postoperative deaths. Complications included hypoglycemia (n = 9), electrolyte imbalance (n = 9), and transient congestive heart failure (n = 5). Fifty-five cats (95% of 58 surviving cats [81% of all cats undergoing surgery]) had improved control of diabetes. Diabetic remission occurred in 41 cats (71% of 58 surviving cats [60% of all cats]) with insulin administration discontinued after a median of 9 days (range, 2-120). Postoperative 4-week serum IGF-1 concentration nadir was significantly lower in cats achieving diabetic remission (median 20 ng/mL [15-708] than those that did not (324 ng/mL [15-1955]; P = .03). All cats received long-term levothyroxine and hydrocortisone PO, alongside desmopressin (conjunctival) in 38 of 53 cats (72%). Recurrence of DM occurred in 5 of 41 cats (12%) after a median of 248 days (range, 84-1232). Median survival time of all cats was 853 days (range, 1-1740). CONCLUSIONS AND CLINICAL IMPORTANCE: Transsphenoidal hypophysectomy is an effective treatment for cats with HST and DM, with a long-term outcome that compares favorably to existing options.

Pilot study assessing the use of cabergoline for the treatment of cats with hypersomatotropism and diabetes mellitus.

OBJECTIVES: An affordable and effective treatment is needed to manage feline hypersomatotropism. The aim of this study was to assess whether treatment with oral cabergoline for 90 days in cats with hypersomatotropism and diabetes mellitus improved diabetic and insulin-like growth factor 1 (IGF-1) control. METHODS: This was a prospective cohort non-blinded pilot study enrolling client-owned cats with spontaneously occurring diabetes mellitus and hypersomatotropism. Cats received oral cabergoline (5-10 µg/kg q24h) for 90 consecutive days. Serum IGF-1 and fructosamine concentrations were measured on days 1, 30 and 90. Quality of life was determined using the DIAQoL-pet questionnaire on days 1 and 90. RESULTS: Nine cats were enrolled and eight completed the study. There was no significant change in the following: IGF-1 (day 1 median 2001 ng/ml [range 890-2001 ng/ml]; day 30 median 2001 ng/ml [range 929-2001 ng/ml]; day 90 median 1828 ng/ml [range 1035-2001 ng/ml]; χ2(2) = 0.667, P = 0.805); fructosamine (day 1 median 499 µmol/l [range 330-887 µmol/l], day 30 median 551 µmol/l [range 288-722 µmol/l], day 90 median 503 [range 315-851 µmol/l]; χ2(2) = 0.581, P = 0.764); or DIAQoL-pet score (median on day 1 -2.79 [range -4.62 to -0.28], median on day 90 -3.24 [range -4.41 to -0.28]; P = 0.715). There was a significant change of insulin dose (χ2(2) = 8.667, P = 0.008) with cats receiving higher insulin doses at day 90 compared with day 1 (median on day 1 was 0.98 [range 0.63-1.49] and median on day 90 was 1.56 [range 0.49-2.55] units/kg q12h; P = 0.026). CONCLUSIONS AND RELEVANCE: Cabergoline did not improve diabetic control or normalise insulin-like growth factor concentration, or improve patient quality of life.

Updates in Feline Diabetes Mellitus and Hypersomatotropism.

Flash glucose monitoring is a novel, noninvasive monitoring technique that is increasingly used in the management of small animal diabetes. This article provides guidance on the use of flash glucose monitoring in cats and demonstrates how this technique can be used in a range of feline diabetic cases, including those where management is proving challenging. Other aspects of complicated feline diabetic care are also discussed, including management of the sick diabetic cat, potassium depletion myopathy, and treatment options for cats with hypersomatotropism-associated diabetes mellitus. The use of insulin glargine 300 U/ml as a promising new long-acting insulin for diabetic cats is also discussed.

Pituitary Pathology and Gene Expression in Acromegalic Cats.

The prevalence of GH-secreting pituitary tumors in domestic cats (Felis catus) is 10-fold greater than in humans. The predominant inhibitory receptors of GH-secreting pituitary tumors are somatostatin receptors (SSTRs) and D2 dopamine receptor (DRD2). The expression of these receptors is associated with the response to somatostatin analog and dopamine agonist treatment in human patients with acromegaly. The aim of this study was to describe pathological features of pituitaries from domestic cats with acromegaly, pituitary receptor expression, and investigate correlates with clinical data, including pituitary volume, time since diagnosis of diabetes, insulin requirement, and serum IGF1 concentration. Loss of reticulin structure was identified in 15 of 21 pituitaries, of which 10 of 15 exhibited acinar hyperplasia. SSTR1, SSTR2, SSTR5, and DRD2 mRNA were identified in the feline pituitary whereas SSTR3 and SSTR4 were not. Expression of SSTR1, SSTR2, and SSTR5 was greater in acromegalic cats compared with controls. A negative correlation was identified between DRD2 mRNA expression and pituitary volume. The loss of DRD2 expression should be investigated as a mechanism allowing the development of larger pituitary tumors.

Acceptance of home blood glucose monitoring by owners of recently diagnosed diabetic cats and impact on quality of life changes in cat and owner.

Objectives This study aimed to evaluate the acceptance of home blood glucose monitoring (HBGM) by owners of recently diagnosed diabetic cats, and the impact of choosing HBGM on the quality of life (QoL) changes of cat and owner, in addition to glycaemic changes during 6 months of follow-up. Methods Owners of cats diagnosed with diabetes mellitus (DM) and treated with insulin for 6-20 weeks were divided into an HBGM group and a non-HBGM group, based on their ability and willingness to perform HBGM after a standardised instruction session. The HBGM acceptance level and reasons for acceptance failure were documented; a questionnaire evaluated owners' experiences. For the following 6 months, changes in QoL, measured using the validated DIAQoL-pet quantification tool, and changes in glycaemic control parameters (clinical signs, serum fructosamine, blood glucose curve average/minimal/maximal/pre-insulin blood glucose) were compared between HBGM and non-HBGM groups at months 1, 3 and 6, as well as within the groups between baseline and months 1, 3 and 6. Results Thirty-eight cats were enrolled; 28 (74%) entered the HBGM group. There was no significant difference between groups in overall DIAQoL-pet score or glycaemic control parameters at any time point apart from the maximal blood glucose at month 6 (lower in the HBGM group). However, the DIAQoL-pet score, including indicators of owner worry about DM, worry about hypoglycaemia and costs, as well as glycaemic parameters, improved at all time points within the HBGM group but not within the non-HBGM group. Remission occurred in 9/28 (32%) HBGM group cats and 1/10 (10%) non-HBGM group cats ( P = 0.236). Conclusions and relevance HBGM was adopted successfully by most diabetic cat owners. Despite the extra task, positive changes in QoL parameters occurred in the HBGM group and not in the non-HBGM group. Although no difference was found in glycaemic control between the HBGM and non-HBGM groups during the 6 months of follow-up, significant glycaemic improvements were documented in the HBGM group.

Prospective evaluation of a protocol for transitioning porcine lente insulin-treated diabetic cats to human recombinant protamine zinc insulin.

Objectives The objective was to evaluate a nadir-led protocol for transitioning porcine lente insulin suspension (PLIS)-treated diabetic cats onto human recombinant protamine zinc insulin (PZIR). Methods Recently diagnosed (<5 months) diabetic cats, treated with PLIS q12h for ⩾6 weeks, were recruited. Fructosamine, 24 h blood glucose curve (BGC), quality of life assessment (DIAQoL-pet score) and Diabetic Clinical Score (DCS) were assessed at enrolment (PLIS-treated) and 2, 4 and 12 weeks after transitioning to PZIR (starting dose 0.2-0.7 U/kg q12h). Short duration of insulin action was defined as <9 h. Linear mixed effects modelling assessed for change in fructosamine, mean blood glucose (MBG) during BGCs, DIAQoL-pet score, DCS and q12h insulin dose. McNemar's tests compared the proportion of cats with hypoglycaemia at week 0 (PLIS-treated) and week 4 (PZIR-treated). Results Twenty-two cats were recruited. Median PLIS dose at enrolment was 0.5 U/kg (interquartile range 0.3-0.7 U/kg) q12h, equalling median PZIR starting dose (0.5 U/kg; interquartile range 0.3-0.7 U/kg q12h). Transitioning was followed by significant decreases in fructosamine ( P = 0.00007), insulin dose ( P = 0.02), DCS ( P = 8.1 × 10-8) and DIAQoL-pet score ( P = 0.003), indicating improved quality of life. MBG did not alter significantly ( P = 0.1). Five cats (22.7%) achieved remission. Hypoglycaemia was recorded in 30/190 12 h BGCs (15.8%) and five cats experienced clinical hypoglycaemia. The proportion of cats with hypoglycaemia did not differ between PLIS (week 0) and PZIR (week 4) ( P = 1.0). Duration of action was analysed in 19 cats. Six cats (31.6%) showed short duration of action on PLIS, compared with two cats (10.5%) after 4 weeks on PZIR. All six cats with short PLIS duration showed duration of ⩾9 h on PZIR. Conclusions and relevance Used alongside a low-carbohydrate diet, transitioning to PZIR was associated with significantly improved clinical signs and quality of life, with some cats achieving remission. Transition to PZIR should be considered for cats with short duration of action on PLIS.

Systematic review of feline diabetic remission: separating fact from opinion.

It is increasingly recognised that diabetic remission is possible in the cat. This systematic review, following Cochrane Collaboration (CC) guidelines, critically appraises the level of evidence on factors influencing remission rate and factors predicting remission. A systematic online, bibliographic search and reference list examination was conducted. A level of evidence was assigned to each identified article by five internists using the Newcastle-Ottawa Scale for follow-up, cohort, case-series and case-control studies, the CC's risk of bias tool for trials and the Cochrane Effective Practice and Organisation of Care Group risk of bias criteria for before and after trials. Twenty-two studies were included in the review, assessing influence of pharmaceutical intervention (n = 14) and diet (n = 4), as well as diagnostic tests (n = 9) and feline patient characteristics (n = 5) as predictors of remission. The current level of evidence was found to be moderate to poor. Common sources of bias included lack of randomisation and blinding among trials, and many studies were affected by small sample size. Failure to provide criteria for the diagnosis of diabetes, or diabetic remission, and poor control of confounding factors were frequent causes of poor study design. Addressing these factors would significantly strengthen future research and ultimately allow meta-analyses to provide an excellent level of evidence. No single factor predicts remission and successful remission has been documented with a variety of insulin types and protocols. Dietary carbohydrate reduction might be beneficial, but requires further study. A lack of well-designed trials prevents reliable remission rate comparison. Factors associated with remission resemble those in human medicine and support the hypothesis that reversal of glucotoxicity is a major underlying mechanism for feline diabetic remission.