Zinc Insulin Research Articles

Weekly Insulin Becoming a Reality

Insulin was first isolated in 1921 and developed as a therapeutic agent in the 1920s. The initial crude preparations were injected multiple times daily because of their short duration of action. Consequently, there were many attempts to develop insulin preparations with prolonged biological availability in the hope that less frequent once-daily administration would be feasible (1). A host of such preparations were introduced, including protamine insulin, protamine zinc insulin, surfen insulin, globin insulin, iso-insulin, isophane insulin (NPH), and insulin zinc suspensions (lente insulins) (1) (Fig. 1). The goal was mainly to reduce the number of injections and thus the patient burden. Yet, with the development of a radioimmunoassay for insulin (2), it became apparent that physiologic insulin secretion involved two components: meal-related insulin secretion with postprandial spikes and basal insulin secretion that remains relatively constant with some minor pulsatility (3). Subsequently, as modern insulin therapy evolved, facilitated by patient self-monitoring of blood glucose (4,5), it became apparent that the inherent peaks in basal insulin preparations, such as with the nonsoluble NPH or lente insulins, created risk of hypoglycemia, especially if the insulin vials were not correctly rolled to create a proper suspension. Moreover, these insulins did not have sufficiently long duration of action to be used once daily. Consequently, in addition to making them soluble, two of the goals in development of basal insulin analogs, such as insulin glargine and insulin detemir, were to eliminate insulin peaks and to prolong the action to approach 24 h (6,7). Second-generation basal insulin analogs, such as insulin degludec and insulin glargine U300, came with …

Prevention of Postprandial Hyperglycemia by Ophthalmic Nanoparticles Based on Protamine Zinc Insulin in the Rabbit.

Postprandial hyperglycemia, a so-called blood glucose spike, is associated with enhanced risks of diabetes mellitus (DM) and its complications. In this study, we attempted to design nanoparticles (NPs) of protamine zinc insulin (PZI) by the bead mill method, and prepare ophthalmic formulations based on the PZI-NPs with (nPZI/P) or without polyacrylic acid (nPZI). In addition, we investigated whether the instillation of the newly developed nPZI and nPZI/P can prevent postprandial hyperglycemia in a rabbit model involving the oral glucose tolerance test (OGTT). The particle size of PZI was decreased by the bead mill to a range for both nPZI and nPZI/P of 80–550 nm with no observable aggregation for 6 d. Neither nPZI nor nPZI/P caused any noticeable corneal toxicity. The plasma INS levels in rabbits instilled with nPZI were significantly higher than in rabbits instilled with INS suspensions (commercially available formulations, CA-INS), and the plasma INS levels were further enhanced with the amount of polyacrylic acid in the nPZI/P. In addition, the rapid rise in plasma glucose levels in OGTT-treated rabbits was prevented by a single instillation of nPZI/P, which was significantly more effective at attenuating postprandial hyperglycemia (blood glucose spike) in comparison with nPZI. In conclusion, we designed nPZI/P, and show that a single instillation before OGTT attenuates the rapid enhancement of plasma glucose levels. These findings suggest a better management strategy for the postprandial blood glucose spike, which is an important target of DM therapy.

67863 Insulin use and depigmentation: a survey of real-world evidence

ABSTRACT IMPACT: Long-acting insulin containing protamine is more likely to be associated with skin depigmentation. OBJECTIVES/GOALS: An acquired disorder, skin depigmentation was found to be significantly correlated with diabetes. While a recent meta-analysis pointed at a possible similar pathogenesis, the possibility of vitiligo occurring as a drug-induced disease was never explored. This study aimed at elucidating whether utilization of specific insulins may play a role. METHODS/STUDY POPULATION: Records from the Medical Panels Expenditure Survey (MEPS) database made available by the Agency for Healthcare Research and Quality were used to identify all injectable insulin users (n=8867). ICD-9/10 codes were abstracted from the medical conditions files for all the subjects reporting any type of injectable insulin use (1996-2017). Skin depigmentation codes identified in our dataset were 709 and L81. Insulins were categorized based on duration of action, short-acting (SA), intermediate-acting (IA), and long-acting (LA), as well as based on formulation ingredients (zinc, protamine-zinc, other), and insulin combination (SA with or without IA/LA containing or not protamine-zinc). The association between skin depigmentation occurrence and insulin type and/or category was assessed by Fisher’s exact test. RESULTS/ANTICIPATED RESULTS: A total of 225 out of 8867 individuals were diagnosed with skin depigmentation. Incidence of skin depigmentation was 2.25% in SA users (n1=3606, p=0.355), 2.24% in LA users (n2=3910, p=0.337), and 2.39% in IA users (n3=4015, p=0.062). Occurrence of skin depigmentation was similar between users of insulin mono- or combo therapy (p=0.758). Interestingly, among IA insulins, insulin protamine-zinc insulin (n4=3992) distinguished as being mainly responsible for the association with the occurrence of skin depigmentation (p=0.062), whereas insulin zinc was not (n5=37, p=1.000). The highest skin depigmentation incidence was observed among Pacific Islanders (2.66%, p=0.110). Males distinguished by a skin depigmentation incidence of 2.34% vs. 1.91% in females (p=0.086). DISCUSSION/SIGNIFICANCE OF FINDINGS: We report that presence of protamine-zinc may play a role in the development of skin depigmentation. It is uncertain whether this risk may be shared equally by insulin users diagnosed with type 1 and type 2 diabetes. Of note, we observed a higher skin depigmentation incidence than that reported by community- (0.2%) or hospital-based (1.8%) studies.

Functionality of receptor targeted zinc-insulin quantum clusters in skin tissue augmentation and bioimaging

Quantum clusters with target specificity are suitable for tissue-specific imaging. In the present work, amorphous zinc insulin quantum clusters (IZnQCs) had been synthesised to promote and monitor wound recovery. Easy synthesis, biocompatibility, stability, enhanced quantum yield, and solubility made the cluster suitable for preclinical/clinical exploration. Zn2+ is known for its binding to insulin hexamer. Here we report the reformation of the structure in a quantum cluster form in the presence of Zn2+. The formation of IZnQCs was confirmed by the change in zeta potential from −25.6 mV to −17.9 mV and also the formation of protein metal interaction was confirmed in FTIR bands at 450, 480, and 613 cm−1 for Zn–O, Zn–N, and Zn–S, respectively. HRTEM-EDS and SAED data analysis showed an amorphous nature of the cluster. The binding of IZnQCs to the cells has been confirmed using confocal microscopy. IZnQCs showed a synergistic effect in wound recovery than insulin or Zn2+ alone. Further due to high fluorescence this recovery process can be monitored under an appropriate setup. Wound healing promotional activity, target specificity, and fluorescence properties make the IZnQCs ideal to use for bioimaging along with promoting and monitoring of wound recovery agent.

Correlation of Obesity Status with Zinc Serum Levels and Insulin Resistance in Perimenopause Obese Women

Background : Obesity is one of the global health problems. The prevalence of obesity in women is higher than men. Various metabolic problems are caused by obesity, such as insulin resistance and deficiency of micronutrients such as zinc. The occurrence of insulin resistance in obesity is also influenced by zinc deficiency.Objectives : To analyse the correlation of obesity status with serum zinc levels and insulin resistance in perimenopause obese women.Methods : Correlational research with 62 perimenopause obese women subject aged 40-50 years old who met the inclusion and exclusion criteria. Serum zinc levels were measurement using AAS and insulin resistance using HOMA IR formula. Serum zinc levels, fasting insulin, fasting blood glucose taken from venous blood. Hypothesis testing uses Pearson correlation.Results : 12.9% had low serum zinc levels and high HOMA IR 9.09%. There was a significant negative correlation between BMI with serum zinc levels (r = -0.402; p = 0.001) and significant positive correlation between BMI with insulin resistance (r = 0.396; p = 0.001). There was a significant negative correlation between WC with serum zinc levels (r = -0.18 , p = 0.161) and significant positive correlation between WC with insulin resistance ( r =0.284 , p =0.025 ). and significant negative correlation between serum zinc levels with insulin resistance (r = -0.404; p = 0.001).Conclusion : There is a correlation between obesity status with serum zinc levels and correlation between obesity status with insulin resistance in perimenopause obese women.

New drugs for small animals in 2019

In 2019, 2 novel pharmaceutical agents for small animals were released on the German market: The non-steroidal, non-cyclooxygenase inhibiting anti-inflammatory agent grapiprant (Galliprant®) of the piprant class as well as fluorescein (Ophtorescein®), a xanthen dye-based diagnostic agent for corneal defects. One substance was authorized for an additional species: The antidiabetic protamine zinc insulin of human origin (ProZinc®) is now additionally authorized for dogs. Additionally, one veterinary drug with a new combination of active ingredients (fluralaner + moxidectin), 5 agents in a novel pharmaceutical formulation (acepromazine, chloramphenicol, dexamethasone, metronidazole, torasemide), one drug (lidocaine) with a new route of administration, as well as one agent (apomorphine) in a new primary packaging with extended opening stability have been launched on the market for small animals.

IS SERUM ZINC LEVEL CORRELATED WITH INSULIN RESISTANCE AMONG LACTATING MOTHERS IN JAKARTA?

Introduction: Insulin resistance is a condition that underlies the development of diabetes mellitus. The prevalence of diabetes mellitus keeps rising, including in Indonesia. A higher proportion of diabetes was found in women. Physiological changes during pregnancy can cause insulin resistance that may persist until postpartum period. Lactation and nutrient like zinc may improve insulin resistance. This study aimed to measure the correlation between zinc serum level and insulin resistance of lactating mothers in Jakarta.Methods: This study used cross-sectional design, was conducted in Puskesmas Kecamatan Grogol Petamburan, West Jakarta and Puskesmas Kecamatan Cilincing, North Jakarta from February to April 2019. A total of 75 lactating mothers at 3–6 months postpartum were selected using consecutive sampling method. Zinc serum was analyzed using atomic absorption spectrophotometry (AAS) method. Insulin resistance was assessed using the homeostasis model assessment-insulin resistance (HOMA-IR).Results: Approximately 76% (n = 57) subjects had low serum zinc level. Spearman correlation test between serum zinc level and HOMA-IR was done (r = 0.003, p = 0.977). Also, correlation test between BMI and HOMA-IR (r = 0.563, p <0.001).Conclusion: No correlation was found between serum zinc level and HOMA-IR however, there was a significant moderate positive correlation between BMI and HOMA-IR.Keywords: Lactation, zinc, insulin resistance, HOMA-IR, BMI

The High Cost of Insulin in the United States: An Urgent Call to Action

The High Cost of Insulin in the United States: An Urgent Call to Action

Role of Tmem163 in zinc-regulated insulin storage of MIN6 cells: Functional exploration of an Indian type 2 diabetes GWAS associated gene

Genome wide association study for type 2 diabetes discovered TMEM163 as a risk locus. Perturbations in TMEM163 expression was reported to be associated with impaired intracellular zinc homeostasis. Physiological concentration of zinc is instrumental to maintain insulin storage and functionality in pancreatic β cells. We found abundant TMEM163 expression in human pancreas, both at transcriptional and translational levels. Knockdown of endogenous Tmem163 in MIN6 cells resulted in increased intracellular zinc and total insulin content, coupled with compromised insulin secretion at high glucose stimuli. Furthermore, Tmem163 knockdown led to enhanced cellular glucose uptake. Upon next generation sequencing, one-third of the studied T2D patients were found to have a novel missense variant in TMEM163 gene. Study participants harboring this missense variant displayed a trend of higher glycemic indices. This is the first report on exploring the biological role of TMEM163 in relation to T2D pathophysiology.

Effectiveness of topical insulin in the management of diabetic foot ulcers.

Introduction: Diabetes mellitus is one of the most common metabolic disorders affecting a large part of our population. Apart from its effect on all organ systems, these metabolic derangements affect other processes in the body as well. Diabetic wounds are difficult to treat with conventional treatments. Delayed wound healing has led to increased morbidity and mortality in the population. Increased blood glucose leads to ineffective angiogenesis and less collagen deposition. In various studies long acting insulin zinc suspension has been shown to augment wound healing without any harmful effects. Objectives: To find out the advantages of topical insulin in the management of diabetic foot ulcers. Study Design: Observational study. Setting: Plastic Surgery and General Surgery Department, Baqai Medical University Karachi. Period: January 2014 to December 2016. Material and Methods: Patients visiting the Surgical OPD with diabetes mellitus and concomitantly having foot ulcers were included in the study. Diabetics having blood glucose levels of 110-130 gm/dl and ulcers measuring more than one cm on the dorsum of the foot were included in the study. All patients having foot ulcers were treated by daily topical spray of 1cc saline mixed with 5 units of insulin. This treatment was continued for 12 weeks or till the time ulcer was completely healed (whichever was earlier) and ulcer size was measured weekly. Ulcer size and depth before and after treatment was measured. Results: We had a total of 65 participants, among them there were 52 males and 13 females presenting with diabetic foot ulcer. Around 87.6% (n=57) patients had type 2 diabetes mellitus whereas 12.3% (n=8) patients had type 1 diabetes mellitus. Upon examination of the patient the location, size and depth of the ulcer was measured as well. These parameters were measured before and after treatment by topical insulin spray. Right foot ulcers were present in 64.6% of the patients and 35.38% patients had left foot ulcers. The mean size and depth of ulcer was 5.1 + 1.1 cm2 and 8.7 + 0.12 mm respectively. After treatment the mean size and depth of ulcer was found to be 1 + 0.04cm2 and 1.4 + 0.12mm respectively. Conclusion: There was significant improvement after treatment of diabetic foot ulcers with topical insulin spray. The wound size and depth were considerably decreased. This treatment had more promising results than conventional treatment methods for diabetic foot ulcers.

Smart thermosensitive copolymer incorporating chitosan–zinc–insulin electrostatic complexes for controlled delivery of insulin: effect of chitosan chain length

This work was designed to optimize the thermosensitive copolymeric depot-based system for delivering insulin at a controlled rate for a prolonged period following a single subcutaneous injection. The intrinsic ability of insulin to form hexamers in the presence of zinc and electrostatic complexes with chitosan (CS) were explored for improving stability and release characteristics of insulin through the copolymeric depot. CS–zinc–insulin complexes were prepared using CS of different chain lengths (5, 30, 50, and 200 kDa). Effect of different chain lengths of CS on the thermal stability, binding constant, and release profile of insulin was determined. Increasing chain length of CS demonstrated increasing thermal stability of insulin. However, the higher chain length of CS adversely affected the release profile of insulin. Hydrolytic degradation analysis showed rapid degradation of the copolymer in a formulation containing higher chain length of CS (200 kDa)–zinc–insulin complexes, implying the formation of bigger pores and channels in the copolymeric matrix during the initial release in this system. However, a formulation containing a smaller chain length of CS (5 kDa)–zinc–insulin complexes demonstrated slow copolymer degradation and sustained insulin release profile. Additionally, CS–zinc–insulin complexes were effective in preserving the stability of insulin during the entire duration of release and storage.

The association between serum zinc levels and insulin resistance among polycystic ovary syndrome patients in Duhok City, Kurdistan Region, Iraq

Background: Polycystic ovary syndrome (PCOS) is a relatively common endocrine and metabolic problem. Patients with PCOS are known to have a higher incidence of insulin resistance. The homeostasis model assessment (HOMA) is an indirect, rapid, accurate, and cost-effective method of assessing insulin resistance based on patient's fasting plasma insulin and glucose concentrations. Several studies have reported a significant correlation between HOMA and the traditional hyperinsulinemic-euglycemic clamp method. Zinc deficiency promotes insulin resistance, and that zinc supplementation can prevent or, at least, alleviate insulin resistance in selected patient populations. Objective: The current study primarily aims at defining the association between insulin resistance and zinc deficiency among both PCOS and selected controls. It also looks at certain risk factors associated with obesity among the study population in Duhok City, Kurdistan Region, Iraq. Materials and Methods: The current case–control study was performed at Azadi Teaching Hospital/Gynecological Outpatient Clinic in Duhok City/Kurdistan Region/Iraq. The study included 80 women (40 cases with PCOS and 40 controls of healthy women). Results: There was no age difference between both groups (Mean = 26.77 years, standard deviation [SD] = 6.42 years for PCOS cases versus mean and SD of 27.57 years and 6.45 years, respectively; P= 0.48). Likewise, there was no difference in the serum zinc levels between cases and controls. However, patients with PCOS had significantly higher Body mass index and HOMA scores compared to the controls (P = 0.005 and 0.007, respectively). Conclusion: Higher serum zinc levels are independently associated with lower HOMA. Patients with PCOS had significantly higher insulin resistance when compared to the controls of similar age and zinc level.

Comparing lente insulin and NPH insulin for treating diabetic dogs

Diabetes mellitus is the second most common endocrinopathy in dogs. Once diagnosed, almost all dogs will require daily insulin administration for life. The most commonly used insulin types are neutral...

Comparison of the pharmacodynamics of protamine zinc insulin and insulin degludec and validation of the continuous glucose monitoring system iPro2 in healthy cats

With the aim to improve current therapeutic and monitoring options for diabetic cats, the present study compared pharmacodynamic parameters of protamine zinc insulin (PZI) and insulin degludec and validated the continuous glucose monitoring system (CGMS) iPro2 with Sof-sensor and Enlite-sensor focusing on the low glycemic range.Three doses (0.1, 0.2 and 0.3IU/kg) of the two insulin preparations and the CGMS iPro2 with two different sensors were tested in six healthy cats. After each insulin administration, onset of action, time to glucose nadir and duration of action were calculated by measuring glucose concentrations with a portable blood glucose meter (PBGM). After sensor placement, paired PBGM and sensor glucose measurements were done and analytical and clinical accuracy were calculated according to the ISO 15197:2013 criteria.Onset of action, time to glucose nadir and glucose nadir were similar for both insulin formulations. Duration of action of insulin degludec was significantly longer than those of PZI at 0.1IU/kg (P=0.043) and 0.2IU/kg (P=0.043). Overall, 166/191 (87%) Sof-sensor measurements and 106/121 (88%) Enlite-sensor measurements met ISO criteria for analytical accuracy, and all sensor measurements fulfilled ISO criteria for clinical accuracy.Insulin degludec was well tolerated in healthy cats and showed longer duration of action than PZI. Further studies on the use of insulin degludec in diabetic cats might be recommended. Both sensors had good clinical accuracy, when used with the CGMS iPro2, but the analytical accuracy was below the minimum set by ISO 15197:2013.

Effect of process variables on formulation, in-vitro characterisation and subcutaneous delivery of insulin PLGA nanoparticles: An optimisation study

This study was initiated to investigate the effect of PLGA concentration, PVA concentration, internal to external phase ratio (IEPR), PEG molecular weight and concentration on mean particle size, zeta potential, polydispersity index (PDI), percentage drug entrapment and in vitro release profile. Using PLGA (50:50) as the carrier, insulin nanoparticles (NP) were prepared using double emulsion solvent evaporation technique. The particle size was analysed by dynamic light scattering (DLS) and the geometrical shape was examined using scanning electron microscopy (SEM). Mean particle size was highly dependent on the combined effect of PLGA and PVA concentrations. Drug entrapment would be greatly controlled by PLGA concentration and internal to external phase ratio. Addition of PEG could modulate in vitro release behavior of insulin with initial burst at the first 12 h and sustain the drug release for 6 days. Insulin integrity was assessed in vitro using MALDI-TOF mass spectroscopy. The optimised NP formulation, had particle size of 202.60 nm and percent entrapment efficiency (EE) equal to 67.72%, was tested in vivo to examine its hypoglycemic effect after subcutaneous injection. Insulin NP had a significant hypoglycemic effect comparing to free insulin (p < 0.01) and insulin zinc suspension (p < 0.05).

Zinc Supplementation Does Not Alter Indicators of Insulin Secretion and Sensitivity in Black and White Female Adolescents

Background: Zinc is a micronutrient involved in the production of, and peripheral sensitivity to, pancreatic β cell-derived insulin. To our knowledge, the effect of zinc supplementation on insulin outcomes, and potential risk of diabetes, in otherwise healthy children in the United States has not been investigated.Objective: The objective of this study was to determine the influence of zinc supplementation on insulin outcomes in black and white girls in the early stages of adolescence. A secondary objective was to determine relations between baseline zinc concentrations and insulin outcomes.Methods: Healthy black and white girls aged 9-11 y were randomly assigned to daily supplementation of zinc (9 mg elemental Zn/d; n = 75; blacks: n = 35) or placebo (n = 72; blacks: n = 32) for 4 wk. Fasting serum insulin, glucose, and C-peptide were assessed at baseline and at 4 wk. C-peptide and glucose values were used to calculate the computer model-derived homeostatic model assessment of insulin resistance (HOMA2-IR). Changes in outcome measures were compared by using repeated-measures, mixed-model ANOVA.Results: Baseline plasma zinc was not correlated with C-peptide (r = -0.07), insulin (r = -0.06), or HOMA2-IR (r = -0.09) (all P > 0.05) after controlling for race and age. Treatment × time interactions for C-peptide and HOMA2-IR were not significant (both P > 0.05). Although the treatment × race × time interactions for C-peptide and HOMA2-IR were not significant (both P = 0.08), black girls who received the placebo experienced slight increases in C-peptide (15.7%) and HOMA2-IR (17.7%) (P = 0.06).Conclusions: Four weeks of zinc supplementation had no effect on insulin outcomes in healthy black and white early-adolescent girls, although C-peptide and HOMA2-IR tended to increase in black girls who received placebo. Additional trials that are appropriately powered should further explore the effect of zinc on markers of diabetes risk, and whether race affects this relation. This trial was registered at clinicaltrials.gov as NCT01892098.

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.

Comparison of the impact of human vs analogue insulins on glycosylated haemoglobin in a population with diabetes mellitus

To compare the effect on metabolic control of treatment with conventional and analogue insulins for patients with diabetes mellitus. Retrospective cohort study held in cities of Colombia (Pereira and Manizales). People insured by the paid healthcare system, who were diagnosed with diabetes mellitus type 1 and 2, and treated with conventional and analogue insulin for at least 6months prior to the start of the study were sampled and followed up for 18months. Data were collected from clinical records for each patient. Treatment groups were compared according to the type of insulin received. A total of 313 patients were included; overall, 56.9% were women and the mean age was 57.3 years. No statistically significant difference was found in glycosylated haemoglobin reduction at 3, 6 and 18months when comparing patients receiving glargine vs NPH insulin (P=.403) and NPH plus zinc crystalline insulin vs glargine plus glulisine (P=.514). The percentage of patients with metabolic control increased from 27.8% to 34.2% during follow-up with all types of insulin. Insulin analogues were not superior to human insulin for glycaemic control. A significant proportion of patients did not attain the treatment goals; therefore, it is necessary to implement measures to improve the monitoring and control of diabetes mellitus.

Local application of low-dose insulin in improving wound healing after deep burn surgery.

The clinical effects of local application of low-dose insulin in improving wound healing after deep burn self-skin transplantation surgery were examined. Fifty-eight patients with deep burns were selected and randomly divided into 3 groups. In the blank control group, normal saline was injected to the subcutaneous tissue of wounds; in large dose insulin group, 1.0 µ long-term suspended zinc insulin was locally injected; and in the low-dose insulin group, 0.1 µ long-term suspended zinc insulin was locally injected. The healing effects were compared. After 7 and 14 days of treatments, wound surface area in the low-dose group was significantly smaller than in the other groups, and differences were statistically significant (P<0.05); wound healing duration and infection rate for patients in the low-dose group were significantly lower, class A healing rate was significantly improved, and the differences were statistically significant (P<0.05). Insulin resistance index (HOMA-IR) in the low-dose group was significantly lower, insulin secretion index (HOMA-β) and the insulin sensitivity index (HOMA-ISI) significantly increased. The expression levels of vascular endothelial growth factor and tumor necrosis factor-α in local tissue for the low-dose group were significantly higher than those in the other two groups. Differences were statistically significant (P<0.05). In conclusion, local application of low-dose insulin can effectively improve wound healing after deep burn surgeries.

Evaluation of insulin-like growth factor-1, total thyroxine, feline pancreas-specific lipase and urinary corticoid-to-creatinine ratio in cats with diabetes mellitus in Switzerland and the Netherlands.

Objectives The aim of the study was to evaluate circulating insulin-like growth factor-1 (IGF-1), feline pancreas-specific lipase (fPLI) and total thyroxine (TT4) concentrations and urinary corticoid-to-creatinine ratio (UCCR) as indicators for the prevalence of acromegaly, pancreatitis, hyperthyroidism and hypercortisolism in cats with diabetes mellitus. Methods Blood and urine samples were collected from diabetic cats treated in primary care clinics in Switzerland and the Netherlands. Standardised questionnaires and physical examination forms provided clinical information from owners and veterinarians. Laboratory testing included serum biochemistry profile analysis and measurement of circulating fructosamine, IGF-1, fPLI, and TT4 concentrations and UCCR. CT of the pituitary gland was performed using a multidetector computed tomography scanner. Results Blood samples were available from 215 cats and urine samples were collected at home from 117 cats. Age ranged from 2-18 years (median 12 years) and body weight from 2.7-12.3 kg (median 5.5 kg). Sixty-five percent of the cats were castrated male and 35% were female (33% spayed); 82% were domestic shorthair cats. Eighty percent of cats received a porcine insulin zinc suspension, 19.5% insulin glargine and 0.5% a human neutral protamine hagedorn insulin. Thirty-six of 202 (17.8%) cats had IGF-1 concentrations >1000 ng/ml. Serum fPLI, and TT4 concentrations and UCCR were increased in 86/196 (43.9%), 9/201 (4.5%) and 18/117 cats (15.3%), respectively. Prevalence did not differ between countries. Conclusions Hyperthyroidism is rare, whereas increased fPLI concentration, possibly reflecting pancreatitis, is common in diabetic cats. The high UCCR may reflect activation of the hypothalamus-pituitary-adrenal axis, which also occurs in diabetic humans. The percentage of cats with increased IGF-1 was high but lower than reported in recent studies.