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Veterinary Medicine (Auckland, N.Z.) 2015Insulin therapy is still the primary therapy for all diabetic dogs and cats. Several insulin options are available for each species, including veterinary registered... (Review)
Review
Insulin therapy is still the primary therapy for all diabetic dogs and cats. Several insulin options are available for each species, including veterinary registered products and human insulin preparations. The insulin chosen depends on the individual patient's requirements. Intermediate-acting insulin is usually the first choice for dogs, and longer-acting insulin is the first choice for cats. Once the insulin type is chosen, the best method of insulin administration should be considered. Traditionally, insulin vials and syringes have been used, but insulin pen devices have recently entered the veterinary market. Pens have different handling requirements when compared with standard insulin vials including: storage out of the refrigerator for some insulin preparations once pen cartridges are in use; priming of the pen to ensure a full dose of insulin is administered; and holding the pen device in place for several seconds during the injection. Many different types of pen devices are available, with features such as half-unit dosing, large dials for visually impaired people, and memory that can display the last time and dose of insulin administered. Insulin pens come in both reusable and disposable options. Pens have several benefits over syringes, including improved dose accuracy, especially for low insulin doses.
PubMed: 30101100
DOI: 10.2147/VMRR.S39984 -
Journal of Veterinary Internal Medicine Sep 2021Day-to-day variability impacts safety of insulin therapy and the choice of monitoring strategies. Side-by-side comparisons of insulin formulations in diabetic dogs are...
BACKGROUND
Day-to-day variability impacts safety of insulin therapy and the choice of monitoring strategies. Side-by-side comparisons of insulin formulations in diabetic dogs are scarce.
HYPOTHESIS/OBJECTIVES
Insulin glargine 300 U/mL (IGla300) and insulin degludec (IDeg) are associated with less day-to-day glucose variability compared to porcine lente (PL) in diabetic dogs.
ANIMALS
Seven intact male purpose-bred beagles with toxin-induced diabetes.
METHODS
In this repeated measured study, PL, IGla300 and IDeg were compared in 2 phases: once-daily (q24h) and twice-daily (q12h) administration. Interstitial glucose concentrations (IG) were measured continuously throughout the study. For each formulation, maximal q24h dose was determined using the same algorithm (while avoiding hypoglycemia) and then maintained for 72 hours. In phase 2, 70% of the maximal q24h dose was administered q12h and maintained for 5 days regardless of hypoglycemia. Coefficient of variation (CV) and glycemic variability percentage (GVP) were calculated to determine day-to-day and intraday variability, respectively.
RESULTS
There was no difference in day-to-day variability between PL, IGla300, and IDeg in the q24h phase. In the q12h phase, day-to-day variability was higher (P = .01) for PL (CV = 42.6 ± 6.8%) compared to IGla300 and IDeg (CV = 30.1 ± 7.7%, 25.2 ± 7.0%, respectively). The GVP of PL was lower (P = .02) compared to IGla300. There was no difference between PL, IGla300 and IDeg in %time IG < 70 mg/dL.
CONCLUSIONS AND CLINICAL IMPORTANCE
Insulin degludec and IGla300 administered q12h were associated with lower day-to-day variability, which might be advantageous in minimizing monitoring requirements without increasing the risk of hypoglycemia.
Topics: Animals; Blood Glucose; Diabetes Mellitus; Diabetes Mellitus, Type 2; Dog Diseases; Dogs; Glycated Hemoglobin; Hypoglycemic Agents; Insulin Glargine; Insulin, Long-Acting; Male; Swine; Swine Diseases
PubMed: 34241910
DOI: 10.1111/jvim.16178 -
Open Heart 2015The α-glucosidase inhibitor acarbose, which slows carbohydrate digestion and blunts postprandial rises in plasma glucose, has long been used to treat patients with type... (Review)
Review
The α-glucosidase inhibitor acarbose, which slows carbohydrate digestion and blunts postprandial rises in plasma glucose, has long been used to treat patients with type 2 diabetes or glucose intolerance. Like metformin, acarbose tends to aid weight control, postpone onset of diabetes and decrease risk for cardiovascular events. Acarbose treatment can favourably affect blood pressure, serum lipids, platelet aggregation, progression of carotid intima-media thickness and postprandial endothelial dysfunction. In mice, lifetime acarbose feeding can increase median and maximal lifespan-an effect associated with increased plasma levels of fibroblast growth factor 21 (FGF21) and decreased levels of insulin-like growth factor-I (IGF-I). There is growing reason to suspect that an upregulation of fasting and postprandial production of glucagon-like peptide-1 (GLP-1)-stemming from increased delivery of carbohydrate to L cells in the distal intestinal tract-is largely responsible for the versatile health protection conferred by acarbose. Indeed, GLP-1 exerts protective effects on vascular endothelium, the liver, the heart, pancreatic β cells, and the brain which can rationalise many of the benefits reported with acarbose. And GLP-1 may act on the liver to modulate its production of FGF21 and IGF-I, thereby promoting longevity. The benefits of acarbose are likely mimicked by diets featuring slowly-digested 'lente' carbohydrate, and by certain nutraceuticals which can slow carbohydrate absorption. Prebiotics that promote colonic generation of short-chain fatty acids represent an alternative strategy for boosting intestinal GLP-1 production. The health benefits of all these measures presumably would be potentiated by concurrent use of dipeptidyl peptidase 4 inhibitors, which slow the proteolysis of GLP-1 in the blood.
PubMed: 25685364
DOI: 10.1136/openhrt-2014-000205 -
Diabetes, Obesity & Metabolism Jan 2017Manufacturers of insulin products for diabetes therapy have long sought ways to modify the absorption rate of exogenously administered insulins in an effort to better... (Review)
Review
Manufacturers of insulin products for diabetes therapy have long sought ways to modify the absorption rate of exogenously administered insulins in an effort to better reproduce the naturally occurring pharmacokinetics of endogenous insulin secretion. Several mechanisms of protraction have been used in pursuit of a basal insulin, for which a low injection frequency would provide tolerable and reproducible glucose control; these mechanisms have met with varying degrees of success. Before the advent of recombinant DNA technology, development focused on modifications to the formulation that increased insulin self-association, such as supplementation with zinc or the development of preformed precipitates using protamine. Indeed, NPH insulin remains widely used today despite a frequent need for a twice-daily dosing and a relatively high incidence of hypoglycaemia. The early insulin analogues used post-injection precipitation (insulin glargine U100) or dimerization and albumin binding (insulin detemir) as methods of increasing therapeutic duration. These products approached a 24-hour glucose-lowering effect with decreased variability in insulin action. Newer basal insulin analogues have used up-concentration in addition to precipitation (insulin glargine U300), and multihexamer formation in addition to albumin binding (insulin degludec), to further increase duration of action and/or decrease the day-to-day variability of the glucose-lowering profile. Clinically, the major advantage of these recent analogues has been a reduction in hypoglycaemia with similar glycated haemoglobin control when compared with earlier products. Future therapies may bring clinical benefits through hepato-preferential insulin receptor binding or very long durations of action, perhaps enabling once-weekly administration and the potential for further clinical benefits.
Topics: Chemistry, Pharmaceutical; Diabetes Mellitus; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin Glargine; Insulin, Isophane; Insulin, Lente; Insulin, Long-Acting; Recombinant Proteins
PubMed: 27593206
DOI: 10.1111/dom.12782 -
BMJ (Clinical Research Ed.) Oct 2014To examine the safety, effectiveness, and cost effectiveness of long acting insulin for type 1 diabetes. (Comparative Study)
Comparative Study Meta-Analysis Review
Safety, effectiveness, and cost effectiveness of long acting versus intermediate acting insulin for patients with type 1 diabetes: systematic review and network meta-analysis.
OBJECTIVE
To examine the safety, effectiveness, and cost effectiveness of long acting insulin for type 1 diabetes.
DESIGN
Systematic review and network meta-analysis.
DATA SOURCES
Medline, Cochrane Central Register of Controlled Trials, Embase, and grey literature were searched through January 2013.
STUDY SELECTION
Randomized controlled trials or non-randomized studies of long acting (glargine, detemir) and intermediate acting (neutral protamine Hagedorn (NPH), lente) insulin for adults with type 1 diabetes were included.
RESULTS
39 studies (27 randomized controlled trials including 7496 patients) were included after screening of 6501 titles/abstracts and 190 full text articles. Glargine once daily, detemir once daily, and detemir once/twice daily significantly reduced hemoglobin A1c compared with NPH once daily in network meta-analysis (26 randomized controlled trials, mean difference -0.39%, 95% confidence interval -0.59% to -0.19%; -0.26%, -0.48% to -0.03%; and -0.36%, -0.65% to -0.08%; respectively). Differences in network meta-analysis were observed between long acting and intermediate acting insulin for severe hypoglycemia (16 randomized controlled trials; detemir once/twice daily versus NPH once/twice daily: odds ratio 0.62, 95% confidence interval 0.42 to 0.91) and weight gain (13 randomized controlled trials; detemir once daily versus NPH once/twice daily: mean difference 4.04 kg, 3.06 to 5.02 kg; detemir once/twice daily versus NPH once daily: -5.51 kg, -6.56 to -4.46 kg; glargine once daily versus NPH once daily: -5.14 kg, -6.07 to -4.21). Compared with NPH, detemir was less costly and more effective in 3/14 cost effectiveness analyses and glargine was less costly and more effective in 2/8 cost effectiveness analyses. The remaining cost effectiveness analyses found that detemir and glargine were more costly but more effective than NPH. Glargine was not cost effective compared with detemir in 2/2 cost effectiveness analyses.
CONCLUSIONS
Long acting insulin analogs are probably superior to intermediate acting insulin analogs, although the difference is small for hemoglobin A1c. Patients and their physicians should tailor their choice of insulin according to preference, cost, and accessibility.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO CRD42013003610.
Topics: Cost-Benefit Analysis; Diabetes Mellitus, Type 1; Humans; Hypoglycemic Agents; Insulin, Long-Acting
PubMed: 25274009
DOI: 10.1136/bmj.g5459 -
The Journal of Nutrition Nov 2007There is a history of interest in the metabolic effects of alterations in small intestinal digestion and colonic fermentation of carbohydrate. It is believed that the... (Review)
Review
There is a history of interest in the metabolic effects of alterations in small intestinal digestion and colonic fermentation of carbohydrate. It is believed that the rate of digestion of carbohydrate determines the place and form in which carbohydrate is absorbed. Slowly absorbed or lente carbohydrate sources may reduce postprandial glucose surges and the need for insulin with important implications for lowering coronary heart disease risk and reducing diabetes incidence. Carbohydrates that are not digested in the small intestine will enter the colon, and those that are fermentable will be salvaged as short-chain fatty acids in the colon and at the same time may stimulate colonic microflora, such as bifidobacteria. This process may have metabolic effects in the gut and throughout the host, possibly related to short-chain fatty acid products, although these effects are less well documented. One important aspect of colonic fermentation is the stimulation of certain populations of the colonic microflora, which may assist in the biotransformation of bioactive food components including the cleaving of plant phenolics from their glycone to produce the more rapidly absorbed aglycone. However, human studies have been limited. Therefore, further studies are required to explore these important aspects of metabolism related to the rate of carbohydrate absorption and fermentation and their implications in health and disease.
Topics: Dietary Carbohydrates; Digestion; Fatty Acids, Volatile; Fermentation; Humans; Intestinal Absorption; Intestinal Mucosa; Intestines; Malabsorption Syndromes
PubMed: 17951499
DOI: 10.1093/jn/137.11.2539S -
Journal of Veterinary Internal Medicine 2006The goals of this study were to compare the efficacy of once-daily administered Glargine insulin to twice-daily administered Lente insulin in cats with diabetes mellitus... (Randomized Controlled Trial)
Randomized Controlled Trial
The goals of this study were to compare the efficacy of once-daily administered Glargine insulin to twice-daily administered Lente insulin in cats with diabetes mellitus and to describe the use of a high-protein, low-carbohydrate diet designed for the management of diabetes mellitus in cats. All cats with naturally occurring diabetes mellitus were eligible for inclusion. Baseline testing included a physical examination, serum biochemistry, urinalysis and urine culture, serum thyroxine concentration, and serum fructosamine concentration. All cats were fed the high-protein, low-carbohydrate diet exclusively. Cats were randomized to receive either 0.5 U/kg Lente insulin q12h or 0.5 U/kg Glargine insulin q24h. Re-evaluations were performed on all cats at weeks 1, 2, 4, 8, and 12, and included an assessment of clinical signs, physical examination, 16-hour blood glucose curve, and serum fructosamine concentrations. Thirteen cats completed the study (Lente, n = 7, Glargine, n = 6). There was significant improvement in serum fructosamine and glucose concentrations in all cats but there was no significant difference between the 2 insulin groups. Four of the 13 cats were in complete remission by the end of the study period (Lente, n = 3; Glargine, n = 1). The results of the study support the use of once-daily insulin Glargine or twice-daily Lente insulin in combination with a high-protein, low-carbohydrate diet for treatment of feline diabetes mellitus.
Topics: Animals; Cat Diseases; Cats; Diabetes Mellitus; Diet; Drug Administration Schedule; Female; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Long-Acting; Male
PubMed: 16594577
DOI: 10.1892/0891-6640(2006)20[234:uogali]2.0.co;2 -
Journal of Veterinary Internal Medicine 2008Anti-insulin antibodies (AIA) occur in diabetic dogs after insulin therapy, although their clinical significance is unclear.
BACKGROUND
Anti-insulin antibodies (AIA) occur in diabetic dogs after insulin therapy, although their clinical significance is unclear.
HYPOTHESIS
Treatment of diabetic dogs with heterologous insulin is more likely to stimulate production of AIA than is treatment with homologous insulin.
ANIMALS
Diabetic dogs sampled before insulin therapy (n = 40), diabetic dogs sampled following treatment with porcine (homologous) insulin (n = 100), bovine (heterologous) lente insulin (n = 100), or bovine protamine zinc (PZI) insulin (n = 20), and nondiabetic control dogs (n = 120).
METHODS
Prospective observational study. Sera were analyzed by ELISA for antibodies against porcine insulin, bovine insulin, insulin A, B, or C peptides, and control antigens; canine distemper virus (CDV) and canine thyroglobulin (TG). Canine isotype-specific antibodies were used to determine total and anti-insulin IgG1 : IgG2 ratios.
RESULTS
There was no difference in CDV or TG reactivity among the groups. AIA were detected in 5 of 40 newly diagnosed (untreated) diabetic dogs. There was no significant difference in AIA (ELISA optical density reactivity) comparing control and porcine insulin-treated diabetic dogs (P > .05). Anti-insulin reactivity was most prevalent in bovine PZI insulin-treated dogs (90%; P < .01), and bovine lente insulin-treated dogs (56%; P < .01). AIA induced by treatment were enriched for the IgG1 isotype.
CONCLUSIONS AND CLINICAL IMPORTANCE
This study indicates that bovine insulin is more immunogenic than porcine insulin when used for treatment of diabetic dogs.
Topics: Animals; Antibodies; Cattle; Diabetes Mellitus; Dog Diseases; Dogs; Drug Administration Schedule; Female; Hypoglycemic Agents; Insulin; Male; Swine
PubMed: 18976287
DOI: 10.1111/j.1939-1676.2008.0194.x -
Archives of Disease in Childhood Dec 1990Fifty two children with insulin dependent diabetes mellitus were randomised to receive human isophane or lente insulin preparations in combination with soluble insulin... (Clinical Trial)
Clinical Trial Comparative Study Randomized Controlled Trial
Fifty two children with insulin dependent diabetes mellitus were randomised to receive human isophane or lente insulin preparations in combination with soluble insulin in a double blind trial. Patients were seen every two months, and crossed over after four months of treatment. Control assessed by glycated haemoglobin was significantly lower in children on human isophane insulin, but fasting blood glucose and fructosamine concentrations and the number of episodes of hypoglycaemia were similar on both regimens. In five children on twice daily insulin regimens, insulin profiles throughout a 24 hour period demonstrated greater variability on lente compared with isophane insulin despite identically administered insulin doses. A questionnaire completed at the end of the study showed that two thirds of the children and/or their parents preferred the isophane insulin, and they gave perceived improvement of metabolic control as the major reason for their choice.
Topics: Adolescent; Blood Glucose; Child; Child, Preschool; Diabetes Mellitus, Type 1; Double-Blind Method; Female; Fructosamine; Glycated Hemoglobin; Hexosamines; Humans; Insulin, Isophane; Insulin, Long-Acting; Male; Patient Participation
PubMed: 2270941
DOI: 10.1136/adc.65.12.1334 -
Scientific Reports Aug 2017Allogeneic islet transplantation into the liver in combination with immune suppressive drug therapy is widely regarded as a potential cure for type 1 diabetes. However,...
Allogeneic islet transplantation into the liver in combination with immune suppressive drug therapy is widely regarded as a potential cure for type 1 diabetes. However, the intrahepatic system is suboptimal as the concentration of drugs and nutrients there is higher compared to pancreas, which negatively affects islet function. Islet encapsulation within semipermeable membranes is a promising strategy that allows for the islet transplantation outside the suboptimal liver portal system and provides environment, where islets can perform their endocrine function. In this study, we develop a macroencapsulation device based on thin microwell membranes. The islets are seeded in separate microwells to avoid aggregation, whereas the membrane porosity is tailored to achieve sufficient transport of nutrients, glucose and insulin. The non-degradable, microwell membranes are composed of poly (ether sulfone)/polyvinylpyrrolidone and manufactured via phase separation micro molding. Our results show that the device prevents aggregation and preserves the islet's native morphology. Moreover, the encapsulated islets maintain their glucose responsiveness and function after 7 days of culture (stimulation index above 2 for high glucose stimulation), demonstrating the potential of this novel device for islet transplantation.
Topics: Animals; Biocompatible Materials; Biological Transport; Cell Line; Cell Survival; Diabetes Mellitus, Type 1; Glucose; Humans; Insulin; Islets of Langerhans; Islets of Langerhans Transplantation; Membranes; Mice; Permeability; Porosity; Tissue Culture Techniques; Tissue Scaffolds
PubMed: 28835662
DOI: 10.1038/s41598-017-09647-7