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Vascular Health and Risk Management 2006Insulin detemir is a soluble long-acting human insulin analogue at neutral pH with a unique mechanism of action. Following subcutaneous injection, insulin detemir binds... (Review)
Review
Insulin detemir is a soluble long-acting human insulin analogue at neutral pH with a unique mechanism of action. Following subcutaneous injection, insulin detemir binds to albumin via fatty acid chain, thereby providing slow absorption and a prolonged metabolic effect. Insulin detemir has a less variable pharmacokinetic profile than insulin suspension isophane or insulin ultralente. The use of insulin detemir can reduce the risk of hypoglycemia (especially nocturnal hypoglycemia) in type 1 and type 2 diabetic patients. However, overall glycemic control, as assessed by glycated hemoglobin, is only marginally and not significantly improved compared with usual insulin therapy. The weight gain commonly associated with insulin therapy is rather limited when insulin detemir is used. In our experience, this new insulin analogue is preferably administrated at bedtime but can be proposed twice a day (in the morning and either before the dinner or at bedtime). Detemir is a promising option for basal insulin therapy in type 1 or type 2 diabetic patients.
Topics: Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin, Long-Acting; Treatment Outcome; Weight Gain
PubMed: 17326333
DOI: 10.2147/vhrm.2006.2.3.277 -
British Medical Journal (Clinical... Mar 1984The greater solubility of human insulin and its possible faster action have led to doubts about whether a sufficiently long acting formulation could be produced to... (Clinical Trial)
Clinical Trial Comparative Study Randomized Controlled Trial
The greater solubility of human insulin and its possible faster action have led to doubts about whether a sufficiently long acting formulation could be produced to provide a basal supply for diabetics. In a double blind crossover study in 18 diabetics human ultralente insulin was as effective as beef ultralente insulin in controlling basal plasma glucose concentrations (median 5.7 mmol/l (103 mg/100 ml) with human and 6.3 mmol/l (114 mg/100 ml) with beef ultralente insulin respectively). There was no significant difference between human and bovine insulin in the rise in plasma glucose concentration from 0400 to 0700 after an injection the previous morning and no difference between patients receiving an adequate or insufficient dose of human ultralente insulin. Bovine insulin antibody binding was reduced with human insulin (p less than 0.002), which suggests that human insulin is less antigenic than beef insulin. Once daily human ultralente insulin provides a suitable formulation for the basal insulin requirement of diabetics.
Topics: Adult; Animals; Blood Glucose; Cattle; Clinical Trials as Topic; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Double-Blind Method; Female; Humans; Insulin Antibodies; Insulin, Long-Acting; Male; Middle Aged; Random Allocation
PubMed: 6421424
DOI: 10.1136/bmj.288.6418.665 -
Biophysical Journal Sep 1998Although x-ray crystal structures exist for many forms of insulin, the hormone involved in glucose metabolism and used in the treatment of diabetes, x-ray structural... (Comparative Study)
Comparative Study
Although x-ray crystal structures exist for many forms of insulin, the hormone involved in glucose metabolism and used in the treatment of diabetes, x-ray structural characterization of therapeutically important long-acting crystalline ultralente insulin forms has been elusive because of small crystal size and poor diffraction characteristics. We describe tapping-mode atomic force microscopy (TMAFM) studies, performed directly in crystallization liquor, of ultralente crystals prepared from bovine, human, and porcine insulins. Lattice images obtained from direct imaging of crystal planes are consistent with R3 space group symmetry for each insulin type, but the morphology of the human and porcine crystals observed by AFM differs substantially from that of the bovine insulin crystals. Human and porcine ultralente crystals exhibited large, molecularly flat (001) faces consisting of hexagonal arrays of close packed hexamers. In contrast, bovine ultralente crystals predominantly exhibited faces with cylindrical features assignable to close-packed stacks of insulin hexamers laying in-plane, consistent with the packing motif of the (010) and (011) planes. This behavior is attributed to a twofold increase in the hydrophobic character of the upper and lower surfaces of the donut-shaped insulin hexamer in bovine insulin compared to its human and porcine counterparts that results from minor sequence differences between these insulins. The increased hydrophobicity of these surfaces can promote hexamer-hexamer stacking in precrystalline aggregates or enhance attachment of single hexamers along the c axis at the crystal surface during crystal growth. Both events lead to enhanced growth of ¿hk0¿ planes instead of (001). The insulin hexamers on the (010) and (110) faces are exposed "edge-on" to the aqueous medium, such that solvent access to the center of the hexamer and to solvent channels is reduced compared to the (001) surface, consistent with the slower dissolution and reputed unique basal activity of bovine ultralente insulin. These observations demonstrate that subtle variations in amino acid sequence can dramatically affect the interfacial structure of crystalline proteins.
Topics: Animals; Biophysical Phenomena; Biophysics; Cattle; Crystallization; Humans; Insulin, Long-Acting; Microscopy, Atomic Force; Models, Molecular; Protein Conformation; Recombinant Proteins; Species Specificity; Swine
PubMed: 9726919
DOI: 10.1016/S0006-3495(98)74036-6 -
Kidney International Jan 2003Earlier studies have provided evidence for increased production of reactive oxygen species (ROS) and altered nitric oxide (NO) metabolism in diabetes. This study was...
BACKGROUND
Earlier studies have provided evidence for increased production of reactive oxygen species (ROS) and altered nitric oxide (NO) metabolism in diabetes. This study was intended to explore the effect of type I diabetes and its treatment with insulin alone or insulin plus antioxidant-fortified diet on expression of NOS isoforms and ROS interactions with lipids, glucose and NO.
METHODS
Rats with streptozotocin-induced diabetes were divided into once-daily insulin (ultralente)-treated, insulin plus antioxidant (vitamin E and vitamin C)-treated and untreated groups. After four weeks, plasma malondialdehyde (MDA) and tissue endothelial (eNOS), neuronal (nNOS) NO synthases, carboxymethyllysine (CML) and nitrotyrosine were determined.
RESULTS
The untreated diabetic animals exhibited severe hyperglycemia, elevated blood pressure, increased plasma MDA, high tissue CML and reduced tissue nitrotyrosine denoting enhanced lipid, glucose and protein oxidation but reduced NO oxidation by ROS. This was coupled with significant reduction of eNOS and nNOS expression in renal cortex and eNOS in the left ventricle. Insulin therapy partially lowered blood pressure, tissue CML, plasma glucose and MDA, but significantly raised eNOS expression and nitrotyrosine abundance to supranormal levels. Combined insulin and antioxidant therapies resulted in normalization of blood pressure, plasma MDA, tissue CML and nitrotyrosine without affecting glucose level or NOS expression.
CONCLUSION
Oxidative stress in untreated diabetes is associated with down-regulation of NOS isoforms and increased ROS-mediated oxidation of lipid and glucose, but not NO. Amelioration of hyperglycemia with once-daily insulin administration alone results in up-regulation of NOS isoforms, reduction of lipid and glucose oxidation and increased NO oxidation. However, insulin plus antioxidant supplementation can normalize all three parameters.
Topics: Animals; Antioxidants; Blood Pressure; Diabetes Mellitus, Type 1; Diabetic Nephropathies; Insulin; Lysine; Male; Malondialdehyde; Nitric Oxide; Nitric Oxide Synthase; Nitric Oxide Synthase Type I; Nitric Oxide Synthase Type III; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species; Tyrosine
PubMed: 12472783
DOI: 10.1046/j.1523-1755.2003.00728.x -
Health Technology Assessment... Oct 2004To assess the clinical and cost-effectiveness of continuous subcutaneous insulin infusion (CSII) compared with multiple daily injections (MDI) in the delivery of... (Comparative Study)
Comparative Study Review
OBJECTIVES
To assess the clinical and cost-effectiveness of continuous subcutaneous insulin infusion (CSII) compared with multiple daily injections (MDI) in the delivery of intensive insulin therapy for the treatment of diabetes mellitus.
DATA SOURCES
Electronic databases, references of retrieved articles and manufacturer submissions. Experts in the field were consulted.
REVIEW METHODS
For the systematic review of clinical and cost-effectiveness, studies were assessed for inclusion according to predefined criteria by two reviewers. Data extraction and quality assessment were undertaken by one reviewer and checked by a second reviewer. Data on clinical effectiveness were synthesised through a narrative review with full tabulation of all eligible studies, with meta-analysis performed where appropriate.
RESULTS
Twenty studies comparing CSII with MDI were identified. Quality was generally poor. In adults with Type 1 diabetes, glycated haemoglobin improved by 0.61% (95% CI -1.29 to 0.07) in longer term studies, although this improvement was smaller when a study using bovine ultralente was excluded. A reduction in insulin dose with CSII of about 12 units per day (-11.90, 95% CI -18.16 to 5.63) was found in short-term studies, with smaller differences in longer term studies. Body weight and cholesterol levels were similar between treatments. Hypoglycaemic events did not differ significantly between CSII and MDI in most trials, but some found fewer events with CSII and one found more hypoglycaemia and hypoglycaemic coma with CSII. There was no consistency between the studies in patient preference, but progress has been made both with insulin pumps and injector pens since the publication of many of the older studies. No difference in glycated haemoglobin between CSII and MDI was found in pregnancy; one study found less insulin was required by patients with CSII, but two other studies found no significant difference. One study of adolescents found lower glycated haemoglobin and insulin dose with CSII whereas a second study found no significant difference. In CSII analogue insulin was associated with lower glycated haemoglobin levels than soluble insulin. No economic evaluations comparing CSII with MDI were identified. The estimated additional cost of CSII compared to MDI varies from GBP1091 per annum to GBP1680 per annum, according to the make of the insulin pump and the estimated life of the device. These estimates include the costs for the insulin pump, the consumables associated with delivery of CSII, and an allowance for the initial education required when patients switch from MDI to CSII. The largest component of the annual cost for CSII is the cost of consumable items (e.g. infusion sets).
CONCLUSIONS
When compared with optimised MDI, CSII results in a modest but worthwhile improvement in glycated haemoglobin in adults with Type 1 diabetes. It has not been possible to establish the longer term benefits of such a difference in glycated haemoglobin, although there is an expectation that it would be reflected in a reduction in long-term complications. More immediate primary benefits from CSII may be associated with an impact on the incidence of hypoglycaemic events and the dawn phenomenon, and greater flexibility of lifestyle. However, there is limited evidence on this, and information presented to offer context on quality-of-life is based on testimonies from those patients who have had a positive experience of CSII. The estimated cost to the NHS per year for CSII would be around GBP3.5 million in England and Wales if 1% of people with Type 1 diabetes used CSII, GBP10.5 million for 3%, and GBP17.5 million for 5%. Further research should focus on wider benefits of CSII, such as flexibility of lifestyle and quality of life, and on the psychological impact of wearing a device for 24 hours every day. Research into the use of CSII in children of different ages is also needed.
Topics: Cost-Benefit Analysis; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Humans; Injections; Insulin; Insulin Infusion Systems; Quality-Adjusted Life Years; Technology Assessment, Biomedical
PubMed: 15488165
DOI: 10.3310/hta8430 -
British Medical Journal Nov 1953
Topics: Humans; Insulin; Insulin, Lente
PubMed: 13094103
DOI: 10.1136/bmj.2.4844.1023 -
Klinische Wochenschrift Jan 1989Diabetic patients under multiple injection insulin therapy (i.e., intensified insulin therapy, IIT) usually start this treatment during hospitalization. We report here... (Clinical Trial)
Clinical Trial Randomized Controlled Trial
Diabetic patients under multiple injection insulin therapy (i.e., intensified insulin therapy, IIT) usually start this treatment during hospitalization. We report here on the logistics, efficacy, and safety of IIT, started in outpatients. Over 8 months, 52 type I and type II diabetics were followed up whose insulin regimens consecutively had been changed from conventional therapy to IIT. Two different IIT strategies were compared: free mixtures of regular and intermediate (12 hrs)-acting insulin versus the basal and prandial insulin treatment with preprandial injections of regular insulin, and ultralente (24 hrs-acting) or intermediate insulin for the basal demand. After 8 months HbA1 levels had decreased from 10.6% +/- 2.4% to 8.0% +/- 1.3% (mean +/- SD). There was no difference between the two regimens with respect to metabolic control; but type II patients maintained the lowered HbA1 levels better than type I patients. Only two patients were hospitalized during the follow-up time because of severe hypoglycemia. An increase of body weight due to the diet liberalization during IIT became a problem in one-third of the patients. Our results suggest that outpatient initiation of IIT is safe and efficacious with respect to near-normoglycemic control. Weight control may become a problem in IIT patients.
Topics: Blood Glucose; Delayed-Action Preparations; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Drug Administration Schedule; Follow-Up Studies; Glycated Hemoglobin; Humans; Insulin
PubMed: 2646469
DOI: 10.1007/BF01735653 -
American Family Physician Aug 2004Type 2 diabetes is characterized by progressive beta-cell failure. Indications for exogenous insulin therapy in patients with this condition include acute illness or...
Type 2 diabetes is characterized by progressive beta-cell failure. Indications for exogenous insulin therapy in patients with this condition include acute illness or surgery, pregnancy, glucose toxicity, contraindications to or failure to achieve goals with oral antidiabetic medications, and a need for flexible therapy. Augmentation therapy with basal insulin is useful if some beta-cell function remains. Replacement therapy with basal-bolus insulin is required for beta-cell exhaustion. Rescue therapy using replacement regimens for several weeks may reverse glucose toxicity. Replacement insulin therapy should mimic normal release patterns. Basal insulin, using long-acting insulins (i.e., neutral protamine Hagedorn [NPH], ultralente, glargine) is injected once or twice a day and continued on sick days. Bolus (or mealtime) insulin, using short-acting or rapid-acting insulins (i.e., regular, aspart, lispro) covers mealtime carbohydrates and corrects the current glucose level. The starting dose of 0.15 units per kg per day for augmentation or 0.5 units per kg per day for replacement can be increased several times as needed. About 50 to 60 percent of the total daily insulin requirement should be a basal type, and 40 to 50 percent should be a bolus type. The mealtime dose is the sum of the corrective dose plus the anticipated requirements for the meal and exercise. Adjustments should be made systematically, starting with the fasting, then the preprandial and, finally, the postprandial glucose levels. Basal therapy with glargine insulin provides similar to lower A1C levels with less hypoglycemia than NPH insulin. Insulin aspart and insulin lispro provide similar A1C levels and quality of life, but lower postprandial glucose levels than regular insulin.
Topics: Algorithms; Blood Glucose; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin Lispro; Insulin, Long-Acting
PubMed: 15317436
DOI: No ID Found -
Journal of Veterinary Internal Medicine 1998Medical records of 104 cats with diabetes mellitus were reviewed. Information from 54 cats that had multiple blood glucose concentrations evaluated at least 5 times over... (Comparative Study)
Comparative Study
Medical records of 104 cats with diabetes mellitus were reviewed. Information from 54 cats that had multiple blood glucose concentrations evaluated at least 5 times over a minimum of 3 months, beginning at the time insulin treatment was initiated, was used to evaluate the efficacy of insulin in treating diabetes mellitus. Fourteen of 54 cats were treated with protamine zinc insulin (PZI), 26 with ultralente insulin, and 14 with lente insulin. Six, 29, and 19 cats had good, mediocre, and poor glycemic control, respectively, based on mean blood glucose concentrations, whereas 31, 21, and 2 owners thought clinical response was good, mediocre, and poor, respectively. No significant difference was found in glycemic control among cats treated with PZI, ultralente, or lente insulin. Glycemic control was significantly (P < .05) better in 33 cats without than in 21 cats with concurrent disease. All 104 cats were used to calculate survival data. Fifty-one of 104 cats were alive at the time of the study. Mean (+/- standard deviation [SD]) and median survival times were 24 (+/- 16) and 20 months, respectively, in the 51 cats still alive at the end of the evaluation, and 25 (+/- 4) and 17 months, respectively, in the 53 cats that had died during the period of evaluation. Pancreatic abnormalities identified in 37 cats that underwent necropsy included chronic pancreatitis (n = 17), acute to subacute pancreatitis (n = 2), exocrine pancreatic adenocarcinoma (n = 7) and adenoma (n = 1), islet cell atrophy and vacuolar degeneration (n = 27), and islet amyloidosis (n = 8). No association was found between glycemic control and islet amyloidosis or exocrine pancreatic neoplasia, or between survival time and chronic pancreatitis, islet amyloidosis, or exocrine pancreatic neoplasia. In conclusion, diabetic cats evaluated in this study showed a variable response to exogenously administered insulin, ranging from excellent to poor. By maintaining mean blood glucose concentrations under 300 mg/dL, clinical signs were improved, and owners were satisfied with insulin treatment. Concurrent potentially insulin-antagonistic diseases were common and deleteriously affected glycemic control and survival time.
Topics: Animals; Blood Glucose; Cat Diseases; Cats; Diabetes Mellitus; Hypoglycemic Agents; Insulin; Insulin, Long-Acting; Retrospective Studies; Survival Analysis; Time Factors
PubMed: 9503353
DOI: 10.1111/j.1939-1676.1998.tb00489.x