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Query: UMLS:C0011860 (type 2 diabetes)
 57,723 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The modern goals of insulin replacement in Type 1 and Type 2 diabetes mellitus (T1, T2DM) are A1C <6.5% long-term, and prevention of hypoglycaemia (blood glucose, BG <70 mg/dl). In addition to appropriate education and motivation of diabetic subjects, the use of rapid- and long-acting insulin analogues, is critical to achieve these goals. The benefits of rapid-acting analogues (lispro, aspart and glulisine have similar pharmacodynamic effects) compared with non-modified human regular insulin, are: (a) lower 1- and 2-h post-prandial blood glucose; (b) lower risk of late post-prandial hypoglycaemia (and therefore lower BG variability); (c) better quality of life (greater flexibility in timing and dosing of insulin). In T1DM, rapid-acting analogues improve A1C only by the extent to which replacement of basal insulin is optimized at the same time, either by multiple daily NPH administrations, or continuous subcutaneous insulin infusion (CSII), or use of the long-acting insulin analogues glargine or detemir. In T2DM, rapid-acting analogues reduce post-prandial hyperglycaemia more than human regular insulin, but systematic studies are needed to examine the effects on A1C. The benefits of long-acting insulin analogues glargine and detemir vs. NPH, are: (1) lower fasting BG combined with lower risk of hypoglycaemia in the interprandial state (night); (2) lower variability of BG. Glargine and detemir differ in terms of potency and duration of action. Detemir should be given twice daily in the large majority of people with T1DM, and in a large percentage of subjects with T2DM as well, usually at doses greater vs those of the once daily glargine. However, when used appropriately for individual pharmacokinetics and pharmacodynamics, glargine and detemir result into similar effects on BG, risk of hypoglycaemia and A1C. Rapid- and long-acting insulin analogues should always be combined in the treatment of T1 and T2DM.
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PMID:Superiority of insulin analogues versus human insulin in the treatment of diabetes mellitus. 1846 53

To clarify the effect of early insulin therapy on nuclear factor kappaB (NFkappaB) pathway and inflammatory cytokine responses in the liver and skeletal muscle in type 2 diabetes. High-fat diet and low dose streptozotocin (STZ) induced diabetic rats were given NPH insulin or gliclazide for 3 weeks initiated at the 3rd day after STZ injection as early treatment and NPH for 3 weeks at 1 month as late treatment. Intraperitoneal glucose tolerance test (IPGTT) was performed at 3rd day after the end of treatment. Early interventions caused a decrease in glucose-insulin index in IPGTT, promoted glucose transporter 4 (Glut4) gene and protein expressions in muscle and reduced phosphoenolpyruvate carboxykinase (PEPCK) protein levels in the liver. There was an increase in inhibitor kappaB (IkappaBalpha) protein and a decrease in NFkappaB p65 DNA binding activity. A decreased level in mRNAs encoding tumor necrosis factor (TNF)alpha in the liver and muscle and interleukin (IL)-1beta in the liver were observed. Our results suggested that early insulin treatment inhibits NFkappaB activity and inflammatory cytokine responses in the liver and skeletal muscle that were involved in the amelioration of insulin resistance in type 2 diabetic rats.
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PMID:Effect of early insulin therapy on nuclear factor kappaB and cytokine gene expressions in the liver and skeletal muscle of high-fat diet, streptozotocin-treated diabetic rats. 1850 Apr 27

The insulin treatment in type 2 diabetes mellitus (DM 2) is an explosive subject within health economics. This article discusses the significance of treating DM 2 patients with long-acting insulin analogues. Several studies have shown that the therapy with insulin glargine ist associated with a markedly lower rate of hypoglycaemia compared to NPH insulin. As the improvement of HbA1c is accompanied by a higher risk for hypoglycaemia, this goal is accomplished more effectively and safely with long acting insulin analogues.
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PMID:[Long acting insulin analogues: results of clinical studies with insulin glargine]. 1868 17

Despite the development of alternative therapies in recent years, insulin injections remain essential treatment for type 2 diabetes once oral therapy alone becomes inadequate. However, neither patients nor physicians are proactive enough with regard to starting insulin, despite the well-known benefits of early insulin initiation and aggressive dose titration. Barriers to starting insulin therapy are being overcome by developments in insulin and delivery device technology and are the subject of this review. A literature search spanning the last 25 years was carried out to identify publications addressing issues of insulin initiation, how insulin analogs can help overcome barriers to initiation, and the advantages of pen-type insulin delivery systems. Seventy-five publications were identified. These references illustrate that the drawbacks associated with regular exogenous human insulins (soluble and NPH) are improved with modern insulin analogs. The more rapid absorption of prandial insulin analogs compared with human insulin eliminates the need for an injection-meal-interval, increasing convenience, while basal analogs have no discernible peak in activity. Modern insulin delivery devices also have advantages over the traditional vial and syringe. Currently available insulin pens are either durable (insulin cartridge is replaceable; e.g., HumaPen, Eli Lilly [Indianapolis, IN]; NovoPen series, Novo Nordisk [Bagsvaerd, Denmark]) or disposable (prefilled; e.g., FlexPen, Novo Nordisk; SoloSTAR, sanofi-aventis [Paris, France]), with features to aid ease-of-use. These include a large dose selector, dial-up and dial-down facility, and audible clicks when selecting the dose. The potential for dosing errors is thus reduced with pen-type devices, with other benefits including a discreet appearance, ease of learning, and greater user confidence. Collectively, these features contribute to overwhelming patient preference when compared with vials and syringes. Despite the greater cost of insulin pens relative to vials and syringes, improvements in treatment adherence with pens-and hence glycemic control-may offset these costs in the long term.
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PMID:Initiating insulin therapy in type 2 diabetes: benefits of insulin analogs and insulin pens. 1871 98

The new rDNA and DNA-derived "basal" insulin analogs, glargine and detemir, represent significant advancement in the treatment of diabetes compared with conventional NPH insulin. This review describes blood glucose homeostasis by insulin in people without diabetes and outlines the physiological application of exogenous insulin in patients with type 1 and type 2 diabetes. The requirements for optimal basal insulin treatment are discussed and the methods used in the evaluation of basal insulins are presented. An essential criterion in the development of an "ideal" basal insulin preparation is that the molecular modifications made to the human insulin molecule do not compromise safety. It is also necessary to obtain a clear understanding of the pharmacokinetic and pharmacodynamic characteristics of the two currently available basal insulin analogs. When comparing glargine and detemir, the different molar concentration ratios of the two insulin formulations should be considered along with the nonspecificity of assay systems used to determine insulin concentrations. However, euglycemic clamp studies in crossover study design provide a good basis for comparing the pharmacodynamic responses. When the latter is analyzed by results of intervention clinical trials, it is concluded that both glargine and detemir are superior to NPH in type 1 and type 2 diabetes. However, there is sufficient evidence to demonstrate that these two long-acting insulin analogs are different in both their pharmacokinetic and pharmacodynamic profiles. These differences should be taken into consideration when the individual analogs are introduced to provide basal insulin supplementation to optimize blood glucose control in patients with type 1 and type 2 diabetes as well. PubMed-Medline was searched for articles relating to pharmacokinetics and pharmacodynamics of glargine and detemir. Articles retrieved were reviewed and selected for inclusion if (1) the euglycemic clamp method was used with a duration >or=24 h, (2) a single subcutaneous dose of glargine/detemir was used, and (3) area under the curve for insulin concentrations or glucose infusion rates were calculated.
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PMID:Beyond the era of NPH insulin--long-acting insulin analogs: chemistry, comparative pharmacology, and clinical application. 1984 80

In people with type 2 diabetes (T2DM), hyperglycemia has a negative impact on cardiac function and cardiovascular risk. Beneficial effects of improved postprandial glycemic control have been shown for cardiovascular risk only. To demonstrate these beneficial effects on myocardial function, we investigated well-controlled T2DM patients on three insulin regimens with different impact on postprandial glucose control. For 24 months, 61 T2DM participants in a randomized study had either conventional therapy (CT) with human premixed insulin b.d. (n=20), intensified therapy (ICT) with Lispro at meals and NPH at bedtime (n=24), or supplementary therapy (SIT) with human regular insulin at meals (n=17). Metabolism and cardiovascular function were assessed before and 2 hours after a standardized carbohydrate breakfast (48 g) using tissue Doppler to measure diastolic myocardial function (E'). Age, BMI, dose of insulin, cardiovascular disease, and medication were comparable between the groups. Hb1Ac was comparable with CT, ICT, and SIT (6.6+/-0.6, 6.2+/-0.6, and 6.4+/-0.7%) and so was fasting glucose. Post-meal glucose increment was 60+/-45 mg/dl with CT, but 15+/-52 and 8+/-58 mg/dl with ICT and SIT (p<0.006). E' was significantly lower (p<0.03) with CT (6.8+/-1.0 cm/s) vs. ICT (7.7+/-1.6) and SIT (7.8+/-1.2 cm/s), and correlated with post-meal glucose (r=-0.2644, p<0.046). Intima-media thickness and arterial stiffness parameters were higher in CT (p<0.04). In T2DM patients, the long-term insulin regimens CT, ICT, and SIT achieved overall good metabolic control with significant differences, however, in postprandial glucose increments. The regimens achieving better post-meal glucose control were associated with better myocardial/vascular function.
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PMID:Optimized postprandial glucose control is associated with improved cardiac/vascular function - comparison of three insulin regimens in well-controlled type 2 diabetes. 1921 20

We studied the weight-sparing effect and treatment satisfaction when switching from NPH to insulin detemir in type 2 diabetes. Mean HbA(1c) (P<0.05) and waist circumference (P<0.05) were reduced while treatment satisfaction improved (P<0.03). No weight gain was observed. Detemir improves glycemic control, treatment satisfaction, and may provide additional weight-sparing benefits.
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PMID:Waist circumference reduction after insulin detemir therapy in type 2 diabetes patients previously treated with NPH. 1929 54

Type 2 diabetes mellitus is a progressive disease characterized by persistent insulin resistance and a relentless decline in insulin secretion that is accelerated by chronic hyperglycemia. Mounting evidence indicates that earlier introduction of insulin therapy may mitigate the deleterious effects of glucotoxicity in patients with early type 2 diabetes, presumably by reducing strain on pancreatic beta-cells and enhancing insulin secretion and also by improving peripheral insulin action. At present, the available data can only be considered hypothesis-generating, but support the notion that beginning basal insulin supplementation immediately after combination oral agents fail to attain glycemic targets has the potential to preserve beta-cell integrity or delay beta-cell loss, leading to more sustained glycemic control. Long-term controlled studies are clearly warranted to confirm this treatment paradigm. In the meantime, the tools for translating this concept to clinical practice can be extrapolated from the Treat-to-Target Trial, which showed that the addition of once-daily basal insulin glargine to oral agents, using a structured titration algorithm based on fasting plasma glucose monitoring, can achieve stringent glycemic control with less risk of nocturnal hypoglycemia than NPH insulin.
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PMID:Redefining insulin therapy in type 2 diabetes mellitus. 1966 76

The progressive nature of type 2 diabetes poses challenges in the clinic: treatment must be continually reviewed and adjusted in response to the patient's changing pathophysiology. Ultimately, insulin replacement therapy will be necessary as the physiological insulin response is compromised. The modern basal insulin analog insulin detemir has been the subject of several clinical trials and observational studies in type 2 diabetes. Compared with NPH insulin, insulin detemir offers an improved balance between achieving current glycemic targets with acceptable tolerability. Insulin detemir also has a unique weight-sparing effect which is associated with body mass index, and this may be a particular advantage to obese patients with type 2 diabetes. This review summarizes data from key clinical studies of insulin detemir, and also provides insights from observational studies.
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PMID:Tolerability, safety and adherence to treatment with insulin detemir injection in the treatment of type 2 diabetes. 1992 Sep 79

Basal insulin analogues are an effective treatment for type 2 diabetes with proven efficacy, and insulins NPH, detemir and glargine have shown comparable glycaemic control. However, pharmacokinetics and clinical studies highlight the advantages of insulins detemir and glargine over insulin NPH in terms of once-daily dosing, reduced risk of hypoglycaemia, reduced within-patient variability, appropriate duration of action and simple titration. Insulin detemir has demonstrated the additional advantage of less weight gain. Introduction of insulin detemir, at the appropriate time, can help empower patients to reach glycaemic targets, with a reduced risk of hypoglycaemia and less weight gain.
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PMID:Basal insulins: Pharmacological properties and patient perspectives. 2039 87


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