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Clinical utility of insulin and insulin analogs.

ABSTRACT: Diabetes is a pandemic disease characterized by autoimmune, genetic and metabolic abnormalities. While insulin deficiency manifested as hyperglycemia is a common sequel of both Type-1 and Type-2 diabetes (T1DM and T2DM), it does not result from a single genetic defect--rather insulin deficiency results from the functional loss of pancreatic ? cells due to multifactorial mechanisms. Since pancreatic ? cells of patients with T1DM are destroyed by autoimmune reaction, these patients require daily insulin injections. Insulin resistance followed by ? cell dysfunction and ? cell loss is the characteristics of T2DM. Therefore, most patients with T2DM will require insulin treatment due to eventual loss of insulin secretion. Despite the evidence of early insulin treatment lowering macrovascular (coronary artery disease, peripheral arterial disease and stroke) and microvascular (diabetic nephropathy, neuropathy and retinopathy) complications of T2DM, controversy exists among physicians on how to initiate and intensify insulin therapy. The slow acting nature of regular human insulin makes its use ineffective in counteracting postprandial hyperglycemia. Instead, recombinant insulin analogs have been generated with a variable degree of specificity and action. Due to the metabolic variability among individuals, optimum blood glucose management is a formidable task to accomplish despite the presence of novel insulin analogs. In this article, we present a recent update on insulin analog structure and function with an overview of the evidence on the various insulin regimens clinically used to treat diabetes.

SUBMITTER: Sanlioglu AD

PROVIDER: S-EPMC4204021 | biostudies-literature | 2013 Mar-Apr

REPOSITORIES: biostudies-literature

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Clinical utility of insulin and insulin analogs.

Sanlioglu Ahter D AD Altunbas Hasan Ali HA Balci Mustafa Kemal MK Griffith Thomas S TS Sanlioglu Salih S

Islets 20130301 2

Diabetes is a pandemic disease characterized by autoimmune, genetic and metabolic abnormalities. While insulin deficiency manifested as hyperglycemia is a common sequel of both Type-1 and Type-2 diabetes (T1DM and T2DM), it does not result from a single genetic defect--rather insulin deficiency results from the functional loss of pancreatic β cells due to multifactorial mechanisms. Since pancreatic β cells of patients with T1DM are destroyed by autoimmune reaction, these patients require daily i ...[more]

PMID: 23584214

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Project description:INTRODUCTION:Premixed insulin analogs represent an alternative to basal or basal-bolus insulin regimens for the treatment of type 2 diabetes (T2D). "Low-mix" formulations with a low rapid-acting to long-acting analog ratio (e.g., 25/75) are commonly used, but 50/50 formulations (Mix50) may be more appropriate for some patients. We conducted a systematic literature review to assess the efficacy and safety of Mix50, compared with low-mix, basal, or basal-bolus therapy, for insulin initiation and intensification. METHODS:MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, ClinicalTrials.gov, LillyTrials.com, and NovoNordisk-trials.com were searched (11 or 13 Dec 2016) using terms for T2D, premixed insulin analogs, and/or Mix50. Studies (randomized, nonrandomized, or observational; English only) comparing Mix50 with other insulins (except human) and reporting key efficacy [glycated hemoglobin (HbA1c), fasting and postprandial glucose] and/or safety (hypoglycemia, weight gain) outcomes were eligible for inclusion. Narrative reviews, letters, editorials, and conference abstracts were excluded. Risk of bias in randomized trials was assessed using the Cochrane tool. RESULTS:MEDLINE and EMBASE searches identified 716 unique studies, of which 32 met inclusion criteria. An additional three studies were identified in the other databases. All 19 randomized trials except one were open label; risk of other biases was generally low. Although not conclusive, the evidence suggests that Mix50 may provide better glycemic control (HbA1c reduction) and, particularly, postprandial glucose reduction in certain patients, such as those with high carbohydrate diets and Asian patients, than low-mix and basal therapy. Based on this evidence and our experience, we provide clinical guidance on factors to consider when deciding whether Mix50 is appropriate for individual patients. CONCLUSIONS:Mix50 may be more suitable than low-mix therapy for certain patients. Clinicians should consider not only efficacy and safety but also patient characteristics and preferences when tailoring insulin treatment to individuals with T2D. FUNDING:Eli Lilly.

Project description:Purpose: There is a quest for novel non-invasive diagnostic markers for the detection of breast cancer. The goal of this study is to identify circulating microRNA signatures using a cohort of Asian Chinese breast cancer patients, and to compare microRNA profiles between tumour and serum samples. Experimental design: MicroRNAs from paired breast cancer tumours, normal tissue and serum samples derived from 32 patients were comprehensively profiled using microarrays (1300 microRNAs against tumour and normal tissues) or LNA RT-PCR panels (742 microRNAs against serum samples). Serum samples from healthy individuals (n=22) were also employed as normal controls. Significant serum microRNAs, identified by logistic regression, were validated in an independent set of serum samples from patients (n=82) and healthy controls (n=53). Results: The 20 most significant microRNAs differentially expressed in breast cancer tumours included miR-21, miR-10b, and miR-145, previously shown to be dysregulated in breast cancer. Interestingly, 16 of the 20 most significant microRNAs differentially expressed in serum samples were novel. MiR-1, miR-92a, miR-133a and miR-133b were identified as the most important diagnostic markers, and were successfully validated; receiver operating characteristic curves derived from combinations of these microRNAs exhibited areas under the curves of 0.944-0.946. Only seven microRNAs were overexpressed in both tumours and serum, suggesting that microRNAs may be released into the serum selectively. Conclusion: The clinical employment of microRNA signatures as a non-invasive diagnostic strategy is promising, but should be further validated for different subtypes of breast cancers. Blood samples were collected in Becton Dickinson (Franklin Lakes, NJ) Vacutainer SST tubes. Serum was harvested by centrifugation at 2200g after allowing blood to clot for 30mins. 32 patient samples and 22 samples from healthy controls were obtained for profiling. Sera samples were stored at -80oC.

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Clinical utility of insulin and insulin analogs.

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Clinical utility of insulin and insulin analogs.

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