{"title":"Intensive insulin regimens: evidence for benefit.","authors":"R G Bretzel","doi":"10.1038/sj.ijo.0802744","DOIUrl":"https://doi.org/10.1038/sj.ijo.0802744","url":null,"abstract":"<p><p>It is now well established that the risk of experiencing diabetic complications is dependent on the degree of glycaemic control in patients with diabetes. Clinical trials such as the Diabetes Control and Complications Trial (DCCT) and Kumamoto study have demonstrated that tight glycaemic control achieved with intensive insulin regimens can reduce the risk of developing or progressing retinopathy, nephropathy or neuropathy in patients with type I or II diabetes. The EDIC trial, a follow-up to the DCCT, has shown that the previous degree and duration of glycaemic exposure are also important determinants of risk of developing microvascular diabetic complications. It appears that beneficial outcomes with regard to microvascular risk can be achieved with the improved metabolic control associated with intensive insulin regimens; however, data examining the effect of intensive insulin regimens on macrovascular risk is inconclusive. Epidemiological data highlight the role of postprandial blood glucose in cardiovascular disease and mortality, especially in patients with type II diabetes. Consequently, it is logical to suppose that insulin regimens that control both fasting plasma glucose and postprandial glucose excursions should also achieve the best macrovascular risk outcomes and there are some data that suggest this. Intensive insulin treatment can also improve prognosis in acute clinical situations such as myocardial infarction in patients with or without diabetes. In summary, intensive insulin regimens achieve strict metabolic control in patients with diabetes and could offer the best possible outcomes with regard to microvascular and macrovascular complications.</p>","PeriodicalId":14227,"journal":{"name":"International journal of obesity and related metabolic disorders : journal of the International Association for the Study of Obesity","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2004-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1038/sj.ijo.0802744","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24633490","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Insulin detemir: improving the predictability of glycaemic control.","authors":"D Russell-Jones","doi":"10.1038/sj.ijo.0802747","DOIUrl":"https://doi.org/10.1038/sj.ijo.0802747","url":null,"abstract":"<p><p>The importance of strict glycaemic control in reducing diabetes-related outcomes is well recognised. Yet, despite the range of available treatment options, clinical experience suggests that individuals with diabetes frequently fail to achieve good glucose control. Instead, patients often have poorly controlled, unpredictable blood glucose levels. In insulin-treated patients, one of the reasons for this may be the inherently variable action of exogenously injected insulin. For example, the currently available longer-lasting insulin preparations that aim to provide a continuous basal level of circulating insulin are associated with markedly variable action both between and within subjects. Unpredictable insulin action contributes to variable blood glucose control, which in addition to increasing the risk of hypoglycaemia has also been shown to be an independent risk factor for mortality. It is hoped that advances in longer-lasting insulin preparations will provide significant benefits to patients, improving control and reducing variability. A new, long-lasting analogue, insulin detemir, has been shown to be significantly less variable than other basal insulin preparations in pharmacological and clinical studies. The improved predictability in insulin response offered by insulin detemir may be associated with a number of clinical benefits including a reduction in hypoglycaemia and weight gain.</p>","PeriodicalId":14227,"journal":{"name":"International journal of obesity and related metabolic disorders : journal of the International Association for the Study of Obesity","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2004-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1038/sj.ijo.0802747","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24633493","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Can we reduce hypoglycaemia with insulin detemir?","authors":"C Mathieu","doi":"10.1038/sj.ijo.0802748","DOIUrl":"https://doi.org/10.1038/sj.ijo.0802748","url":null,"abstract":"<p><p>Tight glycaemic control is essential for reducing the risk of long-term diabetic complications in people with type I or II diabetes. Intensive blood-glucose control attempts to normalise both pre- and postprandial glycaemia, while avoiding severe hypoglycaemia. A basal insulin, providing a low level of insulin to cover postprandial and overnight fasting periods, is central to intensive blood-glucose control. However, hypoglycaemia, particularly nocturnal hypoglycaemia, is a major treatment-related complication of therapy with most basal insulins currently available for use in clinical practice. This is a result of pronounced peaks in absorption, which lead to inappropriate hyperinsulinaemia following evening administration, and especially poorly reproducible pharmacokinetic profiles when injected subcutaneously. Indeed, for many patients and health-care providers, concern around hypoglycaemia forms a critical barrier to the attainment of tight glycaemic control. Insulin detemir is a novel long-acting analogue of human insulin designed to overcome these practical limitations. Clinical evidence from comparative studies with NPH insulin shows that insulin detemir provides a consistent and clinically relevant reduction in hypoglycaemic risk, especially for nocturnal events, at equivalent or better levels of glycaemic control.</p>","PeriodicalId":14227,"journal":{"name":"International journal of obesity and related metabolic disorders : journal of the International Association for the Study of Obesity","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2004-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1038/sj.ijo.0802748","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24631791","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"At last, a weight neutral insulin?","authors":"A Fritsche, H Häring","doi":"10.1038/sj.ijo.0802749","DOIUrl":"https://doi.org/10.1038/sj.ijo.0802749","url":null,"abstract":"<p><p>In the treatment of diabetes, the positive correlation between weight gain and glycaemic control is well known. Inappropriate weight gain has been demonstrated in landmark diabetes studies, with insulin or oral antidiabetic drugs. Weight increase is associated with accelerated deterioration in beta-cell function in type II diabetes, and increases in hypertension and lipid levels in both type I and type II diabetes. Concerns about increasing weight may be a barrier to initiation or to intensification of insulin therapy. Insulin introduction may be delayed in type II diabetes, and patients may under-dose their insulin to avoid gaining weight. Insulin detemir is a new long-acting soluble insulin analogue where protraction is achieved by reversible binding to albumin. As a result, it has consistent absorption and low variability from injection to injection. Studies of insulin detemir in basal-bolus regimens in type I and type II diabetes have shown significantly less weight gain compared with NPH. There is speculation about potential mechanisms for these outcomes and results from ongoing investigations are awaited. The insulin detemir data suggest that weight gain with insulin therapy is not inevitable. The potential therefore exists for improving glycaemic control while maintaining weight stability, resulting in immediate and long-term benefits for patients.</p>","PeriodicalId":14227,"journal":{"name":"International journal of obesity and related metabolic disorders : journal of the International Association for the Study of Obesity","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2004-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1038/sj.ijo.0802749","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24631792","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The pathophysiological basis for intensive insulin replacement.","authors":"A Rolla","doi":"10.1038/sj.ijo.0802743","DOIUrl":"https://doi.org/10.1038/sj.ijo.0802743","url":null,"abstract":"<p><p>Both type I and type II diabetes are characterised by a progressive decrease in beta-cell function and mass. In type I diabetes, autoimmune destruction results in rapid loss of beta-cell function, and insulin therapy is essential to maintain normoglycaemia. In type II diabetes, a diminished or absent first-phase insulin release is the earliest metabolic defect, which is accompanied by lack of prandial suppression of hepatic glucose production, increased postprandial glucose excursions and late insulin hypersecretion. Furthermore, chronic exposure to elevated glucose, even to intermittent postprandial spikes, results in further deterioration of the beta-cell function ('glucotoxicity'). By the time type II diabetes is diagnosed, beta-cell function and mass have declined by about 50%. With the progression of the disease and glucotoxicity there is continuous decrease in beta-cell mass due to increased apoptosis that results in absolute insulin deficiency. By then, patients require insulin administration to maintain glucose control. An increasing body of evidence demonstrates the importance of preserving endogenous beta-cell function both in type I and type II diabetes. Early and intensive glycaemic control, using regimens which re-create a physiological insulin profile, controlling postprandial as well as fasting glucose levels, offers the most promise for preserving beta-cell function, decreasing disease progression, and reducing the chronic complications of diabetes.</p>","PeriodicalId":14227,"journal":{"name":"International journal of obesity and related metabolic disorders : journal of the International Association for the Study of Obesity","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2004-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1038/sj.ijo.0802743","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24633489","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Insulin therapy-realising the potential.","authors":"M Nattrass","doi":"10.1038/sj.ijo.0802742","DOIUrl":"https://doi.org/10.1038/sj.ijo.0802742","url":null,"abstract":"","PeriodicalId":14227,"journal":{"name":"International journal of obesity and related metabolic disorders : journal of the International Association for the Study of Obesity","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2004-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1038/sj.ijo.0802742","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24633488","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Management of obesity in adults: project for European primary care.","authors":"","doi":"10.1038/sj.ijo.0802663","DOIUrl":"https://doi.org/10.1038/sj.ijo.0802663","url":null,"abstract":"","PeriodicalId":14227,"journal":{"name":"International journal of obesity and related metabolic disorders : journal of the International Association for the Study of Obesity","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2004-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1038/sj.ijo.0802663","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24535518","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"13th European Congress on Obesity. Prague, Czech Republic, 26-29 May, 2004. Abstracts.","authors":"","doi":"10.1038/sj.ijo.0802665","DOIUrl":"https://doi.org/10.1038/sj.ijo.0802665","url":null,"abstract":"","PeriodicalId":14227,"journal":{"name":"International journal of obesity and related metabolic disorders : journal of the International Association for the Study of Obesity","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2004-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1038/sj.ijo.0802665","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24535517","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Obesity, inflammation and type II diabetes.","authors":"D T Finegood","doi":"10.1038/sj.ijo.0802490","DOIUrl":"https://doi.org/10.1038/sj.ijo.0802490","url":null,"abstract":"","PeriodicalId":14227,"journal":{"name":"International journal of obesity and related metabolic disorders : journal of the International Association for the Study of Obesity","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2003-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1038/sj.ijo.0802490","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24149149","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
H E Hohmeier, V V Tran, G Chen, R Gasa, C B Newgard
{"title":"Inflammatory mechanisms in diabetes: lessons from the beta-cell.","authors":"H E Hohmeier, V V Tran, G Chen, R Gasa, C B Newgard","doi":"10.1038/sj.ijo.0802493","DOIUrl":"https://doi.org/10.1038/sj.ijo.0802493","url":null,"abstract":"<p><p>Inflammation plays an important role in the destruction of pancreatic islet beta-cells that leads to type I diabetes. This involves infiltration of T-cells and macrophages into the islets and local production of inflammatory cytokines such as interleukin (IL)-1 beta, tumor necrosis factor (TNF)-alpha, and interferon (IFN)-gamma. Our laboratory has developed several strategies for protecting beta-cells against oxidative stress and cytokine-induced cytotoxicity. These include a cytokine selection strategy that results in cell lines that are resistant to the combined effects of IL-1 beta+IFN-gamma. More recently, we have combined the cytokine selection procedure with overexpression of the antiapoptotic gene bcl-2, resulting in cell lines with greater resistance to oxidative stress and cytokine-induced damage than achieved with either procedure alone. This article summarizes this work and the remarkably divergent mechanisms by which protection is achieved in the different model systems. We also discuss the potential relevance of insights gained from these approaches for enhancing islet cell survival and function in both major forms of diabetes.</p>","PeriodicalId":14227,"journal":{"name":"International journal of obesity and related metabolic disorders : journal of the International Association for the Study of Obesity","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2003-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1038/sj.ijo.0802493","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24149151","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}