We searched PubMed and Google Scholar, mainly for original research articles published up to May, 2013, which focused on the pathophysiology and treatment of type 2 diabetes. The main search terms used were “pathophysiology”, “type 2 diabetes”, “prediabetes”, “β-cell”, “insulin resistance”, and “treatment”. We mostly identified full-text articles written in English. We also searched ClinicalTrials.gov for information about ongoing clinical trials in type 2 diabetes.
ReviewPathophysiology and treatment of type 2 diabetes: perspectives on the past, present, and future
Section snippets
The epidemic of type 2 diabetes
The worldwide explosion of obesity has resulted in an ever-increasing prevalence of type 2 diabetes—a non-communicable disease that affects more than 370 million people.1 Without concerted efforts to address the pathogenesis and treatment of this syndrome, the harmful macrovascular and microvascular outcomes of type 2 diabetes will remain a major burden for decades to come. In this Review we examine aspects of the pathogenesis and treatment of type 2 diabetes, and discuss future needs if the
The past: identification of β-cell dysfunction and insulin resistance
Development of the insulin radioimmunoassay led to the finding that patients with early-maturity-onset diabetes produced insulin and secreted this hormone in response to nutrient ingestion.2 Subsequently, defects in the ability of islet β cells to respond to intravenous secretagogues (including glucose) were reported in these patients.3
Additionally, these patients did not respond well to insulin,4 and were thus deemed to be insulin insensitive. This insulin insensitivity was shown to contribute
Oral and injectable drugs: present knowledge, lessons learned, and implications for the future
The increasing prevalence of type 2 diabetes has stimulated development of many new approaches to safely treat hyperglycaemia (figure 3). The aim of these therapies is to reduce and maintain glucose concentrations as close to normal for as long as possible after diagnosis (Panel 1, Panel 2), and thereby prevent development of complications. Although some therapies have been unsuccessful because of adverse effects or negligible therapeutic efficacy, several are very well accepted and are used
The present situation
In 1998, investigators of the landmark UKPDS trial143 reported that improved glucose control (mainly with sulfonylurea antidiabetics and insulin) reduced microvascular complications in recently diagnosed patients with type 2 diabetes. The primary analysis did not show a clear benefit for macrovascular disease, and thus four large intervention studies were designed to examine the effect of more intensive lowering of glucose for cardiovascular outcomes.
Insulin was a major component of the
What does the future hold?
Several of these studies are following up participants for outcomes relevant to type 2 diabetes. In DPP, conversion from impaired glucose tolerance to diabetes has been diagnosed within 6 months; findings from this study will provide a better understanding of the natural history of microvascular and macrovascular complications, and help to establish whether some of these complications (eg, retinopathy) develop before the onset of diagnostic hyperglycaemia. In both DPP and Look AHEAD, assessment
Conclusions
In 1984, Asmal and Marble202 wrote that “despite the availability of oral hypoglycaemic drugs for nearly 30 years, their precise mode of action and role in the management of diabetes mellitus remains poorly defined and controversial”. Nearly 30 years after that statement, doctors and researchers still have a great deal to learn about the pathogenesis of type 2 diabetes and how best to use the therapies available, although great progress has been made in clarification of their modes of action.
Search strategy and selection criteria
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All bariatric surgeries are not created equal: insights from mechanistic comparisons
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Reprogramming of intestinal glucose metabolism and glycemic control in rats after gastric bypass
Science
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