Elsevier

The Lancet

Volume 383, Issue 9911, 4–10 January 2014, Pages 69-82
The Lancet

Seminar
Type 1 diabetes

https://doi.org/10.1016/S0140-6736(13)60591-7Get rights and content

Summary

Over the past decade, knowledge of the pathogenesis and natural history of type 1 diabetes has grown substantially, particularly with regard to disease prediction and heterogeneity, pancreatic pathology, and epidemiology. Technological improvements in insulin pumps and continuous glucose monitors help patients with type 1 diabetes manage the challenge of lifelong insulin administration. Agents that show promise for averting debilitating disease-associated complications have also been identified. However, despite broad organisational, intellectual, and fiscal investments, no means for preventing or curing type 1 diabetes exists, and, globally, the quality of diabetes management remains uneven. This Seminar discusses current progress in epidemiology, pathology, diagnosis, and treatment of type 1 diabetes, and prospects for an improved future for individuals with this disease.

Introduction

Type 1 diabetes is generally thought to be precipitated by an immune-associated, if not directly immune-mediated, destruction of insulin-producing pancreatic β cells.1, 2 Historically, type 1 diabetes was largely considered a disorder in children and adolescents, but this opinion has changed over the past decade, so that age at symptomatic onset is no longer a restricting factor.3 Polydipsia, polyphagia, and polyuria (the classic trio of symptoms associated with disease onset) along with overt hyperglycaemia remain diagnostic hallmarks in children and adolescents, and to a lesser extent in adults. An immediate need for exogenous insulin replacement is also a hallmark of type 1 diabetes, for which lifetime treatment is needed. Key questions remain regarding the epidemiology of type 1 diabetes, effectiveness of current therapies, understanding how the disorder develops, and preventing or curing the disease.

Section snippets

Epidemiology

Although type 1 diabetes can be diagnosed at any age, it is one of the most common chronic diseases of childhood.4 Peaks in presentation occur between 5–7 years of age and at or near puberty.5 Whereas most autoimmune disorders disproportionately affect women, type 1 diabetes is slightly more common in boys and men.6 The incidence of type 1 diabetes varies with seasonal changes and birth month. More cases are diagnosed in autumn and winter,7 and being born in the spring is associated with a

Diagnosis

Diagnosis of diabetes has historically included fasting blood glucose higher than 7 mmol/L (126 mg/dL), any blood glucose of 11·1 mmol/L (200 mg/dL) or higher with symptoms of hyperglycaemia, or an abnormal 2 h oral glucose-tolerance test.34 In 2009, the American Diabetes Association modified their guidelines for diabetes diagnosis to include glycated haemoglobin (HbA1C; a test that averages blood glucose concentrations over 3 months) of 6·5% or higher.35 Despite efforts to standardise

Pathophysiology

Most research articles on the pathogenesis of type 1 diabetes begin by noting that the disorder results from an autoimmune destruction of insulin-secreting pancreatic β cells. The presence of a chronic inflammatory infiltrate that affects pancreatic islets at symptomatic onset of type 1 diabetes is the basis of this observation (figure 2).49 Another dogma is that in patients with longstanding disease, the pancreas is devoid of insulin-producing cells and the remaining β cells are incapable of

Management of type 1 diabetes

The discovery of insulin in 1921–22 was clearly the most significant therapeutic event in the history of type 1 diabetes; however, exogenous insulin replacement does not always provide the metabolic regulation necessary to avoid one or more disease associated-complications (eg, retinopathy, neuropathy, cardiovascular disease, and hypoglycaemia). As a result, diabetes management in modern countries often includes use of insulin analogues and mechanical technologies (eg, insulin pumps and

Burden of type 1 diabetes: complications, excess mortality, and insulin access

The physical, social, and economic costs of type 1 diabetes are difficult to calculate, and attempts to quantify these variables typically do not distinguish between type 1 and type 2 disease. However, two studies have provided cost estimates specifically for type 1 diabetes, proposing an annual figure of $14·4–14·9 billion in the USA.104, 105 Regardless of the financial costs, achieving normoglycaemia is an important therapeutic goal for patients with type 1 diabetes, especially for avoiding

Prevention and cure

Nearly three decades have passed since the first immune-based therapies, using ciclosporin, were attempted to reverse type 1 diabetes.125 Many practical and intellectual advances have been made since then, including improved metabolic testing, better understanding of disease pathogenesis, and availability of immune markers.126 Efforts to prevent or cure type 1 diabetes are now done via large collaborative networks (eg, NIH TrialNet, Immune Tolerance Network, and Islet Cell Transplantation

Unanswered questions

This is a season of change with respect to understanding of the epidemiology, pathogenesis, treatment, and prospects for curing type 1 diabetes. In hindsight, many long-held goals once thought readily achievable have been difficult to realise, and concepts regarded as dogmas have proven to be flawed.

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