Novelties in Diabetes

C. Stettler, E. Christ, P. Diem, C., Stettler, E., Christ, P., Diem, C. Stettler, E. Christ, P. Diem

• Publisher: S. Karger
• Year: 2016
• Print ISBN: 9783318056389
• eBook ISBN: 9783318056396
• Topic: Medicine
• Subtopic: Endocrinology & Metabolism

The field of diabetes mellitus research is currently characterized by rapid and remarkable growth that has led to the development of significant diagnostic and therapeutic advances. This is very important given the fact that the frequency of the disease continues to increase at alarming rates worldwide. This new volume is a comprehensive overview of the contemporary state of the art in the field. Experts shed light on a broad range of relevant aspects, from genetic background to topics related to diabetic complications such as diabetic retinopathy or diabetic nephropathy. This is expanded upon through papers reporting on the present state of diabetes in pregnancy and on the relationship between diabetes and cancer. There is also an inventory of currently used therapeutic tools and a review of novel therapeutic approaches like incretin-based therapies or sodium-glucose transporter-2 inhibitors. Additionally, the latest technological developments such as enhanced features for blood glucose meter or continuous and implantable glucose monitoring devices are included. Providing a concise but comprehensive update, this book will be essential to every clinician involved in the treatment of diabetes mellitus.

Stettler C, Christ E, Diem P (eds): Novelties in Diabetes.
Endocr Dev. Basel, Karger 2016, vol 31, pp 1-27 (DOI: 10.1159/000439364)

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Treatment Goals in Diabetes

Andreas Melmer^a · Markus Laimer^{a, b}

^aDepartment of Internal Medicine, Division of Endocrinology, Gastroenterology and Diabetes, Medical University Innsbruck, Innsbruck, Austria; ^bDivision of Endocrinology, Diabetes and Clinical Nutrition, Inselspital, University of Bern, Bern, Switzerland

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Abstract

The quality of glycaemic control in diabetes mellitus relies on accurate individualization of available treatment options. Treatment targets depend on the type and duration of diabetes, the patients’ abilities and characteristics and the individual risk for acute and/or late-stage complications. These complications include hypoglycaemia, which can be severe and life threatening, hyperglycaemia, which is a main factor for the development of cardiovascular disease, and macrovascular and microvascular disease, both of which are hallmark features of diabetes-associated constraints. Moreover, other treatment goals in diabetic patients influence both glycaemic control and quality of life. Lipoproteins, blood pressure, weight control, mental health and lifestyle are important factors that contribute to the frequency of diabetes-associated complications.

© 2016 S. Karger AG, Basel

Introduction

Diabetes mellitus is a complex, chronic illness requiring continuous medical care involving multifactorial risk reduction strategies beyond glycaemic control. Regardless of diabetes classification, the treatment goals for every diabetic patient include the avoidance of short- and long-term complications and an improvement and maintenance of quality of life. To achieve these central goals, treatment has to be defined with respect to individual patients’ clinical abilities. Significant evidence indicates that a range of interventions aside from glycaemic control alone are necessary to improve diabetes outcomes [1]. Although type 1 diabetes (T1DM) and type 2 diabetes mellitus (T2DM) resemble a central pathophysiologic feature - a (complete) constraint of the functional levels of insulin - both entities differ in certain aspects regarding the short- and long-term targets of glycaemic control.

Type 1 Diabetes

An immediate need for exogenous insulin replacement is the hallmark feature of therapy for T1DM, for which lifetime treatment is necessary. Key questions remain regarding the epidemiology of T1DM, the effectiveness of current therapies, the aetiology of development of this disorder, and strategies to prevent or cure this disease [2]. The discovery of insulin in 1921 was clearly the most significant therapeutic event in the history of T1DM; however, exogenous insulin replacement does not always provide the metabolic regulation necessary to avoid one or more disease-associated complications (e.g. retinopathy, neuropathy, and cardiovascular disease (CVD)). After initial diagnosis and metabolic stabilisation, some patients with T1DM retain the ability to produce endogenous insulin. Although this endogenous secretion is typically low, maintenance is important since it is associated with less retinopathy and less severe hypoglycaemia at later stages of the disease. Despite numerous sophisticated attempts to preserve insulin secretion - including early and intense insulin therapy, novel technologies and interventions on the immune system - therapeutic success is limited in this context. Every patient with T1DM should receive intensive insulin therapy. In addition, the treatment goals for T1DM include education, nutrition, exercise, and psychosocial assistance, as well as evaluation for short- and long-term vascular and neurological complications. Given the mostly younger age of type 1 diabetes manifestation, all of these treatments have to be tempered ab initio, followed and re-evaluated based on individual factors, such as personal requirements, lifestyle, compliance, and complications.

Type 2 Diabetes

T2DM is denoted by a varying degree of insulin resistance and impaired insulin release that results in hyperglycaemia. Several central aspects of its pathophysiology are poorly understood, although several risk determinants for the development of T2DM are known, including genetic and environmental factors. In addition to less common features, T2DM is characterized by a continuous decrease in insulin secretion, thereby impairing beta-cell function and insulin resistance, which is detectable prior to the manifestation of T2DM [3-6]. The severity of insulin resistance depends on numerous factors including weight, age, heredity, oxidative stress, and endocrine background [7-10]. As a net effect, glucose metabolism gets deranged, resulting in elevated fasting glucose levels or impaired glucose tolerance. Even though a considerable amount of variation exists, an estimated 25% of patients with either elevated fasting glucose levels or impaired glucose tolerance will manifest T2DM within 3-5 years [11]. The treatment of patients with T2DM includes education, evaluation for microvascular and macrovascular complications, attempts to normalize glycaemic control, minimization of cardiovascular and other long-term risk factors, and avoidance of drugs that can aggravate abnormalities of insulin or lipid metabolism. All of these treatments need to be tempered based on individual factors, such as age, life expectancy, and comorbidities.

Glycaemic Control in Diabetes Mellitus

Treatment Targets: Differences between Type 1 and Type 2 Diabetes

Treatment goals differ between T1DM and T2DM due to differences in pathophysiology, onset of disease, patient characteristics, and environmental influences. For adult type 1 diabetic patients, glucose homeostasis should reach a near-normal pattern. A total of 20 years of prospectively collected data from the Diabetes Control and Complications Trial (DCCT) and the Epidemiology of Diabetes Interventions and Complications (EDIC) follow-up trial support the importance of stringent glycaemic control in type 1 diabetes. In a cohort study of 879 individuals with type 1 diabetes, those in the highest quartile of glycated haemoglobin A1c (HbA1c ≥12%) showed increased all-cause mortality (relative risk [RR] 2.4, 95% CI 1.5-3.8) and cardiovascular mortality (RR 3.3, 95% CI 1.8-6.1) compared to individuals in the lowest quartile (≤9.4%) [12]. In another study from the Swedish Diabetes Register, which compared 33,915 type 1 diabetic patients with non-diabetic individuals, the mean 8-year risk of mortality was proportionally higher in patients with the greatest HbA1c values (≥9.7%, hazard ratio (HR) for all-cause and cardiovascular mortality 8.51 and 10.46, respectively) [13].

Target HbA1c is generally below 7% in adult type 1 diabetic patients. However, the benefits of maintaining this target level to life expectancy and existing complications have to be weighed against the risk of hypoglycaemia. The target HbA1c values can be set higher in older patients, children, adolescents and patients with frequent hypoglycaemic events or hypoglycaemia unawareness. More stringent target HbA1c values (≤6%) may be indicated in individual patients or during pregnancy, since reducing HbA1c in non-diabetic women during pregnancy provides benefits to the foetus.

Glycaemic control in T2DM is known to gradually improve the risk of microvascular and macrovascular disease with every 1% loss in HbA1c [14]. However, evidence for beneficial effects of tight glycaemic control on macrovascular disease is scarce. Only one randomized controlled trial indicated positive effects of glycaemic control on macrovascular disease; several other trials were unable to identify a correlation, and one trial even showed harmful effects on macrovascular health [15-18]. Regarding HbA1c, a value of HbA1c ≤7.0% might be reasonable for most patients. Therefore, the fasting plasma glucose concentrations should be between 70 and 130 mg/dl (between 3.9 and 7.2 mmol/l), and post-prandial plasma glucose concentrations after 90-120 minutes should be 180 mg/dl (10 mmol/l) or less. Especially in T2DM patients, HbA1c goals must be re-evaluated based on individual needs, abilities and requirements. Older patients or patients with limited life expectancy should reach HbA1c values of approximately 8%.

Short-Term Therapeutic Targets in Type 1 Diabetes

The effectiveness of intensive insulin therapy, which is crucial in the treatment of type 1 diabetes, is modulated by a considerable amount of environmental and individual factors. These factors include the amount of ingested carbohydrates per meal, the circadian concentrations of counterregulatory hormones, illness, and stress. Acute complications due to inadequate insulin substitution consist of hypoglycaemia, hyperglycaemia, and glucose variability. It is of utmost importance to avoid excess variations in blood glucose as well as to target a mean HbA1c value that meets both evidence-based recommendations and individual requirements based on benefits and risks.

Hypoglycaemia in Type 1 Diabetes

The average type 1 diabetic patient experiences two episodes of symptomatic hypoglycaemia per week as well as one potentially disabling episode of severe hypoglycaemia per year [19, 20]. Hypoglycaemia is a major problem in T1DM that results in increased risk for glucose variability, ...

Table of contents

• Cover Page
• Front Matter
• Treatment Goals in Diabetes
• The ‘Old’ Anti-Diabetic Agents: A Systematic Inventory
• Novel Therapeutic Approaches in Diabetes
• Diabetes Technology
• Novelties in Diabetic Retinopathy
• Hypertension and Diabetic Nephropathy
• The Diabetic Foot: The Never-Ending Challenge
• Diabetes and Cancer
• Beta-Cell Replacement: Pancreas and Islet Cell Transplantation
• Gestational Diabetes Mellitus
• Genetic Defects of the β-Cell That Cause Diabetes
• Genetics of Type 2 Diabetes
• Author Index
• Subject Index