University of Oulu’s Professor Riitta Veijola discusses the impact of Type 1 diabetes on society and the challenges associated with tackling the disease
Type 1 diabetes (T1D) is a serious chronic disease which results from the lack of a vital hormone, insulin, which is normally secreted from the pancreas. All patients with T1D need permanent, regular insulin replacement therapy from the diagnosis. There is currently no means to cure this disease, and in the course of time there are significant risks for the development of vascular complications, as well as early death from cardiovascular disease. – Patients or their guardians are educated to inject suitable doses of insulin subcutaneously by using insulin syringes or pens, or by using an insulin pump. Typically, the treatment requires 5 to 7 daily injections or boluses from the insulin pump. The individual insulin doses need to be adjusted according to the size of the meal, the actual level of blood glucose and activities such as physical exercise. Therefore the blood glucose levels have to be carefully self-monitored by repeated fingertip measurements or using a subcutaneous sensor and continuous glucose monitor, in order to keep the blood glucose levels at the target 24 hours a day, 7 days a week. The maintenance of good metabolic control is known to markedly decrease the risk of long-term micro and macrovascular complications (retinopathy, nephropathy, neuropathy and cardiovascular disease), which are threatening to the patient when the duration of the disease increases. The patients are also at risk of severe acute complications such as hypoglycaemia and ketoacidosis. The intensive nature of the treatment required is demanding for the patients and their families and increases the risk of psychosocial problems. All these complications have a severe adverse effect on the health and quality of life of the patients and also remarkably reduce life expectancy.
Type 1 diabetes in Europe – adverse epidemiological trends
T1D is one of the most common chronic diseases occurring in childhood and adolescence. Furthermore, the disease is also commonly diagnosed among young adults aged 15-30 years, but could actually occur at any age. The prevalence of type 1 diabetes approaches 1% among adolescents aged 15 years in the high-incidence countries in northern Europe. In Finland the incidence of type 1 diabetes is the highest in the world reaching 64.2/100 000/year in 2005 in children younger than 15 years, which is almost 5 times higher than the incidence in the 1950’s. Similar trends are observed in other European countries. It is also alarming that T1D is increasingly more frequently diagnosed in young children aged 0-4 years. This trend may also increase the life-time risk of vascular complications, which are known to be associated with long disease duration and insufficient metabolic control. The reasons for the changing incidence are not known, but the fast pace of the change implies environmental causes. Epidemiological studies have indicated that there is a slight male excess in the incidence of T1D during childhood, and a sharp increase up to 1.8 in the male to female ratio in the incidence after puberty.
T1D clusters in families
T1D occurs more frequently in close relatives of patients with T1D than in the general population. The risk of progression to T1D by the age of 30 is 6% for siblings of diabetic children and increases to 10% by the age of 60. Several studies have reported that T1D is transmitted twice more often to the offspring of diabetic fathers than to those of diabetic mothers (6% vs 3%), the explanation for this difference remaining unclear. Familial clustering of Type 1 diabetes indicates genetic susceptibility for the disease. The strongest genetic risk factor for Type 1 diabetes is class II HLA genotype on chromosome 6. This association was found already in the early 1970’s by a candidate gene approach. Class II HLA genes encode a special protein structure expressed on the surface of the human blood white cells, but the mechanisms of how these molecules mediate the increased risk for Type 1 diabetes have remained unknown. Recent genome wide association studies (GWAS) have revealed an additional more than 50 gene regions associated with T1D. Interestingly enough, the genetic factors identified so far appear to be related to the function of the immune system. This is in contrast to the observation that susceptibility genes for type 2 diabetes (T2D) are genes, which encode proteins regulating the function of the insulin-secreting pancreatic beta-cells.
Type 1 diabetes: A high burden in society
More than 50 million people in Europe are affected with diabetes, with an estimated 5 million (10%) of them having type 1 diabetes. The economic burden per case of type 1 diabetes is higher than per case of type 2 diabetes, and the difference increases with age. The reasons behind the high cost of treatment for type 1 diabetes are due to the fact that T1D is most often diagnosed early in life, all patients need intensive insulin therapy from diagnosis, as well as careful blood glucose monitoring to maintain good metabolic control and avoid life-threatening hyper and hypoglycaemia. In addition, good treatment requires regular contact with health care professionals, and in the paediatric age group the expertise of a multidisciplinary team including various experts (pediatrician, diabetes nurse, diabetes educator, dietician, physiotherapist and psychologist). With long disease duration the risk of vascular complications increases and emerging complications cause additional contacts with the health care system. For the patient themselves type 1 diabetes is a devastating disease, and she/he is at risk of depression, emotional stress and a feeling of discrimination. It is of vital importance for the patient that she/he receives the best possible support from health care professionals but also from their family, day care staff, peers, teachers, and the surrounding society. Families of a child with type 1 diabetes experience more anxiety and have more frequent days leave from work than the average family, and the healthy siblings may feel neglected. In day care and at school the staff has to be educated to take care of diabetes, especially in emergency situations like hypoglycaemia. In many schools personal assistants have to be hired for the young children with T1D, who need assistance with diabetes-related procedures during the schoolday. The cost of type 1 diabetes is estimated to be at least €18 billion per year in Europe. Any alleviation in this personal, societal and economical burden, such as prevention or delaying the onset of T1D in children would bring substantial economic savings and improve the quality of life of the children and their families.
The pathogenesis of Type 1 diabetes is still unknown
The etiology and detailed pathomechanisms of type 1 diabetes are not known. – The current concept is that type 1 diabetes develops as a result of an autoimmune process, in which the immune system mediates a specific attack against the pancreatic insulin secreting beta cells, and this process finally leads to severe insulin deficiency. The development of type 1 diabetes is characterised by the presence of multiple beta-cell specific autoantibodies in the sera of the subjects, which emerge months or years before the symptoms of type 1 diabetes are present (excessive thirst and urinating, weight loss and loss of energy). In long-term prospective studies, such as The Type 1 Diabetes Prediction and Prevention (DIPP) Study in Finland, the children at increased genetic risk are regularly followed from birth until the diagnosis of T1D. These studies have revealed that beta-cell autoantibodies most often appear very early in life, with a peak at 1-2 years of age. By combining the data from the Finnish DIPP study and other prospective studies, we have revealed that when multiple autoantibodies are persistently present the risk for progression to clinical diagnosis of T1D approaches almost 100% although the time to clinical diagnosis varies. No effective treatment to prevent type 1 diabetes or a delay of the disease process have been identified despite many clinical trials, which have mainly tested various immunological treatments. In order to develop strategies to prevent and cure T1D in the future it is vital to obtain detailed understanding on the pathogenesis of T1D. The autoimmune process, which ultimately results in insulin deficiency and the diagnosis of type 1 diabetes, most often starts early, at the age of only 1-2 years. This discovery has led to the conclusion that possible exposure and events during the early developmental period of life are critical in the initiation of the disease process resulting in T1D and should be studied more in detail in the future.
Riitta Veijola
Professor, Chief Physician
University of Oulu and Oulu University
Hospital, Department of Paediatrics
Tel: +35883155129
riitta.veijola@oulu.fi
http://www.oulu.fi/pediatr/index_eng.html
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