Diabetes mellitus type 1Type 1 diabetes is characterized by progressive destruction of the insulin-producing beta cells of the pancreas and usually occurs in childhood or adolescence.
Diabetes mellitus type 1: Overview
Primary insulin-dependent diabetes mellitus, Juvenile diabetes, Insulin-dependent diabetes mellitus, Diabetes, Type 1 diabetes, Diabetes mellitus type 1
Diabetes mellitus is the name given to a group of metabolic diseases that are all characterized by hyperglycemia as a result of disturbances in insulin secretion and/or insulin action. Depending on the etiology, different forms are distinguished. Type 1 diabetes usually occurs in childhood or adolescence. Type 1 diabetes is characterized by progressive destruction of the insulin-producing beta cells in the islets of Langerhans in the pancreas. Absolute insulin deficiency develops differently from person to person, either fulminantly within a few months or in a more chronically regulated course over years.
The definition of type 1 diabetes also includes patients who are often first clinically diagnosed with type 2 diabetes and then receive the diagnosis "LADA" (Latent Autoimmune Diabetes in the Adults) either at diagnosis or many years later due to a positive islet autoantibody test. One subtype is idiopathic type 1 diabetes. Patients have permanent insulin deficiency, are prone to repeated episodes of ketoacidosis, but are autoantibody negative.
Epidemiology
Overall, about 0.4% of the population in Germany suffers from type 1 diabetes, half of whom develop the disease at the age of less than 20 years. The disease form is responsible for 90% of all diabetes cases in children and adolescents. In adults, only about 5% of diabetes cases are classified as type 1 diabetes.
Type 1 diabetes is the most common metabolic disease in childhood. For several years now, physicians have been observing a sharp increase in the number of type 1 diabetes cases among children – especially young children – and adolescents worldwide. In Germany, the incidence rate is currently increasing by 3% to 5% annually.
causes
Type 1 diabetes is caused by a cellular-mediated, chronic autoimmune destruction of beta cells. Genetic factors play a predisposing role in type 1 diabetes.
Pathogenesis
In type 1 diabetes, immune system defense cells attack and destroy insulin-producing beta cells in the pancreas. If the destruction of beta cells has exceeded a certain level, insulin deficiency occurs. Blood glucose levels are rising.
The exact background of type 1 diabetes has only been partially elucidated to date. It is known that type 1 diabetes is a polygenic disease. In addition, environmental influences, but also the effect of sex hormones during puberty, play a role in the development of diabetes.
Symptoms
The autoimmune reaction proceeds insidiously and without symptoms for a long time. Only later do typical symptoms such as:
If left untreated, hyperglycemia can lead to diabetic coma and death.
Diagnosis
The diagnosis of type 1 diabetes is based on
– the clinical symptoms and – the fasting plasma glucose (> 126 mg/dl).
In cases of doubt, other parameters can be used to make the diagnosis. These include:
– autoantibodies associated with diabetes (ICA, GAD65, IA2, IAA, ZnT8) – an oral glucose tolerance test (> 200 mg/dl after 2 hours) – an HbA1c determination (> 6,5%).
Therapy
The following medical goals are of primary importance:
– prevention of acute metabolic derailments – prevention of diabetes-related microvascular and macrovascular sequelae – normal physical development (length growth, weight gain, onset of puberty) (in pediatric patients) – least possible impairment of psychosocial development by diabetes and its therapy (in pediatric patients) – HbA1c< 7% – no hypoglycemias – as little blood glucose fluctuations as possible.
Insulin therapy
Insulin therapy should be initiated promptly after diagnosis of type 1 diabetes. In principle, the individual insulin requirement in people with type 1 diabetes is based on the physiological insulin secretion due to the absolute insulin deficiency. This occurs both without food intake (= basal insulin requirement) and after food intake (= prandial insulin requirement) discontinuously, d. h. pulsatile. When dosing insulin, it must be taken into account that the absolute insulin requirement also depends on the individual insulin sensitivity of each patient. For insulin therapy, simple. More elaborate ("intensified") strategies available. Intensified insulin therapy should be the standard of care in pediatric patients with type 1 diabetes. It is defined as the administration of at least three insulin injections per day. Above all, however, it is characterized by a substitution of the basal insulin requirement with long-acting "basal insulin". of the prandial insulin requirement with short-acting "bolus insulin" at mealtimes (basal-bolus principle). Insulin pump therapy should be considered for the following indications:
– small children, especially newborns, infants and preschool children – children and adolescents with pronounced blood glucose rise in the early morning hours (dawn phenomenon) – severe hypoglycemia, recurrent and nocturnal hypoglycemias (despite intensified conventional therapy [ICT]) – HbA1c value outside the target range (despite ICT) – incipient microvascular or macrovascular sequelae – restriction of quality of life due to previous insulin treatment – children with great fear of needles – pregnant adolescents (ideally preconceptional if pregnancy is planned) – competitive athletes – large fluctuations in blood glucose independent of HbA1c value (despite ICT).
The aim of insulin administration is the correct application of the active ingredient into the subcutaneous adipose tie.
Types of insulin
Currently, two different groups of insulins are available in Germany for insulin replacement therapy of people with type 1 diabetes:
All insulin types (normal insulins, human insulins with delay principle, short-acting analogues and long-acting analogues) as well as mixtures of different insulin types differ with respect to their pharmacokinetics. The treatment guidelines recommend short-acting insulin analogues for insulin pump therapy. Normal insulin should be used for intravenous insulin treatment.
Blood sugar control
Insulin therapy requires regular monitoring of progress. Blood glucose should be checked at least four times a day, usually before eating, before exercise, before sleeping, when ill, and when symptoms of hypoglycemia (tremors, palpitations, cravings, concentration problems) occur. Three options are used:
– Collection of a drop of blood using a lancet and conventional measurement of the capillary glucose content in a blood glucose meter (SMBG systems) – Flash Glucose Monitoring (FGM): Determination of the blood glucose concentration in the interstitial tie fluid using a sensor, manual triggering of the measurement – Continuous Glucose Monitoring (CGM): like FGM, but continuous measurement.
Acute complications
Diabetic ketoacidosis
Diabetic ketoacidosis is a potentially life-threatening condition. It should be treated immediately in a specialized facility by a diabetes team experienced with children. The biochemical criteria for ketoacidosis include:
– Hyperglycemia (blood sugar> 200 mg/dl or. > 11 mmol/l), – pH< 7.3 – bicarbonate< 15 mmol/l – ketonemia / ketonuria.
The most frequent cause of ketoacidosis in diabetics is infection, especially pneumonia, urinary tract infections, and abscesses, as well as forgotten or underdosed insulin doses and technical problems with insulin pump therapy.
The clinical symptoms in ketoacidosis are not always clear-cut. Frequent clinical leading symptoms are nausea, vomiting and abdominal pain. In severe derailment, there is severely deepened breathing with an odor of acetone in the air breathed. The following treatment goals should be aimed for:
– Circulatory stabilization with initial volume bolus with isotonic solution – subsequent slow balanced fluid and electrolyte replacement – slow normalization of blood glucose – compensation of acidosis and ketosis – avoidance of therapy complications (cerebral edema, hypokalemia) – diagnosis and therapy of triggering factors.
Hypoglycemia is when the blood glucose level drops below 50 mg/dl. Hypoglycemia can have various causes such as z. B. Overdose of blood glucose-lowering drugs or too low an energy intake (e.g., a heart attack). B. skipping a meal) or heavy physical exertion while maintaining the same insulin or tablet dose. Typical symptoms of hypoglycemia are sweating, trembling, palpitations, feelings of hunger and anxiety, and, when the blood glucose level is below 30 mg/dl, convulsions and unconsciousness. Acute therapy for hypoglycemia consists of ingesting carbohydrates, injecting glucagon, or infusing glucose solution.
Long-term complications and screening
Despite modern drug therapies, it is not possible in all cases to completely normalize blood glucose levels, so that up to 50% of patients suffer chronic secondary diseases and serious complications such as macroangiopathies (coronary heart disease, stroke, arterial occlusive disease), microangiopathies (retinopathy, nephropathy), neuropathies and diabetic foot syndrome (neuropathy and angiopathy) with the risk of amputation.
The HbA1c value should be determined at least every three months to monitor the metabolic control. For the diagnosis of lipohypertrophies, inspection of the injection sites and palpation of the skin should be performed at least annually, and quarterly in the case of abnormalities and especially in the case of unexplained fluctuations in metabolic status. From the age of eleven or after five years of diabetes, people with type 1 diabetes without known diabetes-associated secondary or concomitant diseases should undergo regular examinations for the early detection of nephropathies, neuropathies, diabetic foot syndrome, as well as diseases of the cardiovascular system and the eyes.
In childhood and adolescence, TSH and thyroid autoantibodies (TPO-AK, Tg-AK) should also be determined, and tests for celiac disease should be carried out regularly at one to two yearly intervals or if the patient has the corresponding symptoms.
Prognosis
Type 1 diabetes is usually lifelong and people need to regularly replace the insulin they lack in order to reduce their elevated blood glucose levels. Life expectancy of people with type 1 diabetes is reduced compared to the non-diabetic population.
Prophylaxis
Antibodies and other markers allow prediction and risk calculation with regard to the development of diabetes. However, there is a lack of effective preventive measures that could prevent diabetes manifestation.
Researchers are currently pursuing several strategies to develop prevention and vaccination options:
– protect the beta cell mass from destruction, – prevent islet autoimmunity, or. control and – promote beta cell regeneration. The current spectrum of preventive treatment strategies is diverse. In addition to predominantly immunotherapeutic approaches, this also includes anti-inflammatory therapies and the targeted influencing of environmental factors. Immunotherapies are intended to strengthen the body's own regulatory immune responses. Suppressing destructive immune responses. The goal is to restore immune tolerance to components (antigens) of the beta cells. Two alternative therapeutic approaches are currently available for this purpose, namely antigen-nonspecific immunosuppression and antigen-specific immunomodulation (vaccination).
indications
Curative therapy options under development
To date, no routine curative treatment for diabetes mellitus exists. Pancreatic or insulin-producing islet cells from human donors are transplanted sporadically. However, the availability of transplantable material is low, rejection rates are high, and functional capacity declines relatively quickly. In the future, animal ties or stem cells could also serve as a source of transplants. Techniques to create insulin-producing beta cells from embryonic or adult stem cells offer great medical potential.
In addition, there are already a number of promising research approaches in regenerative diabetes research aimed at preserving beta cell mass and function, respectively. to renew destroyed beta cells. If it were possible to convert human progenitor cells and other pancreatic cells into insulin-producing beta cells, it would be possible to normalize insulin secretion and thus treat diabetes causally. A long-term goal would also be to prevent the onset of type 1 diabetes by preventing the destruction of beta cells in genetically predisposed individuals from the outset.