As the result of epidemiological studies on relationship between diabetes and asthma it was proved that these diseases often accompany each other.
Bronchial asthma is a disease that is characterized by sufficiently strong and pronounced Th2-cytokine expression. Autoimmune diseases, which include 1 type diabetes, gluten enteropathy and rheumatoid arthritis are characterized by Th1-cells expression.
It would be logical to assume that diseases of this types cannot develop together, thanks to certain balance between immune response phenotypes.
Scientists in this area are regularly working on identifying key features of immune response of Th1- or Th2-type at different diseases and giving them a more precise characterization.
Epidemiological Studies Features and Results
Recently a study was conducted, in which cell analysis didn’t found differences of Th1- and Th2-dominant response at patients with diabetes and asthma.
To conduct another study 150 children with 1 type diabetes and 158 children suffering from bronchial asthma were analyzed. The study has also not defined differentiations in gene polymorphism at children suffering from diseases, compared with healthy children.
Another study was conducted using mice with diabetes. In this case, for the first time there appeared opportunity to get asthma symptoms via intranasal allergen provocation.
The fact that asthma and diabetes diseases often develop together, was proved by all studies conducted. In both disorders pathogenesis T-helpers of first and second types are participating.
In one of researches scientists analyzed more than 60 000 young people. Results of the study were as follows: children who have diabetes suffered from asthma consisted 5%. Children who suffered from rheumatoid arthritis (also autoimmune pathology) – 10%.
Another study showed almost twice as many. Presence of asthma was defined in 27 diabetic patients among 226 children studied (12,6%). This suggests that presence of Th1-caused disease did not reduce risk of developing asthma at humans.
In Denmark, there was conducted a large epidemiological study, which also failed to get any evidence of certain relationship between high incidence of juvenile diabetes and atopic eczema at children.
There also was conducted a meta-analysis of 25 random clinical studies, which proved that inverse relationship between 1 type diabetes and asthma still exists.
At the same time significant correlation was identified between 1 type diabetes and atopic dermatitis at children. To a small extent similar relationship is observed between rhinitis and diabetes. General conclusion suggests that children who suffer from 1 type diabetes have a small percentage of risk of developing asthma. But this relationship is not confirmed in cases where other atopic diseases are diagnosed.
A certain inconsistency in above-described data is explained by research results processing features.
Key Factors of Asthma and Diabetes Co-Development
There is a «hygiene» hypothesis, according to which the early body lesion by infections helps to develop immune response and has a protective effect on future diabetes and asthma development. Some studies also show that autoimmune and immune diseases development is greatly influenced by environment.
At patients with asthma a pronounced inverse relationship between insulin and cortisone blood level is observed.
Regardless of asthma and diabetes that are completely different diseases in essence, their «co-existence» is possible. There are the following options of these diseases «neighborhood»:
- First of all, these are situations when a person is sick with asthma and 1 type diabetes. Population studies confirmed that asthma risk at children who have 1 type diabetes is significantly higher compared to patients without autoimmune diseases.
- Regarding 2 type diabetes (non-insulin dependent diabetes), it has no pathogenetic connection with asthma. Most often, this type of disease is diagnosed at older people. Children, of course, can also suffer from it, but it is much more difficult to determine because of lack of clear signs.
- Another option is iatrogenic or steroid diabetes. It most often occurs at patients who are taking systemic glucocorticosteroids for bronchial asthma treatment for a long period. It is worth noting that this combination of diseases is rare.
- There is also quite a rare autosomal recessive disorder – the so-called Alstrom syndrome. With asthma and diabetes combination, children can be diagnosed diseases such as obesity, retinopathy, sensorineural hearing loss.
1 Type Diabetes Description and Diagnosis
Only an endocrinologist can make diagnose a child with 1 type diabetes on the basis of symptoms that have been observed, such as increased urination and increased thirst. These symptoms are not constant, they can appear and disappear in cycles. If the disease is not diagnosed for a long time, a child begins to lose weight.
Symptoms of diabetic ketosis are nausea, vomiting and abdominal pains. They can cause dehydration. If blood sugar content is higher than 6,1 mmol/l or 7,8 mmol/l mark after a couple of hours after OGTT (oral glucose tolerance test), doctors diagnose first type diabetes. To confirm it there also checked:
- presence of antibodies in blood characteristic for diabetes;
- glycated hemoglobin level (at diabetes it is high);
- genetic predisposition to diabetes.
If there are no all listed above criteria, it still does not guarantee freedom from further disease progression.
In contrast to first type diabetes, second type diabetes has no particular symptoms at adolescences, so doctors often make diagnosis at children.
At bronchial asthma diagnosis is carried out, based on some criteria such as:
- genetic predisposition to allergies (family diseases of asthma, dermatitis, allergic rhinoconjunctivitis, allergic rhinitis);
- positive allergic history (allergy to animals, pollen, etc.).
At young children, who have allergic background, which is usually associated with dermatitis, may be coughing at night. Cough may occur due to physical exercises, sudden weather changes, and so on. With allergy diagnosis doctor can confirm asthma presence (positive skin test, increased amount of IgE antibodies in blood).
Patients with asthma who suffer from secondary insulin-dependent diabetes, asthma has severe course, which is why they have to take long-term systemic glucocorticosteroids. However, this asthma treatment technique is ineffective, and modern doctors do not recommend it.
In Western countries asthma is treated with inhalation hormonal therapy. At severe forms short course of prednisone is prescribed, due to which Cushing’s syndrome and some more complications, including secondary insulin dependent diabetes do not develop.
Glucocorticosteroids in high doses during long-term treatment can lead to weight gain, which can cause sleep apnea or muscles respiratory dysfunction.
Many patients with asthma respond positively to glucocorticosteroids inhalation therapy, with its help the disease is controlled. But there is a small percentage of patients, which in addition to high doses of inhaled therapy from time to time need to take oral steroids. Unfortunately, in some cases, patient doesn’t show expected improvement, despite the fact that he takes systemic glucocorticosteroids.
The term was first defined in 1981 by Carmichael. In this form of asthma FEV (forced expiratory volume) responds to treatment with inhaled b-agonists with volume less than 15 per cent after a couple of weeks of taking prednisone (dose – 40 mg a day). Those who, on the contrary, have too high gain are steroid-sensitive.
Unlike steroid-resistant asthma, there is no clear definition for this type of asthma, however, there are also no precise characteristics for patients with this type of asthma. Doctors include in this category those patients who are taking steroids in high doses by inhalation or orally for a very long time.
In order to diagnose steroid-dependent bronchial asthma it is necessary:
- to confirm presence of asthma at patient (lung examination, Tiffeneau index determination);
- to introduce two hundred micrograms of salbutamol, and then measure bronchi dilation;
- to conduct bronchial provocation test;
- to check if medication is inhaled correctly, adherence to treatment, etc.;
- to check bronchoscopy results (characteristic of vocal cords prolapse, eosinophilic granulocytes volume in bronchoalveolar lavage fluid, cell studies, biopsy results, to clarify how thick basement membrane is and endobronchial cancer absence);
- to check how effective two-weeks treatment with prednisone is, examine external breathing, bronchial hypersensitivity and adherence to treatment;
- make sure that there are no other diseases (examine sleep condition for sleep apnea, monitor pH level during the day, conducts vegetative-vascular dystonia test, as well as psyche test, and so on).
The main criterion for steroid-dependent asthma diagnosis is the fact that the disease does not respond to treatment with prednisone orally from one to two weeks at dosage of 40 mg, with forced expiratory volume in one second increase more than by fifteen per cent (or 200 ml), compared to original indicator. Treatment lasting for two weeks is more effective than one-week course. However, there are patients, whose forced expiratory volume remains low (less than fifty or seventy per cent) despite treatment with above method. Those patients who do not respond to prednisolone (40 mg) therapy, may be responsive to larger dose of the drug. However, this fact has not been proved, so specific therapeutic effects at severe asthma at such treatment, even high doses, is not observed.
In order to assess how effective systemic glucocorticosteroid, bronchodilatatory response rate is calculated using the formula: post-treatment FEV1 minus pre-treatment FEV1 multiplies by 100 percent. The result is divided into pre-treatment FEV1.
All patients with this asthma type are necessary to be examined, which is recommended in some asthma forms (determining disease severity, actinology and allergy data, pathology diagnostics, and others).
If we analyze steroid-dependent asthma overall picture, medical books do not prove presence of typical Cushing’s syndrome or secondary insulin-dependent 1 type diabetes at these patients.
At these patients, the disease is usually severe, often acute, they are often hospitalized. Quality of life at these patients is reduced. Because these patients often observe bronchial obstruction, doctors have to prescribe them systemic glucocorticosteroids. This severe disease form is more common at women of eighteen and thirty years old.
Wambolt et al. researchers long observed clinical steroid-dependent asthma course at 34 children. As a result, there were found no features, but collective conclusion was made: asthma severe forms aggravation leads to lower sensitivity to glucocorticosteroids up to its complete absence. Another writer for a year observed steroid-dependent asthma at 11 patients. According to him, receiving prednisone (40 mg) with time changes b2-agonist inhalation test. In other words, steroid-dependent patients acquire status of steroid-sensitive and vice versa.
Among asthmatics such phenomenon is quite rare, but medical and social problem is closely associated with such patients. It is connected with serious treatment costs. In the West, for example, more than half of asthma treatment total cost is spent on treating asthmatics. Glucocorticosteroids resistance also occurs at patients with intestinal diseases and rheumatoid arthritis. Therefore, their treatment for country healthcare system has social and financial importance.
Anti-Asthma Therapy at Diabetes
- Systemic glucocorticosteroids along with beta-agonists are the primary means of asthma treatment. They change blood glucose level, improve it, providing beneficial effects;
- Glucocorticosteroids increase liver glycogen level, trigger glucose synthesis in the liver (gluconeogenesis);
- Nebulized salbutamol not only raises blood glucose level, but also increases chances of developing ketoacidosis at diabetics;
- Terbutaline is another group of beta-agonists. Influences on glucagon content at adults. It has a protective effect at nocturnal hypoglycemia. These data were confirmed experimentally.
N. Wright and J. Wales worked hard to study impact of anti-asthmatic drugs on hypoglycemia, and tried to control glycemia at children with 1 type diabetes. According to their data, 12% of these children were undergoing asthma treatment at the same time. They also took, among other drugs, beta-agonist at least once a week.
Among 27 children, 11 complemented treatment with inhaled glucocorticosteroids. Monitoring lasted for 3 months and showed the following results: hypoglycemia frequency decreased by 20% at children who were treated with anti-asthmatic drugs (initially data showed 72% of diabetic patients, p < 0,05). Moreover, asthmatics, suffering from diabetes, more effectively controlled their blood sugar level (HbA1c 8,8%), which can not be said about patients who were treated only from diabetes (HbA1c 9,3%). Nocturnal hypoglycemia episodes frequency remained unchanged. At children, taking inhaled glucocorticosteroids, hypoglycemia developed more often than at those who did not use steroids. Frequent use of beta-agonists reduces hypoglycemic episodes appearance.
Researchers do not have exact answer about pathologic process influence, observed at asthma, on hypoglycemia development, and they can not accurately answer, if other factors affect possible link between asthma and diabetes. These factors include physical activity, parental influence, compliance changes and so on.
At glucocorticosteroids therapy, hyperglycemia occurs very rarely. At the moment, there is no exact data yet on which glucocorticosteroids dose and treatment period provokes diabetes development. This also includes data on molecular mechanisms of glucocorticosteroid resistance, that applies to patients with asthma.
Combination of severe chronic diseases such as diabetes and asthma requires special approach to treatment tactics and actions, necessary to avoid complications specific to these diseases, choice.
Diseases Emergence and Development Causes
Patients with severe diagnosis must be under constant pulmonologist, endocrinologist and allergologist supervision. These diseases incidence statistics is sad. 70% of deaths in the United States are caused by diabetes, obesity or asthma. The reason for this lies in lack of factors assessment that increase risk of these serious diseases.
These factors are:
- alcohol consumption;
- passive way of life;
- poor diet.
Moreover, smoking, except asthma, also causes ischemic heart disease at patients with non-insulin dependent diabetes, because of blood circulation disorder. Research shows that smoking not only leads to asthma exacerbation, but also often causes its occurrence. Smoking increases probability of occurrence and development of diabetes complications, like nephropathy and neuropathy.
At a time when unhealthy way of life leads to significant increase in number of diseases, it is very important to actively campaign for healthy lifestyle. It is necessary to constantly enhance physical activity, abandon smoking, exclude harmful foods consumption and introduce into daily menu useful products. This can significantly reduce diabetes and asthma incidence.
Medical workers of all countries need to:
- improve quality of treatment;
- train people at risk group;
- support government programs to reduce diabetes and asthma risk factors.
For steroid diabetes prevention, which often occurs at patients with asthma due to systemic glucocorticosteroid medications reception, patients should be transferred to inhaled glucocorticosteroids in combination with other medications to control asthma. This treatment method is safer, but not always acceptable.
Current recommendations for systemic glucocorticosteroids appointment at patients with asthma should be followed as carefully as possible.
Glucocorticosteroids per os are indicated:
- at frequent uncontrolled asthma symptoms and exacerbations;
- at intermittent asthma, not responding to high doses of inhaled glucocorticosteroids;
- if patient is already receiving systemic glucocorticosteroids before and to maintain control over disease or treat exacerbations he needs a higher dose of the drug.
It is very important for patients with asthma to prescribe prednisone in short courses of not more than ten days, in dosage of 1 – 2 mg/kg/day with slow reduction in dosage when taking inhaled glucocorticosteroids. A small amount of prednisolone, required in severe cases of asthma, does not give significant adverse effects on adrenal system and bone tissues of patient. However, no systemic or inhaled glucocorticosteroids prevent occurrence of respiratory system remodeling at any disease severity.
The safest inhaled glucocorticosteroid is considered budesonide. It can be taken by pregnant women and children.
Pulmicort-nebula in suspension is prescribed to year-old children, and Pulmicort-Turbuhaler in powder is prescribed to children older than 6 years. Long-term use of these drugs in children and adults with severe or persistent asthma treatment has no effect on adrenal glands state and allowed to withdraw systemic glucocorticosteroids in 91 percent of patients.
Polcortolone, Kenalog, Dexamethasone and other deposited steroids are absolutely contraindicated for patients with bronchial asthma treatment, since they cause expressed adrenal function suppression. In addition they should not be prescribed for alternating scheme. Deposited steroids often lead to steroid diabetes development.
Steroid-sparing effect in cromones medication group and ketotifen has not received confirmation.
J. Price studies were able to confirm steroid-sparing effect of inhaled glucocorticosteroids – fluticasone in treating children with stable asthma. Patients were divided into two groups: 1st group patients received fluticasone (0,5 mg / 2 ml) twice a day, 2nd group patients – prednisolone once a day according to scheme: 4 days – 2 mg/kg a day (not more 40 mg), 3 days – 1 mg/kg a day (not more 20 mg). Prednisolone pills suppress adrenals much stronger than fluticasone nebula.
Recent studies suggest that ultraviolet can prevent Th1-mediated diseases occurrence such as 1 type diabetes. Perhaps it is facilitated by vitamins D synthesis in skin. It is proved that more than 90% of vitamin D content in human blood plasma appears as a result of ultraviolet rays irradiation. There are even assumption that 1 type diabetes does not occur at people taking vitamin D since birth.
Modern medical science recommends taking vitamin D to all patients with asthma who are receiving systemic glucocorticosteroids, as this increases risk of steroid-induced osteoporosis.
Recently, there appeared data about new drug groups development (PPAγ-receptor activators, agents that inhibit NF-κB nuclear factor activity) that could have impact on immune system serious disorders, appearing at asthma and diabetes.
For patients with asthma diagnosis (read more), complicated by diabetes, the most important task is early prevention of possible complications, timely changes in treatment regimen, if possible with total exclusion of systemic glucocorticosteroids from taken drugs list. In order to control your diabetes and asthma, you need to comply with requirements for diet, keep active lifestyle, fight with obesity and eliminate bad habits.
Patients, diagnosed with diabetes on the background of asthma, need timely appointment of attenuated anti-asthma therapy with latest drugs, making it possible to minimize glucocorticosteroids dosage.