DOI: 10.31038/EDMJ.2020431

Abstract

The immense amounts of research into diabetes reflects the need for a better understanding of what is diabetes (DM), how it can be measured, and how it can be treated and/or managed however despite the enormous amounts invested in diabetes research there is not unanimity from the research community on any of these matters. The issue which faces diabetes researchers is whether to continue with ‘more of the same’ lines of research or whether to strike out and seek more radical solutions.

It is clear that the biology of the pancreas plays a significant role; in particular the many factors which influence the genetic expression of insulin (type 1 diabetes) and the subsequent ability of insulin to react with its reactive substrate (type 2 diabetes); however there must be additional factors which are consistent with the laws of chemistry and physics which are not yet being seriously considered in the etiology of DM i.e. that the known biology of DM is only part of the complex etiology of DM.

The author raises a number of issues in this paper which address a number of inconsistencies in the screening and treatment of diabetes. Heillustrates that type 1 and type 2 diabetes exist as comorbidities, that the onset of diabetes leads inevitably to the onset of a range of diabetic comorbidities,  and that ‘the regulation of blood glucose levels’ exhibits the characteristics of a neurally regulated physiological system. Such observations have immense significance regarding how we screen for diabetes and how we treat diabetes and diabetic comorbidities.

The Biology of Diabetes

The first step to consider in the process of Diabetes (DM) is that of genetic expression in which a wide spectrum of genes, currently considered to be more than 60 genes [1], coherently interact in order to express pre-pro-insulin (type 1 diabetes) however the interpretation of such data is complicated when considering that the spectrum of genes which express pre-pro-insulin can differ [2] e.g. between different racial subtypes.

There are few instances, if any, where a single gene acts independently of all other genes in order to express a particular protein or where a single gene is considered to be responsible for a particular medical indication e.g. in the case of Rett’s syndrome [3], which is considered to be widely attributable to a single mutation in the MECP₂ gene, a more in-depth examination of the literature reveals a lack of certainty surrounding such a conclusion e.g.

• ‘Mutations in a gene called MECP₂ underlie almost all cases of classic Rett syndrome’

• ‘Using a systematic gene screening approach, we have identified mutations in the gene (MECP₂) encoding X-linked methyl-CpG-binding protein 2 (MeCP2) as the cause of some cases of RTT’.

• ‘In 5 of 21 sporadic patients, we found 3 de novo missense mutations in the region encoding the highly conserved methyl-binding domain (MBD) as well as a de novo frameshift and a de novo nonsense mutation, both of which disrupt the transcription repression domain (TRD)’

• ‘In two affected half-sisters of a RTT family, we found segregation of an additional missense mutation not detected in their obligate carrier mother’

This indicates that there is conceivably a phenomenon of greater significance than gene chemistry but which nevertheless involves gene chemistry. It can only be explained if our DNA and genes are continually seeking out more stable states, in a best-fit manner i.e. changing between different conformational and energetic states [4] in order to find the most stable state.

It conceivably explains why therapies, which were designed to influence the genetic profile in order to be effective in their specific areas of application (viruses, virus-like particles and/or and vaccines), are associated with predisposition to type 1 diabetes [5].

1. It is often overlooked that genetic expression is a chemical reaction in which various components e.g. the genetic spectrum,transcriptases and minerals; influence the rate and extent to which pre-pro-insulin is expressed however transcriptases are often dependent upon magnesium and zinc for their structure, function and reactivity.  This is significant in DM becausethe level of essential minerals and/or their reactivity are dependent upon the prevailing intercellular pH therefore a deficit of minerals, in particular magnesium and zinc which is commonly observed in the diabetic [6], must influence the structure and/or reactivity of the enzyme and hence the extent of expression of pre-pro-insulin.

In general, the conversion of pre-pro-insulin to pro-insulin is considered to proceed without any significant hindrances however it should be emphasised that the conversion of pre-pro-insulin is dependent upon the availability and reactivity of signal peptidases and hence is likely to be influenced by the prevailing intercellular pH and levels of minerals and cofactors although the extent to which this occurs is uncertain.

2. Similarly the conversion of pro-insulin to insulin must also be dependent upon the prevailing reaction kinetics. Moreover, it is encoded by the INS gene [7] so any changes of gene structure [1] due to the influence of viruses and/or virus-like particles, the presence of mutant alleles, the influence of epigenetic components, the action of reactive oxygen species upon gene structure, alterations of gene conformation and energetics, and the prevailing reaction conditions e.g. pH and mineral levels;must also influence this process to some extent.

3. It is considered that because pro-insulin has a longer half-life than insulin (if not insulin levels would be in a perpetual deficit)and that this accounts for 5-30% of the insulin-like structures in the blood however there does not appear to be any significant explanations for this broad range of pro-insulin levels [8]. This may be significant, especially so if we consider that only one of the many insulin-like structures – insulin monomer – will react with its receptor protein IRP2.

4. Pro-insulin is converted to insulin by endopeptidases (PC1 & PC2) and Carboxypeptidase E which function at rates determined by their unique chemical properties and the corresponding reaction kinetics involving intercellular pH, levels of minerals, etc.

5. Insulin is a very large and highly reactive protein comprises 51 amino-acids. It exists as a dimer (particularly so when complexed as the zinc-hexamer), comprising an A chain and a B chain which are connected by disulphide bonds but reacts as the monomer. Its chemical properties are that it exists as a coiled moiety, is a polar entity with -NH₂ and –COOH groups at its extremities, is water soluble, and highly reactive (half-life of ca 3 minutes) so if the pH is not maintained at the appropriate level this will influence insulin conformation, energetic state and half-life.

6. The relatively slow genetic expression/productionof insulin, conceivably because it is such a large and highly reactive molecule, requires that insulin is stored in the pancreas as a zinc-hexamer; awaiting metabolic signals and vagal nerve stimulation [9] to be exocytosed from the cell into the circulation;however under pathological conditions i.e. elevated levels of intercellular acidity, reduced levels of essential minerals, alters the redox state and/or bioavailability and levels of transition metals. As a resultinsulin becomes less coiled and circulates as the monomer rather than as the more stable dimer or the hexamer.

It provides a mechanism whereby zinc availability and redox mechanism are linked. Zinc is transported by albumin and transferrin however transferrin also transports iron which reduces the absorption of zinc, and vice versa. Zinc and copper also have an antagonistic relationship. This is consistent with differing levels of intercellular acidity in which there is a biodynamic relationship between essential minerals and the transition minerals at pH 7.35. When intercellular pH decreases to pH of more typically 6.75 the levels of essential minerals such as zinc and magnesium decline whilst the levels of transition metals such as iron, aluminium, copper increase. It explains why most diabetic patients are magnesium and zinc deficient [10-12].

Moreover [13] insulin levels vary throughout the day, from <100pmol/l to >800pmol/l, and in particular (i) following a meal and (ii) in a 3-15 minute oscillating manner i.e. indicatively over a 3-6 minute period for those who are normally healthy and over a 6-15 minute period for the diabetic.Under acidic conditions insulin becomes less coiled and less reactive (the phenomena of ‘protein-resistance’ is common to insulin, leptin, ghrelin and perhaps also in the ‘folding’ of other proteins), the availability of zinc hexamer in the islets declines [14] under acidic conditions, and insulin is supplied over a longer period and/or in a less reactive form.

Pathological onset of DM under acidic conditions (in general, DM does not occur in patients with relatively neutral intercellular pH),is accompanied by the glycation of proteins [15,16] e.g. of insulin, albumin, LDL-Cholesterol, haemoglobin, fibrinogen, immunoglobulin(s), etc. This is indicative of free radical reactions which arise from increased acidity, increased levels of transition minerals [17], and a suitable substrate (glucose). It is confirmed by noting thatanti-oxidants [18] influence such oxidative processes and have a positive influence upon DM.

In addition the reaction of insulin with its receptor protein IRP2 is a magnesium dependent reaction and, as outlined, the supply of magnesium is dependent upon prevailing levels of intercellular pH.

7. That the regulation of intercellular pH is so immensely significant, if not obvious from the above, is further confirmed when considering the role of metformin which is eliminated from the body almost completely unmetabolised therefore its metabolic effect is not pharmacological. A closer examination of metformin’s chemical structure reveals that it exhibits the structure, and hence the function, of a biological buffer [19] which maintains intercellular pH at a level of indicatively 6.75-6.95.

Accordingly if applied to the diabetic patient it will have the effect of reducing intercellular pH in patients with a lower intercellular pH i.e. the severely diabetic and/or obese patient with intercellular pH of indicatively 6.25-6.75. This should have the effect of reducing the severity of their diabetic symptoms however it will not be a substitute for weight-reduction measures. For patients who are pre-diabetic, who have been prescribed metformin, it willlikely have the effect of lowering their intercellular pH and enhancing their diabetic symptoms.

8. The expression of insulin and the reaction of insulin with its receptor protein are sequential processes. If they were parallel processes there would be a selection of one of the two processes – the ‘either or’ scenario – but this is clearly not the case.  The genetic expression of a protein is followed by the reaction of the expressed protein with its reactive substrate. The two processes occur in sequence so type 1DM (genotype) and type 2DM (phenotype) are comorbidities in which there can be several different states e.g.

(i) low levels of type1DM and absence of type 2DM,

(ii) low levels of type 1DM and low levels of type 2DM (diagnosis: prediabetes),

(iii) low levels of type 1DM and high levels of type 2DM (type 2 diabetes),

(iv) high level of type 1DM and absence of type 2DM (diagnosis: type 1 diabetes),

(v) high level of type 1DM and low/moderate level of type 2DM (diagnosis: type 1DM)

(vi) high level of type 1DM and high level of type 2DM (diagnosis: type 1 and type 2DM)

It is not a case of whether the patient has either type 1DM or type 2DM. Both can and do occur as comorbidities as outlined in (ii)-(vi).

9. The GLUT-4 receptor which converts glucose into energy is located in the smooth muscle. Moreover this reaction is a chromium-dependent reaction in which the prevailing redox states of chromium are influenced by the prevailing intercellular pH i.e. the intercellular pH, in combination with the quality and quantity of smooth muscle (physical fitness) influences the ability to metabolise blood glucose.

Measuring Diabetes

The onset of pathological conditions, as outlined, leads to the production of mainly excessblood glucose and elevated levels of advanced glycation end-products, which are manifest as glycated proteins and other lipids, and which subsequently alter blood viscosity and thereby influence the function of the heart, kidneys, etc.  Nevertheless, and as outlined in 1.10 above, this hyperglycaemia which is characteristic of type 1DM, is only one aspect of diabetes.  Hypoglycaemia can be encountered due to suppression of the genetic expression of insulin.  Nevertheless the characteristics of diabetes, in particular of unstable levels of blood glucose, can occur due to pathological onset in other organs (mainly the endocrine glands) and physiological systems e.g. in the case of hysterectomy.

The glycated protein HbA_1c is used as a measure of type 2 diabetes however the validity of the test is often questioned, perhaps with good reason [20]. The processes responsible for type 1 and type 2 occur simultaneously i.e. they are comorbidities;thereby explaining to some extent the misdiagnoses when using the HbA_1c test [21,22], but the test only measures the glycation process.

The A1c form of glycated haemoglobin A was selected because it was considered to be the most prominent of the various forms of glycated haemoglobin however it is likely, perhaps inevitable, that altered reaction conditions will lead to increased/decreased levels of the different glycated haemoglobin isomers and a reduction/increase of HbA_1c.

‘the measurement of HbA1C is likely not a comprehensive indicator of HbA glycation’ [23]

Also, it is assumed that the ratio of haemoglobin Avs other proteins does not vary and hence that the test would be an accurate measure of the glycation process however the level of haemoglobin varies widely [24]. Test outcomes are influenced by many variables including light, pH, levels of minerals, RBC and/or haemoglobin levels, and other factors; and finally haemoglobin A does not play a role in the etiology of diabetes!Accordingly, the scope for misdiagnosis is immense. The possibility of inaccurate test results is inevitable, especially so in cases of non-pancreatic diabetes in which the problems of blood glucose regulation are not caused by the aforementioned pathological processes which are commonly attributed to diabetes but instead to pathological emergence in other organs and physiological systems [25].

All chemical reactions are accompanied by the absorption and emission of energy

i.e., by the emission of biophotons which create the phenomena of auto fluorescenceand/or bioluminescence in blood [26]. The emission of biophotons [27,28], as proteins decay from their reactive state to their base state, is particularly evident in the retina of diabetics as it alters blue-yellow colour perception [29] and serves as a measure of type 1 and type 2 diabetes in a cognitive test.

This occurs because the eye responds to as little as 7*10^2 bio photons per second.  The retina focusses this bioluminescence which can be measured in a cognitive test and used as a precise, digital measure of pathological onset and progression in all medical conditions which are accompanied by changes of colour perception and brain function i.e. across the complete medical spectrum.The company Bio Astral [28], supported by significant UK government grants prior to its demise, was researching advances in space-science imaging technology i.e. to measure the release of bio photons from blood (quote: ‘Our STJ cryogenic detector is 1000 times more powerful at detecting fluorescence in biological assays than current technology, and is unique in giving the colours of photons detected without requiring filters, gratings or other techniques’).

Accordingly a technique which measures the intensity and colour of biophotons has significant potential as a measure of diabetes which is relatively free from side-effects, errors and misdiagnoses.

The Neurology of Type 2 Diabetes

There are two fundamental avenues which influence the autonomic nervous system: (i) via sensory intake (vision, hearing, smell, taste and touch) and (ii) via the visceral organs.

As outlined in this text, genetic and non-genetic (phenotype) changes lead to the onset of type 1 and type 2 diabetes. It is commonly considered that genetic changes occur due to the effect of gene-altering moieties e.g. as viruses; however this text illustrates that genetic changes occur due (i) to the influence of virus-like particles (vaccines) and (ii) increased levels of intercellular pH which accompany stress and generate ROS which have a degenerative effect upon the genetic profile.

Moreover stress (either as psychological stress or as psychophysiological stress i.e. excess weight), which is experienced via the sensory organs and brain, is an acidifying process which increases cortisol levels and influences appetite [30] thereby illustrating the link between molecular biology and sense perception – influencing perception of colour and appetite.

So type 2 Diabetes is a neurological condition which arises because the brain is unable to maintain the calorific balance between appetite, the intake of calories through food and drink, and the expenditure of energy.

The regulation of blood glucose exhibits the characteristics of a neurally regulated physiological system whereby blood glucose levels are maintained between higher and lower levels hence the use of the terms ‘hyper’-glycaemia and ‘hypo’-glycaemia.

The regulation of blood glucose is just one of the 13 physiological systems. The other systems, identified by Grakov IG, are: blood pressure, blood volume, blood cell content, respiration, the consumption of food and drink, the elimination of fluids, intercellular pH, body temperature, posture, osmotic pressure, sexual function and sleep. Each performs an indispensable physiological function which, in most cases, and if not sustained within specific limits, leads to our demise.Each physiological system involves the brain and the endocrine glands.

Moreover, and as outlined earlier, the regulation of blood glucose involves the vagus nerve [9] which stimulates the pulsed release of insulin [13] by the pancreas.

Accordingly pathological onset in organs within this physiological system (network of organs) or in adjacent physiological systems will influence blood glucose levels. It explains the phenomena of non-pancreatic diabetes in which the patient(s) have problems regulating their blood glucose and yet their pancreas’ functions [31] normally e.g. due to endocrine dysfunction, hysterectomy, etc.

The most significant physiological systems [31] which influence the regulation of blood glucose level are sleep, pH [32], what we consume and excrete, and body temperature.

Each physiological system can be neurally regulated.

It is a problem for biomedicine to explain, using a solely chemical mechanism, how the different organ networks act in an apparently coherent manner.  In 2013 the Human Brain Projectwas established to explore the issues. It was tasked by the EC to achieve three fundamental objectives: (i) to understand what the brain does and how it does it; (ii) to use this knowledge to develop a new generation of cognitive diagnostic test, and (iii) to understand and adapt with therapeutic effect the multi-level nature of brain function.  Specific emphasis was placed upon screening the complex pathological coordinates of Alzheimer ’s disease.

Ewing recognised that these fundamental objectives had been completed by Grakov in the period 1981/2-1997-2006 and were incorporated into the Strannik software.  Papers followed which compared the two different techniques [33,34]; identified fundamental limitations of the techniques being deployed to achieve such objectives [34,35], in particular the reliance upon ‘big data’; determined that the brain acts as a neuromodulator [36] of the autonomic nervous system; that Grakov had developed a screening test which can screen for the complex pathological correlates of diabetes and diabetic comorbidities including Alzheimer’s Disease [37-42]; and had understood how this led to an understanding of the multilevel nature of brain function in particular of the mechanism which regulated the stability of the autonomic nervous system and the coherent function of the physiological systems [43].

The specific origins of such a technique can be traced back for over 100 years however it is only in the last 10-20 years that significant progress is being made towards the development of the envisaged new generation of neuromodulation therapy [44-46] which has the potential to improve therapeutic outcomes in [47] a wide range of medical indications [48-55] including multiple sclerosis, Parkinsonism, Alzheimer’s Disease, Migraine, regulation of menstruation, etc.

Discussion

The evidence assembled in this short paper illustrates that type 1 and type 2 diabetes are comorbidities and that‘the regulation of blood glucose levels’exhibits the characteristics of a neurally regulated physiological system and involves the process of neuroregulation [56,57] i.e. the relationship between sense perception, brain function, the autonomic nervous system (the stress response) and physiological systems, and cellular and molecular biology (as genotype and phenotype).

Moreover the evidence for such a conclusion, and its relevance to how we screen or treat diabetes is already evident in various diabetes papers which illustrate that (i) changes of blue-yellow colour perception accompany the onset and progression of diabetes, (ii) that this phenomena is not unique to diabetes but can be used to screen for an extensive range of pathologies [38] including diabetic comorbidities, (iii) that the phenomena is associated with the emission of biophotons, (iv) that the vagus nerve is involved in diabetes etiology, (v) that insulin is released by the pancreas in a pulsatile manner which is indicative of ‘control circuitry’, and (vi) that knowledge of this ‘neuro-regulatory mechanism’ can be used to treat patients with a wide range of pathological indications [39] including type 1 and type 2 diabetes and related diabetic comorbidities e.g. by reducing exposure to stress [30,58].

The future development of neurological knowledge, in particular of how the brain works and what it does, is leading to the development of a new generation of diagnostic and therapeutic technologies as envisaged by the EC’s Human Brain Project although perhaps such technologies [59] have not emanated from Human Brain Project research.

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DOI: 10.31038/EDMJ.2020424

Abstract

COVID19 is regarded as a lifethreatening infection for most people, but especially certain risk-groups including diabetes, and has therefore caused lock-down of societies which may have deleterious consequences.  Many countries have taken steps to shut down schools, companies and businesses,  and entire countries have been isolated. These drastic measures will have seriousconsequences for economy, psychosocial situation and health. There is a risk that people with other diseases like diabetes do not get ordinary adequate care.

Sweden has as the only country chosen another policy with recommended isolation of the most vulnerable populations, mainly people older than 70 years of age, and volontaryisolation of others who have eg serious lung disease och extreme obesity. Forverybody physical distancing, increased hygiene, at home when symptoms of COVID19, crowds < 50 people etc Otherwise open shops, open restaruants, open schools.

In the care of children and adolscents with Type 1 diabetes has some ordinary visits to the diabetesteam been replaced vby telemedicine. Quality has remained the same as 2018 and 2019  with national mean HbA1c 53.8 mmol/mol ( 95% CI 53-5- 54.1) during  Jan 1- April 28, 2020 and the proportion of patients with HbA1c < 57 mmol/l was  67.3% ( 95% CI  66-68.6%). Type 1 diabetes has not been a risk factor for severe COVID19, and no children with T1D are among those who have needed Intensive Care or who have died.

Keywords

COVID19, public health, economic depression, vulnerable groups, isolation

Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (COVID-19), is   a major threat. Many countries have taken steps to shut down schools, companies and businesses,  and entire countries have been isolated. These drastic measures will have serious consequences for economy, psychosocial situation and health.

Sweden has as the only country chosen another policy with recommended isolation of the most vulnerable populations, mainly people older than 70 years of age, and volontary isolation of others who have eg serious lung disease och extreme obesity. Otherwise open shops, open restaurants, open nursery and primary schools. In spite of this open policy and a high rate of infected people fatality rate has  remained in the middle range of  European countries.

Diabetes is regarded as one of the risk factors for COVID19 [1-4]. This seems especially true for Type 2 diabetes connected to metabolic syndrome with hypertension, cardio-vasculare disease, and obesity According to Yang et al., among 52 critically ill patients, diabetes was present in 17% of cases [5]. According to Guan et al., among 1099 patients, diabetes was present in 16.2% of cases and hypertension was present in 23.7% of cases [6] and  according to Zhang et al., among 140 hospitalized patients, diabete was present in 12% of cases and hypertension was present in 30% of cases [7]. In children < 18 years of age, COVID19 is usually a mild disease, which very seldom leads to any dangerous clinical manistestation [8]. For children with Type 1 diabetes ( T1D) the large scale lock-down of society might have verynegative impacts. There is a risk that patients who get symptoms of diabetes do not dare to seek care which could lead to more severe clinical manifestation at onset. Another risk of severe lock-down of society is that patients with diabetes do not get ordinary adequate care.

The aim of this study was to get a picture of  the need for care at Intensive Care Unit  in Sweden until now (April 28th 2020), the proportion of patients with diabetes and need for ICU in children and adolescents.  In addition the aim was to investigate how quality of care of children and adolescents with T1D in Sweden has been influenced by the ongoing pandemic.

Material and Methods

Sweden has next to Finland the highest incidence of T1D in children and adolescents in the world [9]. All patient visits are registered in a national data base, SWEDIABKIDS [10] with information about HbA1c, blood lipids etc. In what way the coronavirus epidemic has influenced care is described after regular contacts between diabetesteams at pediatric clinics. All patients needing intensive care are registered in the Swedish Register for Intensive Care, in which also all patients needing ICU because of COVID19 are registered [11].

Results

Some diabetes clinics have continued in the same way as before. Patients have come to the hospital for ordinary visits and met members of the diabetesteams. Other diabetes teams have during the corona epidemic started to use telemedicine as a complement, meaning that patients, and for children their parents, have been contacted via telephone and/or skype, and in addition blood glucose values have been uploaded from glucose sensors and evaluated using Diasend. National HbA1c has remained stable: For children < 18 year of age mean HbA1c for all Sweden was 2018 54.7 mmol/mol (95% confidence interval 54.4-55), for 2019 53.3 ( 53-53.6) and for 2020 ( jan 1- April 28) 53.8 ( 53-5- 54.1). The proportion of patients with HbA1c < 57 mmol/l was  2018 63.4% (  95% confidence interval 62.3-64.5%), 2019 68.3% (67.2-69.4%) and for 2020 ( Jan 1- April 28) 67.3% ( 66-68.6%). Kolesterolvalues are registered between age 10-18 years and proportion < 4.5 was 2018 69% ( 66.7- 71.3), 2019 69.9% ( 67.5-72.3) and 2020 so far 71.6% (684- 74.8). Looking at any other parameter in the quality register shows the same trend: No difference between 2020 so far (April 28th) and the previous two years.

Regarding severity of COVID19  and the result of the Swedish approach in comparison with the lock-down of other European countries it is difficult to draw conclusions as the different countries have different degree proportions of  infected population. Sweden , with its rather open society has already a high proportion of infected people in the general population, with certain areas having passed 25% of the population, while some countries calculate with much lower proportions. Number of deaths in Sweden are shown in Figure 1. Mean age of  death people was 81 years. A large majority (93%) of the death persons belonged to at least one risk group, with chronic cardiovascular disease being the most prevalent, followed by diabetes, chronic respiratory disease and chronic renal failure  (Table 1). Number of patients at Intensive Care Unit (ICU) is shown in Figure 2 which illustrates that the numbers per day is kept rather stable.Fig 3 shows that males dominate and that there are almost no young individuals needing ICU except for rare cases with severe other underlying diseases, not Type 1 diabetes.

Figure 1. Number of covid19-related deaths per day in Sweden

Figure 2. Number of covid19-related deaths per day in Sweden

Figure 3. ICU in different age groups. Blue: Females, Orange: Males.

Discussion

The Corona virus pandemic threathens ordinary health care, Many contries have  become paralysed and there is a risk that treatment of serious diseases like Type 1 diabetes in children and adolescents deteriorate, which may take long time to repair. With poor metabolic control we know that there is a increasing risk of vaculsar complications, and HbA1c has to be kept quite low to avoid long-term complications [12-14]. Sweden has a tradition of very active treatment of T1D with low mean HbA1c on a national level compared to many other contries [15]. In spite of this active treatment those who have got the diagnosis Type 1 diabetes in childhood have a much shorter expected length of life than a reference population [16]. Iy is therefore mandatory to try to keep quality of care also during the corona pandemic.

When society is closed because of the this pandemic telemedicine is an alternative to ordinary visits to the diabetes team [17]. This may become a valuable experience which in the future might improve care when used as a complement, but there will also be a risk that both diabetes teams and  patients/parents continue with this type of contacts instead of physical visits as it seems comfortable. Health care authorities may also become positive to this cheaper form av care. However, digital visits have certain advantages, but do not give the same type of contact as a physical meeting. This could lead to less motivation and deteriorating metabolic control .

During the corona pandemic Sweden has, unlike many other countries, not imposed any lockdown, with most measures being voluntary. The Swedish constitution prohibits ministerial rule and mandates that the relevant government body, in this case an expert agency, the Public Health Agency, must initiate all actions to prevent the virus, rendering the state epidemiologist a central figure in the crisis. The government can follow agency recommendations, as it has with legislation limiting freedom of assembly, temporarily banning gatherings of over 50 individuals, banning people from visiting nursing homes, as well as physically closing secondary schools and universities. Primary schools have remained open, in part to avoid healthcare workers staying home with their children.

The Public Health Agency and government have issued recommendations to: if possible, work from home; avoid unnecessary travel within the country; to engage in physical distancing; and for people above 70 to stay at home, as much as possible. Those with even minimal symptoms that could be caused by COVID-19 are recommended to stay home. The ‘karensdag‘ or initial day without paid sick-leave has been removed by the government and the length of time one can stay home with pay without a doctor’s note has been raised from 7 to 21 days.This approach has made it possible to keep the infection rate at such a level that the number of individuals needing intensive care because of COVID19 has remained at a steady state, and all the time there has been a reserve capacity of ca 20% of ICU beds.

Although a large proportion of the patients at ICU has had diabetes, most of them have had T2D, and no children or even young adults with T1D has needed ICU. T1D has not been regarded as a riskgroup in children andadolescents, and as society has been kept open the care and treatment of T1D has remained of good quality. There is so far no sign of deterioration of metabolic control, with HbA1c values which remain low compared to what is reported from other contries [15]. Ordinary visits at hospital has sometimes been replaced by virtual meetings with the use of internet. Thus, treatment of children and adolescents with Type 1 diabetes has worked well in spite of some lack of staff in the diabetes teams as some have been ill or stayed at home because of possible COVID19 symptoms, and also because some members of the diabetes teams have been ordered to be part of COVID19 teams.

The result of approach to fight the corona virus pandemic may have to differ between countries. One reason to different approaches in European countries is probably different political culture, where Sweden differs having strong independet expert authorities and a poluation with confidence in these authorities. Other countries may have more need for ”strong” political leaders making their own decisions, not always based on the basis of scientific evidence. The lock-down of societies evidently stop or at least delay the spread of corona virus, but only to some extent. The fatality rate has remained lower in some countries than in Sweden, but also much higher in several other European countries with strict lock-down. This lock-down approach  is not sustainable for an extended period due to its drastic and increasing economic and social consequences. Furthermore, even if successful, universal curfews would have to be implemented over many months or perhaps longer then so. The economic collapse with mass unemployment would have deterious effects on health including increasing mortality also in younger age groups. As an example the much less severe economic turbulence 2009 was calculated to cause the death of 260 000 individuals just by cancer [18] , and the negative effects on health in the developing countries was very large [19]. Another risk is the care of diabetes, as poor metabolic control may lead to long-term serious consequences for a large number of patients, with increased mortaliy many years later. In addition, long lock-down and economic collapse will, over time, destabilize society, not only through tremendous economic losses, but also through the risk of increasing social unrest and the psychological consequences of social isolation [20].

In conclusion, the corona pandemic may have great influence on the the care of Type 1 diabetes, which may have both actual and future effects. Type 1 diabetes is a lifethreatening disease. Too late diagnosis can lead to ketoacidosis and death. Poor metabolic control leads to serious complications and shorter life. The corona virus epidemic tends to paralyse societies and influence health care, which in the long run may ead to more serious effects on morbidity and mortality in young people than the corona virus per se. A more open approach based on isolation of vulnerable groups, mainly the elderly, but otherwise a functioning society is an alternative way to  both manage the pandemic and at the same time keep a high standard of diabetes care.

Acknowledgements

This study has been facilitated by the contacts created by SWEDIABNET ( The Swedish Pediatric Diabetes Trial network) supported by Vinnova and Barndiabetesfonden ( the Swedish Child Diabetes Foundation)

Disclosure

Johnny Ludvigsson has anything to disclose, and no conflict of interest.

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