Category: Metabolic Disorders

Categories : Metabolic DisordersTags :

Metabolite Discovery Could Turn ‘Bad’ Fat to ‘Good’ Fat

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Obesity
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Metabolites are the substances made and used during the body’s metabolic processes – or, as a new discovery out of Scripps Research and its drug development arm, Calibr, indicates, they could also be potent molecules for treating severe diseases.

In a study published in the journal Metabolites, the researchers used novel drug discovery technologies to uncover a metabolite that converts white adipocytes (‘bad’ fat cells) to brown adipocytes (‘good’ fat cells). This discovery suggests a pathway to treating metabolic disorders such as obesity, type 2 diabetes and cardiovascular disease. This creative drug discovery method could also identify countless other potential therapeutics.

“The reason many types of molecules don’t go to market is because of toxicity,” said co-senior author Gary Siuzdak, PhD. “With our technology, we can pull out endogenous metabolites – meaning the ones that the body makes on its own – that can have the same impact as a drug with less side effects. The potential of this approach is even evidenced by the FDA’s recent approval of Relyvrio, the combination of two endogenous metabolites for the treatment of amyotrophic lateral sclerosis (ALS).”

Metabolic diseases are often caused by an imbalance in energy homeostasis. This is why certain therapeutic approaches have centred around converting white adipocytes into brown adipocytes. White adipocytes store excess energy and can eventually result in metabolic diseases like obesity, while brown adipocytes dissolve this stored energy into heat – ultimately increasing the body’s energy expenditure and helping bring balance.

To uncover a therapy that could stimulate the production of brown adipocytes, the researchers searched through Calibr’s ReFRAME drug-repurposing collection – a library of 14 000 known drug compounds that have been approved by the FDA for other diseases or have been extensively tested for human safety. Using high-throughput screening – an automated drug discovery method for searching through large pools of information –the scientists scanned ReFRAME for a drug with these specific capabilities.  

This is how they uncovered zafirlukast, an FDA-approved drug used for treating asthma. Through a set of cell culture experiments, they found zafirlukast could turn adipocyte precursor cells (known as preadipocytes) into predominantly brown adipocytes, as well as convert white adipocytes into brown adipocytes.

Unfortunately, zafirlukast is toxic at higher doses, and it wasn’t entirely clear how zafirlukast was converting the adipocytes. This is when the researchers partnered with Dr Siuzdak and his team of metabolite experts.

“We needed to use additional tools to break down the chemicals in zafirlukast’s mechanism,” explained Kristen Johnson, PhD, co-senior author of the paper. “Framed another way, could we find a metabolite that was providing the same functional effect that zafirlukast was, but without the side effects?”

Dr Siuzdak and his team designed a novel set of experiments, known as drug-initiated activity metabolomics (DIAM) screening, to help answer Johnson’s question. DIAM uses technologies such as liquid chromatography (a tool that separates components in a mixture) and mass spectrometry (an analytical technique that separates particles by weight and charge) to pool through thousands of molecules and identify specific metabolites. In this case, the researchers were searching through adipose tissue for metabolites that could lead to brown adipocyte cell production.

After reducing 30 000 metabolic features to just 17 metabolites, they came upon myristoylglycine – an endogenous metabolite that prompted the creation of brown adipocytes, without harming the cell. Of the thousands of metabolic features measured in the analysis, only myristoylglycine had this special characteristic, even among nearly structurally identical metabolites.

“Identifying myristoylglycine among the thousands of other molecules speaks to the power of Siuzdak’s approach and these technologies,” added Dr Johnson. “Our findings illustrate what happens when an analytical chemistry team and a drug discovery group closely collaborate with each other.”

Source: Scripps Research

Categories : Metabolic DisordersTags :

Late Night Snacks Impact Hunger, Metabolism and Adipose Tissue

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Photo by Aaron Burden on Unsplash

While popular diets discourage midnight snacking, few studies have examined the simultaneous effects of late eating on the weight gain trifecta regulation of calorie intake, the number of calories burnt, and molecular changes in fat tissue. Now, a new study published in Cell Metabolism has found that timing of food intake significantly impacts energy expenditure, appetite, and molecular pathways in adipose tissue.

“We wanted to test the mechanisms that may explain why late eating increases obesity risk,” explained senior author Frank A. J. L. Scheer, PhD, Director of the Medical Chronobiology Program in the Brigham’s Division of Sleep and Circadian Disorders. “Previous research by us and others had shown that late eating is associated with increased obesity risk, increased body fat, and impaired weight loss success. We wanted to understand why.”

“In this study, we asked, ‘Does the time that we eat matter when everything else is kept consistent?'” said first author Nina Vujovic, PhD, a researcher in the Medical Chronobiology Program in the Brigham’s Division of Sleep and Circadian Disorders. “And we found that eating four hours later makes a significant difference for our hunger levels, the way we burn calories after we eat, and the way we store fat.”

Vujovic, Scheer and their team studied 16 patients with a body mass index (BMI) in the overweight or obese range. Each participant completed two laboratory protocols: one with a strictly scheduled early meal schedule, and the other with the exact same meals, each scheduled about four hours later in the day. In the last two to three weeks before starting each of the in-laboratory protocols, participants maintained fixed sleep and wake schedules, and in the final three days before entering the laboratory, they strictly followed identical diets and meal schedules at home. In the lab, participants regularly documented their hunger and appetite, provided frequent small blood samples throughout the day, and had their body temperature and energy expenditure measured. To measure how eating time affected molecular pathways involved in adipogenesis, or how the body stores fat, investigators collected biopsies of adipose tissue from a subset of participants during laboratory testing in both the early and late eating protocols, to enable comparison of gene expression patterns/levels between these two eating conditions.

Results revealed that eating later had profound effects on hunger and appetite-regulating hormones leptin and ghrelin, which influence our drive to eat. Specifically, levels of the hormone leptin, which signals satiety, were decreased across the 24 hours in the late eating condition compared to the early eating conditions. When participants ate later, they also burned calories at a slower rate and exhibited adipose tissue gene expression towards increased adipogenesis and decreased lipolysis, which promote fat growth. Notably, these findings convey converging physiological and molecular mechanisms underlying the correlation between late eating and increased obesity risk.

Vujovic explained that these findings are not only consistent with a large body of research suggesting that eating later increases risk of developing obesity, but they shed new light on how this might occur. By using a randomised crossover study, and tightly controlling for behavioural and environmental factors such as physical activity, posture, sleep, and light exposure, investigators were able to detect changes the different control systems involved in energy balance, a marker of how our bodies use the food we consume.

Future studies will include more female participants. Despite only five female participants, the study was set up to control for menstrual phase, reducing confounding but making recruiting women more difficult. Going forward, Scheer and Vujovic are also interested in better understanding the effects of the relationship between meal time and bedtime on energy balance.

“This study shows the impact of late versus early eating. Here, we isolated these effects by controlling for confounding variables like caloric intake, physical activity, sleep, and light exposure, but in real life, many of these factors may themselves be influenced by meal timing,” said Scheer. “In larger scale studies, where tight control of all these factors is not feasible, we must at least consider how other behavioural and environmental variables alter these biological pathways underlying obesity risk. “

Source: Brigham and Women’s Hospital

Categories : Ageing Metabolic DisordersTags :

Resilient Mindset Helps Older People with Type 2 Diabetes

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Old man
Source: JD Mason on Unsplash

New research suggests that psychological resilience, ie having attitudes and behaviours that help people bounce back after stressful challenges, may help older individuals with type 2 diabetes to experience fewer hospitalisations and have better physical functioning, lower disability, better mental quality of life, and a lower likelihood of becoming frail.

The study, published in published in the Journal of the American Geriatrics Society, recruited 3199 participants, average age 72.2 years, 61% female, 61% white, and followed them for 14 years. The association of resilience with some metrics (grip strength and self-reported disability) varied based on recent hospitalisation history, and results suggested that some associations may differ based on race/ethnicity.

“This study suggests that individuals who report being psychologically resilient also report fewer aging-related concerns,” said lead author KayLoni L. Olson, PhD, of the Warren Alpert Medical School of Brown University. “This study is preliminary but points to the potential role of psychological resilience in helping individuals feel better mentally and physically, which can ultimately enhance their later years of life.”

Source: Wiley

Categories : Metabolic Disorders Neurodegenerative DiseasesTags :

Link Found Between Dementia Indicators and Metabolism

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MRI images of the brain
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A world-first study published in the journal Diabetes, Obesity and Metabolism, has uncovered an association between metabolism and dementia-related brain measures, providing valuable insights about the disease.

Analysing UK Biobank data from 26 239 people, University of South Australia researchers found that those with obesity related to liver stress, or to inflammation and kidney stress, had the most adverse brain findings.

The study measured associations of six diverse metabolic profiles and 39 cardiometabolic markers, using MRI brain scan measures of brain volume, brain lesions, and iron accumulation, to identify early risk factors for dementia.

Participants with metabolic profiles associated with obesity were more likely to have adverse MRI profiles showing lower hippocampal and grey matter volumes, greater burden of brain lesions, and higher accumulation of iron.

UniSA researcher, Dr Amanda Lumsden, says the research adds a new layer of understanding to brain health.

“Dementia is a debilitating disease that affects more than 55 million people worldwide,” Dr Lumsden said.

“Understanding metabolic factors and profiles associated with dementia-related brain changes can help identify early risk factors for dementia.

“In this research, we found that adverse neuroimaging patterns were more prevalent among people who had metabolic types related to obesity.

“These people also had the highest Basal Metabolic Rate (BMR) -how much energy your body requires when resting in order to support its basic functions — but curiously, BMR seemed to contribute to adverse brain markers over and above the effects of obesity.”

Senior investigator Professor Elina Hyppönen said that the finding presents a new avenue for understanding brain health.

“This study indicates that metabolic profiles are associated with aspects of brain health. We also found associations with many individual biomarkers which may provide clues into the processes leading to dementia,” said Prof Hyppönen.

“The human body is complex, and more work is now needed to find out exactly why and how these associations arise.”

Source: University of South Australia

Categories : Diseases, Syndromes and Conditions Metabolic DisordersTags :

Strong Link of Type 1 Diabetes to Enterovirus Infection

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A 3D map of the islets in the human pancreas. Source: Wikimedia

A meta-analysis of molecular studies found a strong link between enterovirus infection and type 1 diabetes. Across 48 abstracts on the topic, people with type 1 diabetes were nearly eight times more likely to have an enterovirus infection than those with normal pancreatic function, according to a presentation at the European Association for the Study of Diabetes (EASD) meeting.

For this review, researchers examined 56 studies using molecular methods to identify enterovirus infection by looking for viral nucleic acid or protein in a human clinical sample.

People with islet autoimmunity were twice as likely to have had an enterovirus infection at any point in time, based on data from 18 studies.

Subgroup analysis of people who were diagnosed with the enterovirus within the past month found 16.22-fold higher odds of recent-onset type 1 diabetes, based upon 28 studies.

“This is very recent onset type 1 diabetes, and that was the highest risk group that we detected,” reported Sonia Isaacs, PhD candidate, of University of New South Wales in Australia, during a press conference.

Looking more closely at other subgroup criteria revealed associations.

First, those who had any islet autoimmunity and eventually progressed to full-blown type 1 diabetes were over five times more likely to have an enterovirus infection than controls; this was a higher risk than those who had islet autoimmunity and never progressed to type 1 diabetes. When it came to timing, only infections at the time of or after islet autoimmunity seroconversion carried higher risk (OR 5.1), whereas the increased risk wasn’t significant for infections prior to seroconversion.

Isaacs noted that those with a familial risk of type 1 diabetes (ie in a first-degree relative) also had a much higher risk for an enterovirus infection (OR 9.8), higher than the subgroup recruited for having a high-risk HLA gene. Those who had the high-risk HLA gene and a familiar risk of type 1 diabetes had 141.1-times higher odds of prior enterovirus infection.

Having several enterovirus infections was also linked with a doubled chance of islet autoimmunity.

Specific type of enterovirus linked to risk of type 1 diabetes included:

  • Enterovirus A: OR 3.7
  • Enterovirus B: OR 12.7
  • Enterovirus C: OR 13.8

“This is where the coxsackieviruses come from,” Isaacs pointed out. “Coxsackievirus B1 and B4 stood out.”

Isaacs suggested the possibility of enterovirus vaccinations and antivirals as a prevention strategy for type 1 diabetes.

Source: MedPage Today

Categories : Mental Health Metabolic DisordersTags :

Genes and Environment Bridge Depression and Endocrine-metabolic Disorders

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While endocrine-metabolic disorders and depression are known to co-occur, genetic and environmental factors are known to underlie both. In a study examining the link, published in the American Journal of Psychiatry, analysis revealed the balance of genetic and environmental influences underlying the co-occurrence of depression for a range of endocrine-metabolic disorders.

It is known that there is elevated co-occurrence between endocrine-metabolic disorders and depression, but the relationship between them is still not well understood.

Familial aggregation

The authors identified 2.2 million individuals born in Sweden between 1973 and 1996, as well as their full and half siblings, and followed them up to age 40. A number of medical conditions were studied; depression and various endocrine-metabolic disorders, including three autoimmune diseases (autoimmune hypothyroidism, Graves’ disease, and type 1 diabetes) and three non-autoimmune disorders (type 2 diabetes, obesity, and polycystic ovary syndrome).

Individuals with endocrine-metabolic disorders had 1.4 to 3.5 times the risk of depression compared to people without these diagnoses. Full and half siblings of these individuals also showed some elevated risk for depression, suggesting that genetic and/or environmental risk factors shared between family members play a role in the co-occurrence of these mental and physical disorders.

Genetic and environmental contributions

By comparing pairs of full sibling (who share about half of their genes) to pairs of half siblings (who share about a quarter of their genes), it was possible to calculate the relative contribution of genetic and environmental factors to the co-occurrence of depression and various endocrine-metabolic disorders. 

The results were a mix of these possibilities; the overlap between depression and non-autoimmune conditions was mainly explained by shared genetic influences, while environmental factors were predominantly involved in the association between depression and autoimmune disorders, particularly type 1 diabetes.

This indicates that the link between depression and different endocrine-metabolic disorders may be driven by different mechanisms. For example, shared biological mechanisms, such as immuno-inflammatory and metabolic dysregulations, may underlie the co-occurrence of depression and type 2 diabetes, obesity, and polycystic ovarian syndrome. In contrast, the absence of shared genetics in the association between type 1 diabetes and depression may reflect the existence of environmental factors influencing the risk of both conditions and/or a direct link between these conditions through mediating factors – eg, biological and psychosocial mechanisms connected to type 1 diabetes, including inflammation, cerebral damage, as well as stress of this lifelong condition that is often diagnosed early in life and that requires a complex management regime for both patients and their families.

“Our results underscore that clinicians should be aware of increased risks of depression in individuals with endocrine-metabolic disorders, and vice versa, and be vigilant for shared symptoms. This study also provides a useful foundation for future research aimed at identifying and targeting the biological mechanisms and modifiable risk factors underlying the co-presentation of endocrine-metabolic disorders and depression”, said Marica Leone, first author for the study.

Source: Karolinska Institutet

Categories : Immunology Metabolic DisordersTags :

A Theory Behind Autoimmunity in Type 1 Diabetes

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A 3D map of the islets in the human pancreas. Source: Wikimedia

The autoimmune destruction of the pancreatic beta-cells in type 1 diabetes (T1D) has been studied extensively, yet the mystery of what causes autoimmunity is unknown. In a new study, researchers present a testable hypothesis to explain the initiation of autoimmunity – which, if validated, this would allow early detection and possible prevention of T1D in susceptible individuals. This hypothesis is discussed in the journal Diabetes.

“Previous studies have focused on the triggers, genes and proteins that differentiate individuals with T1D from those without diabetes with a focus on the b-cell (b-cells create antibodies) as a target of immune destruction and blood glucose as the main abnormality. Our focus is on metabolic communication as an early instigator with the b-cell as an active participant together with the immune cells,” explained corresponding author Barbara Corkey, PhD, professor at Boston University School of Medicine.

Prof Corkey’s research led her to hypothesise that autoimmunity induction results from one or more major inflammatory events in individuals with susceptible human leukocyte antigens phenotypes plus elevated sensitivity to cytokines and free fatty acids (FFA).

“Illnesses or environmental agents that dramatically increase cytokine production and/or elevate FFA initiate autoimmune destruction in individuals with specific genetic features. Thus, early prevention should be aimed at decreasing elevated lipids and diminishing excessive simultaneous elevation of cytokines or cytokine- and lipid-induced immune cell proliferation,” she said.

Prof Corkey believes that the characteristics that make individuals susceptible to autoimmune destruction could also apply to other autoimmune diseases such as toxic shock syndrome and possibly long COVID.

Source: Boston University School of Medicine

Categories : COVID Metabolic DisordersTags : 1 Comment

Is COVID Really Causing New-onset Type 1 Diabetes in Young People?

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New research on Scottish data has found SARS-CoV-2 infection is linked to an increased incidence of new-onset type 1 diabetes in under-35s – but only in the first month after infection, likely due to increased testing as well as COVID bringing forward the progression of diabetes.

The study, presented at this year’s European Association for the Study of Diabetes (EASD) Annual Meeting, linked data on COVID tests results to the Scottish diabetes register for the period between March 2020 and November 2021, and tested whether this period of COVID infection was associated with an increased risk of diabetes.

“Our findings call into question whether a direct association between COVID and new-onset type 1 diabetes in adults and children exists”, says co-lead author Professor Helen Colhoun from Public Health Scotland and the University of Edinburgh, Scotland. “One recent report by researchers at the US Centers for Disease Control and Prevention (CDC), analysing two large insurance-claim databases of those under age 18, found that children with COVID were 2.5 times as likely to be diagnosed with diabetes over a month after infection than those who were never infected. If replicated, this is going to create a large number of people with newly diagnosed diabetes and might also alter the risk–benefit balance for COVID vaccination in young children. Importantly, we did not confirm that finding.”

In type 1 diabetes, which usually appears during childhood or adolescence, the immune system attacks insulin-producing cells, but it is not known why. One theory is that the immune system may be triggered by a viral infection and then accidentally also attacks insulin-producing cells. It has also been suggested that viral infections may increase the rate of progression of type 1 diabetes in people who still have normal blood sugar levels.

In this study, Prof Colhoun and colleagues linked individual-level data on PCR-confirmed SARS-CoV-2 infections from the Electronic Communication of Surveillance Database, which captures all PCR tests for COVID-19 nationally, with precise dates of all new type 1 diabetes diagnoses from the national register in Scotland (that is updated daily).

During the study period a confirmatory PCR test was mandatory for all those with a positive lateral flow test.

The important aspect of this study is the exact dates of diabetes diagnosis were available, unlike in some earlier studies, ensuring that the time sequence of COVID and type 1 diabetes could be established.

Between March 2020 and November 2021, a total of 365 080 children and adults had at least one detected SARS-CoV-2 infection, and 1074 were diagnosed with type 1 diabetes.

The analysis found no association between SARS-CoV-2 infection and new-onset type 1 diabetes 30 days or more after infection, or in those aged younger than 16 years, contrary to several previously reported studies.

However, the researchers did find that children and adults with a first positive SARS-CoV-2 test were 2.5 times as likely to be diagnosed with diabetes within 30 days of infection compared to those who did not have a previous registered infection; this risk was more than three times higher in those younger than 16 years.

But the authors stress strong arguments against a causal effect of COVID underlying this association.

Further analyses investigating the pattern of COVID- testing in relation to type 1 diabetes diagnosis found an increased frequency of SARS-CoV-2 testing in the days before and after diabetes presentation, for both negative and positive results. This suggests, says the authors, that the association may partly be explained by higher detection of infection at this time.

The authors also note that the average time from the onset of type 1 diabetes symptoms to diagnosis under 16s in England is around 25 days. So, it is likely that many of those who tested positive for COVID-19 within 30 days of a diabetes diagnosis already had type 1 diabetes at the time of infection.

No link was found between between COVID vaccination status and new-onset type 1 diabetes in adults (few children were vaccinated during the study period), providing further evidence against a causal effect of SARS-CoV-2 infection on the development of diabetes.

The researchers also looked at trends in type 1 diabetes incidence in Scottish children aged 0–14 years before and during the pandemic, finding that the incidence in 2020–2021 was around 20% higher than the 7-year average for 2015–2021.

However, they point out that based on estimates from England, the time course of the increase in diabetes incidence in those aged 0–14 years predated most of the cumulative incidence of SARS-CoV-2 infection in this age group (June 2021 onwards), suggesting no causal link between COVID and rates of diabetes.

“Our findings show that causes other than COVID infection itself need to be considered in relation to the increased incidence of type 1 diabetes”, said co-lead author Professor Paul McKeigue from Public Health Scotland and the University of Edinburgh, Scotland. “We need to consider what has happened regarding the spread of viruses such as enteroviruses during the pandemic, and whether there are any other environmental factors, such as sunlight exposure and vitamin D levels, that might have altered during lockdown that might also be relevant.”

The authors note that although their study was large, further analyses with more recent data is needed, and that the delay in mass testing meant many COVID cases in the young went undetected.

Source: EurekAlert!

Categories : Diseases, Syndromes and Conditions Metabolic DisordersTags :

New Study Explains Diabetes and UTI Link

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Huge clumps of E. coli (red) infecting diabetic mouse bladder. Photo: Soumitra Mohanty

Lower immunity and recurring infections are common in type 1 and type 2 diabetes. Research has shown that the immune system of people with diabetes has lower levels of the antimicrobial peptide psoriasin, which compromises the urinary bladder’s cell barrier, increasing the risk of urinary tract infection. The study is published in Nature Communications.

One effect of diabetes is that it compromises the innate immune system, leaving many people with increased susceptibility to regular infections, such as urinary tract infections (UTI)s caused by E. coli bacteria. In people with diabetes, these are more likely to lead to general blood poisoning, sepsis, originating in the urinary tract.

An endogenous antibiotic

Karolinska Institutet researchers investigated whether glucose levels in people with diabetes (type 1, type 2, or prediabetes) are linked with psoriasin, an endogenous antibiotic which is a part of the innate immune system.

Using samples of urine, bladder cells and blood serum from patients, the researchers analysed levels of psoriasin and other peptides necessary for ensuring that the bladder mucosa remains intact and protects against infection. The findings were then verified in mice and urinary bladder cells with and without infection.

“We found that high glucose concentrations reduce the levels of the antimicrobial peptide psoriasin, while insulin has no effect,” said Professor Annelie Brauner, who led the study. “People with diabetes have lower levels of psoriasin, which weakens the cells’ protective barrier function and increases the risk of bladder infection.”

Oestrogen therapy reduced bacterial population

Professor Brauner’s research group has previously shown that oestrogen restores the protective function of bladder cells in humans and mice and thereby help to regulate the immune response to a UTI. The researchers therefore tested how oestrogen treatment affects infected cells exposed to high glucose concentrations. They found that the treatment boosted levels of psoriasin and reduced bacterial populations, indicating that the treatment may have an effect also among patients with diabetes.

“We now plan to probe deeper into the underlying mechanisms of infections in individuals with diabetes,” said lead author Soumitra Mohanty. “The ultimate goal is to reduce the risk of infection in this growing patient group.”

Source: Karolinska Institutet

Categories : Metabolic DisordersTags :

30-year Diabetes Study Determines HbA1c Threshold for Complications

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Diabetes - person measures blood glucose
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The levels of long-term blood sugar, HbA1c, can be used to accurately determine the risk of a person with type 1 diabetes developing eye- and kidney complications. A Swedish study, published in Diabetes Care, followed individuals after the onset type 1 diabetes for 30 years and showed that this level should under 53mmol/mol (7%).

People with diabetes may experience damage to the small blood vessels in various organs. The reasons for this are unclear, but it has been known since the 1990s that good control of blood sugar levels reduces the risk of complications. It has, however, not been clear what level of long-term sugar, HbA1c, people with type 1 diabetes should have in order to avoid serious damage to blood vessels in the eyes and kidneys.

“Our study determines accurately the levels of long-term sugar that can avoid complications. This knowledge can increase a person’s motivation to keep their blood sugar level under control,” said study leader Hans Arnqvist, professor emeritus at Linköping University.

Researchers in the current study, known as VISS (Vascular Diabetic Complications in Southeast Sweden), have followed all children and adults under 35 who developed type 1 diabetes during the period 1983–1987 in Southeast Sweden. All 447 newly diagnosed persons in the region during this period were included in the study. The researchers have followed the patients’ HbA1c values, which reflect their average blood sugar levels during a longer period. They have also monitored the development of eye- and kidney damage in these patients for a period of between 32 and 36 years after diagnosis.

In type 1 diabetes, the small blood vessels in the eye are particularly susceptible to damage. Nearly all patients experience small haemorrhages in the eye that do not affect their vision. In some cases, proliferative retinopathy develops, forming new blood vessels which can lead to blindness. The macula of the retina can also be damaged, leading to blurred vision.

While the kidneys are not as sensitive to high blood sugar levels as the eye, the important small blood vessels here can also be damaged, leading to albuminuria. The damage to the kidneys eventually leads to impaired kidney function and, in serious cases, kidney failure.

In healthy individuals, the blood sugar level is very closely controlled, with a maximum HbA1c level of 42mmol/mol (6.0%).

“The results of our study show that people with type 1 diabetes for at least 32 years should keep their mean long-term sugar level below 53mmol/mol (7.0%), if they are to completely avoid serious damage. The risk of eye- and kidney complications increases as the level increases. Our conclusions relate to avoiding complications arising from blood vessel damage. But if a patient has problems with low blood sugar, hypoglycaemia, it’s not possible to control the blood sugar level so strictly,” said Prof Arnqvist.

The target level for HbA1c that is suggested by the results of the VISS study agrees with the individual targets recommended by the American Diabetes Association. In Sweden, target levels are given for groups, rather than individuals.

The previous follow-up by the research group was conducted 20 years after the onset of disease. Now after 30 years, the results show that damage has arisen at lower blood sugar levels than was the case after 20 years.

More patients have experienced damage, despite having blood sugar levels that are not higher than those they have previously had. In other words, it seems that the threshold for developing complications falls gradually with time. This means that the study does not allow any conclusions for the recommended blood sugar levels of people with type 1 diabetes longer than 30 years after diagnosis.

Source: Linköping University