Category: Metabolic Disorders

Categories : Metabolic Disorders Obstetrics & GynaecologyTags :

Dimming the Lights Could Help Reduce Gestational Diabetes Risk

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Researchers at Northwestern Medicine suggest that pregnant persons should dim the lights in their home and turn off or at least dim their screens (computer monitors and smartphones) a few hours before bedtime to reduce the risk of gestational diabetes mellitus.

In their study published in the American Journal of Obstetrics and Gynecology Maternal Fetal Medicine, women who developed gestational diabetes mellitus in the multi-site study had greater light exposure in the three hours before sleep onset. They did not differ in their light exposure during daytime or sleep or in their activity levels compared to those who did not develop it.

“Our study suggests that light exposure before bedtime may be an under-recognised yet easily modifiable risk factor of gestational diabetes,” said lead study author Dr Minjee, Northwestern Medicine neurologist.

While exposure to light at night before bedtime may be linked to impaired glucose regulation in non-pregnant adults, little is known about the effect of evening light exposure during pregnancy on the risk of developing gestational diabetes.

This is believed to be one of the first multi-site studies to examine light exposure before sleep on the risk of developing gestational diabetes, a serious health complication for mother and child.

‘Alarming’ global rise in gestational diabetes

Gestational diabetes is on the rise in the U.S. and globally. About 4.5% of first-time pregnant women with a baby born between 2011 and 2013 developed gestational diabetes, which has been increasing on average 3.4% per three-year period until 2019. In 2020, the rate of gestational diabetes was 7.8% of all births in the US.

“It’s alarming,” Kim said. “Gestational diabetes is known to increase obstetric complications, and the mother’s risk of diabetes, heart disease and dementia. The offspring also are more likely to have obesity and hypertension as they grow up.”

Data show that women who have gestational diabetes are nearly 10 times more likely to develop type 2 diabetes mellitus compared to those do not have glucose issues during pregnancy, Kim said.

Bright light exposure prior to sleep can come from bright indoor lighting and from device screens.

“We don’t think about the potential harm of keeping the environment bright from the moment we wake up until we go to bed,” Kim said. “But it should be pretty dim for several hours before we go to bed. We probably don’t need that much light for whatever we do routinely in the evening.”

Scientists don’t know which source of bright light causes the problem, but it might all add up, Kim said.

“Try to reduce whatever light is in your environment in those three hours before you go to bed,” Kim said. “It’s best not to use your computer or phone during this period. But if you have to use them, keep the screens as dim as possible,” Kim said, suggesting people use the night light option and turn off the blue light.

If pregnant persons develop gestational diabetes with the first pregnancy, they are more likely to have it with the next pregnancy.

Pre-sleep light exposure increases heart rate, with knock-on effects

Pre-sleep light exposure may affect glucose metabolism through sympathetic overactivity, meaning the heart rate goes up before bed when it should go down. “It seems there is inappropriate activation of the fight or flight response when it is time to rest,” Kim said.

Data shows the sympathetic overactivity may lead to cardiometabolic disease, which is a cluster of conditions including abdominal obesity, insulin resistance, increased blood pressure and an imbalance of lipids, all leading to cardiovascular disease.

The study of 741 women in their second trimester was conducted at eight clinical U.S. sites between 2011 and 2013. The participants’ light exposure was measured by an actigraph worn on their wrists. The women were measured during the second trimester of pregnancy, the time when they receive routine screening for gestational diabetes.

After adjusting separately for age, BMI, race/ethnicity, education, commercial insurance, employment schedule, season, sleep duration, sleep midpoint, sleep regularity index, and daytime light exposure, pre-sleep light exposure remained significantly associated with gestational diabetes.

The growing rate of gestational diabetes has been partially attributed to increasing body mass index and the older age of pregnant persons.

“But even after adjusting for BMI and age, gestational diabetes is still rising,” Kim said. “We have a lot to prove, but my personal worry is that light may be silently contributing to this problem without most people realising the potential harm.”

Losing body weight and exercising also reduce the risk of developing gestational diabetes, which are important but take some effort.

Turning down lights is an easy fix

“Turning down the lights is an easy modification you can make,” Kim said.

“Now I’m the light police at home,” Kim said. “I see all this light I never thought about before. I try to dim the light as much as possible. Just for evening activities such as dinner and bathing the kids, you don’t need bright light.”

“This study highlights the importance of reducing light exposure in the hours before bedtime” said senior author Kathryn Reid, research professor of neurology at Feinberg.

Source: Northwestern University

Categories : Cardiovascular Disease Medical Industry Metabolic DisordersTags :

Bempedoic Acid Could be a Viable Alternative to Statins

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Photo by Towfiqu Barbhuiya on Unsplash

Bempedoic acid, a new cholesterol-lowering drug, has the potential to be an effective substitute for patients who can’t tolerate statins. Bempedoic acid is an ATP citrate lyase inhibitor that reduces low-density lipoprotein (LDL) cholesterol levels and is associated with a low incidence of muscle-related adverse events. Its effects on cardiovascular outcomes were uncertain, so researchers used a double-blind, randomised, placebo-controlled trial to determine outcomes on a variety of cardiovascular measures in statins-intolerant patients.

The study, published in the New England Journal of Medicine, recruited patients aged 18–85 years at increased cardiovascular risk and unable or unwilling to take statins due to adverse effects. Patients were first tested with placebo over a 4-week run-in period, and were not randomised if they experience unacceptable adverse effects or if adherence was less than 80%. The 13 970 patients who successfully completed run-in were randomised to receive bempedoic acid 180mg orally per day or matching placebo. 

The mean LDL cholesterol level at baseline was 139.0mg/dL in both groups, and after 6 months, the reduction in the level was greater with bempedoic acid than with placebo by 29.2mg/dL; the observed difference in the percent reductions was 21.1 percentage points in favour of bempedoic acid.

Compared to placebo, risk of fatal or nonfatal stroke, death from cardiovascular causes, and death from any cause after significantly were lower by 13%, after a median of 40.6 months of follow-up. The risk of death from cardiovascular causes, nonfatal stroke, or nonfatal myocardial infarction was 15% lower with bempedoic acid than with placebo, and the risks of fatal or nonfatal myocardial infarction and coronary revascularisation were 23% lower and 19% lower, respectively.

The researchers noted that the LDL-cholesterol lowering effects were similar in magnitude and predicted reduction in cardiovascular risks to that observed with statins. In addition, bempedoic acid did not increase glycated haemoglobin levels or the incidence of new-onset diabetes, unlike statins. Due to the demonstrated benefits, those taking placebo were offered the chance to transition to taking bempedoic acid.

A trial limitation was that it only included patients with statins intolerance, and who therefore had higher LDL cholesterol levels at baseline.

Categories : Metabolic DisordersTags :

Childhood Obesity is a Risk Factor for Blood Clots in Adulthood

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Source: CC0

Being overweight in childhood and in early adulthood are discrete risk factors for blood clots (thrombi) later in life, according to a study using school health care and military service records, according to a study published in the Journal of Internal Medicine.

The association between obesity and blood clots is already established. However, to date it has been unclear how much influence a raised BMI in childhood and puberty exerts. Thrombi usually arise in the legs, often starting in a blood vessel in the calf. Swelling, pain and redness are common symptoms. Though easily treated if caught early, they can result pulmonary embolism may be life-threatening.

The present study comprises 37 672 men in Sweden, born between 1945 and 1961. It is based on information about height, weight, and BMI from the men’s records, first from school health care services (at the age of 8 years) and, second, from medical examinations on enrolment in the Armed Services (at age 20), along with register data on any blood clots up to age 62 on average.

Distinctly elevated thrombus risk

The results showed that BMI at both ages 8 and 20, independently of each other, can be linked to venous blood clots. These may occur in, for example, the leg (deep vein thrombosis, DVT) or the lung (pulmonary embolism).

In adulthood, two groups were found to be at a significantly increased risk of venous thrombi. The first was individuals who had been overweight both as children and as young adults, while the second was composed of those whose weight in childhood was normal and who became overweight only in early adulthood.

Moreover, being overweight in both childhood and young adulthood was found to raise the risk of arterial thrombi – clots resulting from constricted blood vessels with fatty deposits and inflammation. Since there were few cases of arterial blood clots in the study, however, further studies are needed to confirm these findings. All comparisons in the study were made with the control group, whose weight was normal at both 8 and 20 years of age.

Overweight in puberty an important factor

The first and corresponding author of the study is Lina Lilja, a doctoral student at Sahlgrenska Academy, University of Gothenburg, and paediatrician. At the time of the study, she worked at the Kungshöjd paediatric clinic in Gothenburg. Today, she is a senior physician in child health care in Region Västra Götaland.

“Our study shows that both overweight in childhood and overweight in young adulthood increase the risk of venous blood clots later in life. The latter, overweight when the men were young adults, proved to be a more influential factor than overweight when they were children,” Lilja notes.

The study includes data from the BMI Epidemiology Study (BEST) in Gothenburg, a population study, and from Swedish national registers.

Source: University of Gothenburg

Categories : Medical Industry Metabolic DisordersTags :

Biden Urges Drug Companies to Join in Insulin US Price Cuts

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Photo by Dennis Klicker on Unsplash

Following pharmaceutical company Eli Lilly’s much-lauded move to cut US prices for its insulin products, US President Joe Biden is calling on other drugmakers to make similar reductions for the vital medication.

According to Euronews, Lilly is directly slashing its insulin prices by about 70%, since many patients cannot access discounts, and is capping consumer costs at US$35 (R635) a month.

Biden is driving a push for cheaper insulin, signing a law that capped insulin at US$35 a month for senior citizens on Medicare, and urged companies to lower prices on their own. “For far too long, American families have been crushed by drug costs many times higher than what people in other countries are charged for the same prescriptions,” Biden said.

“Insulin costs less than US$10 to make, but Americans are sometimes forced to pay over US$300 for it. It’s flat wrong”.

Biden has called for a national cap on insulin prices, but his current Act does not extend to that.

A Lilly press release revealed that the price of Humalog® (insulin lispro injection) 100 units/mL (Lilly’s most commonly prescribed insulin) and Humulin® (insulin human) injection 100 units/mL by would be cut by 70%. This price change would take effect around the end 2023. Lilly also said it would cut the price for the generic Lispro to US$25 a vial starting in May. In South Africa, a Humulin® 10mL vial costs R525.28, or US$28.08, according to Health-e’s medicine price registry.

Lilly CEO David Ricks said his company was bringing the changes as not all patients could benefit through discounts through insurers or pharmacy benefit managers.

“We are driving for change in repricing older insulins, but we know that 7 out of 10 Americans don’t use Lilly insulin. We are calling on policymakers, employers and others to join us in making insulin more affordable,” said Ricks. “For the past century, Lilly has focused on inventing new and improved insulins and other medicines that address the impact of diabetes and improve patient outcomes. Our work to discover new and better treatments is far from over. We won’t stop until all people with diabetes are in control of their disease and can get the insulin they need.”

Since insurers and pharmacies will take a while to implement the price cuts, Lilly will immediately cap monthly out-of-pocket costs at $35 for people who are not covered by Medicare’s prescription drug programme.

Categories : Metabolic Disorders PaediatricsTags :

Childhood Obesity Linked to Adult Diabetes Risk

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Child obesity is linked to increased risk of developing diabetes in adulthood, both autoimmune forms of diabetes and different forms of type 2 diabetes, according to a new study in the journal Diabetologia. The risk of developing the most insulin-resistant form of diabetes is, for example, three times as high in children with obesity.

Diabetes affects ~7% of the adult population and is one of the world’s fasted growing diseases. It has traditionally been divided into two subgroups – type 1 and type 2 diabetes – but research suggests that this is a simplification.

In 2018, a Swedish study identified five subgroups of adult-onset diabetes, characterised by auto-immunity, severe insulin deficiency, serious insulin resistance, overweight and advanced age.

One way the researchers say that the relevance of these subgroups can be highlighted is to examine if the influence of known risk factors for diabetes differs between the proposed diabetes types.

“Our study is one of the first attempts to find this out,” says the study’s first author Yuxia Wei, doctoral student at Karolinska Institutet. “Childhood obesity has been linked to several chronic diseases, but has never been studied in relation to the recently proposed diabetes subgroups.”

Wanted to investigate the effect of child obesity

The purpose of the present study was therefore to see if the effect of childhood obesity differs. The researchers used a method called Mendelian randomisation, which uses genetic information to study the correlation between an environmental risk factor and disease risk while taking into account the impact of other risk factors.

Basing their analysis on genetic data from over 400 000 UK Biobank participants, the researchers compared children who considered themselves larger than other children with children who rated their weight as normal.

The results showed that overweight/obesity in childhood was linked to a 62% higher risk of autoimmune diabetes, a doubling of the risk of diabetes characterised by insulin deficiency, almost a tripling of the risk of the most insulin-resistant form of diabetes and a seven-times higher risk of the form of diabetes primarily characterised by overweight. 

“Our analyses show that children who are larger than others are more likely to develop four of the five proposed new subgroups of adult-onset diabetes,” says Wei. “In other words, obesity in childhood seems to be a risk factor in effectively all types of adult diabetes, with the exception of age-related diabetes. This underscores how important it is to prevent obesity in children since it can have lasting effects on their future health.”

The study was a collaboration among researchers at Karolinska Institutet, Bristol University (UK) and Sun Yat-Sen University (China).

Source: Karolinska Institutet

Categories : Metabolic DisordersTags :

Designs for Insulin Preparations may Have Been Miscalculated for Decades

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Photo by Towfiqu Barbhuiya on Unsplash

For diabetics, the makeup of insulin doses – governed by the proportion of insulin molecule clusters present – are crucial for effective treatment. Getting too little or too much insulin can lead to hyperglycaemia or hypoglycaemia. A new study appearing in Communications Biology has discovered that though it is not a danger to patients, an assumption underlying the design of insulin preparations is well off the mark.

The absorption of insulin in the body is controlled by how insulin molecules assemble themselves in clusters. Whereas a single molecule provides rapid action in the body, clusters of six molecules – known as hexamers – are long-acting. For decades, it has been assumed that insulin assembles with a certain distribution of molecular clusters of either one, two or six molecules. Pharmaceuticals have been designed based upon this assumption – but now researchers have discovered that this important point has been wrong for years.

“It is now apparent to us that we’ve gotten things wrong by 200 percent. There are only half as many single molecules in insulin compared to what we thought. Conversely, there are far more six-molecule clusters than we assumed. These experiments were not on animals but were performed on a microscope slide and one should be careful how to interpret their direct application to humans,” says study lead author Professor Nikos Hatzakis of the University of Copenhagen.

He adds: “However, our results may mean that when we believe to be administering a certain dose, it may mean that insulin behaves in a different way than expected and that even better insulin therapeutics can be developed.”

This means that insulin taken by diabetics may not be getting absorbed as expected. Though the researchers stress that it is not outright dangerous for patients, there is potential for designing more precise medicines.

From a crude model to detailed view

“Insulin preparations have only gotten better and better over the years, and a great many diabetics are well regulated. However, the development of insulin preparations has been based on a certain assumption about how the molecules assemble. With the crude standard model, this process was never been appreciated at a detailed level. That’s what we can do,” says the study’s other lead author, Professor Knud J. Jensen, of the Department of Chemistry. 

“This doesn’t mean that current insulin medications are bad or that patients have been medicated wrongly. But we now have a basic understanding of how insulin behaves and how much could be available to the body as rapid-acting medication. We now have the right method for providing us with accurate figures. We hope that the industry will use this or a similar tool – both to check current insulin preparations and to develop new ones,” adds Nikos Hatzakis.

The research results were achieved through a mix of chemistry, machine learning, simulations and advanced microscopy. The Department of Chemistry researchers began by directly observing the process in which each insulin molecule joins forces with other molecules to assemble into clusters. This allowed them to see how fast each cluster forms. The researchers looked at about 50 000 clusters.

Knowing the exact distribution of different clusters in a given amount of insulin is fundamental when developing medications that need to have either short- or long-acting effects in the body:

“The clustering of insulin is incredibly important for how preparations work. Because the difference between a rapid- and slow-acting insulin preparation is dependent upon how quickly the molecules assemble in clusters and how quickly they disassemble. Access to highly advanced equipment makes it relatively simple and fast to gain insight into exact concentrations, knowledge that at the same time, is also quite sophisticated,” says lead author Freja Bohr, a PhD fellow in Nikos Hatzakis’ research group at the Department of Chemistry. 

Improving insulin preparations

In addition to the different distribution of molecular clusters, the observations also show that cluster formation is a much more complex process than once presumed. The clusters can both grow and shrink at far more different intervals than previously supposed.

“Without being able to say exactly how just yet, this should make it possible to expand the number of ways in which preparations are designed. This could lead to an insulin with a different effect profile that reduces the fluctuations in patients’ blood sugar – which remains a major challenge,” says Freja Bohr.

Source: University of Copenhagen

Categories : Healthcare Politics and Regulations Metabolic DisordersTags :

Budget: Decision Not to Raise the Sugar Tax ‘Puts Profits Ahead of People’ Say Activists

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The flash mob by HEALA featured a choreographed dance in which learners pretended to refuse sugary drinks. Photo: Ashraf Hendricks

By Daniel Steyn for GroundUp

Health activists demonstrating in Cape Town for a rise in the tax on sugary drinks were disappointed by Finance Minister Enoch Godongwana’s announcement in his Budget speech that the tax would be frozen for two years. Godongwana said this was “due to the difficult operating environment for the sugar industry from the impact of flooding and social unrest.”

The tax on sugary drinks was first introduced in 2018 to reduce consumption. The tax is imposed on drinks with more than 4g of sugar per 100ml. Research from the University of the Witwatersrand in 2021 showed that it has been effective in reducing the consumption of sugar-sweetened drinks.

HEALA, a coalition of organisations focused on nutrition, organised a flash mob in the Cape Town city centre ahead of the Finance Minister’s Budget Speech on Wednesday, advocating for an increase in the sugary drinks tax. They want the tax to be increased from 11% to 20%, following the guidance of the World Health Organisation.

The flash mob was part of HEALA’s “Less Sugar, More Life” campaign, and featured school pupils from Cape Town in a dance.

“We don’t even notice how much sugar we are drinking in sugary drinks and it’s harmful to our health. I want other young people to know that it’s dangerous,” said one of the dancers, Enkosi Stofile.

“The announcement by the Finance Minister, coupled with ineffective increases on other health taxes such as alcohol and tobacco, is a direct attack on the lives of millions of people at risk of serious health conditions such as diabetes, cardiovascular diseases and cancer,” said Nzama Mbalati, HEALA’s Programmes Manager.

Mbalati said there was no rationale for the decision to maintain the rate of tax on sugary drinks. “This decision is not in the interest of ordinary people. Instead, it puts profits ahead of people.”

About 10 000 new cases of diabetes are reported in South Africa each month, according to the International Diabetes Federation. Up to 70% of women and 39% of men are obese or overweight. Sugar is a cause of obesity and tooth decay, and is linked to a range of other non-communicable diseases. The national budget for 2023, tabled by Godongwana in parliament today, includes a R200-million reduction in health spending this year.

Before the budget speech, News24 reported that the South African Sugar Association said 6000 jobs could be lost if the tax was increased. SASA also said 9,000 jobs had already been lost since the levy was introduced.

However, in the aftermath of a fraud scandal at Tongaat Hulett, South Africa’s largest sugar producer, in 2018, 5,000 workers were served with retrenchment letters.

Disclosure: Community Media Trust does work for HEALA. GroundUp was once a project of Community Media Trust and still has a close relationship with Community Media Trust.

Republished from GroundUp under a Creative Commons Attribution-NoDerivatives 4.0 International License.

Source: GroundUp

Categories : Metabolic DisordersTags :

Excess Weight is a Greater Mortality Risk than BMI Alone Suggests

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Photo by I Yunmai on Unsplash

Excess weight or obesity raises mortality risk by between 22% to 91%, a significantly higher rate than previously believed, while the mortality risk of being slightly underweight has likely been overestimated, according to new research published in the journal Population Studies.

The analysis of nearly 18 000 participants counters prevailing wisdom that excess weight boosts mortality risk only in extreme cases, and it also challenges the use of body mass index (BMI) to investigate health outcomes due to its inherent biases. After accounting for those biases, it estimates that about 1 in 6 deaths in the US are related to excess weight or obesity.

“Existing studies have likely underestimated the mortality consequences of living in a country where cheap, unhealthy food has grown increasingly accessible, and sedentary lifestyles have become the norm,” said author Ryan Masters, associate professor of sociology at CU Boulder. “This study and others are beginning to expose the true toll of this public health crisis.”

Challenging the obesity paradox

While numerous studies show that heart disease, high blood pressure and diabetes (which are often associated with being overweight) elevate mortality risk, very few have shown that groups with higher BMIs have higher mortality rates.

Instead, in what some call the “obesity paradox,” most studies show a U-shaped curve: Those in the “overweight” category (BMI 25–30) surprisingly have the lowest mortality risk. Those in the “obese” category (30–35) have little or no increased risk over the so-called “healthy” category (18.5–25). And both the “underweight” (< 18.5) and extremely obese (> 35) are at increased risk of death.

“The conventional wisdom is that elevated BMI generally does not raise mortality risk until you get to very high levels, and that there are actually some survival benefits to being overweight,” said Masters, a social demographer who has spent his career studying mortality trends. “I have been suspicious of these claims.”

He noted that BMI, which doctors and scientists often use as a health measure, is based on weight and height only and doesn’t account for differences in body composition or how long a person has been overweight.

“It’s a reflection of stature at a point in time. That’s it,” said Masters, noting that Tom Cruise (at 170cm and an extremely muscular 91kg at one point), had a BMI of 31.5, famously putting him in the category of “obese.” “It isn’t fully capturing all of the nuances and different sizes and shapes the body comes in.”

Taking these nuances, Masters accessed data from the National Health and Nutrition Examination Survey (NHANES) the from 1988 to 2015, analysing 17 784 people, including 4468 deaths.

He discovered that a full 20% of the sample characterised as “healthy” weight had been in the overweight or obese category in the decade prior. When set apart, this group had a substantially worse health profile than those in the category whose weight had been stable.

Masters pointed out that a lifetime carrying excess weight can lead to illnesses that, paradoxically, lead to rapid weight loss. If BMI data is captured during this time, it can skew study results.

“I would argue that we have been artificially inflating the mortality risk in the low-BMI category by including those who had been high BMI and had just lost weight recently,” he said.

Meanwhile, 37% of those characterised as overweight and 60% of those with obese BMI had been at lower BMIs in the decade prior. Notably, those who had only recently gained weight had better health profiles.

“The health and mortality consequences of high BMI are not like a light switch,” said Masters. “There’s an expanding body of work suggesting that the consequences are duration-dependent.”

By including people who had spent most of their life at low-BMI weight in the high-BMI categories, previous studies have inadvertently made high BMI look less risky than it is, he said.

When he looked at differences in fat distribution within BMI categories, he also found that variations made a huge difference in reported health outcomes.

Exposing a public health problem

Collectively, the findings confirm that studies have been “significantly affected” by BMI-related bias.

When re-crunching the numbers without these biases, he found not a U-shape but a straight upward line, with those with low BMI (18.5–22.5) having the lowest mortality risk.

Contrary to previous research, the study found no significant mortality risk increases for the “underweight” category.

Previous studies attributed 2 to 3% of UA adult deaths to high BMI, but his study estimates an eight times higher rate.

Masters said he hopes the research will alert scientists to be “extremely cautious” when making conclusions based on BMI. But he also hopes the work will draw attention to what he sees not as a problem for individuals alone to solve but rather a public health crisis fuelled by an unhealthy or “obesogenic” environment in the US.

“For groups born in the 1970s or 1980s who have lived their whole lives in this obesogenic environment, the prospects of healthy aging into older adulthood does not look good right now,” he said. “I hope this work can influence higher-level discussions about what we as a society can do about it.”

Source: University of Colorado at Boulder

Categories : Mental Health Metabolic DisordersTags :

Self-stigma Linked to Worse Blood Glucose Control in Type 1 Diabetes

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Diabetes - person measures blood glucose
Photo by Photomix Company from Pexels

Because of their illness, patients with chronic medical conditions may experience self-stigma, or negative beliefs, emotional reactions, and behaviours towards themselves. New research published in the Journal of Diabetes Investigation found a link between self-stigma and glycated haemoglobin (HbA1c) in adults with type 1 diabetes.

The study included 109 adults in Japan with type 1 diabetes who completed questionnaires that generated scores based on a self-stigma scale. Although the findings support a link between self-stigma and sub-optimal HbA1c, additional studies are needed to show whether this is a causal relationship.

“We focused on this issue through clinical experiences with people with type 1 diabetes, whose glycaemic management improved markedly by social supports of eliminating diabetes-related stigma. Although the finding of an association between self-stigma and HbA1c is significant, further longitudinal research is required to determine whether self-stigma leads to sub-optimal HbA1c,” said corresponding author Yukiko Onishi MD, PhD, of the Institute of Medical Science, Asahi Life Foundation, in Tokyo. “This research does support and highlight the importance of eliminating self-stigma when treating people with type 1 diabetes.”

Source: Wiley

Categories : Metabolic DisordersTags :

Periods of Hypoglycaemia Worsen Progression of Diabetic Retinopathy

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Credit: National Eye Institute

People with diabetes who experience periods of hypoglycaemia, a common event in those new to blood sugar management, are more likely to have worsening diabetic eye disease. Now, researchers say they have linked such low blood sugar levels with a molecular pathway that is activated in hypoxic cells in the eye.

The research, involving human and mouse eye cells and intact retinas grown in a low glucose environment in the laboratory, as well as mice with low glucose levels, was published in Cell Reports.

“Temporary episodes of low glucose happen once or twice a day in people with insulin-dependent diabetes and often among people newly diagnosed with the condition,” says Akrit Sodhi, MD, PhD, Johns Hopkins Medicine professor. Low glucose levels can also occur during sleep in people with non-insulin dependent diabetes. “Our results show that these periodic low glucose levels cause an increase in certain retinal cell proteins, resulting in an overgrowth of blood vessels and worsening diabetic eye disease,” adds Sodhi.

Up to a third of diabetic patients will develop diabetic retinopathy, which is characterised by the overgrowth of abnormal blood vessels in the retina.

Sodhi says the current study suggests that people with diabetic retinopathy may be particularly vulnerable to periods of low glucose, and keeping glucose levels stable should be an important part of glucose control.

For the study, the researchers analysed protein levels in human and mouse retinal cells and intact retinas grown in an environment of low glucose in the laboratory, as well as in mice that had occasional low blood sugar.

In human and mouse retinal cells, low glucose levels triggered a cascade of molecular changes that can lead to blood vessel overgrowth. First, the researchers saw that low glucose caused a decrease in retinal cells’ ability to break down glucose for energy.

When the researchers focused on Müller glial cells, which are supportive cells for neurons in the retina and rely primarily on glucose for energy production, they found that the cells increased the expression of the GLUT1 gene, which makes a protein that transports glucose into cells.

The researchers found that, in response to low glucose, the cells increased levels of a transcription factor, hypoxia-inducible factor (HIF)-1α. This turned on the cellular machinery, including GLUT1, needed to improve their ability to utilise available glucose, preserving the limited oxygen available for energy production by retinal neurons.

However, in hypoxic environments, as occurs in the retinas of patients with diabetic eye disease, this normal, physiologic response to low glucose triggered a flood of HIF-1α protein into the nucleus.

This resulted in an increase in the production of proteins such as VEGF and ANGPTL4, which cause the growth of abnormal, leaky blood vessels – the key culprit of vision loss in people with diabetic eye disease.

The researchers plan to study whether low glucose levels in people with diabetes may impact similar molecular pathways in other organs, such as the kidney and brain.

Sodhi says the HIF-1α pathway may serve as an effective target for developing new treatments for diabetic eye disease.

Source: Johns Hopkins Medicine