Tag: Type 2 diabetes

Categories : Metabolic DisordersTags :

Strong Link Between Haem Iron in Red Meat and Type 2 Diabetes Risk

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Higher intake of haem iron, the type found in red meat and other animal products – as opposed to non-haem iron, found mostly in plant-based foods – was associated with a higher risk of developing type 2 diabetes (T2D) in a new study published in Nature Metabolism. While the link between haem iron and T2D has been reported previously, the findings from this study, which was led by Harvard T.H. Chan School of Public Health, more clearly establish and explain the link.

“Compared to prior studies that relied solely on epidemiological data, we integrated multiple layers of information, including epidemiological data, conventional metabolic biomarkers, and cutting-edge metabolomics,” said lead author Fenglei Wang, research associate in the Department of Nutrition. “This allowed us to achieve a more comprehensive understanding of the association between iron intake and T2D risk, as well as potential metabolic pathways underlying this association.”

The researchers assessed the link between iron and T2D using 36 years of dietary reports from 206 615 adults (79% female) enrolled in the Nurses’ Health Studies I and II and the Health Professionals Follow-up Study. They examined participants’ intake of various forms of iron – total, haem, non-haem, dietary (from foods), and supplemental (from supplements) – and their T2D status, controlling for other health and lifestyle factors.

The researchers also analysed the biological mechanisms underpinning haem iron’s relationship to T2D among smaller subsets of the participants. They looked at 37 544 participants’ plasma metabolic biomarkers, including those related to insulin levels, blood sugar, blood lipids, inflammation, and two biomarkers of iron metabolism. They then looked at 9024 participants’ metabolomic profiles – plasma levels of small-molecule metabolites.

The study found a significant association between higher haem iron intake and T2D risk. Participants in the highest intake group had a 26% higher risk of developing T2D than those in the lowest intake group. In addition, the researchers found that haem iron accounted for more than half of the T2D risk associated with unprocessed red meat and a moderate proportion of the risk for several T2D-related dietary patterns. In line with previous studies, the researchers found no significant associations between intakes of non-haem iron from diet or supplements and risk of T2D.

The study also found that higher haem iron intake was associated with blood metabolic biomarkers associated with T2D. A higher haem iron intake was associated with higher levels of biomarkers such as C-peptide, triglycerides, C-reactive protein, leptin, and markers of iron overload, as well as lower levels of beneficial biomarkers like HDL cholesterol and adiponectin.

The researchers also identified a dozen blood metabolites – including L-valine, L-lysine, uric acid, and several lipid metabolites – that may play a role in the link between haem iron intake and TD2 risk. These metabolites have been previously associated with risk of T2D.

On a population level, the study findings carry important implications for dietary guidelines and public health strategies to reduce rates of diabetes, according to the researchers. In particular, the findings raise concerns about the addition of heme to plant-based meat alternatives to enhance their meaty flavor and appearance. These products are gaining in popularity, but health effects warrant further investigation.

“This study underscores the importance of healthy dietary choices in diabetes prevention,” said corresponding author Frank Hu, Fredrick J. Stare Professor of Nutrition and Epidemiology. “Reducing haem iron intake, particularly from red meat, and adopting a more plant-based diet can be effective strategies in lowering diabetes risk.”

The researchers noted that the study had several limitations, including the potential for incomplete accounting for confounders and measurement errors in the epidemiological data. In addition, the findings – based on a study population that was mostly white – need to be replicated in other racial and ethnic groups.

Source: Harvard T.H. Chan School of Public Health

Categories : Metabolic DisordersTags :

Recent Steps in Treatment and Management Show Promise in Stemming the Rise of Diabetes

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A new paper surveying advances in diabetes pathogenesis and treatment explores the complex factors contributing to the onset and progression of the disease, suggesting that an understanding of these dynamics is key to developing targeted interventions to reduce the risk of developing diabetes and managing its complications.

In a paper in a special 50th anniversary issue of the peer-reviewed journal Cell, the authors surveyed hundreds of studies that have emerged over the years looking at the causes underpinning types 1 (T1D) and 2 (T2D) diabetes and new treatments for the disease. They examine the role that genes, environmental factors, and social determinants of health play and diabetes’ effect on cardiovascular and kidney disease.

What they found shows there are many advances in treatments that could stem the tide of a disease that has struck millions of people around the globe and continues to grow. In addition, some of these advances could be used to treat other disorders. But there are still challenges ahead.

“As the prevalence of diabetes continues to grow around the world, it is important to understand the latest advancements in research so that clinicians can provide the best care to their patients, and patients can make informed choices that support improved health outcomes,” said lead author Dr E. Dale Abel, chair of the UCLA Department of Medicine. “This is an educational resource that integrates the latest research and trends in diabetes management, which may have implications for clinical practice as the diabetic patient population continues to grow.

“This review will be the go-to reference for physicians and researchers, providing a state-of-the-art update of where the field is currently, and where it is headed,” Abel added.

Most people are affected by type 2 diabetes, for which inadequate diet and obesity are important underlying causes. Type 1 diabetes accounts for fewer than 5% of all cases. As of 2021 about 529 million people around the world were diagnosed with diabetes, representing about 6.1% of the global population, or about one in 16 people. Prevalence in some regions is as high as 12.3%. Type 2 diabetes comprises about 96% of cases, with more than half due to obesity. Some 1.31 billion people are projected to have the disease by 2050, with prevalence rising as high as 16.8% in North Africa and the Middle East and 11.3% in Latin America and the Caribbean, the researchers write.

Genetics, the central nervous system, and the interplay between various organs as well as social and environmental factors such as food insecurity and air pollution play a role in development of diabetes.

But some recent discoveries represent significant strides toward managing and perhaps even reversing the disease. For instance, a 2019 study found that a 14-day course of the antibody teplizumab delayed the progression of type 1 diabetes from stage 1 to stage 3 by 24 months. A follow-up analysis in 2021 showed that the delay could be up to 32.5 months.

Based on these results, the U.S. Food and Drug Administration approved teplizumab as the first disease-modifying therapy for type 1 diabetes, the researchers write.

Advances in insulins with optimised pharmacokinetics, algorithm-driven subcutaneous insulin pumps, continuous glucose monitoring, and improved tools for self-management have significantly improved the quality of life and outcomes for people with stage 3 type 1 diabetes.

In addition, stem cells could replace insulin-producing cells that are lost in type 1 diabetes, Abel said.

For type 2 diabetes, three classes of glucose-lowering medicines that were introduced in the last 20 years – GLP1RAs (glucagon like peptide-1 receptor agonists), DPP-4 inhibitors, and SGLT-2 inhibitors – have enabled people to control their glucose levels without gaining weight and with a low risk of developing hypoglycaemia. Personalised and precision medicine approaches are being explored to target the molecular mechanisms behind diabetes. However, they must demonstrate that benefits are clinically superior to standard care and are cost-effective. Also, it remains to be seen if precision approaches can be implemented in all settings worldwide, including those with few resources.

Combinations of GLP1Ras and with molecules that target other receptors such as GIP have shown even greater efficacy in treating diabetes. Recent trials have also shown that they are very effective in treating obesity, certain types of heart failure and even sleep apnoea, in part because of their potency to induce weight loss and reduce inflammation. Clinical trials are now underway to test their efficacy in treating other disorders such as Alzheimer’s disease, Abel said.

“Advances in therapy now raise the hope of preventing or curing T1D and treating T2D in ways that not only improve metabolic homeostasis, but also concretely reduce the risk and progression of cardio-renal disease,” the researchers write. “Finally, as we understand and develop tools for discerning the underlying heterogeneity leading to diabetes and its complications, the stage will be set for targeting therapies and prevention strategies to optimize their impact, in ways that will be broadly applicable across diverse populations and availability of health care resources.”

Source: UCLA Health

Categories : Metabolic Disorders OphthalmologyTags :

Study Reveals Association Between Semaglutide Use and Optic Neuropathy

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Photoreceptor cells in the retina. Credit: Scientific Animations

Researchers from Mass Eye and Ear have discovered an association between semaglutide use and an increased risk of nonarteritic anterior ischaemic optic neuropathy (NAION) in patients with type 2 diabetes, overweight or obesity. The findings, which appear in JAMA Ophthalmology, only show an association and cannot establish causation.

Though NAION is relatively rare, occurring in in about 10 in 100 000, it is the second most common cause of optic nerve blindness, behind glaucoma, and it is the most common cause of sudden optic nerve blindness. Caused by decreased blood flow to the optic disc, it usually affects only one eye but in 15% of cases both eyes are involved. There are no treatments for this disease and little prospect for improvement, although it is painless.

The study was led by Joseph Rizzo, MD, director of the Neuro-Ophthalmology Service at Mass Eye and Ear and the Simmons Lessell Professor of Ophthalmology at Harvard Medical School.

In mid-2023 Rizzo, a resident (study co-author Seyedeh Maryam Zekavat, MD, PhD) and other Mass Eye and Ear neuro-ophthalmologists noticed a disturbing trend – three patients in their practice had been diagnosed with vision loss from this relatively uncommon optic nerve disease in just one week. They did notice however that all three were taking semaglutide.

“The use of these drugs has exploded throughout industrialised countries and they have provided very significant benefits in many ways, but future discussions between a patient and their physician should include NAION as a potential risk,” said Rizzo, corresponding author of the study. “It is important to appreciate, however, that the increased risk relates to a disorder that is relatively uncommon.” 

This prompted the Mass Eye and Ear research team to run a retrospective analysis of their patient population to see if they could identify a link between this disease and these drugs.

They performed matched cohort study of 16 827 patients revealed higher risk of NAION in patients prescribed semaglutide compared with patients prescribed non–GLP-1 receptor agonist medications for diabetes or obesity.

The researchers found that patients with diabetes who were prescribed and took semaglutide were four times (hazard ratio [HR], 4.28) more likely to be receive a NAION diagnosis. The odds increased to more than seven times (HR, 7.64) when the prescription was for weight control in obesity.

The researchers analysed the records of more than 17 000 Mass Eye and Ear patients treated over the six years since Ozempic was released and divided the patients in those who were diagnosed with either diabetes or overweight/ obesity. The researchers compared patients who had received prescriptions for semaglutide compared to those taking other diabetes or weight loss drugs. Then, they analysed the rate of NAION diagnoses in the groups, which revealed the significant risk increases.

Study limitations include the fact that Mass Eye and Ear sees an unusually high number of people with rare eye diseases, and the number of NAION cases seen over the six-year study period is relatively small. With small case numbers, statistics can change quickly, Rizzo noted. Medication adherence could also not be assessed.

Only correlation can be shown by the study, not causality. How or why this association exists remains unknown. Likewise, the reason for the reported difference between diabetic and overweight groups – but this does not appear to result from a difference in baseline characteristics. The optic nerve is known to host GLP-1 receptors, but the study did not adequately address all the confounding factors. They also caution against generalising the results (from a majority white population) since Black individuals have a lower risk of NAION.

“Our findings should be viewed as being significant but tentative, as future studies are needed to examine these questions in a much larger and more diverse population,” Rizzo said. “This is information we did not have before and it should be included in discussions between patients and their doctors, especially if patients have other known optic nerve problems like glaucoma or if there is pre-existing significant visual loss from other causes.”

Categories : Metabolic DisordersTags :

Combining Weight Loss and Blood Sugar Control is the Best Diabetes Protection

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People with prediabetes are advised to reduce their weight in order to prevent the development of diabetes. For the first time, new research shows that people achieve the best diabetes protection when they reduce their weight and at the same time normalise blood sugar regulation with lifestyle changes and medication. In an article published in Diabetologia, the authors argue that the normalisation of blood sugar levels in prediabetes should be included as a therapeutic goal in the guidelines in order to improve the prevention of type 2 diabetes.

Diabetes is widespread and is associated with an increased risk of a number of life-threatening complications such as stroke, heart attack and kidney failure. “In order to prevent the development of the disease, early therapies are already important in the prediabetes stage, a preliminary stage of type 2 diabetes. Our results can be used to change the goals of these early lifestyle interventions in order to reduce the overall development rates of diabetes,” explains first author Reiner Jumpertz-von Schwartzenberg.

Prediabetes drastically increases the risk of diabetes

Prediabetes is diagnosed when there is no manifest type 2 diabetes yet, but the fasting blood sugar is already elevated and glucose tolerance is impaired. To prevent prediabetes from becoming diabetes, affected patients are advised to reduce their weight. US guidelines from the American Diabetes Association (ADA), for example, recommend reducing body weight by at least 7%. This recommendation is based on the DPP study.

The research team from the University Tübingen and the National Institute of Diabetes and Digestive and Kidney Diseases in the US, investigated whether this weight loss is sufficient, or whether it is not better to prevent diabetes by also reducing blood sugar levels such that prediabetes goes into remission.

Prevention through one-year lifestyle intervention

They analysed data from 480 people with prediabetes who participated in the US Diabetes Prevention Program (DPP) and had lost at least 7% of their body weight through a one-year lifestyle intervention. In 114 of them, prediabetes also went into remission during the intervention, meaning that their fasting blood sugar, glucose tolerance and HbA1c had normalised. However, the majority of the 366 study participants had not managed to significantly improve their blood sugar regulation despite successfully losing weight. Their prediabetes was not in remission at the end of the intervention.

The researchers found that significantly fewer people in the group that had lost weight and achieved prediabetes remission developed manifest diabetes thereafter. The additional remission of prediabetes resulted in a relative risk reduction for the development of diabetes of 76% compared to those who had not achieved normalisation of their blood sugar levels. The absolute risk reduction was higher than 10%.

“In the group with additional remission of prediabetes, there was even no type 2 diabetes at all in the first 4 years after the lifestyle intervention,” reports last author Andreas Birkenfeld. “In the group that had ‘only’ lost weight, however, some study participants did develop manifest diabetes during that period.”

Jumpertz-von Schwartzenberg and Birkenfeld draw a clear conclusion: “Our results show that remission of prediabetes brings a further significant benefit in addition to weight reduction. We therefore advocate that the goal of prediabetes remission should be included in the objectives of the practice guidelines in order to significantly improve the prevention of type 2 diabetes.”

The study was conducted by researchers from the Institute for Diabetes Research and Metabolic Diseases of Helmholtz Munich at the University of Tübingen, a partner in the German Center for Diabetes Research (DZD), together with US colleagues in the renowned “Diabetes Prevention Program (DPP)”.

Source: University of Tübingen

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Study Links Emulsifiers and Type 2 Diabetes Risk

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Emulsifiers, commonly used additives for improving the texture of food products and extending their shelf life, may be associated with the onset of type 2 diabetes, according to a large cohort study of over 100 000 people in France.

Researchers from Inserm, INRAE, Université Sorbonne Paris Nord, Université Paris Cité and Cnam, as part of the Nutritional Epidemiology Research Team (CRESS-EREN), studied the possible links between the dietary intake of food additive emulsifiers and the onset of type 2 diabetes between 2009 and 2023. They analysed the dietary and health data of 104 139 adults participating in the French NutriNet-Santé cohort study, specifically evaluating their consumption of this type of food additive using dietary surveys conducted every six months. The findings suggest an association between the chronic consumption of certain emulsifier additives and a higher risk of diabetes. The study is published in Lancet Diabetes & Endocrinology.

In Europe and North America, 30 to 60% of dietary energy intake in adults comes from ultra-processed foods. An increasing number of epidemiological studies suggest a link between higher consumption levels of ultra-processed foods with higher risks of diabetes and other metabolic disorders.

Emulsifiers are among the most commonly used additives. They are often added to processed and packaged foods such as certain industrial cakes, biscuits and desserts, as well as yoghurts, ice creams, chocolate bars, industrial breads, margarines and ready-to-eat or ready-to-heat meals, in order to improve their appearance, taste and texture and lengthen shelf life. These emulsifiers include for instance mono- and diglycerides of fatty acids, carrageenans, modified starches, lecithins, phosphates, celluloses, gums and pectins.

As with all food additives, the safety of emulsifiers had been previously evaluated by food safety and health agencies based on the scientific evidence that was available at the time of their evaluation.
However, some recent studies suggest that emulsifiers may disrupt the gut microbiota and increase the risk of inflammation and metabolic disruption, potentially leading to insulin resistance and the development of diabetes.

For the first time worldwide, a team of researchers in France has studied the relationships between the dietary intakes of emulsifiers, assessed over a follow-up period of maximum 14 years, and the risk of developing type 2 diabetes in a large study in the general population.

The results are based on the analysis of data from 104 139 adults in France (average age 43 years; 79% women) who participated in the NutriNet-Santé web-cohort study (see box below) between 2009 and 2023.

The participants completed at least two days of dietary records, collecting detailed information on all foods and drinks consumed and their commercial brands (in the case of industrial products). These dietary records were repeated every six months for 14 years, and were matched against databases in order to identify the presence and amount of food additives (including emulsifiers) in the products consumed. Laboratory assays were also performed in order to provide quantitative data. This allowed a measurement of chronic exposure to these emulsifiers over time.

During follow-up, participants reported the development of diabetes (1056 cases diagnosed), and reports were validated using a multi-source strategy (including data on diabetes medication use). Several well-known risk factors for diabetes, including age, sex, weight (BMI), educational level, family history, smoking, alcohol and levels of physical activity, as well as the overall nutritional quality of the diet (including sugar intake) were taken into account in the analysis.

After an average follow-up of seven years, the researchers observed that chronic exposure – evaluated by repeated data – to the following emulsifiers was associated with an increased risk of type 2 diabetes:

  • carrageenans (total carrageenans and E407; 3% increased risk per increment of 100 mg per day)
  • tripotassium phosphate (E340; 15% increased risk per increment of 500 mg per day)
  • mono- and diacetyltartaric acid esters of mono- and diglycerides of fatty acids (E472e; 4% increased risk per increment of 100 mg per day)
  • sodium citrate (E331; 4% increased risk per increment of 500 mg per day)
  • guar gum (E412; 11% increased risk per increment of 500 mg per day)
  • gum arabic (E414; 3% increased risk per increment of 1000 mg per day)
  • xanthan gum (E415; 8% increased risk per increment of 500 mg per day)

This study constitutes an initial exploration of these relationships, and further investigations are now needed to establish causal links. The researchers mentioned several limitations of their study, such as the predominance of women in the sample, a higher level of education than the general population, and generally more health-promoting behaviours among the NutriNet-Santé study participants. Therefore caution is needed when extrapolating the conclusions to the entire French population.

The study is nevertheless based on a large sample size, and the researchers have accounted for a large number of factors that could have led to confounding bias. They also used unique, detailed data on exposure to food additives, down to the commercial brand name of the industrial products consumed. In addition, the results remain consistent through various sensitivity analyses, which reinforces their reliability.

“These findings are issued from a single observational study for the moment, and cannot be used on their own to establish a causal relationship,”explain Mathilde Touvier, Research Director at Inserm, and Bernard Srour, Junior Professor at INRAE, lead authors of the study. “They need to be replicated in other epidemiological studies worldwide, and supplemented with toxicological and interventional experimental studies, to further inform the mechanisms linking these food additive emulsifiers and the onset of type 2 diabetes. However, our results represent key elements to enrich the debate on re-evaluating the regulations around the use of additives in the food industry, in order to better protect consumers.”

Among the next steps, the research team will be looking at variations in certain blood markers and the gut microbiota linked to the consumption of these additives, to better understand the underlying mechanisms. The researchers will also look at the health impact of additive mixtures and their potential ‘cocktail effects.’

They will also work in collaboration with toxicologists to test the impact of these exposures in in vitro and in vivo experiments, to gather more arguments in favour of a causal link.

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Probing an Outdated Diabetes Drug’s Insulin Resistance Lowering Abilities

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Thiazolidinediones (TZDs) are a class of drug that can be used to treat type 2 diabetes by reversing insulin resistance, one of the main hallmarks of the disease. While TZDs were extremely popular in the 1990s and early 2000s, they have fallen out of use among physicians in recent decades because unwanted side effects emerged, including weight gain and excess fluid accumulation in body tissues.

Now, researchers at University of California San Diego School of Medicine are exploring how to isolate the positive effects of these drugs, which could help yield new treatments that don’t come with the old side effects.

In a new study published in Nature Metabolism, the researchers discovered how one of the most well-known TZD drugs works at the molecular level and were able to replicate its positive effects in mice without giving them the drug itself.

“For decades, TZDs have been the only drugs we have that can reverse insulin resistance, but we seldom use them anymore because of their side effects profile,” said Jerrold Olefsky, MD, a professor of medicine and assistant vice chancellor for integrative research at UC San Diego Health Sciences.

“Impaired insulin sensitivity is the root cause of type 2 diabetes, so any treatment we can develop to safely restore this would be a major step forward for patients.”

The main driver of insulin resistance in type 2 diabetes is obesity. Obesity-related inflammation causes macrophages to accumulate in adipose tissue, where they can comprise up to 40% of the total number of cells in the tissue.

When adipose tissue is inflamed, these macrophages release tiny nanoparticles containing instructions for surrounding cells in the form of microRNAs. These microRNA-containing capsules, called exosomes, are released into the circulation and can travel through the bloodstream to be absorbed by other tissues, such as the liver and muscles. This can then lead to the varied metabolic changes associated with obesity, including insulin resistance.

To understand how TZD drugs, which restore insulin resistance, affect this exosome system, the researchers treated a group of obese mice with the TZD drug rosiglitazone. Those mice became more sensitive to insulin, but they also gained weight and retained excess fluid, known side effects of rosiglitazone.

However, by isolating exosomes from the adipose tissue macrophages of the mice who had received the drug and injecting them into another group of obese mice that had not received it, the researchers were able to deliver the positive effects of rosiglitazone without transferring the negative effects.

“The exosomes were just as effective in reversing insulin resistance as the drug itself but without the same side effects,” said Olefsky.

“This indicates that exosomes can ultimately link obesity-related inflammation and insulin resistance to diabetes. It also tells us that we may be able to leverage this system to boost insulin sensitivity.”

The researchers were also able to identify the specific microRNA within the exosomes that was responsible for the beneficial metabolic effects of rosiglitazone. This molecule, called miR-690, could eventually be leveraged into new therapies for type 2 diabetes.

“It’s likely not practical to develop exosomes themselves as a treatment because it would be difficult to produce and administer them, but learning what drives the beneficial effects of exosomes at the molecular level makes it possible to develop drugs that can mimic these effects,” said Olefsky. “There’s also plenty of precedent for using microRNAs themselves as drugs, so that’s the possibility we’re most excited about exploring for miR-690 going forward.”

Source: University of California – San Diego

Categories : Metabolic Disorders Skeletal SystemTags :

Type 2 Diabetes Alters the Behaviour of Discs in the Vertebral Column

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Type 2 diabetes alters the behaviour of discs in the vertebral column, making them stiffer, and also causes the discs to change shape earlier than normal. As a result, the disc’s ability to withstand pressure is compromised. This is one of the findings of a new rodent-based study published in PNAS Nexus.

Low back pain is a major cause of disability, often associated with intervertebral disc degeneration. People with type 2 diabetes face a higher risk of low back pain and disc-related issues. Yet the precise mechanisms of disc degeneration remain unclear.

Investigating the biomechanical properties of the intervertebral disc is crucial for understanding the disease and developing effective strategies for managing low back pain.

“These findings provide novel insight into the potential mechanisms underlying diabetes-related disc tissue damage and may inform the development of preventative and therapeutic strategies for this debilitating condition,” the research team wrote. The team consisted of engineers and physicians from the University of California San Diego, UC Davis, UCSF and the University of Utah.

The study emphasises that nanoscale deformation mechanisms of collagen fibrils accommodate compressive loading of the intervertebral disc.

In the context of type 2 diabetes, these mechanisms are compromised, resulting in collagen embrittlement.

These findings provide novel insight into the potential mechanisms underlying diabetes-related disc tissue damage and may inform the development of preventative and therapeutic strategies for this debilitating condition.

Researchers employed synchrotron small-angle x-ray scattering (SAXS), an experimental technique that looks at collagen fibril deformation and orientation at the nanoscale.

They wanted to explore how alterations in collagen behaviour contribute to changes in the disc’s ability to withstand compression.

They compared discs from healthy rats to those from rats with type 2 diabetes (UC Davis rat model). The healthy rats showed that collagen fibrils rotate and stretch when discs are compressed, allowing the disc to dissipate energy effectively.

“In diabetic rats, the way vertebral discs dissipate energy under compression is significantly impaired: diabetes reduces the rotation and stretching of collagen fibrils, indicating a compromised ability to handle pressure,” the researchers write.

Further analysis showed that the discs from diabetic rats exhibited a stiffening of collagen fibrils, with a higher concentration of non-enzymatic cross-links.

This increase in collagen cross-linking, induced by hyperglycaemia, limited plastic deformations via fibrillar sliding.

These findings highlight that fibril reorientation, straightening, stretching, and sliding are crucial mechanisms facilitating whole-disc compression.

Type 2 diabetes disrupts these efficient deformation mechanisms, leading to altered whole-disc biomechanics and a more brittle (low-energy) behaviour.

Source: University of California – San Diego

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New, More Accurate Approach to Blood Tests for Determining Diabetes Risks

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A new approach to blood tests could potentially be used to estimate a patient’s risk of type 2 diabetes, according to a new study appearing in BMC’s Journal of Translational Medicine. Currently, the most commonly used inflammatory biomarker currently used to predict the risk of type 2 diabetes is high-sensitivity C-reactive protein (CRP). But new research has suggested that jointly assessing of biomarkers, rather than assessing each individually, would improve the chances of predicting diabetes risk and diabetic complications.

A study by Edith Cowan University (ECU) researcher Dan Wu investigated the connection between systematic inflammation, assessed by joint cumulative high-sensitivity CRP and another biomarker called monocyte to high-density lipoprotein ratio (MHR), and incident type 2 diabetes.

The study followed more than 40 800 non-diabetic participants over a near ten-year period, with more than 4800 of the participants developing diabetes over this period.

Wu said that of those patients presenting with type 2 diabetes, significant interaction between MHR and CRP was observed.

“Specifically, increases in the MHR in each CRP stratum increased the risk of type 2 diabetes; concomitant increases in MHR and CRP presented significantly higher incidence rates and risks of diabetes.

“Furthermore, the association between chronic inflammation (reflected by the joint cumulative MHR and CRP exposure) and incident diabetes was highly age- and sex-specific and influenced by hypertension, high cholesterol, or prediabetes. The addition of the MHR and CRP to the clinical risk model significantly improved the prediction of incident diabetes,” said Wu.

Biological sex a risk factor

The study found that females had a greater risk of type 2 diabetes conferred by joint increases in CRP and MHR, with Wu stating that sex hormones could account for these differences.

Wu said that the research findings corroborated the involvement of chronic inflammation in causing early-onset diabetes and merited specific attention.

“Epidemiological evidence indicates a consistent increase in early-onset diabetes, especially in developing countries. Leveraging this age-specific association between chronic inflammation and type 2 diabetes may be a promising method for achieving early identification of at-risk young adults and developing personalised interventions,” she added.

Wu noted that the chronic progressive nature of diabetes and the enormous burden of subsequent comorbidities further highlighted the urgent need to address this critical health issue.

Although aging and genetics are non-modifiable risk factors, other risk factors could be modified through lifestyle changes.

Inflammation is strongly influenced by life activities and metabolic conditions such as diet, sleep disruptions, chronic stress, and glucose and cholesterol dysregulation, thereby indicating the potential benefits of monitoring risk-related metabolic conditions.

Wu said that the dual advantages of cost effectiveness and the wide availability of cumulative MHR and CRP in current clinical settings, potentiated the widespread use of these measures as a convenient tool for predicting the risk of diabetes.

Source: Edith Cowan University

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Few Patients Successfully Treat their Type 2 Diabetes Through Weight Loss

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People with the most weight loss in the first year were most likely to achieve sustained remission

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A new study finds that very few patients diagnosed with type 2 diabetes are able to achieve normal blood glucose levels through weight loss alone. A team led by Andrea Luk of the Chinese University of Hong Kong, report these findings January 23rd in the open access journal PLOS Medicine.

Clinical trials suggest that people with type 2 diabetes can control their blood glucose levels without medication if they lose weight and keep it off. However, it is unknown how many patients can achieve remission through weight loss alone under real-world conditions. In the new study, researchers looked at 37 326 people in Hong Kong who were newly diagnosed with type 2 diabetes to see whether – and low long – patients could control the disease through weight loss.

The researchers discovered that only 6% of people achieved diabetes remission solely through weight loss by about eight years after diagnosis. For people who initially achieved remission, two-thirds had elevated blood glucose levels by three years after diagnosis. These rates are significantly lower than in clinical trials, where remission occurred in up to 73% of patients at one year post-diagnosis. People with the greatest weight loss in the first year were most likely to have sustained remission.

The study shows that controlling type 2 diabetes through sustained weight loss is possible in real-world settings, but that few patients will achieve normal blood glucose levels through weight management alone, especially over the long-term. One reason for the discrepancy with clinical trials is that trial participants receive intensive lifestyle interventions, including holistic support for dietary changes, physical exercise and mental health. The researchers conclude that patients should receive early weight management interventions as a way to increase the odds that they will achieve sustained remission. Furthermore, the data suggest that early weight management interventions increase the odds of sustained remission and that sustained lifestyle changes are likely to be paramount.

Luk adds, “Greater weight loss within the first year of diabetes diagnosis was associated with an increased likelihood of achieving diabetes remission. However, the incidence of diabetes remission was low with only 6% of people achieving remission over 8 years, and half of those with initial remission returned to hyperglycaemia within 3 years indicating poor sustainability of diabetes remission in real-world setting.”

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In Type 2 Diabetics, Toxic Lipids and a Beneficial One Surge at Certain Times

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Credit: Cell Reports Medicine (2023).

While sugar is most frequently blamed in the development of type 2 diabetes, a better understanding of the role of fats is also essential. By analysing the blood profiles of dozens of people suffering from diabetes or pre-diabetes, or who have had their pancreas partially removed, researchers at the University of Geneva (UNIGE) and Geneva University Hospitals (HUG) have made two major discoveries.

Firstly, the lipid composition of blood and adipose tissues fluctuates during the day, and is altered in a day-time dependent manner in diabetics, who have higher levels of toxic lipids. In addition, one type of lipid, lysoPI, is capable of boosting insulin secretion when the beta cells that normally produce it fail. These results, published in the journals Cell Reports Medicine and Diabetes, may have important implications for the treatment of diabetic patients.

The role of lipids in the physiological and pathological processes of human metabolism is gradually becoming clearer, particularly in type 2 diabetes, one of the most widespread serious metabolic disorders. Thanks to cutting-edge tools, in particular mass spectrometry, researchers are now able to simultaneously measure the levels of several hundred different types of lipids, each with its own specific characteristics and beneficial or harmful effects on our metabolism.

‘‘Identifying which lipids are most present in type 2 diabetics could provide a basis for a wide range of interventions: early detection, prevention, potential therapeutic targets or personalised recommendations – the possibilities are immense,’’ says Charna Dibner, a professor in the Department of Surgery and a specialist in circadian rhythms in metabolic disorders, . ‘‘This is why we carried out a detailed analysis of the blood profiles of patients recruited in four European countries and confirmed some of our results on a mouse model of the disease.’’

Dibner led the studies along with Pierre Maechler, a professor in the Department of Cell Physiology and Metabolism, at the UNIGE Faculty of Medicine, and members of the Diabetes Faculty Centre.

Chronobiology to better identify diabetes

The team carried out a ‘‘lipidomic’’ analysis of two groups of patients in order to establish the profile, over a 24-hour cycle, of multiple lipids present in the blood and adipose tissues. ‘‘The differences between the lipid profiles of type 2 diabetics and people without diabetes are particularly pronounced in the early morning, when there is an increase in certain toxic lipids,’’ explains Dibner. ‘‘Why? We don’t know yet. But this could be a marker of the severity of diabetes and paves the way for personalised care according to each patient’s specific chronotype.”

And implications go beyond diabetes: if samples are taken at very different times of the day, the results can be distorted and give contradictory results. ‘‘It’s the same thing in the clinic: an examination carried out in the morning or evening, or a treatment taken at different times, can have an impact on diagnosis and even on the effectiveness of treatments.’’

A crutch for beta cells

Charna Dibner and Pierre Maechler extended their lipidomic analyses to include not only people with type 2 diabetes but also a mouse model of pre-diabetes and patients who had lost around half their insulin-producing beta cells after a surgery. ‘‘We discovered that a type of lipid, lysoPIs, increases when there is a sharp decrease in functional β cells, even before the onset of clinical symptoms of diabetes.’’

The scientists then administered lysoPI to diabetic mice and observed an increase in insulin production. ‘‘The same phenomenon occurred in vitro, on pancreatic cells from diabetic patients,’’ adds Pierre Maechler. ‘‘The lysoPIs therefore have the capacity to reinforce insulin secretion by acting as a crutch when the number of beta cells decreases or when these cells malfunction. Yet, certain foods, such as legumes, naturally contain lysoPI precursors.’’

By bringing to light the unsuspected role of lysoPIs, researchers will be able to explore new avenues opened by their discoveries. The development of dietary supplements or even molecules specific to lysoPI receptors could be an interesting strategy for controlling diabetes, as could taking better account of the chronobiological profiles of patients. Diabetes is a complex disease that calls for much more personalised management than is currently the case.

Source: University of Geneva