Posted on Diabetes

​​​​​​​UNH research finds venom of cone snail could lead to future diabetes treatments

Cone snail shell


Researchers at the University of New Hampshire have found that variants of this venom, known as cone snail insulin (Con-Ins), could offer future possibilities for developing new fast-acting drugs to help treat diabetics.

The tapered cone shell is popular among seashell collectors for its colorful patterns, but the smooth mottled shells are also home to the cone snail which is capable of spewing a potent insulin-like venom that can paralyze its prey. Researchers at the University of New Hampshire have found that variants of this venom, known as cone snail insulin (Con-Ins), could offer future possibilities for developing new fast-acting drugs to help treat diabetics.

“Diabetes is rising at an alarming rate and it’s become increasingly important to find new alternatives for developing effective and budget-friendly drugs for patients suffering with the disease,” said Harish Vashisth, associate professor of chemical engineering. “Our work found that the modeled Con-Ins variants, or analogs, bind even better to receptors in the body than the human hormone and may work faster which could make them a favorable option for stabilizing blood sugar levels and a potential for new therapeutics.”

In their study, recently published in the journal Proteins: Structure, Function, and Bioinformatics, researchers looked more closely at the cone snail venom which induces a hypoglycemic reaction that lowers blood sugar levels. Unlike insulin made in the body, the venom’s peptide sequence – which allows it to bind to human insulin receptors – is much shorter. To test whether it would still bind effectively, the researchers used sequences of the insulin-like peptides in the venom of the cone snail C. geographus as a template to model six different Con-Ins analogs. The newly created variants were made up of much shorter peptide chains than human insulin – lacking the last eight residues of the B-chain of the human insulin.

To study the stability and variability of the new Con-Ins structures, they conducted multiple independent computer simulations of each Con-Ins variant complex with human insulin receptor in a near-physiological environment (accounting for water solvent, salinity of solution, temperature and pressure). They found that each insulin complex remained stable during the simulations and the designed peptides bound strongly – even better than the naturally occurring human insulin hormone. The interactions were then compared with the human insulin receptor and it was determined that each Con-Ins variant exhibits few feasible residue substitutions in human insulin.

“While more studies are needed, our research shows that despite the shorter peptide sequences, the cone snail venom could be a viable substitute and we are hopeful it will motivate future designs for new fast-acting drug options,” said Biswajit Gorai, postdoctoral research associate and lead author.

The insulin-like venom released by certain cone snails can be highly dangerous causing a hypoglycemic shock that immobilizes fish and potential prey. C. geographus has the most toxic sting known among the species and there have been reports of human fatalities, especially to unsuspected divers who are not aware of the snail’s venom.

Posted on Diabetes

Long-term blood sugar history predicts risk of severe COVID-19 among diabetics

T2D and COVID-19


A long-term history of glycemic control better predicts risk of severe COVID-19 among type 2 diabetics than shorter-term measurements. CREDIT Rensselaer Polytechnic Institute

People with type 2 diabetes who contract COVID-19 are nearly 50% more likely to wind up in intensive care if they have poorly managed their blood sugar levels over the long-term than those with better long-term glycemic control, according to a study using anonymized health care data. The study, which looked at several potential impacts to COVID-19 severity among diabetics, also calculated a lower risk for patients using the common diabetes-control medication metformin, or a combination of metformin and insulin, or corticosteroids.

“We find that two- to three-year longitudinal glycemic levels better indicate the risk of COVID-19 severity than measurements which look at a shorter period of time,” said Deepak Vashishth, corresponding author, professor of biomedical engineering, and director of the Center for Biotechnology and Interdisciplinary Studies at Rensselaer Polytechnic Institute. “We hope these insights aid physicians in better treating and managing high-risk patients.”

“Evaluation and management of COVID-19-related severity in people with type 2 diabetes” looked at records for more than 16,000 people with type 2 diabetes and COVID-19 between 2017 and 2020, and was published in BMJ Open Diabetes Research & Care.

Type 2 diabetes patients are unable to regulate the amount of the sugar glucose in their bloodstream without medication and managing their diet. Chronic high blood-sugar levels, typically tracked as the percentage of hemoglobin A1c (HbA1c) found in the blood, can damage a variety of functions, including the circulatory, nervous, and immune systems.

Poor glycemic control creates a reaction that causes molecules known as advanced glycation end-products (AGEs) to accumulate, deteriorating the quality of bone over time, and Vashishth, an expert in bone, researches the impact of diabetes on bone. At the time the SARS-CoV-2 pandemic began, his research team was investigating whether measurements of longitudinal glycemic control – measures of blood-sugar levels averaged over two to three years – could provide a more accurate predictor of bone fracture risk among diabetics than the current standard predictor, which relies on measurements of bone mineral density.

AGEs are known to contribute to increased oxidant stress and inflammation, which are risk factors in COVID-19 and other respiratory illnesses. The team reasoned that the same longitudinal glycemic control measurement they were testing as a predictor of bone fracture risk might be useful in predicting the severity of COVID-19, said Bowen Wang, first author and a doctoral student in Vashishth’s lab.

Wang divided the records of type 2 diabetic patients in the study into two groups, those with “adequate” longitudinal glycemic control ranging from 6 to 9%, and those with “poor” glycemic control of 9% or above over two to three years. His analysis of the two groups revealed that those with poor glycemic control were 48% more likely to require treatment in an intensive care unit. By another measure, a 1% increase in longitudinal HbA1c is directly associated with a 12% increase in the risk of landing in the ICU.

Other statistically significant findings showed that diabetics who were taking metformin when they contract COVID-19 face a 12% lower risk of visiting the ICU, those on metformin and insulin have an 18% lower risk, and those prescribed corticosteroids have a 29% lower risk.

“People knew that diabetes was a risk factor for COVID-19-related outcomes, but not all diabetic patients are the same. Some people have a longer history of diabetes, some have more severe diabetes, and that has to be accounted for,” said Wang. “What this study does is to better stratify the level of diabetes within the population, so diabetic patients aren’t treated as a single population without any differences among them.”

Vashishth and Wang were joined on the research by Benjamin S. Glicksberg and Girish N. Nadkarni at the Icahn School of Medicine at Mount Sinai. Their work was supported by a grant from the National Institutes of Health.

Posted on Autism

Is Autism An Evolutionary Advantage? Or Disadvantage?

Is Autism An Evolutionary Advantage? Or Disadvantage? - YouTube


Is Autism an evolutionary advantage? Have you ever noticed that “different” is often immediately perceived as a defect? or disadvantage? Being different can seem scary because it’s “new” or “scary” or “unknown”, but can have its advantages too. For an individual, being different may not always be an advantage. But in a population, to have differences is essential for survival. In this video, I share how I see being different comes with pros and cons and how, as a whole, neurological difference is necessary for evolution in general.

Posted on Diabetes

Analysis shows low energy diets with formula meal replacements are the most effective methods for weight management and remission in adults with type 2 diabetes

10 Best Foods For Arthritis | Osteoarthritis & Rheumatoid Arthritis Diet

A new study published in Diabetologia (the journal of the European Association for the Study of Diabetes [EASD]) finds that low energy diets with formula meal replacements are the most effective methods of weight management and remission in adults with type 2 diabetes (T2D), while the macronutrient content is not important to outcomes.

The research was conducted by Professor Mike Lean, Dr Chaitong Churuangsuk and colleagues at the Universities of Glasgow, (with Dr Churuangsuk also affiliated to Prince of Songkla University, Hat Yai, Thailand) and others from Cambridge (UK) and Otago (New Zealand) Universities. The group analysed published meta-analyses of which type of diet is best for achieving and then maintaining weight loss in adults with T2D.

While T2D is influenced by both genetic and environmental factors, it is rising levels of overweight and obesity which have driven the current global epidemic of diabetes. The authors note: “Without strategic commitment internationally on effective prevention strategies, type 2 diabetes will affect an estimated 629 million people worldwide by 2045.”

The onset of T2D is primarily driven by weight gain to the point that it becomes unhealthy. The amount of weight-gain needed varies widely between individuals. The development of the disease involves a complex interaction of gut hormones, low-grade inflammation and possibly metabolites from the gut microbiota. It develops in susceptible individuals and families who tend to have large waists and who accumulate fat in their liver, pancreas and muscles.  This impairs organ functions, resulting in hyperglycaemia (abnormally high blood sugar), commonly associated with hypertension (high blood pressure) and abnormal blood fats.

T2D requires lifelong management, but even with treatment it can cause disabling, painful and life-shortening complications. However, sufficient weight loss can remove the abnormal body fat from liver and pancreas and reverse diabetes.

Weight loss is critical to management and remission of T2D and has been shown to improve all the related cardiometabolic risk factors and reduce the patient’s need for medication.

In the UK DiRECT study, funded by Diabetes UK, almost 80% of people with T2D for up to 6 years who lost over 10kg, and maintained the weight loss of over 10 kg, remained in remission from diabetes for at least 2 years.

While there is widespread awareness of the benefits of weight loss for people withT2D, there is a lack of authoritative guidance over dietary advice, to inform both patients and healthcare providers. Ill-informed controversy over diet types has contributed to inaction and delays in providing effective treatment. Current guidelines stress the importance of personalised weight management and state that various diet strategies may be effective, but do not provide information about diet composition. This can lead to patients following diets based on distorted evidence and misleading claims.

Adherence to any energy-reduced diet will lead to sustained weight loss, provided that energy (calorie) use exceeds intake. However, in practice, adherence rates and weight losses vary widely, even within the same diet programme, and some comparisons between diets appear to show conflicting results.

The researchers wanted to help resolve these uncertainties and to inform clinical decision making and guideline development, as part of a programme of work to update the recommendations of the European Association for the Study of Diabetes (EASD).

For this new study, the researchers collected and systematically reviewed all the relevant world publications of diet trial meta-analyses for weight management of people with T2D, and all studies which have reported remissions of T2D.

Their analysis found that the greatest weight loss was achieved with very low energy formula diets, used as ‘Total Diet Replacement’ at 1.7-2.1 MJ/day [400-500 kcal/day] for 8-12 weeks, which led to an average 6.6kg more weight lost compared to food-based low-energy diets (4.2-6.3 MJ/day [1000-1500 kcal/day]). Formula meal replacements were also found to be superior to food-based low-energy diets alone, achieving 2.4kg greater weight loss over 12-52 weeks.

The published evidence showed that low-carbohydrate diets were no better than higher carbohydrate (low-fat) diets for weight loss.

For remission of T2D, there are no direct comparisons between diet types, but published studies showed the best remission rates of 46-61% at 12 months with programmes that include a formula ‘Total Diet Replacement’ of 830 kcal/day for 12 weeks, followed by a relatively low-fat high carbohydrate diet and meal replacements for long-term maintenance. With low carbohydrate diets, reported remission rates are much lower at 4%-19% of those who tried the diet.

They add: “Mediterranean, high-monounsaturated-fatty-acid, vegetarian and low-glycaemic-index diets all achieved minimal (0.3-2 kg) or no difference from conventional relatively low fat/high carb control diets…The evidence, albeit of variable quality, is rather consistent showing that no one diet type is superior over others for weight management in type 2 diabetes.” 

The researchers conclude: “Published meta-analyses of diets for weight management in people with type 2 diabetes do not support recommending any particular macronutrient profile or style over others. Very low energy diets and formula meal replacement appear the most effective approaches, generally providing less energy than self-administered food-based diets.”

A limitation of the trials examined by this study is that the benefits from weight management depend largely on long-term control of body weight, while most of the currently available evidence relates only to short-term outcomes. Successful long-term maintenance of weight may require different behavioural strategies to those effective for the weight-loss phase.  Few trials have reported data beyond 12 months. The team suggest: “Well-conducted research is needed to assess longer-term impacts on weight, blood sugar control, clinical outcomes and diabetes complications.”