Study shows how high blood sugar increases risk of thrombosis

Discoveries by Brazilian researchers belonging to a FAPESP-supported research center could lead to strategies to prevent cardiovascular disease associated with diabetes
Discoveries could lead to strategies to prevent cardiovascular disease associated with diabetes.

A study conducted at the Center for Research on Redox Processes in Biomedicine (Redoxoma) has enhanced our understanding of how high blood sugar levels (hyperglycemia), a common symptom of diabetes, can lead to thrombosis. The findings, published in the Journal of Thrombosis and Haemostasis, could inform the development of strategies to prevent cardiovascular issues in individuals with diabetes.

“The primary causes of death in Brazil and many other Latin American countries are ischemic events, including heart attacks and strokes, where arterial thrombosis plays a significant role. These cardiovascular disorders can result from various risk factors such as high blood sugar (hyperglycemia), abnormal lipid levels (dyslipidemia), and high blood pressure (hypertension). Among these factors, hyperglycemia is notably associated with an increased risk of cardiovascular disease,” stated Renato Simões Gaspar, the article’s lead author.

The investigation was conducted with support from FAPESP during Gaspar’s postdoctoral research and led by Francisco Laurindo, the last author of the article. Laurindo is a professor at the University of São Paulo’s Medical School (FM-USP) in Brazil and is also a member of Redoxoma, a Research, Innovation, and Dissemination Center (RIDC) established by FAPESP at the Institute of Chemistry (IQ-USP). Gaspar currently teaches at the State University of Campinas (UNICAMP).

The authors state that prolonged hyperglycemia and diabetic ketoacidosis increase the risk of thrombosis. This is due to their effects on endothelial dysfunction, which refers to changes in the inner lining of blood vessels. These changes can lead to the binding of platelets to the endothelial cells, triggering the formation of blood clots.

The study showed that peri/epicellular protein disulfide isomerase A1 (pecPDI) regulates platelet-endothelium interaction in hyperglycemia through adhesion-related proteins and alterations in endothelial membrane biophysics.

“We found that a pathway for this PDI in endothelial cells mediates thrombosis in diabetes when hyperglycemia is present, involving a specific molecular mechanism, which we identified,” Laurindo said.

PDI is an enzyme that resides in the endoplasmic reticulum and has the classic function of catalyzing the insertion of disulfide bridges into nascent proteins so that they merge in the correct shape, i.e. so that the amino acid chain folds to form the three-dimensional structure that makes the molecule functional. It is also found in the extracellular space as pecPDI, a pool secreted or bound to the cell surface, in various cell types including platelets and endothelial cells. Studies have shown that pecPDI regulates thrombosis in several models. 

Biochemical and biophysical modifications

To investigate platelet-endothelium interaction in hyperglycemia, the researchers created a model with human umbilical vein endothelial cells cultured in different glucose concentrations to produce normoglycemic and hyperglycemic cells. They assessed PDI’s contribution using whole-cell PDI or pecPDI inhibitors.

The cells were incubated with platelets derived from healthy donors. The platelets adhered almost three times more in hyperglycemic than normoglycemic cells. PDI inhibition reversed this effect, and the researchers concluded that the process is regulated by endothelial pecPDI.

To better understand the result, they investigated biophysical processes such as endothelial cell cytoskeleton remodelling and found that hyperglycemic cells had more well-structured actin filament fibres than normoglycemic cells. They also measured the production of hydrogen peroxide, an oxidizing compound, because reactive oxygen species are mediators of cytoskeleton reorganization and cell adhesion—hyperglycemic cells produced twice as much hydrogen peroxide as normoglycemic cells.

The researchers then investigated whether cytoskeleton reorganization affected cell membrane stiffness since substrate stiffness increases platelet adhesion. Using atomic force microscopy, they demonstrated that hyperglycemic cells were stiffer than normoglycemic cells.

The microscope images also showed the formation of cell elongations with extracellular vesicles that appeared to separate from the elongations. This observation led the researchers to investigate the secretome – the set of proteins secreted by an organism into the extracellular space – to find out whether it included proteins that enhanced platelet adhesion. “The purpose of this experiment was to detect proteins exclusively expressed by or present in hyperglycemic cells and not in controls or cells treated with PDI inhibitors,” Gaspar explained.

They found 947 proteins in the secretome, from which they selected eight with a role in cellular adhesion. They then silenced gene expression for three of these proteins using RNA interference and arrived at two proteins, SLC3A2 and LAMC1, as modulators of platelet adhesion. SLC3A2 is a membrane protein, and LAMC1 is the gamma subunit of laminin 1, a key extracellular matrix component.

Restricting sugar consumption in utero and in early childhood significantly reduces risk of midlife chronic disease

New research shows combined use of sodium glucose co-transporter 2 inhibitors (SGLT2is) and glucagon-like peptide-1 receptor agonists (GLP1-RAs) is likely to offer additional protection against heart and kidney disease in patients with diabetes

A new study has found that a low-sugar diet in utero and in the first two years of life can meaningfully reduce the risk of chronic diseases in adulthood. This provides compelling new evidence of the lifelong health effects of early-life sugar consumption.

A study published in the journal Science reveals that children who had sugar restrictions during their first 1,000 days after conception faced up to a 35% lower risk of developing Type 2 diabetes and a 20% reduced risk of hypertension in adulthood. The research indicates that low sugar intake by mothers during pregnancy was sufficient to lower these health risks, and maintaining sugar restrictions after birth further enhanced the benefits.

Using an unintended “natural experiment” from World War II, researchers at the USC Dornsife College of Letters, Arts and Sciences, McGill University in Montreal, and the University of California, Berkeley, examined how sugar rationing during the war influenced long-term health outcomes.

The United Kingdom introduced limits on sugar distribution in 1942 as part of its wartime food rationing program. Rationing ended in September 1953.

The researchers used contemporary data from the U.K. Biobank, a database of medical histories and genetic, lifestyle and other disease risk factors, to study the effect of those early-life sugar restrictions on health outcomes of adults conceived in the U.K. just before and after the end of wartime sugar rationing.

“Studying the long-term effects of added sugar on health presents challenges,” explains Tadeja Gracner, a senior economist at the USC Dornsife Center for Economic and Social Research and the study’s corresponding author. “It is difficult to identify situations where individuals are randomly exposed to different nutritional environments early in life and tracked over a span of 50 to 60 years. The end of rationing provided us with a unique natural experiment that helped us overcome these obstacles.”

On average, during rationing, sugar intake was about 8 teaspoons (40 grams) per day. When rationing ended, sugar and sweets consumption skyrocketed to about 16 teaspoons (80 grams) per day. 

Notably, rationing did not involve extreme food deprivation overall. Diets generally appeared to have been within today’s guidelines set by the U.S. Department of Agriculture and the World Health Organization, which recommend no added sugars for children under two and no more than 12 teaspoons (50g) of added sugar daily for adults. 

The immediate and large increase in sugar consumption but no other foods after rationing ended created an interesting natural experiment: Individuals were exposed to varying levels of sugar intake early in life, depending on whether they were conceived or born before or after September 1953. Those conceived or born just before the end of rationing experienced sugar-scarce conditions compared to those born just after who were born into a more sugar-rich environment.

The researchers then identified those born in the U.K. Biobank data collected over 50 years later. Using a very tight birth window around the end of sugar rationing allowed the authors to compare midlife health outcomes of otherwise similar birth cohorts.  

While living through the period of sugar restriction during the first 1,000 days of life substantially lowered the risk of developing diabetes and hypertension, for those later diagnosed with either of those conditions, the onset of disease was delayed by four years and two years, respectively. 

Notably, exposure to sugar restrictions in utero alone was enough to lower risks, but disease protection increased postnatally once solids were likely introduced. 

The researchers say the magnitude of this effect is meaningful as it can save costs, extend life expectancy, and, perhaps more importantly, improve quality of life.

In the United States, individuals with diabetes face average annual medical expenses of approximately $12,000. Additionally, an earlier diagnosis of diabetes is associated with a significantly reduced life expectancy; specifically, for each decade that diagnosis occurs earlier, life expectancy decreases by three to four years.

The researchers note that these numbers underscore the value of early interventions that could delay or prevent this disease.

Experts continue to raise concerns about children’s long-term health as they consume excessive amounts of added sugars during their early life, a critical period of development. Adjusting child sugar consumption, however, is not easy—added sugar is everywhere, even in baby and toddler foods, and children are bombarded with TV ads for sugary snacks, say the researchers.

“Parents need information about what works, and this study provides some of the first causal evidence that reducing added sugar early in life is a powerful step towards improving children’s health over their lifetimes,” says study co-author Claire Boone of McGill University and University of Chicago.  

Co-author Paul Gertler of UC Berkeley and the National Bureau of Economics Research adds: “Sugar early in life is the new tobacco, and we should treat it as such by holding food companies accountable to reformulate baby foods with healthier options and regulate the marketing and tax sugary foods targeted at kids.” 

This study is the first of a larger research effort exploring how early-life sugar restrictions affected a broader set of economic and health outcomes in later adulthood, including education, wealth, and chronic inflammation, cognitive function and dementia. 

Hypertension Among Adults in the United States




Hypertension is commonly known to everyone by the name “High Blood Pressure”. This is one of the most commonly found chronic disease in which the blood pressure levels are at elevated levels.

Hypertension can be easily detected, and can be kept at controlled levels with proper medication. But, it is left untreated can result in dangerous health conditions like, heart attack, stroke, chronic heart failure, and sometimes can result into kidney diseases.

Hypertension Statistics

Nearly 29.1% of American residents are affected with this disease. When we consider this percentage with respect to sex, women and men are almost same with 28.5% and 29.7% respectively.




The risk of developing hypertension increases with age. Only 7.3% of US residents with age group 18 to 39 years are affected with this health condition. Whereas, when it comes to the age group of 40 to 59 years, percentage of people affected are 32.4%.

And it is 65%, when we consider the US residents who are above 60 years of age. Let us see few more statistics in details in the following infographic.

Hypertension Among Adults in the United States




Hypertension prevention – some tips on lowering high blood pressure




The following infographic is devoted to hypertension prevention. High blood pressure is out of control in the US and worldwide. 2 out of 3 adults in the US (that is 150 million people) and over 1 billion people worldwide have pre-hypertension or hypertension! Only 54% have their blood pressure under control.

Hypertension is the leading cause of cardiovascular disease worldwide leading to premature death. High blood pressure is the single most important risk factor for stroke and heart attacks.

Next, high Body Mass Index (BMI) and hypertension can lead to serious cardiovascular issues such as heart attack, stroke, and kidney disease.

A lower-salt diet means eating less than 1,500 mg of sodium p day. High sodium content is present in typical restaurant food and commercially prepared food (e.g. store, canned, frozen).




Hypertension Prevention




Q&A on Epilepsy with Professor Martin Brodie


Although epilepsy is the most common neurological condition in the UK, over a quarter of epilepsy patients say they experience stigma as a result of the condition. Experts warn that the resulting psychological impact can be just as damaging as the seizures themselves.

We are delighted to present a detailed introduction to the subject of epilepsy in the form of a Q&A session with internationally renowned epilepsy expert Professor Martin Brodie.

PATIENTTALK.ORG – What, actually, is epilepsy?

PROFESSOR MARTIN BRODIE – . It’s the most complicated question because it’s a lot of different things and the bottom line is it’s a condition where people get unprovoked seizures that is seizures with no obvious provocation that you can then prevent and therefore prevent the actual seizures and the causes are thousands and thousands, anything that can affect the brain.

In about two thirds of cases there is an anatomical cause, sometimes we can see it on the scan increasingly so, sometimes not. In a third it’s due to low seizure threshold with a genetic component that may not be familiar in some situations that is a singular genetic mutation. In others it’s polygenetic and there’s a lot of different genes involved and so you can have seizures from infancy, from when you were born until when you are in old age and the commonest time now to develop epilepsy is in later life. With over 3% of over 80’s having seizures because they will have a possibility of things like strokes, vascular disease, hypertension, diabetes, dementia and all of these can result in seizures.

The interesting thing is not everybody gets the seizures and you know if you’re looking at say people with brain tumours which is an obvious cause of seizures for me the interesting question for me is not why 10% of people get seizures but why do the other 90% not get seizures, and so what we can see we don’t know the cause of we can get some idea of the possible mechanisms but the actual specific mechanism that the actual individual has is not available to us so therefore we cannot just pick the best drug we have to try the drugs out and try different drugs.


PATIENTTALK.ORG – Are there any clear symptoms of Epilepsy?

PROFESSOR MARTIN BRODIE – Well it depends on the type of Epilepsy that you have, sometimes in children they can stare straight ahead and miss stuff at school, sometimes the hands can jerk and jump or people can fall, sometimes they can stare into space and turn their head and look away and these are focal seizures and of course the severe ones where you fall down, jerk and shake all over, bite your tongue and don’t breathe during it, these are the tonic chronic seizures so there are lots of different types.

PATIENTTALK.ORG – And what are the long term struggles with the condition?

PROFESSOR MARTIN BRODIE – About two thirds of patients we can actually prevent the seizures with reasonable doses of medication and for many of these people after 6 months or a year they can get their driving licence back, you can get employment although there is still stigma against that and you can live a pretty normal life, you know you can’t fly an aeroplane but there’s a lot of other things that you can reasonably do. Unfortunately about a third of people that we don’t fully control the seizures and there it’s really life changing and these people don’t drive, they often have difficulty getting employment and I’m sure my two colleagues can tell you better than me how it effects their lives.

PATIENTTALK.ORG – Ok and what is idiopathic generalized epilepsy?

PROFESSOR MARTIN BRODIE – There are three main causes of idiopathic generalized epilepsy are the absence seizures usually in children and teenagers where they stare straight ahead, myoclonic seizures where their body jerks and then the tonic chronic seizures. The international league against epilepsy has brought out a new classification and I was actually on the body that did that so that we can get away from these terms that no one understands and doesn’t make any sense, so we are now talking about focal epilepsy where the problem is in one part of the brain or genetic epilepsy where there is a lower seizure threshold and there’s a malfunction so the idiopathic generalized epilepsy are the genetic epilepsy.

PATIENTTALK.ORG – And are there any other different types of epilepsy other than those that you have mentioned?

PROFESSOR MARTIN BRODIE – Well there are few rarer types in kids who have these seizures often with single gene mutations affecting the function of the brain, in older people there are a group of conditions called progressive myoclonic epilepsy which again are also single genes although there may be different genes and this causes jerking and seizures and often people can’t even walk because of the severity of it so really anything that can affect the brain as well firstly produce seizures and they are often different.

PATIENTTALK.ORG – Ok and I was going to ask what the relationship between autism and epilepsy is?

PROFESSOR MARTIN BRODIE – Autistic spectrum disorder is what we now call it as we realised its most things it’s not just one problem and I’m not involved in that area although we have patients coming to my clinic who have this problem and this is sort of a malfunction in the brain where the brain doesn’t fully function but if you actually do a brain scan it looks normal it just doesn’t function and a number of patients with autism also have seizures and that’s why they come to me otherwise they get sent to a specialist who works within that area and people with autism can be very intelligent or they can be not intelligent and again that can be one of the reasons to why it’s called Autistic spectrum disorder because the term covers different disorders.

PATIENTTALK.ORG – Ok are there any other conditions where comorbidity with epilepsy is common?

PROFESSOR MARTIN BRODIE – Yes any condition that effects the brain can be associated with seizures because seizures are evidence of brain dysfunction, so is depression, so is anxiety, anything that can affect the brain and many patients who have epilepsy also have one or other of these other symptoms, about a third of patients with newly diagnosed epilepsy also have depression or anxiety to a degree, about a half of patients with difficulties to control the epilepsy have psychiatric comorbidity because if you think about it these are all symptoms of brain dysfunction so it’s not surprising if the brains not working terribly well if they have different symptoms and the more of these symptoms that you have the more difficult the seizures are to control and we do try to control the other symptoms with the other medication and some of my drugs actually work for depression, some of them make depression worst so there is a pharmacological overlap between all these conditions that are associated with brain dysfunction.