Tag: blood glucose

Categories : Metabolic DisordersTags :

DNA Study Hints at How Insulin Resistance Develops after Glucose Challenge

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A study of the DNA of more than 55 000 people worldwide has shed light on what goes wrong in a glucose challenge that might lead to type 2 diabetes. The findings, published today in Nature Genetics, suggests that genetic changes relating to a protein called GLUT4 could be involved.

Several factors contribute to an increased risk of type 2 diabetes, such as older age, being overweight or having obesity, physical inactivity, and genetic predisposition. If untreated, type 2 diabetes can lead to complications, including eye and foot problems, nerve damage, and increased risk of heart attack and stroke.

Most studies to date of insulin resistance have focused on the fasting state when insulin is largely acting on the liver.  But most people’s time is spent in the fed state, when insulin acts on muscle and fat tissues.

It’s thought that the molecular mechanisms underlying insulin resistance after a so-called ‘glucose challenge’ play a key role in the development of type 2 diabetes. Yet these mechanisms are poorly-understood.

Professor Sir Stephen O’Rahilly, Co-Director of the Wellcome-MRC Institute of Metabolic Science at the University of Cambridge, said: “We know there are some people with specific rare genetic disorders in whom insulin works completely normally in the fasting state, where it’s acting mostly on the liver, but very poorly after a meal, when it’s acting mostly on muscle and fat. What has not been clear is whether this sort of problem occurs more commonly in the wider population, and whether it’s relevant to the risk of getting type 2 diabetes.” 

To examine these mechanisms, an international team of scientists used genetic data from 28 studies, encompassing more than 55 000 participants (none of whom had type 2 diabetes), to look for key genetic variants that influenced insulin levels measured two hours after a sugary drink.

The team identified new 10 loci (genome regions) associated with insulin resistance after the sugary drink. Eight of these regions were also shared with a higher risk of type 2 diabetes, highlighting their importance.

One of these newly-identified loci was located within the gene that codes for GLUT4, the critical protein responsible for taking up glucose from the blood into cells after eating. This locus was associated with a reduced amount of GLUT4 in muscle tissue.

To look for additional genes that may play a role in glucose regulation, the researchers turned to cell lines taken from mice to study specific genes in and around these loci. This led to the discovery of 14 genes that played a significant role in GLUT 4 trafficking and glucose uptake – with nine of these never previously linked to insulin regulation.

Further experiments showed that these genes influenced how much GLUT4 was found on the surface of the cells, likely by altering the ability of the protein to move from inside the cell to its surface. The less GLUT4 that makes its way to the surface of the cell, the poorer the cell’s ability to remove glucose from the blood.

Dr Alice Williamson, who carried out the work while a PhD student at the Wellcome-MRC Institute of Metabolic Science, said: “What’s exciting about this is that it shows how we can go from large scale genetic studies to understanding fundamental mechanisms of how our bodies work – and in particular how, when these mechanisms go wrong, they can lead to common diseases such as type 2 diabetes.”

Given that problems regulating blood glucose after a meal can be an early sign of increased type 2 diabetes risk, the researchers are hopeful that the discovery of the mechanisms involved could lead to new treatments in future.

Source: University of Cambridge

Categories : Metabolic DisordersTags :

30-year Diabetes Study Determines HbA1c Threshold for Complications

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

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

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

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

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

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

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

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

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

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

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

Source: Linköping University

Categories : Medical Research & Technology Metabolic DisordersTags :

New Diabetes Management Device Combines Testing and Injection

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By combining blood glucose measurement with insulin administration in a single device, the complicated process of blood sugar management could be made easier for people with diabetes.

Patients with diabetes often use two types of insulin to control their blood sugar levels: long-acting insulin, which helps control glucose levels over a 24-hour period, and short-acting insulin, which is injected at mealtimes. Patients first measure their blood glucose levels with a glucose meter with a finger prick. They must also estimate how many carbohydrates are in their meal and combine this information with their blood glucose levels to calculate and inject the proper insulin dose.

Existing technologies such as continuous blood glucose monitors and insulin pumps can help with some parts of this process. However, these devices are not widely available, so most patients must rely on finger pricks and syringes. To this end, MIT researchers have developed devices to simplify the process, which they describe in the Journal of Controlled Release.

“Every day, many patients need to do this complicated procedure at least three times,” explained MIT postdoc Hen-Wi Huang. “The main goal of this project is to try to facilitate all of these complex procedures and also to eliminate the requirement for multiple devices. We also used a smartphone camera and deep learning to create an app that identifies and quantifies food content, which can aid in carbohydrate counting.”

The researchers came up with two all-in-one devices, both of which incorporate the new smartphone app. Using a photo, the app estimates the volume of food and carbohydrate content.

The first device that consolidates many of the existing tools that patients use now, including a lancet for drawing blood and glucose test strips. The device conveys blood glucose information to the smartphone app via Bluetooth, and the app works out the correct insulin dose, delivered via a needle in the same device.

“What our device is doing is automating the procedures to prick the skin, collect the blood, calculate the glucose level, and do the computation and insulin injection,” Dr Huang says. “The patient no longer needs a separate lancing device, glucose meter, and insulin pen.”

Many of the components included in this device are already FDA-approved, but the device has not been tested in human patients yet. Tests in pigs showed that the system could accurately measure glucose levels and dispense insulin.

For their second device, the researchers wanted to come up with a system that would require just one needle prick. To achieve that, they designed a novel glucose sensor that could be incorporated into the same needle that is used for insulin injection.

The researchers designed a flexible electronic sensor that can be attached to the needle and measure glucose levels in the interstitial fluid, just below the surface of the skin. Once the needle penetrates the skin, it takes between five and 10 seconds to measure the glucose levels. This information is transmitted to the smartphone app, which calculates the insulin dose and delivers it through the inserted needle.

In tests in the pigs, the researchers showed that they could accurately measure glucose levels with this system, and that glucose levels dropped after insulin injection.

Because this device uses a novel type of glucose sensor, the researchers expect that it will require further development to get to a point where it could be tested in patients.

Source: MIT

Categories : Metabolic DisordersTags :

A Needle-free Way of Blood Glucose Monitoring

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In order to find an alternative to lancets for blood glucose monitoring, researchers applied needle-free jet injection, an emerging but well-developed technique in which a drug is delivered directly with a high-speed narrow jet of fluid.

The study, led by ABI researchers Jiali Xu and James McKeage, demonstrated for the first time that a jet injector could also be used to collect blood samples from humans – that is, release enough blood for glucose sampling, sans needles. The findings appear in the Journal of Diabetes Science and Technology.

Fingertips are the preferred site for blood sampling because they have a high density of blood vessels, they are also sensitive, and pain, skin damage, bruising and risk of infection from regular ‘pricking’ has spurred increasing efforts to develop needle-free methods of blood testing for people with diabetes.

Jet injection, which does not rely on a needle, is an appealing alternative. Jiali Xu of the Auckland Bionengineering Institute (ABI) and her team demonstrated that the technology, using electric motors rather than the standard mechanical spring, could also be used to pierce the skin with a small volume of harmless saline solution, releasing enough blood for glucose concentration measurement.

The study involved 20 healthy participants, each of which received a lancet prick and jet injection on four fingertips through three differently shaped and sized nozzles. “Which were designed to mimic the wound left from a lancet prick, in the anticipation that it might release blood in a way similar to a lancet prick,” said Ms Xu.

Some nozzle shapes performing better than others – a ‘slot’ shaped nozzle released more blood than a circle-shaped nozzle, for instance.

Most of the different jet injection nozzles were generally perceived by the participants, who were unable to see the injections, as no more painful than a standard lancet, and in some cases, less so. A questionnaire was given 24 hours later to assess pain, swelling and bleeding.

People with diabetes may find jet injection more acceptable than using a needle, but the researchers caution against jumping to conclusions. “When you know there’s not a device that is pricking your skin, you could speculate that people will find jet injection more acceptable,” says Professor Andrew Taberner, head of the Bioinstrumentation Lab at the ABI, and Ms Xu’s supervisor. “But we don’t have evidence to back that up. That wasn’t part of this study. We were first trying to find out if it worked, and it did.”

He was pleased, but not surprised. “Diesel mechanics have known for years that you should never put your finger in front of a fuel injector, because it will inject fuel into your finger. They found this out the hard way. But we’re taking advantage of what diesel mechanics discovered accidentally years ago, with a very small amount of harmless liquid, to deliberately release blood.”

The team is now trying to see if they can also extract blood with this technology, allowing for the design of an even smaller nozzle.

Moreover, “our technology has the capability to both deliver and withdraw fluid. No other jet projection technology has that capacity,” said Dr Taberner.

Development and commercialisation of the technology will take time but he believes Ms Xu’s research will contribute to the ultimate aim, of the development of a single lancet-free reversible technology that will allow for both blood sampling and insulin delivery based on the glucose measurement in one device.

“I hope that this research will contribute to that, and the improvement in human healthcare, especially in the management of diabetes,” said Ms Xu.

Source: University of Auckland