Hepatic Insulin Clearance in Regulation of Systemic Insulin Concentrations–Role of Carbohydrate and Energy Availability

Hyperinsulinemia is the hallmark of insulin resistance in obesity, and the relative importance of insulin clearance, insulin resistance, and insulin hypersecretion has been widely debated. On the basis of recent experimental evidence, we summarize existing evidence to suggest hepatic insulin clearance as a major and immediate regulator of systemic insulin concentrations responding within days to altered dietary energy and, in particular, carbohydrate intake. Hepatic insulin clearance seems to be closely associated with opposite alterations in hepatic lipid content and glucose production, providing a potential mechanistic link to hepatic insulin sensitivity. The molecular regulation of insulin clearance in the liver is likely to involve changes in insulin binding and receptor internalization in response to the dietary alterations, the molecular mechanisms of which await further research.

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Developmental Programming of Obesity and Diabetes in Mouse, Monkey, and Man in 2018: Where Are We Headed?

Childhood obesity and its comorbidities continue to accelerate across the globe. Two-thirds of pregnant women are obese/overweight, as are 20% of preschoolers. Gestational diabetes mellitus (GDM) is escalating, affecting up to 1 in 5 pregnant women. The field of developmental origins of health and disease has begun to move beyond associations to potential causal mechanisms for developmental programming. Evidence across species compellingly demonstrates that maternal obesity, diabetes, and Western-style diets create a long-lasting signature on multiple systems, including infant stem cells, the early immune system, and gut microbiota. Such exposures accelerate adipogenesis, disrupt mitochondrial metabolism, and impair energy sensing, affecting neurodevelopment, liver, pancreas, and skeletal muscle. Attempts to prevent developmental programming have met with very limited success. A challenging level of complexity is involved in how the host genome, metabolome, and microbiome throughout pregnancy and lactation increase the offspring’s risk of metabolic diseases across the life span. Considerable gaps in knowledge include the timing of exposure(s) and permanence or plasticity of the response, encompassing effects from both maternal and paternal dysmetabolism. Basic, translational, and human intervention studies targeting pathways that connect diet, microbiota, and metabolism in mothers with obesity/GDM and their infants are a critical unmet need and present new challenges for disease prevention in the next generation.

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Mitochondrial ADP Sensitivity and Transport: New Insights Into Diet-Induced Mitochondrial Impairments

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Exosomes or Microvesicles, a Secreted Subcellular Organelle Contributing to Inflammation and Diabetes

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Sydney GP loses appeal over insulin murder

A Sydney doctor has lost an appeal against his conviction for the murder of his second wife with a lethal dose of fast-acting insulin.
Brian Kenneth Crickitt, 65, was jailed for a minimum of 20 years in May 2017 after being found guilty of killing his wife, Christine Crickitt. The murder took place shortly before or after New Year in 2010, at the couple’s home in Woodbine, South-West Sydney.
It was originally found by the trial judge that Crickitt spent the night with his new lover, Linda Livermore, after allegedly administering the injection. The judge also found that Crickitt’s increasing dislike of his wife and new attraction to Ms Livermore provided a motive for the murder.
Crickitt was supported by his third wife, Julie Crickitt, throughout his trial.
Crickitt was found to have performed two internet searches on insulin overdose in the days prior to the murder. The trial judge also found that he had improperly used a prescription he had written for a patient with diabetes to obtain fast-acting insulin from a pharmacy.
The autopsy could not conclude the cause of death, however the judge ruled out suicide and accidental death, ultimately finding the overdose of insulin to be responsible.
Crickitt’s appeal argued that medical experts could not determine his wife’s cause of death and that the verdict was unreasonable and unsupported by evidence.
The appeal court was required to decide if the Crown had proven in the trial, beyond reasonable doubt, that Crickitt was responsible for the death of his wife and so, if the trial judge had made the correct ruling.
The court ultimately rejected all grounds of the appeal, concluding that “in this case, it was well open to the trial judge to infer from the facts that he found that the applicant deliberately and intentionally caused the death of the deceased by administering insulin to her.”
A number of healthcare professionals have been convicted of causing death deliberately with insulin. Thankfully, this form of murder is limited to very rare cases.
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Gum disease treatment linked to improved blood glucose in type 2 diabetes, study finds

New research suggests that treating gum disease may be a factor in lowering blood glucose levels for people with type 2 diabetes.
Healthy gums were also associated with lower risks of developing diabetes complications and with improvements in kidney and blood vessel function, according to the study by UCL Eastman Dental.
This latest study examined the oral health of 264 people with type 2 diabetes who had moderate to severe gum disease. They were split into two groups, with half receiving standard care comprising of teeth cleaning and polishing and the others receiving intensive treatment.
The participants who received the intensive treatment reported an average reduction in HbA1c of 7 mmol/mol (0.6%) after one year, compared to the group receiving normal care.
It was the first study to explore a link between the treatment of gum disease with kidney and blood vessel function improvements as well as chronic inflammation.
Principle investigator Professor Francesco D’Aiuto said: “Our findings suggest preventing and treating gum disease could potentially be a new and important way to help people with type 2 diabetes manage their condition and reduce their risk of its serious complications.
“The improvement in blood glucose control we observed, in people who received intensive treatment, is similar to the effect that’s seen when people with type 2 diabetes are prescribed a second blood glucose lowering drug. We now need to determine if the improvements we found can be maintained in the longer-term and if they apply to everyone with type 2 diabetes.”
One question, which is hard for a start such as this to answer, is whether there were any significant dietary changes between the groups receiving standard or intensive care. It is not inconceivable that the group having more intensive care may have been more aware of their dental health and may have made some improvements, as a result, with regard to food choices.
However, whether improvements in diet played a role or not, the improved treatment still resulted in an improvement, which is significant to note.
People with type 2 diabetes are currently not offered care related to gum disease, known medically as periodontitis, as part of diabetes care, but a Commissioning Standard for dental health for people with type 2 diabetes or those at risk of the condition is being developed.
The study was published in The Lancet Diabetes and Endocrinology journal and was funded by Diabetes UK and the National Institute for Health Research (NIHR).
Working alongside British Society of Periodontology (BSP), Diabetes.co.uk last May published the results of a survey, which revealed that there was low awareness of the link between gum disease and diabetes. It was part of a drive to raise awareness of the issue.
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Breastfeeding impacts gut bacteria which may be a factor in type 1 diabetes

Breastfeeding has been found to impact gut bacteria that might be significant in protecting children from developing type 1 diabetes, according to new research.
The findings have come from two different studies which have both looked at gut bacteria in babies who were deemed at high genetic risk of developing type 1 diabetes.
Both trials are part of an international study programme – The Environmental Determinants of Diabetes in the Young (TEDDY) – which has so far screened more than 250,000 infants around the world, investigating certain factors which might trigger the development of type 1 diabetes.
The first trial focused on gut bacteria changes shortly after the child had been born and the other trial compared differences in the gut between children who had the condition and those who did not.
Previous studies have suggested gut bacteria might impact the chances of someone developing type 1 diabetes, and the research here focused on the gut bacteria specifically within babies.
Both research studies involved taking stool samples from more than 900 babies on a monthly basis from the age of three months. The research team continued to take the samples until either the child had developed type 1 diabetes or just before they believed the condition was about to develop.
The different types of bacteria were analysed in the stool samples and were linked to different key factors, such as the type of birth the child had experienced, siblings, exposure to furry pets and whether they had been breastfed.
One of the studies appeared to show that certain bacteria communities in the gut were impacted by breast milk, vaginal birth, siblings and pets. However, the research team stated that this did not necessarily confirm a direct link to type 1 diabetes.
The second study discovered that short-chain fatty acids might be significant. These short-chain fatty acids were mainly found within the gut bacteria of children who were not diagnosed with type 1 diabetes and who were breastfed as a baby.
In other studies, larger amounts of these short-chain fatty acids in mice have seemed to protect the animals from the condition. However, the research team said more work needs to be carried out before they can say breastfeeding conclusively reduces the chances of type 1 diabetes development.
Rachel Connor, Director of Research Partnerships at JDRF in the UK, said: “These studies found some interesting changes to patterns of gut bacteria development in early childhood. But the relationship between gut bacteria, genetics and type 1 diabetes risk is still a complicated picture.
“We will need to carry out more research to work out how exactly factors like breastfeeding and these short-chain fatty acids may be able to affect the risk of developing type 1 diabetes, and how strong these effects may be.”
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Experimental procedure found to stabilise blood sugars in type 2 diabetes

Scientists in Amsterdam trialled a procedure on people with type 2 diabetes to great effect. The researchers have described their findings as spectacular, but the full extent of long-term safety will still need to be shown.
The results come from a study on 50 people and indicate that the technique, which takes an hour to perform, is successful even a year on.
The procedure involves inflating a balloon with hot water inside the small intestine. This burns off the mucous membrane which lines the gut and, two weeks later, a new membrane grows. This process seems to improve blood sugar control and it was found that 90% of the patients still had stable blood sugars even a year after the treatment.
They conducted the experiment to explore the association between the mucus membrane absorbing nutrients in the small intestine and insulin resistance in those with type 2 diabetes.
Professor Jacques Bergman, from the research team, said: “Because of this treatment the use of insulin can be postponed or perhaps prevented. That is promising.” Bergman added of the procedure that it was “amazing that people suffer very little from this.”
Speaking to Nederlandse Omroep Stichting, a Dutch broadcaster, he added: “With those people we see a spectacular improvement in blood sugar levels one day after the operation, before they even lose one kilo, which has put us on the track.
“Because the question now is whether this is a permanent treatment, or whether it is something that you have to keep repeating – something that in theory should be possible. We looked at whether we could stop their insulin, which is still ongoing, but the first results are truly spectacular, with the lion’s share of patients no longer using insulin after this treatment.”
The findings from the study were presented at a conference which took place this week in Vienna. Next, the researchers will conduct a bigger study involving 100 people.
Type 2 diabetes can be prevented or placed into remission by lowering carbohydrates. So far over 370,000 participants have signed up to the Low Carb Program developed by Diabetes.co.uk and launched on World Diabetes Day 2015.
One-year results from the Low Carb Program, published in the summer, show one in four users put their type 2 diabetes into remission, with significant reductions in weight, HbA1c and medication use.
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PCSK9 inhibitor cholesterol drugs chosen for rapid uptake in the UK

A class of expensive cholesterol-lowering drugs known as PCSK9 inhibitors have been chosen by the Accelerated Access Collaborative (AAC) to be fast-tracked into availability. Pharmaceutical companies Amgen and Sanofi both had their products, Repatha and Praluent, selected for rapid uptake status.
Cholesterol-lowering drugs are often prescribed to people with diabetes, prediabetes or metabolic syndrome who are considered at risk of cardiovascular events such as heart attack or stroke.
The AAC is a collaboration between NHS organisations and industry, directed by the National Institute for Health and Care Excellence (NICE). It has the purpose of speeding up access to “highly transformative technologies” for NHS patients. Chosen technologies are already available to the NHS, and have an evidence base, but have seen poor uptake.
Alongside PCSK9 inhibitors, six other potentially beneficial technologies have been chosen for rapid uptake and will share the £2 million of funding released. These other technologies include Mavenclad (a multiple sclerosis medication), a test for colorectal cancer, a test for heart attack and a test for pre-eclampsia in pregnant women.
NICE have previously recommended both Praluent and Repatha, however this recommendation alone did not ensure widespread uptake across England. NICE therefore hope that this push by the AAC will allow greater access to these costly drugs.
While PCSK9 inhibitors have been shown to significantly lower levels of LDL cholesterol, concerns have been expressed over what benefit this will actually provide to patients. A study of Repatha showed a small but statistically significant reduction in risk of cardiovascular events. However, it did nothing to prevent fatal events, and there was even a greater, albeit statistically insignificant, rate of death in the group that took the drug, compared to those that did not. The study was funded by Amgen.
Commenting on these findings, Dr Aseem Malhotra, NHS consultant cardiologist, said: “NICE needs to urgently revise its recommendations on the prescription of the drug to include information that the drug will not prevent a fatal heart attack or increase a patient’s lifespan by one day.”
Though the benefits of PCSK9 inhibitors is a point of contention between academics and healthcare professionals, it is hoped that overall, the technologies chosen for rapid uptake by the AAC will offer cost-effective benefit to NHS patients.
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Foods that control diabetes

Bildresultat för Foods that control diabetes

In 1550 BC, the famous Ebers Papyrus advised treating diabetes with high fiber wheat grains. Not much has changed since then. Plant foods are the drug of choice for treating diabetes. There are large numbers of scientific research findings to confirm the effectiveness of plant foods in managing this disease. Through the centuries, more than 400 plants have been identified, used, and prescribed as diabetic remedies.

Raw onions and garlic have been long been favorite anti-diabetic drugs in Europe, Asia and the Middle East. The vegetable bitter gourd and the herb ginseng have been widely used for treating diabetes since the ancient time in India and China. Common mushroom is widely used in parts of Europe to lower blood sugar. Barely bread is a popular treatment for diabetes in Iraq. Other foods, used in different countries, in the treatment of diabetes include beans, cabbage, cinnamon, coriander seeds, cucumber, fenugreek seeds, Indian gooseberry and lettuce.

All these foods have anti-diabetic properties. Scientific research has confirmed that most of these foods, or their compounds, either lower blood sugar, or stimulate insulin production. Some of the more important foods that help to lower blood sugar or stimulate insulin production in diabetes patients are discussed here.

Artichoke is a tuberous root with a top like a sunflower. This vegetable contains good amounts of potassium, a fair amount of calcium and some iron and sulphur, all of which are needed by the body for maintaining good health.

Artichoke is beneficial in the treatment of diabetes because of its high insulin content. A fully ripe artichoke is said to contain more than two percent of insulin. Ripe artichokes are generally available only during autumn or fall. The insulin is converted into sugar in winter. Artichokes are most effective when eaten raw in salads. It cooking is required; they should be boiled, unpeeled, in a small quantity of water for about 10 minutes. Artichokes can be effectively combined with other vegetables.


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