Category: Metabolic Disorders

Categories : Genetics Metabolic DisordersTags :

Twin Study Reveals Epigenetic Signature for Obesity

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A susceptibility to gain weight may be written into the epigenetic information of human cells, a Washington State University study indicates.

The proof-of-concept study with a set of 22 twins found an epigenetic signature in buccal cells appearing only for the twins who were obese compared to their thinner siblings. The findings could lead to the development of a simple cheek swab test for an obesity biomarker and enable earlier prevention, the researchers said.

“Obesity appears to be more complex than simple consumption of food. Our work indicates there’s a susceptibility for this disease and molecular markers that are changing for it,” said Michael Skinner, a WSU professor of biology and corresponding author of the study published in the journal Epigenetics.

The study focused on twins to help eliminate the role of genetics and instead focus on epigenetics, molecular processes which are separate from DNA but influence how genes are expressed. The fact that the epigenetic signature was found in cheek cells rather than fat cells also suggests that the obesity signature is likely found throughout the human system.

The signature’s systemic nature also suggests that something may have occurred early in one twin’s life that triggered obesity susceptibility, Skinner added. It’s also possible that it was inherited by one twin and not the other.

For this study, Skinner worked with lead author Glen Duncan, director of the Washington State Twin Registry based at WSU, to identify 22 twin pairs, both identical and fraternal, who were discordant for obesity: one sibling had a body mass index (BMI) of 30 or higher, the standard for obesity defined by the Centers of Disease Control and Prevention, while the other sibling was in the normal range of 25 and below.

The research team analysed cells from cheek swabs provided by the twins. In the cells from the twin siblings who were obese, they found similar epigenetic changes to DNA methylation regions, areas where molecular groups made of methane attach to DNA, regulating gene expression or turning genes on or off.

The study would need to be replicated with larger groups of people to develop a biomarker test for obesity, the authors said.

The goal would be able to identify people earlier in life before they become obese so health care providers might help create interventions such as lifestyle changes, medication or both, said Duncan.

“Ultimately we would like to have some kind of preventative measure instead of our usual approach which is treatment,” he said. “It’s a simple fact that it’s better to prevent a disease, then try to treat it after you have it.”

Source: Washington State University

Categories : Metabolic DisordersTags :

Daily Insulin Injections Could be Replaced with Weekly Ones

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Novolog insulin pen. Photo by Dennis Klicker on Unsplash

Insulin icodec, a once-weekly basal injection to treat type 1 diabetes, has the potential to be as effective in managing the condition as daily basal insulin treatments, according to research from the University of Surrey. The results of the year-long phase 3 clinical trial were published in The Lancet, and could one day revolutionise diabetes care.

During this pioneering study, scientists across 12 countries at 99 sites, led by Professor David Russell-Jones from Surrey, tested the efficacy and safety of a weekly basal injection of icodec (a long-lasting type of insulin) and compared it to a daily basal injection of insulin degludec in adults with type 1 diabetes. Short acting insulin to cover meals was used in both groups.

Professor David Russell-Jones, Professor of Diabetes and Endocrinology at the University of Surrey and a Consultant at the Royal Surrey Foundation Trust, said:

“Many people find managing a long-term condition such as diabetes very difficult and report missing vital insulin injections. Missed injections can affect glycaemic control, and a lack of consistency in the treatment has been linked to increased rates of diabetic ketoacidosis, a serious complication of the condition that can be life-threatening. Reducing insulin injection frequency could lessen the burden of treatment for some people with the condition and improve their glycaemic control.”

To learn more about the efficacy of icodec, scientists recruited 582 participants with type 1 diabetes. Participants were split into two groups; the first received once-weekly injections of icodec (700U/mL), and the second received daily injections of degludec (100U/mL), both in combination with aspart, a short-acting insulin at mealtimes.

After 26 weeks, scientists identified HbA1C levels in those who had taken icodec had decreased from a mean of 7.59% at baseline to an estimated mean of 7.15% , and for degludec, the mean had fallen from 7.63% to 7.10%. The estimated treatment difference between them being 0.05 percent, confirming the non-inferiority of icodec to degludec, but with a significantly reduced injection frequency for patients to manage.

Scientists did also identify higher rates of hypoglycaemic episodes (abnormally low levels of glucose in the blood) in the icodec group compared to degludec. However, despite the higher levels in the icodec group, scientists noted that incidences were low in both groups, with most episodes only requiring oral carbohydrate administration. For icodec, time below 3.0mmol/L was at the threshold of the internationally recommended targets during weeks 22-26 and below recommended targets during weeks 48-52.

Professor Russell-Jones added:

“What we have found is that once-weekly icodec injections showed non inferiority to once-daily injections of degludec in reducing HbA1C after 26 weeks. Although there is a slightly higher rate of hypoglycaemia under this regime, we found this could be easily managed. We’ve concluded this new insulin may have a role in reducing the burden of daily basal injections for patients managing type 1 diabetes.

“Our findings are very promising, but further analysis of continuous glucose monitoring data and real-world studies are needed.”

Source: University of Surrey

Categories : Metabolic DisordersTags :

Study Shows Intermittent Fasting Effective in Type 2 Diabetes

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Time-restricted eating, also known as intermittent fasting, can help people with Type 2 diabetes lose weight and control their blood sugar levels, according to a new study published in JAMA Network Open from researchers at the University of Illinois Chicago.

Participants who ate only during an eight-hour window between noon and 8 pm each day actually lost more weight over six months than participants who were instructed to reduce their calorie intake by 25%. Both groups had similar reductions in long-term blood sugar levels, as measured by a test of haemoglobin A1C, which shows blood sugar levels over the past three months.

The study was conducted at UIC and enrolled 75 participants into three groups: those who followed the time-restricted eating rules, those who reduced calories and a control group. Participants’ weight, waist circumference, blood sugar levels and other health indicators were measured over the course of six months.

Senior author Krista Varady said that participants in the time-restricted eating group had an easier time following the regime than those in the calorie-reducing group. The researchers believe this is partly because patients with diabetes are generally told to cut back on calories by their doctors as a first line of defence, so many of these participants likely had already tried, and struggled with, that form of dieting. And while the participants in the time-restricted eating group were not instructed to reduce their calorie intake, they ended up doing so by eating within a fixed window.

“Our study shows that time-restricted eating might be an effective alternative to traditional dieting for people who can’t do the traditional diet or are burned out on it,” said Varady, a professor of kinesiology and nutrition. “For many people trying to lose weight, counting time is easier than counting calories.”

There were no serious adverse events reported during the six-month study. Occurrences of hypoglycaemia and hyperglycaemia did not differ between the diet groups and control groups.

Just over half the participants in the study were Black and another 40% were Hispanic. This is notable as diabetes is particularly prevalent among those groups, so having studies that document the success of time-restricted eating for them is particularly useful, the researchers said.

The study was small and should be followed up by larger ones, said Varady, who is also a member of the University of Illinois Cancer Center. While it acts as a proof of concept to show that time-restricted eating is safe for those with Type 2 diabetes, Varady said people with diabetes should consult their doctors before starting this sort of diet.

Source: University of Illinois Chicago

Categories : Diet and Nutrition Metabolic DisordersTags :

Red Meat Consumption Linked to Increased Type 2 Diabetes Risk

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“Meat’s back off the menu, boys”

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People who eat just two servings of red meat per week may have an increased risk of developing type 2 diabetes compared to people who eat fewer servings, and the risk increases with greater consumption, according to a new study in The American Journal of Clinical Nutrition. However, substituting plant or diary protein for red meat was associated with reduced risk of type 2 diabetes.

“Our findings strongly support dietary guidelines that recommend limiting the consumption of red meat, and this applies to both processed and unprocessed red meat,” said first author Xiao Gu, postdoctoral research fellow in the Department of Nutrition at Harvard T.H. Chan School of Public Health.

While previous studies have found a link between red meat consumption and type 2 diabetes risk, this study, which analysed a large number of type 2 diabetes cases among participants being followed for an extended period of years, adds a greater level of certainty about the association.

Type 2 diabetes rates are increasing rapidly in the US and worldwide. This is concerning not only because the disease is a serious burden, but it also is a major risk factor for cardiovascular and kidney disease, cancer, and dementia.

For this study, the researchers analysed health data from 216 695 participants from the Nurses’ Health Study (NHS), NHS II, and Health Professionals Follow-up Study (HPFS). Diet was assessed with food frequency questionnaires every two to four years, for up to 36 years. During this time, more than 22 000 participants developed type 2 diabetes.

The researchers found that consumption of red meat, including processed and unprocessed red meat, was strongly associated with increased risk of type 2 diabetes. Participants who ate the most red meat had a 62% higher risk of developing type 2 diabetes compared to those who ate the least. Every additional daily serving of processed red meat was associated with a 46% greater risk of developing type 2 diabetes and every additional daily serving of unprocessed red meat was associated with a 24% greater risk.

The researchers also estimated the potential effects of substituting one daily serving of red meat for another protein source. They found that substituting a serving of nuts and legumes was associated with a 30% lower risk of type 2 diabetes, and substituting a serving of dairy products was associated with a 22% lower risk.

“Given our findings and previous work by others, a limit of about one serving per week of red meat would be reasonable for people wishing to optimise their health and wellbeing,” said senior author Walter Willett, professor of epidemiology and nutrition.

In addition to health benefits, swapping red meat for healthy plant protein sources would help reduce greenhouse gas emissions and climate change, and provide other environmental benefits, according to the researchers.

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

Categories : Metabolic DisordersTags :

Brain Changes from Shift Work Increase Appetite

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Scientists have uncovered why night shift work is associated with changes in appetite in a new University of Bristol-led study. The study shows that circadian disruption can disrupt the brain’s regulation of appetite hormones. The findings, published in Communications Biology, could help the millions of people that work through the night and struggle with weight gain.

Scientists from Bristol and the University of Occupational and Environmental Health in Japan, sought to understand how ‘circadian misalignment’ – a phenomenon commonly associated with ‘jet-lag’ whereby the body’s biological clock is disrupted – affects the hormones responsible for regulating appetite.

Prevalent in night shift workers, in this new study, the international team reveal how circadian misalignment can profoundly alter the brain’s regulation of hormones controlling hunger to the detriment of metabolic health.

The team focused on glucocorticoid hormones in the adrenal gland which regulate many physiological functions including metabolism and appetite. Glucocorticoids are known to directly regulate a group of brain peptides controlling appetitive behaviour, with some increasing appetite (orexigenic) and some decreasing appetite (anorexigenic).

In an experiment using animal models, comprising a control group and a out-of-phase ‘jet-lagged’ group, the team found misalignment between light and dark cues led the out-of-phase group’s orexigenic hypothalamic neuropeptides (NPY) to become dysregulated, driving an increased desire to eat significantly more during the inactive phase of the day.

Strikingly, the team discovered that rats in the control group ate 88.4% of their daily intake during their active phase, and only 11.6% during their inactive phase. In contrast, the ‘jet-lagged’ group consumed 53.8% of their daily calories during their inactive phase (without an increase in activity during this time). This equated to nearly five-times more (460% more) than what the control group consumed during the inactive phase. These results show that it is timing of consumption that has been affected.

This new discovery revealed how completely, and significantly, disordered the neuropeptides become when daily glucocorticoid levels are out of synch with light and dark cues. However, the authors suggest the neuropeptides identified in this study may be promising targets for pharmacological treatments for eating disorders and obesity.

Research Fellow Dr Becky Conway-Campbell, the study’s senior author, said: “For people working throughout the night, a reversed body clock can play havoc with their health.

“For those who are working night shifts long-term, we recommend they try to maintain daylight exposure, cardiovascular exercise and mealtimes at regulated hours. However, internal brain messages to drive increased appetite are difficult to override with ‘discipline’ or ‘routine’ so we are currently designing studies to assess rescue strategies and pharmacological intervention drugs. We hope our findings also provide new insight into how chronic stress and sleep disruption leads to caloric overconsumption.”

Professor Stafford Lightman, co-senior author on the study, added: “The adrenal hormone corticosterone, which is normally secreted in a circadian manner, is a major factor in the daily control of brain peptides that regulate appetite. Furthermore when we disturb the normal relationship of corticosterone with the day to night light cycle it results in abnormal gene regulation and appetite during the period of time that the animals normally sleep.

“Our study shows that when we disturb our normal bodily rhythms this in turn disrupts normal appetite regulation in a way that is at least in part a result of desynchrony between adrenal steroid hormone production and the timing of the light and dark cycle.”

Dr Benjamin Flynn, one of the study’s co-authors who conducted the study while at Bristol but is now based at the University of Bath, added: “This is further evidence of how phase shift ‘jet-lag’ affects feeding behaviours and neuronal gene expression – data important for shift work co-morbidity research.”

Source: University of Bristol

Categories : Gastrointestinal Metabolic DisordersTags :

For Weight Loss, the Side Effects of GLP-1 Agonists can be Hard to Stomach

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GLP-1 agonists are being lauded as game-changers in the fight against obesity, but GLP-1 agonist drugs like semaglutide may come with a heightened risk of severe gastrointestinal problems, according to new research published in JAMA.

Designing their study for the side effects rather than the efficacy of the drugs, the researchers found that GLP-1 agonists are associated with an increased risk of serious medical conditions including gastroparesis (stomach paralysis), pancreatitis and bowel obstruction.

While previous studies highlighted some of these risks in patients with diabetes, this study from the University of British Columbia is the first large, population-level study to examine adverse gastrointestinal events in non-diabetic patients using the drugs specifically for weight loss.

“Given the wide use of these drugs, these adverse events, although rare, must be considered by patients thinking about using them for weight loss,” said first author Mohit Sodhi, a graduate of UBC’s experimental medicine program and fourth year UBC medical student studying the adverse events of commonly prescribed medications. “The risk calculus will differ depending on whether a patient is using these drugs for diabetes, obesity or just general weight loss. People who are otherwise healthy may be less willing to accept these potentially serious adverse events.”

GLP-1 agonists have exploded in popularity over the past decade as an off-label weight-loss tool, reaching approximately 40 million prescriptions in the US in 2022.

It was only in 2021 that some forms of the medications were approved as a treatment for obesity. However, randomised clinical trials examining the efficacy of the medications for weight loss were not designed to capture rare gastrointestinal events due to their small sample sizes and short follow-up periods.

“There have been anecdotal reports of some patients using these drugs for weight loss and then presenting with repeated episodes of nausea and vomiting secondary to a condition referred to as gastroparesis,” said senior author Dr Mahyar Etminan, an epidemiologist and associate professor in the department of ophthalmology and visual sciences at the UBC faculty of medicine. “But until now, there hasn’t been any data from large epidemiologic studies.”

To help fill this knowledge gap, UBC researchers examined health insurance claim records for approximately 16 million US patients and looked at people prescribed either semaglutide or liraglutide, two main GLP-1 agonists, between 2006 and 2020. They included patients with a recent history of obesity, and excluded those with diabetes or who had been prescribed another antidiabetic drug.

The researchers analysed the records to see how many patients developed one of four gastrointestinal conditions, and compared that rate to patients using another weight-loss drug, bupropion-naltrexone. Compared to bupropion-naltrexone, GLP-1 agonists were associated with a:

  • 9.09 times higher risk of pancreatitis, which can cause severe abdominal pain and, in some cases, require hospitalisation and surgery.
  • 4.22 times higher risk of bowel obstruction, resulting in symptoms like cramping, bloating, nausea and vomiting. Depending on the severity, surgery may be required.
  • 3.67 times higher risk of gastroparesis, limiting the passage of food from the stomach to the small intestine and results in symptoms like vomiting, nausea and abdominal pain.

Additionally, the study found a non-significant higher incidence of biliary disease.

The researchers say that although the events are rare, with millions around the world using the drugs, it could still lead to hundreds of thousands of people experiencing these conditions.

“These drugs are becoming increasingly accessible, and it is concerning that, in some cases, people can simply go online and order these kinds of medications when they may not have a full understanding of what could potentially happen. This goes directly against the mantra of informed consent,” said Sodhi.

In the meantime, the researchers hope that regulatory agencies and drug makers will consider updating the warning labels for their products, which currently don’t include the risk of gastroparesis.

“This is critical information for patients to know so they can seek timely medical attention and avoid serious consequences,” said Sodhi.

Source: University of British Columbia

Categories : Metabolic Disorders Obstetrics & GynaecologyTags :

Metformin Trial Offers Hope for Women with Gestational Diabetes

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A significant step forward has been taken in the management of gestational diabetes mellitus after a clinical trial involving pregnant women provided new hope for expectant mothers suffering the condition. The findings from the trial are published in the Journal of American Medical Association.

Gestational diabetes affects almost 3 million pregnant women worldwide every year. It is a condition characterised by elevated blood sugar levels during pregnancy, posing increased health risks for both mothers and their babies.

The EMERGE, randomised, placebo-controlled trial, was conducted by the University of Galway and involved more than 500 pregnant women.

The trial results showed that:

  • Women assigned to metformin were 25% less likely to need insulin, and when insulin was necessary, it was started later in the pregnancy.
  • Fasting and post-meal glycaemic values in the mother were significantly lower in the metformin exposed group at weeks 32 and 38.
  • Women receiving metformin gained less weight throughout the trial and maintained this weight difference at the 12-week post-delivery visit.
  • Importantly, delivery occurred at the same mean gestational age (39.1 weeks) in both groups. There was no evidence of any increase in preterm birth (defined as birth before 37 weeks) among those who received metformin.
  • Infants born to mothers who received metformin weighed, on average, 113g less at birth, with significantly fewer infants classified as large at birth, or weighing over 4kg.
  • While there was a slight reduction in infant length (0.7cm), there were no other significant differences in baby measurements.
  • There were slightly more babies who were small at birth but this did not reach statistical significance.

The study also revealed no differences in adverse neonatal outcomes, including the need for intensive care treatment for new-borns, respiratory support, jaundice, congenital anomalies, birth injuries or low sugar levels.

Additionally there were no variations in rates of labour induction, caesarean delivery, maternal haemorrhage, infection or blood pressure issues during or after birth.

Professor Fidelma Dunne managed the trial, and presented the results at the 59th Annual Meeting of the European Association for the Study of Diabetes in Hamburg, Germany.

Professor Dunne said, “While there is convincing evidence that improved sugar control is associated with improved pregnancy outcomes, there was uncertainty about the optimal management approach following a diagnosis of gestational diabetes.

“In our pursuit of a safe and effective treatment option we explored an alternative approach – administering the drug metformin. A previous trial compared metformin to insulin and found it to be effective, yet concerns remained, especially regarding preterm birth and infant size.”

To address concerns comprehensively, the team at University of Galway conducted a ground-breaking placebo-controlled-trial, filling a critical gap in the gestational diabetes treatment landscape.

  • 535 pregnant women took part, with 268 receiving metformin and 267 a placebo.
  • 98% of women remained in the trial until delivery, with 88% completing the 12-week post-delivery follow up assessment.
  • Only 4.9% of women discontinued medication due to side effects, highlighting the safety of the interventions.

Professor Dunne said, “Traditionally, gestational diabetes has been managed initially through dietary advice and exercise, with insulin introduced if sugar levels remain sub optimal. While effective in reducing poor pregnancy outcomes, insulin use is associated with challenges, including low sugars in both the mother and infant which may require neonatal intensive care, excess weight gain for mothers, and higher caesarean birth rates.” Professor Dunne added: “The results from the EMERGE study are a significant step forward for women with gestational diabetes. Metformin has emerged as an effective alternative for managing gestational diabetes, offering new hope for expectant mothers and healthcare providers worldwide.”

Source: University of Galway

Categories : Gender Metabolic DisordersTags :

Study Suggests Lowering Type 2 Diabetes Diagnosis Threshold in Women under 50

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New research published in the journal Diabetes Therapy suggests that the diagnosis threshold for type 2 diabetes (T2D) should be lowered in women aged under 50 years, since natural blood loss through menstruation could be affecting their blood sugar management.

Analysis of the national diabetes audit results has shown that women of younger age with type 2 diabetes mellitus (T2D) seem to have a higher mortality rate than men. The underlying mechanisms remain unclear. However, it is known that women are on average diagnosed with T2D at a later age than men. In this new study, the authors investigated whether a contributing factor to this late diagnosis may be a sex difference in the levels of glycated haemoglobin (HbA1c) due to haemoglobin replacement linked to menstrual blood loss.

This mechanism behind this could be shorter erythrocyte (red blood cell) survival which results in shorter exposure of haemoglobin to glucose compared with individuals who do not menstruate. Given that the diagnosis of T2D is also based on HbA1c, the use of the same reference range irrespective of age and sex, when a slightly lower point for T2D for premenopausal women may be appropriate, could potentially lead to under diagnosis of T2D in women and missed opportunities for intervention.

The study, by Dr Adrian Heald, Salford Royal Hospital, UK, and colleagues, examined HbA1c testing across seven UK laboratory sites (representing 5% of UK population). They conducted an exploratory analysis in two cohorts: cohort 1 was from one laboratory tested between 2012 and 2019 (146 907 participants). They assessed the sex and age differences of HbA1c in individuals who underwent single testing only, that had not been diagnosed with diabetes and had an HbA1c result of equal to or less than 48mmol/mol (the cutoff for diagnosing diabetes). The process was replicated in cohort 2 results from six laboratories with individuals tested between 2019 and 2021 (total people included 938 678). The possible national impact was estimated by extrapolating findings based on the Office of National Statistics (ONS) England population data and National Diabetes Audit published T2D prevalence and related excess mortality.

At age 50 years, average HbA1c levels in women lag by approximately five years compared to men. The data also show women aged under 50 years old had an HbA1c distribution that was lower than that of men by an average of 1.6mmol/mol (4.7% of the overall mean) while the difference in the distribution of HbA1c for individuals aged 50 years and over was less pronounced.  Further analysis showed that, at HbA1c of 48mmol/mol, 50% fewer women could be diagnosed with T2D than men under the age of 50, whilst only 20% fewer women could be diagnosed with T2D than men over or equal to the age of 50. These findings were consistent with those in cohort 2.

Based on these observations, the authors estimated the effects of lowering the threshold for diagnosis of diabetes from HbA1c (48mmol/mol) by 4.2% to 46mmol/mol for women under the age of 50. This analysis showed that an additional 35 345 currently undiagnosed women in England would be reclassified as being diagnosed with T2D (17% more than the current 208 000 recorded women with T2D aged under 50 years). Lifestyle changes and treatment for diabetes would then be initiated for these women enabling improvement in health outcomes over both the short and longer term.

The authors also highlight that sex and gender difference in adverse cardiovascular risk factors are known to be present prior to the development of T2D. Once diagnosed, the prevalence of atherosclerotic cardiovascular disease is twice as high in patients with diabetes mellitus compared to those without diabetes mellitus. For women, diabetes mellitus is a stronger risk factor for cardiovascular disease than for men: women with diabetes aged 35–59 years have the highest relative cardiovascular death risk across all age and sex groups.

Furthermore, there is disparity in cardiovascular risk factor management between men and women, including in high-risk groups such as women with T2D.  Women are less likely than men to receive treatment and cardiovascular risk reduction interventions that are recommended by international guidelines on diabetes. In addition, concordance with medication or prescription treating cardiovascular risk factors is lower in women than men with T2D, with less use of statins, aspirin and beta blockers. The authors say taken together, these factors mean “timely diagnosis of type 2 diabetes and initiation of preventative treatment has the potential to improve cardiovascular risk profile over lifetime and facilitate longer life quality and expectancy in women. Our findings provide evidence that the HbA1c threshold for this group should be re-evaluated.”

Source: EurekAlert!

Categories : Metabolic DisordersTags :

Researchers Find a Mechanistic Link between Zinc Levels and Risk of Diabetes

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Researchers have identified a mechanistic link between zinc levels in humans and the risk of type 2 diabetes and non-alcoholic fatty liver disease (NAFLD). The research, published today as a Reviewed Preprint in eLife, is described by editors as a fundamental study that substantially advances our understanding of the role of zinc in metabolism. The evidence comes from genetic analysis of a large population of human participants and comprehensive lab studies of a potential therapeutic target for NAFLD and type 2 diabetes.

Converging lines of evidence have shown that zinc plays a crucial role in insulin production and glucose metabolism. “We know that increasing zinc intake improves blood glucose control in people with prediabetes or type 2 diabetes, and people with a mutation in a key zinc transporter protein have reduced risk of diabetes.” says first author Shek Man Chim, Principal Scientist at Regeneron Pharmaceuticals, Inc, New York, US. “However, the mechanism for how zinc influences systemic blood glucose levels and diabetes risk remains unclear.”

To explore the diabetes-protective role of zinc, Chim and colleagues tested loss-of-function mutations from genetic sequence data collected from a large population of participants of European ancestry who took part in the Regeneron Genetics Center-Geisinger Health System DiscovEHR study. This identified a rare mutation that causes loss of function in a zinc transporter protein called SLC39A5, associated with increased circulating zinc levels.

To confirm this, they looked at how loss-of-function mutations in SLC39A5 were associated with type 2 diabetes in a meta-analysis of four multi-ethnic European and US studies totalling >62 000 cases of diabetes and > 518 000 healthy controls. This confirmed that circulating zinc levels in carriers of the SLC39A5 loss-of-function mutation were elevated and associated with a reduced risk of diabetes.

Having identified SLC39A5 as an important clinical link between zinc and diabetes, the team explored its function by genetically deleting the zinc transporter protein in mice. As anticipated, these mice had elevated blood and tissue levels of zinc. When the team fed mice a high-fat, high-fructose diet to induce obesity, there was a significant reduction in fasting glucose compared to the control mice fed the same diet. Similar results were observed in a congenital (leptin receptor-deficiency) model of obesity. Loss of SLC39A5 also resulted in reduced insulin resistance.

As diabetes often coincides with NAFLD, the team explored whether loss of SLC39A5 protects the liver, too. As hoped, mice lacking SLC39A5 had less build-up of fat in the liver and in blood markers of liver damage. Moreover, mice lacking SLC39A5 but fed a high-fat, high-fructose diet also had less fat accumulation in the liver and improved insulin sensitivity compared to control mice.

The improvements seen in the livers of mice lacking SLC39A5 prompted the researchers to see whether loss of SLC39A5 protects against progression of non-alcoholic fatty liver disease to non-alcoholic steatohepatitis (NASH), a more severe liver inflammation that leads to fibrosis. They used a high-fat, high-cholesterol diet to induce NASH in mice and found increased markers of liver damage, body weight, fasting blood glucose and liver fibrosis. By contrast, the mice lacking SLC39A5 had reduced liver damage markers, fasting blood glucose and improvements in liver inflammation and fibrosis.

One concern highlighted by public reviewers was that observed differences in the metabolic consequences of SLC39A5 inactivation between male and female mice remained unclear. Further work will need to explore this further, as well as characterise the role of SLC39A5 in pancreatic cell function and glucose tolerance more fully.

“Our study provides for the first-time genetic evidence demonstrating the protective role of zinc against high blood sugar and unravels the mechanistic basis underlying this effect,” concludes senior author Harikiran Nistala, currently Head of functional Genomics at Alkermes Inc, Waltham, US. “Our observations suggest that blocking SLC39A5 could be a potential therapeutic avenue for type 2 diabetes and other indications where zinc supplementation alone is inadequate.”

Source: eLife

Categories : Diet and Nutrition Metabolic DisordersTags :

Almonds Help Weight Loss and Improve Cardiometabolic Health

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Diets often recommend avoiding nuts as they contain a large amount of fat even though they are high in protein and fibre. Now, a large study published in the journal Obesity demonstrated that including almonds in an energy restricted diet not only helped participants to lose weight, but also improved their cardiometabolic health.

Examining the effects of energy restricted diets supplemented with Californian almonds or with carbohydrate- rich snacks, researchers found that both diets successfully reduced body weight by about 7kg.

Globally, more than 1.9 billion adults are overweight (650 million with obesity). Two in three people (approximately 12.5 million adults) are overweight or have obesity, as do one in every two South Africans.

UniSA researcher Dr Sharayah Carter says the study demonstrates how nuts can support a healthy diet for weight management and cardiometabolic health.

“Nuts, like almonds, are a great snack. They’re high in protein, fibre, and packed with vitamins and minerals, but they also have a high fat content which people can associate with increased body weight,” Dr Carter says.

“Nuts contain unsaturated fats – or healthy fats – which can improve blood cholesterol levels, ease inflammation, and contribute to a healthy heart.

“In this study we examined the effects of an almond-supplemented diet with a nut-free diet to identify any influence on weight and cardiometabolic outcomes.

“Both the nut and nut free diets resulted in approximately 9.3% reduction in body weight over the trial.

“Yet the almond-supplemented diets also demonstrated statistically significant changes in some highly atherogenic lipoprotein subfractions, which may lead to improved cardiometabolic health in the longer term.

“Additionally, nuts have the added benefit of making you feel fuller for longer, which is always a pro when you’re trying to manage your weight.”

The study, funded by the Almond Board of California, had 106 participants complete a 9-month eating program (a three-month energy-restricted diet for weight loss in Phase 1, followed by Phase 2, a six-month energy-controlled diet for weight maintenance). In both phases, 15% of participants’ energy intake comprised unsalted whole almonds with skins (for the nut diet) or 15% carbohydrate-rich snacks – such as rice crackers or baked cereal bars (for the nut-free diet).

Reductions occurred in fasting glucose (−0.2mmol/L), insulin (−8.1pmol/L), blood pressure (−4.9 mmHg systolic, −5.0mmHg diastolic), total cholesterol (−0.3 mmol/L), low-density lipoprotein (LDL) (−0.2mmol/L), very low-density lipoprotein (−0.1mmol/L), and triglycerides (−0.3mmol/L), and high-density lipoprotein increased (0.1mmol/L) by the end of Phase 2 in both groups.

Source: University of South Australia