Study: Weight Management Programme Can Put Type 2 Diabetes into Remission

Almost half of participants achieved and maintained diabetes remission at one year without antidiabetic medications

Type 2 diabetes can be reversed following an intensive weight management programme, according a randomised trial in adults who have had the condition for up to 6 years, published in The Lancet.

The study showed that after 1 year, participants had lost an average of 10kg, and nearly half had reverted to a non-diabetic state without using any diabetes treatment. The findings lend support to the widespread use of this type of intervention in the routine care of type 2 diabetes across health services.

“Our findings suggest that even if you have had type 2 diabetes for 6 years, putting the disease into remission is feasible”, says Professor Michael Lean from the University of Glasgow who co-led the study. “In contrast to other approaches, we focus on the need for long-term maintenance of weight loss through diet and exercise and encourage flexibility to optimise individual results.”

Worldwide, the number of people with type 2 diabetes has quadrupled over 35 years, rising from 108 million in 1980 to 422 million in 2014. This is expected to climb to 642 million by 2040. This increase has been linked to rising levels of obesity and the accumulation of intra-abdominal fat. Type 2 diabetes affects almost 1 in 10 adults in the UK and costs the NHS around £14 billion a year.

“Rather than addressing the root cause, management guidelines for type 2 diabetes focus on reducing blood sugar levels through drug treatments. Diet and lifestyle are touched upon but diabetes remission by cutting calories is rarely discussed”, explains Professor Roy Taylor from Newcastle University, UK, who co-led the study.

“A major difference from other studies is that we advised a period of dietary weight loss with no increase in physical activity, but during the long-term follow up increased daily activity is important. Bariatric surgery can achieve remission of diabetes in about three-quarters of people, but it is more expensive and risky, and is only available to a small number of patients.”

Previous research by the same team confirmed the Twin Cycle Hypothesis-that type 2 diabetes is caused by excess fat within the liver and pancreas-and established that people with the disease can be returned to normal glucose control by consuming a very low calorie diet. But whether this type of intensive weight management is practicable and can achieve remission of type 2 diabetes in routine primary care was not known until now.

The Diabetes Remission Clinical Trial (DiRECT), published today, included 298 adults aged 20-65 years who had been diagnosed with type 2 diabetes in the past 6 years from 49 primary care practices across Scotland and the Tyneside region of England between July 2014 and August 2016. Practices were randomly assigned to provide either the Counterweight-plus weight management programme delivered by practice dieticians or nurses (149 individuals) or best practice care under current guidelines (control; 149 individuals).

The weight management programme began with a diet replacement phase, consisting of a low calorie formula diet (825-853 calories/day for 3 to 5 months), followed by stepped food reintroduction (2-8 weeks), and ongoing support for weight loss maintenance including cognitive behavioural therapy combined with strategies to increase physical activity. Antidiabetic and blood pressure-lowering drugs were all stopped at the start of the programme.

The primary outcomes were weight loss of 15 kg or more (sufficient to achieve remission of diabetes in most cases), and remission of diabetes. Remission was defined as achievement of a glycated haemoglobin A1c (HbA1c) level of less than 6.5% at 12 months, off all medications.

The weight loss programme was acceptable to most participants, with a dropout rate of 21%, mainly for social reasons (e.g., bereavement, change or loss of job, moving house). 128 (86%) participants in the weight management group and 147 (99%) participants in the control group attended the 12 month assessment. For those whose measurements of weight and HbA1c level were not available it was assumed that no remission had occurred.

Almost a quarter (36/149) of the weight management group achieved weight loss of 15 kg or more at 12 months, compared with none in the control group. Additionally, nearly half of the weight management group (68/149) achieved diabetes remission at 1 year, compared with six (4%) in the control group.

On average, participants in the weight management group shed 10 kg of bodyweight compared to 1 kg in the control group. Importantly, the results showed that remission was closely linked with the degree of weight loss and occurred in around 9 out of 10 people who lost 15 kg or more, and nearly three quarters (47/64) of those who lost 10 kg or more.

The researchers also noted an improvement in average triglyceride (blood lipid) concentrations in the weight management group, and almost half remained off all antihypertensive drugs with no rise in blood pressure. Furthermore, the weight management group reported substantially improved quality of life at 12 months, with a slight decrease reported in the control group.

Overall, one person experienced serious adverse events possibly related to the treatment (biliary colic and abdominal pain) but continued in the study.. Some participants experienced constipation, headache, and dizziness.

The authors note that the vast majority of participants were white and British, meaning that the findings may not apply to other ethnic and racial groups such as south Asians, who tend to develop diabetes with less weight gain.

According to Professor Taylor: “Our findings suggest that the very large weight losses targeted by bariatric surgery are not essential to reverse the underlying processes which cause type 2 diabetes. The weight loss goals provided by this programme are achievable for many people. The big challenge is long-term avoidance of weight re-gain. Follow-up of DiRECT will continue for 4 years and reveal whether weight loss and remission is achievable in the long-term.”

Writing in a linked Comment, Professor Emeritus Matti Uusitupa from the University of Eastern Finland discusses whether these findings should change treatment options for type 2 diabetes. He writes, “Lean and colleagues’ results, in addition to those from other studies of type 2 diabetes prevention and some smaller interventions in this setting, indicate that weight loss should be the primary goal in the treatment of type 2 diabetes… The DiRECT study indicates that the time of diabetes diagnosis is the best point to start weight reduction and lifestyle changes because motivation of a patient is usually high and can be enhanced by the professional health-care providers. However, disease prevention should be maintained as the primary goal that requires both individual-level and population-based strategies, including taxation of unhealthy food items to tackle the epidemic of obesity and type 2 diabetes.”

Source : Alpha Galileo


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For Older Adults with Diabetes, Losing Weight through Diet and Exercise Can Improve Blood Circulation in the Brain

Type 2 diabetes affects blood circulation. The disease stiffens blood vessels and reduces the amount of oxygen that circulates throughout your body. This includes your brain. When blood flow in the brain is impaired, it can affect the way we think and make decisions.

People who have type 2 diabetes are often overweight or obese. These are conditions that may also be linked to cognitive problems (problems with thinking abilities). Lowering calorie intake and increasing physical activity are known to reduce the negative effects of type 2 diabetes on the body. However, the effects of these interventions on cognition and the brain are not clear.

Recently, researchers examined information from a 10-year-long study called Action for Health in Diabetes (Look AHEAD). In this study, participants learned how to adopt healthy, long-term behavior changes. In their new study, the researchers focused on whether participants with type 2 diabetes who lowered calories in their diet and increased physical activity had better blood flow to the brain. The researchers published their findings in the Journal of the American Geriatrics Society.

Researchers assigned participants to one of two groups. The first group was called the Intensive Lifestyle Intervention. In this group, participants were given a daily goal of eating between 1200 to 1800 calories in order to lose weight, based on their initial weight. They also had a goal of 175 minutes of physical activity during the week, through activities such as brisk walking.

Participants were seen weekly for the first six months, and three times a month for the next six months. During years 2 through 4, they were seen at least once a month and were regularly contacted by phone or email. They were also encouraged to join group classes. At the study’s end, participants were encouraged to continue individual monthly sessions and other activities.

The second group was called the “control group”. The control group attended Diabetes Support and Education classes. The researchers compared the control group to the group that participated in the lifestyle intervention.

About ten years after enrollment, 321 participants completed an MRI brain scan. (An MRI scan is a non-invasive medical test that uses a powerful magnetic field, radio frequency pulses, and a computer to produce detailed pictures of the brain.) 97 percent of those MRIs met quality control standards set by the researchers for their study.

During the study, the participants had their mental functions tested, including their verbal learning, memory, decision-making ability, and other cognitive functions.

The researchers looked at the group of adults who were overweight or obese at the beginning of the study. They concluded that in that group, those who did the long-term behavioral intervention had greater blood flow in the brain. Furthermore, blood flow tended to be greatest among those who did not do as well on tests of mental functions. This may show how the brain may adapt in response to cognitive decline.

However, the researchers also found that for the heaviest individuals, the intervention may have worked differently. This suggests that the intervention may have been most effective in increasing or maintaining blood flow in the brain for individuals who were overweight but not obese.

This summary is from “Long Term Impact of Intensive Lifestyle Intervention on Cerebral Blood Flow.” It appears online ahead of print in the Journal of the American Geriatrics Society.

Source: The AGS Foundation for Health in Aging


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High-intensity Interval Training Alters Brain Glucose Metabolism in Insulin Resistant People

Researchers at the University of Turku studied how high-intensity interval training (HIIT) alters the brain’s glucose metabolism in physically inactive insulin resistant people. Only two weeks of HIIT training reduced glucose metabolism in all areas of the brain.

​A study lead by Jarna Hannukainen and Kari Kalliokoski at the University of Turku shows that HIIT training reduces brain glucose metabolism of people suffering from type 2 diabetes or prediabetes.

– Previous studies have shown that the brain’s glucose and fatty acid uptake is increased in type 2 diabetes, and that glucose uptake decreases after weight loss. We wanted to study if a similar effect could be achieved by exercise, without a significant weight loss, says Doctoral Candidate Sanna Honkala from Turku PET Centre.

However, the mechanisms behind the changes in the brain’s metabolism are still speculations. During HIIT training, e.g. ketones and lactates are being formed which the brain can use as a source of energy. Glucose being supplemented with ketones, such as D-β-hydroxybutyrate or other substrate, could be one of the explanations for the decreased glucose uptake caused by exercise.

Both High-intensity and Moderate Training Improve Insulin Sensitivity

The participants of the study were middle-aged, non-exercising men and women, who had prediabetes or type 2 diabetes. The research subjects were randomised into two different exercise intensity groups, one of which was for HIIT training and the other for traditional, moderate intensity continuous training. The two-week training intervention included six instructed training sessions which were performed by using exercise bicycles. HIIT training consisted of 30-second training sessions with 4-minute recoveries in between, whereas traditional exercise consisted of uninterrupted, moderate intensity cycling.

– Both forms of exercise improved the whole body’s insulin sensitivity equally efficiently and most likely, we would have seen a change also in the brain’s metabolism after moderate training if the exercise period would have been longer. In order to improve their insulin sensitivity, everyone can choose the form of exercise they are most comfortable with, which also motivates to exercise regularly, says Hannukainen.

The results were published in the Journal of Cerebral Blood Flow & Metabolism.

Source: University of Turku


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Statins May Raise Odds for Type 2 Diabetes

Serena Gordon wrote . . . . . .

Cholesterol-lowering medications known as statins may lower your risk of heart disease, but also might boost the odds you’ll develop type 2 diabetes, new research suggests.

“In a group of people at high risk of type 2 diabetes, statins do seem to increase the risk of developing diabetes by about 30 percent,” said the study’s lead author, Dr. Jill Crandall. She’s a professor of medicine and director of the diabetes clinical trials unit at Albert Einstein College of Medicine in New York City.

But, she added, that doesn’t mean anyone should give up on statins.

“The benefits of statins in terms of cardiovascular risk are so strong and so well established that our recommendation isn’t that people should stop taking statins, but people should be monitored for the development of diabetes while on a statin,” she explained.

At least one other diabetes expert agreed that statins are still beneficial for those at risk of heart trouble.

Dr. Daniel Donovan Jr. is professor of medicine and director of clinical research at the Icahn School of Medicine at Mount Sinai Diabetes, Obesity and Metabolism Institute in New York City.

“We still need to give statins when LDL (bad) cholesterol isn’t under control. A statin intervention can lower the risk of a cardiovascular event by 40 percent, and it’s possible the diabetes may have been destined to happen,” he said.

The new study is an analysis of data collected from another ongoing study. More than 3,200 adults were recruited from 27 diabetes centers across the United States for the study.

The research goal was to prevent the progression of type 2 diabetes in people with a high risk of the disease, Crandall said. All of the study participants were overweight or obese. They also all showed signs that they weren’t metabolizing sugar properly at the start of the study, but not poorly enough to be diagnosed with type 2 diabetes.

Study volunteers were randomly chosen to get treatment with lifestyle changes that would lead to modest weight loss, the drug metformin or a placebo pill.

At the end of the intervention, they were asked to participate in the 10-year follow-up program. They had their blood sugar levels measured twice a year, and their statin use was tracked, too.

At the start of the follow-up period, 4 percent of participants were taking statins. At the end, about one-third were.

Simvastatin (Zocor) and atorvastatin (Lipitor) were the most commonly used statins.

The study was an observational study, so it couldn’t show a cause and effect relationship.

However, Crandall said the researchers measured levels of insulin secretion and insulin resistance. Insulin is a hormone that helps the body usher the sugar from foods into the body’s cells to be used as fuel.

Crandall said insulin secretion goes down when people take statins. Less insulin would lead to higher blood sugar levels. She said there was no indication that statins affected insulin resistance.

Donovan added that the study provides important information. “But I don’t think the message is stop statins,” he said. “Most people are probably developing heart disease before diabetes, and it’s important to treat the risk factors you can.”

Though they weren’t included in this study, people who already have type 2 diabetes should be closely monitored for increases in blood sugar when they start taking a statin, Crandall said. “The evidence so far is rather limited, but there have certainly been anecdotal reports of blood sugar being higher when someone starts statins,” she said.

She also suggested that blood sugar levels likely aren’t as much of a concern for those without diabetes or risk factors for diabetes when starting a statin. Besides excess weight, those risks include older age, high blood pressure and a family history of diabetes.

Crandall added that there are many people 50 and over with prediabetes who don’t know it, so it could be an issue for them.

Findings from the study were published online in BMJ Open Diabetes Research & Care.

Source: HealthDay


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Diabetes Pill Might Replace Injection to Control Blood Sugar

Serena Gordon wrote . . . . . .

An injectable class of diabetes medication — called glucagon-like peptide-1 or GLP-1 — might one day be available in pill form, research suggests.

Based on the results of a global phase 2 clinical trial, the study authors reported a significant drop in blood sugar levels for people on the oral medication, and no significant increase in low blood sugar levels (hypoglycemia) compared to a placebo over six months.

The findings also showed that people taking the highest dose of the pill lost a large amount of weight — about 15 pounds — compared to a weight loss of fewer than 3 pounds for people on the inactive placebo pill.

The research was funded by Novo Nordisk, the company that makes the drug, called oral semaglutide.

“Semaglutide could transform diabetes treatment,” said Dr. Robert Courgi, an endocrinologist at Southside Hospital in Bay Shore, N.Y.

“Glucagon-like peptide receptor agonists are agents that are highly recommended according to diabetes guidelines, but rarely used because they require injection. Most patients prefer a pill,” Courgi explained.

Dr. Joel Zonszein, director of the clinical diabetes center at Montefiore Medical Center in New York City, agreed that these new findings were exciting.

“This medication looks pretty good. The high dose matched the [injection] version. There was low hypoglycemia. It controls blood glucose. There was weight loss and it’s not an injection. This is the same molecule that’s been shown [as an injection] to decrease cardiovascular mortality,” Zonszein said.

“It has all the ingredients for an excellent medication. If this comes to market, it would be very good for people with type 2 diabetes,” he added.

Zonszein and Courgi were not involved in the current study.

The study included just over 1,100 people with type 2 diabetes recruited from 100 centers in 14 countries around the world.

The volunteers’ average age was 57. The average time they’d had type 2 diabetes was six years. On average, they were considered obese.

The participants’ average hemoglobin (HbA1C) levels were between 7 and 9.5 percent. HbA1C — also called A1C — is a measure of average blood sugar control over two to three months. The American Diabetes Association generally recommends an HbA1C of less than 7 percent for most people with type 2 diabetes.

The study volunteers were randomly placed into treatment groups that lasted 26 weeks. One group was given a once-weekly injection containing 1.0 milligram (mg) of semaglutide. Five groups were given one of five doses of oral semaglutide — 2.5, 5, 10, 20 or 40 mg. Another group was given escalating doses of the pill version, starting with the smallest dose and ending at 40 mg. The final group was given an oral placebo.

The highest dose of the pill performed similarly to the injectable form as far as blood sugar control and weight loss. Those on the 40-mg oral dose and those who got the injection saw an average drop in their HbA1C of 1.9 percent, the study showed. More than 70 percent of those who took the pill saw a weight loss of at least 5 percent.

According to the study’s lead author, Dr. Melanie Davies, “The A1C reductions and weight loss were very impressive and similar to what we’ve seen with the weekly injection of semaglutide.” Davies is a professor of diabetes medicine at the Diabetes Research Centre at the University of Leicester in England.

The two forms of the drug were also similar in the reported side effects, which affected up to around 80 percent of those taking both forms of the drug. The most common side effects were mild to moderate digestive concerns that tended to go away with time. Nausea was less common in people who started on the lowest dose and then were given stronger doses.

There were three reported cases of pancreatitis — inflammation of the pancreas — a potentially serious condition that has been linked to this class of medication in previous studies. One person was taking the injectable form of the drug. The other two were on the oral drug — 20 mg and 40 mg.

Zonszein noted that “pancreatitis was a bit more in those who took the drug. This may be an issue we have to pay attention to, and it may help to start with a lower dose.”

He also added that GLP-1 drugs, whether by injection or by mouth, should be given in combination with the standard first line type 2 diabetes drug metformin.

“We get more mileage from combining drugs and patients really do much better,” Zonszein said.

Findings from the study were published in the Journal of the American Medical Association. Davies said phase 3 trials of the pill are already well under way.

Source: HealthDay


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