New research led by experts at the University of Nottingham has found that certain types of medication used to treat diabetes may be effective in reducing alcohol use.
The study looked at whether a type of diabetes medication called GLP-1 receptor agonists (GLP-1 RAs) could also help people reduce their drinking.
The study was led by Dr Mohsen Subhani, Clinical Assistant Professor of Gastroenterology at the NIHR Nottingham Biomedical Research Centre, in the School of Medicine, at the University of Nottingham. It was funded by the National Institute for Health and Care Research (NIHR) and the NIHR Nottingham Biomedical Research Centre.
In the new study, researchers evaluated existing literature on GLP-1 RAs use and the change in alcohol consumption.
They gathered studies up to August 2024 that examined whether GLP-1 RAs affect alcohol use, alcohol-related health problems, hospital visits, and brain reactions to alcohol cues. The team evaluated six articles, including two randomised control trials made up of 88,190 participants, of these 38,740 (43.9%) of participants received GLP-1RA.
Dr Subhani said: “Our findings show that this type of diabetes medication shows promise in reducing alcohol consumption, potentially by targeting the brain’s reward centre, especially in people with a BMI over 30.”
The key findings:
In one prominent study, the medication exenatide did not significantly reduce drinking overall after six months, but people with obesity showed some positive results.
Another study found that people taking the drug dulaglutide were 29% more likely to reduce drinking than those on a placebo.
Observational studies (non-randomised) showed fewer alcohol-related health problems and lower alcohol use in people taking GLP-1 RAs compared to other treatments.
“Whilst further research is needed, our findings suggest this could be a potential treatment option in the future for excessive alcohol use and subsequently could lead to a reduction in alcohol-related deaths,” adds Dr Subhani.
The total number of adults living with either type 1 or type 2 diabetes in the world has surpassed 800 million – over four times the total number in 1990, according to findings from a global analysis published ahead of World Diabetes Day in The Lancet. Additionally, 445 million adults aged 30 years and older with diabetes (59%) did not receive treatment in 2022, three and a half times the number in 1990.
Of the 828 million adults with diabetes in 2022, over a quarter (212 million) lived in India, with another 148 million in China. The USA (42 million), Pakistan (36 million), Indonesia (25 million), and Brazil (22 million) followed.
The study was unable to separate type 1 and type 2 diabetes in adults. However, previous evidence suggests that the vast majority of cases of diabetes in adults are type 2.
Senior author Professor Majid Ezzati, of Imperial College London, said: “Our study highlights widening global inequalities in diabetes, with treatment rates stagnating in many low- and middle-income countries where numbers of adults with diabetes are drastically increasing. This is especially concerning as people with diabetes tend to be younger in low-income countries and, in the absence of effective treatment, are at risk of life-long complications – including amputation, heart disease, kidney damage or vision loss – or in some cases, premature death.”
A global study with global data
The new study, conducted by the NCD Risk Factor Collaboration (NCD-RisC), in collaboration with the World Health Organization (WHO), is the first global analysis of trends in both diabetes rates and treatment which includes all countries. Researchers used data from over 140 million people aged 18 years or older from more than 1,000 studies in populations of different countries.
The authors used statistical tools to bring all the data across different years, ages and countries together, and estimate diabetes rates and treatment in a way that enables comparisons across countries. [1]
Diabetes was defined as having a fasting plasma glucose (FPG) of 7.0 mmol/L or higher, having a glycated haemoglobin (HbA1c) of 6.5% or higher (two commonly used diagnostic criteria options for diabetes according to modern guidelines) or taking medication for diabetes. Treatment was defined as taking medication for diabetes. [2]
Most previous studies looking at diabetes rates relied on high FPG as a single measure of diabetes and did not account for people who have high HbA1c, leading to likely underestimates of rates especially in south Asia, where using FPG alone misses more cases of diabetes than in other regions.
Global rates of diabetes doubled over the last three decades
From 1990 to 2022, global diabetes rates doubled in both men (6.8% in 1990 to 14.3% in 2022) and women (6.9% to 13.9%). With the additional impact of population growth and ageing, this equates to an estimated 828 million adults with diabetes in 2022, an increase of approximately 630 million people from 1990, when roughly 198 million adults were estimated to have the disease.
The changes in diabetes rate from 1990 to 2022 varied drastically across different countries with mostly LMICs experiencing the largest increases (eg. the diabetes rate amongst women in Pakistan rose from 9.0% in 1990 to 30.9% in 2022, the largest increase across all countries). Whilst some higher-income countries, such as Japan, Canada and some countries in western Europe (eg. France, Spain and Denmark), saw no change or even a small decrease in diabetes rate over the last three decades.
Substantial global variations in diabetes rates in 2022
The countries with the lowest rates of diabetes in 2022 were in western Europe and east Africa for both sexes, and in Japan and Canada for women. For example, diabetes rates in 2022 were as low as 2-4% for women in France, Denmark, Spain, Switzerland, and Sweden, and 3-5% for men in Denmark, France, Uganda, Kenya, Malawi, Spain, and Rwanda.
By contrast, countries with the highest rates, where 25% or more of the population had diabetes for both men and women, were the Pacific island nations and those located in the Caribbean and the Middle East and north Africa, as well as Pakistan and Malaysia. Among high-income industrialised nations, diabetes rates in 2022 were highest in the USA (11.4% amongst in women and 13.6% in men).
An important driver of the rise in type 2 diabetes rates, and its variation across countries, is obesity and poor diets. Diabetes rate was either already high or increased more in some of the regions where obesity was or became prevalent between 1990 to 2022, compared to many high-income countries, especially those in the Pacific and western Europe, where, in general, obesity and diabetes rates did not rise or rose by a relatively small amount.
“Given the disabling and potentially fatal consequences of diabetes, preventing diabetes through healthy diet and exercise is essential for better health throughout the world. Our findings highlight the need to see more ambitious policies, especially in lower-income regions of the world, that restrict unhealthy foods, make healthy foods affordable and improve opportunities to exercise through measures such as subsidies for healthy foods and free healthy school meals as well as promoting safe places for walking and exercising including free entrance to public parks and fitness centres,” said Dr Ranjit Mohan Anjana, Madras Diabetes Research Foundation, India.
Widening global inequalities in diabetes treatment
Three out of five (59%) of adults aged 30 years and older with diabetes, a total of 445 million, were not receiving medication for diabetes in 2022, three and half times the number in 1990 (129 million).
Since 1990, some countries, including many in central and western Europe, Latin America and East Asia and the Pacific, as well as Canada and South Korea have seen vast improvements in treatment rates for diabetes resulting in more than 55% of people with diabetes in these countries receiving treatment in 2022. The highest treatment rates were estimated in Belgium, at 86% for women and 77% for men.
However, for many LMICs diabetes treatment coverage has stayed low and changed little over the previous three decades, with over 90% of people with diabetes not receiving treatment in some countries in both 1990 and 2022.
As a result of these trends, the gap between the countries with the highest and lowest treatment coverage for diabetes has widened since 1990 to 2022; from 56 to 78 percentage points in women and from 43 to 71 percentage points in men.
“Our findings suggest there is an increasing share of people with diabetes, especially with untreated diabetes, living in low- and middle-income countries. In 2022, only 5-10% of adults with diabetes in some sub-Saharan Africa countries received treatment for diabetes, leaving a huge number at risk of the serious health complications.” said Professor Jean Claude Mbanya, University of Yaoundé 1, Cameroon.
He continues, “Most people with untreated diabetes will not have received a diagnosis, therefore increasing detection of diabetes must be an urgent priority in countries with low levels of treatment. Better diagnosis of diabetes requires innovations such as workplace and community screening programmes, extended or flexible healthcare hours to enable people to visit outside of standard working hours, integration with screening and care for diseases like HIV/AIDS and TB which have well-established programmes, and the use of trusted community healthcare providers.”
In 2022, almost one third (133 million, 30%) of the 445 million adults aged 30 years or older with untreated diabetes lived in India, more than 50% greater than the next largest number which was in China (78 million) because treatment coverage was higher in China (45% for women and 41% for men) than in India (28% for women and 29% for men). Similarly, Pakistan (24 million) and Indonesia (18 million), the next two countries with the largest number of untreated diabetes, surpassed the USA (13 million), which had higher treatment coverage (65% for women and 67% for men).
The authors acknowledge some limitations to their study including that most survey data did not separate type 1 and type 2 diabetes in adults. Additionally, some countries where estimates were provided on diabetes rates and treatment had very little, or in some cases, no data and their estimates were informed to a stronger degree by data from other countries. The study included two measures for diabetes: FPG and HbA1c. In studies that did not measure HbA1c, the prevalence of elevated HbA1c was predicted based on the relationship between HbA1c, FPG and other predictors in studies that had measured both, which increased the uncertainty of the study estimates.
A study from Rutgers Health and other institutions indicates that stress hormones – not impaired cellular insulin signalling – may be the primary driver of obesity-related diabetes.
“We have been interested in the basic mechanisms of how obesity induces diabetes. Given that the cost of the diabetes epidemic in the U.S. alone exceeds $300 billion per year, this is a critically important question,” said Christoph Buettner, chief of endocrinology, metabolism and nutrition at Rutgers Robert Wood Johnson Medical School and the study’s senior author.
Scientists have long thought obesity causes diabetes by impairing insulin signalling within the liver and fat cells. However, new research shows that overeating and obesity increase the body’s sympathetic nervous system—the “fight or flight” response—and that the increased levels of the stress hormones norepinephrine and epinephrine counteract insulin’s effects even though cellular insulin signalling still works.
The authors observed that overeating in normal mice increases the stress hormone norepinephrine within days, indicating how quickly surplus food stimulates the sympathetic nervous system.
To see what effect this excess hormone production has in spurring disease development, the authors then deployed a new type of genetically engineered mice that are normal in every way but one: They cannot produce stress hormones catecholamines outside of their brains and central nervous systems.
The researchers fed these mice the obesity-inducing high-fat and high-sugar diet, but although they ate as many calories and got just as obese as normal mice, they did not develop metabolic disease.
“We were delighted to see that our mice ate as much because it indicates that the differences in insulin sensitivity and their lack of metabolic disease are not due to reduced food intake or reduced obesity but the greatly reduced stress hormones. These mice cannot increase stress hormones that counteract insulin; hence, insulin resistance does not develop during obesity development.”
The new findings may help explain why some obese individuals develop diabetes while others don’t and why stress can worsen diabetes even with little weight gain.
“Many types of stress – financial stress, marital stress, the stress associated with living in dangerous areas or suffering discrimination or even the physical stress that comes from excessive alcohol consumption — all increase diabetes and synergize with the metabolic stress of obesity,” Buettner said.
“Our finding that even obesity principally induces metabolic disease via increased stress hormones provides new insight into the common basis for all these factors that increase the risk of diabetes. Stress and obesity, in essence, work through the same basic mechanism in causing diabetes, through the actions of stress hormones.”
While it is well known that catecholamines can impair insulin action, the new study suggests that this may be the fundamental mechanism underlying insulin resistance in obesity. The dynamic interplay between stress hormones, which work in opposition to insulin, has long been known. Stress hormones increase glucose and lipids in the bloodstream, while insulin lowers these. However, an unexpected finding of the new study is that insulin signaling can remain intact even in insulin-resistant states like obesity. It’s just that the heightened activity of stress hormones effectively “push the gas pedal harder,” resulting in increased blood sugar and fat levels. Even though the level of insulin’s “braking” effect remains the same, the accelerated gas pedal effect of catecholamines overwhelms the brake effect of insulin and results in relatively diminished insulin action.
“Some colleagues are at first surprised that insulin resistance can exist even though cellular insulin signaling is intact. But let’s not forget that the gas pedal effects of stress hormones are exerted through very different signaling pathways than insulin signaling. That explains why the ability of insulin to ‘brake’ and reduce the release of sugar and fat into the bloodstream is impaired even though insulin signaling is intact because stress signaling is predominant.”
The findings suggest that medications that reduce catecholamines, a term for all the stress-related hormones and neurotransmitters produced by the SNS and the adrenal gland, might help prevent or treat diabetes. However, medicines that block catecholamines, as they are currently used to treat high blood pressure, haven’t shown major benefits for diabetes. This may be because current drugs don’t block the relevant receptors or because they affect the brain and body in complex ways, Buettner said.
Buettner and the study’s first author, Kenichi Sakamoto, an assistant professor of endocrinology at Robert Wood Johnson Medical School, are planning human studies to confirm their findings. They’re also examining the role of the sympathetic nervous system and other forms of diabetes, including Type 1 diabetes.
“We would like to study if short-term overfeeding, as some of us experience during the holidays by gaining five to 10 pounds, increases insulin resistance with heightened sympathetic nervous system activation,” Buettner said.
The findings may ultimately lead to new therapeutic approaches to tackle insulin resistance, diabetes and metabolic disease, focused on reducing stress hormones rather than targeting insulin signaling.
“We hope this paper provides a different take on insulin resistance,” Buettner said. “It may also explain why none of the drugs currently used to treat insulin resistance, except insulin itself, directly increases cellular insulin signaling.”
The work provides novel genetic insights into dietary preferences and opens the possibility of selectively targeting SI to reduce sucrose intake at the population level.
The study was led by Dr. Peter Aldiss, “Excess calories from sugar are an established contributor to obesity and type 2 diabetes. In the UK, we consume 9-12% of our dietary intake from free sugars, such as sucrose, with 79% consuming up to three sugary snacks daily. At the same time, genetic defects in sucrose digestion have been associated with irritable bowel syndrome, a common functional disorder affecting up to 10% of the population.
“Our study suggests that genetic variation in our ability to digest dietary sucrose may impact not only how much sucrose we eat, but how much we like sugary foods.”
The experts began by investigating the dietary behaviours in mice lacking the SI gene. Here, mice developed a rapid reduction in sucrose intake and preference. This was confirmed in two large population-based cohorts involving 6,000 individuals in Greenland and 134,766 in the UK BioBank.
The team took a nutrigenetics approach to understanding how genetic variation in the SI gene impacts sucrose intake and preference in humans. Strikingly, individuals with a complete inability to digest dietary sucrose in Greenland consumed significantly less sucrose-rich foods, while individuals with a defective, partially functional SI gene in the UK liked sucrose-rich foods less.
“These findings suggest that genetic variation in our ability to digest dietary sucrose can influence our intake, and preference, for sucrose-rich foods whilst opening up the possibility of targeting SI to reduce sucrose intake at the population level selectively,” says Dr Aldiss.
“In the future, understanding how defects in the SI gene act to reduce the intake, and preference, of dietary sucrose will facilitate the development of novel therapeutics to help curb population-wide sucrose intake to improve digestive and metabolic health.”
The transformative role digital health technologies play in diabetes management and prevention.
The editorial, written by Dr. Gang Hu and Dr. Yun Shen from Pennington Biomedical, along with Dr. Xiantong Zou from Peking University, emphasizes studies that demonstrate how innovations in digital technology enhance self-management, enable personalized treatments, and facilitate seamless communication between patients and healthcare providers.
“Digital tools provide unique opportunities to enhance patient outcomes through improved monitoring, personalized care, and more effective communication between patients and healthcare providers,” the authors stated.
Digital health tools have the potential to enhance diabetes care by making it more accessible, effective, and tailored to patients’ individual needs. Advances in wearable devices, mobile applications, and telemedicine can empower patients to manage their own health, personalize their treatment, and ultimately improve health outcomes. This editorial highlights key challenges associated with these technologies, such as data privacy and accessibility, and emphasizes the importance of ongoing research and development in this promising field.
“As the field evolves, digital health innovations are set to play an increasingly vital role in preventing and managing diabetes, leading to more efficient and equitable healthcare delivery,” the authors concluded.
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