Diabetes

Cellularsludge in hunger-regulating neurons linked to worsening diabetes and obesity

A recent study published in Nature has identified a mechanism through which inflammation in the hypothalamus promotes fibrotic changes in the perineuronal nets (PNNs), a specialised extracellular matrix (ECM) in the arcuate nucleus (ARC). These changes contribute to metabolic dysfunction, worsening conditions like obesity and diabetes.

Background

When blood glucose levels rise, insulin is released from pancreatic beta cells and signals the ARC to regulate hunger and metabolism. However, loss of insulin sensitivity leads to overeating and fat accumulation, contributing to obesity. The ECM, a network of proteins and sugars surrounding cells, plays a crucial role in this process. In people with obesity, the ECM undergoes fibrotic changes, particularly around Agouti-Related Protein (AgRP)-releasing neurons in the hypothalamus, disrupting insulin signalling and contributing to metabolic diseases.

Study Overview

In the study, researchers fed mice a regular or a high-fat, high-sugar (HFHS) diet to induce diabetes. They investigated whether neuroinflammation contributed to fibrotic buildup in the ECM by performing immunohistochemistry and stereotaxic injections. The team selectively disrupted insulin receptors in AgRP neurons to determine if ECM fibrosis impaired insulin function. They also used insulin tagged with fluorescein isothiocyanate (FITC) to track its signalling in hypothalamic neurons.

To assess the effects of inflammation, the team used adeno-associated viruses (AAVs) expressing receptors for pro-inflammatory TNF-α and anti-inflammatory TGF-β, alongside chondroitinase ABC (chABC), which breaks down fibrotic nets. Patch-clamp electrophysiology tested insulin interaction with PNNs in vitro, and fluorosamine, a drug inhibiting chondroitin sulphate synthesis, was administered to evaluate its therapeutic potential.

Key Findings

The study revealed that obese mice exhibited increased fibrotic PNNs around ARC neurons, disrupting insulin signalling and increasing AgRP neuron firing. Enzymatic breakdown of these PNNs restored insulin sensitivity, improved glucose metabolism, and reduced weight. The fibrosis altered gene expression for insulin receptors, exacerbating insulin resistance. While fibrotic nets impaired insulin activity, they did not affect leptin, the body weight-regulating hormone.

Additionally, obesity heightened levels of the inflammatory marker TNF-α while reducing the anti-inflammatory TGF-β, leading to increased fibrotic buildup. Reducing hypothalamic inflammation improved ECM function, and fluorosamine restored insulin sensitivity and improved metabolic outcomes in obese mice.

Conclusion

This study shows that hypothalamic ECM remodelling plays a significant role in metabolic diseases. Drugs targeting fibrotic PNNs and inflammation in the hypothalamus could improve insulin sensitivity and offer new treatments for obesity and diabetes by enhancing metabolic function.

Ultra-processed foods linked to increasing type 2 diabetes risk

Extensive research has demonstrated that the consumption of ultra-processed foods (UPFs) has a detrimental impact on the development of type 2 diabetes mellitus (T2D). However, the exact influence of other levels of food processing on T2D risk remains uncertain. A recent study published in The Lancet Regional Health sheds new light on this issue, exploring the association between varying degrees of food processing and the risk of developing T2D.

Food Processing and Its Relationship with Type 2 Diabetes

The Nova classification system is widely used to categorise foods based on the extent of their processing. According to this system, foods are divided into four categories: unprocessed or minimally processed foods (MPFs), processed culinary ingredients (PCIs), processed foods (PFs), and ultra-processed foods (UPFs). Research has long associated higher consumption of UPFs with weight gain, obesity, T2D, and cardiovascular diseases. A study conducted as part of the European Prospective Investigation into Cancer and Nutrition (EPIC) initiative revealed that a higher intake of UPFs is also linked to an increased risk of cancer and cardiometabolic multimorbidity.

Despite these findings, the link between T2D and all categories of processed foods, including MPFs, PCIs, and PFs, has yet to be fully elucidated. Further research is necessary to determine whether UPFs or other processed foods are most closely associated with adverse health outcomes. Gaining a deeper understanding of the impact of different types of processed foods may provide researchers with crucial insights into the benefits of replacing UPFs with healthier alternatives, such as MPFs, PCIs, or PFs.

The Study Overview

The recent cohort study used data from the EPIC project to explore the relationship between various food processing categories and T2D risk. Researchers assessed participants’ dietary intake at the start of the study by administering comprehensive dietary questionnaires. Based on this information, food consumption patterns were categorised according to the Nova classification system.

In order to identify cases of T2D, researchers relied on multiple data sources, including participants’ self-reports, primary and secondary care registers, hospital admission records, medication registers, and mortality data. The analysis used Cox regression and statistical substitution models to estimate the associations between T2D risk and the intake of MPFs, PCIs, PFs, and UPFs. Sub-group analyses were also conducted to identify any potential variations in the association between different UPFs and T2D risk.

The average age of the study participants was 52.5 years, and 63.5% of them were female. The average body mass index (BMI) was 25.7 kg/m², indicating that most participants were classified as being slightly overweight. Over the course of a 10.9-year follow-up period, 4.6% of participants were diagnosed with T2D. On average, MPFs and PCIs contributed to 72.1% of participants’ daily dietary intake, while UPFs accounted for 13.0%, and PFs made up 14.9%.

Key Findings of the Study

In examining the relationship between food processing and the development of T2D, the researchers conducted restricted cubic spline analyses to assess the intake of MPFs and PCIs. These analyses revealed a linear relationship between higher consumption of MPFs + PCIs and a lower risk of T2D up until very high intakes. Additionally, the study found that increased consumption of MPFs + PCIs, as well as PFs, was linked to a reduced risk of T2D. In contrast, a higher intake of UPFs was associated with an elevated risk of developing T2D.

To better understand the impact of replacing certain food groups on T2D risk, the researchers performed statistical substitution analyses. These analyses revealed that substituting 10% of UPFs with either MPFs + PCIs or PFs significantly reduced the risk of T2D. Moreover, replacing MPFs + PCIs with PFs also resulted in a reduction in T2D risk. These results held even after accounting for confounding factors such as saturated fat intake, sugar consumption, and adherence to a Mediterranean diet.

When investigating different sub-groups of UPFs, the study uncovered significant heterogeneity in their relationship with T2D. For instance, an increase in the consumption of savoury snacks, ready-to-eat or heat dishes, animal-based products, and artificially or sugar-sweetened beverages (ASBs/SSBs) was associated with a higher risk of T2D. On the other hand, lower T2D risk was linked to the consumption of plant-based alternatives, sweets and desserts, biscuits, breakfast cereals, and breads. Interestingly, no significant association was found between T2D and the consumption of sauces, spreads, condiments, alcoholic beverages, or other miscellaneous UPFs.

The Role of Adiposity in the UPF-T2D Relationship

To further understand the mechanisms underlying the association between UPF consumption and T2D, the researchers conducted mediation analyses focused on the waist-height ratio (WHtR), a measure of adiposity. These analyses revealed that WHtR mediated 46.4% of the association between UPF consumption and T2D risk. This suggests that body fat distribution may play a significant role in the relationship between UPF intake and the development of T2D.

Despite the robustness of the findings, some inconsistencies were noted in sensitivity analyses. For example, in France and Italy, the study did not find a statistically significant association between UPF consumption and T2D risk. Additionally, when the intake of MPFs + PCIs was modelled as kcal/day, %kcal/day, or g/day, no significant association with T2D risk was observed.

Conclusions

This study reinforces the growing body of evidence linking higher consumption of ultra-processed foods with an increased risk of type 2 diabetes mellitus. At the same time, it highlights the protective effect of consuming less processed foods, such as minimally processed or processed culinary ingredients, against the development of T2D.

Importantly, the findings point to the significant heterogeneity within the category of UPFs, suggesting that not all UPFs pose the same level of risk. This variability underscores the need for more nuanced public health guidelines, which should focus on reducing the intake of specific harmful UPFs rather than treating UPFs as a single, homogenous group. By encouraging people to make healthier food choices and reduce their consumption of certain types of UPFs, it may be possible to mitigate the rising global incidence of type 2 diabetes.

Night owls at increased risk for higher BMI, larger waistlines, and type 2 diabetes

Individuals who stay up late and wake up later, often referred to as “night owls,” are more likely to have higher body mass index (BMI), larger waist circumferences, and more hidden body fat. Furthermore, they face an almost 50% greater likelihood of developing type 2 diabetes (T2D) compared to those who follow earlier sleep schedules. These findings are part of new research set to be presented at the Annual Meeting of the European Association for the Study of Diabetes (EASD) in Madrid, Spain (9–13 September, 2024).

Lead researcher Dr Jeroen van der Velde, from Leiden University Medical Centre in the Netherlands, explained: “Previous studies have shown that a late chronotype – a preference for going to bed late and waking up late – is linked to an unhealthy lifestyle. Night owls are more prone to smoking or maintaining unhealthy diets, which has been suggested as a possible reason for their higher risk of obesity and metabolic conditions, such as type 2 diabetes.”

Dr van der Velde continued, “However, we believe that lifestyle factors alone cannot fully account for the relationship between being a late chronotype and the development of metabolic disorders. While it is well-documented that late chronotypes tend to have higher BMI, it remains unclear how exactly sleep timing affects the distribution of body fat.”

To investigate this further, Dr van der Velde and his team explored the associations between sleep timing, type 2 diabetes, and body fat distribution in more than 5,000 individuals as part of the Netherlands Epidemiology of Obesity study, an ongoing research project focused on the impact of body fat on health outcomes.

The analysis involved participants with an average age of 56 years, 54% of whom were women, and a mean BMI of 30 kg/m², placing many in the category of obesity. Participants completed a questionnaire about their typical bedtimes and wake-up times, from which researchers calculated their midpoint of sleep (MPS).

The participants were categorised into three groups:

• Early chronotype (the 20% with the earliest MPS),
• Late chronotype (the 20% with the latest MPS),
• Intermediate chronotype (the remaining 60% of participants).

Researchers measured BMI and waist circumference in all participants. Additionally, visceral fat and liver fat content were evaluated in 1,526 individuals using advanced imaging techniques such as MRI scans and MR spectroscopy.

Over a follow-up period of 6.6 years, 225 participants were diagnosed with type 2 diabetes. The data were adjusted for multiple factors, including age, sex, education, total body fat, and various lifestyle habits, such as physical activity levels, diet quality, alcohol consumption, smoking status, and sleep quality and duration. The findings revealed that those identified as late chronotypes had a 46% higher risk of developing type 2 diabetes compared to individuals with an intermediate chronotype.

This significant increase in risk suggests that lifestyle factors alone cannot explain the heightened risk of type 2 diabetes in late chronotypes.

“We believe that other mechanisms are contributing to this increased risk,” said Dr van der Velde. “A likely explanation is that late chronotypes experience misalignment between their natural circadian rhythms and the work and social schedules imposed by society. This misalignment can disrupt their circadian system, which is known to result in metabolic disturbances, potentially leading to type 2 diabetes.”

The researchers also investigated whether early chronotypes – those who prefer to go to bed and wake up earlier – were at a lower risk of developing type 2 diabetes. “From the literature, we expected early chronotypes to exhibit a risk level similar to those with intermediate chronotypes,” Dr van der Velde said. “Our results did show a slightly increased risk for early chronotypes, but this finding was not statistically significant.”

Beyond the risk of diabetes, the results also highlighted key differences in body composition. Late chronotypes, on average, had a BMI that was 0.7 kg/m² higher than those with an intermediate chronotype. They also had a 1.9 cm larger waist circumference, 7 cm² more visceral fat, and 14% greater liver fat content.

Dr van der Velde concluded, “Individuals with a late chronotype seem to be at greater risk for type 2 diabetes compared to those with an intermediate chronotype. This elevated risk might be due to higher levels of body fat, including visceral fat and liver fat.”

Looking ahead, Dr van der Velde emphasised that the next steps in research will involve studying whether individuals with late chronotypes can improve their metabolic health by adjusting the timing of their lifestyle behaviours. He mentioned that they are currently involved in the TIMED consortium, which investigates how the timing of sleep, eating, and physical activity can influence type 2 diabetes outcomes.

“We’ve already demonstrated that the timing of physical activity plays an important role in reducing insulin resistance,” he noted.

Another promising area of research is exploring the impact of meal timing. “It’s likely that people with late chronotypes are more inclined to eat later into the evening,” explained Dr van der Velde. “While we didn’t examine this in our study, there is growing evidence that time-restricted eating – such as not consuming food after a certain hour, like 6pm – could lead to metabolic benefits.”

For individuals who identify as night owls and are concerned about their increased risk for type 2 diabetes, Dr van der Velde suggested that they may want to experiment with adjusting meal times or avoiding late-night eating. “The evidence isn’t definitive yet, but over time, we aim to provide more specific advice on how changes in lifestyle habits can reduce the risk of metabolic diseases.”

Tirzepatide proves more effective than insulin in diabetes and weight management in clinical trails

A recent meta-analysis involving over 4,300 participants has revealed that the once-weekly administration of tirzepatide, a novel treatment for type 2 diabetes (T2D), significantly reduces blood sugar levels, body weight, and cardiovascular risks more effectively than daily insulin. This breakthrough could mark a paradigm shift in the management of T2D, offering a more potent and efficient therapeutic option.

Research Overview

Published in the International Journal of Obesity, the meta-analysis assessed the efficacy and safety of tirzepatide, a new anti-diabetic and anti-obesity drug, in comparison to traditional long-acting and ultra-long-acting insulin therapies. This comprehensive evaluation was based on data extracted from the SURPASS-3, SURPASS-4, and SURPASS-AP-Combo randomised clinical trials, encompassing a total of 4,339 individuals and ten biochemical assessments.

The study’s findings suggest that tirzepatide not only meets but surpasses the efficacy and safety profile of conventional insulin treatments. This positions the drug as a potentially revolutionary alternative to current non-surgical interventions for managing type 2 diabetes.

Background on Type 2 Diabetes

Type 2 diabetes is a prevalent chronic condition characterised by elevated blood glucose levels, primarily due to insulin resistance. According to the International Diabetes Federation (IDF), approximately 10.5% of adults aged 20 to 79 are affected by diabetes, with type 2 diabetes being the most common form. This condition is closely linked to a range of serious comorbidities, including cardiovascular diseases (CVDs), certain cancers, and obesity.

The global burden of type 2 diabetes is increasing at an alarming rate. From 1990 to 2019, the prevalence of T2D surged by 27.4%, with mortality rates climbing by 47%. These trends underscore the urgent need for effective therapeutic interventions that can mitigate the risk factors associated with this disease. Research indicates that elevated body mass indices (BMIs) are the most significant contributors to T2D risk, making weight management a crucial focus in T2D treatment strategies.

However, many non-surgical interventions provide only short-term relief for individuals living with T2D, and the risk of adverse side effects remains high with current pharmacological treatments. This highlights the necessity for developing and validating new treatments that offer high efficacy with minimal risk. Tirzepatide is one such promising drug, with its dual agonist properties—targeting both glucagon-like peptides (GLP1s) and gastric inhibitory polypeptides (GIPs)—showing potential for unprecedented efficacy and sustained weight loss in preliminary trials.

Despite its promising profile, the long-term safety of tirzepatide in vivo remains to be fully validated. Establishing its effectiveness compared to conventional insulin therapies could facilitate its broader adoption, potentially revolutionising T2D treatment on a global scale.

Study Methodology

The present study employed a rigorous meta-analytic approach to compare the safety and efficacy of tirzepatide against conventional once-weekly insulin therapies in managing type 2 diabetes. Data for the meta-analysis were sourced from four major scientific repositories: PubMed, Scopus, Web of Science, and Google Scholar. The included studies specifically evaluated tirzepatide’s performance against insulin across various outcomes, including body weight, fasting glucose, haemoglobin A1c (HbA1c), blood sugar (BS), blood pressure (BP), triglycerides, and cholesterol (both total and lipoprotein fractions).

The study incorporated a detailed data extraction process, covering study characteristics, population demographics, intervention specifics, and outcome measures (both safety and performance). All extracted data were standardised before being subjected to meta-analysis.

To statistically compare the performance of insulin and tirzepatide, the researchers calculated the mean change, standard deviation (SD) change, odds ratios (ORs), and relative risks (RRs) for each outcome. Between-study heterogeneity was assessed using I2 statistics, and the risk of bias was evaluated with the Cochrane risk of bias tool.

Key Findings

Out of 705 publications initially identified, only three studies—SURPASS-3, SURPASS-4, and SURPASS-AP-Combo—met the stringent inclusion and exclusion criteria. These studies involved 4,339 participants, with 1,580 in the insulin cohort and 2,759 in the tirzepatide cohort.

“All included studies were multi-centre, randomised, open-label, parallel-group phase 3 clinical trials conducted in several countries. Three doses of tirzepatide (5 mg, 10 mg, and 15 mg) were used in all studies. Patients with type 2 diabetes aged 18 years or older were included in all studies.”

The analysis revealed that while selection, reporting, and attrition biases were low across the included studies, detection and performance biases were high due to the open-label design of the SURPASS trials. Despite these limitations, the meta-analysis demonstrated that tirzepatide (at doses of 5 mg, 10 mg, and 15 mg) significantly outperformed both long-acting and ultra-long-acting insulin therapies. Specifically, tirzepatide was associated with an average weight reduction of 10.61 kg, a decrease in systolic blood pressure by 6.47 mmHg, and a reduction in diastolic blood pressure by 2.3 mmHg. Additionally, there was a slight increase in pulse rate by 1.93 beats per minute (bpm).

Furthermore, tirzepatide significantly improved lipid profiles, including a reduction in triglycerides by 14.49% and decreases in total cholesterol (4.78%), LDL cholesterol (5.98%), and very low-density lipoprotein (VLDL) cholesterol (14.18%). These efficacy improvements were dose-dependent, with higher doses (10 mg and 15 mg) yielding greater benefits. The side effects associated with tirzepatide were found to be comparable to or lower than those observed with equivalent insulin doses.

“All in all, these findings suggest that, unlike long-acting insulin, tirzepatide maintains BS levels in a narrow and near-normal range and prevents fluctuations in BS levels. For example, analysis of data from the SURPASS-3 trial by Viljoen et al. revealed that the median time to first achieve the HbA1c of 7.0% was 8.1 weeks for each dose of tirzepatide compared with 12.1 weeks for insulin degludec, suggesting an accelerated treatment response to Tirzepatide.”

Conclusions

This meta-analysis underscores the superior safety and efficacy profile of tirzepatide compared to conventional long-acting and ultra-long-acting insulin therapies. The results indicate that tirzepatide achieves near-normal HbA1c levels in a significantly shorter time frame than insulin (8.1 weeks versus 12.1 weeks). Additionally, tirzepatide outperformed traditional pharmacological interventions across all ten evaluated metrics. While higher doses of tirzepatide were associated with a slightly increased risk of hypoglycaemia and nausea, these side effects were still comparable to or lower than those associated with insulin treatments.

Collectively, these findings suggest that tirzepatide could serve as a superior alternative to insulin, offering a more effective and potentially safer option for managing type 2 diabetes. As this drug becomes more widely adopted, it could transform the global landscape of diabetes treatment, offering new hope to millions of individuals living with this chronic condition.

Gestational diabetes does not increase breast cancer risk, study finds

A recent study has found that gestational diabetes does not elevate the risk of developing breast cancer, providing reassurance to millions of women worldwide. This significant research will be presented at the upcoming Annual Meeting of the European Association for the Study of Diabetes.

Gestational diabetes, a condition that affects nearly 15% of pregnant women globally, has long been a subject of concern due to its association with various long-term health risks. These include a heightened likelihood of developing type 2 diabetes, metabolic syndrome, cardiovascular disease, chronic kidney disease, and certain mental health conditions. However, the link between gestational diabetes and breast cancer, the most common cancer among women, has remained unclear until now.

Women who are older, living with obesity, or have a family history of diabetes are at a greater risk of developing gestational diabetes. This condition, characterised by insulin resistance, has been the focus of much research due to its potential to trigger a range of health issues.

Dr Maria Hornstrup Christensen, the senior author of the study, emphasised the importance of understanding breast cancer risk factors. “Breast cancer is the most common cancer, as well as the leading cause of cancer deaths in women worldwide. It also has a very high treatment cost compared with other cancer types. If we know who is more likely to develop breast cancer, we might be able to detect it earlier when it is easier to treat, reducing deaths and treatment costs and the psychological and physical toll on women,” she said.

To investigate the potential connection between gestational diabetes and breast cancer, a team of researchers conducted an extensive study involving 708,121 women who gave birth in Denmark. Out of these, more than 24,000 women developed gestational diabetes during one or more of their pregnancies. The health outcomes of these women were tracked over an average period of 11 years, during which 7,609 cases of breast cancer were recorded.

The study’s findings revealed that women who had experienced gestational diabetes were no more likely to develop breast cancer than those who had not. This result is particularly significant given the concern surrounding insulin resistance, a key feature of gestational diabetes, which has also been linked to breast cancer in prior studies.

Dr Christensen remarked on the study’s implications, stating, “It will be reassuring for women who have had gestational diabetes to know that they are not at higher risk of developing breast cancer.”

She added a note of caution, however, highlighting the need for continued vigilance regarding other health risks. “They do, however, need to be alert to the fact that they are at higher risk of some conditions, including type 2 diabetes. And all women, regardless of whether or not they have had gestational diabetes, should be breast aware and check their breasts regularly for changes.”

This research provides a new understanding of the health implications of gestational diabetes, offering relief to many while underscoring the importance of ongoing health monitoring and awareness. The study represents a significant step forward in our understanding of the relationship between gestational diabetes and long-term health outcomes.

One-third of NHS diet programme participants achieve type 2 diabetes remission, study finds

A recent study published in The Lancet Diabetes & Endocrinology has revealed that approximately one-third of participants in the National Health Service (NHS) shakes and soups diet programme in England have achieved remission from type 2 diabetes. This study, which evaluated the effectiveness of total dietary replacement (TDR) for insulin-independent diabetes remission, sheds light on the potential of structured diet interventions in managing type 2 diabetes on a large scale.

The escalating rates of diabetes in the United Kingdom have led the NHS to implement the Type 2 Diabetes Path to Remission (T2DR) initiative. This programme is centred around a low-calorie, micronutrient-rich diet, which has been shown to result in significant weight loss and sustained remission of diabetes. While clinical trials have demonstrated the efficacy of such dietary interventions, their effectiveness in broader, real-world contexts has remained unclear until now.

The T2DR programme is designed to help individuals lose weight, maintain that weight loss, and reduce their reliance on glucose-lowering medications. The programme comprises 20 sessions divided into three phases: the TDR phase, the food reintroduction phase, and the weight maintenance phase. The TDR phase, lasting 12 weeks, focuses on strict calorie intake regulation accompanied by coaching. Following this, the food reintroduction phase spans 4 to 6 weeks, during which participants are guided on healthy eating habits and goal-setting. The final phase, weight maintenance, involves monthly coaching sessions aimed at behaviour modification and encouraging physical activity to help participants sustain their weight loss and health improvements.

This study utilised prospective, national-level data to assess whether the NHS’s T2DR programme effectively promotes remission of type 2 diabetes. Researchers analysed data from English adults aged between 18 and 65 who had been diagnosed with type 2 diabetes within the previous six years and were referred to the T2DR programme by their general practitioners between September 2020 and December 2022. Participants included in the study had a body mass index (BMI) of at least 27 kg/m² for white individuals, with a lower threshold of 25 kg/m² for individuals of other ethnicities.

To determine the programme’s effectiveness, the researchers linked programme data with records from the National Diabetes Audit (NDA). They specifically examined glycated haemoglobin (HbA1c) levels and the use of oral hypoglycaemic medications. Eligible participants had recent HbA1c levels ranging from 43 to 87 mmol/mol if they were on glucose-lowering medications, or 48 to 87 mmol/mol if they were not.

The primary outcome of the study was diabetes remission at one year, defined by two HbA1c readings below 48 mmol/mol taken at least three months apart, without the use of glucose-lowering medications. These readings were collected from three months before the initial HbA1c measurement up to 15 months later. Secondary outcomes included the absolute and percentage changes in body weight, as well as the proportion of participants achieving at least 10% and 15% weight loss within one year.

The study focused on participants who began the TDR-based programme before 2022 and had completed it by December 2022, which included having their body weight recorded at the one-year mark. Researchers employed multivariate regression analyses to account for various factors, including demographic characteristics (age, gender, socioeconomic status, and ethnicity), clinical variables (duration of diabetes, baseline BMI, and HbA1c levels), and details about the programme’s delivery method and provider. Sensitivity analyses were also conducted to evaluate different timings for subsequent HbA1c measurements, ranging from 11 to 15 months after the initial reading.

Between September 2020 and December 2022, a total of 7,540 individuals were referred to the T2DR programme. The average age of participants was 50 years, with 43% being male and 64% identifying as white. Of these, 1,740 individuals initiated the TDR phase before 2022, with the aim of completing the programme within one year. Among those who started the programme before 2022, 55% (960 individuals) successfully completed it.

Out of all participants referred to the programme, 34% were not taking glucose-lowering medications, 50% were on one medication, and 16% were on two or more, with metformin being the most commonly prescribed.

The mean weight loss among the 1,710 participants who started the programme before 2022 was 9.40 kg, or 8.3% of their initial body weight. For the 945 participants who completed the programme, the average weight loss increased to 10 kg, or 9.3% of their starting weight. Among those with at least two HbA1c readings, 27% (190 individuals) achieved diabetes remission, with an average weight loss of 15 kg, or 13%. Of the 945 individuals who completed the programme, 48% (450 participants) had two HbA1c readings available, and of these, 32% (145 individuals) achieved remission, with an average weight loss of 16 kg, or 14%.

Furthermore, 42% of the 945 individuals who completed the programme lost at least 10% of their baseline weight, and 20% lost at least 15%. Among those who achieved remission, 76% (110 participants) lost at least 10% of their baseline weight, and 45% (65 participants) lost at least 15%. Sensitivity analyses produced consistent results, reinforcing the findings.

The study concluded that 27% of participants in the NHS T2DR programme achieved diabetes remission, demonstrating that remission is possible outside of controlled research settings with widespread implementation. However, remission rates in real-world applications are lower, and data collection is more limited compared to randomised controlled trials. These findings are significant as they provide valuable insights for policymakers regarding the operational effectiveness of the TDR approach and its potential impact on public health.

Exploring the role of the Mediterranean diet in mitigating gestational diabetes risk

A recent comprehensive study published in the journal Nutrition & Diabetes delves into the potential impact of the Mediterranean diet (MedDiet) on reducing the incidence of gestational diabetes mellitus (GDM), a prevalent complication during pregnancy characterised by impaired insulin utilisation due to placental hormones.

GDM not only poses immediate health risks to both mother and child during pregnancy, including heightened risk of birth complications and future chronic conditions, but also contributes to longer-term health issues. Consequently, managing blood glucose levels through medical and dietary measures is essential.

Prevailing research underscores the efficacy of dietary and lifestyle changes in the early stages of pregnancy, or even prior, in averting GDM. Diets high in saturated fats, cholesterol, carbohydrates, and total fats are typically linked to a higher GDM risk.

The Mediterranean diet is noted for its emphasis on whole grains, vegetables, legumes, and foods high in monounsaturated fatty acids (MUFAs), while limiting processed and red meats. Instead of isolating individual dietary components, assessing overall dietary patterns like the MedDiet may offer a holistic approach to managing or preventing GDM.

Numerous studies corroborate that a strict adherence to the MedDiet correlates with a reduced risk of GDM. However, a systematic review and meta-analysis are crucial to consolidate these findings comprehensively.

The current review collated studies up to August 2023 from databases such as PubMed, Web of Science, Google Scholar, and Scopus, excluding duplicates, animal studies, ecological studies, short communications, and non-English articles.

From the selected studies—two case-control and eight cohort studies—conducted in diverse locations including the USA, various Mediterranean countries, Australia, Iran, Spain, and Greece, researchers analysed data from over 32 million participants aged 18 to 45.

The Mediterranean Diet Adherence Screener (MEDAS) score, higher quartiles of alternate MED (AMED) score, and the Mediterranean-Style Dietary Pattern Score (MSDPS) were tools used to assess dietary adherence. GDM outcomes were evaluated using criteria from the National Diabetes Data Group, and through fasting or postprandial blood sugar levels, or glucose challenge tests.

Findings from seven out of ten studies reviewed demonstrated a significant link between higher MedDiet adherence and lower GDM risk, although results varied due to differences in study designs or dietary assessment periods.

Interestingly, while case-control studies reported a substantial 75% reduction in GDM risk among women with higher MedDiet adherence, cohort studies indicated a more moderate 20% risk reduction. The larger reductions noted in case-control studies might stem from recall biases, possibly exaggerating the risk reduction.

Subgroup analyses showed that the benefits of MedDiet adherence in reducing GDM risk applied across both Mediterranean and non-Mediterranean populations, suggesting universal applicability of this dietary pattern.

Higher consumption of whole grains, fruits, vegetables, extra virgin olive oil, nuts, and legumes, alongside regular fish and seafood intake, characterises greater adherence to the MedDiet. This diet, rich in antioxidants and vitamins, mitigates oxidative stress and inflammation, critical factors in chronic disease progression.

The diet’s high polyphenol content in fruits and vegetables plays multiple roles in reducing GDM risk, including glucose absorption inhibition in the gastrointestinal tract, anti-inflammatory properties, microbiota modification, and enhanced antioxidant capacity.

Previous meta-analyses have linked greater MedDiet adherence to reduced obesity or overweight risks by 9%, noting that obesity and insulin resistance are significant GDM risk factors. Additionally, whole grains and nuts, rich in MUFAs and polyunsaturated fatty acids (PUFAs), help regulate blood glucose levels and control appetite.

Observational studies have suggested that long-term red meat consumption may increase GDM risk, further supporting the reduced GDM incidence among those adhering to the MedDiet.

The current systematic review and meta-analysis provide strong evidence supporting the MedDiet’s role in reducing GDM risk when followed before or during pregnancy. It is advisable for women of reproductive age to consider the MedDiet to prevent GDM and other adverse pregnancy outcomes.

Further research should explore the interaction between the MedDiet, genetic factors, and lifestyle elements to refine preventive strategies for GDM.

Nutritional studies highlight pulses as key to lowering diabetes and cholesterol risks

Research consistently highlights pulses—such as beans, peas, lentils, and chickpeas—as crucial allies in the fight against diabetes and elevated cholesterol levels. This insight comes at a critical time, as projections from a study published in The Lancet last year forecast that diabetes could affect over 1.31 billion people globally by 2050. Concurrently, elevated cholesterol levels remain a significant health issue, with nearly half of adults in the UK exceeding national guidelines.

A detailed review in the journal Nutrients has shown that regular consumption of pulses can significantly improve these concerning health trends. The review meticulously examined thirty studies that looked at various types of pulses, including lentils, chickpeas, and several common beans like pinto, black, and kidney beans. The studies covered a wide array of health outcomes, from lipid profiles and blood pressure to risks of cardiovascular diseases and diabetes management.

The findings from these studies are telling. They specifically note improvements in low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol, systolic and diastolic blood pressure, fasting blood sugar, haemoglobin A1c levels, waist circumference, and markers of inflammation and sensitivity such as C-reactive protein. These outcomes particularly underscore the potential of pulses to enhance lipid profiles and manage blood pressure.

The review emphasised that interventional studies, which typically have larger sample sizes and provide robust data, consistently confirm the health benefits of pulses. These studies often involved dietary adjustments where pulses replaced red meat or were added to diets as fixed servings. The results repeatedly demonstrated improvements in dietary quality and beneficial health outcomes.

Pulses’ potential to prevent heart disease is particularly noteworthy, largely due to their ability to lower total and LDL cholesterol levels. The authors of the review highlight that pulses are low in fat and rich in healthy mono- and polyunsaturated fats, essential micronutrients, and bioactive compounds with antioxidant properties, making them a true “nutritional powerhouse.”

Longitudinal studies also link higher pulse consumption with reduced risks of developing type 2 diabetes. This association is bolstered by interventional studies that document notable improvements in fasting glucose levels and insulin sensitivity with increased pulse intake. Consequently, pulses are not only pivotal in preventing diabetes but also in managing blood glucose levels effectively.

Tim McGreevy, CEO of USA Pulses, commented on the research, stating, “This research accentuates the fact that pulses are beneficial for health in so many ways, underscoring dietary guidelines that endorse plant-based eating patterns,” even though he was not directly involved in the study.

Additionally, awareness about type 2 diabetes is critical as many individuals may be unknowingly afflicted. Symptoms to watch for include increased urination, persistent thirst, excessive tiredness, unexplained weight loss, genital itching or recurrent thrush, delayed healing of wounds, and blurred vision. Recognising these signs can prompt earlier intervention and management of the condition, further reducing long-term health risks.

Concerns arise over rare eye condition linked to popular weight loss injections

Recent research indicates that individuals utilising semaglutide injections, commonly used for weight management and type 2 diabetes, have a quadrupled risk of developing a severe eye disorder compared to non-users. The medications in question, Ozempic and Wegovy, have been associated with an elevated risk of non-arteritic anterior ischemic optic neuropathy (NAION), a rare but potentially harmful eye condition.

Despite the concerning findings, the researchers involved have clarified that the overall incidence of the condition among users remains low, and definitive evidence that semaglutide is the direct cause of NAION is still lacking.

Produced by pharmaceutical giant Novo Nordisk, Wegovy is designed to promote significant weight loss. Clinical trials have shown that some individuals experience a reduction in body weight exceeding 10% after using the medication.

The popularity of these weight loss injections has surged recently, fueled in part by celebrity endorsements and public testimonials about their effectiveness in achieving rapid weight loss.

However, a rise in the unregulated online purchase of semaglutide injections has alarmed health professionals. The absence of proper checks on these internet-sourced medications raises serious concerns about their safety.

Further worries have been voiced over the misuse of semaglutide, with indications that the drug is increasingly being used for cosmetic weight loss, particularly to achieve a ‘beach-body’.

The common side effects associated with semaglutide include stomach pain, nausea, constipation, diarrhoea, and vomiting. Additionally, both Ozempic and Wegovy have been linked to potentially serious changes in vision, according to the latest studies.

NAION, which affects up to 10 in every 100,000 people, leads to vision loss due to diminished blood flow to the optic nerve and currently lacks an effective treatment.

Dr Joseph Rizzo, a leading researcher in the study, stated, “Our findings should be viewed as being significant but tentative, as future studies are needed to examine these questions in a much larger and more diverse population.”

A Novo Nordisk spokesperson responded to the findings by noting that NAION is not recognised as a known adverse drug reaction in the marketed formulations of semaglutide, which include Ozempic, Rybelsus, and Wegovy. They highlighted that semaglutide has been thoroughly examined in extensive real-world evidence studies and robust clinical development programmes.

Professor Graham McGeown from Queen’s University Belfast commented on the issue, emphasising the need for additional research given the sharp rise in semaglutide usage and its potential approval for uses beyond obesity and type 2 diabetes. “This issue deserves further study – but possible drug side-effects always need to be balanced against likely benefits,” he said.

Ozempic and other GLP-1 drugs show promise in reducing obesity-related cancer risks

In a significant medical discovery, a class of diabetes medications, including the widely-used drug Ozempic, has been linked to a decreased risk of numerous obesity-associated cancers. This revelation was detailed in a study published in the Journal of the American Medical Association (JAMA) on Friday, 5th of July, 2024.

The research meticulously analysed the health outcomes of Type 2 diabetes patients from 2005 to 2018, focusing on those treated with insulin compared to those administered GLP-1 agonists, such as Ozempic. The findings indicated a notable reduction in the risk of developing 10 out of 13 types of cancer examined in the study. The cancers showing decreased risk include those of the kidney, pancreas, oesophagus, ovaries, liver, and colorectum.

However, the study observed no substantial reduction in the risk of thyroid cancer and breast cancer among postmenopausal women. These findings underscore the complex relationship between metabolic disorders and cancer risks.

“Obesity is well known to be associated with at least 13 cancer types,” stated Rong Xu, the study’s lead author, in an email correspondence with AFP. Xu further commented, “Our study provides evidence that GLP-1RAs hold promise in breaking the link between obesity and cancer.”

The research not only highlights the efficacy of GLP-1 receptor agonists (GLP-1RAs) in managing diabetes but also their potential role in cancer prevention. The study encompassed several drugs within this category, including semaglutide, marketed as Ozempic, and liraglutide, among others, with Ozempic receiving approval in the United States in 2017.

GLP-1 agonists have been utilised for approximately two decades; however, a new generation of these drugs, including Ozempic, has gained popularity for their enhanced effects on weight loss.

The protective benefits observed might influence healthcare providers to favour GLP-1 treatments over other therapeutic options such as insulin for diabetes patients, as suggested by Xu. This shift could represent a pivotal evolution in the management of diabetes and its associated cancer risks, marking a significant stride forward in integrative disease prevention strategies.

Natural compound found in olives shown to lower blood sugar and aid weight loss, mouse study shows

A novel study conducted using mice models has highlighted the potential of elenolic acid, a natural compound extracted from olives, in mitigating obesity and type 2 diabetes. This groundbreaking research suggests that elenolic acid could serve as a basis for the development of affordable, safe natural products aimed at managing these prevalent health issues.

In a series of experiments, diabetic mice with obesity administered with elenolic acid orally displayed a significant reduction in body weight and enhanced glucose regulation within just one week. These results were noteworthy when compared to a control group of mice with obesity that did not receive the treatment. Remarkably, the glucose-lowering impact of elenolic acid was on par with liraglutide, an injectable diabetes medication, and surpassed the effectiveness of metformin, a commonly used oral diabetes drug.

Professor Dongmin Liu, the lead researcher and a professor at the Department of Human Nutrition, Foods and Exercise at Virginia Tech, explained the motivation behind their focus on natural compounds. “Lifestyle modifications and public health measures have had limited impact on the rising prevalence of obesity, one of the top risk factors for type 2 diabetes. Available obesity drugs are ineffective in weight loss maintenance, expensive and/or carry potential long-term safety risks. Our goal was to develop safer, cheaper and more convenient multi-targeting agents that can prevent the occurrence of metabolic disorders and type 2 diabetes,” stated Liu.

The research findings will be presented by Dr. Hana Alkhalidy, a scientist in Liu’s laboratory, at NUTRITION 2024, the premier annual event of the American Society for Nutrition.

The team at Virginia Tech has previously investigated various natural compounds targeting molecular aspects of metabolism in critical body parts like the pancreas, muscle, fat tissues, and liver. Their latest strategy focuses on stimulating hormone secretion in the gut, a method that could indirectly improve metabolic functions due to natural products’ generally poor bioavailability.

Their screening identified that elenolic acid, found abundantly in mature olives and extra virgin olive oil, stimulates the release of metabolic hormones GLP-1 and PYY in the gut. These hormones are integral during meals, enhancing satiety and regulating blood sugar and metabolism. The researchers synthesized elenolic acid from its precursor, oleuropein, which proved to be a cost-effective method compared to direct extraction from olives.

Further testing revealed that diabetic mice with obesity treated with elenolic acid for four to five weeks showed a 10.7% reduction in obesity and exhibited glucose levels and insulin sensitivity comparable to healthy, lean mice. Additionally, the treatment significantly curbed food intake and fostered weight loss, effects associated with increased levels of PYY and GLP-1 and decreased expression of agouti-related peptide, a hypothalamic peptide that promotes overeating and weight gain when overexpressed.

“Overall, the study showed that elenolic acid from olives has promising effects on hormone release and metabolic health, particularly in obese and diabetic conditions,” Liu remarked. He noted that the compound mimics the physiological conditions of eating to enhance gut metabolic hormone secretion, thereby helping to regulate energy balance and metabolic health.

Despite these promising results, the researchers cautioned that the concentration of elenolic acid in typical olive products is quite low, implying that the health benefits observed in the study are unlikely to be replicated through consumption of olives and olive oil alone.

The research team is now focused on elucidating the metabolic pathway of elenolic acid, from its absorption to its excretion. This exploration will provide further insights into the compound’s efficacy and safety, paving the way for potential clinical trials.

AI enhances efficiency of artificial pancreas, study confirms

Recent research conducted by the University of Virginia’s Center for Diabetes Technology reveals that incorporating artificial intelligence (AI) into an artificial pancreas system can significantly improve its operational efficiency. This innovative study marks a crucial advancement in the management of type 1 diabetes.

The study highlights that an AI-equipped artificial pancreas system is comparable in performance to a state-of-the-art experimental version in maintaining optimal blood glucose levels. The integration of AI not only matches the effectiveness of advanced systems but also offers potential applications in other medical devices that require minimal computational resources, like insulin pumps.

Dr Boris Kovatchev, the study’s lead author, emphasised the novelty of their approach, stating, “So far, this is the first clinical trial of a data-driven artificial pancreas system, which used an extensively trained neural network to deliver insulin automatically.” This system represents a significant shift towards more autonomous patient care in diabetes management.

The experimental setup involved 15 adult participants who used both the advanced artificial pancreas and the AI-enhanced system for 20 hours each. Results showed that the traditional advanced system kept blood sugar levels within the target range 87% of the time, closely followed by the AI-supported system at 86%.

Notably, the research demonstrated that the AI-supported pancreas system drastically cuts down the computational load by six times compared to traditional methods. “The AI-supported artificial pancreas is therefore more suitable for implementation in devices with low processing power, such as insulin pumps or pods,” the report noted, pointing towards a broader applicability in diabetes care technology.

Dr Kovatchev further explained the technical breakthroughs, saying, “Neural-net implementation allows the algorithm to learn from the data of the person wearing the system. This opens the door to real-time, AI-driven personalised insulin delivery.” This adaptation could lead to more tailored and effective diabetes management solutions for individuals.

The findings, published in the journal Diabetes Technology & Therapeutics, set a precedent for the future of diabetes care, highlighting the critical role of AI in enhancing the functionality and efficiency of medical devices aimed at chronic disease management.