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Take a look at a selection of our recent media coverage:

Meal timings are important modifiable factor in type 2 diabetes risk, study confirms

7th August 2023

Eating breakfast after 9am increases the risk of developing type 2 diabetes by 59 per cent compared to people who eat breakfast before 8am, according to a new study.

Researchers from the Barcelona Institute for Global Health (ISGlobal) found that modifying the time at which people eat can reduce the risk of developing type 2 diabetes.

Eating breakfast before 8am and dinner before 10pm and eating more frequently throughout the day were associated with a lower incidence of type 2 diabetes.

The findings are published in the International Journal of Epidemiology and suggest meal timings are an important modifiable factor in managing the incidence of type 2 diabetes.

Type 2 diabetes incidence

The researchers analysed data from 103,312 participants who were part of the French NutriNet-Santé cohort between 2009 and 2021. Each participant recorded what they ate and drank over a 24-hour period on three non-consecutive days for an average of 5.7 days in the first two years of the study.

The researchers then assessed the participant’s health for an average of seven years and looked at the association between meal frequency and timing, the duration of night-time fasting between meals and the incidence of type 2 diabetes.

During the study, there were 963 new cases of type 2 diabetes, and the researchers found that the time at which food was eaten impacts the risk of developing diabetes.

Incidence of type 2 diabetes was higher in the participants who ate their breakfast after 9am compared to those who ate an early breakfast before 8am. Participants who ate an early breakfast and those who ate regularly throughout the day had a lower incidence of type 2 diabetes.

The researchers found no link between fasting and the incidence of type 2 diabetes and found that prolonged fasting was only beneficial if it included having an early breakfast before 8am and an early dinner.

Meals and glucose control

Dr Anna Palomar-Cros, a researcher from ISGlobal and first author of the study, said: ‘We know that meal timing plays a key role in regulating circadian rhythms and glucose and lipid control, but few studies have investigated the relationship between meal timing or fasting and type 2 diabetes.

‘Biologically, this makes sense, as skipping breakfast is known to affect glucose and lipid control, as well as insulin levels.’

The researchers suggest that a first meal before 8am and a last meal before 7pm may help reduce the incidence of type 2 diabetes.

Some 4.3 million people in the UK live with type 2 diabetes, and estimates from Diabetes UK suggest that 2.4 million more people are at high risk of developing the disease. Type 2 diabetes is associated with several modifiable risk factors, including obesity and overweight and smoking.

A version of this story was originally published by our sister publication Nursing in Practice.

Lung disorders are complication of type 2 diabetes, says new study

4th May 2023

Type 2 diabetes has been shown to cause lung disorders for the first time in a new study funded by Diabetes UK.

In the largest-ever genetic study to explore how genes affect blood sugar levels and health outcomes, researchers from Imperial College London concluded that lung disorders should now be considered a complication of type 2 diabetes.

When examining the impact of blood sugar levels on lung function, the researchers found that people with type 2 diabetes who had a three-fold increase in average blood sugar levels, experienced a 20% drop in lung capacity and function.

The findings, presented at the recent Diabetes UK Professional Conference 2023, highlight the need for healthcare professionals to be alert to lung complications within patients with type 2 diabetes, alongside kidney disease, heart attack and strokes.

More than five million people in the UK live with diabetes, and 90% have type 2. These patients often have dangerously high blood sugar levels caused by the body either not making enough insulin or not responding to the insulin that is made.

Chronically high blood sugar levels can damage organs and tissues, causing kidney failure, eye and foot problems, heart attacks and strokes. Previous research has shown that lung conditions, including restrictive lung disease, fibrosis and pneumonia, are more common in people with type 2 diabetes, but no causal link had been established.

Using statistical techniques, the researchers analysed data from almost 500,000 participants on 17 major studies, including the UK BioBank, to determine whether there was a causal link between impaired lung function and high blood sugar levels. Lung function was measured using two standard spirometry tests used to diagnose lung conditions.

High blood sugar levels in people with type 2 diabetes were shown to impair lung function directly. Statistical modelling of the study data showed that an increase in average blood sugar levels from 4 mmol/L to 12 mmol/L could result in a 20% drop in lung capacity and function.

Dr Elizabeth Robertson, director of research at Diabetes UK, said: ‘These results are a reminder of the seriousness of type 2 diabetes and the importance of supporting people with the condition to manage their blood sugar levels so they can live well with the condition and avoid future complications.

‘Lung conditions can be life-changing and life-limiting, and it is crucial that healthcare professionals are aware of the impact of high blood sugar levels on lung health.’

This news story was originally published by our sister publication Nursing in Practice.

Osteoarthritis risk lower in type 2 diabetics taking metformin

2nd May 2023

The risk of developing osteoarthritis is lower in type 2 diabetic patients taking metformin than among those taking sulfonylureas

Osteoarthritis (OA) is a common form of arthritis which globally affects 528 million people. Treatment focuses on drug therapy, self-management and exercise. In addition, there are currently no preventative therapies available. Metformin is an oral hypoglycaemic agent for the treatment of type 2 diabetes. The drug also appears to have other actions including the ability to suppress inflammation. In fact, there appears to be a beneficial effect on long-term knee joint outcomes in those with osteoarthritis and obesity. However, whether metformin can prevent the development OA is less clear.

In the current study, US researchers explored if metformin was able to lower the risk of developing OA as well as the need for joint replacement in type 2 diabetics. The team undertook a retrospective analysis using sulfonylureas as a comparator anti-diabetic therapy. Individuals with a prior diagnosis of OA were not included in their analysis. Researchers propensity-matched metformin and sulfonylurea patients 1:1. The primary outcome of interest was the time to an incident diagnosis of OA, 90 days after starting either medication.

Osteoarthritis development and anti-diabetic therapy

There were 41,874 individuals with a mean age of 62 years (41.8% female) with usable data for analysis. Among this total, 20,937 were receiving metformin.

The risk of developing osteoarthritis was 24% lower in those using metformin than a sulfonylurea (Hazard ratio, HR = 0.76, 95% CI 0.68 – 0.85, p < 0.001). However, there was no significant difference between the two groups in the risk for joint replacement (HR = 0.80, 95% CI 0.50 – 1.27, p = 0.34). Similar findings were obtained in a sensitivity analysis (HR = 0.77, 95% CI 0.65 – 0.90, p < 0.001) for OA.

These findings led the authors to suggest that metformin may have a protective effect against the development of OA.

Cumulative HbA1c levels above 9% linked to greater dementia risk

25th April 2023

HbA1c levels in type 2 diabetics remaining above 9% for extended periods of time poses a risk of developing dementia

Type 2 diabetes increases the risk for developing dementia. Both elevated HbA1c levels and diabetic complications also linked to an increased dementia risk. Moreover, intensive glycaemic control does not seem to reduce cognitive decline. But how long-term glycaemic control affects the risk of dementia is uncertain and was the subject of the current study.

Using a large US healthcare database, researchers looked at type 2 diabetics older than 50 with HbA1c levels recorded over time. Researchers categorised HbA1c measurements as < 6%; 6% to < 7%; 7% to < 8%, 8% to < 9%, 9% to < 10% and 10% or more. They also identified those diagnosed with dementia during follow-up.

HbA1c levels and development of dementia

There were 253,211 eligible participants with a mean age of 61.5 years. The participants were followed for a mean of 5.9 years. During this time, participants with the majority (i.e., > 50%) of HbA1c measurements between 9 and 10%, had an increased the risk of dementia (hazard ratio, HR = 1.31, 95% CI 1.15 – 1.51). Similarly, with most measurements of 10% or above, the risk was also significantly higher (HR = 1.74, 95% CI 1.62 – 1.86).

In contrast, among participants with more than 50% of HbA1c measurements that were less than 6%, the dementia risk was lower (HR = 0.92, 95% CI 0.88 – 0.97). This also held true for HbA1c levels of 6 to 7% and between 7 and 8%. Thus in type 2 diabetics, keeping cumulative HbA1c levels below 8% was associated with a lower risk for developing dementia. The researchers called for further research to determine if these associations were causal.

Moran C et al. Glycemic Control Over Multiple Decades and Dementia Risk in People With Type 2 Diabetes. JAMA Neurol 2023

Higher plasma caffeine levels linked to reduced body fat and type 2 diabetes risk according to genetic study

23rd March 2023

Increased plasma caffeine levels may help reduce body mass index as well as fat mass and the risk of developing type 2 diabetes

A higher plasma caffeine (PC) concentration may produce a lower body mass index (BMI) as well as reducing body fat and the risk of type 2 diabetes according to the findings of a genetic study by Swedish and UK researchers.

Caffeinated beverages such as coffee, tea and soda drinks are widely consumed across the world. Given that caffeine has a known thermogenic effect and which might help lower body weight, there is the potential that caffeine-containing beverages may have a role in lowering the risk of disease related to adiposity. In fact, there is already some data to suggest that caffeine-containing drinks such as coffee are inversely associated with risk of type 2 diabetes.

It is recognised the caffeine metabolism occurs mainly in the liver by the cytochrome P450 isoform 1A2 (CYP1A2) and how genetic variations near two genes, CYP1A2 and AHR (which regulates the expression of CYP1A2) are linked to PC concentrations. In fact, individuals with genetic variants linked to slower caffeine metabolism, although generally consuming less caffeine-related beverages, do have higher plasma caffeine levels. Using Mendelian randomisation, researchers sought to investigate the effects of long-term exposure to higher plasma caffeine concentrations on adiposity, type 2 diabetes and major cardiovascular diseases. They used data from a genome-wide association meta-analysis of 9876 individuals of European ancestry from six population-based studies and which identified genome-wide significant associations of single nucleotide polymorphisms near CYP1A2 and AHR loci with plasma caffeine concentrations.

Plasma caffeine and adiposity-related outcomes

Researchers identified that genetically predicted higher PC concentrations in those carrying the two gene variants, were in fact, associated with a lower BMI, with one standard deviation (SD) increase in predicted PC equal to about 4.8 kg/m2 in BMI (p < .001). Similarly, for whole-body fat mass, one SD increase in PC equated to a reduction of about 9.5 kg (p < .001), although interestingly, there was no association with fat-free body mass (p= 0.17).

Again among genetically predicted higher PC concentrations, there were also significant and lower associations with the risk of developing type 2 diabetes, with the combined odds ratio of type 2 diabetes per SD increase in PC concentration being 0.81 (95% CI 0.74 – 0.89, p < 0.001).

The authors concluded that while their study found evidence of a causal association between a higher plasma caffeine concentration and lower levels of adiposity and a reduced risk of type 2 diabetes, they called for randomised trials to further examine the role of caffeine in reducing the risk of obesity and diabetes.

Larrson SC et al. Appraisal of the causal effect of plasma caffeine on adiposity, type 2 diabetes, and cardiovascular disease: two sample mendelian randomisation study. BMJ 2023

GLP-1 agonists associated with modest weight loss in real-world setting

18th February 2023

The use of GLP-1 agonists in overweight type 2 diabetic patients is associated with a small but significant weight loss after 72 weeks

A retrospective analysis of electronic health records by US researchers has revealed that the use of glucagon-like peptide-1 (GLP-1) agonists in overweight patients with type 2 diabetes in routine clinical practice is associated with a modest degree of weight loss.

It has long been recognised that obesity is an independent risk factor for cardiovascular disease. In addition, cardiovascular disease is often present in those with type 2 diabetes and presents a major cause of death among such patients. Despite this elevated risk, lifestyle modification, in particular weight loss, has been shown to be associated with better control of diabetes and and a reduction in cardiovascular risk factors. Clinical trials in overweight, type 2 diabetic patients have demonstrated that drugs such as semaglutide, which is one of the GLP-1 agonists, achieves superior and clinically meaningful reductions in body weight in comparison to placebo. However, most of the weight loss clinical trials have included a lifestyle intervention to support patients but in the absence of such support, GLP-1 agonist associated weight loss is no better than that achieved with other agents such as metformin.

In the current study, US researchers from the University of Pittsburgh, wanted to understand the degree to which GLP-1 agonists induced weight loss when used as a part of routine clinical care, i.e., in the absence of a specific behavioural weight loss intervention. The team retrospectively examined the electronic health records of those prescribed any drugs from the GLP-1 agonist class and the subsequent weight loss after 72 weeks of therapy.

GLP-1 agonists and real-world weight loss

Outcomes were available for 2,405 participants with a mean age of 48 years (47.4% male) and of whom, 92.1% had type 2 diabetes and mean, baseline body mass index of 37.

Only 8 weeks after the first dispensing of a GLP-1 agonist, the mean weight loss was 1.1% and this increased to 2.2% after 72 weeks. However, some patients did even better. For instance, 11.2% had lost at least 5% of their body weight after 8 weeks but after 72 weeks, this proportion increased to just over a third (33.3%). In fact, at the 72 week mark, nearly half of the entire cohort (42.7%) had lost weight with a small proportion of patients (10.5%) managing to lose 10% or more of their body weight.

The authors concluded that the use of GLP-1 agonists prescribed at standard doses led to a modest degree of weight loss in a real-world setting and in the absence of any specific patient support.

White GE et al. Real-world weight-loss effectiveness of glucagon-like peptide-1 agonists among patients with type 2 diabetes: A retrospective cohort study. Obesity (Silver Spring) 2023

Continued exercise for 10 years linked to reduced risk type 2 diabetes

15th February 2023

Continued moderate or vigorous exercise over a 10-year period is associated with a significantly reduced risk of incident type 2 diabetes

Participants who continued to exercise for up to 10 years following completion of a 12 month randomised trial, had a significantly lower risk of developing incident type 2 diabetes according to the findings of a study by Chinese researchers.

Globally, type 2 diabetes affects around 462 million people or just over 6% of the entire population. Lifestyle modifications such as diet or increased exercise are known to reduce the risk of developing the disease. However, most of the available evidence for effects of lifestyle modification has been derived from high-risk individuals, for instance, those with elevated fasting glucose levels, or those who are both overweight and having impaired glucose tolerance. A further problem is that many of these intervention studies were of a relatively short duration. It is therefore less unclear whether maintenance of lifestyle modifications such as increased physical activity, over the longer term, still reduces the risk of developing T2D.

In the current study, Chinese researchers reported the longer term outcomes of a 12 month randomised trial they had undertaken. In the original trial, participants with non-alcoholic fatty liver disease, were randomised to vigorous to moderate physical activity, moderate exercise (brisk walking) or no exercise for 12 months. The results of the trial showed that both forms of exercise were effective at reducing intrahepatic triglyceride levels compared to those who did not exercise.

Following the trial, the majority of the study participants were followed-up after 2 and 10 years to assess the incidence of T2D, defined as a fasting plasma glucose of 6.9 mmol/L and a HBA1c of > 6.5% and or the use of anti-diabetic treatment.

Continued exercise and incident type 2 diabetes

From an original cohort of 208 participants who completed the year long trial, 195 and 179 remained for subsequent assessment after 2 and 10 years respectively.

The cumulative incidence of T2D was 2.1 per 100 person-years, 1.9 and 4.1 in those who continued with vigorous, moderate or no exercise respectively. In fact, the risk of T2D was reduced by 49% among those performing vigorous exercise (relative risk, RR = 0.51, 95% CI 0.27 – 0.94, p = 0.01) and by 53% among moderate level intensity exercise (RR = 0.47, 95% CI 0.25 – 0.89, p = 0.01) compared to the non-exercising group.

While both exercise groups had significant reductions in HBA1c levels compared to non-exercisers during the follow-up period, fasting plasma glucose levels while numerically lower in the two exercising groups than the non-exercise control group, these differences were non-significant.

The authors suggested that vigorous to moderate aerobic physical activity could be used to prevent T2D, particularly in those with obesity.

Chen Y et al. Effect of Moderate and Vigorous Aerobic Exercise on Incident Diabetes in Adults With Obesity: A 10-Year Follow-up of a Randomized Clinical Trial. JAMA Intern Med 2023

Analysis finds vitamin D supplementation potentially beneficial for type 2 diabetes

14th February 2023

A meta-analysis suggests that vitamin D supplementation reduces fasting plasma glucose and HbA1c levels in patients with type 2 diabetes

Vitamin D supplementation may be of value to patients with type 2 diabetes, especially if they have suboptimal levels of the vitamin according to a meta-analysis undertaken by US and Iranian researchers.

It has been estimated that in 2017, a staggering 462 million individuals had type 2 diabetes, corresponding to just over 6% of the global population. While there are several therapies available for the management of type 2 diabetes, new treatments will always be needed, given the high prevalence of the disorder. One such potential treatment is vitamin D supplementation and while this is usually given to regulate calcium and phosphorus levels, in recent years, a purported role has been suggested for several diseases. For example, data from the prospective Nurses’ Health study found that higher vitamin D and calcium intake was associated with a 33% lower risk of type 2 diabetes. Nevertheless, studies that involved actual vitamin D supplementation produced mixed findings. For example, one study 6-month trial found that supplementing with the vitamin in patients with type 2 diabetes, failed to affect either insulin sensitivity or secretion. In contrast, an 8-week intervention study demonstrated significant reductions in fasting plasma glucose, insulin and HOMA-IR.

As a result, in the current study, researchers performed a meta-analysis to examine the effect of using the vitamin on indices of glycaemic control including fasting plasma glucose (FPG), HbA1c and HOMA-IR.

Vitamin D supplementation and glycaemic measures

A total of 46 eligible trials were identified including 4,313 patients with type 2 diabetes and a mean age of 56.5 years and of whom 2,164 received the vitamin intervention. The majority of the studies (42) used an oral supplement, whereas in four trials, it was given via intramuscular injection.

The pooled analysis for HbA1c showed a significant reduction compared to placebo for vitamin D (weighted mean difference, WMD = -0.20, p < 0.001). Similarly, there was a significant reduction in FPG (WMD = -0.28 mmol/L, p < 0.001) and HOMA-IR (WMD = -0.42, p = 0.019) in those given vitamin D.

The authors concluded that although vitamin D supplementation had a positive impact of glycaemic indices, they cautioned that the substantial heterogeneity between the included studies, raised the possibility of publication bias.

Farahmand MA et al. What is the impact of vitamin D supplementation on glycemic control in people with type-2 diabetes: a systematic review and meta-analysis of randomized controlled trails. BMC Endocr Disord 2023

Semaglutide significantly reduces risk of type 2 diabetes in obese patients

28th September 2022

Semaglutide 2.4 mg given weekly with diet and exercise reduced the 10-year risk of type 2 diabetes in obese patients compared to placebo

Semaglutide 2.4 mg given as a weekly subcutaneous injection to patients with obesity but without type 2 diabetes in combination with diet and exercise, led to a significant reduction in their 10-year risk of developing type 2 diabetes compared to placebo according to the findings of a study by US researchers presented at the 58th European Association for the Study of Diabetes (EASD) 2022.

Obesity is a major public health challenge and several lines of evidence from both observational and clinical studies over the past 30 years have clearly demonstrated a strong link between visceral and ectopic fat and the development of a clinical syndrome characterised by atherogenic dyslipidaemia, hyper-insulinaemia/glucose intolerance, hypertension, atherosclerosis and adverse cardiac remodelling and heart failure.

Although diet and exercise are recommended as a first step to reduce obesity, some evidence shows that among obese individuals who have lost weight, multiple compensatory mechanisms encouraging weight gain, can persist for at least 12 months after weight loss.

Semaglutide is a glucagon-like peptide-1 (GLP-1) analogue that is approved as an adjunct to diet and exercise in adults with insufficiently controlled type 2 diabetes mellitus. However, the STEP 1 trial showed that semaglutide at a dose of 2.4 mg weekly in combination with a lifestyle intervention could also result in sustained, clinically relevant reductions in body weight among patients with a body mass index (BMI) > 30.

Moreover, in a further trial (STEP 4), researchers examined the effect of continuing vs withdrawing treatment with semaglutide on weight loss maintenance and showed that after a 20-week run-in period, maintaining treatment with semaglutide 2.4 mg once weekly, compared with switching to placebo resulted in continued weight loss over the following 48 weeks.

With clear evidence that semaglutide could lead to weight loss, whether this also reduced an individual’s risk of developing type 2 diabetes was unclear and was the objective of the study presented at the EASD meeting. Researchers used data from both STEP 1 and 4, to assess an individual’s 10-year risk of developing type 2 diabetes.

The team used the cardiometabolic disease staging tool which uses three unmodifiable factors (age, sex, and race) and five modifiable factors (BMI, blood pressure, glucose level, high-density lipoprotein (HDL) cholesterol, and triglycerides) to predict an individual’s percentage risk of developing the disease over the next 10 years.

Semaglutide and 10-year diabetes risk

For the STEP 1 trial, the 10-year risk scores of developing T2D after 68 weeks of treatment decreased from 18.2% to 7.1% with semaglutide 2.4 mg, and 17.8% to 15.6% with placebo (p < 0.01). In STEP 4, most of the risk score reduction with semaglutide 2.4 mg occurred during weeks 0-20, from 20.6% to 11.4% but the risk score decreased further to 7.7% with continued semaglutide 2.4 mg during weeks 20-68 but increased to 15.4% after a switch to placebo (p < 0.01).

In addition, data from STEP 4 showed that weight loss was 11% for weeks 0 – 20 and a further 9% with continued semaglutide 2.4 mg vs a 6%
regain with switch to placebo for weeks 20 – 68.

The authors concluded that treatment with semaglutide 2.4 mg reduces the 10-year risk of T2D by
~60% adding that sustained treatment was required to maintain this benefit but suggested that semaglutide 2.4 mg could help prevent type 2 diabetes in people with obesity.

Garvey TW et al. Semaglutide 2.4 mg reduces the 10-year type 2 diabetes risk in people with overweight or obesity Abstract 562. EASD 2022

Elevated aldosterone levels linked with greater risk of disease progression in CKD

12th August 2022

Higher aldosterone levels in chronic kidney disease increases the risk of progression and the development of end-stage kidney disease

Higher serum aldosterone levels in those with chronic kidney disease (CKD) is associated with an increased risk of disease progression and of developing end-stage kidney disease, according to an analysis of data from the Chronic Renal Insufficiency Cohort (CRIC) by US researchers.

Aldosterone is produced by the adrenal glands and is known to play a role in the development of hypertension and kidney disease. Elevated levels of aldosterone (primary aldosteronism) are a factor in the development of hypertension, but while high among hypertensive patients, the condition is often unrecognised.

However, the extent to which aldosterone levels impact on the subsequent risk of progression in patients with CKD is uncertain and was the subject of the current retrospective analysis by the US team.

The researchers turned to data collected as part of the Chronic Renal insufficiency Cohort (CRIC) study and which was designed to investigate risk factors for mortality and worsening of disease in patients with CKD. They included individuals with an estimated glomerular filtration rate (eGFR) of between 20 and 70 ml/min/1.73 m2 and for whom aldosterone levels had been recorded and these levels were divided into quartiles

The researchers also collected demographic and co-morbidity data which was adjusted for in regression analysis. The primary outcome of interest was CKD progression and defined as the composite of a 50% decline in eGFR or incident end-stage kidney disease (ESKD), whichever came first.

Aldosterone levels and disease progression

A total of 3680 individuals with a mean age of 58.1 years (44.7% female) were included in the analysis, of whom 48.1% were diabetics with the overall mean serum aldosterone being 10 ng/dL, although this was significantly higher in men than women (10.5 vs 9.4, p < 0.001).

After a median follow-up of 9.6 years, 1412 individuals developed CKD disease progression and 1129 developed ESKD. In fully adjusted models, those with the highest quartile serum aldosterone level had a 45% higher risk of CKD progression compared to those in the lowest quartile (hazard ratio, HR = 1.45, 95% CI 1.22 – 1.73).

Using aldosterone levels as a continuous variable in the models, indicated that there was an 11% higher risk of CKD progression (HR = 1.11, 95% CI 1.04 – 1.18). Furthermore, those with the highest aldosterone serum levels also had a 46% increased risk of developing ESKD (HR = 1.46).

While there was also a 22% increased risk of all-cause mortality for individuals in the highest versus the lowest aldosterone levels, this became non-significant when levels were considered as a continuous variable (HR = 1.05, 95% CI 0.99 – 1.12). There was also no relationship between the adverse outcomes from higher levels of aldosterone and diabetes status.

The authors concluded by suggesting that aldosteronism may play a role in CKD progression.

Verma A et al. Aldosterone in chronic kidney disease and renal outcomes. Eur Heart J 2022