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Take a look at a selection of our recent media coverage:
7th March 2023
A randomised, placebo-controlled trial found that among adolescents recently diagnosed with type 1 diabetes (T1D), use of verapamil tablets preserved beta cell function to a greater extent than placebo after 52 weeks.
Type 1 diabetes is an autoimmune disorder resulting in the destruction of insulin-producing beta cells in the pancreas. Among patients with T1D, measurement of connecting peptide (C-peptide) which is co-secreted with insulin from the islets of Langerhans cells, allows for an evaluation of the amount of remaining beta cell secretion of insulin. One recently identified therapeutic target is thioredoxin-interacting protein which is elevated in diabetes and over-expression of the protein leads to beta-cell apoptosis. Moreover, it has been found that verapamil can inhibit thioredoxin-interacting protein, thereby enhancing beta cell function and could serve as a means of preventing diabetes. In fact, a 2018 study with 26 T1D patients, observed that use of verapamil improved the area under the curve (AUC) for C-peptide after 3 and 12 months.
In the current study, researchers randomised adolescents recently diagnosed (within 24 days) with T1D, 1:1 to either 60 or 120 mg/day (depending on the participant’s weight) of verapamil or placebo as part of study in which subjects also received either intensive diabetes management or standard care. The primary outcome was set as the AUC values for C-peptide stimulated by a mixed-meal tolerance test, 52 weeks from their date of diabetes diagnosis.
Verapamil and changes in C-peptide area under the curve
A total of 88 participants with a mean age of 12.7 years (41% female) were randomised to either verapamil (47) or placebo.
The mean baseline C-peptide AUC for the verapamil group was 0.66 pmol/mL and 0.65 pmol/mL at 52 weeks. In contrast, in the placebo group C-peptide AUC reduced from 0.60 pmol/mL to 0.44 pmol/mL (adjusted between-group difference = 0.14, 95% CI 0.01 – 0.27, p = 0.04), which equated to a 30% higher C-peptide level at 12 months in the verapamil group.
The authors concluded that use of verapamil was able to partly preserve stimulated C-peptide secretion at 52 weeks and called for further longitudinal studies to confirm the durability of this response and the optimal length of treatment.
Forlenza GP et al. Effect of Verapamil on Pancreatic Beta Cell Function in Newly Diagnosed Pediatric Type 1 Diabetes: A Randomized Clinical Trial. JAMA 2023
11th October 2022
A bionic pancreas can provide better control of glycated haemoglobin levels compared to standard care according to the findings of a randomised trial by a team of US researchers.
The term ‘diabetes’ refers to a group of diseases characterised by high blood glucose levels that occur due to a deficiency in the production or function of insulin or both. Type 1 diabetes is the main form diagnosed in childhood and characterised by increased blood glucose levels resulting from insulin deficiency. It is relatively common and in a 2020 study, it was estimated that globally, the incidence of type 1 diabetes was 15 per 100,000 and had a prevalence of 9.5%.
Multiple studies have confirmed that a higher glycated haemoglobin (HbA1c) level is an independent risk factor for diabetes complications. As a result, according to a consensus report in 2021 by the American Diabetes Association and the European Association for the Study of Diabetes, a HbA1c goal for most adults of <53 mmol/mol (<7.0%) without significant hypoglycaemia is appropriate. Nevertheless, in a US real-world study of 31,430 type 1 patients, only around 20% had a HbA1c of < 7%.
Currently, hybrid closed-loop insulin-delivery systems are able to partially automate insulin delivery and have shown improved glycaemic control in adults and youth with type 1 diabetes by reducing both hyperglycaemia and hypoglycaemia. Another innovation is a bionic pancreas, which represents an automated insulin delivery system initialised only with body weight and without any information about previous insulin dosing. A bionic pancreas works together with a continuous sugar monitoring (CGM) tool to autonomously deliver insulin and/or glucagon to control an individual’s blood glucose level in response to their real-time sensor glucose readings from the CGM.
In the present study, US researchers undertook a randomised trial to compare a bionic pancreas which provided either aspart or insulin lispro with standard care in terms of managing glycated haemoglobin levels. For the study, standard care was defined as any insulin-delivery method with unblinded, real-time continuous glucose monitoring. Individuals aged 6 years and older who were diagnosed with type 1 diabetes and using insulin for at least 12 months, were randomised 2:1 to the bionic pancreas (with insulin aspart or lispro) or standard care. The primary outcome was the glycated haemoglobin level at 13 weeks, whereas secondary outcomes included the percentage time that glucose levels were below 3 mmol/L and the percentage of time that glucose levels remained in the target range of 3.9 to 10 mmol/L.
Bionic pancreas and glycated haemoglobin
A total of 326 adults and children with a mean age of 28 years (49% female in the bionic group) were included in the analysis.
The mean glycated haemoglobin level was 7.3% (down from a baseline of 7.9%) in the bionic group but remained unchanged at 7.7% in the standard care group (mean adjusted difference = -0.5, 95% CI -0.60 to – 0.30, p < 0.001).
However, the percentage of time with glucose levels below 3 mmol/L was not significantly different. In contrast, both the mean glucose level and the percentage time spend in the target range of 3.9 to 10 mmol/L were both statistically significant, favouring the bionic pancreas. In fact, based on the percentage time within the target range, the researchers calculated that the difference of 11% equated to an increase of 2.6 hours/day for the bionic group.
The rate of severe hypoglycaemia was 17.7 events per 100 participant-years in the bionic group and 10.8 events for the standard care group which was non-significant (p = 0.39).
The authors concluded that the bionic pancreas was associated with a greater reduction in glycated haemoglobin compared to standard care.
Bionic Pancreas Research Group. Multicenter, Randomized Trial of a Bionic Pancreas in Type 1 Diabetes N Eng J Med 2022
30th September 2022
A study presented at the European Association for the Study of Diabetes (EASD) annual meeting by Norwegian researchers suggests that the risk of developing new-onset type 1 diabetes is significantly elevated among children and adolescents, more than 30 days after an infection with COVID-19.
Type 1 diabetes (TID) is a chronic, autoimmune disease that is influenced by both genetic and environmental factors and characterised by the destruction of insulin-producing cells. It also appears to be on the increase with a 2019 study finding that the pooled estimate across European centres continued to show a 3.4% increase per annum in incidence rate, suggesting a doubling in incidence rate within approximately 20 years in Europe. There is some data to suggest that the onset of type 1 diabetes can be initiated after respiratory infections that give rise to the common cold, influenza-like illness, sinusitis, and laryngitis/tracheitis. Moreover, while some evidence suggests that COVID-19 can trigger severe diabetic keto-acidosis in those with new-onset diabetes, there is no hard evidence that the virus can induce T1D.
As a result, for the study presented at EASD, the Norwegian team undertook nationwide register-based study to test whether infection with COVID-19 was associated with an increased risk of developing TID in children and adolescents. Using the Norwegian preparedness register that is updated daily with individual-level data on PCR-confirmed COVID-19 infections, vaccinations and disease diagnoses from primary and secondary health care, the team linked individual level data for children and adolescents. Individuals were then followed from the start of the pandemic (March 1st 2020) until diagnosis of type 1 diabetes, age 18 years, death, until March 2022 (whichever came first). The researchers used both a test-negative design and a full population cohort to examine the relationship between the first type 1 diabetes diagnosis within or after 30 days post-COVID-19 infection. The results were expressed as hazard ratios which were adjusted for age, sex, non-Nordic country of origin, geographical area and socio-economic factors.
Type 1 diabetes and COVID-19 infection
A total of 424,354 children with COVID-19 infection (of 1,202,174 children included at study start) and 990 incident cases of T1D were identified .
Using the test negative design, the adjusted HR for type 1 diabetes at least 31 days after COVID-19 infection was 1.63 (95% CI 1.08 – 2.47, p = 0.02). However, less than 30 days post-infection, the adjusted hazard ratio was not significant (HR = 1.25, 95% CI 0.72 – 2.17, p = 0.42).
For the whole population cohort, the adjusted hazard ratio was 1.57 (95% CI 1.06 – 2.33, p = 0.03) and again was not significant for less than 30 days post-infection.
Based on these findings, the authors concluded that COVID-19 infection is associated with increased risk of subsequent T1M.
Gulseth HL et al. SARS-CoV-2 infection and subsequent risk of type 1 diabetes in 1.2 million children
4th August 2022
Daily insulin use increases the risk of developing cancer in patients with type 1 diabetes, with a greater risk among those who use a higher daily dose, according to findings of a study by US and Greek researchers.
Although diabetes and cancer are two heterogeneous, multifactorial, and chronic diseases, there are some epidemiological data indicating a higher risk of several types of cancer (including pancreas, liver, breast, colorectal, urinary tract, and female reproductive organs) in diabetic patients. Moreover, in an analysis of diabetic registries that specifically focused on patients with type 1 diabetes, a higher cancer risk was also identified for several types of cancer. However, whether this observed link is causal remains unclear. For example, in a 2016 meta-analysis of 16 observational studies in type 1 diabetics who used long-acting daily insulin, 13 studies reported no association between insulin glargine and detemir and any cancer and 4 studies reported an increased risk of breast cancer with insulin glargine. The authors concluded that observational studies examining the risk of cancer associated with long-acting insulin analogues have important methodological shortcomings that limit the conclusions that can be drawn. Nevertheless, whilst it is possible that the presence of type 1 diabetes is linked to an increased risk of cancer, no studies have examined potential patient risk factors. Consequently, for the present study, researchers turned to data from the Diabetes Control and Complications trial (DCCT) and the Epidemiology of Diabetes Interventions and Complications study (EDIC) to gain a better understanding of which, if any, factors increased the risk of cancer.
The DCCT enrolled patients between 1983 and 1989 and when the trial was completed in 1993, 1375 survivors continued in the EDIC study and follow-up data was available for 28 years. Daily insulin dose was categorised as low (< 0.5 units/kg), medium (> 0.5 and < 0.8 units/kg) and high (> 0.8 units/kg). The researchers used multivariable models to assess the association between several different factors and cancer incidence.
Daily insulin and cancer
Among a total of 1303 patients who were followed-up for 33,813 person-years, 93 (7%) developed cancer, giving an incidence rate of 2.8 (95% CI 2.2 – 3.3) per 1000 person-years. The mean age of participants at their cancer diagnosis was 50 years and the mean duration of diabetes was 25 years. Among the 93 who developed cancer, 61% were female. The majority of individuals (58%) developed their cancer after 21 and 28 years and the cancers affected the skin (27), breast (15) and digestive tract (6).
Factors associated with the development of cancer were age (hazard ratio, HR = 1.08, 95% CI 1.05 – 1.12) and female gender (HR = 1.74, 95% CI 1.15 – 2.64). Interestingly, participation moderate or strenuous exercise was associated with a reduced risk of cancer (HR = 0.31, 95% CI 0.16 – 0.59, p = 0.001).
In multivariable models, daily insulin use was associated with a 4-fold higher risk of cancer (HR = 4.13, 95% CI 1.13 – 15.17, p = 0.03). The cancer incidence was 2.11, 2.87 and 2.91 per 1000 person-years in the low, medium and high-dose daily insulin groups respectively.
Although the previous 2016 meta-analysis described earlier did not derive a clear association between type 1 diabetes and cancer, the authors of the current study suggested that this was because in the cohorts examined the doses of insulin used were low (< 0.3 units/kg) and many had discontinued treatment during follow-up.
The authors also felt that their observations may have been due to residual confounding and that potentially, the associations may not have been causal. They called for further studies to validate this association.
Zhong W, Moa Y. Daily Insulin Dose and Cancer Risk Among Patients With Type 1 Diabetes JAMA Oncol 2022
7th December 2021
Rates of diabetes-associated ocular complications (DAOC) in children have been found to be much higher in children diagnosed with type 2 as opposed to type 1 disease over the first 15 years after diagnosis. This was the finding of a retrospective analysis by a team from the Department of Ophthalmology, Mayo Clinic,
Diabetes is a common childhood condition, with a recent UK study finding that in 2019, there were an estimated 36,000 children with diabetes under the age of 19, an increase from from 31,500 in 2015. In children, type 1 disease accounts for the vast majority of cases although there is evidence to suggest that the prevalence of type 2 diabetes has increased between 2001 and 2009, in 10 – 19 year olds. Diabetes is associated with the development of micro-vascular complications including retinopathy, which remains the most common cause of blindness in working-age adults in the developed world. While sight loss in children due to diabetic retinopathy is much less common, guidance does recommend retinopathy screening of children with type 1 diabetes. However, far less is known about the development and progression of diabetic retinopathy among children with type 2 diabetes.
For the present study, the US researchers were interested in comparing the DAOC rates in children with both forms of diabetes. They turned to the medical records of children newly diagnosed with diabetes between 1970 and 2019 in Minnesota. They collected demographic and clinical data such as HbA1C and whether the individuals had undergone an eye examination and followed-up on these examinations. The researchers catalogued diabetic-associated ocular complications including non-proliferative diabetic retinopathy (NPDR), proliferative diabetic retinopathy (PDR), diabetic macular oedema (DME), a visually significant cataract (VSC) and the need for pars plana vitrectomy (PPV).
A total of 606 children were diagnosed with diabetes during the 50-year period, of whom, 525 (87.8%) had undergone at least one eye examination and were diagnosed with either type 1 (461) or type 2 (64) diabetes. The mean age of diagnosis among those with type 1 disease was 10.8 years (53.4% male) and 17.3 years (28.1% male) for type 2 disease. A DAOC occurred in 147 (31.9%) of those with type 1 disease,14 years after diagnosis and in 17 (26.6%) of those with type 2 disease. The hazard ratio, HR for developing any diabetic retinopathy between type 2 and type 1 disease was 1.88 (95% CI 1.13 – 3.12, p = 0.02).
Overall, 30.6% of those with type 1 disease developed a DAOC within 15 years compared to 52.7% of those with type 2 disease. While the risk of developing any of the other retinopathy complications included in the analysis was numerically higher among those with type 2 disease, the only statistically significant effect was the need for pars plana vitrectomy (HR = 4.06, 95% CI 1.34 – 12.33, p = 0.07), 15 years after the initial diagnosis.
The authors concluded that children with type 2 diabetes developed vision threatening retinopathy a shorter time after diagnosis than those with type 1 disease and suggested that such children should have ophthalmoscopy evaluations at least as frequently, or even more frequently, than those with type 1 disease.
Bai P et al. Ocular Sequelae in a Population-Based Cohort of Youth Diagnosed With Diabetes During a 50-Year Period. JAMA Ophthalmol 2021