More Evidence Ancient Retrovirus Linked to Type 1 Diabetes

MedicalResearch.com Interview with:

Sandrine Levet PhD Student Preclinical Study Manager GeNeuro

Sandrine Levet

Sandrine Levet PhD
Preclinical Study Manager
GeNeuro

MedicalResearch.com: What is the background for this study?

Response: Human endogenous retroviruses (HERVs), remnants of ancestral viral genomic insertions, are known to represent 8% of the human genome and are associated with several pathologies. In particular, the envelope protein of HERV-W family (HERV-W Env) has been involved in multiple sclerosis pathogenesis.

A previous study published in JCI Insight revealed that HERV-W Env is also involved in Type 1 diabetes (T1D) pathogenesis. In this study, we observed that HERV-W-Env protein and RNA are detected respectively in sera and peripheral blood mononuclear cell (PBMC) of T1D patients.

We also demonstrated that this pathogenic protein is expressed by acinar cells in human T1D pancreas and is associated with the recruitment of macrophages within the pancreas of these patients. HERV-W Env also displays direct pathogenic properties as it inhibits insulin secretion by human islets of Langerhans.

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Pregnancy in Type 1 Diabetes: Glucose Control Can Reduce Fetal Overgrowth

MedicalResearch.com Interview with:

Rachel McGrath BSc (Hons), PhD Senior Research Fellow - Department of Endocrinology, RNSH Clinical Senior Lecturer - Northern Clinical School University of Sydney

Dr. Rachel McGrath

Rachel McGrath BSc (Hons), PhD
Senior Research Fellow – Department of Endocrinology, RNSH
Clinical Senior Lecturer – Northern Clinical School
University of Sydney 

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Women with type 1 diabetes are significantly more likely to experience complications during pregnancy and to have infants with high birth weights. This can result in adverse outcomes at the time of delivery for both mother and baby, and can also predispose infants to obesity and chronic disease in later life.

The relationship between maternal blood glucose levels and foetal growth in type 1 diabetes in pregnancy has not been completely elucidated. Thus, we examined the association between maternal glycaemic control and foetal growth by examining serial ultrasound measurements and also by determining the relationship between HbA1c (a measure of circulating glucose exposure over a three month time period) and infant birth weight.

We found that maternal glucose levels were directly related to foetal abdominal circumference in the late second and third trimesters and also to birth weight. We also confirmed the results of previous studies to show that the optimal HbA1c during pregnancy to reduce the likelihood of large-for-gestational-age neonates is < 6%.  Continue reading

Study Finds ACE Inhibitors and Statins Can Be Safe In Type I Diabetes

MedicalResearch.com Interview with:
M. Loredana Marcovecchio, M.D.
Clinical Scientist and
Professor David Dunger M.D.
Director of Research
Professor of Paediatrics
University of Cambridge

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: The efficacy and safety of ACE Inhibitors and statins in adolescents have been shown in the context of hypertension and familial hypercholesterolemia, respectively. However, there is a lack of data on the long-term use of these drugs in those with type 1 diabetes and, in particular, there is no clear indication for their use in patients with increased albumin excretion.

The Adolescent type 1 Diabetes cardio-renal Intervention Trial (AdDIT) was a multi-centre, international study, set up by investigators in the UK, Australia and Canada to explore if drugs already used to lower blood pressure (ACE inhibitors) and cholesterol levels (Statins) in adults with diabetes could reduce the risk of kidney, eye and cardiovascular disease in adolescents with Type 1 diabetes.

Neither ACE inhibitors nor statins significantly reduced the albumin-creatinine ratio during the 2-4 year trial period. However, some of the secondary outcomes suggest that the drugs may have important benefits.

Treatment with the ACE inhibitor resulted in a 43% reduction in the rates of progression to microalbuminuria, which was not statistically significant, but it could have important clinical implications. Preventing even intermittent cases of microalbuminuria is known to reduce the future risk of kidney and cardiovascular complications.

Statin therapy led to reduced levels of lipid levels, which could reduce long-term risk for cardiovascular complications.

These findings could translate into long-term benefits, but follow-up of this unique cohort will be essential. The essential biological samples and data provided by the participants will continue to inform our future understanding and our options for effective therapies for this vulnerable group of young people with type 1 diabetes.

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Enteroviruses Linked To Development of Type 1 Diabetes in Children

MedicalResearch.com Interview with:
Dr. Hanna Honkanen PhD
University of Tampere.

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: The association between enteroviruses and type 1 diabetes has been suggested for long and analyzed in several studies. However, only few studies have been able to study this association at the time when the disease process starts, which happens several months or years before type 1 diabetes is diagnosed.

Our study made this possible since it was based on a large cohort of children who were followed from birth and samples were collected already before the disease process had started (prospective DIPP-study in Finland). Enterovirus infections were detected by analyzing the presence of viral nucleic acids in longitudinal stool sample series. Infections were found more frequently in case children who developed islet autoantibodies compared to control children. This excess was detected several months before islet autoimmunity appeared. This study is the largest such study carried out so far. The results suggest that enterovirus infections may contribute to the initiation of the disease process that eventually leads to type 1 diabetes.

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Follicular T Cells May Play a Role in Development of Type I Diabetes

MedicalResearch.com Interview with:

Tuure Kinnunen, MD, PhD Academy Research Fellow School of Medicine, University of Eastern Finland Kuopio, Finland

Dr. Tuure Kinnunen

Tuure Kinnunen, MD, PhD
Academy Research Fellow
School of Medicine, University of Eastern Finland
Kuopio, Finland

MedicalResearch.com: What is the background for this study?

Response: Type 1 diabetes is an autoimmune disease where the immune system destroys the insulin-producing beta cells in the pancreas. It typically manifests in childhood and early adolescence.

Diabetes-associated autoantibodies are highly predictive of type 1 diabetes risk and they can be typically detected in the blood of patients even years before the onset of the disease.

Follicular helper T cells are a recently described type of immune cells that have a central role in activating B cells, which in turn are responsible for producing antibodies. Since the emergence of autoantibodies is a common feature of type 1 diabetes development, it is plausible that follicular T helper cells have a role in the disease process. This notion is also supported by evidence recently generated in the murine models of type 1 diabetes.

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Juvenile Diabetes May Be Triggered During Pregnancy By Viral Infections

Prof. Zvi Laron Professor Emeritus of Pediatric Endocrinology TAU's Sackler Faculty of Medicine, Director of the Endocrinology and Diabetes Research Unit Schneider Children's Medical Center of Israel Head of the WHO Collaborating Center for the Study of Diabetes in YouthMedicalResearch.com Interview with:
Prof. Zvi Laron
Professor Emeritus of Pediatric Endocrinology
TAU’s Sackler Faculty of Medicine,
Director of the Endocrinology and Diabetes Research Unit
Schneider Children’s Medical Center of Israel
Head WHO Collaborating Center for the Study of Diabetes in Youth

Medical Research: What are the main findings of the study? What was most surprising about results?

Prof. Laron: The main findings were the finding of specific antibodies to the pancreatic insulin secreting beta cells together with antibodies against rota-virus in both the mother at delivery and in the newborn’s cord blood. We were not surprised, but pleased to find proof to our hypothesis that part, if not the majority of childhood onset Type 1 (autoimmune diabetes) starts “in utero”.
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