Cardiac repolarization during hypoglycaemia and hypoxaemia in healthy males: impact of renin-angiotensin system activity

Due-Andersen, Rikke; Høi-Hansen, Thomas; Olsen, Niels Vidiendal; Larroudé, Charlotte Ellen; Kanters, Jørgen K.; Boomsma, Frans; Pedersen‐Bjergaard, Ulrik; Thorsteinsson, Birger

doi:10.1093/europace/eum286

Cited by 4 publications

(5 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A number of genes have been linked to CAN in particular, based on their involvement in autonomic dysfunction in animal models and in human patients of T1DM or other cardiac complication, or due to their involvement in inflammatory responses that are thought to contribute to neuronal injury. These candidate genes include ACE ( 134 ), ADRB2 ( 135 ), AKR1B1 ( 47 , 136 ), APOE ( 137 ), CAT ( 138 ), GNAS ( 139 ), MTHFR ( 140 ), NF- κ B ( 141 ), NOS ( 142 , 143 ), TLR2 and TLR4 ( 144 ), and SREBP-1 ( 145 ). The only genetic polymorphisms that have been associated with the risk of CAN in T2DM patients are TCF7L2 ( 9 ), TNF- α ( 133 , 146 ), and CHT1 (Table 2 ) ( 132 ).…”

Section: Genetics Of Diabetic Neuropathiesmentioning

confidence: 99%

“…The ACE I/D polymorphism alone, and haplotypes including this and other markers within the ACE gene, have been associated with DN progression and end stage renal disease in particular, which in turn leads to UN ( 84 , 170 – 172 ). The ACE D/D genotype has also been linked with impaired circadian blood pressure variation in T2DM, which is associated with autonomic neuropathy, hypertension, and limited kidney function ( 134 , 173 ). Studies investigating the association between the ACE I/D polymorphism and diabetic complications have produced very contradictory results, providing a good example of an issue encountered in the majority of genetic studies of T2DM risk factors.…”

Section: Genetics Of Diabetic Neuropathiesmentioning

confidence: 99%

See 1 more Smart Citation

Identifying Common Genetic Risk Factors of Diabetic Neuropathies

et al. 2015

View full text Add to dashboard Cite

Type 2 diabetes mellitus (T2DM) is a global public health problem of epidemic proportions, with 60–70% of affected individuals suffering from associated neurovascular complications that act on multiple organ systems. The most common and clinically significant neuropathies of T2DM include uremic neuropathy, peripheral neuropathy, and cardiac autonomic neuropathy. These conditions seriously impact an individual’s quality of life and significantly increase the risk of morbidity and mortality. Although advances in gene sequencing technologies have identified several genetic variants that may regulate the development and progression of T2DM, little is known about whether or not the variants are involved in disease progression and how these genetic variants are associated with diabetic neuropathy specifically. Significant missing heritability data and complex disease etiologies remain to be explained. This article is the first to provide a review of the genetic risk variants implicated in the diabetic neuropathies and to highlight potential commonalities. We thereby aim to contribute to the creation of a genetic-metabolic model that will help to elucidate the cause of diabetic neuropathies, evaluate a patient’s risk profile, and ultimately facilitate preventative and targeted treatment for the individual.

show abstract

Section: Genetics Of Diabetic Neuropathiesmentioning

confidence: 99%

Section: Genetics Of Diabetic Neuropathiesmentioning

confidence: 99%

Identifying Common Genetic Risk Factors of Diabetic Neuropathies

et al. 2015

View full text Add to dashboard Cite

show abstract

“…The first three were designed to evaluate the effect of activity in the renin–angiotensin system on hormonal, cardiac and cognitive function parameters during experimental hypoglycaemia (34, 35, 36). The fourth study was a randomised controlled trial (RCT) designed to evaluate the effect of exogenous erythropoietin on cognitive function during hypoglycaemia in patients prone to severe hypoglycaemia (37).…”

Section: Methodsmentioning

confidence: 99%

“…An overview of the four studies is available in Table 2. Specific details about the experimental protocol, including ethical issues and consent to participate, are reported elsewhere (34, 35, 36, 37). …”

Section: Methodsmentioning

confidence: 99%

“…In the RCT (37), baseline values from both arms of the cross-over study were pooled. Only data from the hypoglycaemic (and not normoglycaemic (control) or hypoxic) study days in the three other studies (34, 35, 36) were included. Peak values of glucagon concentration were defined as the highest glucagon concentration measured during the hypoglycaemic clamp.…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Impact of the TCF7L2 genotype on risk of hypoglycaemia and glucagon secretion during hypoglycaemia

Kristensen

Pedersen‐Bjergaard

Due-Andersen

et al. 2016

Endocrine Connections

View full text Add to dashboard Cite

IntroductionIn healthy carriers of the T allele of the transcription factor 7-like 2 (TCF7L2), fasting plasma glucagon concentrations are lower compared with those with the C allele. We hypothesised that presence of the T allele is associated with a diminished glucagon response during hypoglycaemia and a higher frequency of severe hypoglycaemia (SH) in type 1 diabetes (T1DM).Material and methodsThis is a post hoc study of an earlier prospective observational study of SH and four mechanistic studies of physiological responses to hypoglycaemia. 269 patients with T1DM were followed in a one-year observational study. A log-linear negative binomial model was applied with events of SH as dependent variable and TCF7L2 alleles as explanatory variable. In four experimental studies including 65 people, TCF7L2 genotyping was done and plasma glucagon concentration during experimental hypoglycaemia was determined.ResultsIncidences of SH were TT 0.54, TC 0.98 and CC 1.01 episodes per patient-year with no significant difference between groups. During experimental hypoglycaemia, the TCF7L2 polymorphism did not influence glucagon secretion.DiscussionPatients with T1DM carrying the T allele of the TCF7L2 polymorphism do not exhibit diminished glucagon response during hypoglycaemia and are not at increased risk of severe hypoglycaemia compared with carriers of the C allele.

show abstract

Hypoglycaemia and QT interval prolongation in type 1 diabetes – bridging the gap between clamp studies and spontaneous episodes

Christensen

Cichosz

Tarnow

et al. 2014

Journal of Diabetes and its Complications

View full text Add to dashboard Cite

Cardiac repolarization during hypoglycaemia and hypoxaemia in healthy males: impact of renin-angiotensin system activity

Abstract: Basal RAS activity has significant impact on QT dynamics, but not the corrected QT interval, during recovery from hypoglycaemia and hypoxaemia. The impact, however, is modest and more subtle than initially expected. The clinical relevance is unclear.

Cited by 4 publications

References 49 publications

Identifying Common Genetic Risk Factors of Diabetic Neuropathies

Identifying Common Genetic Risk Factors of Diabetic Neuropathies

Impact of the TCF7L2 genotype on risk of hypoglycaemia and glucagon secretion during hypoglycaemia

Hypoglycaemia and QT interval prolongation in type 1 diabetes – bridging the gap between clamp studies and spontaneous episodes

Contact Info

Product

Resources

About