Reduced Myocardial 123I-Metaiodobenzylguanidine Uptake in Newly Diagnosed IDDM Patients

Schnell, Oliver; Muhr, Daniela; Weiss, Mia C.; Dresel, S.; Haslbeck, M.; Standl, Eberhard

doi:10.2337/diab.45.6.801

Cited by 60 publications

(13 citation statements)

References 19 publications

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“…Scintigraphically, cardiac sympathetic dysinnervation was identified in 77% of newly diagnosed metabolically stabilized type 1 diabetic patients [27]. The pattern of cardiac sympathetic dysinnervation of newly diagnosed type 1 diabetic patients is heterogeneous with a predominant affection of the posterior myocardial region [25,27].…”

Section: Pathophysiology / Etiologymentioning

confidence: 99%

“…The pattern of cardiac sympathetic dysinnervation of newly diagnosed type 1 diabetic patients is heterogeneous with a predominant affection of the posterior myocardial region [25,27]. More recent publications, however, emphasize that neither impairment of metabolic control nor the presence of CV denervation may be a prerequisite for the development of impaired vasodilatory reserve.…”

Section: Pathophysiology / Etiologymentioning

confidence: 99%

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Type 1 diabetes and cardiovascular disease

Schnell

Cappuccio

Genovese

et al. 2013

Cardiovasc Diabetol

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The presence of cardiovascular disease (CVD) in Type 1 diabetes largely impairs life expectancy. Hyperglycemia leading to an increase in oxidative stress is considered to be the key pathophysiological factor of both micro- and macrovascular complications. In Type 1 diabetes, the presence of coronary calcifications is also related to coronary artery disease. Cardiac autonomic neuropathy, which significantly impairs myocardial function and blood flow, also enhances cardiac abnormalities. Also hypoglycemic episodes are considered to adversely influence cardiac performance. Intensive insulin therapy has been demonstrated to reduce the occurrence and progression of both micro- and macrovascular complications. This has been evidenced by the Diabetes Control and Complications Trial (DCCT) / Epidemiology of Diabetes Interventions and Complications (EDIC) study. The concept of a metabolic memory emerged based on the results of the study, which established that intensified insulin therapy is the standard of treatment of Type 1 diabetes. Future therapies may also include glucagon-like peptide (GLP)-based treatment therapies. Pilot studies with GLP-1-analogues have been shown to reduce insulin requirements.

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Section: Pathophysiology / Etiologymentioning

confidence: 99%

Section: Pathophysiology / Etiologymentioning

confidence: 99%

Type 1 diabetes and cardiovascular disease

Schnell

Cappuccio

Genovese

et al. 2013

Cardiovasc Diabetol

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“…Deficits of LV [ 123 I]MIBG and [ 11 C]HED retention have been identified in T1DM and T2DM subjects [114–116] with [114–116] and without [36] abnormal cardiovascular reflex testing.…”

Section: Clinical Evaluation and Diagnosis Criteriamentioning

confidence: 99%

What Do We Know and We Do Not Know About Cardiovascular Autonomic Neuropathy in Diabetes

Pop‐Busui

2012

J. of Cardiovasc. Trans. Res.

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Cardiovascular autonomic neuropathy (CAN) in diabetes is generally overlooked in practice, although awareness of its serious consequences is emerging. Challenges in understanding the complex, dynamic changes in the modulation of the sympathetic/parasympathetic systems’ tone and their interactions with physiologic mechanisms regulating the control of heart rate, blood pressure, and other cardiovascular functions in the presence of acute hyper-or-hypoglycemic stress, other stressors or medication, and challenges with sensitive evaluations have contributed to lower CAN visibility compared with other diabetes complications. Yet, CAN is a significant cause of morbidity and mortality, due to a high-risk of cardiac arrhythmias, silent myocardial ischemia and sudden death. While striving for aggressive risk factor control in diabetes practice seemed intuitive, recent reports of major clinical trials undermine established thinking concerning glycemic control and cardiovascular risk. This review covers current understanding and gaps in that understanding of the clinical implications of CAN and prevention and treatment of CAN.

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“…NET is responsible for the reuptake of as much as 90% of released NE and thus plays a crucial role in NE inactivation and homeostasis (Schömig et al, 1989; Xu et al, 2000). Altered sympathetic nerve terminal NET uptake sites and/or activity are found in hypertension, diabetes, cardiomyopathy, heart failure and ischemia (Böhm et al, 1998; Merlet et al, 1992; Rumantir et al, 2000; Schnell et al, 1996; Schömig et al, 1991). …”

Section: Introductionmentioning

confidence: 99%

Norepinephrine transporter variant A457P knock-in mice display key features of human postural orthostatic tachycardia syndrome

Shirey-Rice

Klar

Fentress

et al. 2013

Disease Models &Amp; Mechanisms

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SUMMARYPostural orthostatic tachycardia syndrome (POTS) is a common autonomic disorder of largely unknown etiology that presents with sustained tachycardia on standing, syncope and elevated norepinephrine spillover. Some individuals with POTS experience anxiety, depression and cognitive dysfunction. Previously, we identified a mutation, A457P, in the norepinephrine (NE; also known as noradrenaline) transporter (NET; encoded by SLC6A2) in POTS patients. NET is expressed at presynaptic sites in NE neurons and plays a crucial role in regulating NE signaling and homeostasis through NE reuptake into noradrenergic nerve terminals. Our in vitro studies demonstrate that A457P reduces both NET surface trafficking and NE transport and exerts a dominant-negative impact on wild-type NET proteins. Here we report the generation and characterization of NET A457P mice, demonstrating the ability of A457P to drive the POTS phenotype and behaviors that are consistent with reported comorbidities. Mice carrying one A457P allele (NET+/P) exhibited reduced brain and sympathetic NE transport levels compared with wild-type (NET+/+) mice, whereas transport activity in mice carrying two A457P alleles (NETP/P) was nearly abolished. NET+/P and NETP/P mice exhibited elevations in plasma and urine NE levels, reduced 3,4-dihydroxyphenylglycol (DHPG), and reduced DHPG:NE ratios, consistent with a decrease in sympathetic nerve terminal NE reuptake. Radiotelemetry in unanesthetized mice revealed tachycardia in NET+/P mice without a change in blood pressure or baroreceptor sensitivity, consistent with studies of human NET A457P carriers. NET+/P mice also demonstrated behavioral changes consistent with CNS NET dysfunction. Our findings support that NET dysfunction is sufficient to produce a POTS phenotype and introduces the first genetic model suitable for more detailed mechanistic studies of the disorder and its comorbidities.

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Reduced Myocardial 123I-Metaiodobenzylguanidine Uptake in Newly Diagnosed IDDM Patients

Cited by 60 publications

References 19 publications

Type 1 diabetes and cardiovascular disease

Type 1 diabetes and cardiovascular disease

What Do We Know and We Do Not Know About Cardiovascular Autonomic Neuropathy in Diabetes

Norepinephrine transporter variant A457P knock-in mice display key features of human postural orthostatic tachycardia syndrome

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