Genetic Studies of “Dead in Bed Syndrome” in Young Australians with Type 1 Diabetes

Since the autoimmune nature of type 1 diabetes mellitus came to become known some 40 years ago, continuous investigations have been carried out in an attempt to improve approaches to prognostication of this disease and develop new safe and efficacious methods for its prevention. For all that, many aspects of diabetes pathogenesis still remain far from clear. In most cases (roughly 85%), type 1 diabetes mellitus (DM1) develops sporadically in the absence of a relevant familial or hereditary history of this condition. Accordingly, the first-degree relatives account for only 15% of all DM1 patients. The risk of development of DM1 in the Russian population estimated by the researchers of the Children' Department, Endocrinological Research Centre, is relatively low (0.2%). It depends on many factors, such as the number of ill and healthy relatives, the chronological age of a given patient and the age of onset of clinical manifestations in his (her) relatives. Type 1 diabetes-predisposing and protective haplotypes were identified in the Russian population based on the results of molecular-genetic studies involving 599 children and adolescents with DM1. These and immunological data were used to distinguish between risk groups in the families of diabetic patients and the rationale was proposed for the dynamic follow-up of these subjects. It is concluded that estimation of the risk of type 1 diabetes mellitus based on the results of molecular-genetic studies and monitoring immunological markers constitutes the first step in the elaboration of preventive measures designed to prevent or delay the development of the disease.

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Abstract P005: Evaluation of the Association between the Free Fatty Acid to serum Albumin Ratio with the Time to Cardiac Repolarization

Circulation ◽

10.1161/circ.129.suppl_1.p005 ◽

2014 ◽

Vol 129 (suppl_1) ◽

Author(s):

Baqiyyah N Conway ◽

Rhobert W Evans ◽

Orchard Trevor

Keyword(s):

Type 1 Diabetes ◽

Fatty Acid ◽

Free Fatty Acid ◽

Serum Albumin ◽

Colorimetric Method ◽

Albumin Excretion Rate ◽

Cardiac Autonomic Neuropathy ◽

Cardiac Repolarization ◽

Dead In Bed Syndrome

Background: Elevated free fatty acid (FFA) levels have been shown to increase cardiac repolarization time and are a hypothesized mediator of arrhythmic death. However, as albumin binds and transports FFA, it has been argued that it is the ratio of serum FFA to serum albumin (SA) that is critical. As FFA are chronically elevated in type 1 diabetes and form a major part of the counterregulatory response to hypoglycemia, we investigated the association of the FFA-to-SA ratio with the corrected Q-T (Q-Tc) interval in 87 men and 96 women with type 1 diabetes from the Pittsburgh Epidemiology of Diabetes Complications Study. We also investigated whether this relationship varied by cardiac autonomic neuropathy (CAN: R-R interval<1.1) status. Methods: FFAs were measured using a colorimetric method in participants with a mean age and diabetes duration of 44 and 33 years, respectively. The corrected Q-T interval was calculated using Hogdes formula and the FFA-SA ratio determined as FFA (mmol/L) ÷ SA (mg/dL). Because of the sexual dimorphism in FFA metabolism and the Q-T interval, analyses were also conducted sex-specifically. Results: Mean (std) FFA levels were 0.95 (o.48) mmol/l and did not vary by sex (men vs women: 0.93 (0.46) vs 0.96 (0.49) mmol/L, p=0.76). The FFA-SA ratio demonstrated a modest association with Q-Tc interval in men (r=0.23, p=0.03), but no association in women (r=-0.07, p=0.48). Overall, in multivariable analyses controlling for sex, visceral adipose tissue, blood glucose levels and albumin excretion rate, FFA-SA, and CAN, a significant interaction was observed between the FFA-SA ratio and CAN in the association of the Q-Tc interval (p=0.03). FFA remained significantly associated with the Q-Tc interval in those without CAN (p<0.05), but not in those with CAN (p=0.30). Sex-specific analyses revealed that although no significant FFA-SA ratio and CAN interaction was observed in men (p=0.42), a relationship between the FFA-SA ratio and Q-Tc interval existed in men free of CAN (p=0.04). No association was observed in women with or without CAN. Conculsion: We conclude that a higher FFA-SA ratio is associated with an increased time to cardiac repolarization in those without CAN, particularly in men, helping to explain why the "dead in bed" syndrome is predominantly seen in men.

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Hypoglycaemia and cardiac arrhythmias in diabetes

Therapeutic Advances in Endocrinology and Metabolism ◽

10.1177/2042018820911803 ◽

2020 ◽

Vol 11 ◽

pp. 204201882091180

Author(s):

Andreas Andersen ◽

Peter G. Jørgensen ◽

Filip K. Knop ◽

Tina Vilsbøll

Keyword(s):

Type 2 Diabetes ◽

Type 1 Diabetes ◽

Cardiac Arrhythmias ◽

Severe Hypoglycaemia ◽

Qt Prolongation ◽

Cardiac Autonomic Neuropathy ◽

Consistent Finding ◽

Dead In Bed Syndrome

Hypoglycaemia remains an inevitable risk in insulin-treated type 1 diabetes and type 2 diabetes and has been associated with multiple adverse outcomes. Whether hypoglycaemia is a cause of fatal cardiac arrhythmias in diabetes, or merely a marker of vulnerability, is still unknown. Since a pivotal report in 1991, hypoglycaemia has been suspected to induce cardiac arrhythmias in patients with type 1 diabetes, the so-called ‘dead-in-bed syndrome’. This suspicion has subsequently been supported by the coexistence of an increased mortality and a three-fold increase in severe hypoglycaemia in patients with type 2 diabetes receiving intensive glucose-lowering treatment in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial. Studies have investigated the association between hypoglycaemia-induced cardiac arrhythmias. In a rat-model, severe hypoglycaemia resulted in a specific pattern of cardiac arrhythmias including QT-prolongation, ventricular tachycardia, second- and third-degree AV block and ultimately cardiorespiratory arrest. In clinical studies of experimentally induced hypoglycaemia, QTc-prolongation, a risk factor of ventricular arrhythmias, is an almost consistent finding. The extent of QT-prolongation seems to be modified by several factors, including antecedent hypoglycaemia, diabetes duration and cardiac autonomic neuropathy. Observational studies indicate diurnal differences in the pattern of electrocardiographic alterations during hypoglycaemia with larger QTc-prolongations during daytime, whereas the risk of bradyarrhythmias may be increased during sleep. Daytime periods of hypoglycaemia are characterized by shorter duration, increased awareness and a larger increase in catecholamines. The counterregulatory response is reduced during nightly episodes of hypoglycaemia, resulting in prolonged periods of hypoglycaemia with multiple nadirs. An initial sympathetic activity at plasma glucose nadir is replaced by increased vagal activity, which results in bradycardia. Here, we provide an overview of the existing literature exploring potential mechanisms for hypoglycaemia-induced cardiac arrhythmias and studies linking hypoglycaemia to cardiac arrhythmias in patients with diabetes.

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