Cardiac arrhythmia and nocturnal hypoglycaemia in type 1 diabetes—the ‘dead in bed’ syndrome revisited

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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Use of continuous glucose monitoring trend arrows in the younger population with type 1 diabetes

Diabetes and Vascular Disease Research ◽

10.1177/14791641211062155 ◽

2021 ◽

Vol 18 (6) ◽

pp. 147916412110621

Author(s):

Nancy Elbarbary ◽

Othmar Moser ◽

Saif Al yaarubi ◽

Hussain Alsaffar ◽

Adnan Al Shaikh ◽

...

Keyword(s):

Type 1 Diabetes ◽

Young People ◽

Continuous Glucose Monitoring ◽

Glucose Monitoring ◽

Vascular Complications ◽

Rate Of Change ◽

Rapid Expansion ◽

Nocturnal Hypoglycaemia ◽

Glucose Levels

Early control of glycaemia is key to reduce vascular complications in individuals with Type 1 diabetes. Therefore, encouraging children and adolescents with T1DM to take responsibility for controlling glucose levels is an important yet a challenging task. The rapid expansion of continuous glucose monitoring (CGM) systems has allowed for more comprehensive analysis of glycaemia in T1D. Moreover, CGM devices have the ability to calculate rate of change in glucose levels and display the information as trend arrows. In turn, this can help to take evasive actions to return glucose levels to near physiological glycaemia, which can be highly motivating for young people with T1DM. In the absence of standardised, evidence-based guidance, this consensus document, generated by experts from the Arab Society of Paediatric Endocrinology and Diabetes and international advisors, summarises recent literature on the use of trend arrows in young people with T1DM. The use of trend arrows in different CGM systems is reviewed and their clinical significance is highlighted. Adjusting insulin doses according to trend arrows is discussed while also addressing special situations, such as exercise, fasting, nocturnal hypoglycaemia and menstruation. Adequate understanding of trend arrows should facilitate optimisation of glycaemic control in the T1D population.

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Changes in cardiac repolarisation during spontaneous nocturnal hypoglycaemia in subjects with type 1 diabetes: a preliminary report

Acta Diabetologica ◽

10.1007/s00592-016-0941-2 ◽

2016 ◽

Vol 54 (3) ◽

pp. 251-256 ◽

Cited By ~ 7

Author(s):

Minna L. Koivikko ◽

Tuomas Kenttä ◽

Pasi I. Salmela ◽

Heikki V. Huikuri ◽

Juha S. Perkiömäki

Keyword(s):

Type 1 Diabetes ◽

Preliminary Report ◽

Nocturnal Hypoglycaemia ◽

Cardiac Repolarisation

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A systematic review of the effect of prior hypoglycaemia on cognitive function in type 1 diabetes

Therapeutic Advances in Endocrinology and Metabolism ◽

10.1177/2042018820906017 ◽

2020 ◽

Vol 11 ◽

pp. 204201882090601

Author(s):

Suresh Rama Chandran ◽

Peter Jacob ◽

Pratik Choudhary

Keyword(s):

Systematic Review ◽

Type 1 Diabetes ◽

Early Childhood ◽

Cognitive Function ◽

Older Age ◽

Nocturnal Hypoglycaemia ◽

Adult Onset ◽

Onset Diabetes ◽

The Impact

Background: The effect of prior hypoglycaemia on cognitive function in type 1 diabetes is an important unresolved clinical question. In this systematic review, we aimed to summarize the studies exploring the impact of prior hypoglycaemia on any aspect of cognitive function in type 1 diabetes. Methods: We used a multidatabase search platform Healthcare Database Advanced Search to search Medline, PubMed, EMBASE, EMCARE, CINAHL, PsycINFO, BNI, HMIC, and AMED from inception until 1 May 2019. We included studies on type 1 diabetes of any age. The outcome measure was any aspect of cognitive function. Results: The 62 studies identified were grouped as severe hypoglycaemia (SH) in childhood (⩽18 years) and adult-onset (>18 years) diabetes, nonsevere hypoglycaemia (NSH) and nocturnal hypoglycaemia (NH). SH in early childhood-onset diabetes, especially seizures and coma, was associated with poorer memory (verbal and visuospatial), as well as verbal intelligence. Among adult-onset diabetes, SH was associated with poorer cognitive performance in the older age (>55 years) group only. Early versus late exposure to SH had a significant association with cognitive dysfunction (CD). NSH and NH did not have any significant association with CD, while impaired awareness of hypoglycaemia was associated with poorer memory and cognitive-processing speeds. Conclusion: The effect of SH on cognitive function is age dependent. Exposure to SH in early childhood (<10 years) and older age groups (>55 years) was associated with a moderate effect on the decrease in cognitive function in type 1 diabetes [PROSPERO ID: CRD42019141321].

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