Acute hypoglycemia and risk of cardiac arrhythmias in insulin-treated type 2 diabetes and controls

Abstract

Objective. Hypoglycemia is associated with increased risk of cardiovascular disease including cardiac arrhythmias. We investigated the effect of hypoglycemia in the setting of acute glycemic fluctuations on cardiac rhythm and cardiac repolarization in insulin-treated patients with type 2 diabetes compared with matched controls without diabetes. Design. A non-randomised, mechanistic intervention study Methods. Insulin-treated patients with type 2 diabetes (n=21, [mean±SD] age 62.8±6.5 years, BMI 29.0±4.2 kg/m2, HbA1c 6.8±0.5% [51.0±5.4 mmol/mol]) and matched controls (n=21, age 62.2±8.3 years, BMI 29.2±3.5 kg/m2, HbA1c 5.3±0.3% [34.3±3.3 mmol/mol]) underwent a sequential hyperglycemic and hypoglycemic clamp with three steady-states of plasma glucose: 1) fasting plasma glucose, 2) hyperglycemia (fasting plasma glucose+10 mmol/L) and 3) hyperinsulinemic hypoglycemia (plasma glucose<3.0 mmol/L). Participants underwent continuous ECG monitoring and blood samples for counterregulatory hormones and plasma potassium were obtained. Results. Both groups experienced progressively increasing heart rate corrected QT (Fridericia’s formula)) interval prolongations during hypoglycemia ([∆mean (95% CI)] 31 ms [16, 45] and 39 ms [24, 53] in the group of patients with type 2 diabetes and controls, respectively) with similar increases from baseline at the end of the hypoglycemic phase (P=0.43). The incidence of ventricular premature beats increased significantly in both groups during hypoglycemia (P=0.033 and P<0.0001, respectively). One patient with type 2 diabetes developed atrial fibrillation during recovery from hypoglycemia. Conclusions. In insulin-treated patients with type 2 diabetes and controls without diabetes, hypoglycemia causes clinically significant and similar increases in cardiac repolarization that might increase vulnerability for serious cardiac arrythmias and sudden cardiac death.

Acute changes in plasma glucose increases left ventricular systolic function in insulin‐treated patients with type 2 diabetes and controls

“…Detailed data on baseline characteristics were previously published elsewhere 7 and are therefore included in Table S1. Both the groups consisted of 24% women, and age and BMI were similar in the T2D group (62.8 ± 6.5 years, BMI 29.0 ± 4.2 kg/m 2 , HbA1c 51.0 ± 5.4 mmol/mol [6.8 ± 0.5%]) and the control group (age 62.2 ± 8.3 years, BMI 29.2 ± 3.5 kg/m 2 , HbA1c 34.3 ± 3.3 mmol/mol [5.3 ± 0.3%]).…”

“…Furthermore, four patients with T2D and one participant in the control group were unable to complete the experimental day, mainly due to vasovagal symptoms, nausea and vomiting during the decline in PG and were subsequently replaced, which could potentially have biased the data. 7 The reported changes in cardiac function during hypoglycaemia should be seen in the context of rapid glycaemic fluctuations. Nevertheless, rapid and large glycaemic fluctuations are not unusual in patients with insulintreated T2D.…”

“…Detailed data on baseline characteristics were previously published elsewhere 7 and are therefore included in Table S1. Both the groups consisted of 24% women, and age and BMI were similar and LDL cholesterol was lower in patients with T2D (1.9 ± 0.6 vs. 3.2 ± 1.1).…”

Celebrities in the heart, strangers in the pancreatic beta cell: Voltage‐gated potassium channels Kv7.1 and Kv11.1 bridge long QT syndrome with hyperinsulinaemia as well as type 2 diabetes

“…Acute hypoglycaemia has not just been associated with a prolonged QT interval, but also with cardiac arrhythmia 145 . Hypoglycaemic events increase both the QTc interval and the incidence of ventricular premature beats, both in individuals with and without diabetes 147 . Hypoglycaemia has also been implicated in the nocturnal ‘dead‐in‐bed’ syndrome in patients with diabetes, in particular in those with type 1 diabetes in the setting of intensive glycaemic control 148 …”

“…145 Hypoglycaemic events increase both the QTc interval and the incidence of ventricular premature beats, both in individuals with and without diabetes. 147 Hypoglycaemia has also been implicated in the nocturnal 'dead-in-bed' syndrome in patients with diabetes, in particular in those with type 1 diabetes in the setting of intensive glycaemic control. 148 Since any prolongation of the QTc is particularly precarious in the setting of an already prolonged QT interval, 149 blood glucose monitoring may be considered in the treatment of LQTS.…”