Severe hypoglycemia requiring medical assistance in patients with diabetes is associated with simultaneous prolongation of QTc interval

Transcription

1 Severe hypoglycemia requiring medical assistance in patients with diabetes is associated with simultaneous prolongation of QTc interval M. Mylona¹, G. Anastasiadis², K. Zerva², V. Vasgiourakis², K. Tsakalis², S. Liatis¹ ¹ Diabetes Center, First Department of Internal Medicine, Laiko Hospital, Athens, Athens, Greece, ² Department of Cardiology, Laiko Hospital, Athens, Athens, Greece.

2 CLINICAL DEFINITION OF HYPOGLYCEMIA Whipple's triad: Symptoms known or likely to be caused by hypoglycemia especially after fasting or heavy exercise A low plasma glucose measured at the time of the symptoms Relief of symptoms when the glucose is raised to normal

3 Plasma glucose mg/dl (mmol/l) 80 (4.4) Suppression of insulin release 70 (3.9) Clinical presentation NO SYMPTOMS Autonomic symptoms onset of counterregulatory hormone release Counterregulatory response or physical consequence Adrenaline Glucagon Cortisol Growth Factor 55 (3.1) Onset of cognitive dysfunction Neuroglycopenic symptoms 25 (1.3) Seizures Coma EEG changes

4 FREQUENCY OF HYPOGLYCEMIC EVENTS TYPE 1 DM Very common TYPE 2 DM Associated with: Duration of diabetes Degree of lack of insulin Treatment 1. Insulin 2. SUs 3. Glinides

5 QT interval =electrical depolarization and repolarization of the ventricles

6 QTc interval measurement The QT interval should be measured in either lead II or V5-6 Several successive beats should be measured, with the maximum interval taken. Large U waves (> 1mm) that are fused to the T wave should be included in the measurement. Smaller U waves and those that are separate from the T wave should be excluded.

7 QTc interval The corrected QT interval (QTc) estimates the QT interval at a heart rate of 60 bpm. This allows comparison of QT values over time at different heart rates and improves detection of patients at increased risk of arrhythmias. Bazett s formula: QTC = QT / RR Fredericia s formula: QTC = QT / RR 1/3 Framingham formula: QTC = QT (1 RR) Hodges formula: QTC = QT (heart rate 60)

8 QTc interval: Bazett s Formula QTc is prolonged, if > 440ms in men or > 460ms in women. QTc > 500 is associated with increased risk of torsades de pointes. CAUSES 1. Hypokalemia 2. Hypomagnesaemia 3. Hypocalcaemia 4. Hypothermia 5. Myocardial ischemia 6. Post-cardiac arrest 7. Raised intracranial pressure 8. Congenital long QT syndrome 9. DRUGS

9 AIM OF STUDY It has been shown that hypoglycemia induces multiple pre-arrhythmic changes, mainly increase pre-existent QT prolongation, produce intracellular Ca2+ overload, and decrease serum K+. As a consequence, hypoglycemia is considered a state that may lead to sudden death, as a result of cardiac arrhythmia. Few data, however, directly link episodes of severe hypoglycemia with pre-arrhythmic conditions, such as QT prolongation. Aim of our study was to explore the association between severe hypoglycemic events requiring medical assistance and QTc interval, in diabetic patients.

10 METHODS (1) Prospective survey (16-month) of documented iatrogenic hypoglycemia at the emergency departments (ED). 8 general hospitals participated: Laiko (2 clinics) Lamia Nikaia Larissa Tzaneio Agrinio Konstantopouleio Volos Frequency of hypoglycemic events/ characteristics of diabetic patients versus matched control group Liatis S et al, Diabetes Metab Apr;41(2):126-31

11 METHODS (2) According to the protocol, a 12-lead ECG was obtained simultaneously or immediately after the management of hypoglycemia and no later than 30 minutes after the administration of glucose. The ECGs obtained from hypoglycemic patients were compared to those from a control group consisted of patients with diabetes, matched for age and gender, visiting the outpatient diabetes clinics of the same hospitals, during the same time period.

12 METHODS (3) QT and RR intervals were measured blindly by three independent cardiologists. QTc was calculated according to the Bazett formula: QTc = QT interval/square root of the R-R interval. QTc measurements of 440msec were considered abnormally prolonged and those of 500msec as highly prolonged. Patients receiving medications possibly affecting the QTc interval and those with hypokalaemia (serum potassium < 3.5mEq/l) were excluded from the analysis.

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14 FACTORS CONNECTED WITH SEVERE HYPOGLYCEMIA

15 PATIENTS DATA 177 ECGs from hypoglycemic patients were analyzed mean age 72.7±15.7 years, 48.6% women, 9% with type 1 diabetes. These were compared to 91 age and gender matched controls.

16 SU = sulfonylureas, MET = Metformin, DDP-4 = DDP-4 inhibitors TZD = thiazolidinediones, CAD = history of coronary artery disease PATIENTS DATA Patients Controls p Age(±SD) 72.7 (±15.7) (±11.4) NS Duration of DM (years ±SD) 15.6 (±4.0) 16.3 (±9.3) NS Males (%) 91 (51.4%) 44 (48.4%) NS Type 1 diabetes 16 (9.2%) 6 (7.9%) NS Insulin 94 (53.1%) 49 (53.8%) NS SU 99 (56.3%) 12 (10.8%) <0.001 MET 77 (43.8%) 56 (42.1%) NS DDP-4 18 (10.1%) 15 (16.4%) NS TZD 7 (3.9%) 1 (1.09%) NS CAD 65 (36.7%) 20 (21.9%) 0.07

17 Mean QTc interval in patients with hypoglycemia and controls P<0.001

18 Proportion of individuals with QTc > 440msec P< patients with QTc ( 500msec) (7.9%) and none in the control group. Severe iatrogenic hypoglycemia requiring medical assistance is associated with a both statistically and clinically significant prolongation of QTc interval.

19 QTc correlation QTc did not correlate with variables such as: gender age type of diabetes duration of diabetes

20 Discussion

21 ACUTE EPISODE HYPOGLYCEMIA DIRECTLY: CNS CARDIOVASCULAR SYSTEM INDIRECTLY: TRAUMA FEAR OF NEXT HYPOGLYCEMIC EVENT

22 ~85000 patients > 65 years old 440 events mortality: x 3.2 in hospitalized patients After statistical analysis: x 2.5 Mujamdar et al. Diabetes Care 2013; 3585-

23 SUDDEN DEATHS IN DIABETICS Dead in bed syndrome Sudden unexplained death in diabetics at night Tattersall RB, Gill GV. Unexplained deaths of type 1 diabetic patients. Diabet Med 1991; 8:49-58.

24 Registered dead in bed syndrome Σύνδρομο Dead in bed Αιφνίδιος ανεξήγητος θάνατος σε άτομο με διαβήτη τη νύχτα Cases of T1DM patients found dead in bed during the night Practical Diabetes 2013; 30(1): 33 35

25 Mechanisms of cardiovascular damage in hypoglycemia Σύνδρομο Dead in bed Αιφνίδιος ανεξήγητος θάνατος σε άτομο με διαβήτη τη νύχτα Tattersall RB, Gill GV. Unexplained deaths of type 1 diabetic patients. Diabet Med 1991; 8:49-58.

26 Electrocardiographic changes during hypoglycemia Pre-arrythmic changes QT prolongation ST fragment depression Premature ventricular contractions SR bradycardia Diabetologia 2009: 42

27 CONCLUSIONS In patients with diabetes, severe iatrogenic hypoglycemia requiring medical assistance is associated with a both statistically and clinically significant prolongation of QTc interval.

28 ΣΑΣ ΕΥΧΑΡΙΣΤΩ