High risk of abnormal QT prolongation in the early morning in diabetic and non-diabetic patients with severe hypoglycemia

Figures & data

Table I. Characteristics of the study patients.

Characteristics	T1DM (n = 28)	T2DM (n = 164)	Non-DM (n = 95)
Age (years)	49 (40–59)	76 (65–83)	66 (53–78)
Female	17.9%	36.6%	33.7%
History of coronary heart disease^a	0.0%	12.8%	1.1%
Hypertension	32.1%	69.5%	17.9%
Atrial fibrillation	0.0%	14.0%	10.5%
Blood glucose (mg/dL) (n = 286)	25 (20–34)	31 (24–38)	45 (26–64)
HbA1c (%) (n = 82)^b	7.3 (6.8–7.7)	6.5 (6.0–7.2)	–
Duration of diabetes (years) (n = 112)	22 (16–29)	14 (6–23)	–
Treatment for diabetes
Sulfonylurea	0.0%	51.9%	–
Insulin	100%	45.6%	–
Estimated GFR (mL/min/1.73 m^2) (n = 278)^c	80.3 (61.6–89.3)	52.8 (29.8–77.4)	74.7 (48.8–100.1)
Serum potassium level (mEq/L) (n = 283)^d	3.4 (3.2–3.8)	3.6 (3.3–4.2)	3.8 (3.4–4.3)
Causes of severe hypoglycemia
Glucose-lowering medications	96.4%	94.5%	2.2%^e
Sulfonylurea	0.0%	48.7%	1.1%
Insulin	96.4%	43.7%	1.1%
Others	3.6%	5.5%	97.8%
Abnormal QT prolongation (QTc ≥ 0.44 s)^f	42.9%	60.4%	56.8%
Highly abnormal QT prolongation (QTc ≥ 0.50s)	0.0%	15.2%	22.1%

Data are presented as number, %, or median (IQR). SI conversion factors: to convert blood glucose to mmol/L, multiply by 0.0555.

^aHistory of coronary heart disease was defined as a history of myocardial infarction and angina pectoris.

^bHbA1c levels were measured at the nearest time within three months of arrival. T1DM: 7.3% (6.8%–7.7%) = 56 (51–61) mmoL/moL. T2DM: 6.5% (6.0%–7.2%) = 48 (42–55) mmoL/moL.

^cEstimated GFR was calculated using the following formula: estimated GFR (mL/min/1.73 m²) = 194 × Cre^{− 1.094} × Age^{− 0.287} (× 0.739 if the patient was female).

^dSerum potassium levels were measured upon arrival at the hospital.

^eOne patient attempted suicide using insulin, and one patient took a sulfonylurea incorrectly. Both patients were discharged safely from the hospital.

^fQTc was calculated using Bazett's formula: QTc = QT interval ÷ square root of the RR interval.

DM = diabetes; GFR = glomerular filtration rate; HbA1c = glycated hemoglobin; non-DM = no diabetes; T1DM = type 1 diabetes; T2DM = type 2 diabetes.

Figure 1. Circadian variations in rate of abnormal QT prolongation in patients with severe hypoglycemia. Rate of abnormal QT prolongation at each period in the DM and non-DM groups (A), and in the T1DM and T2DM groups (B). DM = diabetes; non-DM = no diabetes; T1DM = type 1 diabetes; T2DM = type 2 diabetes.

Figure 2. Circadian variations in blood pressure and heart rate in patients with severe hypoglycemia. Blood pressure and heart rate in the DM group (A) and non-DM group (B). Data are presented as median (IQR). The values for blood pressure and heart rate in the DM and non-DM groups did not differ significantly using Kruskal–Wallis tests. BP = blood pressure; bpm = beats per minute; HR = heart rate.

Figure 3. Rate of abnormal QT prolongation at night-time and in the early morning. Rate of abnormal QT prolongation at night-time and in the day-time (A) and in the early morning and at all other times (B).

Table II. Multivariate analysis of the clinical variables for abnormal QT prolongation during severe hypoglycemia at night-time.

Multivariate analysis (DM group)
Variables	Odds ratio	95% CI	P value
Age (years)	1.00	0.98–1.02	0.56
Female	1.07	0.54–2.11	0.83
History of coronary heart disease^a	0.46	0.17–1.22	0.12
Hypertension	1.39	0.68–2.81	0.35
Blood glucose on arrival (mg/dL)	0.98	0.96–1.00	0.06
Hypokalemia (< 3.5 mEq/L)^b	0.88	0.46–1.67	0.70
Severe hypoglycemia in the night-time	2.17	1.14–4.11	0.01

Multivariate analysis (non-DM group)
Variables	Odds ratio	95% CI	P value
Age (years)	1.03	1.00–1.06	0.01
Female	0.48	0.18–1.30	0.15
Hypertension	0.83	0.24–2.89	0.78
Blood glucose on arrival (mg/dL)	0.98	0.96–1.00	0.24
Hypokalemia (< 3.5 mEq/L)	1.11	0.40–3.08	0.83
Severe hypoglycemia in the night-time	4.07	1.44–11.44	0.008

^aCoronary heart disease was defined as myocardial infarction or angina pectoris.

^bSerum potassium levels were measured upon arrival at the hospital.

95% CI = 95% confidence interval.

Table III. Multivariate analysis of the clinical variables for abnormal QT prolongation during severe hypoglycemia in the early morning.

Multivariate analysis (DM group)
Variables	Odds ratio	95% CI	P value
Age (years)	1.00	0.98–1.02	0.64
Female	1.02	0.51–2.01	0.95
History of coronary heart disease^a	0.46	0.17–1.24	0.12
Hypertension	1.33	0.66–2.68	0.42
Blood glucose on arrival (mg/dL)	0.98	0.95–1.00	0.06
Hypokalemia (< 3.5 mEq/L)^b	0.94	0.49–1.80	0.86
Severe hypoglycemia in the early morning	2.80	1.15–6.80	0.02

Multivariate analysis (non-DM group)
Variables	Odds ratio	95% CI	P value
Age (years)	1.02	1.00–1.05	0.02
Female	0.55	0.20–1.47	0.23
Hypertension	0.78	0.23–2.67	0.70
Blood glucose on arrival (mg/dL)	0.98	0.96–1.00	0.13
Hypokalemia (< 3.5 mEq/L)	1.19	0.43–3.25	0.73
Severe hypoglycemia in the early morning	4.53	1.30–15.74	0.01

^aCoronary heart disease was defined as myocardial infarction or angina pectoris.

^bSerum potassium levels were measured upon arrival at the hospital.

95% CI = 95% confidence interval.