J Clin Med Res

Journal of Clinical Medicine Research, ISSN 1918-3003 print, 1918-3011 online, Open Access

Article copyright, the authors; Journal compilation copyright, J Clin Med Res and Elmer Press Inc

Journal website http://www.jocmr.org

Original Article

Volume 11, Number 3, March 2019, pages 213-218

Risk Factors of Hypoglycemic Encephalopathy and Prolonged Hypoglycemia in Patients With Severe Hypoglycemia

Figure 2. Major causative anti-hyperglycemic agents of severe hypoglycemia in the overall patient population (n = 173) (a) and those with type 2 diabetes (n = 119) (b).

Figure 3. Distribution of age and eGFR in sulfonylurea- or insulin-induced severe hypoglycemia. Black circles indicate sulfonylurea-induced hypoglycemia, white circles indicate insulin-induced hypoglycemia, and gray circles indicate other severe hypoglycemic patients.

**Table 1.** Baseline Demographic and Clinical Parameters of Participants (n = 173)
Overall clinical parameters
Data are expressed as mean ± standard deviation (SD), and skewed variables are described as median and interquartile range. BMI: body mass index; HbA1c: glycated hemoglobin; eGFR: estimated glomerular filtration rate.
Type of diabetes
Type 1 diabetes, n (%)	33 (19.1)
Type 2 diabetes, n (%)	119 (68.8)
Others, n (%)	21 (12.1)
Age (years)	73 (64 - 81)
Male, n (%)	89 (51.4)
Duration of diabetes (years)	20.1 ± 10.5
BMI (kg/m²)	22.8 ± 4.4
eGFR (mL/min/1.73 m²)	56.8 (26.6 - 78.5)
Blood glucose (mg/dL)	32.1 ± 11.1
HbA1c (%)	7.2 (6.2 - 7.9)
Causes of hypoglycemia
Medication, n (%)	168 (97.1)
Alcohol abuse, n	1 (0.6)
Others, n	4 (2.3)
Severe complications
No, n (%)	162 (93.6)
Yes, n (%)	11 (6.4)
Complications, n
Cardiovascular disease	2
Death	7
Others (fracture, subdural hemorrhage)	2
Prior history of severe hypoglycemia
No, n (%)	130 (75.1)
Yes, n (%)	43 (24.9)

Table 1. Baseline Demographic and Clinical Parameters of Participants (n = 173)

Overall clinical parameters

Data are expressed as mean ± standard deviation (SD), and skewed variables are described as median and interquartile range. BMI: body mass index; HbA1c: glycated hemoglobin; eGFR: estimated glomerular filtration rate.

Type of diabetes

Type 1 diabetes, n (%)

33 (19.1)

Type 2 diabetes, n (%)

119 (68.8)

Others, n (%)

21 (12.1)

Age (years)

73 (64 - 81)

Male, n (%)

89 (51.4)

Duration of diabetes (years)

20.1 ± 10.5

BMI (kg/m²)

22.8 ± 4.4

eGFR (mL/min/1.73 m²)

56.8 (26.6 - 78.5)

Blood glucose (mg/dL)

32.1 ± 11.1

HbA1c (%)

7.2 (6.2 - 7.9)

Causes of hypoglycemia

Medication, n (%)

168 (97.1)

Alcohol abuse, n

1 (0.6)

Others, n

4 (2.3)

Severe complications

No, n (%)

162 (93.6)

Yes, n (%)

11 (6.4)

Complications, n

Cardiovascular disease

Death

Others (fracture, subdural hemorrhage)

Prior history of severe hypoglycemia

No, n (%)

130 (75.1)

Yes, n (%)

43 (24.9)

**Table 2.** Comparison of Age and Renal Function Between Insulin and Sulfonylurea Users With Severe Hypoglycemia
	Insulin (n = 102)	Sulfonylurea (n = 61)	Other (n = 10)
eGFR: estimated glomerular filtration rate. *P < 0.001 vs. insulin users.
Age (years)	69 (57.3 - 79)	77 (72.0 - 84)*	74 (68.5 - 80.8)
eGFR (mL/min/1.73 m²)	64.9 (27.4 - 86.7)	52.9 (28.3 - 67.4)	31.0 (13.6 - 55.1)

Table 2. Comparison of Age and Renal Function Between Insulin and Sulfonylurea Users With Severe Hypoglycemia

Insulin (n = 102)

Sulfonylurea (n = 61)

Other (n = 10)

eGFR: estimated glomerular filtration rate. *P < 0.001 vs. insulin users.

Age (years)

69 (57.3 - 79)

77 (72.0 - 84)*

74 (68.5 - 80.8)

eGFR (mL/min/1.73 m²)

64.9 (27.4 - 86.7)

52.9 (28.3 - 67.4)

31.0 (13.6 - 55.1)

**Table 3.** Difference Between the Hypoglycemic Encephalopathy Group and the Severe Hypoglycemic Group
Clinical parameters	HE (n = 94)	GCS ≥ 12 (n = 79)	P value	Presence of data (%)
Data are expressed as mean ± standard deviation (SD), and skewed variables are described as median and interquartile range. eGFR: estimated glomerular filtration rate.
Type 1 diabetes (%)	15 (16.0)	18 (22.8)	0.319
Age (years)	73 (66.3 - 81)	72 (63.5 - 80.5)	0.364
Sex (male, n/female, n)	49/45	40/39	0.845
Causes of hypoglycemia
Medication, n	91	77
Alcohol abuse, n	1	0
Others, n	2	2
Causative drugs
Insulin-induced, n (%)	53 (56.4)	49 (62.0)
Sulfonylurea induced, n (%)	35 (37.2)	26 (32.9)
Others, n (%)	6 (6.4)	4 (5.1)
Time to hospital (min)	41 (31 - 49.8)	39 (31 - 52.0)	0.577	86.2/82.3
Blood glucose (mg/dL)	28.8 ± 11.3	36.0 ± 9.7	< 0.001	100/100
eGFR (mL/min/1.73 m²)	63.1 (28.75 - 79.2)	49.9 (21.1 - 74.6)	0.286	93.6/92.4
Body temperature (°C)	35.8 (35.4 - 36.5)	36.0 (35.7 - 36.3)	0.812	78.7/78.5
Lactic acid (mmol/L)	11.8 (9.6 - 16.35)	9.5 (8.2 - 13.7)	0.176	54.3/21.5
Sodium (mEq/L)	138.5 ± 4.7	139.2 ± 4.4	0.346	97.9/94.9
Potassium (mEq/L)	3.9 ± 0.8	4.1 ± 1.0	0.226	97.9/94.9
Prior history of severe hypoglycemia, n (%)	25 (26.6)	18 (22.8)	0.563

Table 3. Difference Between the Hypoglycemic Encephalopathy Group and the Severe Hypoglycemic Group

Clinical parameters

HE (n = 94)

GCS ≥ 12 (n = 79)

P value

Presence of data (%)

Data are expressed as mean ± standard deviation (SD), and skewed variables are described as median and interquartile range. eGFR: estimated glomerular filtration rate.

Type 1 diabetes (%)

15 (16.0)

18 (22.8)

0.319

Age (years)

73 (66.3 - 81)

72 (63.5 - 80.5)

0.364

Sex (male, n/female, n)

49/45

40/39

0.845

Causes of hypoglycemia

Medication, n

Alcohol abuse, n

Others, n

Causative drugs

Insulin-induced, n (%)

53 (56.4)

49 (62.0)

Sulfonylurea induced, n (%)

35 (37.2)

26 (32.9)

Others, n (%)

6 (6.4)

4 (5.1)

Time to hospital (min)

41 (31 - 49.8)

39 (31 - 52.0)

0.577

86.2/82.3

Blood glucose (mg/dL)

28.8 ± 11.3

36.0 ± 9.7

< 0.001

100/100

eGFR (mL/min/1.73 m²)

63.1 (28.75 - 79.2)

49.9 (21.1 - 74.6)

0.286

93.6/92.4

Body temperature (°C)

35.8 (35.4 - 36.5)

36.0 (35.7 - 36.3)

0.812

78.7/78.5

Lactic acid (mmol/L)

11.8 (9.6 - 16.35)

9.5 (8.2 - 13.7)

0.176

54.3/21.5

Sodium (mEq/L)

138.5 ± 4.7

139.2 ± 4.4

0.346

97.9/94.9

Potassium (mEq/L)

3.9 ± 0.8

4.1 ± 1.0

0.226

97.9/94.9

Prior history of severe hypoglycemia, n (%)

25 (26.6)

18 (22.8)

0.563

**Table 4.** Difference in Clinical Parameters Between the Prolonged and Recovered Groups of Patients With Hypoglycemic Encephalopathy
Clinical parameters	Prolonged (n = 12)	Recovered (n = 82)	P value	Presence of data (%)
Data are expressed as mean ± standard deviation (SD), and skewed variables are described as median and interquartile range. SU: sulfonylurea; eGFR: estimated glomerular filtration rate.
Type 1 diabetes, n (%)	1 (8.3)	14 (17.1)	1.000	75/90.2
Age (years)	73 (65.5 - 82.5)	73 (67.0 - 80.8)	0.883
Sex (male, n/female, n)	6/6	43/39	1.000
Causes of hypoglycemia
Medication, n	10	81
Alcohol abuse, n	1	0
Others, n	1	1
Causative drugs
Insulin induced, n (%)	5 (41.7)	48 (58.5)
Sulfonylurea induced, n (%)	4 (33.3)	31 (37.8)
Others, n (%)	3 (25.0)	3 (3.7)
Time to hospital (min)	54 (41.0 - 79.5)	41 (30.5 - 48.0)	0.051	91.7/86.6
Blood glucose (mg/dL)	22.2 ± 14.1	29.8 ±10.6	0.028	100/100
eGFR (mL/min/1.73 m²)	69.7 ± 27.5	56.7 ± 37.3	0.250	100/92.7
Body temperature (°C)	36.6 ± 1.15	35.8 ± 0.66	0.002	83.3/78.0
< 35 (°C), n (%)	0 (0)	6 (8.8)	0.587
Lactic acid (mmol/L)	17.2 (12.25 - 22.6)	11.3 (8.9 - 14.6)	0.084	91.7/48.8
Sodium (mEq/L)	140 (132.8 - 141.5)	140 (137.0 - 141.0)	0.820	100/97.6
Potassium (mEq/L)	4.00 ± 0.81	3.8 ± 0.76	0.574	100/97.6
Prior history of severe hypoglycemia, n (%)	3 (25)	22 (26.8)	1.000

Table 4. Difference in Clinical Parameters Between the Prolonged and Recovered Groups of Patients With Hypoglycemic Encephalopathy

Clinical parameters

Prolonged (n = 12)

Recovered (n = 82)

P value

Presence of data (%)

Data are expressed as mean ± standard deviation (SD), and skewed variables are described as median and interquartile range. SU: sulfonylurea; eGFR: estimated glomerular filtration rate.

Type 1 diabetes, n (%)

1 (8.3)

14 (17.1)

1.000

75/90.2

Age (years)

73 (65.5 - 82.5)

73 (67.0 - 80.8)

0.883

Sex (male, n/female, n)

6/6

43/39

1.000

Causes of hypoglycemia

Medication, n

Alcohol abuse, n

Others, n

Causative drugs

Insulin induced, n (%)

5 (41.7)

48 (58.5)

Sulfonylurea induced, n (%)

4 (33.3)

31 (37.8)

Others, n (%)

3 (25.0)

3 (3.7)

Time to hospital (min)

54 (41.0 - 79.5)

41 (30.5 - 48.0)

0.051

91.7/86.6

Blood glucose (mg/dL)

22.2 ± 14.1

29.8 ±10.6

0.028

100/100

eGFR (mL/min/1.73 m²)

69.7 ± 27.5

56.7 ± 37.3

0.250

100/92.7

Body temperature (°C)

36.6 ± 1.15

35.8 ± 0.66

0.002

83.3/78.0

< 35 (°C), n (%)

0 (0)

6 (8.8)

0.587

Lactic acid (mmol/L)

17.2 (12.25 - 22.6)

11.3 (8.9 - 14.6)

0.084

91.7/48.8

Sodium (mEq/L)

140 (132.8 - 141.5)

140 (137.0 - 141.0)

0.820

100/97.6

Potassium (mEq/L)

4.00 ± 0.81

3.8 ± 0.76

0.574

100/97.6

Prior history of severe hypoglycemia, n (%)

3 (25)

22 (26.8)

1.000