Topic Highlight
Copyright ©The Author(s) 2015.
World J Diabetes. Feb 15, 2015; 6(1): 30-36
Published online Feb 15, 2015. doi: 10.4239/wjd.v6.i1.30
Table 1 Published articles about the drug-induced hypoglycemia in patients with diabetes
Ref.SubjectsYearNationSettingOADInsulinCombination
Kim et al[27]Type 2 (n = 298)2004-2009South KoreaThe Emergency Department of two general hospitalsGlimepiride (24.2%) Gliclazide (5.4%) Glibenclamide (8.4%)NPH/RI (38.3%) Premixed (11.1%) Glargine/Detemir (13.1%)
Tsujimoto et al[28]Type 1 (n = 85)2006-2012JapanRetrospective cohort study in one medical centerInsulin (100%)
Type 2 (n = 305)SU (42.3%) Others (6.6%)Insulin (51.1%)
Signorovitch et al[29]Type 2 not treated with insulin (n = 5582)1998-2010United StatesUS-based employer claims databaseSU (38.2%) Biguanides (56.3%) a-GI (0.9%) Sitagliptin (1.0%) Incretin mimetics (0.5%) TZD (14.9%)
Moisan et al[30]Not determined (n = 3575)2000-2008CanadaInception cohort study using the database of the Quebec health insurance board and the Quebec registry of hospitalizationsSU (32.1%) Metformin (45.0%) SU + Metformin (12.3%) Others (2.1%)Insulin (8.5%)
Hsu et al[31]Type 2 (n = 500)1998-2009TaiwanA nationwide population-based study using the National Health Insurance Research DatabaseSU (67.8%) Others (61.4%)Insulin (24.2%)
Holstein et al[32]Type 1 (n = 92)1997-2000GermanA longitudinal population-based studyConventional (27.2%) Intensified (69.6%) CSII (3.3%)
Type 1 (n = 121)2007-2010Conventional (6.6%) Intensified (79.3%) CSII (13.2%)
Type 2 (n = 148)1997-2000SU (30.4%)Conventional (52.7%) Intensified (0%) CSII (0%)SU + Insulin (16.9%)
Type 2 (n = 225)2007-2010SU (29.8%) Metformin (0.9%)Conventional (40.8%) Intensified (21.8%) CSII (0%)SU + Insulin (6.7%)
Ha et al[33]Not determined (n = 320)2006-2009South KoreaRetrospective analysis of hypoglycemic patients presented to emergency room of Uijeongbu St. Mary’s HospitalGlimepiride (29.7%) Glibenclamide (4.7%) Gliclazide (4.7%) Gliquidone (1.3%) Glipizide (0.9%) Others (24.7%)Insulin (29.1%)SU + Insulin (5.0%)
Geller et al[34]Not determined (n = 8100)2007-2011United StatesNationally representative public health surveillance of adverse drug events among insulin-treated patients seeking emergency department careInsulin (83.4%)Insulin + Biguanide (8.5%) SU (6.6%) TZD (3.6%) DPP-4 inhibitors (1.3%) GLP-1 analogues (0.2%) Others (0.9%)
Ben-Ami et al[35]Type 1 and 2 (n = 99)1986-1992IsraelRetrospective analysis of the medical record in Rambam Medical CenterGlyburide (51.5%) Glyburide + Metformin (10.2%)Insulin (23.2%)Insulin + Glyburide (13.1%) Insulin + Metformin (2.0%)
Quilliam et al[36]Type 2 (n = 536581)2004-2008United StatesRetrospective cohort designed to assess the rate and costs of hypoglycemia among working-age patients with type 2 diabetes in the MarketScan databaseSU (42.3%) Metformin (75.7%) TZD (33.3%) Other oral agents (4.4%)Insulin (6.0%) Other injectable agents (2.7%)
Parsaik et al[37]Type 1 (n = 210)2003-2009United StatesPopulation-basedstudySimple insulin (10.0%) MDI (67.0%) CSII(18.0%)OAD + Insulin (1.0%)
Type 2 (n = 503)OAD (23.0%)Simple insulin (27.0%) MDI (37.0%) CSII (1.0%)OAD + Insulin(11.0%)
Table 2 Published articles about the underlying clinical factors for the development of hypoglycemia in patients with diabetes
Ref.Clinical factorsHypoglycemiaNo hypoglycemiaP value
Yaffe et al[49]Black race/ethnicity (%)72.144.9< 0.01
Education (< high school education) (%)36.124.00.04
Glycated hemoglobin level (%)8.07.2< 0.01
Prevalent diabetes mellitus (%)85.247.9< 0.01
MMSE score [mean (SD)]89.6 (5.7)91.5 (5.2)< 0.01
Hsu et al[31]Hypertension (%)63.651.2< 0.0001
Liver cirrhosis (%)3.01.30.0074
Renal disease (%)17.45.2< 0.0001
Mental disease (%)21.412.5< 0.0001
Cancer (%)8.02.4< 0.0001
Stroke (%)15.04.0< 0.0001
Heart disease (%)13.23.6< 0.0001
Leese et al[51]Age (mean, yr)
Type 1 treated with insulin37.732.80.009
Type 2 treated with insulin66.663.20.038
Diabetes duration (mean, years)
Type 1 treated with insulin20.716.70.013
BMI (mean, kg/m2)
Type 2 treated with insulin26.730.1< 0.001
Signorovitch et al[29]Mental disorders (%)15.211.4< 0.001
Neurological disorders (%)17.210.7< 0.001
Cardiovascular disorders (%)60.459.00.05
Renal disorders (%)16.512.3< 0.001
Epilepsy (%)1.20.7< 0.001
Stroke (%)4.92.9< 0.001
CCI [mean (SD)]1.42 (1.70)1.3< 0.001
Punthakee et al[50]Age [yr, mean (SD)]63.91 (6.41)62.41 (5.77)0.002
Female (%)55.646.10.019
Race< 0.0001
Non-Hispanic white (%)60.070.9
African American (%)30.015.4
Hispanic (%)6.37.1
Others (%)3.86.6
Education
Less than high school (%)16.312.8
High school graduate (%)35.025.2
Some college (%)26.935.10.01
College graduate (%)21.926.9
BMI [mean (SD), kg/m2]32.08 (5.64)33.03 (5.33)0.029
Diabetes duration [mean (SD) of years]14.13 (8.74)10.18 (7.22)< 0.0001
HbA1c (%)8.46 (1.06)8.27 (1.05)0.021
History of stroke (%)11.34.60.0002
History of cardiovascular disease (%)41.928.40.0003
Neuropathy score [mean (SD)]0.53 (0.50)0.45 (0.50)0.049
UACR (mg/mmol)< 0.0001
< 30 (%)58.872.4
30-300 (%)27.521.9
> 300 (%)13.85.7
DSST score [mean (SD)]46.45 (17.01)52.89 (15.76)< 0.0001
RAVLT score [mean (SD)]6.90 (2.72)7.55 (2.53)0.002
Stroop score [mean (SD)]37.69 (22.02)31.66 (16.25)< 0.0001
MMSE score [mean (SD)]26.83 (2.80)27.45 (2.49)0.002
Table 3 Summary of the underlying clinical factors for the development of hypoglycemia in patients with diabetes
1 Socioeconomic status (education, race)
2 Aging
3 State of diabetes (duration, HbA1c, body mass index)
4 Cognitive and mental function
5 Comorbidity
6 Failure of organ which influence on clearance of insulin and oral anti-diabetic drugs (Heart, liver, renal failure)
7 Hypoglycemia-associated autonomic failure