Article Figures & Data
Tables
Characteristic Value Disease and treatment history Diabetes duration, No. (%) <1 year 31 (3.5) 1-2 years 65 (7.2) 3-4 years 85 (9.5) ≥5 years 717 (79.8) Diabetes duration, mean (SD), y 14.0 (9.8) Current use of hypoglycemic agents, No. (%) Insulin only 530 (59.0) Sulfonylurea only 313 (34.9) Sulfonylurea and insulin 55 (6.1) Duration of insulin use, No. (%)a <1 year 103 (17.6) 1-2 years 142 (24.3) 3-4 years 106 (18.1) ≥5 years 234 (40.0) Duration of sulfonylurea use, No. (%)b <1 year 23 (6.3) 1-2 years 59 (16.1) 3-4 years 59 (16.1) ≥5 years 225 (61.5) Sociodemographics Sex, No. (%) Male 443 (49.3) Female 455 (50.7) Age group, No. (%) 20-39 years 61 (6.8) 40-69 years 643 (71.6) 70-89 years 194 (21.6) Age, mean (SD), y 59.9 (12.3) Highest education level, No. (%) Illiteracy/elementary 268 (29.8) Junior high 170 (18.9) Senior high 263 (29.3) College and above 197 (21.9) Marital status, No. (%) Married 675 (75.2) Single 104 (11.6) Widowed/divorced 119 (13.3) Disease and treatment history Residence, No. (%) Urban 482 (53.7) Rural 416 (46.3) Occupation, No. (%) Services workers 100 (11.1) Housekeepers 152 (16.9) Manufacturing, construction, sales 207 (23.1) Not actively employed 328 (36.5) Otherc 111 (12.4) Living arrangement, No. (%) Living alone 104 (11.6) Living with others 794 (88.4) Medical care Outpatient visit for diabetes care in past year, No. (%) Almost every month 4 (0.4) Once every 2-3 months 847 (94.3) Once every 4-6 months 34 (3.8) Only once in 12 months 3 (0.3) Irregular 10 (1.1) Blood glucose test in past 3 months, No. (%) No 392 (43.7) Yes 506 (56.3) Urine microalbumin test in past year, No. (%) No 179 (19.9) Yes 719 (80.1) Retina examination in past year, No. (%) No 251 (30.0) Yes 647 (70.0) Foot examination in past year, No. (%) No 186 (20.7) Yes 712 (79.3) Health status Perceived health score, mean (SD)d 69.8 (13.2) Limited daily activities for ≥6 months, No. (%) Not at all 704 (78.4) Mild 181 (20.2) Severe 13 (1.4) - Table 2.
Prevalence of Impaired Awareness of Hypoglycemia, by Duration of Antihyperglycemic Drug Use and Overall
Group and Duration of Use Gold-TW Criteriaa Clarke-TW Criteriab Score, Median (Range) IAH Prevalence Rate (95% CIc) Score, Median (Range) IAH Prevalence Rate (95% CIc) Insulin users (n = 585) Duration of use <1 year 5 (1-7) 57.3 (47.7-66.9) 3 (0-5) 30.1 (21.2-39.0) 1-2 years 3 (1-7) 44.4 (36.2-52.6) 3 (0-5) 31.7 (24.0-39.4) 3-4 years 3 (1-7) 41.5 (32.1-50.9) 3 (0-5) 26.4 (18.0-34.8) ≥5 years 2 (1-7) 31.6 (25.6-37.6) 2.5 (0-6) 26.1 (20.5-31.7) Overall 2 (1-7) 41.0 (37.0-45.0) 3 (0-6) 28.2 (24.6-31.8) Sulfonylurea users (n = 366) Duration of use <1 year 3 (1-7) 47.8 (27.4-68.2) 3 (0-4) 30.4 (11.6-49.2) 1-2 years 5 (1-7) 62.7 (50.4-75.0) 4 (1-5) 50.9 (38.1-63.7) 3-4 years 4 (1-7) 54.2 (41.5-66.9) 3 (0-5) 39.0 (26.6-51.4) ≥5 years 5 (1-7) 70.7 (64.8-76.6) 4 (0-5) 56.9 (50.4-63.4) Overall 5 (1-7) 65.3 (60.4-70.2) 4 (0-5) 51.3 (46.2-56.4) Clarke-TW = Chinese version of Clarke questionnaire; Gold-TW = Chinese version of Gold questionnaire; IAH = impaired awareness of hypoglycemia.
↵a Possible scores range from 1 to 7. A score of 4 or higher was defined as IAH.
b Possible scores range from 0 to 7. A score of 4 or more “reduced awareness” responses was defined as IAH.
c The 95% CI was calculated by the normal approximation method.
- Table 3.
Odds Ratios for Impaired Awareness of Hypoglycemia Assessed by Gold-TW Criteria, According to Duration of Insulin and Sulfonylurea Use
Drug and Duration of Use Model 1 Crude OR (95% CI) Model 2a Adjusted OR (95% CI) Model 3b Adjusted OR (95% CI) Model 4c Adjusted OR (95% CI) Duration of insulin use No use 1.00 1.00 1.00 1.00 <1 year 0.72 (0.46-1.13) 0.72 (0.45-1.15) 0.72 (0.42-1.23) 0.73 (0.42-1.26) 1-2 years 0.43 (0.28-0.64) 0.43 (0.28-0.65) 0.55 (0.35-0.88) 0.55 (0.35-0.88) 3-4 years 0.38 (0.24-0.60) 0.37 (0.23-0.59) 0.52 (0.31-0.87) 0.54 (0.32-0.92) ≥5 years 0.25 (0.17-0.35) 0.23 (0.16-0.33) 0.32 (0.21-0.48) 0.33 (0.22-0.49) Duration of sulfonylurea use No use 1.00 1.00 1.00 1.00 <1 year 1.46 (0.63-3.38) 1.46 (0.62-3.46) 0.43 (0.17-1.08) 0.42 (0.17-1.03) 1-2 years 2.68 (1.54-4.68) 2.92 (1.64-5.21) 1.11 (0.57-2.15) 1.09 (0.56-2.12) 3-4 years 1.89 (1.10-3.25) 1.91 (1.10-3.29) 1.11 (0.58-2.12) 1.06 (0.54-2.09) ≥5 years 3.84 (2.75-5.38) 3.91 (2.78-5.52) 3.56 (2.45-5.19) 3.50 (2.39-5.13) Gold-TW = Chinese version of Gold questionnaire; OR = odds ratio.
Note: Multiple logistic regression models with sequential adjustment for potential confounders. The “no use” groups are the reference groups.
↵a Adjusted for sociodemographics: age, sex, highest education level, marital status, living area, occupation, living arrangement.
↵b Adjusted for sociodemographics and disease history and medical care: diabetes duration, outpatient visit for diabetes care in past year, blood glucose test in past 3 months, urine microalbumin test in past year, retina examination in past year, foot examination in past year.
↵c Adjusted for sociodemographics, disease history and medical care, and health status: perceived health, limited daily activities for ≥6 months.
- Table 4.
Odds Ratios for Impaired Awareness of Hypoglycemia Assessed by Clarke-TW Criteria, According to Duration of Insulin and Sulfonylurea Use
Drug and Duration of Use Model 1 Crude OR (95% CI) Model 2a Adjusted OR (95% CI) Model 3b Adjusted OR (95% CI) Model 4c Adjusted OR (95% CI) Duration of insulin use No use 1.00 1.00 1.00 1.00 <1 year 0.42 (0.26-0.67) 0.39 (0.24-0.63) 0.51 (0.29-0.87) 0.51 (0.30-0.88) 1-2 year 0.45 (0.30-0.68) 0.45 (0.29-0.69) 0.57 (0.35-0.93) 0.57 (0.35-0.92) 3-4 year 0.35 (0.21-0.57) 0.34 (0.20-0.56) 0.52 (0.30-0.91) 0.53 (0.30-0.93) ≥5 year 0.34 (0.24-0.49) 0.33 (0.23-0.48) 0.52 (0.35-0.78) 0.52 (0.34-0.78) Duration of sulfonylurea use No use 1.00 1.00 1.00 1.00 <1 year 1.27 (0.51-3.16) 1.33 (0.51-3.43) 0.57 (0.22-1.50) 0.54 (0.21-1.42) 1-2 years 3.01 (1.74-5.20) 3.27 (1.85-5.81) 0.99 (0.50-1.99) 1.05 (0.52-2.12) 3-4 years 1.86 (1.06-3.25) 2.03 (1.14-3.62) 0.99 (0.52-1.87) 0.98 (0.51-1.89) ≥5 years 3.84 (2.77-5.33) 3.84 (2.74-5.37) 3.04 (2.10-4.38) 3.06 (2.11-4.44) Clarke-TW = Chinese version of Clarke questionnaire; OR = odds ratio.
Note: Multiple logistic regression models with sequential adjustment for potential confounders. The “no use” groups are the reference groups.
↵a Adjusted for sociodemographics: age, sex, highest education level, marital status, living area, occupation, living arrangement.
↵b Adjusted for sociodemographics and disease history and medical care: diabetes duration, outpatient visit for diabetes care in past year, blood glucose test in past 3 months, urine microalbumin test in past year, retina examination in past year, foot examination in past year.
↵c Adjusted for sociodemographics, disease history and medical care, and health status: perceived health, limited daily activities for ≥6 months.
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PLAIN-LANGUAGE ARTICLE SUMMARY
Original Research
Long-Term Sulfonylurea Use Linked to Higher Risk of Low Blood Sugar Unawareness in Type 2 Diabetes Patients
Background and Goal:Sulfonylureas are a class of oral medications used to manage blood glucose levels in patients with type 2 diabetes. These drugs increase insulin production regardless of blood sugar levels. For this reason, the drugs can cause blood sugar to drop too low, leading to hypoglycemia. The goal of this study was to compare how prevalent impaired awareness of hypoglycemia was when patients with type 2 diabetes were treated with either insulin or sulfonylureas for both long and short-term periods.
Study Approach:Researchers collected data from a group of 898 participants with type 2 diabetes enrolled in pharmacies, clinics, and health bureaus of Tainan City, Taiwan. Participants were treated with insulin or sulfonylurea between August and November 2022. Researchers assessed the participants’ degree of impaired awareness of their hypoglycemia status, using the Chinese versions of the Clarke and Gold questionnaires.
Main Results:
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Up to 94.3% of participants, half male and half female and mostly aged 40-69, visited a clinician as an outpatient every 2-3 months for diabetes care. For participants who used the medication for less than a year, the prevalence of impaired awareness of hypoglycemia in sulfonylurea users was 47.8% (Gold) and 30.4% (Clarke). The prevalence increased to 70.7% (Gold) and 56.9% (Clarke) for users treated with sulfonylurea for more than five years.
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For insulin user participants who used the medication for less than a year, the prevalence of impaired hypoglycemia awareness was 57.3% (Gold) and 30.1% (Clarke). This decreased to 41% (Gold) and 28.2% (Clarke) for participants who used the medication for more than five years. Regular ambulatory care with tests, including blood glucose and retina exams, was associated with lower odds of impaired awareness of hypoglycemia in both sulfonylurea and insulin users.
Why It Matters:Using sulfonylureas long-term is associated with impaired awareness of low blood sugar in patients with type 2 diabetes. The longer the patient uses this medication, the higher the risk of hypoglycemia unawareness. Current guidelines recommend using newer classes of medications that offer a reduced risk of hypoglycemia to treat type 2 diabetes over sulfonylureas, which are commonly used due to their affordability.
Visual Abstract:
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