Beta-cell function in type 2 diabetic patients who failed to maintain good glycemic status with a combination of maximum dosages of metformin and sulfonylurea

Figures & data

Figure 1 Study protocol in type 2 diabetic patients who failed to maintain optimal glycemic control with a combination of maximum dosages of metformin and sulfonylurea (MFM-SUF group). Notes: After enrollment, the patients were standardized for lifestyle management and were assigned to continue the maximum daily dosage of the same sulfonylurea and the same dosages of metformin for 2 weeks, and then underwent the first OGTT, the Max-SU OGTT. After the Max-SU OGTT, the patients were assigned to discontinue their SU but continue taking the same dosages of metformin. After discontinuation of SU for 4 weeks, the second OGTT, the Discont-SU OGTT, was performed and then the same SU was restarted at 25% of the recommended maximum dose. After taking 25%Max-SU for 4 weeks, the third OGTT, the 25%Max-SU OGTT, was performed. Abbreviations: CBG, capillary blood glucose; OGTT, oral glucose tolerance test; SU, sulfonylurea.

Table 1 Baseline characteristics of type 2 diabetic patients who failed to maintain optimal glycemic control with a combination of maximum dosage of metformin and sulfonylurea (MFM-SUF group), and the normal glucose tolerance (NGT) group

Variable	MFM-SUF group (n=25)	NGT group (n=28)	p-value
Age (years)	56.8±9.8 (range 37–78)	53.8±6.7 (range 46–68)	0.29
Gender, women	14 (56)	26 (92.9)	0.02
Duration of diabetes (years)	12 (7.5, 14)	N/A
BMI (kg/m^2)	25.8±4.7 (range 18.1–37.2)	26.4±3.6 (range 19.7–36.6)	0.77
HbA1c (%)	9.5±1.4	N/A
HbA1c (mmol/mol)	80.0±7.3	N/A
FPG (mmol/L)	11.0±2.2	N/A
Metformin dose (g/day)	2.2±0.8	N/A

Notes: Data are shown as mean±SD, n (%), or median (IQR).

Abbreviations: BMI, body mass index; FPG, fasting plasma glucose; NA, not applicable.

Table 2 Plasma glucose, insulin, Beta-cell function, insulin resistance indexes and mean fasting capillary blood glucose in the two groups during the OGTT

Variable after 75 g OGTT	Max-SU (n=25)	Discont-SU (n=25)	25%Max-SU (n=25)	NGT (n=28)	p-values (max-SU vs Discont-SU vs 25%Max-SU)	p-values (max-SU vs NGT)
Glucose 0 minutes (mmol/L)	9.8±2.5*	14.3±3.6**	11.4±3.3***	4.9±0.4	<0.0001	<0.001
Glucose 30 minutes (mmol/L)	14.5±2.8*	18.7±3.9**	15.9±3.4	7.3±1.0	<0.0001	<0.001
Glucose 60 minutes (mmol/L)	18.1±3.0*	22.6±3.8**	19.5±3.3***	7.9±1.2	<0.0001	<0.001
Glucose 90 minutes (mmol/L)	20.4±2.9*	25.2±4.4**	22.3±3.5***	7.4±1.2	<0.0001	<0.001
Glucose 120 minutes (mmol/L)	20.6±3.0*	25.9±4.4**	22.2±3.5***	6.4±1.2	<0.0001	<0.001
Insulin 0 minutes (pmol/L)	146.1* (95.2, 261.1)	126.1 (77.6, 176.6)	135.4 (88.6, 196.1)	45.8 (11.5, 93.4)	0.04	<0.001
Insulin 30 minutes (pmol/L)	30.47* (211.6, 369.3)	158.3 (116.7, 217.9)	202.5 (130.8, 328.3)	300.4 (195.4, 373.3)	0.04	0.139
Insulin 60 minutes (pmol/L)	239.5* (144.5, 372.3)	165.0** (123.0, 252.0)	226.0 (143.6, 304.5)	340.3 (248.3, 496.6)	<0.0001	0.038
Insulin 90 minutes (pmol/L)	241.8* (181.9, 396.6)	23.64 (164.2, 251.9)	231.5*** (164.3, 282.2)	350.7 (227.5, 541.7)	<0.0001	0.065
Insulin 120 minutes (pmol/L)	288.2* (181.1, 490.2)	198.4** (140.8, 258.1)	220.1 (146.8, 379.8)	329.9 (170.9, 524.4)	<0.0001	0.514
AUC Insulin0–120/Glucose0–120	0.10* (0.08, 0.17)	0.06** (0.04, 0.09)	0.09 (0.07, 0.12)	0.34 (0.24, 0.44)	<0.001	<0.001
HOMA-IR	7.84 (5.4, 15.87)	11.65 (6.44, 16.70)	10.15 (5.16, 13.45)	1.39 (0.37, 2.83)	0.179	<0.001
Matsuda index	1.76 (0.92, 2.87)	1.55 (1.08, 2.81)	1.60 (1.23, 2.27)	5.67 (3.67, 13.50)	0.759	<0.001
Mean FCBG (mmol/L)	10.3±2.4*	14.2±3.7**	12.3±3.4***	N/A	<0.001	N/A

Notes: Data are shown as mean±SD or median (IQR). *Max-SU vs Discont-SU: p<0.05; **Discont-SU vs 25%Max-SU: p<0.05; ***Max-SU vs 25%Max-SU: p<0.05.

Abbreviations: Max-SU, during maximum dosage of sulfonylurea; Discont-SU, during discontinuation of sulfonylurea; 25%Max-SU, during dosage of 25% of the recommended maximum dosage of sulfonylurea; AUC, area under the curve; FCBG, fasting capillary blood glucose; HOMA-IR, Homeostasis Model Assessment of Insulin Resistance; OGTT, oral glucose tolerance test.

Figure 2 (A) Plasma glucose and (B) plasma insulin levels during OGTTs in patients in the MFM-SUF and NGT groups. Notes: For the MFM-SUF group, the OGTT was performed three times, while taking the maximum dosage of sulfonylurea (Max-SU), discontinuing sulfonylurea (Discont-SU), and taking 25% of the maximum dosage of sulfonylurea (25%Max-SU). During the treatment with Max-SU, all MFM-SUF patients had significantly higher fasting plasma insulin levels than did the subjects with NGT, but the plasma insulin response to OGTT in Max-SU was much lower than in the NGT group. Abbreviations: MSM-SUF, maximum dosages of metformin and sulfonylurea; NGT, normal glucose tolerance; OGTT, oral glucose tolerance test; SU, sulfonylurea.

Figure 3 Beta-cell function during OGTTs in the MFM-SUF and NGT groups. Notes: For the MFM-SUF group, the OGTT was performed three times, while taking the maximum dosage of sulfonylurea (Max-SU), discontinuing sulfonylurea (Discont-SU), and taking 25% of the maximum dosage of sulfonylurea (25%Max-SU). Median (IQR) beta-cell function during treatment with Max-SU was 0.1 (0.08, 0.17), which was significantly higher than during Discont-SU (0.06; 0.04, 0.09) (p<0.001), and also higher, but not significantly so, than during 25%Max-SU (p=0.269). Median beta-cell function during 25%Max-SU was 0.09 (0.01, 0.32), which was significantly higher than during Discont-SU (0.06; 0.04, 0.09) (p<0.001). Median beta-cell function during Max-SU was 0.1 (0.08, 0.17), which was significantly lower than in the NGT group (0.34; 0.24, 0.44) (p<0.001). Abbreviations: AUC, area under the curve; MSM-SUF, maximum dosages of metformin and sulfonylurea; NGT, normal glucose tolerance; OGTT, oral glucose tolerance test; SU, sulfonylurea.

Data availability

The data sets generated and analyzed during the current study are available from the corresponding author on reasonable request.