Circulating microRNAs Signature for Predicting Response to GLP1-RA Therapy in Type 2 Diabetic Patients: A Pilot Study
Abstract
:1. Introduction
2. Results
2.1. GLP1-RA Treatment Outcomes in T2D Patients
2.2. Baseline Levels of the Selected miRNAs Distinguish Patients with Better Treatment Outcomes
3. Discussion
4. Materials and Methods
4.1. Patients
4.2. Clinical and Biochemical Parameters
4.3. Blood Collection Procedure
4.4. RNA Extraction from Plasma Samples
4.5. Circulating microRNAs qRT-Real-Time PCR Analysis
4.6. Statistics
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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T0 (n = 26) | T6 (n = 21) | T12 (n = 20) | |
---|---|---|---|
Age (years) | 60.3 ± 10.3 (35–79) | / | / |
Disease Duration (years) | 10.2 ± 8.7 (1–32) | / | / |
Weight (kg) | 95.6 ± 20.6 (56–134.7) | 92.9 ± 20.2 (58–133) * | 93.3 ± 17.8 (51–121) § |
BMI (kg/m2) | 33.7 ± 6.5 (21.9–49.5) | 32.0 ± 5.9 (23.2–48.5) * | 32.4 ± 4.9 (19.9–41.9) § |
HbA1c (%) | 7.7 ± 0.58 (6–8.8) | 6.4 ± 1.0 (5.3–10.1) * | 6.7 ± 1.7 (5.5–13.2) |
FPG (mg/dL) | 159.1 ± 27.9 (112–223) | 128.9 ± 37.5 (86–251) * | 134.7 ± 56.3 (91–355) |
Total Cholesterol (mg/dL) | 157.5 ± 42.4 (54–258) | 155.6 ± 26.5 (106–208) | 150.2 ± 24.8 (104–200) |
Triglycerides (mg/dL) | 138.7 ± 63.1 (56–313) | 129.9 ± 49.3 (60–257) | 132.6 ± 58.5 (61–232) |
HDL (mg/dL) | 46.3 ± 11.7 (28–72) | 44.9 ± 10.9 (28–71) | 46.5 ± 11.8 (29–76) |
LDL (mg/dL) | 92.2 ± 34.9 (50–173) | 84.7 ± 22.6 (49–130) | 76.2 ± 24.1 (45–131) |
Creatinine (mg/dL) | 0.91 ± 0.23 (0.64–1.34) | 0.93 ± 0.19 (0.67–1.27) | 0.93 ± 0.26 (0.59–1.56) |
eGFR (mL/min/1.73 m2) | 84.7 ± 21.1 (44–116) | 85.0 ± 17.4 (47–112) | 84.3 ± 21.5 (37–122) |
Albuminuria (mg/dL) | 46.0 ± 104.4 (0–462) | 199.0 ± 681.2 (0–2834) | 73.8 ± 171.4 (0–575) |
%WL | / | 4.9 ± 5.8 (−5.2–23.3) | 5.5 ± 6.1 (−2.9–18.1) |
%EWL | / | 18.9 ± 26.8 (−41.2–81.2) | 15.5 ± 16.4 (−9.7–50) |
HbA1c reduction (%) | / | 16.5 ± 14.4 (−31.2–36.9) | 12.7 ± 22.3 (−69.2–33.3) |
Dulaglutide | Liraglutide | p Value | |||||
---|---|---|---|---|---|---|---|
T0 (n = 18) | T6 (n = 14) | T12 (n = 13) | T0 (n = 8) | T6 (n = 7) | T12 (n = 7) | ||
Age (years) | 60.1 ± 12.1 (35–79) | / | / | 61.0 ± 4.9 (55–67) | / | / | * 0.83 |
Disease Duration (years) | 10.8 ± 9.4 (1–32) | / | / | 8.8 ± 7.3 (1–23) | / | / | * 0.65 |
Weight (kg) | 93.6 ± 19.3 (56–127) | 91.4 ± 17.6 (58–124) | 93.4 ± 17.6 (51–119) | 100.0 ± 24.2 (72–134.7) | 95.8 ± 26.0 (65.5–133) | 93.4 ± 19.5 (70–121) | * 0.61; § 0.87; # 0.8 |
BMI (kg/m2) | 32.5 ± 5.1 (21.9–41) | 32.4 ± 4.5 (23.5–40.0) | 32.4 ± 4.6 (19.9–40.2) | 36.3 ± 8.7 (25.5–49.5) | 33.3 ± 8.5 (23.2–48.9) | 32.4 ± 5.8 (24.8–41.9) | * 0.53; § 0.91; # 0.81 |
HbA1c (%) | 7.6 ± 0.6 (6.0–8.4) | 6.6 ± 1.2 (5.3–10.1) | 6.2 ± 0.6 (5.5–7.4) | 7.8 ± 0.6 (7.0–8.8) | 6.2 ± 0.6 (5.7–7.5) | 7.5 ± 2.6 (5.8–13.2) | * 0.77; § 0.42; # 0.23 |
FPG (mg/dL) | 156.9 ± 30.9 (112–223) | 133.7 ± 41.4 (86–251) | 120.2 ± 14.4 (94–141) | 164.0 ± 20.7 (143–201) | 119.3 ± 28.4 (92–176) | 166.0 ± 95.8 (91–355) | * 0.45; § 0.36; # 0.23 |
Total Cholesterol (mg/dL) | 145.9 ± 36.8 (54–220) | 157.7 ± 27.7 (106–208) | 144.8 ± 18.7 (112–178) | 182 ± 45.3 (123–258) | 151.6 ± 25.5 (119–187) | 161.8 ± 33.8 (104–200) | * 0.1; § 0.57; # 0.14 |
Triglycerides (mg/dL) | 138.1 ± 68.1 (56–313) | 129.9 ± 56.0 (60–257) | 120.8 ± 55.0 (61–222) | 140.0 ± 55. (77–229) | 129.7 ± 37.8 (88–187) | 163.2 ± 61.9 (110–232) | * 0.74; § 0.89; # 0.11 |
HDL (mg/dL) | 46.3 ± 12.8 (28–72) | 44.8 ± 11.9 (28–71) | 48.5 ± 13.0 (31–76) | 46.4 ± 9.6 (30–61) | 45.1 ± 9.6 (28–57) | 42.5 ± 8.3 (29–52) | * 0.76; § 0.86; # 0.43 |
LDL (mg/dL) | 83.0 ± 29.3 (51–147) | 87.0 ± 22.9 (54–130) | 71.9 ± 20.7 (47–110) | 114.5 ± 39.44 (50–173) | 80.5 ± 23.0 (49–106) | 86.4 ± 31.1 (45–131) | * 0.08; § 0.65; # 0.31 |
Creatinine (mg/dL) | 0.94 ± 0.2 (0.64–1.34) | 0.96 ± 0.2 (0.67–1.27) | 0.94 ± 0.3 (0.59–1.56) | 0.9 ± 0.2 (0.64–1.23) | 0.87 ± 0.2 (0.67–1.06) | 0.89 ± 0.3 (0.66–1.37) | * 0.5; § 0.52; # 0.61 |
eGFR (mL/min/1.73 m2) | 85.1 ± 23.9 (44–116) | 84.5 ± 20.9 (47–112) | 84.5 ± 23.7 (37–122) | 83.8 ± 14.1 (61–97) | 86.0 ± 9.3 (72–98) | 83.6 ± 16.7 (54–93) | * 0.69; § 0.83; # 0.75 |
Albuminuria (mg/dL) | 51.6 ± 120.3 (0–462) | 314.0 ± 887.5 (0–2834) | 88.9 ± 187.9 (0− 575) | 30.5 ± 39.6 (4–97.6) | 34.9 ± 51.3 (3.2–143) | 6.0 ± 1.4 (5–7) | * 0.89; § 0.98; # 0.54 |
%WL | / | 5.0 ± 6.9 (−5.3–23.3) | 5.3 ± 6.3 (−2.9–18.1) | / | 4.7 ± 3.2 (1.3–9.0) | 5.8 ± 6.2 (−1.9–15.4) | § 0.74; # 0.81 |
%EWL | / | 17.2 ± 27.7 (−41.2–64.3) | 14.3 ± 18.5 (−9.7–50) | / | 22.5 ± 26.7 (2.3–81.2) | 17.5 ± 13.4 (−6.5–34.1) | § 0.7; # 0.53 |
HbA1c reduction (%) | / | 14.8 ± 16.3 (−31.2–36.9) | 18.0 ± 11. (−8.3–33.3) | / | 19.8 ± 9.8 (3.8–35.2) | 2.9 ± 33.5 (−69.2–29.5) | § 0.59; # 0.35 |
Low Expressing (n = 13) | High Expressing (n = 13) | p Value | |||||
---|---|---|---|---|---|---|---|
T0 | T6 | T12 | T0 | T6 | T12 | ||
Age (years) | 59.5 ± 10.7 (35–74) | / | / | 61.9 ± 10.1 (41–79) | / | / | * 0.65 |
Disease Duration (years) | 9.3 ± 10.5 (1–32) | / | / | 11.1 ± 6.7 (2–23) | / | / | * 0.24 |
Weight (kg) | 97.3 ± 19.7 (56–129) | 97.4 ± 17.1 (74–124) | 93.3 ± 20.8 (51–121) | 93.9 ± 22.2 (64–134.7) | 90.1 ± 22.1 (58–133) | 93.4 ± 15.4 (70–114) | * 0.65 § 0.3 ¶ 0.69 |
BMI (kg/m2) | 34.1 ± 6.3 (21.8–46.6) | 32.1 ± 4.2 (26.3–38.3) | 32.1 ± 5.3 (19.9–40.2) | 33.3 ± 6.9 (25.5–49.5) | 31.9 ± 6.9 (23.2–48.8) | 32.8 ± 4.7 (24.8–41.9) | * 0.67 § 0.74 ¶ > 0.9 |
HbA1c (%) | 7.7 ± 0.7 (6–8.8) | 6.2 ± 0.75 (5.3–7.5) | 7.1 ± 2.3 (5.5–13.2) | 7.7 ± 0.4 (7–8.4) | 6.7 ± 1.2 (5.8–10.1) | 6.2 ± 0.4 (5.6–6.8) | * 0.24 § 0.5 ¶ 0.4 |
FPG (mg/dL) | 160.4 ± 32.0 (112–201) | 123.0 ± 30.3 (86–176) | 146.5 ± 75.5 (94–355) | 157.8 ± 24.5 (128–223) | 132.5 ± 42.0 (93–251) | 121.6 ± 17.5 (91–145) | * 0.62 § 0.76 ¶ 0.7 |
Total Cholesterol (mg/dL) | 148.6 ± 49.3 (54–258) | 147.3 ± 31.4 (106–187) | 143.8 ± 23.7 (104–190) | 167.1 ± 32.7 (124–220) | 160.0 ± 23.6 (131–208) | 157.3 ± 25.4 (112–200) | * 0.17 § 0.3 ¶ 0.19 |
Triglycerides (mg/dL) | 140.0 ± 72.6 (73–313) | 151.4 ± 61.8 (72–257) | 127.0 ± 72.5 (54–232) | 137.3 ± 54.1 (56–245) | 118.2 ± 39.0 (60–188) | 129.3 ± 48.6 (62–219) | * 0.75 § 0.3 ¶ 0.56 |
HDL (mg/dL) | 47.6 ± 11.5 (30–68) | 42.4 ± 10.2 (28–54) | 56.7 ± 31.7 (29–136) | 45.1 ± 12.3 (28–72) | 46.2 ± 11.4 (28–71) | 45.4 ± 12.8 (31–76) | * 0.5 § 0.49 ¶ 0.49 |
LDL (mg/dL) | 89.7 ± 40.3 (51–173) | 74.7 ± 19.6 (49–99) | 68.9 ± 18.9 (45–96) | 94.8 ± 30.2 (50–149.8) | 90.9 ± 23.7 (55.4–130) | 84.9 ± 28.4 (47–131) | * 0.47 § 0.29 ¶ 0.86 |
Creatinine (mg/dL) | 0.94 ± 0.26 (0.64–1.34) | 0.96 ± 0.18 (0.67–1.27) | 0.98 ± 0.31 (0.59–1.56) | 0.88 ± 0.21 (0.67–1.34) | 0.90 ± 0.19 (0.67–1.24) | 0.85 ± 0.18 (0.66–1.19) | * 0.69 § 0.46 ¶ 0.28 |
eGFR (mL/min/1.73 m2) | 83.1 ± 25.0 (44–116) | 83.9 ± 20.4 (47–113) | 81.7 ± 26.8 (37–123) | 85.9 ± 16.9 (56–111) | 84.3 ± 18.1 (57–112) | 88.4 ± 13.9 (65 – 110) | * 0.9 § 0.95 ¶ 0.7 |
Albuminuria (mg/dL) | 81.1 ± 157.1 (0–462) | 534.3 ± 1130 (2–2834) | 128.5 ± 225.4 (5–575) | 20.5 ± 25.0 (2–67) | 16.1 ± 17.9 (0–57) | 8.2 ± 9.68 (0–23) | * 0.59 § 0.2 ¶ 0.09 |
%WL | / | 6.36 ± 7.2 (0.86–23.3) | 4.4 ± 6.1 (−1.9–18.1) | / | 14.2 ± 15.7 (−31.2–29.3) | 6.5 ± 6.2 (−2.8–15.4) | § 0.79 ¶ 0.4 |
%EWL | / | 22.9 ± 23.2 (3.2–64.3) | 11.5 ± 17.7 (−7.8–50) | / | 16.5 ± 29.5 (−41.2–81.2) | 19.0 ± 15.1 (−9.7–42.4) | § 0.68 ¶ 0.3 |
HbA1c reduction (%) | / | 20.2 ± 12.0 (3.85–36.9) | 6.8 ± 30.1 (−69.2–33.3) | / | 14.2 ± 15.7 (−31.2–29.3) | 18.6 ± 8.2 (8.1–30.9) | § 0.69 ¶ 0.48 |
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Formichi, C.; Fignani, D.; Nigi, L.; Grieco, G.E.; Brusco, N.; Licata, G.; Sabato, C.; Ferretti, E.; Sebastiani, G.; Dotta, F. Circulating microRNAs Signature for Predicting Response to GLP1-RA Therapy in Type 2 Diabetic Patients: A Pilot Study. Int. J. Mol. Sci. 2021, 22, 9454. https://doi.org/10.3390/ijms22179454
Formichi C, Fignani D, Nigi L, Grieco GE, Brusco N, Licata G, Sabato C, Ferretti E, Sebastiani G, Dotta F. Circulating microRNAs Signature for Predicting Response to GLP1-RA Therapy in Type 2 Diabetic Patients: A Pilot Study. International Journal of Molecular Sciences. 2021; 22(17):9454. https://doi.org/10.3390/ijms22179454
Chicago/Turabian StyleFormichi, Caterina, Daniela Fignani, Laura Nigi, Giuseppina Emanuela Grieco, Noemi Brusco, Giada Licata, Claudia Sabato, Elisabetta Ferretti, Guido Sebastiani, and Francesco Dotta. 2021. "Circulating microRNAs Signature for Predicting Response to GLP1-RA Therapy in Type 2 Diabetic Patients: A Pilot Study" International Journal of Molecular Sciences 22, no. 17: 9454. https://doi.org/10.3390/ijms22179454