MALDI-TOF Protein Profiling Reflects Changes in Type 1 Diabetes Patients Depending on the Increased Amount of Adipose Tissue, Poor Control of Diabetes and the Presence of Chronic Complications
Abstract
:1. Introduction
2. Materials and Methods
2.1. Study Groups
2.2. Methods
- Obesity (BMI < 30 vs. BMI > 30 kg/m2): BMI was calculated from the formula of the ratio of body weight to squared height.
- Presence of diabetic complications (retinopathy, nephropathy, and neuropathy, all complications or any of them)
- HbA1c value < 7% and > 7%: A reasonable A1C goal according to American Diabetes Association Guidelines 2020 for many nonpregnant adults [4].
2.2.1. Assessment of Diabetic Complications
Assessment of Diabetic Kidney Disease (DKD)
Assessment of Diabetic Retinopathy
Assessment of Diabetic Neuropathy
2.2.2. Laboratory Analysis
2.2.3. MALDI-TOF MS Profiling
Sample Pretreatment
MALDI-TOF MS Analysis
nanoLC MALDI-TOF/TOF MS Identification of Discriminatory Peaks
2.2.4. Statistical Analysis
3. Results
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Conflicts of Interest
References
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Variable | Median (IQR) |
---|---|
Sex [M/F], n (%) | 50 (48.5)/ 53 (51.5) |
Age [y] | 34 (30–42) |
DD [y] | 17 (12–23) |
IFI [y] | 12 (8–18) |
WHR [n] | 0.9 (0.8–0.9) |
BMI [kg/m2] | 26 (23–29) |
TBF [kg] | 19 (14–27) |
VF [n] | 5 (3–8) |
DDI [µ/kg/d] | 0.5 (0.4–0.6) |
HbA1c [%] | 8 (7–9) |
AST [U/L] | 19 (16–24) |
ALT [U/L] | 19 (14–26) |
Creatynine, [μmol/L] | 80 (71–88) |
eGFR [mL/min/1.73 m2] | 88 (77–90) |
hsCRP [mg/dL] | 2 (1–3) |
T-ch [mmol/L] | 48 (42–54) |
TAG [mmol/L] | 1 (1–2) |
HDL-ch [mmol/L] | 2 (1–2) |
LDL-ch [mmol/L] | 3 (2–3) |
non-HDL-c [mmol/L] | 3 (3–4) |
Complications | Incidence Frequency in Numbers (n = 103) | Incidence Frequency as a Ratio (103 = 100%) |
---|---|---|
Diabetic retinopathy | 39 | 37.9% |
Diabetic renal disease | 9 | 8.7% |
Autonomic neuropathy | 21 | 20.4% |
Peripheral neuropathy | 32 | 31.1% |
The group with any complications | 54 | 52.4 |
Value | EBF N = 46 | NBF N = 57 | EBF/NBF P < 0.05 | HbA1c > 7% N = 80 | HbA1c < 7% N = 23 | HbA1cp < 0.05 | PofC N = 55 | AofC N = 48 | PofC/ AofC P < 0.05 |
---|---|---|---|---|---|---|---|---|---|
Age [y] | 35.0 (31.0–46.0) | 33.0 (29.0–40.0) | 0.09 | 34.0 (25.0–40.0) | 35.0 (31.0–42.0) | 0.64 | 38.0 (32.0–47.0) | 32.0 (24.0–37.0) | 0.00 |
Sex [M/F] | 23/23 | 27/30 | 0.82 | 35/45 | 15/8 | 0.07 | 25/30 | 25/23 | 0.51 |
DD [y] | 18.0 (12.0–23.5) | 16.0 (11.0–23.0) | 0.90 | 15.0 (11.0–20.0) | 19.0 (7.0–21.0) | 0.38 | 20.0 (15.0–29.0) | 13.0 (8.0–17.0) | 0.00 |
TBF [kg] | 27.6 (23.1–33.2) | 14.1 (10.9–18.2) | 0.00 | 21.7 (14.1–29.7) | 17.3 (11.8–20.0) | 0.07 | 20.0 (14.1–27.1) | 18.2 (13.5–25.0) | 0.32 |
BMI [kg/m2] | 29.3 (27.8–30.6) | 23.7 (21.4–25.7) | 0.00 | 27.1 (24.0–29.8) | 24.2 (22.1–28.3) | 0.06 | 26.4 (23.4–30.3) | 27.1 (23.0–28.8) | 0.66 |
VF [n] | 8.0 (6.5–10.0) | 4.0 (2.0–5.0) | 0.00 | 5.0 (3.0–8.0) | 6.0 (3.0–7.0) | 0.93 | 6.0 (4.0–8.0) | 5.0 (2.0–7.0) | 0.12 |
WHR [n] | 0.9 (0.8–0.9) | 0.8 (0.8–0.9) | 0.00 | 0.9 (0.8–0.9) | 0.8 (0.9–1.0) | 0.04 | 6.0 (4.0–8.0) | 5.0 (2.0–7.0) | 0.05 |
HbA1c [%] | 8.4 (7.3–8.9) | 7.8 (6.8–8.9) | 0.18 | 8.9 (8.4–9.8) | 6.5 (6.2–6.8) | 0.00 | 7.9 (6.9–9.0) | 8.4 (7.2–8.9) | 0.75 |
AST [IU/L] | 19.0 (15.5–27.0) | 19.0 (16.0–22.0) | 0.54 | 18.0 (16.0–27.0) | 19.0 (15.0–22.0) | 0.66 | 19.0 (15.0–24.0) | 19.0 (16.0–27.0) | 0.38 |
ALT [IU/L] | 21.0 (14.0–28.5) | 17.0 (14.0–25.0) | 0.13 | 18.0 (13.0–27.0) | 21.0 (15.0–25.0) | 0.61 | 18.0 (14.0–24.0) | 21.0 (14.0–29.0) | 0.25 |
Creatinine [µmol/L] | 70.7 (61.9–88.4) | 77.8 (70.7–88.4) | 0.19 | 70.7 (61.9–79.6) | 79.6 (70.7–88.4) | 0.14 | 79.6 (70.7–88.4) | 79.6 (70.7–88.4) | 0.18 |
GFR [mL/min/1.72 m2] | 88.2 (82.2–90.0) | 86.0 (75.7–90.0) | 0.31 | 90.0 (75.5–90.0) | 84.1 (76.5–90.0) | 0.38 | 83.1 (73.4–90.0) | 90.0 (84.5–90.0) | 0.01 |
CRP [mg/dL] | 2.2 (1.0–4.5) | 1.2 (0.6–2.1) | 0.00 | 2.1 (1.0–4.1) | 1.0 (0.4–2.0) | 0.03 | 1.4 (0.7–3.1) | 1.7 (0.8–3.1) | 0.85 |
TCh [mmol/L] | 4.9 (4.5–5.7) | 4.6 (3.9–5.1) | 0.00 | 4.8 (4.2–5.3) | 4.7 (4.1–5.5) | 0.96 | 4.9 (4.3–5.4) | 4.6 (4.0–5.2) | 0.31 |
TAG [mmol/L] | 1.2 (1.0–1.8) | 0.9 (0.7–1.3) | 0.00 | 1.1 (0.9–1.7) | 0.9 (0.7–1.2) | 0.00 | 1.3 (0.9–1.5) | 1.3 (0.8–1.4) | 0.45 |
HDL-ch [mmol/L] | 1.5 (1.3–1.9) | 1.7 (1.4–2.0) | 0.11 | 1.6 (1.3–1.9) | 1.7 (1.4–2.3) | 0.13 | 1.6 (1.3–2.0) | 1.6 (1.3–2.0) | 0.96 |
LDL-ch [mmol/L] | 2.7 (2.5–3.3) | 2.4 (1.9–2.9) | 0.01 | 2.6 (2.1–3.1) | 2.5 (1.9–3.4) | 0.84 | 2.7 (2.6–3.2) | 2.5 (1.9–3.1) | 0.18 |
non-HDL-ch [mmol/L] | 3.2 (2.9–4.0) | 2.7 (2.2–3.3) | 0.00 | 3.1 (2.6–3.6) | 2.7 (2.3–3.9) | 0.41 | 3.2 (2.7–3.6) | 2.8 (2.4–3.8) | 0.33 |
ACR [mg/d] | 3.5 (2.5–5.2) | 3.8 (2.7–5.4) | 0.82 | 3.8 (2.5–5.4) | 3.7 (2.9–5.3) | 0.88 | 4.3 (2.9–8.1) | 3.3 (2.3–4.3) | 0.00 |
Division Due to Excess Fat | ||||
---|---|---|---|---|
Model | Cross Validation [%] | Recognition Capability [%] | External Validation—Correct Classified Part of Valid Spectra [%]—TEST | External Validation—Correct Classified Part of Valid Spectra [%]—CONTROL |
GA | 49.5 | 93.8 | 52.9 | 82.1 |
SNN | 59.2 | 67.1 | 60.8 | 38.5 |
QC | 58.0 | 63.4 | 43.1 | 74.4 |
Identified peaks (m/z) classified as discriminatory based on GA | ||||
1537.88 | fibrinogen alpha chain | |||
1519.99 | complement C3 (oxidation) | |||
1449.61 | complement C4A | |||
Identified peaks (m/z) classified as discriminatory based on SNN | ||||
1519.99 | complement C3 (oxidation) | |||
1537.88 | fibrinogen alpha chain | |||
Identified peaks (m/z) classified as discriminatory based on QC | ||||
1435.73 | complement C4A | |||
1449.61 | complement C4A | |||
1519.99 | complement C3 (oxidation) | |||
1537.88 | fibrinogen alpha chain |
Division Due to Diabetes Control (HbA1c > 7%) | ||||
---|---|---|---|---|
Model | Cross Validation [%] | Recognition Capability [%] | External Validation—Correct Classified Part of Valid Spectra [%]—TEST | External Validation—Correct Classified Part of Valid Spectra [%]—CONTROL |
GA | 62.2 | 85.8 | 63.6 | 30.6 |
SNN | 64.6 | 53.7 | 0 | 88.9 |
QC | 66.9 | 66.9 | 56.8 | 55.6 |
Identified peaks (m/z) classified as discriminatory based on GA | ||||
1537.88 | fibrinogen alpha chain | |||
1449.61 | complement C4A | |||
1520.00 | complement C3 (oxidation) | |||
Identified peaks (m/z) classified as discriminatory based on SNN | ||||
1519.99 | complement C3 (oxidation) | |||
1537.88 | fibrinogen alpha chain | |||
Identified peaks (m/z) classified as discriminatory based on QC | ||||
1537.88 | fibrinogen alpha chain |
Division Due to Diabetes Complications | ||||
---|---|---|---|---|
Model | Cross Validation [%] | Recognition Capability [%] | External Validation—Correct Classified Part of Valid Spectra [%]—TEST | External Validation—Correct Classified Part of Valid Spectra [%]—CONTROL |
GA | 48.2 | 84.6 | 46.2 | 67.6 |
SNN | 48.1 | 65.6 | 53.8 | 79.4 |
QC | 38.0 | 63.1 | 46.2 | 58.8 |
Identified peaks (m/z) classified as discriminatory based on GA | ||||
1537.88 | fibrinogen alpha chain | |||
1617.79 | fibrinogen alpha chain (peak 1537 phosphorylation) | |||
1435.73 | complement C4A | |||
Identified peaks (m/z) classified as discriminatory based on SNN | ||||
1537.88 | fibrinogen alpha chain | |||
1435.73 | complement C4A | |||
1520.00 | complement C3 (oxidation) | |||
1617.79 | fibrinogen alpha chain (peak 1537 phosphorylation) | |||
Identified peaks (m/z) classified as discriminatory based on QC | ||||
1537.88 | fibrinogen alpha chain |
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Zawada, A.; Naskręt, D.; Matuszewska, E.; Kokot, Z.; Grzymisławski, M.; Zozulińska-Ziółkiewicz, D.; Dobrowolska, A.; Matysiak, J. MALDI-TOF Protein Profiling Reflects Changes in Type 1 Diabetes Patients Depending on the Increased Amount of Adipose Tissue, Poor Control of Diabetes and the Presence of Chronic Complications. Int. J. Environ. Res. Public Health 2021, 18, 2263. https://doi.org/10.3390/ijerph18052263
Zawada A, Naskręt D, Matuszewska E, Kokot Z, Grzymisławski M, Zozulińska-Ziółkiewicz D, Dobrowolska A, Matysiak J. MALDI-TOF Protein Profiling Reflects Changes in Type 1 Diabetes Patients Depending on the Increased Amount of Adipose Tissue, Poor Control of Diabetes and the Presence of Chronic Complications. International Journal of Environmental Research and Public Health. 2021; 18(5):2263. https://doi.org/10.3390/ijerph18052263
Chicago/Turabian StyleZawada, Agnieszka, Dariusz Naskręt, Eliza Matuszewska, Zenon Kokot, Marian Grzymisławski, Dorota Zozulińska-Ziółkiewicz, Agnieszka Dobrowolska, and Jan Matysiak. 2021. "MALDI-TOF Protein Profiling Reflects Changes in Type 1 Diabetes Patients Depending on the Increased Amount of Adipose Tissue, Poor Control of Diabetes and the Presence of Chronic Complications" International Journal of Environmental Research and Public Health 18, no. 5: 2263. https://doi.org/10.3390/ijerph18052263