1Department of General Medicine, First Affiliated Hospital of Soochow University, Suzhou, China
2Department of Nephrology, Affiliated Hospital 2 of Nantong University, and First People’s Hospital of Nantong City, Nantong, China
3Department of Endocrinology, Affiliated Hospital 2 of Nantong University, and First People’s Hospital of Nantong City, Nantong, China
4Medical Research Center, Affiliated Hospital 2 of Nantong University, and First People’s Hospital of Nantong City, Nantong, China
5Department of Clinical Laboratory, Affiliated Hospital 2 of Nantong University, and First People’s Hospital of Nantong City, Nantong, China
Copyright © 2021 Korean Diabetes Association
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
CONFLICTS OF INTEREST
No potential conflict of interest relevant to this article was reported.
AUTHOR CONTRIBUTIONS
Conception or design: H.X.H., Y.X., J.B.S.
Acquisition, analysis, or interpretation of data: L.L.S., H.Y.H., L.H.Z., F.X., D.M.Z., X.L.Z., T.C., X.Q.W.
Drafting the work or revising: H.X.H., Y.X., J.B.S.
Final approval of the manuscript: H.X.H., L.L.S., H.Y.H., L.H.Z., F.X., D.M.Z., X.L.Z., T.C., X.Q.W., Y.X., J.B.S.
FUNDING
The study was funded by the Social Development Projects of Nantong (HS2012028, MS22015065, MS12019019), the Medical Research Project of Nantong Health Commission (MB201-9010, 2020JCC010), and the Medical Research Project of Jiangsu Health Commission (QNRC2016408).
Values are presented as mean±standard deviation, number (%), or median (interquartile range). Student’s t-test and chi-square test were applied to detect differences in their corresponding type of data, and corresponding test statistics (F and x2 values) were also provided.
DKD, diabetic kidney disease; BMI, body mass index; SBP, systolic blood pressure; DBP, diastolic blood pressure; AGI, α-glucosidase inhibitor; DPP-4I, dipeptidyl peptidase-4 inhibitor; GLP-1RA, glucagon-like peptide-1 receptor agonist; TG, triglyceride; TC, total cholesterol; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol; UA, uric acid; ISHOMAcp, homeostasis model assessment of insulin resistance using C-peptide; AUCcp, area under the C-peptide curve; AUCglu, area under the glucose curve; HbA1c, glycosylated hemoglobin; AUCgla, area under the glucagon curve; eGFR, estimated glomerular filtration rate; UACR, urinary albumin-to-creatinine ratio.
Values are presented as range, number, mean±standard deviation, or mean difference (95% confidence interval).
Model 0: crude; Model 1: adjusted for age, sex, diabetic duration, body mass index, systolic blood pressure, diastolic blood pressure, statins medication, and hypertension; Model 2: additionally adjusted for lipid profiles, serum uric acid, serum albumin, hemoglobin, homeostasis model assessment of insulin resistance using C-peptide, area under the C-peptide curve, area under the glucose curve, postchallenge 2-hour glucose, and glycosylated hemoglobin; Model 3: additionally adjusted for glucose-lowering therapies.
CI, confidence interval; T2DM, type 2 diabetes mellitus; eGFR, estimated glomerular filtration rate; UACR, urinary albumin-to-creatinine ratio.
Values are presented as range, number, mean±standard deviation, or mean difference (95% confidence interval).
Model 0: crude; Model 1: adjusted for age, sex, diabetic duration, body mass index, systolic blood pressure, diastolic blood pressure, statins medication, and hypertension; Model 2: additionally adjusted for lipid profiles, serum uric acid, serum albumin, hemoglobin, homeostasis model assessment of insulin resistance using C-peptide, area under the C-peptide curve, area under the glucose curve, postchallenge 2-hour glucose, and glycosylated hemoglobin; Model 3: additionally adjusted for glucose-lowering therapies.
CI, confidence interval; AUCgla, area under the glucagon curve; T2DM, type 2 diabetes mellitus; eGFR, estimated glomerular filtration rate; UACR, urinary albumin-to-creatinine ratio.
Values are presented as range, number (%), or odds ratio (95% confidence interval).
Model 0: crude; Model 1: adjusted for age, sex, diabetic duration, body mass index, systolic blood pressure, diastolic blood pressure, statins medication, and hypertension; Model 2: additionally adjusted for lipid profiles, serum uric acid, serum albumin, hemoglobin, homeostasis model assessment of insulin resistance using C-peptide, area under the C-peptide curve, area under the glucose curve, postchallenge 2-hour glucose, and glycosylated hemoglobin; Model 3: additionally adjusted for glucose-lowering therapies.
OR, odds ratio; CI, confidence interval; DKD, diabetic kidney disease; T2DM, type 2 diabetes mellitus; AUCgla, area under the glucagon curve.
Variable | Type 2 diabetes mellitus |
F/x2 value | P value | ||
---|---|---|---|---|---|
Total | Without DKD | With DKD | |||
Number | 2,436 | 1,665 | 771 | - | - |
Age, yr | 55.7±11.4 | 54.7±11.3 | 57.8±11.4 | 6.298 | <0.001 |
Female sex | 1,078 (44.3) | 705 (42.3) | 373 (48.4) | 7.784 | 0.005 |
BMI, kg/m2 | 25.44±3.63 | 25.18±3.56 | 26.01±3.71 | 5.299 | <0.001 |
SBP, mm Hg | 135.2±17.2 | 133.0±16.3 | 139.9±18.3 | 9.351 | <0.001 |
DBP, mm Hg | 79.4±10.5 | 79.1±10.1 | 80.3±11.0 | 2.691 | 0.007 |
Diabetic duration, yr | 5.57±4.45 | 5.07±4.08 | 6.64±5.01 | 8.189 | <0.001 |
Glucose-lowering therapies | |||||
Diabetes drug-free | 257 (10.6) | 185 (11.1) | 72 (9.3) | 1.755 | 0.185 |
Insulin treatments | 611 (25.1) | 388 (23.3) | 223 (28.9) | 8.858 | 0.003 |
Insulin-secretagogues | 1,226 (50.3) | 842 (50.6) | 384 (49.8) | 0.123 | 0.725 |
Metformin | 1,335 (54.8) | 943 (56.6) | 392 (50.8) | 7.141 | 0.008 |
Pioglitazone | 733 (30.1) | 514 (30.9) | 219 (28.4) | 1.524 | 0.217 |
AGIs | 584 (24.0) | 385 (23.1) | 199 (25.8) | 2.088 | 0.148 |
DPP-4Is | 642 (26.4) | 423 (25.4) | 219 (28.4) | 2.442 | 0.118 |
GLP-1RAs | 65 (2.7) | 42 (2.5) | 23 (3.0) | 0.431 | 0.512 |
Hypertension | 1,089 (44.7) | 636 (38.2) | 453 (58.8) | 90.086 | <0.001 |
Statin medication | 954 (39.2) | 618 (37.1) | 336 (43.6) | 9.238 | 0.002 |
TG, mmol/L | 1.71 (1.11–2.77) | 1.61 (1.04–2.59) | 1.94 (1.29–3.18) | 5.197 | <0.001 |
TC, mmol/L | 4.46±1.11 | 4.40±0.95 | 4.57±1.38 | 3.187 | <0.001 |
HDL-C, mmol/L | 1.09±0.29 | 1.10±0.29 | 1.06±0.29 | –2.408 | 0.016 |
LDL-C, mmol/L | 2.59±0.79 | 2.57±0.77 | 2.63±0.84 | 1.509 | 0.131 |
Serum UA, μmol/L | 300.4±96.5 | 289.7±91.6 | 323.7±102.5 | 8.207 | <0.001 |
Serum albumin, g/L | 39.2±4.1 | 39.4±3.9 | 38.7±4.4 | –3.779 | <0.001 |
Haemoglobin, g/L | 137.5±16.1 | 138.4±15.4 | 135.7±17.0 | –4.272 | <0.001 |
ISHOMAcp | 4.08 (2.30–8.05) | 4.22 (2.44–8.76) | 3.77 (2.04–7.10) | –4.057 | <0.001 |
AUCcp, ng/mL · hr | 12.4±5.9 | 12.3±5.7 | 12.6±6.3 | 1.494 | 0.135 |
AUCglu, mmol/L · hr | 41.8±9.2 | 41.4±9.3 | 42.5±8.9 | 2.624 | 0.009 |
HbA1c, % | 8.73±1.34 | 8.68±1.37 | 8.82±1.28 | 2.189 | 0.029 |
Postchallenge 2-hr glucose, mmol/L | 15.51±1.74 | 15.33±1.75 | 15.90±1.65 | 7.610 | <0.001 |
Fasting glucagon, pg/mL | 126.5±30.2 | 124.3±28.6 | 131.4±32.7 | 5.446 | <0.001 |
AUCgla, pg/mL · hr | 403.7±175.0 | 380.2±149.4 | 454.5±211.7 | 9.939 | <0.001 |
eGFR, mL/min/1.73 m2 | 100.8±24.6 | 104.6±21.4 | 92.7±28.8 | –11.358 | <0.001 |
UACR, mg/g | 20.1 (14.5–37.0) | 16.2 (13.0–20.9) | 60.6 (39.3–140.0) | 19.799 | <0.001 |
Log10UACR, mg/g | 1.44±0.44 | 1.21±0.16 | 1.93±0.46 | 57.842 | <0.001 |
Model | Q1 | Q2 | Q3 | Q4 | P value for trend |
---|---|---|---|---|---|
Fasting glucagon, pg/mL | 25.0–108.2 | 108.3–125.5 | 125.6–141.7 | 141.8–209.3 | - |
Number | 609 | 602 | 613 | 612 | - |
eGFR, mL/min/1.73 m2 | 104.27±23.58 | 102.91±25.68 | 99.96±24.85 | 96.30±23.64 | <0.001 |
Model 0 | 0–reference | –1.359 (–4.114 to –1.397) | –4.310 (–7.053 to –1.567) | –7.968 (–10.71 to –5.224) | <0.001 |
Model 1 | 0–reference | –2.340 (–4.703 to –0.006) | –3.871 (–6.193 to –1.549) | –7.618 (–9.947 to –5.289) | <0.001 |
Model 2 | 0–reference | –1.245 (–3.527 to 1.036) | –2.133 (–4.424 to 0.158) | –5.204 (–7.517 to –2.891) | <0.001 |
Model 3 | 0–reference | –1.167 (–3.435 to 1.101) | –1.984 (–4.259 to 0.290) | –5.087 (–7.383 to –2.790) | <0.001 |
Log10UACR, mg/g | 1.365±0.424 | 1.401±0.442 | 1.443±0.435 | 1.545±0.445 | <0.001 |
Model 0 | 0–reference | 0.035 (–0.014 to 0.085) | 0.078 (0.029 to 0.127) | 0.180 (0.131 to 0.229) | <0.001 |
Model 1 | 0–reference | 0.037 (–0.010 to 0.083) | 0.076 (0.030 to 0.123) | 0.174 (0.127 to 0.220) | <0.001 |
Model 2 | 0–reference | 0.023 (–0.024 to 0.070) | 0.065 (0.018 to 0.112) | 0.125 (0.078 to 0.173) | <0.001 |
Model 3 | 0–reference | 0.021 (–0.026 to 0.068) | 0.063 (0.016 to 0.110) | 0.124 (0.076 to 0.171) | <0.001 |
Model | Q1 | Q2 | Q3 | Q4 | P value for trend |
---|---|---|---|---|---|
AUCgla, pg/mL·hr | 53–289 | 290–372 | 373–484 | 485–1,603 | - |
Number | 599 | 617 | 609 | 611 | - |
eGFR, mL/min/1.73 m2 | 113.95±25.85 | 100.70±20.72 | 96.09±23.57 | 92.90±22.89 | <0.001 |
Model 0 | 0–reference | –13.26 (–15.89 to –10.64) | –17.85 (–20.49 to –15.22) | –21.05 (–23.68 to –18.42) | <0.001 |
Model 1 | 0–reference | –10.87 (–13.11 to –8.629) | –14.73 (–16.99 to –12.47) | –16.69 (–18.95 to –14.22) | <0.001 |
Model 2 | 0–reference | –9.698 (–11.91 to –7.490) | –12.63 (–14.87 to –10.38) | –13.93 (–16.22 to –11.63) | <0.001 |
Model 3 | 0–reference | –9.918 (–11.21 to –7.718) | –12.58 (–14.82 to –10.35) | –13.89 (–16.18 to –11.60) | <0.001 |
Log10UACR, mg/g | 1.341±0.461 | 1.344±0.372 | 1.495±0.473 | 1.575±0.409 | <0.001 |
Model 0 | 0–reference | 0.004 (–0.045 to 0.052) | 0.154 (0.106 to 0.203) | 0.234 (0.186 to 0.283) | <0.001 |
Model 1 | 0–reference | 0.007 (–0.040 to 0.053) | 0.149 (0.102 to 0.195) | 0.221 (0.174 to 0.268) | <0.001 |
Model 2 | 0–reference | 0.008 (–0.038 to 0.054) | 0.121 (0.074 to 0.168) | 0.190 (0.141 to 0.238) | <0.001 |
Model 3 | 0–reference | 0.009 (–0.038 to 0.055) | 0.119 (0.072 to 0.167) | 0.188 (0.140 to 0.236) | <0.001 |
Variable | Q1 | Q2 | Q3 | Q4 | P value for trend |
---|---|---|---|---|---|
Fasting glucagon, pg/mL | 25.0–108.2 | 108.3–125.5 | 125.6–141.7 | 141.8–209.3 | - |
Number | 609 | 602 | 613 | 612 | - |
DKD | 166 (27.3) | 166 (27.6) | 199 (32.5) | 240 (39.2) | <0.001 |
Model 0 | 1–reference | 1.016 (0.789–1.308) | 1.283 (1.003–1.640) | 1.722 (1.353–2.191) | <0.001 |
Model 1 | 1–reference | 1.029 (0.791–1.340) | 1.305 (1.010–1.686) | 1.770 (1.375–2.278) | <0.001 |
Model 2 | 1–reference | 0.957 (0.706–1.298) | 1.218 (0.902–1.644) | 1.532 (1.138–2.061) | 0.001 |
Model 3 | 1–reference | 0.946 (0.697–1.284) | 1.209 (0.895–1.634) | 1.521 (1.129–2.049) | 0.001 |
AUCgla, pg/mL · hr | 53–289 | 290–372 | 373–484 | 485–1603 | - |
Number | 599 | 617 | 609 | 611 | - |
DKD | 155 (25.9) | 140 (22.7) | 205 (33.7) | 271 (44.4) | <0.001 |
Model 0 | 1–reference | 0.841 (0.647–1.093) | 1.454 (1.134–1.863) | 2.283 (1.791–2.910) | <0.001 |
Model 1 | 1–reference | 0.849 (0.645–1.116) | 1.476 (1.137–1.915) | 2.290 (1.772–2.959) | <0.001 |
Model 2 | 1–reference | 0.823 (0.611–1.110) | 1.331 (0.996–1.778) | 2.071 (1.552–2.763) | <0.001 |
Model 3 | 1–reference | 0.825 (0.611–1.114) | 1.323 (0.989–1.769) | 2.066 (1.546–2.760) | <0.001 |
Values are presented as mean±standard deviation, number (%), or median (interquartile range). Student’s DKD, diabetic kidney disease; BMI, body mass index; SBP, systolic blood pressure; DBP, diastolic blood pressure; AGI, α-glucosidase inhibitor; DPP-4I, dipeptidyl peptidase-4 inhibitor; GLP-1RA, glucagon-like peptide-1 receptor agonist; TG, triglyceride; TC, total cholesterol; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol; UA, uric acid; ISHOMAcp, homeostasis model assessment of insulin resistance using C-peptide; AUCcp, area under the C-peptide curve; AUCglu, area under the glucose curve; HbA1c, glycosylated hemoglobin; AUCgla, area under the glucagon curve; eGFR, estimated glomerular filtration rate; UACR, urinary albumin-to-creatinine ratio.
Values are presented as range, number, mean±standard deviation, or mean difference (95% confidence interval). Model 0: crude; Model 1: adjusted for age, sex, diabetic duration, body mass index, systolic blood pressure, diastolic blood pressure, statins medication, and hypertension; Model 2: additionally adjusted for lipid profiles, serum uric acid, serum albumin, hemoglobin, homeostasis model assessment of insulin resistance using C-peptide, area under the C-peptide curve, area under the glucose curve, postchallenge 2-hour glucose, and glycosylated hemoglobin; Model 3: additionally adjusted for glucose-lowering therapies. CI, confidence interval; T2DM, type 2 diabetes mellitus; eGFR, estimated glomerular filtration rate; UACR, urinary albumin-to-creatinine ratio.
Values are presented as range, number, mean±standard deviation, or mean difference (95% confidence interval). Model 0: crude; Model 1: adjusted for age, sex, diabetic duration, body mass index, systolic blood pressure, diastolic blood pressure, statins medication, and hypertension; Model 2: additionally adjusted for lipid profiles, serum uric acid, serum albumin, hemoglobin, homeostasis model assessment of insulin resistance using C-peptide, area under the C-peptide curve, area under the glucose curve, postchallenge 2-hour glucose, and glycosylated hemoglobin; Model 3: additionally adjusted for glucose-lowering therapies. CI, confidence interval; AUCgla, area under the glucagon curve; T2DM, type 2 diabetes mellitus; eGFR, estimated glomerular filtration rate; UACR, urinary albumin-to-creatinine ratio.
Values are presented as range, number (%), or odds ratio (95% confidence interval). Model 0: crude; Model 1: adjusted for age, sex, diabetic duration, body mass index, systolic blood pressure, diastolic blood pressure, statins medication, and hypertension; Model 2: additionally adjusted for lipid profiles, serum uric acid, serum albumin, hemoglobin, homeostasis model assessment of insulin resistance using C-peptide, area under the C-peptide curve, area under the glucose curve, postchallenge 2-hour glucose, and glycosylated hemoglobin; Model 3: additionally adjusted for glucose-lowering therapies. OR, odds ratio; CI, confidence interval; DKD, diabetic kidney disease; T2DM, type 2 diabetes mellitus; AUCgla, area under the glucagon curve.