Adiponectin Paradox More Evident in Non-Obese Than in Obese Patients with Diabetic Microvascular Complications

Figures & data

Table 1 Characteristics of the Study Patients

Parameters	Category		P value
	Non-Obese (20.0≦BMI<25.0)	Obese (32.0≦BMI)
N (Male/Female)	197 (98/99)	197 (104/93)	0.755
Age (years)	55 (45–61)	54 (44–63)	0.726
BMI (kg/m^2)	23.0 (22.0–23.9)	35.1 (33.4–38.5)	<0.001
Diabetes duration (years)	5 (1–12)	8 (2.7–14)	0.005
HbA1c (%)	9.9 (8.5–11.7)	8.8 (7.4–10.3)	<0.001
AST (U/mL)	18 (14–23)	31 (21–51)	<0.001
ALT (U/mL)	20 (14–30)	39 (24–69)	<0.001
γ-GT (U/mL)	30 (18–47)	54 (33–91)	<0.001
UA (mg/dl)	4.9 (3.9–5.8)	6.2 (5.2–7.2)	<0.001
eGFR (mL/min/1.73m^2)	92.6 (76.3–114.2)	78.8 (64.4–99.5)	<0.001
UAE (mg/g creatinine)	11.9 (5.0–36.0)	21.7 (8.5–100.5)	<0.001
S-CPR (ng/mL)	1.37 (0.98–1.93)	2.50 (1.51–3.14)	<0.001
Adiponectin (μg/mL)	3.00 (2.00–5.00)	2.36 (1.38–4.00)	0.005
Leptin (ng/mL)	5.3 (3.2–9.4)	22.0 (13.8–33.0)	<0.001
VFA (cm^2)	126 (97–156)	243 (201–314)	<0.001
SFA (cm^2)	129 (100–170)	378 (298–463)	<0.001
PWV (m/s)	1462 (1292–1721)	1405 (1257–1623)	0.033
Max IMT (mm)	1.50 (1.21–2.1)	1.25 (0.86–1.65)	0.001
Diabetic Retinopathy, n	57	48	0.077
Diabetic Nephropathy, n	57	79	0.004
Diabetic Neuropathy, n	33	25	0.775
Hypertension, n (%)	80 (41)	139 (71)	<0.001
Dyslipidemia, n (%)	100 (51)	125 (63)	<0.001

Notes: Median values (25th-75th percentile) are shown. The Mann–Whitney U-test or the chi-square test was used for all analyses. The values are expressed as either the number of examples (ratio: %) or the median (interquartile range).

Abbreviations: N, number; BMI, body mass index; HbA1c, hemoglobin A1c; AST, aspartate aminotransferase; ALT, alanine aminotransferase; γ-GT, gamma-glutamyl transferase; UA, uric acid; eGFR, estimated glomerular filtration rate; UAE, urinary albumin excretion; CPR, C-peptide; VFA, visceral fat area; SFA, subcutaneous fat area; PWV, Pulse Wave Velocity; IMT, Intima Media Thickness.

Table 2 Comparison of Factors Related to Diabetic Retinopathy Within Each Group

Parameters	Category
	Non-Obese		Obese
	Diabetic Retinopathy (-)	Diabetic Retinopathy (+)	Diabetic Retinopathy (-)	Diabetic Retinopathy (+)
	(n=95)	(n=57)	(n=121)	(n=48)
Age (years)	53 (44–60)	58 (49–64)	53(43–60)	56 (48–63)
Gender:Male, n (%)	49 (52)	26 (46)	66 (54)	22 (46)
BMI (kg/m^2)	23.2 (22.1–24.2)	22.9 (21.6–23.7)	34.7 (33.2–37.7)	34.9 (33.3–37.8)
Diabetes duration (years)	2 (1–7)	10 (1–19)**	5 (1–10)	12 (8–18)**
HbA1c (%)	9.8 (8.6–11.6)	10.2 (8.5–11.8)	9.3 (8.0–10.6)	8.9 (7.9–10.3)
AST (U/mL)	19 (15–25)	18 (13–22)	35 (23–55)	26 (17–36)**
ALT (U/mL)	23 (16–35)	17 (11–26)**	46 (29–81)	31 (18–44)**
γ-GT (U/mL)	31 (22–47)	24 (16–42)*	65 (37–113)	37 (24–56)**
UA (mg/dl)	4.9 (3.8–6.0)	4.9 (4.2–6.2)	6.1 (5.2–7.3)	6.2 (5.2–7.2)
eGFR (mL/min/1.73m^2)	92.7 (78.6–111.1)	89.6 (64.0–109.2)	84.3 (68.5–99.5)	72.5 (47.8–99.8)*
UAE (mg/g creatinine)	6.4 (5.0–15.0)	24.5 (9.2–250.8)**	17.0 (6.2–60.6)	41.3 (15.2–512.6)**
S-CPR (ng/mL)	1.51 (1.01–1.94)	1.28 (0.88–1.87)	2.57 (1.73–3.20)	1.73 (1.38–2.65)*
Adiponectin (μg/mL)	2.52 (1.53–4.00)	3.00 (2.32–6.12)**	2.03 (1.09–4.00)	2.68 (2.04–5.02)*
Leptin (ng/mL)	5.2 (3.1–9.3)	5.4 (3.3–9.4)	21.3 (12.7–29.7)	21.3 (15.8–37.3)
VFA (cm^2)	135 (105–167)	116 (86–147)*	237 (201–314)	237 (193–311)
SFA (cm^2)	136 (104–172)	114 (92–166)	363 (289–439)	364 (300–437)
PWV (m/s)	1369 (1236–1488)	1709 (1387–1844)**	1338 (1224–1504)	1613 (1396–1701)**
Max IMT (mm)	1.4 (0.9–1.8)	2.0 (1.3–2.1)*	1.2 (0.8–1.5)	1.5 (1.0–1.9)*
Hypertension, n (%)	30 (32)	30 (53)*	84 (69)	42 (88)*
Dyslipidemia, n (%)	50 (53)	27 (47)	83 (68)	30 (63)

Notes: Median values (25th-75th percentile) or number of examples (ratio: %) are shown. The Mann–Whitney U-test or the chi-square test was used for all analyses. *p<0.05, **p<0.01.

Abbreviations: n, number; BMI, body mass index; HbA1c, hemoglobin A1c; AST, aspartate aminotransferase; ALT, alanine aminotransferase; γ-GT, gamma-glutamyl transferase; UA, uric acid; eGFR, estimated glomerular filtration rate; UAE, urinary albumin excretion; CPR, C-peptide; VFA, visceral fat area; SFA, subcutaneous fat area; PWV, Pulse Wave Velocity; IMT, Intima Media Thickness.

Table 3 Comparison of Factors Related to Diabetic Nephropathy Within Each Group

Parameters	Category
	Non-Obese		Obese
	Diabetic Nephropathy (-)	Diabetic Nephropathy (+)	Diabetic Nephropathy (-)	Diabetic Nephropathy (+)
	(n=138)	(n=59)	(n=113)	(n=83)
Age (years)	54 (45–61)	55 (49–61)	53 (44–61)	54 (43–64)
Gender:Male, n (%)	70 (51)	28 (47)	48 (42)	56 (67)**
BMI (kg/m^2)	23.0 (22.0–24.0)	22.8 (21.9–23.9)	34.8 (33.4–38.4)	35.1 (33.4–38.5)
Diabetes duration (years)	3 (1–9)	10 (5–17)**	6 (1–12)	10 (5–15)**
HbA1c (%)	10.0 (8.6–11.6)	9.8 (8.2–11.7)	9.1 (7.9–10.5)	8.6 (7.3–10.1)
AST (U/mL)	18 (14–23)	18 (14–22)	33 (22–53)	28 (19–44)
ALT (U/mL)	20 (15–30)	19 (14–29)	40 (26–77)	37 (23–60)
γ-GT (U/mL)	27 (17–44)	33 (20–62)	47 (33–76)	59 (34–114)
UA (mg/dl)	4.8 (3.8–5.6)	5.2 (4.3–6.5)**	5.8 (4.8–6.8)	6.7 (5.8–7.6)**
eGFR (mL/min/1.73m^2)	94.5 (81.9–114.4)	87.2 (60.7–111.4)*	84.8 (70.5–101.0)	69.6 (42.8–93.0)**
UAE (mg/g creatinine)	6.15 (5.0–13.2)	77.4 (41.0–335.0)**	10.0 (5.0–16.6)	110.6 (52.1–552.5)**
S-CPR (ng/mL)	1.35 (1.00–1.84)	1.55 (0.84–2.31)	2.42 (1.53–3.08)	2.54 (1.52–3.30)
Adiponectin (μg/mL)	2.80 (2.00–4.09)	4.00 (2.13–7.00)**	2.43 (1.21–4.00)	2.36 (1.62–4.24)
Leptin (ng/mL)	5.3 (3.1–9.1)	6.4 (3.6–10.0)	22.0 (14.5–32.9)	22.3 (12.7–35.0)
VFA (cm^2)	127 (97–149)	125 (93–162)	230 (194–302)	251 (202–325)
SFA (cm^2)	130 (103–167)	124 (92–177)	391 (315–463)	368 (284–462)
PWV (m/s)	1399 (1246–1657)	1664 (1400–1801)**	1325 (1243–1501)	1494 (1363–1711)**
Max IMT (mm)	1.4 (1.0–2.1)	1.5 (1.4–2.1)	1.1 (0.8–1.4)	1.4 (0.9–1.9)*
Hypertension, n (%)	45 (33)	35 (59)**	77 (68)	61 (73)
Dyslipidemia, n (%)	67 (49)	33 (56)	72 (64)	53 (64)

Notes: Median values (25th-75th percentile) or number of examples (ratio: %) are shown. The Mann–Whitney U-test or the chi-square test was used for all analyses. *p<0.05, **p<0.01.

Abbreviations: n, number; BMI, body mass index; HbA1c, hemoglobin A1c; AST, aspartate aminotransferase; ALT, alanine aminotransferase; γ-GT, gamma-glutamyl transferase; UA, uric acid; eGFR, estimated glomerular filtration rate; UAE, urinary albumin excretion; CPR, C-peptide; VFA, visceral fat area; SFA, subcutaneous fat area; PWV, Pulse Wave Velocity; IMT, Intima Media Thickness.

Table 4 Comparison of Factors Related to Diabetic Neuropathy Within Each Group

Parameters	Category
	Non-Obese		Obese
	Diabetic Neuropathy (-)	Diabetic Neuropathy (+)	Diabetic Neuropathy (-)	Diabetic Neuropathy (+)
	(n=161)	(n=33)	(n=134)	(n=25)
Age (years)	54 (45–60)	58 (50–68)	52 (43–59)	61 (54–66)**
Gender:Male, n (%)	79 (49)	19 (58)	76 (57)	5 (20)**
BMI (kg/m^2)	23.0 (22.0–24.0)	22.5 (21.9–23.7)	34.7 (33.2–37.5)	34.4 (33.5–37.5)
Diabetes duration (years)	4 (1–10)	12 (6–18)**	6 (1–12)	10 (6–13)
HbA1c (%)	9.8 (8.5–11.7)	10.2 (8.9–11.2)	9.3 (8.0–10.5)	8.6 (7.9–10.3)
AST (U/mL)	18 (14–23)	19 (13–23)	33 (21–52)	27 (17–44)
ALT (U/mL)	20 (15–31)	19 (14–26)	41 (25–73)	32 (20–46)*
γ-GT (U/mL)	30 (20–50)	26 (15–45)	57 (36–104)	45 (36–80)
UA (mg/dl)	4.9 (3.9–6.0)	4.7 (3.9–5.5)	6.2 (5.2–7.3)	5.8 (4.5–6.2)
eGFR (mL/min/1.73m^2)	91.9 (77.0–111.9)	95.4 (61.4–118.9)	83.6 (67.4–101.2)	67.0 (50.1–87.9)*
UAE (mg/g creatinine)	11.9 (5.0–36.0)	13.5 (5.8–39.0)	18.7 (6.8–80.4)	21.1 (5.2–86.3)
S-CPR (ng/mL)	1.38 (1.00–2.01)	1.22 (0.86–1.64)	2.53 (1.67–3.22)	1.68 (1.29–2.72)*
Adiponectin (μg/mL)	2.76 (2.00–4.41)	5.00 (3.40–8.00)**	2.18 (1.15–4.00)	2.65 (2.18–4.60)
Leptin (ng/mL)	5.3 (3.2–9.3)	5.3 (3.2–9.3)	20.9 (11.8–32.8)	28.1 (17.9–36.8)*
VFA (cm^2)	130 (102–162)	100 (82–138)**	237 (198–315)	224 (157–306)
SFA (cm^2)	130 (100–167)	119 (86–166)	362 (292–439)	357 (282–391)
PWV (m/s)	1422 (1279–1674)	1712 (1461–1884)**	1413 (1249–1619)	1391 (1350–1642)
Max IMT (mm)	1.5 (1.0–2.1)	2.1 (1.4–2.6)	1.1 (0.8–1.5)	1.6 (1.3–1.8)*
Hypertension, n (%)	67 (42)	13 (39)	100 (75)	19 (76)
Dyslipidemia, n (%)	87 (54)	13 (39)	91 (68)	17 (68)

Notes: Median values (25th-75th percentile) or number of examples (ratio: %) are shown. The Mann–Whitney U-test or the chi-square test was used for all analyses. *p<0.05, **p<0.01.

Abbreviations: n, number; BMI, body mass index; HbA1c, hemoglobin A1c; AST, aspartate aminotransferase; ALT, alanine aminotransferase; γ-GT, gamma-glutamyl transferase; UA, uric acid; eGFR, estimated glomerular filtration rate; UAE, urinary albumin excretion; CPR, C-peptide; VFA, visceral fat area; SFA, subcutaneous fat area; PWV, Pulse Wave Velocity; IMT, Intima Media Thickness.

Table 5 Multivariate Logistic Regression Analysis for the Presence of Diabetic Vascular Complications Within the Non-Obese and Obese Groups

Parameters	Category
	Non-Obese			Obese
	Retinopathy	Nephropathy	Neuropathy	Retinopathy	Nephropathy	Neuropathy
Age	1.01 (0.968–1.060)	1.10 (1.044–1.164)**	0.98 (0.949–1.021)	1.00 (0.950–1.057)	1.03 (0.971–1.109)	1.02 (0.987–1.067)
Male	0.52 (0.193–1.445)	2.43 (0.794–7.449)	0.55 (0.223–1.398)	2.08 (0.599–7.274)	0.15 (0.031–0.789)*	2.69 (1.013–7.148)*
Diabetes duration	1.11 (1.048–1.186)**	1.07 (1.017–1.126)**	1.05 (1.013–1.107)*	1.12 (1.047–1.202)**	1.01 (0.933–1.106)	1.08 (1.022–1.154)**
HbA1c	1.06 (0.881–1.292)	1.09 (0.897–1.334)	1.02 (0.879–1.200)	0.99 (0.793–1.247)	0.98 (0.743–1.312)	0.88 (0.736–1.074)
ALT	0.98 (0.963–1.004)	1.00 (0.993–1.016)	1.00 (0.988–1.014)	0.98 (0.964–1.001)	0.98 (0.743–1.312)	0.99 (0.986–1.006)
UA	1.26 (0.928–1.728)	1.14 (0.811–1.607)	1.33 (1.061–1.688)*	0.91 (0.649–1.284)	0.78 (0.463–1.329)	1.25 (0.974–1.627)
eGFR	1.00 (0.986–1.020)	1.02 (1.004–1.042)*	1.01 (0.978–1.067)	1.00 (0.984–1.019)	0.99 (0.964–1.017)	0.99 (0.902–1.030)
Adiponectin	1.13 (1.004–1.289)*	1.19 (1.077–1.319)**	1.21 (1.071–1.384)**	1.00 (0.863–1.166)	0.93 (0.756–1.143)	0.99 (0.868–1.138)
Hypertension	2.13 (0.909–4.997)	0.53 (0.191–1.488)	2.68 (1.238–5.828)*	3.94 (1.071–14.553)*	0.74 (0.168–3.311)	0.87 (0.334–2.309)
Dyslipidemia	0.66 (0.291–1.506)	0.55 (0.215–1.418)	1.44 (0.686–3.056)	0.18 (0.051–0.660)**	2.36 (0.495–11.303)	0.53 (0.185–1.531)

Notes: Odds ratios (95% CI) determined by multivariate logistic regression analyses are shown. *p<0.05, **p<0.01.

Abbreviations: HbA1c, hemoglobin A1c; ALT, alanine aminotransferase; UA, uric acid; eGFR, estimated glomerular filtration rate.