The effect of circulating adiponectin levels on incident gestational diabetes mellitus: systematic review and meta‑analysis

Figures & data

Figure 1. Flow chart of study selection.

Table 1. Characteristics of included studies.

First author, year	Design	Country	GDM risk of study participants	Sample size		Adiponectin assay time	Circulating adiponectin level (unit)		Odds ratio (95%CI)
				GDM	Control		GDM	Control
Ye, 2022	matched nested case-control study	China	Low risk	332	664	6–15 GW	6.5 μg/ml	7.8 μg/ml	Q1: reference Q2: 0.88 (0.60–1.29) Q3: 0.66 (0.43–1.00) Q4: 0.60 (0.38–0.95)
Lomakova, 2022	cohort study	US	Low risk	77	1406	16.83 GW	14.79 ± 1.04 μg/ml	17.87 ± 0.24 μg/ml	Q1: 1.72 (1.05–2.84) Q2 + Q3 + Q4: reference
Al-Mushara, 2021	cohort study	Saudi	Low risk	99	133	8–12 GW	79.0 ± 74.2 μg/ml	84.9 ± 75.4 μg/ml	NR
Florian, 2021	cohort study	Romania	Low risk	21	47	11–14 GW	26.8 (17.6–70.1)	28.4 (18.2–50.79)	NR
Schuitemaker, 2020	matched nested case-control study	Dutch	Low risk	50	100	10–12.85 GW	2.83 ± 0.23^a ng/ml	2.94 ± 0.20^a ng/ml	Per 1 unit increase in log10 transformed concentration: 0.12 (0.02–0.68)
Francis, 2020	matched nested case-control study	US	Low risk	107	214	10–14 GW	NR	NR	Q1: reference Q2: 0.55 (0.26–1.15) Q3: 0.30 (0.13–0.69) Q4: 0.20 (0.07–0.56)
Ramachandrayya, 2020	nested case-control study	India	Low risk	38	38	12–14 GW	9.7 ± 1.96 μg/ml	10.2 ± 3.2 μg/ml	NR
Madhu, 2019	nested case-control study	India	Low risk	45	45	11–13 GW	7.21 ± 2.49 μg/ml	12.20 ± 2.91 μg/ml	NR
Lee, 2019	cohort study	Korea	Low risk	36	572	10–14 GW	1.95 (1.32–2.93) μg/ml	5.34 (3.13–8.28) μg/ml	< 1.72 μg/ml: 5.09 (2.25–11.36) ≥1.72 μg/m: reference
Zhu, 2019	matched nested case-control study	US	Low risk	115	230	16–19 GW	NR	NR	Q1: 5.51 (1.45–21.0) Q2: 2.07 (0.59–7.24) Q3: 0.76 (0.18–3.17) Q4: reference
Sweeting, 2019	matched nested case-control study	Australia	Low risk	248	732	11–14 GW	0.86 (0.69–1.07)^b	1.00 (0.79–1.26)^b	NR
Corcoran, 2018	cohort study	Ireland	High risk	46	178	<15 GW	NR	NR	Per 1 SD increase: 0.64 (0.41–0.99)
Yuan, 2018	cohort study	China	Low risk	86	273	16–18 GW	8.60 (5.03–9.76) μg/ml	10.68 (9.24–12.86) μg/ml	Per 1 unit decrease: 3.57 (2.13–6.00)
Abell, 2017	cohort study	Australia	High risk	25	78	12–15 GW	1.43 (1.30-2.14) μg/ml	2.59 (1.75-3.38) μg/ml	Per 1 unit increase: 0.37 (0.19–0.74)
Thagaard, 2017	cohort study	Denmark	Both high risk and low risk	107	2483	6–14 GW	NR	NR	Per 1 unit increase in log10 transformed concentration: 0.19 (0.06–0.60) in normal weight women 0.21 (0.10–0.40) in moderately obese women 0.40 (0.18–0.91) in severely obese women
White, 2016	cohort study	UK	High risk	337	966	15–18 GW	3.0 ± 0.9^c μg/ml	3.5 ± 0.9^c μg/ml	Per 1 unit increase in log2 transformed concentration: 0.73 (0.60–0.89)
Ravnsborg, 2016	matched nested case-control study	Denmark	Both high risk and low risk	149	156	8–14 GW	6.49 ± 4.34 μg/ml (obesity)	8.80 ± 3.91 μg/ml (obesity)	NR
							8.88 ± 4.47 μg/ml (non-obesity)	11.13 ± 4.75 μg/ml (non-obesity)
Maitland, 2014	cohort study	UK	High risk	29	77	15–17 GW	4.97(1.72)^d	7.34(1.76)^d	M1: 4.04 (1.69–9.64) M2: reference
Lacroix, 2013	cohort study	Canada	Low risk	38	407	6–13 GW	9.67 ± 3.84 μg/ml	11.92 ± 4.59 μg/ml	Per 1 unit decrease: 1.12 (1.02–1.23)
Ianniello, 2013	cohort study	Italy	High risk	16	16	<14 GW	1.41 ± 0.14 μg/ml	2.27 ± 0.27 μg/ml	NR
Nanda, 2011	matched nested case-control study	UK	Low risk	80	300	11–13 GW	7591(4552–10,870) ng/ml	12,035(8595–17,085) ng/ml	NR
Ferreira, 2011	matched nested case-control study	UK	Low risk	100	300	11-13 GW	7591 (4552–11,059) μg/L	12,035 (8595–17,085) μg/L	NR
Paradisi, 2010	cohort study	Rome	High risk	12	38	7-10 GW	1.98 ± 0.76 ng/ml	2.32 ± 0.99 ng/ml	NR
Savvidou, 2010	matched nested case-control study	UK	Low risk	124	248	11-14 GW	7.38 ± 4.19 μg/ml	9.88 ± 5.57 μg/ml	NR
Lain, 2008	matched nested case-control study	US	Low risk	30	29	9.3 ± 2.6 GW	4.3 ± 0.4 μg/ml	6.9 ± 0.6 μg/ml	Q1: 10.2 (1.3–78.7) Q2: 1.9 (0.3–12.2) Q3: 1.0 (0.2–5.7) Q4: reference
Georgiou, 2008	matched nested case-control study	Australia	Low risk	14	14	11 GW	3.0 ± 0.2 μg/ml	4.9 ± 0.6 μg/ml	NR
Gao, 2008	nested case-control study	China	Low risk	20	20	14-20 GW	5.06 ± 1.25 ng/ml	9.18 ± 1.95 ng/ml	NR
Williams, 2004	nested case-control study	US	Low risk	41	70	<16 GW	4.4 μg/ml	8.1 μg/ml	T1: 4.6 (1.8–11.6) T2 + T3: reference

GDM: gestational diabetes mellitus; GW: gestational week; Q1–Q4: the first to the fourth quartiles; T1–T3: the first to the third tertiles; M1–M2: the first to the second medians; NR: not reported.

^alog10 transformed concentrations.

^bMOM, multiples of the expected normal median.

^clog2 transformed concentration.

^dGeometric means and ratios of geometric means.

Table 2. Methodological quality of studies included in meta-analysis.

First author, year	Cases definition	Representativeness of cases	Selection of controls	Definition of controls	Control for important factor or additional factors^a	Ascertainment of exposure	Same method of ascertainment for participants	Nonresponsive rate^b	Total quality scores
Ye, 2022	⋆	⋆	⋆	–	⋆⋆	⋆	⋆	–	7
Schuitemaker, 2020	–	⋆	⋆	–	⋆⋆	⋆	⋆	–	6
Francis, 2020	⋆	⋆	⋆	–	⋆⋆	⋆	⋆	–	7
Ramachandrayya, 2020	⋆	⋆	⋆	⋆	⋆⋆	⋆	⋆	–	8
Madhu, 2019	⋆	⋆	⋆	–	⋆⋆	⋆	⋆	–	7
Zhu, 2019	⋆	⋆	⋆	⋆	⋆⋆	⋆	⋆	–	8
Sweeting, 2019	⋆	⋆	⋆	–	⋆	⋆	⋆	–	6
Ravnsborg, 2016	⋆	⋆	⋆	–	⋆	⋆	⋆	–	6
Nanda, 2011	⋆	⋆	⋆	–	–	⋆	⋆	–	5
Ferreira, 2011	⋆	⋆	⋆	–	–	⋆	⋆	–	5
Savvidou, 2010	⋆	⋆	⋆	–	⋆⋆	⋆	⋆	–	7
Lain, 2008	⋆	⋆	⋆	–	⋆⋆	⋆	⋆	–	7
Georgiou, 2008	⋆	⋆	⋆	–	⋆⋆	⋆	⋆	–	7
Gao, 2008	⋆	⋆	⋆	⋆	⋆	⋆	⋆	–	7
Williams, 2004	⋆	⋆	⋆	⋆	⋆⋆	⋆	⋆	⋆	8
First author (year)	Representativeness of the exposed cohort	Selection of unexposed cohort	Assessment of exposure	Absence of outcome at start of study	Control for important factor or additional factors^a	Outcome assessment	Follow-up period	Adequacy of follow-up^b	Total quality scores
Lomakova, 2022	⋆	⋆	⋆	–	⋆⋆	⋆	⋆	⋆	8
Al-Musharaf, 2021	⋆	⋆	⋆	–	⋆⋆	⋆	⋆	–	7
Florian, 2021	⋆	⋆	⋆	–	–	⋆	⋆	–	5
Lee, 2019	⋆	⋆	⋆	⋆	⋆⋆	⋆	⋆	⋆	9
Corcoran, 2018	–	⋆	⋆	⋆	⋆⋆	⋆	⋆	⋆	8
Yuan, 2018	⋆	⋆	⋆	–	⋆⋆	⋆	⋆	–	7
Abell, 2017	–	⋆	⋆	–	⋆⋆	⋆	⋆	⋆	7
Thagaard, 2017	–	⋆	⋆	–	⋆⋆	⋆	⋆	⋆	7
White, 2016	–	⋆	⋆	–	⋆⋆	⋆	⋆	⋆	7
Maitland, 2014	–	⋆	⋆	–	⋆⋆	⋆	⋆	⋆	7
Lacroix, 2013	⋆	⋆	⋆	–	⋆⋆	⋆	⋆	⋆	8
Ianniello, 2013	–	⋆	⋆	–	⋆⋆	⋆	⋆	–	6
Paradisi, 2010	–	⋆	⋆	–	⋆⋆	⋆	⋆	⋆	7

^aStudies that controlled for age received one star. Studies that controlled for BMI received an additional star.

^bCase control studies with a responsive rate more than 80%, or cohort studies with a follow-up rate more than 80% received one star.

Figure 2. The pooled SMD and 95% CI of circulating adiponectin levels between GDM and NGT.

Figure 3. Subgroup analyses of circulating adiponectin levels between GDM and NGT by (A) continents, (B) GDM risk of study population, (C) study design, (D) GW of adiponectin detection, (E) GDM diagnostic approach, (F) methodological quality.

Figure 4. The pooled OR and 95%CI of increased circulating adiponectin levels for incident GDM.

Figure 5. Subgroup analyses of the relationship between circulating adiponectin levels and GDM risks by (A) continents, (B) GDM risk of study population, (C) study design, (D) GW of adiponectin detection, (E) GDM diagnostic approach, (F) methodological quality.

Data availability statement

All data in the article and its supplementary materials are available.