Diabetes & Metabolism Journal

Original Articles

Metabolic Risk/Epidemiology
Birth Weight, Adult Fat Distribution, and Type 2 Diabetes Mellitus Risk: Sex-Specific Study in a Large Prospective Cohort: Ding Ding, Xiaoyi Luo, Shuhao Chen, Zhilin Liu, Xiaojing Kuang, Tianrui Zhuang, Gaoli She, Hailan Huang, Xingfen Yang, Jie Li, Ran An; Received June 29, 2025 Accepted October 23, 2025 Published online January 29, 2026; DOI: https://doi.org/10.4093/dmj.2025.0569 [Epub ahead of print]

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Abstract PDF Supplementary Material PubReader ePub: Background
Regional fat distribution is a key determinant of metabolic risk, independent of total adiposity. However, the developmental origins of fat depot-specific accumulation and its contribution to type 2 diabetes mellitus (T2DM) remain unclear. We aimed to investigate whether adult fat distribution mediates the association between birth weight (BW) and T2DM risk.
Methods
We analyzed 30,718 diabetes-free UK Biobank participants with magnetic resonance imaging/dual-energy X-ray absorptiometry derived measures of visceral adipose tissue (VAT), abdominal subcutaneous adipose tissue, and gynoid adipose tissue (GAT), liver fat fraction (LFF), pancreatic fat fraction (PFF), and muscle fat infiltration (MFI). Fat depots were adjusted for body mass index (BMI) using sex-specific residuals. Cox regression assessed associations of BW and fat depots with T2DM risk. Mediation analysis assessed indirect effects of fat distribution.
Results
Lower BW was associated with a higher risk of T2DM (hazard ratio per 1 kg increase, 0.71; 95% confidence interval, 0.64 to 0.79), with stronger effects in women. Lower BW was linked to greater VAT, LFF, and PFF, and lower GAT, independent of BMI. Higher levels of VAT, LFF, and PFF were associated with increased T2DM risk, while GAT was protective. Mediation analysis revealed that fat distribution partially mediated the BW-T2DM relationship, with LFF showing the strongest mediation effect (11%). Mediation patterns differed by sex: LFF and VAT were the predominant mediators in women, while LFF and GAT contributed substantially in men.
Conclusion
Fat distribution—particularly liver and visceral fat—partially mediates the BW-T2DM relationship, independent of BMI. These findings highlight the clinical importance of fat depot profiling in understanding the developmental origins of diabetes and guiding early risk stratification.

Technology/Device
First Trimester Mean Glucose Level on Continuous Glucose Monitoring Is Associated with Infant Birth Weight: Phaik Ling Quah, Lay Kok Tan, Serene Pei Ting Thain, Ngee Lek, Shephali Tagore, Bernard Su Min Chern, Seng Bin Ang, Ann Wright, Michelle Jong, Kok Hian Tan; Diabetes Metab J. 2025;49(6):1262-1271. Published online June 2, 2025; DOI: https://doi.org/10.4093/dmj.2024.0700

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Abstract PDF Supplementary Material PubReader ePub: Background
Comparisons between continuous glucose monitoring (CGM) metrics during the first and second trimesters and conventional mid-pregnancy oral glucose tolerance test (OGTT) values in pregnant women without pre-existing diabetes for predicting infant birth weight are scarce.
Methods
In a longitudinal observational study, 113 participants had first and second trimester CGM data collected over a 7- to 14-day period, as well as three-point OGTT (fasting, 1-hour, and 2-hour) performed at mid-pregnancy (24 to 28 weeks). Multinomial logistic regression, adjusting for maternal ethnicity, education level, age, pre-pregnancy body mass index, parity, gestational diabetes mellitus diagnosis, gestational age at delivery, and type of CGM sensor was used to analyse the relationship between CGM metrics, OGTT glucose values and infant birth weight tertile (Clinical trial identification number: NCT05123248).
Results
In the univariate analysis, CGM-derived metrics including higher mean glucose in the first trimester, higher % time above range in the second trimester, and higher % time in range (TIR) and lower % time below range (TBR) in both the first and second trimesters were associated with infants in the highest birth weight tertile. After adjusting for confounders, a 1-standard deviation increase in mean glucose level during the first trimester was significantly associated with the likelihood of the neonatal birthweight being in the highest tertile (adjusted odds ratio, 3.11; 95% confidence interval, 1.18 to 8.21; P=0.022). No significant associations were found between OGTT glucose values and infant birth weight outcomes.
Conclusion
CGM-derived mean glucose levels in early pregnancy may be a better predictor of an infant’s birth weight within the highest tertile, compared to mid-pregnancy OGTT glucose values.

Metabolic Risk/Epidemiology
Birth Weight, Cardiovascular Health, and Microvascular Complications in Individuals with Diabetes Mellitus: Chaolun Yu, Anping Feng, Xia Zou, Siqi Chen, Lingyan Dai, Qingmei Cui, Xiaojing Kuang, Gaoli She, Ying Ma, Haixia Guan, Jie Li; Diabetes Metab J. 2025;49(5):1075-1086. Published online May 23, 2025; DOI: https://doi.org/10.4093/dmj.2024.0518

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Abstract PDF Supplementary Material PubReader ePub: Background
Diabetes often leads to microvascular complications, including nephropathy, neuropathy, and retinopathy. Understanding the impact of early-life factors like birth weight and modifiable behaviors such as cardiovascular health (CVH) is essential for preventing these complications.
Methods
We included 11,515 participants with diabetes but without microvascular complications at baseline from the UK Biobank Study. CVH was evaluated using the Life’s Essential 8 score. Independent and joint associations of birth weight and CVH with microvascular complications were analyzed using Cox proportional hazard models. Two-sample Mendelian randomization (MR) analyses estimated unconfounded associations between birth weight and microvascular complications.
Results
Over a median follow-up of 13.1 years, 3,010 microvascular complications occurred. Compared with normal birth weight (2.5–4.0 kg), low birth weight (LBW; <2.5 kg) was associated with 15% higher risk of diabetic nephropathy (hazard ratio [HR], 1.15; 95% confidence interval [CI], 1.01 to 1.31), but not with neuropathy and retinopathy. High birth weight (>4.0 kg) was not associated with the risk of diabetic microvascular complications. MR analysis confirmed the association between LBW and nephropathy. Adherence to high CVH was associated with a reduced risk of microvascular complications compared to low CVH, regardless of birth weight. The HRs were 0.70 (95% CI, 0.59 to 0.84) for the LBW group and 0.74 (95% CI, 0.68 to 0.80) for the group with birth weight ≥2.5 kg (P for interaction=0.69).
Conclusion
LBW was an independent risk factor for nephropathy among diabetic patients. However, the detrimental effects of LBW might be mitigated by improvement in CVH.

Metabolic Risk/Epidemiology
Postprandial Free Fatty Acids at Mid-Pregnancy Increase the Risk of Large-for-Gestational-Age Newborns in Women with Gestational Diabetes Mellitus: So-Yeon Kim, Young Shin Song, Soo-Kyung Kim, Yong-Wook Cho, Kyung-Soo Kim; Diabetes Metab J. 2022;46(1):140-148. Published online August 9, 2021; DOI: https://doi.org/10.4093/dmj.2021.0023

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Graphical Abstract Abstract PDF Supplementary Material PubReader ePub

Background
To investigate the association between free fatty acid (FFA) level at mid-pregnancy and large-for-gestational-age (LGA) newborns in women with gestational diabetes mellitus (GDM).
Methods
We enrolled 710 pregnant women diagnosed with GDM from February 2009 to October 2016. GDM was diagnosed by a ‘two-step’ approach with Carpenter and Coustan criteria. We measured plasma lipid profiles including fasting and 2-hour postprandial FFA (2h-FFA) levels at mid-pregnancy. LGA was defined if birthweights of newborns were above the 90th percentile for their gestational age.
Results
Mean age of pregnant women in this study was 33.1 years. Mean pre-pregnancy body mass index (BMI) was 22.4 kg/m². The prevalence of LGA was 8.3% (n=59). Levels of 2h-FFA were higher in women who delivered LGA newborns than in those who delivered non-LGA newborns (416.7 μEq/L vs. 352.5 μEq/L, P=0.006). However, fasting FFA was not significantly different between the two groups. The prevalence of delivering LGA newborns was increased with increasing tertile of 2h-FFA (T1, 4.3%; T2, 9.8%; T3, 10.7%; P for trend <0.05). After adjustment for maternal age, pre-pregnancy BMI, and fasting plasma glucose, the highest tertile of 2h-FFA was 2.38 times (95% confidence interval, 1.11 to 5.13) more likely to have LGA newborns than the lowest tertile. However, there was no significant difference between groups according to fasting FFA tertiles.
Conclusion
In women with GDM, a high 2h-FFA level (but not fasting FFA) at mid-pregnancy is associated with an increasing risk of delivering LGA newborns.

Citations

Citations to this article as recorded by

Postpartum Glucose Intolerance in Women with a History of Gestational Diabetes Mellitus: An In-Depth Review
Kyung-Soo Kim, Soo-Kyung Kim, Yong-Wook Cho
Endocrinology and Metabolism.2026; 41(1): 26. CrossRef
Longitudinal Trajectory of Free Fatty Acids in Pregnancy According to First-Trimester Maternal Metabolic Status and the Presence of Gestational Diabetes
Otilia Perichart-Perera, Isabel González-Ludlow, Omar Piña-Ramírez, Maricruz Tolentino-Dolores, Guadalupe Estrada-Gutierrez, Sandra B. Parra-Hernández, Maribel Sánchez-Martínez, Omar Granados-Portillo, Ameyalli M. Rodríguez-Cano
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Medicine.2025; 104(51): e46580. CrossRef
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Journal of Translational Medicine.2024;[Epub] CrossRef
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Modulation of gut microbiota and lipid metabolism in rats fed high-fat diets by Ganoderma lucidum triterpenoids
Aijun Tong, Weihao Wu, Zhengxin Chen, Jiahui Wen, Ruibo Jia, Bin Liu, Hui Cao, Chao Zhao
Current Research in Food Science.2023; 6: 100427. CrossRef
Fetal Abdominal Obesity Detected at 24 to 28 Weeks of Gestation Persists until Delivery Despite Management of Gestational Diabetes Mellitus (Diabetes Metab J 2021;45:547-57)
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Diabetes & Metabolism Journal.2021; 45(6): 970. CrossRef

Relationship of Insulin-like Growth Factor(IGF)-1, IGF-2, IGF Binding Protein(IGFBP)-3, and Mitochondrial DNA Amount in the Umbilical Cord Blood to Birth Weight.: Yun Yong Lee, Do Joon Park, Chan Soo Shin, Kyong Soo Park, Hong Kyu Lee, Jong Kwan Jun, Boh Yun Yoon, Jih Yeun Song, Bong Sun Kang; Korean Diabetes J. 1999;23(1):36-45. Published online January 1, 2001

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Abstract PDF: BACKGROUND
Reaven proposed a syndrome (syndrome X), consisting of glucose intolerance, hypertension, hyperinsulinemia, dyslipidemia, as a clinical entity. The fundamental metabolic defect of this syndrome was recognized as insulin resistance, but the pathophysiology of insulin resistance is not clarified as of yet. Recent evidence, suggests that non-insulin dependent diabetes mellitus (NIDDM) ancl lipid and cardiovascular abnormalities-syndrome X-are associated with intrauterine growth retar- dation (IUGR). Recently Shin reported that the amounts of mitochondrial DNA (mtDNA) in a given amount of genomic DNA were lower in NIDDM patients than in healthy controls, and the amount of mtDNA is negatively correlated with blood pressure ancl waist-hip ratio. Birth weight is known to be correlated with levels of insulin-like growth factors (IGFs). The purpose of this study was to identify the correlation of low birth weight with reduced mtDNA and syndrome X. We investigated the relationship of birth weight to IGFs and the amount of mtDNA METHODS: 72 singleton pregnancy babies and their mathers admitted in Seoul National University Hospital from March to May, 1997 were studied. After delivery, the cord blcxxl and maternal venous blood sampling was done. Using the imnnmoradiometric assay (IRMA) the IGF-l, IGF-2, IGFBP-3 was measured from cord and maternal plasma. Among them only 27 pairs samples were measured mtDNA amount with competitive PCR method in their buffy coat. Then statistical analysis was done within these paratneters. RESULTS: Birth weight is correlated significantly with cord plasma IGF-1 (r=0.32, p<0.01), IGFBP-3 (r=0.44, p<0.01), prepregnancy maternal body weight (r=0.45, p<0.01), maternal mtDNA amount (r=0.63, p<0.01). Cord blood mtDNA is correlated with maternal mtDNA amount (r=0.55, p<0,01). In multiple regression analysis, the maternal mtDNA was found to be the only independent factor related to birth weight (p<0.01). COMCLUSION: We have found the correlation between birth weight and maternal prepregnancy body weight and mtDNA amount. The clinical implications of this result remain yet to be deiermined.

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