# Mapping sex-based multimorbidity networks in type 1 diabetes: a real-world study from Shanghai

**Authors:** Yuxuan Sheng, Ping He, Junlei Su, Zhongyun Zhang, Tingyu Zhang, Haolei Pan, Huayan Yao, Yanbin Xue, Xueyuan Li, Bin Cui, Zizheng Zhang, Weiqiong Gu

PMC · DOI: 10.3389/fendo.2026.1712484 · Frontiers in Endocrinology · 2026-02-18

## TL;DR

This study maps sex-specific patterns of multiple chronic conditions in type 1 diabetes patients in Shanghai, revealing differences in disease networks between males and females.

## Contribution

The paper introduces sex-stratified multimorbidity networks in T1DM using real-world data, identifying sex-specific comorbidity clusters.

## Key findings

- Female T1DM patients showed more complex and connected multimorbidity networks compared to males.
- Subgroup-specific comorbid pairs like neuropathy–osteoporosis were identified in female T1DM patients.
- Hypertension and dyslipidemia emerged as central comorbidities across both diabetes types and sexes.

## Abstract

Type 1 diabetes mellitus (T1DM) is a chronic autoimmune disorder associated with a substantial metabolic burden. However, large-scale, real-world studies assessing sex-specific multimorbidity patterns in T1DM remain limited.

To characterize the clinical profiles and multimorbidity patterns in patients with T1DM, using age- and sex-matched individuals with type 2 diabetes mellitus (T2DM) as comparators.

Using the Shanghai Hospital Link Database, we identified patients aged 10–79 years with a first T1DM-coded diagnosis between 2014 and 2023 and selected 1:1 sex- and index-age–matched T2DM comparators. Clinical characteristics were compared between groups overall and stratified by sex. Sex-stratified multimorbidity networks were constructed and analyzed using standard network metrics. Subgroup-unique comorbid disease pairs were identified using the Salton Cosine Index.

We included 18,971 patients with T1DM and 18,971 matched T2DM comparators. Compared with T2DM, T1DM showed shorter observed follow-up, higher glycated hemoglobin, higher high-density lipoprotein cholesterol, and lower triglyceride, with more pronounced differences among females. Hypertension and dyslipidemia were the most central comorbidities across all networks, closely linked to cardiovascular and cerebrovascular conditions. The female T1DM network exhibited greater complexity and connectivity than the male T1DM network. Subgroup-unique pairs were more frequent in T1DM, including peripheral vascular disease–nonalcoholic fatty liver disease and diabetic eye complications–stroke in males, and neuropathy–osteoporosis, nephropathy–chronic gastritis, and chronic gastritis–asthma in females.

We identified shared cardiometabolic comorbidities (hypertension and dyslipidemia) across diabetes types and sexes, and sex-specific multimorbidity co-occurrence signatures in T1DM. These findings support integrating blood pressure and lipid optimization with glycemic management, and underscore the need for sex-sensitive surveillance of subgroup-specific clusters, highlighting broader multisystem clustering in females and vascular-risk co-occurrence signals in males that may warrant intensified multifactorial atherosclerotic cardiovascular disease prevention.

## Linked entities

- **Diseases:** type 1 diabetes mellitus (MONDO:0005147), type 2 diabetes mellitus (MONDO:0005148), dyslipidemia (MONDO:0002525), peripheral vascular disease (MONDO:0005294), nonalcoholic fatty liver disease (MONDO:0013209), stroke (MONDO:0005098), neuropathy (MONDO:0005244), osteoporosis (MONDO:0005298), chronic gastritis (MONDO:0005001), asthma (MONDO:0004979)

## Full-text entities

- **Genes:** GGTLC5P (gamma-glutamyltransferase light chain 5 pseudogene) [NCBI Gene 653590] {aka GGT}, GPT (glutamic--pyruvic transaminase) [NCBI Gene 2875] {aka AAT1, ALT, ALT1, GPT1, SGPT}, ALPP (alkaline phosphatase, placental) [NCBI Gene 250] {aka ALP, PALP, PLAP, PLAP-1}, SLC17A5 (solute carrier family 17 member 5) [NCBI Gene 26503] {aka AST, ISSD, NSD, SD, SIALIN, SIASD}, GGT1 (gamma-glutamyltransferase 1) [NCBI Gene 2678] {aka CD224, D22S672, D22S732, GGT, GGT 1, GGTD}
- **Diseases:** systemic inflammation (MESH:D007249), complication (MESH:D008107), chronic hepatitis (MESH:D006521), macrovascular diseases (MESH:D004194), circulatory diseases (MESH:D012769), cardiometabolic disturbances (MESH:D024821), cirrhosis (MESH:D005355), PVD (MESH:D016491), atherogenic dyslipidemia (MESH:D050171), NAFLD (MESH:D065626), endothelial dysfunction (MESH:D014652), Diabetes mellitus (MESH:D003920), anxiety (MESH:D001007), asthma (MESH:D001249), autoimmune disease (MESH:D001327), stroke (MESH:D020521), metabolic disorder (MESH:D008659), SCI (MESH:C566784), SHLD (MESH:D003428), microvascular disorders (MESH:D017566), diabetic eye complications (MESH:D048909), Hypertension (MESH:D006973), ASCVD (MESH:D050197), cardiovascular and cerebrovascular conditions (MESH:D002318), hypoglycemia (MESH:D007003), diabetic neuropathy (MESH:D003929), DR (MESH:D003930), ischemic heart disease (MESH:D017202), cerebrovascular disease (MESH:D002561), insulin resistance (MESH:D007333), osteoporosis (MESH:D010024), T2DM (MESH:D003924), PAD (MESH:D058729), nephropathy (MESH:D007674), depression (MESH:D003866), diabetic ketoacidosis (MESH:D016883), T1DM (MESH:D003922), chronic gastritis (MESH:D005756), diabetic kidney disease (MESH:D003928), neuropathy (MESH:D009422)
- **Chemicals:** TC (MESH:D013667), uric acid (MESH:D014527), TG (MESH:D014280), cholesterol (MESH:D002784), LDL-C (-), lipid (MESH:D008055)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

_Full body text omitted from this summary view._ Fetch the complete paper as Markdown: https://tomesphere.com/paper/PMC12957172/full.md

## Figures

1 figure with captions in the complete paper: https://tomesphere.com/paper/PMC12957172/full.md

## References

36 references — full list in the complete paper: https://tomesphere.com/paper/PMC12957172/full.md

---
Source: https://tomesphere.com/paper/PMC12957172