Sex differences in type 2 diabetes: focus on disease course and outcomes
Open accessAbstract
BACKGROUND: Women with type 2 diabetes (T2D) are less likely to reach the goals for hemoglobin A1c compared with men, and have higher all-cause mortality. The risk of cardiovascular disease is elevated among both men and women with T2D, however, the risk has declined among men over recent years while it remains stationary in women. Reasons for these sex differences remain unclear, and guidelines for diabetes treatment do not differentiate between sexes. Possible causes for varying outcome include differences in physiology, treatment response, and psychological factors. This review briefly outlines sex differences in hormonal pathophysiology, and thereafter summarizes the literature to date on sex differences in disease course and outcome. METHODS: Systematic searches were performed on PubMed using "sex", "gender", and various glucose-lowering therapies as keywords. Earlier reviews are summarized and results from individual studies are reported. Reference lists from studies were used to augment the search. RESULTS: There is an increased risk of missing the diagnosis of T2D when screening women with only fasting plasma glucose instead of with an oral glucose tolerance test. The impact of various risk factors for complications may differ by sex. Efficacy and side effects of some glucose-lowering drugs differ between men and women. Men with T2D appear to suffer more microvascular complications, while women have higher morbidity and mortality in cardiovascular disease and also fare worse psychologically. CONCLUSION: Few studies to date have focused on sex differences in T2D. Several questions demand further study, such as whether risk factors and treatment guidelines should be sex-specific. There is a need for clinical trials designed specifically to evaluate sex differences in efficacy and outcome of the available treatments.
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The pathophysiology of sex-specific differences in T2DM is to a great extent hormonally regulated, with estrogen playing a key role in females.
“The pathophysiology of these sex-specific differences is to a great extent hormonally regulated, with estrogen playing a key role in the disease process in females [13].”
From Sex Differences in Response to Treatment with Glucagon-like Peptide 1 Receptor Agonists: Opportunities for a Tailored Approach to Diabetes and Obesity Care (2022) · cites this paper as [13]
The sections on hormonal pathophysiology and estrogen describe sex-related hormonal effects on glycemic control, including an association between declining estrogen after menopause and increased risk of elevated fasting plasma glucose. But the Introduction says the reasons for sex differences remain unclear and lists other possible contributors; the paper does not establish that they are to a great extent hormonally regulated. (LLM, conf=0.86)
Experimental — accuracy not yet measuredIncreased total cholesterol and LDL levels act as significant risk factors for CVD in males, whereas in females hypertriglyceridemia and low HDL levels may constitute stronger risk factors.
“It has been recognized that increased total cholesterol and LDL levels act as significant risk factors for CVD in males, whereas in females hypertriglyceridemia and low HDL levels may constitute stronger risk factors [13].”
From Sex Differences in Response to Treatment with Glucagon-like Peptide 1 Receptor Agonists: Opportunities for a Tailored Approach to Diabetes and Obesity Care (2022) · cites this paper as [13]
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- Authors
- Arnetz, L., Rajamand Ekberg, N., & Alvarsson, M.
- Affiliations
- Karolinska Institutet (SE)
- Corresponding author
- Alvarsson, Michael
- ORCID
- Arnetz, Lisa
- Venue
- Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy
- Publisher
- Informa UK Limited
- Published
- 2014-09
- Volume
- 7
- Pages
- 409
- ISSN
- 1178-7007 (ISSN-L)
- PMC
- PMC4172102
- OpenAlex
- W2004032034
- Cited by
- 175
- References
- 190
- Citations by year
- 2026: 8 · 2025: 13 · 2024: 16 · 2023: 19 · 2022: 25 · 2021: 21 · 2020: 24 · 2019: 10 · 2018: 10 · 2017: 10 · 2016: 10 · 2015: 9
- FWCI
- 1.51
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Diabetes Metabolic Syndrome and Obesity (publishedVersion, cc-by-nc)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Dove Medical Press (Taylor and Francis Group) (submittedVersion, cc-by-nc)
- Topics
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Sex and Gender in Healthcare
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Keywords
- type 2 diabetes, sex differences, women with diabetes, clinical course, cardiovascular risk, all-cause mortality, glycemic control, HbA1c, diabetes screening, fasting blood glucose, oral glucose tolerance test, microvascular complications, psychological factors, antidiabetic drugs
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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