Beta-cell failure in type 2 diabetes: mechanisms, markers, and clinical implications
Open accessAbstract
It is well known that type 2 diabetes mellitus (T2D) is a globally increasing health burden. Despite recent therapeutic advances and the availability of many different classes of antihyperglycemic therapy, a large proportion of people do not achieve glycemic control. A decline in pancreatic beta-cell function has been defined as a key contributing factor to progression of T2D. In fact, a significant proportion of beta-cell secretory capacity is thought to be lost well before the diagnosis of T2D is made. Several models have been proposed to explain the reduction in beta-cell function, including reduced beta-cell number, beta-cell exhaustion, and dedifferentiation or transdifferentiation into other cell types. However, there have been reports that suggest remission of T2D is possible, and it is believed that beta-cell dysfunction may be, in part, reversible. As such, the question of whether beta cells are committed to failure in people with T2D is complex. It is now widely accepted that early restoration of normoglycemia may protect beta-cell function. Key to the successful implementation of this approach in clinical practice is the appropriate assessment of individuals at risk of beta-cell failure, and the early implementation of appropriate treatment options. In this review, we discuss the progression of T2D in the context of beta-cell failure and describe how C-peptide testing can be used to assess beta-cell function in primary care practice. In conclusion, significant beta…
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Although body mass index has a stronger association with type 2 diabetes than genetic risk scores, approximately 10% of individuals with type 2 diabetes do not have overweight or obesity.
“Although body mass index has a stronger association with type 2 diabetes than genetic risk scores,16 approximately 10% of individuals with type 2 diabetes do not have overweight or obesity.3”
From Diagnosis and Treatment of Type 2 Diabetes in Adults (2025) · cites this paper as [3]
Diabetes is a leading cause of kidney failure, nontraumatic lower extremity amputation, and death (30.4 deaths per 100 000 population).
“Diabetes is a leading cause of kidney failure, nontraumatic lower extremity amputation, and death (30.4 deaths per 100 000 population).3,18”
From Diagnosis and Treatment of Type 2 Diabetes in Adults (2025) · cites this paper as [3]
In the US, 1 in 10 individuals with diabetes have severe vision loss or blindness.
“In the US, 1 in 10 individuals with diabetes have severe vision loss or blindness.3”
From Diagnosis and Treatment of Type 2 Diabetes in Adults (2025) · cites this paper as [3]
Type 2 diabetes accounts for 90% to 95% of all cases of diabetes globally.
“Type 2 diabetes accounts for 90% to 95% of all cases of diabetes globally”
From Diagnosis and Treatment of Type 2 Diabetes in Adults (2025) · cites this paper as [3]
Type 2 diabetes affects up to 14% of the global population.
“Type 2 diabetes affects up to 14% of the global population and is associated with preventable long-term complications such as cardiovascular disease, kidney failure, vision loss and increased mortality.”
From Diagnosis and Treatment of Type 2 Diabetes in Adults (2025) · cites this paper as [3]
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Diagnosis and Treatment of Type 2 Diabetes in Adults
Kalyani, R. R., Neumiller, J. J., Maruthur, N. M., & Wexler, D. J. (2025) · JAMA · doi:10.1001/jama.2025.5956 · Cited by 145 · see citing works
- Authors
- Wysham, C., & Shubrook, J.
- Affiliations
- Rockwood Clinic (US)
- Touro University California (US)
- Corresponding author
- Wysham, Carol
- Venue
- Postgraduate Medicine
- Publisher
- Informa UK Limited
- Published
- 2020-06-16
- Volume
- 132
- Issue
- 8
- Pages
- 676-686
- ISSN
- 0032-5481 (ISSN-L)
- 1941-9260
- OpenAlex
- W3035682390
- Cited by
- 193
- References
- 25
- Citations by year
- 2026: 42 · 2025: 50 · 2024: 34 · 2023: 29 · 2022: 23 · 2021: 14 · 2020: 1
- FWCI
- 3.80
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Postgraduate Medicine (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Touro Scholar (Touro College) (submittedVersion)
- Funders
- Sanofi US, Inc (NA)
- Topics
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
- Keywords
- type 2 diabetes, beta-cell failure, beta-cell dysfunction, beta-cell exhaustion, beta-cell dedifferentiation, beta-cell transdifferentiation, HbA1c, disease progression, antihyperglycemic therapy, primary care
- MeSH terms
- C-Peptide, Diabetes Mellitus, Type 2, Glycated Hemoglobin, Humans, Hypoglycemic Agents, Insulin, Insulin Resistance, Biomarkers, Oxidative Stress, Disease Progression, Insulin-Secreting Cells, Incretins
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