The Pathogenesis of Type II Diabetes Mellitus:A Polygenic Disease
Abstract
Diabetes mellitus is the most common endocrine disease, consuming almost 15% of annual health care expenditures in the United States. The focus of this review is on type II (non-insulin-dependent) diabetes mellitus, which accounts for approximately 90% of diabetic patients. The current understanding of the pathogenesis of type II diabetes is multifaceted. Complex defects in both insulin action and insulin secretion produce the metabolic derangements responsible for the disease. The pathophysiology is the result of a combination of polygene defects and environmental factors. The search for the responsible gene or genes is described and several candidate genes are discussed. Diabetogenes are addressed in the context of type II diabetes representing a prototype for the identification of the genetic basis of common diseases.
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Type 2 diabetes is a heterogenous polygenic disease with both resistance to the action of insulin and defective insulin secretion.
“Type 2 diabetes is a heterogenous polygenic disease with both resistance to the action of insulin and defective insulin secretion (4,5).”
From Guidelines and Recommendations for Laboratory Analysis in the Diagnosis and Management of Diabetes Mellitus (2023) · cites this paper as [5]
Measurement of C-peptide can aid in instances in which it is difficult to differentiate between the diagnosis of type 1 and type 2 diabetes.
“Measurement of the C-peptide, in the fasting state or in response to intravenous glucagon, can aid in instances in which it is difficult to differentiate between the diagnosis of type 1 and type 2 diabetes (5,511).”
From Guidelines and Recommendations for Laboratory Analysis in the Diagnosis and Management of Diabetes Mellitus (2023) · cites this paper as [5]
The Loss of β-Cell Function section discusses insulin responses to intravenous glucose and other secretagogues, but not C-peptide testing for distinguishing type 1 from type 2 diabetes. Searches for C-peptide and diagnostic differentiation found no passage addressing that use; the indexed passages provide no page number. (LLM, conf=0.74)
Experimental — accuracy not yet measuredType 2 diabetes mellitus is caused by a combination of insulin resistance and inadequate insulin secretion.
“Type 2 diabetes mellitus, formerly known as non-IDDM or adultonset diabetes, is caused by a combination of insulin resistance and inadequate insulin secretion (3,4).”
From Guidelines and recommendations for laboratory analysis in the diagnosis and management of diabetes mellitus (2011) · cites this paper as [4]
Type 2 diabetes is a heterogeneous polygenic disorder involving both insulin resistance and impaired insulin secretion.
“Type 2 diabetes is a heterogeneous polygenic disease with both resistance to the action of insulin and defective insulin secretion (3,4).”
From Guidelines and recommendations for laboratory analysis in the diagnosis and management of diabetes mellitus (2011) · cites this paper as [4]
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Self-citation
- Authors
- Sacks, D. B., & McDonald, J. M.
- Affiliations
- Brigham and Women's Hospital (US)
- University of Alabama at Birmingham (US)
- ORCID
- Sacks, David B.
- Venue
- American Journal of Clinical Pathology
- Publisher
- Oxford University Press (OUP)
- Published
- 1996-02-01
- Volume
- 105
- Issue
- 2
- Pages
- 149-156
- ISSN
- 0002-9173 (ISSN-L)
- 1943-7722
- OpenAlex
- W25782933
- Semantic Scholar
- ce3643b7eba42e10b98ebc1c2b514d4840030947
- Cited by
- 93
- References
- 38
- Citations by year
- 2025: 4 · 2024: 1 · 2023: 7 · 2022: 2 · 2021: 5 · 2020: 4 · 2019: 2 · 2018: 4 · 2017: 2 · 2016: 1 · 2015: 1 · 2014: 2 · 2013: 4 · 2012: 4
- FWCI
- 1.21
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Journal of Clinical Pathology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
- Keywords
- type 2 diabetes, pathogenesis, polygenic disease, insulin resistance, insulin secretion defect, candidate genes, genetic susceptibility, environmental factors
- MeSH terms
- Insulin Secretion, Aged, Diabetes Mellitus, Type 2, Glucose, Humans, Insulin, Insulin Resistance, Islets of Langerhans, Middle Aged, Phosphorylation, Proteins, Receptor, Insulin
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