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Pathogenesis of type 2 diabetes: the relative contribution of insulin resistance and impaired insulin secretion

Groop, Leif LU (2000) In International journal of clinical practice. Supplement p.3-13
Abstract
Type 2 diabetes is characterised by both impaired insulin secretion and insulin resistance but their relative contribution to the development of hyperglycaemia may differ due to heterogeneity of the disease. Under most circumstances, insulin resistance is the earliest detectable defect in pre-diabetic individuals but it is not known whether this is the primary defect or secondary to other abnormalities such as abdominal obesity with excessive free fatty acid turnover and increased lipid deposits in muscle. Initially, enhanced insulin secretion can compensate for the insulin resistance but early phase insulin secretion is impaired. In the transition from normal to impaired and diabetic glucose tolerance, insulin sensitivity deteriorates... (More)
Type 2 diabetes is characterised by both impaired insulin secretion and insulin resistance but their relative contribution to the development of hyperglycaemia may differ due to heterogeneity of the disease. Under most circumstances, insulin resistance is the earliest detectable defect in pre-diabetic individuals but it is not known whether this is the primary defect or secondary to other abnormalities such as abdominal obesity with excessive free fatty acid turnover and increased lipid deposits in muscle. Initially, enhanced insulin secretion can compensate for the insulin resistance but early phase insulin secretion is impaired. In the transition from normal to impaired and diabetic glucose tolerance, insulin sensitivity deteriorates about 40% whereas insulin secretion deteriorates 3-4 fold. In addition to insulin resistance, the metabolic syndrome includes hypertension, dyslipidaemia, obesity and microalbuminuria. In patients with manifest diabetes, chronic hyperglycaemia can result in further deterioration of insulin sensitivity and secretion (glucotoxicity), which is aggravated by elevated free fatty acids (lipotoxicity). Abdominal obesity and insulin resistance are strongly correlated and studies have aimed at understanding the genetic basis. Candidate genes for the metabolic syndrome include those for the beta 3-adrenergic receptor, lipoprotein lipase, hormone sensitive lipase, peroxisome proliferator-activated receptor-gamma, insulin receptor substrate-1 and glycogen synthase. Therefore, type 2 diabetes is multigenic and appears to represent a collision between thrifty genes and an affluent society. Successful management will require treatments targeted at defects of both insulin secretion and insulin resistance. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
International journal of clinical practice. Supplement
issue
113
pages
3 - 13
publisher
Wiley-Blackwell
external identifiers
  • pmid:11965829
ISSN
1368-504X
language
English
LU publication?
yes
id
2116b745-8e9b-426a-a7bc-8eba08981507 (old id 1118023)
date added to LUP
2008-04-30 08:14:09
date last changed
2016-04-16 03:59:14
@article{2116b745-8e9b-426a-a7bc-8eba08981507,
  abstract     = {Type 2 diabetes is characterised by both impaired insulin secretion and insulin resistance but their relative contribution to the development of hyperglycaemia may differ due to heterogeneity of the disease. Under most circumstances, insulin resistance is the earliest detectable defect in pre-diabetic individuals but it is not known whether this is the primary defect or secondary to other abnormalities such as abdominal obesity with excessive free fatty acid turnover and increased lipid deposits in muscle. Initially, enhanced insulin secretion can compensate for the insulin resistance but early phase insulin secretion is impaired. In the transition from normal to impaired and diabetic glucose tolerance, insulin sensitivity deteriorates about 40% whereas insulin secretion deteriorates 3-4 fold. In addition to insulin resistance, the metabolic syndrome includes hypertension, dyslipidaemia, obesity and microalbuminuria. In patients with manifest diabetes, chronic hyperglycaemia can result in further deterioration of insulin sensitivity and secretion (glucotoxicity), which is aggravated by elevated free fatty acids (lipotoxicity). Abdominal obesity and insulin resistance are strongly correlated and studies have aimed at understanding the genetic basis. Candidate genes for the metabolic syndrome include those for the beta 3-adrenergic receptor, lipoprotein lipase, hormone sensitive lipase, peroxisome proliferator-activated receptor-gamma, insulin receptor substrate-1 and glycogen synthase. Therefore, type 2 diabetes is multigenic and appears to represent a collision between thrifty genes and an affluent society. Successful management will require treatments targeted at defects of both insulin secretion and insulin resistance.},
  author       = {Groop, Leif},
  issn         = {1368-504X},
  language     = {eng},
  number       = {113},
  pages        = {3--13},
  publisher    = {Wiley-Blackwell},
  series       = {International journal of clinical practice. Supplement},
  title        = {Pathogenesis of type 2 diabetes: the relative contribution of insulin resistance and impaired insulin secretion},
  year         = {2000},
}