Insulin action and dyslipidaemia in non-insulin-dependent diabetes
Insulin action and dyslipidaemia in non-insulin-dependent diabetes
Atherosclerosis is a common cause of morbidity and mortality in non-insulin-dependent diabetes (NIDDM) and may, in part, be due to disturbances of lipoprotein metabolism. Insulin resistance is a universal feature in NIDDM and may contribute to atherosclerosis by mediating abnormalities of circulating lipids and lipoproteins although the mechanisms are unclear. Several aspects of carbohydrate and lipid metabolism were studied in patients with NIDDM. The sensitivity of glucose disposal to insulin was assessed by hyperinsulinaemic isoglycaemic clamp studies with concurrent estimation of hepatic glucose production by tritiated glucose infusion while the in vivo sensitivity of adipose tissue lipolysis to insulin was assessed by changes in non-esterified fatty acids and glycerol during the clamp studies. Fasting plasma lipids, lipoproteins and apolipoproteins were assessed by standard methods and plasma lipolytic enzyme activities (lipoprotein lipase and hepatic lipase) were measured in post-heparin plasma. Patients with NIDDM and fasting hypertriglyceridaemia were insulin resistant in terms of both glucose disposal and antilipolytic effect when compared with their normotriglyceridaemic counterparts. These differences were not solely due to differences in obesity. HDL cholesterol and apolipoprotein A1 were positively related to insulin sensitivity but were more closely dependent upon fasting C-peptide concentration. Hepatic lipase activity showed a strong positive correlation with fasting C-peptide independently of insulin sensitivity suggesting that the B cell response to insulin resistance might be important in the regulation of this enzyme and hence of HDL cholesterol concentration. Treatment with a sulphonylurea for three months produced no change in circulating lipids and lipoproteins despite significant improvements in glucose control and insulin sensitivity suggesting that factors other than (or in addition to) insulin resistance determine the abnormal lipid metabolism in NIDDM.
University of Southampton
Baynes, Christopher
3d7821a5-e3b1-4c53-9a32-54c0dc2b40fc
1992
Baynes, Christopher
3d7821a5-e3b1-4c53-9a32-54c0dc2b40fc
Baynes, Christopher
(1992)
Insulin action and dyslipidaemia in non-insulin-dependent diabetes.
University of Southampton, Doctoral Thesis.
Record type:
Thesis
(Doctoral)
Abstract
Atherosclerosis is a common cause of morbidity and mortality in non-insulin-dependent diabetes (NIDDM) and may, in part, be due to disturbances of lipoprotein metabolism. Insulin resistance is a universal feature in NIDDM and may contribute to atherosclerosis by mediating abnormalities of circulating lipids and lipoproteins although the mechanisms are unclear. Several aspects of carbohydrate and lipid metabolism were studied in patients with NIDDM. The sensitivity of glucose disposal to insulin was assessed by hyperinsulinaemic isoglycaemic clamp studies with concurrent estimation of hepatic glucose production by tritiated glucose infusion while the in vivo sensitivity of adipose tissue lipolysis to insulin was assessed by changes in non-esterified fatty acids and glycerol during the clamp studies. Fasting plasma lipids, lipoproteins and apolipoproteins were assessed by standard methods and plasma lipolytic enzyme activities (lipoprotein lipase and hepatic lipase) were measured in post-heparin plasma. Patients with NIDDM and fasting hypertriglyceridaemia were insulin resistant in terms of both glucose disposal and antilipolytic effect when compared with their normotriglyceridaemic counterparts. These differences were not solely due to differences in obesity. HDL cholesterol and apolipoprotein A1 were positively related to insulin sensitivity but were more closely dependent upon fasting C-peptide concentration. Hepatic lipase activity showed a strong positive correlation with fasting C-peptide independently of insulin sensitivity suggesting that the B cell response to insulin resistance might be important in the regulation of this enzyme and hence of HDL cholesterol concentration. Treatment with a sulphonylurea for three months produced no change in circulating lipids and lipoproteins despite significant improvements in glucose control and insulin sensitivity suggesting that factors other than (or in addition to) insulin resistance determine the abnormal lipid metabolism in NIDDM.
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Published date: 1992
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Local EPrints ID: 461658
URI: http://eprints.soton.ac.uk/id/eprint/461658
PURE UUID: 16f14415-b350-4937-9849-a4ef2335b922
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Date deposited: 04 Jul 2022 18:51
Last modified: 23 Jul 2022 01:08
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Author:
Christopher Baynes
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