Skip to main content
Top
Published in: Diabetologia 2/2015

01-02-2015 | Article

Isolated hyperglycaemia does not increase VLDL-triacylglycerol secretion in type 1 diabetic men

Authors: Rakel F. Johansen, Esben Søndergaard, Lars Peter Sørensen, Birgitte Nellemann, Jens S. Christiansen, Søren Nielsen

Published in: Diabetologia | Issue 2/2015

Login to get access

Abstract

Aims/hypothesis

In type 1 diabetes, abnormalities of both glucose and lipoprotein metabolism are seen. The relationship between these factors is not understood, but studies indicate that hyperglycaemia may increase hepatic VLDL-triacylglycerol (VLDL-TG) secretion and reduce VLDL-TG fatty acid oxidation, which could lead to the development of dyslipidaemia. The aim of this study was to determine the isolated effect of hyperglycaemia on VLDL-TG and NEFA kinetics in men with type 1 diabetes.

Methods

VLDL-TG and palmitate kinetics were measured in eight men with type 1 diabetes using ex vivo labelled VLDL-TG and palmitate tracers. A 2.5 h basal period (plasma glucose 5 mmol/l) was followed by a 4 h hyperglycaemic period (plasma glucose 16 mmol/l). Steady-state VLDL-TG kinetics (VLDL-TG secretion, clearance and oxidation rates) were assessed by an isotope dilution technique using an intravenous primed-constant infusion of ex vivo labelled [1-14C]VLDL-TG in combination with sampling of blood and expired air. Palmitate turnover was measured using [9,10-3H]palmitate.

Results

The VLDL-TG secretion rate (36.0 ± 9.6 vs 30.8 ± 6.1 μmol/min, NS) and clearance rate (209 ± 30.4 vs 197 ± 41.7 ml/min, NS) were unchanged during the basal and hyperglycaemic periods, resulting in unchanged VLDL-TG concentrations (0.25 ± 0.11 μmol/l vs 0.28 ± 0.10 μmol/l, NS). In addition, VLDL-TG fatty acid oxidation and palmitate flux were not changed during hyperglycaemia.

Conclusions/interpretation

Four hours of acute hyperglycaemia (16 mmol/l) without a concomitant increase in insulin does not alter VLDL-TG and NEFA kinetics in men with type 1 diabetes.
Clinical trial registry number: NCT01178957
Literature
1.
go back to reference Morrish NJ, Wang SL, Stevens LK, Fuller JH, Keen H (2001) Mortality and causes of death in the WHO Multinational Study of Vascular Disease in Diabetes. Diabetologia 44(Suppl 2):S14–S21PubMedCrossRef Morrish NJ, Wang SL, Stevens LK, Fuller JH, Keen H (2001) Mortality and causes of death in the WHO Multinational Study of Vascular Disease in Diabetes. Diabetologia 44(Suppl 2):S14–S21PubMedCrossRef
2.
go back to reference Danaei G, Lawes CM, Vander HS, Murray CJ, Ezzati M (2006) Global and regional mortality from ischaemic heart disease and stroke attributable to higher-than-optimum blood glucose concentration: comparative risk assessment. Lancet 368:1651–1659PubMedCrossRef Danaei G, Lawes CM, Vander HS, Murray CJ, Ezzati M (2006) Global and regional mortality from ischaemic heart disease and stroke attributable to higher-than-optimum blood glucose concentration: comparative risk assessment. Lancet 368:1651–1659PubMedCrossRef
3.
go back to reference Khaw KT, Wareham N, Bingham S, Luben R, Welch A, Day N (2004) Association of hemoglobin A1c with cardiovascular disease and mortality in adults: the European prospective investigation into cancer in Norfolk. Ann Intern Med 141:413–420PubMedCrossRef Khaw KT, Wareham N, Bingham S, Luben R, Welch A, Day N (2004) Association of hemoglobin A1c with cardiovascular disease and mortality in adults: the European prospective investigation into cancer in Norfolk. Ann Intern Med 141:413–420PubMedCrossRef
4.
go back to reference Nathan DM, Cleary PA, Backlund JY et al (2005) Intensive diabetes treatment and cardiovascular disease in patients with type 1 diabetes. N Engl J Med 353:2643–2653PubMedCrossRef Nathan DM, Cleary PA, Backlund JY et al (2005) Intensive diabetes treatment and cardiovascular disease in patients with type 1 diabetes. N Engl J Med 353:2643–2653PubMedCrossRef
5.
go back to reference Hokanson JE, Austin MA (1996) Plasma triglyceride level is a risk factor for cardiovascular disease independent of high-density lipoprotein cholesterol level: a meta-analysis of population-based prospective studies. J Cardiovasc Risk 3:213–219PubMedCrossRef Hokanson JE, Austin MA (1996) Plasma triglyceride level is a risk factor for cardiovascular disease independent of high-density lipoprotein cholesterol level: a meta-analysis of population-based prospective studies. J Cardiovasc Risk 3:213–219PubMedCrossRef
6.
go back to reference Duca L, Sippl R, Snell-Bergeon JK (2013) Is the risk and nature of CVD the same in type 1 and type 2 diabetes? Curr Diab Rep 13:350–361PubMedCrossRef Duca L, Sippl R, Snell-Bergeon JK (2013) Is the risk and nature of CVD the same in type 1 and type 2 diabetes? Curr Diab Rep 13:350–361PubMedCrossRef
7.
go back to reference Taskinen MR (2003) Diabetic dyslipidaemia: from basic research to clinical practice. Diabetologia 46:733–749PubMedCrossRef Taskinen MR (2003) Diabetic dyslipidaemia: from basic research to clinical practice. Diabetologia 46:733–749PubMedCrossRef
8.
go back to reference Azad K, Parkin JM, Court S, Laker MF, Alberti KG (1994) Circulating lipids and glycaemic control in insulin dependent diabetic children. Arch Dis Child 71:108–113PubMedCentralPubMedCrossRef Azad K, Parkin JM, Court S, Laker MF, Alberti KG (1994) Circulating lipids and glycaemic control in insulin dependent diabetic children. Arch Dis Child 71:108–113PubMedCentralPubMedCrossRef
9.
go back to reference Maahs DM, Ogden LG, Dabelea D et al (2010) Association of glycaemia with lipids in adults with type 1 diabetes: modification by dyslipidaemia medication. Diabetologia 53:2518–2525PubMedCentralPubMedCrossRef Maahs DM, Ogden LG, Dabelea D et al (2010) Association of glycaemia with lipids in adults with type 1 diabetes: modification by dyslipidaemia medication. Diabetologia 53:2518–2525PubMedCentralPubMedCrossRef
10.
go back to reference Sidossis LS, Mittendorfer B, Walser E, Chinkes D, Wolfe RR (1998) Hyperglycemia-induced inhibition of splanchnic fatty acid oxidation increases hepatic triacylglycerol secretion. Am J Physiol 275:E798–E805PubMed Sidossis LS, Mittendorfer B, Walser E, Chinkes D, Wolfe RR (1998) Hyperglycemia-induced inhibition of splanchnic fatty acid oxidation increases hepatic triacylglycerol secretion. Am J Physiol 275:E798–E805PubMed
11.
go back to reference Parks EJ, Hellerstein MK (2000) Carbohydrate-induced hypertriacylglycerolemia: historical perspective and review of biological mechanisms. Am J Clin Nutr 71:412–433PubMed Parks EJ, Hellerstein MK (2000) Carbohydrate-induced hypertriacylglycerolemia: historical perspective and review of biological mechanisms. Am J Clin Nutr 71:412–433PubMed
12.
go back to reference Yamashita H, Takenoshita M, Sakurai M et al (2001) A glucose-responsive transcription factor that regulates carbohydrate metabolism in the liver. Proc Natl Acad Sci U S A 98:9116–9121PubMedCentralPubMedCrossRef Yamashita H, Takenoshita M, Sakurai M et al (2001) A glucose-responsive transcription factor that regulates carbohydrate metabolism in the liver. Proc Natl Acad Sci U S A 98:9116–9121PubMedCentralPubMedCrossRef
13.
go back to reference Koo SH, Dutcher AK, Towle HC (2001) Glucose and insulin function through two distinct transcription factors to stimulate expression of lipogenic enzyme genes in liver. J Biol Chem 276:9437–9445PubMedCrossRef Koo SH, Dutcher AK, Towle HC (2001) Glucose and insulin function through two distinct transcription factors to stimulate expression of lipogenic enzyme genes in liver. J Biol Chem 276:9437–9445PubMedCrossRef
14.
go back to reference Chong MF, Hodson L, Bickerton AS et al (2008) Parallel activation of de novo lipogenesis and stearoyl-CoA desaturase activity after 3 d of high-carbohydrate feeding. Am J Clin Nutr 87:817–823PubMed Chong MF, Hodson L, Bickerton AS et al (2008) Parallel activation of de novo lipogenesis and stearoyl-CoA desaturase activity after 3 d of high-carbohydrate feeding. Am J Clin Nutr 87:817–823PubMed
15.
go back to reference Schwarz JM, Linfoot P, Dare D, Aghajanian K (2003) Hepatic de novo lipogenesis in normoinsulinemic and hyperinsulinemic subjects consuming high-fat, low-carbohydrate and low-fat, high-carbohydrate isoenergetic diets. Am J Clin Nutr 77:43–50PubMed Schwarz JM, Linfoot P, Dare D, Aghajanian K (2003) Hepatic de novo lipogenesis in normoinsulinemic and hyperinsulinemic subjects consuming high-fat, low-carbohydrate and low-fat, high-carbohydrate isoenergetic diets. Am J Clin Nutr 77:43–50PubMed
16.
go back to reference Brown AM, Wiggins D, Gibbons GF (1999) Glucose phosphorylation is essential for the turnover of neutral lipid and the second stage assembly of triacylglycerol-rich ApoB-containing lipoproteins in primary hepatocyte cultures. Arterioscler Thromb Vasc Biol 19:321–329PubMedCrossRef Brown AM, Wiggins D, Gibbons GF (1999) Glucose phosphorylation is essential for the turnover of neutral lipid and the second stage assembly of triacylglycerol-rich ApoB-containing lipoproteins in primary hepatocyte cultures. Arterioscler Thromb Vasc Biol 19:321–329PubMedCrossRef
17.
go back to reference Sondergaard E, Sorensen LP, Rahbek I, Gormsen LC, Christiansen JS, Nielsen S (2012) Postprandial VLDL-triacylglycerol secretion is not suppressed in obese type 2 diabetic men. Diabetologia 55:2733–2740PubMedCrossRef Sondergaard E, Sorensen LP, Rahbek I, Gormsen LC, Christiansen JS, Nielsen S (2012) Postprandial VLDL-triacylglycerol secretion is not suppressed in obese type 2 diabetic men. Diabetologia 55:2733–2740PubMedCrossRef
18.
go back to reference Ginsberg HN, Jacobs A, Le NA, Sandler J (1982) Effect of somatostatin-induced suppression of postprandial insulin response upon the hypertriglyceridemia associated with a high carbohydrate diet. J Clin Invest 70:1225–1233PubMedCentralPubMedCrossRef Ginsberg HN, Jacobs A, Le NA, Sandler J (1982) Effect of somatostatin-induced suppression of postprandial insulin response upon the hypertriglyceridemia associated with a high carbohydrate diet. J Clin Invest 70:1225–1233PubMedCentralPubMedCrossRef
19.
go back to reference Durrington PN, Newton RS, Weinstein DB, Steinberg D (1982) Effects of insulin and glucose on very low density lipoprotein triglyceride secretion by cultured rat hepatocytes. J Clin Invest 70:63–73PubMedCentralPubMedCrossRef Durrington PN, Newton RS, Weinstein DB, Steinberg D (1982) Effects of insulin and glucose on very low density lipoprotein triglyceride secretion by cultured rat hepatocytes. J Clin Invest 70:63–73PubMedCentralPubMedCrossRef
20.
go back to reference Lewis GF, Uffelman KD, Szeto LW, Weller B, Steiner G (1995) Interaction between free fatty acids and insulin in the acute control of very low density lipoprotein production in humans. J Clin Invest 95:158–166PubMedCentralPubMedCrossRef Lewis GF, Uffelman KD, Szeto LW, Weller B, Steiner G (1995) Interaction between free fatty acids and insulin in the acute control of very low density lipoprotein production in humans. J Clin Invest 95:158–166PubMedCentralPubMedCrossRef
21.
go back to reference Caruso M, Divertie GD, Jensen MD, Miles JM (1990) Lack of effect of hyperglycemia on lipolysis in humans. Am J Physiol 259:E542–E547PubMed Caruso M, Divertie GD, Jensen MD, Miles JM (1990) Lack of effect of hyperglycemia on lipolysis in humans. Am J Physiol 259:E542–E547PubMed
22.
go back to reference Cersosimo E, Coppack S, Jensen M (1993) Lack of effect of hyperglycemia on lipolysis in humans. Am J Physiol 265:E821–E824PubMed Cersosimo E, Coppack S, Jensen M (1993) Lack of effect of hyperglycemia on lipolysis in humans. Am J Physiol 265:E821–E824PubMed
23.
go back to reference Gormsen LC, Jensen MD, Nielsen S (2006) Measuring VLDL-triglyceride turnover in humans using ex vivo-prepared VLDL tracer. J Lipid Res 47:99–106PubMedCrossRef Gormsen LC, Jensen MD, Nielsen S (2006) Measuring VLDL-triglyceride turnover in humans using ex vivo-prepared VLDL tracer. J Lipid Res 47:99–106PubMedCrossRef
24.
go back to reference Frayn KN (1983) Calculation of substrate oxidation rates in vivo from gaseous exchange. J Appl Physiol 55:628–634PubMed Frayn KN (1983) Calculation of substrate oxidation rates in vivo from gaseous exchange. J Appl Physiol 55:628–634PubMed
25.
go back to reference Sidossis LS, Coggan AR, Gastaldelli A, Wolfe RR (1995) A new correction factor for use in tracer estimations of plasma fatty acid oxidation. Am J Physiol 269:E649–E656PubMed Sidossis LS, Coggan AR, Gastaldelli A, Wolfe RR (1995) A new correction factor for use in tracer estimations of plasma fatty acid oxidation. Am J Physiol 269:E649–E656PubMed
26.
go back to reference Mittendorfer B, Sidossis LS, Walser E, Chinkes DL, Wolfe RR (1998) Regional acetate kinetics and oxidation in human volunteers. Am J Physiol 274:E978–E983PubMed Mittendorfer B, Sidossis LS, Walser E, Chinkes DL, Wolfe RR (1998) Regional acetate kinetics and oxidation in human volunteers. Am J Physiol 274:E978–E983PubMed
27.
go back to reference Wu K, Cappel D, Martinez M, Stafford JM (2010) Impaired-inactivation of FoxO1 contributes to glucose-mediated increases in serum very low-density lipoprotein. Endocrinology 151:3566–3576PubMedCentralPubMedCrossRef Wu K, Cappel D, Martinez M, Stafford JM (2010) Impaired-inactivation of FoxO1 contributes to glucose-mediated increases in serum very low-density lipoprotein. Endocrinology 151:3566–3576PubMedCentralPubMedCrossRef
28.
go back to reference Sindelar DK, Balcom JH, Chu CA, Neal DW, Cherrington AD (1996) A comparison of the effects of selective increases in peripheral or portal insulin on hepatic glucose production in the conscious dog. Diabetes 45:1594–1604PubMedCrossRef Sindelar DK, Balcom JH, Chu CA, Neal DW, Cherrington AD (1996) A comparison of the effects of selective increases in peripheral or portal insulin on hepatic glucose production in the conscious dog. Diabetes 45:1594–1604PubMedCrossRef
Metadata
Title
Isolated hyperglycaemia does not increase VLDL-triacylglycerol secretion in type 1 diabetic men
Authors
Rakel F. Johansen
Esben Søndergaard
Lars Peter Sørensen
Birgitte Nellemann
Jens S. Christiansen
Søren Nielsen
Publication date
01-02-2015
Publisher
Springer Berlin Heidelberg
Published in
Diabetologia / Issue 2/2015
Print ISSN: 0012-186X
Electronic ISSN: 1432-0428
DOI
https://doi.org/10.1007/s00125-014-3422-6

Other articles of this Issue 2/2015

Diabetologia 2/2015 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.