Short-Term Hyperglycemic Dysregulation in Patients With Type 1 Diabetes Does Not Change Myocardial Triglyceride Content or Myocardial Function

Hammer, Sebastiaan; Jonker, Jacqueline T.; Lamb, Hildo J.; Meer, R.W. van der; Zondag, Wendy; Sepers, Jan M.; Roos, Albert de; Smit, Johannes W. A.; Romijn, Johannes A.

doi:10.2337/dc08-0513

Cited by 11 publications

(7 citation statements)

References 6 publications

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“…Similarly, in fasting conditions, glycogen depots tended to be lower and RPP was higher. In line with our findings, elevations in HR and RPP have been observed in patients with type 2 diabetes or those fed a high-fat diet [1,16] while no change in haemodynamic variables has been observed following an acute exposure to isolated hyperglycaemia [38] or combined hyperinsulinaemiahyperglycaemia [34].…”

Section: Discussionsupporting

confidence: 78%

“…However, the increase in myocardial GU did not translate into a significant elevation in myocardial TG accumulation compared with that of the hyperinsulinaemic state alone. Hammer et al [38] reported that 24 h of hyperglycaemia achieved by partial insulin deprivation in patients with type 1 diabetes did not affect the myocardial TG content. In contrast, Winhofer et al [34] demonstrated that combined hyperglycaemia and hyperinsulinaemia induced myocardial lipid accumulation in normal individuals, independent of insulin resistance and while plasma NEFA were suppressed; the authors suggested that insulinaemia rather than glycaemia was responsible.…”

Section: Discussionmentioning

confidence: 99%

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Independent effects of circulating glucose, insulin and NEFA on cardiac triacylglycerol accumulation and myocardial insulin resistance in a swine model

et al. 2014

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Aims/hypothesis Cardiac steatosis and myocardial insulin resistance elevate the risk of cardiac complications in obesity and diabetes. We aimed to disentangle the effects of circulating glucose, insulin and NEFA on myocardial triacylglycerol (TG) content and myocardial glucose uptake. Methods Twenty-two pigs were stratified according to four protocols: low NEFA+low insulin (nicotinic acid), high NEFA+low insulin (fasting) and high insulin+low NEFA± high glucose (hyperinsulinaemia-hyperglycaemia or hyperinsulinaemia-euglycaemia). Positron emission tomography, [U-13 C]palmitate enrichment techniques and tissue biopsies were used to assess myocardial metabolism. Heart rate and rate-pressure product (RPP) were monitored. Results Myocardial glucose extraction was increased by NEFA suppression and was similar in the hyperinsulinaemiahypergylcaemia, hyperinsulinaemia-euglycaemia and nicotinic acid groups. Hyperglycaemia enhanced myocardial glucose uptake due to a mass action. Myocardial TG content was greatest in the fasting group, whereas hyperinsulinaemia had a mild effect. Heart rate and RPP increased in hyperinsulinaemia-euglycaemia, in which cardiac glycogen content was reduced. Heart rate correlated with myocardial TG and glycogen content. Conclusions/interpretation Elevated NEFA levels represent a powerful, self-sufficient promoter of cardiac TG accumulation and are a downregulator of myocardial glucose uptake, indicating that the focus of treatment should be to 'normalise' adipose tissue function to lower the risk of cardiac TG accumulation and myocardial insulin resistance. The observation that hyperinsulinaemia and nicotinic acid led to myocardial fuel deprivation provides a potential explanation for the cardiovascular outcomes reported in recent intensive glucoselowering and NEFA-lowering clinical trials.

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Section: Discussionsupporting

confidence: 78%

Section: Discussionmentioning

confidence: 99%

Independent effects of circulating glucose, insulin and NEFA on cardiac triacylglycerol accumulation and myocardial insulin resistance in a swine model

et al. 2014

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“…Our data is in line with previous publications of a large cohort of patients with T1DM participating in the diabetes control and complications trial (DCCT), in which cardiac geometry and function was normal 33 . Also, short-term hyperglycemic dysregulation after partial insulin deprivation for 24 hours had no effect on MYCL 34 . Thus, MYCL adapts differently in T1DM compared to insulin sensitive, healthy subjects, in which even in the absence of circulating free fatty acids an elevation in glucose concentrations significantly increased lipid deposition within the myocardium 24 .…”

Section: Discussionmentioning

confidence: 87%

Reduced hepatocellular lipid accumulation and energy metabolism in patients with long standing type 1 diabetes mellitus

Wolf

Fellinger

Pfleger

et al. 2019

Sci Rep

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The prevalence of obesity and metabolic syndrome increases in patients with type 1 diabetes mellitus (T1DM). In the general population this is linked with ectopic lipid accumulation in liver (HCL) and skeletal muscle (IMCL), representing hallmarks in the development of insulin resistance. Moreover, hepatic mitochondrial activity is lower in newly diagnosed patients with T1DM. If this precedes later development of diabetes related fatty liver disease is currently not known. This study aims to investigate energy metabolism in liver ( k ATP ) and skeletal muscle ( k CK ) and its impact on HCL, IMCL, cardiac fat depots and heart function in 10 patients with long standing T1DM compared to 11 well-matched controls by 31 P/ 1 H magnetic resonance spectroscopy. HCL was almost 70% lower in T1DM compared to controls (6.9 ± 5% vs 2.1 ± 1.3%; p = 0.030). Also k ATP was significantly reduced (0.33 ± 0.1 s −1 vs 0.17 ± 0.1 s −1 ; p = 0.018). In T1DM, dose of basal insulin strongly correlated with BMI (r = 0.676, p = 0.032) and HCL (r = 0.643, p = 0.045), but not with k ATP . In the whole cohort, HCL was significantly associated with BMI (r = 0.615, p = 0.005). In skeletal muscle k CK was lower in patients with T1DM (0.25 ± 0.05 s −1 vs 0.31 ± 0–04 s −1 ; p = 0.039). No significant differences were found in IMCL. Cardiac fat depots as well as heart function were not different. Our results in patients with long standing T1DM show that HCL is lower compared to matched controls, despite reduced energy metabolism in liver and skeletal muscle.

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“…It is possible that this risk was minimized by patients giving themselves larger boluses of insulin following meals, which we had to allow for safety. Recently though, short term glycemic dysregulation in patients with type 1 diabetes has been shown not to modulate cardiac function(29) which is compatible with no significant rise in markers of oxidative stress with short term hyperglycemia.…”

Section: Discussionmentioning

confidence: 99%

Consequences of delayed pump infusion line change in patients with type 1 diabetes mellitus treated with continuous subcutaneous insulin infusion

Thethi

Rao

Kawji

et al. 2010

Journal of Diabetes and its Complications

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Objective-To systematically investigate the effect of lack of adherence to the recommended change in insulin pump infusion line use beyond 48 hrs and determine whether the type of insulin made a difference.Research design and methods-This was a double-blind, randomized, cross over trial with 20 patients with DM I using Insulins Aspart and Lispro without a line change for up to 100 hrs. Using retrospective continuous glucose monitoring, we analyzed the average glucose over the day. Changes in serum 1,5-anhydroglucitol, carboxymethyllysine, and Free 15-F 2t Isoprostane were also studied.Results-From day 2 to day 5 of the pump line use the daily avg. glucose level increased from 122.7 to 163.9 mg/dL (P < 0.05), fasting glucose from 120.3 to 154.5 mg/dL (P < 0.05): post prandial glucose from 114.6 to 172.1 (P < 0.05): and the daily maximum glucose from 207.7 to 242.8 (P < 0.05 for the trend). Time period that the glucose was > 180 mg/dL increased from 14.5 % to 38.3 (P < 0.05). Loss of control occurred despite increase in total daily insulin dose from 48.5 ± 11.8 units to 55.3 ± 17.9 units (P = 0.05). There was no difference in loss of control between insulin types and biomarkers measured did not change significantly.Conclusions-The insulin pump infusion should be changed every 48 hours in patients using CSII, to avoid loss of glycemic control. In the short term, this loss of glycemic control has no impact on oxidative stress and glycation.

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Short-Term Hyperglycemic Dysregulation in Patients With Type 1 Diabetes Does Not Change Myocardial Triglyceride Content or Myocardial Function

Cited by 11 publications

References 6 publications

Independent effects of circulating glucose, insulin and NEFA on cardiac triacylglycerol accumulation and myocardial insulin resistance in a swine model

Independent effects of circulating glucose, insulin and NEFA on cardiac triacylglycerol accumulation and myocardial insulin resistance in a swine model

Reduced hepatocellular lipid accumulation and energy metabolism in patients with long standing type 1 diabetes mellitus

Consequences of delayed pump infusion line change in patients with type 1 diabetes mellitus treated with continuous subcutaneous insulin infusion

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