Glucose homeostasis, pancreatic endocrine function, and outcomes in advanced heart failure

Vojtech Melenovsky, Jan Benes, Janka Franekova, Jan Kovar, Barry A Borlaug, Marketa Segetova, Andrea Tura, Tereza Pelikanova

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Background--The mechanisms and relevance of impaired glucose homeostasis in advanced heart failure (HF) are poorly understood. The study goals were to examine glucose regulation, pancreatic endocrine function, and metabolic factors related to prognosis in patients with nondiabetic advanced HF. Methods and Results--In total, 140 advanced HF patients without known diabetes mellitus and 21 sex-, age-, and body mass index-matched controls underwent body composition assessment, oral glucose tolerance testing, and measurement of glucoseregulating hormones to model pancreatic β-cell secretory response. Compared with controls, HF patients had similar fasting glucose and insulin levels but higher levels after oral glucose tolerance testing. Insulin secretion was not impaired, but with increasing HF severity, there was a reduction in glucose, insulin, and insulin/glucagon ratio-a signature of starvation. The insulin/C-peptide ratio was decreased in HF, indicating enhanced insulin clearance, and this was correlated with lower cardiac output, hepatic insufficiency, right ventricular dysfunction, and body wasting. After a median of 449 days, 41% of patients experienced an adverse event (death, urgent transplant, or assist device). Increased glucagon and, paradoxically, low fasting plasma glucose displayed the strongest relations to outcome (P = 0.01). Patients in the lowest quartile of fasting plasma glucose (3.8-5.1 mmol·L-1, 68-101 mg·dL-1) had 3-times higher event risk than in the top quartile (6.0-7.9 mmol·L-1, 108-142 mg·dL-1; relative risk: 3.05 [95% confidence interval, 1.46-6.77]; P=0.002). Conclusions--Low fasting plasma glucose and increased glucagon are robust metabolic predictors of adverse events in advanced HF. Pancreatic insulin secretion is preserved in advanced HF, but levels decrease with increasing HF severity due to enhanced insulin clearance that is coupled with right heart failure and cardiac cachexia.

Original languageEnglish (US)
Article numbere005290
JournalJournal of the American Heart Association
Volume6
Issue number8
DOIs
StatePublished - Aug 1 2017

Fingerprint

Homeostasis
Heart Failure
Glucose
Insulin
Fasting
Glucagon
Glucose Tolerance Test
Right Ventricular Dysfunction
Hepatic Insufficiency
Cachexia
C-Peptide
Starvation
Body Composition
Cardiac Output
Diabetes Mellitus
Body Mass Index
Hormones
Confidence Intervals
Transplants
Equipment and Supplies

Keywords

  • Cachexia
  • Glucagon/glucagon-like peptide
  • Glucose
  • Heart failure
  • Insulin
  • Metabolism
  • Obesity paradox
  • Right ventricular dysfunction
  • Starvation

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Glucose homeostasis, pancreatic endocrine function, and outcomes in advanced heart failure. / Melenovsky, Vojtech; Benes, Jan; Franekova, Janka; Kovar, Jan; Borlaug, Barry A; Segetova, Marketa; Tura, Andrea; Pelikanova, Tereza.

In: Journal of the American Heart Association, Vol. 6, No. 8, e005290, 01.08.2017.

Research output: Contribution to journalArticle

Melenovsky, V, Benes, J, Franekova, J, Kovar, J, Borlaug, BA, Segetova, M, Tura, A & Pelikanova, T 2017, 'Glucose homeostasis, pancreatic endocrine function, and outcomes in advanced heart failure', Journal of the American Heart Association, vol. 6, no. 8, e005290. https://doi.org/10.1161/JAHA.116.005290
Melenovsky, Vojtech ; Benes, Jan ; Franekova, Janka ; Kovar, Jan ; Borlaug, Barry A ; Segetova, Marketa ; Tura, Andrea ; Pelikanova, Tereza. / Glucose homeostasis, pancreatic endocrine function, and outcomes in advanced heart failure. In: Journal of the American Heart Association. 2017 ; Vol. 6, No. 8.
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abstract = "Background--The mechanisms and relevance of impaired glucose homeostasis in advanced heart failure (HF) are poorly understood. The study goals were to examine glucose regulation, pancreatic endocrine function, and metabolic factors related to prognosis in patients with nondiabetic advanced HF. Methods and Results--In total, 140 advanced HF patients without known diabetes mellitus and 21 sex-, age-, and body mass index-matched controls underwent body composition assessment, oral glucose tolerance testing, and measurement of glucoseregulating hormones to model pancreatic β-cell secretory response. Compared with controls, HF patients had similar fasting glucose and insulin levels but higher levels after oral glucose tolerance testing. Insulin secretion was not impaired, but with increasing HF severity, there was a reduction in glucose, insulin, and insulin/glucagon ratio-a signature of starvation. The insulin/C-peptide ratio was decreased in HF, indicating enhanced insulin clearance, and this was correlated with lower cardiac output, hepatic insufficiency, right ventricular dysfunction, and body wasting. After a median of 449 days, 41{\%} of patients experienced an adverse event (death, urgent transplant, or assist device). Increased glucagon and, paradoxically, low fasting plasma glucose displayed the strongest relations to outcome (P = 0.01). Patients in the lowest quartile of fasting plasma glucose (3.8-5.1 mmol·L-1, 68-101 mg·dL-1) had 3-times higher event risk than in the top quartile (6.0-7.9 mmol·L-1, 108-142 mg·dL-1; relative risk: 3.05 [95{\%} confidence interval, 1.46-6.77]; P=0.002). Conclusions--Low fasting plasma glucose and increased glucagon are robust metabolic predictors of adverse events in advanced HF. Pancreatic insulin secretion is preserved in advanced HF, but levels decrease with increasing HF severity due to enhanced insulin clearance that is coupled with right heart failure and cardiac cachexia.",
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T1 - Glucose homeostasis, pancreatic endocrine function, and outcomes in advanced heart failure

AU - Melenovsky, Vojtech

AU - Benes, Jan

AU - Franekova, Janka

AU - Kovar, Jan

AU - Borlaug, Barry A

AU - Segetova, Marketa

AU - Tura, Andrea

AU - Pelikanova, Tereza

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N2 - Background--The mechanisms and relevance of impaired glucose homeostasis in advanced heart failure (HF) are poorly understood. The study goals were to examine glucose regulation, pancreatic endocrine function, and metabolic factors related to prognosis in patients with nondiabetic advanced HF. Methods and Results--In total, 140 advanced HF patients without known diabetes mellitus and 21 sex-, age-, and body mass index-matched controls underwent body composition assessment, oral glucose tolerance testing, and measurement of glucoseregulating hormones to model pancreatic β-cell secretory response. Compared with controls, HF patients had similar fasting glucose and insulin levels but higher levels after oral glucose tolerance testing. Insulin secretion was not impaired, but with increasing HF severity, there was a reduction in glucose, insulin, and insulin/glucagon ratio-a signature of starvation. The insulin/C-peptide ratio was decreased in HF, indicating enhanced insulin clearance, and this was correlated with lower cardiac output, hepatic insufficiency, right ventricular dysfunction, and body wasting. After a median of 449 days, 41% of patients experienced an adverse event (death, urgent transplant, or assist device). Increased glucagon and, paradoxically, low fasting plasma glucose displayed the strongest relations to outcome (P = 0.01). Patients in the lowest quartile of fasting plasma glucose (3.8-5.1 mmol·L-1, 68-101 mg·dL-1) had 3-times higher event risk than in the top quartile (6.0-7.9 mmol·L-1, 108-142 mg·dL-1; relative risk: 3.05 [95% confidence interval, 1.46-6.77]; P=0.002). Conclusions--Low fasting plasma glucose and increased glucagon are robust metabolic predictors of adverse events in advanced HF. Pancreatic insulin secretion is preserved in advanced HF, but levels decrease with increasing HF severity due to enhanced insulin clearance that is coupled with right heart failure and cardiac cachexia.

AB - Background--The mechanisms and relevance of impaired glucose homeostasis in advanced heart failure (HF) are poorly understood. The study goals were to examine glucose regulation, pancreatic endocrine function, and metabolic factors related to prognosis in patients with nondiabetic advanced HF. Methods and Results--In total, 140 advanced HF patients without known diabetes mellitus and 21 sex-, age-, and body mass index-matched controls underwent body composition assessment, oral glucose tolerance testing, and measurement of glucoseregulating hormones to model pancreatic β-cell secretory response. Compared with controls, HF patients had similar fasting glucose and insulin levels but higher levels after oral glucose tolerance testing. Insulin secretion was not impaired, but with increasing HF severity, there was a reduction in glucose, insulin, and insulin/glucagon ratio-a signature of starvation. The insulin/C-peptide ratio was decreased in HF, indicating enhanced insulin clearance, and this was correlated with lower cardiac output, hepatic insufficiency, right ventricular dysfunction, and body wasting. After a median of 449 days, 41% of patients experienced an adverse event (death, urgent transplant, or assist device). Increased glucagon and, paradoxically, low fasting plasma glucose displayed the strongest relations to outcome (P = 0.01). Patients in the lowest quartile of fasting plasma glucose (3.8-5.1 mmol·L-1, 68-101 mg·dL-1) had 3-times higher event risk than in the top quartile (6.0-7.9 mmol·L-1, 108-142 mg·dL-1; relative risk: 3.05 [95% confidence interval, 1.46-6.77]; P=0.002). Conclusions--Low fasting plasma glucose and increased glucagon are robust metabolic predictors of adverse events in advanced HF. Pancreatic insulin secretion is preserved in advanced HF, but levels decrease with increasing HF severity due to enhanced insulin clearance that is coupled with right heart failure and cardiac cachexia.

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KW - Glucagon/glucagon-like peptide

KW - Glucose

KW - Heart failure

KW - Insulin

KW - Metabolism

KW - Obesity paradox

KW - Right ventricular dysfunction

KW - Starvation

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