Adrenergic activation, fuel substrate availability, and insulin resistance in patients with congestive heart failure

Nir Uriel, Jose Gonzalez-Costello, Andrea Mignatti, Kerry A. Morrison, Nadav Nahumi, Paolo C. Colombo, Ulrich P. Jorde

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Objectives: This study sought to investigate plasma levels of glucose and free fatty acids (FFA) and their relationship with adrenergic activation and insulin resistance (IR) in patients with advanced congestive heart failure (CHF). Background: Adrenergic activation and IR are hallmarks of advanced heart failure. The resulting changes in fuel substrate availability and their implications for exercise capacity have not been elucidated. Methods: Subjects with CHF underwent maximal exercise testing. Plasma glucose, FFA, insulin, and norepinephrine (NE) levels were measured at rest and at peak exercise. Beta-receptor sensitivity to NE was assessed using the Chronotropic Responsiveness Index (CRI). Homeostasis Model Assessment Index >2.5 defined IR. Left ventricular ejection fraction was estimated by 2-dimensional echocardiography. Results: Ninety-six subjects were enrolled. CHF subjects without IR (CHF/No-IR), but not those with IR (CHF/IR), significantly increased glucose and insulin in response to exercise. Only CHF/No-IR subjects increased FFA in response to exercise (0.14 ± 0.27 mmol/l; p= 0.027). NE increased significantly less with exercise, and CRI was lower in CHF/IR subjects compared with CHF/No-IR subjects (1.3 ± 1.4 vs. 2.5 ± 2.1; 6.4 ± 2.6 vs. 8.5 ± 3.4; p= 0.069). CRI correlated with the exercise-induced increase in FFA (r= 0.41; p< 0.005). These results stayed the same after excluding diabetic patients from the CHF/IR group. Conclusions: Circulating FFA levels increased during exercise in CHF subjects without IR, but not in those with IR or DM. Increased FFA availability during exercise may represent a catecholamine-dependent compensatory fuel shift in CHF.

Original languageEnglish (US)
Pages (from-to)331-337
Number of pages7
JournalJACC: Heart Failure
Volume1
Issue number4
DOIs
StatePublished - Aug 2013
Externally publishedYes

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Adrenergic Agents
Insulin Resistance
Heart Failure
Exercise
Nonesterified Fatty Acids
Norepinephrine
Glucose
Insulin
Stroke Volume
Catecholamines
Echocardiography
Homeostasis

Keywords

  • Free fatty acids
  • Glucose
  • Heart failure
  • Insulin resistance

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Adrenergic activation, fuel substrate availability, and insulin resistance in patients with congestive heart failure. / Uriel, Nir; Gonzalez-Costello, Jose; Mignatti, Andrea; Morrison, Kerry A.; Nahumi, Nadav; Colombo, Paolo C.; Jorde, Ulrich P.

In: JACC: Heart Failure, Vol. 1, No. 4, 08.2013, p. 331-337.

Research output: Contribution to journalArticle

Uriel, Nir ; Gonzalez-Costello, Jose ; Mignatti, Andrea ; Morrison, Kerry A. ; Nahumi, Nadav ; Colombo, Paolo C. ; Jorde, Ulrich P. / Adrenergic activation, fuel substrate availability, and insulin resistance in patients with congestive heart failure. In: JACC: Heart Failure. 2013 ; Vol. 1, No. 4. pp. 331-337.
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T1 - Adrenergic activation, fuel substrate availability, and insulin resistance in patients with congestive heart failure

AU - Uriel, Nir

AU - Gonzalez-Costello, Jose

AU - Mignatti, Andrea

AU - Morrison, Kerry A.

AU - Nahumi, Nadav

AU - Colombo, Paolo C.

AU - Jorde, Ulrich P.

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N2 - Objectives: This study sought to investigate plasma levels of glucose and free fatty acids (FFA) and their relationship with adrenergic activation and insulin resistance (IR) in patients with advanced congestive heart failure (CHF). Background: Adrenergic activation and IR are hallmarks of advanced heart failure. The resulting changes in fuel substrate availability and their implications for exercise capacity have not been elucidated. Methods: Subjects with CHF underwent maximal exercise testing. Plasma glucose, FFA, insulin, and norepinephrine (NE) levels were measured at rest and at peak exercise. Beta-receptor sensitivity to NE was assessed using the Chronotropic Responsiveness Index (CRI). Homeostasis Model Assessment Index >2.5 defined IR. Left ventricular ejection fraction was estimated by 2-dimensional echocardiography. Results: Ninety-six subjects were enrolled. CHF subjects without IR (CHF/No-IR), but not those with IR (CHF/IR), significantly increased glucose and insulin in response to exercise. Only CHF/No-IR subjects increased FFA in response to exercise (0.14 ± 0.27 mmol/l; p= 0.027). NE increased significantly less with exercise, and CRI was lower in CHF/IR subjects compared with CHF/No-IR subjects (1.3 ± 1.4 vs. 2.5 ± 2.1; 6.4 ± 2.6 vs. 8.5 ± 3.4; p= 0.069). CRI correlated with the exercise-induced increase in FFA (r= 0.41; p< 0.005). These results stayed the same after excluding diabetic patients from the CHF/IR group. Conclusions: Circulating FFA levels increased during exercise in CHF subjects without IR, but not in those with IR or DM. Increased FFA availability during exercise may represent a catecholamine-dependent compensatory fuel shift in CHF.

AB - Objectives: This study sought to investigate plasma levels of glucose and free fatty acids (FFA) and their relationship with adrenergic activation and insulin resistance (IR) in patients with advanced congestive heart failure (CHF). Background: Adrenergic activation and IR are hallmarks of advanced heart failure. The resulting changes in fuel substrate availability and their implications for exercise capacity have not been elucidated. Methods: Subjects with CHF underwent maximal exercise testing. Plasma glucose, FFA, insulin, and norepinephrine (NE) levels were measured at rest and at peak exercise. Beta-receptor sensitivity to NE was assessed using the Chronotropic Responsiveness Index (CRI). Homeostasis Model Assessment Index >2.5 defined IR. Left ventricular ejection fraction was estimated by 2-dimensional echocardiography. Results: Ninety-six subjects were enrolled. CHF subjects without IR (CHF/No-IR), but not those with IR (CHF/IR), significantly increased glucose and insulin in response to exercise. Only CHF/No-IR subjects increased FFA in response to exercise (0.14 ± 0.27 mmol/l; p= 0.027). NE increased significantly less with exercise, and CRI was lower in CHF/IR subjects compared with CHF/No-IR subjects (1.3 ± 1.4 vs. 2.5 ± 2.1; 6.4 ± 2.6 vs. 8.5 ± 3.4; p= 0.069). CRI correlated with the exercise-induced increase in FFA (r= 0.41; p< 0.005). These results stayed the same after excluding diabetic patients from the CHF/IR group. Conclusions: Circulating FFA levels increased during exercise in CHF subjects without IR, but not in those with IR or DM. Increased FFA availability during exercise may represent a catecholamine-dependent compensatory fuel shift in CHF.

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KW - Glucose

KW - Heart failure

KW - Insulin resistance

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