Hypoglycemia as a manifestation of sepsis

doi:10.1016/0002-9343(80)90250-8

The American Journal of Medicine

Volume 68, Issue 5, May 1980, Pages 649-654

https://doi.org/10.1016/0002-9343(80)90250-8 Get rights and content

Abstract

Hypoglycemia has rarely been described as a clinical sign of severe bacterial sepsis. We recently encountered nine patients in whom hypoglycemia (mean serum glucose of 22 mg/dl) was associated with overwhelming sepsis. Clinical disease in these patients included pneumonia and cellulitis; in three patients, no focus of infection was apparent. Altered mental status, metabolic acidosis, leukopenia, abnormal clotting studies and bacteremia were common features in these cases. In four patients, no cause for hypoglycemia other than sepsis was present. In five patients, another possible metabolic cause for hypoglycemia was present (alcoholism in four and chronic renal insufficiency in one) although none had been observed to be hypoglycemic on previous hospitalizations. Streptococcus pneumoniae (three cases) and Hemophilus influenzae, type b, (two cases) were the most common pathogens, and the over-all mortality was 67 per cent.

The mechanism(s) for hypoglycemia with sepsis is not well defined. Depleted glycogen stores, impaired gluconeogenesis and increased peripheral glucose utilization may all be contributing factors. Incubation of bacteria in fresh blood at room temperature does not increase the normal rate of breakdown of glucose suggesting that the hypoglycemia occurs in vivo. Hypoglycemia is an important sign of overwhelming sepsis that may be more common than has previously been recognized.

References (54)

UG Hodgin et al.
Gram-negative rod bacteremia
Am J Med
(1965)
C Singer et al.
Bacteremia and fungemia complicating neoplastic disease
Am J Med
(1977)
EJ Winslow et al.
Hemodynamic studies and results of therapy in 50 patients with bacteremic shock
Am J Med
(1973)
CY Yeung
Hypoglycemia in neonatal sepsis
J Pediatr
(1970)
CY Yeung et al.
Glucose disappearance rate in neonatal infection
J Pediatr
(1973)
DW Wilmore
Impaired gluconeogenesis in extensively injured patients with gram-negative bacteremia
Am J Clin Nutr
(1977)
AJS McFadzean et al.
Hypoglycaemia in suppurative pancholangiitis due to clonorchis sinensis
Trans R Soc Trop Med Hyg
(1965)
J Torres et al.
Hyposplenism and pneumococcemia
Am J Med
(1973)
PB Neame et al.
Postalcoholic hypoglycemia and toxic hepatitis
Lancet
(1961)
KF LaNoue et al.
The impairment of glucogenesis by gram negative infection
Metabolism
(1968)

LE Mallette et al.

Control of gluconeogenesis from amino acids in the perfused rat liver

J Biol Chem

(1969)

EB Marliss et al.

Amino acid metabolism in lactic acidosis

Am J Med

(1972)

JH Magnusson

Contribution to the knowledge of acute suprarenal insufficiency in children

Acta Paediatr

(1934)

WJ Martin et al.

Severe liver disease complicated by bacteremia

Arch Intern Med

(1962)

VN Udhoji et al.

Hemodynamic and metabolic studies on shock associated with bacteremia

Ann Intern Med

(1965)

RE Bryant et al.

Factors affecting mortality of gram-negative rod bacteremia

Arch Intern Med

(1971)

DW Wilmore et al.

Impaired glucose flow in burned patients with gram-negative sepsis

Surg Gynecol Obstet

(1976)

B Lucke et al.

The fulminant form of epidemic hepatitis

Am J Pathol

(1946)

P Felig et al.

Glucose homeostasis in viral hepatitis

N Engl J Med

(1970)

P Nader et al.

Varicella and hypoglycemia with recovery

Am J Dis Child

(1965)

BL Congeni et al.

Three infants with neonatal pertussis

Clin Pediatr

(1978)

AL Bisno et al.

The syndrome of asplenia, pneumococcal sepsis, and disseminated intravascular coagulation

Ann Intern Med

(1970)

MD Grant et al.

Waterhouse-Friderichsen syndrome induced by pneumococcemic shock

JAMA

(1970)

V Gopal et al.

Fulminant pneumococcal infections in “normal” asplenic hosts

Arch Intern Med

(1977)

JD Coonrod et al.

Antigenemia in fulminant pneumococcemia

Ann Intern Med

(1976)

Post-splenectomy sepsis, Case Records of the Massachusetts General Hospital

N Engl J Med

(1975)

E Hultman

Rapid specific method for determination of aldosaccharides in body fluids

Nature

(1958)

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Citation Excerpt :
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¹: From the Departments of Medicine, Microbiology and Immunology, Baylor College of Medicine, Houston, Texas; and the Program in Infectious Diseases and Clinical Microbiology, University of Texas Health Science Center, Houston, Texas.

View full text

Clinical studyHypoglycemia as a manifestation of sepsis

Abstract

Am J Med

Am J Med

Am J Med

J Pediatr

J Pediatr

Am J Clin Nutr

Trans R Soc Trop Med Hyg

Am J Med

Lancet

Metabolism

J Biol Chem

Am J Med

Contribution to the knowledge of acute suprarenal insufficiency in children

Acta Paediatr

Severe liver disease complicated by bacteremia

Arch Intern Med

Hemodynamic and metabolic studies on shock associated with bacteremia

Ann Intern Med

Factors affecting mortality of gram-negative rod bacteremia

Arch Intern Med

Impaired glucose flow in burned patients with gram-negative sepsis

Surg Gynecol Obstet

The fulminant form of epidemic hepatitis

Am J Pathol

Glucose homeostasis in viral hepatitis

N Engl J Med

Varicella and hypoglycemia with recovery

Am J Dis Child

Three infants with neonatal pertussis

Clin Pediatr

The syndrome of asplenia, pneumococcal sepsis, and disseminated intravascular coagulation

Ann Intern Med

Waterhouse-Friderichsen syndrome induced by pneumococcemic shock

JAMA

Fulminant pneumococcal infections in “normal” asplenic hosts

Arch Intern Med

Antigenemia in fulminant pneumococcemia

Ann Intern Med

Post-splenectomy sepsis, Case Records of the Massachusetts General Hospital

N Engl J Med

Rapid specific method for determination of aldosaccharides in body fluids

Nature

Clinical study
Hypoglycemia as a manifestation of sepsis