Diabetes mellitus in cystic fibrosis: genetic and immunological markers.
Family history, as well as genetic and immunological markers of diabetes mellitus, were studied in cystic fibrosis (CF) patients with and without diabetes mellitus. Positive family history of diabetes mellitus in first-degree relatives was found in only 6 of 210 (3%) CF patients, with no difference between non-diabetic and diabetic patients. The frequency distributions of the HLA types DR3, DR4 and DR3/4, which normally confer susceptibility to insulin-dependent diabetes mellitus and of HLA-DR2, which normally confers resistance to insulin-dependent diabetes mellitus, were not different in non-diabetic CF patients, diabetic CF patients and normal subjects. The genotypic frequencies of tumor necrosis factor-beta and of heat shock protein 70, located within the HLA region on chromosome 6, in CF patients with diabetes were not different from those in patients with insulin-dependent diabetes mellitus, while non-diabetic CF patients and normal subjects shared other patterns. The frequencies of the interleukin-1 beta alleles, located on chromosome 2, were not different in non-diabetic and diabetic CF patients, insulin-dependent diabetic patients and normal subjects. Islet cell cytoplasmic antibodies, measured before, at and after the diagnosis of diabetes in 33 diabetic CF patients and in 32 matched non-diabetic CF patients, were detected in only 2 of 236 (0.8%) serum samples: in a pre-diabetic patient and in a non-diabetic control patient. Birth weights were not different in diabetic and non-diabetic CF patients, arguing against the importance of the intrauterine environment as a determinant in the transmission of diabetes mellitus in CF patients.(ABSTRACT TRUNCATED AT 250 WORDS)
Lanng
S
S
CF Center Copenhagen, Department of Pediatrics, Rigshospitalet, Denmark.
Thorsteinsson
B
B
Pociot
F
F
Marshall
M O
MO
Madsen
H O
HO
Schwartz
M
M
Nerup
J
J
Koch
C
C
D000293:Adolescent; D000328:Adult; D001323:Autoantibodies / Q000235:genetics / Q000276:immunology; D015415:Biomarkers; D001724:Birth Weight; D002648:Child; D002675:Child, Preschool; D003550:Cystic Fibrosis / Q000150:complications* / Q000235:genetics / Q000276:immunology; D048909:Diabetes Complications; D003920:Diabetes Mellitus / Q000235:genetics / Q000276:immunology; D003922:Diabetes Mellitus, Type 1 / Q000150:complications / Q000235:genetics / Q000276:immunology; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000235:genetics / Q000276:immunology; D005260:Female; D006360:Heat-Shock Proteins / Q000235:genetics / Q000276:immunology; D006801:Humans; D007375:Interleukin-1; D007515:Islets of Langerhans / Q000276:immunology; D008233:Lymphotoxin-alpha / Q000235:genetics / Q000276:immunology; D008285:Major Histocompatibility Complex; D008297:Male; D012150:Polymorphism, Restriction Fragment Length
D001323:Autoantibodies; D015415:Biomarkers; D006360:Heat-Shock Proteins; D007375:Interleukin-1; D008233:Lymphotoxin-alpha; C024211:islet cell antibody