An association between Type 2 diabetes and alpha-antitrypsin deficiency.
OBJECTIVE
Alpha(1)-Antitrypsin (AAT) is a serine protease inhibitor which recently has been shown to prevent Type 1 diabetes development, to prolong islet allograft survival and to inhibit pancreatic B-cell apoptosis in vivo. It has also been reported that Type 1 diabetic patients have significantly lower plasma concentrations of AAT, suggesting the potential role of AAT in the pathogenesis of Type 1 diabetes. We have investigated whether plasma AAT levels are altered in Type 2 diabetes.


METHODS
The study included patients with Type 2 diabetes (n = 163) and non-diabetic control subjects matched for age, sex and smoking habits (n = 158) derived from the population-based Malmö Diet and Cancer study. Plasma samples were analysed for AAT concentration and phenotype and serum glucose, insulin, C-reactive protein and lipid levels were measured. Glycated haemoglobin was also measured.


RESULTS
In the diabetic group, the women had higher mean plasma AAT levels than men (P < 0.05). The mean plasma AAT levels did not differ between diabetic and control subjects. However, the number of individuals with low AAT levels (< 1.0 mg/ml) was 50% higher in the diabetic group (P < 0.05) and the frequency of AAT deficiency genotypes was 50% higher (NS) in diabetic compared with control subjects. In the group of diabetic patients with AAT < 1 mg/ml, AAT directly correlated with systolic blood pressure (P = 0.048) and inversely correlated with waist-hip ratio (P = 0.031).


CONCLUSIONS
Our results provide evidence that deficiency of AAT may be associated with an increased risk of developing Type 2 diabetes.
Sandström
C S
CS
Chronic and Degenerative Disease Research Unit, University Hospital Malmoe, Lund University, Malmo, Sweden.
Ohlsson
B
B
Melander
O
O
Westin
U
U
Mahadeva
R
R
Janciauskiene
S
S
D000704:Analysis of Variance; D001786:Blood Glucose / Q000378:metabolism*; D016022:Case-Control Studies; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000517:prevention & control; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000175:diagnosis; D005260:Female; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D008297:Male; D008875:Middle Aged; D012737:Sex Factors; D000515:alpha 1-Antitrypsin / Q000378:metabolism*; D019896:alpha 1-Antitrypsin Deficiency / Q000097:blood* / Q000175:diagnosis
D001786:Blood Glucose; D006442:Glycated Hemoglobin; D000515:alpha 1-Antitrypsin