Background Because visceral obesity predicts insulin resistance,we studied whether alterations in the gene encoding for the3-adrenergic receptor in visceral fat are associated with insulinresistance.
Methods We studied the frequency of a cytosine-to-thymidinemutation that results in the replacement of tryptophan by arginineat position 64 (Trp64Arg) of the 3-adrenergic receptor by restriction-enzymedigestion with BstOI in 335 subjects from western Finland, 207of whom were nondiabetic and 128 of whom had non-insulin-dependentdiabetes mellitus (NIDDM). We also determined the frequencyof the mutation in 156 subjects from southern Finland. Sensitivityto insulin was measured by the hyperinsulinemic–euglycemicclamp technique in 66 randomly selected nondiabetic subjects.
Results In the subjects from western Finland, the frequencyof the mutated allele was similar in the nondiabetic subjectsand the subjects with NIDDM (12 vs. 11 percent). The mean ageof the subjects at the onset of diabetes was lower among thosewith the mutation than those without it (56 vs. 61 years, P= 0.04). Among the nondiabetic subjects, those with the mutationhad a higher ratio of waist to hip circumference (P = 0.02),a greater increase in the serum insulin response after the oraladministration of glucose (P = 0.05), a higher diastolic bloodpressure (82 vs. 78 mm Hg, P = 0.01), and a lower rate of glucosedisposal during the clamp study (5.3 vs. 6.5 mg [29 vs. 36 µmol]per kilogram of body weight per minute; P = 0.04) than the subjectswithout the mutated allele. In an analysis of sibling pairs,the siblings with the mutation generally had higher waist:hipratios (P = 0.05) and higher responses of blood glucose andserum insulin after the oral administration of glucose thantheir siblings without the mutation (P = 0.02 and P = 0.005,respectively).
Conclusions The Trp64Arg allele of the 3-adrenergic receptoris associated with abdominal obesity and resistance to insulinand may contribute to the early onset of NIDDM.
Source Information
From the Department of Endocrinology, University of Lund, Lund, Sweden (E.W., M.L., T.K., L.C.G.); the Fourth Department of Medicine, Helsinki University Hospital, Helsinki, Finland (E.W.); and the Division of Geriatric Medicine and Gerontology, Johns Hopkins University School of Medicine, Baltimore (J.W., A.R.S.).
Address reprint requests to Dr. Groop at the Department of Endocrinology, Malmö University Hospital, 205 02 Malmö, Sweden.
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3-adrenergic receptor in visceral fat are associated with insulin resistance. 
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