OBJECTIVE: To investigate the possible association of the variants in the nucleotide binding fold regions of the sulfonylurea receptor 1 (SUR1) gene with gestational diabetes mellitus (GDM), type 2 diabetes, and altered insulin secretion in Finnish subjects. RESEARCH DESIGN AND METHODS: The nucleotide binding fold regions of the SUR1 gene were amplified with polymerase chain reaction and screened by the single-strand conformational polymorphism analysis in 42 subjects with GDM and 40 subjects with type 2 diabetes. Detected variants were further investigated in 377 normoglycemic subjects by restriction fragment-length polymorphism analysis. The effect of the variants of the SUR1 gene on first-phase insulin secretion was studied in 295 normoglycemic subjects. RESULTS: In subjects with GDM or type 2 diabetes, one amino acid change (S1369A), four silent substitutions (R1273R, L829L, T759T, and K649K), and three intron variants were identified in the nucleotide binding fold regions of the SUR1 gene. A tagGCC allele of exon 16 splice acceptor site was more frequent in subjects with GDM (0.55 allele frequency, n = 42) and type 2 diabetes (0.60, n = 40) than in normoglycemic subjects (0.43, n = 377) (P1 = 0.024 and P2 = 0.009, respectively). Similarly, an AGG allele of the R1273R polymorphism was more common in subjects with GDM (0.87) and type 2 diabetes (0.87) than in normoglycemic subjects (0.74) (P1 = 0.009 and P2 = 0.001, respectively). However, the S1369A, R1273R, and cagGCC-->tagGCC variants of the SUR1 gene were not associated with altered first-phase insulin secretion in 295 normoglycemic subjects. CONCLUSIONS: These results suggest that a functional variant that contributes to the risk of GDM and type 2 diabetes may locate close to the SUR1 gene.

Birth weight and length serve as indicators of the intrauterine environment, and a small body size at birth is a predictor of type 2 diabetes and hypertension. Insulin is one of the growth factors regulating fetal growth. The plasma cell glycoprotein 1 (PC-1) gene impairs insulin signaling at the insulin receptor level. Therefore, we investigated whether the K121Q polymorphism of the PC-1 gene association with insulin sensitivity, insulin levels, and the prevalence of diabetes and hypertension in adult life depends on size at birth in 489 subjects born in Helsinki during 1924-1933. We found that the effect of the PC-1 gene polymorphism on insulin levels and insulin sensitivity, measured as the homeostasis model assessment for insulin resistance, depended on birth length because fasting insulin levels and insulin resistance were highest in subjects carrying the 121Q allele who were small at birth (P for interaction = 0.04 and 0.05). Additionally, in those whose birth length was up to 49 cm, the K121Q polymorphism of the PC-1 gene was associated with a 2-fold higher incidence of type 2 diabetes. Moreover, subjects who were short at birth and who had the 121Q allele had the highest incidence (31.6%) of type 2 diabetes together with hypertension. We conclude that the interaction between the K121Q polymorphism of the PC-1 gene and birth length affects insulin sensitivity and increases susceptibility to type 2 diabetes and hypertension in adulthood.

In the treatment of rheumatoid arthritis (RA) by gold, it has been customary to administer the gold by weekly injections of equal amounts, e.g. 50 mg. sodium aurothiomalate weekly (Freyberg, 1957). According to reports in the literature the percentage of satisfactory therapeutic results may vary from 23 to 85 per cent., and the percentage of toxic reactions from 5 to 62 per cent. (Fraser, 1945; Freyberg, 1966).Gold levels in blood and urine may change from one day to another after gold injections, but the differences between individual patients receiving the same treatment and their relationships to the therapeutic effect have received little attention. Freyberg, Block, and Levey (1941) assayed the gold content of plasma and urine after injections of different gold preparations and during toxic reactions, but found no correlation with the plasma gold level. The same conclusion was drawn by Lawrence (1961) in studies with radioactive gold. Smith, Peak, Kron, Hermann, Del Toro, and Goldman (1958), however, found that a poor therapeutic effect was related to a high urinary excretion of gold and toxic reactions to a low excretion; they performed no gold assays of the blood.In the present study, gold levels in blood and urine were determined in 25 patients with rheumatoid arthritis who were receiving gold therapy, and correlated with therapeutic effect and toxic reaction. Material and MethodsAll the 25 patients studied were suffering from classical rheumatoid arthritis according to the ARA diagnostic criteria (Ropes, Bennett, Cobb, Jacox, and Jessar, 1959). All were in an active stage of the disease, with functional grades II and III (Steinbrocker, Traeger, and Batterman, 1949). The erythrocyte sedimentation rate varied from 13 to 103 mm./lst hr, and the number of affected joints from two to twelve. Both the Waaler-Rose and the latex-fixation test were positive in nineteen cases, and the latter only in three; both were negative in three cases.The therapeutic effect, good (Grades I to III) or poor (Grade IV), was evaluated after 6 months' therapy from changes in the stage of RA according to the ARA criteria. Complications due to gold therapy were also registered.Sodium aurothiomalate (Myocrisin) was given intramuscularly in doses beginning with 10 mg., 20 mg., 20 mg., and then 50 mg. once a week for 12 to 16 weeks and thereafter at longer intervals, usually once a month, according to the therapeutic effect. The dosage of antiinflammatory drugs was kept constant throughout the study: none of the patients received corticosteroids.The plasma gold content and the urinary gold excretion were assayed during the week after the second injection of 50 mg. Myocrisin (equal to 25 mg. gold). At that time the patients had received a total of 150 mg. Myocrisin (75 mg. gold). The gold content was studied on the 1st, 3rd, 5th, and 7th days after the injection, and also in a control specimen taken on the morning before the injection.In four patients on long-term treatment with one injection a month, the gold assay was made three to ...

No abstract