We studied prospectively 49 non-diabetic identical twins of recently-diagnosed Type 1 (insulin-dependent) diabetic patients for up to 24 years (median 9 years). During this time 15 developed Type 1 diabetes. Actuarial analysis indicates that by 12 years 34% of the twins will have developed Type 1 diabetes and that thereafter only another 2% will do so. Inevitable bias in ascertainment of the twins makes it likely that the true figure is less. We conclude that factors which are not genetically determined must be important in the pathogenesis of the disease. The rates of developing Type 1 diabetes in the co-twins declines sharply in the years after diagnosis of the index twin, which suggests that the initiation of the process leading to Type 1 diabetes occurs within a finite, and not a prolonged, period.
Objective: Infants born from overweight and obese mothers with glucose-controlled gestational diabetes (GDM) tend to be large-for-gestational age (LGA). It is hypothesized that this is due to an excessive rise in maternal triglyceride levels. Methods: Two-hundred and seventy nine singleton GDM pregnancies were divided into three groups according to prepregnancy BMI: normal weight (BMI 5 20-24.9; n 5 128), overweight (BMI 5 25-29.9; n 5 105), and obese (BMI 30; n 5 46). Individual z-scores (ZS) of maternal triglycerides and of newborn weight (NWZS) were calculated as deviations from published 50th percentiles. Mean z-scores (MZS) were the average of triglyceride ZSs. MZS of triglycerides, HbA1c and NWZS were compared. Variables are expressed as mean 6 SD. Results: In the three groups respectively: LGA (%) 5 10.1%, 19.0% and 30.4% (P 5 0.015). Birth weight (g) 5 3274.2 6 501.3, 3342.4 6 620.2 and 3366.36644.7 (R SPEARMAN 5 0.111, P 5 0.027). HbA1c (%) 5 5.2 6 0.39, 5.3 6 0.50 and 5.4 6 0.47 (P 5 NS). Triglyceride MZS 5 1.20 6 1.13, 1.52 6 1.37 and 1.62 6 1.42 (R SPEARMAN 5 0.116, P 5 0.024). Correlations between triglyceride MZS and NWZS were, respectively: r 5 0.12 (P 5 NS), r 5 0.42 (P <0.001), and r 5 0.47 (P < 0.001). Conclusions: In overweight and obese GDM mothers, maternal triglycerides are partially responsible for LGA infants despite good maternal glucose control during pregnancy.
Borzone G, Liberona L, Olmos P, Sáez C, Meneses M, Reyes T, Moreno R, Lisboa C. Rat and hamster species differences in susceptibility to elastase-induced pulmonary emphysema relate to differences in elastase inhibitory capacity. Am J Physiol Regul Integr Comp Physiol 293: R1342-R1349, 2007. First published July 18, 2007; doi:10.1152/ajpregu.00343.2007.-Syrian Golden hamsters develop severe emphysema after a single intratracheal dose of elastase, whereas Sprague-Dawley rats exhibit mild emphysema with the same dose per kilogram body weight. We hypothesized that the development of severe emphysema is prevented in rats by the high serum level of ␣1-antitrypsin reported in rats, compared with hamsters, which provides for a high lung elastase inhibitory capacity (EIC). To explore this possibility, we challenged the antiprotease system of the rats by treating them with three similar weekly doses of elastase. Four months after treatment, we evaluated changes in histology, volume, and elastic properties of rat lungs and compared them with those of hamsters receiving a single dose of elastase. We also measured serum ␣1-antitrypsin levels and serum and lung EIC in control rats and hamsters. Results showed that, in association with 40% less serum and lung EIC compared with rats (P Ͻ 0.001), hamster lungs had upperlobe bullae formation, severe microscopic emphysema, a fourfold increase in lung volume (P Ͻ 0.01) and a threefold increase in constant k, an index of compliance, of the lung deflation pressurevolume curve (P Ͻ 0.01). In contrast, rats developed mild emphysema, with only 50% increase in volume (P Ͻ 0.05) and 60% increase in constant k (P Ͻ 0.01). In conclusion, two species that differ in serum and lung EIC exhibit significant differences in emphysema development after elastase. Rats with high EIC, despite receiving three doses of elastase, showed significantly less derangement of morphological and physiological parameters than hamsters with low EIC receiving a single dose. alpha1-antitrypsin; disease models; lung mechanics; susceptibility THE DISCOVERY OF AN ASSOCIATION between emphysema and severe alpha1-antitrypsin (␣1-AT) deficiency (23, 24) and the finding that instilled papain into the lungs of experimental animals resulted in emphysema (15), support the hypothesis that an imbalance between proteases and antiproteases plays a major role in the pathogenesis of chronic obstructive pulmonary disease (COPD) (15,23,24,47). Animal models of intratracheal (IT) instillation of elastase have since been used to induce in a short period of time protease/antiprotease imbalance for the purpose of studying mechanisms involved in the pathogenesis of emphysema downstream protease release. Several investigators have shown that a single dose of elastase induces diffuse alveolar damage and rapid destruction of the alveolar septa, resulting in airspace enlargement (25, 40 -43).To date, studies specifically designed to compare the magnitude and/or the pattern of elastase-induced emphysema between rodent species are unavailable,...
Abstractj og_1681 208..214Aim: Good glycemic control in gestational diabetes mellitus (GDM) seems not to be enough to prevent macrosomia (large-for-gestational-age newborns). In GDM pregnancies we studied the effects of glycemic control (as glycosylated hemoglobin [HbA1c]), pre-pregnancy body mass index (PP-BMI) and gestational weight gain per week (GWG-W) on the frequency of macrosomia. Methods: We studied 251 GDM pregnancies, divided into two groups: PP-BMI < 25.0 kg/m 2 (the nonoverweight group; n = 125), and PP-BMI Ն 25.0 kg/m 2 (the overweight group; n = 126). A newborn weight Z-score > 1.28 was considered large-for-gestational-age. Statistical analysis was carried out using the Student's t-test and c 2 -test, receiver-operator characteristic curves and linear and binary logistic regressions. Results: Prevalence of macrosomia was 14.9% among GDM (n = 202/251, 88.4%) with good glycemic control (mean HbA1c < 6.0%), and 28.1% in those with mean HbA1c Ն 6.0% (n = 49/251, P < 0.025). Macrosomia rates were 10.4% in the non-overweight group and 24.6% in the overweight group (P = 0.00308), notwithstanding both having similar mean HbA1c (5.48 Ϯ 0.065 and 5.65 Ϯ 0.079%, P = 0.269), and similar GWG-W (0.292 Ϯ 0.017 and 0.240 Ϯ 0.021 kg/week, P = 0.077). Binary logistic regressions showed that PP-BMI (P = 0.012) and mean HbA1c (P = 0.048), but not GWG-W (P = 0.477), explained macrosomia. Conclusions: Good glycemic control in GDM patients was not enough to reduce macrosomia to acceptable limits (<10% of newborns). PP-BMI and mean HbA1c (but not GWG-W) were significant predictors of macrosomia. Thus, without ceasing in our efforts to improve glycemic control during GDM pregnancies, patients with overweight/obesity need to be treated prior to becoming pregnant.
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