OBJECTIVE -Cardiac autonomic nerve tests have predicted increased mortality in adults with diabetes, predominantly due to nephropathy, cardiac disease, and hypoglycemia. The significance of subclinical autonomic nerve test abnormalities has not been systematically studied in adolescents. We aimed to reassess an adolescent cohort, whose autonomic nervous system had been tested 12 years earlier by both pupillometry and cardiovascular tests. -From 1990-From to 1993, adolescents with type 1 diabetes (n ϭ 335) were assessed for autonomic neuropathy (median age 14.7 years [interquartile range 13.0 -16.8], duration of diabetes 6.3 years [4.0 -9.6], and A1C 8.3% [7.5-9.4]). Between 2003 and 2005, contact was made with 59% of the original group. Individual assessment 12 years later included completion of a validated hypoglycemia unawareness questionnaire (n ϭ 123) and urinary albumin-to-creatinine ratio (n ϭ 99) and retinal (n ϭ 102) screening, as well as analysis of reports from external doctors (n ϭ 35). RESEARCH DESIGN AND METHODSRESULTS -At baseline, there was no difference in age, duration of diabetes, or complications between those who participated in the follow-up phase (n ϭ 137) and those who did not participate (n ϭ 196). However, baseline A1C was lower in the follow-up participants (8.2 vs. 8.5% for participants vs. nonparticipants, respectively, P ϭ 0.031). At 12 years of follow-up, 93% were aware and 7% were unaware that they had hypoglycemia; 32 (31%) had no retinopathy, but 10% required laser therapy, and 80 (81%) had no microalbuminuria. Small pupil size at baseline was independently associated with the development of microalbuminuria (odds ratio 4.36 [95% CI 1.32-14.42], P ϭ 0.016) and retinopathy (4.83 [1.3-17.98], P ϭ 0.019) but not with the development of hypoglycemia unawareness. There was no association with baseline cardiovascular tests and the development of complications 12 years later.CONCLUSIONS -In this study, we found an association between baseline pupillometry tests and the presence of microalbuminuria and retinopathy at 12 years of follow-up. This suggests that pupillometry abnormalities may be early indicators of patients who are at high risk of future microvascular disease. (1) presented a landmark study that reported a predictive relationship between symptomatic autonomic neuropathy and mortality in adults with type 1 diabetes. Deaths 5 years later were predominantly due to associated vascular disease (1), which other authors (2) have considered to be an explanation for the increased mortality related to abnormal cardiac autonomic tests. Deaths were also due to hypoglycemia and "sudden death" (1). Owing to the era of the Ewing et al. study, A1C was not measured; therefore, it was not controlled for, and questions remained unanswered. These questions include whether increased mortality was directly related to glycemic control (i.e., a shared mechanism of damage causing both neuropathy and cardiovascular disease by accumulation of advanced glycation end products) or whether there may be...

Over the past 5 years, there has been increasing evidence for the role of primary (9+0) cilia in renal physiology and in establishing the left-right axis. The cilia in the renal tract are immotile and thought to have a sensory function. Cilia at the murine embryonic node have a vortical movement that sets up a leftward flow. Inversin, the protein defective in the inv mouse and in patients with type-2 nephronophthisis, localizes to both renal and node primary cilia. However, we present evidence that it is also expressed before the node forms and that its subcellular localization in renal tubular cells is not confined to the cilia. Its role in both the pathway determining left-right axis and renal function remains to be elucidated.

Growth hormone deficiency (GHD) in adults and children is associated with decreased lean tissue mass (LTM), increased fat mass and reduced bone mineral density (BMD). The changes in BMD and body composition, 6 and 12 months after ceasing GH treatment, were assessed using dual‐energy X‐ray absorptiometry in eight patients with GHD (age range, 13.8–17.5 years). Seven age‐matched normal subjects who had completed growth were assessed at 0 and 12 months. Total body BMD was low at baseline (p < 0.05) in patients with GHD compared with the predicted values based on sex‐specific regression equations, with height, weight and age taken into account. Total body, lumbar spine and femoral neck BMD increased in the patients and controls at 12 months. LTM decreased significantly by a mean of 1.37 kg in the patients with GHD at 12 months whereas there was a non‐significant increase in LTM in the control group. The percentage of body fat increased in all patients with GHD at 6 and 12 months, from 27.2 ± 11% (mean ± SD) at baseline to 32 ± 9.9% at 12 months (p= 0.009). There was no significant increase in mean percentage body fat in the control group. The ratio of android (trunk):gynoid (legs) fat was calculated using default settings of dual‐energy X‐ray absorptiometry. The mean android:gynoid fat ratio increased, though non‐significantly, in patients with GHD at 12 months, with 6 of 7 showing an increase; no change was observed in the control group. These results indicate that BMD continues to increase 12 months after ceasing GH therapy in adolescents with GHD, but that unfavourable alterations in body composition occur.

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