OBJECTIVE:To investigate rates and risk factors of hospital admission for diabetic ketoacidosis (DKA) or severe hypoglycemia in young patients with established type 1 diabetes.DESIGN:In total, 31,330 patients with type 1 diabetes (median age 12.7 years) from the Diabetes Patienten Verlaufsdokumentation (DPV) Prospective Diabetes Registry treated between 2011 and 2013 in Germany were included.METHODS:Admission rates for DKA (pH < 7.3 or bicarbonate <15 mmol/l) and severe hypoglycemia (requiring assistance from another person) were calculated by negative binomial regression analysis. Associations of DKA or hypoglycemia with patient and treatment characteristics were assessed by multivariable regression analysis.RESULTS:The mean admission rate for DKA was 4.81/100 patient-years (95% CI, 4.51-5.14). The highest DKA rates were observed in patients with HbA1c ≥ 9.0% (15.83 (14.44-17.36)), age 15-20 years (6.21 (5.61-6.88)) and diabetes duration of 2-4.9 years (5.60 (5.00-6.27)). DKA rate was higher in girls than in boys (5.35 (4.88-5.86) vs 4.34 (3.95-4.77), P = 0.002), and more frequent in migrants than in non-migrants (5.65 (4.92-6.49) vs 4.57 (4.23-4.93), P = 0.008). The mean admission rate for severe hypoglycemia was 1.45/100 patient-years (1.30-1.61). Rates were higher in migrants compared to non-migrants (2.13 (1.72-2.65) vs 1.28 (1.12-1.47), P < 0.001), and highest in individuals with severe hypoglycemia within the preceding year (17.69 (15.63-20.03) vs patients without preceding hypoglycemia 0.42 (0.35-0.52), P < 0.001). Differences remained significant after multivariable adjustment.CONCLUSIONS:The identification of at-risk individuals for DKA (patients with high HbA1c, longer diabetes duration, adolescents, girls) and for severe hypoglycemia (patients with preceding severe hypoglycemia, migrants) may facilitate targeted diabetes counselling in order to prevent these complications.

Die primäre ziliäre Dyskinesie (PCD) ist eine seltene angeborene Erkrankung der Zilien, die sich zumeist im respiratorischen System manifestiert.

Genetic defects affecting motility of cilia and flagella cause chronic destructive airway disease, randomization of left-right body asymmetry, and, frequently, male infertility in primary ciliary dyskinesia (PCD). The most frequent defects involve outer and inner dynein arms (ODAs and IDAs) that are large multiprotein complexes responsible for cilia-beat generation and regulation, respectively. Here, we demonstrate that large genomic deletions, as well as point mutations involving LRRC50, are responsible for a distinct PCD variant that is characterized by a combined defect involving assembly of the ODAs and IDAs. Functional analyses showed that LRRC50 deficiency disrupts assembly of distally and proximally DNAH5- and DNAI2-containing ODA complexes, as well as DNALI1-containing IDA complexes, resulting in immotile cilia. On the basis of these findings, we assume that LRRC50 plays a role in assembly of distinct dynein-arm complexes.

Cilia and flagella are highly conserved organelles that have diverse roles in cell motility and sensing extracellular signals. Motility defects in cilia and flagella often result in primary ciliary dyskinesia. However, the mechanisms underlying cilia formation and function, and in particular the cytoplasmic assembly of dyneins that power ciliary motility, are only poorly understood. Here we report a new gene, kintoun (ktu), involved in this cytoplasmic process. This gene was first identified in a medaka mutant, and found to be mutated in primary ciliary dyskinesia patients from two affected families as well as in the pf13 mutant of Chlamydomonas. In the absence of Ktu/PF13, both outer and inner dynein arms are missing or defective in the axoneme, leading to a loss of motility. Biochemical and immunohistochemical studies show that Ktu/PF13 is one of the long-sought proteins involved in pre-assembly of dynein arm complexes in the cytoplasm before intraflagellar transport loads them for the ciliary compartment.

Die primäre Ziliendyskinesie (PCD) ist eine seltene Erkrankung. Therapiestudien mit betroffenen Patienten wurden bisher kaum durchgeführt, sodass es in der wissenschaftlichen Fachliteratur nur wenige verwertbare Angaben zur Behandlung gibt. Der behandelnde Arzt ist daher überwiegend auf eigene Überlegungen und Erfahrungen angewiesen. Auch dies gestaltet sich jedoch schwierig, da die meisten Ärzte nur wenige Patienten mit PCD betreuen. Ein Ziel dieser Tagung war daher, die aus verschiedenen Quellen verfügbaren Erkenntnisse zu sammeln und in komprimierter Form darzustellen.