Delineation of the genetic and clinical spectrum, including candidate genes, of monogenic diabetes: a multicenter study in South Korea.

OBJECTIVES: Monogenic diabetes includes a group of heterogeneous diabetes types. We aimed to identify the frequency, clinical and molecular features of monogenic diabetes in a Korean pediatric cohort. METHODS: A retrospective cohort and multicenter study of Korean children suspected to have monogenic diabetes, managed by four pediatric endocrine centers in the southeast region of South Korea, from February 2016 to February 2020. We recruited 27 pediatric Korean patients suspected to have monogenic diabetes who had at least two of the following three criteria (age at diagnosis, family history, and clinical presentation). Targeted exome sequencing was conducted in these patients. The functional consequences of the variants were predicted by bioinformatics and protein structure analysis. RESULTS: Molecular genetic analysis identified 16 patients (59.3%) with monogenic diabetes. We identified a total of eight unique variants, including five novel variants (HNF4A c.1088C>T, CEL c.1627C>T and c.1421C>T, PAX4 c.538+8G>C, INS c.71C>T). We also identified two potential candidate gene variants for monogenic diabetes, namely c.650T>C in the SLC2A2 gene and c.629G>A in the PTF1A gene. Other variants were identified in the WFS1and NPHP3 genes in two rare genetic disorders. Variant-positive individuals had a lower presence of autoantibody positivity at the time of diagnosis and higher glycosylated hemoglobin levels at last follow-up when compared to variant-negative patients (p<0.001 and p=0.029, respectively). CONCLUSIONS: These results further expand the spectrum of known variants as well as potential candidate gene variants associated with monogenic diabetes in Korea.

Bone age in unilateral spastic cerebral palsy: is there a correlation with hand function and limb length?

BACKGROUND: The purpose of this study was to analyze the bone age and the upper extremity segmental lengths between the affected and the unaffected side and to reveal the correlation between the difference of bone age and the upper limb length discrepancy in the unilateral spastic cerebral palsy (CP). We also evaluated the relationship between difference of bone age and hand function. METHODS: Seventy-eight patients participated in this study. The bone ages of hand-wrists of the patients were determined by the Greulich and Pyle atlas. Upper extremity segmental lengths were measured by radiograph. The side-to side length discrepancy was calculated as a percentage. Hand function was classified according to the Manual Ability Classification System (MACS). RESULTS: There was significant difference in the bone age between the affected and unaffected side (p<0.001). Segmental lengths of the upper extremities showed significant differences between the affected and unaffected side (p<0.001). The hand function of 56 patients was evaluated by MACS and the MACS level showed correlation with difference of side-to-side bone age (r=0.29, p=0.03) and all segmental upper limb length discrepancies (p<0.05). The hand function in the bone-age-delayed group was significantly better than the hand function in the bone-age-symmetrical group (p<0.01). CONCLUSIONS: The bone age of the affected side compared to the unaffected side is delayed and the hand function of the affected side is correlated with the difference of side-to-side bone age and the upper limb length discrepancy. Hand function might be helpful for predicting potential limb shortness and delayed bone age.

Incidence trends and associated factors of diabetes mellitus in Korean children and adolescents: a retrospective cohort study in Busan and Gyeongnam.

PURPOSE: This study investigated the incidence trends and associated factors of type 1 (T1DM) and type 2 diabetes mellitus (T2DM) in children and adolescents under 15 years of age in Busan and Gyeongnam, Korea from 2001 to 2010. METHODS: Medical records of newly diagnosed diabetes patients (n=328; 160 males, 168 females) were collected in questionnaire form from 5 tertiary and 42 general hospitals in Busan and Gyeongnam. RESULTS: The average crude incidence rate of T1DM and T2DM was 2.01/100,000 (95% confidence interval [CI], 1.76-2.28) and 0.75/100,000 (95% CI, 0.60-0.92), respectively. The incidence rate ratio (IRR) of T1DM was 1.31 (95% CI, 1.01-1.69), and that of T2DM was 1.97 (95% CI, 1.25-3.11) in the latter half-decade (2006 to 2010) compared to the early half-decade (2001 to 2005). There were gradually increasing incidence trends in both T1DM and T2DM over the 10-year period (P for trend: T1DM, 0.0009; T2DM, <0.0001). Age-specific IRR was highest in the 10- to 14-year-old group, regardless of diabetes type. In particular, a rapid increase in incidence of T2DM occurred in the 10- to 14-year-old group. IRR for females was 1.07 (95% CI, 0.83-1.38) for T1DM and 1.56 (95% CI, 1.01-2.41) for T2DM. IRR for Busan (urban) was 1.41 (95% CI, 1.09-1.83) for T1DM and 1.49 (95% CI, 0.96-2.30) for T2DM. CONCLUSION: T1DM and T2DM incidence both increased over time in youth under age 15 living in Busan and Gyeongnam; in particular, the incidence of T2DM in adolescents increased more rapidly.

Rosiglitazone inhibits proliferation of renal proximal tubular cells via down-regulation of ERK and Akt.

Rosiglitazone has been reported to exert the protective effect against acute renal failure in animal models. However, the underlying mechanisms by which it protects the damaged kidney cells are poorly understood. The present study was therefore undertaken to examine the effect of rosiglitazone on cell proliferation and to determine its molecular mechanism in opossum kidney (OK) cells, an established renal proximal tubular cell line. Rosiglitazone treatment inhibited cell proliferation in a dose- and time-dependent manner, and such effects were not associated with induction of cell death. The anti-proliferative effect of rosiglitazone was accompanied by the cell cycle arrest at the G1 phase. Western blot analysis data showed that rosiglitazone caused down-regulation of extracellular signal-regulated kinase (ERK) and Akt pathway. Transfection of constitutively active forms of MEK (an upstream kinase of ERK) and Akt prevented the proliferation inhibition induced by rosiglitazone. Rosiglitazone facilitated the recovery of cells after cisplatin-mediated injury. Taken together, these data suggest that rosiglitazone induces inhibition of cell proliferation through ERK and Akt-dependent cell cycle arrest at the G1 phase. The cell cycle arrest may play a protective role in kidney cells by preventing injured cells from progressing in the cell cycle.