Serum dipeptidyl peptidase 4 activity in children with type 1 diabetes mellitus.

BACKGROUND: It is poorly understood whether dipeptidyl peptidase 4 (DPP4) activity is altered and how DPP4 contributes to glycemic control in patients with type 1 diabetes mellitus (T1DM). AIM: The aim of this study was to measure serum DPP4 activity and to assess its relationships to metabolic variables in T1DM children. METHODS: Serum DPP4 activity was determined using a fluorometric assay in 43 T1DM and 26 control children. RESULTS: Serum DPP4 activity was significantly higher in T1DM children than in controls (3.57 ± 0.99 vs. 2.67 ± 0.77 U/mL, p<0.001). In the T1DM children, DPP4 activity was not correlated with HbA1c, blood glucose, or diabetes duration. A significant negative correlation was found between DPP4 activity and serum adiponectin levels in the T1DM group (r=-0.35, p<0.05). CONCLUSIONS: Serum DPP4 activity was increased in the T1DM children, whereas it was not associated with glycemic control. Given the negative correlation between serum DPP4 and adiponectin levels, further investigations are warranted to elucidate the role of DPP4 on insulin sensitivity in T1DM children.

Clinical characteristics, etiologies and pathophysiology of patients with severe short stature with severe GH deficiency: questionnaire study on the data registered with the foundation for growth science, Japan.

In this study, we sent questionnaires to doctors treating severe short stature with severe GH deficiency (GHD) (height SDS (HtSDS) below -4 and all peak GH to provocative stimuli below 2 micro/L) (abbreviated as Severe Case), and obtained effective replies of 51 cases. The clinical characteristics, etiologies, and pathophysiology of these patients were examined. Among the 51 Severe Cases no consanguinity was observed, 44 were IGHD (24 males and 20 females), 3 were GH-1 gene deletion, 2 were Pit-1 gene mutation, and 2 were achondroplasia. HtSDS in these Severe Cases was already remarkably low at 12 (-3.0) and 24 months old (-3.9), while their birth weight and birth length were within normal ranges. Among 44 patients with IGHD, 12 were isolated GHD, and the remaining 32 were combined pituitary hormone deficiency (CPHD). Pituitary MRI was undergone in 25 idiopathic GHD, and abnormal findings (pituitary atrophy, interruption of stalk, and ectopic posterior lobe) were observed in 21 patients with CPHD. More than half of these patients had the history of breech delivery. Three patients with GH-1 gene mutation showed normal pituitary MRI, whereas one of two patients with Pit-1 mutation showed pituitary atrophy and narrowing of pituitary stalk. In conclusion, Severe Cases tended to have CPHD, and the incidence of Severe Case was only 0.6% of total IGHD. Although GHD due to genetic disorders is considered to be extremely rare (0.06% of total IGHD), the incidence reaches high levels (9.8%) among Severe Cases. Growth disorders in these Severe Cases seem to occur soon after delivery. Much earlier diagnosis and hGH treatment are desirable to attain better final height in the Severe Cases. GH-1 and Pit-1 gene analyses are crucial, when genetic abnormalities other than achondroplasia are suspected.

Studies of very severe short stature with severe GH deficiency: from the data registered with the foundation for growth science.

The ratio, clinical characteristics, and therapeutic efficacy of hGH treatment in patients with severe short stature (HtSDS below -4SD) with severe GHD (all peak GH values to provocation tests: below 2 mug/L) were studied. From March 1986 to January 1998, 23,110 patients with idiopathic GH deficiency (IGHD) were registered with the Foundation for Growth Science, Japan. These subjects were divided into 5 groups as follows: Group 1 (G1), all subjects; Group 2 (G2), at least one GH peak to provocative test > or = 5 microg/L; Group 3 (G3), 2 microg/L < or = GH peak<5 microg/L; Group 4 (G4), all GH peaks<2 microg/L and HtSDS>-4; Group 5 (G5), all GH peaks<2 microg/L and HtSDS< or = -4. The ratio of G5 was 139 patients (0.6%) out of 23,110 patients with IGHD. In G5, there were no significant differences in birth weight, birth length, gestational age and parental height between G2, G3 and G4. However, asphyxia at delivery was more frequent in G5 and G4 than G2 and G3. Chronological age (CA), bone age (BA) and BA/CA ratio at registration were significantly lower in G5 than G2, G3 and G4. Further, the IGF-I SD score in G5 was significantly lower than those in G2 and G3. After hGH treatment, the final height and final height SDS in G5 remained the lowest, while the DeltaHtSDS value in G5 was the greatest among G2 to G5 groups. In conclusion, the ratio of severe short stature with severe GH deficiency (G5) is only 0.6% of all IGHD cases. Growth failure in G5 seems to occur after birth, and its etiology in G5 seems to be different from that of patients with other forms of IGHD. Early diagnosis and hGH treatment are needed to attain better final height.