Adults with type 1 diabetes mellitus (T1DM) are at risk of premature osteoporosis and fractures. The onset of T1DM typically starts during childhood and adolescence. Thus, the effects of DM on the skeleton may be established during this period. Studies in children with T1DM primarily use DXA with conflicting results. We present the first study in adolescents assessing the impact of T1DM on skeletal microstructure and strength using HRpQCT. We recruited 22 patients aged 12 to 16 years with T1DM who were matched by age, gender, and pubertal stage with healthy controls. Paired t tests were applied to assess differences in cortical and trabecular microarchitecture measurements from HRpQCT, and skeletal strength from HRpQCT-derived microfinite element analysis. Subtotal body, lumbar, and pelvic parameters were assessed using DXA. There was no significant difference in subtotal body, lumbar spine, and pelvic BMD between T1DM and control pairs. However, tibial trabecular thickness was lower (−0.005 mm; 95% CI, −0.01 to −0.001; p = 0.029) and trabecular loading was lower at the distal radius (ratio of the load taken by the trabecular bone in relation to the total load at the distal end (Tb.F/TF) distal: −6.2; 95% CI, −12.4 to −0.03; p = 0.049), and distal and proximal tibia (Tb.F/TF distal: −5.2, 95% CI, −9.2 to −1.2; p = 0.013; and Tb.F/TF proximal: −5.0, 95% CI, −9.8 to −0.1; p = 0.047) in T1DM patients. A subanalysis of radial data of participants with duration of T1DM of at least 2 years and their matched controls demonstrated a reduced trabecular bone number (−0.15, 95% CI, −0.26 to −0.04; p = 0.012), increased trabecular separation (0.041 mm, 95% CI, 0.009-0.072; p = 0.015), an increased trabecular inhomogeneity (0.018, 95% CI, 0.003-0.034; p = 0.021). Regression models demonstrated a reduction in tibial stiffness (−0.877 kN/mm; p = 0.03) and tibial failure load (−0.044 kN; p = 0.03) with higher HbA1C. Thus, in adolescents with T1DM, detrimental changes are seen in tibial and radial microarchitecture and tibial and radial strength before changes in DXA occur and may result from poor diabetic control.

Summary This case report describes a family pedigree of a mother and her children with an E227K mutation in the KCNJ11 gene. People with this particular gene mutation typically present with transient neonatal diabetes; with more than half the cohort relapsing into permanent diabetes in adolescence or early adulthood. However, the mother developed diabetes as an adolescent and thus was initially diagnosed as having Type 1 Diabetes. All her children have inherited the same genetic mutation but with differing presentations. Her second, third and fourth child presented with transient neonatal diabetes which remitted at varying times. Her first child is 16 years old but had not developed diabetes at the time of writing. The KCNJ11 gene codes for the KIR6.2 subunit of the KATP channels of the pancreatic beta cells. Mutations in this gene limit insulin release from beta cells despite high blood glucose concentrations. Most people with diabetes caused by this genetic mutation can be successfully managed with glibenclamide. Learning of the genetic mutation changed the therapeutic approach to the mother’s diabetes and enabled rapid diagnosis for her children. Through this family, we identified that an identical genetic mutation does not necessarily lead to the same diabetic phenotype. We recommend clinicians to consider screening for this gene in their patients whom MODY is suspected; especially in those presenting before the age of 25 who remain C-peptide positive. Learning points: KATP channel closure in pancreatic beta cells is a critical step in stimulating insulin release. Mutations in the KIR6.2 subunit can result in the KATP channels remaining open, limiting insulin release. People with KCNJ11 mutations may not present with neonatal diabetes as the age of presentation of diabetes can be highly variable. Most affected individuals can be treated successfully with glibenclamide, which closes the KATP channels via an independent mechanism. All first degree relatives of the index case should be offered genetic testing, including asymptomatic individuals. Offspring of affected individuals should be monitored for neonatal diabetes from birth. Affected individuals will require long-term follow-up as there is a high risk of recurrence in later life.

Summary An 11-year-old girl presented with acute lower limb weakness, dehydration, hypernatraemia and secondary rhabdomyolysis on a background of an 8-month history of polyuria. Radiological investigations revealed a suprasellar tumour which was diagnosed on biopsy as a non-metastatic germinoma. Further endocrinological investigations confirmed panhypopituitarism and she commenced desmopressin, hydrocortisone and thyroxine. Her chemotherapeutic regime consisted of etoposide, carboplatin and ifosfamide, the latter of which required 4 litres of hyperhydration therapy daily. During the first course of ifosfamide, titration of oral desmopressin was trialled but this resulted in erratic sodium control leading to disorientation. Based on limited literature, we then trialled an arginine-vasopressin (AVP) infusion. A sliding scale was developed to adjust the AVP dose, with an aim to achieve a urine output of 3–4 mL/kg/h. During the second course of ifosamide, AVP infusion was commenced at the outset and tighter control of urine output and sodium levels was achieved. In conclusion, we found that an AVP infusion during hyperhydration therapy was required to achieve eunatraemia in a patient with cranial diabetes insipidus. Developing an AVP sliding scale requires individual variation; further reports/case series are required to underpin practice. Learning points Certain chemotherapeutic regimens require large fluid volumes of hyperhydration therapy which can result in significant complications secondary to rapid serum sodium shifts in patients with diabetes insipidus. The use of a continuous AVP infusion and titrating with a sliding scale is more effective than oral desmopressin in regulating plasma sodium and fluid balance during hyperhydration therapy. No adverse effects were found in our patient using a continuous AVP infusion. Adjustment of the AVP infusion rate depends on urine output, fluid balance, plasma sodium levels and sensitivity/response of the child to titrated AVP doses.

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