Background Patients referred for HNF1B testing present very heterogeneous phenotypes. Despite suggestive characteristics, many do not harbor mutations in HNF1B. Objectives To evaluate the clinical characteristics of probands referred for HNF1B genetic testing through a nationwide monogenic diabetes screening programme. Subjects Probands tested for HNF1B mutations in the 2005‐2018 period (N=50) were identified in the Polish Monogenic Diabetes Registry, which prospectively recruits primarily pediatric patients and their families on a nationwide scale. Methods Variants that had been reported pathogenic were reassessed using criteria of the American College of Medical Genetics and Genomics (ACMG). A structured medical interview was performed with all available individuals, their parents, and/or their physicians. For each patient, HNF1B‐score was calculated based on available clinical information. Results The study group numbered 36 unrelated probands (28% lost to follow‐up): 14 with pathogenic or likely‐pathogenic variants in HNF1B, one with a variant of uncertain significance and 21 negative for HNF1B mutations. Presence of cystic kidneys (OR=9.17, 95%CI:1.87‐44.92), pancreatic abnormalities (OR=15, 95%CI:1.55‐145.23), elevated liver enzymes (OR=15, 95%CI:1.55‐145.23) best discriminated HNF1B‐positive cases from the negative ones. Presence of impaired glucose tolerance coupled with kidney disease in the proband and one parent was also highly predictive for HNF1B mutations (OR=11.11, 95%CI:1.13‐109.36). HNF1B‐score with recommended cut‐off distinguished patients with and without HNF1B findings with 100% sensitivity and 47.6% specificity. Addition of four clinical variables to select patients based on HNF1B‐score improved specificity to 71.4% (95%CI:47.8%‐88.7%) whilst retaining 100% sensitivity. Conclusions Detailed medical interview may enable more accurate patient selection for targeted genetic testing.

Background: Fibroblast growth factor 19 (FGF19), fibroblast growth factor 21 (FGF21) and Klotho are regulators of energy homeostasis. However, in the pediatric population, the relationships between obesity, metabolic disorders and the aforementioned factors have not been clearly investigated. We analyzed the role of FGF19, FGF21 and Klotho protein in children with normal body weight as well as in overweight and obese subjects and explored their associations with insulin resistance (IR) and metabolic syndrome (MS) and its components. Methods: This was a cross-sectional study conducted in a group of hospitalized children and adolescents. Laboratory investigations included serum analysis of FGF19, FGF21, and Klotho with ELISA kits as well as the analysis of the lipid profile and ALT serum concentrations. Moreover, each subject underwent an oral glucose tolerance test (OGTT) with fasting insulinemia measurement to detect glucose tolerance abnormalities and calculate the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) index. Furthermore, the clinical analysis included blood pressure measurement, body fat percentage estimation and assessment of the prevalence of MS and its components. Results: The study was conducted with 174 children/adolescents aged 6–17 years with normal body weight (N = 48), obesity (N = 92) and overweight (N = 34). Klotho concentration was significantly higher in the obese children [median 168.6 pg/ml (90.2 to 375.9)]) than in the overweight [131.3 pg/ml (78.0 to 313.0)] and normal-body-weight subjects [116.6 pg/ml (38.5 to 163.9)] (p = 0.0334) and was also significantly higher in insulin-resistant children than in insulin-sensitive children [185.3 pg/ml (102.1 to 398.2) vs 132.6 pg/ml (63.9 to 275.6), p = 0.0283]. FGF21 was elevated in patients with MS compared to the FGF21 levels in other subjects [136.2 pg/ml (86.5 to 239.9) vs 82.6 pg/ml (41.8 to 152.4), p = 0.0286]. The multivariable model showed that FGF19 was an independent predictor of IR after adjusting for pubertal stage and BMI Z-score. Conclusions: Klotho levels were associated with body weight status in children and adolescents. Moreover, Klotho, FGF19 and FGF21 concentrations correlated with IR status and/or components of MS.

People with type 1 diabetes have an increased risk of developing microvascular complications, which have a negative impact on the quality of life and reduce life expectancy. Numerous studies in animals with experimental diabetes show that c-peptide supplementation exerts beneficial effects on diabetes-induced damage in peripheral nerves and kidneys. There is substantial evidence that c-peptide counteracts the detrimental changes caused by hyperglycemia at the cellular level, such as decreased activation of endothelial nitric oxide synthase and sodium potassium ATPase, and increase in formation of pro-inflammatory molecules mediated by nuclear factor kappa-light-chain-enhancer of activated B cells: cytokines, chemokines, cell adhesion molecules, vascular endothelial growth factor, and transforming growth factor beta. However, despite positive results from cell and animal studies, no successful c-peptide replacement therapies have been developed so far. Therefore, it is important to improve our understanding of the impact of c-peptide on the pathophysiology of microvascular complications to develop novel c-peptide-based treatments. This article aims to review current knowledge on the impact of c-peptide on diabetic neuro- and nephropathy and to evaluate its potential therapeutic role.

Our aim was to compere diabetes-related distress (DD) in young patients with type 1 diabetes mellitus (T1DM) and in their parents before and during the national COVID-19-related lockdown when schools operated on-line. Problems Areas in Diabetes-Child (PAID-Ch), Teen (PAID-T) and Parent (P-PAID-Ch, P-PAID-T) questionnaires in paper version were used to evaluate DD before COVID-19 pandemic (November 2019–February 2020) and during the lockdown (April 2020) the same surveys were performed by phone. We enrolled 76 patients (median age (Q1–Q3): 13.6 (11.8–15.2) years; 21 children, 55 adolescents; T1DM duration 3.7 (1.7–6.8) years). Initial PAID score was lower in teenage boys than in girls (34.0 (24.0–42.0) vs. 44.5 (40.0–50.5), p = 0.003). In teens PAID score decreased significantly during the lockdown (−3.0 (−11.0–3.0), p = 0.018), more in girls than boys (p = 0.028). In children (−3.0 (−14.0–7.0), p = 0.131) and parents PAID did not change (teens’ parents: 3.0 (−9.0–10.0), p = 0.376; children’s parents: −5.0 [−9.0–1.0], p = 0.227). In the studied group COVID-19 pandemic-related lockdown was associated with decrease in DD in teens with T1DM, particularly in girls, while no significant change in DD was observed in children or parents. DD decrease in teens during the pandemic should attract attention to the potential “rebound” of DD related to return to regular on-site school routine.