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Aims: In this study we evaluated the use of Continuous Glucose Monitoring system in adults with insulin-dependent diabetes in the course of Wolfram syndrome (WFS) in comparison to patients with type 1 diabetes (T1D)., Methods: Individuals with WFS (N = 10) used continuous glucose monitoring for 14 days and were compared with 30 patients with T1D matched using propensity score for age and diabetes duration. Glycemic variability was calculated with Glyculator 3.0., Results: We revealed significant differences in glycemic indices between adults with Wolfram syndrome-related diabetes and matched comparison group. Patients with Wolfram syndrome presented lower mean glucose in 24-h and nighttime records [24h: 141.1 ± 30.4mg/dl (N = 10) vs 164.9 ± 31.3mg/dl (N = 30), p = 0.0427; nighttime: 136.7 ± 39.6mg/dl vs 166.2 ± 32.1mg/dl (N = 30), p = 0.0442]. Moreover, they showed lower standard deviation of sensor glucose over all periods [24h: 50.3 ± 9.2mg/dl (N = 10) vs 67.7 ± 18.7 mg/dl (N = 30), p = 0.0075; daytime: 50.8 ± 8.7mg/dl (N = 10) vs 67.4 ± 18.0mg/dl (N = 30), p = 0.0082; nighttime: 45.1 ± 14.9mg/dl (N = 10) vs 65.8 ± 23.2mg/dl (n = 30), p = 0.0119] and coefficient of variation at night [33.3 ± 5.8% (N = 10) vs 40.5 ± 8.8% (N = 30), p = 0.0210]. Additionally, WFS patients displayed lower time in high-range hyperglycemia (> 250mg/dl) across all parts of day [24h: 4.6 ± 3.8% (N = 10) vs 13.4 ± 10.5% (N = 30), p = 0.0004; daytime: 4.7 ± 3.9% (N = 10) vs 13.8 ± 11.2% (N = 30), p = 0.0005; nighttime: 4.2 ± 5.5% (N = 10) vs 12.1 ± 10.3% (N = 30), p = 0.0272]., Conclusions: Adult patients with Wolfram syndrome show lower mean blood glucose, less extreme hyperglycemia, and lower glycemic variability in comparison to patients with type 1 diabetes., (© 2024. The Author(s).)

Aims: Wolfram syndrome (WFS) is a recessively inherited monogenic form of diabetes coexisting with optic atrophy and neurodegenerative disorders with no currently recognized markers of disease progression. The aim of the study was to evaluate retinal parameters by using optical coherence tomography (OCT) in WFS patients after 2 years of follow-up and analysis of the parameters in relation to visual acuity., Methods: OCT parameters and visual acuity were measured in 12 WFS patients and 31 individuals with type 1 diabetes., Results: Total thickness of the retinal nerve fiber layer (RNFL), average retinal thickness and total retinal volume decreased in comparison with previous OCT examination. Significant decreases were noted for RNFL (average difference -17.92 µm 95% CI -30.74 to -0.10; p = 0.0157), macular average thickness (average difference -5.38 µm 95% CI -10.63 to -2.36; p = 0.0067) and total retinal volume (average difference -0.15 mm 3 95% CI -0.30 to -0.07; p = 0.0070). Central thickness remained unchanged (average difference 1.5 µm 95% CI -7.61 to 10.61; p = 0.71). Visual acuity of WFS patients showed a strong negative correlation with diabetes duration (R = -0.82; p = 0.0010). After division of WFS patients into two groups (with low-vision and blind patients), all OCT parameters except for the RNFL value were lower in blind WFS patients., Conclusions: OCT measures structural parameters and can precede visual acuity loss. The OCT study in WFS patients should be performed longitudinally, and serial retinal examinations may be helpful as a potential end point for future clinical trials.

Patients with diabetes caused by single-gene mutations generally exhibit an altered course of diabetes. Those with mutations of the glucokinase gene (GCK-MODY) show good metabolic control and low risk of cardiovascular complications despite paradoxically lowered high-density lipoprotein (HDL) cholesterol levels. In order to investigate the matter, we analyzed the composition of low-density lipoprotein (LDL) and HDL subpopulations in such individuals. The LipoPrint(©) system (Quantimetrix, USA) based on non-denaturing, linear polyacrylamide gel electrophoresis was used to separate and measure LDL and HDL subclasses in fresh-frozen serum samples from patients with mutations of glucokinase or HNF1A, type 1 diabetes (T1DM) and healthy controls. Fresh serum samples from a total of 37 monogenic diabetes patients (21 from GCK-MODY and 16 from HNF1A-MODY), 22 T1DM patients and 15 healthy individuals were measured in this study. Concentrations of the small, highly atherogenic LDL subpopulation were similar among the compared groups. Large HDL percentage was significantly higher in GCK-MODY than in control (p = 0.0003), T1DM (p = 0.0006) and HNF1A-MODY groups (p = 0.0246). Patients with GCK-MODY were characterized by significantly lower intermediate HDL levels than controls (p = 0.0003) and T1DM (p = 0.0005). Small, potentially atherogenic HDL content differed significantly with the GCK-MODY group showing concentrations of that subfraction from control (p = 0.0096), T1DM (p = 0.0193) and HNF1A-MODY (p = 0.0057) groups. Within-group heterogeneity suggested the existence of potential gene-gene or gene-environment interactions. GCK-MODY is characterized by a strongly protective profile of HDL cholesterol subpopulations. A degree of heterogeneity within the groups suggests the existence of interactions with other genetic or clinical factors.

Treatment with continuous subcutaneous insulin infusion (CSII) allows a large degree of treatment individualization and intensification in children with diabetes. The study's aim was to evaluate the impact of treatment with CSII on glycated haemoglobin level (HbA1c) in children with diabetes and investigate whether introduction of CSII is associated with an increased risk of acute complications of diabetes. Patients treated throughout the recruitment period exclusively with multiple daily injections (MDI) were matched for duration of diabetes and HbA1c level at baseline with patients treated exclusively with CSII in a 1:1 group ratio (n = 223 and 231 for MDI and CSII, respectively). The CSII group showed lower HbA1c after the observation period (7.98 ± 1.38 vs. 7.56 ± 0.97; P = 0.002). HbA1c variability measured as standard deviations of average values was also lower in the CSII group (0.73 ± 0.45 vs. 0.84 ± 0.54; P = 0.049). The rate of hospitalization due to acute events was similar in both groups (14.7/100 vs. 14.0/100 person/years in the MDI and CSII group, P = 0.72). Duration of hospital stay per year was on average 1.25 days shorter in the CSII group (P = 0.0004), but the risk of acute complications resulting in hospitalization did not differ between the groups (hazard ratio (HR) 1.16; 95% confidence interval (95% CI) 0.68-1.63). The most significant risk factor for hospitalization due to acute complications was baseline HbA1c concentration (HR 1.25; 95% CI 1.14-1.37). In conclusion, CSII treatment may improve glycemic control and reduce its variability. Change of MDI to CSII does not alter the risk of hospitalization and may reduce the annual duration of hospitalization in children with diabetes.

Monogenic diabetes caused by mutations in the glucokinase gene (GCK-MODY) is usually characterized by a mild clinical phenotype. The clinical course of diabetes may be, however, highly variable. The authors present a child with diabetes manifesting with ketoacidosis during the neonatal period, born in a large family with ten members bearing a heterozygous p.Gly223Ser mutation in GCK. DNA sequencing and multiplex ligation-dependent probe amplification were used to confirm GCK mutation and exclude other de novo mutations in other known genes associated with monogenic diabetes. Continuous glucose monitoring (CGM) was used to assess daily glycemic profiles. At the onset of diabetes the child had hyperglycemia 765 mg/dl with pH 7.09. Her glycated hemoglobin level was 8.6% (70.5 mmol/mol). The C-peptide level was below normal range (<0.5 pmol/ml) at onset, and the three- and 6-month follow-up examinations. Current evaluation at age 3 still showed unsatisfactory metabolic control with HbA1c level equal to 8.1% (65.0 mmol/mol). CGM data showed glucose concentrations profile similar to poorly controlled type 1 diabetes. The patient was confirmed to be heterozygous for the p.Gly223Ser mutation and did not show any point mutations or deletions within other monogenic diabetes genes. Other family members with p.Gly223Ser mutation had retained C-peptide levels and mild diabetes manageable with diet (five individuals), oral hypoglycemizing agents (five patients), or insulin (one patient). This mutation was absent within all healthy family members. Heterozygous mutations of the GCK gene may result in neonatal diabetes similar to type 1 diabetes, the cause of such phenotype variety is still unknown. The possibility of other additional, unknown mutations seems to be the most likely explanation for the unusual presentation of GCK-MODY.