Next- generation sequencing is an effective method for diagnosing patients with different forms of monogenic diabetes.

AIM: Monogenic diabetes (MD) represents 5-7% of antibody-negative diabetes cases and is a heterogeneous group of disorders. METHODS: We used targeted next-generation sequencing (NGS) on Illumina NextSeq 550 platform involving the SureSelect assay to perform genetic and clinical characteristics of a study group of 684 individuals, including 542 patients referred from 12 Polish Diabetes Centers with suspected MD diagnosed between December 2016 and December 2019 and their 142 family members (FM). RESULTS: In 198 probands (36.5%) and 66 FM (46.5%) heterozygous causative variants were confirmed in 11 different MD-related genes, including 31 novel mutations, with the highest number in the GCK gene (206/264), 22/264 in the HNF1A gene and 8/264 in the KCNJ11 gene. Of the 183 probands with MODY1-5 diabetes, 48.6% of them were diagnosed at the pre-diabetes stage and most of them (68.7%) were on diet only at the time of genetic diagnosis, while 31.3% were additionally treated with oral hypoglycaemic drugs and/or insulin. CONCLUSIONS: In summary, the results obtained confirm the efficacy of targeted NGS method in the molecular diagnosis of patients with suspected MD and broaden the spectrum of new causal variants, while updating our knowledge of the clinical features of patients defined as having MD.

Low-grade Albuminuria and Risk Factors of Atherosclerosis in Children with in Type 1 Diabetes.

AIMS: Microalbuminuria reflects generalized vascular dysfunction and the risk of cardiovascular disease. The study aim was to examine the relationship between low-grade albuminuria and the selected risk factors for atherosclerosis, markers of endothelial dysfunction and inflammation in diabetic children and adolescents. METHODS: In 154 children with diabetes duration of at least 5 years we assessed: HbA1c, lipid profile, apolipoproteins, lipoprotein (a), asymmetric dimethylarginine (ADMA), von Willebrand factor, fibrinogen, uric acid, cystatin C, creatinine, 24-h blood pressure monitoring (ABPM) and albuminuria. RESULTS: Median albuminuria in the whole group was 2.02 µg/min. No correlations were found between albuminuria and lipids, apolipoproteins, fibrinogen, von Willebrand factor, cystatin C and GFR, HbA1c, and uric acid. A significant negative correlation was found between AER and ADMA (R=-0.24, p=0.0023) and positive correlation with all ABPM variables: mean SBP (R=0.23, p=0.0049), mean DBP (R=0.24, p=0.0023), daytime MAP (R=0.31, p=0.0001), nocturnal MAP (r=0.31, p<0.0001) and with percentage of blood pressure dipping (R=-0.17, p=0.0323). A trend was noted for a positive correlation between albuminuria and Lp(a) (R=0.15, p=0.059) and BMI Z-score (R=0.14, p=0.089).Children with albuminuria below 5 µg/min. had significantly lower level of fibrinogen (2.96±0.57 g/l vs. 3.29±0.66 g/l, p=0.0167) and mean 24-h systolic and diastolic blood pressure, mean day and nocturnal blood pressure in comparison to the subjects with higher albuminuria. CONCLUSIONS: diabetic children with acceptable diabetes control but high-normal albuminuria together with higher level of Lp(a), fibrinogen and blood pressure may require more attention in terms of prevention of early macroangiopathy development.