Maturity-onset diabetes of the young (MODY) is a form of monogenic diabetes with autosomal dominant inheritance. GCK -MODY and HNF1A -MODY are the prevalent subtypes. Currently, there is growing concern regarding the correct interpretation of molecular genetic findings. The American College of Medical Genetics and Genomics (ACMG) updated guidelines to interpret and classify molecular variants. This study aimed to determine the prevalence of MODY ( GCK / HNF1A ) in a large cohort of Brazilian families, to report variants related to phenotype, and to classify them according to ACMG guidelines. One hundred and nine probands were investigated, 45% with clinical suspicion of GCK -MODY and 55% with suspicion of HNF1A -MODY. Twenty-five different variants were identified in GCK gene (30 probands-61% of positivity), and 7 variants in HNF1A (10 probands-17% of positivity). Fourteen of them were novel (12- GCK /2- HNF1A ). ACMG guidelines were able to classify a large portion of variants as pathogenic (36%- GCK /86%- HNF1A ) and likely pathogenic (44%- GCK /14%- HNF1A ), with 16% (5/32) as uncertain significance. This allows us to determine the pathogenicity classification more efficiently, and also reinforces the suspected associations with the phenotype among novel variants.

Objective: Insulin Icodec is a novel basal insulin analogue designed for once-weekly administration, therefore might propitiate reduction in the frequency of injections and facilitate treatment adherence. This study aimed to determine the glycemic control and safety profile of Insulin Icodec, compared with Glargine U100 in patients with diabetes mellitus type 2. Materials and methods: We performed a systematic review and meta-analysis of randomized controlled trials (RCT) data comparing Once-Weekly Insulin Icodec and Once-Daily Insulin Glargine U100 in patients with type 2 diabetes mellitus. PubMed, Embase, and Cochrane databases were searched for trials published up to May 14, 2022. Data were extracted from published reports and quality assessment was performed per Cochrane recommendations. Results: Three studies were included comprising 453 patients, 230 (50.77%) using Once-Weekly Insulin Icodec and 223 (49.22%) using Once-Daily Insulin Glargine U100. In the pooled data, Glycated Hemoglobin (MD -0.20% CI -0.33 to -0.07%; P=0.002) change from baseline demonstrated a significantly higher reduction in the Icodec group. Time with Glucose in Range (MD 6.60% CI 3.63 to 9.57%; P < 0.0001) and Insulin Dose Difference (MD 0.97UI CI 0.76 to 1.18UI; P < 0.0001) were higher in the Icodec group. There was no significant difference in fasting plasma glucose, body weight change, hypoglycemia or any adverse event evaluated. Conclusions: Once-Weekly Insulin Icodec was associated with a small reduction in Glycated Hemoglobin, as well as higher Time with Glucose in Range, with similar hypoglycemic adverse events, when compared with Once-Daily Insulin Glargine U100. KeywordsType 2 diabetes mellitus; insulin; insulin long-acting; insulin glargine; insulin icodec; glycemic control; glycated hemoglobin A Insulin Icodec vs. Glargine for type 2 diabetes: a systematic review and meta-meta-analysis

Neonatal diabetes mellitus (NDM) is defined as the occurrence of severe hyperglycemia in infants under 6 months old and may be permanent (PNDM) or transient (TNDM).When diabetes is diagnosed at 6-12 months of age (early onset diabetes [EOD]), the etiology may be monogenic; however, most cases consist of type 1 diabetes mellitus (T1DM). Molecular diagnosis was determined in a cohort of 35 unrelated Brazilian patients with NDM or EOD based on targeted next-generation sequencing panel and/or chromosome 6q24 abnormalities. The impact of genetic testing on treatment and follow-up was evaluated. Overall, 24 patients had NDM: with 18 (75.0%) having PNDM, 5 TNDM (20.8%) and 1 case in which this information was unknown. Eleven patients had EOD. Genetic testing was positive in 20/24 patients with NDM (83.3%) and in 18.2% of cases of EOD. The commonest causes were ATP-sensitive potassium (KATP) channel genes, and GCK and IPEX mutations (37.1%, 11.4% and 5.7%, respectively). Patients with PNDM due to KCNJ11 and ABCC8 mutations transitioned successfully to sulfonylureas in almost 60% of cases, reinforcing the benefit of performing genetic testing in NDM as early as possible. This report refers to the largest series of cases of NDM (TNDM and PNDM) and EOD in Brazil in which patients were submitted to molecular investigation and in which the clinical impact of genetic diagnosis was also evaluated.

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Federal Universitv of P a r a d . Curitiba. Brasll.Enciocrinol. Sheba Med. Ctr . . Tel-Hashomer. I s r a e l . Tel Aviv Univ. Chronic e m s u r e -t o sex steroids d&ing childhccd accelerates s k e l e t a l maturation and may corn-crromise f i n a l height. The growth of 26 children (18 g i r l s , 8 Soys) disease-free of ACC f o r maze than 1 yr were reviewed. The i r i t i a l c l i n i c a l siw appeared a t ~. 9 2 2.8 y r and t h e diap.osis wa.; made a t 3.6 2 2.8 yr. Time of follow-up a f t e r surgery was 6.2 2 3 . 5 yr (range 1 . 5 -1 3 . 0 ) . 50% had adrenogenital sp-drome (AS), 38% mixed syndrome (US: Gushing's plus AS), 8% no endocrine s m t o m s and 4% C~s h l n g syndrow. A t t h e time of d i a g o s i s t h e mean H-SDS was higher than t a r g e t height-SDS (W-SDS; p < 0.0001). H-SDS was not d i f f e r e n t between AS and M S groups ( p > 0 . 1 ) . Bone age 18.9; 6.2 53.6) was grearer than helght age (HA; 4.2 2 2 . 7 ) and chronological age (CA; 3 . 8 2 2.9) ( p < 0.05), whereas :iA m d CA were not d i f f e r e n t . B A advcnced more than CA i n t h e 1st year followino tumor removal: i n the 2nd year and t h e r e a f t e r we observed catch-doh?l arohTh t h a t was m r e intense i n B A +Am i n H-SDS. Only one patient of t k e s e r i e s , with no B A catch-down, developed t r u e precocious puberty. I n l t i a l predicted adult height (?.AH; Bayley & Tinneau) of 10 patients was lower than tar-t height (TH; p < 0:Ol); however, i n t h e l a s t evaluation (16 p t s ) PAH and W were not d i f f e r e z t ( p > 0 . 1 ) . I n conclssion: a ) children exposed t o with/without glucocorticoid for a l i q i t e d w r i @ of time usuallv increase B A more than H-SDS: b ) a f t e r tumor exclsion both 5.4Medical Schcol, I s r a e l . Insulin l i k e growth factor-1 (1Gr"-1) increases during normal adolescence and in CPP secondary t o t h e r i s e in sex s t e r o i d s and GH.Treatment of CP? using GnRH malog suppresses GH a s well a s gonadotropins. W e e x z~i n e d IGF-1 and its m j o r bmnding protein-IGF3P-3 i n sera of t e n g i r l s d i a g o s e d with CPP, before and during the f i r s t 3 months of GnRH analog therapy. Serum IGF-1 w a s increased i n ~a t i e n t s with CPP a s comwared with controls (48.8 + 6 . 5 vs 23.1 + 41 9 m l / L , p < 0.01 ) . G& analog therapy ca&ed serum E2 levels t o return t o p r e p b e r t a l l e v e l s i n a l l 10 p a t i e n t s , whereas semi IGF-1 l e v e l s decreased minimally a f t e r one (43.2 ?: 5.6 ~m l / L ) , two (42.3 t 6.4 m l / L ) , m d three ( 4 4 . 1 2 7.2 m l / L ) months of therapy. Serum IGFBP-3 concentratiors measured using IRW were a l s o higher i n CPP c o m p~e d with controls (4.7 + 0.37 vs 3.7 t 0.42 mg/L w < 0.01). These d~f f e r e n c e s were a l s o evident when a l l IGF bincino proteins' were measwed by Western ligand blotting. GnXa therap? cacsed a small md insignificant decrease i n serum IGFBP-3 levels a f t e r one (4.57 2 0.33 mg/L), two (4.48 t 0.4 mg/L) and three (4.42 t 0 . 3 mo/L) months of therawv. This...