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The article focuses on the limitations of using A1C as a diagnostic and monitoring tool for diabetes, highlighting cases of misdiagnosis due to analytical interference. Topics include the impact of conditions affecting erythrocyte turnover on A1C, potential interference with hemoglobin variants, and the importance of critically interpreting A1C results.

The article presents a case study of an 18 year-old man diagnosed with insulin-dependent diabetes as an infant. He was identified as an appropriate candidate for genetic testing based on publications identifying a monogenic cause of diabetes in patients diagnosed in the first 6 months of life. At the time of his diagnosis, permanent neonatal diabetes mellitus (PNDM) was medically treated as type 1 diabetes. The study discusses the psychosocial barriers to implementing oral treatment of PNDM.

Background/objective: Mutations in KCNJ11, ABCC8, or INS are the cause of permanent neonatal diabetes mellitus in about 50% of patients diagnosed with diabetes before 6 months of age and in a small fraction of those diagnosed between 6 and 12 months. The aim of this study was to identify the genetic cause of diabetes in 77 consecutive patients referred to the University of Chicago with diabetes diagnosed before 1 yr of age. Methods: We used Oragene™ DNA Self-Collection kit to obtain a saliva sample for DNA. We sequenced the protein-coding regions of KCNJ11, ABCC8, and INS using standard methods. Results: We enrolled 32 patients diagnosed with diabetes before 6 months of age and 45 patients diagnosed between 6 and 12 months. We identified a mutation in KCNJ11 in 14 patients from 12 families and in INS in 7 patients from 4 families. Three of the patients with an INS mutation were diagnosed with diabetes between 6 and 12 months of age. Finally, we found that two patients had an abnormality of chromosome 6q24 associated with transient neonatal diabetes mellitus. Conclusions: We were able to establish a genetic cause of diabetes in 63% of patients diagnosed with diabetes before 6 months of age and in 7% of patients diagnosed between 6 and 12 months. Genetic testing, which is critical for guiding appropriate management, should be considered in patients diagnosed with diabetes before 1 yr of age, especially if they are autoantibody negative, although the presence of autoantibodies does not rule out a monogenic cause. [ABSTRACT FROM AUTHOR]

OBJECTIVE--Mutations in the insulin (INS) gene can cause neonatal diabetes. We hypothesized that mutations in INS could also cause maturity-onset diabetes of the young (MODY) and autoantibody-negative type 1 diabetes. RESEARCH DESIGN AND METHODS--We screened INS in 62 probands with MODY, 30 probands with suspected MODY, and 223 subjects from the Norwegian Childhood Diabetes Registry selected on the basis of autoantibody negativity or family history of diabetes. RESULTS--Among the MODY patients, we identified the INS mutation c.137G>A (R46Q) in a proband, his diabetic father, and a paternal aunt. They were diagnosed with diabetes at 20, 18, and 17 years of age, respectively, and are treated with small doses of insulin or diet only. In type 1 diabetic patients, we found the INS mutation c.163C>T (R55C) in a girl who at 10 years of age presented with ketoacidosis and insulin-dependent, GAD, and insulinoma-associated antigen-2 (IA-2) antibody-negative diabetes. Her mother had a de novo R55C mutation and was diagnosed with ketoacidosis and insulin-dependent diabetes at 13 years of age. Both had residual β-cell function. The R46Q substitution changes an invariant arginine residue in position B22, which forms a hydrogen bond with the glutamate at A17, stabilizing the insulin molecule. The R55C substitution involves the first of the two arginine residues localized at the site of proteolytic processing between the B-chain and the C-peptide. CONCLUSIONS--Our findings extend the phenotype of INS mutation carriers and suggest that INS screening is warranted not only in neonatal diabetes, but also in MODY and in selected cases of type 1 diabetes. [ABSTRACT FROM AUTHOR]

OBJECTIVE--Insulin gene (INS) mutations have recently been described as a cause of permanent neonatal diabetes (PND). We aimed to determine the prevalence, genetics, and clinical phenotype of INS mutations in large cohorts of patients with neonatal diabetes and permanent diabetes diagnosed in infancy, childhood, or adulthood. RESEARCH DESIGN AND METHODS--The INS gene was sequenced in 285 patients with diabetes diagnosed before 2 years of age, 296 probands with maturity-onset diabetes of the young (MODY), and 463 patients with young-onset type 2 diabetes (nonobese, diagnosed <45 years). None had a molecular genetic diagnosis of monogenic diabetes. RESULTS--We identified heterozygous INS mutations in 33 of 141 probands diagnosed at <6 months, 2 of 86 between 6 and 12 months, and none of 58 between 12 and 24 months of age. Three known mutations (A24D, F48C, and R89C) account for 46% of cases. There were six novel mutations: H29D, L35P, G84R, C96S, S101C, and Y103C. INS mutation carriers were all insulin treated from diagnosis and were diagnosed later than ATP-sensitive K+ channel mutation carriers (11 vs. 8 weeks, P < 0.01). In 279 patients with PND, the frequency of KCNJ11, ABCC8, and INS gene mutations was 31, 10, and 12%, respectively. A heterozygous R6C mutation cosegregated with diabetes in a MODY family and is probably pathogenic, but the L68M substitution identified in a patient with young-onset type 2 diabetes may be a rare nonfunctional variant. CONCLUSIONS--We conclude that INS mutations are the second most common cause of PND and a rare cause of MODY. Insulin gene mutation screening is recommended for all diabetic patients diagnosed before 1 year of age. [ABSTRACT FROM AUTHOR]