Review on monogenic diabetes

Department of Pathology, Immunology, and Laboratory Medicine, University of Florida, Gainesville, Florida, United States
Current opinion in endocrinology, diabetes, and obesity (Impact Factor: 3.37). 08/2011; 18(4):252-8. DOI: 10.1097/MED.0b013e3283488275
Source: PubMed


The goal of this review is to provide an update on the different forms of monogenic diabetes, including maturity-onset diabetes of the young (MODY) and neonatal diabetes (permanent and transient neonatal diabetes).
Monogenic diabetes accounts for approximately 1-2% of diabetes cases and results from mutations that primarily reduce β-cell function. Individuals with islet autoantibody negative youth-onset forms of diabetes should be evaluated for either glucokinase-MODY or transcription factors MODY. The mild-fasting hyperglycemia found in glucokinase-MODY typically does not necessitate pharmacological treatment, whereas patients with MODY caused by transcription factor mutations can often be successfully treated with low-dose sulfonylurea. Neonatal diabetes is defined as diabetes onset within the first 6 months of life and most individuals with permanent neonatal diabetes can be treated with high-dose sulfonylurea.
The discovery of the genetic cause of monogenic diabetes has greatly advanced our understanding and management of these uncommon forms of diabetes.

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    • "MODY probands display a positive family history of hyperglycemia with autosomal dominant mode of inheritance, age at diagnosis typically before 25 years and disrupted pancreatic beta cell function (OMIM #606391, Since 1992, mutations in 13 genes causing MODY have been reported [1] [2]. Correct genetic diagnosis has implications for the treatment and prognosis of patients. "
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    ABSTRACT: We report the first results from whole-exome sequencing performed in families with Maturity-Onset Diabetes of the Young without a known genetic cause of diabetes (MODYX). This next generation sequencing technique pointed out that routine testing of MODY needs constant awareness and regular re-evaluation of both clinical criteria and primer sequences.
    No preview · Article · Jun 2014 · Diabetes research and clinical practice
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    • "Among children and adolescents, the major cause of IGT is unknown, while the major cause of diabetes remains isolated defects in insulin production as seen following auto-immune beta cell destruction in T1DM, with a prevalence of 0.23% among adolescents compared to a prevalence of 0.042% for T2DM in this age range [21]. Limitations in insulin release are also seen in monogenic forms of diabetes such as the group of genes comprising MODY, also with a low overall prevalence at approximately 1% of pediatric diabetes cases [42,43]. Whereas insulin resistance and MetS are more prevalent in overweight/obese children and adolescents [44] (contributing to an improved sensitivity of MetS for IGT identification among overweight/obese adolescents, Table 2), primary defects in insulin release such as T1DM and MODY would be expected to be present across the weight spectrum in childhood. "
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    ABSTRACT: The presence of impaired glucose tolerance (IGT) and metabolic syndrome (MetS) are two risk factors for Type 2 diabetes. The inter-relatedness of these factors among adolescents is unclear. We evaluated the sensitivity and specificity of MetS for identifying IGT in an unselected group of adolescents undergoing oral glucose tolerance tests (OGTT) in the National Health and Nutrition Evaluation Survey 1999-2010. We characterized IGT as a 2-hour glucose >=140 mg/dL and MetS using ATP-III-based criteria and a continuous sex- and race/ethnicity-specific MetS Z-score at cut-offs of +1.0 and +0.75 standard deviations (SD) above the mean. Among 1513 adolescents, IGT was present in 4.8 %, while ATP-III-MetS was present in 7.9 %. MetS performed poorly in identifying adolescents with IGT with a sensitivity/specificity of 23.7 %/92.9 % for ATP-III-MetS, 23.6 %/90.8 % for the MetS Z-score at +1.0 SD and 35.8 %/85.0 for the MetS Z-score at +0.75 SD. Sensitivity was higher (and specificity lower) but was still overall poor among overweight/obese adolescents: 44.7 %/83.0 % for ATP-III-MetS, 43.1 %/77.1 % for the MetS Z-score at +1.0 SD and 64.3 %/64.3 % for MetS Z-score at +0.75 SD. This lack of overlap between MetS and IGT may indicate that assessment of MetS is not likely to be a good indicator of which adolescents to screen using OGTT. These data further underscore the importance of other potential contributors to IGT, including Type 1 diabetes and genetic causes of poor beta-cell function. Practitioners should keep these potential causes of IGT in mind, even when evaluating obese adolescents with IGT.
    Full-text · Article · Apr 2014 · Cardiovascular Diabetology
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