Model for Integration of Monogenic Diabetes Diagnosis Into Routine Care: The Personalized Diabetes Medicine Program.

Objective: To implement, disseminate, and evaluate a sustainable method for identifying, diagnosing, and promoting individualized therapy for monogenic diabetes.

Research Design And Methods: Patients were recruited into the implementation study through a screening questionnaire completed in the waiting room or through the patient portal, physician recognition, or self-referral. Patients suspected of having monogenic diabetes based on the processing of their questionnaire and other data through an algorithm underwent next-generation sequencing for 40 genes implicated in monogenic diabetes and related conditions.

Monogenic Diabetes in Youth With Presumed Type 2 Diabetes: Results From the Progress in Diabetes Genetics in Youth (ProDiGY) Collaboration.

Objective: Maturity-onset diabetes of the young (MODY) is frequently misdiagnosed as type 1 or type 2 diabetes. Correct diagnosis may result in a change in clinical treatment and impacts prediction of complications and familial risk. In this study, we aimed to assess the prevalence of MODY in multiethnic youth under age 20 years with a clinical diagnosis of type 2 diabetes.

Monogenic diabetes in overweight and obese youth diagnosed with type 2 diabetes: the TODAY clinical trial.

PurposeMonogenic diabetes accounts for 1-2% of diabetes cases. It is often undiagnosed, which may lead to inappropriate treatment. This study was performed to estimate the prevalence of monogenic diabetes in a cohort of overweight/obese adolescents diagnosed with type 2 diabetes (T2D).

The Genetic Architecture of Diabetes in Pregnancy: Implications for Clinical Practice.

The genetic architecture of diabetes mellitus in general and in pregnancy is complex, owing to the multiple types of diabetes that comprise both complex/polygenic forms and monogenic (largely caused by a mutation in a single gene) forms such as maturity-onset diabetes of the young (MODY). Type 1 diabetes (T1D) and type 2 diabetes (T2D) have complex genetic etiologies, with over 40 and 90 genes/loci, respectively, implicated that interact with environmental/lifestyle factors. The genetic etiology of gestational diabetes mellitus has largely been found to overlap that of T2D.

Undiagnosed MODY: Time for Action.

Maturity-onset diabetes of the young (MODY) is a monogenic form of diabetes that accounts for at least 1 % of all cases of diabetes mellitus. MODY classically presents as non-insulin-requiring diabetes in lean individuals typically younger than 25 with evidence of autosomal dominant inheritance, but these criteria do not capture all cases and can also overlap with other diabetes types. Genetic diagnosis of MODY is important for selecting the right treatment, yet ~95 % of MODY cases in the USA are misdiagnosed.

Augmented Stat5 Signaling Bypasses Multiple Impediments to Lactogen-Mediated Proliferation in Human β-Cells.

Pregnancy in rodents is associated with a two- to threefold increase in β-cell mass, which is attributable to large increases in β-cell proliferation, complimented by increases in β-cell size, survival, and function and mediated mainly by the lactogenic hormones prolactin (PRL) and placental lactogens. In humans, however, β-cell mass does not increase as dramatically during pregnancy, and PRL fails to activate proliferation in human islets in vitro. To determine why, we explored the human PRL-prolactin receptor (hPRLR)-Janus kinase 2 (JAK2)-signal transducer and activator of transcription 5 (STAT5)-cyclin-cdk signaling cascade in human β-cells.

Personalized medicine in diabetes mellitus: current opportunities and future prospects.

Diabetes mellitus affects approximately 382 million individuals worldwide and is a leading cause of morbidity and mortality. Over 40 and nearly 80 genetic loci influencing susceptibility to type 1 and type 2 diabetes, respectively, have been identified. In addition, there is emerging evidence that some genetic variants help to predict response to treatment.

Cytoplasmic-nuclear trafficking of G1/S cell cycle molecules and adult human β-cell replication: a revised model of human β-cell G1/S control.

Harnessing control of human β-cell proliferation has proven frustratingly difficult. Most G1/S control molecules, generally presumed to be nuclear proteins in the human β-cell, are in fact constrained to the cytoplasm. Here, we asked whether G1/S molecules might traffic into and out of the cytoplasmic compartment in association with activation of cell cycle progression.

Human pancreatic β-cell G1/S molecule cell cycle atlas.

Expansion of pancreatic β-cells is a key goal of diabetes research, yet induction of adult human β-cell replication has proven frustratingly difficult. In part, this reflects a lack of understanding of cell cycle control in the human β-cell. Here, we provide a comprehensive immunocytochemical "atlas" of G1/S control molecules in the human β-cell.

cMyc is a principal upstream driver of beta-cell proliferation in rat insulinoma cell lines and is an effective mediator of human beta-cell replication.

Adult human β-cells replicate slowly. Also, despite the abundance of rodent β-cell lines, there are no human β-cell lines for diabetes research or therapy. Prior studies in four commonly studied rodent β-cell lines revealed that all four lines displayed an unusual, but strongly reproducible, cell cycle signature: an increase in seven G(1)/S molecules, i.