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Kurt J Griffin

Publications and source records attributed to Kurt J Griffin.

2 recordsLinked to original sources
PubMed2026

International consensus guidance for general population screening for islet autoantibodies to diagnose early-stage type 1 diabetes: a nominal group technique process.

Type 1 diabetes is an autoimmune disease that targets and destroys insulin-producing beta cells in the pancreatic islets. The incidence of type 1 diabetes is rising globally. At the clinical diagnosis of type 1 diabetes, between 20% and 67% of children and adolescents present with diabetic ketoacidosis (DKA) requiring hospitalisation, and one-third of these require intensive care. Type 1 diabetes can be detected in early stages, prior to the insulin-requiring clinical diagnosis, through screening for islet autoantibodies (IAbs). Identifying individuals with early-stage type 1 diabetes, combined with monitoring of and education on disease progression, prevents DKA and results in a milder clinical onset. This allows for timely insulin initiation in outpatient settings and improved long-term glucose management. Early diagnosis also enables access to novel disease-modifying therapies that can delay the clinical onset of diabetes. In this international consensus, we provide guidance on the principles and practice of implementing general population screening for IAbs to diagnose early-stage type 1 diabetes. We also outline the minimum requirements for establishing effective population screening programmes to diagnose early-stage type 1 diabetes through IAb detection. This consensus statement has been endorsed by the following professional associations: Advanced Technologies & Treatments for Diabetes (ATTD); Association of Diabetes Care and Education Specialists (ADCES); Association Belge Du Diabète; Associazione Medici Diabetologi (AMD); Australian Diabetes Society (ADS); Belgian Diabetes Liga; Breakthrough T1D; Czech Diabetes Society (ČDS); EASD; Finnish Diabetes Association (FDS); Fondazione Italiana Diabete (FID); International Diabetes Federation (IDF)-Europe; International Society of Paediatric and Adolescent Diabetes (ISPAD); Paediatric Endocrinology Nursing Society (PENS); Polish Diabetes Society; Portuguese Diabetes Association (APDP); Sociedade Portuguesa de Diabetologia (SPD); Società Italiana di Diabetologia (SID); Société Francophone du Diabète (SFD) and Type 1 Diabetes Exchange (T1D Exchange).

Consensus report↗
PubMed2010

Mouse Prkar1a haploinsufficiency leads to an increase in tumors in the Trp53+/- or Rb1+/- backgrounds and chemically induced skin papillomas by dysregulation of the cell cycle and Wnt signaling.

PRKAR1A inactivation leads to dysregulated cAMP signaling and Carney complex (CNC) in humans, a syndrome associated with skin, endocrine and other tumors. The CNC phenotype is not easily explained by the ubiquitous cAMP signaling defect; furthermore, Prkar1a(+/-) mice did not develop skin and other CNC tumors. To identify whether a Prkar1a defect is truly a generic but weak tumorigenic signal that depends on tissue-specific or other factors, we investigated Prkar1a(+/-) mice when bred within the Rb1(+/-) or Trp53(+/-) backgrounds, or treated with a two-step skin carcinogenesis protocol. Prkar1a(+/-) Trp53(+/-) mice developed more sarcomas than Trp53(+/-) mice (P < 0.05) and Prkar1a(+/-) Rb1(+/-) mice grew more (and larger) pituitary and thyroid tumors than Rb1(+/-) mice. All mice with double heterozygosity had significantly reduced life-spans compared with their single-heterozygous counterparts. Prkar1a(+/-) mice also developed more papillomas than wild-type animals. A whole-genome transcriptome profiling of tumors produced by all three models identified Wnt signaling as the main pathway activated by abnormal cAMP signaling, along with cell cycle abnormalities; all changes were confirmed by qRT-PCR array and immunohistochemistry. siRNA down-regulation of Ctnnb1, E2f1 or Cdk4 inhibited proliferation of human adrenal cells bearing a PRKAR1A-inactivating mutation and Prkar1a(+/-) mouse embryonic fibroblasts and arrested both cell lines at the G0/G1 phase of the cell cycle. In conclusion, Prkar1a haploinsufficiency is a relatively weak tumorigenic signal that can act synergistically with other tumor suppressor gene defects or chemicals to induce tumors, mostly through Wnt-signaling activation and cell cycle dysregulation, consistent with studies in human neoplasms carrying PRKAR1A defects.

Animals↗