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Activating mutations in the gene encoding the ATP-sensitive potassium-channel subunit Kir6.2 and permanent neonatal diabetes.
TLDR
Heterozygous activating mutations in the gene encoding Kir6.2 cause permanent neonatal diabetes and may also be associated with developmental delay, muscle weakness, and epilepsy, and Identification of the genetic cause of permanent newborn diabetes may facilitate the treatment of this disease with sulfonylureas.
Switching from insulin to oral sulfonylureas in patients with diabetes due to Kir6.2 mutations.
TLDR
Sulfonylurea therapy is safe in the short term for patients with diabetes caused by KCNJ11 mutations and is probably more effective than insulin therapy, and may result from the closing of mutant K(ATP) channels, thereby increasing insulin secretion in response to incretins and glucose metabolism.
ISPAD Clinical Practice Consensus Guidelines 2018: The diagnosis and management of monogenic diabetes in children and adolescents
TLDR
Well over 40 different genetic subtypes of monogenic diabetes have been identified to date, each having a typical phenotype and a specific pattern of inheritance.
The genetic architecture of type 2 diabetes
TLDR
Large-scale sequencing does not support the idea that lower-frequency variants have a major role in predisposition to type 2 diabetes, but most fell within regions previously identified by genome-wide association studies.
Physical Activity Attenuates the Influence of FTO Variants on Obesity Risk: A Meta-Analysis of 218,166 Adults and 19,268 Children
TLDR
A fairly substantial attenuation by physical activity on the effects of this genetic variant on the risk of obesity in adults is reported.
Loss-of-function mutations in SLC30A8 protect against type 2 diabetes
TLDR
Loss-of-function mutations in humans provide strong evidence that SLC30A8 haploinsufficiency protects against type 2 diabetes, suggesting ZnT8 inhibition as a therapeutic strategy in T2D prevention.
Long-range gene regulation links genomic type 2 diabetes and obesity risk regions to HHEX, SOX4, and IRX3
TLDR
It is reported that human highly conserved noncoding elements in LD with the risk SNPs drive expression in endoderm or pancreas in transgenic mice and zebrafish, suggesting a direct link of pancreatic IRX3 function to both obesity and type 2 diabetes.
Permanent neonatal diabetes due to mutations in KCNJ11 encoding Kir6.2: patient characteristics and initial response to sulfonylurea therapy.
TLDR
Apparently insulin-dependent patients with mutations in Kir6.2 may be managed on an oral sulfonylurea with sustained metabolic control rather than insulin injections, illustrating the principle of pharmacogenetics applied in diabetes treatment.
A novel syndrome of diabetes mellitus, renal dysfunction and genital malformation associated with a partial deletion of the pseudo-POU domain of hepatocyte nuclear factor-1beta.
TLDR
Functional studies strongly suggest that heterozygous mutations in the HNF-1beta gene are associated with a syndrome characterized by MODY and severe, non-diabetic renal disease and the presence of internal genital malformations in two females suggests that additional clinical features may be associated with H NF-1 beta mutations.
Mutations in the CEL VNTR cause a syndrome of diabetes and pancreatic exocrine dysfunction
TLDR
Findings link diabetes to the disrupted function of a lipase in the pancreatic acinar cells and some evidence for an association between common insertions in the CEL VNTR and exocrine dysfunction is found in a group of 182 unrelated subjects with diabetes.
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