The study to understand the genetics of the acute response to metformin and glipizide in humans (SUGAR-MGH): design of a pharmacogenetic resource for type 2 diabetes.

Objective: Genome-wide association studies have uncovered a large number of genetic variants associated with type 2 diabetes or related phenotypes. In many cases the causal gene or polymorphism has not been identified, and its impact on response to anti-hyperglycemic medications is unknown. The Study to Understand the Genetics of the Acute Response to Metformin and Glipizide in Humans (SUGAR-MGH, NCT01762046) is a novel resource of genetic and biochemical data following glipizide and metformin administration.

The association of ENPP1 K121Q with diabetes incidence is abolished by lifestyle modification in the diabetes prevention program.

Context: Insulin resistance is an important feature of type 2 diabetes. Ectoenzyme nucleotide pyrophosphatase phosphodiesterase 1 (ENPP1) inhibits insulin signaling, and a recent meta-analysis reported a nominal association between the Q allele in the K121Q (rs1044498) single nucleotide polymorphism in its gene ENPP1 and type 2 diabetes. OBJECTIVE AND INTERVENTION: We examined the impact of this polymorphism on diabetes incidence as well as insulin secretion and sensitivity at baseline and after treatment with a lifestyle intervention or metformin vs.

An unusual case of primary hyperparathyroidism with profoundly elevated parathyroid hormone levels.

Objective: To report the case of a man who presented with profoundly elevated parathyroid hormone levels in the setting of hypercalcemia, a palpable neck mass, renal disease, and metabolic bone disease.

Methods: We describe the clinical, imaging, and laboratory findings of the patient, including results from genetic testing of the CDC73 gene (HRPT2), and review the relevant literature.

Results: A 28-year-old man with a history of childhood abdominal neuroblastoma treated with chemotherapy and field radiation therapy presented with a 2-week history of persistent left scapular pain and swelling.

Extension of type 2 diabetes genome-wide association scan results in the diabetes prevention program.

Objective: Genome-wide association scans (GWASs) have identified novel diabetes-associated genes. We evaluated how these variants impact diabetes incidence, quantitative glycemic traits, and response to preventive interventions in 3,548 subjects at high risk of type 2 diabetes enrolled in the Diabetes Prevention Program (DPP), which examined the effects of lifestyle intervention, metformin, and troglitazone versus placebo.

Research Design And Methods: We genotyped selected single nucleotide polymorphisms (SNPs) in or near diabetes-associated loci, including EXT2, CDKAL1, CDKN2A/B, IGF2BP2, HHEX, LOC387761, and SLC30A8 in DPP participants and performed Cox regression analyses using genotype, intervention, and their interactions as predictors of diabetes incidence.

Genetic susceptibility to type 2 diabetes and implications for antidiabetic therapy.

Despite major advances in our knowledge of glycemic pathophysiology and the availability of multiple therapeutic options to confront type 2 diabetes, unraveling the complex link between genetic risk and environmental factors in this burgeoning epidemic has proven difficult. Linkage approaches have clarified the etiology of monogenic diabetic syndromes and congenital lipodystrophies, and candidate gene association studies have identified a number of common variants implicated in type 2 diabetes. This year we have witnessed the advent of genome-wide association scanning: As many as nine genetic loci have now been reproducibly associated with type 2 diabetes in five genome-wide scans.

Sunitinib (sutent)-induced thyrotoxicosis due to destructive thyroiditis: a case report.

Numerous drugs have been associated with destructive thyroiditis (subacute thyroiditis). Sunitinib, a tyrosine kinase inhibitor employed in renal cell carcinoma and gastrointestinal stromal tumors, has recently been linked to destructive thyroiditis with resultant hypothyroidism. We report a patient with transient overt thyrotoxicosis followed by hypothyroidism, apparently related to sunitinib therapy.