OBJECTIVE: To determine the rate of adherence to postpartum glycemic testing in women with gestational diabetes mellitus (GDM) and the performance of fasting plasma glucose (FPG) versus the 75-g oral glucose tolerance test (OGTT) in detecting postpartum glucose intolerance. RESEARCH DESIGN AND METHODS: The study was a retrospective cohort of 1,006 women with GDM attending a pregnancy diabetes clinic. RESULTS: Postpartum screening was completed in 438 (48%) women. Women nonadherent to testing had higher parity (1.10 vs. 0.87) and were less likely to require insulin for management of their GDM. Among women who were tested, 89 (21%) had an abnormal result, only 25 (28%) of whom were identified by FPG. Factors associated with abnormal postpartum diabetes screening include non-Caucasian ethnicity, previous GDM, higher A1C, and OGTT values during pregnancy and treatment with insulin. CONCLUSIONS: The rate of postpartum diabetes screening is low, and FPG lacks sensitivity as a screening test in comparison with OGTT.
31 December 1989 in Progress in Biophysics and Molecular Biology
When depression accompanies diabetes, it complicates treatment, portends worse outcomes and increases health care costs. A collaborative care case-management model, previously tested in an urban managed care organization in the US, achieved significant reduction of depressive symptoms, improved diabetes disease control and patient-reported outcomes, and saved money. While impressive, these findings need to be replicated and extended to other healthcare settings. Our objective is to comprehensively evaluate a collaborative care model for comorbid depression and type 2 diabetes within a Canadian primary care setting.
In this study, we investigated the mechanisms through which norepinephrine (NE) regulates MAPK phosphatase-1 (MKP-1) expression in rat pinealocytes. Stimulation with NE (a mixed - and-adrenergic agonist) caused a rapid increase inMKP-1 mRNA and protein that peaked around 1 h post stimulation, and the response was sustained for at least 4 h. Selective activationof-adrenergicreceptorswithisoproterenolfor1h caused a similar increase in MKP-1 mRNA and protein as ob- served with NE, but at 3 h, the isoproterenol response was much lower relative to NE. In contrast, selective activation of -adrenergic receptors caused only small increases in MKP-1 mRNA and protein and appeared to function primarily in prolonging the -adrenergic-stimulated responses. In NE- stimulated pinealocytes, blockade of -adrenergic receptors causedarapidreductioninMKP-1mRNA,butithadaminimal effect on MKP-1 protein. In contrast, blockade of-adrenergic receptors specifically reduced NE-induced MKP-1 protein but notmRNA.Atthepostreceptorlevel,treatmentwithdibutyryl cAMP caused parallel increases in MKP-1 mRNA and protein. However, treatment with a protein kinase C activator caused a significant increase in MKP-1 protein but had little effect on MKP-1 mRNA. Together, these results suggest that, in rat pi- nealocytes, NE activates the -adrenergic receptor 3 protein kinase A pathway to induce transcription and translation of MKP-1 expression and the -adrenergic receptor 3 protein kinase C pathway to prolong the stimulated responses through increased stability of the MKP-1 protein. (Endocri- nology 145: 5723-5733, 2004)
The papillary subtype of craniopharyngioma (CP) rarely occurs in children and commonly presents as a suprasellar lesion. Patients with papillary CPs frequently harbor the BRAF-V600E mutation, and treatment with a BRAF inhibitor results in tumor shrinkage in several patients. Herein, we report a patient with childhood-onset papillary CP treated with vemurafenib for 40 months after multiple surgeries. At age 10, he presented with growth failure secondary to an intrasellar cystic lesion. He had 3 transsphenoidal surgeries before age 12 and a 4th surgery 25 years later for massive tumor recurrence. Pathology showed a papillary CP with positive BRAF-V600E mutation. Rapid tumor regrowth 4 months after surgery led to treatment with vemurafenib that resulted in tumor reduction within 6 weeks. Gradual tumor regrowth occurred after a dose reduction of vemurafenib because of elevated liver enzymes. He had further surgeries and within 7 weeks after stopping vemurafenib, there was massive tumor recurrence. He resumed treatment with vemurafenib before radiation therapy and similar tumor shrinkage occurred within 16 days. In this patient with childhood-onset papillary CP that was refractory to multiple surgeries, the use of vemurafenib resulted in significant tumor shrinkage that allowed for the completion of radiation therapy and tumor control.
The risk and mortality due to cancer in patients with acromegaly have been previously investigated. Although GH/IGF-1 excess provides a probable pathophysiological explanation, the degree of IGF-1 excess and the role in acromegaly-associated neoplasms of diabetes, a common comorbidity in acromegaly with known association with cancer, remains unclear. Acromegalic patients treated in three Canadian referral centers (Toronto, Montreal, Edmonton) were included. All available clinical information was recorded including: age, initial and last percentage of the upper limit of normal (%ULN) IGF-1 levels, comorbidities and other neoplasms (benign and malignant). 408 cases were assessed. 185 were women (45.3%), 126 (30.9%) developed extra-pituitary neoplasms: 55 malignant and 71 benign. The most frequent anatomic site was the gastrointestinal tract (46 [11.3%]), followed by head and neck (36 [8.8%]) and multiple locations (14 [3.4%]). 106 (26.0%) cases had diabetes. Initial IGF-1 was significantly higher in men older than 50 (380.15 vs. 284.78, p = 0.001) when compared to men younger than 50. Diabetics showed significantly higher initial IGF-1 (389.38 vs. 285.27, p = 0.009), as did diabetics older than 50 compared with those without diabetes. 45.3% (48/106) of cases with diabetes developed extra-pituitary neoplasms vs. 24.3% (71/292) without diabetes (p = 0.001, OR: 2.576 95%CI 1.615–4.108). 22.6% (24/106) of cases with diabetes developed malignant tumors vs. 9.2% (27/292), (p < 0.001, OR 2.873, 95%CI 1.572–5.250). These data suggest that acromegalic patients with diabetes are more likely to develop extra-pituitary neoplasms and their initial IGF-1 levels are higher. The contribution of IGF-1 vs. diabetes alone or in combination in the development of extra-pituitary neoplasms warrants further investigation.