Socioeconomic Status and Care Metrics for Women Diagnosed With Gestational Diabetes Mellitus.

IN BRIEF Appropriate management of hyperglycemia can significantly attenuate perinatal risks associated with a diagnosis of gestational diabetes mellitus (GDM). This article reports on a study evaluating the independent associations of maternal income and education with select measures of GDM management. This exploratory study demonstrates notable socioeconomic differences in select measures of GDM management. Additional studies are needed to determine the reasons for these differences and whether they exist in broader populations.

Predicting posttransplantation diabetes mellitus by regulatory T-cell phenotype: implications for metabolic intervention to modulate alloreactivity.

Chronic inflammation and decreased frequency of regulatory T cells (Tregs) in visceral adipose tissue contribute to the propagation of insulin resistance to diabetes mellitus. We tested the hypothesis that new-onset posttransplantation diabetes mellitus (PTDM) is associated with measurable changes in Treg subsets after allogeneic hematopoietic stem cell transplantation (HSCT). PTDM before day 100 and Treg phenotype at engraftment were determined in 36 HSCT recipients without preceding history of diabetes mellitus. Among patients with new-onset PTDM (N = 24), the frequency of circulating CLA(+) (skin-homing) Tregs was decreased (1.53% vs 3.99%; P = .002) and the percentage of α(4)ß(7)(+) (gut-homing) Tregs was increased (17.9% vs 10.7%; P = .048). In multivariate analysis, patients with PTDM continued to demonstrate elevated ratios of α(4)ß(7)(+) Tregs to CLA(+) Tregs (odds ratio, 18.1; P = .020). PTDM is associated with altered immune regulation after HSCT and could represent a target to modulate alloreactivity.

Inpatient management of women with gestational and pregestational diabetes in pregnancy.

For women with type 1 diabetes (T1DM), type 2 diabetes (T2DM), and gestational diabetes (GDM), poor maternal glycemic control can significantly increase maternal and fetal risk for adverse outcomes. Outpatient medical and nutrition therapy is recommended for all women with diabetes in order to facilitate euglycemia during the antepartum period. Despite intensive outpatient therapy, women with diabetes often require inpatient diabetes management prior to delivery as maternal hyperglycemia can significantly increase neonatal risk of hypoglycemia. Consensus guidelines recommend maternal glucose range of 80-110 mg/dL in labor. The most optimal inpatient strategies for the prevention of hyperglycemia and hypoglycemia proximate to delivery remain unclear and will depend upon factors such as maternal diabetes diagnosis, her baseline insulin resistance, duration and route of delivery etc. Low dose intravenous insulin and dextrose protocols are necessary to achieve optimal predelivery glycemic control for women with T1DM and T2DM. For most with GDM however, euglycemia can be maintained without intravenous insulin. Women treated with a subcutaneous insulin pump during the antepartum period represent a unique challenge to labor and delivery staff. Strategies for self-managed subcutaneous insulin infusion (CSII) use prior to delivery require intensive education and coordination of care with the labor team in order to maintain patient safety. Hospitalization is recommended for most women with diabetes prior to delivery and in the postpartum period despite appropriate outpatient glycemic control. Women with poorly controlled diabetes in any trimester have an increased baseline maternal and fetal risk for adverse outcomes. Common indications for antepartum hospitalization of these women include failed outpatient therapy and/or diabetic ketoacidosis (DKA). Inpatient management of DKA is a significant cause of maternal and fetal morbidity and remains a common indication for hospitalization of the pregnant woman with diabetes. Changes in maternal physiology increase insulin resistance and the risk for DKA. A systematic approach to its management will be reviewed.

Disparities in postpartum follow-up in women with gestational diabetes mellitus.

In Brief Postpartum follow-up for patients with gestational diabetes mellitus (GDM) is essential to manage future disease risk. In a diverse, urban population of GDM patients at a major medical center, high fasting glucose, high BMI at diagnosis, and low education level were associated with not following up in the endocrinology clinic after delivery; patients least likely to follow up are, therefore, also at greatest risk of GDM complications. Although race/ethnicity was not a significant predictor of follow-up, Hispanic/Latina and African-American patients were more likely to have risk factors for postpartum clinical attrition.

How I treat late effects in adults after allogeneic stem cell transplantation.

More than 25,000 allogeneic hematopoietic stem cell transplantations (allo-HCTs) are expected to be performed worldwide in 2010, a number that has been increasing yearly. With broadening indications, more options for allo-HCT, and improvement in survival, by 2020 there may be up to half a million long-term survivors after allo-HCT worldwide. These patients have increased risks for various late complications, which can cause morbidity and mortality. Most long-term survivors return to the care of their local hematologists/oncologists or primary care physicians, who may not be familiar with specialized monitoring recommendations for this patient population. The purpose of this article is to describe practical approaches to screening for and managing these late effects, with the goal of reducing preventable morbidity and mortality associated with allo-HCT.

Pretransplantation C-Peptide level predicts early posttransplantation diabetes mellitus and has an impact on survival after allogeneic stem cell transplantation.

Posttransplantation diabetes mellitus (PTDM) is a frequent complication after allogeneic stem cell transplantation (allo-SCT), important for its negative impact on cardiovascular health. Risk factors for PTDM are not well defined. We conducted a prospective study to investigate the risk factors and incidence for PTDM in the first 100 days after allo-SCT. A total of 84 patients completed the study, 60% of whom developed PTDM. In a multivariate logistic regression model, pretransplantation c-peptide level (>3.6 ng/mL; odds ratio [OR], 5.9; 95% confidence interval [CI], 1.77-20.22; P = .004), unrelated donor allo-SCT (OR, 4.3; 95% CI, 1.34-14.2; P = .014), and peak steroid dose >1 mg/kg/day (OR, 5.09; 95% CI, 1.19-23.2; P = .035) were identified as independent predictors of PTDM. In addition, overall survival (OS) was inferior in patients with PTDM compared with those without PTDM (mean survival, 2.26 years vs 2.7 years; P = .021). Pretransplantation c-peptide level greater than the cohort median (>3.6 ng/mL) also was associated with inferior OS (mean, 1.7 years vs 2.9 years; P = .012). In a multivariate Cox proportional hazards model, high-risk disease (hazard ratio [HR], 2.34; 95% CI, 1.09-5.28; P = .029) and pretransplantation c-peptide level >3.6 ng/mL (HR, 1.05; 95% CI, 1.01-1.09; P = .013) were independent predictors of OS when adjusted for systemic steroids and regimen intensity. We suspect that diabetes mellitus in the immediate posttransplantation period may be mediated via an inflammatory pathway that contributes to insulin resistance in the host adipose tissue. Our study is the first to report the risk factors of early PTDM in patients undergoing allo-SCT and identifies pretransplantation c-peptide as an independent predictor of diabetes and survival.

Thyroid abnormalities in patients treated with lenalidomide for hematological malignancies: results of a retrospective case review.

Lenalidomide is an antiangiogenic drug associated with hypothyroidism. We describe a case-series of lenalidomide use in hematological cancers and the prevalence of thyroid abnormalities. We reviewed medical records of patients treated with lenalidomide at a single center form 2005 to 2010 and extracted demographic, clinical, and laboratory data. Of 170 patients with confirmed lenalidomide use (age 64.9 ± 15 years), 148 were treated for multiple myeloma and 6% had thyroid abnormalities attributable only to lenalidomide. In patients with a previous diagnosis of thyroid dysfunction, the addition of lenalidomide therapy was associated with a higher incidence of subsequent TFTF abnormality (17%) as compared to patients with no previous diagnosis of thyroid dysfunction (6%) (P=0.0001). Many patients (44%) with pre-existing disease and a change in thyroid function before or while on lenalidomide had no further follow-up of their thyroid abnormalities, Of 20 patients who did not undergo any thyroid function testing either before starting or while on lenalidomide for a median of 9.4 months (± 6.5), 35% developed new symptoms compatible with hypothyroidism, including worsened fating, constipation or cold intolerance. Symptoms of thyroid dysfunction overlap with side effects of lenalidomide. Thyroid hormone levels are not regularly evaluated in patients on lenalidomide. While on this treatment, thyroid abnormalities can occur in patients with no previous diagnoses and in patients with pre-existing abnormalities. Because symptoms of thyroid dysfunction could be alleviated by appropriate treatment, thyroid function should be evaluated during the course of lenalidomide to improve patients quality of life.

Diagnostic and therapeutic dilemmas of hypercortisolemia during pregnancy: a case report.

Pregnancy and Cushing's syndrome rarely coexist. When they do, it is generally the result of the presence of an adrenal adenoma. Because of significantly increased morbidity and mortality in both the mother and fetus when hypercortisolism is present, it is imperative that it be treated when recognized. This treatment can take the form of definitive surgical treatment or temporary medical treatment until after delivery, both of which carry risks and benefits. Complicating the evaluation, however, it is well known that pregnancy itself can induce many of the symptoms and laboratory abnormalities associated with hypercortisolism. We present the case of a 35-year-old woman who was noted to have an adrenal mass before pregnancy, but then during evaluation became pregnant. Her case is particularly intriguing because she had only vague clinical symptoms and mild laboratory abnormalities but also had a complicating pituitary mass noted on MRI. We outline the evaluation process and eventual laparoscopic adrenalectomy during the second trimester in this unique and difficult case, and discuss risks and benefits of different treatment options for hypercortisolism during pregnancy.

A Case of Cushing's Syndrome due to Ectopic Adrenocorticotropic Hormone Secretion from Esthesioneuroblastoma with Long Term Follow-Up after Resection.

We present a case of a 52-year-old male who developed Cushing's Syndrome due to ectopic adrenocorticotrophic hormone (ACTH) secretion from a large esthesioneuroblastoma (ENB) of the nasal sinuses. The patient initially presented with polyuria, polydipsia, weakness, and confusion. Computed tomography scan of the head and magnetic resonance imaging showed a 7 cm skull base mass centered in the right cribriform plate without sella involvement. Work-up revealed ACTH-dependent hypercortisolemia, which did not suppress appropriately after high-dose dexamethasone. Subsequent imaging of the chest, abdomen, and pelvis did not reveal other possible ectopic sources of ACTH secretion besides the ENB. His hospital course was complicated by severe hypokalemia and hyperglycemia before successful surgical resection of the tumor, the biopsy of which showed ENB. Postoperatively, his ACTH level dropped below the limit of detection. In the ensuing 4 months, he underwent adjuvant chemoradiation with carboplatin and docetaxel with good response and resolution of hypokalemia and hyperglycemia, with no sign of recurrence as of 30 months postoperatively. His endogenous cortisol production is rising but has not completely recovered.

Variation in the relationship between gestational diabetes diagnosis and total gestational weight gain by race/ethnicity.

Prior research suggests that women diagnosed and treated for gestational diabetes mellitus (GDM) gain less total gestational weight than normoglycemic women. Our study finds that race/ethnicity modifies this association. Relative to normoglycemic women, non-Hispanic white women with GDM gain less weight but non-Hispanic black and Hispanic women gain more weight.

Clinical markers implying the need for treatment in women with gestational diabetes mellitus.

OBJECTIVE: To assess the association of the point-of-care hemoglobin A1c (POC A1C), fasting blood glucose (FBG), and BMI with fetal macrosomia and the need for medication in women with gestational diabetes (GDM). METHODS: POC A1C, FBG, and BMI values at GDM diagnosis and fetal weight at delivery were obtained for women identified from a prospective patient registry. These outcomes were compared between women who did not require medication for GDM and women who did require medication. RESULTS: Mean values of POC A1C, FBG, and BMI in 67 patients who required medication were higher than those in 71 patients who did not require medication (POC A1C: 5.72 ± 0.45% vs 5.35 ± 0.46% [P<.001]; FBG: 97.4 ± 12.3 mg/dL vs 86.4 ± 9.5 mg/dL [P<.001]; BMI: 35.4 ± 6.4 kg/m2 vs 30.4 ± 6.2 kg/m(2) [P<.001]). There was a modest correlation between POC A1C and FBG (Spearman rho 0.4, P<.001) and between POC A1C and BMI (Spearman rho 0.366, P<.001). Maternal POC A1C was not correlated with fetal weight at delivery (Spearman rho -0.010, P = .915). CONCLUSIONS: Higher POC A1C, FBG, and BMI values were associated with the need for medication in women with GDM. The use of clinical markers to assess glycemic control sooner in pregnancy may lead to the earlier identification of women at risk for GDM and earlier intervention to decrease the risk for complications.

Endocrine complications in long-term survivors after allogeneic stem cell transplant.

As survival rates continue to increase after allogeneic stem cell transplant (allo-SCT), the associated long-term complications of transplant need to be taken into consideration. Here, we review the endocrine and metabolic complications associated with transplant survivors, including diabetes, dyslipidemia, hypertension, cardiovascular disease, hypogonadism, vitamin D deficiency, osteoporosis, thyroid disease, adrenal dysfunction, and pituitary disorders, and provide a brief summary of evaluation and treatment of these conditions.

Diabetes mellitus after hematopoietic stem cell transplantation.

OBJECTIVE: To review the current literature on posttransplant diabetes mellitus after hematopoietic stem cell transplantation, including its epidemiologic features, transplant-related risk factors, and treatment. METHODS: A literature search was conducted in PubMed for articles on diabetes mellitus after hematopoietic stem cell transplantation and effects of immunosuppressants on glucose metabolism. RESULTS: Within 2 years after hematopoietic stem cell transplantation, up to 30% of patients may have diabetes. Although some of these cases resolve, the rates of diabetes and metabolic syndrome remain elevated in comparison with those in the nontransplant patient population during long-term follow-up. Traditional risk factors for diabetes as well as features related to the transplantation process, including immunosuppressive medications, are associated with posttransplant diabetes. Cardiovascular risk also appears to be increased in this population. Limited data are available on hypoglycemic agents for posttransplant diabetes; thus, treatment decisions must be based on safety, efficacy, and tolerability, with consideration of each patient's transplant-related medications and comorbidities. CONCLUSION: Treatment of diabetes mellitus in patients who have undergone hematopoietic stem cell transplantation necessitates attention to the posttransplant medication regimen and clinical course. Although no guidelines specific to treatment of posttransplant diabetes in this patient population currently exist, treatment to goals similar to those for nontransplant patients with diabetes should be considered in an attempt to help reduce long-term morbidity and mortality.

Gestational diabetes mellitus resulting from impaired beta-cell compensation in the absence of FoxM1, a novel downstream effector of placental lactogen.

OBJECTIVE: The objectives of the study were to determine whether the cell cycle transcription factor, FoxM1, is required for glucose homeostasis and beta-cell mass expansion in maternal islets during pregnancy and whether FoxM1 is essential for placental lactogen (PL)-induced beta-cell proliferation. RESEARCH DESIGN AND METHODS: beta-Cell mass, beta-cell proliferation, and glucose homeostasis were assessed in virgin, pregnant, and postpartum mice with a pancreas-wide Foxm1 deletion (FoxM1(Deltapanc)). Wild-type islets were cultured with or without PL and examined for Foxm1 induction. Transgenic mice overexpressing PL in beta-cells were bred with FoxM1(Deltapanc) mice, and beta-cell proliferation was examined. RESULTS: Foxm1 was upregulated in maternal islets during pregnancy. In contrast to controls, beta-cell proliferation did not increase in pregnant FoxM1(Deltapanc) females. Mutant islets showed increased Menin and nuclear p27. FoxM1(Deltapanc) females developed gestational diabetes mellitus as pregnancy progressed. After parturition, euglycemia was restored in FoxM1(Deltapanc) females, but islet size was significantly reduced. Strikingly, beta-cell mass was normal in postpartum FoxM1(Deltapanc) pancreata due to a combination of increased beta-cell size and islet neogenesis. Evidence for neogenesis included increased number of endocrine clusters, increased proportion of smaller islets, and increased neurogenin 3 or insulin expression in cells adjacent to ducts. PL induced Foxm1 expression in cultured islets, and FoxM1 was essential for PL-mediated increases in beta-cell proliferation in vivo. CONCLUSIONS: FoxM1 is essential for beta-cell compensation during pregnancy. In the absence of increased beta-cell proliferation, neogenesis is induced in postpartum FoxM1(Deltapanc) pancreata. Our results suggest that FoxM1 functions downstream of PL to mediate its effects on beta-cell proliferation.

Type B insulin resistance syndrome associated with systemic lupus erythematosus.

OBJECTIVE: To document a case of type B insulin resistance syndrome associated with systemic lupus erythematosus. METHODS: We present the clinical course of a female patient with type B insulin resistance syndrome, from the onset, diagnosis, and empiric treatment until remission of her disease. RESULTS: A 40-year-old African American woman with systemic lupus erythematosus presented with a relatively acute onset of severe hyperglycemia in January 2004. Her hyperglycemia was resistant to treatment with high doses of insulin (up to an equivalent dose of regular insulin of 4,500 units daily). The diagnosis of type B insulin resistance syndrome was confirmed after her insulin receptor antibody was found to be strongly positive. The patient's hemoglobin Ale level improved substantially after she had been treated with azathioprine for 3 months. By November 2004, she was able to discontinue insulin therapy. Repeated insulin receptor antibody testing in February 2005 revealed that her insulin receptor antibody had become negative. The patient's fasting glucose level became normal, and only occasional mild postprandial hyperglycemic episodes have been noted. CONCLUSION: Immunosuppressive therapy with azathioprine seems to be responsible for our patient's remission of type B insulin resistance, although the possibility of the occurrence of a spontaneous remission cannot be completely excluded.