Physiogenomic comparison of edema and BMI in patients receiving rosiglitazone or pioglitazone.

BACKGROUND: The thiazolidinediones (TZDs) improve tissue sensitivity to insulin in patients with type II diabetes, resulting in reduced levels of fasting blood glucose and glycated hemoglobin. However, TZDs unpredictably demonstrate adverse effects of increased body weight, fluid retention, and edema. The balance of efficacy and safety of TZD varies widely from patient to patient. Genetic variability may reveal pathophysiological pathways underlying weight gain associated with TZD therapy and due to adiposity and/or edema. METHODS: We analyzed 384 single nucleotide polymorphisms (SNPs) from 222 cardiovascular and metabolic genes in 87 outpatients with type 2 diabetes receiving thiazolidinedione therapy. Physiogenomic analysis was used to discover associations with body mass index (BMI) and edema. RESULTS: The 5 most significant gene associations found between BMI and SNPs were ADORA1, adenosine A1 receptor (rs903361, p<0.0003), PKM2, pyruvate kinase-muscle (rs2856929, p<0.002); ADIPOR2, adiponectin receptor 2 (rs7975375, p<0.007); UCP2, uncoupling protein 2 (rs660339, p<0.008); and APOH, apolipoprotein H (rs8178847, p<0.010). For edema, the 5 most significant gene associations were NPY, neuropeptide Y (rs1468271, p<0.006); GYS1, glycogen synthase 1-muscle (rs2287754, p<0.013); CCL2, chemokine C-C motif ligand 2 (rs3760396, p<0.015); OLR1, oxidized LDL receptor 1 (rs2742115, p<0.015); and GHRH, growth hormone releasing hormone (rs6032470, p<0.023). After accounting for multiple comparisons, ADORA1 was significantly associated with BMI at a false discovery rate (FDR) of <10%. CONCLUSION: Physiogenomic associations were discovered suggesting mechanistic links between adenosine signaling and BMI, and between vascular permeability and drug-induced edema.

Primary adrenal lymphoma presenting as adrenal insufficiency. A case report and review of literature.

Primary adrenal lymphoma (PAL) with adrenal insufficiency is a rare entity that has a unique presentation and prognosis when compared to other high-grade B-cell Non-Hodgkin's Lymphomas (NHL). Radiologic characteristics and image-guided biopsy are helpful in diagnosis. Current chemotherapy of choice is CHOP [Cyclophosphamide, Hydroxydaunomycin (doxorubicin), Oncovin (vincristine sulfate) and Prednisone]. More cases need to be documented to formulate an effective approach to PAL.

Medical evaluation and treatment of diabetic peripheral neuropathy.

Diabetes mellitus is a major health concern that is only expected to become more prevalent over the next few decades. It causes much morbidity and mortality through various macro- and microvascular complications, including diabetic neuropathy. Currently, there is no treatment that directly affects the natural course of diabetic neuropathy except for rigorous glycemic control, a goal that is not always achievable. Despite these therapeutic limitations, the morbidity caused by diabetic neuropathy can be minimized by early and accurate diagnosis. A detailed history and physical examination, along with carefully selected laboratory tests will confirm the presence of diabetic neuropathy while excluding other etiologies that may require alternative management strategies. Treatment is always tailored to the patient's symptoms. In addition to improved glycemic control, health care providers can provide education, support, and symptomatic relief. There are many pain modulating therapies that are effective in diabetic neuropathy as discussed above. Nortriptyline at low doses is an inexpensive well-tolerated medication that is effective. Gabapentin is an excellent choice when nortriptyline is ineffective or not tolerated. Other anticonvulsants, such as lamotrigine, carbamazepine, oxycarbazepine, and topiramate, may also provide benefit. Judicious use of narcotics is appropriate when other treatment modalities fail. The importance of treating underlying depression cannot be overemphasized. When gait becomes impaired as a result of neuropathy, appropriate prescription of assistive devices will prevent injuries from falls. Ankle-foot orthoses and other orthotic devices may allow patients to remain ambulatory and independent for a longer period. Despite the challenges ahead, the future holds the promise of more effective treatments for diabetes mellitus and its complications.

Inpatient management of diabetes mellitus.

There is now widespread appreciation of the importance of maintaining glucose levels as close to the normal range as possible among outpatients with diabetes. However, the importance of tight glucose control in inpatients is less well established. During the past several years, it has become apparent that hyperglycemia in hospitalized patients, especially those in the postoperative setting, is associated with poorer outcomes. In addition, two randomized trials have shown improved outcomes with intensive glucose management in acutely ill patients. Based on these studies and our own experience, we propose guidelines and a framework for improving the glycemic control of hospitalized patients.