Inpatient Diabetes Management in the Twenty-First Century.

In hospitalized patients, both hyperglycemia and hypoglycemia have been associated with poor outcomes. During the inpatient period, hyperglycemia has been associated with increased risk of infection, cardiovascular events, and mortality. It is also associated with longer length of hospital stay. Hypoglycemia has also been associated with an increased risk of mortality. Therefore, current evidence supports avoidance of both conditions among hospitalized patients whether they are admitted to critical care units or noncritical care units.

The effects of thiazolidinediones on human bone marrow stromal cell differentiation in vitro and in thiazolidinedione-treated patients with type 2 diabetes.

Thiazolidinedione (TZD) therapy has been associated with an increased risk of bone fractures. Studies in rodents have led to a model in which decreased bone quality in response to TZDs is due to a competition of lineage commitment between osteoblasts (OBs) and adipocytes (ADs) for a common precursor cell, resulting in decreased OB numbers. Our goal was to investigate the effects of TZD exposure on OB-AD lineage determination from primary human bone marrow stromal cells (hBMSCs) both in vitro and in vivo from nondiabetic subjects and patients with type 2 diabetics. Our experimental design included 2 phases. Phase 1 was an in vitro study of TZD effects on the differentiation of hBMSCs into OBs and ADs in nondiabetic subjects. Phase 2 was a randomized, placebo-controlled trial to determine the effects of 6-month pioglitazone treatment in vivo on hBMSC differentiation using AD/OB colony forming unit assays in patients with type 2 diabetes. In vitro, TZDs (pioglitazone and rosiglitazone) enhanced the adipogenesis of hBMSCs, whereas neither altered OB differentiation or function as measured by alkaline phosphatase activity, gene expression, and mineralization. The ability of TZDs to enhance adipogenesis occurred at a specific time/stage of the differentiation process, and pretreating with TZDs did not further enhance adipogenesis. In vivo, 6-month TZD treatment decreased OB precursors, increased AD precursors, and increased total colony number in patients with type 2 diabetes. Our results indicate that TZD exposure in vitro potently stimulates adipogenesis but does not directly alter OB differentiation/mineralization or lineage commitment from hBMSCs. However, TZD treatment in type 2 diabetic patients results in decreased osteoblastogenesis from hBMSCs compared with placebo, indicating an indirect negative effect on OBs and suggesting an alternative model by which TZDs might negatively regulate bone quality.

Vitamin D-mediated calcium absorption in patients with clinically stable Crohn's disease: a pilot study.

Vitamin D is the critical hormone for intestinal absorption of calcium. Optimal calcium absorption is important for proper mineralization of bone in the prevention of osteoporosis and osteoporotic fractures, among other important functions. Diseases associated with gut inflammation, such as Crohn's disease (CD), may impair calcium absorption. This pilot study evaluated vitamin D- dependent calcium absorption in subjects with CD. Male subjects with CD (n=4) and healthy age-matched controls (n=5) were studied. All subjects had fractional calcium absorption (FCA; by the dual calcium isotope method), serum 25-hydroxyvitamin D, serum calcium and 24 h urinary calcium excretion measurements at baseline. The FCA in response to vitamin D therapy was re-assessed following administration of oral calcitriol 0.25 mcg twice daily for 1 wk, followed by oral calcitriol 0.50 mcg twice daily for 1 wk. Serum calcium and 24 h urinary calcium determinations were re-assessed after each increasing dose of calcitriol as safety measures. There was no significant difference in calcium FCA at baseline or after increasing doses of calcitriol between the CD and controls. FCA in the control and CD group was approximately 35% at baseline, which increased to 60% after calcitriol therapy. No subject developed hypercalcemia or hypercalciuria. Our results suggest that CD patients have a normal response to vitamin D in enhancing the efficacy of calcium absorption. This suggests that stable CD patients can follow calcium and vitamin D guidelines of non-CD adults. Other factors independent of vitamin D status may impair intestinal calcium absorption in CD, including the degree and location of inflammation, presence of surgical resection and/or use of glucocorticoids.

Diabetes and fractures: an overshadowed association.

PURPOSE OF REVIEW: To review recent literature on fracture risk in patients with type 1 and type 2 diabetes. RECENT FINDINGS: Observational and population studies have reported a higher risk of fractures in patients with type 1 and type 2 diabetes, especially at the hip. Type 2 diabetic patients have a higher bone mineral density compared with the general population, and yet, remain unprotected from fractures. Type 1 diabetic patients have a greater risk of fractures and a lower bone mineral density compared with the general population. Their lower bone mineral density, however, does not fully account for the raised fracture risk. Therefore, impaired bone quality rather than lower bone density appears to mediate the increased fracture risk in patients with type 1 and 2 diabetes.Recently, studies have shown an association between advanced glycation end products with increased fracture risk in diabetic patients. These studies support the hypothesis of poor glycemic control and chronic hyperglycemia having a direct detrimental effect on bone quality. In addition, increased fracture risk has been reported in patients with peripheral and autonomic neuropathy, recurrent hypoglycemic events, vitamin D deficiency, and those receiving thiazolidinedione therapy. SUMMARY: Diabetes is associated with an increased risk of fractures in patients with type 1 and type 2 diabetes. Appropriate measures aimed at fracture prevention should be considered in the complex care of the diabetic patient.

Treatment and prevention of vitamin D insufficiency in cystic fibrosis patients: comparative efficacy of ergocalciferol, cholecalciferol, and UV light.

BACKGROUND: The optimal treatment for correcting or preventing vitamin D insufficiency in cystic fibrosis (CF) patients has not been established. OBJECTIVE: The aim of the study was to assess the relative efficacy of three modes of vitamin D therapy: cholecalciferol (D3), ergocalciferol (D2), and UV light in raising or maintaining 25(OH)D levels above 30 ng/ml. DESIGN: Thirty adult CF subjects with vitamin D insufficiency were randomized into one of three treatment arms: D3, D2, or UV light. Subjects randomized to D3 or D2 ingested 50,000 IU of vitamin D weekly, and those randomized to UV exposed their skin to UV light from a lamp five times a week. Serum was collected for 25(OH)D and PTH at baseline and at 12 wk. RESULTS: Treatment with D3 and D2 raised 25(OH)D levels significantly, from a mean of 21.2 +/- 10.18 to 47.1 +/- 20.5 ng/ml (P < 0.001) and 24.4 +/- 10.3 to 32.7+/- 9.7 ng/ml (P = 0.01), with 100% and 60% reaching 25(OH)D levels above 30 ng/ml, respectively. Treatment with UV did not raise 25(OH)D levels significantly; however, only 55% of subjects were adherent with UV therapy. CONCLUSION: This study demonstrates that CF subjects are able to achieve or maintain optimal vitamin D status (>30 ng/ml) with two oral regimens of either D3 or D2 treatment, the former being more efficacious. A confounding variable for this observation is the fact that the D3 and D2 capsules contained different carriers, powder-based vs. oil-based, respectively. UV therapy did not alter vitamin D status, possibly due to poor adherence to UV therapy.