IMPORTANCE Chronic periodontitis, a destructive inflammatory disorder of the supporting structures of the teeth, is prevalent in patients with diabetes. Limited evidence suggests that periodontal therapy may improve glycemic control. OBJECTIVE To determine if nonsurgical periodontal treatment reduces levels of glycated hemoglobin (HbA 1c) in persons with type 2 diabetes and moderate to advanced chronic periodontitis. DESIGN, SETTING, AND PARTICIPANTS The Diabetes and Periodontal Therapy Trial (DPTT), a 6-month, single-masked, multicenter, randomized clinical trial. Participants had type 2 diabetes, were taking stable doses of medications, had HbA 1c levels between 7% and less than 9%, and untreated chronic periodontitis. Five hundred fourteen participants were enrolled between November 2009 and March 2012 from diabetes and dental clinics and communities affiliated with 5 academic medical centers. INTERVENTIONS The treatment group (n = 257) received scaling and root planing plus chlorhexidine oral rinse at baseline and supportive periodontal therapy at 3 and 6 months. The control group (n = 257) received no treatment for 6 months. MAIN OUTCOMES AND MEASURES Difference in change in HbA 1c level from baseline between groups at 6 months. Secondary outcomes included changes in probing pocket depths, clinical attachment loss, bleeding on probing, gingival index, fasting glucose level, and Homeostasis Model Assessment (HOMA2) score. RESULTS Enrollment was stopped early because of futility. At 6 months, mean HbA 1c levels in the periodontal therapy group increased 0.17% (SD, 1.0), compared with 0.11% (SD, 1.0) in the control group, with no significant difference between groups based on a linear regression model adjusting for clinical site (mean difference, −0.05% [95% CI, −0.23% to 0.12%]; P = .55). Periodontal measures improved in the treatment group compared with the control group at 6 months, with adjusted between-group differences of 0.28 mm (95% CI, 0.18 to 0.37) for probing depth, 0.25 mm (95% CI, 0.14 to 0.36) for clinical attachment loss, 13.1% (95% CI, 8.1% to 18.1%) for bleeding on probing, and 0.27 (95% CI, 0.17 to 0.37) for gingival index (P < .001 for all). CONCLUSIONS AND RELEVANCE Nonsurgical periodontal therapy did not improve glycemic control in patients with type 2 diabetes and moderate to advanced chronic periodontitis. These findings do not support the use of nonsurgical periodontal treatment in patients with diabetes for the purpose of lowering levels of HbA 1c .

Several lines of evidence indicate that insulin-like growth factor-I (IGF-I) is a potent mediator of vasodilation. To elucidate the mechanism and site of action of IGF-I, we performed continuous monitoring of nitric oxide (NO) release from endothelial cells using a highly-sensitive amperometric NO-sensor. Two types of cultured cells were used: human umbilical vein endothelial cells and immortalized rat renal interlobar artery endothelial cells. In separate experiments, [Ca2+]i changes in response to IGF-I were measured spectrofluorometrically in fura-2-loaded cells. Stimulation with IGF-I resulted in a rapid, dose-dependent increase in [NO] as detected by the NO-probe positioned 1 mm above the monolayers, followed by a sustained elevation lasting for at least five minutes. The effect of IGF-I was significantly suppressed by pretreatment with anti-IGF-I antibody, suggesting that it was specific for IGF-I. NG-nitro-L-arginine methyl ester, an inhibitor of NO synthesis, significantly blunted responses to IGF-I, but dexamethasone preincubation did not reduce the IGF-I-induced release of NO. These results indicate that the observed IGF-I-induced release of NO is a result of activation of the constitutive, rather than the inducible type of NO synthase in endothelial cells. Genistein, a tyrosine kinase inhibitor, resulted in a profound suppression of the IGF-I-induced release of NO. IGF-I did not affect [Ca2+]i in either type of cells. Therefore, IGF-I-induced NO production by both types of endothelial cells is mediated via a tyrosine kinase-dependent mechanism.(ABSTRACT TRUNCATED AT 250 WORDS)

These findings indicate a relationship between RBP4, insulin sensitivity, and percent trunk fat in individuals who may not have features of insulin resistance.

The purpose of the present study was to determine 1) whether exogenous administration of tumor necrosis factor-alpha (TNF-alpha) alters insulin-like growth factor-I (IGF-I) and IGF-binding proteins (BPs) and 2) whether the enhanced endogenous production of TNF mediates the lipopolysaccharide (LPS)-induced changes in the IGF system. The overnight infusion of murine TNF-alpha reduced circulating concentrations of both growth hormone (GH) and IGF-I in fasted rats. Furthermore, TNF-alpha decreased IGF-I content in liver, gastrocnemius muscle, and pituitary. In contrast, TNF-alpha increased IGF-I content in kidney and brain. IGFBP-1 was increased in plasma, liver, and muscle in response to TNF-alpha. In a second study, rats were injected with LPS after treatment with a neutralizing anti-TNF antibody (Ab), and blood and tissues were collected 4 h later. In LPS-treated rats, plasma concentrations of GH and IGF-I were reduced. LPS also decreased the IGF-I content in liver and skeletal muscle and increased plasma, liver, and muscle concentrations of IGFBP-1. Pretreatment with anti-TNF Ab attenuated the LPS-induced reduction in IGF-I and the increased IGFBP-1 in plasma and liver and completely prevented the decrease in IGF-I observed in muscle. In contrast, the LPS-induced decrease in plasma GH and the increased IGFBP-1 observed in muscle were unaltered by the anti-TNF Ab.(ABSTRACT TRUNCATED AT 250 WORDS)