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Folestad A.,CapioLundby Hospital | Alund M.,Sahlgrenska University Hospital | Asteberg S.,Sahlgrenska University Hospital | Fowelin J.,Diabetes Care Unit | And 4 more authors.
Journal of Foot and Ankle Research | Year: 2015

Background: Little is currently known of the pathophysiological mechanisms triggering Charcot arthropathy and regulating its recovery although foot trauma has been proposed as a major initiating factor by activation of proinflammatory cytokines leading to increased osteoclastogenic activity and progressive bone destruction. Several members of the IL-17 family of proinflammatory cytokines have been shown to play a key role in the pathogenesis of inflammatory conditions affecting bone and joints but none has previously been studied in Charcot foot patients. The aim of this study was to investigate the role of IL-17A, IL-17E and IL-17F in patients presenting with Charcot foot. Methods: Twenty-six consecutive Charcot patients were monitored during 2 years by repeated foot radiographs, MRI and circulating levels of IL-17A, IL-17E and IL-17F. Analysis of cytokines was done by ultra-sensitive chemiluminescence technique and data were analyzed by one-way repeated measures ANOVA. Neuropathic diabetic patients (n = 20) and healthy subjects (n = 20) served as controls. Results: Plasma IL-17A and IL-17E in weight-bearing Charcot patients at diagnosis were at the level of diabetic controls, whereas IL-17F was significantly lower than diabetic controls. A significant increase in IL-17A and IL-17E reaching a peak 2-4 months after inclusion and start of offloading treatment in Charcot patients was followed by a gradual decrease to the level of diabetic controls at 2 years postinclusion. In contrast, IL-17F increased gradually from inclusion to a level not significantly different from diabetic controls after 2 years. Conclusions: Charcot patients display a significant elevation of all three IL-17 cytokines during the follow-up period relative values at diagnosis and values in control patients supporting a role in the bone repair and remodeling activity during the recovery phase. The rapid increase of IL-17A and IL-17E shortly after initiating off-loading treatment could suggest this to be a response to immobilization and stabilization of the diseased foot. © 2015 Folestad et al.


Derosa G.,University of Pavia | Ragonesi P.D.,Diabetes Care Unit | Fogari E.,University of Pavia | D'Angelo A.,University of Pavia | And 2 more authors.
Expert Opinion on Pharmacotherapy | Year: 2012

Objective: To evaluate the action of vildagliptin + metformin on some adipocytokine levels, glycemic control, and β-cell function in type 2 diabetic patients. Research design and Methods: A total of 171 patients with poor glycemic control were instructed to add after a 8 ± 2 month-run-in period with metformin, vildagliptin 50 mg twice a day or placebo for 12 months. Main outcome measures: We evaluated at 3, 6, 9, and 12 months, the body mass index (BMI), glycemic control, fasting plasma insulin (FPI), homeostasis model assessment insulin resistance index (HOMA-IR), homeostasis model assessment β-cell function index (HOMA-β), fasting plasma proinsulin (FPr), proinsulin/fasting plasma insulin ratio (Pr/FPI ratio), C-peptide, glucagon, resistin, retinol-binding protein-4 (RBP-4), chemerin, and tumor necrosis factor-α (TNF-α). Patients also underwent a combined euglycemic hyperinsulinemic and hyperglycemic clamp, with subsequent arginine stimulation to assess insulin sensitivity and insulin secretion. Results: After 12 months of vildagliptin + metformin, we observed a better decrease of body weight, glycemic control, HOMA-IR, and glucagon, and a better increase of HOMA-β, and of all the measures of β-cell function, compared to placebo + metformin. Vildagliptin + metformin also decreased resistin, RBP-4, and chemerin better. Conclusion: Vildagliptin seems to have a positive action on some adipocytokines related to inflammation. © 2012 Informa UK, Ltd.


Derosa G.,University of Pavia | Maffioli P.,University of Pavia | Salvadeo S.A.T.,University of Pavia | Ferrari I.,University of Pavia | And 8 more authors.
Diabetes Technology and Therapeutics | Year: 2010

Background: Incretin-based therapies have provided additional options for the treatment of type 2 diabetes mellitus. The aim of our study was to evaluate the effects of exenatide compared to glibenclamide on body weight, glycemic control, β-cell function, insulin resistance, and inflammatory state in patients with diabetes. Methods: One hundred twenty-eight patients with uncontrolled type 2 diabetes mellitus receiving therapy with metformin were randomized to take exenatide 5μg twice a day or glibenclamide 2.5mg three times a day and titrated to exenatide 10μg twice a day or glibenclamide 5mg three times a day. We evaluated body weight, body mass index (BMI), glycated hemoglobin (HbA1c), fasting plasma glucose (FPG), postprandial plasma glucose (PPG), fasting plasma insulin (FPI), homeostasis model assessment insulin resistance (HOMA-IR) index, homeostasis model assessment β-cell function (HOMA-β) index, plasma proinsulin (PPr), PPr/FPI ratio, resistin, retinol binding protein-4 (RBP-4), and high-sensitivity C-reactive protein (Hs-CRP) at baseline and after 3, 6, 9, and 12 months. Results: Body weight and BMI decreased with exenatide and increased with glibenclamide. A similar improvement of HbA1c, FPG, and PPG was obtained in both groups, whereas FPI decreased with exenatide and increased with glibenclamide. The HOMA-IR index decreased and the HOMA-β index increased with exenatide but not with glibenclamide. A decrease of PPr was reported in both groups, but only glibenclamide decreased the PPr/FPI ratio. Resistin and RBP-4 decreased with exenatide and increased with glibenclamide. A decrease of Hs-CRP was obtained with exenatide, whereas no variations were observed with glibenclamide. Conclusions: Both exenatide and glibenclamide gave a similar improvement of glycemic control, but only exenatide gave improvements of insulin resistance and β-cell function, giving also a decrease of body weight and of inflammatory state. Copyright 2010 Mary Ann Liebert, Inc.


Derosa G.,University of Pavia | Maffioli P.,University of Pavia | Ferrari I.,University of Pavia | Mereu R.,University of Pavia | And 8 more authors.
Hormone and Metabolic Research | Year: 2010

The aim of the study was to compare the effects of vildagliptin added to pioglitazone or glimepiride on metabolic and insulin resistance related-indices in poorly controlled type 2 diabetic patients (T2DM). 168 patients with T2DM were randomized to take either pioglitazone 30mg once a day plus vildagliptin 50mg twice a day or glimepiride 2mg 3 times a day plus vildagliptin 50mg twice a day. We evaluated body weight, body mass index (BMI), glycated hemoglobin (HbA1c), fasting plasma glucose (FPG), postprandial plasma glucose (PPG), fasting plasma insulin (FPI), homeostasis model assessment insulin resistance index (HOMA-IR), homeostasis model assessment -cell function index (HOMA-), fasting plasma proinsulin (FPPr), proinsulin/fasting plasma insulin ratio (Pr/FPI ratio), adiponectin (ADN), resistin (R), tumor necrosis factor- (TNF-), and high sensitivity C-reactive protein (Hs-CRP) at their baseline values, and after 3, 6, 9, and 12 months of treatment. We observed a similar improvement of HbA1c, FPG, PPG, and Hs-CRP compared to baseline in the 2 groups. Fasting plasma insulin, FPPr, Pr/FPI ratio, R, and TNF- were significantly decreased and ADN was significantly increased with pioglitazone plus vildagliptin, but not with glimepiride plus vildagliptin. HOMA-IR, and HOMA- values obtained with pioglitazone plus vildagliptin were significantly better than the values obtained with glimepiride plus vildagliptin. Pioglitazone plus vildagliptin were found to be more effective in preserving -cell function, and in reducing insulin resistance, and inflammatory state parameters. © Georg Thieme Verlag KG Stuttgart - New York.


Derosa G.,University of Pavia | Maffioli P.,University of Pavia | Salvadeo S.A.T.,University of Pavia | Ferrari I.,University of Pavia | And 8 more authors.
Metabolism: Clinical and Experimental | Year: 2010

The aim of the study was to compare the effects of the addition of sitagliptin or metformin to pioglitazone monotherapy in poorly controlled type 2 diabetes mellitus patients on body weight, glycemic control, β-cell function, insulin resistance, and inflammatory state parameters. One hundred fifty-one patients with uncontrolled type 2 diabetes mellitus (glycated hemoglobin [HbA1c] >7.5%) in therapy with pioglitazone 30 mg/d were enrolled in this study. We randomized patients to take pioglitazone 30 mg plus sitagliptin 100 mg once a day, or pioglitazone 15 mg plus metformin 850 mg twice a day. We evaluated at baseline and after 3, 6, 9, and 12 months these parameters: body weight, body mass index, HbA1c, fasting plasma glucose (FPG), postprandial plasma glucose (PPG), fasting plasma insulin (FPI), homeostasis model assessment insulin resistance index (HOMA-IR), homeostasis model assessment β-cell function index, fasting plasma proinsulin (Pr), Pr/FPI ratio, adiponectin, resistin (R), tumor necrosis factor-α (TNF-α), and high-sensitivity C-reactive protein. A decrease of body weight and body mass index was observed with metformin, but not with sitagliptin, at the end of the study. We observed a comparable significant decrease of HbA1c, FPG, and PPG and a significant increase of homeostasis model assessment β-cell function index compared with baseline in both groups without any significant differences between the 2 groups. Fasting plasma insulin, fasting plasma Pr, Pr/FPI ratio, and HOMA-IR values were decreased in both groups even if the values obtained with metformin were significantly lower than the values obtained with sitagliptin. There were no significant variations of ADN, R, or TNF-α with sitagliptin, whereas a significant increase of ADN and a significant decrease of R and TNF-α values were recorded with metformin. A significant decrease of high-sensitivity C-reactive protein value was obtained in both groups without any significant differences between the 2 groups. There was a significant correlation between HOMA-IR decrease and ADN increase, and between HOMA-IR decrease and R and TNF-α decrease in pioglitazone plus metformin group after the treatment. The addition of both sitagliptin or metformin to pioglitazone gave an improvement of HbA1c, FPG, and PPG; but metformin led also to a decrease of body weight and to a faster and better improvement of insulin resistance and inflammatory state parameters, even if sitagliptin produced a better protection of β-cell function. © 2010 Elsevier Inc. All rights reserved.

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