The effects of pioglitazone treatment in lipidemic profile and elastographic indices in non-diabetic patients with nash

2020 ◽  
Vol 315 ◽  
pp. e263
Author(s):  
G. Kalambokis ◽  
E. Klouras ◽  
S. Filippas-Ntekouan ◽  
I. Tsiakas ◽  
G. Despotis ◽  
...  
Keyword(s):  
Diabetic Patients ◽  
Pioglitazone Treatment

The effects of pioglitazone treatment on pancreatic cancer-related insulin resistance.

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 329-329
Author(s):  
Jennifer Stern ◽  
Yull Edwin Arriaga ◽  
Arjun Gupta ◽  
Udit Verma ◽  
Sirisha Karri ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Pancreatic Cancer ◽  
Insulin Sensitivity ◽  
Ppar Gamma ◽  
Post Treatment ◽  
Oral Glucose ◽  
Diabetic Patients ◽  
Fasting Insulin ◽  
Diabetes Status ◽  
Pioglitazone Treatment

329 Background: Insulin resistance (IR) in pancreatic cancer (PC) patients is associated with cachexia and poor outcome. Pioglitazone (PIO) improves insulin sensitivity via activation of peroxisome proliferator-activated receptor (PPAR gamma). Effects of PIO on insulin sensitivity, glucose homeostasis, and circulating adipokine levels in PC have not been examined. Methods: Patients with metastatic PC were administered PIO 45mg/day orally for 8 weeks concurrent with chemotherapy. Patients with known DM at enrollment were identified Fasting plasma was collected at baseline, weeks 2, 4, 6, 8 of pioglitazone treatment and at 2 weeks-post treatment. The primary objective was to describe changes in indicators of IR, including glucoregulatory hormone levels, glucose tolerance, and inflammatory cytokines. Results: Fourteen patients (age 64y), with a mean BMI of 28 were enrolled. Mean adiponectin increased from baseline to week 8 of treatment (14.2± 3.3 and 46.9±11.4µg/ml, respectively, P ≤ 0.01), and returned to baseline levels at 2 weeks post-treatment (15.1±1.9 µg/ml). Markers of IR (serum glucose, insulin, glucagon, and response to an oral glucose bolus) did not correlate with tumor size, inflammatory cytokine levels, GM-CSF, or CA19-9. A dichotomous response to PIO treatment was observed between non-diabetic and T2DM patients. Fasting insulin increased 70.6±31.3% from baseline to treatment week 8 in patients with T2DM. In contrast, treatment of non-diabetic patients decreased fasting insulin by 40.2±6.3%, demonstrating a significant, P ≤ 0.01, difference in treatment response between PC patients with or without T2DM. Conclusions: We have demonstrated that PC patients respond to 8 weeks of PIO treatment with a significant rise in the insulin sensitizing adipokine, Adiponectin, with a complete wash-out after 2 weeks of cessation. PIO results in opposing fasting insulin responses in non-diabetic and DM patients suggests that diabetes status plays a significant role in the glucoregulatory effects of PIO treatment in PC patients. Clinical trial information: NCT01838317.

scholarly journals Effect of Pioglitazone on Abdominal Fat Distribution and Insulin Sensitivity in Type 2 Diabetic Patients

2002 ◽  
Vol 87 (6) ◽  
pp. 2784-2791 ◽  
Author(s):  
Yoshinori Miyazaki ◽  
Archana Mahankali ◽  
Masafumi Matsuda ◽  
Srikanth Mahankali ◽  
Jean Hardies ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Visceral Fat ◽  
Fat Distribution ◽  
Abdominal Fat ◽  
Hepatic Insulin Resistance ◽  
Diabetic Patients ◽  
Visceral Fat Area ◽  
Insulin Clamp ◽  
Pioglitazone Treatment

We examined the effect of pioglitazone on abdominal fat distribution to elucidate the mechanisms via which pioglitazone improves insulin resistance in patients with type 2 diabetes mellitus. Thirteen type 2 diabetic patients (nine men and four women; age, 52 ± 3 yr; body mass index, 29.0 ± 1.1 kg/m2), who were being treated with a stable dose of sulfonylurea (n = 7) or with diet alone (n = 6), received pioglitazone (45 mg/d) for 16 wk. Before and after pioglitazone treatment, subjects underwent a 75-g oral glucose tolerance test (OGTT) and two-step euglycemic insulin clamp (insulin infusion rates, 40 and 160 mU/m2·min) with [3H]glucose. Abdominal fat distribution was evaluated using magnetic resonance imaging at L4–5. After 16 wk of pioglitazone treatment, fasting plasma glucose (179 ± 10 to 140 ± 10 mg/dl; P < 0.01), mean plasma glucose during OGTT (295 ± 13 to 233 ± 14 mg/dl; P < 0.01), and hemoglobin A1c (8.6 ± 0.4% to 7.2 ± 0.5%; P < 0.01) decreased without a change in fasting or post-OGTT insulin levels. Fasting plasma FFA (674 ± 38 to 569 ± 31 μEq/liter; P < 0.05) and mean plasma FFA (539 ± 20 to 396 ± 29 μEq/liter; P < 0.01) during OGTT decreased after pioglitazone. In the postabsorptive state, hepatic insulin resistance [basal endogenous glucose production (EGP) × basal plasma insulin concentration] decreased from 41 ± 7 to 25 ± 3 mg/kg fat-free mass (FFM)·min × μU/ml; P < 0.05) and suppression of EGP during the first insulin clamp step (1.1 ± 0.1 to 0.6 ± 0.2 mg/kg FFM·min; P < 0.05) improved after pioglitazone treatment. The total body glucose MCR during the first and second insulin clamp steps increased after pioglitazone treatment [first MCR, 3.5 ± 0.5 to 4.4 ± 0.4 ml/kg FFM·min (P < 0.05); second MCR, 8.7 ± 1.0 to 11.3 ± 1.1 ml/kg FFM·min (P < 0.01)]. The improvement in hepatic and peripheral tissue insulin sensitivity occurred despite increases in body weight (82 ± 4 to 85 ± 4 kg; P < 0.05) and fat mass (27 ± 2 to 30 ± 3 kg; P < 0.05). After pioglitazone treatment, sc fat area at L4–5 (301 ± 44 to 342 ± 44 cm2; P < 0.01) increased, whereas visceral fat area at L4–5 (144 ± 13 to 131 ± 16 cm2; P < 0.05) and the ratio of visceral to sc fat (0.59 ± 0.08 to 0.44 ± 0.06; P < 0.01) decreased. In the postabsorptive state hepatic insulin resistance (basal EGP × basal immunoreactive insulin) correlated positively with visceral fat area (r = 0.55; P < 0.01). The glucose MCRs during the first (r = −0.45; P < 0.05) and second (r = −0.44; P < 0.05) insulin clamp steps were negatively correlated with the visceral fat area. These results demonstrate that a shift of fat distribution from visceral to sc adipose depots after pioglitazone treatment is associated with improvements in hepatic and peripheral tissue sensitivity to insulin.

The effects of pioglitazone treatment on pancreatic cancer-related insulin resistance.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e15752-e15752
Author(s):  
Jennifer Stern ◽  
Yull Edwin Arriaga ◽  
Arjun Gupta ◽  
Udit N. Verma ◽  
Sirisha Karri ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Pancreatic Cancer ◽  
Clinical Trial ◽  
Insulin Sensitivity ◽  
Ppar Gamma ◽  
Post Treatment ◽  
Diabetic Patients ◽  
Fasting Insulin ◽  
Pioglitazone Treatment ◽  
Clinical Trial Information

e15752 Background: Insulin resistance (IR) in pancreatic cancer (PC) patients is associated with cachexia and poor outcome. Pioglitazone (PIO) improves insulin sensitivity via activation of peroxisome proliferator-activated receptor (PPAR gamma). Effects of PIO on insulin sensitivity, glucose homeostasis, and circulating adipokine levels in PC have not been examined. Methods: Patients with metastatic PC were administered PIO 45mg/day orally for 8 weeks concurrent with chemotherapy. Patients with known DM at enrollment were identified Fasting plasma was collected at baseline, weeks 2, 4, 6, 8 of pioglitazone treatment and at 2 weeks-post treatment. The primary objective was to describe changes in indicators of IR, including glucoregulatory hormone levels, glucose tolerance, and inflammatory cytokines. Results: Fourteen patients (age 64y), with a mean BMI of 28 were enrolled. Mean adiponectin increased from baseline to week 8 of treatment (14.2± 3.3 and 46.9±11.4µg/ml, respectively, P ≤ 0.01), and returned to baseline levels at 2 weeks post-treatment (15.1±1.9 µg/ml). Markers of IR (serum glucose, insulin, glucagon, and response to an oral glucose bolus) did not correlate with tumor size, inflammatory cytokine levels, GM-CSF, or CA19-9. A dichotomous response to PIO treatment was observed between non-diabetic and T2DM patients. Fasting insulin increased 70.6±31.3% from baseline to treatment week 8 in patients with T2DM. In contrast, treatment of non-diabetic patients decreased fasting insulin by 40.2±6.3%, demonstrating a significant, P ≤ 0.01, difference in treatment response between PC patients with or without T2DM. Conclusions: We have demonstrated that PC patients respond to 8 weeks of PIO treatment with a significant rise in the insulin sensitizing adipokine, Adiponectin, with a complete wash-out after 2 weeks of cessation. PIO results in opposing fasting insulin responses in non-diabetic and DM patients suggests that diabetes status plays a significant role in the glucoregulatory effects of PIO treatment in PC patients. Clinical trial information Clinical trial information: NCT01838317.

scholarly journals Pharmacologic PPAR-γ activation reprograms bone marrow macrophages and partially rescues HSPC mobilization in human and murine diabetes

2020 ◽  
Author(s):  
Ada Admin ◽  
Serena Tedesco ◽  
Stefano Ciciliot ◽  
Lisa Menegazzo ◽  
Marianna D’Anna ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stromal Cells ◽  
Oncostatin M ◽  
Diabetic Patients ◽  
Double Knockout ◽  
M1 Macrophages ◽  
Hematopoietic Stem ◽  
Ppar Γ ◽  
Pioglitazone Treatment

Mobilization of hematopoietic stem/progenitor cells (HSPCs) from the bone marrow (BM) is impaired in diabetes. Excess oncostatin M (OSM) produced by M1 macrophages in the diabetic BM signals through p66Shc to induce <i>Cxcl12</i> in stromal cells and retain HSPCs. BM adipocytes are another source of CXCL12 that blunts mobilization. We tested a strategy of pharmacologic macrophage reprogramming to rescue HSPC mobilization. <i>In vitro</i>, PPAR-γ activation with pioglitazone switched macrophages from M1 to M2, reduced <i>Osm</i> expression, and prevented transcellular induction of <i>Cxcl12</i>. In diabetic mice,<i> </i>pioglitazone treatment downregulated <i>Osm</i>, <i>p66Shc</i> and <i>Cxcl12</i> in the hematopoietic BM, restored the effects of granulocyte-colony stimulation factor (G-CSF), and partially rescued HSPC mobilization, but it increased BM adipocytes. <i>Osm</i> deletion recapitulated the effects of pioglitazone on adipogenesis, which was p66Shc-independent, and double knockout of Osm and p66Shc completely rescued HSPC mobilization<i>. </i>In the absence of OSM, BM adipocytes produced less CXCL12, being arguably devoid of HSPC-retaining activity, whereas pioglitazone failed to downregulate <i>Cxcl12</i> in BM adipocytes. In diabetic patients under pioglitazone therapy, HSPC mobilization after G-CSF was partially rescued. In summary, pioglitazone reprogrammed BM macrophages and suppressed OSM signaling, but sustained <i>Cxcl12</i> expression by BM adipocytes could limit full recovery of HSPC mobilization.

scholarly journals Pharmacologic PPAR-γ activation reprograms bone marrow macrophages and partially rescues HSPC mobilization in human and murine diabetes

2020 ◽  
Author(s):  
Ada Admin ◽  
Serena Tedesco ◽  
Stefano Ciciliot ◽  
Lisa Menegazzo ◽  
Marianna D’Anna ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stromal Cells ◽  
Oncostatin M ◽  
Diabetic Patients ◽  
Double Knockout ◽  
M1 Macrophages ◽  
Hematopoietic Stem ◽  
Ppar Γ ◽  
Pioglitazone Treatment

Mobilization of hematopoietic stem/progenitor cells (HSPCs) from the bone marrow (BM) is impaired in diabetes. Excess oncostatin M (OSM) produced by M1 macrophages in the diabetic BM signals through p66Shc to induce <i>Cxcl12</i> in stromal cells and retain HSPCs. BM adipocytes are another source of CXCL12 that blunts mobilization. We tested a strategy of pharmacologic macrophage reprogramming to rescue HSPC mobilization. <i>In vitro</i>, PPAR-γ activation with pioglitazone switched macrophages from M1 to M2, reduced <i>Osm</i> expression, and prevented transcellular induction of <i>Cxcl12</i>. In diabetic mice,<i> </i>pioglitazone treatment downregulated <i>Osm</i>, <i>p66Shc</i> and <i>Cxcl12</i> in the hematopoietic BM, restored the effects of granulocyte-colony stimulation factor (G-CSF), and partially rescued HSPC mobilization, but it increased BM adipocytes. <i>Osm</i> deletion recapitulated the effects of pioglitazone on adipogenesis, which was p66Shc-independent, and double knockout of Osm and p66Shc completely rescued HSPC mobilization<i>. </i>In the absence of OSM, BM adipocytes produced less CXCL12, being arguably devoid of HSPC-retaining activity, whereas pioglitazone failed to downregulate <i>Cxcl12</i> in BM adipocytes. In diabetic patients under pioglitazone therapy, HSPC mobilization after G-CSF was partially rescued. In summary, pioglitazone reprogrammed BM macrophages and suppressed OSM signaling, but sustained <i>Cxcl12</i> expression by BM adipocytes could limit full recovery of HSPC mobilization.

scholarly journals Effects of Pioglitazone in Nondiabetic Patients with Arterial Hypertension: A Double-Blind, Placebo-Controlled Study

2002 ◽  
Vol 87 (12) ◽  
pp. 5503-5506 ◽  
Author(s):  
S. Füllert ◽  
F. Schneider ◽  
E. Haak ◽  
H. Rau ◽  
K. Badenhoop ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Cardiovascular Disease ◽  
Arterial Hypertension ◽  
Controlled Study ◽  
Diabetic Patients ◽  
Prediabetic State ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Increased Risk ◽  
Pioglitazone Treatment

Abstract Hypertension is often associated with insulin resistance, dyslipidemia and obesity, which indicate a prediabetic state and increased risk of cardiovascular disease. Pioglitazone treatment of patients with type 2 diabetes reduces insulin resistance and improves lipid profiles. The present double-blind placebo-controlled study is the first study to report effects of pioglitazone in non-diabetic patients with arterial hypertension. Following a one week run-in, 60 patients were randomized to receive either pioglitazone (45 mg/day) or placebo for 16 weeks. Insulin sensitivity (M-value) increased by 1.2 ± 1.7 mg/min/kg with pioglitazone compared with 0.4 ± 1.4 mg/min/kg (P = 0.022) with placebo. HOMA index was decreased (−22.5 ± 45.8) by pioglitazone but not by placebo (+0.8 ± 26.5; P &lt; 0.001). Decreases in fasting insulin and glucose were significantly (P = 0.002 and P = 0.004, respectively) greater with pioglitazone than placebo. Body weight did not change significantly with either treatment. HDL-cholesterol was increased and apolipoprotein B was decreased to a significantly greater extent with pioglitazone. There was a significantly (P = 0.016) greater decrease from baseline in diastolic blood pressure with pioglitazone. These changes would suggest improved glucose metabolism and a possible reduction in risk of cardiovascular disease with pioglitazone treatment of non-diabetic patients with arterial hypertension.

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