scholarly journals Atorvastatin administration is associated with dose-related changes in IGF bioavailability

2013 ◽  
Vol 168 (4) ◽  
pp. 543-548 ◽  
Author(s):  
Ram P Narayanan ◽  
Matthew Gittins ◽  
Kirk W Siddals ◽  
Robert L Oliver ◽  
Julie E Hudson ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Statin Therapy ◽  
Group Differences ◽  
High Dose ◽  
Differential Impact ◽  
Atorvastatin Treatment ◽  
Atorvastatin Therapy ◽  
Design And Methods ◽  
Trial Participants

ObjectiveIGF levels, their binding proteins (IGFBPs) and high-dose statin therapy have been linked to the development of diabetes. We aimed to identify whether atorvastatin caused dose-related changes in IGF proteins.Design and methodsWe measured IGF1, IGF2, IGFBP1 and IGFBP3 concentrations at baseline, 6 and 12 months in Protection Against Nephropathy in Diabetes with Atorvastatin trial participants with type 2 diabetes randomised to 10 mg (n=59) vs 80 mg (n=60) of atorvastatin (n=119; mean (s.d.): age 64 (10) years; 83% male; HbA1c 61 (10) mmol/mol; blood pressure 131/73 mmHg).ResultsAtorvastatin was associated with overall reductions in circulating IGF1, IGF2 and IGFBP3 concentrations (P<0.05 for all changes). The adjusted mean (95% CI) between-group differences that indicate dose-related changes in IGF proteins were not significant for IGF1: −3 (−21 to 14) ng/ml; IGF2: −23 (−65 to 18) ng/ml and IGFBP3: −0.34 (−0.71 to 0.03) μg/ml, negative values indicating numerically greater lowering with high dose. The IGFBP1 concentration did not change with atorvastatin therapy overall but the adjusted mean (95% CI) between-group difference indicating a dose-related change in log IGFBP1 was highly significant −0.41 (−0.69 to 0.13, P=0.004).ConclusionIGF1, IGF2 and IGFBP3 concentrations decreased following atorvastatin therapy. A differential effect of low- vs high-dose atorvastatin on IGFBP1 concentrations was observed with likely implications for IGF bioavailability. The dose-related differential impact of atorvastatin treatment on concentration of IGF proteins merits investigation as a mechanism to explain the worsening of glucose tolerance with statin therapy.

23-OR: The Effect of 14-Day Atorvastatin Treatment on Postprandial Glucose Metabolism in Healthy Males—A Link to Why Statin Therapy Increases the Risk of Type 2 Diabetes?

Diabetes ◽  
2019 ◽  
Vol 68 (Supplement 1) ◽  
pp. 23-OR
Author(s):  
MARTIN L. THOMASEN ◽  
DAVID P. SONNE ◽  
MARTIN L. KÅRHUS ◽  
ANDREAS BRØNDEN ◽  
BART STAELS ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Glucose Metabolism ◽  
Statin Therapy ◽  
Postprandial Glucose ◽  
Atorvastatin Treatment ◽  
Healthy Males

scholarly journals Benchmarking the cost-effectiveness of interventions delaying diabetes: a simulation study based on NAVIGATOR data

2020 ◽  
Author(s):  
Jose Leal ◽  
Shelby D Reed ◽  
Rishi Patel ◽  
Oliver Rivero-Arias ◽  
Yanhong Li ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Cost Effective ◽  
Diabetes Onset ◽  
Life Years ◽  
One Year ◽  
Design And Methods ◽  
The Impact ◽  
Trial Participants ◽  
Quality Adjusted Life

<b>Objective</b>: To estimate using the United Kingdom Prospective Diabetes Study Outcomes Model Version 2 (UKPDS-OM2) the impact of delaying type 2 diabetes onset on costs and quality-adjusted life expectancy using trial participants who developed diabetes in the NAVIGATOR study. <p><b>Research design and methods</b>: We simulated the impact of delaying diabetes onset by one to nine years, utilising data from the 3058 of 9306 NAVIGATOR trial participants who developed type 2 diabetes. Costs and utility weights associated with diabetes and diabetes-related complications were obtained for US and UK settings, with costs expressed in 2017 values. We estimated discounted lifetime costs and quality-adjusted life years (QALYs) with 95% confidence intervals.</p> <p><b>Results</b>: Gains in QALYs increased from 0.02 (95% CI: 0.01, 0.03; US setting) to 0.15 (95% CI: 0.11, 0.20; US setting) as the imposed time to diabetes onset was increased from one to nine years, respectively. Savings in complication costs increased from $1,388 (95%CI: $1,092, $1,669) for one-year delay to $8,437 (95% CI: $5603, $8630) for a delay of nine years. Interventions costing up to $567-$2,680 and £201-£947 per year would be cost-effective at $100,000 per QALY and £20,000 per QALY thresholds in the US and UK, respectively, as the modelled delay in diabetes onset was increased from one to nine years. </p> <p><b>Conclusions</b>: Simulating a hypothetical diabetes-delaying intervention provides guidance concerning the maximum cost and minimum delay in diabetes onset needed to be cost-effective. These results can inform the ongoing debate about diabetes prevention strategies and the design of future intervention studies. </p>

The effect of high dose atorvastatin therapy on lipids and lipoprotein subfractions in overweight patients with type 2 diabetes

2004 ◽  
Vol 174 (1) ◽  
pp. 141-149 ◽  
Author(s):  
J.M Lawrence ◽  
J Reid ◽  
G.J Taylor ◽  
C Stirling ◽  
J.P.D Reckless
Keyword(s):  
Type 2 Diabetes ◽  
High Dose ◽  
Lipoprotein Subfractions ◽  
Atorvastatin Therapy

scholarly journals Benchmarking the cost-effectiveness of interventions delaying diabetes: a simulation study based on NAVIGATOR data

2020 ◽  
Author(s):  
Jose Leal ◽  
Shelby D Reed ◽  
Rishi Patel ◽  
Oliver Rivero-Arias ◽  
Yanhong Li ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Cost Effective ◽  
Diabetes Onset ◽  
Life Years ◽  
One Year ◽  
Design And Methods ◽  
The Impact ◽  
Trial Participants ◽  
Quality Adjusted Life

<b>Objective</b>: To estimate using the United Kingdom Prospective Diabetes Study Outcomes Model Version 2 (UKPDS-OM2) the impact of delaying type 2 diabetes onset on costs and quality-adjusted life expectancy using trial participants who developed diabetes in the NAVIGATOR study. <p><b>Research design and methods</b>: We simulated the impact of delaying diabetes onset by one to nine years, utilising data from the 3058 of 9306 NAVIGATOR trial participants who developed type 2 diabetes. Costs and utility weights associated with diabetes and diabetes-related complications were obtained for US and UK settings, with costs expressed in 2017 values. We estimated discounted lifetime costs and quality-adjusted life years (QALYs) with 95% confidence intervals.</p> <p><b>Results</b>: Gains in QALYs increased from 0.02 (95% CI: 0.01, 0.03; US setting) to 0.15 (95% CI: 0.11, 0.20; US setting) as the imposed time to diabetes onset was increased from one to nine years, respectively. Savings in complication costs increased from $1,388 (95%CI: $1,092, $1,669) for one-year delay to $8,437 (95% CI: $5603, $8630) for a delay of nine years. Interventions costing up to $567-$2,680 and £201-£947 per year would be cost-effective at $100,000 per QALY and £20,000 per QALY thresholds in the US and UK, respectively, as the modelled delay in diabetes onset was increased from one to nine years. </p> <p><b>Conclusions</b>: Simulating a hypothetical diabetes-delaying intervention provides guidance concerning the maximum cost and minimum delay in diabetes onset needed to be cost-effective. These results can inform the ongoing debate about diabetes prevention strategies and the design of future intervention studies. </p>

scholarly journals Pharmacogenetics of statin therapy and the endothelial function parameters in patients with type 2 diabetes mellitus

2016 ◽  
Vol 19 (3) ◽  
pp. 204-211
Author(s):  
Nadezhda O. Lebedeva ◽  
Olga K. Vikulova ◽  
Alexei G. Nikitin ◽  
Minara Sh. Shamkhalova ◽  
Marina V. Shestakova ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Endothelial Function ◽  
Statin Therapy ◽  
Lipid Lowering ◽  
Before And After ◽  
Atorvastatin Therapy

Aim. To investigate the association of variation in lipid-lowering response and endothelial function (EF) parameters after atorvastatin therapy in patients with type 2 diabetes mellitus (T2DM) with genetic markers of atherosclerosis.Methods. We included 97 patients with T2DM who were prescribed atorvastatin. Fasting lipid profiles and EF parameters were assessed before and after 12 months of statin therapy. For EF evaluation, we performed pulse-wave analysis during reactive hyperaemia. The genotypes for polymorphic markers were identified by real-time polymerase chain reaction with TaqMan probes. The statistical analysis included Wilcoxon, Mann–Whitney and Kruskal–Wallis tests. P-values 0.05 were considered statistically significant.Results. With statin therapy, PPARG2Pro/Pro patients had significantly lower TC and LDL-C levels than PPARG2 Pro/Ala and PPARG2 Ala/Ala patients (TC: 20.74% vs. 4.6% and 5.61%; p = 0.04 and LDL-C: 26.00% vs. 6.11% and 7.32%; p = 0.029). Patients with АРОЕЕ4/Е4 had significantly lower TC and TG levels than other АРОЕ patients (TC: -46.25% for Е4/Е4 vs. +33.33% for Е4/Е2, +5.73% for Е3/Е2, +11.80% for Е3/Е4, -10.92% for Е3/Е3, р = 0,01; TG: -56.52% for Е4/Е4 vs. +24.43% for Е4/Е2, +19.63% for Е3/Е2, +8.05% for Е3/Е4, -20.00% for Е3/Е3, р = 0.04). The patients with GG for TNFα G(238)A and GA for TNFα G(308)A had significantly greater amplitude of post-occlusive wave increase (Apw) than patients with GA for TNFα G(238)A and GG for TNFα G(308)A (+8.16 % vs. -0.93%, р = 0,04; +44% vs. -4.4%, p = 0.004, respectively).Conclusion. PPARG2Pro12Ala and АРОЕE2/Е3/Е4 polymorphism contributed to the between-patient variability in the response to statin therapy in patients with T2DM. Significant associations of the TNFαgene polymorphism with EF in patients with T2DM suggest an important role of inflammation in the pathogenesis of MVD.

scholarly journals Further improvement in glycemic control after switching from exenatide two times per day to exenatide once-weekly autoinjected suspension in patients with type 2 diabetes: 52-week results from the DURATION-NEO-1 study

2020 ◽  
Vol 8 (1) ◽  
pp. e000773
Author(s):  
Carol H Wysham ◽  
Julio Rosenstock ◽  
Marion L Vetter ◽  
Hui Wang ◽  
Elise Hardy ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Body Weight ◽  
Phase Iii ◽  
Open Label ◽  
Open Label Study ◽  
Registration Number ◽  
Efficacy Measures ◽  
Design And Methods ◽  
To Receive

IntroductionInvestigate the effects of switching from two times per day exenatide to once-weekly exenatide administered by autoinjector (exenatide once-weekly suspension by autoinjector (QWS-AI)) or treatment with exenatide QWS-AI for 1 year.Research design and methodsIn this phase III open-label study, adults with type 2 diabetes were randomized to receive exenatide QWS-AI (2 mg) or exenatide two times per day (5 mcg for 4 weeks, followed by 10 mcg) for 28 weeks. During a subsequent non-randomized 24-week extension, patients who received exenatide two times per day were switched to exenatide QWS-AI and those randomized to exenatide QWS-AI continued this treatment. Efficacy measures included changes from baseline in glycated hemoglobin (A1C), fasting plasma glucose (FPG), and body weight.ResultsIn total, 315 patients (mean baseline A1C of 8.5%) completed the initial 28 weeks of randomized treatment with exenatide QWS-AI (n=197) or exenatide two times per day (n=118) and were included in the 24-week extension (mean A1C of 7.0% and 7.3%, respectively, at week 28). From weeks 28–52, patients who switched from exenatide two times per day to exenatide QWS-AI had additional A1C reductions of approximately 0.5% (mean A1C change from baseline of –1.4% at week 52) and further reductions from baseline in FPG. Patients who continued exenatide QWS-AI treatment for 52 weeks showed clinically relevant A1C reductions (mean A1C change from baseline of –1.3% at week 52). Body-weight reductions achieved through week 28 were sustained at week 52 in both groups. There were no unexpected safety concerns or changes in the safety profile among patients who switched from exenatide two times per day to exenatide QWS-AI or those who continued exenatide QWS-AI treatment for 52 weeks.ConclusionsSwitching from exenatide two times per day to exenatide QWS-AI resulted in further A1C reductions and maintenance of earlier decreases in body weight, while continued therapy with exenatide QWS-AI for 52 weeks maintained A1C and body-weight reductions, without additional safety or tolerability concerns.Trial registration numberNCT01652716.

scholarly journals Increased stress, weight gain and less exercise in relation to glycemic control in people with type 1 and type 2 diabetes during the COVID-19 pandemic

2021 ◽  
Vol 9 (1) ◽  
pp. e002035
Author(s):  
Merel M Ruissen ◽  
Hannah Regeer ◽  
Cyril P Landstra ◽  
Marielle Schroijen ◽  
Ingrid Jazet ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Type 1 Diabetes ◽  
Weight Gain ◽  
Glycemic Control ◽  
Perceived Stress ◽  
Medical Center ◽  
Short Term ◽  
Design And Methods

IntroductionLockdown measures have a profound effect on many aspects of daily life relevant for diabetes self-management. We assessed whether lockdown measures, in the context of the COVID-19 pandemic, differentially affect perceived stress, body weight, exercise and related this to glycemic control in people with type 1 and type 2 diabetes.Research design and methodsWe performed a short-term observational cohort study at the Leiden University Medical Center. People with type 1 and type 2 diabetes ≥18 years were eligible to participate. Participants filled out online questionnaires, sent in blood for hemoglobin A1c (HbA1c) analysis and shared data of their flash or continuous glucose sensors. HbA1c during the lockdown was compared with the last known HbA1c before the lockdown.ResultsIn total, 435 people were included (type 1 diabetes n=280, type 2 diabetes n=155). An increase in perceived stress and anxiety, weight gain and less exercise was observed in both groups. There was improvement in glycemic control in the group with the highest HbA1c tertile (type 1 diabetes: −0.39% (−4.3 mmol/mol) (p<0.0001 and type 2 diabetes: −0.62% (−6.8 mmol/mol) (p=0.0036). Perceived stress was associated with difficulty with glycemic control (p<0.0001).ConclusionsAn increase in perceived stress and anxiety, weight gain and less exercise but no deterioration of glycemic control occurs in both people with relatively well-controlled type 1 and type 2 diabetes during short-term lockdown measures. As perceived stress showed to be associated with glycemic control, this provides opportunities for healthcare professionals to put more emphasis on psychological aspects during diabetes care consultations.

scholarly journals Plasma heat shock protein response to euglycemia in type 2 diabetes

2021 ◽  
Vol 9 (1) ◽  
pp. e002057
Author(s):  
Alexander S Atkin ◽  
Abu Saleh Md Moin ◽  
Ahmed Al-Qaissi ◽  
Thozhukat Sathyapalan ◽  
Stephen L Atkin ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Heat Shock ◽  
Protein Interactions ◽  
Glucose Variability ◽  
Interacting Protein ◽  
Ubiquitin Conjugating Enzyme ◽  
Shock Proteins ◽  
Protein Response ◽  
Design And Methods

IntroductionGlucose variability is associated with mortality and macrovascular diabetes complications. The mechanisms through which glucose variability mediates tissue damage are not well understood, although cellular oxidative stress is likely involved. As heat shock proteins (HSPs) play a role in the pathogenesis of type 2 diabetes (T2D) complications and are rapidly responsive, we hypothesized that HSP-related proteins (HSPRPs) would differ in diabetes and may respond to glucose normalization.Research design and methodsA prospective, parallel study in T2D (n=23) and controls (n=23) was undertaken. T2D subjects underwent insulin-induced blood glucose normalization from baseline 7.6±0.4 mmol/L (136.8±7.2 mg/dL) to 4.5±0.07 mmol/L (81±1.2 mg/dL) for 1 hour. Control subjects were maintained at 4.9±0.1 mmol/L (88.2±1.8 mg/dL). Slow Off-rate Modified Aptamer-scan plasma protein measurement determined a panel of HSPRPs.ResultsAt baseline, E3-ubiquitin-protein ligase (carboxyl-terminus of Hsc70 interacting protein (CHIP) or HSPABP2) was lower (p=0.03) and ubiquitin-conjugating enzyme E2G2 higher (p=0.003) in T2D versus controls. Following glucose normalization, DnaJ homolog subfamily B member 1 (DNAJB1 or HSP40) was reduced (p=0.02) in T2D, with HSP beta-1 (HSPB1) and HSP-70-1A (HSP70-1A) (p=0.07 and p=0.09, respectively) also approaching significance relative to T2D baseline levels.ConclusionsKey HSPRPs involved in critical protein interactions, CHIP and UBE2G2, were altered in diabetes at baseline. DNAJB1 fell in response to euglycemia, suggesting that HSPs are reacting to basal stress that could be mitigated by tight glucose control with reduction of glucose variability.

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