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

Narayanan, Ram Prakash; Gittins, Matthew; Siddals, Kirk; Oliver, R.; Hudson, Julie E; White, Anne; Durrington, Paul N.; Davies, R.R.; Rutter, Martin K.; Gibson, John M.

doi:10.1530/eje-12-0844

Cited by 12 publications

(6 citation statements)

References 29 publications

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“…Nevertheless, we have to keep in mind that these results were obtained from subjects who belonged to different study populations with different patient's medical records. Recent data showed that many drugs may affect the IGF system like ACE inhibitors (drugs are used for management hypertension) [57] and statins [58, 59] (drugs are used for management dyslipidemia). Thus, concurrent drug usage may be a confounder affecting the outcomes.…”

Section: Discussionmentioning

confidence: 99%

Effect of Calcium and Vitamin D Supplements as an Adjuvant Therapy to Metformin on Menstrual Cycle Abnormalities, Hormonal Profile, and IGF-1 System in Polycystic Ovary Syndrome Patients: A Randomized, Placebo-Controlled Clinical Trial

Kadoura

Alhalabi

Nattouf

2019

Advances in Pharmacological Sciences

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Objective. This study aims to investigate the effect of combining calcium and vitamin D supplements with metformin on menstrual cycle abnormalities, gonadotropins, and IGF-1 system in vitamin D-deficient/insufficient PCOS women. Study Design. This is a randomized, placebo-controlled clinical trial. Setting. This study was performed in Damascus University of Obstetrics and Gynecology Hospital and Orient Hospital, in Damascus, Syria. Materials and Methods. Forty PCOS women with 25-OH-vitamin D < 30 ng/ml were randomly assigned to take either metformin (1500 mg/daily) plus placebo or metformin (1500 mg/daily) plus calcium (1000 mg/daily) and vitamin D3 (6000 IU/daily) orally for 8 weeks. Serum levels of gonadotropins (luteinizing hormone (LH) and follicle-stimulating hormone (FSH)), insulin-like growth factor-1 (IGF-1), and insulin-like growth factor binding protein-1 (IGFBP-1) were detected at the baseline during the early follicular phase of a spontaneous or induced menstrual cycle and after 8 weeks of intervention (except for the final gonadotropins levels which were assayed from samples obtained during the early follicular phase of a spontaneous menstrual cycle). Results. Thirty-four patients (85%) completed the study. After 8 weeks of intervention, calcium and vitamin D co-supplementation led to a significant increase in 25-OH-vitamin D levels and calcium levels in the supplementation group compared to the other group (change in 25-OH-vitamin D levels: +19.38 ± 7.78 vs +0.11 ± 4.79 ng/ml, respectively; p value=0.0001) (change in calcium levels: +0.83 ± 0.82 vs +0.01 ± 0.86 mg/dl, respectively; p value=0.014). An improvement in menstrual cycle irregularity was detected in 38.5% and 58.8% of patients in metformin-placebo group and metformin-calcium-vitamin D group, respectively; but the change was statistically significant only in the supplementation group (p value=0.002). Nevertheless, the means of changes from baseline in gonadotropins levels (serum levels of LH, FSH, and LH to FSH ratio) and the studied parameters of IGF-1 system (serum levels of IGF-1, IGFBP-1, and IGF-1 to IGFBP-I ratio) did not differ significantly between the two groups. Conclusions. Calcium and vitamin D supplements can support metformin effect on regulation of menstrual cycle irregularity in vitamin D-deficient/insufficient PCOS patients, but this effect is not associated with any significant changes in gonadotropins or IGF-1 system. These results suggest a possible role of calcium and vitamin D supplements in managing PCOS. However, further studies are needed to identify the underlying mechanisms. The Clinical Trial Registration Number is NCT03792984.

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Section: Discussionmentioning

confidence: 99%

Effect of Calcium and Vitamin D Supplements as an Adjuvant Therapy to Metformin on Menstrual Cycle Abnormalities, Hormonal Profile, and IGF-1 System in Polycystic Ovary Syndrome Patients: A Randomized, Placebo-Controlled Clinical Trial

Kadoura

Alhalabi

Nattouf

2019

Advances in Pharmacological Sciences

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“…Изменение концентрации ИРФСП1 зависело от дозы аторвастатина: высокие его дозы (80 мг) снижали уровень ИРФСП1, низкие (10 мг) -повышали. Причины этого предположительно связаны с влиянием статинов на углеводный обмен [16]. Исследования с участием пациентов без диабета не проводились.…”

Section: обсуждение основного результата исследованияunclassified

Statin administration is associated with higher IGF-1 levels in patients without diabetes mellitus

Shpagina¹,

Бондаренко²,

Колесникова³

2018

Probl Endokrinol (Mosk)

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Background: Research makes it clear that the IGF-1 level correlates with cardiovascular disease, chronic heart failure, and mortality. Yet, little is known about the effect of statins on IGF-1. Aims: to evaluate the effect of statin treatment on IGF-1 and its association with a cardiovascular risk. Material and methods: The study included 115 patients (mean age, 55.8±6.1 years) who either were overweight or had mild obesity (body mass index 28.6±3.8 kg/m2) without diabetes. Group 1 consisted of 70 patients with verified coronary artery disease receiving statin therapy; group 2 included 45 healthy subjects. Coronary angiography and treadmill test were used to diagnose coronary artery disease. Impaired glucose tolerance and total cholesterol, triglycerides, LPHD, LPLD, fibrinogen, and IGF-1 levels were evaluated in all the subjects. Heart chamber geometry was assessed by echocardiography. Results: The IGF-1 level was significantly higher in group 1 compared to the control group (196 and 167 ng/ml, respectively; р=0.014). Serum levels of IGF-1 were associated with duration of statin therapy (R=0.311; p=0.000), stage of hypertension (R=0.187; p=0.04), fibrinogen (R=0.274; p=0.033), TG (R=0.316; p=0.006), total cholesterol (R=–0.213; p=0.016), LPLD (R=–0.184; p=0.038), smoking (R=0.3; p=0.009), ejection fraction (R=0.298; p=0.041), end-diastolic volume (R=0.422; p=0.036), end-systolic volume (R=0.407; p=0.042), end-diastolic dimension (R=0.27; p=0.014), interventricular septal thickness (R=0.247; p=0.02), and left ventricular posterior wall thickness (R=0.258; p=0.019). Rosuvastatin dose positively correlated with the IGF-1 level (R=0.521; p=0.028). Conclusions: Statin administration is associated with higher IGF-1 levels in patients without diabetes. High IGF-1 level correlates with the risk factors of coronary artery disease: hypertension, lipid profile, and fibrinogen level and has an adverse effect on chronic heart failure by altering the cardiac remodeling.

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“…23 Insulin-like growth factor proteins have been shown to decrease in a dosedependent fashion after atorvastatin therapy, providing another potential mechanism whereby statins could worsen glucose tolerance. 24 Finally, in an animal model, statin-induced myopathy is associated with an increase in insulin resistance in muscle. 25 …”

Section: Statins and Nodmentioning

confidence: 99%

Cardiovascular drugs that increase the risk of new-onset diabetes

Barter

Waters

2014

American Heart Journal

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The prevalence of type 2 diabetes is increasing worldwide, and diabetes is a strong adverse prognostic factor among patients with cardiovascular (CV) disease. Four classes of drugs that are commonly used for CV risk reduction, statins, niacin, thiazide diuretics, and ß-blockers, have been shown to increase the risk of new-onset diabetes (NOD) by 9% to 43% in meta-analyses or large-scale clinical trials. Clinical predictors for drug-related NOD appear to be similar to the predictors that have been described for NOD unrelated to drugs: fasting blood glucose N100 mg/dL and features of the metabolic syndrome such as body mass index N30 kg/m 2 , serum triglycerides N150 mg/dL, and elevated blood pressure, among others. The mechanisms whereby these drugs increase the risk of NOD are incompletely understood, although different hypotheses have been suggested. Lifestyle intervention consisting of diet and exercise has been shown in multiple studies to reduce the risk of NOD by approximately 50%, with persistent benefit during long-term follow-up. In patients at high risk for NOD, niacin should be avoided, and for hypertension, an angiotensin-converting enzyme inhibitor or even a ß 1 -selective blocker might be a better choice than a standard ß-blocker. For thiazide diuretics and particularly statins, benefit in terms of CV event reduction outweighs the risk of NOD. (Am Heart J 2014;167:421-8.) Worldwide, the prevalence of type 2 diabetes continues to increase rapidly, with more than 371 million cases in the year 2012.1 Diabetes is thus becoming a more prevalent risk factor for cardiovascular (CV) disease, and a higher proportion of patients with CV disease have diabetes. Among patients with CV disease, diabetes is a strong adverse prognostic factor. Controlling for blood pressure, low-density lipoprotein cholesterol, and glycosylated hemoglobin (HbA 1C ) levels reduces CV risk in patients with diabetes; however, only a minority of them successfully attains these multiple goals, 2 despite recent increasing use of drug treatment. 3Within this context, it is troublesome that some of the drugs used to reduce CV risk have been shown either to increase the risk of new-onset diabetes (NOD) or to interfere with glucose control in patients with established diabetes. The purpose of this article is to review clinical trial data for 4 commonly used classes of drugs, statins, niacin, thiazide diuretics, and ß-blockers. For each drug class, an attempt will be made to quantify the benefit of treatment and potential harm based on clinical trial results and meta-analyses of trials. The data from these sources documenting the increased risk of NOD with these drugs are summarized in Figure 1. Predictors of NODStudies in different populations have consistently identified the same cluster of risk factors for NOD. Impaired fasting glucose (IFG; defined as a fasting blood sugar from 100 to 125 mg/dL), a family history of diabetes, and features of the metabolic syndrome are associated with an increased risk of NOD.4 Lifestyle factors, low bo...

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

Cited by 12 publications

References 29 publications

Effect of Calcium and Vitamin D Supplements as an Adjuvant Therapy to Metformin on Menstrual Cycle Abnormalities, Hormonal Profile, and IGF-1 System in Polycystic Ovary Syndrome Patients: A Randomized, Placebo-Controlled Clinical Trial

Effect of Calcium and Vitamin D Supplements as an Adjuvant Therapy to Metformin on Menstrual Cycle Abnormalities, Hormonal Profile, and IGF-1 System in Polycystic Ovary Syndrome Patients: A Randomized, Placebo-Controlled Clinical Trial

Statin administration is associated with higher IGF-1 levels in patients without diabetes mellitus

Cardiovascular drugs that increase the risk of new-onset diabetes

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