isotretinoin and Insulin-Resistance

Previous studies reporting the influence of isotretinoin treatment on glucose metabolism have produced conflicting results. We therefore aimed to examine the effects of isotretinoin treatment on changes in insulin resistance and serum levels of adiponectin in patients with acne. A systematic review and meta-analysis of the literature published from the inception of isotretinoin to March 31, 2019 were conducted. In the absence of controlled trials, open-label studies on acne patients receiving isotretinoin treatment were included. Twelve studies met the inclusion criteria. The outcomes included changes in the homeostasis model assessment for insulin resistance (HOMA-IR) values and serum levels of adiponectin after isotretinoin treatment. Pooled analysis showed that HOMA-IR values did not change significantly after isotretinoin treatment (standardized mean difference [SMD] = 0.183; 95 % confidence interval [CI] = -0.004-0.371; I

Topics: Acne Vulgaris; Adiponectin; Adolescent; Adult; Dermatologic Agents; Female; Glucose; Humans; Insulin Resistance; Isotretinoin; Male; Young Adult

Isotretinoin treatment causes hypertriglyceridaemia. Insulin resistance is also associated with hypertriglyceridaemia. It is not known if isotretinoin is related to insulin resistance.. To test this hypothesis, we measured insulin resistance in 48 patients with acne vulgaris (AV) before and after 3 months of isotretinoin treatment.. In total, 48 patients with AV who attended the dermatology outpatient clinic at Kecioren Research and Training Hospital were included. Screening for biochemical parameters was performed just before the start of treatment (pretreatment) and after 4 months of isotretinoin therapy (post-treatment). The parameters measured were insulin, C peptide, fasting blood glucose, aspartate and alanine aminotransferases (AST, ALT), total cholesterol (TC), triglyceride, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein (LDL-C) and very low-density lipoprotein cholesterol. Insulin resistance was measured using the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) method.. Compared with initial values, AST, ALT, TC, LDL-C and triglyceride levels were significantly increased (P < 0.01, < 0.05, < 0.01, < 0.05 and < 0.01, respectively), but there was no significant change in fasting blood glucose, insulin, C-peptide levels or HOMA-IR.. Three months of isotretinoin treatment did not change insulin sensitivity in patients with AV. Further studies with insulin resistance models may even reveal an improvement in insulin resistance, as experimental animal studies have previously shown.

Topics: Acne Vulgaris; Adolescent; Adult; Alanine Transaminase; Aspartate Aminotransferases; Blood Glucose; Dermatologic Agents; Female; Follow-Up Studies; Humans; Insulin; Insulin Resistance; Isotretinoin; Lipids; Male; Young Adult

We previously reported that treatment of acne with 13-cis-retinoic acid causes insulin resistance and disturbances in lipid metabolism resembling those of the insulin-resistance syndrome. It is not known whether this is associated with alterations in the concentrations of serum adiponectin, an insulin-sensitising hormone secreted by adipocytes.. Eleven men (age 24+/-2 years, BMI 22.1+/-0.9 kg/m(2)) received 13-cis-retinoic acid (Roaccutan) treatment for acne for an average of 5 months. The insulin sensitivity of the subjects and concentrations of serum adiponectin were measured before, during and 1 month after the treatment by a euglycaemic-hyperinsulinaemic clamp and ELISA, respectively.. There was a reversible reduction in whole-body insulin sensitivity during therapy with 13-cis-retinoic acid. This was associated with a transient 34% increase in serum adiponectin concentration (from 5.3+/-0.9 to 7.1+/-1.2 mug/ml, p<0.05), with a return to pretreatment levels by 1 month after the end of therapy. In the pretreatment study, as well as in the study performed 1 month after the end of therapy, there was a small yet significant decrease in serum adiponectin concentration during a 4-h euglycaemic-hyperinsulinaemic clamp. This decrease was not observed in the clamp performed during treatment with 13-cis-retinoic acid.. There is a paradoxical increase in fasting serum adiponectin concentration during the 13-cis-retinoic acid-induced reduction in insulin sensitivity.

Topics: Acne Vulgaris; Adipocytes; Adiponectin; Adult; Data Interpretation, Statistical; Enzyme-Linked Immunosorbent Assay; Fasting; Glucose; Glucose Clamp Technique; Humans; Insulin; Insulin Resistance; Isotretinoin; Lipids; Male; Time Factors

Topics: Acne Vulgaris; Blood Glucose; Dermatologic Agents; Diabetes Mellitus, Type 1; Female; Humans; Insulin; Insulin Resistance; Isotretinoin; Young Adult

Vitamin A and its metabolites are key regulators of the development of adipose tissue and associated metabolic complications. The aim of this study was to determine the effect of high fat diet and 13-cis retinoic acid (13 cRA) application on metabolic parameters, adipogenic and inflammatory indicators in female Lewis rats. Female rats of Lewis strain were fed standard laboratory diet (STD) and high fat diet (HFD, 45% of saturated fatty acids) during 30 days. The groups were divided into additional 3 groups (6 rats each): two experimental groups that received 13 cRA orally on a daily basis during 30 days (7.5 mg/kg and 15 mg/kg, respectively) and the control group that was given sunflower oil. Animals were sacrificed after 60 days. Feeding of Lewis rats with chronic HFD diet with 13 cRA supplementation increased weight gain, adiposity index, dyslipidaemia, hyperleptinaemia, insulin resistance, VLDL concentrations, oxidative stress and atherogenic indices. Administration of 13 cRA in Lewis rats fed STD did not change the weight of the animals, but it slightly increased the atherogenic parameters. 13 cRA and HFD affect metabolic parameters, glucose and lipid metabolism in Lewis rats and its administration has a completely different effect on metabolism in rats fed STD, highlighting the complex role of vitamin A supplementation in obesity. Other factors, such as genetics, age, sex, adipose tissue distribution, also must be taken into consideration.

Topics: Adipogenesis; Animals; Diet, High-Fat; Female; Glucose; Insulin Resistance; Isotretinoin; Lipid Metabolism; Obesity; Oxidative Stress; Rats, Inbred Lew; Weight Gain

Recent data draw attention to the effect of body composition, insulin resistance, and adipocytokines to acne vulgaris (AV) development. The aim of this study was to assess the association of AV with insulin resistance and adipocytokine levels and to evaluate the effect of isotretinoin on insulin resistance and adipocytokine levels.. In 29 AV patients and 29 healthy volunteers, body mass index (BMI) and body fat mass (BFM), lipid, adiponectin, leptin, resistin, retinol binding protein-4 (RBP4), and insulin levels were measured and insulin resistance was assessed by HOMA-IR index in serum samples taken twice from patients before and after isotretinoin treatment.. In AV patients, pretreatment HOMA-IR and adipocytokine levels were not found to correlate with disease severity. With five months of isotretinoin treatment, higher HOMA-IR values were found (P = 0.028). Isotretinoin therapy maintained lower mean resistin levels (P = 0.016), higher mean RBP4 levels (P = 0.040), but not affected the mean adiponectin and leptin levels (P = 0.113, P = 0.125, respectively).. All data suggests that five months of isotretinoin therapy in AV patients causes insulin resistance and the increase in in-sulin resistance is not dependent on age, BMI, BFM, and lipid levels of these patients.

Topics: Acne Vulgaris; Adipokines; Adolescent; Adult; Case-Control Studies; Female; Humans; Insulin Resistance; Isotretinoin; Male; Young Adult

Isotretinoin, the drug of choice for severe acne, might be associated with a decrease in insulin sensitivity. Adiponectin is an adipose tissue-derived protein that increases insulin sensitivity. In this study, we aimed to investigate adiponectin levels in postadolescent severe acne and the effect of isotretinoin on adiponectin levels.. Participants included 18 female patients with severe acne and 18 healthy women matched for age and body mass index (BMI). Acne patients completed a 6-month isotretinoin treatment. Anthropometric measurements, serum adiponectin, lipids, fasting glucose, fasting insulin, and homeostatic model assessment for insulin resistance (HOMA-IR) were determined, and a standard 2-h oral glucose tolerance test (OGTT) was performed in healthy women once and in patients with acne before and after treatment.. At baseline, patients with acne had significantly lower serum adiponectin levels than controls. Isotretinoin treatment resulted in a significant increase in weight, BMI, and triglyceride and adiponectin levels. Glucose metabolism markers in patients with acne and controls were similar at baseline and did not change after treatment. Baseline OGTT in acne patients revealed an increased adiponectin response at 2 h, which was not present in healthy controls. Remarkably, this OGTT-induced adiponectin increment in acne patients was diminished after isotretinoin treatment.. Adiponectin levels are differently regulated in women with severe acne and healthy controls in that circulating basal levels in patients are suppressed and show an increase in response to oral glucose load. Suppression of baseline adiponectin ameliorates after 6 months of isotretinoin treatment, reaching levels similar to those of healthy controls.

Topics: Acne Vulgaris; Adiponectin; Adult; Biomarkers; Blood Glucose; Body Mass Index; Dermatologic Agents; Female; Glucose Tolerance Test; Humans; Insulin Resistance; Isotretinoin; Prognosis; Severity of Illness Index; Thinness; Young Adult

The effect of isotretinoin (ISO) on adipokines and insulin resistance has been investigated in a few studies, and the results are conflicting.. The aim of this study was to investigate the effect of ISO treatment on insulin resistance and adipokines.. Thirty-three patients with acne vulgaris and a control group of 30 healthy volunteers were included in our study. Screening for the biochemical parameters was performed just before the initiation and after 3 months of ISO treatment.. In the acne group, basal leptin levels were significantly lower (p = 0.003) and basal adiponectin levels significantly higher (p = 0.008) compared with the control group. After ISO treatment, leptin levels (p = 0.0005) decreased and adiponectin levels (p = 0.003) increased significantly. However, measurements of fasting blood glucose, insulin, C peptide, retinol-binding protein 4 (RBP4), homeostasis model assessment insulin resistance and BMI did not differ after ISO treatment.. ISO may affect leptin and adiponectin levels. It does not, however, affect insulin resistance and RBP4 levels.

Topics: Acne Vulgaris; Adiponectin; Administration, Topical; Adolescent; Dermatologic Agents; Female; Humans; Insulin Resistance; Isotretinoin; Leptin; Male; Retinol-Binding Proteins, Plasma; Young Adult

Androgens appear to play a role in the development of acne, and presence of acne is a potential marker of hyperandrogenism.. The authors evaluated androgens and insulin sensitivity markers before and after treatment with isotretinoin in women with post-adolescent severe acne who do not have hirsutism and/or ovulatory dysfunction.. Androgens, lipids, glucose and insulin levels were measured in 26 patients and 21 controls during oral glucose tolerance test. Homeostasis model assessment for insulin resistance, area under curve (AUC)glucose and AUCinsulin were calculated. Twenty patients completed a minimum of 6-month isotretinoin treatment.. All studied parameters were similar in patients and controls at baseline. Isotretinoin therapy increased body mass index and triglyceride levels without any effect on androgens or insulin sensitivity.. Severe acne itself is not associated with hyperandrogenemia and/or insulin resistance. Isotretinoin treatment does not alter serum androgens or insulin sensitivity, although it increases body weight and serum triglycerides.

Topics: Acne Vulgaris; Adolescent; Androgens; Blood Glucose; Dermatologic Agents; Female; Humans; Insulin Resistance; Isotretinoin; Young Adult

Topics: Acne Vulgaris; Administration, Oral; Adult; Cholesterol, HDL; Diabetes Mellitus, Type 1; Humans; Insulin Resistance; Isotretinoin; Male

13-cis-Retinoic acid treatment causes insulin resistance and disturbances in lipid and glucose metabolism. We studied how 13-cis-retinoic acid affects inflammatory factors and adiponectin. A total of 23 healthy patients (age, 24.9 +/- 0.9 years; body mass index, 22.6 +/- 0.7 kg/m(2)) who received 13-cis-retinoic acid treatment of acne participated in the study. The patients were studied before the treatment, after 3 months of therapy, and 1 month after the treatment. Inflammatory parameters were measured, and a 4-hour oral glucose tolerance test was performed at each visit. Treatment with 13-cis-retinoic acid resulted in a significantly elevated serum adiponectin concentration (from 24.9 +/- 2.5 to 29.4 +/- 3.6 mg/L, P < .05), hemoglobin A(1c) (from 5.27% +/- 0.05% to 5.42% +/- 0.06%, P < .01), C-peptide area under the curve (from 314.2 +/- 16.6 to 350.0 +/- 21.0 (nmol . min)/L, P < .05), and triglycerides (from 0.97 +/- 0.06 to 1.29 +/- 0.10 mmol/L, P < .05), whereas high-density lipoprotein cholesterol decreased (from 1.50 +/- 0.07 to 1.38 +/- 0.08 mmol/L, P < .05). The increase in adiponectin during 13-cis-retinoic acid therapy correlated with baseline triglycerides (r = 0.51, P < .02). Many inflammatory markers, which were nonsignificantly elevated during therapy, decreased significantly after cessation of treatment. These were C-reactive protein (median from 1.78 to 1.23 mg/L, P < .05), soluble intercellular adhesion molecule 1 (from 210 +/- 10 to 204 +/- 10 microg/L, P < .02), ceruloplasmin (256 +/- 17 to 231 +/- 17 microg/L, P < .02), and erythrocyte sedimentation rate (from 6.4 +/- 1.3 to 4.7 +/- 0.9 mm/h, P < .02). Interleukin 6 concentration was unaffected by the therapy, but decreased significantly after the treatment (from 2.18 +/- 0.46 to 1.65 +/- 0.43 ng/L, P < .05). In conclusion, although treatment with 13-cis-retinoic acid results in disturbances in glucose and lipid metabolism, paradoxically serum adiponectin concentration increases. 13-cis-Retinoic acid has profound effects on the regulation of inflammatory markers.

Topics: Adiponectin; Adult; Area Under Curve; C-Reactive Protein; Complement C3; Female; Humans; Insulin Resistance; Interleukin-6; Isotretinoin; Lipids; Male; Orosomucoid; Serum Amyloid A Protein

Topics: Acanthosis Nigricans; Acne Vulgaris; Adult; Dermatologic Agents; Female; Humans; Hyperandrogenism; Insulin Resistance; Isotretinoin; Pyoderma Gangrenosum; Syndrome

The mechanism underlying hypertriglyceridemia-associated insulin resistance in humans remains poorly understood. It has been proposed that hypertriglyceridemia only produces insulin resistance when associated with an increased lipid delivery to muscle. Accordingly, hypertriglyceridemia secondary to a decreased clearance of triglyceride-rich particles should not cause insulin resistance. To verify this hypothesis, we assessed whole body and adipose tissue insulin sensitivity in 15 healthy male volunteers before and after a 5-day administration of isotretinoin (1 mg/kg/d), a vitamin A derivative that decreases the clearance of triglyceride-rich particles. Whole body insulin-mediated glucose disposal (6,6 (2)H(2)glucose), glucose oxidation (indirect calorimetry), lipolysis ((2)H(5) glycerol), and subcutaneous adipose lipolysis (microdialysis) were evaluated during a 3-step hyperinsulinemic euglycemic clamp. Isotretinoin increased plasma triglyceride from 0.97 +/- 0.15 to 1.30 +/- 0.22 mmol/L (P <.02), but did not change whole body insulin-mediated glucose disposal and lipolysis. These observations are consistent with an isotretinoin-induced inhibition of very-low-density lipoprotein (VLDL)-triglyceride clearance. The suppression of endogenous glucose production and the reduction in subcutaneous adipose glycerol concentrations by insulin remained equally unaffected after isotretinoin administration. We conclude that the impaired clearance of triglyceride-rich particles secondary to a 5-day isotretinoin administration does not impair insulin-mediated antilipolysis or glucose disposal. The data support the concept that hypertriglyceridemia-associated insulin resistance develops primarily when triglyceride production is increased.

Topics: Adipose Tissue; Adult; Blood Glucose; Calorimetry, Indirect; Deuterium; Epinephrine; Fasting; Glucose Clamp Technique; Glycerol; Humans; Hypertriglyceridemia; Insulin; Insulin Resistance; Isotretinoin; Kinetics; Lipolysis; Lipoproteins, VLDL; Male; Microdialysis; Oxidation-Reduction; Triglycerides

To investigate the effect of transcription-modulating drugs, fenofibrate and isotretinoin, on metabolic profile, insulin sensitivity of adipose and muscle tissues and gene expression in a genetic model of insulin resistance syndrome, polydactylous rat strain (PD/Cub).. Administration of fenofibrate (100 mg/kg/day), isotretinoin (30 mg/kg/day) or vehicle to adult male PD/Cub rats fed standard laboratory chow for 15 days.. Parameters of lipid and carbohydrate metabolism-oral glucose tolerance test, serum concentrations of insulin, triglycerides (TG), free fatty acids (FFA), glycerol, total cholesterol (CH); morphometric variables, in vitro insulin sensitivity of adipose and muscle tissues, catecholamine-stimulated lipolysis and the expression of ApoC-III and Hnf-4 genes in liver.. Both experimental groups displayed an increase in adiposity with contrasting effects on TG (lowered by fenofibrate and increased by isotretinoin) and gene expression (no change in fibrate-treated rats and increased expression of ApoC-III and Hnf-4 in isotretinoin-treated group). Fenofibrate-treated rats also showed decreased concentrations of FFA and CH with concomitant decrease of catecholamine-induced lipolysis in adipocytes, but also hyperinsulinemia and the highest insulin/glucose ratio. Isotretinoin increased glycerol concentrations and decreased the insulin sensitivity of peripheral tissues.. The PD/Cub rat showed a distinct pharmacogenetic reaction to fenofibrate and isotretinoin administration. Several lines of evidence now implicate specific variant(s) of ApoC-III and/or ApoA-V alleles as responsible for the dyslipidemia observed in this genetic model. The PD/Cub strain may also serve as a pharmacogenetic model for dissection of the retinoid-induced hypertriglyceridemia.

Topics: Adipose Tissue; Animals; Apolipoprotein C-III; Apolipoproteins C; Disease Models, Animal; DNA-Binding Proteins; Fenofibrate; Gene Expression Regulation; Glucose Tolerance Test; Hepatocyte Nuclear Factor 4; Hypertriglyceridemia; Hypolipidemic Agents; Insulin; Insulin Resistance; Isotretinoin; Lipids; Lipolysis; Male; Muscle, Skeletal; Obesity; Organ Size; Phosphoproteins; Rats; Rats, Inbred Strains; Transcription Factors