Clinical outcome of metformin treatment in patients of acanthosis nigricans with insulin resistance

Background: Acanthosis nigricans (AN) is known to be associated with obesity, insulin resistance (IR) and other systemic morbid conditions. Proper treatment modalities of AN has not been established yet. Metformin may have some therapeutic effects on AN by reducing IR. Objective of the study was to examine the effect of metformin on AN in insulin resistant cases.Methodology and Results: This prospective, controlled trial was conducted in Dermatology OPD of BIRDEM General Hospital, Dhaka from September 2012 to August 2013. All the participants of the study had clinical presentation of AN on different anatomic locations such as neck, axilla, elbow, knuckle and knee and biochemical evidence of IR. Participants were of either sex with age ranging from 18 to 80 years. Any case who had contraindications to metformin therapy were excluded. Severity of AN was examined and assessed by a quantitative scale for measuring acanthosis nigricans. After detecting IR by Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), cases and controls were selected by random sampling method. Randomization was done for metformin in ratio of 2:1. Every third patient was a control. Forty study participants were assigned to receive tablet metformin 500mg thrice daily after meal for three months and twenty control participants were continued on their existing therapy. To maintain a static metabolic status, patients were allowed to remain with their previous diet and lifestyle habit. After 3 months of metformin therapy, improvement was assessed and was compared with control group.Mean age of the participants in case of male: 19.75±2.36 and in case of female: 26.58±9.38, M:F= 1:14, BMI of male: 32.15±4.15 and female: 33.18± 8.05. Mean baseline neck severity score of AN: 3.57 ± 0.78 and after metformin therapy: 2.65 ± 1.02, t-test value: 4.53. Baseline neck texture score of AN: 1.87±0.80, after metformin therapy: 1.25 ± 0.86, ttest value: 3.30. Baseline AN on axilla: 3.05 ± 0.94, after metformin therapy: 2.10 ± 0.98, ttest value: 4.56. Significant improvement of AN was observed clinically on neck and axilla (P<0.005) when compared with control. However, in case of AN on knuckle, elbow and knee, improvement rates were not statistically significant. No side-effect except nausea in 4 patients was reported during study period.Conclusion: Metformin therapy for AN with IR had a significant beneficial effect clinically and was safe and well-tolerated. The effect was more pronounced in neck and axilla.IMC J Med Sci 2016; 10(1): 18-23

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VITAMIN D AND HSCRP LEVELS AMONG INSULIN RESISTANT PATIENTS IN A TERTIARY CARE HOSPITAL AT KOLKATA.

International Journal of Medical and Biomedical Studies ◽

10.32553/ijmbs.v4i1.901 ◽

2020 ◽

Vol 4 (1) ◽

Author(s):

Kaushik Kar ◽

Satwika Sinha

Keyword(s):

Insulin Resistance ◽

Vitamin D ◽

Tertiary Care ◽

Serum Vitamin ◽

High Sensitivity ◽

Model Assessment ◽

Care Hospital ◽

Serum Vitamin D ◽

Insulin Resistant ◽

Homeostatic Model Assessment

Vitamin D deficiency probably takes a part in the development of insulin resistance. Insulin resistance also markedly affects the obese population. High-sensitivity C-reactive protein is a sensitive marker of subclinical inflammation and strongly predicts increased risks of insulin resistance. In this study, 123 obese persons were selected, and homeostatic model assessment (HOMA-IR) was measured in them. Serum Vitamin D and hsCRP were also measured in all participants. Among participants with HOMA-IR >2.7, significantly higher BMI, serum hsCRP and lower vitamin D were observed; Keywords: Obesity, BMI, HOMA-IR, Vitamin D, hsCRP.

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Surgical site peptidylarginine deaminase 4 (PAD4), a biomarker of NETosis, correlates with insulin resistance in total joint arthroplasty patients: A preliminary report

PLoS ONE ◽

10.1371/journal.pone.0245594 ◽

2021 ◽

Vol 16 (1) ◽

pp. e0245594

Author(s):

Vitor F. Martins ◽

Christopher R. Dobson ◽

Maedha Begur ◽

Jesal Parekh ◽

Scott T. Ball ◽

...

Keyword(s):

Insulin Resistance ◽

Skeletal Muscle ◽

Wound Healing ◽

Total Joint Arthroplasty ◽

Joint Arthroplasty ◽

Neutrophil Extracellular Trap ◽

Wound Complications ◽

Model Assessment ◽

Insulin Resistant ◽

Homeostatic Model Assessment

While obesity and insulin resistance are known risk factors for wound complications after total joint arthroplasty (TJA), the biologic causes remain to be elucidated. Recently, neutrophil extracellular trap formation (NETosis) was identified as a mediator of delayed wound healing in insulin resistant states. Herein, we explored the relationship between obesity, insulin resistance and biomarkers of NET formation in TJA subjects. We enrolled 14 obese (body mass index [BMI]≥30 kg/m2), and 15 lean (BMI<30 kg/m2) subjects undergoing primary knee or hip TJA. On the day of surgery, skeletal muscle proximal to the operated joint and plasma were collected. Protein abundance of NETosis biomarkers, peptidylarginine deaminase 4 (PAD4) and neutrophil elastase (NE) were assessed in skeletal muscle by immunoblotting and metabolic parameters (glucose, insulin, triglycerides, free fatty acids) and cell-free double-stranded DNA (cf-dsDNA) were assessed in plasma and were correlated with obesity and insulin resistance (as measured by the homeostatic model assessment for insulin resistance). When comparing lean and obese subjects, there were no significant differences in plasma cf-dsDNA or skeletal muscle NE or PAD4 abundance. In contrast, skeletal muscle PAD4 abundance, but not NE or plasma cf-dsDNA, was positively correlated with insulin resistance. Compared to insulin sensitive subjects, insulin resistant TJA subjects have higher expression of PAD4 at the surgical site and therefore may have higher rates of NET formation, which may lead to delayed surgical site wound healing.

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Hypothalamic miR-1983 Targets Insulin Receptor β and the Insulin-mediated miR-1983 Increase Is Blocked by Metformin

Endocrinology ◽

10.1210/endocr/bqab241 ◽

2021 ◽

Vol 163 (1) ◽

Author(s):

Jennifer A Chalmers ◽

Prasad S Dalvi ◽

Neruja Loganathan ◽

Emma K McIlwraith ◽

Leigh Wellhauser ◽

...

Keyword(s):

Insulin Resistance ◽

Insulin Receptor ◽

Protein A ◽

Neuronal Cell ◽

Model Assessment ◽

Messenger Rnas ◽

Insulin Resistant ◽

Homeostatic Model Assessment

Abstract MicroRNAs (miRNAs) expressed in the hypothalamus are capable of regulating energy balance and peripheral metabolism by inhibiting translation of target messenger RNAs (mRNAs). Hypothalamic insulin resistance is known to precede that in the periphery, thus a critical unanswered question is whether central insulin resistance creates a specific hypothalamic miRNA signature that can be identified and targeted. Here we show that miR-1983, a unique miRNA, is upregulated in vitro in 2 insulin-resistant immortalized hypothalamic neuronal neuropeptide Y-expressing models, and in vivo in hyperinsulinemic mice, with a concomitant decrease of insulin receptor β subunit protein, a target of miR-1983. Importantly, we demonstrate that miR-1983 is detectable in human blood serum and that its levels significantly correlate with blood insulin and the homeostatic model assessment of insulin resistance. Levels of miR-1983 are normalized with metformin exposure in mouse hypothalamic neuronal cell culture. Our findings provide evidence for miR-1983 as a unique biomarker of cellular insulin resistance, and a potential therapeutic target for prevention of human metabolic disease.

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Association of Serum Levels of Zinc, Copper, and Iron with Risk of Metabolic Syndrome

Nutrients ◽

10.3390/nu13020548 ◽

2021 ◽

Vol 13 (2) ◽

pp. 548

Author(s):

Chia-Wen Lu ◽

Yi-Chen Lee ◽

Chia-Sheng Kuo ◽

Chien-Hsieh Chiang ◽

Hao-Hsiang Chang ◽

...

Keyword(s):

Insulin Resistance ◽

Metabolic Syndrome ◽

Linear Models ◽

Serum Zinc ◽

Serum Levels ◽

Least Square ◽

Model Assessment ◽

Serum Concentrations ◽

Metabolic Factors ◽

Homeostatic Model Assessment

The association between serum concentrations of zinc, copper, or iron and the risk of metabolic syndrome are inconclusive. Therefore, we conduct a case-control study to explore the relationship between serum levels of zinc, copper, or iron and metabolic syndrome as well as each metabolic factor and insulin resistance. We enrolled 1165 adults, aged ≥ 40 (65.8 ± 10) years in a hospital-based population to compare the serum levels of zinc, copper, and iron between subjects with and without metabolic syndrome by using multivariate logistic regression analyses. The least square means were computed by general linear models to compare serum concentrations of zinc, copper, and iron in relation to the number of metabolic factors. The mean serum concentrations of zinc, copper, and iron were 941.91 ± 333.63 μg/L, 1043.45 ± 306.36 μg/L, and 1246.83 ± 538.13 μg/L, respectively. The odds ratios (ORs) of metabolic syndrome for the highest versus the lowest quartile were 5.83 (95% CI: 3.35–10.12; p for trend < 0.001) for zinc, 2.02 (95% CI: 1.25–3.25; p for trend: 0.013) for copper, and 2.11 (95% CI: 1.24–3.62; p for trend: 0.021) for iron after adjusting for age, sex, personal habits, body mass index, and homeostatic model assessment insulin resistance. Additionally, the serum zinc, copper, and iron concentrations increased as the number of metabolic factors rose (p for trend < 0.001). This was the first study to clearly demonstrate that higher serum levels of zinc, copper, and iron were associated with the risk of metabolic syndrome and the number of metabolic factors independent of BMI and insulin resistance.

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Metabolic syndrome and insulin resistance in pre-pubertal children with psoriasis

European Journal of Pediatrics ◽

10.1007/s00431-020-03924-w ◽

2021 ◽

Author(s):

Francesca Caroppo ◽

Alfonso Galderisi ◽

Laura Ventura ◽

Anna Belloni Fortina

Keyword(s):

Metabolic Disease ◽

Insulin Resistance ◽

Metabolic Syndrome ◽

Model Assessment ◽

Limited Data ◽

Single Center ◽

Increased Risk ◽

High Prevalence ◽

Homeostatic Model Assessment ◽

Homeostatic Model

AbstractPsoriasis in adults is associated with an increased risk of metabolic disease. Various cardiometabolic comorbidities have been reported in childhood psoriasis, but only a few studies have analyzed the prevalence of metabolic syndrome. We performed a single-center prospective study investigating the prevalence of metabolic syndrome and insulin resistance in children with psoriasis. The prevalence of metabolic syndrome was evaluated in 60 pre-pubertal children with psoriasis (age: 3–10 years), accordingly to recently established criteria for the diagnosis of metabolic syndrome in children. Insulin resistance was considered altered when the homeostatic model assessment (HOMA-IR) for insulin resistance was ≥ 90th sex- and age-specific percentile and HOMA 2-IR was > 1.8. Eighteen (30%) children with psoriasis were found to have metabolic syndrome. Sixteen (27%) children were found to have insulin resistance.Conclusion: Our data underline the importance of assessing metabolic syndrome not only in adults and adolescents but also in young children with psoriasis. What is Known:• Psoriasis in adults is strongly associated with metabolic disease and insulin resistance.• Very limited data are available on the prevalence of metabolic syndrome and insulin resistance in pre-pubertal children with psoriasis. What is New:• This study reports that in pre-pubertal children with psoriasis, there is a high prevalence of metabolic syndrome and insulin resistance.• In children with psoriasis metabolic syndrome risk factors should be assessed.

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P1279INSULIN RESISTANCE IN HEMODIALYSIS PATIENS

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfaa142.p1279 ◽

2020 ◽

Vol 35 (Supplement_3) ◽

Author(s):

Pavel Filinyuk ◽

Aleksander Rumyantsev

Keyword(s):

Insulin Resistance ◽

Systemic Inflammation ◽

Clinical Manifestations ◽

Biological Response ◽

Fold Increase ◽

Atherogenic Dyslipidemia ◽

Model Assessment ◽

Peripheral Tissues ◽

Reactive Protein ◽

Homeostatic Model Assessment

Abstract Background and Aims insulin resistance (IR) is a decrease in the biological response of sensitive tissues to insulin. IR is known as an adverse risk factor in cardiovascular disease, which largely determines the prognosis of patients receiving hemodialysis (HD). But this issue is not well understood. For the screening of IR, special indices have been developed that characterize the sensitivity of tissues to insulin. The aim of the study was to compare the methods of screening for IR in patients receiving HD in relation to the markers of systemic inflammation and atherogenic dyslipidemia (AtD). Method 124 patients receiving HD for 75.4 ± 44.5 months were examined including 66 men and 58 women aged 57.6 ± 13.6 years. For IR screening, the Homeostatic Model Assessment-1 and 2 indices (HOMA-1 and HOMA-2), the Quantitative Insulin Sensitivity Check Index (QUICKI) and triglycerides / glucose (Tri/G) were used. Patients were examined in accordance with the recommendations of KDIGO. Data analysis was carried out using “STATISTICA 10.0”. Results fasting insulin levels were elevated in 19% of patients. But, the calculated indices were consistent with the idea that IR is much more common. So, the IR index in the HOMA -1 model was increased in 47%, in the HOMA -2 model - in 33%, in the QUICKI model - in 36%, the TriH indicator - in 91%. The sensitivity of peripheral tissues in the HOMA-1 and HOMA-2 models was equally reduced by 35-40%. The results of the correlation analysis between indicators of IR and plasma concentration of C-reactive protein and lipid profile are presented in table 1. Informativeness of IR indicators depending on the presence of obesity is presented in table 2 We were also interested in whether insulin resistance affects the development of clinical manifestations of atherosclerosis, cardiac arrhythmias, and heart failure. An analysis of this relationship did not reveal. Only the IR index in the HOMA-1 model with a value of more than 2.7 units was associated with a 4.5-fold increase in the risk of developing clinical manifestations of atherosclerotic lesions (χ2 = 4.582 p = 0.032). Statistically significant it was only in men. Given our data, perhaps IR is one of the reasons for the higher morbidity and mortality of men at HD. Conclusion a comparison of IR models allows us to distinguish HOMA-2 as the most accurate index. The highest correlation with systemic inflammation and AtD was in the HOMA-1 and HOMA-2 indices.

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Pharyngeal collapsibility during sleep is elevated in insulin-resistant females with morbid obesity

European Respiratory Journal ◽

10.1183/13993003.00918-2015 ◽

2016 ◽

Vol 47 (6) ◽

pp. 1718-1726 ◽

Cited By ~ 1

Author(s):

Oscar L. Llanos ◽

Panagis Galiatsatos ◽

Edmarie Guzmán-Vélez ◽

Susheel P. Patil ◽

Philip L. Smith ◽

...

Keyword(s):

Insulin Resistance ◽

Fasting Glucose ◽

Sleep Apnoea ◽

Model Assessment ◽

Rapid Eye Movement Sleep ◽

Homeostasis Model Assessment ◽

Tonsillar Hypertrophy ◽

Insulin Resistant ◽

Bariatric Patients ◽

Respiratory Disturbance

Insulin resistance is associated with sleep apnoea, leading us to hypothesise that it is also associated with elevations in pharyngeal collapsibility, even in the absence of sleep apnoea.90 bariatric patients were characterised for sleep apnoea, pharyngeal collapsibility and insulin resistance. Patients with a respiratory disturbance index (RDI) >10 events·h−1, diabetes mellitus, tonsillar hypertrophy and pulmonary disease were excluded. The remaining 14 females underwent collapsibility measurements (passive critical pressure, Pcritp) during non-rapid eye movement sleep. The homeostasis model assessment (HOMA) index, a measure of insulin resistance, was derived from measurements of fasting glucose and insulin levels, and compared to Pcritp.Groups with high Pcritp compared to low Pcritp did not differ in age, body mass index or RDI. HOMA and insulin were elevated in the high Pcritp group compared to the low Pcritp group (p<0.02). Pcritp correlated with HOMA (Spearman's ρ=0.565, 95% CI 0.104–0.862; p=0.035) and insulin (Spearman's ρ=0.609 95% CI 0.196–0.835; p=0.021).Obese insulin-resistant subjects without frank diabetes or sleep apnoea demonstrate preclinical elevations in pharyngeal collapsibility, which may increase their susceptibility to sleep apnoea. Our findings suggest that insulin resistance could play a significant role in sleep apnoea pathogenesis by generating requisite elevations in pharyngeal collapsibility.

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The Relationship between Insulin Resistance and the Cardiovascular Biomarker Growth Differentiation Factor-15 in Obese Patients

Clinical Chemistry ◽

10.1373/clinchem.2010.153726 ◽

2011 ◽

Vol 57 (2) ◽

pp. 309-316 ◽

Cited By ~ 73

Author(s):

Greisa Vila ◽

Michaela Riedl ◽

Christian Anderwald ◽

Michael Resl ◽

Ammon Handisurya ◽

...

Keyword(s):

Insulin Resistance ◽

Gastric Bypass ◽

Insulin Sensitivity ◽

Oral Glucose ◽

Model Assessment ◽

Obese Patients ◽

Growth Differentiation Factor 15 ◽

Homeostatic Model Assessment ◽

Homeostatic Model ◽

The Relationship

BACKGROUND Growth differentiation factor-15 (GDF-15) is a stress-responsive cytokine linked to obesity comorbidities such as cardiovascular disease, inflammation, and cancer. GDF-15 also has adipokine properties and recently emerged as a prognostic biomarker for cardiovascular events. METHODS We evaluated the relationship of plasma GDF-15 concentrations with parameters of obesity, inflammation, and glucose and lipid metabolism in a cohort of 118 morbidly obese patients [mean (SD) age 37.2 (12) years, 89 females, 29 males] and 30 age- and sex-matched healthy lean individuals. All study participants underwent a 75-g oral glucose tolerance test; 28 patients were studied before and 1 year after Roux-en-Y gastric bypass surgery. RESULTS Obese individuals displayed increased plasma GDF-15 concentrations (P < 0.001), with highest concentrations observed in patients with type 2 diabetes. GDF-15 was positively correlated with age, waist-to-height ratio, mean arterial blood pressure, triglycerides, creatinine, glucose, insulin, C-peptide, hemoglobin A1c, and homeostatic model assessment insulin resistance index and negatively correlated with oral glucose insulin sensitivity. Age, homeostatic model assessment index, oral glucose insulin sensitivity, and creatinine were independent predictors of GDF-15 concentrations. Roux-en-Y gastric bypass led to a significant reduction in weight, leptin, insulin, and insulin resistance, but further increased GDF-15 concentrations (P < 0.001). CONCLUSIONS The associations between circulating GDF-15 concentrations and age, insulin resistance, and creatinine might account for the additional cardiovascular predictive information of GDF-15 compared to traditional risk factors. Nevertheless, GDF-15 changes following bariatric surgery suggest an indirect relationship between GDF-15 and insulin resistance. The clinical utility of GDF-15 as a biomarker might be limited until the pathways directly controlling GDF-15 concentrations are better understood.

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