Does insulin resistance co-exist with glucocorticoid resistance in the metabolic syndrome? Studies comparing skin sensitivity to glucocorticoids in individuals with and without acanthosis nigricans

Surujpal Teelucksingh,Lexley Pinto Pereira,Terence Seemungal,Sarada Jaimungal,Shivananda Nayak

doi:10.1186/1475-2840-11-31

Surujpal Teelucksingh, Lexley Pinto Pereira + Show 3 more

Open Access

https://doi.org/10.1186/1475-2840-11-31

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Abstract

BackgroundThe metabolic syndrome is associated with increased risk for both diabetes and coronary artery disease, which insulin resistance alone does not satisfactorily explain. We propose an additional and complementary underlying mechanism of glucocorticoid resistance.ResultsUsing acanthosis nigricans (AN) and skin vasoconstrictor (SVC) response to topically applied beclomethasone dipropionate as markers of insulin and glucocorticoid resistance, respectively, we compared anthropometric, biochemical, pro-inflammatory markers and the SVC response in subjects with AN in two studies: STUDY 1 was used to compare subjects with AN (Grade 4, n = 32), with those without AN (n = 68) while STUDY 2 compared these responses among a cross-section of diabetic patients (n = 109) with varying grades of AN (grade 0, n = 30; grade 1, n = 24; grade 2, n = 18; grade 3, n = 25; grade 4, n = 12).FindingsIn both studies there was an inverse relationship between AN Grade 4 and the SVC response, (P < 0.001). In STUDY 1, AN Grade 4 was associated with age, waist circumference, BMI, fasting blood glucose, plasma lipids and hs-CRP (P < 0.05). SVC was an independent predictor of CRP and those with combined AN and a negative SVC response, CRP levels were highest. In Study 2 when the SVC response in subjects with type 2 diabetes mellitus with varying degrees of AN was studied, it showed that for any degree of AN, the SVC response is more likely to be negative and was independent of gender and ethnicity.ConclusionAn absent SVC response represents a new biomarker for the metabolic syndrome and the exaggerated inflammatory response, which characterizes the metabolic syndrome, may be an outcome of deficient glucocorticoid action in vascular tissue.

Highlights

Cardiovascular disease, the leading cause of death in developed countries for many decades, is gaining fresh momentum from the pandemic of obesity which is an emergent major public health problem in developing countries globally [1]
An absent skin vasoconstrictor (SVC) response represents a new biomarker for the metabolic syndrome and the exaggerated inflammatory response, which characterizes the metabolic syndrome, may be an outcome of deficient glucocorticoid action in vascular tissue
Genetic susceptibility to cardiovascular disease has been linked to polymorphisms of the glucocorticoid receptor gene which in the case of haplotype 3, a common genetic variant, gives rise to a highly active proinflammatory system as evidenced by serum C-reactive protein (CRP) which is attributed to diminished sensitivity to cortisol[12]

Summary

Results

Study 1 Baseline characteristics A total of 100 patients were recruited with mean (SD) age 29.90 (11.87) years, weight 72.99 (21.09) Kg, BMI 25.91 (7.41) kg/m2. AN and SVC In Study 1, while 76% of those without AN responded with a positive SVC only 19% of subjects with AN grade 4 showed a similar response. 1 there is an obvious tendency for AN grade 4 subjects to have SVC response of grade 0 CRP and AN and SVC Table 6 shows the relationship between inflammatory markers for those with and without acanthosis nigricans. For the 100 subjects in study 1 there was significant correlation between CRP and the following variables (rho, p < 0.001): age (0.475), waist circumference (0.451), weight (0.397), AN (0.522), SVC graded as zero or above zero (-0.355). The magnitude of the test of trend was similar in both Study 1 and Study 2

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Introduction

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