A commonly prescribed anti-inflammatory may increase the risk of diabetes after just one week of treatment, according to new findings presented at The Society for Endocrinology Annual Conference. Healthy men given doses of the drug comparable to those used to treat inflammatory disorders had changes in markers of blood sugar metabolism associated with an increased risk of developing diabetes. The study findings highlight the potential long-term health implications for people regularly taking these drugs and that medical professionals may need to consider and monitor the potential side-effects, to avoid future debilitating conditions.
Glucocorticoids (GCs) are one of the most commonly prescribed anti-inflammatories for conditions such as arthritis, asthma, allergies and adrenal insufficiency. GC treatment at high doses for a long duration is known to be associated with metabolic side-effects that may increase risk of diabetes and obesity but there are currently no studies examining the short-term effects of GCs at the more regularly prescribed, lower doses. As 2-3% of the UK population take GCs for conditions of varying severity, it is important to investigate whether these metabolic side-effects occur in lower dose, short-term therapy.
Dr Riccardo Pofi, from Sapienza University of Rome and Prof Jeremy Tomlinson from the University of Oxford, measured markers of metabolism in healthy men given commonly prescribed doses (10 and 15mg) of GCs (prednisolone) after just one week of treatment. Although commonly checked clinical and biochemical parameters such as fasting blood sugar levels, weight and general health was unaffected, changes in metabolic markers indicated that their blood sugar regulation was impaired.
"This is the first study to examine the very short-term metabolic effects of commonly prescribed doses of glucocorticoids on healthy men and indicates, that even at these lower doses, glucose metabolism is impaired, suggesting an increased risk of diabetes with continued treatment," Dr Pofi comments.
These novel findings not only highlight the importance of determining the best GC dose that balances effectiveness with potentially negative metabolic effects, but also that medical professionals should be more aware of these risks and may need to monitor them in patients both on short and longer-term therapy.
Dr Pofi says, "This suggests that we need to more accurately assess GC use in patients to prevent and reduce the undesired effects, especially in patients for which steroid treatment is essential for life."
Future larger studies are required to confirm these findings and improve our understanding of how they are caused. Dr Pofi now plans to investigate the metabolic effects of taking GCs alongside diabetes drugs, to assess whether the unwanted side effects of GCs can be reduced or prevented with combined treatment.
Conference abstract, observational study, human
Glucocorticoid treatment is associated with dose-dependent effects in healthy male volunteers
Riccardo Pofi, Ilaria Bonaventura, Nanthia Othonos, Thomas Marjot, Ahmed Moolla, Andrea M. Isidori, Leanne Hodson, Jeremy W. Tomlinson
OBJECTIVE: 2-3% of the population of the UK receive glucocorticoid(GC) therapy. Significant adverse effects are not confined to chronic use: recurrent short-course administration is associated with increased morbidity and mortality. Data about the cumulative dose responsible for drawbacks during GC treatment are still lacking. The aim of this study was to test the impact of 7 days of 10 or 15mg of Prednisolone on metabolism in healthy male volunteers.
METHODS: 16 healthy male volunteers were recruited from the Oxford Bio-Bank and divided into 2 age- and BMI-matched control groups as following: 6 volunteers received 10 mg of Prednisolone and 10 volunteers received 15 mg of Prednisolone for 7 days. Anthropometric and metabolic parameters were recorded and all patients underwent low dose hyperinsulinaemic-euglycaemic clamp(HEC), before(pre) and after(post) treatment. The main outcome measure was the M-value gathered from the HEC.
RESULTS: Age, BMI and fasting blood glucose were not different between the groups at baseline. After one week of prednisolone 10 or 15 mg, no differences were found in delta(Δ=post-pre) fasting glucose(FG) (median ΔFG15mg 0.15±0.36 nmol/L vs ΔFG10mg 0.15±0.36 nmol/L, p=0.635). However, M-value was significantly reduced in patients taking 15 mg of prednisolone (median ΔM15mg -2.5±2.0 mg/Kg/min vs ΔM10mg -0.4±1.3 mg/Kg/min, p=0.016), as well as serum potassium (median ΔK15mg -0.3±0.2 mEq/L vs ΔK10mg 0.10±0.18 mEq/L, p=0.011). No differences were found in Δcholesterol (total, HDL and non-HDL), liver or kidney function.
CONCLUSIONS: In this small cohort of healthy male volunteers, we demonstrated that GC treatment is associated with a worsening of insulin sensitivity through a dose-dependent effect. In addition, the decrease of serum potassium underpin the dose-dependent mineralocorticoid activity of GC. Further studies are needed to confirm our findings in larger cohort of patients.