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Free access

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

Ram P Narayanan, Matthew Gittins, Kirk W Siddals, Robert L Oliver, Julie E Hudson, Anne White, Paul Durrington, Robert R Davies, Martin K Rutter, and J Martin Gibson

Objective

IGF levels, their binding proteins (IGFBPs) and high-dose statin therapy have been linked to the development of diabetes. We aimed to identify whether atorvastatin caused dose-related changes in IGF proteins.

Design and methods

We measured IGF1, IGF2, IGFBP1 and IGFBP3 concentrations at baseline, 6 and 12 months in Protection Against Nephropathy in Diabetes with Atorvastatin trial participants with type 2 diabetes randomised to 10 mg (n=59) vs 80 mg (n=60) of atorvastatin (n=119; mean (s.d.): age 64 (10) years; 83% male; HbA1c 61 (10) mmol/mol; blood pressure 131/73 mmHg).

Results

Atorvastatin was associated with overall reductions in circulating IGF1, IGF2 and IGFBP3 concentrations (P<0.05 for all changes). The adjusted mean (95% CI) between-group differences that indicate dose-related changes in IGF proteins were not significant for IGF1: −3 (−21 to 14) ng/ml; IGF2: −23 (−65 to 18) ng/ml and IGFBP3: −0.34 (−0.71 to 0.03) μg/ml, negative values indicating numerically greater lowering with high dose. The IGFBP1 concentration did not change with atorvastatin therapy overall but the adjusted mean (95% CI) between-group difference indicating a dose-related change in log IGFBP1 was highly significant −0.41 (−0.69 to 0.13, P=0.004).

Conclusion

IGF1, IGF2 and IGFBP3 concentrations decreased following atorvastatin therapy. A differential effect of low- vs high-dose atorvastatin on IGFBP1 concentrations was observed with likely implications for IGF bioavailability. The dose-related differential impact of atorvastatin treatment on concentration of IGF proteins merits investigation as a mechanism to explain the worsening of glucose tolerance with statin therapy.

Open access

ENDOCRINOLOGY IN THE TIME OF COVID-19: Remodelling diabetes services and emerging innovation

Deborah J Wake, Fraser W Gibb, Partha Kar, Brian Kennon, David C Klonoff, Gerry Rayman, Martin K Rutter, Chris Sainsbury, and Robert K Semple

The COVID-19 pandemic is a major international emergency leading to unprecedented medical, economic and societal challenges. Countries around the globe are facing challenges with diabetes care and are similarly adapting care delivery, with local cultural nuances. People with diabetes suffer disproportionately from acute COVID-19 with higher rates of serious complications and death. In-patient services need specialist support to appropriately manage glycaemia in people with known and undiagnosed diabetes presenting with COVID-19. Due to the restrictions imposed by the pandemic, people with diabetes may suffer longer-term harm caused by inadequate clinical support and less frequent monitoring of their condition and diabetes-related complications. Outpatient management need to be reorganised to maintain remote advice and support services, focusing on proactive care for the highest risk, and using telehealth and digital services for consultations, self-management and remote monitoring, where appropriate. Stratification of patients for face-to-face or remote follow-up should be based on a balanced risk assessment. Public health and national organisations have generally responded rapidly with guidance on care management, but the pandemic has created a tension around prioritisation of communicable vs non-communicable disease. Resulting challenges in clinical decision-making are compounded by a reduced clinical workforce. For many years, increasing diabetes mellitus incidence has been mirrored by rising preventable morbidity and mortality due to complications, yet innovation in service delivery has been slow. While the current focus is on limiting the terrible harm caused by the pandemic, it is possible that a positive lasting legacy of COVID-19 might include accelerated innovation in chronic disease management.

Free access

Vitamin D, parathyroid hormone and the metabolic syndrome in middle-aged and older European men

David M Lee, Martin K Rutter, Terence W O'Neill, Steven Boonen, Dirk Vanderschueren, Roger Bouillon, Gyorgy Bartfai, Felipe F Casanueva, Joseph D Finn, Gianni Forti, Aleksander Giwercman, Thang S Han, Ilpo T Huhtaniemi, Krzysztof Kula, Michael E J Lean, Neil Pendleton, Margus Punab, Alan J Silman, Frederick C W Wu, and the European Male Ageing Study Group

Objectives

Low serum 25-hydroxyvitamin D (25(OH)D) and elevated parathyroid hormone (PTH) levels have been linked to insulin resistance, the metabolic syndrome (MetS) and its components. Data in healthy, community-dwelling Europeans are lacking, and previous studies have not excluded subjects receiving drug treatments that may distort the relationship between 25(OH)D/PTH and MetS. The aim of our analysis was to examine the association of 25(OH)D and PTH with Adult Treatment Panel III-defined MetS in middle-aged and older European men.

Design

This was a population-based, cross-sectional study of 3369 men aged 40–79 years enrolled in the European Male Ageing Study.

Results

After exclusion of subjects with missing data, 3069 men with a mean (±s.d.) age of 60±11 years were included in the analysis. Age-adjusted 25(OH)D levels were inversely associated with waist circumference, systolic blood pressure (BP), triglycerides, and glucose (all P<0.01). Age-adjusted PTH levels were only associated with waist and diastolic BP (both P<0.05). After adjusting for age, centre, season and lifestyle factors the odds for MetS decreased across increasing 25(OH)D quintiles (odds ratios 0.48 (95% confidence intervals 0.36–0.64) highest versus lowest quintile; P trend<0.001). This relationship was unchanged after adjustment for PTH, but was attenuated after additional adjustment for homoeostasis model assessment of insulin resistance (0.60 (0.47–0.78); P trend<0.001). There was no association between PTH and MetS.

Conclusions

Our results demonstrate an inverse relationship between 25(OH)D levels and MetS, which is independent of several confounders and PTH. The relationship is partly explained by insulin resistance. The clinical significance of these observations warrants further study.