Assessment of the effect of the COVID-19 lockdown on glycaemic control in people with type 1 diabetes using flash glucose monitoring.

AIM: To describe the effect of the stringent lockdown measures, introduced in the UK on 23 March 2020 to curtail the transmission of COVID-19, on glycaemic control in people with type 1 diabetes using flash glucose monitoring. METHODS: We undertook an observational study of 572 individuals with type 1 diabetes for whom paired flash glucose monitoring data were available between early March and May 2020. The primary outcome was change in flash glucose monitoring variables. We also assessed clinical variables associated with change in glycaemic control. RESULTS: Percentage of time in range increased between March and May 2020 [median (interquartile range) 53 (41-64)% vs 56 (45-68)%; P < 0.001], with associated improvements in standard deviation of glucose (P <0.001) and estimated HbA1c (P <0.001). There was a small reduction in the number of individuals meeting the hypoglycaemia target of <5% per day (64% vs 58%; P = 0.004). Comparing changes in flash glucose monitoring data from March to May in 2019 with the same period in 2020 confirmed that these differences were confined to 2020. Socio-economic deprivation was an independent predictor of a ≥5% reduction in time in range during lockdown (odds ratio 0.45 for people in the two most affluent Scottish Index of Multiple Deprivation quintiles; P <0.001). CONCLUSIONS: Lockdown was not associated with a significant deterioration in glycaemic control in people with type 1 diabetes using flash glucose monitoring. However, socio-economic deprivation appeared to increase the risk of decline in glycaemic control, which has implications for how support is focused in challenging times.

Diurnal profile of interstitial glucose following dexamethasone prophylaxis for chemotherapy treatment of gynaecological cancer.

AIMS: Hyperglycaemia, a side-effect of acute glucocorticoid exposure, is associated with poor outcome in those undergoing chemotherapy. The incidence, risk factors and diurnal profile of glucocorticoid-induced glucose dysregulation in the context of chemotherapy treatment remain incompletely understood. METHODS: Blinded continuous interstitial glucose monitoring was performed on 16 women without diabetes for 24 h prior to and 5 days following carboplatin/paclitaxel chemotherapy combined with dexamethasone treatment for gynaecological cancer. At the end of the treatment period, glucose data were analysed and integrated with baseline metabolic and anthropomorphic variables. RESULTS: 15/16 (94%) women exhibited elevated glucose levels (> 11.1 mmol/l). Peak glucose levels were highest on the day of treatment (median 14.45 mmol/l, range 10.2-22.2 mmol/l) and total time spent with an elevated interstitial glucose level was highly variable (median 3.6 h, range 0.0-55.1 h). Peak interstitial glucose levels occurred predominantly, but not exclusively, in the afternoon (13.00-15.00) and evening (19.00-22.00); however elevated levels were noted throughout the 24-h period. Baseline HbA1c was independently associated with severity and duration of elevated glucose levels in a regression adjusted for baseline BMI. CONCLUSIONS: These data report for the first time that high glucose levels are encountered by nearly all women following this regimen, the severity and duration of which are independently associated with HbA1c . Further work is required to determine if controlling glucose levels during treatment influences outcome.

Intra-vascular glucocorticoid metabolism as a modulator of vascular structure and function.

The ability of glucocorticoids to directly alter arterial function, structure and the inflammatory response to vascular injury may contribute to their well-established link with the development of cardiovascular disease. Recent studies have emphasised the importance of tissue-specific regulation of glucocorticoid availability by the 11 beta-hydroxysteroid dehydrogenase (11HSD) isozymes, which inter-convert active glucocorticoids and their inactive metabolites. The expression of both type 1 and type 2 11HSDs in the arterial wall suggests that prereceptor metabolism of glucocorticoids may have a direct impact on vascular physiology. Indeed there is evidence that 11HSDs influence glucocorticoid-mediated changes in vascular contractility, vascular structure, the inflammatory response to injury and the growth of new blood vessels. Hence, inhibition of 11HSD isozymes may provide a novel therapeutic target in vascular disease.

Inducible nitric oxide synthase activity contributes to the regulation of peripheral vascular tone in patients with cirrhosis and ascites.

BACKGROUND: Overexpression of inducible nitric oxide synthase (iNOS) and increased nitric oxide generation may be associated with the hyperdynamic circulation of patients with cirrhosis. We have, for the first time, used the highly selective iNOS inhibitor, 1400W, to determine whether iNOS activity contributes to the regulation of vascular tone in patients with cirrhosis and ascites. METHODS: Bilateral forearm blood flow was measured using strain gauge plethysmography in eight patients with cirrhosis and ascites, and eight matched healthy volunteers during intrabrachial infusion of 1400W (0.1-1 micromol/min), N(G)-monomethyl-L-arginine (L-NMMA, a non-selective NOS inhibitor; 2-8 micromol), and norepinephrine (a control vasoconstrictor; 60-480 pmol/min). RESULTS: In patients with cirrhosis, 1400W, L-NMMA, and norepinephrine caused dose dependent reductions in forearm blood flow: peak reductions of 11 (5)%, 37 (4)%, and 48 (5)%, respectively (p < 0.05 for all). In contrast, 1400W had no effect on blood flow (+4 (8)%; NS) in healthy controls despite similar reductions in blood flow with L-NMMA and norepinephrine (39 (5)% and 49 (5)%, respectively; p < 0.05 for both). CONCLUSIONS: We have, for the first time, demonstrated that 1400W causes peripheral vasoconstriction in patients with cirrhosis but not healthy matched controls. This suggests that iNOS contributes to the regulation of peripheral vascular tone in patients with cirrhosis and ascites, and may contribute towards the hyperdynamic circulation associated with this condition.