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AimsImpaired awareness of hypoglycaemia (IAH) has been associated with increased diabetes distress and use of sensor technology can reduce diabetes distress. The aim of this study was to examine diabetes‐specific distress (emotions, cognitions, behaviours) in relation to IAH status and use of glucose sensors in people with type 1 diabetes.MethodsIndividuals with type 1 diabetes from an academic diabetes outpatient clinic completed the Clarke questionnaire (to assess hypoglycaemic awareness), Problem Areas in Diabetes (PAID‐5), Hypoglycaemia Fear Survey‐II (HFS‐II), Attitudes to Awareness of Hypoglycaemia Survey (A2A), Nijmegen Clinical Screening Instrument Survey (NCSI) and Hyperglycaemia Avoidance Scale (HAS).ResultsOf the 422 participants (51.9% male, diabetes duration 30 [16–40] years, HbA1c 60 ± 11 mmol/mol [7.6 ± 1.0%], 351 [88.2%] used a glucose sensor; 82 [19.4%]) had IAH. Compared to individuals with normal awareness, those with IAH more often had PAID‐5 scores ≥8 (35.4% vs. 21.5%, p = 0.008) and higher scores on all HFS‐II subscores (total [40.2 ± 21.5 vs. 27.9 ± 17.2, p < 0.001]), HFS‐II behaviour (18.5 ± 10.0 vs. 15.1 ± 8.0, p = 0.005), HFS‐II worry (21.8 ± 13.5 vs. 12.7 ± 10.9, p < 0.001), HAS worries (17.5 ± 7.3 vs. 14.3 ± 7.0, p < 0.001) and NCSI hypoglycaemia items. HAS behaviour, A2A and NCSI hyperglycaemia scores did not differ between individuals with or without IAH. Restricting the analyses to individuals using a glucose sensor did not materially change the results.ConclusionsDiabetes‐specific distress remains a major problem among individuals with type 1 diabetes, particularly those with IAH, despite the widespread use of (intermittently scanned) sensor technology. Further studies are needed to examine strategies to lower diabetes‐specific distress in individuals with IAH.

Aim: To investigate whether a history of severe hypoglycaemia (SH) or the associated presence of impaired awareness of hypoglycaemia (IAH) is characterized by a proinflammatory profile in people with type 1 diabetes. Research design and methods: We measured circulating inflammatory markers and pro-and anti-inflammatory cytokine production after ex vivo stimulation of peripheral blood mononuclear cells (PBMCs) in a well-characterized cohort of individuals with type 1 diabetes (n = 239) and in people without diabetes (n = 56). Data were corrected for confounders by using multivariate linear regression models. Results: People with type 1 diabetes had higher circulating concentrations of highsensitivity C-reactive protein (hs-CRP; 0.91 [0.36-2.25] vs. 0.52 [0.20-0.98] pg/mL, P < 0.001 and interleukin-18-binding protein (IL-18BP; 1746 [1304-2112] vs. 1381 [1191-1807] pg/mL; P = 0.001) than those without diabetes. In multivariate analysis, only higher hs-CRP concentrations persisted. Neither circulating immune cells nor ex vivo cytokine levels produced by PBMCs in response to an extensive panel of stimuli differed in groups defined by awareness state or a history of SH, apart from N A. and A.W.M.J. share first authorship.

IntroductionVarious studies have shown a number of glycemic parameters to improve over several weeks in people with type 1 diabetes during the first surge of the COVID-19 pandemic. Whether and to what extent such improvement is sustained during following COVID-19 surges remains unknown. Therefore, the aim of this study was to investigate glycemic parameters during the first year of the COVID-19 pandemic in people with type 1 diabetes and to determine factors associated with glycemic improvement.Research design and methodsThis was an observational cohort study in people with type 1 diabetes, aged ≥16 years. We compared glycated hemoglobin (HbA1c) and flash glucose monitoring (FGM) downloads between the prelockdown period and approximately 1 year thereafter. Using logistic regression analysis, we assessed associations between an HbA1c reduction of at least 0.5% (~5.5 mmol/mol) with baseline clinical characteristics and self-reported changes in psychological well-being and lifestyle behavior related to COVID-19.ResultsA total of 437 participants were included. As compared with prepandemic data, 1 year after the start of the COVID-19 pandemic and associated lockdowns, HbA1c had decreased from 7.9%±1.1% (63±12 mmol/mol) to 7.5%±1.0% (59±11 mmol/mol) (p<0.001), whereas time in range increased from 55.8%±16.7% to 58.6%±16.7% (p=0.004) and time below (<3.9 mmol/L) and above (>13.9 mmol/L) range and glucose variability all decreased (all p<0.05). FGM use, higher HbA1c at baseline and current smoking were independently associated with an HbA1c decrease of at least 0.5%, whereas self-reported changes in psychological well-being and lifestyle behavior related to the first surge of the COVID-19 pandemic and associated lockdowns were not.ConclusionsThe COVID-19 pandemic and related lockdown measures were associated with improvement in glucometrics, including HbA1c and FGM data, in individuals with type 1 diabetes, particularly in FGM users, those with higher HbA1c at baseline or current smokers.

Objective-Hypoglycemia is associated with increased mortality. The reasons for this remain unclear and the effects of low glucose exposure on vascular endothelial function remain largely unknown. We endeavored to determine the effects of low glucose on endothelial cells and intact human arterioles.Methods and Results-We exposed human umbilical vein endothelial cells to low glucose conditions in a clinically relevant range (40-70 mg/dL) and found rapid and marked reductions in nitric oxide (NO) bioavailability (P<0.001). This was associated with concomitantly increased mitochondrial superoxide production (P<0.001) and NO-dependent mitochondrial hyperpolarization (P<0.001). Reduced NO bioavailability was rapid and attributable to reduced eNOS activity and destruction of NO. Low glucose rapidly activated AMP Kinase but physiological activation failed to restore NO bioavailability. Pharmacological AMP Kinase activation led to phosphorylation of eNOS's Ser633 activation site, reversing the adverse effects of low glucose, and this protective effect was prevented by L-NAME. Intact human arterioles exposed to low glucose demonstrated marked endothelial dysfunction which was prevented by either metformin or TEMPOL.Conclusions-Our data suggest that moderate low glucose exposure rapidly impairs NO bioavailability and endothelial function in the human endothelium, and that pharmacological AMP Kinase activation can inhibit this effect in an NO-dependent manner.