Diet and Physical Activity as Determinants of Continuously Measured Glucose Levels in Persons at High Risk of Type 2 Diabetes

We examined how dietary and physical activity behaviors influence fluctuations in blood glucose levels over a seven-day period in people at high risk for diabetes. Twenty-eight participants underwent a mixed meal tolerance test to assess glucose homeostasis at baseline. Subsequently, they wore an accelerometer to assess movement behaviors, recorded their dietary intakes through a mobile phone application, and wore a flash glucose monitoring device that measured glucose levels every 15 min for seven days. Generalized estimating equation models were used to assess the associations of metabolic and lifestyle risk factors with glycemic variability. Higher BMI, amount of body fat, and selected markers of hyperglycemia and insulin resistance from the meal tolerance test were associated with higher mean glucose levels during the seven days. Moderate- to vigorous-intensity physical activity and polyunsaturated fat intake were independently associated with less variation in glucose levels (CV%). Higher protein and polyunsaturated fatty acid intakes were associated with more time-in-range. In contrast, higher carbohydrate intake was associated with less time-in-range. Our findings suggest that dietary composition (a higher intake of polyunsaturated fat and protein and lower intake of carbohydrates) and moderate-to-vigorous physical activity may reduce fluctuations in glucose levels in persons at high risk of diabetes.

Impact of COVID-19 Vaccination on Glycemia in Individuals With Type 1 and Type 2 Diabetes: Substudy of the COVAC-DM Study

Vaccination and potentially related side effects might impact glucose management in people with diabetes. In this study, we investigated effects of COVID-19 vaccination on glycemia assessed by continuous glucose monitoring (CGM) in people with type 1 and type 2 diabetes. <br> 74 participants of the ongoing multicenter prospective COVAC-DM-study, investigating the immune response to COVID-19 vaccines in people with diabetes, were willing to participate in this CGM sub-study. Time spent in glycemic ranges (time in range [TIR] 70-180 mg/dL; time below range [TBR] <70 mg/dL and time above range [TAR] >180 mg/dL) was assessed daily from two days prior to three days after the first COVID-19 vaccination. Participants were asked to document side effects in response to vaccination, insulin injections, and carbohydrate intake.<br> 58 participants with type 1 (27 female, mean age 39.5 years, HbA1c 57 ± 12 mmol/mol) and 16 with type 2 diabetes (9 females, mean age 60.6 years, HbA1c 63 ± 11mmol/mol) were included in this study. The mean TIR did not change on the day of the vaccination and the following 3 days (p>0.05). In people with type 1 diabetes, the TIR (p=0.033) and the TAR (p= 0.043) deteriorated on days with side effects as compared to those without. <br> Side effects occurring after COVID-19 vaccination significantly reduce the TIR and increase the TAR in people with type 1 diabetes, while no impact was observed in people with type 2 diabetes.

Impact of COVID-19 Vaccination on Glycemia in Individuals With Type 1 and Type 2 Diabetes: Substudy of the COVAC-DM Study

Vaccination and potentially related side effects might impact glucose management in people with diabetes. In this study, we investigated effects of COVID-19 vaccination on glycemia assessed by continuous glucose monitoring (CGM) in people with type 1 and type 2 diabetes. <br> 74 participants of the ongoing multicenter prospective COVAC-DM-study, investigating the immune response to COVID-19 vaccines in people with diabetes, were willing to participate in this CGM sub-study. Time spent in glycemic ranges (time in range [TIR] 70-180 mg/dL; time below range [TBR] <70 mg/dL and time above range [TAR] >180 mg/dL) was assessed daily from two days prior to three days after the first COVID-19 vaccination. Participants were asked to document side effects in response to vaccination, insulin injections, and carbohydrate intake.<br> 58 participants with type 1 (27 female, mean age 39.5 years, HbA1c 57 ± 12 mmol/mol) and 16 with type 2 diabetes (9 females, mean age 60.6 years, HbA1c 63 ± 11mmol/mol) were included in this study. The mean TIR did not change on the day of the vaccination and the following 3 days (p>0.05). In people with type 1 diabetes, the TIR (p=0.033) and the TAR (p= 0.043) deteriorated on days with side effects as compared to those without. <br> Side effects occurring after COVID-19 vaccination significantly reduce the TIR and increase the TAR in people with type 1 diabetes, while no impact was observed in people with type 2 diabetes.

Time in range, as measured by continuous glucose monitor, as a predictor of microvascular complications in type 2 diabetes: a systematic review

Continuous glucose monitoring (CGM)-derived time in range (TIR) correlates with hemoglobin A1c (A1c) among patients with type 2 diabetes mellitus (T2DM); however, there is a paucity of data evaluating its association with microvascular complications. We conducted this systematic review to examine the association between TIR and microvascular complications of diabetic retinopathy (DR), diabetic nephropathy (DN), and diabetic peripheral neuropathy (DPN). We conducted a comprehensive literature search on PubMed, Scopus, and Web of Science online databases following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Full-text original articles that evaluated the association between CGM-derived TIR and risk of microvascular complications and were published between 2010 and June 2021 were included in our systematic review. The quality of the included studies was evaluated using the National Heart, Lung, and Blood Institute Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies. Data were analyzed using qualitative synthesis. Eleven studies on a total of 13 987 patients were included in the systematic review. The median sample size, baseline A1c, and diabetes duration were 466 patients (range: 105–5901), 8.2% (SD 0.5%), and 11.3 years (1.0), respectively. Majority of the studies were conducted in Asia (10 out of 11). Four studies evaluated the relationship between CGM-derived TIR and DR and CGM-derived TIR and DN, while seven studies evaluated the relationship between CGM-derived TIR and DPN. A 10% increase in TIR was associated with a reduction in albuminuria, severity of DR, and prevalence of DPN and cardiac autonomic neuropathy. In addition, an association was observed between urinary albumin to creatinine ratio but not with estimated glomerular filtration rate. This review summarizes recent evidence supporting an association between CGM-derived TIR and microvascular complications among patients with T2DM. A larger-scale multicenter investigation that includes more diverse participants is warranted to further validate the utility of TIR as a predictor of diabetic microvascular complications.

Digitally enabled flash glucose monitoring for inpatients with COVID-19: Feasibility and pilot implementation in a teaching NHS Hospital in the UK

Background COVID-19 placed significant challenges on healthcare systems. People with diabetes are at high risk of severe COVID-19 with poor outcomes. We describe the first reported use of inpatient digital flash glucose monitoring devices in a UK NHS hospital to support management of people with diabetes hospitalized for COVID-19. Methods Inpatients at University Hospitals Coventry & Warwickshire (UHCW) NHS Trust with COVID-19 and diabetes were considered for digitally enabled flash glucose monitoring during their hospitalization. Glucose monitoring data were analysed, and potential associations were explored between relevant parameters, including time in hypoglycaemia, hyperglycaemia, and in range, glycated haemoglobin (HbA1c), average glucose, body mass index (BMI), and length of stay. Results During this pilot, digital flash glucose monitoring devices were offered to 25 inpatients, of whom 20 (type 2/type 1: 19/1; mean age: 70.6 years; mean HbA1c: 68.2 mmol/mol; mean BMI: 28.2 kg/m2) accepted and used these (80% uptake). In total, over 2788 h of flash glucose monitoring were recorded for these inpatients with COVID-19 and diabetes. Length of stay was not associated with any of the studied variables (all p-values >0.05). Percentage of time in hyperglycaemia exhibited significant associations with both percentage of time in hypoglycaemia and percentage of time in range, as well as with HbA1c (all p-values <0.05). The average glucose was significantly associated with percentage of time in hypoglycaemia, percentage of time in range, and HbA1c (all p-values <0.05). Discussion We report the first pilot inpatient use of digital flash glucose monitors in an NHS hospital to support care of inpatients with diabetes and COVID-19. Overall, there are strong arguments for the inpatient use of these devices in the COVID-19 setting, and the findings of this pilot demonstrate feasibility of this digitally enabled approach and support wider use for inpatients with diabetes and COVID-19.

Spironolactone is associated with reduced mitotane levels in adrenocortical carcinoma patients

Adrenocortical carcinoma (ACC) is a rare endocrine malignancy with a poor prognosis. Mitotane, a derivative of the pesticide DDT, has been used successfully as first line chemotherapy since the 1960s, if maintained within a narrow therapeutic window. Spironolactone (SPL) is frequently used to treat glucocorticoid excess-associated adverse effects such as severe hypokalemia. Although data of a previous case report indicate a link, valid data regarding SPL use and mitotane plasma concentrations in a human cohort are lacking. This retrospective analysis includes data from 54 mitotane-receiving ACC patients (14 co-administered with SPL) treated between January 2005 and April 2020 (20 male, mean age 54.1 ± 2.2 yrs). All available mitotane concentrations, treatment doses, tumor stage and evidence of hormone activity were collected. Primary outcomes included mitotane levels and concentration/dose-ratios as well as time-in-range in patients with and without additional SPL treatment. The SPL group was characterized by higher glucocorticoid secretion. Other features such as tumor stage, size and anthropometrics were similar between groups. Interestingly, the SPL group had significantly lower mitotane levels despite higher doses. Mitotane time-in-range was significantly reduced in the SPL group, as was time-in-range to progression. These data provide first evidence in a human cohort for potential SPL-mitotane interactions (beyond mentioned case report), which affect dose response and may modulate treatment outcomes. This should caution clinicians to carefully adjust mitotane doses during SPL treatment in ACC patients or choose alternative therapeutic options.