Retrospective trial of long acting analogues detemir and degludec usage in children and adolescents to overcome glucose variability caused by dawn phenomenon and reverse dawn phenomenon

Backgraund: Children with type 1 diabetes mellitus (T1DM) need more insulin late in the evening (reverse dawn phenomenon (RDP)), and adolescents need more insulin yearly in the morning (dawn phenomenon (DP)); these cause blood glucose variability. Modern long acting insulin analogues allow to achieve satisfactory glycemic control.Aims: To study the characteristics of insulin therapy in children and adolescents with T1DM using insulin analogues detemir and degludec to overcome blood glucose variability caused by DP and RDP in different age periods.Materials and methods: We analyzed medical documents of 200 patients using detemir, admitted to pediatric endocrinology department in 2013–2019, at mean age 9.0 years (5.4; 13.0), with T1DM for 1.3 years (0.5; 3.0); and medical documents of 50 patients switched to degludec in 2018–2019 at mean age 12.0 years (10.5; 14.5) with T1DM for 3.0 years (1.5; 6.0). Before degludec they were on intensive insulin therapy with glargine (22), detemir (26), or insulin pump (2); 16 patients (32%) presented with clinical characteristics of DP, and 5 (10%) — RDP.Results: 67 children of 108 (62%) aged 1–9 years had redistribution of detemir doses to daytime; 58 adolescents of 92 (63%) aged 10–17 лет — to nighttime. Patients switched to degludec demonstrated decrease in HbA1с from 8.7% (7.8; 9.9) to 8.0% (7.4; 9.0) (р<0.001); fasting blood glucose from 9.8 mmol/l (7.4; 11.7) to 7.7 mmol/l (6.4; 8.6) (р<0.001); within-day variability from 35.2% (31.6; 40.9) to 23.5% (19.7; 28.6) (р<0.001); daily insulin dose from 0.98 U/kg/day (0.82; 1.14) to 0.87 U/kg/day (0.75; 1.07) (р=0.002). Sub-groups of patients with DP and RDP demonstrated decrease in fasting blood glucose (from 11.5 mmol/l (9.8; 13.8) to 7.5 mmol/l (6.6; 9.1) (р<0.001)), and late evening blood glucose (from 11.0 mmol/l (10.2; 11.2) to 8.0 mmol/l (6.7; 9.5) (р= 0.03)) correspondently. Achieved levels of glycemic control did not differ between sub-groups of patients initially using glargine or detemir.Conclusions: Compensation of T1DM may be complicated due to DP and RDP. Switching to degludec allowed to achieve better glycemic control and lowering of blood glucose variability caused by DP and DRP.

The dawn phenomenon in type 2 diabetes: its association with glucose excursions and changes after oral glucose-lowering drugs

Background: We investigated the association between glucose excursions and the dawn phenomenon, and the effects of oral-glucose lowering drugs on the dawn phenomenon in patients with type 2 diabetes (T2D). Methods: We conducted a post hoc analysis using data from a previous randomized trial. Patients with T2D on metformin monotherapy were randomized to receive add-on acarbose or glibenclamide for 16 weeks. Ambulatory continuous glucose monitoring (CGM) was conducted before randomization and at the end of the study. Using the CGM data, we assessed glucose excursions as indicated by mean amplitude of glycemic excursions (MAGE). The magnitude of the dawn phenomenon was calculated as the difference between the nocturnal nadir (0:00 to 6:00 a.m.) and prebreakfast glucose level. Results: A total of 50 patients with T2D [mean age 53.5 ± 8.2 years, mean glycated hemoglobin (HbA1c) 8.4 ± 1.2%] were analyzed. There was an independent association between MAGE and the dawn phenomenon [β coefficient 0.199, 95% confidence interval (CI) 0.074–0.325, p = 0.003]. HbA1c improved significantly after treatment with acarbose or glibenclamide. However, only treatment with acarbose significantly improved glucose excursions. The dawn phenomenon decreased significantly only in patients treated with acarbose (from 35.9 ± 15.7–28.3 ± 16.5 mg/dl, p = 0.037), but not in those treated with glibenclamide (from 35.9 ± 20.6–34.6 ± 17.0 mg/dl, p = 0.776). Conclusion: Glucose excursions were independently associated with the dawn phenomenon in patients with T2D on metformin monotherapy. Both glucose excursions and the dawn phenomenon improved after treatment with acarbose, but not after treatment with glibenclamide.

Patients with Type 1 Diabetes Treated with Insulin Pumps Need Widely Heterogeneous Basal Rate Profiles Ranging from Negligible to Pronounced Diurnal Variability

Background: Pump-treated patients with type 1 diabetes have widely differing basal insulin infusion profiles. We analyzed consequences of such heterogeneity for glycemic control under fasting conditions. Methods: Data from 339 adult patients with type 1 diabetes on insulin pump therapy undergoing a 24-hour fast (basal rate test) were retrospectively analyzed. Hourly programmed basal insulin infusion rates and plasma glucose concentrations as well as their proportions within, below, or above arbitrarily defined target ranges were assessed for specific periods of the day (eg, 1-7 hours, “dawn” period, 16-19 hours, “dusk” period, reference period 20-1 hours/10-14 hours), by tertiles of a predefined “dawn” index (mean basal insulin infusion rate during the “dawn” divided by the reference periods). Results: The “dawn” index varied interindividually from 0.7 to 4.4. Basal insulin infusion profiles exhibited substantial differences ( P = .011), especially overnight. Despite higher insulin infusion rates at 4 and 6.45 hours, patients with the most pronounced “dawn” phenomenon exhibited higher plasma glucose concentrations at those time points ( P < .012). Patients with a marked “dawn” phenomenon exhibited a lower probability for low (<4.4 mmol/L) and a higher probability of high values (>7.2 mmol/L) during the dawn period (all P values <.01). Conclusions: We observe substantial interindividual heterogeneity in the “dawn” phenomenon. However, widely different empirically derived basal insulin infusion profiles appear appropriate for individual patients, as indicated by similar plasma glucose concentrations, mainly in the target range, during a 24-hour fasting period.

Effects of Exercise on Blood Glucose and Glycemic Variability in Type 2 Diabetic Patients with Dawn Phenomenon

Background. The dawn phenomenon (DP) is the primary cause of difficulty in blood glucose management in type 2 diabetic (T2D) patients, and the use of oral hypoglycemic agents has shown weak efficacy in controlling DP. Thus, this study is aimed at investigating the effect of moderate-intensity aerobic exercise before breakfast on the blood glucose level and glycemic variability in T2D patients with DP. Methods. A total of 20 T2D patients with DP confirmed via continuous glucose monitoring (CGM) participated in the current study. After collecting baseline measurements by CGM as a control, CGM was reinstalled and 30 minutes of moderate-intensity aerobic exercise was performed prior to breakfast. Dawn blood glucose increase, blood glucose levels, and glycemic variability were measured before and after exercise. Results. Dawn blood glucose increase (ΔGlu, 1.25±0.84vs.2.15±1.07, P=0.005), highest blood glucose value before breakfast (Gmax, 8.01±1.16vs. 8.78±1.09, P=0.005), and mean blood glucose (MBG, 7.80±0.97vs. 8.37±0.95, P=0.001) were all lower, and time in range (TIR, 90.75±12.27vs. 83.5±15.41, P=0.015) was higher after exercise than before exercise. Among the glycemic variability indicators, blood glucose standard deviation (SD, 1.1±0.5vs. 1.48±0.63, P=0.001), coefficient of variation (CV, 14.14±5.94vs.17.69±7.46, P=0.006), mean amplitude of glucose excursion (MAGE, 2.71±1.52vs.3.73±1.98, P=0.006), and largest amplitude of glucose excursion (LAGE, 4.97±2.07vs.6.41±2.36, P=0.002) were all decreased following exercise. Conclusions. Acute moderate-intensity aerobic exercise before breakfast reduced the morning rise of blood glucose in T2D patients, partially counteracting DP. Furthermore, exercise significantly reduced blood glucose fluctuations and improved blood glucose control throughout the day. We recommend that T2D patients with DP take moderate-intensity aerobic exercise before breakfast to improve DP and glycemic control.

Impact of free-living pattern of sedentary behaviour on intra-day glucose regulation in type 2 diabetes

Purpose To investigate how the pattern of sedentary behaviour affects intra-day glucose regulation in type 2 diabetes. Methods This intensive longitudinal study was conducted in 37 participants with type 2 diabetes (age, 62.8 ± 10.5 years). Glucose and sedentary behaviour/physical activity were assessed with a continuous glucose monitoring (Abbott FreeStyle Libre) and an activity monitor (activPAL3) for 14 days. Multiple regression models with generalised estimating equations (GEEs) approach were used to assess the associations of sedentary time and breaks in sedentary time with pre-breakfast glucose, pre-lunch glucose, pre-dinner glucose, post-breakfast glucose, post-lunch glucose, post-dinner glucose, bedtime glucose, the dawn phenomenon, time in target glucose range (TIR, glucose 3.9–10 mmol/L) and time above target glucose range (TAR, glucose > 10 mmol/L). Results Sedentary time was associated with higher pre-breakfast glucose (p = 0.001), pre-dinner glucose (p < 0.001), post-lunch glucose (p = 0.005), post-dinner glucose (p = 0.013) and the dawn phenomenon (p < 0.001). Breaks in sedentary time were associated with lower pre-breakfast glucose (p = 0.023), pre-dinner glucose (p = 0.023), post-breakfast glucose (p < 0.001) and the dawn phenomenon (p = 0.004). The association between sedentary time and less TIR (p = 0.022) and the association between breaks in sedentary time and more TIR (p = 0.001) were also observed. Conclusions Reducing sedentary time and promoting breaks in sedentary time could be clinically relevant to improve intra-day glucose regulation in type 2 diabetes.