Bedtime snacking and glycemic deterioration in young children with Type 1 diabetes on multiple daily injections: a randomized controlled crossover trial

Of 28 children, characteristics, insulin intake, and meal management at the baseline are shown in Table 1. In brief, the mean age of 28 children (13 female (46%)) was 6.6 ± 0.8 years with diabetes duration of 2.7 ± 1.3 years, and HbA1c of 7.0 ± 0.5% (53 mmol/mol). While all children were using insulin glargine (100 IU/mL) and insulin lispro (100 IU/mL), the mean total daily dose/kg/day was 0.8 ± 0.2 IU, basal/total daily insulin ratio was 42.8 ± 8.9%. According to WHO references [13], there were no children with a BMI Z score below -1SD, 60.7% of children were classified as normal (≥-1SD -<1 SD), 32.1% as overweight (≥1 SD–<2 SD) and 7% as obese (≥2 SD). There was no significant difference by sex for all variables in Table 1 (p = ns for all).

Table 1 Baseline characteristics of 28 children.

The dinner meals were similar on all trial days regarding total energy, carbohydrate, protein, fat, and fiber (p = ns for all). The macronutrients and energy values of the dinner on all trial days are shown in Supplementary Table 1S.

On 112 trial days, 62% had the test snack or control between 09 and 10.00 p.m., 24% had between 10 and 11.00 p.m., 12% had between 08-09.00 p.m., and 2% had between 11.00 p.m. and 12.00 a.m. Mean glucose values just before the test snack consumptions were 137.8 ± 14.5 mg/dL (7.7 ± 0.8 mmol/L) for milk, 141.9 ± 16.9 mg/dL (7.9 ± 0.9 mmol/L) for yoghurt, 136 ± 19.1 mg/dL (7.6–1.1 mmol/L) for kefir, and 140.8 ± 17.0 mg/dL (7.8 ± 0.9 mmol/L) for control without a significant difference (p = 0.548). The 6-hour test period was divided into 3 2-hour periods 0–2 h, 2-4 h, and 4–6 h, additionally, 0–2 h was considered early and 2–6 h was the late period. As shown in Table 2, glucose values on control days were significantly lower than on milk, yoghurt, and kefir days in all time periods (p < 0.001). Glucose values were similar in all periods between milk, yoghurt, and kefir days. The fastest increase was within the first hour and the peak was reached in the second hour after test snacks (Fig. 2).

Fig. 2figure 2

Continuous glucose monitoring glucose values by hours following a bedtime snack (n = 28).

Table 2 Mean glucose values before and after control and test snacks (n = 28).

CGM data in test periods were analyzed according to International consensus CGM metrics (Table 3). During all trial period (0–6 h), TIR was 34.7% for milk, 38.7%. for yoghurt, 45.9% for kefir, and 75.5% for control. TIR on the control day was significantly higher than the milk (p < 0.001), yoghurt (p < 0.001), and kefir days (p = 0.004). TBR1 was not observed on the milk days. TBR1 differences between the control, yoghurt, and kefir days were similar (p = 0.054). TAR1 was significantly lower on control days than on milk (p = 0.002) and yoghurt days (p < 0.001). Similarly, TAR2 on the control day was significantly lower than milk (p < 0.001), yoghurt (p = 0.007), and kefir (p = 0.012) days. CV was <36% in all days and similar in pairwise comparison (p = 0.565).

Table 3 Continuous Glucose Monitoring metrics in milk, yoghurt, kefir and control days.

In the early period (0-2 hours), TIR was 47.3% for the milk, 49.1% for the yoghurt, and 58.8% for the kefir, 74.8% for the control day. TIR on the control day was significantly higher than the milk (p = 0.002) and yoghurt (p = 0.014). TAR1 was lower on the control day than the yoghurt meal (p = 0.031). TAR2 on the control day was significantly lower than milk (p = 0.009) and kefir days (p = 0.012). TBR2 was not observed, TBR1 and CV were similar between groups in the early period.

In the late period (2–6 hours), TIR was 22.8% for the milk, 30.5% for the yoghurt, 41.8% for the kefir, and 75.3% for the control day. The TIR on control days was significantly higher than the milk (p < 0.001), yoghurt (p = 0.001), and kefir days (p = 0.012). TAR1 in the late period was significantly higher in yoghurt than the control (p = 0.004). Milk day was found to be higher than the control for TAR2 (p < 0.001). CV was less on the milk and yoghurt days compared to the control day (p = 0.001 and p < 0.001, respectively).

When the early (0–2 h) and late (2–6 h) period’s TIR were examined, the TIR value decreased significantly on the trial days of the milk (47.3% to 22.8%, p < 0.001), yoghurt (49.1% to 30.5%, p = 0.006), and kefir (58.8% to 41.8%, p = 0.01). Early and late TIR values remained similar on the control day (p = 0.839) (Table 3).

Of 112 trial days, 13 trial days were terminated early due to hyperglycemia (>300 mg/dL (16.7 mmol/L)) and 3 trial days due to hypoglycemia (<70 mg/dL (3.9 mmol/L)) that required treatment. The timing of hyperglycemia and hypoglycemia events by test groups is shown in Table 4.

Table 4 Termination events by test snacks and control (n = 112).

The mean glucose values at the end of 6 hours for milk, yoghurt, and kefir meals were similar (milk-yoghurt p = 0.342, milk-kefir p = 0.187, yoghurt-kefir p = 0.542), and the mean glucose values on the control day were lower than the milk day (p < 0.001), yoghurt day (p = 0.002) and kefir day (p < 0.001).

After trial termination at 6 h, CGM data were collected during extension phase (6-9 h). Mean glucose values at 6th hour, at 9th hour, and between 6-9 hours after the test meals are shown in Table 5. The mean glucose values at the end of 9 hours (at 9th h) were similar for milk, yoghurt and kefir meals (milk-yoghurt p = 0.193, milk-kefir p = 0.574, yoghurt-kefir p = 0.681) and the mean glucose values on the control day were lower than the milk day (p = 0.014) and kefir day (p = 0.026).

Table 5 Mean glucose values at 6th hour, at 9th hour and between 6-9 hours after the test meals (mg/dL) (mmol/L).

The mean glucose values during extension period (6–9 h) were also similar for milk, yoghurt and kefir meals (milk-yoghurt p = 0.429, milk-kefir p = 0.090, yoghurt-kefir p = 0.546) and the mean glucose values on the control day were lower than the milk day (p = 0.004), yoghurt day (p = 0.012) and kefir day (p = 0.042).

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