Effectiveness of SmartGuard Technology in the Prevention of Nocturnal Hypoglycemia After Prolonged Physical Activity

Abstract

Background:

The prevention of postexercise nocturnal hypoglycemia after prolonged physical activity using sensor-augmented pump (SAP) therapy with predictive low-glucose management (PLGM) has not been well studied. We conducted a study at a pediatric diabetes camp to determine whether a SAP with PLGM reduces the frequency of nocturnal hypoglycemia after prolonged physical activity more effectively than a SAP with a carbohydrate intake algorithm.

Methods:

During a 1-week sport camp, 20 children (aged 10–13 years) with type 1 diabetes (T1D) managed by SAP therapy either with (n = 7) or without PLGM (n = 13) were studied. The hypoglycemia management strategy and the continuous glucose monitoring (CGM)/PLGM settings were standardized. The incidence, severity, and duration of hypoglycemia and carbohydrate intake were documented and compared.

Results:

The PLGM system was activated on 78% of all nights (once per night on average). No difference was found between the SAP and PLGM groups in the mean overnight glucose curve or mean morning glucose (7.8 ± 2 mmol/L vs. 7.4 ± 3 mmol/L). There was no difference in the frequency and severity of hypoglycemia. However, the SAP group consumed significantly more carbohydrates to prevent and treat hypoglycemia than those in the PLGM group; the values were 10 ± 2 and 1 ± 2 gS (grams of saccharides or carbohydrates) (P < 0.0001) in the SAP and PLGM groups, respectively. Moreover, the SAP group spent a significantly longer time in hypoglycemia (64 ± 2 min vs. 38 ± 2 min, P < 0.05). We observed a difference in the time distribution of nocturnal hypoglycemia (10 to 12 p.m. in the PLGM group and 3 to 7 a.m. in the SAP group, P < 0.05).

Conclusion:

With PLGM system, euglycemia after prolonged physical activity was largely maintained with a minimal carbohydrate intake.

Introduction

Decreasing the risk of hypoglycemia is one of the most important and difficult goals of T1D treatment. Continuous glucose monitoring studies have shown that hypoglycemic events occurring at night are often prolonged and therefore potentially dangerous.¹ Children with type 1 diabetes (T1D) are particularly vulnerable to severe hypoglycemic events while asleep at night¹ due to defective symptomatic responses to hypoglycemia.² Moreover, hypoglycemia has been associated with a decrease in neurocognitive function in children with T1D,³ and thus, the prevention of nocturnal hypoglycemia may be particularly important to reduce the risk of long-term neurological damage.⁴

Children and adolescents with type T1D are encouraged to exercise regularly because of its beneficial effects, which include improved insulin sensitivity, improved body composition, and improved lipid profile.⁵ However, plasma glucose concentrations are often difficult to manage during prolonged periods of physical activity.⁶ This difficulty occurs largely because glucose production by the liver, regardless of prior carbohydrate intake, does not match the elevated rates of glucose utilization in the muscle during both exercise and recovery.⁷ There is also an inability to naturally reduce insulin levels before and after exercise.⁸ The frequency of nocturnal hypoglycemia is increased twofold on nights after exercise.^9,10 The DirecNet consortium found that following 1 h of afternoon exercise, 48% of children experienced hypoglycemia (blood glucose [BG] <3.3 mmol/L, 60 mg/dL) during the ensuing night. The hypoglycemia occurred most often between midnight and 2 a.m. after an afternoon exercise session between 4 and 6 p.m.⁹ To avoid these negative outcomes, some children with T1D may avoid regular exercise altogether, whereas others may consume excessive amounts of carbohydrates or lower their insulin intake too dramatically, thereby causing hyperglycemia. In addition, the fear of hypoglycemia, particularly overnight, has a major adverse impact on the quality of life of children with T1D and their families.¹¹ This fear has been labeled one of the main barriers to achieving glycemic control targets.¹²

The automatic functions of the pump help to limit hypoglycemia. The low suspend system (LGS) (MiniMed Paradigm REAL-Time Veo pump; Metronic) will suspend insulin delivery for up to 2 h or until the patient responds to the hypoglycemic alarm when a low-glucose threshold is reached.^13,14 Published studies provided evidence that the LGS algorithm reduces the frequency of hypoglycemia in children and adolescents with type 1 diabetes under real-life conditions.^15,16 However, the patient may already be hypoglycemic before insulin is suspended, and with the currently available insulin, there is a 60-min delay before the effective insulin action has been attenuated sufficiently so that the glucose level increases above the hypoglycemic threshold.¹⁷

The most advanced approach to hypoglycemia prevention is sensor-augmented pump (SAP) therapy. The most sophisticated system is Predictive Low Glucose Management (PLGM) (Minimed G640; Medtronic), which suspends insulin delivery to prevent hypoglycemia according to a prediction algorithm.^18
–20 This system was recently tested in 15- to 45-year-old participants and led to an 81% reduction of the frequency of hypoglycemia and a 74% reduction in hypoglycemia lasting >2 h.^21
–23 However, there is limited information about the efficacy of PLGM in preventing nocturnal hypoglycemia after repeated prolonged physical activity.

This study was designed to evaluate the effectiveness of a PLGM system in the prevention of nocturnal hypoglycemia after prolonged physical activity.

Materials and Methods

Our observational study was conducted at a diabetes sports camp. This sports camp offers daily regular physical activity sessions, including both aerobic and anaerobic exercise. The average time of physical activity was 5 h per day divided into 4–5 sessions. The last daily session started at 7 p.m. The physical activities included running, football, volleyball, interval training, dancing, and games.

The study included 20 children with continuous glucose monitoring (CGM) and continuous subcutaneous insulin infusion (CSII) technology among 43 children participating in the camp. All used an insulin pump and sensor continuously before entering the study for ≥3 months. They had no episodes of severe hypoglycemia in the last 3 months before the camp. The remaining 23 children did not fulfill the criteria or were treated by multiple daily injections (MDI). Children were divided into two groups according to their current pump equipment to either with PLGM function (PLGM group, n = 7) or without (SAP group, n = 13). SAP group included children with SAP only (n = 5) and SAP with low-glucose suspend (n = 8). All participants wore the SAP during the whole study period. The children did not have any other chronic medical conditions known to affect BG levels.

The glucose concentrations in interstitial fluid were measured by CGM using either a Dexcom G4 Platinum glucose sensor (DexCom, San Diego, CA) or an Enlite glucose sensor (Medtronic MiniMed, Inc., Northridge, CA). The data gained were recorded and analyzed to assess nocturnal hypoglycemia. The sensor glucose values were regularly confirmed by capillary BG measurements using an Abbott Freestyle glucose meter (Abbott, Diabetes Care, Alameda, CA) or Accu-Chek Performa Nano glucose meter (Roche Diagnostics Deutschland GmbH, Mannheim, Germany) at 10 p.m., 00:00 a.m., and 7.30 a.m. and always when a child reported hypoglycemia or the interstitial glucose concentration detected by a sensor was <3.9 mmol/L (70 mg/dL). A total of seven nights were included in the analyses. Nocturnal hypoglycemia was defined as any CGM interstitial glucose concentration ≤3.9 mmol/L (70 mg/dL) confirmed by SMBG testing between 10 p.m. and 7.30 a.m.

The settings of the alarms and automatic pump functions are shown in Table 1. If glycemia exceeded 12 mmol/L (216 mg/dL) overnight, correction doses of insulin estimated according to a bolus calculator and the investigator were administered. We used a carbohydrate intake algorithm based on the Riddell recommendation²⁰ and our 5 years of experience with diabetes camps for preventing and treating nocturnal hypoglycemia. The detailed description of the algorithm for carbohydrate intake is presented in Table 2. The overnight carbohydrate intake was recorded. When a patient on either LGS or PLGM experienced nocturnal hypoglycemia treated by either carbohydrates (grape sugar–dextrose) or starch (biscuits with fiber), we manually resupplied the insulin infusion after the hypoglycemia management. Ketonuria was monitored in all participants each morning using urine-testing strips (Diaphan).

Table 1.

Settings of the Predictive Low-Glucose Management and Sensor Alarms During the Diabetes Camp

Treatment mode	Glycemia (mmol/L)	Glycemia (mg/dL)
SAP group
SAP only, n	5
Alarm: Hypoglycemia (<11 years)	3.9	70
Alarm: Hypoglycemia (≥11 years)	3.3	59
Alarm: Hyperglycemia (all)	16.0	288
SAP-LGS, n	8
Low-glucose suspend
10 p.m.–7.30 a.m.	3.0	54
7.30 a.m.–10 p.m.	Off
Alarm: hypoglycemia
10 p.m.–7.30 a.m.	3.0	54
7.30 a.m.–10 p.m.	4.0	72
Alarm: hyperglycemia
10 p.m.–7.30 a.m.	16.0	288
7.30 a.m.–10 p.m.	16.0	288
PLGM group
PLGM, n	7
PLGM suspend
10 p.m.–7.30 a.m.	3.4	61
7.30 a.m.–10 p.m.	Off
Alarm: hypoglycemia
10 p.m.–7.30 a.m.	3.0	54
7.30 a.m.–10 p.m.	4.0	72
Alarm: hyperglycemia
10 p.m.–7.30 a.m.	16.0	288
7.30 a.m.–10 p.m.	16.0	288

SAP group: SAP only; SAP-LGS. PLGM group: SAP+PLGM.

LGS, low-suspend system; n, number of children included in the group; PLGM, Predictive Low-Glucose Management; SAP, sensor-augmented pump therapy.

Table 2.

Algorithm of Hypoglycemia Management During Diabetes Camp

	SAP group, BW <60 kg				PLGM group, BW <60 kg
	Carbohydrate substitution (g)
	Carbs	Starch	Carbs	Starch	Carbs	Starch	Carbs	Starch
Before night (10 p.m.)
Glycemia <4.0 mmol/L (<72 mg/dL)	12	12	18	18	12		18
Glycemia <6.0 mmol/L (<108 mg/dL)		12		18
During night (10 p.m.–7.30 a.m.)
Glycemia <4.00 mmol/L (<72 mg/dL)	12	12	18	18	12		18
Glycemia <5.00 mmol/L (90 mg/dL)		12		18

Carbs, carbohydrates; SAP group: SAP only. PLGM group: SAP+PLGM.

BW, body weight.

The main outcomes were the frequency of hypoglycemia, time spent in hypoglycemia, severity of hypoglycemia (rate of hypoglycemia ≤3.9 mmol/L, 70 mg/dL; rate of hypoglycemia ≤3.5 mmol/L, 60 mg/dL; rate of hypoglycemia ≤2.9 mmol/L, 52 mg/dL; rate of hypoglycemia ≤2.4 mmol/L, 43 mg/dL; and rate of hypoglycemia <2 mmol/L, 36 mg/dL), mean blood overnight glucose, and the amount of administered carbohydrates. The distribution of hypoglycemia during the night was assessed as the rate of hypoglycemia from 10 to 12 p.m., from 12 p.m. to 3 a.m., and from 3 to 7 a.m.

The differences between the SAP and PLGM groups were analyzed using nonparametric tests (Kruskal-Wallis and ANOVA-repeated measurement). The data for mean overnight glucose in the SAP and SAP-PLGM groups, consisting of repeated measurements over seven nights, were compared using a linear mixed-effects model. P-values less than 0.05 were considered statistically significant. The analyses were conducted using the R statistical package, version 3.1.1.

Children and parents met the study team before the camp, and written informed consent was obtained from the parents after thorough explanation of the study protocol. The study was approved by the ethics committee of the hospital.

Results

All participants completed the study. Their mean age was 11.7 (±2.24) years, and they had a mean diabetes duration of 5.50 (±6.41) years. Ten of the subjects (50%) were female. The metabolic control of the subjects was similar between groups with a mean HbA1c of 61 mmol/mol (range 55.8–66.3 mmol/mol; International Federation of Clinical Chemistry (IFCC)), (HbA1c 7.7%; range 7.3%–8.2% Diabetes Control and Complications Trial (DCCT)). There were no significant differences in the insulin dose, bolus versus basal ratio, and body mass index (BMI) SD score (SDS) (for more details see Table 3).

Table 3.

Detailed Characteristics of the Study Subjects

	All children	SAP group	PLGM group
Number of patients	20	13 (65%)	7 (35%)
Age (mean ± SD), years	11.7 ± 2.24	11.6 ± 2.63	11.7 ± 1.44
BMI SDS (mean ± SD)	0.347 ± 0.919	0.363 ± 0.812	0.316 ± 1.216
Diabetes duration (mean ± SD), years	5.50 ± 2.48	5.57 ± 2.98	5.38 ± 1.25
HbA1c (med; IQR), mmol/mol, IFCC	61.0 (55.8; 66.3)	61.0 (57.0; 67.0)	59.0 (49.0; 65.5)
HbA1c (med; IQR), % DCCT	7.7 (7.3; 8.2)	7.7 (7.4; 8.3)	7.5 (6.6; 8.1)
Duration of CSII treatment (mean ± SD), years	2.41 ± 3.05	2.15 ± 3.05	2.88 ± 1.83
Insulin dose (mean ± SD), U/kg/day	0.757 ± 0.155	0.761 ± 0.151	0.749 ± 0.175
Basal (mean), %	48	48	48
Bolus (mean), %	52	52	52

SAP group: SAP only. PLGM group: SAP+PLGM.

BMI SDS, body mass index (BMI) SD score (SDS); CSII, continuous subcutaneous insulin infusion; DCCT, Diabetes Control and Complications Trial; IFCC, International Federation of Clinical Chemistry.

There was no difference in the incidence of nocturnal hypoglycemia over all seven nights (0.6 vs. 0.4 hypoglycemia events per night) between the PLGM and SAP groups. There was no difference in the severity of hypoglycemia; however, the SAP group spent a significantly longer time in hypoglycemia (64 ± 25 min, 12% vs. 38 ± 13 min, 7% per night, P < 0.05). The frequency and severity of hypoglycemia did not significantly differ during all seven nights between the two groups. The time of occurrence of nocturnal hypoglycemia differed significantly between the groups. The PLGM group primarily developed hypoglycemia between 10 and 12 p.m. (82%), in contrast to the SAP group, in which hypoglycemia was most frequently recorded between 3 and 7 a.m. (46%), P < 0.05. The SAP group consumed significantly more carbohydrates for hypoglycemia prevention and treatment, with values of 10 ± 8 g of carbohydrates and 3.5 ± 0 g carbohydrates per night (P < 0.0001) for the SAP and PLGM groups, respectively.

Figure 1 shows the glucose levels recorded by CGM during the seven nights of the camp. There were no differences in the mean overnight BG value and mean morning glycemia (7.9 ± 3 mmol/L vs. 7.5 ± 3 mmol/L) (142 ± 54 mg/dL vs. 135 ± 54 mg/dL) between the PLGM and SAP groups.

FIG. 1.

The median and scatter plot of overnight glucose levels during the seven nights of the camp based on a robust linear mixed-effects model.

The PLGM system was activated on 78% (38/49) of all nights. The median of activation was 1 (0–4) per night per patient. The median glycemia during PLGM activation was 5.1 mmol/L (92 mg/dL), with a range of 2.4–6.3 mmol/L (range 43–113 mg/dL), and the median glycemia during PLGM deactivation was 5.2 mmol/L (93 mg/dL), with a range of 3.9–6.7 mmol/L (range 70–120 mg/dL). The total duration of insulin suspension was 55 min (median, range 5–120 min) per night. No participant developed morning ketonuria in either group. During physical activity in daytime, we reduced the basal rate by ∼50% and boluses by ∼10% to 20%; at nighttime, we reduced the basal rate by ∼20%. This strategy was employed all seven days and nights. The insulin dose reductions were, on average, similar in both groups.

Conclusion

This is the first study to evaluate the effectiveness of PLGM system in preventing nocturnal hypoglycemia after prolonged physical activity under camp conditions. We demonstrated that despite regular activation of the PLGM system, there was no difference in the number or severity of hypoglycemia events between the PLGM and SAP groups. However, the PLGM group spent significantly less time in hypoglycemia and consumed significantly less carbohydrates for hypoglycemia prevention.

There are several specific strategies directed at preventing delayed nocturnal hypoglycemia after prolonged daytime exercise. The Riddell group^12,24 showed that preventive carbohydrate consumption appears effective in preventing hypoglycemia and maintaining glucose levels in a targeted range. However, the amount, type, and timing of carbohydrate intake often vary. Carbohydrate consumption does not completely eliminate the risk of hypoglycemia and increases the risk of subsequent hyperglycemia.^25

–28 Although additional carbohydrate intake results in an increased caloric intake, this strategy remains the mainstay of exercise management in patients with T1D. In our study, we demonstrated that the PLGM system allows hypoglycemia prevention without increased carbohydrate consumption. Moreover, the PLGM system was more effective in reducing the time spent in hypoglycemia than SAP and carbohydrate intake. This finding is consistent with a study by Abraham et al. in which SAP with PLGM reduced the need for hypoglycemia treatment after moderate-intensity exercise in an in-clinic setting.²⁹

Reduction or cessation of basal insulin infusion is the second approach. For young patients using CSII, Taplin et al.³⁰ demonstrated that reducing the basal rate by ∼20% between 9:00 p.m. and 3:00 a.m. largely prevented nocturnal hypoglycemia caused by afternoon aerobic exercise. However, reductions in the basal and/or bolus insulin administration may also cause hyperglycemia and may not always completely prevent hypoglycemia.^31
–33 An additional strategy to help limit hypoglycemia is to use CGM and initiate carbohydrate intake only when needed, perhaps in conjunction with preexercise insulin dose adjustments.²⁴

All these observations are consistent with our study, in which hypoglycemic events were detected in both groups after all interventions mentioned above. The number of hypoglycemic episodes was the same in the group with the PLGM system, which functions by stopping insulin delivery based on predicted sensor glucose levels. However, the highest frequency of hypoglycemia in the PLGM group occurred between 10 and 12 p.m., which may have been due to insufficient reduction of the evening meal bolus or late activation of the PLGM system (10 p.m.).

However, in contrast to the Buckingham study,²² no difference was observed between the SAP and PLGM groups in the mean overnight glucose curves and mean morning glucose. The mean glucose at first suspension was lower (4.9 mmol/l; 86 mg/dL) in our study than the value (5.8 mol/L; 105 mg/dL) observed in the Buckingham study.²² However, the median duration of the pump suspensions was similar (60 min). These differences can be explained by the lower limits set for the predictive algorithm in the PLGM setting in our study.

There are some limitations to this study.

All children included in the study kept their own pump devices, and thus, there was no randomized allocation to the SAP and PLGM groups. The camp conditions also limit the number of participants. All children had regular physical activity sessions, but varying levels of physical fitness. The PLGM system (insulin suspension) depends on sensor accuracy, which could be affected by whole-day physical activity. The lack of difference in the severity of hypoglycemia between the PLGM and SAP groups may be affected by the inclusion of eight children with SAP-LGS (Sensor-Augmented Pump Therapy–Low Glucose Suspend) in the SAP group. However, this automatic function was activated a total of 10 times among all eight children over all seven nights at 3 mmol/L (54 mg/L).

We therefore conclude that the PLGM system is more effective than the carbohydrate intake algorithm in hypoglycemia prevention after prolonged physical activity. Moreover, hypoglycemia can be prevented with a minimal amount of carbohydrate intake and assistance. Thus, PLGM may offer a therapeutic option for children with T1D and their families with planned or unplanned physical activity and fear of following overnight hypoglycemia.

Footnotes

Acknowledgments

The study was supported by grant IPL 699 001 and by the Project for Conceptual Development of Research Organization 00064203/6001 (Ministry of Health, Czech Republic). We thank Mrs. Jana Kaprová, Mrs. Zuzana Reifová, MD, Miss Martina Mullerová, Mr. Michal Barna, MD, Miss Jana Malíková, MD, and the other professional staff of the camp. We also thank all study participants and their families.

Author Disclosure Statement

No competing financial interests exist.

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