Hypoglycemia Prevalence in Prepubertal Children With Type 1 Diabetes on Standard Insulin Regimen: Use of Continuous Glucose Monitoring System RAKESH AMIN, MBCLB, MRCP 1 KAREN ROSS, BSC 2 CARLO L. ACERINI, MD, MRCP 1 JULIE A. EDGE, MD, MRCP 2 JUSTIN WARNER, MD, MRCP 2 DAVID B. DUNGER, FRCPL 1 OBJECTIVE — To determine hypoglycemia prevalence in prepubertal children on thrice (TID) and twice (BID) daily insulin regimens, using the Medtronic Minimed Continuous Glucose Monitoring System. RESEARCH DESIGN AND METHODS — Twenty-eight children aged 12 years (me- dian 9.8, range 6.9 –11.8) wore the sensor for three consecutive days and nights. Hypoglycemia was defined as glucose 60 mg/dl for 15 min. Data are expressed as the percentage of time period spent hypoglycemic. RESULTS — Hypoglycemia prevalence was 10.1% (mean 2.6 h  subject -1  day -1 ). Hypo- glycemia was more common at night compared with daytime (18.81 vs. 4.4%, P  0.001); 78 and 43% of subjects showed hypoglycemia on at least one night and two or more nights, respectively. Nocturnal episodes were prolonged (median 3.3 h) and asymptomatic (91% of episodes). Prevalence was greater between 0400 and 0730 h than between 2200 and 0400 h (25.5 vs. 15.4%, P  0.001). On a TID compared with a BID regimen, nocturnal hypoglycemia prevalence was reduced, particularly between 0400 – 0730 h (22.9 vs. 27.4%, P = 0.005), whereas hypoglycemia the following morning (0730 –1200 h) was greater (7.8 vs. 2.8%, P  0.001). Nocturnal hypoglycemia risk was associated with decreasing age (by a factor of 0.6 for a year less in age), increased insulin dose (by 1.6 for an increase of 0.1 units  kg -1  day -1 ), insulin regimen (by 0.2 on a BID compared with a TID regimen), and increased weight standard deviation score (SDS) (by 2.7 for a one SDS rise). CONCLUSIONS — Use of standard insulin regimens results in high prevalence and large intraindividual variation in hypoglycemia, particularly at night. Independent risk factors for nocturnal hypoglycemia were younger age, greater daily insulin dose, insulin regimen, and increasing weight. Diabetes Care 26:662– 667, 2003 T he development of microvascular complications in type 1 diabetic subjects is recognized to be related to poor glycemic control (1). It is now acknowledged that prepubertal glycemic control may contribute to this risk (2), and as a result, there has been a call for more strict metabolic control in this age group. However improved glycemic con- trol comes at an increased risk of hypo- glycemia, which is already present in up to 50% of children on standard insulin regimens, with episodes being largely nocturnal, prolonged, and profound (3). In our experience, most children in the U.K. are on standard thrice (TID) or twice (BID) daily insulin regimens. Due to timing of injections, free insulin levels dif- fer between these regimens (4) and con- tribute to hypoglycemic risk. This risk may be influenced further by other factors that alter intraindividual rate of insulin absorption (5) and counter-regulatory re- sponses (3). Although data are conflicting (6 –18), in children risk factors for hypo- glycemia include lower HbA 1c (6,9,10,16), younger age (9,14), duration of diabetes (9,12,16,17), insulin dose (7,18), previous hypoglycemia (7,16,18), and multiple injection therapy (10,15). However, current data suggest no differ- ence in hypoglycemia prevalence on thrice versus twice a day insulin regimens. The variations in findings are in part re- lated to differences in populations, collec- tion of data, definitions of outcome, and data analysis, thus making comparisons between studies difficult. In addition, lit- tle data exist as to the intraindividual vari- ations in hypoglycemia prevalence. The Medtronic Minimed Continuous Glucose Monitoring System (CGMS) records 5-min subcutaneous glucose readings for up to 3 consecutive days. The CGMS allows reliable assessment of true glycemic fluctuation through the day and night (19), and it provides an opportunity to study, relatively noninvasively, intra- and interindividual variation in hypogly- cemia prevalence. We used the CGMS to determine characteristics and risk factors for hypoglycemia in prepubertal type 1 diabetic children on standard insulin reg- imens. Study design Thirty-four prepubertal subjects with type 1 diabetes were recruited from the pediatric diabetes clinics at the John Rad- ●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●● From the 1 University Departments of Paediatrics, Addenbrookes Hospital, Cambridge, U.K.; and 2 John Radcliffe Hospital, Oxford, U.K Address correspondence and reprint requests to Professor David B. Dunger Box 116, Level 8, University Department of Paediatrics, Addenbrookes Hospital, Cambridge, U.K., CB2 2QQ. E-mail: dbd25@cam.ac. uk. Received for publication 7 October 2002 and accepted in revised form 10 December 2002. Abbreviations: BID, twice a day; CGMS, Continuous Glucose Monitoring System; GH, growth hormone; HPLC, high-performance liquid chromatography; IQR, interquartile range; SDS, standard deviation score; TID, three times a day. A table elsewhere in this issue shows conventional and Syste `me International (SI) units and conversion factors for many substances. Epidemiology/Health Services/Psychosocial Research O R I G I N A L A R T I C L E 662 DIABETES CARE, VOLUME 26, NUMBER 3, MARCH 2003