Adolescents with type 1 diabetes can achieve glycemic targets on intensive insulin therapy without excessive weight gain

Abstract Introduction The aim of this study was to compare glycemic control and body mass index standard deviation score (BMI‐SDS) before and after implementation of intensive insulin therapy using multiple daily injection (MDI) or continuous subcutaneous insulin infusion (CSII) in adolescents with type 1 diabetes (T1D) attending a large multidisciplinary paediatric diabetes clinic in Australia. Methods Prospective data were collected for cross‐sectional comparison of youth aged 10.0–17.9 years (n = 669) from routine follow‐up visits to the diabetes clinic in 2004, 2010, and 2016. Outcome measures included HbA1c; BMI‐SDS; and insulin regimen. Results BMI‐SDS remained stable between 2004 to 2016 in the 10–13 and 14–17 year age group (0.7 vs. 0.5, p = .12 and 0.7 vs. 0.7, p = .93, respectively). BMI‐SDS was not different across HbA1c groups; <53 mmol/mol (7.0%), 53 to <75 mmol/mol (<7.0 to <9.0%) and >75 mmol/mol (>9.0%) in 2004 (p = .873), 2010 (p = .10) or 2016 (p = .630). Mean HbA1c decreased from 2004 to 2016 in the 10–13 year (69 mmol/mol (8.4%) vs. 57 mmol/mol (7.4%), p = <.001) and 14–17 year group (72 mmol/mol (8.7%) vs. 63 mmol/mol (7.9%), p = <.001). Prior to the implementation of MDI and CSII in 2004 only 10% of 10–13 year olds and 8% of 14–17 year olds achieved the international target for glycemic control (HbA1c 53 mmol/mol [<7.0%]). In 2016, this increased to 31% of 10–13 year olds and 21% of 14–17 year olds. Conclusions BMI‐SDS did not increase with the change to intensive insulin therapy despite a doubling in the number of adolescents achieving the recommended glycemic target of <7.0% (53 mmol/mol). HbA1c was not associated with weight gain.

value (0.65 vs. 0.33). 3 Similarly, our clinic identified rates of overweight and obesity in T1D exceeding those of individuals in the general Australian population (37% vs. 23%). 4 It was shown in the Diabetes Control and Complications Trial that adolescents and adults on intensive insulin therapy gain significantly more weight, with an average increase of 4 kg more than those following conventional therapy. 5  The introduction of insulin to carbohydrate ratios across the whole clinic enabled greater flexibility in carbohydrate intake at meals and snacks 8 although upper limits of carbohydrate intake were still recommended for age. Individuals attended 3-monthly outpatient visits across the entire study period.
The aim of this study was to compare BMI-SDS and glycemic control before and after implementation of intensive insulin therapy in adolescents with T1D.

Ethics approval was granted by the Hunter New England Human
Research Ethics Committee (Reference, 08/11/19/5.04). Inclusion criteria were T1D diagnosis and aged 10.0-17.9 years at time of visit.
Routine clinical data including age, sex, diabetes duration, HbA1c, height, weight and insulin regimen were collected prospectively dur- Statistical analyses were performed using STATA I/C version 15.0 (StataCorp LLC). 10 Descriptive statistics reported as mean ± standard deviation (SD) for continuous variables and frequency and percentage (%) for categorical variables. To determine statistical significance of continuous variables, we used one-way analysis of variance for normally distributed data and Wilcoxon rank test (Mann-Whitney) for non-parametric data, and Fisher's exact test for categorical variables. Tests were performed as two-sided analysis with a level of <0.05 considered significant.

| RE SULTS
The characteristics of 669 eligible youth are summarized in Table 1. There was no significant difference in severe hypoglycemic

| DISCUSS ION
This data suggests that in adolescents with T1D, it is possible to achieve target glycemic control on an intensified insulin regimen without excessive weight gain, and that there is no association between BMI-SDS and HbA1c or therapy type. Our findings are in contrast to those from adolescents in the DCCT trial which saw a two-fold greater risk of becoming overweight with intensive management. 11 Contrary to other reports that demonstrate adolescents are a group that have suboptimal glycemic outcomes, 12 (17) HbA1c Category NGSP (IFCC) <6.5 (48) 6 (6) 5 (4) 10 (10) 10 (8) 15 (15) 14 (11) ≥6.5 < 7.0 (≥48 < 53) 4 (4) 4 (3) 7 (7) 10 (8) 17 (17) 13 (10) ≥7.0 < 7.5 (>53 < 58) 9 (9) 11 (9) 14 (14) 17 (14) (12-17 years) in the general population. 16 However, rates of overweight and obesity in adolescents with T1D still exceed those seen in the Australian population. 4 The pathophysiology of excess weight gain in youth with T1D is not clear; however, multiple factors are common across adolescents with or without T1D, such as sedentary behaviour, reduced exercise (especially in females) and unhealthy eating habits which may contribute to favour a positive energy balance. 17 Factors unique to people with T1D include fear of hypoglycemia and fear of loss of diabetes control as barriers to physical activity, 18 and consumption of additional carbohydrates to prevent or correct hypoglycemia. 19 It is important that centres implement a model of care that supports proactive insulin adjustment around physical activity, and meal-time routines focusing on healthy eating habits which meet nutrient requirements and avoid excess snacking. These factors likely play a pivotal role in supporting adolescents to achieve target glycemic control without excessive weight gain.
There were several limitations in this study. A limitation is that we report from a single diabetes centre, however JHCH is a large university teaching hospital, providing care to all youth with type 1 diabetes across a wide socio-economic background in a nationalized health scheme, in the Hunter Region of NSW, Australia. Body composition analysis was not performed so it is possible muscular individuals may be miscategorised as overweight. Data were captured across three time-points, thus some participants may have been included at more than one timepoint. The year 2020 was not included in this analysis due to the possible COVID-19 pandemic effects on bodyweight, with one large US population study observing a doubling of mean adjusted BMI in 10-13 year olds during the pandemic. 20 Puberty may have impacted body weight but we did not record pubertal status.
In conclusion, the results of this study challenge the opinion that weight gain is a side effect of intensified insulin regimens and improvements in glycemic control. Adolescence remains a challenging period for individuals with T1D with declining glycemic control and a high prevalence of overweight and obesity. Further investigation into the causes of weight gain in adolescents with T1D is vital to informing future interventions.