***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Objective Increased weight gain has been reported prior to disease onset ( accelerator hypothesis ) and as a side effect of intensified insulin therapy in type 1 diabetes ( T1D ) . Paediatric studies are complicated by the age-dependency and gender-dependency of BMI , and also by a trend towards obesity in the general population . The aim of this study was to evaluate factors related to the increase in BMI during the course of diabetes in children and adolescents with T1D in a large multicentre survey . Design Within the DPV data base ( Diabetespatienten Verlaufsdokumentation ) a st and ardised , prospect i ve , computer-based documentation programme , data of 53 108 patients with T1D , aged < 20 years , were recorded in 248 centres . 12 774 patients ( 53 % male , mean age 13.4±3.9 , mean diabetes duration 4.7±3.0 years and mean age at diabetes onset 8.7±4.0 years ) were included in this analysis . Population -based German reference data were used to calculate BMI -SDS and define overweight and obesity . Results 12.5 % of T1D patients were overweight and 2.8 % were obese . Multiple longitudinal regression analysis revealed that female gender , low BMI at diabetes onset , intensified insulin therapy and higher insulin dose , as well as pubertal diabetes onset , long diabetes duration and onset in earlier calendar years among girls , were related to higher BMI -SDS increase during the course of diabetes ( p<0.01 ; all ) . Conclusions Intensified insulin regimen  is associated with weight gain during T1D treatment , in addition to demographic variables . Optimisation of diabetes management , especially in females , might limit weight gain in order to reduce overweight and obesity together with comorbidities among paediatric T1D patients BACKGROUND Insulin resistance increases during adolescence in those with type 1 diabetes mellitus ( T1DM ) , complicating glycemic control and potentially increasing cardiovascular disease ( CVD ) risk . Metformin , typically used in type 2 diabetes mellitus ( T2DM ) , is a possible adjunct therapy in T1DM to help improve glycemic control and insulin sensitivity . OBJECTIVE We hypothesized that metformin would improve metabolic parameters in adolescents with T1DM . DESIGN , SETTING , AND PARTICIPANTS This r and omized , double-blinded , placebo-controlled trial included 74 pubertal adolescents ( ages : 13 - 20 yr ) with T1DM . Participants were r and omized to receive either metformin or placebo for 6 months . Glycated hemoglobin ( HbA1c ) , insulin dose , waist circumference , body mass index ( BMI ) , and blood pressure were measured at baseline , 3 and 6 months , with fasting lipids measured at baseline and 6 months . RESULTS Total daily insulin dose , BMI z-score and waist circumference significantly decreased at 3 and 6 months compared to baseline within the metformin group , even among normal-weight participants . In the placebo group , total insulin dose and systolic blood pressure increased significantly at 3 months and total insulin dose increased significantly at 6 months . No significant change was observed in HbA1c at any time point between metformin and placebo groups or within either group . CONCLUSIONS Low-dose metformin likely improves BMI as well as insulin sensitivity in T1DM adolescents , as indicated by a decrease in total daily insulin dose . The decrease in waist circumference indicates that fat distribution is also likely impacted by metformin in T1DM . Further studies with higher metformin doses and more detailed measurements are needed to confirm these results , their underlying mechanisms , and potential impact on CVD in T1DM youth OBJECTIVE The authors developed and vali date d a semi-structured interview ; the Diabetes Self-Management Profile ( DSMP ) , to measure self-management of type 1 diabetes .  The DSMP includes the following regimen components : exercise , management of hypoglycemia , diet , blood glucose testing , and insulin administration and dose adjustment . RESEARCH DESIGN AND METHODS Families of youths with type 1 diabetes ( n = 105 ) who were entering a controlled trial of intensive therapy ( IT ) versus usual care ( UC ) were administered the DSMP Analyses assessed the reliability and validity of the DSMP , including its associations with HbA1c and quality of life . RESULTS The DSMP total score has adequate internal consistency ( Cronbach 's alpha 0.76 ) , 3-month test-retest reliability ( Pearson correlation , r = 0.67 ) , inter-interviewer agreement ( r = 0.94 ) , and parent-adolescent agreement ( r = 0.61 ) . DSMP total scores ( r = -0.28 ) and 3 subscales correlated significantly with HbA1c ( diet [ r = -0.27 ] , blood glucose testing [ r = -0.37 ] , and insulin administration and dose adjustment [ r = -0.25 ] ) . Adolescents ' reports of self-management did not differ from parental reports . Higher DSMP scores were associated with more favorable quality of life for mothers and youths . CONCLUSIONS The DSMP is a convenient measure that yields a reliable and valid assessment of diabetes self-management . Compared with extant similar measures , the DSMP is more strongly correlated with HbA1c Background : The growth deceleration observed in children with type 1 diabetes ( T1D ) has been related to poor glycemic control . It is unclear whether growth impairment persists despite the optimization of therapy . We analyzed the effects of intensive insulin treatment on prepubertal growth . Methods : One hundred and four T1D children were evaluated from T1D diagnosis up to puberty onset .  Height , weight , insulin requirement and glycated hemoglobin ( HbA1c ) were recorded at 3- to 6-month intervals . Residual β-cell mass was estimated by fasting C-peptide at T1D onset . Results : Age at T1D onset was 5.91 ± 1.9 years . Follow-up duration was 4.84 ± 1.58 years . Height velocity st and ard deviation score ( SDS ) was -0.14 ± 1.84 . Height SDS changed from 0.52 ± 1.04 at T1D onset , to 0.36 ± 1.10 at the end of follow-up ( p = 0.04 ) . BMI SDS increased from -0.04 ± 1.48 to 0.32 ± 1.03 ( p = 0.01 ) . Multivariate analysis showed that height velocity was directly affected by C-peptide ( p = 0.03 ) and insulin requirement ( p = 0.004 ) and inversely related to HbA1c ( p = 0.006 ) . BMI gain was negatively influenced by HbA1c ( p = 0.01 ) and positively related to T1D duration ( p = 0.01 ) . Conclusion : Despite insulin intensive therapy , T1D still negatively affects growth . Residual β-cell mass has a direct positive impact on growth , independently from the quality of glycemic control AIM To assess the effect of a 5-day structured education course ( Kids in Control of Food ; KICk-OFF ) on biomedical and psychological outcomes in young people with Type 1 diabetes . METHODS This was a cluster-r and omized trial involving 31 UK paediatric centres . Participants were recruited prior to stratified centre r and omization . Intervention centres delivered KICk-OFF courses , whereas control centres delivered usual care .  Participants were 11 - 16 years of age and had Type 1 diabetes for at least one year . The KICk-OFF course was delivered by trained educators to eight participants per course . Glycaemic control and quality of life were measured at baseline , 6 , 12 and 24 months . Secondary outcomes were hypoglycaemia , ketoacidosis , fear of hypoglycaemia and diabetes self-efficacy . RESULTS Three hundred and ninety-six participants provided baseline data ( 199 intervention and 197 control ) . At 6 and 12 months the intervention group showed significantly improved total generic quality of life scores compared with controls ( baseline : 80 vs. 82 ; 6 months : 82 vs. 82 ; P = 0.04 ) . Across the whole intervention group mean HbA1c levels were not significantly different from controls ; baseline HbA1c mean ( 95 % confidence interval ) , 78 mmol/mol ( 75 - 81 ) vs. 76 mmol/mol ( 74 - 79 ) [ 9.3 % ( 9 - 9.6 % ) vs. 9.1 % ( 8.9 - 9.4 % ) ; 24 months : 77 mmol/mol ( 74 - 79 ) vs. 78 mmol/mol ( 75 - 81 ) ( 9.2 % ( 8.9 - 9.4 % ) vs. 9.3 % ( 9 - 9.6 % ) ] , adjusted mean difference , -2.0 mmol/mol ( 6.5 - 2.5 ) [ 2.3 % ( -2.7 % to 2.4 % ) ] , P = 0.38 . CONCLUSIONS Attending a KICk-OFF course was associated with significantly improved total quality of life scores within 6 months . Glycaemic control , as measured by HbA1c , was no different at 24 months . ( Clinical Trial Registry No : IS RCT N3704268 ) Type 2 diabetes is a leading cause of morbidity and mortality . While genetic variants have been found to influence the risk of type 2 diabetes mellitus , relatively few studies have focused on genes associated with glycated hemoglobin , an index of the mean blood glucose concentration of the preceding 8–12 weeks . Epidemiologic studies and r and omized clinical trials have documented the relationship between glycated hemoglobin levels and the development of long-term complications in diabetes ; moreover , higher glycated hemoglobin levels in the subdiabetic range have been shown to predict type 2 diabetes risk and cardiovascular disease . To examine the common genetic determinants of glycated hemoglobin levels , we performed a genome-wide association study that evaluated 337,343 SNPs in 14,618 apparently healthy Caucasian women . The results show that glycated hemoglobin levels are associated with genetic variation at the GCK ( rs730497 ; P = 2.8 × 10−12 ) , SLC30A8 ( rs13266634 ; P = 9.8 × 10−8 ) , G6PC2 ( rs1402837 ; P = 6.8 × 10−10 ) , and HK1 ( rs7072268 ; P = 6.4 × 10−9 ) loci . While associations at the GCK , SLC30A8 , and G6PC2 loci are confirmatory , the findings at HK1 are novel . We were able to replicate this novel association in an independent validation sample of 455 additional non-diabetic men and women . HK1 encodes the enzyme hexokinase , the first step in glycolysis and a likely c and i date for the control of glucose metabolism . This observed genetic association between glycated hemoglobin levels and HK1 polymorphisms paves the way for further studies of the role of HK1 in hemoglobin glycation , glucose metabolism , and diabetes OBJECTIVE Continuous glucose monitoring ( CGM ) has been demonstrated to improve glycemic control in adults with type 1 diabetes but less so in children . We design ed a study to assess CGM benefit in young children aged 4 to 9 years with type 1 diabetes . RESEARCH DESIGN AND METHODS After a run-in phase , 146 children with type 1 diabetes ( mean age 7.5 ± 1.7 years , 64 % on pumps , median diabetes duration 3.5 years ) were r and omly assigned to CGM or to usual care . The primary outcome was reduction in HbA1c at 26 weeks by ≥0.5 % without the occurrence of severe hypoglycemia . RESULTS The primary outcome was achieved by 19 % in the CGM group and 28 % in the control group ( P = 0.17 ) . Mean change in HbA1c was −0.1 % in each group ( P = 0.79 ) . Severe hypoglycemia rates were similarly low in both groups . CGM wear decreased over time , with only 41 % averaging at least 6 days/week at 26 weeks . There was no correlation between CGM use and change in HbA1c ( rs = −0.09 , P = 0.44 ) . CGM  wear was well tolerated , and parental satisfaction with CGM was high . However , parental fear of hypoglycemia was not reduced . CONCLUSIONS CGM in 4- to 9-year-olds did not improve glycemic control despite a high degree of parental satisfaction with CGM . We postulate that this finding may be related in part to limited use of the CGM glucose data in day-to-day management and to an unremitting fear of hypoglycemia . Overcoming the barriers that prevent integration of these critical glucose data into day-to-day management remains a challenge O 
    Output:
    
Our review shows the complexity of explaining HbA1c level variations , which involves numerous correlated predictors .
Overall , our review underlines the lack of studies investigating jointly genetic and non-genetic factors and their interactions to better underst and factors influencing glycaemic control for T1D patients