***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 Insulin degludec ( IDeg ) is a basal insulin that forms soluble multihexamers after subcutaneous injection , result ing in an ultra-long action profile . We assessed the efficacy and safety of IDeg formulations administered once daily in combination with mealtime insulin aspart in people with type 1 diabetes . RESEARCH DESIGN AND METHODS In this 16-week , r and omized , open-label trial , participants ( mean : 45.8 years old , A1C 8.4 % , fasting plasma glucose [ FPG ] 9.9 mmol/L , BMI 26.9 kg/m2 ) received subcutaneous injections of IDeg(A ) ( 600 μmol/L ; n = 59 ) , IDeg(B ) ( 900 μmol/L ; n = 60 ) , or insulin glargine ( IGlar ; n = 59 ) , all given once daily in the evening . Insulin aspart was administered at mealtimes . RESULTS At 16 weeks , mean A1C was comparable for IDeg(A ) ( 7.8 ± 0.8 % ) , IDeg(B ) ( 8.0 ± 1.0 % ) , and IGlar ( 7.6 ± 0.8 % ) , as was FPG ( 8.3 ± 4.0 , 8.3 ± 2.8 , and 8.9 ± 3.5 mmol/L , respectively ) . Estimated mean rates of confirmed hypoglycemia were 28 % lower for IDeg(A ) compared with IGlar ( rate ratio [ RR ] : 0.72 [ 95 % CI 0.52–1.00 ] ) and 10 % lower for IDeg(B ) compared with IGlar ( RR : 0.90 [ 0.65–1.24 ] ) ; rates of nocturnal hypoglycemia were 58 % lower for IDeg(A ) ( RR : 0.42 [ 0.25–0.69 ] ) and 29 % lower for IDeg(B ) ( RR : 0.71 [ 0.44–1.16 ] ) . Mean total daily insulin dose was similar to baseline . The frequency and pattern of adverse events was similar between insulin treatments . CONCLUSIONS In this clinical exploratory phase 2 trial in people with type 1 diabetes  , IDeg is safe and well tolerated and provides comparable glycemic control to IGlar at similar doses , with reduced rates of hypoglycemia BACKGROUND Intensive basal-bolus insulin therapy has been shown to improve glycaemic control and reduce the risk of long-term complications that are associated with type 1 diabetes mellitus .  Insulin degludec is a new , ultra-longacting basal insulin . We therefore compared the efficacy and safety of insulin degludec and insulin glargine , both administered once daily with mealtime insulin aspart , in basal-bolus therapy for type 1 diabetes . METHODS In an open-label , treat-to-target , non-inferiority trial , undertaken at 79 sites ( hospitals and centres ) in six countries , adults ( aged ≥18 years ) with type 1 diabetes ( glycated haemoglobin [ HbA(1c ) ] ≤10 % [ 86 mmol/mol ] ) , who had been treated with basal-bolus insulin for at least 1 year , were r and omly assigned in a 3:1 ratio , with a computer-generated blocked allocation sequence , to insulin degludec or insulin glargine without stratification by use of a central interactive response system . The primary outcome was non-inferiority of degludec to glargine , assessed as a reduction in HbA(1c ) after 52 weeks , with the intention-to-treat analysis . This trial is registered with Clinical Trials.gov , number NCT00982228 . FINDINGS Of 629 participants , 472 were r and omly assigned to insulin degludec and 157 to insulin glargine ; all were analysed in their respective treatment groups . At 1 year , HbA(1c ) had fallen by 0·40 % points ( SE 0·03 ) and 0·39 % points ( 0·07 ) , respectively , with insulin degludec and insulin glargine ( estimated treatment difference -0·01 % points [ 95 % CI -0·14 to 0·11 ] ; p<0·0001 for non-inferiority testing ) and 188 ( 40 % ) and 67 ( 43 % ) participants achieved a target HbA(1c ) of less than 7 % ( < 53 mmol/mol ) . Rates of overall confirmed hypoglycaemia ( plasma glucose < 3·1 mmol/L or severe ) were similar in the insulin degludec and insulin glargine groups ( 42·54 vs 40·18 episodes per patient-year of exposure ; estimated rate ratio [ degludec to glargine ] 1·07 [ 0·89 to 1·28 ] ; p=0·48 ) . The rate of nocturnal confirmed hypoglycaemia was 25 % lower with degludec than with glargine ( 4·41 vs 5·86 episodes per patient-year of exposure ; 0·75 [ 0·59 to 0·96 ] ; p=0·021 ) . Overall serious adverse event rates ( 14 vs 16 events per 100 patient-years of exposure ) were similar for the insulin degludec and insulin glargine groups . INTERPRETATION Insulin degludec might be a useful basal insulin for patients with type 1 diabetes because it provides effective glycaemic control while lowering the risk of nocturnal hypoglycaemia , which is a major limitation of insulin therapy . FUNDING Novo Nordisk OBJECTIVE To evaluate efficacy and tolerability of a co-formulation of insulin degludec and insulin aspart ( IDegAsp ) with insulin aspart ( IAsp ) at other meals compared with basal-bolus therapy using insulin detemir ( IDet ) and IAsp . RESEARCH DESIGN AND METHODS Adults ( n = 548 ) with type 1 diabetes ( A1C 7.0–10.0 % ; BMI ≤35.0 kg/m2 ) were r and omized 2:1 in a 26-week , multinational , parallel-group , treat-to-target trial to IDegAsp or IDet . IDegAsp was given with a meal , and IDet was given in the evening , with a second ( breakfast ) dose added if needed . RESULTS Non-inferiority for IDegAsp versus IDet was confirmed ; A1C improved by 0.75 % with IDegAsp and 0.70 % with IDet to 7.6 % in both groups ( estimated treatment difference IDegAsp − IDet : –0.05 % [ 95 % CI –0.18 to 0.08 ] ) . There was no statistically significant difference between IDegAsp and IDet in the rates of severe hypoglycemia ( 0.33 and 0.42 episodes/patient-year , respectively ) or overall confirmed ( plasma glucose < 3.1 mmol/L ) hypoglycemia ( 39.17 and 44.34 episodes/patient-year , respectively ) . Nocturnal confirmed hypoglycemia rate was 37 % lower with IDegAsp than IDet ( 3.71 vs. 5.72 episodes/patient-year , P < 0.05 ) . Weight gain was 2.3 and 1.3 kg with IDegAsp and IDet , respectively ( P < 0.05 ) . Total insulin dose was 13 % lower in the IDegAsp group ( P < 0.0001 ) . No treatment differences were detected in Health-Related Quality of Life , laboratory measurements , physical examination , vital signs , electrocardiograms , fundoscopy , or adverse events . CONCLUSIONS IDegAsp in basal-bolus therapy with IAsp at additional mealtimes improves overall glycemic control and was non-inferior to IDet , with a reduced risk of nocturnal hypoglycemia and fewer injections in comparison with IDet + IAsp basal-bolus therapy AIMS Insulin is lipogenic and may invoke inflammation . We wished to determine if well controlled human and mice with type 1 diabetes had iatrogenic hyperinsulinemia as an explanation for the increased rate of coronary artery disease ( CAD ) in type 1 diabetes . METHODS Type 1 diabetic subjects with HbA1C less than 7.0 % had  plasma insulin measured before and one hour after a Boost ® challenge and a dose of subcutaneously administered insulin . These levels were compared with non-diabetic humans . Plasma insulin levels in well controlled NOD mice with type 1 diabetes were measured 3 h and 17 h after their usual dose of insulin .  Hepatic cholesterol-relevant CAD and inflammation markers were measured in the NOD mice . RESULT Marked iatrogenic hyperinsulinemia was observed in patients at levels of approximately two times higher than in non-diabetic controls . Similar findings were present in the NOD mice . Hepatic CAD risk markers were increased by insulin , but did not exceed normal expression levels in non-diabetic mice with lower insulin . In contrast , insulin-mediated stimulation of pro-inflammatory mediators TNF-α and IL-1β remained significantly higher in hyperinsulinemic NOD than non-diabetic mice . CONCLUSION Optimal insulin therapy in mice and humans with type 1 diabetes causes iatrogenic hyperinsulinemia and subsequently promotes pro-inflammatory macrophage response independent of hepatic cholesterol-relevant CAD markers . The tight glycemic control in type 1 diabetes may thus increase the risk for atherogenesis via inflammation 
    Output:
    
Conclusions Basal – bolus treatment with insulin degludec was superior to long-acting insulin analogues detemir and glargine in reducing the rate of nocturnal hypoglycaemia .
In comparison with other long-acting analogues , treatment with insulin degludec was safe and patients obtained similar metabolic control expressed by HbA1c and FPG levels with the added benefit of a reduced basal and total insulin dose