***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 Recent epidemiological studies suggested that some insulin analogues could be associated with increased risk of cancer . The present study is aim ed at assessing the long-term association of different insulin analogues with  cancer incidence . RESEARCH DESIGN AND METHODS A nested case-control study data set was generated from the cohort study data set ( n = 1,340 insulin-treated diabetic out patients ) by sampling control subjects from the risk sets . For each case subject , the control subjects ( up to five ) were chosen r and omly from those members of the cohort who are at risk for the same follow-up time of the case subject . Five-year age classes , sex , and BMI classes ( < 18.5 , 18.5–24.9 , 25–29.9 , and ≥30 kg/m2 ) were considered as additional categorical matching variables . RESULTS During a median follow-up of 75.9 months ( interquartile range 27.4–133.7 ) , 112 case subjects of incident cancer were compared with 370 matched control subjects . A significantly higher mean daily dose of glargine was observed in case subjects than in control subjects ( 0.24 IU/kg/day [ 0.10–0.39 ] versus 0.16 IU/kg/day [ 0.12–0.24 ] , P = 0.036 ) . Incident cancer was associated with a dose of glargine ≥0.3 IU/kg/day even after adjusting for Charlson comorbidity score , other types of insulin administration , and metformin exposure ( odds ratio 5.43 [ 95 % CI 2.18–13.53 ] , P < 0.001 ) . No association between incident cancer and insulin doses was found for human insulin or other analogues . CONCLUSIONS The possibility of association between cancer and higher glargine doses suggests that dosages should always be considered when assessing the possible association of insulin and its analogues with cancer Aims /hypothesisIn the light of a report suggesting that insulin glargine may increase cancer occurrence , the EASD asked us to perform this study . Methods We followed 114,841 individuals who had a prescription dispensed for insulin between 1 July and 31 December 2005 . From 1 January 2006 to 31 December 2007 , we noted the occurrence of malignancies . Seven different nationwide registers were used to obtain information on insulin exposure , outcome and possible confounders ; these were linked using the unique personal identity number assigned to every Swedish resident . Results After adjustment for age and , when appropriate , sex , users of insulin glargine alone ( no other types of insulin ) , compared with users of types of insulin other than insulin glargine , had an RR of 1.99 ( 95 % CI 1.31–3.03 ) for breast cancer , 0.93 ( 95 % CI 0.61–1.40 ) for gastrointestinal cancer , 1.27 ( 95 % CI 0.89–1.82 ) for prostate cancer and 1.07 ( 95 % CI 0.91–1.27 ) for any type of malignancy . Adjustment for age , smoking , BMI , age at onset of diabetes , age at birth of first child , cardiovascular disease and oestrogen use gave an RR for breast cancer of 1.97 ( 95 % CI 1.29–3.00 ) . The 95 % CIs crossed 1.0 for the RR calculated in all analyses of users of insulin glargine in combination with other types of insulin . Conclusions /interpretationIn Sweden , during 2006 and 2007 , women using  insulin glargine alone ( no other types of insulin ) had an increased incidence rate of breast cancer as compared with women using types of insulin other than insulin glargine . This result may be due to a r and om fluctuation ; the possibilities for examining validity are limited , and no statistically significant results were obtained for any other individual cancer site or for the outcome ‘ all malignancies ’ . No definitive conclusions regarding a possible causal relationship between insulin glargine use and the occurrence of malignancies can be drawn from the results of this study Background A large prospect i ve study in patients with type 2 diabetes ( T2D ) , the German D2C cohort , is presently being enumerated to investigate risk factors of incident cancer in diabetic patients . Study setting A disease management program was offered , on a voluntary basis , to all T2D patients who were members of a statutory health insurance fund in Germany . This first feasibility report uses data from 26.742 T2D patients , who were 40 to 79 years old , resided in the Muenster District , and who were enrolled between June 2003 and July 2008 . Cancer cases were identified through the regional Cancer Registry . Methods Invasive cancer cases were identified using probabilistic record linkage procedures and pseudonymised personal identifiers . Censoring date was December 31 , 2008 . We included only first cancers , leaving 12.650 male and 14.092 female T2D with a total of 88.778 person-years ( py ) . We computed st and ardised incidence ratios ( SIR ) for external comparisons and we employed Cox regression models and hazard ratios ( HR ) within the cohort . Results We identified 759 first cancers among male T2D patients ( 18.7 per 1,000 py ) and 605 among females ( 12.7 per 1,000 py ) . The risk of any incident cancer in T2D was raised ( SIR = 1.14 ; 95 % confidence interval [ 1.10 - 1.21 ] ) , in particular for cancer of the liver ( SIR = 1.94 [ 1.15 - 2.94 ] ) and pancreas ( SIR = 1.45 [ 1.07 - 1.92 ] ) . SIRs decreased markedly with time after T2D diagnosis . In Cox models , adjusting for diabetes duration , body mass index and sex , insulin therapy was related to higher cancer risk ( HR = 1.25 [ 1.17 - 1.33 ] ) . No effect was seen for metformin . Discussion Our study demonstrates feasibility of record linkage between DMP and cancer registries . These first cohort results confirm previous reports . It is envisaged to enhance this cohort by inclusion of further regions of the state , expansion of the follow-up times , and collection of a more detailed medication history Aims /hypothesisDespite the vast body of epidemiological literature on the risk of  cancer in people with diabetes , few studies have examined the pattern of cancer risk during different time windows following diabetes onset . The objective of the study was to examine the risks of site-specific cancer in people with incident type 2 diabetes during different time windows following diabetes onset . Methods This was a population -based retrospective cohort study . The study period was 1 April 1994 to 31 March 2006 ; censoring occurred at 31 March 2006 , at death or on departure from British Columbia , Canada . Using linked health data bases , we identified incident cohorts with and without diabetes , who were matched by age , sex and index year . Following a minimum 2-year cancer washout period , first site-specific cancers were identified prospect ively in both cohorts . Results Within 3 months following diabetes onset , participants with diabetes had significantly increased risks of colorectal , lung , liver , cervical , endometrial , ovarian , pancreatic and prostate cancers . After the initial 3-month period , the risks for colorectal ( HR 1.15 , 95 % CI 1.05 , 1.25 ) , liver ( HR 2.53 , 95 % CI 1.93 , 3.31 ) and endometrial ( HR 1.58 , 95 % CI 1.28 , 1.94 ) cancers remained significantly elevated compared with those without diabetes . The diabetes cohort remained at increased risk of pancreatic cancer in later years , but followed a different pattern : HR 3.71 at 3 months–1 year , 2.94 at 1–2 years , 1.78 at 2–3 years and 1.65 at 3–10 years ( p value for all < 0.01 ) . After an initial period of elevated risk , men with type 2 diabetes subsequently had a decreased risk of prostate cancer ( HR 0.82 , 95 % CI 0.76 , 0.88 ) . Conclusions /interpretationPeople with type 2 diabetes are at increased risk of select cancers ; this risk is particularly elevated at the time of diabetes onset , which is likely to be due to increased ascertainment Aims /hypothesisUsing the Echantillon Généraliste de Bénéficiaires : r and om 1/97 permanent sample of the French national healthcare insurance system data base ( EGB ) , we investigated whether , as previously suspected , the risk of cancer in  insulin glargine ( A21Gly , B31Arg , B32Arg human insulin ) users is higher than in  human insulin users . The investigation period was from 1 January 2003 to 30 June 2010 . Methods We used Cox proportional hazards time-dependent models that were stratified on propensity score quartiles for use of insulin glargine vs human insulin , and adjusted for insulin , biguanide and sulfonylurea possession rates to assess the risk of cancer or death in all or incident exclusive or predominant ( ≥80 % use time ) users of insulin glargine compared with equivalent human insulin users . Results Only type 2 diabetic patients were studied . Exposure rates varied from 2,273 and 614 patient-years for incident exclusive users of insulin glargine or human insulin , respectively , to 3125 and 2341 patient-years for all patients predominantly using insulin glargine or human insulin , respectively . All-type cancer HRs  with insulin glargine vs human insulin ranged from 0.59 ( 95 % CI 0.28 , 1.25 ) in incident exclusive users to 0.58 ( 95 % CI 0.34 , 1.01 ) in all predominant users . Cancer risk increased with exposure to insulin or sulfonylureas in these patients . Adjusted HRs for death or cancer associated with insulin glargine compared with human insulin ranged from 0.58 ( 95 % CI 0.32 , 1.06 ) to 0.56 ( 95 % CI 0.36 , 0.87 ) . Conclusions /interpretationThere was no excess risk of cancer in type 2 diabetic patients on insulin glargine alone compared with those  on human insulin  alone . The overall risk of death or cancer in patients on insulin glargine was about half that of patients on human insulin , thereby excluding a competitive risk bias BACKGROUND The provision of sufficient basal insulin to normalize fasting plasma glucose levels may reduce cardiovascular events , but such a possibility has not been formally tested . METHODS We r and omly assigned 12,537 people ( mean age , 63.5 years ) with cardiovascular risk factors plus impaired fasting glucose , impaired glucose tolerance , or type 2 diabetes to receive insulin glargine ( with a target fasting blood glucose level of ≤95 mg per deciliter [ 5.3 mmol per liter ] ) or st and ard care and to receive n-3 fatty acids or placebo with the use of a 2-by-2 factorial design . The results of the comparison between insulin glargine and st and ard care are reported here . The co primary outcomes were nonfatal myocardial infa rct ion , nonfatal stroke , or death from cardiovascular causes and these events plus revascularization or hospitalization for heart failure . Microvascular outcomes , incident diabetes , hypoglycemia , weight , and cancers were also compared between groups . RESULTS The median follow-up was 6.2 years ( interquartile range , 5.8 to 6.7 ) . Rates of incident cardiovascular outcomes were similar in the insulin-glargine and st and ard-care groups : 2.94 and 2.85 per 100 person-years , respectively , for the first co primary outcome ( hazard ratio , 1.02 ; 95 % confidence interval [ CI ] , 0.94 to 1.11 ; P=0.63 ) and 5.52 and 5.28 per 100 person-years , respectively , for the second co primary outcome ( hazard ratio , 1.04 ; 95 % CI , 0.97 to 1.11 ; P=0.27 ) . New diabetes was diagnosed approximately 3 months after therapy was stopped among 30 % versus 35 % of 1456 participants without baseline diabetes ( odds ratio , 0.80 ; 95 % CI , 0.64 to 1.00 ; P=0.05 ) . Rates of severe hypoglycemia were 1.00 versus 0.31 per 100 person-years . Median weight increased by 1.6 kg in the insulin-glargine group and fell by 0.5 kg in the st and ard-care group . There was no significant difference in cancers ( hazard ratio , 1.00 ; 95 % CI , 0.88 to 1.13 ; P=0.97 ) . CONCL 
    Output:
    
Meta-analyses were significant for : Insulin vs No Insulin : Increased risk for pancreas , liver , kidney , stomach and respiratory cancer , decreased risk for prostate cancer .
Insulin vs Non-Insulin Antidiabetics : Increased risk for any , pancreatic and colorectal cancer .
Glargine vs Non-Glargine Insulin : Increased risk for breast cancer , decreased risk for colon cancer .
Conclusions : Insulin use was associated with  risk of cancer at several sites .
Choice of study design may have a profound effect on estimated cancer risk