***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 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 OBJECTIVE The antidiabetic properties of metformin are mediated through its ability to activate the AMP-activated protein kinase ( AMPK ) . Activation of AMPK can suppress tumor formation and inhibit cell growth in addition to lowering blood glucose levels . We tested the hypothesis that metformin reduces the risk of cancer in people with type 2 diabetes . RESEARCH DESIGN AND METHODS In an observational cohort study using record-linkage data bases and based in Tayside , Scotl and , U.K. , we identified people with type 2 diabetes who were new users of metformin in 1994–2003 . We also identified a set of diabetic comparators , individually matched to the metformin users by year of diabetes diagnosis , who had never used metformin . In a survival analysis we calculated hazard ratios for diagnosis of cancer , adjusted for baseline characteristics of the two groups using Cox regression . RESULTS Cancer was diagnosed among 7.3 % of 4,085 metformin users compared with 11.6 % of 4,085 comparators  , with median times to cancer of 3.5 and 2.6 years , respectively ( P < 0.001 ) . The unadjusted hazard ratio ( 95 % CI ) for cancer was 0.46 ( 0.40–0.53 ) . After adjusting for sex , age , BMI , A1C , deprivation , smoking , and other drug use , there was still a significantly reduced risk of cancer associated with metformin : 0.63 ( 0.53–0.75 ) . CONCLUSIONS These results suggest that metformin use may be associated with a reduced risk of cancer . A r and omized trial is needed to assess whether metformin is protective in a population at high risk for cancer Background : Information on major harms of medical interventions comes primarily from epidemiologic studies performed after licensing and marketing . Comparison with data from large-scale r and omized trials is occasionally feasible . We compared evidence from r and omized trials with that from epidemiologic studies to determine whether they give different estimates of risk for important harms of medical interventions . Methods : We targeted well-defined , specific harms of various medical interventions for which data were already available from large-scale r and omized trials ( > 4000 subjects ) . Nonr and omized studies involving at least 4000 subjects addressing these same harms were retrieved through a search of MEDLINE . We compared the relative risks and absolute risk differences for specific harms in the r and omized and nonr and omized studies . Results : Eligible nonr and omized studies were found for 15 harms for which data were available from r and omized trials addressing the same harms . Comparisons of relative risks between the study types were feasible for 13 of the 15 topics , and of absolute risk differences for 8 topics . The estimated increase in relative risk differed more than 2-fold between the r and omized and nonr and omized studies for 7 ( 54 % ) of the 13 topics ; the estimated increase in absolute risk differed more than 2-fold for 5 ( 62 % ) of the 8 topics . There was no clear predilection for r and omized or nonr and omized studies to estimate greater relative risks , but usually ( 75 % [ 6/8 ] ) the r and omized trials estimated larger absolute excess risks of harm than the nonr and omized studies did . Interpretation : Nonr and omized studies are often conservative in estimating absolute risks of harms . It would be useful to compare and scrutinize the evidence on harms obtained from both r and omized and nonr and omized studies Abstract Aims /hypothesis . To further investigate the association of  cancer occurrence with the use of insulin glargine . Methods . We followed 114 838 individuals using insulin between 1 July and 31 December 2005 . From 1 January 2006 to 31 December 2008 , we noted the occurrence of malignancies ( cohort I ) .  Insulin users between 1 July and 31 December 2006 were followed for the occurrence of malignancies in 2007 and 2008 ( cohort II ) . Users of insulin  during three consecutive six-month periods from 1 July 2005 to 31 December 2006 were followed for the occurrence of malignancies in 2007 and 2008 ( cohort III ) . The Prescribed Drug Register , the Cancer Register , and the Causes of Death Register were used to obtain information on targeted person-time and outcome . We retrieved variables reflecting potential confounding factors from the Swedish National Diabetes Register , the Prescribed Drug Register , the Patient Register , the Medical Birth Register and the National Education Register . With Poisson regression we evaluated the association between insulin use and malignancy outcome with adjustment for confounders . Results . The adjusted incidence rate ratio ( and 95 % confidence interval ) for women who used insulin glargine alone compared with those who used other types of insulin , was 1.60 ( 1.10–2.32 ) for breast cancer but included 1.0 for malignancy outcomes other than breast cancer for men and women when analyzing cohort I with follow-up in 2006–2008 . For cohort II and III the corresponding incidence rate ratios were 1.38 ( 0.87–2.18 ) , and 0.87 ( 0.41–1.85 ) , respectively . Conclusion /interpretation . We do not see an increased risk during 2008 for breast cancer in the  insulin  glargine group . We need data for additional years before we can state with reasonable certainty that the increase in breast cancer incidence that we observed in Sweden in 2006 and 2007 was due to a r and om fluctuation or whether there is an association with the use of insulin glargine BACKGROUND Little is known about the timing of changes in glucose metabolism before occurrence of type 2 diabetes . We aim ed to characterise trajectories of fasting and postload glucose , insulin sensitivity , and insulin secretion in individuals who develop type 2 diabetes . METHODS We analysed data from our prospect i ve occupational cohort study ( Whitehall II study ) of 6538 ( 71 % male and 91 % white ) British civil servants without diabetes mellitus at baseline . During a median follow-up period of 9.7 years , 505 diabetes cases were diagnosed ( 49.1 % on the basis of oral glucose tolerance test ) . We assessed retrospective trajectories of fasting and 2-h postload glucose , homoeostasis model assessment ( HOMA ) insulin sensitivity , and HOMA beta-cell function from up to 13 years before diabetes diagnosis ( diabetic group ) or at the end of follow-up ( non-diabetics ) . FINDINGS Multilevel models adjusted for age , sex , and ethnic origin confirmed that all metabolic measures followed linear trends in the group of non-diabetics ( 10,989 measurements ) , except for insulin secretion that did not change during follow-up . In the diabetic group ( 801 measurements ) , a linear increase in fasting glucose was followed by a steep quadratic increase ( from 5.79 mmol/L to 7.40 mm 
    Output:
    
New use of insulin or insulin glargine was associated with an increased risk of pancreatic cancer , possibly due to reverse causality .
New use of insulin glargine was associated with a decreased risk of colorectal cancer but an increased risk of prostate cancer .