En 21 and 1 ), or increase in HbA1c (increase 23148522 in HbA1c of greater than 1 ). To adjust for potential confounders of the relationship between HbA1c and mortality we identified diagnoses in the last 365 days of: coronary heart disease, arrhythmia, heart failure, stroke or transient ischemic attack, cancer, hypertension, renal failure, liver disease and malnutrition or malabsorption. Analysis also adjusted for treatment with lipid lowering therapies, including statins, within the last 365 days, most recent smoking status (3 categories: non-smoker, ex-smoker, current smoker) and BMI value recorded within the last 365 days (3 categories: normal/underweight, overweight, obese), and treatment with glucose lowering medications within 180 days (insulins, Indolactam V chemical information sulphonylureas, biguanides, pioglitazone, rosiglitazone, and other hypoglycemic medications). The 365 days time frame was informed by the likelihood that severe chronic illnesses will be monitored on at least yearly basis and thus using a 365 days period would allow identification of all patients previously diagnosed with a severe chronic condition. The use of 180 days period for drug therapy was based on the typical length of prescriptions in CPRD. The aim was to capture 86168-78-7 information concerning glucose therapy at the time of death. Participants who were not prescribed glucose lowering drugs were assumed to be on therapy with diet or exercise, though these interventions are not comprehensively recorded in GPRD.MethodsA nested case-control study was implemented using data from family practices contributing to the Clinical Practice Research Datalink (CPRD, formerly known as the General Practice Research Database) between 1 July 2000 and 30 April 2008. The CPRD contains comprehensive information on patients’ medical diagnoses, drug prescriptions, lifestyle advice, specialist referrals, laboratory tests, hospital admissions, and clinical findings (i.e. BMI, smoking, and blood pressure). For entry into the GPRD, practice data must be up to standard (UTS) for research as set out by the GPRD group. The validity of CPRD data for diagnoses and prescribing has been documented in several studies [15,16]. Data for the present study was based on a research project developed in 2009 and thus the latest available data for analysis was to the end of December, 2008. The case-control study was nested in a cohort of people with type 2 diabetes. A case-control design was preferred because it is more efficient than a cohort design for a rare outcome such as mortality. The study also intended to validate Currie et al.’s [12] findings by using a different approach to design. Participants were included in the cohort if they had ever been diagnosed with diabetes mellitus, or prescribed oral hypoglycemic drugs or insulin. Date of diabetes onset was defined as the earlier of first recorded medical or referral code for diabetes or first date of prescription of oral hypoglycemic drugs or insulin. Participants were excluded if they had ever been diagnosed with type 1 diabetes mellitus; were aged less than 30 years at diabetes onset; or were prescribed insulin within 180 days of diabetes onset. Participant follow-up started from the later of: date of onset of diabetes, date of registration with a CPRD practice, date at which the practice began contributing UTS data to CPRD, or 1 July 2000. Participants were censored when they transferred out of a CPRD practice, at the last date at which their practice contributed up to standar.En 21 and 1 ), or increase in HbA1c (increase 23148522 in HbA1c of greater than 1 ). To adjust for potential confounders of the relationship between HbA1c and mortality we identified diagnoses in the last 365 days of: coronary heart disease, arrhythmia, heart failure, stroke or transient ischemic attack, cancer, hypertension, renal failure, liver disease and malnutrition or malabsorption. Analysis also adjusted for treatment with lipid lowering therapies, including statins, within the last 365 days, most recent smoking status (3 categories: non-smoker, ex-smoker, current smoker) and BMI value recorded within the last 365 days (3 categories: normal/underweight, overweight, obese), and treatment with glucose lowering medications within 180 days (insulins, sulphonylureas, biguanides, pioglitazone, rosiglitazone, and other hypoglycemic medications). The 365 days time frame was informed by the likelihood that severe chronic illnesses will be monitored on at least yearly basis and thus using a 365 days period would allow identification of all patients previously diagnosed with a severe chronic condition. The use of 180 days period for drug therapy was based on the typical length of prescriptions in CPRD. The aim was to capture information concerning glucose therapy at the time of death. Participants who were not prescribed glucose lowering drugs were assumed to be on therapy with diet or exercise, though these interventions are not comprehensively recorded in GPRD.MethodsA nested case-control study was implemented using data from family practices contributing to the Clinical Practice Research Datalink (CPRD, formerly known as the General Practice Research Database) between 1 July 2000 and 30 April 2008. The CPRD contains comprehensive information on patients’ medical diagnoses, drug prescriptions, lifestyle advice, specialist referrals, laboratory tests, hospital admissions, and clinical findings (i.e. BMI, smoking, and blood pressure). For entry into the GPRD, practice data must be up to standard (UTS) for research as set out by the GPRD group. The validity of CPRD data for diagnoses and prescribing has been documented in several studies [15,16]. Data for the present study was based on a research project developed in 2009 and thus the latest available data for analysis was to the end of December, 2008. The case-control study was nested in a cohort of people with type 2 diabetes. A case-control design was preferred because it is more efficient than a cohort design for a rare outcome such as mortality. The study also intended to validate Currie et al.’s [12] findings by using a different approach to design. Participants were included in the cohort if they had ever been diagnosed with diabetes mellitus, or prescribed oral hypoglycemic drugs or insulin. Date of diabetes onset was defined as the earlier of first recorded medical or referral code for diabetes or first date of prescription of oral hypoglycemic drugs or insulin. Participants were excluded if they had ever been diagnosed with type 1 diabetes mellitus; were aged less than 30 years at diabetes onset; or were prescribed insulin within 180 days of diabetes onset. Participant follow-up started from the later of: date of onset of diabetes, date of registration with a CPRD practice, date at which the practice began contributing UTS data to CPRD, or 1 July 2000. Participants were censored when they transferred out of a CPRD practice, at the last date at which their practice contributed up to standar.