Does cancer risk increase with HbA1c, independent of diabetes?
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ABSTRACT:
SUBMITTER: de Beer JC
PROVIDER: S-EPMC4007234 | biostudies-other | 2014 Apr
REPOSITORIES: biostudies-other
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Project description:BACKGROUND: Opportunistic screening using hemoglobin A1c (HbA1c) may improve detection of undiagnosed diabetes but remains controversial. OBJECTIVE: To evaluate the predictive validity of HbA1c as a screening test for undiagnosed diabetes in a risk-stratified sample of the US population. DESIGN: Weighted cross-sectional analysis of diabetes risk factors, HbA1c, and fasting plasma glucose (FPG) in National Health and Nutrition Examination Survey (NHANES), 1999-2004. SUBJECTS: Six thousand seven hundred and twenty-three NHANES participants from morning examination session, aged > or = 18 years and without prior physician-diagnosed diabetes. MEASUREMENTS: HbA1c and undiagnosed diabetes defined by FPG > or = 7.0 mmol/l (126 mg/dl). RESULTS: The estimated prevalence of undiagnosed diabetes in the US population was 2.8% (5.5 million people). HbA1c had strong correlation with undiagnosed diabetes, with an area under the receiver-operating characteristic curve of 0.93. Independent predictors of undiagnosed diabetes were older age, male sex, black race, hypertension, elevated waist circumference, elevated triglycerides, and low high-density lipoprotein cholesterol. We derived a risk score for undiagnosed diabetes and stratified participants into low (0.44% prevalence), moderate (4.1% prevalence), and high (11.1% prevalence) risk subgroups. In moderate and high risk groups, a threshold HbA1c value > or = 6.1% identified patients requiring confirmatory FPG; HbA1c < or = 5.4% identified patients for whom diabetes could be reliably excluded. Intermediate HbA1c (5.5-6.0%) may exclude diabetes in moderate, but not high risk groups). CONCLUSIONS: Risk stratification improves the predictive validity of HbA1c in screening for undiagnosed diabetes in the US population. Although opportunistic screening with HbA1c would improve detection of undiagnosed diabetes, cost-effectiveness studies are needed before implementation of specific screening strategies using HbA1c.
| S-EPMC2517991 | biostudies-other
Project description:Associations between type 2 diabetes, anti-diabetic medications and pancreatic cancer are controversial. This study aims to clarify such associations with new-onset type 2 diabetes and repeated measurements of glycated haemoglobin (HbA1c) levels.A nested case-control study was initiated from the Health Improvement Network (THIN) in UK from 1996 to 2010. Information of pancreatic cancer cases was retrieved electronically from the medical records and manually validated. Control subjects were randomly selected and frequency-matched to the cases on sex, age, and calendar years. Multivariable unconditional logistic regression was performed to estimate odds ratios (OR) and 95% confidence intervals (CI), and adjusted for potential confounders.Among 1,574,768 person-years of follow-up, 529 pancreatic cancer cases and 5000 controls were identified. Type 2 diabetes, or changed HbA1c levels (rather than HbA1c levels at diabetes diagnosis) in diabetes patients (?4?mmol?mol(-1) compared with <0?mmol?mol(-1)) were followed by an increased OR of pancreatic cancer (OR, 2.16, 95% CI 1.72-2.72 and OR, 5.06, 95% CI 1.52-16.87, respectively). Among the anti-diabetic medications in diabetes patients, the OR for insulin users was 25.57 (95% CI 11.55-56.60), sulphonylureas 2.22 (95% CI 1.13, 4.40), and metformin users 1.46 (95% CI 0.85-2.52), compared with no use of any anti-diabetic medications.New-onset type 2 diabetes and, particularly, diabetes with rising HbA1c seem to be independent risk factors for pancreatic cancer. The relation between different anti-diabetic medications and pancreatic cancer seems to vary in strength, with the highest risk among users of insulin.
| S-EPMC4705881 | biostudies-literature
Project description:We recently reported that glycated albumin (GA) is increased in subjects with longer duration of diabetes and with decreased insulin secretory function. Based on this, we investigated whether GA increases with time relative to glycated hemoglobin (HbA1c) and the association between GA and beta-cell function. We analyzed 340 type 2 diabetes patients whose serum GA and HbA1c levels had been repeatedly measured over 4 years. We assessed the pattern of changes with time in glycemic indices (GA, HbA1c, and GA/HbA1c ratio) and their relationship with beta-cell function. In all patients, glycemic indices decreased and maintained low levels around 15 and 27 months. However, from 39 months to 51 months, GA significantly increased but HbA1c tended to increase without statistical significance. We defined ΔGA/HbA1c as the difference between the nadir point (at 15 to 27 months) and the end point (at 39 to 51 months) and found that ΔGA/HbA1c was positively correlated with diabetes duration and negatively related to beta-cell function. In multivariable linear regression analyses, ΔGA/HbA1c was independently associated with diabetes duration. In conclusion, this study demonstrated that serum GA levels increase relative to HbA1c levels with time.
| S-EPMC4592895 | biostudies-literature
Project description:Diabetes confers a very high risk of lower-extremity amputation (LEA); however, few studies have assessed whether blood glucose control can reduce LEA risk among patients with diabetes, especially in practice settings where low-income patients predominate.We performed a prospective cohort study (2000-2009) on patients with diabetes that included 19,808 African Americans and 15,560 whites. The cohort was followed though 31 May 2012. Cox proportional hazards regression models were used to estimate the association of HbA1c with LEA risk.During a mean follow-up of 6.83 years, 578 LEA incident cases were identified. The multivariable-adjusted hazard ratios of LEA associated with different levels of HbA1c at baseline (<6.0% [reference group], 6.0-6.9, 7.0-7.9, 8.0-8.9, 9.0-9.9, and ?10.0%) were 1.00, 1.73 (95% CI 1.07-2.80), 1.65 (0.99-2.77), 1.96 (1.14-3.36), 3.02 (1.81-5.04), and 3.30 (2.10-5.20) (P trend <0.001) for African American patients with diabetes and 1.00, 1.16 (0.66-2.02), 2.28 (1.35-3.85), 2.38 (1.36-4.18), 2.99 (1.71-5.22), and 3.25 (1.98-5.33) (P trend <0.001) for white patients with diabetes, respectively. The graded positive association of HbA1c during follow-up with LEA risk was observed among both African American and white patients with diabetes (all P trend <0.001). With stratification by sex, age, smoking status, blood pressure, LDL cholesterol, BMI, use of glucose-lowering agents, and income, this graded association of HbA1c with LEA was still present.The current study conducted in a low-income population suggests a graded association between HbA1c and the risk of LEA among both African American and white patients with type 2 diabetes.
| S-EPMC3816880 | biostudies-other
Project description:Several prospective studies have evaluated the association between glycosylated hemoglobin (HbA1c) and death risk among diabetic patients. However, the results have been inconsistent.We performed a prospective study which included 13,334 men and 21,927 women with type 2 diabetes. Cox proportional hazards regression models were used to estimate the association of different levels of HbA1c with all-cause mortality.During a mean follow up of 8.7 years, 4199 (2082 men and 2117 women) patients died. The multivariable-adjusted hazard ratios (HRs) of all-cause mortality associated with different levels of HbA1c at baseline (<6.0%, 6.0-6.9% [reference], 7.0-7.9, 8.0-8.9%, 9.0-9.9%, 10.0-10.9%, and ?11.0%) were 1.06, 1.00, 1.10, 0.93, 1.26, 1.18 and 1.31 (Pnon-linear=0.008) for men, and 1.21, 1.00, 1.01, 1.08, 1.30, 1.30 and 1.74 (Pnon-linear<0.001) for women, respectively. The J-shaped association of HbA1c with all-cause mortality was confirmed among African American and white diabetic patients, patients who were more than 50 years old, never smoked or used insulin. When we used an updated mean value of HbA1c, the J-shaped association of HbA1c with the risk of all-cause mortality did not change.Our study demonstrated a J-shaped association between HbA1c and the risk of all-cause mortality among men and women with type 2 diabetes. Both high and low levels of HbA1c were associated with an increased risk of all-cause mortality.
| S-EPMC4656101 | biostudies-literature
Project description:Diabetes mellitus (DM) has been associated with an increased risk of colorectal cancer (CRC). The American College of Gastroenterology Guidelines for Colorectal Cancer Screening 2008 recommend that clinicians be aware of an increased CRC risk in patients with smoking and obesity, but do not highlight the increase in CRC risk in patients with DM. To provide an updated quantitative assessment of the association of DM with colon cancer (CC) and rectal cancer (RC), we conducted a meta-analysis of case-control and cohort studies. We also evaluated whether the association varied by sex, and assessed potential confounders including obesity, smoking, and exercise.We identified studies by searching the EMBASE and MEDLINE databases (from inception through 31 December 2009) and by searching bibliographies of relevant articles. Summary relative risks (RRs) with 95% confidence intervals (CIs) were calculated with fixed- and random-effects models. Several subgroup analyses were performed to explore potential study heterogeneity and bias.DM was associated with an increased risk of CC (summary RR 1.38, 95% CI 1.26-1.51; n=14 studies) and RC (summary RR 1.20, 95% CI 1.09-1.31; n=12 studies). The association remained when we limited the meta-analysis to studies that either controlled for smoking and obesity, or for smoking, obesity, and physical exercise. DM was associated with an increased risk of CC for both men (summary RR 1.43, 95% CI 1.30-1.57; n=11 studies) and women (summary RR 1.35, 95% CI 1.14-1.53; n=10 studies). For RC, there was a significant association between DM and cancer risk for men (summary RR 1.22, 95% CI 1.07-1.40; n=8 studies), but not for women (summary RR 1.09, 95% CI=0.99-1.19; n=8 studies).These data suggest that DM is an independent risk factor for colon and rectal cancer. Although these findings are based on observational epidemiological studies that have inherent limitations due to diagnostic bias and confounding, subgroup analyses confirmed the consistency of our findings across study type and population. This information can inform risk models and specialty society CRC screening guidelines.
| S-EPMC3741453 | biostudies-literature
Project description: Not available
| S-EPMC4891496 | biostudies-literature
Project description:United States Veterans are at excess risk for type 2 diabetes, but population differentials in risk have not been characterized. We determined risk of type 2 diabetes in relation to prediabetes and dyslipidemic profiles in Veterans at the VA New York Harbor (VA NYHHS) during 2004-2014. Prediabetes was based on American Diabetes Association hemoglobin A1c (HbA1c) testing cut-points, one of several possible criteria used to define prediabetes. We evaluated transition to type 2 diabetes in 4,297 normoglycemic Veterans and 7,060 Veterans with prediabetes. Cox proportional hazards regression was used to relate HbA1c levels, lipid profiles, demographic, anthropometric and comorbid cardiovascular factors to incident diabetes (Hazard Ratio [HR] and 95% confidence intervals). Compared to normoglycemic Veterans (HbA1c: 5.0-5.6%; 31-38 mmol/mol), risks for diabetes were >2-fold in the moderate prediabetes risk group (HbA1c: 5.7-5.9%; 39-41 mmol/mol) (HR 2.37 [1.98-2.85]) and >5-fold in the high risk prediabetes group (HbA1c: 6.0-6.4%; 42-46 mmol/mol) (HR 5.59 [4.75-6.58]). Risks for diabetes were increased with elevated VLDL (?40mg/dl; HR 1.31 [1.09-1.58]) and TG/HDL (?1.5mg/dl; HR 1.34 [1.12-1.59]), and decreased with elevated HDL (?35mg/dl; HR 0.80 [0.67-0.96]). Transition to diabetes in Veterans was related in age-stratified risk score analyses to HbA1c, VLDL, HDL and TG/HDL, BMI, hypertension and race, with 5-year risk differentials of 62% for the lowest (5-year risk, 13.5%) vs. the highest quartile (5-year risk, 21.9%) of the risk score. This investigation identified substantial differentials in risk of diabetes in Veterans, based on a readily-derived risk score suitable for risk stratification for type 2 diabetes prevention.
| S-EPMC6136717 | biostudies-literature
Project description:BackgroundPrevalence of prediabetes and type 2 diabetes mellitus (T2DM) is increasing worldwide. The objective of this study was to determine the proportion of people in Northern Iceland with prediabetes, at risk of developing T2DM or with manifest undiagnosed T2DM, as this information is lacking in Iceland.MethodsA cross-sectional study. Clients of the three largest primary health care centres in the Health Care Institution of North Iceland (HSN) were invited to participate if fulfilling the following inclusion criteria: a) aged between 18 and 75 years, b) not diagnosed with diabetes, c) speaking and understanding Icelandic or English fluently and d) living in the included service area. Data collection took place via face-to-face interviews between 1 March 2020 and 15 May 2021. Participation included answering the Finnish Diabetes Risk Score (FINDRISC), measuring the HbA1c levels and background information.ResultsOf the 220 participants, 65.9% were women. The mean age was 52.1 years (SD ± 14.1) and FINDRISC scores were as follows: 47.3% scored ≤8 points, 37.2% scored between 9 and 14 points, and 15.5% scored between 15 and 26 points. The mean HbA1c levels in mmol/mol, were 35.5 (SD ± 3.9) for men and 34.4 (SD ± 3.4) for women, ranging from 24 to 47. Body mass index ≥30 kg/m2 was found in 32% of men and 35.9% of women. Prevalence of prediabetes in this cohort was 13.2%. None of the participants had undiagnosed T2DM. Best sensitivity and specificity for finding prediabetes was by using cut-off points of ≥11 on FINDRISC, which gave a ROC curve of 0.814.ConclusionsThe FINDRISC is a non-invasive and easily applied screening instrument for prediabetes. Used in advance of other more expensive and invasive testing, it can enable earlier intervention by assisting decision making, health promotion actions and prevention of the disease burden within primary health care.Trial registrationThis study is a pre-phase of the registered study "Effectiveness of Nurse-coordinated Follow up Program in Primary Care for People at risk of T2DM" at www.Clinicaltrialsgov (NCT01688359). Registered 30 December 2020.
| S-EPMC9887861 | biostudies-literature
Project description:This study aimed to evaluate mortality within 365 days of HbA1c values of <6.5% or >9.0% in participants with clinical type 2 diabetes mellitus. A matched nested case-control study was implemented, within a cohort of participants with type 2 diabetes from 2000 to 2008. Conditional logistic regression was used to model the odds ratio for mortality adjusting for comorbidity and drug utilisation. There were 97,450 participants with type 2 diabetes; 16,585 cases that died during follow up were matched to 16,585 controls. The most recent HbA1c value was <6.5% (48 mmol/mol) for 22.2% of cases and 24.2% of controls, the HbA1c was >9.0% for 9.0% of cases and 7.7% of controls. In a complete case analysis, the adjusted odds ratio (AOR) for mortality associated with most recent HbA1c <6.5% was 1.31 (95% confidence interval (CI): 1.21,1.42). After multiple imputation of missing HbA1c values the AOR was 1.20 (CI: 1.12,1.28). The complete case analysis gave an AOR for HbA1c >9.0% of 1.51 (CI: 1.33, 1.70), in the multiple imputation analysis this was 1.29 (1.17,1.41). The risk associated with HbA1c <6.5% was age dependent. In the multiple imputation analysis the AOR was 1.53 (CI: 0.84 to 2.79) at age<55 years but 1.04 (CI: 0.92, 1.17) at age 85 years and over. In non-randomised data, values of HbA1c that are either <6.5% or >9.0% may be associated with increased mortality within one year in clinical type 2 diabetes. Relative risks may be higher at younger ages.
| S-EPMC3702542 | biostudies-literature