Association between a biomarker of glucose spikes, 1,5-anhydroglucitol, and cancer mortality (original) (raw)
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Diabetes Care, 2016
Anhydroglucitol (1,5-AG) is a biomarker of glucose peaks and has been associated with clinical cardiovascular disease. However, the association between 1,5-AG and subclinical cardiovascular disease is unknown. We investigated the association of 1,5-AG with subclinical myocardial damage (assessed by highsensitivity cardiac troponin T [hs-cTnT]) and atherosclerosis (assessed by carotid intima-media thickness [CIMT] and carotid plaque). RESEARCH DESIGN AND METHODS We measured 1,5-AG, hs-cTnT, CIMT, and carotid plaque among 10,072 people without diabetes and 681 with diabetes who attended the second examination of the Atherosclerosis Risk in Communities (ARIC) Study (baseline, 1990-1992). We used Poisson regression to characterize the associations between 1,5-AG and prevalent elevated hs-cTnT, thick CIMT, or carotid plaque. Among 9,145 people with a second hs-cTnT measurement 6 years later, we used multinomial logistic regression to assess associations with incident elevation in hs-cTnT. RESULTS We found that in people with diabetes, lower 1,5-AG (<6 mg/mL) was crosssectionally associated with elevated hs-cTnT (prevalence ratio 2.06, 95% CI 1.23-3.46) compared with higher 1,5-AG (‡10 mg/mL). Associations in people without diabetes and with thick CIMT or the presence of carotid plaque were less robust. Low 1,5-AG was prospectively associated with the 6-year incident elevation in hs-cTnT (relative risk 2.90, 95% CI 1.23-6.85) in people with diabetes. All associations were strongly attenuated with further adjustment for HbA 1c. CONCLUSIONS In people with diabetes, 1,5-AG was associated with subclinical cardiovascular disease, particularly chronic subclinical myocardial damage. Nonetheless, whether observed associations are truly independent of average glycemia is unclear. 1,5-Anhydroglucitol (1,5-AG) is a dietary monosaccharide that resembles glucose structurally (1,2). Plasma 1,5-AG competes with glucose for reabsorption in the renal tubules and demonstrates stable concentrations when its intake and excretion are balanced. However, in the setting of hyperglycemia, high amounts of glucose block tubular reabsorption of 1,5-AG, causing increased urinary losses and reduced
Abnormal Glucose Tolerance and the Risk of Cancer Death in the United States
American Journal of Epidemiology, 2003
Although abnormal glucose tolerance is a well-established risk factor for cardiovascular disease, its relation to cancer risk is less certain. Therefore, the authors performed a prospective cohort study using data from the Second National Health and Nutrition Examination Survey and the Second National Health and Nutrition Examination Survey Mortality Study to determine this relation. This analysis focused upon a nationally representative sample of 3,054 adults aged 30-74 years who underwent an oral glucose tolerance test at baseline (1976)(1977)(1978)(1979)(1980). Deaths were identified by searching national mortality files through 1992. Adults were classified as having either previously diagnosed diabetes (n = 247), undiagnosed diabetes (n = 180), impaired glucose tolerance (n = 477), or normal glucose tolerance (n = 2250). There were 195 cancer deaths during 40,024 person-years of follow-up. Compared with those having normal glucose tolerance, adults with impaired glucose tolerance had the greatest adjusted relative hazard of cancer mortality (relative hazard = 1.87, 95% confidence interval (CI): 1.06, 3.31), followed by those with undiagnosed diabetes (relative hazard = 1.31, 95% CI: 0.48, 3.56) and diabetes (relative hazard = 1.13, 95% CI: 0.49, 2.62). These data suggest that, in the United States, impaired glucose tolerance is an independent predictor for cancer mortality.
EBioMedicine
Background: Impaired glucose regulation, measured with an oral glucose-tolerance test, has been associated with the risk of cancer. Here, we explored whether the response to an intravenous glucose-tolerance test (IVGTT) is associated with the risk of cancer. Methods: A cohort of 945 healthy men, aged 40-59 years in 1972-75, was followed for 40 years. An IVGTT was performed at baseline. Blood samples for glucose determinations were drawn immediately before glucose injection and thereafter every 10 min for 1 h. Associations were assessed with incidence rate ratios (IRR) and Cox models. Findings: Cancer incidence was higher among men with 10-min glucose levels below the median than in men with levels above the median (IRR: 1.5, 95% CI: 1.2-1.9). This association remained significant after adjusting for relevant confounders (HR: 1.6, 95% CI: 1.3-2.1) and when excluding the first 10 years of follow-up to minimize the possibility of reverse causality (HR: 1.5, 95% CI: 1.2-2.0). Interpretation: Healthy middle-aged males that responded to an intravenous glucose injection with rapid glucose elimination during the first phase had an elevated risk of cancer during 40 years of follow-up. First phase response to a glucose load might be related to cancer development.
Fasting blood glucose and cancer risk in a cohort of more than 140,000 adults in Austria
2006
Aims/hypothesis: We investigated relations between fasting blood glucose and the incidence of cancer. Methods: A population-based cohort of more than 140,000 Austrian adults (63,585 men, 77,228 women) was followed over an average of 8.4 years. Incident cancer (other than non-melanoma skin cancers) was ascertained by a population-based cancer registry (n=5,212). Cox proportional-hazards models were used to estimate hazard rate ratios (HR) stratified for age and adjusted for smoking, occupational group and body mass index.
Diabetes, Obesity and Metabolism, 2019
Aims: To evaluate 1,5-anhydroglucitol (1,5-AG) according to clinical outcomes and assess the effects of glucose-and blood pressure-lowering interventions on change in 1,5-AG levels in people with type 2 diabetes. Methods: We measured 1,5-AG in 6826 stored samples at baseline and in a random subsample of 684 participants at the 1-year follow-up visit in the ADVANCE trial. We examined baseline 1,5-AG [< 39.7, 39.7-66.2, ≥ 66.2 μmol/L (<6, 6-10, ≥10 μg/mL)] and microvascular and macrovascular events and mortality using Cox regression models during 5 years of follow-up. Using an intention-to-treat approach, we examined 1-year change in 1,5-AG (mean and percent) in response to the glucose-and blood pressure-lowering interventions in the subsample. Results: Low 1,5-AG level [<39.7 μmol/L vs ≥ 66.2 μmol/L (<6 μg/mL vs ≥10 μg/mL)] was associated with microvascular events (hazard ratio 1.28, 95% confidence interval 1.03-1.60) after adjustment for risk factors and baseline glycated haemoglobin (HbA1c); however, the associations for macrovascular events and mortality were not independent of HbA1c. The glucose-lowering intervention was associated with a significant 1-year increase in 1,5-AG (vs standard control) of 6.69 μmol/L (SE 2.52) [1.01 μg/mL (SE 0.38)], corresponding to an 8.26% (SE 0.10%) increase from baseline. We also observed an increase in 1,5-AG of similar magnitude in response to the blood pressure intervention independent of the glucose-lowering effect. Conclusions: Our results suggest that 1,5-AG is a marker of risk in adults with type 2 diabetes, but only for microvascular events independently of HbA1c. We found that 1,5-AG was improved (increased) in response to an intensive glucose-lowering intervention, although the independent effect of the blood pressure-lowering intervention on 1,5-AG suggests potential non-glycaemic influences.
Rational diagnoses of diabetes: the comparison of 1,5-anhydroglucitol with other glycemic markers
SpringerPlus, 2015
Diabetes mellitus (DM) is a frequently encountered disease with important morbidity and mortality. The aim of this study is to document the importance of 1,5-anhydroglucitol (1,5-AG) for the diagnosis of prediabetes and DM, as well as to compare the 1,5-AG with other glycemic markers in order to understand which one is the better diagnostic tool. Between April 2012 and December 2012, 128 participants enrolled in the study. Participants were split into five groups that are IFG, IGT, IFG+IGT, diabetic and control groups by their OGTT results. The diagnostic value of markers was compared by ROC (receiver operating characteristic) method. The mean serum 1,5-AG levels in the diabetic group (33.38 nmol/ml) were lower than, IFG (59.83 nmol/ml), IGT (54.44 nmol/ml), IFG+IGT (51.98 nmol/ml) and control groups (73.24 nmol/ml). When analyzed in the total study population serum 1,5-AG levels did not differ by gender significantly. When analyzed in the total study population, 1,5-AG correlates inversely with age significantly (p = 0.036). In subgroup analysis, in the control group, serum 1,5-AG level was also inversely correlated with age (p = 0.087). The best marker for the diagnosis of prediabetes and DM was fasting plasma glucose (FPG). 1,5-AG was not found to be effective for the diagnosis of DM. This study, contributes to our knowledge of the efficiency and cutoff values of 1,5-AG for the diagnosis of prediabetes and DM. In future, there is a need for larger studies with more standardized and commonly used measurement methods for 1,5-AG, in order to evaluate the efficiency of 1,5-AG for the diagnosis of prediabetes and DM.
Diabetes Research and Clinical Practice, 2009
Recent studies have suggested that postprandial hyperglycemia (PPH) is an independent risk factor for the development of diabetes and cardiovascular diseases (CVDs) [1,2]. In addition, meta-analysis of large prospective studies has confirmed that PPH in the non-diabetic range is associated with an increased risk of both fatal and non-fatal CVD. These CVD events appear to increase in a linear fashion with 120-min post-challenge plasma glucose (PPG 120) levels even in the range below the diagnostic levels of diabetes [3]. Glycated hemoglobin, HbA1c (A1C), is regarded as the gold standard index of glycemic control in patients with diabetes [4]. However, previous studies showed that A1C does not discriminate between relative contributions of fasting plasma glucose (FPG) and PPG to mean glycemia [5,6]. Moreover, because A1C measures long-term glycemia, it is not a good indicator of glycemic control over shorter periods or of glucose
Cancer Causes & Control, 2010
Insulin and glucose may influence cancer mortality via their proliferative and anti-apoptotic properties. Using longitudinal data from the nationally representative Third National Health and Nutrition Examination Survey (NHANES III;1988-1994), with an average follow-up of 8.5y to mortality, we evaluated markers of glucose and insulin concentrations, with cancer mortality, ascertained using death certificates using the National Death Index. Plasma glucose, insulin, Cpeptide, and lipid concentrations were measured. Anthropometrics, lifestyle, medical and demographic information was obtained during in-person interviews. After adjusting for age, race, sex, smoking status, physical activity and body mass index, for every increase in 50 mg/dl of plasma glucose, there was a 22% increased risk of overall cancer mortality. Insulin resistance was associated with a 41% (95% confidence interval (CI)(1.07-1.87;p=0.01) increased risk of overall cancer mortality. These associations were stronger after excluding lung cancer deaths for insulin resistant individuals (HR:1.67; 95% CI:1.15-2.42;p=0.01), specifically among those with lower levels of physical activity (HR:2.06; 95% CI:1.4-3.0;p=0.0001). Similar associations were observed for other blood markers of glucose and insulin, albeit not statistically significant. In conclusions, hyperglycemia and insulin resistance may be 'high-risk' conditions for cancer mortality. Managing these conditions may be effective cancer control tools.