In conclusion , polyphenols can successfully reduce HbA1c in T2DM without any intervention at glycemia , and could contribute to the prevention of diabetes complications
ABSTRACT Polyphenols have been extensively studied for their antioxidant and anti-inflammatory properties .
Recently , their antiglycative actions by oxidative stress modulation have been linked to the prevention of diabetes and associated complications .
This article assesses the evidence for polyphenol interventions on glycohemoglobin ( HbA1c ) in non-diabetic , pre-diabetic , and type 2 diabetes mellitus ( T2DM ) subjects .
Association of Hemoglobin A1c with Cardiovascular Disease and Mortality in Adults: The European Prospective Investigation into Cancer in Norfolk
Context Several studies suggest that blood glucose levels are associated with cardiovascular disease , even at blood glucose values that do not meet diagnostic criteria for diabetes . Contribution Among adult residents of Norfolk , United Kingdom , there was a continuous relationship between hemoglobin A1c levels and cardiovascular disease and total mortality . This relationship was apparent even among persons without diabetes . Implication s These observations justify the need for studies that address whether improvements in glycemic control might improve health outcomes in persons who do not have diabetes . The Editors Diabetes mellitus is of major and increasing global public health importance ( 1 ) . Persons with diabetes are at increased risk for premature disability and death associated with vascular , renal , retinal , and neuropathic complications . Raised fasting and postchallenge blood glucose levels in an oral glucose tolerance test are used to diagnose diabetes . The diagnostic threshold is based on the shape of the risk curve between glucose levels and specific microvascular complications of diabetes ( 2 - 6 ) . Diabetes also increases the risk for macrovascular diseases , such as coronary heart disease and stroke ( 7 ) . In contrast to microvascular disease , increasing evidence suggests that the relationship between blood glucose level and macrovascular disease is continuous and does not have an obvious threshold ( 2 , 8 , 9 ) . Hemoglobin A1c concentration is an indicator of average blood glucose concentrations over the preceding 3 months ; it is useful for characterizing dysglycemia in population studies because it is simpler to perform than the oral glucose tolerance test ( 10 ) . In a 3-year follow-up of men in a prospect i ve study , we previously reported that hemoglobin A1c concentrations were related to cardiovascular disease and all-cause mortality ( 11 ) . However , we had insufficient power to examine risk relationships at concentrations close to the diagnostic threshold of 7 % or to examine the relationship in women . We report the relation between hemoglobin A1c concentrations and fatal and nonfatal coronary heart disease , cardiovascular disease events , and all-cause mortality in men and women after an average of 6 years of follow-up . Methods The European Prospect i ve Investigation into Cancer in Norfolk ( EPICNorfolk ) is a prospect i ve population study of 25 623 men and women who were between 40 and 79 years of age and who resided in Norfolk , United Kingdom . Participants were recruited from general practice registers . Information on the recruitment process is available elsewhere ( 12 ) . Between 1993 and 1997 , participants completed a health and lifestyle question naire . Participants were asked whether a doctor had ever told them that they have any of the conditions contained in a list that included diabetes , heart attack , and stroke . People with known diabetes were defined as those who responded yes to the diabetes option of this question . Smoking history was derived from responses ( yes or no ) to the questions : Have you ever smoked as much as 1 cigarette a day for as long as a year ? and Do you smoke cigarettes now ? At a clinic , trained nurses performed a health examination for each participant . Body mass index was estimated as weight (kg)/height ( m2 ) , and waist-to-hip ratio was determined by measurements of the circumference of the waist and hips . Blood pressure was measured by using an Accutorr ( Data scope , Mahwah , New Jersey ) noninvasive  blood pressure  monitor after the participant had been seated for 5 minutes . The mean of 2 readings was used for analysis . Nonfasting blood sample s were taken ; sample s for assay were stored in a refrigerator at 4 C until transport within 1 week of sampling to the Department of Clinical Biochemistry , University of Cambridge . Starting in 1995 , hemoglobin A1c was measured on fresh EDTA blood sample s by using high-performance liquid chromatography ( BioRad Diamat Automated Glycosylated Haemoglobin Analyser , Hemel Hempstead , United Kingdom ) . We report results for follow-up to January 2003 , an average of about 6 years . All participants were flagged for death certification at the Office of National Statistics ; vital status was obtained for the entire cohort . Trained nosologists coded death certificates according to the International Classification of Diseases , Ninth or Tenth Revisions ( ICD-9 or ICD-10 ) . Cardiovascular death ( stroke , coronary heart disease , and other vascular causes ) was defined as those whose underlying cause of death was coded as ICD-9 400448 or ICD-10 I10I79 . Death from coronary heart disease was defined as those whose cause of death was coded as ICD-9 410414 or ICD-10 I22I25 . Participants admitted to a hospital were identified by their National Health Service number . Hospitals were linked to the East Norfolk Health Authority data base , which identifies all hospital contacts throughout Engl and and Wales for Norfolk residents . We used the same ICD diagnostic codes described in the preceding paragraphs to ascertain hospital episodes of cardiovascular disease and coronary heart disease in our cohort . Participants were identified as having a coronary heart disease event during follow-up if they had a hospital admission or died with coronary heart disease as the cause of death . Of the coronary heart disease events identified , 21 % ( 112 of 529 ) were fatal ; of the cardiovascular disease events , 23 % ( 197 of 806 ) were fatal . In men , 24 % ( 76 of 321 ) of deaths were attributed to heart disease and 29 % ( 117 of 321 ) were attributed to cardiovascular disease . In women , 18 % ( 36 of 200 ) of deaths were attributed to heart disease and 35 % ( 70 of 200 ) were attributed to cardiovascular causes . The Norwich Ethics Committee approved the study , and participants gave signed informed consent . Statistical Analysis These analyses , undertaken by using SPSS software , version 10.0 ( SPSS , Inc. , Chicago , Illinois ) , included 10 232 men and women age 45 to 79 years who completed the health and lifestyle question naire and had available hemoglobin A1c measurements . We divided the cohort into 7 categories on the basis of baseline data : known diabetes , high likelihood of previously undiagnosed diabetes ( no personal history of diabetes but a hemoglobin A1c concentration 7 % ) , and hemoglobin A1c concentrations in 0.5percentage point intervals ( < 5 % , 5 % to 5.4 % , 5.5 % to 5.9 % , 6.0 % to 6.4 % , and 6.5 % to 6.9 % ) . We examined risk factor distributions and then coronary heart disease , cardiovascular disease , and all-cause mortality rates by hemoglobin A1c and diabetes category . Age-adjusted odds ratios were calculated by using logistic regression models . We used a Cox proportional hazards model to determine the independent contribution of hemoglobin A1c to total mortality and cardiovascular and coronary heart disease after adjustment for age , body mass index , waist-to-hip ratio , systolic blood pressure , blood cholesterol concentrations , cigarette smoking , and history of heart attack or stroke . Participants with missing baseline data for 1 or more risk factors ( 130 men and 186 women ) were excluded from the multivariate analyses . Role of the Funding Sources The funding sources had no role in the design , conduct , and reporting of the study or in the decision to su bmi t the manuscript for publication . Results Table 1 presents characteristics of the participants according to hemoglobin A1c concentration and self-reported diabetes . Those with known diabetes had higher mean ( SD ) hemoglobin A1c concentrations ( 8.0 % 1.9 % ) than the rest of the study sample ( 5.3 % 0.7 % ) . They were older and had a higher body mass index , waist-to-hip ratio , and systolic blood pressure ; they were also more likely to report having had a previous heart attack or stroke . Participants with probable but previously undiagnosed diabetes ( hemoglobin A1c 7 % ) shared these characteristics . Mean risk factor levels rose with increasing concentration of hemoglobin A1c less than 7 % . Table 1 . Distribution of Variables by  Hemoglobin A1c Concentration and Known Diabetes in 4662 Men and 5570 Women Age 45 to 79 Years ( European Prospect i ve Investigation into Cancer in Norfolk , 1995 to 1997 ) Table 2 shows adjusted odds ratios for hemoglobin A1c concentrations , diabetes status , and outcomes .  Persons with known or undiagnosed diabetes had a greater risk for all-cause mortality and cardiovascular or coronary heart disease than those without diabetes . Risk for coronary heart or cardiovascular disease and total mortality increased throughout the whole range of hemoglobin A1c concentrations ; those with hemoglobin A1c concentrations less than 5 % had the lowest rates . For men , a gradient of increasing rates through the distribution was apparent for all end points . For women , odds ratios for cardiovascular or coronary heart disease did not increase significantly until the hemoglobin A1c concentration reached 6 % ; odds ratios were very high in women with concentrations greater than 7 % . Table 2 . Rates and Age-Adjusted Relative Risks for Total Coronary Heart Disease Events , Cardiovascular Disease Events , and All-cause Mortality by Category of Hemoglobin A1c Concentration and Known Diabetes in 4462 Men and 5570 Women Age 45 to 79 Years ( European Prospect i ve Investigation into Cancer in Norfolk , 1995 to 2003 ) Table 3 shows outcomes after adjustment for age alone and then after adjustment for age and other risk factors . In men , known diabetes predicted coronary heart and cardiovascular disease events and total mortality with approximate 2-fold relative risks . These relative risks were only slightly attenuated after adjustment for known risk factors . In women , known diabetes status predicted an approximate 5-fold increase in risk for coronary heart and 3-fold increase in risk for cardiovascular disease events ; these increases were attenuated after adjustment for known risk factors to 3-fold and 2-fold risk , respectively . In men and women , hemoglobin A1c concentrations predicted an increased risk for
In conclusion , polyphenols can successfully reduce HbA1c in T2DM without any intervention at glycemia , and could contribute to the prevention of diabetes complications
ABSTRACT Polyphenols have been extensively studied for their antioxidant and anti-inflammatory properties .
Recently , their antiglycative actions by oxidative stress modulation have been linked to the prevention of diabetes and associated complications .
This article assesses the evidence for polyphenol interventions on glycohemoglobin ( HbA1c ) in non-diabetic , pre-diabetic , and type 2 diabetes mellitus ( T2DM ) subjects .