[Show abstract][Hide abstract] ABSTRACT: To examine trends in the prevalence of type 2 diabetes and related conditions in Asian Americans compared with non-Hispanic whites.
We analyzed data from the National Health Interview Survey (NHIS) from 1997 to 2008 to construct a nationally representative sample of 230,503 U.S. adults aged ≥ 18 years. Of these adults, 11,056 identified themselves as Asian Americans and 219,447 as non-Hispanic whites.
The age- and sex-adjusted prevalence of type 2 diabetes was higher in Asian Americans than in whites throughout the study period (4.3-8.2% vs. 3.8-6.0%), and there was a significant upward trend in both ethnic groups (P < 0.01). BMI also was increased in both groups, but age- and sex-adjusted BMI was consistently lower in Asian Americans. In fully adjusted logistic regression models, Asian Americans remained 30-50% more likely to have diabetes than their white counterparts. In addition, Asian Indians had the highest odds of prevalent type 2 diabetes, followed by Filipinos, other Asians, and Chinese.
Compared with their white counterparts, Asian Americans have a significantly higher risk for type 2 diabetes, despite having substantially lower BMI. Additional investigation of this disparity is warranted, with the aim of tailoring optimal diabetes prevention strategies to Asian Americans.
Diabetes care 02/2011; 34(2):353-7. · 7.74 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Previous studies examining the relationship between the C282Y and H63D HFE mutations and presence of nonalcoholic fatty liver disease (NAFLD) have yielded conflicting results. The goal of this study was to systematically evaluate and summarize data on the association between these two variants and the presence of NAFLD.
The authors searched EMBASE and PUBMED from August 1, 1996 to August 12, 2010. Two investigators independently conducted data abstraction. Ethnic specific weighted prevalence was calculated and pooled odds ratios were estimated using the random effects model.
From 2542 references, the authors included 16 case-control studies and 14 case-only studies, or 2610 cases and 7298 controls. The majority of the studies came from Caucasian populations (2287 cases and 4275 controls). The weighted prevalence of HFE mutations in cases was comparable to controls. The meta-analysis was restricted to Caucasians only because of the small sample size of non Caucasian participants. The pooled odds ratio for the presence of any HFE genetic variant in cases was 1.03 (95%CI: 0.90, 1.17; I(2): 65.8%, 95%CI: 38.5, 81.0). The presence of other genotypes and secondary analyses yielded similar non significant findings.
Our systematic review does not support an association between the HFE genetic variants and the presence of NAFLD.
Journal of Hepatology 02/2011; 55(5):1079-85. · 9.86 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The goal of this study was to perform a systematic review and meta-analysis to examine the effect of pre-existing diabetes on breast cancer-related outcomes.
We searched EMBASE and MEDLINE databases from inception through July 1, 2009, using search terms related to diabetes mellitus, cancer, and prognostic outcome. Studies were included if they reported a prognostic outcome by diabetes status, evaluated a cancer population, and contained original data published in the English language. We performed a meta-analysis of pre-existing diabetes and its effect on all-cause mortality in patients with breast cancer and qualitatively summarized other prognostic outcomes. Results: Of 8,828 titles identified, eight articles met inclusion/exclusion criteria and described outcomes in patients with breast cancer and diabetes. Pre-existing diabetes was significantly associated with all-cause mortality in six of seven studies. In a meta-analysis, patients with breast cancer and diabetes had a significantly higher all-cause mortality risk (pooled hazard ratio [HR], 1.49; 95% CI, 1.35 to 1.65) compared with their nondiabetic counterparts. Three of four studies found pre-existing diabetes to be associated with more advanced stage at presentation. Diabetes was also associated with altered regimens for breast cancer treatment and increased toxicity from chemotherapy.
Compared with their nondiabetic counterparts, patients with breast cancer and pre-existing diabetes have a greater risk of death and tend to present at later stages and receive altered treatment regimens. Studies are needed to investigate pathophysiologic interactions between diabetes and breast cancer and determine whether improvements in diabetes care can reduce mortality in patients with breast cancer.
Journal of Clinical Oncology 01/2011; 29(1):40-6. · 18.04 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Evidence suggests glucose transporter-1 (GLUT1) genetic variation affects diabetic nephropathy and albuminuria. Our aim was to evaluate associations with albuminuria of six GLUT1 single nucleotide polymorphisms(SNPs), particularly XbaI and the previously associated Enhancer-2 (Enh2) SNP.
A two-stage case-control study was nested in a prospective cohort study of 2156 African Americans and 8122 European Americans with urinary albumin-to-creatinine ratio (ACR). Cases comprised albuminuria (N = 825; ≥ 30 μg/mg) and macroalbuminuria (N = 173; ≥ 300 μg/mg). ACR < 30 μg/mg classified controls (n = 9453). Logistic regression and odds ratios (OR) assessed associations. The evaluation phase (stage 1, n = 2938) tested associations of albuminuria (n = 305) with six GLUT1 SNPs: rs841839, rs3768043, rs2297977, Enh2(rs841847) XbaI (rs841853), and rs841858. Enh2 was examined separately in the replication phase (stage 2, n = 7340) and the total combined sample (n = 10,278), with all analyses stratified by race and type 2 diabetes.
In European Americans, after adjusting for diabetes and other GLUT1 SNPs in stage 1, Enh2 risk genotype (TT) was more common in albuminuric cases (OR = 3.37, P = 0.090) whereas XbaI (OR = 0.94, p = 0.931) and remaining SNPs were not. In stage 1, the Enh2 association with albuminuria was significant among diabetic European Americans (OR = 2.36, P = 0.025). In African Americans, Enh2 homozygosity was rare (0.3%); XbaI was common (18.0% AA) and not associated with albuminuria. In stage 2 (n = 7,340), Enh2 risk genotype had increased but non-significant OR among diabetic European Americans (OR = 1.66, P = 0.192) and not non-diabetics (OR = 0.99, p = 0.953), not replicating stage 1. Combining stages 1 and 2, Enh2 was associated with albuminuria (OR 2.14 [1.20-3.80], P = 0.009) and macroalbuminuria (OR 2.69, [1.02-7.09], P = 0.045) in diabetic European Americans. The Enh2 association with macroalbuminuria among non-diabetic European Americans with fasting insulin (OR = 1.84, P = 0.210) was stronger at the highest insulin quartile (OR = 4.08, P = 0.040).
As demonstrated with type 1 diabetic nephropathy, the GLUT1 Enh2 risk genotype, instead of XbaI, may be associated with type 2 diabetic albuminuria among European Americans, though an association is not conclusive. The association among diabetic European Americans found in stage 1 was not replicated in stage 2; however, this risk association was evident after combining all diabetic European Americans from both stages. Additionally, our results suggest this association may extend to non-diabetics with high insulin concentrations. Rarity of the Enh2 risk genotype among African Americans precludes any definitive conclusions, although data suggest a risk-enhancing role.
BMC Medical Genetics 01/2011; 12:16. · 2.54 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Although A1C is now recommended to diagnose diabetes, its test performance for diagnosis and prognosis is uncertain. Our objective was to assess the test performance of A1C against single and repeat glucose measurements for diagnosis of prevalent diabetes and for prediction of incident diabetes.
We conducted population-based analyses of 12,485 participants in the Atherosclerosis Risk in Communities (ARIC) study and a subpopulation of 691 participants in the Third National Health and Nutrition Examination Survey (NHANES III) with repeat test results.
Against a single fasting glucose ≥126 mg/dl, the sensitivity and specificity of A1C ≥6.5% for detection of prevalent diabetes were 47 and 98%, respectively (area under the curve 0.892). Against repeated fasting glucose (3 years apart) ≥126 mg/dl, sensitivity improved to 67% and specificity remained high (97%) (AUC 0.936). Similar results were obtained in NHANES III against repeated fasting glucose 2 weeks apart. The accuracy of A1C was consistent across age, BMI, and race groups. For individuals with fasting glucose ≥126 mg/dl and A1C ≥6.5% at baseline, the 10-year risk of diagnosed diabetes was 88% compared with 55% among those individuals with fasting glucose ≥126 mg/dl and A1C 5.7-<6.5%.
A1C performs well as a diagnostic tool when diabetes definitions that most closely resemble those used in clinical practice are used as the "gold standard." The high risk of diabetes among individuals with both elevated fasting glucose and A1C suggests a dual role for fasting glucose and A1C for prediction of diabetes.
Diabetes care 01/2011; 34(1):84-9. · 7.74 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To evaluate the association between non-alcoholic fatty liver disease and all cause and cause specific mortality in a representative sample of the US general population.
Prospective cohort study.
US Third National Health and Nutrition Examination Survey (NHANES III: 1988-94) with follow-up of mortality to 2006.
11,371 adults aged 20-74 participating in the Third National Health and Nutrition Examination Survey, with assessment of hepatic steatosis.
Mortality from all causes, cardiovascular disease, cancer, and liver disease (up to 18 years of follow-up).
The prevalence of non-alcoholic fatty liver disease with and without increased levels of liver enzymes in the population was 3.1% and 16.4%, respectively. Compared with participants without steatosis, those with non-alcoholic fatty liver disease but normal liver enzyme levels had multivariate adjusted hazard ratios for deaths from all causes of 0.92 (95% confidence interval 0.78 to 1.09), from cardiovascular disease of 0.86 (0.67 to 1.12), from cancer of 0.92 (0.67 to 1.27), and from liver disease of 0.64 (0.12 to 3.59). Compared with participants without steatosis, those with non-alcoholic fatty liver disease and increased liver enzyme levels had adjusted hazard ratios for deaths from all causes of 0.80 (0.52 to 1.22), from cardiovascular disease of 0.59 (0.29 to 1.20), from cancer of 0.53 (0.26 to 1.10), and from liver disease of 1.17 (0.15 to 8.93).
Non-alcoholic fatty liver disease was not associated with an increased risk of death from all causes, cardiovascular disease, cancer, or liver disease.
[Show abstract][Hide abstract] ABSTRACT: Accumulating evidence implicates insufficient oxidative capacity in the development of type 2 diabetes. This notion has not been well tested in large, population-based studies.
To test this hypothesis, we assessed the cross-sectional association of plasma lactate, an indicator of the gap between oxidative capacity and energy expenditure, with type 2 diabetes in 1709 older adults not taking metformin, who were participants in the Atherosclerosis Risk in Communities (ARIC) Carotid MRI Study.
The prevalence of type 2 diabetes rose across lactate quartiles (11, 14, 20 and 30%; P for trend <0.0001). Following adjustment for demographic factors, physical activity, body mass index and waist circumference, the relative odds of type 2 diabetes across lactate quartiles were 0.98 [95% confidence interval (CI) 0.59-1.64], 1.64 (95% CI 1.03-2.64) and 2.23 (95% CI 1.38-3.59), respectively. Furthermore, lactate was associated with higher fasting glucose among non-diabetic adults.
Plasma lactate was strongly associated with type 2 diabetes in older adults. Plasma lactate deserves greater attention in studies of oxidative capacity and diabetes risk.
International Journal of Epidemiology 12/2010; 39(6):1647-55. · 6.98 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Glycated hemoglobin was recently recommended for use as a diagnostic test for diabetes. We examined the association between 2010 American Diabetes Association diagnostic cut points for glycated hemoglobin and microvascular outcomes (chronic kidney disease, end-stage renal disease [ESRD], and retinopathy) and formally tested for the presence of risk thresholds in the relationships of glycated hemoglobin with these outcomes.
Prospective cohort and cross-sectional analyses of 11,357 participants (773 with a history of diagnosed diabetes) from the Atherosclerosis Risk in Communities (ARIC) Study.
During a median of 14 years of follow-up of individuals without diagnosed diabetes at baseline, clinical categories of glycated hemoglobin were associated with risk of chronic kidney disease, with adjusted hazard ratios (HRs) of 1.12 (0.94-1.34) and 1.39 (1.04-1.85) for glycated hemoglobin 5.7-6.4% and ≥6.5%, respectively, as compared with <5.7% (P trend = 0.002). The corresponding HRs for ESRD were 1.51 (0.82-2.76) and 1.98 (0.83-4.73), respectively (P trend = 0.047). In the absence of diagnosed diabetes, glycated hemoglobin was cross sectionally associated with the presence of moderate/severe retinopathy, with adjusted odds ratios of 1.42 (0.69-2.92) and 2.91 (1.19-7.11) for glycated hemoglobin 5.7-<6.5% and ≥6.5%, respectively, compared with <5.7% (P trend = 0.011). Risk associations were stronger among individuals with a history of diabetes. We did not observe significant thresholds in the associations of glycated hemoglobin with kidney disease risk or retinopathy.
These data from a community-based, biracial population support the use of new 2010 American Diabetes Association glycated hemoglobin cut points for the diagnosis of diabetes.
[Show abstract][Hide abstract] ABSTRACT: Serum potassium levels affect insulin secretion by pancreatic β-cells, and hypokalemia associated with diuretic use has been associated with dysglycemia. We hypothesized that adults with lower serum potassium levels and lower dietary potassium intake are at higher risk for incident diabetes mellitus (DM), independent of diuretic use.
We analyzed data from 12 209 participants from the Atherosclerosis Risk in Communities (ARIC) Study, an ongoing prospective cohort study, beginning in 1986, with 9 years of in-person follow-up and 17 years of telephone follow-up. Using multivariate Cox proportional hazard models, we estimated the hazard ratio (HR) of incident DM associated with baseline serum potassium levels.
During 9 years of in-person follow-up, 1475 participants developed incident DM. In multivariate analyses, we found an inverse association between serum potassium and risk of incident DM. Compared with those with a high-normal serum potassium level (5.0-5.5 mEq/L), adults with serum potassium levels lower than 4.0 mEq/L, 4.0 to lower than 4.5 mEq/L, and 4.5 to lower than 5.0 mEq/L had an adjusted HR (95% confidence interval [CI]) of incident DM of 1.64 (95% CI, 1.29-2.08), 1.64 (95% CI, 1.34-2.01), and 1.39 (95% CI, 1.14-1.71), respectively. An increased risk persisted during an additional 8 years of telephone follow-up based on self-report with HRs of 1.2 to 1.3 for those with a serum potassium level lower than 5.0 mEq/L. Dietary potassium intake was significantly associated with risk of incident DM in unadjusted models but not in multivariate models.
Serum potassium level is an independent predictor of incident DM in this cohort. Further study is needed to determine if modification of serum potassium could reduce the subsequent risk of DM.
Archives of internal medicine 10/2010; 170(19):1745-51. · 11.46 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Weight loss through lifestyle changes is recommended for nonalcoholic fatty liver disease (NAFLD). However, its efficacy in patients with type 2 diabetes is unproven.
Look AHEAD (Action for Health in Diabetes) is a 16-center clinical trial with 5,145 overweight or obese adults with type 2 diabetes, who were randomly assigned to an intensive lifestyle intervention (ILI) to induce a minimum weight loss of 7% or a control group who received diabetes support and education (DSE). In the Fatty Liver Ancillary Study, 96 participants completed proton magnetic resonance spectroscopy to quantify hepatic steatosis and tests to exclude other causes of liver disease at baseline and 12 months. We defined steatosis >5.5% as NAFLD.
Participants were 49% women and 68% white. The mean age was 61 years, mean BMI was 35 kg/m(2), mean steatosis was 8.0%, and mean aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were 20.5 and 24.2 units/l, respectively. After 12 months, participants assigned to ILI (n = 46) lost more weight (-8.5 vs. -0.05%; P < 0.01) than those assigned to DSE and had a greater decline in steatosis (-50.8 vs. -22.8%; P = 0.04) and in A1C (-0.7 vs. -0.2%; P = 0.04). There were no significant 12-month changes in AST or ALT levels. At 12 months, 26% of DSE participants and 3% (1 of 31) of ILI participants without NAFLD at baseline developed NAFLD (P < 0.05).
A 12-month intensive lifestyle intervention in patients with type 2 diabetes reduces steatosis and incident NAFLD.
Diabetes care 10/2010; 33(10):2156-63. · 7.74 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A substantial portion of the public health burden of heart failure is due to hospitalizations, many of which are for causes other than cardiovascular disease. We assessed whether left ventricular (LV) systolic dysfunction was associated with increased risk of both cardiovascular and noncardiovascular hospitalizations in a community sample of African Americans.
African American participants from the Jackson, MS, site of the Atherosclerosis Risk in Communities (ARIC) study who underwent echocardiography were followed for 12 years. Hospitalization rates among individuals with and without LV systolic dysfunction were compared using negative binomial regression.
Among 2,416 participants with echocardiograms, LV systolic dysfunction was found in 61 (2.5%). Participants with LV dysfunction experienced 366 hospitalizations, a rate of 1.27 per person-year, compared with 0.25 per person-year among individuals without LV dysfunction. The incidence rate ratio adjusted for demographics, comorbidities, and other risk factors was 3.11 (95% CI 2.22-4.35). The adjusted rate ratios were 4.76 (95% CI 2.90-7.20) for cardiovascular and 2.67 (95% CI 1.82-3.90) for noncardiovascular diagnoses, with similar findings in the subset of individuals with asymptomatic LV dysfunction. The percentage attributable risks for hospitalizations were 87% and 74% for cardiovascular and noncardiovascular causes (79% and 63% after adjustment).
African American individuals with LV dysfunction are at an increased risk of hospitalization due to a wide range of causes, with noncardiovascular hospitalizations accounting for nearly half the increased risk. To the extent that estimates of risk focus on cardiovascular morbidity, they may underestimate the true health burden of LV dysfunction.
American heart journal 09/2010; 160(3):488-95. · 4.65 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Although variants in the transcription factor 7-like 2 (TCF7L2) gene are consistently associated with impaired fasting glucose (IFG) in Caucasians, data from large population-based studies of African Americans are lacking. Moreover, few studies have investigated the effects of TCF7L2 on IFG in the context of metabolic risk factors for diabetes.
We investigated the association between the TCF7L2 rs7903146 polymorphism and incident IFG defined as fasting serum glucose levels of 100-125 mg/dL (5.6-6.9 mmol/L) in 1377 African American and 5152 Caucasian participants without diabetes and IFG at intake who participated in the Atherosclerosis Risk in Communities (ARIC) Study from 1987 to 1989 and were followed for 9 years.
Incident IFG was identified in 810 (58.8%) African American and 2652 (51.5%) Caucasian participants. Compared to homozygous CC Caucasian individuals, heterozygous CT [hazard ratio (HR) = 1.09 (95% CI = 1.03-1.15)] and homozygous TT [1.18 (1.05-1.33)] individuals had significantly higher risk of developing IFG over 9-year follow-up. The association between rs7903146 and IFG risk was stronger in Caucasians with obesity [HR(CTvs.CC) = 1.28 (1.12, 1.47); HR(TTvs.CC) = 1.65 (1.25, 2.17)] or high triglycerides [HR(CTvs.CC) = 1.31(1.10, 1.56); HR(TTvs.CC) = 1.72 (1.21, 2.43)]. No association of the TCF7L2 rs7903146 polymorphism and incident IFG was noted in African Americans.
Our study replicates the association between rs7903146 and IFG risk in a population-based, longitudinal cohort of Caucasians but not in African Americans. For the first time, our study provides evidence for interactions between TCF7L2 and metabolic risk factors on the occurrence of IFG in Caucasians.
Diabetes/Metabolism Research and Reviews 07/2010; 26(5):371-7. · 2.97 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Diabetes appears to increase risk for some cancers, but the association between preexisting diabetes and postoperative mortality in cancer patients is less clear. Our objective was to systematically review postoperative mortality in cancer patients with and without preexisting diabetes and summarize results using meta-analysis. RSEARCH DESIGN AND METHODS: We searched the Medical Literature Analysis and Retrieval System Online (MEDLINE) and Excerpta Medica Database (EMBASE) for articles published on or before 1 July 2009, including references of qualifying articles. We included English language investigations of short-term postoperative mortality after initial cancer treatment. Titles, abstracts, and articles were reviewed by at least two independent readers. Study population and design, results, and quality components were abstracted with standard protocols by one reviewer and checked for accuracy by additional reviewers.
Of 8,828 titles identified in our original search, 20 articles met inclusion criteria for qualitative systematic review. Of these, 15 reported sufficient information to be combined in meta-analysis. Preexisting diabetes was associated with increased odds of postoperative mortality across all cancer types (OR = 1.85 [95% CI 1.40-2.45]). The risk associated with preexisting diabetes was attenuated but remained significant when we restricted the meta-analysis to models that controlled for confounders (1.51 [1.13-2.02]) or when we accounted for publication bias using the trim and fill method (1.52 [1.13-2.04]).
Compared with their nondiabetic counterparts, cancer patients with preexisting diabetes are approximately 50% more likely to die after surgery. Future research should investigate physiologic pathways to mortality risk and determine whether improvements in perioperative diabetes care can reduce postoperative mortality.
Diabetes care 04/2010; 33(4):931-9. · 7.74 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To measure relative and absolute educational disparities in mortality among U.S. adults with diabetes and to compare their magnitude with disparities observed within the nondiabetic population.
A total of 85,867 individuals (5,007 with diabetes), aged 35-84 years, who participated in the National Health Interview Survey from 1986 to 1996 were followed for mortality through 31 December 2002. Relative and absolute educational disparities in all-cause, cardiovascular disease (CVD), and non-CVD mortality were measured.
In relative terms, the risk of all-cause mortality was 28% higher in diabetic adults with the lowest versus the highest position on the educational scale (relative index of inequality 1.28 [95% CI 1.08-1.53]). This inverse relationship reflected marked disparities in CVD mortality and was found in all age, sex, and race/ethnicity groups except Hispanics. Although substantial, this relative educational gradient in mortality among adults with diabetes was smaller than in the nondiabetic population. In absolute terms, diabetic adults with the lowest position on the educational scale suffered 503 excess deaths per 10,000 person-years of follow-up compared with those with the highest position. These absolute disparities were stronger than in the nondiabetic population. The results were even more striking for CVD mortality.
The risk of mortality differs substantially according to educational level among individuals with diabetes in the U.S. Although relative educational disparities in mortality are weaker in adults with versus without diabetes, their absolute impact is greater and translates into a major mortality burden.
Diabetes care 03/2010; 33(6):1200-5. · 7.74 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Fasting glucose is the standard measure used to diagnose diabetes in the United States. Recently, glycated hemoglobin was also recommended for this purpose.
We compared the prognostic value of glycated hemoglobin and fasting glucose for identifying adults at risk for diabetes or cardiovascular disease. We measured glycated hemoglobin in whole-blood samples from 11,092 black or white adults who did not have a history of diabetes or cardiovascular disease and who attended the second visit (occurring in the 1990-1992 period) of the Atherosclerosis Risk in Communities (ARIC) study.
The glycated hemoglobin value at baseline was associated with newly diagnosed diabetes and cardiovascular outcomes. For glycated hemoglobin values of less than 5.0%, 5.0 to less than 5.5%, 5.5 to less than 6.0%, 6.0 to less than 6.5%, and 6.5% or greater, the multivariable-adjusted hazard ratios (with 95% confidence intervals) for diagnosed diabetes were 0.52 (0.40 to 0.69), 1.00 (reference), 1.86 (1.67 to 2.08), 4.48 (3.92 to 5.13), and 16.47 (14.22 to 19.08), respectively. For coronary heart disease, the hazard ratios were 0.96 (0.74 to 1.24), 1.00 (reference), 1.23 (1.07 to 1.41), 1.78 (1.48 to 2.15), and 1.95 (1.53 to 2.48), respectively. The hazard ratios for stroke were similar. In contrast, glycated hemoglobin and death from any cause were found to have a J-shaped association curve. All these associations remained significant after adjustment for the baseline fasting glucose level. The association between the fasting glucose levels and the risk of cardiovascular disease or death from any cause was not significant in models with adjustment for all covariates as well as glycated hemoglobin. For coronary heart disease, measures of risk discrimination showed significant improvement when glycated hemoglobin was added to models including fasting glucose.
In this community-based population of nondiabetic adults, glycated hemoglobin was similarly associated with a risk of diabetes and more strongly associated with risks of cardiovascular disease and death from any cause as compared with fasting glucose. These data add to the evidence supporting the use of glycated hemoglobin as a diagnostic test for diabetes.
New England Journal of Medicine 03/2010; 362(9):800-11. · 54.42 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To summarize the influence of pre-existing diabetes on mortality and morbidity in men with prostate cancer. We searched MEDLINE and EMBASE from inception through 1 October 2008. Search terms were related to diabetes, cancer and prognosis. Studies were included if they reported an original data analysis of prostate cancer prognosis, compared outcomes between men with and without diabetes and were in English. Titles, abstracts and articles were reviewed independently by two authors. Conflicts were settled by consensus or third review. We abstracted data on study design, analytic methods, outcomes and quality. We summarized mortality and morbidity outcomes qualitatively and conducted a preliminary meta-analysis to quantify the risk of long-term (>3 months), overall mortality. In total, 11 articles were included in the review. Overall, one of four studies found increased prostate cancer mortality, one of two studies found increased nonprostate cancer mortality and one study found increased 30-day mortality. Data from four studies could be included in a preliminary meta-analysis for long-term, overall mortality and produced a pooled hazard ratio of 1.57 (95% CI: 1.12-2.20). Diabetes was also associated with receiving radiation therapy, complication rates, recurrence and treatment failure. Our analysis suggests that pre-existing diabetes affects the treatment and outcomes of men with prostate cancer.
Prostate cancer and prostatic diseases 03/2010; 13(1):58-64. · 2.10 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Earlier studies have shown an association between high-normal glucose and increasing glycosylated hemoglobin (HbA1c) levels and cardiovascular events. The objective of this investigation was to study the association between increasing levels of HbA1c in asymptomatic individuals without diabetes mellitus (DM) and coronary plaque characteristics.
The study population consisted of 1043 asymptomatic Korean individuals without DM who underwent 64-slice cardiac computed tomography angiography as part of a health screening evaluation. We excluded 147 individuals with known history of DM and/or fasting glucose of at least 126 mg/dl, no HbA1c data, or missing risk factor information. The associations between coronary atherosclerosis and plaque subtype burden with increasing HbA1c levels were assessed using multivariable regression analyses.
The final study population consisted of 906 individuals without DM (mean age: 49+/-9 years, 62% males); 19 and 9% of the population had any and two or more segments with coronary plaque, respectively. Unadjusted analysis showed a positive association between increasing levels of HbA1c and the number of coronary segments with any (P<0.001) and with mixed coronary plaques (P<0.0001). The association persisted even when traditional risk factors were taken into account. No significant relationship was found between increasing HbA1c levels and the burden of noncalcified or calcified plaque.
Increasing levels of HbA1c in asymptomatic individuals without DM are associated with the presence of coronary atherosclerosis, but more specifically with the presence and burden of mixed coronary plaques. Elements of plaque instability have been associated with mixed coronary plaques.
[Show abstract][Hide abstract] ABSTRACT: Studies have suggested differences in the association between obesity and ischemic stroke in black versus white populations. In this study, we explored ischemic stroke risk in relation to a variety of obesity measures by sex and race.
Using data from the Atherosclerosis Risk in Communities Study, we obtained information on body mass index, waist circumference, and waist-to-hip ratio from 13 549 black and white participants who were aged 45 to 65 years between 1987 and 1989. All were free of cardiovascular disease and cancer at baseline. Incident strokes over a median follow-up of 16.9 years were ascertained from hospital records.
Although crude incidence rates of ischemic stroke varied more than 3-fold by race and sex, the relationship between higher measures of obesity and ischemic stroke risk was positive and linear across all groups. The crude incidence of ischemic stroke was 1.2 per 1000 person-years for white women with the lowest body mass index, ranging up to 8.0 per 1000 person-years for black men with the highest body mass index. Hazard ratios for the highest versus lowest quintile of body mass index, waist circumference, and waist-to-hip ratio ranged from 1.43 to 3.19, indicating increased stroke risk associated with obesity, however it was measured, even after adjustment for potential confounders. Additional adjustment for factors that may mediate the relationship, such as diabetes and hypertension, significantly attenuated the associations, suggesting that these factors may explain much of the stroke risk associated with obesity.
Degree of obesity, defined by body mass index, waist circumference, or waist-to-hip ratio, was a significant risk factor for ischemic stroke regardless of sex or race.
[Show abstract][Hide abstract] ABSTRACT: Nonalcoholic fatty liver disease (NAFLD) is associated with obesity, insulin resistance, and impaired glucose tolerance. We investigated whether metformin or changes in metabolic measurements (weight, fasting plasma glucose (FPG), or fasting insulin (FI)) improved serum alanine aminotransferase (ALT) activity, as a marker for NAFLD, in the Diabetes Prevention Program (DPP). From 1996 to 1999, 2,153 participants without marked elevations of serum ALT at baseline were randomized (1,081 to placebo, 1,072 to metformin) and treated for an average of 3.2 years. ALT increased during the first 2 years of the study, and was slightly but significantly lower in the participants randomized to metformin. In regression models adjusted for sex, baseline age, FPG, and FI, these differences remained significant, but disappeared after adjustment for weight, FPG, and FI changes at each examination. The 3-year cumulative incidence for development of abnormal ALT concentrations was not significantly different ((mean +/- s.e.) 21.4 +/- 1.4% and 24.6 +/- 1.4%, P = 0.11) in the metformin vs. placebo groups but was lower in individuals in both groups that lost more weight by the end of year 1 (metformin: 19.4 +/- 2.4% vs. 27.5 +/- 3.7%, for highest vs. lowest quartile of weight loss; placebo: 18.7 +/- 3.4% vs. 28.8 +/- 2.6%). Over 3 years of follow-up in persons at high risk for development of diabetes, serum ALT was consistently lower in those treated with metformin compared with placebo. This effect was mediated by weight loss, indicating that the effects of metformin therapy on ALT is via its effects on weight.