Background

The American Diabetes Association recently included glycated hemoglobin in the diagnostic criteria for diabetes, but research on the utility of this biomarker in Southeast Asians is scant. The aim of this study was to evaluate the association between percent HbA1c and incident diabetes in an Asian population of adult men and women without reported diabetes.

Methods

Data analysis of 5,770 men and women enrolled in the Singapore Chinese Health Study who provided a blood sample at the follow-up I visit (1999-2004) and had no cancer and no reported history of diabetes or cardiovascular disease events. Diabetes was defined as self-report of physician diagnosis, identified at the follow-up II visit (2006-2010).

Results

Hazard ratios (and 95% confidence intervals) for incident diabetes by 5 categories of HbA1c were estimated with Cox regression models and continuous HbA1c with cubic spline analysis. Compared to individuals with an HbA1c ≤ 5.7% (≤39 mmol/mol), individuals with HbA1c 5.8-5.9% (40-41 mmol/mol), 6.0-6.1% (42-43 mmol/mol), 6.2-6.4% (44-47 mmol/mol), and ≥ 6.5% (≥48 mmol/mol) had significantly increased risk for incident diabetes during follow-up. In cubic spline analysis, levels below 5.7% HbA1c were not significantly associated with incident diabetes.

Conclusions

Our study found a strong and graded association with HbA1c 5.8% and above with incident diabetes in Chinese men and women.

Aims/hypothesis

The impact of marijuana use on metabolic health is largely unknown. This study sought to clarify the cross-sectional and longitudinal associations between self-reported marijuana use, and prediabetes (defined as fasting glucose 5.6-6.9 mmol/l, 2 h glucose post OGTT 7.8-11.0 mmol/l or HbA1c 5.7-6.4% [39-47 mmol/mol]) and diabetes.

Methods

Data from the community-based Coronary Artery Risk Development in Young Adults (CARDIA) study were used to determine marijuana use and the presence of prediabetes and diabetes among participants. The association between marijuana use and the prevalence of prediabetes and diabetes was examined in 3,034 participants at CARDIA examination year 25 (2010-2011), while the incidence of prediabetes and diabetes according to previous marijuana use was assessed in 3,151 individuals who were free from prediabetes/diabetes at year 7 (1992-1993) and who returned for at least one of the four subsequent follow-up examinations over 18 years.

Results

The percentage of individuals who self-reported current use of marijuana declined over the course of the study's follow-up. After multivariable adjustment, higher odds of prediabetes were found for individuals who reported current use of marijuana (OR 1.65 [95% CI 1.15, 2.38]) and a lifetime use of 100 times or more (OR 1.49 [95% CI 1.06, 2.11]), compared with individuals who reported never using marijuana. There was no association between marijuana use and diabetes at CARDIA examination year 25. Over 18 years of follow-up, a greater risk of prediabetes (but not diabetes) was found for individuals who reported a lifetime use of marijuana of 100 times or more (HR 1.39 [95% CI 1.13, 1.71]), compared with individuals who had never used marijuana.

Conclusions/interpretation

Marijuana use in young adulthood is associated with an increased risk of prediabetes by middle adulthood, but not with the development of diabetes by this age.

Objective

Glycated hemoglobin (HbA₁c) is a robust biomarker of the preceding 2 to 3 months average blood glucose level. The aim of this study was to examine the association between HbA₁c and mortality in a cohort of Southeast Asians.

Research design and methods

Analysis of 7,388 men and women, mean age 62 years, from the Singapore Chinese Health Study who provided a blood sample at the follow-up I visit (1999-2004) and reported no history of diabetes, previous adverse cardiovascular events, or cancer. A total of 888 deaths were identified through 31 December 2011 via registry linkage. Participants represented a random study sample of potential control subjects for a nested case-control genome-wide association study of type 2 diabetes in the population. Hazard ratios (HRs) for all-cause and cause-specific mortality by six categories of HbA1c were estimated with Cox regression models.

Results

Relative to participants with an HbA₁c of 5.4-5.6% (36-38 mmol/mol), participants with HbA₁c ≥6.5% (≥48 mmol/mol) had an increased risk of all-cause, cardiovascular, and cancer mortality during an average of 10.1 years of follow-up; HRs (95% CIs) were 1.96 (1.56-2.46), 2.63 (1.77-3.90), and 1.51 (1.04-2.18), respectively. No level of HbA1c was associated with increased risk of respiratory mortality. Levels <6.5% HbA₁c were not associated with mortality during follow-up. The results did not materially change after excluding observation of first 3 years post-blood draw.

Conclusions

HbA₁c levels consistent with undiagnosed type 2 diabetes (≥6.5%) are associated with an increased risk of all-cause and cause-specific mortality in Chinese men and women.

Background

A limitation of the Agatston coronary artery calcium (CAC) score is that it does not use all of the calcium density information in the computed tomography scan such that many individuals have a score of zero. We examined the predictive validity for incident coronary heart disease (CHD) events of the spatially weighted coronary calcium score (SWCS), an alternative scoring method for CAC that assigns scores to individuals with Agatston CAC=0.

Methods

The MESA (Multi-Ethnic Study of Atherosclerosis) is a longitudinal study that conducted a baseline exam from 2000 to 2002 in 6814 participants including computed tomography scanning for CAC. Subsequent exams and systematic follow-up of the cohort for outcomes were performed. Statistical models were adjusted using the MESA risk score based on age, sex, race/ethnicity, systolic blood pressure, use of hypertension medications, diabetes, total and HDL (high-density lipoprotein) cholesterol, use of lipid-lowering medications, smoking status, and family history of heart attack.

Results

In the 3286 participants with Agatston CAC=0 at baseline and for whom SWCS was computed, 98 incident CHD events defined as definite or probably myocardial infarction or definite CHD death occurred during a median follow-up of 15.1 years. In this group, SWCS predicted incident CHD events after multivariable adjustment (hazard ratio=1.30 per SD of natural logarithm [SWCS] [95% CI, 1.04-1.60]; P=0.005); and progression from Agatston CAC=0 at baseline to CAC>0 at subsequent exams (multivariable-adjusted incidence rate difference per SD of natural logarithm [SWCS] per 100 person-years 1.68 [95% CI, 1.03-2.33]; P<0.0001).

Conclusions

SWCS predicts incident CHD events in individuals with Agatston CAC score=0 as well as conversion to Agatston CAC>0 at repeat computed tomography scanning at later exams. SWCS has predictive validity as a subclinical phenotype and marker of CHD risk in individuals with Agatston CAC=0.

Background & aims

Insulin resistance is a risk marker for non-alcoholic fatty liver disease, and a risk factor for liver disease progression. We assessed temporal trajectories of insulin resistance and β-cell response to serum glucose concentration throughout adulthood and their association with diabetes risk in non-alcoholic fatty liver disease.

Methods

Three thousand and sixty participants from Coronary Artery Risk Development in Young Adults, a prospective bi-racial cohort of adults age 18-30 years at baseline (1985-1986; Y0) who completed up to 5 exams over 25 years and had fasting insulin and glucose measurement were included. At Y25 (2010-2011), non-alcoholic fatty liver disease was assessed by noncontrast computed tomography after exclusion of other liver fat causes. Latent mixture modelling identified 25-year trajectories in homeostatic model assessment insulin resistance and β-cell response homeostatic model assessment-β.

Results

Three distinct trajectories were identified, separately, for homeostatic model assessment insulin resistance (low-stable [47%]; moderate-increasing [42%]; and high-increasing [12%]) and homeostatic model assessment-β (low-decreasing [16%]; moderate-decreasing [63%]; and high-decreasing [21%]). Y25 non-alcoholic fatty liver disease prevalence was 24.5%. Among non-alcoholic fatty liver disease, high-increasing homeostatic model assessment insulin resistance (referent: low-stable) was associated with greater prevalent (OR 95% CI = 8.0, 2.0-31.9) and incident (OR = 10.5, 2.6-32.8) diabetes after multivariable adjustment including Y0 or Y25 homeostatic model assessment insulin resistance. In contrast, non-alcoholic fatty liver disease participants with low-decreasing homeostatic model assessment-β (referent: high-decreasing) had the highest odds of prevalent (OR = 14.1, 3.9-50.9) and incident (OR = 10.3, 2.7-39.3) diabetes.

Conclusion

Trajectories of insulin resistance and β-cell response during young and middle adulthood are robustly associated with diabetes risk in non-alcoholic fatty liver disease. Thus, how persons with non-alcoholic fatty liver disease develop resistance to insulin provides important information about risk of diabetes in midlife above and beyond degree of insulin resistance at the time of non-alcoholic fatty liver disease assessment.

Objective

To determine whether intraindividual variability in fasting glucose (FG) below the threshold of diabetes is associated with cognitive function in middle adulthood beyond increasing FG.

Research design and methods

We studied 3,307 CARDIA (Coronary Artery Risk Development in Young Adults) Study participants (age range 18-30 years and enrolled in 1985-1986) at baseline and calculated two measures of long-term glucose variability: the coefficient of variation about the mean FG (CV-FG) and the absolute difference between successive FG measurements (average real variability [ARV-FG]) before the onset of diabetes over 25 and 30 years of follow-up. Cognitive function was assessed at years 25 (2010-2011) and 30 (2015-2016) with the Digit Symbol Substitution Test (DSST), Rey-Auditory Verbal Learning Test (RAVLT), Stroop Test, Montreal Cognitive Assessment, and category and letter fluency tests. We estimated the association between glucose variability and cognitive function test score with adjustment for clinical and behavioral risk factors, mean FG level, change in FG level, and diabetes development, medication use, and duration.

Results

After multivariable adjustment, 1-SD increment of CV-FG was associated with worse cognitive scores at year 25: DSST, standardized regression coefficient -0.95 (95% CI -1.54, -0.36); RAVLT, -0.14 (95% CI -0.27, -0.02); and Stroop Test, 0.49 (95% CI 0.04, 0.94). Findings were similar between CV-FG with each cognitive test score at year 30 and when we used an alternative measure of variability (ARV-FG) that captures variability in successive FG values.

Conclusions

Higher intraindividual FG variability during young adulthood below the threshold of diabetes was associated with worse processing speed, memory, and language fluency in midlife independent of FG levels.

The aims of this study are to assess the relationships of visit-to-visit blood pressure (BP) variability in young adulthood to hippocampal volume and integrity at middle age. We used data over 8 examinations spanning 25 years collected in the CARDIA study (Coronary Artery Risk Development in Young Adults) of black and white adults (age, 18-30 years) started in 1985 to 1986. Visit-to-visit BP variability was defined as by SD_BP and average real variability (ARV_BP, defined as the absolute differences of BP between successive BP measurements). Hippocampal tissue volume standardized by intracranial volume (%) and integrity assessed by fractional anisotropy were measured by 3-Tesla magnetic resonance imaging at the year-25 examination (n=545; mean age, 51 years; 54% women and 34% African Americans). Mean systolic BP (SBP)/diastolic BP levels were 110/69 mm Hg at year 0 (baseline), 117/73 mm Hg at year 25, and ARV_SBP and SD_SBP were 7.7 and 7.9 mm Hg, respectively. In multivariable-adjusted linear models, higher ARV_SBP was associated with lower hippocampal volume (unstandardized regression coefficient [standard error] with 1-SD higher ARV_SBP: -0.006 [0.003]), and higher SD_SBP with lower hippocampal fractional anisotropy (-0.02 [0.01]; all P<0.05), independent of cumulative exposure to SBP during follow-up. Conversely, cumulative exposure to SBP and diastolic BP was not associated with hippocampal volume. There was no interaction by sex or race between ARV_SBP or SD_SBP with hippocampal volume or integrity. In conclusion, visit-to-visit BP variability during young adulthood may be useful in assessing the potential risk for reductions in hippocampal volume and integrity in midlife.

BACKGROUNDPreclinical studies suggest that cholesterol accumulation leads to insulin resistance. We previously reported that alterations in a monocyte cholesterol metabolism transcriptional network (CMTN) - suggestive of cellular cholesterol accumulation - were cross-sectionally associated with obesity and type 2 diabetes (T2D). Here, we sought to determine whether the CMTN alterations independently predict incident prediabetes/T2D risk, and correlate with cellular cholesterol accumulation.METHODSMonocyte mRNA expression of 11 CMTN genes was quantified among 934 Multi-Ethnic Study of Atherosclerosis (MESA) participants free of prediabetes/T2D; cellular cholesterol was measured in a subset of 24 monocyte samples.RESULTSDuring a median 6-year follow-up, lower expression of 3 highly correlated LXR target genes - ABCG1 and ABCA1 (cholesterol efflux) and MYLIP (cholesterol uptake suppression) - and not other CMTN genes, was significantly associated with higher risk of incident prediabetes/T2D. Lower expression of the LXR target genes correlated with higher cellular cholesterol levels (e.g., 47% of variance in cellular total cholesterol explained by ABCG1 expression). Further, adding the LXR target genes to overweight/obesity and other known predictors significantly improved prediction of incident prediabetes/T2D.CONCLUSIONThese data suggest that the aberrant LXR/ABCG1-ABCA1-MYLIP pathway (LAAMP) is a major T2D risk factor and support a potential role for aberrant LAAMP and cellular cholesterol accumulation in diabetogenesis.FUNDINGThe MESA Epigenomics and Transcriptomics Studies were funded by NIH grants 1R01HL101250, 1RF1AG054474, R01HL126477, R01DK101921, and R01HL135009. This work was supported by funding from NIDDK R01DK103531 and NHLBI R01HL119962.