Metformin prescription for U.S. veterans with prediabetes, 2010-2019.

Affecting an estimated 88 million Americans, prediabetes increases the risk for developing type 2 diabetes mellitus (T2DM), and independently, cardiovascular disease, retinopathy, nephropathy, and neuropathy. Nevertheless, little is known about the use of metformin for diabetes prevention among patients in the Veterans Health Administration, the largest integrated healthcare system in the U.S. This is a retrospective observational cohort study of the proportion of Veterans with incident prediabetes who were prescribed metformin at the Veterans Health Administration from October 2010 to September 2019. Among 1,059,605 Veterans with incident prediabetes, 12,009 (1.1%) were prescribed metformin during an average 3.4 years of observation after diagnosis. Metformin prescribing was marginally higher (1.6%) among those with body mass index (BMI) ≥35 kg/m2, age <60 years, HbA1c≥6.0%, or those with a history of gestational diabetes, all subgroups at a higher risk for progression to T2DM. In a multivariable model, metformin was more likely to be prescribed for those with BMI ≥35 kg/m2 incidence rate ratio [IRR] 2.6 [95% confidence intervals (CI): 2.1-3.3], female sex IRR, 2.4 [95% CI: 1.8-3.3], HbA1c≥6% IRR, 1.93 [95% CI: 1.5-2.4], age <60 years IRR, 1.7 [95% CI: 1.3-2.3], hypertriglyceridemia IRR, 1.5 [95% CI: 1.2-1.9], hypertension IRR, 1.5 [95% CI: 1.1-2.1], Major Depressive Disorder IRR, 1.5 [95% CI: 1.1-2.0], or schizophrenia IRR, 2.1 [95% CI: 1.2-3.8]. Over 20% of Veterans with prediabetes attended a comprehensive structured lifestyle modification clinic or program. Among Veterans with prediabetes, metformin was prescribed to 1.1% overall, a proportion that marginally increased to 1.6% in the subset of individuals at highest risk for progression to T2DM.

Association of Fish Oil Supplementation with Risk of Coronary Heart Disease in Individuals with Diabetes and Prediabetes: A Prospective Study in the UK Biobank.

This study aimed to explore the association between habitual intake of fish oil supplementation and the risk of developing CHD in patients with prediabetes and diabetes. Habitual use of fish oil was assessed by repeated questionnaires. Cox proportional hazard models were applied to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). Over a median follow-up of 11.6 years, 4304 and 3294 CHD cases were documented among 47,663 individuals with prediabetes and 22,146 patients with diabetes in the UK Biobank, respectively. After multivariable adjustment, the HRs (95% CI) of CHD were 0.91 (0.85-0.98) and 0.87 (0.80-0.95) for individuals utilizing fish oil supplementation compared with non-users among the participants with prediabetes and diabetes, respectively. Furthermore, we identified an inverse relationship between fish oil use and CHD incidence, which was significantly mediated by serum C-reactive protein (CRP) levels in individuals with prediabetes and by very-low-density lipoprotein cholesterol (VLDL-C) in patients with diabetes at baseline. The inverse associations were consistent in the analyses stratified by potential confounders. In conclusion, the consumption of fish oil supplements was linked to decreased serum CRP and VLDL-C levels and subsequent CHD risk among adults with prediabetes and diabetes. Our findings highlight the important role of the habitual intake of fish oil supplements in preventing CHD in individuals with impaired glucose metabolism.

Exposure to herbicides mixtures in relation to type 2 diabetes mellitus among Chinese rural population: Results from different statistical models.

BACKGROUND: Although it has been reported that herbicides exposure is related to adverse outcomes, available evidence on the associations of quantitatively measured herbicides with type 2 diabetes mellitus (T2DM) and prediabetes is still scant. Furthermore, the effects of herbicides mixtures on T2DM and prediabetes remain unclear among the Chinese rural population. AIMS: To assess the associations of plasma herbicides with T2DM and prediabetes among the Chinese rural population. METHODS: A total of 2626 participants were enrolled from the Henan Rural Cohort Study. Plasma herbicides were measured with gas chromatography coupled to triple quadrupole tandem mass spectrometry. Generalized linear regression analysis was employed to assess the associations of a single herbicide with T2DM, prediabetes, as well as indicators of glucose metabolism. In addition, the quantile g-computation and environmental risk score (ERS) structured by adaptive elastic net (AENET), and Bayesian kernel machine regression (BKMR) were used to estimate the effects of herbicides mixtures on T2DM and prediabetes. RESULTS: After adjusting for covariates, positive associations of atrazine, ametryn, and oxadiazon with the increased odds of T2DM were obtained. As for prediabetes, each 1-fold increase in ln-transformed oxadiazon was related to 8.4% (95% confidence interval (CI): 1.033, 1.138) higher odds of prediabetes. In addition, several herbicides were significantly related to fasting plasma glucose, fasting insulin, and HOMA2-IR (false discovery rates adjusted P value < 0.05). Furthermore, the quantile g-computation analysis showed that one quartile increase in multiple herbicides was associated with T2DM (OR (odds ratio): 1.099, 95%CI: 1.043, 1.158), and oxadiazon was assigned the largest positive weight, followed by atrazine. In addition, the ERS calculated by the selected herbicides from AENET were found to be associated with T2DM and prediabetes, and the corresponding ORs and 95%CIs were 1.133 (1.108, 1.159) and 1.065 (1.016, 1.116), respectively. The BKMR analysis indicated a positive association between mixtures of herbicides exposure and the risk of T2DM. CONCLUSIONS: Exposure to mixtures of herbicides was associated with an increased risk of T2DM among Chinese rural population, indicating that the impact of herbicides exposure on diabetes should be paid attention to and measures should be taken to avoid herbicides mixtures exposure.

Changes in Prediabetes Status Among Adults During a 6-Month Randomized Placebo-controlled Supplement Trial With Nutrition and Lifestyle Counselling and 6-Month Follow-up.

OBJECTIVES: In this work, we present an exploratory within-trial analysis of the changing prevalence of prediabetes in response to nutrition and lifestyle counselling provided as part of a randomized placebo-controlled supplement trial with follow-up. We aimed to identify factors associated with changing glycemia status. METHODS: Participants (n=401) in this clinical trial were adults with a body mass index (BMI) of ≥25 kg/m2 and prediabetes (defined by the American Diabetes Association as a fasting plasma glucose [FPG] of 5.6 to 6.9 mmol/L or a glycated hemoglobin [A1C] of 5.7% to 6.4%) within 6 months before trial entry. The trial consisted of a 6-month randomized intervention with 2 dietary supplements and/or placebo. At the same time, all participants received nutrition and lifestyle counselling. This was followed by a 6-month follow-up. Glycemia status was assessed at baseline and at 6 and 12 months. RESULTS: At baseline, 226 participants (56%) met a threshold for prediabetes, including 167 (42%) with elevated FPG and 155 (39%) with elevated A1C. After the 6-month intervention, the prevalence of prediabetes decreased to 46%, driven by a reduction in prevalence of elevated FPG to 29%. The prevalence of prediabetes then increased to 51% after follow-up. Risk of prediabetes was associated with older age (odds ratio [OR], 1.05; p<0.01), BMI (OR, 1.06; p<0.05), and male sex (OR, 1.81; p=0.01). Participants who reverted to normoglycemia had greater weight loss and lower baseline glycemia. CONCLUSIONS: Glycemia status can fluctuate over time and improvements can be gained from lifestyle interventions, with certain factors associated with a higher likelihood of reverting to normoglycemia.

Is iron status associated with markers of non-communicable disease in adolescent Indian children?

BACKGROUND: High body iron status has been associated with non-communicable diseases (NCD) like diabetes (high fasting blood glucose, FBG), hypertension (HTN) or dyslipidaemia (high total cholesterol, TC) in adults, but this has not been examined in adolescent children. This is relevant to iron supplementation and food iron fortification programs that are directed at Indian children. METHODS: The association of NCD with Serum Ferritin (SF) was examined using logistic additive models, adjusted for confounders such as age, body mass index, C-Reactive Protein, haemoglobin and sex, in adolescent (10-19 years old) participants of the Indian Comprehensive National Nutrition Survey. The interaction of these associations with wealth and co-existing prediabetes was also examined. A scenario analysis was also done to understand the impact of iron fortification of cereals on the prevalence NCD among adolescents. RESULTS: The odds ratio (OR) of high FBG, HTN and TC were 1.05 (95% CI: 1.01-1.08), 1.02 (95% CI: 1.001-1.03) and 1.04 (95% CI: 1.01-1.06) respectively for every 10 µg/L increase in SF. The odds for high TC increased with co-existing prediabetes. The scenario analysis showed that providing 10 mg of iron/day by fortification could increase the prevalence of high FBG by 2-14% across states of India. Similar increments in HTN and TC can also be expected. CONCLUSIONS: High SF is significantly associated with NCD in adolescents, dependent on wealth and co-existing prediabetes. This should be considered when enhancing iron intake in anaemia prevention programs, and the NCD relationship with body iron stores should be studied.

Prevalence of prediabetes and diabetes vary by ethnicity among U.S. Asian adults at healthy weight, overweight, and obesity ranges: an electronic health record study.

BACKGROUND: Asian adults develop Type 2 diabetes at a lower body mass index (BMI) compared to other racial/ethnic groups. We examined the variation in prevalence of prediabetes and diabetes among Asian ethnic groups within weight strata by comparing middle-aged Chinese, Filipino, South Asian, and White adults receiving care in the same integrated healthcare delivery system. METHODS: Our retrospective cross-sectional U.S. study examined data from 283,110 (non-Hispanic) White, 33,263 Chinese, 38,766 Filipino, and 17,959 South Asian adults aged 45-64 years who were members of a Northern California health plan in 2016 and had measured height and weight. Prediabetes and diabetes were classified based on laboratory data, clinical diagnoses, or diabetes pharmacotherapy. Age-standardized prevalence of prediabetes and diabetes were compared by race/ethnicity within healthy weight, overweight, and obesity categories, using standard BMI thresholds for White adults (18.5 to < 25, 25 to < 30, ≥ 30 kg/m2) and lower BMI thresholds for Asian adults (18.5 to < 23, 23 to < 27.5, ≥ 27.5 kg/m2). Prevalence ratios (PRs) were used to compare the prevalence of diabetes and prediabetes for Asian groups to White adults in each weight category, adjusted for age and BMI. RESULTS: Across all weight categories, diabetes prevalence was higher for Asian than White adults, and among Asian groups it was highest for Filipino and South Asian adults. Compared to White, PRs for South Asian men/women at healthy BMI were 1.8/2.8 for prediabetes and 5.9/8.0 for diabetes, respectively. The PRs for Filipino men/women at healthy BMI were 1.8/2.6 for prediabetes and 5.0/7.5 for diabetes, respectively. For Chinese men/women at healthy BMI, the PRs for prediabetes (2.1/2.9) were similar to Filipino and South Asian, but the PRs for diabetes were lower (2.1/3.4). CONCLUSION: Chinese, Filipino, and South Asian adults have higher prevalence of prediabetes and diabetes than White adults in all weight categories, despite using lower BMI thresholds for weight classification in Asian groups. Within Asian ethnic groups, Filipino and South Asian adults had considerably higher diabetes prevalence than Chinese adults. Our data emphasize the disproportionate metabolic risk among middle-aged Asian adults and underscore the need for diabetes screening among high-risk Asian groups at healthy BMI levels.

Mindfulness in adolescents and young adults with diabetes: An integrative review.

BACKGROUND AND PURPOSE: Type 1 diabetes (T1D), type 2 diabetes, and prediabetes are increasing in incidence. Adolescents and young adults with diabetes experience psychosocial comorbidities at an increased incidence. As such, exploring interventions that can improve psychosocial and glycemic outcomes are needed. The purpose of this integrative review is to examine and synthesize the literature on mindfulness in adolescents and young adults with type 1 or type 2 diabetes or prediabetes. METHODS: Four databases were searched during May 2021. Included studies were published between 2000 and 2021, evaluated adolescents and young adults, diagnosed with type 1 or type 2 diabetes or prediabetes. Studies were excluded if they were not in English; not original research; evaluated complementary/alternative therapies as a group. To assess for risk of bias, the National Institutes of Health quality assessment tools and the Cochrane Collaboration's tool were utilized. Whittemore and Knafl's (2005) method for conducting an integrative review was utilized to synthesize results. RESULTS: We identified 137 articles in our initial search and 74 articles remained after removing for duplicates. Ten articles were included in the review, with 5 including adolescents and young adults with T1D and 5 including adolescents and young adults with prediabetes. No studies evaluated mindfulness in adolescents and young adults with type 2 diabetes. CONCLUSION: Mindfulness is an acceptable intervention in adolescents and young adults with T1D and prediabetes, resulting in positive psychosocial and glycemic outcomes. There were issues with feasibility of the intervention and mobile health technology delivery methods should be evaluated.

Higher selenium was associated with higher risk of diabetes: Consistent evidence from longitudinal and cross-sectional studies based on nail and serum selenium measures.

Although the association between selenium (Se) and diabetes has been well-discussed in recent years, few studies have focused on the effects of long-term natural Se exposure and rarely concerned the effects of different Se biomarkers. To address this question, we carried out a 7-year longitudinal study on older adults aged over 65 and another cross-sectional study on middle-aged and older adults aged 40 and above from Chinese soil Se-deplete and Se-optimum areas. Cox proportional hazard models were used to evaluate the associations between nail Se levels and incidence risk of diabetes. Unconditional logistic regression models and analysis of variance models were used to examine the associations between serum Se levels and the prevalence risk of diabetes. The nail and serum Se levels were 0.47 ± 0.20 µg/g and 111.09 ± 55.01 µg/L for the two study populations, respectively. For both of the independent studies, higher Se levels were observed to be associated with a higher risk of diabetes and prediabetes. Compared with the Second nail Se quartile (Q2), the adjusted hazard ratios (HRs) and 95 % confidence intervals (95 % CIs) of diabetes for Q1, Q3 and Q4 were 1.24(0.70, 2.21), 1.53(0.98, 2.39) and 1.31(0.76, 2.26), respectively, and the adjusted HRs (95 % CIs) of prediabetes were 1.47(0.77, 2.81), 1.38(0.83, 2.30), and 1.97(1.13, 3.44), respectively. Compared with the first serum Se quintile (Q1), the adjusted odds ratios (ORs) and 95 % CIs of diabetes for higher quintiles were 1.12(0.75, 1.66), 1.05(0.71, 1.57), 1.09(0.73, 1.62) and 1.51(1.02, 2.19), and the adjusted ORs (95 % CIs) of prediabetes were 1.27(0.77, 2.09), 1.70(1.05, 2.74), 1.94(1.21, 3.11) and 1.67(1.03, 2.71). Our findings consistently suggest that higher Se status is associated with a higher risk of diabetes in adults.

The impact of the National Health Program on diabetes incidence among working-age men with prediabetes: A regression discontinuity analysis of a nation-wide database in Japan.

AIM: This study aimed to investigate the impact of the National Health Program in Japan ("Specific Health Check-ups and Specific Health Guidance") on diabetes prevention among working-age men with prediabetes. METHODS: This study used a regression discontinuity design, based on the program's criterion that the program starts at age 40 or older and that the intervention is provided only to prediabetic individuals with abdominal obesity, to assess the impact of the program on the diabetes incidence in a total of 49,848 men with prediabetes, aged 37-42 years. RESULTS: The National Health Program in which interventions were provided for individuals aged 40 years or over with both prediabetes and abdominal obesity was associated with a decrease in diabetes incidence rate equivalent to 10.1 reduction/1000 person-years. The relative risk was 0.75. However, among those without abdominal obesity and not subjected to the intervention, there was no significant change in the diabetes incidence at age 40. CONCLUSIONS: The National Health Program in Japan was associated with a decrease in the incidence of diabetes among working-age men with prediabetes and abdominal obesity and may have a meaningful impact among working-age men.

The effect of vitamin D supplementation on cardiovascular risk in patients with prediabetes: A secondary analysis of the D2d study.

AIMS: Low blood 25(OH)D level is associated with increased cardiovascular disease (CVD) risk. Additionally, individuals with prediabetes are at higher risk for CVD than individuals with normoglycemia. We investigated the effects of vitamin D supplementation on CVD outcomes in the vitamin D and type 2 diabetes (D2d) study, a large trial among adults with prediabetes. METHODS: 2423 participants were randomized to 4000 IU/day of vitamin D3 or placebo and followed for median 3.0 years for new-onset diabetes. In pre-specified secondary analyses, we examined the effect of vitamin D supplementation on composite Major Adverse Cardiovascular Events (MACE); expanded MACE (MACE + revascularization); atherosclerotic CVD (ASCVD) risk score; and individual CVD risk factors (blood pressure, lipids, high-sensitivity C-reactive protein). Cox models compared hazard ratios (HR) between the two groups on MACE and expanded MACE. RESULTS: Mean age was 60 years, 45 % were women, 13 % had history of CVD. Twenty-one participants assigned to vitamin D and 12 participants assigned to placebo met the MACE outcome (HR 1.81, 95%CI 0.89 to 3.69). There were 27 expanded MACE outcomes in each group (HR 1.02, 95%CI, 0.59 to 1.76). There were no significant differences between vitamin D and placebo in individual CVD risk factors, but change in ASCVD risk score favored the vitamin D group (-0.45 %, 95%CI -0.75 to -0.15). CONCLUSIONS: In people with prediabetes not selected for vitamin D insufficiency and with intermediate CVD risk, vitamin D supplementation did not decrease MACE but had a small favorable effect on ASCVD risk score. TRIAL REGISTRATION: D2d ClinicalTrials.gov number, NCT01942694, prospectively registered September 16, 2013.

Prediabetes and insulin resistance are associated with lower trabecular bone score (TBS): cross-sectional results from the Study of Women's Health Across the Nation TBS Study.

In pre- and early perimenopausal women, prediabetes (with blood glucose ≥ 110 mg/dL) and greater insulin resistance are associated with worse trabecular bone quality (as assessed by trabecular bone score). PURPOSE: Diabetes mellitus (DM) is associated with lower trabecular bone score (TBS) and fracture; less certain is whether the precursor states of prediabetes and increased insulin resistance are also related to adverse bone outcomes. We examined, in women who do not have DM, the associations of glycemic status (prediabetes vs. normal) and insulin resistance with TBS. METHODS: This was a cross-sectional analysis of baseline data collected from 42- to 52-year-old, pre- and perimenopausal participants in the Study of Women's Health Across the Nation (SWAN) TBS Study. Women with prediabetes were categorized as having either high prediabetes if their fasting glucose was between 110 and 125 mg/dL or low prediabetes if their fasting glucose was between 100 and 109 mg/dL. Normoglycemia was defined as a fasting glucose below 100 mg/dL. RESULTS: In multivariable linear regression, adjusted for age, race/ethnicity, menopause transition stage, cigarette use, calcium and vitamin D supplementation, lumbar spine bone mineral density, and study site, women with high prediabetes had 0.21 (p < 0.0001) standard deviations (SD) lower TBS than those with normoglycemia. Low prediabetes was not associated with lower TBS. When HOMA-IR levels were ≥ 1.62, each doubling of HOMA-IR was associated with a 0.11 SD decrement in TBS (p = 0.0001). CONCLUSION: Similar to diabetics, high prediabetics have lower TBS than normoglycemic individuals. Women with greater insulin resistance have lower TBS even in the absence of DM. Future studies should examine the associations of high prediabetes and insulin resistance with incident fracture.

Effectiveness of a Yoga-Based Lifestyle Protocol (YLP) in Preventing Diabetes in a High-Risk Indian Cohort: A Multicenter Cluster-Randomized Controlled Trial (NMB-Trial).

Introduction: Though several lines of evidence support the utility of yoga-based interventions in diabetes prevention, most of these studies have been limited by methodological issues, primarily sample size inadequacy. Hence, we tested the effectiveness of yoga-based lifestyle intervention against diabetes risk reduction in multicentre, large community settings of India, through a single-blind cluster-randomized controlled trial, Niyantrita Madhumeha Bharat Abhiyan (NMB). Research Design and Methods: NMB-trial is a multicentre cluster-randomized trial conducted in 80 clusters [composed of rural units (villages) and urban units (Census Enumeration Blocks)] randomly assigned in a 1:1 ratio to intervention and control groups. Participants were individuals (age, 20-70 years) with prediabetes (blood HbA1c values in the range of 5.7-6.4%) and IDRS ≥ 60. The intervention included the practice of yoga-based lifestyle modification protocol (YLP) for 9 consecutive days, followed by daily home and weekly supervised practices for 3 months. The control cluster received standard of care advice for diabetes prevention. Statistical analyses were performed on an intention-to-treat basis, using available and imputed datasets. The primary outcome was the conversion from prediabetes to diabetes after the YLP intervention of 3 months (diagnosed based upon HbA1c cutoff >6.5%). Secondary outcome included regression to normoglycemia with HbA1c <5.7%. Results: A total of 3380 (75.96%) participants were followed up at 3 months. At 3 months post-intervention, overall, diabetes developed in 726 (21.44%) participants. YLP was found to be significantly effective in halting progression to diabetes as compared to standard of care; adjusted RRR was 63.81(95% CI = 56.55-69.85). The YLP also accelerated regression to normoglycemia [adjusted Odds Ratio (adjOR) = 1.20 (95% CI, 1.02-1.43)]. Importantly, younger participants (≤40 years) were found to regress to normoglycemia more effectively than the older participants Pinteraction<0.001. Conclusion: Based on the significant risk reduction derived from the large sample size, and the carefully designed randomized yoga-based intervention on high-risk populations, the study is a preliminary but strong proof-of-concept for yoga as a potential lifestyle-based treatment to curb the epidemic of diabetes. The observed findings also indicate a potential of YLP for diabetes prevention in low/moderate risk profile individuals that needs large-scale validation. Trial Registration: Clinical Trial Registration Number: CTRI/2018/03/012804.

Association of folate, vitamin B-12 and vitamin B-6 intake with diabetes and prediabetes in adults aged 20 years and older.

BACKGROUND AND OBJECTIVES: This study aimed to assess the association of folate, vitamin B-12 and vitamin B-6 from diet and supplements with diabetes and prediabetes in U.S. adults. METHODS AND STUDY DESIGN: We used data from the National Health and Nutrition Examination Survey (NHANES) 2007-2016 to conduct this crosssectional study. Diabetes and prediabetes status were based on self-report, medication use, fasting plasma glucose levels (FPG), haemoglobin A1c (HbA1c) levels and the two hours plasma glucose (PG) value during a 75-g oral glucose tolerance test (OGTT). Logistic regression models and restricted cubic spline models were used to evaluate the associations between dietary folate, vitamin B-12, vitamin B-6 and diabetes. RESULTS: After adjustment for the potential confounders, compared with the lowest quartile, the ORs (odds ratios) with 95%CIs (confidence intervals) of diabetes for the highest quartile intakes of folate and vitamin B-6 were 0.65 (0.47-0.90) and 0.61 (0.42-0.89), the OR with 95% CI of diabetes for the third quartile of dietary vitamin B-12 was 0.76 (0.60-0.97). Further excluded participants with diabetes history, the ORs with 95% CI of newly diagnosed diabetes were 0.60 (0.39-0.94), 0.84 (0.58-1.23), and 0.65 (0.43-0.98) for the third quartile of dietary folate, vitamin B-12 and vitamin B-6, respectively. A linear inverse relationship was found between vitamin B12 and diabetes, and a nonlinear inverse relationship was found between dietary folate, dietary vitamin B6 and diabetes. CONCLUSIONS: Our study suggested that folate, vitamin B-12 and vitamin B-6 intake were inversely associated with the risk of diabetes in US adults.

Vitamin D Supplementation for Prevention of Type 2 Diabetes Mellitus: To D or Not to D?

CONTEXT: Over the last decade, vitamin D has emerged as a risk determinant for type 2 diabetes and vitamin D supplementation has been hypothesized as a potential intervention to lower diabetes risk. Recently, several trials have reported on the effect of vitamin D supplementation on diabetes prevention in people with prediabetes. EVIDENCE ACQUISITION: A comprehensive literature review was performed using PubMed, Embase, and ClinicalTrials.gov to identify: (1) recent meta-analyses of longitudinal observational studies that report on the association between blood 25-hydroxyvitamin D (25[OH]D) level and incident diabetes, and (2) clinical trials of adults with prediabetes that have reported on the effect of vitamin D supplementation on incident diabetes. EVIDENCE SYNTHESIS: Longitudinal observational studies report highly consistent associations between higher blood 25(OH)D levels and a lower risk of incident diabetes in diverse populations, including populations with prediabetes. Trials in persons with prediabetes show risk reduction in incident diabetes with vitamin D supplementation. In the 3 large trials that were specifically designed and conducted for the prevention of diabetes, vitamin D supplementation, when compared with placebo, reduced the risk of developing diabetes by 10% to 13% in persons with prediabetes not selected for vitamin D deficiency. CONCLUSIONS: Results from recent trials are congruent with a large body of evidence from observational studies indicating that vitamin D has a role in modulating diabetes risk. Participant-level meta-analysis of the 3 largest trials should provide a more refined estimate of risk reduction and identify patient populations that are likely to benefit the most from vitamin D supplementation.

Interactions of Habitual Coffee Consumption by Genetic Polymorphisms with the Risk of Prediabetes and Type 2 Diabetes Combined.

Habitual coffee consumption and its association with health outcomes may be modified by genetic variation. Adults aged 40 to 69 years who participated in the Korea Association Resource (KARE) study were included in this study. We conducted a genome-wide association study (GWAS) on coffee consumption in 7868 Korean adults, and examined whether the association between coffee consumption and the risk of prediabetes and type 2 diabetes combined was modified by the genetic variations in 4054 adults. In the GWAS for coffee consumption, a total of five single nucleotide polymorphisms (SNPs) located in 12q24.11-13 (rs2074356, rs11066015, rs12229654, rs11065828, and rs79105258) were selected and used to calculate weighted genetic risk scores. Individuals who had a larger number of minor alleles for these five SNPs had higher genetic risk scores. Multivariate logistic regression models were used to estimate the odds ratios (ORs) and 95% confidence intervals (95% CIs) to examine the association. During the 12 years of follow-up, a total of 2468 (60.9%) and 480 (11.8%) participants were diagnosed as prediabetes or type 2 diabetes, respectively. Compared with non-black-coffee consumers, the OR (95% CI) for ≥2 cups/day by black-coffee consumers was 0.61 (0.38-0.95; p for trend = 0.023). Similarly, sugared coffee showed an inverse association. We found a potential interaction by the genetic variations related to black-coffee consumption, suggesting a stronger association among individuals with higher genetic risk scores compared to those with lower scores; the ORs (95% CIs) were 0.36 (0.15-0.88) for individuals with 5 to 10 points and 0.87 (0.46-1.66) for those with 0 points. Our study suggests that habitual coffee consumption was related to genetic polymorphisms and modified the risk of prediabetes and type 2 diabetes combined in a sample of the Korean population. The mechanisms between coffee-related genetic variation and the risk of prediabetes and type 2 diabetes combined warrant further investigation.

Impact of Acarbose on Incident Diabetes and Regression to Normoglycemia in People With Coronary Heart Disease and Impaired Glucose Tolerance: Insights From the ACE Trial.

OBJECTIVE: We examined the impact of acarbose, an α-glucosidase inhibitor, on incident diabetes and regression to normoglycemia in 6,522 Acarbose Cardiovascular Evaluation (ACE) trial participants in China who had impaired glucose tolerance (IGT) and coronary heart disease (CHD). RESEARCH DESIGN AND METHODS: Participants were randomly assigned to acarbose or placebo and followed with four monthly fasting plasma glucose (FPG) tests and annual oral glucose tolerance tests. Incident diabetes was defined as two successive diagnostic FPG levels ≥7 mmol/L or 2-h plasma glucose (PG) levels ≥11.1 mmol/L while taking study medication or a masked adjudicated confirmation of this diagnosis. Regression to normoglycemia was defined as FPG <6.1 mmol/L and 2-h PG <7.8 mmol/L. Intention-to-treat and on-treatment analyses were conducted using Poisson regression models, overall and for subgroups (age, sex, CHD type, HbA1c, FPG, 2-h PG, BMI, estimated glomerular filtration rate, for IGT alone, for IGT + impaired fasting glucose, and for use of thiazides, ACE inhibitors [ACEis]/angiotensin receptor blockers [ARBs], ß-blockers, calcium channel blockers, or statins). RESULTS: Incident diabetes was less frequent with acarbose compared with placebo (3.2 and 3.8 per 100 person-years, respectively; rate ratio 0.82 [95% CI 0.71, 0.94], P = 0.005), with no evidence of differential effects within the predefined subgroups after accounting for multiple testing. Regression to normoglycemia occurred more frequently in those randomized to acarbose compared with placebo (16.3 and 14.1 per 100 person-years, respectively; 1.16 [1.08, 1.25], P < 0.0001). This effect was greater in participants not taking an ACEi or ARB (1.36 [1.21, 1.53], P interaction = 0.0006). The likelihood of remaining in normoglycemic regression did not differ between the acarbose and placebo groups (P = 0.41). CONCLUSIONS: Acarbose reduced the incidence of diabetes and promoted regression to normoglycemia in Chinese people with IGT and CHD.

Gamma glutamyltransferase and risk of dementia in prediabetes and diabetes.

Diabetes is associated with cognitive impairment and greater risk for dementia, but the role of gamma-glutamyltransferase (γ-GT) in dementia has not been elucidated. We determined incident dementia including Alzheimer's disease and vascular dementia, analyzing data from participants aged 40 years or older in the National Health Insurance Database, collected by the National Health Insurance Service in Korea, from January 2009 to December 2015. During a median follow-up of 7.6 years, 272,657 participants were diagnosed as having dementia. Higher serum γ-GT was associated with increased risk of dementia (HR = 1.22, 95% CI = 1.20-1.24), and had a strong positive association with early onset dementia (HR = 1.32, 95% CI = 1.24-1.40). An additive impact of higher γ-GT on dementia was observed regardless of glycemic status, and prevalent diabetes with the highest γ-GT quartile had a 1.8-fold increased dementia risk (HR = 1.82, 95% CI = 1.78-1.85). This effect of γ-GT concentration in diabetes was more prominent in individuals with vascular dementia (HR = 1.94, 95% CI = 1.84-2.04). In subgroup analysis, young age, male sex, and relatively healthy subjects with a higher γ-GT quartile had more increased dementia risk. In conclusion, γ-GT concentration as well as glycemic status could be a future risk factor for dementia in the general population.

Underweight Increases the Risk of End-Stage Renal Diseases for Type 2 Diabetes in Korean Population: Data From the National Health Insurance Service Health Checkups 2009-2017.

OBJECTIVE: There is a controversy over the association between obesity and end-stage renal disease (ESRD) in people with or without type 2 diabetes; therefore, we examined the effect of BMI on the risk of ESRD according to glycemic status in the Korean population. RESEARCH DESIGN AND METHODS: The study monitored 9,969,848 participants who underwent a National Health Insurance Service health checkup in 2009 from baseline to the date of diagnosis of ESRD during a follow-up period of ∼8.2 years. Obesity was categorized by World Health Organization recommendations for Asian populations, and glycemic status was categorized into the following five groups: normal, impaired fasting glucose (IFG), newly diagnosed diabetes, diabetes <5 years, and diabetes ≥5 years. RESULTS: Underweight was associated with a higher risk of ESRD in all participants after adjustment for all covariates. In the groups with IFG, newly diagnosed type 2 diabetes, diabetes duration <5 years, and diabetes ≥5 years, the hazard ratio (HR) of the underweight group increased with worsening glycemic status (HR 1.431 for IFG, 2.114 for newly diagnosed diabetes, 4.351 for diabetes <5 years, and 6.397 for diabetes ≥5 years), using normal weight with normal fasting glucose as a reference. The adjusted HRs for ESRD were also the highest in the sustained underweight group regardless of the presence of type 2 diabetes (HR 1.606 for nondiabetes and 2.14 for diabetes). CONCLUSIONS: Underweight showed more increased HR of ESRD according to glycemic status and diabetes duration in the Korean population. These associations also persisted in the group with sustained BMI during the study period.

Sociodemographic and lifestyle-related risk factors for identifying vulnerable groups for type 2 diabetes: a narrative review with emphasis on data from Europe.

BACKGROUND: Type 2 diabetes mellitus (T2DM) comprises the vast majority of all diabetes cases in adults, with alarmingly increasing prevalence over the past few decades worldwide. A particularly heavy healthcare burden of diabetes is noted in Europe, where 8.8% of the population aged 20-79 years is estimated to have diabetes according to the International Diabetes Federation. Multiple risk factors are implicated in the pathogenesis of T2DM with complex underlying interplay and intricate gene-environment interactions. Thus, intense research has been focused on studying the role of T2DM risk factors and on identifying vulnerable groups for T2DM in the general population which can then be targeted for prevention interventions. METHODS: For this narrative review, we conducted a comprehensive search of the existing literature on T2DM risk factors, focusing on studies in adult cohorts from European countries which were published in English after January 2000. RESULTS: Multiple lifestyle-related and sociodemographic factors were identified as related to high T2DM risk, including age, ethnicity, family history, low socioeconomic status, obesity, metabolic syndrome and each of its components, as well as certain unhealthy lifestyle behaviors. As Europe has an increasingly aging population, multiple migrant and ethnic minority groups and significant socioeconomic diversity both within and across different countries, this review focuses not only on modifiable T2DM risk factors, but also on the impact of pertinent demographic and socioeconomic factors. CONCLUSION: In addition to other T2DM risk factors, low socioeconomic status can significantly increase the risk for prediabetes and T2DM, but is often overlooked. In multinational and multicultural regions such as Europe, a holistic approach, which will take into account both traditional and socioeconomic/socioecological factors, is becoming increasingly crucial in order to implement multidimensional public health programs and integrated community-based interventions for effective T2DM prevention.