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Im J, Jung S, Yang Y, Kim KN. A Longitudinal Increase in Serum Gamma-Glutamyl Transferase Levels, but Not in Alanine Aminotransferase Levels, Improves the Prediction of Risk of Impaired Fasting Glucose in Male. J Korean Med Sci 2025; 40:e13. [PMID: 39962938 PMCID: PMC11832883 DOI: 10.3346/jkms.2025.40.e13] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/16/2024] [Accepted: 09/30/2024] [Indexed: 02/21/2025] Open
Abstract
BACKGROUND Impaired fasting glucose (IFG), being a pre-diabetic condition, can increase the risk of overt diabetes; thus early detection and prediction of IFG are important to reduce the incidence of overt diabetes. Some predictive factors, including serum alanine aminotransferase (ALT) and gamma-glutamyl transferase (GGT), have been reported in several studies, but none of the studies have investigated the effect of longitudinal changes in individual serum ALT and GGT levels on the risk of IFG. METHODS We aimed to investigate the association between changes in the serum ALT and GGT levels and the risk of IFG using a checkup database between 1999 and 2014. RESULTS A total of 3,598 males and 3,275 females were enrolled in the study. We performed a follow-up test of serum ALT or GGT in each individual, and classified the cases in which the serum ALT or GGT level was increased or decreased during the follow-up test compared to the baseline. According to the multivariate Cox proportional hazards model, the hazard ratio was 1.76 (95% confidence interval, 1.45-2.12; P < 0.001) in male subjects with an increased serum GGT level compared to male subjects with a decrease in the serum GGT level at follow-up compared to the baseline. However, the relationship between the serum ALT level and incidence of new-onset IFG was not statistically significant in both sexes; and in females, the relationship between the serum GGT level and incidence of new-onset IFG was also not statistically significant. CONCLUSION We revealed that a longitudinal increase in serum GGT levels was related to an increased risk of IFG in males. Therefore, monitoring the changes in serum GGT levels is important for predicting new-onset IFG, and it can be used as an early indicator of onset of overt diabetes in males.
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Affiliation(s)
- Jisoon Im
- Department of Family Practice and Community Health, Ajou University School of Medicine, Suwon, Korea
| | - Susie Jung
- Department of Family Practice and Community Health, Ajou University School of Medicine, Suwon, Korea
| | - Yuri Yang
- Department of Family Practice and Community Health, Ajou University School of Medicine, Suwon, Korea
| | - Kyu-Nam Kim
- Department of Family Practice and Community Health, Ajou University School of Medicine, Suwon, Korea.
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Tang SS, Zhao XF, An XD, Sun WJ, Kang XM, Sun YT, Jiang LL, Gao Q, Li ZH, Ji HY, Lian FM. Classification and identification of risk factors for type 2 diabetes. World J Diabetes 2025; 16:100371. [PMID: 39959280 PMCID: PMC11718467 DOI: 10.4239/wjd.v16.i2.100371] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/14/2024] [Revised: 10/24/2024] [Accepted: 11/26/2024] [Indexed: 12/30/2024] Open
Abstract
The risk factors for type 2 diabetes mellitus (T2DM) have been increasingly researched, but the lack of systematic identification and categorization makes it difficult for clinicians to quickly and accurately access and understand all the risk factors, which are categorized in this paper into five categories: Social determinants, lifestyle, checkable/testable risk factors, history of illness and medication, and other factors, which are discussed in a narrative review. Meanwhile, this paper points out the problems of the current research, helps to improve the systematic categorisation and practicality of T2DM risk factors, and provides a professional research basis for clinical practice and industry decision-making.
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Affiliation(s)
- Shan-Shan Tang
- College of Traditional Chinese Medicine, Changchun University of Chinese Medicine, Changchun 130117, Jilin Province, China
| | - Xue-Fei Zhao
- Department of Endocrinology, Guang’anmen Hospital, Beijing 100053, China
| | - Xue-Dong An
- Department of Endocrinology, Guang’anmen Hospital, Beijing 100053, China
| | - Wen-Jie Sun
- Department of Endocrinology, Guang’anmen Hospital, Beijing 100053, China
| | - Xiao-Min Kang
- Department of Endocrinology, Guang’anmen Hospital, Beijing 100053, China
| | - Yu-Ting Sun
- Department of Endocrinology, Guang’anmen Hospital, Beijing 100053, China
| | - Lin-Lin Jiang
- Department of Endocrinology, Guang’anmen Hospital, Beijing 100053, China
| | - Qing Gao
- Department of Endocrinology, Guang’anmen Hospital, Beijing 100053, China
| | - Ze-Hua Li
- Department of Endocrinology, Guang’anmen Hospital, Beijing 100053, China
| | - Hang-Yu Ji
- Department of Endocrinology, Guang’anmen Hospital, Beijing 100053, China
| | - Feng-Mei Lian
- Department of Endocrinology, Guang’anmen Hospital, Beijing 100053, China
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3
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Egan AM, Wood-Wentz CM, Mohan S, Bailey KR, Vella A. Baseline Fasting Glucose Level, Age, Sex, and Body Mass Index and the Development of Diabetes in US Adults. JAMA Netw Open 2025; 8:e2456067. [PMID: 39847352 PMCID: PMC11758592 DOI: 10.1001/jamanetworkopen.2024.56067] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/30/2024] [Accepted: 11/18/2024] [Indexed: 01/24/2025] Open
Abstract
Importance Understanding the interplay between diabetes risk factors and diabetes development is important to develop individual, practice, and population-level prevention strategies. Objective To evaluate the progression from normal and impaired fasting glucose levels to diabetes among adults. Design, Setting, and Participants This retrospective community-based cohort study used data from the Rochester Epidemiology Project, in Olmsted County, Minnesota, on 44 992 individuals with at least 2 fasting plasma glucose (FPG) measurements from January 1, 2005, to December 31, 2017. People who met criteria for diabetes on or before their first FPG measurement were excluded. Data were electronically retrieved in December 2019 with analyses finalized in November 2024. Exposures The exposure was baseline FPG level, with covariates including the following measures that are consistently recorded in the electronic health record: body mass index (BMI), age, and sex. Main Outcomes and Measures The cumulative probability of freedom from diabetes was estimated and presented graphically using a Kaplan-Meier curve. Multivariable Cox proportional hazards regression modeling was used to estimate the partial hazard ratios (HRs) for variables of interest. Diabetes was defined as an FPG level greater than 125 mg/dL. Results A total of 44 992 individuals (mean [SD] age at baseline, 43.7 [11.8] years; 26 025 women [57.8%]) were included. The baseline mean (SD) BMI was 28.9 (6.6). Over a median follow-up of 6.8 years (IQR, 3.6-9.7 years), 3879 individuals (8.6%) developed diabetes. The Kaplan-Meier 10-year cumulative risk of incident diabetes was 12.8% (95% CI, 12.4%-13.2%). All initial FPG levels outside a range of 80 to 94 mg/dL were associated with increased risk for diabetes (ie, FPG <70 mg/dL: HR, 3.49 [95% CI, 2.19-5.57]; FPG 120-125 mg/dL: HR, 12.47 [10.84-14.34]). Other independent risk factors were male sex (HR, 1.31 [95% CI, 1.22-1.40]), older age (≥60 years: HR, 1.97 [95% CI, 1.71-2.28]), and any abnormal category of BMI, including underweight (BMI <18.5: HR, 2.42 [95% CI, 1.77-3.29]; BMI ≥40: HR, 4.03 [95% CI, 3.56-4.56]). There was a significant additive association of variables, particularly FPG level and BMI. For instance, a woman aged 55 to 59 years with a BMI of 18.5 to 24.9 and an FPG level of 95 to 99 mg/dL had an estimated 10-year diabetes risk of 7.0%. However, an almost doubling of risk to 13.0% was observed if the BMI was 30.0 to 34.9, and risk more than doubled again to 28.0% if FPG level also increased to 105 to 109 mg/dL. A nomogram was generated to facilitate individual classification into one of four 10-year risk categories. Conclusions and Relevance This retrospective cohort study of 44 992 individuals suggests that FPG level, age, BMI, and male sex were all associated with development of diabetes, with significant interaction between these variables. These data contribute to understanding the clinical course of diabetes and highlight the substantial individual variation in diabetes risk according to commonly measured clinical variables. The findings facilitate lifestyle and pharmacologic interventions to treat those at highest risk of diabetes to reduce future morbidity and mortality. Further work is needed to validate this risk categorization tool for different populations.
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Affiliation(s)
- Aoife M. Egan
- Division of Endocrinology, Diabetes and Metabolism, Mayo Clinic, Rochester, Minnesota
| | | | - Sneha Mohan
- Division of Endocrinology, Diabetes and Metabolism, Mayo Clinic, Rochester, Minnesota
| | - Kent R. Bailey
- Division of Clinical Trials and Biostatistics, Mayo Clinic, Rochester, Minnesota
| | - Adrian Vella
- Division of Endocrinology, Diabetes and Metabolism, Mayo Clinic, Rochester, Minnesota
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Xu Q, Sun M, Wang W, Shi Y. All-Dielectric Metasurface-Based Terahertz Molecular Fingerprint Sensor for Trace Cinnamoylglycine Detection. BIOSENSORS 2024; 14:440. [PMID: 39329815 PMCID: PMC11430580 DOI: 10.3390/bios14090440] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/07/2024] [Revised: 08/30/2024] [Accepted: 09/11/2024] [Indexed: 09/28/2024]
Abstract
Terahertz (THZ) spectroscopy has emerged as a superior label-free sensing technology in the detection, identification, and quantification of biomolecules in various biological samples. However, the limitations in identification and discrimination sensitivity of current methods impede the wider adoption of this technology. In this article, a meticulously designed metasurface is proposed for molecular fingerprint enhancement, consisting of a periodic array of lithium tantalate triangular prism tetramers arranged in a square quartz lattice. The physical mechanism is explained by the finite-difference time-domain (FDTD) method. The metasurface achieves a high quality factor (Q-factor) of 231 and demonstrates excellent THz sensing capabilities with a figure of merit (FoM) of 609. By varying the incident angle of the THz wave, the molecular fingerprint signal is strengthened, enabling the highly sensitive detection of trace amounts of analyte. Consequently, cinnamoylglycine can be detected with a sensitivity limit as low as 1.23 μg·cm-2. This study offers critical insights into the advanced application of THz waves in biomedicine, particularly for the detection of urinary biomarkers in various diseases, including gestational diabetes mellitus (GDM).
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Affiliation(s)
| | | | | | - Yanpeng Shi
- School of Integrated Circuits, Shandong University, Jinan 250100, China
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Walton B, Kaplan N, Hrdlicka B, Mehta K, Arendt LM. Obesity Induces DNA Damage in Mammary Epithelial Cells Exacerbated by Acrylamide Treatment through CYP2E1-Mediated Oxidative Stress. TOXICS 2024; 12:484. [PMID: 39058136 PMCID: PMC11281187 DOI: 10.3390/toxics12070484] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/16/2024] [Revised: 06/20/2024] [Accepted: 06/28/2024] [Indexed: 07/28/2024]
Abstract
Obesity and environmental toxins are risk factors for breast cancer; however, there is limited knowledge on how these risk factors interact to promote breast cancer. Acrylamide, a probable carcinogen and obesogen, is a by-product in foods prevalent in the obesity-inducing Western diet. Acrylamide is metabolized by cytochrome P450 2E1 (CYP2E1) to the genotoxic epoxide, glycidamide, and is associated with an increased risk for breast cancer. To investigate how acrylamide and obesity interact to increase breast cancer risk, female mice were fed a low-fat (LFD) or high-fat diet (HFD) and control water or water supplemented with acrylamide at levels similar to the average daily exposure in humans. While HFD significantly enhanced weight gain in mice, the addition of acrylamide did not significantly alter body weights compared to respective controls. Mammary epithelial cells from obese, acrylamide-treated mice had increased DNA strand breaks and oxidative DNA damage compared to all other groups. In vitro, glycidamide-treated COMMA-D cells showed significantly increased DNA strand breaks, while acrylamide-treated cells demonstrated significantly higher levels of intracellular reactive oxygen species. The knockdown of CYP2E1 rescued the acrylamide-induced oxidative stress. These studies suggest that long-term acrylamide exposure through foods common in the Western diet may enhance DNA damage and the CYP2E1-induced generation of oxidative stress in mammary epithelial cells, potentially enhancing obesity-induced breast cancer risk.
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Affiliation(s)
- Brenna Walton
- Molecular and Environmental Toxicology, University of Wisconsin-Madison, Madison, WI 53715, USA
| | - Noah Kaplan
- Comparative Biosciences, University of Wisconsin-Madison, Madison, WI 53715, USA
| | - Brooke Hrdlicka
- Comparative Biosciences, University of Wisconsin-Madison, Madison, WI 53715, USA
| | - Kavi Mehta
- Comparative Biosciences, University of Wisconsin-Madison, Madison, WI 53715, USA
| | - Lisa M. Arendt
- Molecular and Environmental Toxicology, University of Wisconsin-Madison, Madison, WI 53715, USA
- Comparative Biosciences, University of Wisconsin-Madison, Madison, WI 53715, USA
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Kim SH. Reframing prediabetes: A call for better risk stratification and intervention. J Intern Med 2024; 295:735-747. [PMID: 38606904 DOI: 10.1111/joim.13786] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 04/13/2024]
Abstract
Prediabetes is an intermediate state of glucose homeostasis whereby plasma glucose concentrations are above normal but below the threshold of diagnosis for diabetes. Over the last several decades, criteria for prediabetes have changed as the cut points for normal glucose concentration and diagnosis of diabetes have shifted. Global consensus does not exist for prediabetes criteria; as a result, the clinical course and risk for type 2 diabetes vary. At present, we can identify individuals with prediabetes based on three glycemic tests (hemoglobin A1c, fasting plasma glucose, and 2-h plasma glucose during an oral glucose tolerance test). The majority of individuals diagnosed with prediabetes meet only one of these criteria. Meeting one, two, or all glycemic criteria changes risk for type 2 diabetes, but this information is not widely known and does not currently guide intervention strategies for individuals with prediabetes. This review summarizes current epidemiology, prognosis, and intervention strategies for individuals diagnosed with prediabetes and suggests a call for more precise risk stratification of individuals with prediabetes as elevated (one prediabetes criterion), high risk (two prediabetes criteria), and very high risk (three prediabetes criteria). In addition, the roles of oral glucose tolerance testing and continuous glucose monitoring in the diagnostic criteria for prediabetes need reassessment. Finally, we must reframe our goals for prediabetes and prioritize intensive interventions for those at high and very high risk for type 2 diabetes.
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Affiliation(s)
- Sun H Kim
- Division of Endocrinology, Gerontology and Metabolism, Stanford University School of Medicine, Stanford, California, USA
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Park HB, Gwark JY, Jung J. Associations of normal fasting glucose levels and of insulin resistance with degenerative rotator cuff tear : Normoglycemia and rotator cuff tear. BMC Musculoskelet Disord 2023; 24:973. [PMID: 38102571 PMCID: PMC10724963 DOI: 10.1186/s12891-023-06899-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/10/2023] [Accepted: 09/20/2023] [Indexed: 12/17/2023] Open
Abstract
BACKGROUND The upper normoglycemic range has been proposed as a risk factor for degenerative rotator cuff tendon tear (RCT), and insulin resistance has been suggested as a risk factor for tendinopathy. However, no research has established their association with degenerative RCT in the general population. This study aimed to determine whether fasting glucose levels and insulin resistance are risk factors for degenerative RCT in the normoglycemic population and identify the risk range for fasting glucose. METHODS This study included 418 normoglycemic participants from a rural cohort. Participants completed questionnaires, physical exams, blood tests, and MRI evaluations of both shoulders. Insulin resistance was assessed using a triglyceride/high-density-lipoprotein (TG/HDL) ≥ 3.5. Logistic regression analysis was used to determine the association between fasting glucose level, TG/HDL ≥ 3.5, and other factors and degenerative RCT. The study calculated the areas under the receiver operating characteristic curve (AUC) to determine the more appropriate predicting value between the scale and categorical values of fasting glucose levels, and compared the AUCs using the DeLong method. RESULTS In the multivariable analyses, both scale and categorical values of fasting glucose levels, and TG/HDL ≥ 3.5 were significantly associated with degenerative RCT. Fasting glucose levels ≥ 90.5 mg/dL (OR: 3.87, 95% CI: 2.10-7.06) in scale value and 90-99 mg/dL (OR: 4.13, 95% CI: 2.87-8.12) in categorical value were significantly associated with degenerative RCT (P < .001). The AUC of the scale value of fasting glucose levels ≥ 90.5 mg/dL was 0.68. The AUC of the categorical value of fasting glucose levels of 90-99 mg/dL was 0.70. Because of the significantly larger AUC of the categorical value of fasting glucose levels of 90-99 mg/dL, those fasting glucose levels were determined to be independently associated with degenerative RCT (P < .001). CONCLUSIONS High fasting glucose levels within the normal range may link to increase insulin resistance and risk of degenerative RCT. Normoglycemic levels of 90-99 mg/dL and insulin resistance may be risk factors for degenerative RCT. LEVEL OF EVIDENCE Level III, prognostic study.
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Affiliation(s)
- Hyung Bin Park
- Department of Orthopaedic Surgery, Gyeongsang National University School of Medicine, Gyeongsang National University Changwon Hospital, 11 Samjeongja-ro Seongsan- gu, Changwon, 51472, Republic of Korea.
- Gyeongsang institute of medical sciences, Gyeongsang national university, Jinju, Republic of Korea.
| | - Ji-Yong Gwark
- Department of Orthopaedic Surgery, Gyeongsang National University School of Medicine, Gyeongsang National University Changwon Hospital, 11 Samjeongja-ro Seongsan- gu, Changwon, 51472, Republic of Korea
- Gyeongsang institute of medical sciences, Gyeongsang national university, Jinju, Republic of Korea
| | - Jaehoon Jung
- Division of Endocrinology, Department of Internal Medicine, School of Medicine, Gyeongsang National University, Gyeongsang National University Changwon Hospital, Changwon, Republic of Korea
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Mittendorfer B, Patterson BW, Haire-Joshu D, Cahill AG, Cade WT, Stein RI, Klein S. Insulin Sensitivity and β-Cell Function During Early and Late Pregnancy in Women With and Without Gestational Diabetes Mellitus. Diabetes Care 2023; 46:2147-2154. [PMID: 37262059 PMCID: PMC10698210 DOI: 10.2337/dc22-1894] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/28/2022] [Accepted: 05/04/2023] [Indexed: 06/03/2023]
Abstract
OBJECTIVE To evaluate the metabolic alterations associated with gestational diabetes mellitus (GDM) in women with overweight or obesity. RESEARCH DESIGN AND METHODS We compared fasting and postprandial plasma glucose and free fatty acid (FFA) concentrations, insulin sensitivity (IS; Matsuda index), and β-cell function (i.e., β-cell responsiveness to glucose) by using a frequently sampled oral glucose tolerance test (OGTT) at 15 and 35 weeks' gestation in women with overweight or obesity who had GDM (n = 29) or did not have GDM (No-GDM; n = 164) at 35 weeks. RESULTS At 15 weeks, IS and β-cell function were lower, and fasting, 1-h, and total area-under-the-curve plasma glucose concentrations during the OGTT were higher (all P < 0.05) in the GDM than in the No-GDM group. At 35 weeks compared with 15 weeks, IS decreased, β-cell function increased, and postprandial suppression of plasma FFA was blunted in both the GDM and No-GDM groups, but the decrease in IS and the increase in postprandial FFA concentration were greater and the increase in β-cell function was less (all P ≤ 0.05) in the GDM than in the No-GDM group. A receiver operating characteristic curve analysis showed that both fasting plasma glucose and 1-h OGTT glucose concentration at 15 weeks are predictors of GDM, but the predictive power was <30%. CONCLUSIONS Women with overweight or obesity and GDM, compared with those without GDM, have worse IS and β-cell function early during pregnancy and a greater subsequent decline in IS and blunted increase in β-cell function. Increased fasting and 1-h OGTT plasma glucose concentration early during pregnancy are markers of increased GDM risk, albeit with weak predictive power.
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Affiliation(s)
| | | | | | - Alison G. Cahill
- Department of Obstetrics and Gynecology, Washington University, St. Louis, MO
- Department of Women’s Health, The University of Texas at Austin, Dell Medical School, Austin, TX
| | - W. Todd Cade
- Program in Physical Therapy, Washington University, St. Louis, MO
| | - Richard I. Stein
- Center for Human Nutrition, Washington University, St. Louis, MO
| | - Samuel Klein
- Center for Human Nutrition, Washington University, St. Louis, MO
- Sansum Diabetes Research Institute, Santa Barbara, CA
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Retnakaran R, Ye C, Kramer CK, Hanley AJ, Connelly PW, Sermer M, Zinman B. Deteriorating beta cell function is the dominant determinant of progression from normal glucose tolerance to prediabetes/diabetes in young women following pregnancy. Diabetologia 2023; 66:2154-2163. [PMID: 37612415 DOI: 10.1007/s00125-023-05994-5] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/10/2023] [Accepted: 07/24/2023] [Indexed: 08/25/2023]
Abstract
AIMS/HYPOTHESIS Excess adiposity, insulin resistance and beta cell dysfunction each contribute to the development of prediabetes (impaired glucose tolerance and/or impaired fasting glucose)/diabetes but their comparative impact in relation to one another remains uncertain. We thus ranked their contributions to incident dysglycaemia over the first 5 years postpartum in women reflecting the full spectrum of gestational glucose tolerance (spanning normoglycaemia to gestational diabetes) and hence a range of future diabetic risk. METHODS In this study, 302 women with normal glucose tolerance (NGT) on OGTT at 3 months postpartum underwent repeat OGTT at 1 year, 3 years and 5 years, enabling serial assessment of glucose tolerance, insulin sensitivity/resistance (Matsuda index, HOMA-IR) and beta cell function (insulin secretion-sensitivity index-2 [ISSI-2], insulinogenic index [IGI]/HOMA-IR). Determinants of prediabetes/diabetes were ranked by change in concordance index (CCI) of Cox proportional hazard regression models. RESULTS Over 5 years of follow-up, 89 women progressed from NGT to prediabetes/diabetes (progressors). At 3 months postpartum, though all women were normoglycaemic, future progressors had higher fasting glucose (p=0.03) and 2 h glucose (p<0.0001) than non-progressors, coupled with higher BMI (p=0.001), greater insulin resistance (both Matsuda index and HOMA-IR, p≤0.02) and poorer beta cell function (both ISSI-2 and IGI/HOMA-IR, p≤0.006). Unlike their peers, progressors exhibited deteriorating beta cell function from 1 year to 5 years (both p<0.0001). On regression analyses, the dominant determinants of progression to prediabetes/diabetes were time-varying ISSI-2 (change in CCI 25.2%) and IGI/HOMA-IR (13.0%), in contrast to time-varying Matsuda index (2.9%) and HOMA-IR (0.5%). Neither time-varying BMI nor waist were significant predictors after adjustment for beta cell function and insulin sensitivity/resistance. CONCLUSION/INTERPRETATION Declining beta cell function is the dominant determinant of incident prediabetes/diabetes in young women following pregnancy.
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Affiliation(s)
- Ravi Retnakaran
- Leadership Sinai Centre for Diabetes, Mount Sinai Hospital, Toronto, ON, Canada.
- Division of Endocrinology, University of Toronto, Toronto, ON, Canada.
- Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada.
| | - Chang Ye
- Leadership Sinai Centre for Diabetes, Mount Sinai Hospital, Toronto, ON, Canada
| | - Caroline K Kramer
- Leadership Sinai Centre for Diabetes, Mount Sinai Hospital, Toronto, ON, Canada
- Division of Endocrinology, University of Toronto, Toronto, ON, Canada
- Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada
| | - Anthony J Hanley
- Leadership Sinai Centre for Diabetes, Mount Sinai Hospital, Toronto, ON, Canada
- Division of Endocrinology, University of Toronto, Toronto, ON, Canada
- Department of Nutritional Sciences, University of Toronto, Toronto, ON, Canada
| | - Philip W Connelly
- Division of Endocrinology, University of Toronto, Toronto, ON, Canada
- Keenan Research Centre for Biomedical Science of St Michael's Hospital, Toronto, ON, Canada
- Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada
| | - Mathew Sermer
- Department of Obstetrics and Gynecology, Mount Sinai Hospital, Toronto, ON, Canada
| | - Bernard Zinman
- Leadership Sinai Centre for Diabetes, Mount Sinai Hospital, Toronto, ON, Canada
- Division of Endocrinology, University of Toronto, Toronto, ON, Canada
- Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada
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Abstract
OBJECTIVE In this commentary I will evaluate whether prediabetes should be treated pharmacologically. To consider this question, certain information concerning prediabetes is relevant. BACKGROUND INFORMATION (1) Prediabetes is not independently associated with cardiovascular disease; the other factors in the metabolic syndrome increase that risk; (2) various tests and criteria for diagnosing prediabetes are recommended, yielding prevalences varying from 6% to 38% depending on which are used; (3) one-third of patients with prediabetes revert to normal over time; (4) up to two-thirds of patients with prediabetes do not develop diabetes; (5) people with prediabetes have insulin resistance and impaired insulin secretion; (6) although pharmacological treatment of the dysglycemia temporarily lowers it, when the drugs are discontinued, incident diabetes develops similarly as that in those who received placebos; (7) when the drugs are discontinued, there are no changes in insulin resistance or impaired insulin secretion; (8) incident diabetes was similar at 10 years in people remaining on metformin in the Diabetes Prevention Program Outcome Study compared with those who did not receive the drug; (9) no current drugs will directly increase insulin secretion (except sulfonylureas and glinides which have not been used to treat prediabetes because of hypoglycemia concerns); (10) sufficient weight loss to lower insulin resistance by nutritional means is challenging and especially difficult to maintain. CONCLUSIONS Pharmacological treatment of the dysglycemia of prediabetes is not warranted. On the other hand, the ability of high doses of glucagon-like peptide (GLP)-1 receptor agonists and the combination of a GLP-1 receptor agonist and the glucose-dependent insulinotropic polypeptide (GIP) to lower weight by 15% and 20%, respectively, deserves consideration for the treatment of prediabetes. This amount of weight loss should decrease insulin resistance, allowing endogenous insulin secretion to be more effective and lower the risk for developing diabetes.
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Affiliation(s)
- Mayer B Davidson
- Charles R. Drew University, 1731 East 120th Street, Los Angeles, CA, 90059, USA.
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11
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Panigrahi A, Mohanty S. Efficacy and safety of HIMABERB® Berberine on glycemic control in patients with prediabetes: double-blind, placebo-controlled, and randomized pilot trial. BMC Endocr Disord 2023; 23:190. [PMID: 37679692 PMCID: PMC10483788 DOI: 10.1186/s12902-023-01442-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/22/2022] [Accepted: 08/24/2023] [Indexed: 09/09/2023] Open
Abstract
BACKGROUND Prediabetes and diabetes involve alterations in glucose homeostasis, including increased fasting blood glucose and impaired glucose tolerance. Berberine has been identified as a potential regulator of glucose homeostasis with implications on the management of type 2 diabetes mellitus (DM). Given a paucity of data on berberine in prediabetes, evaluation of its effect in individuals with prediabetes may prove clinically valuable. OBJECTIVE The present pilot study aimed to investigate the effect of daily oral berberine on markers of glycemic control and insulin resistance among individuals with prediabetes. METHODS A randomized, double-blinded, placebo-controlled trial was conducted for 12 weeks among 34 individuals with prediabetes as defined by the American Diabetes Association (fasting plasma glucose (FPG) between 5.6 and 6.9 mmol/L, glycosylated hemoglobin (HbA1c) between 5.7% and 6.4%, or 2-hour 75-gram oral glucose tolerance test (2 h-OGTT) between 7.8 and 11.1 mmol/L). HIMABERB® 500 mg was given three times daily to the treatment group, and placebo was administered three times daily to the control group. Glycemic control markers and physical parameters were evaluated for both groups on days 0, 28, 56, and 84. The glycemic control markers assessed included FPG, fasting insulin (FI), 2 h-OGTT, HbA1c, and homeostatic model assessment-insulin resistance (HOMA-IR). The observed outcomes were analyzed using independent t-test statistics to determine the significance of differences over time after treatment initiation and between treatment and control groups. RESULTS Significant decreases in all markers of glycemic control were observed in the treatment group at intermediate time points and the endpoint of the study compared to baseline levels and to the control group. For the treatment group, FPG decreased from 6.75 ± 0.23 mmol/L to 5.33 ± 0.28 mmol/L, FI from 9.81 ± 0.36 to 7.88 ± 0.52 mmol/L, 2 h-OGTT from 10.44 ± 0.52 to 8.12 ± 0.40 mmol/L, HbA1c from 6.40% ± 0.20-5.43% ± 0.21%, and HOMA-IR from 3.61 ± 0.31 to 2.41 ± 0.14. The decreases in glycemic control markers compared to the control group were clinically and statistically significant (p<10- 5). No severe adverse effects, kidney or liver toxicity were detected. CONCLUSION After 12 weeks, berberine (HIMABERB®) intervention in individuals with prediabetes significantly reduced glycemic control markers, with mean FPG and 2 h-OTGG being reduced to below prediabetic thresholds, supporting the investigation of the use of HIMABERB® for delaying progression to diabetes mellitus. TRIAL REGISTRATION http://ctri.nic.in (CTRI/2021/12/038751) (20/12/2021).
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Affiliation(s)
- Antarmayee Panigrahi
- Department of Pedodontics and Preventive Dentistry, Institute of Dental Sciences, Siksha O Anusandhan (Deemed to be University), Bhubaneshwar, 751030, Odisha, India.
| | - Susant Mohanty
- Department of Pedodontics and Preventive Dentistry, Institute of Dental Sciences, Siksha O Anusandhan (Deemed to be University), Bhubaneshwar, 751030, Odisha, India
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12
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Lv K, Cui C, Fan R, Zha X, Wang P, Zhang J, Zhang L, Ke J, Zhao D, Cui Q, Yang L. Detection of diabetic patients in people with normal fasting glucose using machine learning. BMC Med 2023; 21:342. [PMID: 37674168 PMCID: PMC10483877 DOI: 10.1186/s12916-023-03045-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/20/2023] [Accepted: 08/23/2023] [Indexed: 09/08/2023] Open
Abstract
BACKGROUND Diabetes mellitus (DM) is a chronic metabolic disease that could produce severe complications threatening life. Its early detection is thus quite important for the timely prevention and treatment. Normally, fasting blood glucose (FBG) by physical examination is used for large-scale screening of DM; however, some people with normal fasting glucose (NFG) actually have suffered from diabetes but are missed by the examination. This study aimed to investigate whether common physical examination indexes for diabetes can be used to identify the diabetes individuals from the populations with NFG. METHODS The physical examination data from over 60,000 individuals with NFG in three Chinese cohorts were used. The diabetes patients were defined by HbA1c ≥ 48 mmol/mol (6.5%). We constructed the models using multiple machine learning methods, including logistic regression, random forest, deep neural network, and support vector machine, and selected the optimal one on the validation set. A framework using permutation feature importance algorithm was devised to discover the personalized risk factors. RESULTS The prediction model constructed by logistic regression achieved the best performance with an AUC, sensitivity, and specificity of 0.899, 85.0%, and 81.1% on the validation set and 0.872, 77.9%, and 81.0% on the test set, respectively. Following feature selection, the final classifier only requiring 13 features, named as DRING (diabetes risk of individuals with normal fasting glucose), exhibited reliable performance on two newly recruited independent datasets, with the AUC of 0.964 and 0.899, the balanced accuracy of 84.2% and 81.1%, the sensitivity of 100% and 76.2%, and the specificity of 68.3% and 86.0%, respectively. The feature importance ranking analysis revealed that BMI, age, sex, absolute lymphocyte count, and mean corpuscular volume are important factors for the risk stratification of diabetes. With a case, the framework for identifying personalized risk factors revealed FBG, age, and BMI as significant hazard factors that contribute to an increased incidence of diabetes. DRING webserver is available for ease of application ( http://www.cuilab.cn/dring ). CONCLUSIONS DRING was demonstrated to perform well on identifying the diabetes individuals among populations with NFG, which could aid in early diagnosis and interventions for those individuals who are most likely missed.
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Affiliation(s)
- Kun Lv
- Key Laboratory of Non-Coding RNA Transformation Research of Anhui Higher Education Institutes, Wuhu, China.
- Central Laboratory, First Affiliated Hospital of Wannan Medical College, Wuhu, People's Republic of China.
| | - Chunmei Cui
- Department of Biomedical Informatics, State Key Laboratory of Vascular Homeostasis and Remodeling, School of Basic Medical Sciences, Peking University, Beijing, People's Republic of China.
| | - Rui Fan
- Department of Biomedical Informatics, State Key Laboratory of Vascular Homeostasis and Remodeling, School of Basic Medical Sciences, Peking University, Beijing, People's Republic of China
| | - Xiaojuan Zha
- Laboratory Medicine, First Affiliated Hospital of Wannan Medical College, Wuhu, People's Republic of China
| | - Pengyu Wang
- Department of Pathophysiology, Harbin Medical University, Harbin, People's Republic of China
| | - Jun Zhang
- Medical College of Shihezi University, Shihezi, People's Republic of China
| | - Lina Zhang
- Department of Laboratory Diagnosis, Daqing Oil Field General Hospital, Daqing, People's Republic of China
| | - Jing Ke
- Beijing Key Laboratory of Diabetes Research and Care, Center for Endocrine Metabolism and Immune Diseases, Beijing Luhe Hospital, Capital Medical University, Beijing, People's Republic of China
| | - Dong Zhao
- Beijing Key Laboratory of Diabetes Research and Care, Center for Endocrine Metabolism and Immune Diseases, Beijing Luhe Hospital, Capital Medical University, Beijing, People's Republic of China.
| | - Qinghua Cui
- Department of Biomedical Informatics, State Key Laboratory of Vascular Homeostasis and Remodeling, School of Basic Medical Sciences, Peking University, Beijing, People's Republic of China.
| | - Liming Yang
- Department of Pathophysiology, Harbin Medical University, Harbin, People's Republic of China.
- National Key Laboratory of Frigid Zone Cardiovascular Diseases (NKLFZCD), Harbin Medical University, Harbin, People's Republic of China.
- NHC Key Laboratory of Cell Transplantation, The First Affiliated Hospital of Harbin Medical University, Harbin, People's Republic of China.
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13
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Mittendorfer B, Patterson BW, Magkos F, Yoshino M, Bradley DP, Eagon JC, Klein S. β Cell function after Roux-en-Y gastric bypass surgery or reduced energy intake alone in people with obesity. JCI Insight 2023; 8:e170307. [PMID: 37166995 PMCID: PMC10371232 DOI: 10.1172/jci.insight.170307] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2023] [Accepted: 05/08/2023] [Indexed: 05/12/2023] Open
Abstract
BackgroundThe effects of diet-induced weight loss (WL) and WL after Roux-en-Y gastric bypass (RYGB) surgery on β cell function (BCF) are unclear because of conflicting results from different studies, presumably because of differences in the methods used to measure BCF, the amount of WL between treatment groups, and baseline BCF. We evaluated the effect of WL after RYGB surgery or reduced energy intake alone on BCF in people with obesity with and without type 2 diabetes.MethodsBCF (insulin secretion in relationship to plasma glucose) was assessed before and after glucose or mixed-meal ingestion before and after (a) progressive amounts (6%, 11%, 16%) of WL induced by a low-calorie diet (LCD) in people with obesity without diabetes, (b) ~20% WL after RYGB surgery or laparoscopic adjustable gastric banding (LAGB) in people with obesity without diabetes, and (c) ~20% WL after RYGB surgery or LCD alone in people with obesity and diabetes.ResultsDiet-induced progressive WL in people without diabetes progressively decreased BCF. Marked WL after LAGB or RYGB in people without diabetes did not alter BCF. Marked WL after LCD or RYGB in people with diabetes markedly increased BCF, without a difference between groups.ConclusionMarked WL increases BCF in people with obesity and diabetes but not in people with obesity without diabetes. The effect of RYGB-induced WL on BCF is not different from the effect of matched WL after LAGB or LCD alone.trial registrationNCT00981500, NCT02207777, NCT01299519.FundingNIH grants R01 DK037948, P30 DK056341, P30 DK020579, UL1 TR002345.
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14
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Herrmann A, Gonnet A, Millogo RM, d'Arc Kabré WJ, Beremwidougou TR, Coulibaly I, Ouili I, Zoromé S, Weil K, Fuelbert H, Soura A, Danquah I. Sustainable dietary weight loss intervention and its effects on cardiometabolic parameters and greenhouse gas emissions: study protocol of a randomised controlled trial with overweight and obese adults in Ouagadougou, Burkina Faso. BMJ Open 2023; 13:e070524. [PMID: 37015795 PMCID: PMC10083789 DOI: 10.1136/bmjopen-2022-070524] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/25/2022] [Accepted: 03/02/2023] [Indexed: 04/06/2023] Open
Abstract
INTRODUCTION The global obesity epidemic and its adverse health effects have reached sub-Saharan Africa. In some urban settings, like Burkina Faso's capital Ouagadougou, up to 43% of the adult population are overweight or obese. At the same time, modernised food systems are responsible for 26% of global greenhouse gas emissions, 50% of land use and 70% of freshwater use. International guidelines on the treatment of overweight and obesity recommend dietary intervention programmes that promote reduced calorie intake and increased physical activity. So far, weight loss interventions rarely consider sustainable dietary concepts, including healthfulness, affordability, cultural appropriateness and environmental friendliness. Therefore, we present a study protocol of a novel randomised controlled trial that aims to establish the effects of a sustainable weight loss intervention on cardiometabolic and environmental outcomes in urban Burkina Faso. METHODS AND ANALYSIS We conduct a non-blinded randomised controlled trial, comparing a 6-month sustainable diet weight loss intervention programme (n=125) with a standard weight loss information material and 5 min oral counselling at baseline (n=125). Primary outcome is a reduction in fasting plasma glucose of ≥0.1 mmol/L. Outcome measures are assessed at baseline, after 6 months and after 12 months. ETHICS AND DISSEMINATION Ethical approval for the study has been obtained from the Medical Faculty of Heidelberg University (S-376/2019) and from the Ministry of Health and the Ministry of Higher Education, Scientific Research and Innovation in Ouagadougou, Burkina Faso (No 2021-01-001). The results of the study will be disseminated to local stakeholders at a final project meeting and to the wider research community through peer-reviewed publications and conferences. TRIAL REGISTRATION NUMBER DRKS00025991.
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Affiliation(s)
- Alina Herrmann
- Heidelberg Institute of Global Health (HIGH), Heidelberg University Hospital and Medical Faculty, Heidelberg University, Heidelberg, Germany
| | - Anais Gonnet
- Heidelberg Institute of Global Health (HIGH), Heidelberg University Hospital and Medical Faculty, Heidelberg University, Heidelberg, Germany
| | - Roche Modeste Millogo
- Institut Supérieur des Sciences de la Population (ISSP), University of Ouagadougou, Ouagadougou, Burkina Faso
| | | | - Tenin Rosine Beremwidougou
- Institut Supérieur des Sciences de la Population (ISSP), University of Ouagadougou, Ouagadougou, Burkina Faso
| | - Issa Coulibaly
- Institut Supérieur des Sciences de la Population (ISSP), University of Ouagadougou, Ouagadougou, Burkina Faso
| | - Idrissa Ouili
- Institut Supérieur des Sciences de la Population (ISSP), University of Ouagadougou, Ouagadougou, Burkina Faso
| | - Souleymane Zoromé
- Institut Supérieur des Sciences de la Population (ISSP), University of Ouagadougou, Ouagadougou, Burkina Faso
| | - Konstantin Weil
- Heidelberg Institute of Global Health (HIGH), Heidelberg University Hospital and Medical Faculty, Heidelberg University, Heidelberg, Germany
| | - Hannah Fuelbert
- Heidelberg Institute of Global Health (HIGH), Heidelberg University Hospital and Medical Faculty, Heidelberg University, Heidelberg, Germany
| | - Abdramane Soura
- Institut Supérieur des Sciences de la Population (ISSP), University of Ouagadougou, Ouagadougou, Burkina Faso
| | - Ina Danquah
- Heidelberg Institute of Global Health (HIGH), Heidelberg University Hospital and Medical Faculty, Heidelberg University, Heidelberg, Germany
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15
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He L, Zheng W, Li Z, Chen L, Kong W, Zeng T. J-shape relationship between normal fasting plasma glucose and risk of type 2 diabetes in the general population: results from two cohort studies. J Transl Med 2023; 21:175. [PMID: 36872318 PMCID: PMC9985867 DOI: 10.1186/s12967-023-04006-9] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2022] [Accepted: 02/16/2023] [Indexed: 03/07/2023] Open
Abstract
BACKGROUND Previous studies have reported that high fasting plasma glucose (FPG), even that within the normal range, is associated with the risk of type 2 diabetes (T2D). Nevertheless, these findings are limited to specific populations. Thus, studies in the general population are imperative. METHODS This study included two cohorts comprising 204 640 individuals who underwent physical examinations at the Rich Healthcare Group present at 32 locations in 11 cities of China from 2010 to 2016 and 15 464 individuals who underwent physical tests at the Murakami Memorial Hospital in Japan. Cox regression, restricted cubic spline (RCS), Kaplan-Meier (KM) curves, and subgroup analysis were used to determine the relationship between FPG and T2D. Receiver operating characteristic (ROC) curves were used to evaluate the predictive power of FPG for T2D. RESULTS The mean age of the 220 104 participants (204 640 Chinese and 15 464 Japanese participants) was 41.8 years (41.7 years for the Chinese and 43.7 years for the Japanese participants). During follow-up, 2611 individuals developed T2D (2238 Chinese and 373 Japanese participants). The RCS demonstrated a J-shaped relationship between FPG and T2D risk, with inflexion points of 4.5 and 5.2 for the Chinese and Japanese populations, respectively. Multivariate-adjusted hazard ratio (HR) was 7.75 for FPG and T2D risk after the inflexion point (7.3 for Chinese and 21.13 for Japanese participants). CONCLUSIONS In general Chinese and Japanese populations, the normal baseline FPG range showed a J-shaped relationship with the risk of T2D. Baseline FPG levels help identify individuals at high risk of T2D and may enable early primary prevention to improve their outcomes.
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Affiliation(s)
- Linfeng He
- Department of Endocrinology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.,Hubei Provincial Clinical Research Center for Diabetes and Metabolic Disorders, Huazhong University of Science and Technology, Wuhan, Hubei, China.,Hubei Key Laboratory of Metabolic Abnormalities and Vascular Aging, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Wenbin Zheng
- Department of Endocrinology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.,Hubei Provincial Clinical Research Center for Diabetes and Metabolic Disorders, Huazhong University of Science and Technology, Wuhan, Hubei, China.,Hubei Key Laboratory of Metabolic Abnormalities and Vascular Aging, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Zeyu Li
- Department of Endocrinology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.,Hubei Provincial Clinical Research Center for Diabetes and Metabolic Disorders, Huazhong University of Science and Technology, Wuhan, Hubei, China.,Hubei Key Laboratory of Metabolic Abnormalities and Vascular Aging, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Lu Chen
- Department of Endocrinology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.,Hubei Provincial Clinical Research Center for Diabetes and Metabolic Disorders, Huazhong University of Science and Technology, Wuhan, Hubei, China.,Hubei Key Laboratory of Metabolic Abnormalities and Vascular Aging, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Wen Kong
- Department of Endocrinology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.,Hubei Provincial Clinical Research Center for Diabetes and Metabolic Disorders, Huazhong University of Science and Technology, Wuhan, Hubei, China.,Hubei Key Laboratory of Metabolic Abnormalities and Vascular Aging, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Tianshu Zeng
- Department of Endocrinology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China. .,Hubei Provincial Clinical Research Center for Diabetes and Metabolic Disorders, Huazhong University of Science and Technology, Wuhan, Hubei, China. .,Hubei Key Laboratory of Metabolic Abnormalities and Vascular Aging, Huazhong University of Science and Technology, Wuhan, Hubei, China.
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16
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Lin HJ, Wang J, Tseng PY, Fu LC, Lee YC, Wu MS, Yang WS, Chiu HM. Lower-than-normal glycemic levels to achieve optimal reduction of diabetes risk among individuals with prediabetes: A prospective cohort study. Diabetes Res Clin Pract 2023; 197:110567. [PMID: 36740021 DOI: 10.1016/j.diabres.2023.110567] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/29/2022] [Revised: 01/16/2023] [Accepted: 01/30/2023] [Indexed: 02/05/2023]
Abstract
AIMS/HYPOTHESIS To determine whether lower than currently accepted glycemic levels could lead to optimal risk reduction of incident diabetes among individuals with prediabetes. METHODS We enrolled 9903 individuals with prediabetes and 16,902 individuals with normoglycemia from a prospective cohort participating health check-ups between 2006 and 2017. While classifying fasting glucose into <5.0, 5.0-5.5, and 5.6-6.9 mmol/L and postprandial glucose into <6.7, 6.7-7.7, and 7.8-11.0 mmol/L, we grouped fasting/postprandial glucose into five categories (<5.0/<6.7, <5.0/6.7-7.7, 5.0-5.5/<6.7, 5.0-5.5/6.7-7.7 mmol/L, 5.6-6.9/7.8-11.0 mmol/L). The primary outcome was incident diabetes. RESULTS In individuals with prediabetes, the presence of a baseline fasting glucose <5.0 mmol/L or a postprandial glucose <6.7 mmol/L led to a greater risk reduction of incident diabetes with hazard ratios of 0.34 (95% confidence interval, 0.27-0.42) and 0.47 (0.41-0.54), respectively, relative to a fasting glucose 5.6-6.9 mmol/L and a postprandial glucose 7.8-11.0 mmol/L. For individuals with prediabetes having fasting/postprandial glucose <5.0/<6.7 mmol/L, the incidence of 6.4 (4.7-8.8) per 1000 person-years corresponded to that of 5.8 (4.2-8.0) per 1000 person-years for individuals with normoglycemia having 5.0-5.5/6.7-7.7 mmol/L. CONCLUSIONS/INTERPRETATION Given that lower-than-normal glycemic levels were plausible for optimal risk reduction of diabetes, stringent glycemic management could be beneficial for diabetes prevention among individuals with prediabetes.
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Affiliation(s)
- Hung-Ju Lin
- Health Management Center, National Taiwan University Hospital, Taipei, Taiwan; Department of Internal Medicine, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan.
| | - Jui Wang
- Health Management Center, National Taiwan University Hospital, Taipei, Taiwan.
| | - Po-Yuan Tseng
- All Vista Healthcare Center, Center for Artificial Intelligence and Advanced Robotics, National Taiwan University, Taiwan.
| | - Li-Chen Fu
- Department of Electrical Engineering, Department of Computer Science and Information Engineering, and Center for Artificial Intelligence & Advanced Robotics, National Taiwan University, Taipei, Taiwan.
| | - Yi-Chia Lee
- Health Management Center, National Taiwan University Hospital, Taipei, Taiwan; Department of Internal Medicine, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan; Integrative Medical Database Center, Department of Medical Research, National Taiwan University Hospital, Taipei, Taiwan; Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan..
| | - Ming-Shiang Wu
- Department of Internal Medicine, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan.
| | - Wei-Shiung Yang
- Department of Internal Medicine, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan; Integrative Medical Database Center, Department of Medical Research, National Taiwan University Hospital, Taipei, Taiwan; Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan.
| | - Han-Mo Chiu
- Health Management Center, National Taiwan University Hospital, Taipei, Taiwan; Department of Internal Medicine, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan.
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17
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Choi Y, Jacobs DR, Bancks MP, Lewis CE, Cha E, Yan F, Carnethon MR, Schreiner PJ, Duprez DA. Association of Cardiovascular Health Score With Early- and Later-Onset Diabetes and With Subsequent Vascular Complications of Diabetes. J Am Heart Assoc 2023; 12:e027558. [PMID: 36565184 PMCID: PMC9973601 DOI: 10.1161/jaha.122.027558] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Abstract
BACKGROUND Little attention has been paid to how well the American Heart Association's cardiovascular health (CVH) score predicts early-onset diabetes in young adults. We investigated the association of CVH score with early- and later-onset diabetes and with subsequent complications of diabetes. METHODS AND RESULTS Our sample included 4547 Black and White adults in the CARDIA (Coronary Artery Risk Development in Young Adults) study without diabetes at baseline (1985-1986; aged 18-30 years) with complete data on the CVH score at baseline, including smoking, body mass index, physical activity, diet quality, total cholesterol, blood pressure, and fasting blood glucose. Incident diabetes was determined based on fasting glucose, 2-hour postload glucose, hemoglobin A1c, or self-reported medication use throughout 8 visits for 30 years. Multinomial logistic regression was used to assess the association between CVH score and diabetes onset at age <40 years (early onset) versus age ≥40 years (later onset). Secondary analyses assessed the association between CVH score and risk of complications (coronary artery calcium, clinical cardiovascular disease, kidney function markers, diabetic retinopathy, and diabetic neuropathy) among a subsample with diabetes. We identified 116 early- and 502 later-onset incident diabetes cases. Each 1-point higher CVH score was associated with lower odds of developing early-onset (odds ratio [OR], 0.64 [95% CI, 0.58-0.71]) and later-onset diabetes (OR, 0.78 [95% CI, 0.74-0.83]). Lower estimates of diabetic complications were observed per 1-point higher CVH score: 19% for coronary artery calcification≥100, 18% for cardiovascular disease, and 14% for diabetic neuropathy. CONCLUSIONS Higher CVH score in young adulthood was associated with lower early- and later-onset diabetes as well as diabetic complications.
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Affiliation(s)
- Yuni Choi
- Division of Epidemiology and Community Health, School of Public Health University of Minnesota Minneapolis MN
| | - David R Jacobs
- Division of Epidemiology and Community Health, School of Public Health University of Minnesota Minneapolis MN
| | - Michael Patrick Bancks
- Department of Epidemiology and Prevention Wake Forest School of Medicine Winston-Salem NC
| | - Cora E Lewis
- Department of Epidemiology University of Alabama at Birmingham Birmingham AL
| | - EunSeok Cha
- College of Nursing Chungnam National University Daejeon South Korea.,Nell Hodgson Woodruff School of Nursing Emory University Atlanta GA
| | - Fengxia Yan
- Department of Community Health and Preventive Medicine Morehouse School of Medicine Atlanta GA
| | - Mercedes R Carnethon
- Department of Preventive Medicine, Feinberg School of Medicine Northwestern University Chicago IL
| | - Pamela J Schreiner
- Division of Epidemiology and Community Health, School of Public Health University of Minnesota Minneapolis MN
| | - Daniel A Duprez
- Cardiovascular Division, Department of Medicine University of Minnesota-Twin Cities Minneapolis MN
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18
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Mattei J, Díaz-Alvarez CB, Alfonso C, O’Neill HJ, Ríos-Bedoya CF, Malik VS, Godoy-Vitorino F, Cheng C, Spiegelman D, Willett WC, Hu FB, Rodríguez-Orengo JF. Design and Implementation of a Culturally-Tailored Randomized Pilot Trial: Puerto Rican Optimized Mediterranean-Like Diet. Curr Dev Nutr 2023; 7:100022. [PMID: 37181130 PMCID: PMC10100940 DOI: 10.1016/j.cdnut.2022.100022] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2022] [Revised: 11/23/2022] [Accepted: 12/05/2022] [Indexed: 12/25/2022] Open
Abstract
Background Adhering to a Mediterranean Diet (MedDiet) is associated with a healthier cardiometabolic profile. However, there are limited studies on the MedDiet benefits for non-Mediterranean racial/ethnic minorities, for whom this diet may be unfamiliar and inaccessible and who have a high risk of chronic diseases. Objectives To describe the study design of a pilot trial testing the efficacy of a MedDiet-like tailored to adults in Puerto Rico (PR). Methods The Puerto Rican Optimized Mediterranean-like Diet (PROMED) was a single-site 4-mo parallel two-arm randomized pilot trial among a projected 50 free-living adults (25-65 y) living in PR with at least two cardiometabolic risk factors (clinicaltrials.gov registration #NCT03975556). The intervention group received 1 individual nutritional counseling session on a portion-control culturally-tailored MedDiet. Daily text messages reinforced the counseling content for 2 mo, and we supplied legumes and vegetable oils. Participants in the control group received cooking utensils and one standard portion-control nutritional counseling session that was reinforced with daily texts for 2 mo. Text messages for each group were repeated for two more months. Outcome measures were assessed at baseline, 2 and 4 m. The primary outcome was a composite cardiometabolic improvement score; secondary outcomes included individual cardiometabolic factors; dietary intake, behaviors, and satisfaction; psychosocial factors; and the gut microbiome. Results PROMED was designed to be culturally appropriate, acceptable, accessible, and feasible for adults in PR. Strengths of the study include applying deep-structure cultural components, easing structural barriers, and representing a real-life setting. Limitations include difficulty with blinding and with monitoring adherence, and reduced timing and sample size. The COVID-19 pandemic influenced implementation, warranting replication. Conclusions If PROMED is proven efficacious in improving cardiometabolic health and diet quality, the findings would strengthen the evidence on the healthfulness of a culturally-appropriate MedDiet and support its wider implementation in clinical and population-wide disease-prevention programs.
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Affiliation(s)
- Josiemer Mattei
- Department of Nutrition, Harvard TH Chan School of Public Health, Boston, MA, USA
- FDI Clinical Research, San Juan, PR, USA
| | | | - Charmaine Alfonso
- College of Nutritionists and Dietitians of Puerto Rico, San Juan, PR, USA
- School of Health Sciences, Ana G. Méndez University, Gurabo Campus, Gurabo, PR, USA
| | - H June O’Neill
- Department of Nutrition, Harvard TH Chan School of Public Health, Boston, MA, USA
| | - Carlos F. Ríos-Bedoya
- FDI Clinical Research, San Juan, PR, USA
- McLaren Health Care, Graduate Medical Education, Grand Blanc, MI, USA
| | - Vasanti S. Malik
- Department of Nutrition, Harvard TH Chan School of Public Health, Boston, MA, USA
- Department of Nutritional Sciences, University of Toronto, Ontario, Canada
| | - Filipa Godoy-Vitorino
- Department of Microbiology, School of Medicine, University of Puerto Rico Medical Sciences Campus, San Juan, PR, USA
| | - Chao Cheng
- Department of Biostatistics and Center for Methods in Implementation and Prevention Science, Yale School of Public Health, New Haven, CT, USA
| | - Donna Spiegelman
- Department of Biostatistics and Center for Methods in Implementation and Prevention Science, Yale School of Public Health, New Haven, CT, USA
| | - Walter C. Willett
- Department of Nutrition, Harvard TH Chan School of Public Health, Boston, MA, USA
| | - Frank B. Hu
- Department of Nutrition, Harvard TH Chan School of Public Health, Boston, MA, USA
| | - José F. Rodríguez-Orengo
- FDI Clinical Research, San Juan, PR, USA
- Department of Biochemistry, School of Medicine, University of Puerto Rico Medical Sciences Campus, San Juan, PR, USA
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19
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Magkos F, Reeds DN, Mittendorfer B. Evolution of the diagnostic value of "the sugar of the blood": hitting the sweet spot to identify alterations in glucose dynamics. Physiol Rev 2023; 103:7-30. [PMID: 35635320 PMCID: PMC9576168 DOI: 10.1152/physrev.00015.2022] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2022] [Revised: 05/23/2022] [Accepted: 05/24/2022] [Indexed: 11/22/2022] Open
Abstract
In this paper, we provide an overview of the evolution of the definition of hyperglycemia during the past century and the alterations in glucose dynamics that cause fasting and postprandial hyperglycemia. We discuss how extensive mechanistic, physiological research into the factors and pathways that regulate the appearance of glucose in the circulation and its uptake and metabolism by tissues and organs has contributed knowledge that has advanced our understanding of different types of hyperglycemia, namely prediabetes and diabetes and their subtypes (impaired fasting plasma glucose, impaired glucose tolerance, combined impaired fasting plasma glucose, impaired glucose tolerance, type 1 diabetes, type 2 diabetes, gestational diabetes mellitus), their relationships with medical complications, and how to prevent and treat hyperglycemia.
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Affiliation(s)
- Faidon Magkos
- Department of Nutrition, Exercise and Sports, University of Copenhagen, Frederiksberg, Denmark
| | - Dominic N Reeds
- Center for Human Nutrition, Washington University School of Medicine, St. Louis, Missouri
| | - Bettina Mittendorfer
- Center for Human Nutrition, Washington University School of Medicine, St. Louis, Missouri
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20
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Harada KH, Harada Sassa M. Potential confounders in the association between per- and polyfluoroalkyl substance exposure and diabetes. Diabetologia 2022; 65:1745-1746. [PMID: 35840662 DOI: 10.1007/s00125-022-05758-7] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/02/2022] [Accepted: 05/24/2022] [Indexed: 11/30/2022]
Affiliation(s)
- Kouji H Harada
- Department of Health and Environmental Sciences, Kyoto University Graduate School of Medicine, Kyoto, Japan.
| | - Mariko Harada Sassa
- Department of Health and Environmental Sciences, Kyoto University Graduate School of Medicine, Kyoto, Japan
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21
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Aizawa T, Nakasone Y, Murai N, Oka R, Nagasaka S, Yamashita K, Sakuma T, Kiyosawa K. Hepatic Steatosis and High-normal Fasting Glucose as Risk Factors for Incident Prediabetes. J Endocr Soc 2022; 6:bvac110. [PMID: 35958436 PMCID: PMC9359444 DOI: 10.1210/jendso/bvac110] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/07/2022] [Indexed: 11/26/2022] Open
Abstract
Context The role of hepatic steatosis (HS) in the initial stages of developing type 2 diabetes remains unclear. Objective We aimed to clarify the impact of HS indexed by Fatty Liver Index (FLI) and high-normal fasting plasma glucose (FPG) as risk factors for incident prediabetes in a nonobese cohort. Methods Data from 1125 participants with ADA-defined normal glucose metabolism (median age 52 years; BMI 23.1 kg/m2) were used for retrospective analysis. In the entire population, correlation between normal FPG and FLI was evaluated by multiple regression adjusted for age and sex. Follow-up data from 599 participants in whom 75-g OGTT was repeated 3.7 years later showed that 169 developed prediabetes. This was analyzed by the multivariate Cox proportional hazards model. Results In the entire population, FLI was positively correlated with FPG (P < 0.01): mean FLI increased from 15.8 at FPG 4.2 mmol/L to 31.6 at FPG 5.5 mmol/L. Analysis of the 599 participants (2061 person-years) by Cox model, adjusted for sex, age, family history of diabetes, ISIMATSUDA, and Stumvoll-1, clarified an increased risk of prediabetes with high-normal FPG and FLI. Risk was increased 2.2 times with FLI ≥ 16.5 vs FLI < 16.5, P < 0.001, and increased 2.1 times in participants with FPG ≥ 5.3 mmol/L, P < 0.001. Cutoff values (unadjusted) were obtained by ROC at the point of the largest Youden’s index using the entire range of the variables. Conclusion Even among nonobese individuals, HS indexed by FLI and a high-normal FPG (≥ 5.3 mmol/L) are risk factors for prediabetes, independently from insulin.
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Affiliation(s)
- Toru Aizawa
- Diabetes Center, Aizawa Hospital , Matsumoto, Japan
| | | | - Norimitsu Murai
- Division of Diabetes, Metabolism and Endocrinology, Showa University Fujigaoka Hospital , Yokohama, Japan
| | - Rie Oka
- Department of Internal Medicine, Hokuriku Central Hospital , Toyama, Japan
| | - Shoichiro Nagasaka
- Division of Diabetes, Metabolism and Endocrinology, Showa University Fujigaoka Hospital , Yokohama, Japan
| | | | - Takahiro Sakuma
- Department of Internal Medicine, Ina Central Hospital , Ina, Japan
| | - Kendo Kiyosawa
- Department of Gastroenterology, Aizawa Hospital , Matsumoto, Japan
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22
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Reutrakul S, Martyn-Nemeth P, Quinn L, Rydzon B, Priyadarshini M, Danielson KK, Baron KG, Duffecy J. Effects of Sleep-Extend on glucose metabolism in women with a history of gestational diabetes: a pilot randomized trial. Pilot Feasibility Stud 2022; 8:119. [PMID: 35659776 PMCID: PMC9166192 DOI: 10.1186/s40814-022-01076-2] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2021] [Accepted: 05/24/2022] [Indexed: 11/25/2022] Open
Abstract
Objectives Women with a history of gestational diabetes (GDM) are at 7-fold increase in the risk of developing diabetes. Insufficient sleep has also been shown to increase diabetes risk. This study aimed to explore the feasibility of a sleep extension in women with a history of GDM and short sleep, and effects on glucose metabolism. Methods Women age 18–45 years with a history of GDM and actigraphy confirmed short sleep duration (<7 h/night) on weekdays were randomized at a ratio of 1 control (heathy living information) to 2 cases (6 weeks of “Sleep-Extend” intervention: use of a Fitbit, weekly digital content, and weekly coaching to increase sleep duration). An oral glucose tolerance test (OGTT), 7-day actigraphy recording, and questionnaires were obtained at baseline and 6 weeks. Mean differences between baseline and end-of-intervention parameters were compared using independent samples t-tests. Results Mean (SD) sleep duration increased within the Sleep-Extend group (n=9, +26.9 (42.5) min) but decreased within the controls (n=5, − 9.1 (20.4) min), a mean difference (MD) of 35.9 min (95% confidence interval (CI) − 8.6, 80.5). Fasting glucose increased, but less in Sleep-Extend vs. control groups (1.6 (9.4) vs 10.4 (8.2) mg/dL, MD − 8.8 mg/dL (95% CI − 19.8, 2.1), while 2-h glucose levels after an OGTT did not differ. Compared to controls, Sleep-Extend had decreased fatigue score (MD − 10.6, 95%CI − 20.7, − 0.6), and increased self-report physical activity (MD 5036 MET- minutes/week, 95%CI 343, 9729. Fitbit compliance and satisfaction in Sleep-Extend group was high. Conclusion Sleep extension is feasible in women with a history of GDM, with benefits in fatigue and physical activity, and possibly glucose metabolism. These data support a larger study exploring benefits of sleep extension on glucose metabolism in these high-risk women. Trial registration ClinicalTrials.gov, NCT03638102 (8/20/2018)
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Affiliation(s)
- Sirimon Reutrakul
- Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Illinois at Chicago, 835 S. Wolcott, Suite E625, Chicago, IL, 60612, USA.
| | - Pamela Martyn-Nemeth
- Department of Biobehavioral Nursing Science, College of Nursing, University of Illinois at Chicago, 845 S. Damen, Chicago, IL, 60612, USA
| | - Lauretta Quinn
- Department of Biobehavioral Nursing Science, College of Nursing, University of Illinois at Chicago, 845 S. Damen, Chicago, IL, 60612, USA
| | - Brett Rydzon
- Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Illinois at Chicago, 835 S. Wolcott, Suite E625, Chicago, IL, 60612, USA
| | - Medha Priyadarshini
- Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Illinois at Chicago, 835 S. Wolcott, Suite E625, Chicago, IL, 60612, USA
| | - Kirstie K Danielson
- Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Illinois at Chicago, 835 S. Wolcott, Suite E625, Chicago, IL, 60612, USA
| | - Kelly G Baron
- Division of Public Health, Department of Family and Preventive Medicine, The University of Utah, 375 Chipeta Way, Salt Lake City, USA.,Departments of Psychology and Psychiatry, The University of Utah, 501 Chipeta Way, Salt Lake City, UT, 84108, USA
| | - Jennifer Duffecy
- Department of Psychiatry, University of Illinois at Chicago, 912 S. Wood Street, Chicago, IL, 60612, USA
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23
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Climstein M, Walsh J, Adams K, Sevene T, Heazlewood T, DeBeliso M. Prevalence of hyperglycemia in masters athletes. PeerJ 2022; 10:e13389. [PMID: 35663526 PMCID: PMC9159136 DOI: 10.7717/peerj.13389] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2022] [Accepted: 04/15/2022] [Indexed: 01/14/2023] Open
Abstract
Background Ageing is associated with decreased physical activity, obesity and subsequently an increased risk of developing type 2 diabetes mellitus (T2dm). Master athletes (MA) have initiated exercise or sport later in life or pursued a physically active lifestyle for an extended period. Subsequently, MAs have been proposed as a model of successful ageing as this active lifestyle is associated with health benefits including decreased health risk of chronic diseases and a reduction in premature mortality. Given long-term physical activity/exercise has previously been shown to be protective against hyperglycemia, a risk factor for T2dm, it is plausible that MA may have protective benefit against developing hyperglycemia. Therefore, the aim of this study was to investigate the prevalence of hyperglycemia via fasting plasma glucose (FPG) in MAs competing at the World Masters Games (WMG). Methods This cross-sectional, observational survey utilized an online survey using open-source web-based software was used to investigate MAs physiological and medical-related parameters. Over 28,000 MAs competed in the WMG, of which 8,072 MAs completed the survey. Of these MAs, a total of 486 (males 277, females 209; range 27 to 91 years, mean age 55.1 ± 10.2 years) attained recent pathology results which included FPG which was subsequently analyzed for this study. FPG and other outcome variables were compared between genders and to the Australian and United States general population. Results Mean FPG for MAs was 5.03 mmol (±1.2, 95% CI [4.9-5.1] mmol) with majority (75.5%) of MAs reporting a normal (<5.5 mmol) FPG, followed by pre-diabetes (20.2%, >5.51 to <5.99 mmol) and abnormal (4.3%, >7.0 mmol). There was no significant difference (P = 0.333) in FPG between genders however, males had a slightly higher (+2.1%) FPG as compared to females (5.08 ± 1.2 mmol (95% CI [4.9-5.22] mmol) versus 4.98 ± 1.1 mmol (95% CI 4.8-5.1 mmol)). The majority of males (71.8%) and females (80.3%) were classified with a normal FPG. With regard to an abnormal FPG level, only 4.0% of males and 4.9% of females were classified abnormal which was suggestive of undiagnosed T2dm. With regard to age by decade, there was no significant difference (P = 0.06-1.00) between age groups and no relationship between the MAs' age and FPG (r = .054, P = 0.24). As a group, MAs had a significantly lower FPG as compared to the Australian (-3.2%, P = 0.005) and United States general populations (-13.9%, P < 0.001). Conclusions Most, however not all, MAs were found to have normal glycaemia, with only a small percentage indicating a risk of developing T2dm (i.e., impaired fasting glucose) and a smaller percentage identified with an abnormal FPG, suggestive of T2dm. These findings suggest MAs appear to be at low metabolic risk for developing T2dm based upon FPG and the physical activity/exercise they complete as MAs may indeed be protective against hyperglycemia whilst maintaining an active lifestyle.
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Affiliation(s)
- Mike Climstein
- Clinical Exercise Physiology, Faculty of Health, Southern Cross University, Bilinga, Queensland, Australia,Exercise and Sport Science Exercise, Health & Performance, Faculty Research Group, Faculty of Health Sciences, University of Sydney, Sydney, Australia
| | - Joe Walsh
- Sport Science Institute, Sydney, New South Wales, Australia
| | - Kent Adams
- Kinesiology Department, California State University Monterey Bay, Seaside, CA, United States of America
| | - Trish Sevene
- Kinesiology Department, California State University Monterey Bay, Seaside, CA, United States of America
| | - Tim Heazlewood
- Sport Science Institute, Sydney, New South Wales, Australia
| | - Mark DeBeliso
- Department of Kinesiology and Outdoor Recreation, Southern Utah University, Cedar City, CA, United States of America
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24
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Mittendorfer B, Patterson BW, Smith GI, Yoshino M, Klein S. Beta-cell function and plasma insulin clearance in people with obesity and different glycemic status. J Clin Invest 2021; 132:154068. [PMID: 34905513 PMCID: PMC8803344 DOI: 10.1172/jci154068] [Citation(s) in RCA: 38] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2021] [Accepted: 12/08/2021] [Indexed: 12/02/2022] Open
Abstract
Background It is unclear how excess adiposity and insulin resistance affect β cell function, insulin secretion, and insulin clearance in people with obesity. Methods We used a hyperinsulinemic-euglycemic clamp procedure and a modified oral glucose tolerance test to evaluate the interrelationships among obesity, insulin sensitivity, insulin kinetics, and glycemic status in 5 groups of individuals: normoglycemic lean and obese individuals with (a) normal fasting glucose and normal glucose tolerance (Ob-NFG-NGT), (b) NFG and impaired glucose tolerance (Ob-NFG-IGT), (c) impaired fasting glucose and IGT (Ob-IFG-IGT), or (d) type 2 diabetes (Ob-T2D). Results Glucose-stimulated insulin secretion (GSIS), an assessment of β cell function, was greater in the Ob-NFG-NGT and Ob-NFG-IGT groups than in the lean group, even when insulin sensitivity was matched in the obese and lean groups. Insulin sensitivity, not GSIS, was decreased in the Ob-NFG-IGT group compared with the Ob-NFG-NGT group, whereas GSIS, not insulin sensitivity, was decreased in the Ob-IFG-IGT and Ob-T2D groups compared with the Ob-NFG-NGT and Ob-NFG-IGT groups. Insulin clearance was directly related to insulin sensitivity and inversely related to the postprandial increase in insulin secretion and plasma insulin concentration. Conclusion Increased adiposity per se, not insulin resistance, enhanced insulin secretion in people with obesity. The obesity-induced increase in insulin secretion, in conjunction with a decrease in insulin clearance, sufficiently raised the plasma insulin concentrations needed to maintain normoglycemia in individuals with moderate, but not severe, insulin resistance. A deterioration in β cell function, not a decrease in insulin sensitivity, was a determinant of IFG and ultimately leads to T2D. CLINICAL TRIALS REGISTRATION ClinicalTrials.gov NCT02706262, NCT04131166, and NCT01977560. FUNDING NIH (P30 DK056341, P30 DK020579, and UL1 TR000448); American Diabetes Association (1-18-ICTS-119); Longer Life Foundation; Pershing Square Foundation; and Washington University-Centene ARCH Personalized Medicine Initiative (P19-00559).
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Affiliation(s)
- Bettina Mittendorfer
- Center for Human Nutrition, Washington University School of Medicine, St. Louis, United States of America
| | - Bruce W Patterson
- Center for Human Nutrition, Washington University School of Medicine, St. Louis, United States of America
| | - Gordon I Smith
- Center for Human Nutrition, Washington University School of Medicine, St. Louis, United States of America
| | - Mihoko Yoshino
- Center for Human Nutrition, Washington University School of Medicine, St. Louis, United States of America
| | - Samuel Klein
- Center for Human Nutrition, Washington University School of Medicine, St. Louis, United States of America
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25
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Khan S, Al Heraki S, Kupec JT. Noninvasive Models Screen New-Onset Diabetics at Low Risk of Early-Onset Pancreatic Cancer. Pancreas 2021; 50:1326-1330. [PMID: 34860819 DOI: 10.1097/mpa.0000000000001917] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/10/2022]
Abstract
OBJECTIVES Several noninvasive models have been developed to identify new-onset diabetics at higher risk of developing pancreatic ductal adenocarcinoma (PDAC). However, they need external validation before implementation. METHODS This study validated one such model (Boursi model) among a cohort of new-onset diabetics. A bivariate analysis of the model's components was done between patients who developed PDAC and type 2 diabetics. The model performance was assessed through receiver-operative characteristic curve analysis. RESULTS Patients with PDAC had significantly lower total cholesterol and alkaline phosphatase at diagnosis of diabetes (P < 0.01). They were observed losing body mass index (BMI) preceding diagnosis (ΔBMI = -0.42 kg/m2, P < 0.01). The model's area under the curve was 0.83 (95% confidence interval, 0.79-0.88). The cutoff that maximized the Youden index was at 0.8%. At this cutoff, the sensitivity was 75%, specificity was 80%, and the prevalence of pancreatic cancer increased from 0.19% at baseline to 0.69%. CONCLUSIONS Boursi model enriches the prevalence of PDAC among new-onset diabetics.
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Affiliation(s)
- Salman Khan
- From the Section of General Internal Medicine
| | | | - Justin T Kupec
- Section of Gastroenterology and Hepatology, Department of Medicine, West Virginia University School of Medicine, Morgantown, WV
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26
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Chung GE, Cho EJ, Yoon JW, Yoo JJ, Chang Y, Cho Y, Park SH, Han K, Shin DW, Yu SJ. Nonalcoholic fatty liver disease increases the risk of diabetes in young adults: A nationwide population-based study in Korea. Metabolism 2021; 123:154866. [PMID: 34411553 DOI: 10.1016/j.metabol.2021.154866] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/11/2021] [Revised: 08/08/2021] [Accepted: 08/10/2021] [Indexed: 12/18/2022]
Abstract
BACKGROUND Nonalcoholic fatty liver disease (NAFLD) is associated with an increased risk of diabetes but has been rarely investigated in young adults. In this study, we investigated the relationship between NAFLD and incident diabetes risk in young adults using nationwide Korean population data. METHODS This population-based cohort study from the Korean National Health Insurance Service included adults aged 20 through 39 years who underwent a health examination from 2009 to 2012. NAFLD was defined as a fatty liver index (FLI) ≥60 in the absence of alcohol consumption of ≥30 g/day. Newly diagnosed diabetes during follow-up was identified using claims data. Cox regression was used to calculate the hazard ratio for incident diabetes after adjusting for classical confounders. FINDINGS Among the 5,254,786 participants, 9.3% had an FLI ≥60. During the median follow-up of 8.6 years, 91,885 cases of incident diabetes occurred. In multivariable analysis, the risk of incident diabetes was significantly higher in the NAFLD group than the control group (adjusted hazard ratio = 4.97, 95% confidence interval, 4.90-5.05). Stratified analyses showed higher associations in those who were ≥30 years, male, obese, smokers, alcohol consumers, and did not regularly exercise (all P < 0.001). CONCLUSIONS NAFLD is associated with a five-fold increased risk of incident diabetes in young adults. These results suggest an independent high risk for incident diabetes in young adults and underscore the importance of paying early attention to patients who develop NAFLD before middle age.
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Affiliation(s)
- Goh Eun Chung
- Department of Internal Medicine and Healthcare Research Institute, Seoul National University Hospital Healthcare System Gangnam Center, Seoul, Republic of Korea
| | - Eun Ju Cho
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Ji Won Yoon
- Department of Internal Medicine and Healthcare Research Institute, Seoul National University Hospital Healthcare System Gangnam Center, Seoul, Republic of Korea
| | - Jeong-Ju Yoo
- Department of Gastroenterology and Hepatology, Soonchunhyang University Bucheon Hospital, Gyeonggi-do, Republic of Korea
| | - Young Chang
- Department of Gastroenterology and Hepatology, Soonchunhyang University Seoul Hospital, Seoul, Republic of Korea
| | - Yuri Cho
- Center for Liver and Pancreatobiliary Cancer, National Cancer Center, Goyang, Republic of Korea
| | - Sang-Hyun Park
- Department of Biostatistics, College of Medicine, Soongsil University, Seoul, Republic of Korea
| | - Kyungdo Han
- Department of Biostatistics, College of Medicine, Soongsil University, Seoul, Republic of Korea
| | - Dong Wook Shin
- Department of Family Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea; Department of Clinical Research Design and Evaluation, Samsung Advanced Institute for Health Science, Republic of Korea; Supportive Care Center, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea; Department of Digital Health, Samsung Advanced Institute for Health Science, Republic of Korea.
| | - Su Jong Yu
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.
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27
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Wang Z, Liu Z, He S. Fasting plasma glucose and risk of type 2 diabetes mellitus in a group of Chinese people with normoglycemia and without obesity. J Diabetes 2021; 13:601-602. [PMID: 33728817 DOI: 10.1111/1753-0407.13180] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/11/2021] [Accepted: 03/12/2021] [Indexed: 02/05/2023] Open
Affiliation(s)
- Ziqiong Wang
- Department of Cardiology, West China Hospital of Sichuan University, Chengdu, China
| | - Zheng Liu
- Nursing Department, West China School of Nursing, West China Hospital of Sichuan University, Chengdu, China
| | - Sen He
- Department of Cardiology, West China Hospital of Sichuan University, Chengdu, China
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28
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Practical use of electronic health records among patients with diabetes in scientific research. Chin Med J (Engl) 2021; 133:1224-1230. [PMID: 32433055 PMCID: PMC7249716 DOI: 10.1097/cm9.0000000000000784] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
Electronic health (medical) records, which are also considered as patients’ information that are routinely collected, provide a great chance for researchers to develop an epidemiological understanding of disease. Electronic health records systems cannot develop without the advance of computer industries. While conducting clinical trials that are always costly, feasible and reasonable analysis of routine patients’ information is more cost-effective and reflective of clinical practice, which is also called real world study. Real world studies can be well supported by big data in healthcare industry. Real world studies become more and more focused and important with the development of evidence-based medicine. These big data will definitely help in making decisions, making policies and guidelines, monitoring of effectiveness and safety on new drugs or technologies. Extracting, cleaning, and analyzing such big data will be a great challenge for clinical researchers. Successful applications and developments of electronic health record in western countries (eg, disease registries, health insurance claims, etc) have provided a clear direction for Chinese researchers. However, it is still at primary stages in China. This review tries to provide a full perspective on how to translate the electronic health records into scientific achievements, for example, among patients with diabetes. As a summary in the end, resource sharing and collaborations are highly recommended among hospitals and healthcare groups.
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29
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Khan S, Safarudin RF, Kupec JT. Validation of the ENDPAC model: Identifying new-onset diabetics at risk of pancreatic cancer. Pancreatology 2021; 21:550-555. [PMID: 33583686 PMCID: PMC8393564 DOI: 10.1016/j.pan.2021.02.001] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/25/2020] [Revised: 01/20/2021] [Accepted: 02/02/2021] [Indexed: 12/11/2022]
Abstract
BACKGROUND Patients with new-onset diabetes are known to be at a higher risk of developing pancreatic cancer. The Enriching New-Onset Diabetes for Pancreatic Cancer (ENDPAC) model was recently developed to identify new-onset diabetics with this higher risk. Further validation is needed before the ENDPAC model is implemented as part of a screening program to identify pancreatic cancer. METHODS A retrospective case-control study was performed; a cohort of patients with new-onset diabetes was identified using hemoglobin A1c. Patients were scored by the ENDPAC model and then divided based on whether pancreatic cancer was diagnosed after the diagnosis of diabetes. The performance of the model was assessed globally and at different cutoffs. RESULTS There were 6254 controls and 48 cases of pancreatic cancer. Bivariate analysis showed that patients with pancreatic cancer lost weight before diagnosis while controls gained weight (-0.93 kg/m2 vs. 0.45 kg/m2, p < 0.00∗). Cases had a more significant increase in their HbA1C from one year before (1.3% vs. 0.82%, p = 0.02). Smoking and pancreatitis rates were higher in cases compared to controls (p < 0.00∗). The area under the curve (AUC) of the ENDPAC model was 0.72. A score >1 was the optimal cutoff. At this cutoff, the sensitivity was 56%, specificity was 75%, and pancreatic cancer prevalence increased from 0.78% at baseline to 1.7%. CONCLUSION The ENDPAC model was validated in an independent cohort of patients with new-onset diabetes.
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Affiliation(s)
- Salman Khan
- Department of Medicine, School of Medicine, West Virginia University, USA,Corresponding author. (S. Khan)
| | - Rudi Fnu Safarudin
- Department of Pharmaceutical Systems and Policy, West Virginia University School of Pharmacy, USA,School of Mathematics and Natural Sciences, Tadulako University, Indonesia
| | - Justin T. Kupec
- Section of Gastroenterology & Hepatology, West Virginia University, Morgantown, West Virginia, USA
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30
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Wang Z, Zhao L, He S. Triglyceride-glucose index as predictor for future type 2 diabetes mellitus in a Chinese population in southwest China: a 15-year prospective study. Endocrine 2021; 72:124-131. [PMID: 33433893 DOI: 10.1007/s12020-020-02589-7] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/08/2020] [Accepted: 12/09/2020] [Indexed: 02/05/2023]
Abstract
PURPOSE Triglyceride-glucose (TyG) index is an emerging surrogate predictor of incident type 2 diabetes mellitus (T2DM). The study aimed to examine the association between TyG index and incident T2DM in a prospective Chinese cohort. METHODS The data were collected in 1992 and recollected in 2007 from the same group of 687 participants. The association between TyG index and T2DM was analysed. RESULTS During follow-up, 74 participants developed T2DM and the risk of T2DM increased with TyG index. The adjusted hazard ratio (HR) was 3.36 (95% CI: 1.52-7.39, P < 0.001) comparing the top TyG quartile to the bottom quartile. Smooth curve fitting revealed a nonlinear association and threshold effect between TyG index and incident T2DM with a nadir of risk when TyG index was around 8.51. For TyG ≤ 8.51, the risk of incident T2DM tended to decrease with per SD increase in TyG but no statistical significance was achieved (adjusted HR: 0.69, 95% CI: 0.43-1.12, P = 0.133). For TyG > 8.51, the risk of incident T2DM significantly increased by 38% with per SD increase in TyG (adjusted HR: 1.38, 95% CI: 1.14-1.67, P = 0.001). Time-dependent receiver operating curve suggested helpful discriminative power of TyG index for T2DM. It also significantly promoted the reclassification ability beyond the baseline risk model with net reclassification index of 0.159 (P = 0.020). Sensitivity analysis excluding participants with prediabetes demonstrated similar results. CONCLUSIONS The TyG index was a significant and independent predictor for future T2DM development. The shape of relationship will require further studies.
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Affiliation(s)
- Ziqiong Wang
- Department of Cardiology, West China Hospital of Sichuan University, Chengdu, China
| | - Liming Zhao
- Department of Cardiovascular Medicine, Hospital of Chengdu Office of People's Government of Tibet Autonomous Region, Chengdu, China
| | - Sen He
- Department of Cardiology, West China Hospital of Sichuan University, Chengdu, China.
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Different Curve Shapes of Fasting Glucose and Various Obesity-Related Indices by Diabetes and Sex. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2021; 18:ijerph18063096. [PMID: 33802865 PMCID: PMC8002721 DOI: 10.3390/ijerph18063096] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/02/2021] [Revised: 03/11/2021] [Accepted: 03/15/2021] [Indexed: 02/06/2023]
Abstract
Fasting plasma glucose (FPG) and obesity-related indices are prognostic factors for adverse outcomes in both subjects with and without diabetes. A few studies have investigated sex differences in obesity indices related to the risk of diabetes, however no studies have compared the relationship between FPG and obesity-related indices by diabetes and sex. Therefore, in this study, we compared the curve shapes of FPG and various obesity-related indices by diabetes, and further explored sex differences in these associations. Data were derived from the Taiwan Biobank database, which included 5000 registered individuals. We used an adjusted generalized linear regression model and calculated the difference of least square means (Lsmean; standard error, SE) for males and females with and without diabetes. Associations between obesity-related indices and fasting glucose level by diabetes and sex groups were estimated, and the ORTHOREG procedure was used to construct B-splines. The post-fitting for linear models procedure was used to determine the range at which the trends separated significantly. The diabetes/sex/FPG interaction term was significant for all obesity-related indices, including body mass index, waist circumference, hip circumference, waist-to-hip ratio, waist-to-height ratio, lipid accumulation product, body roundness index, conicity index, body adiposity index and abdominal volume index. B-spline comparisons between males and females did not reach significance. However, FPG affected the trend towards obesity-related indices. As the fasting glucose level increased, the values of obesity-related indices varied more obviously in the participants without diabetes than in those with diabetes mellitus. The current study revealed that there was a different relationship between FPG and obesity-related indices by diabetes and sex. FPG affected the trend towards obesity-related indices more obviously in participants without diabetes than in those with diabetes. Further studies with a longitudinal design would provide a better understanding of the underlying mechanisms for the relationships.
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Wang L, Yu X, Xu X, Ming J, Wang Z, Gao B, Xing Y, Zhou J, Fu J, Liu T, Liu X, Garstka MA, Wang X, Ji Q. The Fecal Microbiota Is Already Altered in Normoglycemic Individuals Who Go on to Have Type 2 Diabetes. Front Cell Infect Microbiol 2021; 11:598672. [PMID: 33680988 PMCID: PMC7930378 DOI: 10.3389/fcimb.2021.598672] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2020] [Accepted: 01/04/2021] [Indexed: 12/19/2022] Open
Abstract
Objective Mounting evidence has suggested a link between gut microbiome characteristics and type 2 diabetes (T2D). To determine whether these alterations occur before the impairment of glucose regulation, we characterize gut microbiota in normoglycemic individuals who go on to develop T2D. Methods We designed a nested case-control study, and enrolled individuals with a similar living environment. A total of 341 normoglycemic individuals were followed for 4 years, including 30 who developed T2D, 33 who developed prediabetes, and their matched controls. Fecal samples (developed T2D, developed prediabetes and controls: n=30, 33, and 63, respectively) collected at baseline underwent metagenomics sequencing. Results Compared with matched controls, individuals who went on to develop T2D had lower abundances of Bifidobacterium longum, Coprobacillus unclassified, and Veillonella dispar and higher abundances of Roseburia hominis, Porphyromonas bennonis, and Paraprevotella unclassified. The abundance of Bifidobacterium longum was negatively correlated with follow-up blood glucose levels. Moreover, the microbial Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways of carbohydrate metabolism, methane metabolism, amino acid metabolism, fatty acid metabolism, and membrane transport were changed between the two groups. Conclusions We found that fecal microbiota of healthy individuals who go on to develop T2D had already changed when they still were normoglycemic. These alterations of fecal microbiota might provide insights into the development of T2D and a new perspective for identifying individuals at risk of developing T2D.
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Affiliation(s)
- Li Wang
- Endocrinology Research Center, Xijing Hospital, Fourth Military Medical University, Xi'an, China
| | - Xinwen Yu
- Endocrinology Research Center, Xijing Hospital, Fourth Military Medical University, Xi'an, China
| | - Xiaoqiang Xu
- Department of Bioinformatics, Aimigene Institute, Shenzhen, China
| | - Jie Ming
- Endocrinology Research Center, Xijing Hospital, Fourth Military Medical University, Xi'an, China
| | - Zhifeng Wang
- Department of Bioinformatics, Aimigene Institute, Shenzhen, China
| | - Bin Gao
- Endocrinology Research Center, Xijing Hospital, Fourth Military Medical University, Xi'an, China
| | - Ying Xing
- Endocrinology Research Center, Xijing Hospital, Fourth Military Medical University, Xi'an, China
| | - Jie Zhou
- Endocrinology Research Center, Xijing Hospital, Fourth Military Medical University, Xi'an, China
| | - Jianfang Fu
- Endocrinology Research Center, Xijing Hospital, Fourth Military Medical University, Xi'an, China
| | - Tao Liu
- Endocrinology Research Center, Xijing Hospital, Fourth Military Medical University, Xi'an, China
| | - Xiangyang Liu
- Endocrinology Research Center, Xijing Hospital, Fourth Military Medical University, Xi'an, China
| | - Malgorzata A Garstka
- Core Research Laboratory, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Xiaokai Wang
- Department of Bioinformatics, Aimigene Institute, Shenzhen, China
| | - Qiuhe Ji
- Endocrinology Research Center, Xijing Hospital, Fourth Military Medical University, Xi'an, China
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Park HB, Gwark JY, Kam M, Jung J. Association between fasting glucose levels and adhesive capsulitis in a normoglycemic population: a case-control study. J Shoulder Elbow Surg 2020; 29:2240-2247. [PMID: 32713668 DOI: 10.1016/j.jse.2020.03.017] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/14/2020] [Revised: 03/14/2020] [Accepted: 03/20/2020] [Indexed: 02/01/2023]
Abstract
BACKGROUND Hyperglycemia is the most commonly cited risk factor for adhesive capsulitis. However, no study has established whether fasting glucose levels within the normoglycemic range are associated with idiopathic adhesive capsulitis (IAC). This study hypothesized that increments of fasting glucose levels within the normoglycemic range would be linked to IAC. This study investigated any association between normoglycemic fasting glucose levels and IAC. METHODS This case-control study comprised a group of 151 patients with IAC without intrinsic shoulder lesions, extrinsic causes, or known metabolic risk factors such as diabetes, dyslipidemia, and thyroid dysfunction. The control group comprised 453 age- and sex-matched persons seeking general check-ups at the authors' health promotion center during the same period as the case group. Control subjects had normal shoulder function, no previous diagnosis of adhesive capsulitis or of metabolic disease, and no history of trauma or of shoulder surgery. The studied variables were body mass index, serum lipid profiles, thyroid hormone levels, fasting glucose levels, glycosylated hemoglobin A1c, and high-sensitivity C-reactive protein. Fasting glucose levels were studied as scale data and categorical data (<85, 85-89, 90-94, and 95-99 mg/dL). Multivariable conditional logistic regression analysis evaluated the matched sets of subjects. Odds ratios and 95% confidence intervals were determined for various potentially associated factors. RESULTS Fasting glucose level, hypercholesterolemia, and high-sensitivity C-reactive protein were significantly associated with IAC (P ≤ .030). Fasting glucose levels in the <85 mg/dL quartile were significantly negatively associated with IAC (P ≤ .001). In contrast, fasting glucose levels in the 90-94 mg/dL quartile or higher were significantly positively associated with IAC (P ≤ .034). CONCLUSION IAC is positively associated with fasting glucose levels of 90-99 mg/dL, which are currently considered normoglycemic.
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Affiliation(s)
- Hyung Bin Park
- Department of Orthopaedic Surgery, Gyeongsang National University School of Medicine and Gyeongsang National University Changwon Hospital, Changwon, Republic of Korea; Gyeongsang Institute of Health Sciences, Gyeongsang National University, Jinju, Republic of Korea.
| | - Ji-Yong Gwark
- Department of Orthopaedic Surgery, Gyeongsang National University School of Medicine and Gyeongsang National University Changwon Hospital, Changwon, Republic of Korea
| | - Mincheol Kam
- Department of Orthopaedic Surgery, Himchan Hospital, Changwon, Republic of Korea
| | - Jaehoon Jung
- Department of Internal Medicine, Gyeongsang National University School of Medicine and Gyeongsang National University Changwon Hospital, Changwon, Republic of Korea
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Kaneko K, Yatsuya H, Li Y, Uemura M, Chiang C, Hirakawa Y, Ota A, Tamakoshi K, Aoyama A. Risk and population attributable fraction of metabolic syndrome and impaired fasting glucose for the incidence of type 2 diabetes mellitus among middle-aged Japanese individuals: Aichi Worker's Cohort Study. J Diabetes Investig 2020; 11:1163-1169. [PMID: 32022993 PMCID: PMC7477517 DOI: 10.1111/jdi.13230] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/11/2019] [Revised: 01/13/2020] [Accepted: 02/03/2020] [Indexed: 12/14/2022] Open
Abstract
AIMS/INTRODUCTION The Japanese government started a nationwide screening program for metabolic syndrome (MetS) to prevent cardiovascular diseases and diabetes in 2008. Although impaired fasting glucose (IFG) is a strong predictor for type 2 diabetes mellitus, the program does not follow up IFG in non-MetS individuals. This study aimed to examine the risk and the population attributable fraction (PAF) of MetS and IFG for incidence of type 2 diabetes mellitus. MATERIALS AND METHODS Japanese workers (3,417 men and 714 women) aged 40-64 years without a history of diabetes were prospectively followed. MetS was defined as either abdominal obesity plus two or more metabolic risk factors, or being overweight in the case of normal waist circumference plus three or more metabolic risk factors. IFG was defined as fasting blood glucose 100-125 mg/dL. RESULTS During a mean 6.3 years, 240 type 2 diabetes mellitus cases were identified. Compared with those without MetS and IFG, the multivariable-adjusted hazard ratios (95% confidence interval) of non-MetS individuals with IFG, MetS individuals without IFG and MetS individuals with IFG for type 2 diabetes mellitus were 4.9 (3.4-7.1), 2.4 (1.6-3.5) and 8.3 (5.9-11.5), respectively. The corresponding PAFs for type 2 diabetes mellitus incidence were 15.6, 9.1 and 29.7%, respectively. CONCLUSIONS IFG represented a higher risk and PAF than MetS for type 2 diabetes mellitus incidence in middle-aged Japanese individuals. The coexistence of MetS and IFG showed the highest risk and PAF for type 2 diabetes mellitus incidence. The current Japanese MetS screening program should be reconsidered to follow up non-MetS individuals with IFG.
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Affiliation(s)
- Kayo Kaneko
- Department of Public Health and Health SystemsNagoya University Graduate School of MedicineNagoyaJapan
| | - Hiroshi Yatsuya
- Department of Public Health and Health SystemsNagoya University Graduate School of MedicineNagoyaJapan
- Department of Public HealthFujita Health University School of MedicineToyoakeJapan
| | - Yuanying Li
- Department of Public HealthFujita Health University School of MedicineToyoakeJapan
| | - Mayu Uemura
- Department of Public Health and Health SystemsNagoya University Graduate School of MedicineNagoyaJapan
| | - Chifa Chiang
- Department of Public Health and Health SystemsNagoya University Graduate School of MedicineNagoyaJapan
| | - Yoshihisa Hirakawa
- Department of Public Health and Health SystemsNagoya University Graduate School of MedicineNagoyaJapan
| | - Atsuhiko Ota
- Department of Public HealthFujita Health University School of MedicineToyoakeJapan
| | - Koji Tamakoshi
- Department of NursingNagoya University School of Health SciencesNagoyaJapan
| | - Atsuko Aoyama
- Department of Public Health and Health SystemsNagoya University Graduate School of MedicineNagoyaJapan
- Nagoya University of Arts and SciencesNissinJapan
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Davidson MB. Metformin Should Not Be Used to Treat Prediabetes. Diabetes Care 2020; 43:1983-1987. [PMID: 32936780 DOI: 10.2337/dc19-2221] [Citation(s) in RCA: 36] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/05/2020] [Accepted: 04/28/2020] [Indexed: 02/03/2023]
Abstract
Based on the results of the Diabetes Prevention Program Outcomes Study (DPPOS), in which metformin significantly decreased the development of diabetes in individuals with baseline fasting plasma glucose (FPG) concentrations of 110-125 vs. 100-109 mg/dL (6.1-6.9 vs. 5.6-6.0 mmol/L) and A1C levels 6.0-6.4% (42-46 mmol/mol) vs. <6.0% and in women with a history of gestational diabetes mellitus, it has been suggested that metformin should be used to treat people with prediabetes. Since the association between prediabetes and cardiovascular disease is due to the associated nonglycemic risk factors in people with prediabetes, not to the slightly increased glycemia, the only reason to treat with metformin is to delay or prevent the development of diabetes. There are three reasons not to do so. First, approximately two-thirds of people with prediabetes do not develop diabetes, even after many years. Second, approximately one-third of people with prediabetes return to normal glucose regulation. Third, people who meet the glycemic criteria for prediabetes are not at risk for the microvascular complications of diabetes and thus metformin treatment will not affect this important outcome. Why put people who are not at risk for the microvascular complications of diabetes on a drug (possibly for the rest of their lives) that has no immediate advantage except to lower subdiabetes glycemia to even lower levels? Rather, individuals at the highest risk for developing diabetes-i.e., those with FPG concentrations of 110-125 mg/dL (6.1-6.9 mmol/L) or A1C levels of 6.0-6.4% (42-46 mmol/mol) or women with a history of gestational diabetes mellitus-should be followed closely and metformin immediately introduced only when they are diagnosed with diabetes.
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Prats-Puig A, García-Retortillo S, Puig-Parnau M, Vasileva F, Font-Lladó R, Xargay-Torrent S, Carreras-Badosa G, Mas-Parés B, Bassols J, López-Bermejo A. DNA Methylation Reorganization of Skeletal Muscle-Specific Genes in Response to Gestational Obesity. Front Physiol 2020; 11:938. [PMID: 32848869 PMCID: PMC7412435 DOI: 10.3389/fphys.2020.00938] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2020] [Accepted: 07/13/2020] [Indexed: 12/25/2022] Open
Abstract
The goals were to investigate in umbilical cord tissue if gestational obesity: (1) was associated with changes in DNA methylation of skeletal muscle-specific genes; (2) could modulate the co-methylation interactions among these genes. Additionally, we assessed the associations between DNA methylation levels and infant's variables at birth and at age 6. DNA methylation was measured in sixteen pregnant women [8-gestational obesity group; 8-control group] in umbilical cord using the Infinium Methylation EPIC Bead Chip microarray. Differentially methylated CpGs were identified with Beta Regression Models [false discovery rate (FDR) < 0.05 and an Odds Ratio > 1.5 or < 0.67]. DNA methylation interactions between CpGs of skeletal muscle-specific genes were studied using data from Pearson correlation matrices. In order to quantify the interactions within each network, the number of links was computed. This identification analysis reported 38 differential methylated CpGs within skeletal muscle-specific genes (comprising 4 categories: contractibility, structure, myokines, and myogenesis). Compared to control group, gestational obesity (1) promotes hypermethylation in highly methylated genes and hypomethylation in low methylated genes; (2) CpGs in regions close to transcription sites and with high CpG density are hypomethylated while regions distant to transcriptions sites and with low CpG density are hypermethylated; (3) diminishes the number of total interactions in the co-methylation network. Interestingly, the associations between infant's fasting glucose at age 6 and MYL6, MYH11, TNNT3, TPM2, CXCL2, and NCAM1 were still relevant after correcting for multiple testing. In conclusion, our study showed a complex interaction between gestational obesity and the epigenetic status of muscle-specific genes in umbilical cord tissue. Additionally, gestational obesity may alter the functional co-methylation connectivity of CpG within skeletal muscle-specific genes interactions, our results revealing an extensive reorganization of methylation in response to maternal overweight. Finally, changes in methylation levels of skeletal muscle specific genes may have persistent effects on the offspring of mothers with gestational obesity.
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Affiliation(s)
- Anna Prats-Puig
- University School of Health and Sport (EUSES), University of Girona, Girona, Spain
| | - Sergi García-Retortillo
- University School of Health and Sport (EUSES), University of Girona, Girona, Spain
- Complex Systems in Sport, National Institute of Physical Education and Sport of Catalonia (INEFC), Universitat de Barcelona (UB), Barcelona, Spain
| | - Miquel Puig-Parnau
- University School of Health and Sport (EUSES), University of Girona, Girona, Spain
| | - Fidanka Vasileva
- Faculty of Physical Education, Sport and Health, Ss. Cyril and Methodius University, Skopje, North Macedonia
| | - Raquel Font-Lladó
- University School of Health and Sport (EUSES), University of Girona, Girona, Spain
| | - Sílvia Xargay-Torrent
- Pediatric Endocrinology, Girona Institute for Biomedical Research, Dr. Josep Trueta Hospital, Girona, Spain
| | - Gemma Carreras-Badosa
- Pediatric Endocrinology, Girona Institute for Biomedical Research, Dr. Josep Trueta Hospital, Girona, Spain
| | - Berta Mas-Parés
- Maternal & Fetal Metabolic Research, Girona Institute for Biomedical Research, Salt, Spain
| | - Judit Bassols
- Maternal & Fetal Metabolic Research, Girona Institute for Biomedical Research, Salt, Spain
| | - Abel López-Bermejo
- Pediatric Endocrinology, Girona Institute for Biomedical Research, Dr. Josep Trueta Hospital, Girona, Spain
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Lee PN, Coombs KJ. Systematic review with meta-analysis of the epidemiological evidence relating smoking to type 2 diabetes. World J Meta-Anal 2020; 8:119-152. [DOI: 10.13105/wjma.v8.i2.119] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/05/2020] [Revised: 04/02/2020] [Accepted: 04/20/2020] [Indexed: 02/06/2023] Open
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Large body mass index and waist circumference are associated with high blood pressure and impaired fasting glucose in young Chinese men. Blood Press Monit 2019; 24:289-293. [PMID: 31567186 DOI: 10.1097/mbp.0000000000000404] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/13/2023]
Abstract
BACKGROUND Obesity is closely related to many chronic diseases and metabolic risk factors. The present study examined the relationship of obesity-related indices to blood pressure (BP) and fasting plasma glucose (FPG) among young Chinese men. METHODS A total of 1193 male college students aged 18-22 years participated in the study. Height, weight, waist circumference (WC), body mass index (BMI), waist-to-height ratio (WHtR), systolic blood pressure (SBP), diastolic blood pressure (DBP) and FPG were measured. High BP was defined as SBP ≥140 mmHg and/or DBP ≥90 mmHg. Impaired fasting glucose (IFG) was defined as FPG ≥5.6 mmol/L. RESULTS BMI, WC and WHtR were positively correlated with BP and FPG (rBMI-SBP = 0.455, rBMI-DBP = 0.367, rBMI-FPG = 0.113, rWC-SBP = 0.445, rWC-DBP = 0.382, rWC-FPG = 0.115, rWHtR-SBP = 0.396, rWHtR-DBP = 0.302, rWHtR-FPG = 0.106, P all < 0.01). When categorized by BMI (underweight, normal weight, overweight and obesity), the mean values of SBP, DBP, FPG and the prevalence of high BP and IFG increased with BMI, significant differences were observed among the four groups (P < 0.01). When categorized by WC and WHtR, similar differences were observed, with subjects in the large WC/WHtR group had a higher BP and FPG than their counterparts in the low WC/WHtR group (P < 0.01). CONCLUSION Large BMI and WC/WHtR are associated with high BP and IFG. Our results suggested that prevention of obesity in youth may be an effective approach for preventing the development of diabetes and hypertension in the future.
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Feinberg T, Wieland LS, Miller LE, Munir K, Pollin TI, Shuldiner AR, Amoils S, Gallagher L, Bahr-Robertson M, D'Adamo CR. Polyherbal dietary supplementation for prediabetic adults: study protocol for a randomized controlled trial. Trials 2019; 20:24. [PMID: 30616613 PMCID: PMC6323847 DOI: 10.1186/s13063-018-3032-6] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2018] [Accepted: 11/01/2018] [Indexed: 12/15/2022] Open
Abstract
Background Prediabetes describes a state of hyperglycemia outside of normal limits that does not meet the criteria for diabetes diagnosis, is generally symptomless, and affects an estimated 38% of adults in the United States. Prediabetes typically precedes the diagnosis of type 2 diabetes, which accounts for increased morbidity and mortality. Although the use of dietary and herbal supplements is popular worldwide, and a variety of single herbal medicines have been examined for glycemic management, the potential of increasingly common polyherbal formulations to return glycemic parameters to normal ranges among adults with prediabetes remains largely unexplored. The purpose of this study is to evaluate the efficacy of a commercially available, polyherbal dietary supplement on glycemic and lipid parameters in prediabetic individuals. Methods In this multi-site, double-blinded, randomized controlled clinical trial, 40 participants with prediabetes will be randomized to either a daily oral polyherbal dietary supplement (GlucoSupreme™ Herbal; Designs for Health®, Suffield, CT, USA; containing cinnamon bark (Cinnamomum cassia), banaba leaf (Lagerstroemia speciosa standardized to 1% corosolic acid), kudzu root (Pueraria lobata standardized to 40% isoflavones), fenugreek seed (Trigonella foenum-graceum standardized to 60% saponins), gymnema leaf (Gymnema sylvestre standardized to 25% gymnemic acid), American ginseng root (Panax quinquefolius standardized to 5% ginsenosides), and berberine HCl derived from bark (Berberis aristata)) or placebo for 12 weeks. Short-, medium-, and comparatively long-term markers of glycemic control (blood glucose and fasting insulin, fructosamine, and glycated hemoglobin/A1c, respectively), and other glycemic parameters (GlycoMark, β-cell function, and insulin sensitivity/resistance) will be obtained. Lipid profile (total cholesterol, LDL, HDL, and triglycerides), inflammation (hs-CRP), progression to type 2 diabetes mellitus, as well as safety indices (ALT, AST) will be obtained. An intention-to-treat analysis will be used to assess changes in study outcomes. Discussion Treatment options for adults with prediabetes are currently limited. This study aims to evaluate the safety and efficacy of a commercially available dietary supplement in the popular, but as yet insufficiently studied, category of polyherbal formulas for the management of glycemic parameters and other biomarkers associated with prediabetes. Trial registration ClinicalTrials.gov, ID: NCT03388762. Retrospectively registered on 4 January 2018. Electronic supplementary material The online version of this article (10.1186/s13063-018-3032-6) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Termeh Feinberg
- University of Maryland School of Medicine Center for Integrative Medicine, Baltimore, MD, USA. .,Yale University School of Medicine Center for Medical Informatics, New Haven, CT, USA.
| | - L Susan Wieland
- University of Maryland School of Medicine Center for Integrative Medicine, Baltimore, MD, USA
| | | | - Kashif Munir
- University of Maryland School of Medicine Center for Diabetes and Endocrinology, Baltimore, MD, USA
| | - Toni I Pollin
- University of Maryland School of Medicine Department of Medicine, Baltimore, MD, USA
| | - Alan R Shuldiner
- University of Maryland School of Medicine Department of Medicine, Baltimore, MD, USA
| | - Steve Amoils
- Alliance Integrative Medicine, Cincinatti, OH, USA
| | | | - Mary Bahr-Robertson
- University of Maryland School of Medicine Center for Integrative Medicine, Baltimore, MD, USA
| | - Christopher R D'Adamo
- University of Maryland School of Medicine Center for Integrative Medicine, Baltimore, MD, USA
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Low fasting plasma glucose level as a predictor of new-onset diabetes mellitus on a large cohort from a Japanese general population. Sci Rep 2018; 8:13927. [PMID: 30224631 PMCID: PMC6141503 DOI: 10.1038/s41598-018-31744-4] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2017] [Accepted: 08/23/2018] [Indexed: 01/08/2023] Open
Abstract
Although fasting plasma glucose levels <70 mg/dL are associated with a high incidence of cardiovascular disease (CVD), whether there is any risk of new-onset diabetes mellitus owing to fasting plasma glucose at this range has not been clarified. We measured the odds ratio (OR) of new-onset diabetes mellitus relative to fasting plasma glucose levels at various ranges in a nation-wide Japanese population with and without CVD history. Of 186,749 participants without diabetes in 2008, 171,408 had no history of CVD, while 15,341 did. Participants were classified into 8 categories according to their fasting plasma glucose levels. Unadjusted and multivariable-adjusted logistic regression models were used to measure the OR of new-onset diabetes mellitus in the 3-year follow up. In all participants, multivariable-adjusted OR increased when fasting plasma glucose levels were <70 mg/dL or 90–125 mg/dL. Participants without CVD showed increased OR when glucose levels were <70 mg/dL or 90–125 mg/dL. Participants with a history of CVD showed increased OR with glucose levels of 95–125 mg/dL. The risk of new-onset diabetes mellitus is higher when fasting glucose levels are <70 mg/dL, indicating that the paradox of fasting glucose seeks a new risk stratification for new-onset diabetes mellitus.
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Liu L, Kerr WL, Kong F, Dee DR, Lin M. Influence of nano-fibrillated cellulose (NFC) on starch digestion and glucose absorption. Carbohydr Polym 2018; 196:146-153. [DOI: 10.1016/j.carbpol.2018.04.116] [Citation(s) in RCA: 40] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2018] [Revised: 04/10/2018] [Accepted: 04/27/2018] [Indexed: 10/17/2022]
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Sharma A, Kandlakunta H, Nagpal SJS, Ziding F, Hoos W, Petersen GM, Chari ST. Model to Determine Risk of Pancreatic Cancer in Patients With New-Onset Diabetes. Gastroenterology 2018; 155:730-739.e3. [PMID: 29775599 PMCID: PMC6120785 DOI: 10.1053/j.gastro.2018.05.023] [Citation(s) in RCA: 230] [Impact Index Per Article: 32.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/19/2018] [Revised: 05/03/2018] [Accepted: 05/09/2018] [Indexed: 12/22/2022]
Abstract
BACKGROUND & AIMS Of patients with new-onset diabetes (NOD; based on glycemic status) older than 50 years, approximately 1% are diagnosed with pancreatic cancer (PC) within 3 years. We aimed to develop and validate a model to determine risk of PC in patients with NOD. METHODS We retrospectively collected data from 4 independent and nonoverlapping cohorts of patients (N = 1,561) with NOD (based on glycemic status; data collected at date of diagnosis and 12 months previously) in the Rochester Epidemiology Project from January 1, 2000 through December 31, 2015 to create our model. The model weighed scores for 3 factors identified in the discovery cohort to be most strongly associated with PC (64 patients with PC and 192 with type 2 diabetes): change in weight, change in blood glucose, and age at onset of diabetes. We called our model Enriching New-Onset Diabetes for Pancreatic Cancer (ENDPAC). We validated the locked-down model and cutoff score in an independent population-based cohort of 1,096 patients with diabetes; of these, 9 patients (82%) had PC within 3 years of meeting the criteria for NOD. RESULTS In the discovery cohort, the END-PAC model identified patients who developed PC within 3 years of diabetes onset (area under receiver operating characteristic curve 0.87); a score of at least 3 identified patients who developed PC with 80% sensitivity and specificity. In the validation cohort, a score of at least 3 identified 7 of 9 patients with PC (78%) with 85% specificity; the prevalence of PC in patients with a score of at least 3 (3.6%) was 4.4-fold greater than in patients with NOD. A high END-PAC score in patients who did not have PC (false positives) was often due to such factors as recent steroid use or different malignancy. An ENDPAC score no higher than 0 (in 49% of patients) meant that patients had an extremely low risk for PC. An END-PAC score of at least 3 identified 75% of patients in the discovery cohort more than 6 months before a diagnosis of PC. CONCLUSIONS Based on change in weight, change in blood glucose, and age at onset of diabetes, we developed and validated a model to determine risk of PC in patients with NOD based on glycemic status (END-PAC model). An independent prospective study is needed to further validate this model, which could contribute to early detection of PC.
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Affiliation(s)
- Ayush Sharma
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN
| | | | | | - Feng Ziding
- Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - William Hoos
- Pancreatic Cancer Action Network, Manhattan Beach, CA
| | | | - Suresh T. Chari
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN
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Kreider KE, Feinglos M. The relationship of baseline fasting plasma glucose and cardiovascular morbidity and mortality. Eur J Intern Med 2018; 54:e25-e26. [PMID: 29773415 DOI: 10.1016/j.ejim.2018.05.017] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/07/2018] [Accepted: 05/09/2018] [Indexed: 11/24/2022]
Affiliation(s)
- Kathryn Evans Kreider
- Duke University School of Nursing, United States; Division of Endocrinology, Metabolism and Nutrition, Duke University Medical Center, United States.
| | - Mark Feinglos
- Division of Endocrinology, Metabolism and Nutrition, Duke University Medical Center, United States
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Bergman M, Jagannathan R, Buysschaert M, Pareek M, Olsen MH, Nilsson PM, Medina JL, Roth J, Chetrit A, Groop L, Dankner R. Lessons learned from the 1-hour post-load glucose level during OGTT: Current screening recommendations for dysglycaemia should be revised. Diabetes Metab Res Rev 2018; 34:e2992. [PMID: 29460410 DOI: 10.1002/dmrr.2992] [Citation(s) in RCA: 33] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/07/2017] [Revised: 01/14/2018] [Accepted: 02/02/2018] [Indexed: 02/06/2023]
Abstract
This perspective covers a novel area of research describing the inadequacies of current approaches for diagnosing dysglycaemia and proposes that the 1-hour post-load glucose level during the 75-g oral glucose tolerance test may serve as a novel biomarker to detect dysglycaemia earlier than currently recommended screening criteria for glucose disorders. Considerable evidence suggests that a 1-hour post-load plasma glucose value ≥155 mg/dl (8.6 mmol/L) may identify individuals with reduced β-cell function prior to progressing to prediabetes and diabetes and is highly predictive of those likely to progress to diabetes more than the HbA1c or 2-hour post-load glucose values. An elevated 1-hour post-load glucose level was a better predictor of type 2 diabetes than isolated 2-hour post-load levels in Indian, Japanese, and Israeli and Nordic populations. Furthermore, epidemiological studies have shown that a 1-hour PG ≥155 mg/dl (8.6 mmol/L) predicted progression to diabetes as well as increased risk for microvascular disease and mortality when the 2-hour level was <140 mg/dl (7.8 mmol/L). The risk of myocardial infarction or fatal ischemic heart disease was also greater among subjects with elevated 1-hour glucose levels as were risks of retinopathy and peripheral vascular complications in a Swedish cohort. The authors believe that the considerable evidence base supports redefining current screening and diagnostic recommendations with the 1-hour post-load level. Measurement of the 1-hour PG level would increase the likelihood of identifying a larger, high-risk group with the additional practical advantage of potentially replacing the conventional 2-hour oral glucose tolerance test making it more acceptable in a clinical setting.
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Affiliation(s)
- Michael Bergman
- Division of Endocrinology and Metabolism, Department of Medicine and of Population Health, School of Medicine, NYU Langone Diabetes Prevention Program, New York, NY, USA
| | - Ram Jagannathan
- Hubert Department of Global Health, Rollins School of Public Health, Emory University, Atlanta, GA, USA
| | - Martin Buysschaert
- Department of Endocrinology and Diabetology, Université Catholique de Louvain, University Clinic Saint-Luc, Brussels, Belgium
| | - Manan Pareek
- Centre for Individualized Medicine in Arterial Diseases (CIMA), Odense University Hospital, University of Southern Denmark, Odense, Denmark
- Cardiology Section, Department of Internal Medicine, Holbaek Hospital, Holbaek, Denmark
| | - Michael H Olsen
- Centre for Individualized Medicine in Arterial Diseases (CIMA), Odense University Hospital, University of Southern Denmark, Odense, Denmark
- Cardiology Section, Department of Internal Medicine, Holbaek Hospital, Holbaek, Denmark
| | - Peter M Nilsson
- Department of Clinical Sciences and Lund University Diabetes Centre, Lund University, Skåne University Hospital, Malmö, Sweden
| | | | - Jesse Roth
- The Feinstein Institute for Medical Research, Manhasset, NY, USA
| | - Angela Chetrit
- Unit for Cardiovascular Epidemiology, The Gertner Institute for Epidemiology and Health Policy Research, Sheba Medical Center, Tel Hashomer, Israel
| | - Leif Groop
- Lund University Diabetes Centre, Lund University, Malmö, Sweden
| | - Rachel Dankner
- The Feinstein Institute for Medical Research, Manhasset, NY, USA
- Unit for Cardiovascular Epidemiology, The Gertner Institute for Epidemiology and Health Policy Research, Sheba Medical Center, Tel Hashomer, Israel
- Department of Epidemiology and Preventive Medicine, School of Public Health, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
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Lee SH. Hidden Risks behind Normal Fasting Glucose: Is It Significant? Diabetes Metab J 2018; 42:196-197. [PMID: 29938402 PMCID: PMC6015962 DOI: 10.4093/dmj.2018.0083] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Affiliation(s)
- Seung Hwan Lee
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.
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Hwang YC, Fujimoto WY, Kahn SE, Leonetti DL, Boyko EJ. Predictors of Incident Type 2 Diabetes Mellitus in Japanese Americans with Normal Fasting Glucose Level. Diabetes Metab J 2018; 42:198-206. [PMID: 29885113 PMCID: PMC6015963 DOI: 10.4093/dmj.2017.0100] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/18/2017] [Accepted: 02/19/2018] [Indexed: 12/27/2022] Open
Abstract
BACKGROUND Little is known about the natural course of normal fasting glucose (NFG) in Asians and the risk factors for future diabetes. METHODS A total of 370 Japanese Americans (163 men, 207 women) with NFG levels and no history of diabetes, aged 34 to 75 years, were enrolled. Oral glucose tolerance tests were performed at baseline, 2.5, 5, and 10 years after enrollment. RESULTS During 10 years of follow-up, 16.1% of participants met criteria for diabetes diagnosis, and 39.6% of subjects still had NFG levels at the time of diabetes diagnosis. During 5 years of follow-up, age (odds ratio [OR], 1.05; 95% confidence interval [CI], 1.01 to 1.10; P=0.026) and family history of diabetes (OR, 3.24; 95% CI, 1.42 to 7.40; P=0.005) were independently associated with future diabetes diagnosis; however, fasting glucose level was not an independent predictor. During 10 years of follow-up, family history of diabetes (OR, 2.76; 95% CI, 1.37 to 5.54; P=0.004), fasting insulin level (OR, 1.01; 95% CI, 1.00 to 1.02; P=0.037), and fasting glucose level (OR, 3.69; 95% CI, 1.13 to 12.01; P=0.030) were associated with diabetes diagnosis independent of conventional risk factors for diabetes. CONCLUSION A substantial number of subjects with NFG at baseline still remained in the NFG range at the time of diabetes diagnosis. A family history of diabetes and fasting insulin and glucose levels were associated with diabetes diagnosis during 10 years of follow-up; however, fasting glucose level was not associated with diabetes risk within the relatively short-term follow-up period of 5 years in subjects with NFG.
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Affiliation(s)
- You Cheol Hwang
- Division of Endocrinology and Metabolism, Department of Medicine, Kyung Hee University Hospital at Gangdong, Kyung Hee University School of Medicine, Seoul, Korea.
| | - Wilfred Y Fujimoto
- Division of Metabolism, Endocrinology and Nutrition, Department of Medicine, University of Washington School of Medicine, Seattle, WA, USA
| | - Steven E Kahn
- Division of Metabolism, Endocrinology and Nutrition, Department of Medicine, University of Washington School of Medicine, Seattle, WA, USA
- Hospital and Specialty Medicine Service, VA Puget Sound Health Care System, Seattle, WA, USA
| | - Donna L Leonetti
- Department of Anthropology, University of Washington, Seattle, WA, USA
| | - Edward J Boyko
- Seattle Epidemiologic Research and Information Center, VA Puget Sound Health Care System, Seattle, WA, USA
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Gong Y, Smith SM, Handberg EM, Pepine CJ, Cooper‐DeHoff RM. Intensive blood pressure lowering reduces adverse cardiovascular outcomes among patients with high-normal glucose: An analysis from the Systolic Blood Pressure Intervention Trial database. J Clin Hypertens (Greenwich) 2018; 20:620-624. [PMID: 29532983 PMCID: PMC8031176 DOI: 10.1111/jch.13247] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2017] [Revised: 12/21/2017] [Accepted: 01/01/2018] [Indexed: 09/08/2024]
Abstract
The objective of this analysis is to determine the effect of intensive (<120 mm Hg) versus standard (<140 mm Hg) systolic blood pressure (SBP) targets on cardiovascular (CV) outcomes among SPRINT participants with low-normal or high-normal fasting glucose (FG). We categorized the 5425 SPRINT participants with FG <100 mg/dL into 2 groups: <85 mg/dL (low-normal) and 85 to <100 mg/dL (high-normal). Among participants with low-normal glucose, there was no significant difference in the primary outcome (PO) between the 2 treatment arms (adjusted hazard ratio, HR: 1.27 (95% confidence interval [CI] 0.68-2.37, P = .46). However, the intensive SBP target was associated with 27% lower risk for the PO compared with the standard SBP target in those with high-normal glucose (HR 0.73, 0.57-0.93, P = .01). Our results indicate that hypertensive patients with high-normal FG may benefit from intensive SBP lowering, whereas benefits were inconclusive among those with low-normal FG.
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Affiliation(s)
- Yan Gong
- Department of Pharmacotherapy and Translational ResearchCollege of PharmacyUniversity of FloridaGainesvilleFLUSA
- Center for PharmacogenomicsCollege of PharmacyUniversity of FloridaGainesvilleFLUSA
- UF Health Cancer CenterUniversity of FloridaGainesvilleFLUSA
| | - Steven M. Smith
- Department of Pharmacotherapy and Translational ResearchCollege of PharmacyUniversity of FloridaGainesvilleFLUSA
| | - Eileen M. Handberg
- Division of Cardiovascular MedicineDepartment of MedicineUniversity of FloridaGainesvilleFLUSA
| | - Carl J. Pepine
- Division of Cardiovascular MedicineDepartment of MedicineUniversity of FloridaGainesvilleFLUSA
| | - Rhonda M. Cooper‐DeHoff
- Department of Pharmacotherapy and Translational ResearchCollege of PharmacyUniversity of FloridaGainesvilleFLUSA
- Center for PharmacogenomicsCollege of PharmacyUniversity of FloridaGainesvilleFLUSA
- Division of Cardiovascular MedicineDepartment of MedicineUniversity of FloridaGainesvilleFLUSA
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Gao Q, Praticò G, Scalbert A, Vergères G, Kolehmainen M, Manach C, Brennan L, Afman LA, Wishart DS, Andres-Lacueva C, Garcia-Aloy M, Verhagen H, Feskens EJM, Dragsted LO. A scheme for a flexible classification of dietary and health biomarkers. GENES & NUTRITION 2017; 12:34. [PMID: 29255495 PMCID: PMC5728065 DOI: 10.1186/s12263-017-0587-x] [Citation(s) in RCA: 67] [Impact Index Per Article: 8.4] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/16/2017] [Accepted: 11/14/2017] [Indexed: 01/05/2023]
Abstract
Biomarkers are an efficient means to examine intakes or exposures and their biological effects and to assess system susceptibility. Aided by novel profiling technologies, the biomarker research field is undergoing rapid development and new putative biomarkers are continuously emerging in the scientific literature. However, the existing concepts for classification of biomarkers in the dietary and health area may be ambiguous, leading to uncertainty about their application. In order to better understand the potential of biomarkers and to communicate their use and application, it is imperative to have a solid scheme for biomarker classification that will provide a well-defined ontology for the field. In this manuscript, we provide an improved scheme for biomarker classification based on their intended use rather than the technology or outcomes (six subclasses are suggested: food compound intake biomarkers (FCIBs), food or food component intake biomarkers (FIBs), dietary pattern biomarkers (DPBs), food compound status biomarkers (FCSBs), effect biomarkers, physiological or health state biomarkers). The application of this scheme is described in detail for the dietary and health area and is compared with previous biomarker classification for this field of research.
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Affiliation(s)
- Qian Gao
- Department of Nutrition, Exercise and Sports, University of Copenhagen, Copenhagen, Denmark
| | - Giulia Praticò
- Department of Nutrition, Exercise and Sports, University of Copenhagen, Copenhagen, Denmark
- Department of Food Science, University of Copenhagen, Copenhagen, Denmark
| | - Augustin Scalbert
- Biomarkers Group, Nutrition and Metabolism Section, International Agency for Research on Cancer (IARC), Lyon, France
| | - Guy Vergères
- Agroscope, Federal Office of Agriculture, Berne, Switzerland
| | | | - Claudine Manach
- INRA, Human Nutrition Unit, Université Clermont Auvergne, INRA, F63000 Clermont-Ferrand, France
| | - Lorraine Brennan
- UCD Institute of Food & Health, UCD School of Agriculture and Food Science, University College Dublin, Dublin, Ireland
| | - Lydia A. Afman
- Division of Human Nutrition, Wageningen University & Research, Wageningen, The Netherlands
| | - David S. Wishart
- Department of Biological Sciences, University of Alberta, Edmonton, Canada
| | - Cristina Andres-Lacueva
- Biomarkers and Nutrimetabolomic Laboratory, Department of Nutrition, Food Sciences and Gastronomy, University of Barcelona, Barcelona, Spain
- CIBER de Fragilidad y Envejecimiento Saludable (CIBERFES), Instituto de Salud Carlos III, Barcelona, Spain
| | - Mar Garcia-Aloy
- Biomarkers and Nutrimetabolomic Laboratory, Department of Nutrition, Food Sciences and Gastronomy, University of Barcelona, Barcelona, Spain
- CIBER de Fragilidad y Envejecimiento Saludable (CIBERFES), Instituto de Salud Carlos III, Barcelona, Spain
| | - Hans Verhagen
- European Food Safety Authority (EFSA), Parma, Italy
- University of Ulster, Coleraine, Northern Ireland UK
| | - Edith J. M. Feskens
- Division of Human Nutrition, Wageningen University & Research, Wageningen, The Netherlands
| | - Lars O. Dragsted
- Department of Nutrition, Exercise and Sports, University of Copenhagen, Copenhagen, Denmark
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Yli-Piipari S, Berg A, Laing EM, Hartzell DL, Parris KO, Udwadia J, Lewis RD. A Twelve-Week Lifestyle Program to Improve Cardiometabolic, Behavioral, and Psychological Health in Hispanic Children and Adolescents. J Altern Complement Med 2017; 24:132-138. [PMID: 29017015 DOI: 10.1089/acm.2017.0130] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
Abstract
OBJECTIVES To examine the effectiveness of a 12-week lifestyle program on cardiometabolic, behavioral, and psychological outcomes among overweight Hispanic children and adolescents. DESIGN A case series study with pre- and post-test analyses. Subjects/Settings/Location: A convenience sample of high-risk pediatric primary care patients (n = 22; 6 girls, 16 boys; M age = 11.73 ± 1.39 years) and their guardians in the Southeast United States. INTERVENTION Twice per week 60 min (total of 24 h) of moderate-to-vigorous intensity boxing exercise training, 12 h of nutrition education for guardians, and a 30-min pediatrician appointment. OUTCOME MEASURES Cardiometabolic (height [m], weight [kg], waist circumference [cm], body-mass index [BMI], BMI-z, BMI%, cholesterol [mg/dL], triglycerides [mg/dL], glucose [mg/dL], and low-density lipoprotein and high-density lipoprotein cholesterol [mg/dL]), behavioral (objective free time physical activity [PA] and sedentary time [min/day]), and psychological (self-determined exercise motivation) outcomes were measured/calculated, and paired-samples t-tests were conducted. RESULTS A significant reduction was observed in waist circumference t(17) = -2.57, p = 0.020, d = 0.64; BMI% t(15) = -2.53, p = 0.023, d = 0.20; fasting glucose t(15) = -6.43, p < 0.001, d = 1.67; and amotivation (-) t(17) = -2.29, p = 0.036, d = 0.64; whereas a significant increase was identified in moderate t(10) = 4.01, p = 0.002, d = 1.23 and vigorous t(10) = 3.41, p = 0.007, d = 1.07 intensity PA; intrinsic motivation t(17) = 2.71, p = 0.015, d = 0.38; and introjected regulation t(17) = 2.74, p = 0.014, d = 0.64. CONCLUSIONS A 12-week lifestyle program can be effective in improving selected health markers among overweight Hispanic children and adolescents. The positive changes in fasting glucose, BMI, and waist suggest that the participants are currently at lower risk for both type 2 diabetes and cardiovascular disease as a result of the Confidence, Ownership, Responsibility, and Exercise program.
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Affiliation(s)
- Sami Yli-Piipari
- 1 Children's Physical Activity, Fitness, and School Health Promotion, Department of Kinesiology, College of Education, University of Georgia , Athens, GA
| | - Alison Berg
- 2 Department of Foods and Nutrition, College of Family and Consumer Sciences, University of Georgia , Athens, GA
| | - Emma M Laing
- 2 Department of Foods and Nutrition, College of Family and Consumer Sciences, University of Georgia , Athens, GA
| | | | | | - Jon Udwadia
- 5 Department of Pediatrics, GRU/UGA Medical Partnership , Athens, GA
| | - Richard D Lewis
- 2 Department of Foods and Nutrition, College of Family and Consumer Sciences, University of Georgia , Athens, GA
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50
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Bress AP, King JB, Kreider KE, Beddhu S, Simmons DL, Cheung AK, Zhang Y, Doumas M, Nord J, Sweeney ME, Taylor AA, Herring C, Kostis WJ, Powell J, Rastogi A, Roumie CL, Wiggers A, Williams JS, Yunis R, Zias A, Evans GW, Greene T, Rocco MV, Cushman WC, Reboussin DM, Feinglos MN, Papademetriou V. Effect of Intensive Versus Standard Blood Pressure Treatment According to Baseline Prediabetes Status: A Post Hoc Analysis of a Randomized Trial. Diabetes Care 2017; 40:dc170885. [PMID: 28793997 PMCID: PMC5606306 DOI: 10.2337/dc17-0885] [Citation(s) in RCA: 66] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/03/2017] [Accepted: 07/14/2017] [Indexed: 02/03/2023]
Abstract
OBJECTIVE To determine whether the effects of intensive (<120 mmHg) compared with standard (<140 mmHg) systolic blood pressure (SBP) treatment are different among those with prediabetes versus those with fasting normoglycemia at baseline in the Systolic Blood Pressure Intervention Trial (SPRINT). RESEARCH DESIGN AND METHODS This was a post hoc analysis of SPRINT. SPRINT participants were categorized by prediabetes status, defined as baseline fasting serum glucose ≥100 mg/dL versus those with normoglycemia (fasting serum glucose <100 mg/dL). The primary outcome was a composite of myocardial infarction, acute coronary syndrome not resulting in myocardial infarction, stroke, acute decompensated heart failure, or death from cardiovascular causes. Cox regression was used to calculate hazard ratios for study outcomes with intensive compared with standard SBP treatment among those with prediabetes and normoglycemia. RESULTS Among 9,361 participants randomized (age 67.9 ± 9.4 years; 35.5% female), 3,898 and 5,425 had baseline prediabetes and normoglycemia, respectively. After a median follow-up of 3.26 years, the hazard ratio for the primary outcome was 0.69 (95% CI 0.53, 0.89) and 0.83 (95% CI 0.66, 1.03) among those with prediabetes and normoglycemia, respectively (P value for interaction 0.30). For all-cause mortality, the hazard ratio with intensive SBP treatment was 0.77 (95% CI 0.55, 1.06) for prediabetes and 0.71 (95% CI 0.54, 0.94) for normoglycemia (P value for interaction 0.74). Effects of intensive versus standard SBP treatment on prespecified renal outcomes and serious adverse events were similar for prediabetes and normoglycemia (all interaction P > 0.05). CONCLUSIONS In SPRINT, the beneficial effects of intensive SBP treatment were similar among those with prediabetes and fasting normoglycemia.
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Affiliation(s)
- Adam P Bress
- Division of Health System Innovation and Research, Department of Population Health Sciences, University of Utah, Salt Lake City, UT
- VA Salt Lake City Health Care System, Salt Lake City, UT
| | - Jordan B King
- Department of Pharmacy, Kaiser Permanente Colorado, Aurora, CO
| | | | - Srinivasan Beddhu
- Division of Nephrology and Hypertension, Department of Internal Medicine, University of Utah, Salt Lake City, UT
| | - Debra L Simmons
- VA Salt Lake City Health Care System, Salt Lake City, UT
- Division of Endocrinology and Metabolism, Department of Internal Medicine, University of Utah, Salt Lake City, UT
| | - Alfred K Cheung
- Division of Nephrology and Hypertension, Department of Internal Medicine, University of Utah, Salt Lake City, UT
| | - Yingying Zhang
- Division of Epidemiology, Department of Internal Medicine, University of Utah, Salt Lake City, UT
| | - Michael Doumas
- Washington Veterans Affairs Medical Center, Washington, DC
| | - John Nord
- Division of General Internal Medicine, Department of Internal Medicine, University of Utah, Salt Lake City, UT
| | - Mary Ellen Sweeney
- Division of Endocrinology, Metabolism and Lipids, Emory University School of Medicine, Atlanta, GA
| | - Addison A Taylor
- Michael E. DeBakey VA Medical Center and Baylor College of Medicine, Houston, TX
| | - Charles Herring
- Department of Pharmacy Practice, Campbell University, Buies Creek, NC
| | - William J Kostis
- Division of Cardiovascular Disease and Hypertension, Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ
| | - James Powell
- Division of General Internal Medicine, Brody School of Medicine, East Carolina University, Greenville, NC
| | - Anjay Rastogi
- Division of Nephrology, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA
| | - Christianne L Roumie
- VA Tennessee Valley Healthcare System Geriatrics Research Education Clinical Center, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN
| | - Alan Wiggers
- Department of Medicine, CWRU School of Medicine, Cleveland, OH
| | - Jonathan S Williams
- Division of Endocrinology, Diabetes, and Hypertension, Brigham and Women's Hospital, and Harvard Medical School, and VA Boston Healthcare Systems, Boston, MA
| | - Reem Yunis
- Department of Medicine, Stanford University, Palo Alto, CA
| | - Athena Zias
- Northport VA Medical Center, Northport, NY
- Stony Brook University School of Medicine, Stony Brook, NY
| | - Greg W Evans
- Department of Biostatistical Sciences, Wake Forest School of Medicine, Winston-Salem, NC
| | - Tom Greene
- Division of Epidemiology, Department of Internal Medicine, University of Utah, Salt Lake City, UT
- Division of Epidemiology, Department of Internal Medicine, University of Utah, Salt Lake City, UT
| | - Michael V Rocco
- Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, NC
| | - William C Cushman
- Preventive Medicine Section, Veterans Affairs Medical Center, Memphis, TN
| | - David M Reboussin
- Department of Biostatistical Sciences, Wake Forest School of Medicine, Winston-Salem, NC
| | - Mark N Feinglos
- Department of Medicine, Duke University School of Medicine, Durham, NC
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