Association of endothelial dysfunction with incident prediabetes, type 2 diabetes and related traits: the KORA F4/FF4 study

IntroductionPeripheral arterial tonometry (PAT) is an operator-independent and non-invasive measurement method to assess microvascular endothelial function in the fingertips. PAT-derived measures of endothelial function were associated with type 2 diabetes in cross-sectional studies. However, longitudinal studies are lacking. The study aims to investigate the association of two PAT-derived endothelial function parameters reactive hyperemia index (RHI) and mean baseline amplitude (MBA) with follow-up glucose and insulin parameters and the development of (pre)diabetes and type 2 diabetes.Research design and methodsThe study included 673 participants initially without diabetes (328 men and 345 women) aged 52–71 years from the prospective population-based Cooperative Health Research in the Region of Augsburg F4/FF4 cohort study conducted in Southern Germany (baseline examination F4: 2006–2008; follow-up FF4: 2013–2014). An oral glucose tolerance test was performed at baseline and follow-up to define type 2 diabetes, prediabetes, fasting glucose, fasting insulin, 2-hour glucose, homeostasis model assessment of insulin resistance (HOMA-IR), homeostasis model assessment of beta-cell function and hemoglobin A1c.ResultsIn multivariable adjusted logistic/linear regression models, a 1 SD increase in baseline RHI was inversely associated with incident type 2 diabetes (OR 0.69 (95% CI 0.48 to 0.97)) as well as with fasting insulin (β −0.069 (95% CI −0.131 to −0.007)) and HOMA-IR (β −0.072 (95% CI −0.133 to −0.010)) at follow-up in participants with initial normoglycemia. A 1 SD increase in baseline MBA was positively associated with incident (pre)diabetes (OR 1.62 (95% CI 1.25 to 2.11)) and fasting glucose (β 0.096 (95% CI 0.047 to 0.146)) at follow-up in participants with initial normoglycemia.ConclusionsMicrovascular endothelial dysfunction seems to be involved in the development of early derangements in glucose metabolism and insulin resistance and could thereby trigger the development of prediabetes and type 2 diabetes.

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Homeostasis Model Assessment Is a Reliable Indicator of Insulin Resistance During Follow-up of Patients With Type 2 Diabetes

Diabetes Care ◽

10.2337/diacare.24.2.362 ◽

2001 ◽

Vol 24 (2) ◽

pp. 362-365 ◽

Cited By ~ 221

Author(s):

A. Katsuki ◽

Y. Sumida ◽

E. C. Gabazza ◽

S. Murashima ◽

M. Furuta ◽

...

Keyword(s):

Insulin Resistance ◽

Type 2 Diabetes ◽

Reliable Indicator ◽

Model Assessment ◽

Homeostasis Model Assessment

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The Effect of Laparoscopic Gastric Bypass Surgery on Insulin Resistance and Glycosylated Hemoglobin A1c: a 2-Year Follow-up Study

Obesity Surgery ◽

10.1007/s11695-020-04599-w ◽

2020 ◽

Vol 30 (9) ◽

pp. 3489-3495

Author(s):

Erik Stenberg ◽

Eva Rask ◽

Eva Szabo ◽

Ingmar Näslund ◽

Johan Ottosson

Keyword(s):

Insulin Resistance ◽

Type 2 Diabetes ◽

Gastric Bypass ◽

Bypass Surgery ◽

Gastric Bypass Surgery ◽

Glycosylated Hemoglobin ◽

Model Assessment ◽

Fasting Insulin

Abstract Background Bariatric surgery improves insulin sensitivity and secretion in patients with type 2 diabetes, but the effect on patients with prediabetes or even normal glucose tolerance deserves further consideration. Methods Cohort study including patients operated with laparoscopic Roux-en-Y gastric bypass surgery (LRYGB) between November 2012 and June 2017 at the Örebro University Hospital (n = 813) with follow-up of 742 patients 2 years after surgery. Fasting insulin, glucose, glycosylated hemoglobin (HbA1c), and homeostatic model assessment of insulin resistance (HOMA-IR) were analyzed at baseline and 2 years after surgery for patients with overt type 2 diabetes, prediabetes, or non-diabetes. Results Fasting insulin levels improved for all groups (diabetics baseline 25.5 mIU/L, IQR 17.5–38.0, 2 years 7.6 mIU/L, IQR 5.4–11.1, p < 0.001; prediabetics baseline 25.0 mIU/L, IQR 17.5–35.0, 2 years 6.7mIU/L, IQR 5.3–8.8, p < 0.001; non-diabetics baseline 20.0 mIU/L, IQR 14.0–30.0, 2 years 6.4 mIU/L, IQR 5.0–8.5, p < 0.001). HbA1c improved in all groups (diabetics baseline 56 mmol/mol, IQR 49–74 [7.3%, IQP 6.6–8.9], 2 years 38 mmol/mol, IQR 36–47 [5.6%, IQR 5.4–6.4], p < 0.001; prediabetics baseline 40 mmol/mol, IQR 39–42 [5.8%, IQR5.7–6.0], 2 years 36 mmol/mol, IQR 34–38 [5.5%, IQR 5.3–5.6], p < 0.001; non-diabetics baseline 35 mmol/mol, IQR 33–37 [5.4%, IQR 5.2–5.5]; 2 years 34 mmol/mol, IQR 31–36 [5.3%, IQR 5.0–5.4], p < 0.001). HOMA-IR improved in all groups (diabetics baseline 9.3 mmol/mol, IQR 5.4–12.9, 2 years 1.9 mmol/mol, IQR 1.4–2.7, p < 0.001; prediabetics baseline 7.0 mmol/mol, IQR 4.3–9.9, 2 years 1.6 mmol/mol, IQR 1.2–2.1, p < 0.001; non-diabetics 4.9 mmol/mol, IQR 3.4–7.3, 2 years 1.4 mmol/mol, IQR 1.1–1.9, p < 0.001). Conclusion Insulin homeostasis and glucometabolic control improve in all patients after LRYGB, not only in diabetics but also in prediabetics and non-diabetic obese patients, and this improvement is sustained 2 years after surgery.

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Magnesium intake, insulin resistance and markers of endothelial function among women

Public Health Nutrition ◽

10.1017/s1368980021001063 ◽

2021 ◽

pp. 1-9

Author(s):

Narges Ghorbani Bavani ◽

Parvane Saneei ◽

Ammar Hassanzadeh Keshteli ◽

Ahmadreza Yazdannik ◽

Ebrahim Falahi ◽

...

Keyword(s):

Insulin Resistance ◽

Insulin Sensitivity ◽

Endothelial Dysfunction ◽

Endothelial Function ◽

Adhesion Molecule ◽

Cell Function ◽

Intercellular Adhesion Molecule ◽

Model Assessment ◽

Serum Concentrations ◽

Homeostasis Model Assessment

Abstract Objective: We investigated the association of dietary Mg intake with insulin resistance and markers of endothelial function among Iranian women. Design: A cross-sectional study. Setting: Usual dietary intakes were assessed using a validated FFQ. Dietary Mg intake was calculated by summing up the amount of Mg in all foods. A fasting blood sample was taken to measure serum concentrations of glycemic indices (fasting plasma glucose and insulin) and endothelial function markers (E-selectin, soluble intercellular adhesion molecule-1 (sICAM-1) and soluble vascular cell adhesion molecule-1). Insulin resistance and sensitivity were estimated using the Homeostasis Model Assessment-Insulin Resistance (HOMA-IR), Homeostasis Model Assessment β-cell function (HOMA-β) and quantitative insulin sensitivity check index (QUICKI). Participants: Iranian female nurses (n 345) selected by a multistage cluster random sampling method. Results: The Mg intake across energy-adjusted quartiles was 205 (se 7), 221·4 (se 8), 254·3 (se 7) and 355·2 (se 9) mg/d, respectively. After adjustments for potential confounders, QUICKI level was significantly different across quartiles of Mg intake (Q1: 0·34 (se 0·02), Q2: 0·36 (se 0·01), Q3: 0·40 (se 0·01), and Q4: 0·39 (se 0·02), P = 0·02); however, this association disappeared after considering markers of endothelial function, indicating that this relation might be mediated through endothelial dysfunction. After controlling for all potential confounders, Mg intake was inversely, but not significantly, associated with serum concentrations of sICAM (Q1: 239 (se 17), Q2: 214 (se 12), Q3: 196 (se 12), and Q4: 195 (se 17), P = 0·29). There was no other significant association between dietary Mg intake and other indicators of glucose homoeostasis or endothelial markers. Conclusions: Higher dietary Mg intake was associated with better insulin sensitivity in Iranian females. This linkage was mediated through reduced endothelial dysfunction.

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Decreased Plasma Maresin 1 Concentration Is Associated with Diabetic Foot Ulcer

Mediators of Inflammation ◽

10.1155/2020/4539035 ◽

2020 ◽

Vol 2020 ◽

pp. 1-7 ◽

Cited By ~ 1

Author(s):

Tian Miao ◽

Bangliang Huang ◽

Niexia He ◽

Lihua Sun ◽

Guangsheng Du ◽

...

Keyword(s):

Insulin Resistance ◽

Blood Pressure ◽

Type 2 Diabetes ◽

Insulin Secretion ◽

Diabetic Foot ◽

Foot Ulcer ◽

Diabetic Foot Ulcer ◽

Model Assessment ◽

Homeostasis Model Assessment

Aims. To assess the maresin 1 (MaR1) contents in type 2 diabetic patients with or without diabetic foot ulcer and to analyze the association of MaR1 concentrations with several metabolism-related parameters. Methods. Plasma MaR1 concentrations were analyzed in 96 subjects with normal glucose tolerant (NC, n=43), type 2 diabetes (T2DM, n=40), or diabetic foot ulcer (DFU, n=13). The intravenous glucose tolerance test (IVGTT) and biochemical parameters were measured in all participants. Results. Plasma MaR1 concentrations were significant decreased in type 2 diabetes patient with or without DFU compared with NC (both P<0.001) and were lowest in DFU patients among these 3 groups. (DFU vs. T2DM, P<0.05). Plasma MaR1 concentrations were negatively correlated with BMI, waist circumference (Wc), waist hip ratio (WHR), systolic blood pressure (SBP), diastolic blood pressure (DBP), LDL-c, FPG, 2hPG, HbA1c, and homeostasis model assessment for insulin resistance (HOMA-IR) (all P<0.05) and were positively correlated with HDL-c, acute insulin response (AIR), area under the curve of the first-phase (0-10 min) insulin secretion (AUC), and homeostasis model assessment for beta-cell function (HOMA-β) (all P<0.05). After adjusting for age and sex, Wc, WHR, TG, FPG, 2hPG, HbA1c, HOMA-IR, AIR, AUC, and HOMA-β remain statistically significant (all P<0.05). Conclusions. Plasma MaR1 concentration were decreased in T2DM with or without DFUs and were the lowest in DFU patients. The decreased plasma MaR1 strongly associated with obesity, impaired glucose and lipid metabolism, reduced first-phase of glucose-stimulated insulin secretion, and enhanced insulin resistance.

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Legume consumption and its association with fasting glucose, insulin resistance and type 2 diabetes in the Indian Migration Study

Public Health Nutrition ◽

10.1017/s1368980016001233 ◽

2016 ◽

Vol 19 (16) ◽

pp. 3017-3026 ◽

Cited By ~ 8

Author(s):

Preet K Dhillon ◽

Liza Bowen ◽

Sanjay Kinra ◽

Ankalmadugu Venkatsubbareddy Bharathi ◽

Sutapa Agrawal ◽

...

Keyword(s):

Physical Activity ◽

Insulin Resistance ◽

Type 2 Diabetes ◽

Large Scale ◽

Fasting Glucose ◽

Epidemiological Studies ◽

Model Assessment ◽

Dietary Intakes ◽

Migration Status

AbstractObjectiveLegume consumption is associated with lower fasting glucose (FG) and insulin levels in nutrition trials and lower CVD mortality in large-scale epidemiological studies. In India, legumes are widely consumed in various preparations, yet no epidemiological study has evaluated the association of legumes with FG levels, insulin resistance and diabetes risk. The present study aimed to fill this gap.DesignFasting blood samples, in-person interviews to obtain information on demographic/socio-economic factors, physical activity, alcohol and tobacco use, and anthropometric measurements were collected. Dietary intakes were assessed by an interviewer-administered, validated, semi-quantitative FFQ.SettingLucknow, Nagpur, Hyderabad and Bangalore, India.SubjectsMen and women (n 6367) aged 15–76 years – urban residents, urban migrants and their rural siblings.ResultsIn multivariate random-effects models adjusted for age, BMI, total energy intake, macronutrients, physical activity and rural/migration status, daily legume consumption was not associated with FG (P-for-trend=0·78), insulin resistance (homeostasis model assessment score; P-for-trend=0·73) or the prevalence of type 2 diabetes mellitus (P-for-trend=0·41). Stratified analyses by vegetarian diet and migration status did not change the findings. Inverse associations between legumes and FG emerged for participants with lower BMI and higher carbohydrate, protein, fat and sugar intakes.ConclusionsAlthough legumes are essential in traditional Indian diets, as well as in prudent and Mediterranean diets in the West, we did not find an association between legumes and markers of glycaemic control, insulin resistance or diabetes, except for subgroups based on BMI and macronutrient intake. The ubiquitous presence and complexity of legume preparations in Indian diets may contribute to these findings.

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Homeostasis Model Assessment of Insulin Resistance and Survival in Patients With Diabetes and Acute Coronary Syndrome

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2017-02772 ◽

2018 ◽

Vol 103 (7) ◽

pp. 2522-2533 ◽

Cited By ~ 2

Author(s):

Barbara E Stähli ◽

Anna Nozza ◽

Ilse C Schrieks ◽

John B Buse ◽

Klas Malmberg ◽

...

Keyword(s):

Insulin Resistance ◽

Type 2 Diabetes ◽

Acute Coronary Syndrome ◽

Cardiovascular Events ◽

Major Adverse Cardiovascular Events ◽

Model Assessment ◽

Homeostasis Model Assessment ◽

Risk Of Death ◽

Coronary Syndrome

Abstract Objective Insulin resistance has been linked to development and progression of atherosclerosis and is present in most patients with type 2 diabetes. Whether the degree of insulin resistance predicts adverse outcomes in patients with type 2 diabetes and acute coronary syndrome (ACS) is uncertain. Design The Effect of Aleglitazar on Cardiovascular Outcomes after Acute Coronary Syndrome in Patients with Type 2 Diabetes Mellitus trial compared the peroxisome proliferator-activated receptor-α/γ agonist aleglitazar with placebo in patients with type 2 diabetes and recent ACS. In participants not treated with insulin, we determined whether baseline homeostasis model assessment of insulin resistance (HOMA-IR; n = 4303) or the change in HOMA-IR on assigned study treatment (n = 3568) was related to the risk of death or major adverse cardiovascular events (cardiovascular death, myocardial infarction, and stroke) in unadjusted and adjusted models. Because an inverse association of HOMA-IR with N-terminal pro-B-type natriuretic peptide (NT-proBNP) has been described, we specifically examined effects of adjustment for the latter. Results In unadjusted analysis, twofold higher baseline HOMA-IR was associated with lower risk of death [hazard ratio (HR): 0.79, 95% CI: 0.68 to 0.91, P = 0.002]. Adjustment for 24 standard demographic and clinical variables had minimal effect on this association. However, after further adjustment for NT-proBNP, the association of HOMA-IR with death was no longer present (adjusted HR: 0.99, 95% CI: 0.83 to 1.19, P = 0.94). Baseline HOMA-IR was not associated with major adverse cardiovascular events, nor was the change in HOMA-IR on study treatment associated with death or major adverse cardiovascular events. Conclusions After accounting for levels of NT-proBNP, insulin resistance assessed by HOMA-IR is not related to the risk of death or major adverse cardiovascular events in patients with type 2 diabetes and ACS.

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Glycolysis/gluconeogenesis- and tricarboxylic acid cycle–related metabolites, Mediterranean diet, and type 2 diabetes

American Journal of Clinical Nutrition ◽

10.1093/ajcn/nqaa016 ◽

2020 ◽

Vol 111 (4) ◽

pp. 835-844 ◽

Cited By ~ 3

Author(s):

Marta Guasch-Ferré ◽

José L Santos ◽

Miguel A Martínez-González ◽

Clary B Clish ◽

Cristina Razquin ◽

...

Keyword(s):

Insulin Resistance ◽

Type 2 Diabetes ◽

Relative Risk ◽

Mediterranean Diet ◽

Tca Cycle ◽

Tricarboxylic Acid ◽

Model Assessment ◽

Weighted Score

ABSTRACT Background Glycolysis/gluconeogenesis and tricarboxylic acid (TCA) cycle metabolites have been associated with type 2 diabetes (T2D). However, the associations of these metabolites with T2D incidence and the potential effect of dietary interventions remain unclear. Objectives We aimed to evaluate the association of baseline and 1-y changes in glycolysis/gluconeogenesis and TCA cycle metabolites with insulin resistance and T2D incidence, and the potential modifying effect of Mediterranean diet (MedDiet) interventions. Methods We included 251 incident T2D cases and 638 noncases in a nested case-cohort study within the PREDIMED Study during median follow-up of 3.8 y. Participants were allocated to MedDiet + extra-virgin olive oil, MedDiet + nuts, or control diet. Plasma metabolites were measured using a targeted approach by LC–tandem MS. We tested the associations of baseline and 1-y changes in glycolysis/gluconeogenesis and TCA cycle metabolites with subsequent T2D risk using weighted Cox regression models and adjusting for potential confounders. We designed a weighted score combining all these metabolites and applying the leave-one-out cross-validation approach. Results Baseline circulating concentrations of hexose monophosphate, pyruvate, lactate, alanine, glycerol-3 phosphate, and isocitrate were significantly associated with higher T2D risk (17–44% higher risk for each 1-SD increment). The weighted score including all metabolites was associated with a 30% (95% CI: 1.12, 1.51) higher relative risk of T2D for each 1-SD increment. Baseline lactate and alanine were associated with baseline and 1-y changes of homeostasis model assessment of insulin resistance. One-year increases in most metabolites and in the weighted score were associated with higher relative risk of T2D after 1 y of follow-up. Lower risks were observed in the MedDiet groups than in the control group although no significant interactions were found after adjusting for multiple comparisons. Conclusions We identified a panel of glycolysis/gluconeogenesis-related metabolites that was significantly associated with T2D risk in a Mediterranean population at high cardiovascular disease risk. A MedDiet could counteract the detrimental effects of these metabolites. This trial was registered at controlled-trials.com as ISRCTN35739639.

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Homeostasis model assessment of insulin resistance for evaluating insulin sensitivity in patients with type 2 diabetes on insulin therapy

Endocrine Journal ◽

10.1507/endocrj.ej12-0320 ◽

2013 ◽

Vol 60 (3) ◽

pp. 283-290 ◽

Cited By ~ 35

Author(s):

Kohei Okita ◽

Hiromi Iwahashi ◽

Junji Kozawa ◽

Yukiyoshi Okauchi ◽

Tohru Funahashi ◽

...

Keyword(s):

Insulin Resistance ◽

Type 2 Diabetes ◽

Insulin Sensitivity ◽

Insulin Therapy ◽

Model Assessment ◽

Homeostasis Model Assessment

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Correlation between Blood Activin Levels and Clinical Parameters of Type 2 Diabetes

Experimental Diabetes Research ◽

10.1155/2012/410579 ◽

2012 ◽

Vol 2012 ◽

pp. 1-9 ◽

Cited By ~ 10

Author(s):

Hui Wu ◽

Michael Wu ◽

Yi Chen ◽

Carolyn A. Allan ◽

David J. Phillips ◽

...

Keyword(s):

Insulin Resistance ◽

Type 2 Diabetes ◽

Glucose Tolerance ◽

Fasting Glucose ◽

Serum Levels ◽

Activin A ◽

Oral Glucose ◽

Clinical Parameters ◽

Model Assessment

Aims. Activins A and B, and their binding protein, follistatin, regulate glucose metabolism and inflammation. Consequently, their role in type 2 diabetes (T2D) was examined.Methods. Blood was taken from fasted participants (34 males; 58 females; 50–75 years) with diabetes or during an oral glucose tolerance test (OGTT). Clinical parameters were assessed, and blood assayed for activins, follistatin, and C-reactive protein.Results. Serum levels of activin A (93.3 ± 27.0 pg/mL, mean ± SD), B (81.8 ± 30.8 pg/mL), or follistatin (6.52 ± 3.15 ng/mL) were not different (P>0.05) between subjects with normal OGTT (n=39), impaired glucose tolerance and/or fasting glucose (n=17), or T2D (n=36). However, activin A and/or activin B were positively correlated with parameters of insulin resistance and T2D, including fasting glucose (P<0.001), fasting insulin (P=0.02), glycated hemoglobin (P=0.003), and homeostasis model assessment of insulin resistance (HOMA-IR;P<0.001). Follistatin was positively correlated with HOMA-IR alone (P=0.01).Conclusions. These data indicate that serum measurements of activin A, B, or follistatin cannot discriminate risk for T2D in individual patients, but the activins display a positive relationship with clinical parameters of the disease.

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Endothelial dysfunction and inflammatory biomarkers as a response factor of concurrent coenzyme Q10 add-on metformin in patients with type 2 diabetes mellitus

Journal of Laboratory Physicians ◽

10.4103/jlp.jlp_123_19 ◽

2019 ◽

Vol 11 (04) ◽

pp. 317-322

Author(s):

Hayder M. Al-Kuraishy ◽

Ali I. Al-Gareeb ◽

Hala A. Shams ◽

Farah Al-Mamorri

Keyword(s):

Diabetes Mellitus ◽

Insulin Resistance ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Endothelial Dysfunction ◽

Coenzyme Q10 ◽

Healthy Subjects ◽

Model Assessment ◽

Inflammatory Changes

Abstract OBJECTIVES: The objective of the study was to evaluate the effect of metformin alone or in combination with coenzyme Q10 (CoQ10) on inflammatory changes and endothelial dysfunction in patients with type 2 diabetes mellitus (T2DM). MATERIALS AND METHODS: A total numbers of 54 patients with T2DM compared to 30 healthy subjects were divided into three groups: Group A (n = 30): healthy subjects without any medications; Group B (n = 24): T2DM patients treated with metformin 1 g/day; and Group C (n = 30): T2DM patients treated with metformin 1 g/day plus CoQ10, 300 mg/day. The duration of the study was 8 weeks. Fasting blood glucose, glycated hemoglobin, lipid profile, blood pressure variables, fasting insulin, insulin resistance, homeostatic model assessment of insulin resistance, vascular cell adhesion molecule 1 (VCAM-1), and E-selectin were measured before and after therapy. RESULTS: Metformin and/or CoQ10 therapy illustrated an insignificant effect on the fody mass index. This combination produced a significant improvement of metabolic changes in patients with T2DM (P < 0.01). sVCAM-1 serum level was decreased significantly after the initiation of metformin and/or CoQ10 therapy compared to the baseline P < 0.05. E-selectin was declined significantly following metformin monotherapy and after metformin plus CoQ10 therapy (P = 0.0001). CONCLUSION: CoQ10 add-on metformin therapy improves endothelial dysfunction and inflammatory changes in patients with T2DM alongside with amelioration of metabolic profile.

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