Incidence of type 2 diabetes in familial combined hyperlipidemia

ObjectiveFamilial combined hyperlipidemia (FCHL) is common among survivors of a premature myocardial infarction. FCHL patients are characterized by visceral obesity, fatty liver, and insulin resistance. The aim of the present study was to determine the incidence and determinants of type 2 diabetes (T2D) in a longitudinal cohort of FCHL pedigrees.Research design and methodsFCHL patients, their unaffected relatives and spouses included in our baseline cohort in 1998–2005 (n=596) were re-invited to determine the incidence of self-reported T2D (that was confirmed by medical records), used as the primary outcome measure. The Fatty Liver Index (FLI) and Homeostasis Model Assessment Insulin Resistance (HOMA2-IR) were used as markers of fatty liver and insulin resistance, respectively. A subset of the original cohort underwent ultrasound of the liver, and subcutaneous and visceral fat in 2002–2005 (n=275; ‘ultrasound subcohort’).ResultsFollow-up data (median: 15 years) was acquired for 76%. The incidence rate of T2D was significantly higher in FCHL patients compared with spouses (19.2 per 1000 person-years vs 2.8 per 1000 person-years; HR : 6.3, 95% CI: 2.4 to 16.8), whereas no differences were observed between unaffected relatives and spouses (HR: 0.9, 95% CI: 0.3 to 2.6). Cox’s proportional hazard regression analyses showed that baseline HOMA2-IR and FLI≥60, but not waist circumference, BMI, or the FCHL affected state, were independently associated with incident T2D. Similar results were obtained in the ultrasound subcohort (median follow-up: 11 years), in which baseline HOMA2-IR and fatty liver (assessed by ultrasound) were independently associated with incident T2D.ConclusionThis study further corroborates the suggestion that the liver plays a central role in the pathogenesis of cardiometabolic complications in FCHL. It supports periodical screening for T2D in this high-risk population.

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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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A Follow-up Study on BMI-SDS and Insulin Resistance in Overweight and Obese Children at Risk for Type 2 Diabetes Mellitus

Global Pediatric Health ◽

10.1177/2333794x14568451 ◽

2015 ◽

Vol 2 ◽

pp. 2333794X1456845 ◽

Cited By ~ 1

Author(s):

Soulmaz Fazeli Farsani ◽

Marloes P. van der Aa ◽

Catherijne A. J. Knibbe ◽

Anthonius de Boer ◽

Marja M. J. van der Vorst

Keyword(s):

Diabetes Mellitus ◽

Insulin Resistance ◽

Type 2 Diabetes ◽

At Risk ◽

Type 2 Diabetes Mellitus ◽

Model Assessment ◽

Children At Risk ◽

The Mean

Objectives. To evaluate body mass index standard deviation score (BMI-SDS), insulin sensitivity, and progression to type 2 diabetes mellitus (T2DM) in children at risk for T2DM approximately 3 years after being diagnosed with overweight/obesity and insulin resistance (measured by Homeostasis Model Assessment of Insulin Resistance [HOMA-IR]). Methods. Out of 86 invited children, 44 (mean age 15.4 ± 3.6 years) participated. Medical history, physical examination, and laboratory workup were performed. Results. While the mean BMI-SDS significantly increased from 2.9 to 3.4, the mean HOMA-IR significantly decreased from 5.5 to 4.6 (baseline vs follow-up visit). Change in HOMA-IR was only due to a decrease in mean fasting plasma insulin (24.1 vs 21.1, P = .073). Conclusions. Although increase in BMI-SDS in these children is worrisome, the American Diabetes Association recommended screening interval of 3 years for children at risk for T2DM is not too long based on the fact that none of our study participants developed T2DM.

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

BMJ Open Diabetes Research & Care ◽

10.1136/bmjdrc-2020-001321 ◽

2020 ◽

Vol 8 (1) ◽

pp. e001321

Author(s):

Marie-Theres Huemer ◽

Cornelia Huth ◽

Florian Schederecker ◽

Stefanie J Klug ◽

Christa Meisinger ◽

...

Keyword(s):

Insulin Resistance ◽

Type 2 Diabetes ◽

Endothelial Dysfunction ◽

Endothelial Function ◽

Fasting Glucose ◽

Model Assessment ◽

Fasting Insulin ◽

Homeostasis Model Assessment

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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The Effects of Vitamin D Supplementation on Metabolic and Oxidative Stress Markers in Patients With Type 2 Diabetes: A 6-Month Follow Up Randomized Controlled Study

Frontiers in Endocrinology ◽

10.3389/fendo.2021.610893 ◽

2021 ◽

Vol 12 ◽

Author(s):

Milena Cojic ◽

Radivoj Kocic ◽

Aleksandra Klisic ◽

Gordana Kocic

Keyword(s):

Oxidative Stress ◽

Insulin Resistance ◽

Type 2 Diabetes ◽

Vitamin D ◽

Vitamin D Supplementation ◽

Controlled Study ◽

Model Assessment ◽

Endocrine Society

Vitamin D deficiency could play an important role in the pathogenesis of type 2 diabetes mellitus (T2DM) as it may alter several crucial processes in the development of diabetes and its complications, such as pancreatic insulin secretion, peripheral insulin resistance, persistence of systemic „sterile” inflammation and immune activation. Vitamin D may also have an antioxidant effect through the inhibition of free radicals generation. The reported study was designed with eligible consecutively recruited patients with T2DM on standard metformin therapy (n=130), randomized in 1:1 ratio, considered to have undergone Vitamin D supplementation according to the guidelines proposed by the Endocrine Society, or to have continued with metformin only. The potential benefit was monitored through the influence on glycemia level, glycated haemoglobin (HbA1c), insulin resistance index (calculated as homeostatic model assessment; HOMA-IR), Castelli Risk Index I and Tryglicerides/Thiobarbituric acid-reactive substances (TG/TBARS) Index in a 6-month follow up period. Our study indicates that oral daily doses of vitamin D improve HbA1c levels over the 3-month and 6-month period, followed by a significant decrease in advanced oxidation protein products levels over the 3-month period when higher vitamin D doses are given. The effect of vitamin D on HOMA-IR index, malondialdehyde levels and TG/TBARS index was not statistically significant. Further investigation should consider defining the doses of vitamin D in patients with T2DM which may attenuate the oxidative stress risk, the risk of metabolic syndrome and the risk of related cardiovascular events.

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Modelling ethnic differences in the distribution of insulin resistance via Bayesian nonparametric processes: an application to the SABRE cohort study

The International Journal of Biostatistics ◽

10.1515/ijb-2019-0108 ◽

2020 ◽

Vol 0 (0) ◽

Author(s):

Marco Molinari ◽

Maria de Iorio ◽

Nishi Chaturvedi ◽

Alun Hughes ◽

Therese Tillin

Keyword(s):

Insulin Resistance ◽

Type 2 Diabetes ◽

Mcmc Methods ◽

Model Assessment ◽

Bayesian Nonparametric ◽

Nonparametric Prior ◽

Posterior Inference ◽

Regression Framework ◽

Analyse Data

AbstractWe analyse data from the Southall And Brent REvisited (SABRE) tri-ethnic study, where measurements of metabolic and anthropometric variables have been recorded. In particular, we focus on modelling the distribution of insulin resistance which is strongly associated with the development of type 2 diabetes. We propose the use of a Bayesian nonparametric prior to model the distribution of Homeostasis Model Assessment insulin resistance, as it allows for data-driven clustering of the observations. Anthropometric variables and metabolites concentrations are included as covariates in a regression framework. This strategy highlights the presence of sub-populations in the data, characterised by different levels of risk of developing type 2 diabetes across ethnicities. Posterior inference is performed through Markov Chains Monte Carlo (MCMC) methods.

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Elevated circulating follistatin associates with an increased risk of type 2 diabetes

Nature Communications ◽

10.1038/s41467-021-26536-w ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Chuanyan Wu ◽

Yan Borné ◽

Rui Gao ◽

Maykel López Rodriguez ◽

William C. Roell ◽

...

Keyword(s):

Insulin Resistance ◽

Type 2 Diabetes ◽

Adipose Tissue ◽

Genome Wide Association Study ◽

Regulatory Protein ◽

Alcoholic Fatty Liver ◽

Increased Risk

AbstractThe hepatokine follistatin is elevated in patients with type 2 diabetes (T2D) and promotes hyperglycemia in mice. Here we explore the relationship of plasma follistatin levels with incident T2D and mechanisms involved. Adjusted hazard ratio (HR) per standard deviation (SD) increase in follistatin levels for T2D is 1.24 (CI: 1.04–1.47, p < 0.05) during 19-year follow-up (n = 4060, Sweden); and 1.31 (CI: 1.09–1.58, p < 0.01) during 4-year follow-up (n = 883, Finland). High circulating follistatin associates with adipose tissue insulin resistance and non-alcoholic fatty liver disease (n = 210, Germany). In human adipocytes, follistatin dose-dependently increases free fatty acid release. In genome-wide association study (GWAS), variation in the glucokinase regulatory protein gene (GCKR) associates with plasma follistatin levels (n = 4239, Sweden; n = 885, UK, Italy and Sweden) and GCKR regulates follistatin secretion in hepatocytes in vitro. Our findings suggest that GCKR regulates follistatin secretion and that elevated circulating follistatin associates with an increased risk of T2D by inducing adipose tissue insulin resistance.

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Docking protein 1 and free fatty acids are associated with insulin resistance in patients with type 2 diabetes mellitus

Journal of International Medical Research ◽

10.1177/03000605211048293 ◽

2021 ◽

Vol 49 (11) ◽

pp. 030006052110482

Author(s):

Xiaoqin Ha ◽

Xiaoling Cai ◽

Huizhe Cao ◽

Jie Li ◽

Bo Yang ◽

...

Keyword(s):

Diabetes Mellitus ◽

Insulin Resistance ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Effective Means ◽

Model Assessment ◽

High Concentration ◽

Obesity And Diabetes ◽

Docking Protein

Objective Insulin resistance (IR) is a key defect in type 2 diabetes mellitus (T2DM); therefore, effective means of ameliorating IR are sought. Methods We performed a retrospective cohort study of 154 patients with T2DM and 39 with pre-diabetes (pre-DM). The effects of IR and a high concentration of FFA on gene expression were determined using microarray analysis and quantitative reverse transcription polymerase chain reaction (RT-qPCR) in patients with T2DM or pre-DM. Results Serum FFA concentration and homeostasis model assessment of IR (HOMA-IR) were significantly higher in patients with T2DM but no obesity and in those with pre-DM than in controls. HOMA-IR was significantly associated with T2DM. RT-qPCR showed that the expression of FBJ murine osteosarcoma viral oncogene homolog ( FOS) and AE binding protein 1 ( AEBP1) was much lower in the circulation of participants with obesity and diabetes. RT-qPCR showed that the expression of docking protein 1 ( DOK1) was significantly lower in the blood of participants with diabetes but no obesity and in those with pre-DM than in controls. Conclusions FFA and DOK1 are associated with IR in patients with T2DM but no obesity or pre-DM. The downregulation of DOK1 might inhibit lipid synthesis and induce lipolysis, inducing or worsening IR.

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Serum and urinary concentrations of calprotectin as markers of insulin resistance and type 2 diabetes

Acta Endocrinologica ◽

10.1530/eje-12-0374 ◽

2012 ◽

Vol 167 (4) ◽

pp. 569-578 ◽

Cited By ~ 34

Author(s):

Francisco J Ortega ◽

Mónica Sabater ◽

José M Moreno-Navarrete ◽

Neus Pueyo ◽

Patricia Botas ◽

...

Keyword(s):

Insulin Resistance ◽

Type 2 Diabetes ◽

Weight Loss ◽

Lipid Metabolism ◽

Inflammatory Markers ◽

Low Grade ◽

Model Assessment ◽

Glucose And Lipid Metabolism ◽

Obese Subjects

ObjectiveIncreased circulating calprotectin has been reported in obese subjects but not in association with measures of insulin resistance and type 2 diabetes (T2D). The main aim of this study was to determine whether calprotectins in plasma and urine are associated with insulin resistance.DesignWe performed both cross-sectional and longitudinal (diet-induced weight loss) studies.MethodsCirculating calprotectin concentrations (ELISA), other inflammatory markers, homeostasis model assessment of insulin resistance (HOMA-IR), and parameters of glucose and lipid metabolism were evaluated in 298 subjects (185 with normal (NGT) and 62 with impaired (IGT) glucose tolerance and 51 T2D subjects). Calprotectin was also evaluated in urine samples from 71 participants (50 NGT and 21 subjects with IGT). Insulin sensitivity (SI, Minimal Model) was determined in a subset of 156 subjects, and the effects of weight loss were investigated in an independent cohort of obese subjects (n=19).ResultsCirculating calprotectin was significantly increased in IGT–T2D (independently of BMI) and positively associated with HOMA-IR, obesity measures, inflammatory markers, and parameters of glucose and lipid metabolism. Similar findings were reported for calprotectin concentrations in urine. In the subset of subjects, the association of calprotectin withSIwas independent of BMI and age. In fact,SItogether with C-reactive protein contributed to 27.4% of calprotectin variance after controlling for age and blood neutrophils count. Otherwise, weight loss led to decreased circulating calprotectin in parallel to fasting glucose and HOMA-IR.ConclusionThese findings suggest that circulating and urinary concentrations of calprotectin are linked to chronic low-grade inflammation and insulin resistance beyond obesity.

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