Measurement and Correlation of Indices of Insulin Resistance in Patients on Peritoneal Dialysis

BackgroundInsulin resistance (IR) is common in maintenance dialysis patients and is associated with excess mortality. Hyperinsulinemic euglycemic glucose clamp (HEGC) is the gold standard for measuring IR. There are limited studies using HEGC for comparison to other indirect indices of IR in peritoneal dialysis (PD) patients, nor have there been direct comparisons between patients receiving PD and those on maintenance hemodialysis (MHD) with regard to severity of IR, methods of measurement, or factors associated with the development of IR.MethodsThis is a cross-sectional, single-center study performed in 10 prevalent PD patients of median age 48 years (range 41 – 54); 50% were female and 60% were African American. Insulin resistance was assessed by HEGC (glucose disposal rate [GDR]), homeostatic model assessment of IR (HOMA-IR), HOMA-IR corrected by adiponectin (HOMA-AD), leptin adiponectin ratio (LAR), quantitative insulin sensitivity check index (QUICKI), McAuley's index, and oral glucose tolerance test (OGTT) at each time point for a total of 18 studies. Retrospective analysis compared this cohort to 12 hemodialysis patients who had previously undergone similar testing.ResultsThe median GDR was 6.4 mg/kg/min (interquartile range [IQR] 6.0, 7.8) in the PD cohort compared with the MHD group, which was 5.7 mg/kg/min (IQR 4.3, 6.6). For both the PD and MHD cohorts, the best predictors of GDR by HEGC after adjusting for age, gender, and body mass index (BMI), were HOMA-AD (PD: r = -0.69, p = 0.01; MHD: r = -0.78, p = 0.03) and LAR (PD: r = -0.68, p < 0.001; MHD: r = -0.65, p = 0.04). In both groups, HOMA-IR and QUICKI failed to have strong predictive value. Eight of 10 PD patients had at least 1 abnormal OGTT, demonstrating impaired glucose tolerance.ConclusionsInsulin resistance is highly prevalent in PD patients. The adipokine based formulas, HOMA-AD and LAR, correlated well in both the PD and MHD populations in predicting GDR by HEGC, outperforming HOMA-IR. The use of these novel markers could be considered for large-scale, epidemiological outcome studies.

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Decreased Circulating MANF in Women with PCOS is Elevated by Metformin Therapy and is Inversely Correlated with Insulin Resistance and Hyperandrogenism

Hormone and Metabolic Research ◽

10.1055/a-1082-1080 ◽

2020 ◽

Vol 52 (02) ◽

pp. 109-116

Author(s):

Jie Wei ◽

Cong Wang ◽

Gangyi Yang ◽

Yanjun Jia ◽

Yang Li ◽

...

Keyword(s):

Insulin Resistance ◽

Glucose Tolerance ◽

Neurotrophic Factor ◽

Tolerance Test ◽

Oral Glucose ◽

Model Assessment ◽

Metformin Treatment ◽

Fat Percentage ◽

Cross Sectional ◽

Metformin Therapy

AbstractMesencephalic astrocyte-derived neurotrophic factor (MANF) is a novel neurotrophic factor. Although recent studies have suggested that MANF appeared to be associated with insulin resistance, the results have been inconsistent. The aim of our study was to determine the serum MANF levels in women with PCOS and controls, to investigate their relationship to insulin resistance, and to evaluate circulating MANF changes with metformin intervention in PCOS women. We conducted a series of cross-sectional and interventional studies in 90 newly diagnosed patients with PCOS and 60 age- and gender-matched controls. Oral glucose tolerance test and euglycemic-hyperinsulinemic clamps were performed to assess the glucose tolerance and insulin sensitivity. Forty-three women with PCOS were randomly assigned to six months of oral metformin therapy. Serum MANF levels were significantly lower in women with PCOS than in controls. Serum MANF levels were positively correlated with M-value and negatively correlated with body mass index (BMI), body fat percentage (FAT), homeostatic model assessment of insulin resistance (HOMA-IR), and free androgen index (FAI). Multivariate stepwise regression demonstrated that serum MANF levels were independently associated with M-value and FAI. After six months of metformin treatment, there was a significant increase in serum MANF levels in PCOS women. Serum MANF levels are decreased in women with PCOS, and are reversely related to insulin resistance and hyperandrogenism. Metformin treatment elevates serum MANF levels and alleviates insulin resistance and hyperandrogenism in PCOS women.

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The “Lipid Accumulation Product” Is Associated with 2-Hour Postload Glucose Outcomes in Overweight/Obese Subjects with Nondiabetic Fasting Glucose

International Journal of Endocrinology ◽

10.1155/2015/836941 ◽

2015 ◽

Vol 2015 ◽

pp. 1-8 ◽

Cited By ~ 4

Author(s):

Alexis Elias Malavazos ◽

Emanuele Cereda ◽

Federica Ermetici ◽

Riccardo Caccialanza ◽

Silvia Briganti ◽

...

Keyword(s):

Insulin Resistance ◽

Glucose Tolerance ◽

Lipid Accumulation ◽

Fasting Glucose ◽

Tolerance Test ◽

Continuous Variable ◽

Oral Glucose ◽

Model Assessment ◽

Lipid Accumulation Product ◽

Adult Age

“Lipid accumulation product” (LAP) is a continuous variable based on waist circumference and triglyceride concentration previously associated with insulin resistance. We investigated the accuracy of LAP in identifying oral glucose tolerance test (OGTT) abnormalities and compared it to the homeostasis model assessment of insulin resistance (HOMA-IR) in a population of overweight/obese outpatients presenting with nondiabetic fasting glucose. We studied 381 (male: 23%) adult (age: 18–70 years) overweight/obese Caucasians (body mass index: 36.9 ± 5.4 Kg/m2) having fasting plasma glucose < 7.0 mmol/L. OGTT was used to diagnose unknown glucose tolerance abnormalities: impaired glucose tolerance (IGT) and type-2 diabetes mellitus (T2-DM). According to OGTT 92, subjects had an IGT and 33 were diagnosed T2-DM. Logistic regression analysis detected a significant association for both LAP and HOMA-IR with single (IGT and T2-DM) and composite (IGT + T2-DM) abnormal glucose tolerance conditions. However, while the association with diabetes was similar between LAP and HOMA-IR, the relationship with IGT and composite outcomes by models including LAP was significantly superior to those including HOMA-IR (P=0.006andP=0.007, resp.). LAP seems to be an accurate index, performing better than HOMA-IR, for identifying 2-hour postload OGTT outcomes in overweight/obese patients with nondiabetic fasting glucose.

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Abdominal adiposity and insulin resistance in obese men

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00469.2001 ◽

2002 ◽

Vol 282 (3) ◽

pp. E657-E663 ◽

Cited By ~ 159

Author(s):

Robert Ross ◽

James Aru ◽

Jennifer Freeman ◽

Robert Hudson ◽

Ian Janssen

Keyword(s):

Insulin Resistance ◽

Glucose Tolerance ◽

Tolerance Test ◽

Cardiovascular Fitness ◽

Glucose Disposal ◽

Oral Glucose ◽

Lower Glucose ◽

Strong Correlate ◽

Metabolic Variable ◽

Magnetic Resonance Imaging Mri

We examined the independent relationships among various visceral and abdominal subcutaneous adipose tissue (AT) depots, glucose tolerance, and insulin sensitivity in 89 obese men. Measurements included an oral glucose tolerance test (OGTT), glucose disposal by euglycemic clamp, and abdominal and nonabdominal (e.g., peripheral) AT by magnetic resonance imaging (MRI). OGTT glucose and glucose disposal rates were related ( P < 0.05) to visceral AT ( r = 0.50 and −0.41, respectively). These observations remained significant ( P < 0.05) after control for nonabdominal and abdominal subcutaneous AT, and maximal O2 consumption (V˙o 2 max). Abdominal subcutaneous AT was not a significant correlate ( P > 0.05) of any metabolic variable after control for nonabdominal and visceral AT andV˙o 2 max. Division of abdominal subcutaneous AT into deep and superficial depots and visceral AT into intra- and extraperitoneal AT depots did not alter the observed relationships. Further analysis matched two groups of men for abdominal subcutaneous AT but also for low and high visceral AT. Men with high visceral AT had higher OGTT glucose values and lower glucose disposal rates compared with those with low visceral AT values ( P < 0.05). A similar analysis performed on two groups of men matched for visceral AT but also for high and low abdominal subcutaneous AT revealed no statistically different values for any metabolic variable ( P > 0.10). In conclusion, visceral AT alone is a strong correlate of insulin resistance independent of nonabdominal and abdominal subcutaneous AT and cardiovascular fitness. Subdivision of visceral and abdominal subcutaneous AT by MRI did not provide additional insight into the relationship between abdominal obesity and metabolic risk in obese men.

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Insulin Resistance Diagnosed by HOMA-IR may be Overestimated in Adults with Greater Fat-Free Mass: The ELSA-Brasil Study

10.21203/rs.3.rs-16471/v1 ◽

2020 ◽

Author(s):

Divanei Zaniqueli ◽

Rafael de Oliveira Alvim ◽

Rosane Harter Griep ◽

Isabela Martins Benseñor ◽

Sandhi Maria Barreto ◽

...

Keyword(s):

Insulin Resistance ◽

Body Fat ◽

Bioelectrical Impedance ◽

Tolerance Test ◽

Fat Free Mass ◽

Percent Body Fat ◽

Oral Glucose ◽

Model Assessment ◽

Fasting Insulin ◽

Cross Sectional

Abstract Background Conflicting results have been reported on the association of fat-free mass (FFM) and insulin resistance (IR). The way of indexing FFM may be a bias. This study sought to test the association of FFM and IR after indexing FFM to avoid collinearity. Methods This cross-sectional study comprised 11,284 volunteers, ages 38-79 years. Body composition was assessed by multi-frequency bioelectrical impedance. FFM indexed to body surface area (FFMbsa) was calculated. Excess body fat was assigned to individuals with percent body fat ≥ 85th percentile for age and sex. Fasting insulin and glucose, and 2h glucose in the oral glucose tolerance test were obtained. Homeostasis model assessment-insulin resistance (HOMA-IR) > 3.0 was set as the cut-off for IR.Results Percent body fat decreased from the 1st to the 5th quintile of FFMbsa in both women (Eta 2 = 0.166) and men (Eta 2 = 0.133). In women, fasting insulin (Eta 2 = 0.002), glucose (Eta 2 = 0.006), and HOMA-IR (Eta 2 = 0.007) increased slightly, whereas 2h glucose did not change towards the highest quintile of FFMbsa. In men, fasting insulin and HOMA-IR were similar across the quintiles of FFMbsa, whereas fasting glucose increased slightly (Eta 2 = 0.002) and 2h glucose decreased (Eta 2 = 0.005) towards the highest quintile of FFMbsa. Greater FFMbsa explained 1.8% of the odds of IR among women and 0.9% among men.Conclusion The lack of association of FFM and 2h glucose contrasted with greater odds of IR (by HOMA-IR) associated with greater FFM. The association of greater FFM and IR may be overestimated when the diagnosis is provided by HOMA-IR.

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Lifetime congenital isolated GH deficiency does not protect from the development of diabetes

Endocrine Connections ◽

10.1530/ec-13-0014 ◽

2013 ◽

Vol 2 (2) ◽

pp. 112-117 ◽

Cited By ~ 10

Author(s):

Taísa A R Vicente ◽

Ívina E S Rocha ◽

Roberto Salvatori ◽

Carla R P Oliveira ◽

Rossana M C Pereira ◽

...

Keyword(s):

Glucose Tolerance ◽

Cell Function ◽

Gh Deficiency ◽

Receptor Gene ◽

Area Under The Curve ◽

Tolerance Test ◽

Oral Glucose ◽

Insulinogenic Index ◽

Model Assessment ◽

Cross Sectional

ObjectivesAdult subjects with untreated, lifetime, isolated GH deficiency (IGHD) due to a homozygous GHRH receptor gene mutation (MUT/MUT) residing in Itabaianinha, Brazil, present with lower BMI, higher prevalence of impaired glucose tolerance (IGT), increased insulin sensitivity (IS), and reduced β-cell function (βCF) when compared with non-BMI-matched homozygous normal controls. However, the prevalence of diabetes mellitus (DM) in this cohort is unknown. Comparing their IS and βCF with BMI-matched individuals heterozygous for the same mutation (MUT/N) may be useful to elucidate the role of the GH–IGF1 axis in IS and βCF. The purposes of this work were to verify the prevalence of IGT and DM in adult MUT/MUT subjects from this kindred and to compare IS and βCF in MUT/MUT and MUT/N.DesignCross-sectional study.MethodsWe studied most (51) of the living IGHD adults of this kindred who are GH naive. The oral glucose tolerance test (OGTT) could be performed in 34 subjects, fasting glucose was measured in 15, while two had a previous diagnosis of DM. The OGTT results of 24 MUT/MUT subjects were compared with those of 25 BMI-matched MUT/N subjects. IS was assessed by homeostatic model assessment of insulin resistance (HOMA–IR), quantitative IS check index, and oral glucose IS index for 2 and 3 h. βCF was assayed by HOMA-β, insulinogenic index, and the area under the curve of insulin:glucose ratio.ResultsThe prevalence of DM and IGT in IGHD was 15.68 and 38.23% respectively. IS was increased and βCF was reduced in MUT/MUT in comparison with MUT/N.ConclusionsLifetime, untreated IGHD increases IS, impairs βCF, and does not provide protection from diabetes.

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Serum apoA1 (Apolipoprotein A-1), Insulin Resistance, and the Risk of Gestational Diabetes Mellitus in Human Pregnancy—Brief Report

Arteriosclerosis Thrombosis and Vascular Biology ◽

10.1161/atvbaha.119.313195 ◽

2019 ◽

Vol 39 (10) ◽

pp. 2192-2197 ◽

Cited By ~ 2

Author(s):

Ravi Retnakaran ◽

Chang Ye ◽

Philip W. Connelly ◽

Anthony J. Hanley ◽

Mathew Sermer ◽

...

Keyword(s):

Insulin Resistance ◽

Glucose Tolerance ◽

Cell Function ◽

Density Lipoprotein ◽

Tolerance Test ◽

Oral Glucose ◽

Model Assessment ◽

Human Pregnancy ◽

Matsuda Index ◽

Β Cell Function

Objective: apoA1 (apolipoprotein A-1) is the main lipoprotein associated with HDL (high-density lipoprotein) cholesterol. It was recently reported that intravenous infusion of apoA1 could lower insulin resistance in pregnant rats, leading to the suggestion that apoA1 could provide a target for reducing pregnancy-induced insulin resistance and the risk of gestational diabetes mellitus (GDM) in humans. However, the effects of apoA1 on insulin resistance and risk of GDM in human pregnancy are not known. Thus, we sought to systematically evaluate the relationships of apoA1 with glucose homeostasis and metabolic function in pregnant women. Approach and Results: In this study, 870 pregnant women were recruited in late second trimester and underwent metabolic characterization, including an oral glucose tolerance test on which 214 were diagnosed with GDM. Metabolic characterization included assessment of glucose tolerance, insulin sensitivity/resistance (Matsuda index, homeostasis model assessment of insulin resistance), pancreatic β-cell function, lipids (LDL [low-density lipoprotein] cholesterol, HDL cholesterol, triglycerides, apoB [apolipoprotein B], and apoA1), CRP (C-reactive protein), and adiponectin. Serum apoA1 was strongly correlated with HDL (r=0.79, P <0.0001) and weakly so with adiponectin (r=0.12, P =0.0004) but showed no association with measures of insulin sensitivity/resistance, β-cell function, glycemia, or CRP. There were no significant differences across apoA1 tertiles in mean adjusted Matsuda index ( P =0.24), homeostasis model assessment of insulin resistance ( P =0.08), or area under the glucose curve on the oral glucose tolerance test ( P =0.96). Moreover, there were no differences in risk of GDM across tertiles of apoA1, both before ( P =0.67) and after covariate adjustment ( P =0.78). Conclusions: Serum apoA1 is not associated with insulin resistance or the risk of GDM in human pregnancy.

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Regional and Overall Aortic Function In Nondiabetic Individuals With Insulin Resistance and Normal Glucose Tolerance

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2013-2276 ◽

2013 ◽

Vol 98 (11) ◽

pp. 4457-4463 ◽

Cited By ~ 2

Author(s):

Dimitrios A. Stakos ◽

Konstantinos D. Boudoulas ◽

Trudy R. Gaillard ◽

Dara P. Schuster ◽

Kwame Osei ◽

...

Keyword(s):

Insulin Resistance ◽

Glucose Tolerance ◽

Vascular Function ◽

Glucose Tolerance Test ◽

Tolerance Test ◽

Stiffness Index ◽

Oral Glucose ◽

Sensitivity Index ◽

Cross Sectional ◽

Over Time

Context: Insulin resistance is associated with altered vascular function in diabetes. Objective: The objective of the study was to define the overall and regional aortic function as well as the changes of aortic function over time in nondiabetic individuals with insulin resistance and a normal oral glucose tolerance test (OGTT). Design: This was a cross-sectional and longitudinal analysis with 12 months follow-up. Setting: The setting of the study was in primary care. Patients: Nondiabetic individuals (n = 181, mean age 42 ± 8 y) with a normal OGTT and insulin resistance as defined by the insulin sensitivity index (ISI) participated in the study. Interventions: ISI was estimated from serial measurements of plasma insulin and glucose during an iv glucose tolerance test. Ascending and abdominal aortic distensibility (AoD) and stiffness index-β (AoSI) were assessed using echocardiography. Carotid-to-femoral artery pulse wave velocity (PWVc-f; an index of overall aortic function) was measured from carotid and femoral arteries Doppler flow velocities recorded simultaneously with an electrocardiogram. Associations between ISI, AoD, AoSI, and PWVc-f were assessed using linear regression analyses and ANOVA. Differences between baseline and 12 months were compared using a paired t test. Main Outcome Measures: AoD and AoSI associations as well as changes over a 12-month period in relation to ISI were measured. Results: Ascending AoD (P = .01) and ascending AoSI (P = .025) were significantly associated with ISI; in contrast, abdominal AoD and AoSI and PWVc-f did not. Changes in AoD, AoSI, and PWVc-f over time were more prominent in individuals with low ISI compared with those with high ISI. Conclusions: The significant associations between ISI and aortic function suggest that insulin resistance may affect the cardiovascular system, even when OGTT is normal.

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Visceral adiposity and liver fat as mediators of the association between cardiorespiratory fitness and plasma glucose-insulin homeostasis

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00251.2020 ◽

2020 ◽

Vol 319 (3) ◽

pp. E548-E556

Author(s):

Dominic J. Chartrand ◽

Eric Larose ◽

Paul Poirier ◽

Patrick Mathieu ◽

Natalie Alméras ◽

...

Keyword(s):

Insulin Resistance ◽

Glucose Tolerance ◽

Cardiorespiratory Fitness ◽

Plasma Glucose ◽

Tolerance Test ◽

Liver Fat ◽

Oral Glucose ◽

Model Assessment ◽

Insulin Levels ◽

Insulin Homeostasis

Cardiorespiratory fitness (CRF) is positively associated with insulin sensitivity, whereas excessive levels of visceral adipose tissue (AT) and liver fat (LF) are both associated with insulin resistance and impaired plasma glucose-insulin homeostasis. To what extent levels of visceral AT and LF content contribute to the relationship between CRF and indices of plasma glucose-insulin homeostasis is uncertain. Our objective was to explore the interactions among CRF, visceral AT, and LF with glucose tolerance/insulin levels in asymptomatic and apparently healthy individuals. CRF was measured in 135 women and 177 men with a maximal treadmill graded exercise test. Indices of plasma glucose-insulin homeostasis were derived from a 3-h oral glucose tolerance test (OGTT) performed in the morning after a 12-h fast. Visceral AT levels and LF content were measured using magnetic resonance imaging and spectroscopy. For any given CRF level, women presented significantly lower visceral AT and LF than men as well as lower homeostasis model assessment of insulin resistance (HOMA-IR) and plasma glucose-insulin levels during the OGTT compared with men. In both sexes, there were significant negative correlations between CRF and HOMA-IR as well as glucose and insulin levels measured during the OGTT. Both glucose and insulin levels during the OGTT correlated positively with visceral AT and LF. In women and men, being in the top CRF tertile was associated with low levels of visceral AT and LF. Multivariable linear regression analyses suggested that visceral AT and LF were plausible mediators of the association between CRF and indices of plasma glucose-insulin homeostasis.

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Changes in glucose tolerance after pancreatectomy in patients with pancreatic ductal adenocarcinoma.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.4_suppl.668 ◽

2020 ◽

Vol 38 (4_suppl) ◽

pp. 668-668

Author(s):

Sachiyo Shirakawa ◽

Hirochika Toyama ◽

Shohei Komatsu ◽

Jun Ishida ◽

Masahiro Kido ◽

...

Keyword(s):

Insulin Resistance ◽

Glucose Tolerance ◽

Pancreatic Ductal Adenocarcinoma ◽

Plasma Glucose ◽

Tolerance Test ◽

Ductal Adenocarcinoma ◽

Oral Glucose ◽

Significant Prognostic Factor ◽

Model Assessment ◽

Glucagon Test

668 Background: Diabetes mellitus (DM) is reported to be related to pancreatic ductal adenocarcinoma (PDAC). Long-standing DM is a risk factor for PDAC, meanwhile, quite a few patients with PDAC develop DM as a paraneoplastic disorder and some papers reported that DM affected prognosis for PDAC. In this study, we investigated pre- and post-operative glucose tolerance in patients with pancreatectomy for PDAC or other disease. Methods: This single-center prospective study included 69 patients with pancreatectomy (40 pancreaticoduodenectomy (PD) and 29 distal pancreatectomy (DP) ) who received 75-g oral glucose tolerance test (OGTT) and glucagon test pre- and one month postoperatively. Plasma glucose, insulin, and C-peptide (CPR) at 0-, 30-, 60-, and 120-min during OGTT; and 0- and 6-min during glucagon test were obtained. These data and survival outcomes were analyzed. Results: There were 20 (29%) PDAC patients: 12 (30%) in PD group and eight (28%) in DP group. Nine patients with PDAC (45%) and seven patients (18%) without PDAC demonstrated DM type in preoperative OGTT. After pancreatectomy, 11 patients (55%) with PDAC and seven patients (15%) without PDAC experienced improvement in OGTT (P=0.0005). Greater improvement in homeostasis model assessment insulin resistance that were obtained by OGTT and used to measure insulin resistance, was noted after surgery in PDAC patients compared with non-PDAC patients (-1.4 vs -0.5 in PD group, P=0.07; -0.8 vs +0.06 P=0.05 in DP group). Delta CPRs obtained by glucagon test were significantly decreased postoperatively (3.0 to 1.1 ng/mL, P<0.0001 in PD group; 3.3 to 1.8 ng/mL, P<0.0001 in DP group). In survival analysis, fasting plasma glucose >110 mg/dL (HR 3.9, 95%CI 1.5-10, P=0.005) and the average of plasma insulin > 25 µIU/mL during OGTT (HR 0.36, 95%CI 0.14-0.93, P=0.035) were significant prognostic factor for PDAC. Conclusions: Pancreatectomy impaired insulin secretion and improve insulin resistance especially in PDAC patients. About half of PDAC patients demonstrated the improvement of glucose tolerance after surgery. Of note, glucose tolerance differed between PDAC and other disease, and affect the survival outcome for PDAC patients.

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