scholarly journals Beta-cell failure rather than insulin resistance is the major cause of abnormal glucose tolerance in Africans: insight from the Africans in America study

2021 ◽  
Vol 9 (1) ◽  
pp. e002447
Author(s):  
M C Sage Ishimwe ◽  
Annemarie Wentzel ◽  
Elyssa M Shoup ◽  
Nana H Osei-Tutu ◽  
Thomas Hormenu ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Particle Size ◽  
Glucose Tolerance ◽  
Beta Cell ◽  
Density Lipoprotein ◽  
Model Assessment ◽  
Abnormal Glucose Tolerance ◽  
Β Cell ◽  
Beta Cell Failure ◽  
Matsuda Index

IntroductionUncertainties exist on whether the main determinant of abnormal glucose tolerance (Abnl-GT) in Africans is β-cell failure or insulin resistance (IR). Therefore, we determined the prevalence, phenotype and characteristics of Abnl-GT due to β-cell failure versus IR in 486 African-born blacks (male: 64%, age: 38±10 years (mean±SD)) living in America.Research design and methodsOral glucose tolerance test were performed. Abnl-GT is a term which includes both diabetes and prediabetes and was defined as fasting plasma glucose (FPG) ≥5.6 mmol/L and/or 2-hour glucose ≥7.8 mmol/L. IR was defined by the lowest quartile of the Matsuda Index (≤2.98) and retested using the upper quartile of homeostatic model assessment of insulin resistance (HOMA-IR) (≥2.07). Abnl-GT-IR required both Abnl-GT and IR. Abnl-GT-β-cell failure was defined as Abnl-GT without IR. Beta-cell compensation was assessed by the Disposition Index (DI). Fasting lipids were measured. Visceral adipose tissue (VAT) volume was obtained with abdominal CT scan.ResultsThe prevalence of Abnl-GT was 37% (182/486). For participants with Abnl-GT, IR occurred in 38% (69/182) and β-cell failure in 62% (113/182). Compared with Africans with Abnl-GT-IR, Africans with Abnl-GT-β-cell failure had lower body mass index (BMI) (30.8±4.3 vs 27.4±4.0 kg/m2), a lower prevalence of obesity (52% vs 19%), less VAT (163±72 vs 107±63 cm2), lower triglyceride (1.21±0.60 vs 0.85±0.42 mmol/L) and lower FPG (5.9±1.4 vs 5.3±0.6 mmol/L) and 2-hour glucose concentrations (10.0±3.1 vs 9.0±1.9 mmol/L) (all p<0.001) and higher DI, high-density lipoprotein (HDL), low-density lipoprotein particle size and HDL particle size (all p<0.01). Analyses with Matsuda Index and HOMA-IR yielded similar results. Potential confounders such as income, education, alcohol and fiber intake did not differ by group.ConclusionsBeta-cell failure occurred in two-thirds of participants with Abnl-GT and may be a more frequent determinant of Abnl-GT in Africans than IR. As BMI category, degree of glycemia and lipid profile appeared more favorable when Abnl-GT was due to β-cell failure rather than IR, the clinical course and optimal interventions may differ.Trial registration numberNCT00001853.

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

2019 ◽  
Vol 39 (10) ◽  
pp. 2192-2197 ◽  
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.

scholarly journals The Role ofHelicobacter pyloriSeropositivity in Insulin Sensitivity, Beta Cell Function, and Abnormal Glucose Tolerance

Scientifica ◽  
2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Lou Rose Malamug ◽  
Rudruidee Karnchanasorn ◽  
Raynald Samoa ◽  
Ken C. Chiu
Keyword(s):  
Insulin Resistance ◽  
Risk Factor ◽  
Glucose Tolerance ◽  
Beta Cell ◽  
Beta Cell Function ◽  
Cell Function ◽  
Model Assessment ◽  
Abnormal Glucose Tolerance ◽  
Significant Difference ◽  
H Pylori

Infection, for example,Helicobacter pylori(H. pylori), has been thought to play a role in the pathogenesis of type 2 diabetes mellitus (T2DM). Our aim was to determine the role ofH. pyloriinfection in glucose metabolism in an American cohort. We examined data from 4,136 non-Hispanic white (NHW), non-Hispanic black (NHB), and Mexican Americans (MA) aged 18 and over from the NHANES 1999-2000 cohort. We calculated the odds ratios for states of glucose tolerance based on theH. pyloristatus. We calculated and compared homeostatic model assessment insulin resistance (HOMA-IR) and beta cell function (HOMA-B) in subjects without diabetes based on theH. pyloristatus. The results were adjusted for age, body mass index (BMI), poverty index, education, alcohol consumption, tobacco use, and physical activity. TheH. pyloristatus was not a risk factor for abnormal glucose tolerance. After adjustment for age and BMI and also adjustment for all covariates, no difference was found in either HOMA-IR or HOMA-B in all ethnic and gender groups except for a marginally significant difference in HOMA-IR in NHB females.H. pyloriinfection was not a risk factor for abnormal glucose tolerance, nor plays a major role in insulin resistance or beta cell dysfunction.

scholarly journals PPARαAgonist Fenofibrate Reduced the Secreting Load ofβ-Cells in Hypertriglyceridemia Patients with Normal Glucose Tolerance

PPAR Research ◽  
2016 ◽  
Vol 2016 ◽  
pp. 1-7
Author(s):  
Jia Liu ◽  
Rui Lu ◽  
Ying Wang ◽  
Yanjin Hu ◽  
Yumei Jia ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Glucose Tolerance ◽  
Cell Function ◽  
Density Lipoprotein ◽  
Normal Glucose Tolerance ◽  
Model Assessment ◽  
Homeostasis Model Assessment ◽  
Cell Dysfunction ◽  
Fenofibrate Treatment ◽  
Normal Glucose

Hypertriglyceridemia is an important risk factor associated with insulin resistance andβ-cell dysfunction. This study investigated the effects of hypertriglyceridemia and fenofibrate treatment on insulin sensitivity andβ-cell function in subjects with normal glucose tolerance. A total of 1974 subjects with normal glucose tolerance were divided into the normal TG group (NTG group,n=1302) and hypertriglyceridemia group (HTG group,n=672). Next, 92 patients selected randomly from 672 patients with hypertriglyceridemia were assigned to a 24-week fenofibrate treatment. The HTG group had increased waist circumference (WC), body mass index (BMI), homeostasis model assessment of insulin resistance (HOMA-IR), and homeostasis model assessment ofβ-cell function (HOMA-β) and decreased high-density lipoprotein cholesterol (HDL-C) compared with the NTG group (allP<0.01). The 24-week fenofibrate treatment significantly decreased the WC, BMI, TG, HOMA-IR, and HOMA-βlevels and increased the HDL-C levels in the patients with hypertriglyceridemia (WC, BMI, and HOMA-IR:P<0.05; TG, HDL-C, and HOMA-β:P<0.01). The fenofibrate treatment significantly alleviated insulin resistance and reduced the secreting load ofβ-cells in the hypertriglyceridemia patients with normal glucose tolerance.

Large birth size, infancy growth pattern, insulin resistance and β-cell function

2021 ◽  
Author(s):  
Rong Huang ◽  
Yu Dong ◽  
Anne Monique Nuyt ◽  
Emile Levy ◽  
Shu-Qin Wei ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Beta Cell ◽  
Gestational Age ◽  
Growth Pattern ◽  
Beta Cell Function ◽  
Cell Function ◽  
Birth Size ◽  
Model Assessment ◽  
Β Cell ◽  
Β Cell Function

Objective: Large birth size programs an elevated risk of type 2 diabetes in adulthood, but data are absent concerning glucose metabolic health impact in infancy. We sought to determine whether large birth size is associated with insulin resistance and β-cell function in infancy, and evaluate the determinants. Design and Participants: In the Canadian 3D birth cohort, we conducted a nested matched (1:2) study of 70 large-for-gestational-age (LGA, birth weight >90th percentile) and 140 optimal-for-gestational-age (OGA, 25th-75th percentiles) control infants. The primary outcomes were homeostasis model assessment of insulin resistance (HOMA-IR) and beta-cell function (HOMA-β) at age 2-years. Results: HOMA-IR and HOMA-β were similar in LGA and OGA infants. Adjusting for maternal and infant characteristics, decelerated growth in length during early infancy (0-3 months) was associated a 25.8% decrease (95% confidence intervals 6.7-41.0%) in HOMA-β. During mid-infancy (3-12 months), accelerated growth in weight was associated with a 25.5% (0.35-56.9%) increase in HOMA-IR, in length with a 69.3% increase (31.4-118.0%) in HOMA-IR and a 24.5% (0.52-54.3%) increase in HOMA-β. Decelerated growth in length during late infancy (1-2 years) was associated with a 28.4% (9.5-43.4%) decrease in HOMA-IR and a 21.2% (3.9-35.4%) decrease in HOMA-β. Female sex was associated with higher HOMA-β, Caucasian ethnicity with lower HOMA-IR, and maternal smoking with lower HOMA-β. Conclusions: The study is the first to demonstrate that large birth size is not associated with insulin resistance and β-cell function in infancy, but infancy growth pattern matters. Decelerated infancy growth may be detrimental to beta-cell function.

scholarly journals Type 2 diabetes and impaired glucose tolerance in European children and adolescents with obesity -- a problem that is no longer restricted to minority groups

2004 ◽  
pp. 199-206 ◽  
Author(s):  
S Wiegand ◽  
U Maikowski ◽  
O Blankenstein ◽  
H Biebermann ◽  
P Tarnow ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Glucose Tolerance ◽  
Impaired Glucose Tolerance ◽  
Children And Adolescents ◽  
Fasting Glucose ◽  
Sensitivity Index ◽  
Model Assessment ◽  
Abnormal Glucose Tolerance

BACKGROUND: The incidence of childhood obesity and type 2 diabetes is an increasing problem in Europe. We determined the prevalence of impaired glucose regulation in a predominantly Caucasian cohort of 491 children and adolescents with obesity. METHODS: Fasting glucose and insulin levels were determined in all 491 subjects. Patients with an abnormal fasting glucose or with additional risk factors (positive family history of type 2 diabetes, acanthosis nigricans, hyperlipidemia; n=102) underwent an oral glucose tolerance test (OGTT; 1.75 g glucose/kg body weight). Homeostasis model assessment was used to estimate insulin resistance in all subjects. The insulin sensitivity index was determined in those subjects who underwent an OGTT. Screening for mutations in the melanocortin 4 receptor (MC4R) gene and the coding region of the brain-derived neutrophic factor (BDNF) in 37 patients with an impaired glucose tolerance was performed by WAVE analysis. RESULTS: Out of the total of 491 patients, 12 had an abnormal fasting glucose level. Of the 102 patients who underwent an OGTT, 37 had impaired glucose tolerance; 6 out of the 102 patients were diagnosed with type 2 diabetes. Eighty-eight per cent of patients with abnormal glucose tolerance and 66% of patients with type 2 diabetes were Caucasian. Insulin resistance indices correlated well with the degree of abnormal glucose tolerance. Using the screening algorithm for type 2 diabetes as advocated by the American Diabetes Association, 68% of patients with impaired glucose tolerance and 66% of patients with type 2 diabetes would have been missed. No abnormalities in the MC4R and BDNF genes were detected. CONCLUSIONS: Impaired glucose tolerance and type 2 diabetes are far more common in obese European children of Caucasian origin than previously thought. Using fasting glucose levels as the main screening tool appears to be insufficient in detecting these children.

scholarly journals Impaired Suppression of Glucagon in Obese Subjects Parallels Decline in Insulin Sensitivity and Beta-Cell Function

2021 ◽  
Author(s):  
Xi Chen ◽  
Enrique Maldonado ◽  
Ralph A DeFronzo ◽  
Devjit Tripathy
Keyword(s):  
Insulin Resistance ◽  
Insulin Sensitivity ◽  
Glucose Tolerance ◽  
Beta Cell ◽  
Beta Cell Function ◽  
Cell Function ◽  
Plasma Glucagon ◽  
Euglycemic Hyperinsulinemic Clamp ◽  
Matsuda Index ◽  
Obese Subjects

Abstract Aim To examine the relationship between plasma glucagon levels and insulin sensitivity and insulin secretion in obese subjects. Methods Suppression of plasma glucagon was examined in 275 obese Hispanic Americans with varying glucose tolerance. All subjects received a 2-hour oral glucose tolerance test (OGTT) and a subset (n = 90) had euglycemic hyperinsulinemic clamp. During OGTT, we quantitated suppression of plasma glucagon concentration, Matsuda index of insulin sensitivity, and insulin secretion/insulin resistance (disposition) index. Plasma glucagon suppression was compared between quartiles of insulin sensitivity and beta-cell function. Results Fasting plasma glucagon levels were similar in obese subjects with normal glucose tolerance (NGT), prediabetes, and type 2 diabetes (T2D), but the fasting glucagon/insulin ratio decreased progressively from NGT to prediabetes to T2D (9.28 ± 0.66 vs 6.84 ± 0.44 vs 5.84 ± 0.43; P &lt; 0.001). Fasting and 2-hour plasma glucagon levels during OGTT progressively increased and correlated positively with severity of insulin resistance (both Matsuda index and euglycemic hyperinsulinemic clamp). The fasting glucagon/insulin ratio declined with worsening insulin sensitivity and beta-cell function, and correlated with whole-body insulin sensitivity (Matsuda index, r = 0.81; P &lt; 0.001) and beta-cell function (r = 0.35; P &lt; 0.001). The glucagon/insulin ratio also correlated and with beta-cell function during OGTT at 60 and 120 minutes (r = −0.47; P &lt; 0.001 and r = −0.32; P &lt; 0.001). Conclusion Insulin-mediated suppression of glucagon secretion in obese subjects is impaired with increasing severity of glucose intolerance and parallels the severity of insulin resistance and beta-cell dysfunction.

Association between insulin resistance and cardinal rheological parameters in young healthy Japanese individuals during 75 g oral glucose tolerance test

2021 ◽  
Vol 21 ◽  
Author(s):  
Larasati Martha ◽  
Takao Kimura ◽  
Akihiro Yoshida ◽  
Katsuhiko Tsunekawa ◽  
Tomoyuki Aoki ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Platelet Count ◽  
Density Lipoprotein ◽  
Tolerance Test ◽  
Rheological Parameters ◽  
Oral Glucose ◽  
Insulinogenic Index ◽  
Model Assessment ◽  
Matsuda Index ◽  
Wbc Count

Background: Insulin resistance is a well-known predictor and risk factor for Type 2 Diabetes Mellitus (T2DM). Higher hematocrit induced by higher insulin resistance affects blood rheology. Objective: This study intended to reveal the association between indices of insulin resistance and hemorheological parameters during a 75 g oral glucose tolerance test (75-g OGTT). Methods: A total of 575 healthy young Japanese participants took 75-g OGTT. We then analyzed the association between insulin resistance indices and hematological parameters. Results: The Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) was significantly correlated with hematocrit (Ht), hemoglobin (Hb), Red Blood Cell (RBC), White Blood Cell (WBC), platelet count, lipid parameters, and Body Mass Index (BMI). The Matsuda index was negatively correlated with RBC count, WBC count, platelet count, Total Cholesterol (TC), Low-Density Lipoprotein-Cholesterol (LDL-C), triglyceride (TG), and positively correlated with High-Density Lipoprotein-Cholesterol (HDL-C). The disposition index was negatively correlated with Hb, RBC count, LDL-C, and BMI, while remaining positively correlated with HDL-C. The Homeostasis Model Assessment of beta cell (HOMA- IR ) was positively correlated with WBC count, platelet count, TC, LDL-C, and TG. The insulinogenic index was positively correlated with WBC count, platelet count, and TC. Multiple regression analysis revealed that HOMA-IR was independently associated with TG, and the Matsuda index was independently associated with TG, WBC count, and platelet count. The insulinogenic index was independently associated with WBC count. Conclusion: Cardinal rheological parameters reflected insulin resistance and were released even in the young, healthy Japanese individuals within the physiological range of glycemic control.

scholarly journals Effects of the long-acting somatostatin analogue Lanreotide Autogel on glucose tolerance and insulin resistance in acromegaly

2006 ◽  
Vol 155 (1) ◽  
pp. 73-78 ◽  
Author(s):  
B Steffin ◽  
B Gutt ◽  
M Bidlingmaier ◽  
C Dieterle ◽  
F Oltmann ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Blood Glucose ◽  
Glucose Tolerance ◽  
Cell Function ◽  
Oral Glucose ◽  
Model Assessment ◽  
Β Cell ◽  
Igf I ◽  
Β Cell Function ◽  
Lanreotide Autogel

Object: Treatment with somatostatin analogues (SA) not only inhibits GH secretion but may also impair insulin secretion. In order to evaluate the influence of SA on glucose metabolism, we investigated insulin resistance (IR) and β-cell function, using the recommended combination of homeostatic model assessment of IR (HOMA-IR) and β-cell function (HOMA-β). Design and methods: This is a prospective, cross-sectional study. We measured fasting insulin, blood glucose and IGF-I. Insulin and blood glucose measurements were taken 120 min after an oral glucose tolerance test with 75 g glucose. We studied 51 patients (27 female/24 male, age 54 years (20–75)). Eighteen patients were on Lanreotide Autogel (LA) treatment, 33 had no medical treatment. GH-levels of more than 2.5 ng/ml was reached by 59% of the patients, 74.5% had normal IGF-I levels. Results: We found no significant influence of disease activity on HOMA-IR and HOMA-β. In the 33 of 51 subjects without any drug treatment, median HOMA-β was 170.4% (36.0–624.0%). In contrast, in the 18 patients on LA treatment, median HOMA-β was found to be significantly lower (84.2% (36.5–346.2%); P = 0.001). Despite this, there was no difference in HOMA-IR in both groups (2.4 (0.7–8.4) vs 2.3 (0.7–6.1); P < 0.001) despite similar insulin values. Conclusion: In conclusion, we found that LA decreases β-cell function significantly without affecting IR. Therefore, we think that insulin secretagogues are probably more effective in the treatment of diabetes mellitus in acromegalic patients on LA therapy than insulin sensitizers.

scholarly journals Cardiac Diastolic Evaluation in Pregnant Women with Abnormal Glucose Tolerance: An Opportunity to Detect the Early and Subclinical Alterations and Prevent Cardiovascular Diseases

2013 ◽  
Vol 2013 ◽  
pp. 1-6 ◽  
Author(s):  
B. Pintaudi ◽  
G. Di Vieste ◽  
F. Corrado ◽  
M. F. Creazzo ◽  
A. Fazio ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Cardiovascular Diseases ◽  
Glucose Tolerance ◽  
Pregnant Women ◽  
Diastolic Function ◽  
Wave Velocity ◽  
Model Assessment ◽  
Abnormal Glucose Tolerance ◽  
Diastolic Velocity ◽  
Increased Risk

Objectives of this study were to assess diastolic function in pregnant women with abnormal glucose tolerance (AGT), compared with normal glucose tolerance (NGT) women, and to evaluate the insulin resistance status and its association with Doppler-echocardiographic indexes. Echocardiograms of 108 consecutive Caucasian women with singleton pregnancies were performed. Insulin resistance status was estimated by the homeostasis model assessment of insulin resistance (HOMA-IR) and the quantitative insulin sensitivity check index (QUICKI). All the studied women showed normal diastolic patterns. Patients with AGT (50.9%), as compared with NGT women, had higher HOMA-IR (1.70±1.30versus1.01±0.81,P=0.003), lower QUICKI (0.36±0.005versus0.40±0.06,P=0.004), higher lateral mitral annulus late diastolic velocity (13.6±4.9versus11.9±4.9,P=0.03), and higher A-wave velocity, the wave responsible for the active atrial contraction component (75.2±14.2versus67.7±16.2,P=0.01). At multivariate regression analysis HOMA-IR was the only parameter associated with A-wave velocity. In conclusion, women with AGT had an increased subclinical diastolic active participation, which is associated with higher levels of insulin resistance. For the increased risk of deterioration of cardiac diastolic function, earlier and more seriously than normal pregnancy, AGT women may have a careful followup to detect the early signs of cardiac alteration and to prevent cardiovascular diseases.

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