HDL Containing Apolipoprotein C-III is Associated with Insulin Sensitivity: a Multi-Center Cohort Study

Author(s):  
Rain Yamamoto ◽  
Majken K Jensen ◽  
Sarah Aroner ◽  
Jeremy D Furtado ◽  
Bernard Rosner ◽  
...  

Abstract Context HDL in humans is composed of a heterogeneous group of particles varying in protein composition as well as biological effects. Objective We investigated the prospective associations between HDL subspecies containing and lacking apoC-III at baseline and insulin sensitivity at year 3. Design, Setting, and Participants A prospective cohort study of 864 healthy volunteers drawn from the RISC study, a multi-center European clinical investigation, whose recruitment initiated in 2002 with a follow-up of 3 years. Main Measures Insulin sensitivity was estimated from an oral glucose tolerance test (OGTT) at baseline and year 3, and by euglycemic-hyperinsulinemic clamp at baseline only. The apolipoprotein concentrations were measured at baseline by a sandwich ELISA-based method. Results The two HDL subspecies demonstrated significantly opposite associations with insulin sensitivity at year 3 (p-heterogeneity=0.004). The highest quintile of HDL containing apoC-III was associated with a 1.2% reduction in insulin sensitivity (p-trend=0.02), while the highest quintile of HDL lacking apoC-III was associated with a 1.3% increase (p-trend=0.01), compared to the lowest quintile. No significant association was observed for total HDL, and VLDL and LDL containing apoC-III. ApoC-III contained in HDL was associated with a decrease in insulin sensitivity even more strongly than plasma total apoC-III. Conclusion Both HDL containing apoC-III and apoC-III in HDL adversely affect the beneficial properties of HDL on insulin response to glucose. Our results support the potential of HDL-associated apoC-III as a promising target for diabetes prevention and treatment.

2021 ◽  
pp. 1-12
Author(s):  
Tetyana Chaychenko ◽  
Jesús Argente ◽  
Bessie E. Spiliotis ◽  
Martin Wabitsch ◽  
Claude Marcus

<b><i>Introduction:</i></b> The obesity epidemic has become one of the most important public health issues of modern times. Impaired insulin sensitivity seems to be the cornerstone of multiple obesity related comorbidities. However, there is no accepted definition of impaired insulin sensitivity. <b><i>Objective:</i></b> We hypothesize that assessment of insulin resistance differs between centers. <b><i>Methods:</i></b> The ESPE Obesity Working Group (ESPE ObWG) Scientific Committee developed a questionnaire with a focus on the routine practices of assessment of hyperinsulinemia and insulin resistance, which was distributed through Google Docs platform to the clinicians and researchers from the current ESPE ObWG database (<i>n</i> = 73). Sixty-one complete responses (84% response rate) from clinicians and researchers were analyzed: 32 from European Union (EU) centers (representatives of 14 countries) and 29 from Non-EU centers (representatives from 10 countries). Standard statistics were used for the data analysis. <b><i>Results:</i></b> The majority of respondents considered insulin resistance (IR) as a clinical tool (85.2%) rather than a research instrument. For the purpose of IR assessment EU specialists prefer analysis of the oral glucose tolerance test (OGTT) results, whereas non-EU ones mainly use Homeostatic Model Assessment of Insulin Resistance (HOMA-IR; <i>p</i> = 0.032). There was no exact cutoff for the HOMA-IR in either EU or non-EU centers. A variety of OGTT time points and substances measured per local protocol were reported. Clinicians normally analyzed blood glucose (88.52% of centers) and insulin (67.21%, mainly in EU centers, <i>p</i> = 0.0051). Furthermore, most participants (70.5%) considered OGTT insulin levels as a more sensitive parameter of IR than glucose. Meanwhile, approximately two-thirds (63.9%) of the centers did not use any cutoffs for the insulin response to the glucose load. <b><i>Conclusions:</i></b> Since there is no standard for the IR evaluation and uniform accepted indication of performing, an OGTT the assessment of insulin sensitivity varies between EU and non-EU centers. A widely accepted standardized protocol is needed to allow comparison between centers.


1983 ◽  
Vol 104 (1) ◽  
pp. 77-84 ◽  
Author(s):  
A. Wajngot ◽  
R. Luft ◽  
S. Efendić

Abstract. Oral and iv glucose tolerance, insulin response to iv and oral glucose load as well as insulin sensitivity were evaluated in 58 'low insulin responders'. They were selected from a group of 226 healthy subjects with normal fasting blood glucose and normal iv glucose tolerance test on the basis of a low insulin response during a standardized glucose infusion test (GIT). The insulin response to GIT was analysed by parameter identification in a mathematical model (parameter KI). Insulin sensitivity was also measured by computer analysis of GIT (parameter KG) and, in a limited group of subjects, by a somatostatin infusion test. Thirty-three low insulin responders had normal OGTT, whereas 5 demonstrated borderline-1, 16 borderline-2, and 4 decreased OGTT. The first group of subjects demonstrated normal or enhanced insulin sensitivity. Borderline and decreased OGTT, in most instances, was accompanied by decreased insulin sensitivity, implying that a subgroup of low insulin responders exhibited signs of both impaired insulin response to glucose and insulin resistance. Since these defects characterize manifest type-2 diabetes, these subjects possibly may run a high risk to develop this type of diabetes. On the other hand, low insulin response in combination with increased insulin sensitivity may reflect adaptation of the secretory capacity of B-cells to the need of insulin.


2010 ◽  
Vol 95 (8) ◽  
pp. 4048-4051 ◽  
Author(s):  
Rebecca E. Hasson ◽  
Tanja C. Adam ◽  
Jaimie N. Davis ◽  
Marc J. Weigensberg ◽  
Emily E. Ventura ◽  
...  

Introduction: African-American children have a greater acute insulin response to iv glucose (AIR) compared with Latino children despite a similar degree of insulin resistance and body composition. It is unclear whether African-Americans demonstrate an exaggerated insulin response to an oral glucose challenge and whether any differences are seen in more obese children in advanced pubertal development. Purpose: Our objective was to compare glucose and insulin indices derived from an oral glucose tolerance test (OGTT) and iv glucose tolerance test (IVGTT) in sedentary, obese African-American (n = 59) and Latino (n = 83) adolescents. Methods: Glucose and insulin incremental area under the curve was measured during an OGTT, and AIR, insulin sensitivity, disposition index, and glucose effectiveness were assessed during an IVGTT. Body composition was assessed via dual-energy x-ray absorptiometry and magnetic resonance imaging. Results: From the OGTT, glucose and insulin IAUC were 29.1 and 22.5% lower (P = 0.01) in African-Americans compared with Latino adolescents. From the IVGTT, insulin sensitivity and glucose effectiveness were 41.7% (P &lt; 0.01) and 50.0% (P = 0.02) lower in African-Americans compared to Latinos. AIR (P = 0.001) and disposition index (P = 0.02) were 63.0 and 48.8% higher in African-Americans, respectively, compared with Latinos. These findings persisted after controlling for body composition and fat distribution. Conclusions: There were marked differences in glucose and insulin indices derived from the OGTT and IVGTT. African-Americans were more insulin resistant as measured by the IVGTT compared with the Latino adolescents. However, the well-described hyperinsulinemia in response to iv glucose was not observed after oral glucose in African-American adolescents.


Nutrients ◽  
2019 ◽  
Vol 11 (12) ◽  
pp. 2876 ◽  
Author(s):  
Patrick M. Solverson ◽  
Theresa R. Henderson ◽  
Hawi Debelo ◽  
Mario G. Ferruzzi ◽  
David J. Baer ◽  
...  

Evidence supports the beneficial effects of berries on glucoregulation, possibly related to flavonoid content, fiber content, or both. The purpose of this study was to assess the potential of mixed berries to improve insulin sensitivity and to identify the potential role of flavonoids and fiber. In a randomized cross-over trial with four treatment periods, overweight/obese men and women were fed a controlled 45% fat diet for one week prior to a meal-based glucose tolerance test. The same base diet was provided during each feeding period with the addition of one of four treatments: whole mixed berries, sugar matched mixed berry juice, sugar matched gelatin, and sugar/fiber matched gelatin. Subjects then completed a meal-based oral glucose tolerance test. Serum glucose, insulin and non-esterified fatty acids were not different between individual treatments. However, in a secondary analysis, the combined berry preparations resulted in a lower serum insulin area under the curve (difference of 0.15 ± 0.066 ln pmol min/mL, mean ± SE, p = 0.0228), compared to the combined gelatin treatments, while the difference for serum glucose did not quite meet statistical significance (difference of 0.17 ± 0.093 ln mg·min/dL, mean ± SE, p = 0.0738). These results suggest the potential for mixed berry preparations to improve post-prandial insulin response.


2010 ◽  
Vol 2010 ◽  
pp. 1-7 ◽  
Author(s):  
Yi-Chyan Chen ◽  
Wei-Win Lin ◽  
Yu-Jung Chen ◽  
Wei-Chung Mao ◽  
Yi-Jen Hung

Growing evidence suggests that mood disorder is associated with insulin resistance and inflammation. Thus the effects of antidepressants on insulin sensitivity and proinflammatory responses will be a crucial issue for depression treatment. In this study, we enrolled 43 non-diabetic young depressed males and adapted standard testing procedures to assess glucose metabolism during 4-week hospitalization. Before and after the 4-week antidepressant treatment, participants underwent oral glucose tolerance test (OGTT) and frequently sampled intravenous glucose tolerance test (FSIGT). Insulin sensitivity (SI), glucose effectiveness (SG), acute insulin response, and disposition index (DI) were estimated using the minimal model method. The plasma levels of C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor-α(TNF-α), and adiponectin were measured. The Hamilton depression rating scale (HAM-D) total scores were reduced significantly during the course of treatment. There were no significant changes in the parameters ofSI,SG, and DI. Compared to drug naïve status, the level of plasma IL-6 was significantly elevated (0.77to1.30 pg/ml;P=.001) after antidepressant therapy. However, the concentrations of CRP, TNF-α, and adiponectin showed no differences during the course of treatment. The results suggest that antidepressants may promote stimulatory effect on the IL-6 production in the early stage of antidepressant treatment.


1985 ◽  
Vol 59 (1) ◽  
pp. 154-159 ◽  
Author(s):  
J. L. Ivy ◽  
B. A. Frishberg ◽  
S. W. Farrell ◽  
W. J. Miller ◽  
W. M. Sherman

The effects of an exercise-induced muscle glycogen reduction and an elevated muscle glycogen concentration on glucose tolerance and the insulin response to an oral glucose tolerance test (GTT) were examined. GTTs were administered to seven male subjects after 3 days on a mixed diet (C), after exhaustive exercise and 1 day on a high-fat protein diet (L-FP), after exhaustive exercise and 1 day on a mixed diet (L-M), and after exhaustive exercise and 3 days on a high-carbohydrate diet (H-CHO). The L-M treatment resulted in a significant reduction in muscle glycogen (C, 79.6 +/- 4.2 mmol/kg wet wt vs. L-M, 53.9 +/- 1.2 mmol/kg wet wt) and a 31.7% reduction in the insulin-glucose (IG) index, a measure of insulin sensitivity in vivo. Muscle glycogen was also significantly reduced by the L-FP treatment (49.1 +/- 2.4 mmol/kg wet wt), but there was no change in the IG index. Preventing a decrease in the IG index during the L-FP treatment may have been a result of elevated free fatty acids (67%) and ketones (552%) prior to the GTT. Muscle glycogen was significantly increased by the H-CHO treatment (124.8 +/- 11.1 mmol/kg wet wt); however, the IG index was not different from that of the C treatment. The results suggest that an exercise-induced reduction in muscle glycogen can improve insulin sensitivity in vivo but that this effect is diet dependent.


2021 ◽  
Vol 13 (1) ◽  
pp. e2021021
Author(s):  
Vincenzo De Sanctis

Summary. Objective: To  study the function of the endocrine pancreas in transfusion-dependent ?-thalassemia (?-TDT) patients with normal oral glucose tolerance test (OGTT) and hypoinsulinemia. Patients and methods: Seven ?-TDT patients  (mean age 22.4 ± 4.2 years) with normal glucose tolerance test (NGT) and poor insulin response (hypoinsulinemia) to OGTT,  not associated with ?-cell autoimmunity, were referred for a second opinion to an Italian Centre, part of the International Network of Clinicians for Endocrinopathies in Thalassemia and Adolescence Medicine (ICET-A). In this pilot study,  the first-phase insulin response (FPIR), expressed as the sum of 1 and  3 minutes insulin, of ?-TDT patients to intravenous glucose tolerance test (IVGTT), was tested. Moreover, the long-term natural history was followed prospectively using an annual OGTT, with the aim of detecting any abnormality of glucose metabolism. Results: The FPIR value  was between the 1st and 3rd percentile in two patients and between the 3rd and 10th percentile in  five. After 43 ± 26 months (range 11 - 80 months) of follow-up, 2 patients developed impaired glucose tolerance (IGT), 3 both IGT and impaired fasting glucose (IFG) and two overt diabetes mellitus (DM). Interestingly, the patients who developed DM had, at baseline the lowest value of insulinogenic index (IGI, 0.08 and 0.25), defined as the ratio of the increment of plasma insulin to plasma glucose during the first 30 minutes after OGTT. Moreover, a significant correlation was found between the IGI at baseline and at follow-up in the patients who developed IGT with or without IFG (R= 0.927; P: 0.023). A significant reduction of Matsuda insulin sensitivity index (ISIM) and Insulin Secretion-Sensitivity Index-2 (ISSI-2) was documented in the study cohort at diagnosis of IFG, IGT and DM. There was a significant inverse correlation between ISSI-2 and area under the curve of plasma glucose (AUC-PG). Conclusions: These data demonstrated, for the first time, a progressive deterioration in glucose homeostasis in ?-TDT subjects with NGT and hypoinsulinemia.  Thus, we consider that variations of insulin sensitivity could possibly have an impact on glucose tolerance in adult patients with TDT. Further investigations should focus on factors that might positively influence insulin sensitivity, including nutrition, drugs and physical activity.  


Sign in / Sign up

Export Citation Format

Share Document