scholarly journals Switching to unboosted atazanavir improves glucose tolerance in highly pretreated HIV-1 infected subjects

2007 ◽  
Vol 156 (4) ◽  
pp. 503-509 ◽  
Author(s):  
Monica Guffanti ◽  
Andrea Caumo ◽  
Laura Galli ◽  
Alba Bigoloni ◽  
Andrea Galli ◽  
...  
Keyword(s):  
Insulin Sensitivity ◽  
Glucose Tolerance ◽  
Fasting Glucose ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Second Phase ◽  
Β Cell ◽  
C Peptide ◽  
Metabolic Alterations ◽  
Hiv 1

Objective: To evaluate the 24-week effects on glucose tolerance of switching from a protease inhibitor (PI)-based to an unboosted atazanavir-including regimen in highly pretreated HIV-1 infected subjects with metabolic alterations. Design: Prospective, open-label, single-center, 24-week pilot study. Methods: Twenty-one subjects underwent an oral glucose tolerance test (OGTT) at baseline (BL) and after 24 weeks of unboosted atazanavir. Insulin sensitivity and β-cell responsiveness were evaluated on the basis of static and dynamic data; fasting glucose, insulin, C-peptide, triglycerides (TG), total cholesterol (TC), high-density lipoprotein-cholesterol (HDL-c), low-density lipoprotein-cholesterol (LDL-c), TC/HDL-c ratio, CD4+ cell count and HIV-1 RNA were measured. Results: After 24 weeks of unboosted atazanavir, the 120-min glucose level was significantly lower than the one measured at BL (P=0.021); there were no statistically significant differences in the insulin concentration profile. The SIoral, an OGTT-based index of insulin sensitivity, was significantly higher at week 24 (P=0.017); the indices of first- and second-phase β-cell responsiveness did not significantly change. There was no significant difference between BL and 24-week fasting glucose, insulin or C-peptide levels, and consequently no change in fasting homeostasis model assessment indices of insulin sensitivity and β-cell function. There were significant improvements in TG (P=0.009), TC (P=0.0001), LDL-c (P=0.019) and TC/HDL-c ratio (P=0.001), and a similar trend in HDL-c levels (P=0.069). No significant changes in the immunological and virological parameters were detected. Conclusions: Our results show that switching from a PI-based to an unboosted atazanavir-including regimen leads to a significant improvement in glucose tolerance in highly pretreated HIV-1 infected subjects with metabolic alterations.

scholarly journals The Influence of the Levonorgestrel-Releassing Intrauterine System (Lng Ius) on Metabolic Markers in Women with Normal Body Mass and Overweight Women

2013 ◽  
Vol 13 (2) ◽  
pp. 27-32
Author(s):  
Ineta Vasaraudze ◽  
Dace Rezeberga ◽  
Renars Erts ◽  
Aivars Lejnieks
Keyword(s):  
Insulin Sensitivity ◽  
Body Mass ◽  
Cell Function ◽  
Fasting Glucose ◽  
Density Lipoprotein ◽  
Β Cell ◽  
C Peptide ◽  
Overweight Women ◽  
Normal Body ◽  
Β Cell Function

Abstract Introduction. In Latvia, the number of overweight women is increasing, while the rate of cardio vascular disease (CVD) is one of the highest in the European Union. The influence of hormonal contraception on the development of CVD has not been studied in Latvia so far. Aim of the study. A nonrandomized open-label prospective trial of healthy reproductive-age women desiring to use the LNG IUS. Materials and methods. Before starting the use of contraception and six months after starting the use of contraception, the homeostasis model assessment insulin resistant (HOMA-IR) score, insulin sensitivity (HOMA-%S) and β-cell function (HOMA-%B) were calculated using fasting glucose (FG) and C peptide values. There were also determined other cardio-metabolic parameters: total cholesterol, high density lipoprotein cholesterol, low density lipoprotein cholesterol, triglyceride level, systolic and diastolic blood pressure, and abdominal circumference. Results. Thirty women were involved in the study: seventeen women with a normal body-mass index (BMI) (BMI below 25) and thirteen overweight women (BMI above 25). When using the LNG IUS, the fasting glucose level increased in women with normal body mass, the level of insulin sensitivity decreased in both study groups; C peptide level, β-cell function and insulin resistance increased in both groups, but the changes were not statistically reliable (p>0.05). Conclusion. Although during the study there were determined changes in the FG level, insulin sensitivity, C peptide, β-cell function and insulin resistance parameters, these changes are not clinically significant, and the LNG IUS may be safely used clinically both by women with normal body mass and overweight women.

scholarly journals Ectopic Fat Storage in the Pancreas, Liver, and Abdominal Fat Depots: Impact on β-Cell Function in Individuals with Impaired Glucose Metabolism

2011 ◽  
Vol 96 (2) ◽  
pp. 459-467 ◽  
Author(s):  
N. J. van der Zijl ◽  
G. H. Goossens ◽  
C. C. M. Moors ◽  
D. H. van Raalte ◽  
M. H. A. Muskiet ◽  
...  
Keyword(s):  
Insulin Sensitivity ◽  
Magnetic Resonance ◽  
Glucose Tolerance ◽  
Cell Function ◽  
Ectopic Fat ◽  
Β Cell ◽  
C Peptide ◽  
Pancreatic Fat ◽  
Β Cell Function ◽  
Peptide Secretion

abstract Context: Pancreatic fat content (PFC) may have deleterious effects on β-cell function. Objective: We hypothesized that ectopic fat deposition, in particular pancreatic fat accumulation, is related to β-cell dysfunction in individuals with impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT). Design, Setting and Participants: This was a cross-sectional study in 64 age- and body mass index-matched individuals, with normal glucose tolerance (NGT; n = 16, 60% males), IFG (n = 29, 52% males), or IFG/IGT (n = 19, 63% males) was conducted. Intervention and Main Outcome Measures: Participants underwent the following: 1) a combined hyperinsulinemic-euglycemic and hyperglycemic clamp, with subsequent arginine stimulation to quantify insulin sensitivity and β-cell function; 2) proton-magnetic resonance spectroscopy to assess PFC and liver fat content (LFC); and 3) magnetic resonance imaging to quantify visceral (VAT) and sc (SAT) adipose tissue. The disposition index (DI; insulin sensitivity adjusted β-cell function) was assessed. Results: IFG and IFG/IGT were more insulin resistant (P < 0.001) compared with NGT. Individuals with IFG/IGT had the lowest values of glucose- and arginine-stimulated C-peptide secretion (both P < 0.03) and DI (P < 0.001), relative to IFG and NGT. PFC and LFC gradually increased between NGT, IFG, and IFG/IGT (P = 0.02 and P = 0.01, respectively), whereas VAT and SAT were similar between groups. No direct associations were found between PFC, LFC, VAT, and SAT and C-peptide secretion. The DI was inversely correlated with PFC, LFC, and VAT (all P < 0.05). Conclusions: PFC was increased in individuals with IFG and/or IGT, without a direct relation with β-cell function.

scholarly journals Determining pancreatic β-cell compensation for changing insulin sensitivity using an oral glucose tolerance test

2014 ◽  
Vol 307 (9) ◽  
pp. E822-E829 ◽  
Author(s):  
Thomas P. J. Solomon ◽  
Steven K. Malin ◽  
Kristian Karstoft ◽  
Sine H. Knudsen ◽  
Jacob M. Haus ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Insulin Secretion ◽  
Insulin Sensitivity ◽  
Glucose Tolerance ◽  
Oral Glucose ◽  
Pancreatic Β Cell ◽  
Β Cell ◽  
C Peptide ◽  
Normal Glucose

Plasma glucose, insulin, and C-peptide responses during an OGTT are informative for both research and clinical practice in type 2 diabetes. The aim of this study was to use such information to determine insulin sensitivity and insulin secretion so as to calculate an oral glucose disposition index (DIOGTT) that is a measure of pancreatic β-cell insulin secretory compensation for changing insulin sensitivity. We conducted an observational study of n = 187 subjects, representing the entire glucose tolerance continuum from normal glucose tolerance to type 2 diabetes. OGTT-derived insulin sensitivity (SI OGTT) was calculated using a novel multiple-regression model derived from insulin sensitivity measured by hyperinsulinemic euglycemic clamp as the independent variable. We also validated the novel SI OGTT in n = 40 subjects from an independent data set. Plasma C-peptide responses during OGTT were used to determine oral glucose-stimulated insulin secretion (GSISOGTT), and DIOGTT was calculated as the product of SI OGTT and GSISOGTT. Our novel SI OGTT showed high agreement with clamp-derived insulin sensitivity (typical error = +3.6%; r = 0.69, P < 0.0001) and that insulin sensitivity was lowest in subjects with impaired glucose tolerance and type 2 diabetes. GSISOGTT demonstrated a significant inverse relationship with SI OGTT. GSISOGTT was lowest in normal glucose-tolerant subjects and greatest in those with impaired glucose tolerance. DIOGTT was sequentially lower with advancing glucose intolerance. We hereby derive and validate a novel OGTT-derived measurement of insulin sensitivity across the entire glucose tolerance continuum and demonstrate that β-cell compensation for changing insulin sensitivity can be readily calculated from clinical variables collected during OGTT.

scholarly journals Red meat, dairy, and insulin sensitivity: a randomized crossover intervention study

2015 ◽  
Vol 101 (6) ◽  
pp. 1173-1179 ◽  
Author(s):  
Kirsty M Turner ◽  
Jennifer B Keogh ◽  
Peter M Clifton
Keyword(s):  
Insulin Sensitivity ◽  
Glucose Tolerance ◽  
Fasting Glucose ◽  
Red Meat ◽  
Processed Meat ◽  
Model Assessment ◽  
C Peptide ◽  
Dairy Consumption ◽  
High Consumption ◽  
Meat Diet

ABSTRACT Background: Epidemiologic studies have linked high consumption of red and processed meat with risk of developing type 2 diabetes, whereas high dairy consumption has been associated with decreased risk, but interventions have been limited. Objective: We compared the effects on insulin sensitivity of consuming a diet high in lean red meat with minimal dairy, a diet high in primarily low-fat dairy (from milk, yogurt, or custard) with no red meat, and a control diet that contained neither red meat nor dairy. Design: A randomized crossover study was undertaken with 47 overweight and obese men and women divided into 2 groups as follows: those with normal glucose tolerance and those with impaired fasting glucose or impaired glucose tolerance. Participants followed the 3 weight-stable dietary interventions for 4 wk with glucose, insulin, and C-peptide measured by using oral-glucose-tolerance tests at the end of each diet. Results: Fasting insulin was significantly higher after the dairy diet than after the red meat diet (P < 0.01) with no change in fasting glucose resulting in a decrease in insulin sensitivity after the high-dairy diet (P < 0.05) as assessed by homeostasis model assessment of insulin resistance (HOMA-IR). A significant interaction between diet and sex was observed such that, in women alone, HOMA-IR was significantly lower after the red meat diet than after the dairy diet (1.33 ± 0.8 compared with 1.71 ± 0.8, respectively; P < 0.01). Insulin sensitivity calculated by using the Matsuda method was 14.7% lower in women after the dairy diet than after the red meat diet (P < 0.01) with no difference between diets in men. C-peptide was not different between diets. Conclusion: In contrast to some epidemiologic findings, these results suggest that high consumption of dairy reduces insulin sensitivity compared with a diet high in lean red meat in overweight and obese subjects, some of whom had glucose intolerance. This trial was registered at the Australian New Zealand Clinical Trials Registry as ACTRN12613000441718.

scholarly journals Increased β-Cell Responsivity Independent of Insulin Sensitivity in Healthy African American Adults

2020 ◽  
Vol 105 (7) ◽  
pp. e2429-e2438
Author(s):  
Latif Armiyaw ◽  
Camila Sarcone ◽  
Andin Fosam ◽  
Ranganath Muniyappa
Keyword(s):  
Insulin Secretion ◽  
Insulin Sensitivity ◽  
Fat Free Mass ◽  
Glucose Disposal ◽  
Second Phase ◽  
Β Cell ◽  
Intravenous Glucose ◽  
C Peptide ◽  
Glucose Clamp Technique ◽  
Cell Glucose

Abstract Background Primary insulin hypersecretion predicts type 2 diabetes (T2DM) independent of insulin resistance. Enhanced β-cell glucose responsivity contributes to insulin hypersecretion. African Americans (AAs) are at a higher risk for T2DM than non-Hispanic Whites (NHWs). Whether AAs manifest primary insulin hypersecretion is an important topic that has not been examined systematically. Objective To examine if nondiabetic AA adults have a higher β-cell glucose responsivity compared with NHWs. Methods Healthy nondiabetic AA (n = 18) and NHW (n=18) subjects were prospectively recruited. Indices of β-cell function, acute C-peptide secretion (X0); basal (Φ B), first-phase (Φ 1), second-phase (Φ 2), and total β-cell responsivity to glucose (Φ TOT), were derived from modeling of insulin, C-peptide, and glucose concentrations during an intravenous glucose tolerance test. Insulin sensitivity was assessed by the hyperinsulinemic–euglycemic glucose clamp technique. Results Glucose disposal rate (GDR) during clamp was similar in AAs and NHWs (GDR: [AA] 12.6 ± 3.2 vs [NHW] 12.6 ± 4.2 mg/kg fat free mass +17.7/min, P = .49). Basal insulin secretion rates were similar between the groups. AA had significantly higher X0 (4423 ± 593 vs 1807 ± 176 pmol/L, P = .007), Φ 1 [377.5 ± 59.0 vs 194.5 ± 26.6 (109) P = 0.03], and Φ TOT [76.7 ± 18.3 vs 29.6 ± 4.7 (109/min), P = 0.03], with no significant ethnic differences in Φ B and Φ 2. Conclusions Independent of insulin sensitivity, AAs showed significantly higher first-phase and total β-cell responsivity than NHWs. We propose that this difference reflects increased β-cell responsivity specifically to first-phase readily releasable insulin secretion. Future studies are warranted to identify mechanisms leading to primary β-cell hypersensitivity in AAs.

scholarly journals Relationship Between Insulin Resistance and β-Cell Dysfunction in Subphenotypes of Prediabetes and Type 2 Diabetes

2015 ◽  
Vol 100 (2) ◽  
pp. 707-716 ◽  
Author(s):  
Kristine Færch ◽  
Nanna B. Johansen ◽  
Daniel R. Witte ◽  
Torsten Lauritzen ◽  
Marit E. Jørgensen ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Insulin Sensitivity ◽  
Glucose Tolerance ◽  
Glucose Tolerance Test ◽  
Fasting Glucose ◽  
Tolerance Test ◽  
Oral Glucose ◽  
Oral Glucose Tolerance ◽  
Β Cell

Abstract Context: There is little overlap between diabetes diagnosed by glycated hemoglobin (HbA1c) and blood glucose, and it is unclear which pathophysiological defects are captured when using HbA1c for diagnosis. Objective: We examined and compared the relationship between insulin sensitivity and β-cell function in different subphenotypes of prediabetes and type 2 diabetes (T2D). Design, Setting, and Participants: A cross-sectional analysis of the Danish ADDITION-PRO study was performed (n = 1713). Participants without known diabetes were classified into subgroups of prediabetes and T2D based on fasting or 2-hour glucose criteria or HbA1c. Insulin sensitivity and insulin release were determined from glucose and insulin concentrations during the oral glucose tolerance test, and disposition indices were calculated. Results: Individuals with prediabetes or T2D diagnosed by fasting glucose had lower absolute insulin release (P ≤ .01) and higher insulin sensitivity in response to glucose intake (P ≤ .01) but a similar disposition index (P ≥ .36), compared with individuals with elevated 2-hour glucose concentrations. Individuals with HbA1c-defined T2D or prediabetes had a mixture of the pathophysiological defects observed in the glucose-defined subgroups, and individuals with normoglycemia by HbA1c had worse pathophysiological abnormalities than individuals with normoglycemia by the glucose criteria. Conclusions: On average, the diagnostic HbA1c criteria for diabetes and prediabetes identified individuals with a mixture of the pathophysiological characteristics found when using the glucose criteria, but the diversity and pathophysiology captured by the oral glucose tolerance test cannot be captured when applying the more simple HbA1c criteria. Whether the disease progression and prognosis will differ in individuals diagnosed by fasting glucose, 2-hour glucose, or HbA1c should be examined in longitudinal studies.

Effects on insulin secretion and insulin action of a 48-h reduction of plasma free fatty acids with acipimox in nondiabetic subjects genetically predisposed to type 2 diabetes

2007 ◽  
Vol 292 (6) ◽  
pp. E1775-E1781 ◽  
Author(s):  
Kenneth Cusi ◽  
Sangeeta Kashyap ◽  
Amalia Gastaldelli ◽  
Mandeep Bajaj ◽  
Eugenio Cersosimo
Keyword(s):  
Type 2 Diabetes ◽  
Insulin Secretion ◽  
Family History ◽  
Second Phase ◽  
Β Cell ◽  
C Peptide ◽  
Hyperglycemic Clamp ◽  
History Of ◽  
Plasma Ffa

Elevated plasma FFA cause β-cell lipotoxicity and impair insulin secretion in nondiabetic subjects predisposed to type 2 diabetes mellitus [T2DM; i.e., with a strong family history of T2DM (FH+)] but not in nondiabetic subjects without a family history of T2DM. To determine whether lowering plasma FFA with acipimox, an antilipolytic nicotinic acid derivative, may enhance insulin secretion, nine FH+ volunteers were admitted twice and received in random order either acipimox or placebo (double-blind) for 48 h. Plasma glucose/insulin/C-peptide concentrations were measured from 0800 to 2400. On day 3, insulin secretion rates (ISRs) were assessed during a +125 mg/dl hyperglycemic clamp. Acipimox reduced 48-h plasma FFA by 36% ( P < 0.001) and increased the plasma C-peptide relative to the plasma glucose concentration or ΔC-peptide/Δglucose AUC (+177%, P = 0.02), an index of improved β-cell function. Acipimox improved insulin sensitivity (M/I) 26.1 ± 5% ( P < 0.04). First- (+19 ± 6%, P = 0.1) and second-phase (+31 ± 6%, P = 0.05) ISRs during the hyperglycemic clamp also improved. This was particularly evident when examined relative to the prevailing insulin resistance [1/(M/I)], as both first- and second-phase ISR markedly increased by 29 ± 7 ( P < 0.05) and 41 ± 8% ( P = 0.02). There was an inverse correlation between fasting FFA and first-phase ISR ( r2 = 0.31, P < 0.02) and acute (2–4 min) glucose-induced insulin release after acipimox ( r2 =0.52, P < 0.04). In this proof-of-concept study in FH+ individuals predisposed to T2DM, a 48-h reduction of plasma FFA improves day-long meal and glucose-stimulated insulin secretion. These results provide additional evidence for the important role that plasma FFA play regarding insulin secretion in FH+ subjects predisposed to T2DM.

scholarly journals The role of sex steroids in the regulation of insulin sensitivity and serum lipid concentrations during male puberty: a prospective study with a P450-aromatase inhibitor

2002 ◽  
pp. 339-346 ◽  
Author(s):  
S Wickman ◽  
T Saukkonen ◽  
L Dunkel
Keyword(s):  
Insulin Sensitivity ◽  
Aromatase Inhibitor ◽  
Sex Steroids ◽  
Ldl Cholesterol ◽  
Density Lipoprotein ◽  
Treated Group ◽  
Lipoprotein Cholesterol ◽  
Cholesterol Concentration ◽  
Igf I ◽  
Letrozole Treatment

OBJECTIVE: Our purpose was to study the sex steroid-mediated changes in serum insulin and lipid concentrations in boys during puberty. DESIGN AND METHODS: We treated boys with constitutional delay of puberty either with testosterone plus placebo or with testosterone plus an aromatase inhibitor, letrozole, which inhibits the conversion of androgens to oestrogens. We demonstrated previously that during treatment with testosterone plus letrozole the increase in testosterone concentration was more than 5-fold higher than during treatment with testosterone plus placebo. The concentrations of 17beta-oestradiol, IGF-I and IGF-binding protein-3 increased during testosterone-plus-placebo treatment, but during testosterone-plus-letrozole treatment the concentrations remained unchanged. These divergent changes in the two groups enabled us to study the effects of sex steroids and GH on insulin sensitivity and lipid concentrations. RESULTS: The insulin concentration in the testosterone-plus-placebo-treated group did not change. In contrast, in the testosterone-plus-letrozole-treated group, the concentration decreased during letrozole treatment, indicating improved insulin sensitivity. Changes in insulin and IGF-I concentrations within 12 and 18 months were correlated. In the testosterone-plus-placebo-treated group, the high-density lipoprotein cholesterol concentration did not change but in the testosterone-plus-letrozole-treated group the concentration decreased. The concentrations of low-density lipoprotein cholesterol (LDL-cholesterol) and triglycerides did not change in either of the groups. CONCLUSIONS: The findings indicate that androgens do not directly alter insulin sensitivity in boys during puberty. In contrast, the observations suggest tight regulation of glucose--insulin homeostasis by GH in boys at this stage. Furthermore, our findings indicate that sex steroids do not significantly participate in the regulation of serum concentrations of LDL-cholesterol or triglycerides in boys during early and mid-puberty.

Increased prevalence of β-cell dysfunction despite normal HbA1c in youth and young adults with Turner Syndrome

2021 ◽  
Author(s):  
Nicole Sheanon ◽  
Deborah Elder ◽  
Jane Khoury ◽  
Lori Casnellie ◽  
Iris Gutmark-Little ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Insulin Sensitivity ◽  
Glucose Tolerance ◽  
Turner Syndrome ◽  
P Value ◽  
Oral Glucose ◽  
Adult Women ◽  
Β Cell ◽  
Cell Dysfunction ◽  
The Impact

Intro: Adult women with Turner syndrome (TS) have a high prevalence of diabetes and β-cell dysfunction that increases morbidity and mortality, but, it is unknown if there is β-cell dysfunction present in youth with TS. This study aimed to determine the prevalence of β-cell dysfunction in youth with TS and the impact of traditional therapies on insulin sensitivity and insulin secretion. Methods: Cross-sectional, observational study recruited 60 girls with TS and 60 healthy controls (HC) matched on pubertal status. Each subject had a history, physical exam and oral glucose tolerance test (OGTT). Oral glucose and c-peptide minimal modeling was used to determine β-cell function. Results: Twenty-one TS girls (35%) met criteria for pre-diabetes. Impaired fasting glucose (IFG) was present in 18% of girls with TS and 2% HC (p-value = 0.0003). Impaired glucose tolerance (IGT) was present in 23% of TS girls and 0% HC (p-value < 0.001). The HbA1c was not different between TS and HC (median 5%, p= 0.42). Youth with TS had significant reductions in insulin sensitivity (SI), β-cell responsivity (Φ), and disposition index (DI) compared to HC. These differences remained significant when controlling for BMI z-score (p-values: 0.0006, 0.002, <0.0001 for SI, Φtotal, DI, respectively). Conclusions: β-cell dysfunction is present in youth with TS compared to controls. The presence of both reduced insulin secretion and insulin sensitivity suggest a unique TS-related glycemic phenotype. Based on the data from this study, we strongly suggest that providers employ serial OGTT to screen for glucose abnormalities in TS youth.

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