Abstract 1924: Carriers of Loss-of-Function Mutations in ABCA1 Display Pancreatic Beta Cell Dysfunction

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Menno Vergeer ◽  
Liam R Brunham ◽  
Joris Koetsveld ◽  
Janine K Kruit ◽  
C B Verchere ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Insulin Sensitivity ◽  
Plasma Glucose ◽  
Sensitivity Index ◽  
Loss Of Function ◽  
Β Cell ◽  
C Peptide ◽  
Cell Dysfunction ◽  
Time Interaction

Background The ATP Binding Cassette transporter A1 (ABCA1) transports free cholesterol to nascent high-density lipoproteins (HDL) and maintains plasma HDL levels. In mice, ABCA1 is essential in regulating intracellular cholesterol homeostasis and insulin secretion in the β cell. The role of ABCA1 in human glucose metabolism is unclear. Objective and methods To assess the effects of ABCA1 dysfunction on glucose homeostasis in humans , we matched heterozygous carriers of disruptive mutations in ABCA1 and non-carriers for age, gender and BMI and performed oral glucose tolerance tests (OGTT; 9 vs. 8 respectively) and hyperglycemic clamping experiments (6 vs. 6). Results Carriers had lower HDL-C levels than non-carriers (0.58 ± 0.3 vs. 1.46 ± 0.4 mmol/L, p=0.001) but LDL-C did not differ (3.4 ± 1.0 vs. 2.8 ± 0.8 mmol/L, p=0.21). Fasting plasma glucose was not different (5.2 ± 1.5 vs. 5.0 ± 0.4 mmol/L). Glucose curves after OGTT were significantly higher in carriers than in non-carriers (genotype * time interaction, p=0.005; plasma glucose at t=60 min 9.0 ± 3.0 mmol/L vs. 6.0 ± 1.4 mmol/L respectively, p=0.02). During hyperglycemic clamps, carriers showed a lower first phase insulin and C-peptide response than non-carriers (genotype * time interaction, p<0.05 and p<0.01 respectively; insulin at t=5 min 164±118 vs. 352 ±141 pmol/L, p<0.05; C-peptide at t=5 min 1033 ± 628 vs. 1942 ± 723 pmol/L, p<0.05) but no difference in insulin sensitivity index (0.0216 ± 0.012 mg kg −1 . min −1 . pM −1 for carriers and 0.0197 ± 0.005 mg kg −1 . min −1 . pM −1 for non-carriers; p=0.73). Disposition index - a measure of β cell function, adjusted for insulin sensitivity - was lower in carriers than in non-carriers (1037 ± 610 vs. 2718 ± 1524; p<0.05). Non-carriers responded to an arginine stimulus with an increase in C-peptide levels (from 3558 ± 1240 pM to 6817 ± 1665 pM; p<0.005), whereas in carriers this increase did not reach statistical significance (from 3727 ± 1843 pM to 5480 ± 1757 pM; p=0.12). Conclusion Carriers of loss-of-function mutations in ABCA1 show impaired insulin secretion without insulin resistance, resulting in glucose intolerance. Our data confirm previous studies in mice and provide evidence for a role of ABCA1 in β cell dysfunction and the pathophysiology of diabetes mellitus in man.

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.

Association between Genetic Polymorphisms of β-Cell Differentiation Genes and Insulin Resistance (β-Cell Dysfunction) in Childhood Acute Lymphoblastic Leukemia (ALL) Survivors.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4281-4281
Author(s):  
Pacharapan Surapolchai ◽  
Suradej Hongeng ◽  
Samart Pakakasama ◽  
Pat Mahachoklertwattana ◽  
Angkana Winaichatsak ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Insulin Sensitivity ◽  
Glucose Tolerance ◽  
Cell Function ◽  
Sensitivity Index ◽  
Insulin Sensitivity Index ◽  
Β Cell ◽  
Childhood All ◽  
Cell Dysfunction ◽  
Β Cell Function

Abstract Background: The purposes of the study were to determine β-cell function and insulin sensitivity after ALL therapy cessation and the association between genetic polymorphisms of β-cell differentiation genes, TCF7L2 and PAX4, with insulin resistance (β-cell dysfunction) in childhood ALL survivors. Methods: Childhood ALL patients diagnosed during 1997–2004 finished the treatment for at least 6 months. The oral glucose tolerance test and lipid screening were performed. Impaired glucose tolerance and diabetes mellitus (DM) were defined according to WHO criteria. β-cell function was estimated by homeostasis model assessment β-cell (HOMA β-cell) and insulinogenic index (IGI) and insulin sensitivity was estimated by whole body insulin sensitivity index (WBISI). The polymorphisms of TCF7L2 (rs12255372 and rs7903146) and PAX4 (A1186C) were genotyped and assessed for the association between these polymorphisms and the β-cell function and the insulin sensitivity. Results: 126 patients were studied (52 females, 74 males and age at the time of study; 4–20 yrs). 116 patients (92%) had normal glucose tolerance (NGT) while the others 10 patients (8%) had impaired glucose tolerance (IGT). Comparing between IGT and NGT groups respectively, we found statistically significant differences in age at the diagnosis (7.5 and 5.2 yrs, p=0.041), age at the study (14 and 10.3 yrs, p=0.001), the duration of post ALL therapy cessation (43 and 26 months, p=0.015), and insulin sensitivity index (WBISI) (5.75 and 9.52, p<0.001). HOMA β-cell and IGI were not different between NGT and IGT group (190.8 and 139.5, p=0.332; 23.6 and 15.8, p=0.310, respectively). Moreover, 32 of 126 patients (25%) had insulin resistance (modified from the criteria of WBISI in obese children and adolescents). These 32 patients who had insulin resistance demonstrated significant pictures of metabolic syndrome i.e. hypertriglyceridemia (116.6 and 85.4 mg/dL, p=0.036), low HDL-C (43.0 and 48.3 mg/dL, p=0.015), obesity (BMI SDS 1.03 and 0.38, p=0.044) and were also older age at the study (12.8 and 9.9 yrs, p<0.001). The genotype frequencies and allele frequencies of polymorphisms of TCF7L2 and PAX4 genes between IGT and NGT groups and between insulin resistance and nonresistance were not difference (p>0.05). Conclusion: The childhood ALL survivors who had IGT were associated with the longer duration of ALL therapy cessation, the older age at diagnosis and at the time of study, and insulin resistance while β-cell function was still relatively preserved. Long-term childhood ALL survivors have potential risks of IGT, insulin resistance and metabolic syndrome. Our findings with such small representatives are not yet applicable to associate TCF7L2 and PAX4 polymorphisms with the insulin resistance (β-cell dysfunction) in the childhood ALL survivors.

scholarly journals Association of Hematological Parameters with Insulin Resistance and β-Cell Dysfunction in Nondiabetic Subjects

2009 ◽  
Vol 94 (10) ◽  
pp. 3824-3832 ◽  
Author(s):  
Anthony J. G. Hanley ◽  
Ravi Retnakaran ◽  
Ying Qi ◽  
Hertzel C. Gerstein ◽  
Bruce Perkins ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Insulin Sensitivity ◽  
Blood Cell ◽  
Cell Count ◽  
Hematological Parameters ◽  
Sensitivity Index ◽  
Blood Cell Count ◽  
Β Cell ◽  
Cell Dysfunction

Objective: Previous studies reported independent associations of hematological parameters with risk of incident type 2 diabetes, although limited data are available on associations of these parameters with insulin resistance (IR) and (especially) pancreatic β-cell dysfunction in large epidemiological studies. Our objective was to evaluate the associations of hematological parameters, including hematocrit (HCT), hemoglobin (Hgb), red blood cell count (RBC), and white blood cell count with IR and β-cell dysfunction in a cohort of nondiabetic subjects at high metabolic risk. Methods: Nondiabetic subjects (n = 712) were recruited in Toronto and London, Ontario, Canada, between 2004 and 2006, based on the presence of one or more risk factors for type 2 diabetes mellitus including obesity, hypertension, a family history of diabetes, and/or a history of gestational diabetes. Fasting blood samples were collected and oral glucose tolerance tests administered, with additional samples for glucose and insulin drawn at 30 and 120 min. Measures of IR included the homeostasis model assessment (HOMA-IR) and Matsuda’s insulin sensitivity index, whereas measures of β-cell dysfunction included the insulinogenic index divided by HOMA-IR as well as the insulin secretion-sensitivity index-2. Associations of hematological parameters with IR and β-cell dysfunction were assessed using multiple linear regression and analysis of covariance with adjustments for age, gender, ethnicity, smoking, cardiovascular disease, systolic and diastolic blood pressure, and waist circumference. Results: HOMA-IR increased across quartiles of HCT, Hgb, RBC, and white blood cell count after adjustment for age, gender, ethnicity, and smoking (all P (trend) &lt;0.0001). Similarly, there was a strong stepwise decrease in the Matsuda’s insulin sensitivity index across increasing quartiles of these hematological measures (all P (trend) &lt;0.0001). The associations remained significant after further adjustment for previous cardiovascular disease, blood pressure, and waist circumference (all P (trend) &lt;0.0001). Similarly, there was a strong pattern of decreasing β-cell function across increasing quartiles of all hematological patterns (all P (trend) &lt;0.0001). The findings for HCT, Hgb, and RBC were attenuated slightly after full multivariate adjustment, although the trend across quartiles remained highly significant. Conclusion: These findings suggest that standard, clinically relevant hematological variables may be related to the underlying pathophysiological changes associated with type 2 diabetes mellitus. In a large sample of non-diabetic subjects with metabolic risk factors, hematological parameters were significantly associated with insulin sensitivity and β-cell dysfunction, the main physiological disorders underlying type 2 diabetes.

scholarly journals Influence of Tacrolimus on Glucose Metabolism before and after Renal Transplantation: A Prospective Study

2001 ◽  
Vol 12 (3) ◽  
pp. 583-588 ◽  
Author(s):  
ELLY M. VAN DUIJNHOVEN ◽  
JOHANNES M. M. BOOTS ◽  
MAARTEN H. L. CHRISTIAANS ◽  
BRUCE H. R. WOLFFENBUTTEL ◽  
JOHANNES P. VAN HOOFF
Keyword(s):  
Insulin Resistance ◽  
Insulin Secretion ◽  
Insulin Sensitivity ◽  
Glucose Metabolism ◽  
Sensitivity Index ◽  
Intravenous Glucose ◽  
Prospective Longitudinal Study ◽  
C Peptide ◽  
Before And After ◽  
Prospective Longitudinal

Abstract. Most studies concerning the influence of tacrolimus on glucose metabolism have been performed either in animals or after organ transplantation. These clinical studies have largely been transversal with patients who were using steroids. Therefore, this prospective, longitudinal study investigated the influence of tacrolimus on glucose metabolism before and after transplantation. Eighteen Caucasian dialysis patients underwent an intravenous glucose tolerance test before and 5 d after the start of tacrolimus. Insulin sensitivity index (kG), insulin resistance (insulin/glucose ratio and homeostasis model assessment), and C-peptide and insulin secretion were calculated. Trough levels of tacrolimus were measured. After transplantation, the occurrence of posttransplantation diabetes mellitus (PTDM) was prospectively monitored. Statistical analysis was performed using the Wilcoxon signed ranks test and Spearman's rho for correlation. Before tacrolimus, kG was indeterminate in three patients. During tacrolimus, kG decreased in 16 of 18 patients, from a median of 1.74 mmol/L per min to 1.08 mmol/L per min (P < 0.0001). The correlation between C-peptide and insulin data was excellent. Insulin secretion decreased from 851.0 mU × min/L to 558.0 mU × min/L (P = 0.014), whereas insulin resistance did not change. Insulin sensitivity correlated negatively with tacrolimus trough level. After transplantation, three patients developed PTDM; before tacrolimus, two had an indeterminate and one a low normal kG. During tacrolimus administration, kG decreased in almost all patients as a result of a diminished insulin secretion response to a glucose load, whereas insulin resistance did not change. Patients with an abnormal or indeterminate kG seem to be at risk of developing PTDM while on tacrolimus.

Acute enhancement of insulin secretion by FFA in humans is lost with prolonged FFA elevation

1999 ◽  
Vol 276 (6) ◽  
pp. E1055-E1066 ◽  
Author(s):  
André Carpentier ◽  
Steven D. Mittelman ◽  
Benoǐt Lamarche ◽  
Richard N. Bergman ◽  
Adria Giacca ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Insulin Secretion ◽  
Insulin Sensitivity ◽  
Cell Function ◽  
Peak Plasma ◽  
Sensitivity Index ◽  
Β Cell ◽  
Intravenous Glucose ◽  
Hyperglycemic Clamp

The in vivo effect of elevated free fatty acids (FFA) on β-cell function in humans remains extremely controversial. We examined, in healthy young men, the acute (90 min) and chronic (48 h) effects of an approximately twofold elevation of plasma FFA vs. control on glucose-stimulated insulin secretion (GSIS). GSIS was studied in response to a graded intravenous glucose infusion (peak plasma glucose, ∼10 mmol/l, n = 8) and a two-step hyperglycemic clamp (10 and 20 mmol/l, n = 8). In the acute studies, GSIS was significantly higher, insulin sensitivity index (SI) was lower, and disposition index (DI = insulin sensitivity × insulin secretion) was unchanged with elevated FFA vs. control [2-step clamp: DI = 8.9 ± 1.4 × 10−3l2 ⋅ kg−1 ⋅ min−2in control vs. 10.0 ± 1.9 × 10−3l2 ⋅ kg−1 ⋅ min−2with high FFA, P = nonsignificant (NS)]. In the chronic studies, there was no difference in absolute GSIS between control and high FFA studies, but there was a reduction in SI and a loss of the expected compensatory increase in insulin secretion as assessed by the DI (2-step clamp: DI = 10.0 ± 1.2 × 10−3l2 ⋅ kg−1 ⋅ min−2in control vs. 6.1 ± 0.7 × 10−3l2 ⋅ kg−1 ⋅ min−2with high FFA, P = 0.01). In summary, 1) acute and chronic FFA elevation induces insulin resistance; 2) with acute FFA elevation, this insulin resistance is precisely countered by an FFA-induced increase in insulin secretion, such that DI does not change; and 3) chronic FFA elevation disables this β-cell compensation.

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.

Abstract 13615: High-Dose Simvastatin Induce Insulin Resistance During Acute Myocardial Infarction by Inhibiting Intracellular Insulin Signaling, Without Attenuating Its Clinical Benefit

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Luiz S Carvalho ◽  
Filipe A Moura ◽  
Riobaldo M Cintra ◽  
Patrícia O Prada ◽  
Mario J Saad ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Insulin Secretion ◽  
Plasma Glucose ◽  
Insulin Signaling ◽  
High Dose ◽  
Sensitivity Index ◽  
Stress Hyperglycemia ◽  
Euglycemic Hyperinsulinemic Clamp ◽  
C Peptide ◽  
Risk Of Death

Background: Hyperglycemia during the acute phase of myocardial infarction (MI) is a strong marker of mortality, but statin use in this set can potentially induce dysglycemia. We aimed to identify whether statins also induce hyperglycemia during MI and the related mechanisms as well as to evaluate its clinical relevance. Methods: We prospectively studied 550 patients with ST-elevation MI treated without (WS) or with simvastatin (S) at 20, 40 or 80 mg/day. Of these, 27 non-diabetics were randomized to S10 or S80mg/day and performed euglycemic hyperinsulinemic clamp (EHC) associated with abdominal adipose tissue biopsy after 40 minutes of insulin infusion in the second (D2) and sixth (D6) days after MI. Measurements of plasma glucose, insulin, C-peptide on admission (D1) and fifth (D5) day were performed in all patients. Results: Between D2 and D6, insulin sensitivity index (ISi) measured by EHC increased (20±60%) in the S10 group and reduced (-6±28%) in S80 (p=0.025). Analysis of the biopsies by Western-blot showed a reduction in phosphorylation/activation of Akt and IRS-1 in patients treated with S80 compared to those treated with S10. Among the 550 patients, ISi was estimated by HOMA2S (plasma glucose and insulin) and varied in 40±145% (WS), 22±117% (S20), 16±61 % (S40) and -2%±88% (S80) between D1 and D5 (p=0.001). Insulin secretion at D1 estimated by HOMA2B (glucose and C-peptide) (p=0.001) and the dose of S (p=0.009) were the only independent markers of a fall in HOMA2S between D1 and D5. Among patients not treated with statins or taking 20mg/day (WS + S20), plasma glucose ≥140mg/dl at admission (stress hyperglycemia) increased by 2.25x (95% confidence interval [CI] 1.30-3.85, p=0.004) the risk of death or MI after mean 634±501 days; but not in those treated with S40 or S80 (p=0.727). Stress hyperglycemia also increased the incidence of death in 30 days after MI in the WS + S20 group (HR 3.15, 95%CI 1.41-7.01; p=0.003), but not in the S40 + S80 group (p=0.858) Conclusion: The use of high-dose simvastatin in MI reduces IS through the inhibition of intracellular insulin signaling pathways. IS impairment is dependent on the dose of statin and the reserve of insulin secretion. However, high-dose statins attenuate the short- and long-term clinical impact of hyperglycemia in MI.

Role of miRNAs in the pathogenesis of T2DM, insulin secretion, insulin resistance, and β cell dysfunction: the story so far

2020 ◽  
Vol 76 (4) ◽  
pp. 485-502
Author(s):  
Prabhsimran Kaur ◽  
Sushil Kotru ◽  
Sandeep Singh ◽  
Bidwan Sekhar Behera ◽  
Anjana Munshi
Keyword(s):  
Insulin Resistance ◽  
Insulin Secretion ◽  
Β Cell ◽  
Cell Dysfunction

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 Islet Function and Insulin Sensitivity in Latent Autoimmune Diabetes in Adults Taking Sitagliptin: A Randomized Trial

2021 ◽  
Author(s):  
Lin Yang ◽  
Huiying Liang ◽  
Xinyuan Liu ◽  
Xia Wang ◽  
Ying Cheng ◽  
...  
Keyword(s):  
Insulin Sensitivity ◽  
Cell Function ◽  
Autoimmune Diabetes ◽  
Sensitivity Index ◽  
Β Cell ◽  
C Peptide ◽  
Latent Autoimmune Diabetes ◽  
Dipeptidyl Peptidase 4 Inhibitors ◽  
Cont Group ◽  
Β Cell Function

Abstract Context The long-term effects of dipeptidyl peptidase-4 inhibitors on β-cell function and insulin sensitivity in latent autoimmune diabetes in adults (LADA) are unclear. Objective To investigate the effects of sitagliptin on β-cell function and insulin sensitivity in LADA patients receiving insulin. Design and Setting A randomized controlled trial at the Second Xiangya Hospital. Methods Fifty-one patients with LADA were randomized to sitagliptin + insulin (SITA) group or insulin alone (CONT) group for 24 months. Main Outcome Measures Fasting C-peptide (FCP), 2-hour postprandial C-peptide (2hCP) during mixed-meal tolerance test, △CP (2hCP – FCP), and updated homeostatic model assessment of β-cell function (HOMA2-B) were determined every 6 months. In 12 subjects, hyperglycemic clamp and hyperinsulinemic euglycemic clamp (HEC) tests were further conducted at 12-month intervals. Results During the 24-month follow-up, there were no significant changes in β-cell function in the SITA group, whereas the levels of 2hCP and △CP in the CONT group were reduced at 24 months. Meanwhile, the changes in HOMA2-B from baseline were larger in the SITA group than in the CONT group. At 24 months, first-phase insulin secretion was improved in the SITA group by hyperglycemia clamp, which was higher than in the CONT group (P &lt; .001), while glucose metabolized (M), insulin sensitivity index, and M over logarithmical insulin ratio in HEC were increased in the SITA group (all P &lt; .01 vs baseline), which were higher than in the CONT group. Conclusion Compared with insulin intervention alone, sitagliptin plus insulin treatment appeared to maintain β-cell function and improve insulin sensitivity in LADA to some extent.

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