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The Beta-Cell Function and Glucose Profile of Newly Diagnosed Acromegalic Patients with Normal Glucose Tolerance.

ABSTRACT: Objectives:Untreated acromegaly is a nature model for unveiling the diabetogenic effects of GH. CGMS can uncover more glucose profile of acromegaly. This study aimed to evaluate the insulin resistance (IR), β-cell function, and glycemic spectrum of patients with newly diagnosed acromegaly with normal glucose tolerance (NGT). Methods:This study was conducted in Huashan Hospital from January 2015 to February 2019. Eight newly diagnosed acromegalic patients without history of diabetes and eight age- and gender-matched healthy subjects were enrolled. All participants underwent oral glucose tolerance test (OGTT) and 72 h continuous glucose monitoring (CGM). Parameters on β-cell function and IR were calculated. Mean blood glucose (MBG) in 24 hours was adopted for the evaluation of the glycemic level, and standard deviation of blood glucose (SDBG) and mean amplitude of glycemic excursion (MAGE) were used for glucose fluctuation. Results:HbA1c in the acromegaly group was significantly higher than in the control. During OGTT, glucose peaked at 60 min in acromegaly and at 30 min in controls. After glucose load, the acromegaly group had significantly higher insulin levels than controls, especially in 120 min and 180 min. Both insulin sensitivity index and disposal index after glucose load of acromegaly were significantly lower than those of controls. Moreover, acromegalic subjects had significantly higher MBG than controls. Conclusions:The newly diagnosed acromegalic patients with NGT were characterized by IR and impaired β-cell function after glucose load. CGM showed that MBG of NGT acromegaly patients was higher than that of normal people.

SUBMITTER: Sun Q

PROVIDER: S-EPMC8670947 | biostudies-literature |

REPOSITORIES: biostudies-literature

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CACNA1E variants affect beta cell function in patients with newly diagnosed type 2 diabetes. the Verona newly diagnosed type 2 diabetes study (VNDS) 3.

Project description:BACKGROUND: Genetic variability of the major subunit (CACNA1E) of the voltage-dependent Ca(2+) channel Ca(V)2.3 is associated to risk of type 2 diabetes, insulin resistance and impaired insulin secretion in nondiabetic subjects. The aim of the study was to test whether CACNA1E common variability affects beta cell function and/or insulin sensitivity in patients with newly diagnosed type 2 diabetes. METHODOLOGY/PRINCIPAL FINDINGS: In 595 GAD-negative, drug naïve patients (mean ± SD; age: 58.5 ± 10.2 yrs; BMI: 29.9 ± 5 kg/m(2), HbA1c: 7.0±1.3) with newly diagnosed type 2 diabetes we: 1. genotyped 10 tag SNPs in CACNA1E region reportedly covering ?93% of CACNA1E common variability: rs558994, rs679931, rs2184945, rs10797728, rs3905011, rs12071300, rs175338, rs3753737, rs2253388 and rs4652679; 2. assessed clinical phenotypes, insulin sensitivity by the euglycemic insulin clamp and beta cell function by state-of-art modelling of glucose/C-peptide curves during OGTT. Five CACNA1E tag SNPs (rs10797728, rs175338, rs2184945, rs3905011 and rs4652679) were associated with specific aspects of beta cell function (p<0.05-0.01). Both major alleles of rs2184945 and rs3905011 were each (p<0.01 and p<0.005, respectively) associated to reduced proportional control with a demonstrable additive effect (p<0.005). In contrast, only the major allele of rs2253388 was related weakly to more severe insulin resistance (p<0.05). CONCLUSIONS/SIGNIFICANCE: In patients with newly diagnosed type 2 diabetes CACNA1E common variability is strongly associated to beta cell function. Genotyping CACNA1E might be of help to infer the beta cell functional phenotype and to select a personalized treatment.

| S-EPMC3302892 | biostudies-literature

Do East Asians With Normal Glucose Tolerance Have Worse β-Cell Function? A Meta-Analysis of Epidemiological Studies.

Project description:BackgroundThe difference in the relationship between β-cell function and insulin resistance among Africans, Caucasians and East Asians with normal glucose tolerance (NGT) was not well investigated.MethodsWe searched PubMed and Web of Science with keywords and identified studies that used the homeostasis model assessment (HOMA) model to evaluate β-cell function (HOMA-B) and insulin sensitivity/resistance (HOMA-S/HOMA-IR) in certain ethnic groups. We used random-effect model to pool data of HOMAs and compared the combined data among the three ethnic groups using subgroup analysis. Linear regression analysis was used to estimate the coefficient of HOMA-S on HOMA-B in these ethnic groups.ResultsWe evaluated pooled data of HOMAs in eight African, 26 Caucasian, and 84 East Asian cohorts with NGT, and also 2,392, 6,645 and 67,317 individuals, respectively. The three ethnic groups had distinct HOMA-B but similar HOMA-IR. The regression coefficient of lnHOMA-B on lnHOMA-S was different between Africans and Caucasians (-1.126 vs -0.401, P = 0.0006) or East Asian (-1.126 vs -0.586, P = 0.0087), but similar between Caucasians and East Asians (-0.401 vs -0.586, P = 0.1282). The coefficient in all ethnic groups was similar when age, BMI, and gender were adjusted (African vs Caucasian P = 0.0885, African vs East Asian P = 0.1092, and Caucasian vs East Asian P = 0.6298).ConclusionsIn subjects with NGT, East Asians had lower HOMA-B but similar β-cell response relative to insulin resistance with Caucasians and Africans when age, BMI, and gender were controlled. This result may challenge the allegation that there was an Asian-specific diabetes phenotype with worse β-cell function.

| S-EPMC8669805 | biostudies-literature

Variants of GCKR affect both β-cell and kidney function in patients with newly diagnosed type 2 diabetes: the Verona newly diagnosed type 2 diabetes study 2.

Project description:ObjectiveIn genome-wide association studies, performed mostly in nondiabetic individuals, genetic variability of glucokinase regulatory protein (GCKR) affects type 2 diabetes-related phenotypes, kidney function, and risk of chronic kidney disease (CKD). We tested whether GCKR variability affects type 2 diabetes or kidney-related phenotypes in newly diagnosed type 2 diabetes.Research design and methodsIn 509 GAD-negative patients with newly diagnosed type 2 diabetes, we 1) genotyped six single nucleotide polymorphisms in GCKR genomic region: rs6717980, rs1049817, rs6547626, rs780094, rs2384628, and rs8731; 2) assessed clinical phenotypes, insulin sensitivity by the euglycemic insulin clamp, and β-cell function by state-of-the-art modeling of glucose/C-peptide curves during an oral glucose tolerance test; and 3) estimated glomerular filtration rate (eGFR) by the Modification of Diet in Renal Disease formula.ResultsThe major alleles of rs6717980 and rs2384628 were associated with reduced β-cell function (P < 0.05), with mutual additive effects of each variant (P < 0.01). The minor alleles of rs1049817 and rs6547626 and the major allele of rs780094 were associated with reduced eGFR according to a recessive model (P < 0.03), but with no mutual additive effects of the variants. Additional associations were found between rs780094 and 2-h plasma glucose (P < 0.05) and rs8731 and insulin sensitivity (P < 0.05) and triglycerides (P < 0.05).ConclusionsOur findings are compatible with the idea that GCKR variability may play a pathogenetic role in both type 2 diabetes and CKD. Genotyping GCKR in patients with newly diagnosed type 2 diabetes might help in identifying patients at high risk for metabolic derangements or CKD.

| S-EPMC3114499 | biostudies-literature

Korean red ginseng improves glucose control in subjects with impaired fasting glucose, impaired glucose tolerance, or newly diagnosed type 2 diabetes mellitus.

Project description:This study was designed to evaluate the effect of Korean red ginseng (KRG) supplementation on glucose control in subjects with impaired fasting glucose (IFG), impaired glucose tolerance (IGT), or newly diagnosed type 2 diabetes mellitus (T2DM). The study was a 12-week randomized, double-blinded, placebo-controlled (5?g of KRG [n=21] or placebo [n=20] in tablet form) trial. Glucose-related biomarkers, including serum and whole blood levels of glucose, insulin, and C-peptide, were measured by 2-h oral glucose tolerance tests (OGTTs) at baseline and after the 12-week intervention. After the intervention, the test group showed a significant decrease in serum levels of glucose at 30?min (-22.24±10.77?mg/dL) and whole blood levels of glucose at 30?min (-17.52±5.22?mg/dL). In addition, the test group tended to have lower whole blood levels of glucose at 0?min and glucose area under curve (AUC). However, the placebo group did not show any changes in blood glucose-related indices. The changes (difference from baseline) in serum glucose levels at 30?min, whole blood glucose levels at 60?min, and glucose AUC during OGTTs in the test group exhibited a tendency toward a decrease from those in the placebo group. There were significant decreases or trends toward a decrease in both serum insulin and C-peptide concentrations at most time intervals in the test group. In conclusion, KRG supplementation (5?g/day) may be beneficial for controlling serum and whole blood glucose levels compared with placebo among patients with IFG, IGT, or T2DM.

| S-EPMC3901349 | biostudies-literature

Gut bacterial profile in patients newly diagnosed with treatment-naive Crohn's disease.

Project description:ObjectivesThe aim of this study was to define the composition of the gut bacterial flora in Norwegian patients with early stage Crohn's disease (CD).MethodsBy using a nonselective metagenomics approach, the general bacterial composition in mucosal biopsies from the ileum and the colon of five subjects, four patients with different phenotypes of CD, and one noninflammatory bowel disease control, was characterized. After partial 16S ribosomal RNA (rRNA) gene sequencing, BLAST homology searches for species identification and phylogenetic analysis were performed.ResultsAn overall biodiversity of 106 different bacterial operational taxonomic units (OTUs) was detected in the cloned libraries. Nearly all OTUs belonged to the phylae Bacteroidetes (42% in CD, 71% in the control) or Firmicutes (42% in CD, 28% in the control), except for some OTUs that belonged to the phylum Proteobacteria (15% in CD, 0% in the control) and a few OTUs that could not be assigned to a phylum (2% in CD, 1% in the control).ConclusionBased on the high incidence of inflammatory bowel disease (IBD) in Norway, this pilot study represents a relevant determination of the gut microbiota in Norwegian patients compared to previous findings in other countries. The bacterial profile of Norwegian CD patients was found to be similar to that of CD patients in other countries. The findings do not support a particular bacterial composition as a predominant causative factor for the high incidence of IBD that exists in some countries.

| S-EPMC3459595 | biostudies-literature

Single cell analysis of newly diagnosed AML patients

Project description:Acute Myeloid Leukemia (AML) is a heterogenous disease characterized by immature blasts at different maturation stage. We used single cell sequencing technique to analyze newly diagnosed AML patients.

2023-12-18 | GSE239721 | GEO

Associations of lipid profiles with insulin resistance and β cell function in adults with normal glucose tolerance and different categories of impaired glucose regulation.

Project description:AimsTo investigate the associations of dyslipidemia with insulin resistance and β cell function in individuals with normal glucose tolerance (NGT) and different categories of impaired glucose regulation (IGR).Methods544 subjects (365 with dyslipidemia and/or IGR and 179 with normal lipid and glucose tolerance) were enrolled in the study. All subjects underwent oral glucose tolerance test (OGTT). HOMA-IR was used to evaluate insulin sensitivity. Disposition index (DI) was used to evaluate β cell function. Multiple linear regression analysis was performed to assess correlations among lipid profiles, insulin resistance and β cell function.ResultsAmong subjects with NGT, those with dyslipidemia had higher level of HOMA-IR but lower level of DI. While among subjects with different categories of IGR, those with dyslipidemia and CGI had significantly decreased DI. No obvious differences of insulin resistance or β cell function were found in IFG or IGT subjects with or without dyslipidemia. TG and HDL-C were correlated with HOMA-IR (β = 0.79, p <0.001; β = -0.38, p = 0.027, respectively, compared with subjects in the low level groups). Moreover, TG and TC were negatively correlated with DI (β = -2.17, p = 0.013; β = -2.01, p = 0.034 respectively, compared with subjects in the low level groups) after adjusting for confounding parameters.ConclusionsDyslipidemia induces insulin resistance and impaired β cell response to insulin resistance in individuals with NGT. Furthermore, dyslipidemia diminishes β cell function in subjects with CGI. TG and HDL-C were correlated with insulin resistance, and TG, TC were negatively correlated with β cell response to insulin resistance in non-diabetic individuals.

| S-EPMC5310856 | biostudies-literature

Changes in profile of lipids and adipokines in patients with newly diagnosed hypothyroidism and hyperthyroidism.

Project description:Changes in profile of lipids and adipokines have been reported in patients with thyroid dysfunction. But the evidence is controversial. The present study aimed to explore the relationships between thyroid function and the profile of lipids and adipokines. A cross-sectional study was conducted in 197 newly diagnosed hypothyroid patients, 230 newly diagnosed hyperthyroid patients and 355 control subjects. Hypothyroid patients presented with significantly higher serum levels of total cholesterol, triglycerides, low-density lipoprotein cholesterol (LDLC), fasting insulin, resistin and leptin than control (p?<?0.05). Hyperthyroid patients presented with significantly lower serum levels of high-density lipoprotein cholesterol, LDLC and leptin, as well as higher levels of fasting insulin, resistin, adiponectin and homeostasis model insulin resistance index (HOMA-IR) than control (p?<?0.05). Nonlinear regression and multivariable linear regression models all showed significant associations of resistin or adiponectin with free thyroxine and association of leptin with thyroid-stimulating hormone (p?<?0.001). Furthermore, significant correlation between resistin and HOMA-IR was observed in the patients (p?<?0.001). Thus, thyroid dysfunction affects the profile of lipids and adipokines. Resistin may serve as a link between thyroid dysfunction and insulin resistance.

| S-EPMC4872157 | biostudies-other

Association of Habitual Daily Physical Activity With Glucose Tolerance and β-Cell Function in Adults With Impaired Glucose Tolerance or Recently Diagnosed Type 2 Diabetes From the Restoring Insulin Secretion (RISE) Study.

Project description:ObjectiveWe examined the relationship between habitual daily physical activity and measures of glucose tolerance, insulin sensitivity, and β-cell responses in adults with impaired glucose tolerance (IGT) or drug-naive, recently diagnosed type 2 diabetes.Research design and methodsParticipants included 230 adults (mean ± SD age 54.5 ± 8.5 years, BMI 35 ± 5.5 kg/m2; 42.6% women) who underwent a 3-h oral glucose tolerance test (OGTT) and hyperglycemic clamp. Wrist accelerometers worn for 7 consecutive days measured total physical activity counts (TAC) (daily mean 233,460 [∼50th percentile for age]). We evaluated whether TAC was associated with fasting plasma glucose, OGTT 2-h plasma glucose or glucose incremental area under the curve (G-iAUC), hyperglycemic clamp measures of insulin sensitivity (steady-state glucose infusion rate/insulin [M/I]) and β-cell responses (acute C-peptide response to glucose, steady-state C-peptide, and maximal β-cell response), and OGTT C-peptide index (ΔC-peptide0-30/Δglucose0-30).ResultsAfter adjustments for confounders, there was no association of TAC with fasting plasma glucose, 2-h glucose, or G-iAUC. Higher TAC was associated with higher insulin sensitivity (M/I). After adjusting for M/I, higher TAC was not associated with measures of β-cell response.ConclusionsIn adults with IGT or drug-naive, recently diagnosed type 2 diabetes, higher levels of habitual physical activity are associated with higher insulin sensitivity. Further studies are needed to understand why higher levels of physical activity are not associated with better β-cell response.

| S-EPMC6647043 | biostudies-literature

Thresholds of oxidative stress in newly diagnosed diabetic patients on intensive glucose-control therapy.

Project description:Cellular and animal studies suggest that oxidative stress could be the central defect underlying both beta-cell dysfunction and insulin resistance in type 2 diabetes mellitus. A reduction of glycemic stress in diabetic patients on therapy alleviates systemic oxidative stress and improves insulin resistance and beta-cell secretion. Monitoring oxidative stress systematically with glucose can potentially identify an individual's recovery trajectory. To determine a quantitative model of serial changes in oxidative stress, as measured via the antioxidant glutathione, we followed patients newly diagnosed with diabetes over 8 weeks of starting anti-diabetic treatment. We developed a mathematical model which shows recovery is marked with a quantal response. For each individual the model predicts three theoretical quantities: an estimate of maximal glutathione at low stress, a glucose threshold for half-maximal glutathione, and a rate at which recovery progresses. Individual patients are seen to vary considerably in their response to glucose control. Thus, model estimates can potentially be used to determine whether an individual patient's response is better or worse than average in terms of each of these indices; they can therefore be useful in reassessing treatment strategy. We hypothesize that this method can aid the personalization of effective targets of glucose control in anti-diabetic therapy.

| S-EPMC4074157 | biostudies-literature

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