Explore the vast range of titles available.

Objective Glycemic control deteriorates more rapidly in youth vs adults. We compared model‐derived measures of β‐cell function between youth and adults with either impaired glucose tolerance (IGT) or type 2 diabetes to determine if a β‐cell defect differentiates these age groups. Methods This is a cross‐sectional analysis of baseline data from the Restoring Insulin Secretion (RISE) Study. Youth (54 Y‐IGT, 33 Y‐D) and adults (250 A‐IGT, 104 A‐D) underwent 3‐hour oral glucose tolerance tests for modeling of insulin secretion rates (ISRs), glucose sensitivity, and rate sensitivity. Insulin sensitivity was quantified as the glucose infusion rate/insulin (M/I) from a hyperglycemic clamp. Results Youth had lower insulin sensitivity despite similar body mass index. Analyses were adjusted for insulin sensitivity. Youth had higher basal ISRs (Y‐IGT 200 ± 161 vs A‐IGT 152 ± 74, P < .001; Y‐D 245 ± 2.5 vs A‐D 168 ± 115 pmol/min/m2, P = .007) and total ISRs (Y‐IGT 124 ± 86 vs A‐IGT 98 ± 39, P < .001; Y‐D 116 ± 110 vs A‐D 97 ± 62 nmol/m2, P = .002). Within IGT, glucose sensitivity (Y‐IGT 140 ± 153 vs A‐IGT 112 ± 70 pmol/min/m2/mM, P = .004) and rate sensitivity (median[interquartile range]:Y‐IGT 2271[1611, 3222] vs A‐IGT 1164[685, 1565] pmol/m2/mM, P < .001) were higher in youth, but not different by age group within diabetes. Conclusions Model‐derived measures of β‐cell function provide additional insight into the pathophysiology of type 2 diabetes in youth with higher ISRs and β‐cell secretion more responsive to glucose in youth relative to adults even after adjusting for differences in insulin sensitivity. It is unknown whether these findings in youth reflect β‐cells that are healthier or whether this is a defect that contributes to more rapid loss of function.

Cannabinoid 1 receptors (CB1Rs) are expressed in peripheral tissues, including islets of Langerhans, where their function(s) is under scrutiny. Using mouse β‐cell lines, human islets and CB1R‐null (CB1R−/−) mice, we have now investigated the role of CB1Rs in modulating β‐cell function and glucose responsiveness. Synthetic CB1R agonists diminished GLP‐1‐mediated cAMP accumulation and insulin secretion as well as glucose‐stimulated insulin secretion in mouse β‐cell lines and human islets. In addition, silencing CB1R in mouse β cells resulted in an increased expression of pro‐insulin, glucokinase (GCK) and glucose transporter 2 (GLUT2), but this increase was lost in β cells lacking insulin receptor. Furthermore, CB1R−/− mice had increased pro‐insulin, GCK and GLUT2 expression in β cells. Our results suggest that CB1R signalling in pancreatic islets may be harnessed to improve β‐cell glucose responsiveness and preserve their function. Thus, our findings further support that blocking peripheral CB1Rs would be beneficial to β‐cell function in type 2 diabetes.

Objective To identify genetic loci that exhibit potential interactions with smoking status on insulin sensitivity and islet β‐cell function within normal glucose tolerance (NGT) populations. Methods All participants underwent an OGTT to confirm NGT status, followed by assessments of insulin sensitivity and β‐cell function. Analyses were performed in NGT participants from Nanjing (N = 4808) and Jurong (N = 508) for discovery and validation, respectively. Smoking status was categorized into nonsmokers and smokers. After excluding ineligible individuals, a two‐stage genome‐wide interaction association analysis (GWIS) was conducted in NGT individuals, with the discovery phase (N = 1377) identifying gene–environment interactions and the validation phase (N = 485) confirming significant loci. Subsequent analyses included stratified analysis and expression quantitative trait locus (eQTL) colocalization. Results GWIS identified ten SNPs in three loci, including rs4713207 (OR14J1, Pmeta = 3.95 × 10−8) for insulin resistance, rs17708475 (NKAIN2, Pmeta = 4.83 × 10−8) for insulin sensitivity, and rs201613 (MYH3, Pmeta = 1.05 × 10−8) for disposition index. Stratified analyses revealed differential effects of smoking across genotypes at these loci. Specifically, smoking was associated with increased insulin resistance in rs4713207 homozygotes (p = 2.15 × 10−5), while an opposite effect was observed in wild‐type individuals (p = 0.022). Colocalization analysis indicated that the smoking‐related interaction near rs4713207 is driven by a shared causal variant influencing HCG4 (PP.H4 = 0.70) and ZNF311 (PP.H4 = 0.74) expression in the pancreas. Conclusions Our findings reveal gene‐smoking interactions that affect insulin sensitivity and β‐cell function, providing new insights into the heterogeneity of metabolic phenotypes and advancing personalized risk assessment. Gene‐smoking interactions in insulin sensitivity and β‐cell function in normoglycemic individuals.

Aims/Introduction Previous studies have shown that glucose peak time during the oral glucose tolerance test varies in type 2 diabetes patients; however, characteristics of this heterogeneity remain unclear. This research aimed to investigate the characteristics of delayed glucose peak time in type 2 diabetes. Materials and Methods A total of 178 participants who underwent the oral glucose tolerance test were divided into five groups according to glucose peak time. Results A total of 25 participants with normal glucose tolerance had a glucose peak at 30 min. Among participants with type 2 diabetes, 28 had a glucose peak at 60 min, 48 at 90 min, 45 at 120 min and 32 at 150 min. With the glucose peak time delayed, glycated hemoglobin, area under the glucose curve and homeostatic model assessment of insulin resistance increased gradually (P = 0.038, P < 0.0001, P < 0.0001, respectively), and oral glucose insulin sensitivity, homeostatic model assessment of β‐cell function, insulinogenic index, modified β‐cell function index and disposition indices decreased (P < 0.0001 for all). On multinominal logistic regression, insulinogenic index (odds ratio 0.73, 95% confidence interval 0.57–0.93, P = 0.01), modified β‐cell function index (odds ratio 0.67, 95% confidence interval 0.47–0.94, P = 0.023) and oral glucose insulin sensitivity (odds ratio 0.91, 95% confidence interval 0.87–0.96, P < 0.0001) were independently correlated with delayed glucose peak time. Conclusions Delay in glucose peak time indicated an increase in blood glucose and a decrease in insulin sensitivity and secretion. Furthermore, insulinogenic index, modified β‐cell function index and oral glucose insulin sensitivity contributed to delayed glucose peak time. The purpose of this research was to investigate the characteristics of delayed glucose peak time of type 2 diabetes. Along with the delay of glucose peak time, blood glucose increased while insulin sensitivity and secretion decreased. Insulinogenic index, modified beta‐cell function index, oral glucose insulin sensitivity contributed to delayed glucose peak time.

Aim Circulating Gremlin 2 (Grem2) has recently been linked to human obesity, but its role in type 2 diabetes (T2D) remains unclear. This study aims to explore the association of circulating Grem2 with β‐cell function. Methods A post hoc analysis was conducted using data from three clinical trials, in which all participants underwent the oral glucose tolerance test (OGTT). Circulating Grem2 levels were measured at 0, 1, and 2 h during the OGTT. In Trial 1, Grem2 levels were compared between participants with T2D (n = 59) and without T2D (n = 119). We further examined changes in Grem2 levels in response to oral antidiabetic drugs in participants with T2D in Trial 2 (n = 67) and calorie restriction in participants with prediabetes in Trial 3 (n = 231). The relationship between Grem2 levels and β‐cell function was analyzed across all trials. Results Fasting and 1‐h Grem2 levels were lower in participants with T2D compared with those without T2D (728 ± 25 vs. 649 ± 31 pg/mL, p = 0.020; 631 ± 26 vs. 537 ± 31 pg/mL, p = 0.007). Fasting Grem2 levels were restored after antidiabetic treatment (550 ± 12 vs. 575 ± 12 pg/mL, p = 0.019), and 1‐h Grem2 levels increased following calorie restriction (1118 ± 89 vs. 1144 ± 90 vs. 1253 ± 89 pg/mL, p for trend = 0.002). The 1‐h Grem2 levels were positively associated with β‐cell function assessed by the oral disposition index and HOMA‐β. Conclusion Reduced circulating Grem2 levels are associated with impaired β‐cell function in T2D, and could be restored through antidiabetic interventions. Trial Registration: ClinicalTrials.gov: NCT01959984, NCT01758471, NCT03856762

Abstract Context Fruit, but not fruit juice, intake is inversely associated with type 2 diabetes mellitus (T2DM). However, questions remain about the mechanisms by which fruits may confer protection. Objective The aims of this work were to examine associations between intake of fruit types and 1) measures of glucose tolerance and insulin sensitivity and 2) diabetes at follow-up. Methods Among participants of the Australian Diabetes, Obesity and Lifestyle Study, fruit and fruit juice intake was assessed by food frequency questionnaire at baseline. Associations between fruit and fruit juice intake and 1) fasting plasma glucose, 2-hour postload plasma glucose, updated homeostasis model assessment of insulin resistance of β-cell function (HOMA2-%β), HOMA2 of insulin sensitivity (HOMA2-%S), and fasting insulin levels at baseline and 2) the presence of diabetes at follow-up (5 and 12 years) were assessed using restricted cubic splines in logistic and linear regression models. Results This population of 7675 Australians (45% males) had a mean ± SD age of 54 ± 12 years at baseline. Total fruit intake was inversely associated with serum insulin and HOMA2-%β, and positively associated with HOMA2-%S at baseline. Compared to participants with the lowest intakes (quartile 1), participants with moderate total fruit intakes (quartile 3) had 36% lower odds of having diabetes at 5 years (odds ratio, 0.64; 95% CI, 0.44-0.92), after adjusting for dietary and lifestyle confounders. Associations with 12-year outcomes were not statistically significant. Conclusion A healthy diet including whole fruits, but not fruit juice, may play a role in mitigating T2DM risk.

Aims This study investigated the association of capillary blood glucose (CBG)‐assessed time in range (TIR) (3.9–10.0 mmol/L) with insulin sensitivity and islet β‐cell function. Materials and Methods We recruited 455 patients with type 2 diabetes mellitus. Seven‐point glucose‐profile data (pre‐ and 120 min post‐main meals, bedtime) were collected over three consecutive days. Plasma glucose and serum insulin concentrations were measured at 0, 60, and 120 min after a 100 g standard steamed bread meal test. The homeostasis model assessment of insulin resistance (HOMA‐IR) and Matsuda index were computed to evaluate insulin resistance. The HOMA of β‐cell function (HOMA‐β) and the area under the curve between insulin and blood glucose (IAUC0−120/GAUC0−120) were used to estimate β‐cell function. Results TIR was positively correlated with the 60 and 120 min insulin values, IAUC0−120, the Matsuda index, HOMA‐β, and IAUC0−120/GAUC0−120 (rs: 0.154, 0.129, 0.137, 0.194, 0.341, and 0.334, respectively; P < 0.05) but inversely correlated with HOMA‐IR (rs: –0.239, P < 0.001). After adjusting for confounders, multinomial multiple logistic regression analysis revealed that the odds ratios (ORs) of achieving the target time in range (>70%) increased by 12% (95% confidence interval [CI]: 3–21%), 7% (95% CI: 1–14%), 10% (95% CI: 5–16%), and 45% (95% CI: 25–68%) for each 10 mIU/L increase in the 60 and 120 min insulin values, 10 unit increase in HOMA‐β, and unit increase in IAUC0−120/GAUC0−120, respectively (P < 0.05). Nevertheless, the OR decreased by 10% (95% CI: 1–18%) for each unit increase in HOMA‐IR (P < 0.05). Conclusions Insulin resistance and islet β‐cell function are related to capillary blood glucose‐assessed TIR. 1. To our knowledge this is the first study looking at insulin resistance and TIR in patients with T2DM. 2. Insulin resistance is negatively correlated with TIR in patients with T2DM 3. Impaired ‐cell function has negative effects on TIR in patients with T2DM

Background In adults, the time‐to‐glucose‐peak at or after 30 minutes during an oral glucose tolerance test (OGTT) identifies physiologically distinct groups with differences in insulin sensitivity, β‐cell function and risk for type 2 diabetes. In obese non‐diabetic adolescents, we investigated if the OGTT‐time‐to‐glucose‐peak also reflects incretin and free fatty acid (FFA) responses besides insulin sensitivity and β‐cell function, measured by the clamp. Methods Obese adolescents (n = 278) were categorized according to their OGTT‐time‐to‐glucose‐peak by Early‐peak (at 30 minutes) vs Late‐peak (>30 minutes) groups. Body composition, visceral adipose tissue, oral disposition index and OGTT‐area under the curve (AUC) were examined. A subset of 102 participants had both hyperinsulinemic‐euglycemic and hyperglycemic clamps to measure in vivo insulin sensitivity, insulin secretion, and β‐cell function relative to insulin sensitivity. Results Compared with the Early‐peak group, the Late‐peak group had impaired β‐cell function relative to insulin sensitivity, lower glucose‐dependent insulinotropic polypeptide‐AUC, and higher FFA‐AUC despite higher insulin‐ and C‐peptide‐AUC. They also had lower hepatic and peripheral insulin sensitivity despite similar percent body fat and visceral adipose tissue, and had higher prevalence of impaired glucose tolerance (all P < .05). Conclusions In obese non‐diabetic youth, those with a Late‐peak vs an Early‐peak glucose during an OGTT showed diminished β‐cell function, blunted incretin secretion, and lower insulin sensitivity of glucose and FFA metabolism. It remains to be determined if Late‐peak glucose predicts the future development of type 2 diabetes in these high‐risk youth.

Background Type 2 diabetes (T2DM) is a disease marked by inadequate insulin secretion by pancreatic beta‐cell function (BCF) failure and insulin resistance (IR). Assessing and managing the BCF and IR should be started early to prevent or delay the progression of the disease. The aim of this study was to determine the usefulness of the estimated average glucose (eAG)/fasting blood glucose (FBG) ratio for pancreatic BCF in hyperglycemia. Methods This cross‐sectional study consecutively selected 10,594 subjects who underwent a health checkup at 16 health checkup centers in 13 Korean cities between 2019 and 2021. The subjects consisted of 3003 patients with normoglycemia, 3413 with impaired fasting glucose and 4178 with T2DM. The eAG was calculated using Nathan's regression equation. BCF and IR were estimated by the homeostasis model assessment (HOMA)‐β and HOMA‐IR, respectively. Multivariate (adjusted) regression analysis was performed to evaluate the association between the eAG/FBG ratio and HOMA. Results The median values among FBG groups for the eAG/FBG ratio, HOMA‐β, ‐IR and insulin differed significantly (p < 0.001). The second‐, third‐ and fourth‐quartile groups of the eAG/FBG ratio had positive higher correlation coefficients [9.533, 10.080 and 12.021, respectively (all p < 0.001)] for HOMA‐β than the first quartile group, and higher negative coefficients for HOMA‐IR [−0.696, −0.727 and −0.598, respectively (all p = 0.001)]. Conclusion The eAG/FBG ratio was significantly correlated with both HOMA‐β and ‐IR, which suggests that eAG/FBG ratio reveals BCF and IR in hyperglycemia. Measurement of this ratio could be useful for monitoring BCF and IR in prediabetes and T2DM.

Objective To evaluate β‐cell function in obese children and adolescents meeting clinical criteria for isolated obesity (iOB), isolated components of dysmetabolism (cMD), or metabolic syndrome (MS), and in obese children and adolescents with normal glucose tolerance (NGT), impaired glucose regulation (IGR), or type 2 diabetes (T2DM). Study Design We undertook a prospective study of Han Chinese children and adolescents aged 8‐16 years (median 11 ± 1.4) seen in an obesity clinic between May 2013 and 2018. Patients were classified as iOB (53), cMD (139), and MS (139) groups based on clinical criteria. The same patients were also classified as NGT (212), IGR (111), or T2DM (8) based on results of an oral glucose tolerance test (OGTT). The MS patients were classified as NGT [MS](59) and IGR [MS](72) for the further study. All participants also completed a mixed‐meal tolerance test (MMTT). Results Compared with the iOB group, the MS group had significantly higher area under the curve of C‐peptide up to the 2 hours (AUC CP) (P = .03) and peak C‐peptide (P = .03), adjusted for BMI, age and Tanner stage, on MMTT. However, there was no difference in the insulinogenic index (ΔI30/ΔG30) or oral disposition index (oDI) derived from the OGTT among the three groups. However, 52% of participants with MS had IGR, compared to 28% in the cMD group. Compared with the NGT group, the individuals with IGR had significantly lower ΔI30/ΔG30 (P = .001) and oDI (P < .001). Compared with the iOB group, the NGT[MS] had significantly higher AUC CP (P = .004), peak C‐peptide (P = .004) and ΔI30/ΔG30 (P = .007) adjusted for age, but no difference in oDI. Compared with the NGT[MS], the IGR[MS] had significantly lower ΔI30/ΔG30 (P = .005) and oDI (P < .001), but the AUC CP and peak C‐peptide had no difference. Conclusion Although the MS youth have β‐cell hyperfunction as a whole, β‐cell dysfunction is present in the early stages of dysmetabolism in obese youth with cMD or MS and worsened across the spectrum from iOB to cMD and MS, contributing to development of T2DM.