Beta Cell Function Index Research Articles

PS-C29-3: CHANGE OF PANCREAS VOLUME AND GLUCOSE METABOLIC INDEX WITH THE INCREASE OF WEIGHTS: ANALYSES OF COMPREHENSIVE HEALTH CHECKUP DATA

Objective: Pancreas volume measured using imaging techniques has been shown to be increased in subjects with obesity and reduced in subjects with diabetes. Beta-cell mass of pancreas also was reported to be increased with obesity in autopsy samples. While, the increase in beta-cell mass of pancreas with obesity was reported to limit in Japanese autopsy studies, suggesting that Japanese have less compensatory changes of beta-cell associated with insulin resistance. Therefore, we aimed to explore the changes of pancreas volume and glucose metabolic index including beta-cell function with the increase of weights in analyses of comprehensive health checkup data. Design and method: We collected subjects to have the following characteristics: 1) had our health checkup between April 2014 and March 2015 at aged 20–80 years; 2) had our health checkup between April 2015 and March 2017 with an increase in body mass index (BMI) of at least 1 kg/m2 from the baseline period; 3) no diagnosis of diabetes (HbA1c < 6.5%, fasting plasma glucose < 126 mg/dl and no medication); 4) had the adequate quality in CT images to assess the pancreas volume. The pancreas was outlined by hand in each CT image and the pancreas volume was computed by summing the product of pancreas area (cm2) of each image and the CT section thickness. Homeostasis model assessment of insulin resistance (HOMA-IR) and beta-cell function (HOMA-beta) were calculated as indices of insulin resistance and beta-cell function, respectively. Paired t-test was used to analyze changes in parameters. Results: Thirty-five subjects (29 men, mean age 59 years, mean height 167 cm, mean weight 71 kg) were included in this analysis and mean follow-up was 21 months. BMI and HOMA-IR increased significantly from the baseline (25.5 kg/m2 vs. 27.0 kg/m2, P < 0.001 and 1.58 vs. 1.89, P < 0.05). While, there were no significant change in HOMA-beta and blood pressure from the baseline (56.4 vs. 65.7 and 122/79 mmHg vs. 126/82 mmHg, all P > 0.05). Conclusion: The change in beta-cell function with the increase of weights and insulin resistance was modest, consistent with the change of beta-cell mass with obesity in Japanese autopsy samples. We report the change of pancreas volume evaluating with CT image in addition to these results.

“Ogtt-Plus” – A Novel Web-App for Model Assessment of Cardio-Vascular Risk in Obesity, Dysmetabolism & Dysglycemia

We developed this web based ‘Dysmetabolism-Risk Calculator’ after analysing 1800 individuals, who underwent ‘standard two hour 75 gram OGTT’ along with insulin levels. It calculates the basal and post-glucose indexes of insulin secretion (ISec), insulin resistance (IRes) and beta cell function (BCF), based on areas under the curve of both glucose (AUCg) and insulin (AUCi). It generates dynamic graphs of glucose and insulin along with population-norm values and determines various stages of dys-insulinemia, obesity, and diabetes. On the dysmetabolism time-line, ‘Euglycemic Hyperinsulinemia’ and ‘Midzone Hyperglycemia’, are specially important categories. These categories, characteristically, occur before ‘Prediabetes’ stage, (Pre-Prediabetes), and are known to be associated with increased cardio-vascular morbidity such as hypertension, dyslipidemia, endothelial dysfunction, and stroke. IRes is calculated using “AUCg*AUCi*k” formula. ISec and central IRes is calculated by measuring ‘rate of rise of insulin’ and the angle theta, which is subtended by the 30 min insulin curve with ‘x’ axis. Insulin disposal and peripheral IRes is determined by calculating angle zeta which is subtended by the 90-120 min insulin curve with ‘y’ axis. Disposition index (Isec*Ires*k) is calculated by the formula “1/(AUCg) 2”, which, noticeably, is independent of AUCi. The discordance between Insulin Secretion Index and OGTT Disposition Index will be useful in predicting the reversibility of diabetes and dysmetabolism. BMI, 0-30 & 90-120 min AUCis are used as parameters, while calculating the probable site of ‘Tissue IRes’. Cardio-Vascular risk calculations are based on hyperinsulinemia (as macrovascular risk), hyperglycemia (as microvascular risk), and their combination as they occur on dysmetabolism time-time.

LBSUN161 Relationship Of Shape Of Glucose OGTT Curves With Measures Of Cardiometabolic Health In African American Adolescents

Abstract Background and Aims Studies in youth and adults have shown that the shape of oral glucose tolerance test (OGTT) response curve may be a biomarker for insulin secretion and insulin sensitivity (IS). Individuals with monophasic (MPh) glucose response curve have lower IS and decreased beta-cell function compared to those with biphasic (BPh) pattern. The aim of this study was to assess if the shape of the glucose response curve of OGTT is associated with 2-D ECHO based indices of heart structure and function. Methods In a cross-sectional study, African American (AA) adolescents with and without obesity between the ages of 13-18 years were recruited to assess the relationship of blood pressure, obesity, and measures of cardiac health. Metabolic and inflammatory markers, 2-D ECHO and OGTT data were collected. The shape of the OGTT glucose response was classified based on a change from nadir to glucose-120 min of ≥ 4.5 mg/dL, and its association with cardiac health indices was calculated. R v.4.1.2 was used for analysis. Results Of the 276 individuals with available OGTT data (mean age 16.18 ± 1.70 years, 47.5% females), 39 (14.1%) had BPh curve. The individuals with BPh were lower in age (15.61 ± 1.68 vs 16.28 ± 1.68, p=0. 02), but similar in sex, BMI, BMIz and metabolic parameters. There was no difference in impaired glucose tolerance (27% [BPh] vs 15% [MPh], p=. 08). At 120 min, glucose (6.96 ± 0. 07 vs 6.31 ± 0. 07 mmol/L, p=. 05), and insulin (362.86 ± 13.69 vs 276.48 ± 13.61 uIU/mL, p=. 04) levels were higher in BPh. The glucose area under the curve (AUC) was lower in individuals with BPh (13.2 ± 1.23 vs 14.7 ± 1.16 mmol/L/hr, p <. 001) while the insulinogenic index (1.5 ± 3.79 vs 1.17 ± 2.74, p =. 03) and oral glucose disposition index were higher in both univariate analyses and after adjusting for age, sex and BMIz. The aortic root size was associated with the shape of the curve adjusting for age, sex and BMIz (p=. 03), but not ventricular or atrial mass, systolic or diastolic function. Conclusions There was lower proportion of individuals with BPh in this cohort of AA adolescents compared to published studies. Individuals with BPh had healthier beta-cell function indices. No significant relationship of the shape of the OGTT curve was seen with the metrics of heart structure or function at this age. Replication of results in adult cohort(s) is ongoing. Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.

Endogenous GLP-1 levels play an important role in determining the efficacy of DPP-IV Inhibitors in both prediabetes and type 2 diabetes.

BackgroundIn contrast to Western population, glucagon-like peptide-1 (GLP-1) levels are preserved in some East Asian population with type 2 diabetes (T2D), explaining why dipeptidyl peptidase-IV (DPP-IV) inhibitors are more effective in East Asians. We assessed whether differences in endogenous GLP-1 levels resulted in different treatment responses to DPP-IV inhibitors in prediabetes and T2D.MethodsA prospective 12-week study using linagliptin 5mg once daily in 50 subjects (28 prediabetes and 22 T2D) who were stratified into high versus low fasting GLP-1 groups. A 75-g oral glucose tolerance test (OGTT) was performed at week 0 and 12. Primary outcomes were changes in HbA1c, fasting and post-OGTT glucose after 12 weeks. Secondary outcomes included changes in insulin resistance and beta cell function indices.ResultsThere was a greater HbA1c reduction in subjects with high GLP-1 compared to low GLP-1 levels in both the prediabetes and T2D populations [least-squares mean (LS-mean) change of -0.33% vs. -0.11% and -1.48% vs. -0.90% respectively)]. Linagliptin significantly reduced glucose excursion by 18% in high GLP-1 compared with 8% in low GLP-1 prediabetes groups. The reduction in glucose excursion was greater in high GLP-1 compared to low GLP-1 T2D by 30% and 21% respectively. There were significant LS-mean between-group differences in fasting glucose (-0.95 mmol/L), 2-hour glucose post-OGTT (-2.4 mmol/L) in the high GLP-1 T2D group. Improvement in insulin resistance indices were seen in the high GLP-1 T2D group while high GLP-1 prediabetes group demonstrated improvement in beta cell function indices. No incidence of hypoglycemia was reported.ConclusionsLinagliptin resulted in a greater HbA1c reduction in the high GLP-1 prediabetes and T2D compared to low GLP-1 groups. Endogenous GLP-1 level play an important role in determining the efficacy of DPP-IV inhibitors irrespective of the abnormal glucose tolerance states.

Circulating interleukin-6 and cardiovascular disease risk in patients with rheumatoid arthritis with low disease activity due to active therapy.

Interleukin-6 (IL-6) has been implicated in the pathophysiology of rheumatoid arthritis (RA) and in the development of atherosclerosis in the general population. In the present work we aimed to study if IL-6 serum levels have an influence on factors associated with cardiovascular (CV) disease in a cohort of Spanish patients with RA. Cross-sectional study that encompassed 407 patients with RA. Serum IL-6 levels were assessed. Multivariable analysis was performed to examine the relationship of IL-6 to subclinical carotid atherosclerosis and classic CV risk factors, including a comprehensive lipid molecule profile and indices of insulin resistance and beta-cell function. Circulating levels of IL-6 showed a correlation with acute phase reactants, disease activity, and other features of RA. However, classic CV risk factors, lipid profile and indices of insulin resistance, as well as subclinical carotid atherosclerosis, were not associated with serum IL-6 levels. Although a direct association between IL-6 levels and traditional CV risk factors and subclinical carotid atherosclerosis was not observed, circulating IL-6 was associated with disease activity and acute-phase reactants, which have been associated with an increased risk of CV in these patients.

Interleukin 1 receptor antagonist relation to cardiovascular disease risk in patients with rheumatoid arthritis

Interleukin (IL) 1, and its family member, IL-1 receptor antagonist (IL-1ra), are involved in the pathogenesis and inflammation perpetuation of patients with rheumatoid arthritis (RA). Besides, IL-1 has been linked to an increased risk and greater severity of cardiovascular (CV) disease. We aimed to study if IL-1ra is related to the CV manifestations—including lipid pattern and insulin resistance or subclinical atherosclerosis—that accompanies the disease in a large series of patients with RA. Cross-sectional study that encompassed 430 patients with RA. Serum IL-1ra levels were assessed. A multivariable analysis was performed to analyze the relation of IL-1ra to subclinical carotid atherosclerosis, and to traditional CV factors including a complete lipid molecules profile and insulin resistance or beta cell function indices. Body mass index, abdominal circumference, and the presence of obesity were significantly and positively associated with circulating IL-1ra. Similarly, erythrocyte sedimentation rate, and disease activity scores were significantly related to higher IL-1ra serum levels after adjustment for confounders. Neither carotid intima-media thickness nor the presence of carotid plaque were associated with serum levels of IL-1ra. However, after multivariable analysis circulating IL-1ra was independently and positively associated with higher serum levels of total cholesterol, triglycerides, and apolipoproteins B and C-III. Similarly, IL-1ra was related to higher levels of beta-cell function in the univariable analysis, although, in this case, significance was lost after adjustment. Among patients with RA, IL-1ra is associated with both disease activity and several traditional CV risk factors such as obesity and the presence of higher lipid levels. Our findings suggest that IL-1ra can represent a link between the inflammation and the CV disease risk that are present in patients with RA.

Type 2 diabetes subgroups and response to glucose-lowering therapy: Results from the EDICT and Qatar studies.

To examine the efficacy of glucose-lowering medications in subgroups of patients with type 2 diabetes mellitus (T2DM). Cluster analysis was performed in participants in the Efficacy and Durability of Initial Combination Therapy for Type 2 Diabetes (EDICT) study and the Qatar study using age, body mass index (BMI), glycated haemoglobin (HbA1c), and homeostatic model assessment of insulin resistance (HOMA-IR) and beta-cell function (HOMA-β). Participants also underwent an oral glucose tolerance test with measurement of plasma glucose, insulin and C-peptide concentrations to derive independent measures of insulin secretion and insulin sensitivity. The response to glucose-lowering therapies (change in HbA1c) was measured in each participant cluster for 3 years. Three distinct and comparable clusters/groups of T2DM patients were identified in both the EDICT and Qatar studies. Participants in Group 1 had the highest HbA1c and manifested severe insulin deficiency. Participants in Group 3 had comparable insulin sensitivity to those in Group 1 but better beta-cell function and better glucose control. Participants in Group 2 had the highest BMI with severe insulin resistance accompanied by marked hyperinsulinaemia, which was primarily attributable to decreased insulin clearance. Unexpectedly, participants in Group 1 had better response to combination therapy with pioglitazone plus exenatide than with insulin therapy or metformin sequentially followed by glipizide and basal insulin, while participants in Group 2 responded equally well to both therapies despite very severe insulin resistance. Distinct metabolic phenotypes characterize different T2DM clusters and differential responses to glucose-lowering therapies. Participants with severe insulin deficiency respond better to agents that preserve beta-cell function, while, surprisingly, patients with severe insulin resistance did not respond favourably to insulin sensitizers.

Long-Term Metabolic Outcomes after Gestational Diabetes Mellitus (GDM): Results from the Odense GDM Follow-Up Study (OGFUS).

Aims To compare metabolic profiles and the long-term risk of metabolic dysfunction between women with previous gestational diabetes mellitus (pGDM) and women without pGDM (non-GDM) matched on age, prepregnancy body mass index (BMI), and parity. Methods In total, 128 women with pGDM (median follow-up: 7.8 years) and 70 non-GDM controls (median follow-up: 10.0 years) completed a 2 h oral glucose tolerance test (OGTT) with assessment of glucose, C-peptide, insulin, and other metabolic measures. Additionally, anthropometrics, fat mass, and blood pressure were assessed and indices of insulin sensitivity and beta cell function were calculated. Results The prevalence of type 2 diabetes mellitus (T2DM) was significantly higher in the pGDM group compared to the non-GDM group (26% vs. 0%). For women with pGDM, the prevalence of prediabetes (38%) and the metabolic syndrome (MetS) (59%) were approximately 3-fold higher than in non-GDM women (p's < 0.001). Both insulin sensitivity and beta cell function were significantly reduced in pGDM women compared to non-GDM women. Conclusion Despite similar BMI, women with pGDM had a substantially higher risk of developing T2DM, prediabetes, and the MetS compared to controls. Both beta cell dysfunction and reduced insulin sensitivity seem to contribute to this increased risk.

Effects of Glimepiride Combined with Recombinant Human Insulin Injection on Serum IGF-1, VEGF and TRACP-5b Oxidative Stress Levels in Patients with Type 2 Diabetes Mellitus.

Objective This study was designed to explore the effect of glimepiride combined with recombinant human insulin injection on serum insulin-like growth factor 1 (IGF-1), vascular endothelial growth factor (VEGF), tartrate-resistant acid phosphatase 5b (TRACP-5b) and oxidative stress levels in patients with type 2 diabetes. Methods A total of 217 patients with type 2 diabetes who were treated in our hospital from November 2018 to March 2020 were selected and divided into control group and treatment group. The control group was treated with glimepiride (n = 107). The study group was given glimepiride and recombinant human insulin injection) (n = 107). The levels of blood glucose, blood lipids, IGF-1, VEGF, TRACP-5b, and oxidative stress in the two groups were measured, respectively. We summarize the main results as follows. Insulin resistance index (HOMA-IR), fasting blood glucose (FPG), 2h postprandial blood glucose (2hBG), serum glycated hemoglobin (HbA1c), triglyceride (TG), total cholesterol (TC), serum malondialdehyde (MDA), reactive oxygen species (ROS), VEGF, and TRACP-5b levels were significantly lower than those before treatment, and the degree of reduction in the study group was greater than that in the control group (P < 0.05). The levels of insulin (INS), insulin beta cell function index (HOMA-beta), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and IGF-1 were significantly higher than those before treatment. Further, the study group demonstrated better results than the control group (P < 0.05). Conclusion Glimepiride combined with recombinant human insulin injection can improve insulin sensitivity, reduce insulin resistance, significantly reduce glucose and lipids in patients, reduce the occurrence of oxidative stress, promote the secretion of oxidative resistance enzymes, lower the vascular endothelial growth factor (VEGF), reduced the formation of new blood vessels, and inhibit the growth and metastasis of cancer cells. Additionally, we found out that glimepiride combined with recombinant human insulin injection had a good prognosis for patients; it significantly reduced the bone resorption marker TRACP-5b and prevented the occurrence of complications such as osteoporosis. The combined use of the two is more effective than glimepiride alone. In conclusion, glimepiride combined with recombinant human insulin injection has higher application value in the treatment of patients with type 2 diabetes.

Metformin for Preventing Progression From Prediabetes to Diabetes Mellitus in People Living With Human Immunodeficiency Virus.

BackgroundDiabetes mellitus (DM) and human immunodeficiency virus (HIV) itself increase the risk for cardiovascular diseases in people living with HIV (PLHIV). Prediabetes, a condition preceding DM, is common in PLHIV receiving antiretroviral therapy (ART). Both metformin and lifestyle interventions have been established to reduce the risk of progression from prediabetes to DM in the general population. This study aimed to evaluate the efficacy of metformin for preventing DM in prediabetic PLHIV.MethodsAn open-label randomized controlled clinical trial was conducted in HIV-positive persons with prediabetes. The participants were randomized into two groups: the metformin group (received metformin) and the control group (did not receive metformin). All participants were counseled regarding diet control and lifestyle modification and followed for 12 months. The primary endpoint was the development of DM. Fasting plasma glucose (FPG), two-hour plasma glucose (2-h PG) after 75 g oral glucose tolerance test (OGTT), hemoglobin A1c (HbA1c), and computer-based homeostatic model assessment index of beta-cell function (HOMA%B) and insulin resistance (HOMA-IR) were analyzed.ResultsSeventy-four participants were enrolled, 37 in each group. The mean age was 49.6 years, and 68.9% were males. At baseline, the mean CD4 cell count was 570 cells/mm3, and the mean body mass index (BMI) was 24.6 kg/m2. Baseline characteristics including age, sex, BMI, waist/hip ratio, duration of ART, ART regimen, CD4 cell count, and HIV RNA were similar between the two groups. The mean FPG, 2-h PG, HbA1c, HOMA%B, and HOMA-IR at baseline were also similar between the two groups. At 12 months, one participant in the metformin group and three in the control group developed DM (risk reduction: 5.41%; 95% confidence interval (CI): −6.92%-18.78%). When we compared changes in parameters between the two groups, there were trends toward more changes in HbA1c (DeltaHbA1c) at both six months (metformin group versus control group: -0.17% ± 0.20% versus 0.02% ± 0.58%; p = 0.074) and 12 months (metformin group versus control group: -0.05% ± 0.23% versus 0.06% ± 0.27%; p = 0.065). When we considered changes in all parameters in each group, the metformin group had significant reductions in body weight (BW) and BMI at both six and 12 months, and significant reductions in HbA1c and HOMA-IR at six months. No participant had adverse effects that led to the discontinuation of metformin. No cardiovascular event was observed during the study period.ConclusionsMetformin tends to improve HbA1c and insulin resistance and may prevent progression from prediabetes to DM in HIV-positive persons with prediabetes. A further large study with a longer study period is needed to evaluate the long-term benefit of metformin.

Abstract 115: Lean PCOS and IR: A sine QUA non?

Background: There is conflicting evidence with regards to insulin resistance (IR) among lean and obese PCOS. There is a lack of consensus on optimal screening strategy for IR in lean PCOS.Aims and Objectives: The objective was to compare indices of IR, insulin sensitivity and beta cell function (ßF) on a detailed 5 point OGTT (0,30,60,90,120 minute) between Obese (n= 52) and lean (n=28) (BMI ≥23/<23 kg/m2) PCOS and their age- and BMI-matched controls.Results: The OGTT showed cases had higher insulin values and Area Under Curve (AUC) with similar glucose levels as compared to their respective controls (p<0.05). Lean PCOS were more hyperinsulinemic as compared to obese controls (p<0.05). Matsuda index was significantly higher while first and 2nd phase Glucose Stimulated Insulin Secretion (GSIS) with ßF though higher wasn’t significant in lean cases as compared to obese cases (p<0.009). Though both the groups were hyperinsulinemic, lean cases had preserved insulin sensitivity compared to the obese cases. On applying ROC to OGTT values, 90 minute insulin value (52.3 μIU/ml) had the best predictive power for IR. 40% subjects classified as non IR on the basis of fasting value were found to cross this threshold, with more lean cases demonstrating this phenomenon as compared to obese.Conclusion: Increased IR was found in lean PCOS compared to lean and obese controls with 90 minute insulin value diagnosing additional IR missed on routine OGTT.

Evidence of dysregulated iron homeostasis in newly diagnosed diabetics, but not in pre-diabetics.

Diabetes mellitus has been reported to be associated with increased serum levels of ferritin. The basis of this association is unclear. It is also not precisely known whether other iron-related parameters, including hepcidin (the central regulator of systemic iron homeostasis), are affected under these circumstances. This study attempted to determine this. Adult men (normoglycemic or newly diagnosed with diabetes or pre-diabetes) were recruited. Anthropometric, metabolic, and hematological and iron-related parameters in blood were measured. Indices of insulin resistance (HOMA-IR) and pancreatic beta cell function (HOMA-β) were calculated. Subjects in the 3 groups were similar in age, and anthropometric and hematological parameters. Serum ferritin and hepcidin levels were higher in diabetics, than in pre-diabetics and in control subjects. These elevations seen were not linked to the presence of inflammation. HOMA-IR was higher in diabetics, and HOMA-β lower in diabetics and pre-diabetics, than in control subjects. HOMA-IR and serum ferritin were positively correlated with one another. Elevated levels of serum ferritin and hepcidin in newly diagnosed diabetics (but not pre-diabetics) indicate dysregulated iron homeostasis, with the former positively associated with insulin resistance in these patients.

Insulin Resistance Is Not Increased in Inflammatory Bowel Disease Patients but Is Related to Non-Alcoholic Fatty Liver Disease.

Background. Insulin resistance (IR) has been linked to inflammatory states. The aim of this study was to determine whether IR is increased in a cohort of inflammatory bowel disease (IBD) patients with low disease activity. We additionally intended to establish which factors were the determinants of IR in this population, including the presence of nonalcoholic fatty liver disease (NAFLD). Methods. Cross-sectional study encompassing 151 IBD patients and 174 non-diabetic controls. Insulin and C-peptide serum levels and IR and beta cell function (%B) indices based on homoeostatic model assessment (HOMA2) were assessed in patients and controls. Liver stiffness as measured by transient elastography, and the presence of NAFLD detected via ultrasound were additionally assessed. A multivariable regression analysis was performed to evaluate the differences in IR indexes between patients and controls, and to determine which predictor factors were associated with IR in IBD patients. Results. Neither HOMA2-IR (beta coef. −0.26 {95%CI −0.64–0.13}, p = 0.19) nor HOMA2-%B (beta coef. 15 {95%CI −14–44}, p = 0.31) indexes differed between patients and controls after fully multivariable analysis. Among classic IR risk factors, obesity, abdominal circumference, and triglycerides significantly and positively correlated with IR indexes in IBD patients. However, most features related to IBD, such as disease patterns, disease activity, and inflammatory markers, were not associated with IR. The presence of NAFLD was independently and significantly associated with beta cell dysfunction in patients with IBD (HOMA2—B grade 4, 251 ± 40 vs. grade 1, 107 ± 37, p = <0.001). Conclusions. IR is not increased in IBD patients with low disease activity compared to controls. However, the presence of NAFLD favors the development of IR in patients with IBD.

Cardiovascular Risk Factor Progression in Adolescents and Young Adults With Type 2 Diabetes

Background: Onset of type 2 diabetes (T2D) in youth confers a high risk of early adverse cardiovascular outcomes. We describe the cumulative incidence of hypertension, LDL-cholesterol dyslipidemia, hypertriglyceridemia, and prevalence of smoking over time, and examine the relationships with body mass index and measures of glycemia, insulin sensitivity, and beta-cell function in an adolescent cohort with T2D enrolled in the Treatment Options for type 2 Diabetes in Adolescents and Youth (TODAY) study. Methods: Longitudinal data from the TODAY clinical trial and TODAY2 observational follow-up study were used to evaluate the relationships between hypertension, LDL-C dyslipidemia, hypertriglyceridemia, and smoking with risk factors using time-to-event models and generalized estimating equation models. Findings: Data were available on 677 participants. Mean age at baseline was 14±2 years and mean follow-up 10·2±4·5 years. The 14-year cumulative incidence of hypertension, LDL-C dyslipidemia, and hypertriglyceridemia was 59%, 33%, and 37% respectively, and the average prevalence of reported smoking was 23%. Male sex, non-Hispanic white race/ethnicity, obesity, poor glycemic control, lower insulin sensitivity, and reduced beta-cell function were significantly associated with an unfavorable cardiovascular risk profile. After an average of 10·2 years of follow-up, 54% of the cohort had ≥2 cardiovascular risk factors in addition to T2D. Interpretation: Cardiovascular risk factor incidence and prevalence was high over a decade of follow-up in young adults with youth-onset T2D. Addressing glucose control and insulin sensitivity, as well as medical management of cardiovascular risk factors will be critical in youth with T2D for prevention of cardiovascular morbidity and mortality. Trial Registration: Clinicaltrials.gov NCT00081328. Funding: United States National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Disease. Declaration of Interest: None of the authors reported a conflict of interest. Ethical Approval: The TODAY and TODAY2 studies were approved by institutional review boards at all 15 centers and all participants and guardians provided written informed assent and/or consent as appropriate for age.

Establishment of long-term high-fat diet and low dose streptozotocin-induced experimental type-2 diabetes mellitus model of insulin resistance and evaluation of seed extracts of Syzygium cumini

Introduction: The principal mechanism responsible for reducing blood glucose is through insulin-stimulated glucose transport into skeletal muscle. The transporter protein that mediates this uptake is GLUT-4. A defect in this step is associated with reduced glucose utilization in muscle and adipose tissue, as observed in insulin-resistant type-2 diabetes mellitus (T2DM) patients. This study aimed to develop an experimental T2DM model and evaluate altered glucose transporter type 4 (GLUT-4) levels as a biomarker of insulin resistance. Antidiabetic activities of Syzygium cumini hydro-ethanolic seed extracts (SCE) were also evaluated. Methods: Adult male Wistar albino rats were fed a high-fat diet for 12 weeks and dosed intraperitoneally with streptozotocin (35 mg/kg). After treatment for 21 days, all investigations were done. The homeostasis model of assessment (HOMA) was used for the calculation of insulin resistance (HOMA-IR) and beta-cell function (HOMA-B) index. Diaphragm muscle and retroperitoneal fat were collected for real-time polymerase chain reaction (RT-PCR) studies. Results: A significant increase in fasting blood glucose, HOMA-IR, and serum lipids, and a decrease in serum insulin and HOMA-B were observed in the diabetic group, effects that reversed following pioglitazone and SCE treatment. The diabetic group showed a downregulation of GLUT-4 expression in skeletal muscle while an increase was observed in adipose tissue. Conclusion: A high-fat diet and low dose streptozotocin-induced experimental T2DM model of insulin resistance was developed to screen novel insulin sensitizers. Data generated demonstrated that altered GLUT-4 levels could be used as a biomarker of insulin resistance. Antidiabetic activity of S. cumini hydro-ethanolic seed extract was also confirmed in this study.

Association between plasma homocysteine levels and pancreatic islet beta-cell function in the patients with type 2 diabetes mellitus: a cross-sectional study from China.

This study sought to investigate the association between plasma homocysteine (HCY) levels and pancreatic islet beta-cell function in type 2 diabetes mellitus (T2DM) patients. 430 hospitalized T2DM patients were enrolled in this cross-sectional study from December 2013 to December 2016. All participants were requested to complete a detailed questionnaire and undergo anthropometric measurements. Blood samples were collected from all participants. A 75-g oral glucose tolerance test (OGTT) was performed to diagnose T2DM in each individual, and an insulin releasing test (IRT) was used to calculate selected parameters for glucose, insulin, and C-peptide. Linear correlation and multivariate regression analyses were performed to assess the association between serum HCY concentration and these parameters. Patients were divided into the following subgroups based on quartiles of serum HCY levels: Group Q1: <17.03 µmol/L; Group Q2: 17.03-19.50 µmol/L; Group Q3: 19.5-24.7 µmol/L; and Group Q4: >24.7 µmol/L. The levels of fasting blood glucose (FBG), 2 h postprandial blood glucose (2hPBG), glycated hemoglobin A1c (HbA1c), fasting C-peptide and fasting insulin increased significantly as HCY levels increased (P<0.05). The area under the curves (AUCs) of serum glucose and insulin in IRT increased significantly and that of serum C-peptide decreased as HCY levels increased (P<0.05). The levels of Homeostasis Model Assessment-β (HOMA-β), Modified Beta-cell function Index (MBCI), Disposal Index (DI), C-peptide immunoreactivity (CPR), Insulinogenic Index 30 (IGI 30), and Secretory Units of Islets in Transplantation (SUIT) decreased as HCY levels increased. An inverse linear correlation was found between HOMA-β, MBCI, DI, CPR, IGI 30, SUIT 0 h, and HCY plasma concentration (R2, 0.539, 0.569, 0.500, 0.676, 0.579, and 0.588, respectively; P<0.001), and this association was independent of many confounders, such as age, gender, body mass index, glucose and insulin levels, and HbA1c. Serum HCY levels were inversely related to the parameters for pancreatic islet beta-cell function. Thus, the insulin releasing function of beta cells in the pancreas can be well elucidated by plasma HCY concentration.

CORRELATION OF SERUM VISFATIN WITH ANTHROPOMETRIC AND GLYACEMIC PARAMETERS IN NON-DIABETIC SUBJECTS WITH AND WITHOUT PARENTAL HISTORY OF TYPE II DIABETES MELLITUS

Background: Visfatin has insulin like metabolic effects and has a key role in insulin secretion in response to glucose stimulus. This existed link of visfatin with obesity and glucose metabolism is still to be explored and debatable. We aimed to find out the correlation between visfatin and selected anthropometric and biochemical parameters in non-diabetic subjects with type II diabetic parents and with non-diabetic parents. Methods: This cross-sectional analytic study was conducted at the Diabetes Clinic of Lahore General Hospital and Department of Physiology, Postgraduate Medical Institute, Lahore. It comprised of 40 on-diabetic subjects with non-diabetic parents (Group I) aged 30–50 years, and 40 age and sex matched non-diabetic subjects with type II diabetic parents (Group II). Blood pressure, BMI and waist hip ratio, fasting levels of serum visfatin, insulin and glucose were measured and indices of insulin resistance (HOMA-IR), sensitivity (HOMA-%S) and beta cell function (HOMA-%?) were calculated. Results: Serum visfatin did not correlate with any of the anthropometric and glycaemic parameters assessed in group I and II. However, in combined analysis of female non-diabetic subjects, a statistically significant negative correlation between serum visfatin and waist circumference/waist hip ratio, and a positive correlation of serum visfatin with insulin sensitivity index (HOMA-%S) was found. Conclusion: A decline in visfatin production is seen with increasing visceral obesity in non-diabetic female subjects. The fall in visfatin levels seems to play a part in lowering insulin sensitivity in them. Pak J Physiol 2021;17(2):10–4

200-OR: Optimal Use of Measures of Insulin Secretion and Sensitivity in Predicting Diabetes: Beyond the Disposition Index

In persons without diabetes, the product of estimated insulin secretion and sensitivity, the disposition index (DI), is used as an index of beta cell function and a predictor of T2D. However, its use in predicting T2D disregards differences in insulin secretion and sensitivity among persons with the same DI. We studied diabetes incidence in 420 persons without diabetes followed for a median of 9.9 years during which time 146 (35%) developed diabetes. Insulin secretion was measured 3-5 min after a 25gm glucose bolus (AIR) and sensitivity (M) by the hyperinsulinemic-euglycemic clamp. The Figure plots AIR by M and shows bands representing a range of lowest to highest incidence. Different (hyperbolic) lines of constant DI are superimposed. A single DI line crosses several risk zones; subjects with the same DI but lower M had higher T2D incidence, suggesting that DI is not optimal for prediction. We also compared the performance of different Cox models in predicting T2D using the area under the receiver operating characteristic curve (AUC). In prediction by separate secretion and sensitivity variables, AUC=0.72, higher (p Disclosure E. Vazquez arreola: None. R. L. Hanson: None. C. Bogardus: None. W. C. Knowler: None.

1181-P: Consumption of Naturally Enriched Complex Carbohydrate Meal Improves Insulin Sensitivity and Disposition Index in Type 2 Diabetes

The triple tracer method has enabled accurate and concurrent measurements of glucose turnover as well as indices of insulin action and beta cell function in people with diabetes. We have previously utilized the natural enrichment of 13C polysaccharide in commercially available grains, and compared indices obtained after a complex carbohydrate (CC) meal to those obtained after a simple carbohydrate (SC) mixed meal in healthy humans. We have now completed studies in 6 subjects with type 2 diabetes (4M, age 65±6 y; BMI 33±4 kg/m2; HbA1c 50±10 mM/mol) after ~75 gm of either sorghum (naturally enriched 13C) or glucose labeled with 13C mixed meals containing ~75 gm carbs and matched protein and fat in random order. Results in figure. Glucose, insulin and C-peptide concentrations achieved were significantly lower with CC meal as compared to SC meal (p Disclosure D. Romeres: None. A. Basu: None. Y. R. Yadav: None. C. Cobelli: None. C. Dalla man: Research Support; Self; Becton, Dickinson and Company, Sanofi-Aventis Deutschland GmbH. R. Basu: None. Funding National Institutes of Health (R01DK029953 to R.B.), (R01DK085516 to A.B.), (DK059637, DK020593)

The Association of Serum Uric Acid with Beta-Cell Function and Insulin Resistance in Nondiabetic Individuals: A Cross-Sectional Study.

PurposeHigher serum levels of uric acid (SUA) are associated with an increased risk of developing type 2 diabetes. Meanwhile, insulin resistance and beta-cell dysfunction are critical factors that mediate the progression from normal glucose tolerance to impaired fasting glucose (IFG) and type 2 diabetes. We aimed to investigate the association between SUA levels and insulin resistance and beta-cell dysfunction in individuals without diabetes, thus explicating the role of uric acid in the early stage of the natural history of type 2 diabetes.Patients and MethodsWe used cross-sectional data from the China Health and Nutrition Survey to examine the association. Insulin resistance and beta-cell dysfunction were estimated using the homeostasis model assessment of insulin resistance (HOMA-IR) index and homeostasis model assessment of beta-cell function (HOMA-beta) index, respectively. The associations were analyzed by using partial correlation analysis and multivariate logistic regressionl analysis.ResultsSUA levels were positively associated with fasting glucose, fasting insulin, HOMA-IR in the total population. After adjustment for age, drinking, smoking, living area, daily dietary nutrient intake, body mass index (BMI), estimated glomerular filtration rate (eGFR), hypertension, and dyslipidemia, compared with participants in the lowest quartile of SUA, the adjusted odds ratios for the fourth quartiles were 1.56(1.09-2.24) for IFG, 1.51(1.27-1.78) for insulin resistance, and 1.06(0.88-1.27) for beta-cell dysfunction. In the subgroup analysis, no interactions were found between serum uric acid and age, drinking status, smoking status, BMI, hypertension, or dyslipidemia (all p for interaction>0.05).ConclusionIn nondiabetic individuals, SUA levels are independently associated with IFG and insulin resistance, while no significant association exists between SUA and beta-cell dysfunction.