Beta Cell Function Index Research Articles

Development of a Diabetes Dietary Quality Index: Reproducibility and Associations with Measures of Insulin Resistance, Beta Cell Function, and Hyperglycemia.

Various dietary risk factors for type 2 diabetes have been identified. A short assessment of dietary patterns related to the risk for type 2 diabetes mellitus may be relevant in clinical practice given the largely preventable nature of the disease. The aim of this study was to investigate the reproducibility of a short food frequency questionnaire based on available knowledge of diabetes-related healthy diets. In addition, we aimed to investigate whether a Diabetes Dietary Quality Index based on this questionnaire was related to metabolic risk factors, including measures of beta cell function and insulin sensitivity. A short food frequency questionnaire was composed by selecting fourteen questions (representing eight dietary factors) from existing food frequency questionnaires on the basis of their reported relationship with diabetes risk. Healthy participants (N = 176) from a Dutch family study completed the questionnaire and a subgroup (N = 123) completed the questionnaire twice. Reproducible items from the short questionnaire were combined into an index. The association between the Diabetes Dietary Quality index and metabolic risk factors was investigated using multiple linear regression analysis. Measures of beta cell function and insulin sensitivity were derived from a mixed meal test and an euglycemic-hyperinsulinemic and modified hyperglycemic clamp test. Our results show that this new short food frequency questionnaire is reliable (Intraclass Correlations ranged between 0.5 and 0.9). A higher Diabetes Dietary Quality index score was associated with lower 2 h post-meal glucose (β -0.02, SE 0.006, p < 0.05), HbA1c (β -0.07, SE 0.02, p < 0.05), total cholesterol, (β -0.02, SE 0.07, p < 0.05), LDL cholesterol, (β -0.19, SE 0.07, p < 0.05), fasting (β -0.4, SE 0.16, p < 0.05) and post-load insulin, (β -3.9, SE 1.40, p < 0.05) concentrations and the incremental AUC of glucose during MMT (β -1.9, SE 0.97, p < 0.05). The scores obtained for the oral glucose insulin sensitivity-derived mixed meal test were higher in subjects who scored higher on the Diabetes Dietary Quality index (β 0.89, 0.39, p < 0.05). In contrast, we found no significant associations between the Diabetes Dietary Quality index and clamp measures of beta cell function. We identified a questionnaire-derived Diabetes Dietary Quality index that was reproducible and inversely associated with a number of type 2 diabetes mellitus and metabolic risk factors, like 2 h post-meal glucose, Hba1c and LDL, and total cholesterol. Once relative validity has been established, the Diabetes Dietary Quality index could be used by health care professionals to identify individuals with diets adversely related to development of type 2 diabetes.

Dapagliflozin in heart failure and type 2 diabetes: Efficacy, cardiac and renal effects, safety.

Heart failure (HF), especially HF with reduced ejection fraction (HFrEF), presents complex challenges, particularly in the aging population where it often coexists with type 2 diabetes mellitus (T2DM). To analyze the effect of dapagliflozin treatment on cardiac, renal function, and safety in patients with HFrEF combined with T2DM. Patients with T2DM complicated with HFrEF who underwent treatment in our hospital from February 2018 to March 2023 were retrospectively analyzed as the subjects of this study. The propensity score matching method was used, and a total of 102 eligible samples were scaled. The clinical efficacy of the two groups was evaluated at the end of the treatment, comparing the results of blood glucose, insulin, cardiac function, markers of myocardial injury, renal function indexes, and 6-min walk test (6MWT) before and after the treatment. We compared the occurrence of adverse effects on the treatment process of the two groups of patients. The incidence of adverse outcomes in patients within six months of treatment was counted. The overall clinical efficacy rate of patients in the study group was significantly higher than that of patients in the control group (P = 0.013). After treatment, the pancreatic beta-cell function index, left ventricular ejection fraction, and glomerular filtration rate of patients in the study group were significantly higher than control group (P < 0.001), while their fasting plasma glucose, 2-h postprandial glucose, glycosylated hemoglobin, insulin resistance index, left ventricular end-systolic diameter, left ventricular end-diastolic diameter, cardiac troponin I, creatine kinase-MB, N-terminal pro b-type natriuretic peptide, serum creatinine, and blood urea nitrogen were significantly lower than those of the control group. After treatment, patients in the study group had a significantly higher 6MWT than those in the control group (P < 0.001). Hypoglycemic reaction (P = 0.647), urinary tract infection (P = 0.558), gastrointestinal adverse effect (P = 0.307), respiratory disturbance (P = 0.558), and angioedema (P = 0.647) were not statistically different. There was no significant difference between the incidence of adverse outcomes between the two groups (P = 0.250). Dapagliflozin significantly enhances clinical efficacy, cardiac and renal function, and ambulatory capacity in patients with HFrEF and T2DM without an increased risk of adverse effects or outcomes.

A secondary analysis of indices of hepatic and beta cell function following 12 weeks of carbohydrate and energy restriction vs. free-living control in adults with type 2 diabetes

BackgroundSubstantial weight loss in people living with type 2 diabetes (T2D) can reduce the need for glucose-lowering medications while concurrently lowering glycemia below the diagnostic threshold for the disease. Furthermore, weight-loss interventions have also been demonstrated to improve aspects of underlying T2D pathophysiology related to ectopic fat in the liver and pancreatic beta-cell function. As such, the purpose of this secondary analysis was to explore the extent to which a low-carbohydrate and energy-restricted (LCER) diet intervention improves markers of beta-cell stress/function, liver fat accumulation, and metabolic related liver function in people with type 2 diabetes.MethodsWe conducted secondary analyses of blood samples from a larger pragmatic community-based parallel-group randomized controlled trial involving a 12-week pharmacist implemented LCER diet (Pharm-TCR: <50 g carbohydrates; ~850–1100 kcal/day; n = 20) versus treatment-as-usual (TAU; n = 16). Participants were people with T2D, using ≥ 1 glucose-lowering medication, and a body mass index of ≥ 30 kg/m2. Main outcomes were C-peptide to proinsulin ratio, circulating microRNA 375 (miR375), homeostatic model assessment (HOMA) beta-cell function (B), fatty liver index (FLI), hepatic steatosis index (HSI), HOMA insulin resistance (IR), and circulating fetuin-A and fibroblast growth factor 21 (FGF21). Data were analysed using linear regression with baseline as a covariate.ResultsThere was no observed change in miR375 (p = 0.42), C-peptide to proinsulin ratio (p = 0.17) or HOMA B (p = 0.15). FLI and HSI were reduced by -25.1 (p < 0.0001) and − 4.9 (p < 0.0001), respectively. HOMA IR was reduced by -46.5% (p = 0.011). FGF21 was reduced by -161.2pg/mL (p = 0.035) with a similar tendency found for fetuin-A (mean difference: -16.7ng/mL; p = 0.11). These improvements in markers of hepatic function were accompanied by reductions in circulating metabolites linked to hepatic insulin resistance (e.g., diacylglycerols, ceramides) in the Pharm TCR group.ConclusionsThe Pharm-TCR intervention did not improve fasting indices of beta-cell stress; however, markers of liver fat accumulation and and liver function were improved, suggesting that a LCER diet can improve some aspects of the underlying pathophysiology of T2D.Trial registrationClinicaltrials.gov (NCT03181165).

Insulin Resistance/Sensitivity Measures as Screening Indicators of Metabolic-Associated Fatty Liver Disease and Liver Fibrosis.

Measures of insulin resistance (IR)/sensitivity (IS) are emerging tools to identify metabolic-associated fatty liver disease (MAFLD). However, the comprehensive assessment of the performance of various indicators is limited. Moreover, the utility of measures of IR/IS in detecting liver fibrosis remains unclear. To evaluate the predictive ability of seventeen IR/IS and two beta cell function indices to identify MAFLD and liver fibrosis. A cross-sectional study was conducted on individuals aged 25-75years. Transient elastography was used to estimate liver stiffness and controlled attenuation parameter. The following measures were computed: homeostatic model assessment (HOMA/HOMA2) for IR, IS, and beta cell function; QUICKI; Bennett index; glucose/insulin; FIRI; McAuley index; Reynaud index; SPISE index; TyG; TyG-BMI; TyG-WC; TyG-WHtR; TG/HDL; and METS-IR. Subgroup analyses were performed according to age, gender, diabetes status, and body weight. A total of 644 individuals were included in our analysis. MAFLD and significant liver fibrosis were detected in 320 (49.7%) and 80 (12.4%) of the participants, respectively. All measures of IR/IS identified MAFLD and liver fibrosis. However, TyG-WC, TyG-BMI, and TyG-WHtR were the top three indicators that identified MAFLD. Measures that include insulin level in their mathematical calculation, namely, Raynaud index, HOMA-IR, HOMA 2-IR, FIRI, and QUICKI had the best performance in identifying liver fibrosis in the entire population, as well as among the study subgroups. TyG-WC, TyG-BMI, and TyG-WHtR were the best predictors of MAFLD. Insulin-based measures had better performances in the detection of advanced fibrosis. This was independent of age, gender, obesity, or diabetes status.

The importance of intravenous glucose tolerance test glucose stimulus for the evaluation of insulin secretion

For 100 years, the Intravenous glucose tolerance test (IVGTT) has been used extensively in researching the pathophysiology of diabetes mellitus and AIRg—the IVGTT-induced acute insulin response to the rapid rise in circulating glucose—is a key measure of insulin secretory capacity. For an effective evaluation of AIRg, IVGTT glucose loading should be adjusted for glucose distribution volume (gVOL) to provide an invariant, trend-free immediate rise in circulating glucose (ΔG0). Body weight-based glucose loads have been widely used but whether these achieve a trend-free ΔG0 does not appear to have been investigated. By analysing variation in AIRg, ΔG0 and gVOL with a range of IVGTT loads, both observed and simulated, we explored the hypothesis that there would be an optimum anthropometry-based IVGTT load calculation that, by achieving a trend-free ΔG0, would not compromise evaluation of AIRg as an index of beta cell function. Data derived from patient and research volunteer records for 3806 IVGTT glucose and insulin profiles. Among the non-obese, as gVOL rose, weight increased disproportionately rapidly. Consequently, the IVGTT glucose load needed for an invariant ΔG0 was progressively overestimated, accounting for 47% of variation in AIRg. Among the obese, ΔG0 was trend-free yet AIRg increased by 11.6% per unit body mass index, consistent with a more proportionate increase in weight with gVOL and a hyperinsulinaemic adaptation to adiposity-associated insulin resistance. Simulations further confirmed our hypothesis by demonstrating that a body surface area-based IVGTT load calculation could provide for a more generally invariant IVGTT ΔG0.

Malondialdehyde Serum Levels in a Full Characterized Series of 430 Rheumatoid Arthritis Patients

Background. Oxidative stress has been involved in the pathogenesis of rheumatoid arthritis (RA). The serum malondialdehyde (MDA) level is a reliable biomarker of oxidative stress status. In the present work, we aimed to analyze how a comprehensive characterization of the disease characteristics in RA, including a lipid profile, insulin resistance, and subclinical atherosclerosis, relates to serum MDA levels. Methods. In a cross-sectional study that included 430 RA patients, serum MDA levels were evaluated. Multivariable analysis was performed to examine the relationship of MDA with disease activity scores and disease characteristics, including subclinical carotid atherosclerosis, a comprehensive lipid molecule profile, and indices of insulin resistance and beta cell function indices. Results. The erythrocyte sedimentation rate (ESR) showed a significant and positive relationship with MDA. However, this did not occur for other acute phase reactants such as C-reactive protein or interleukin-6. Although the DAS28-ESR score (Disease Activity Score in 28 joints) had a positive and significant association with MDA serum levels, other disease activity scores that do not use the erythrocyte sedimentation rate in their formula did not show a significant relationship with MDA. Other disease characteristics, such as disease duration and the existence of rheumatoid factor and antibodies against citrullinated protein, were not related to serum MDA levels. This also occurred for lipid profiles, insulin resistance indices, and subclinical carotid atherosclerosis, for which no associations with circulating MDA were found. Conclusions. The disease characteristics are not related to circulating MDA levels in patients with RA.

Glucometabolism in Kidney Transplant Recipients with and without Posttransplant Diabetes: Focus on Beta-Cell Function.

Posttransplant diabetes mellitus (PTDM) is a common complication after kidney transplantation. Pathophysiologically, whether beta-cell dysfunction rather than insulin resistance may be the predominant defect in PTDM has been a matter of debate. The aim of the present analysis was to compare glucometabolism in kidney transplant recipients with and without PTDM. To this aim, we included 191 patients from a randomized controlled trial who underwent oral glucose tolerance tests (OGTTs) 6 months after transplantation. We derived several basic indices of beta-cell function and insulin resistance as well as variables from mathematical modeling for a more robust beta-cell function assessment. Mean ± standard deviation of the insulin sensitivity parameter PREDIM was 3.65 ± 1.68 in PTDM versus 5.46 ± 2.57 in NON-PTDM. Model-based glucose sensitivity (indicator of beta-cell function) was 68.44 ± 57.82 pmol∙min-1∙m-2∙mM-1 in PTDM versus 143.73 ± 112.91 pmol∙min-1∙m-2∙mM-1 in NON-PTDM, respectively. Both basic indices and model-based parameters of beta-cell function were more than 50% lower in patients with PTDM, indicating severe beta-cell impairment. Nonetheless, some defects in insulin sensitivity were also present, although less marked. We conclude that in PTDM, the prominent defect appears to be beta-cell dysfunction. From a pathophysiological point of view, patients at high risk for developing PTDM may benefit from intensive treatment of hyperglycemia over the insulin secretion axis.

Insulin sensitivity and beta cell function after duodenal mucosal resurfacing: an open-label, mechanistic, pilot study

Background and AimsThe duodenum has been shown to play a key role in glucose homeostasis. Duodenal mucosal resurfacing (DMR) is an endoscopic procedure for patients with type 2 diabetes (T2D) in which the duodenal mucosa is hydrothermally ablated. DMR improves glycemic control, but the underlying mechanisms remain unclear. Here, we report changes in glucoregulatory hormones and indices of insulin sensitivity and beta cell function after DMR. MethodsWe included 28 patients on non-insulin glucose lowering medications who underwent open-label DMR and a mixed meal test (MMT) in Revita-1 or Revita-2. Inclusion criteria were hemoglobin A1c (HbA1c) 7.6-10.4% and BMI 24-40kg/m2. Baseline and 3-months MMT data included plasma glucose, insulin, C-peptide, glucagon-like peptide-1 (GLP-1), and gastric inhibitory polypeptide (GIP) concentrations. Glucoregulatory hormones, insulin sensitivity indices (homeostatic model assessment for insulin resistance [HOMA-IR], Matsuda index [MI] and hepatic insulin resistance [HIR]), and beta cell function (insulinogenic index [IGI], disposition index [DI] and insulin secretion rate [ISR]) were assessed. ResultsFasting insulin, glucagon, and C-peptide decreased significantly. Insulin sensitivity (HOMA-IR, MI, and HIR) and beta cell function (DI and ISR) all improved significantly. Decline in postprandial glucose, mainly driven by a decrease in fasting levels, was observed, as well as a decline in postprandial glucagon whereas GLP-1 and GIP did not change. ConclusionsInsulin sensitivity and insulin secretion improved 3 months after DMR. It is unlikely that incretin changes are responsible for improved glucose control after DMR. These data add to the growing evidence validating the duodenum as a therapeutic target for patients with T2D.

Critical Evaluation of Indices Used to Assess β-Cell Function.

The assessment of beta-cell function-defined as insulin secretion rate (ISR) in relationship to plasma glucose-is not standardized and often involves any of a number of beta-cell function indices. We compared beta-cell function by using popular indices obtained during basal conditions and after glucose ingestion, including the HOMA-B index, the basal ISR (or plasma insulin)-to-plasma glucose concentration ratio, the insulinogenic and "ISRogenic" indices, the ISR (or plasma insulin)-to-plasma glucose concentration areas (or incremental areas) under the curve ratio, and the disposition index, which integrates a specific beta-cell function index value with an estimate of insulin sensitivity, in 50 lean people with normal fasting glucose (NFG) and normal glucose tolerance (NGT) and four groups of people with obesity (n=188) with: i) NFG-NGT; ii) NFG and impaired glucose tolerance (IGT); iii) impaired fasting glucose and IGT, and iv) type 2 diabetes. We also plotted the ISR-plasma glucose relationship before and after glucose ingestion and used a statistical mixed effects model to evaluate group differences in this relationship (i.e. beta-cell function). Index-based group differences in beta-cell function produced contradicting results and did not reflect the group differences of the actual observed ISR-glucose relationship, or, in the case of the disposition index, group differences in glycemic status. The discrepancy in results is likely due to incorrect mathematical assumptions that are involved in computing indices, which can be overcome by evaluating the relationship between ISR and plasma glucose with an appropriate statistical model. Data obtained with common beta-cell function indices should be interpreted cautiously.

Mean Platelet Volume in a Series of 315 Patients with Rheumatoid Arthritis: Relationship with Disease Characteristics, including Subclinical Atherosclerosis and Cardiovascular Comorbidity.

Mean platelet volume (MPV) refers to the average platelet size in femtoliters. Increased or decreased MPV has been associated with several disorders, including inflammatory and cardiovascular diseases. In the present study, our objective was to analyze the relationship of MPV with disease activity in a large and well-characterized series of patients with rheumatoid arthritis (RA). This is a cross-sectional study that included 315 patients with RA and 208 controls matched by sex and age. Complete blood count, including MPV, was assessed. Multivariable analysis was performed to examine the relationship of MPV with RA disease characteristics, carotid atherosclerosis, and traditional cardiovascular factors, including a comprehensive profile of lipid molecules and insulin resistance or beta cell function indices. The multivariable analysis, which includes other hematological modifications produced by the disease and platelet values, showed that MPV levels were significantly lower in RA patients than in controls. Erythrocyte sedimentation rate and interleukin-6, but not C-reactive protein, were negatively correlated with MPV after adjustment for covariates. Similarly, disease activity and MPV had a significant and independent negative correlation. No relationships were found between MPV and cardiovascular risk factors, lipid profile or insulin resistance indices or subclinical atherosclerosis. In conclusion, patients with RA have lower levels of MPV than controls. MPV is negatively related to acute phase reactants and disease activity in RA.

Red Cell Distribution Width Association with Subclinical Cardiovascular Disease in Patients with Rheumatoid Arthritis.

Red cell distribution width (RDW) is a measure of the variation in mean corpuscular volume that reflects the degree of anisocytosis on the peripheral blood smear. RDW value variation has been implicated in several disorders including chronic inflammatory processes and cardiovascular (CV) diseases. In the present work, our objective was to study the relationship that RDW has with the characteristics of the disease in patients with rheumatoid arthritis (RA), focusing on CV risk factors and subclinical atherosclerosis. A cross-sectional study was conducted that included 430 patients with RA and 208 controls matched by sex and age. Complete blood count, including RDW, was assessed. Multivariable analysis was performed to analyze the relationship of RDW with RA disease characteristics, subclinical carotid atherosclerosis, and traditional CV factors, including a comprehensive profile of lipid molecules and insulin resistance and beta cell function indices. After multivariable adjustment, the RDW was significantly higher in RA patients compared with controls (beta coefficient 1.0 [95% confidence interval 0.2 to 1.8] %, p = 0.020). Furthermore, although the erythrocyte sedimentation rate showed a positive and significant relationship with RDW, this association was not found with C-reactive protein and interleukin-6. A positive and independent relationship was observed between DAS28-ESR disease activity score and RDW. However, no association was found between the RDW and other disease activity scores that do not include erythrocyte sedimentation rate in their formula. The SCORE2 CV risk algorithm was positively and significantly associated with higher RDW values. Likewise, a negative relationship was found between RDW with total cholesterol and low-density lipoprotein cholesterol, and a positive relationship was found between RDW and insulin resistance indices. In conclusion, RDW values are higher in RA patients compared to matched controls. Although the relationship of RDW with disease activity was not consistent, RDW shows associations with subclinical CV disease risk factors, including dyslipidemia and insulin resistance, and with the SCORE2 CV disease-risk prediction algorithm.

OR31-05 Long-Term Effects Of Gender Affirming Hormone Therapy On Insulin Sensitivity, Insulin Secretion, And Glucose Tolerance

Abstract Disclosure: S. Pinkson: None. J. Trejo: None. A. Mendoza: None. L. Gondin Hernandez: None. S. Chen: None. S. ahuja: None. D. Tripathy: None. Over the past 15 years, transgender veterans seeking Gender Affirming Hormone Therapy (GAHT) have increased significantly. The metabolic effects of long-term GAHT have been controversial possibly because of multiple confounding factors and different methodologies. We examined long-term effects of estradiol and testosterone on insulin sensitivity and insulin secretion in nondiabetic transwomen and transmen. A total of 4 groups (i) 7 transwomen (age 50 ± 4 yr, BMI 31 ± 2 kg/m2) (ii) 6 transmen (age 38 ± 4yr, BMI 33 ± 2 mg/m2) followed for 52 ± 9 months and as a control group (iii) six cisgender men (age 36 ± 4 yrs, BMI 32 ± 2 kg/m2) and (iv) 8 cisgender women (age 39 ± 4 yr, BMI 28 ± 2 kg/m2) participated in an OGTT and Botnia clamp (IV glucose tolerance test: IVGTT followed by hyperinsulinemic (80 mU.m2/min euglycemic clamp). Total testosterone (by equilibration dialysis method), estradiol, sex hormone binding globulin (SHBG) and lipid profile was measured in all subjects. Insulin, and C-peptide were measured every 30 min during the OGTT. Insulin sensitivity was measured as the M-value form last 30 minutes of insulin clamp and as Matsuda index of insulin sensitivity from the OGTT. Indices of insulin secretion (data pending) was calculated as the first phase insulin response from IVGTT (FPIR: 2-10min) and as indices of beta cell function from OGTT: Insulin secretion/insulin resistance index (Insulin 0-120/Glucose 0-120 X Matsuda index). Plasma estradiol in transwomen was 209 ± 92 pg/ml vs. 32 ± 6 pg/ml in cisgender men. Similarly, the total testosterone level in transmen was 319 ± 57 vs. 19 ± 4 ng/dl in cisgender women. There was no difference in SHBG levels between the groups. The body fat content was not different between trans or cis men (36 ± 3 vs 35 ± 1.4 % ) while it was higher in trans vs cis women (40 ± 0.8 vs 30 ± 3%). There was no difference in HbA1c (5.4 ± 0.2 vs 5.2 ± 0.2%, p=ns) between transwomen and cismen and (5.6 ± 0.1 vs 5.5 ± 0.1, p=ns) transmen and ciswomen. The glucose AUC was higher in transmen vs cisgender women (5,487 ± 994 vs. 3,420 ± 533; P &amp;lt; 0.05). There was no difference in glucose AUC between the transwomen and cismen. There was no difference in insulin sensitivity (M-value) between transwomen and cisgender men (6.9 ± 1.2 vs 7.0 ± 1.4 mg.kg/min, p=ns), while it tended to be worse in transmen compared to cisgender women ( 6.03 ± 1.0 vs 7.7± 0.6 mg.kg/min, p=0.1). In both groups M-Value was inversely related to BMI (r=-0.59; p&amp;lt;0.05). There was no relationship between insulin sensitivity and plasma total testosterone level. HDL cholesterol was lower in transmen (41 ± 2.5 vs 55 ± 4 mg/dL, p&amp;lt;0.05) versus cisgender women though there was no difference in triglyceride, total or LDL cholesterol between the groups. In conclusion long-term GAHT therapy does not adversely affect insulin sensitivity in trans men or women and the mildly altered glucose tolerance is likely a result of higher BMI in transmen. Presentation: Sunday, June 18, 2023

The Ratio of Monocytes to HDL-Cholesterol Is Associated with Cardiovascular Risk and Insulin Resistance in Patients with Rheumatoid Arthritis.

The monocytes to high-density lipoprotein (HDL)-cholesterol ratio (MHR) indicates inflammation based on the anti-inflammatory properties of HDL-cholesterol as well as the pro-inflammatory effect of monocytes. Several studies have investigated MHR in various disorders, specifically in cardiovascular diseases. Consequently, MHR has been significantly associated with cardiovascular and all-cause mortality in the general population, regardless of established risk factors. However, its role in the augmented risk of cardiovascular disease found in rheumatoid arthritis (RA) has not been studied to date. This is a cross-sectional study that encompassed 430 patients with RA and 208 controls matched by sex and age. Complete blood cell count and complete lipid profile were evaluated. Multivariable analysis was made to analyze the relationship between MHR and RA disease and features subclinical carotid atherosclerosis, and traditional CV factors including insulin resistance and beta cell function indices. MHR values did not differ between controls and patients after multivariable adjustment (12 ± 6 vs. 11 ± 6, p = 0.18). No relationship between this ratio and the characteristics of the disease was found excluding ESR, which showed a significant and positive association with MHR after adjustment for covariates. MHR significantly correlated with Systematic Coronary Risk Evaluation-2 (SCORE2) cardiovascular risk algorithm, and insulin resistance and beta cell function parameters after adjustment. In conclusion, MHR does not differ between patients with RA and controls. The relationship of this biomarker with disease-related data is poor. However, MHR is highly and positively related to cardiovascular risk and insulin resistance in RA.

Association of Serum Very-Long-Chain Saturated Fatty Acids With Changes in Insulin Sensitivity and β-Cell Function: The Prospective Metabolism and Islet Cell Evaluation (PROMISE) Cohort.

A unique group of circulating very long-chain saturated fatty acids (VLCSFA), including arachidic acid (20:0), behenic acid (22:0), and lignoceric acid (24:0), have been associated with lower risk of type 2 diabetes, although associations with early metabolic risk phenotypes preceding type 2 diabetes have received limited study. We aimed to examine the associations of VLCSFA with longitudinal changes in insulin sensitivity and beta-cell function in a cohort at risk of type 2 diabetes. VLCSFA in the four main serum pools (phospholipid, triacylglycerol, cholesteryl ester, and non-esterified fatty acid) were extracted from fasting baseline samples (n=467). Generalized Estimating Equations were used to determine the associations between VLCSFA and changes over 9 years in validated indices of insulin sensitivity (HOMA2-%S and ISI) and beta-cell function (IGI, IGI/IR and ISSI-2). Associations of VLCSFA with outcomes were strongest in the triacylglycerol lipid pool: 20:0 was positively associated with both insulin sensitivity and beta-cell function (5.01% increase in HOMA2-%S and 4.01-6.28% increase in IGI/IR and ISSI-2 per SD increase in 20:0); 22:0 was positively associated with insulin sensitivity with 6.55% increase in HOMA2-%S and a 5.80% increase in ISI per SD increase in 22:0. Lastly, 24:0 was positively associated with insulin sensitivity and beta-cell function (7.94-8.45% increase in HOMA2-%S and ISI, and 4.61-6.93% increase in IGI/IR and ISSI-2 per SD increase in 24:0). Fewer significant associations were observed in the cholesteryl ester and non-esterified pools. Overall, our results indicate positive longitudinal associations of VLCSFA with insulin sensitivity and beta-cell function, especially within the triacylglycerol pool.

The role of bariatric surgery on beta-cell function and insulin resistance in patients with nonalcoholic fatty liver disease and steatohepatitis

BackgroundNonalcoholic fatty liver disease (NAFLD) and steatohepatitis (NASH) are strongly associated with obesity, metabolic syndrome, and insulin resistance (IR). ObjectiveThe aim of this study was to investigate the effects of metabolic surgery on pancreatic beta cell function and IR in patients with obesity and NAFLD. SettingUniversity Hospital, Germany. MethodsLiver biopsies were taken intraoperatively from 112 patients undergoing sleeve gastrectomy (n = 68) or Roux-en-Y gastric bypass (n = 44) and analyzed histologically for the presence of simple steatosis (NAFL) or NASH. Clinical and biochemical parameters were collected over up to 2 years. Beta cell function and IR were assessed using the homeostasis model assessment of beta-cell function (HOMA2-%B) and insulin resistance (HOMA2-IR) index. ResultsNASH was present in 53.6% (n = 60) of the patients and NAFL in 25.9% (n = 29). Liver enzymes, adiponectin/leptin ratio, triglycerides, and HbA1C were improved at 6 months, 1, and 2 years after surgery. HOMA2-IR was significantly lower in patients without NAFLD while HOMA2-IR did not differ between patients with NAFL and/or NASH. HOMA2-%B was highest in the NAFLD group and lowest in patients with NASH. While there was no change in HOMA2-%B and HOMA2-IR in the No-NAFLD group, HOMA2-%B decreased and IR improved in the NAFL and NASH groups. ConclusionInsufficient compensatory beta-cell function may contribute to the progression from NAFL alongside with IR to NASH. Our findings suggest that bariatric surgery decreases IR while at the same time reducing compensatory insulin oversecretion. These results are associated with beneficial changes in adipose tissue function after bariatric surgery.

Metabolic Markers Associated with Progression of Type 2 Diabetes Induced by High-Fat Diet and Single Low Dose Streptozotocin in Rats.

Science is still searching for readily available, cost-effective biomarkers to assess metabolic disorders occurring before the onset and during the development of type-2 diabetes (T2DM). The aim of the present study was to induce T2DM in rats through a high-fat diet, followed by a single administration of low dose streptozotocin (STZ), and make an assessment of the development of the disease. The rats were divided into two groups-experimental and control-and were monitored for a period of 10 days. Changes in anthropometric parameters, glucose, insulin, lipids, uric acid, advanced oxidation protein products (AOPP), as well as the histological changes in the liver and pancreas, were recorded. To assess insulin resistance, we used the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) and beta cell function (HOMA-β) and visceral obesity-adiposity index (AI). The data demonstrate that the increasing values of glucose, HOMA-IR, AI, total cholesterol, triacylglycerols, low- and very-low-density lipoproteins are important markers of the pre-diabetic state. The stable hyperglycemia and increased levels of TC, TG, VLDL, LDL, uric acid and AOPP in experimental rats strongly suggest the development of T2DM. HOMA-IR, HOMA-β, AI, and uric acid are reliable criteria for T2DM in rats.

A CORRELATIVE STUDY OF FASTING BLOOD SUGAR, BODY MASS INDEX AND DURATION OF DIABETES WITH FASTING C-PEPTIDE LEVEL IN TYPE 2 DIABETES MELLITUS PATIENTS

Background: Diabetes mellitus refers to a group of common metabolic disorders that share the phenotype of hyperglycemia. It occurs either due to insulin deficiency or insulin resistance. It is an ongoing progressive disorder. The long term complications can be prevented by early screening of diabetes and initiating treatment. Progression of the disease is depicted in the form of worsening hyperglycemia, which may either be due to decreasing secretory activity of beta cells of pancreas or increasing insulin resistance, or in the form of progression of complications. The worldwide prevalence of diabetes mellitus has risen dramatically over the past two decades, from an estimated 30 million cases in 1985 to 415 million in 2017. Adding to this burden is the increasing incidence of type 2 diabetes mellitus. Hence, there is a need to understand the pathophysiology of diabetes, insulin secretion and insulin resistance and overcome them. One such way is to measure beta cell secretory activity. Measurement of C-peptide, which is secreted along with Insulin, provides a better index of endogenous insulin production and pancreatic beta cell function. Materials And Methods: It is a prospective interventional study done by simple random procedure, over a period of 18 months (1st March 2021 to 31st August 2022) with 200 cases. Results: Study reveals that there is no statistically significant difference of mean FBS with Quantile C-peptide levels. But there is statistically significant negative correlation between duration of diabetes and C-peptide levels in the study population (p&lt;0.05). As duration of diabetes increases, C-peptide value decreases. And, there was statistically highly significant positive correlation between BMI and C-peptide levels in the study population (p&lt;0.001). As BMI value increases, C-peptide level also increases. Conclusion: This study suggests that BMI and duration of diabetes are major factors in ß cell function in people with diabetes.

Relationship of Blood Inflammatory Composite Markers with Cardiovascular Risk Factors and Subclinical Atherosclerosis in Patients with Rheumatoid Arthritis.

The neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammatory index (SIRI, neutrophils × monocytes/lymphocytes) have been described as potential blood-derived inflammatory biomarkers in several diseases. Rheumatoid arthritis is an inflammatory disease that has been related to an increased risk of cardiovascular (CV) disease. In the present work, we analyze how these hematological composite scores of inflammation are related to classic CV risk factors and subclinical atherosclerosis in patients with RA. In this cross-sectional study that included 430 patients with RA, the NLR, MLR, PLR, and SIRI scores were calculated. Multivariable analysis was performed to examine the relationships of these composite blood scores with subclinical carotid atherosclerosis and with traditional cardiovascular factors, producing a complete profile of lipid molecules and insulin resistance or indices of beta-cell function, and a Systematic Coronary Risk Assessment (SCORE2) calculation. C-reactive protein and disease activity were significantly and positively associated with the four blood composite scores. SCORE2 was significantly associated with higher values of SIRI, NLR, and MLR, but not PLR. These relationships were maintained when SCORE 2 was considered categorical; patients in the very high CV risk category had higher values in all hematological composite scores, except PLR. In the multivariable analysis, SIRI and NLR were independently associated with higher levels of beta cell dysfunction. In conclusion, SCORE2 and the values of the hematological composite scores were positively correlated in patients with RA. In addition, there were some relationships of these scores with traditional CV risk factors, with their association with beta cell dysfunction being the most consistent.

96-LB: Dorzagliatin Improves Beta-Cell Function in Patients with Type 2 Diabetes

Objective: The oral minimal model (OMM) is a powerful tool to assess beta-cell function, including both the dynamic and static states. Dorzagliatin, a novel dual-acting glucokinase activator, has been reported the potential to improve pancreatic function in patients with type-2 diabetes mellitus (T2DM). In this study, we aimed to evaluate the effects of dorzagliatin on beta-cell function by using OMM. Methods: A randomized, double-blind, placebo-controlled study of dorzagliatin following multiple ascending doses in T2DM was completed (NCT02077452) and the data collected were used for beta-cell function parameters (Φb, Φd, Φs, and Φtot) estimation by using the SAAM II package integrating OMM. These parameters represent the non-glucose stimulated index, the dynamic responsivity of insulin secretion, the static responsivity of insulin secretion, and the global index of beta-cell responsivity, respectively. Results: All treatments except for the 200 mg dose group, compared with baseline, were associated with higher beta-cell function indices. Among them, Φb was significantly higher in the 25, 50, 100, and 150 mg dose groups (p &amp;lt; 0.05, p &amp;lt; 0.01, or p &amp;lt; 0.001), indicating basal beta-cell responsivity improved. Φd has an increase in the 25 and 100 mg dose groups (p &amp;lt; 0.05), indicating promptly releasable insulin responsivity improved. Φs was higher in the 25, 50, 100, and 150 mg dose groups (p &amp;lt; 0.05 or p &amp;lt; 0.01), indicating insulin secretion responsivity at steady state improved. Φtot significantly increased in the 25, 50, 100, and 150 mg dose groups (p &amp;lt; 0.05 or p &amp;lt; 0.001), indicating total beta-cell responsivity improved. No statistically significant difference was observed within the placebo group. Conclusions: This study suggested dorzagliatin can improve postprandial glucose control through its positive effects on beta-cell function. Disclosure Y. Zhang: None. L. Feng: Employee; Hua Medicine. L. Chen: Employee; Hua Medicine. D. Liu: None.

The complement system is linked to insulin resistance in patients with systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) patients more commonly have insulin resistance (IR) than control subjects. Recent studies have revealed that the complement (C) system is not only a mediator of the immune system but is also related to the pathogenesis of atherosclerosis in the general population. Given that the C alteration is a characteristic of SLE, in the present work we set out to analyse if there is a relationship between the C system and IR in patients with SLE. New generation functional assays of the three pathways of the C system were performed in 225 non-diabetic patients with SLE. In addition, the serum levels of inactive (C1q, C2, C3, C4, factor D), activated (C3a) and regulators (C1 inhibitor and factor H) molecules of the C system were evaluated. Insulin and C-peptide serum levels were measured, and insulin resistance and indices of beta cell function were calculated using the homeostatic model assessment (HOMA). Metabolic syndrome criteria fulfillments were applied. Multivariable linear regression analysis was performed to assess the relationship between C system and IR indices and the presence of metabolic syndrome. After adjusting for covariates that included traditional cardiovascular risk factors associated with IR and prednisone, serum C3a and factor H levels were positively related to higher levels of the HOMA2-IR index. Besides, in the multivariable analysis, after adjustment for covariates, serum levels of C1q and C3 associated with a higher odds ratio for the presence of metabolic syndrome. IR and metabolic syndrome are positively and independently related to higher serum levels of some serum C elements in patients with SLE with a predominant role of the alternative pathway elements.