Post-load Glucose Research Articles

Genetic Evidence of Causal Relation Between Intestinal Glucose Absorption and Early Postprandial Glucose Response: A Mendelian Randomization Study.

The post-prandial glucose response is an independent risk factor for type 2 diabetes. Observationally, early glucose response after an oral glucose challenge has been linked to intestinal glucose absorption, largely influenced by the expression of sodium-glucose-co-transporter-1 (SGLT1). This study utilizes Mendelian randomization (MR) to estimate the causal effect of intestinal SGLT1 expression on early glucose response. Involving 1547 subjects with class II/III obesity from the ABOS cohort, the study employs SGLT1 genotyping, oral glucose tolerance tests, and jejunal biopsies to measure SGLT1 expression. A loss-of-function SGLT1 haplotype served as the instrumental variable, with intestinal SGLT1 expression as the exposure and the change in 30-minute post-load glycemia from fasting glycemia (Δ30 glucose) as the outcome. Results showed that 12.8% of the 1,342 genotyped patients carried the SGLT1 loss-of-function haplotype, associated with a mean Δ30 glucose reduction of -0.41 mmol/L and a significant decrease in intestinal SGLT1 expression. The observational study linked a one standard deviation decrease in SGLT1 expression to a Δ30 glucose reduction of -0.097 mM/L. MR analysis paralleled these findings, associating a statistically significant reduction in genetically instrumented intestinal SGLT1 expression with a Δ30 glucose decreases of -0.353. In conclusion, the MR analysis provides genetic evidence that reducing intestinal SGLT1 expression causally lowers early post-load glucose response. This finding has a potential translational impact on managing early glucose response in type 2 diabetes.

Efficacy of 1-hour postload plasma glucose as a suitable measurement in predicting type 2 diabetes and diabetes-related complications: A post hoc analysis of the 30-year follow-up of the Da Qing IGT and Diabetes Study.

To evaluate whether 1-hour plasma glucose (1hPG) can be a comparable measurement to 2-hour plasma glucose (2hPG) in identifying individuals at high risk of developing diabetes. A total of 1026 non-diabetic subjects in the Da Qing IGT and Diabetes Study were included and classified according to baseline postload 1hPG. The participants were followed up and assessed at 6-, 20- and 30year follow-up for outcomes including diabetes, all-cause and cardiovascular mortality, cardiovascular disease (CVD) events, and microvascular disease. We then conducted a proportional hazards analysis in this post hoc study to determine the risks of developing type 2 diabetes and its complications in a '1hPG-normal' group (1hPG <8.6 mmol/L) and a '1hPG-high' group (≥8.6 mmol/L). The predictive values of 1hPG and 2hPG were evaluated using a time-dependent receiver-operating characteristic (ROC) curve. Compared with the 1hPG-normal group, the 1hPG-high group had increased risk of diabetes (hazard ratio [HR] 4.45, 95% CI 3.43-5.79), all-cause mortality (HR 1.46, 95% CI 1.07-2.01), CVD mortality (HR 1.84, 95% CI 1.16-2.95), CVD events (HR 1.39, 95% CI 1.03-1.86) and microvascular disease (HR 1.70, 95% CI: 1.03-2.79) after adjusting for confounders. 1hPG exhibited a higher area under the ROC curve (AUC) for predicting diabetes than 2hPG during the long-term follow-up (AUC [1hPG vs. 2hPG]: 10 years: 0.86 vs. 0.84, p = 0.08; 20 years: 0.88 vs. 0.87, p = 0.04; 30 years: 0.85 vs. 0.82, p = 0.009). Elevated 1hPG level (≥8.6 mmol/L) was associated with increased risk of developing type 2 diabetes and its long-term complications, and could be considered as a suitable measurement for identifying individuals at high risk of type 2 diabetes.

Post-load glucose is a stronger predictor of adverse pregnancy outcomes than first-trimester HbA1c in women without gestational diabetes.

A debate exists on the relation of adverse pregnancy outcomes with glycemic levels in early pregnancy. We aimed to investigate the association of maternal characteristics including post-load glucose and first-trimester HbA1c test results with adverse pregnancy outcomes in women without gestational diabetes mellitus. A dataset (January 2011 and September 2017) from a hospital prenatal clinic was explored to find the important predictors of adverse pregnancy outcomes using maternal characteristics and glucose assessments in mothers without gestational diabetes. We used two machine learning algorithms to capture nonlinearity in selecting important maternal characteristics and developed predictive models for each outcome. In total, 1,618 pregnant women were included in the analytic dataset with a mean (SD) age of 26.8 (3.5) years and gravida of 1.7 (0.9). Important associations were detected between maternal features and primary cesarean section, fetal distress, premature rupture of membranes, macrosomia, small or large for gestational age, APGAR <7 at 1 or 5 min, hyperbilirubinemia, and poly- or oligo-hydramnios. Overall, the predictive models showed good performance and large areas under the curves (0.732, 0.765, 0.646, 0.651, 0.730, 0.646, 0.684, 0.716, and 0.678, respectively). Specifically, they had high positive likelihood ratios. High glucose levels were associated with adverse pregnancy outcomes. Post-load glucose was the most reliable test for predicting the outcomes. Overall, fasting blood sugar was of more predictive value than HbA1c. Our study showed that further research should account for the nonlinearity and interactions inherent in the data.

Serum betaine and dimethylglycine in mid-pregnancy and the risk of gestational diabetes mellitus: a case-control study.

To investigate the associations of choline, betaine, dimethylglycine (DMG), L-carnitine, and Trimethylamine-N-oxide (TMAO) with the risk of Gestational diabetes mellitus (GDM) as well as the markers of glucose homeostasis. We performed a case-control study including 200 diagnosed GDM cases and 200 controls matched by maternal age (±2 years) and gestational age (±2 weeks). Concentrations of serum metabolites were measured by the high-performance liquid chromatography - tandem mass spectrometry (HPLC-MS/MS). Compared to the control group, GDM group had significantly lower serum betaine concentration and betaine/choline ratio, and higher DMG concentration. Furthermore, decreased betaine concentration and betaine/choline ratio, increased DMG concentration showed significant association with the risk of GDM. In addition, serum betaine concentrations were negatively associated with blood glucose levels at 1-h post-glucose load (OGTT-1h), and both betaine and L-carnitine concentrations were positively associated with 1,5-anhydroglucitol levels. Betaine/choline ratio was negatively associated with OGTT-1h and blood glucose levels at 2-h post-glucose load (OGTT-2h) and serum choline concentrations were negatively associated with fasting blood glucose and positively associated with OGTT-2h. Decreased serum betaine concentrations and betaine/choline ratio, and elevated DMG concentrations could be significant risk factors for GDM. Furthermore, betaine may be associated with blood glucose regulation and short-term glycemic fluctuations.

International Diabetes Federation Position Statement on the 1-hour post-load plasma glucose for the diagnosis of intermediate hyperglycaemia and type 2 diabetes

Many individuals with intermediate hyperglycaemia (IH), including impaired fasting glycaemia (IFG) and impaired glucose tolerance (IGT), as presently defined, will progress to type 2 diabetes (T2D). There is confirmatory evidence that T2D can be prevented by lifestyle modification and/or medications, in people with IGT diagnosed by 2-h plasma glucose (PG) during a 75-gram oral glucose tolerance test (OGTT). Over the last 40 years, a wealth of epidemiological data has confirmed the superior value of 1-h plasma glucose (PG) over fasting PG (FPG), glycated haemoglobin (HbA1c) and 2-h PG in populations of different ethnicity, sex and age in predicting diabetes and associated complications including death. Given the relentlessly rising prevalence of diabetes, a more sensitive, practical method is needed to detect people with IH and T2D for early prevention or treatment in the often lengthy trajectory to T2D and its complications. The International Diabetes Federation (IDF) Position Statement reviews findings that the 1-h post-load PG ≥ 155 mg/dL (8.6 mmol/L) in people with normal glucose tolerance (NGT) during an OGTT is highly predictive for detecting progression to T2D, micro- and macrovascular complications, obstructive sleep apnoea, cystic fibrosis-related diabetes mellitus, metabolic dysfunction-associated steatotic liver disease, and mortality in individuals with risk factors. The 1-h PG of 209 mg/dL (11.6 mmol/L) is also diagnostic of T2D. Importantly, the 1-h PG cut points for diagnosing IH and T2D can be detected earlier than the recommended 2-h PG thresholds. Taken together, the 1-h PG provides an opportunity to avoid misclassification of glycaemic status if FPG or HbA1c alone are used. The 1-h PG also allows early detection of high-risk people for intervention to prevent progression to T2D which will benefit the sizeable and growing population of individuals at increased risk of T2D. Using a 1-h OGTT, subsequent to screening with a non-laboratory diabetes risk tool, and intervening early will favourably impact the global diabetes epidemic. Health services should consider developing a policy for screening for IH based on local human and technical resources. People with a 1-h PG ≥ 155 mg/dL (8.6 mmol/L) are considered to have IH and should be prescribed lifestyle intervention and referred to a diabetes prevention program. People with a 1-h PG ≥ 209 mg/dL (11.6 mmol/L) are considered to have T2D and should have a repeat test to confirm the diagnosis of T2D and then referred for further evaluation and treatment. The substantive data presented in the Position Statement provides strong evidence for redefining current diagnostic criteria for IH and T2D by adding the 1-h PG.

First-trimester HbA1c in relation to plasma glucose concentrations in an oral glucose tolerance test at 12 to 16 weeks’ gestation—a population-based study

BackgroundEarly-onset GDM often requires pharmacological treatment and is associated with adverse perinatal outcomes, but data is insufficient regarding the best methods to identify high-risk women requiring early GDM screening. The aim of this study was to analyze the diagnostic accuracy of HbA1c in the prediction of (1) plasma glucose concentrations > 90th percentile in an oral glucose tolerance test (OGTT) at 12–16 weeks’ gestation; and (2) pharmacologically treated early- or late-onset GDM.MethodsHbA1c was measured at 8—14 weeks’ gestation in a population-based cohort of 1394 Finnish women recruited for the Early Diagnosis of Diabetes in Pregnancy (EDDIE) study between 3/2013 and 12/2016. Information on maternal risk factors were collected at recruitment. Subsequently, a 2-hour 75 g OGTT was performed at 12—16 weeks’ gestation (OGTT1), and if normal, repeated at 24–28 weeks’ gestation (OGTT2). Early- and late-onset GDM were diagnosed using the same nationally endorsed cut-offs for fasting, 1 h- and 2 h-plasma glucose: ≥5.3, ≥ 10.0mmol/l, and/or ≥ 8.6mmol/l, respectively. In total, 52/1394 (3.7%) women required metformin or insulin treatment for GDM, including 39 women with early-onset GDM diagnosed at OGTT1 and 13 women with late-onset GDM diagnosed at OGTT2.ResultsMaternal early-pregnancy HbA1c ≥ 35mmol/mol (≥ 5.4%) was the best cut-off to predict fasting or post-load plasma glucose > 90th percentile in OGTT1, but its diagnostic accuracy was low [AUC (95% CI) 0.65 (0.62 to 0.69), sensitivity 0.55 (0.49 to 0.60) and specificity 0.67 (0.64 to 0.70)] both alone and in combination with other maternal risk factors. However, HbA1c ≥ 35mmol/mol correlated positively with plasma glucose concentrations at all time points of OGTT1 and predicted pharmacologically treated GDM diagnosed at OGTT1 or OGTT2; AUC (95% CI) 0.75 (0.68 to 0.81), sensitivity 0.75 (0.61 to 0.86), specificity 0.64 (0.61 to 0.66).ConclusionsIn our population-based cohort, early-pregnancy HbA1c ≥ 35mmol/mol was positively associated with fasting and post-load plasma glucose concentrations in an OGTT at 12—16 weeks’ gestation and predicted pharmacologically-treated early- and late-onset GDM, suggesting potential utility in first-trimester identification of women at high risk of severe GDM subtypes.

The association between plasma angiopoietin-like protein 4, glucose and lipid metabolism during pregnancy, placental function, and risk of delivering large-for-gestational-age neonates

BackgroundLarge-for-gestational-age (LGA) neonates have increased risk of adverse pregnancy outcomes and adult metabolic diseases. We aimed to investigate the relationship between plasma angiopoietin-like protein 4 (ANGPTL4), a protein involved in lipid and glucose metabolism during pregnancy, placental function, growth factors, and the risk of LGA. MethodsWe conducted a prospective cohort study and recruited women with singleton pregnancies at the National Taiwan University Hospital between 2013 and 2018. First trimester maternal plasma ANGPTL4 concentrations were measured. ResultsAmong 353 pregnant women recruited, the LGA group had higher first trimester plasma ANGPTL4 concentrations than the appropriate-for-gestational-age group. Plasma ANGPTL4 was associated with hemoglobin A1c, post-load plasma glucose, plasma triglyceride, plasma free fatty acid concentrations, plasma growth hormone variant (GH-V), and birth weight, but was not associated with cord blood growth factors. After adjusting for age, body mass index, hemoglobin A1c, and plasma triglyceride concentrations, plasma ANGPTL4 concentrations were significantly associated with LGA risk, and its predictive performance, as measured by the area under the receiver operating characteristic curve, outperformed traditional risk factors for LGA. ConclusionsPlasma ANGPTL4 is associated with glucose and lipid metabolism during pregnancy, plasma GH-V, and birth weight, and is an early biomarker for predicting the risk of LGA.

Perceived stress and progression of cardiometabolic risk factors among South Asians with prediabetes in a lifestyle intervention trial

AimsTo examine associations between perceived stress and cardiometabolic risk factors in South Asians with prediabetes and assess whether a diabetes prevention program mitigates the impact of stress on cardiometabolic health. MethodsWe conducted a secondary analysis of the Diabetes Community Lifestyle Improvement Program, a lifestyle modification trial for diabetes prevention in India (n = 564). Indicators for cardiometabolic health (weight, waist circumference, blood pressure, glucose, HbA1c, and lipids) were measured at each visit while perceived stress was assessed via questionnaire at baseline. Multivariable linear regression assessed associations between stress and cardiometabolic parameters at baseline and 3-year follow up. ResultsAt baseline, perceived stress was associated with higher weight (b=0.16; 95% CI: 0.04, 0.29) and waist circumference (b=0.11; 95% CI: 0.01, 0.21) but lower 30-minute postload glucose (b=−0.44; 95% CI: −0.76, −0.14) and LDL cholesterol (b=−0.40; 95% CI: −0.76, −0.03). Over the study period, perceived stress was associated with weight gain (b=0.20; 95% CI: 0.07, 0.33) and increased waist circumference (b=0.14; 95% CI: 0.04, 0.24). Additionally, higher perceived stress was associated with lower HDL cholesterol among the control arm (pinteraction = 0.02). ConclusionsBaseline stress was associated with negative cardiometabolic risk factor outcomes over time in those with prediabetes.

METABOLICALLY ASSOCIATED FATTY LIVER DISEASE IN PATIENTS WITH VERY HIGH CARDIOVASCULAR RISK: PREVALENCE, CLINICAL SIGNIFICANCE, GENDER DIFFERENCES

Introduction. Recently, metabolically associated fatty liver disease (MAFLD) had been proposed as a new term. Due to increasing prevalence, significant morbidity and hepatic and cardiovascular mortality, the association of MAFLD with cardiovascular diseases is gaining considerable relevance and needs further study. The aim of our study was to determine the proportion of MAFLD among patients with a very high cardiovascular risk, and to elucidate clinical features and gender differences in this cohort. Materials and methods. All patients underwent a comprehensive examination to assess both cardiovascular risk and MAFLD. Hepatic steatosis was diagnosed after liver ultrasonography. Participants who met MAFLD criteria were included into the group 1 (n=77; 32 women, 45 men), other patients were assigned to the group 2 (n=39; 19 women, 20 men). Results. Among patients with very high cardiovascular risk, proportion of MAFLD was 66.7 %. Although mild alanine aminotransferase elevation was much more common among patients with MAFLD (16 women (50.0 %) vs. 2 women (10.5 %) in group 2, P = 0.006; 21 men (46.7 %) vs. 2 men in group 2 (10.0 %), P = 0.005), none of the participants met the criteria for steatohepatitis. Despite, the presence of metabolic disorders in the vast majority of participants, proportion of obesity, metabolic dyslipidaemia, prediabetes and type 2 diabetes were significantly higher in patients with MAFLD. Besides, patients with MAFLD usually met 4 or 5 metabolic syndrome criteria, had higher median values of lipid accumulation product (LAP) and HOMA-IR index, but lower median values of Matsuda index. Significant direct correlations were found between MAFLD and LAP, logarithmic index (TG/HDL-C), and HOMA-IR; negative correlations were observed between MAFLD and insulin sensitivity indices. Women with MAFLD had significantly higher median values of glycated haemoglobin, post-load glucose, fasting insulin levels; there was direct correlation between MAFLD and non-HDL-C. Among women with MAFLD, a history of menopause before 45 years of age had 15 persons (46.9 %) vs. one person (5.3 %) in group 2 (P &lt; 0.002); the median age when ASCVD was diagnosed was 58.5 [53.0; 64.0] years vs. 68.0 [63.0; 69.0] years in group 2 (P = 0.002); cardiac valve calcinosis was detected in 31 women (96.6 %) vs. 9 women (47.4 %) in group 2 (P = 0.0001); the left ventricular myocardial mass (LVM) index was 77.5 [62.1; 86.9] g/m2.7 vs. 64.0 [50.6; 74.0] g/m2.7 in women without MAFLD, 67.0 [55.1; 74.0] g/m2.7 in men with MAFLD, and 63.9 [50.0; 73.5] g/m2.7 in men without MAFLD (Kruskal–Wallis ANOVA P &lt;0.0001; median test P=0.002). The prevalence of smoking and alcohol intake was significantly more common among men (gender differences P &lt;0.0001 and P=0.0001 in group 1; P = 0.0004 and P=0.0023 in group 2 for smoking and alcohol intake, respectively). Men with MAFLD had significantly higher median values of fasting plasma glucose, fasting and post-load insulin levels than men without MAFLD; there was a significant direct correlation between MAFLD and serum TG level. In addition, 11 men with MAFLD (24.4 %) had hypertriglyceridemia &gt;2.3 mmol/l that was not observed among men without MAFLD (P=0.013). The proportion of men with fasting and post-load hyperinsulinemia was much higher in group 1 than in group 2 (28 persons (62.2%) vs. 3 persons (15.0 %), P=0.0005 and 26 persons (57.8%) vs. 2 persons (10.0 %), P = 0.0003, respectively). Conclusions: among patients with a very high cardiovascular risk, the prevalence of MAFLD was significantly higher than in the general population. Concomitant MAFLD was associated with more severe metabolic disorders (i.e., obesity, metabolic dyslipidaemia, hyperglycaemia, insulin resistance), which usually combined. The LAP index is a simple available tool that may be used in routine clinical practice to determine the need for MAFLD screening. Women with MAFLD frequently had early menopause, cardiac valve calcification, and much higher median value of LVM index; direct correlation was observed between MAFLD and non-HDL-C. Men with MAFLD more often had fasting and/or post-load hyperinsulinemia and moderate hypertriglyceridemia.

Phenotypic characterization of nonautoimmune diabetes in adult Ugandans with low body mass index.

Type 2 diabetes is common in relatively lean individuals in sub-Saharan Africa. It is unclear whether phenotypic differences exist between underweight and normal-weight African patients with type 2 diabetes. This study compared specific characteristics between underweight (body mass index <18.5 kg/m2) and normal-weight (body mass index of 18.5-24.9 kg/m2) adult Ugandans with new-onset nonautoimmune diabetes. We collected the demographic, clinical, anthropometric, and metabolic characteristics of 160 participants with nonobese new-onset type 2 diabetes (defined as diabetes diagnosed <3 months, body mass index <25 kg/m2, and absence of islet-cell autoimmunity). These participants were categorized as underweight and normal weight, and their phenotypic characteristics were compared. Of the 160 participants with nonobese new-onset type 2 diabetes, 18 participants (11.3%) were underweight. Compared with those with normal weight, underweight participants presented with less co-existing hypertension (5.6% versus 28.2%, p = 0.04) and lower median visceral fat levels [2 (1-3) versus 6 (4-7), p < 0.001], as assessed by bioimpedance analysis. Pathophysiologically, they presented with a lower median 120-min post-glucose load C-peptide level [0.29 (0.13-0.58) versus 0.82 (0.39-1.50) nmol/l, p = 0.04] and a higher prevalence of insulin deficiency (66.7% versus 31.4%, p = 0.003). This study demonstrates that nonautoimmune diabetes occurs in underweight individuals in sub-Saharan Africa and is characterized by the absence of visceral adiposity, reduced late-phase insulin secretion, and greater insulin deficiency. These findings necessitate further studies to inform how the prevention, identification, and management of diabetes in such individuals can be individualized.

Association of ABO and RH Blood Groups with Gestational Diabetes Mellitus in Patients Attending a Tertiary Care Hospital of Lahore, Pakistan

Objective: To find out any association of ABO and Rh blood groups with gestational diabetes mellitus (GDM). Study Design: Comparative cross-sectional study. Place and Duration of Study: Pathology and Gynecology departments of Combined Military Hospital-Lahore from Jun to Sep 2020. Methodology: A total of 250 patients of GDM and 250 pregnant ladies with normal glucose tolerance (NGT) were included in the study. The Oral glucose tolerance test (OGTT) was performed with a 75g glucose load, and results were interpreted according to the American Diabetes Association 2020 criteria. Blood glucose samples were taken in sodium fluoride containers in fasting conditions, 1 hour and 2 hours post-glucose load. Samples for blood groups were obtained in plain and EDTA containers. Blood glucose samples were analyzed using the Hexokinase method's automated chemistry analyzer, Cobas c-501. ABO and RhD blood grouping were carried out by forward and reverse techniques in the blood bank of CMH Lahore. Results: A total of 250 (50%) pregnant ladies with OGTT suggestive of Gestational Diabetes Mellitus and 250 (50%) pregnant ladies with OGTT suggestive of Normal Glucose Tolerance (NGT) were included in the study. No statistically significant difference was observed with ABO and RhD blood groups among them (p=0.944). Conclusion: There is no significant association found between ABO and RhD blood groups with Gestational Diabetes Mellitus.

The relationship between obstructive sleep apnea and haemoglobin A1c and the moderating role of glycaemic status in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL).

This study investigated the relationship between obstructive sleep apnea and haemoglobin A1c (HbA1c) among Hispanics/Latinos in the United States and assessed whether this relationship was moderated by glycaemic status. This was a cross-sectional analysis of the Hispanic Community Health Study/Study of Latinos cohort. The sample consisted of 13,394 participants with valid measures of obstructive sleep apnea, HbA1c, and study covariates. Obstructive sleep apnea was assessed with the apnea-hypopnea index and categorised as obstructive sleep apnea if the apnea-hypopnea index was ≥5 events/h. HbA1c measures were obtained through fasting blood samples. Fasting plasma glucose (FPG), 2-h post-load plasma glucose (2h-PG) and use of antihyperglycaemic medications were used to define glycaemic status (i.e., normoglycaemia [FPG < 5.6 mmol/L (< 100 mg/dL) and 2h-PG < 7.8 mmol/L (140 mg/dL)], prediabetes [FPG 5.6-6.9 mmol/L (100-125 mg/dL), and/or 2h-PG 7.8-11.0 mmol/L (140-199 mg/dL)], diabetes without treatment [FPG > 7.0 mmol/L (≥ 126 mg/dL) and/or 2h-PG ≥ 11.1 mmol/L (≥ 200 mg/dL)], and diabetes with treatment. Multivariable linear regression was used to calculate adjusted least square means. Overall, 25.9% of the sample had obstructive sleep apnea and 49.2% had normal glycaemic levels, 36.1% had prediabetes, 6.5% diabetes without receiving treatment, and 8.3% diabetes and undergoing treatment for it. Participants with obstructive sleep apnea had significantly higher adjusted mean HbA1c (adjusted mean [standard error] 5.85 [0.03)]) than those without (5.70 [0.02)]; p < 0.001). Models stratified by diabetes status showed that the association between obstructive sleep apnea (versus not) and higher HbA1c was only for participants with normal glycaemic status (adjusted mean [standard error] 5.27 [0.01] versus 5.30 [0.01]; p = 0.013) and prediabetes (5.59 [0.01] versus 5.66 [0.01]; p < 0.001). In conclusion, obstructive sleep apnea was associated with higher HbA1c in a diverse sample of Hispanic/Latino adults in the United States. This association was present only for participants with normal glycaemic status or with prediabetes. Studies are needed to further understand the clinical implications of the association between obstructive sleep apnea and HbA1c according to glycaemic status.

One-hour post-load glucose levels are associated with hepatic steatosis assessed by transient elastography.

To examine the association between 1-hour plasma glucose (PG) concentration and markers of non-alcoholic fatty liver disease (NAFLD) assessed by transient elastography (TE). We performed TE in 107 metabolically well-characterized non-diabetic White individuals. Controlled attenuation parameter (CAP) was used to quantify liver steatosis, while liver stiffness marker (LS) was used to evaluate fibrosis. Controlled attenuation parameter correlated significantly with 1-hour PG (r = 0.301, P < 0.01), fasting insulin (r = 0.285, P < 0.01), 2-hour insulin (r = 0.257, P < 0.02), homeostasis model assessment index of insulin resistance (r = 0.252, P < 0.01), high-density lipoprotein cholesterol (r = -0.252, P < 0.02), body mass index (BMI; r = 0.248, P < 0.02) and age (r = 0.212, P < 0.03), after correction for age, sex and BMI. In a multivariable linear regression analysis, 1-hour PG (β = 0.274, P = 0.008) and fasting insulin levels (β = 0.225, P = 0.029) were found to be independent predictors of CAP. After excluding subjects with prediabetes, 1-hour PG was the sole predictor of CAP variation (β = 0.442, P < 0.001). In a logistic regression model, we observed that the group with 1-hour PG ≥ 8.6 mmol/L (155 mg/dL) had a significantly higher risk of steatosis (odds ratio 3.98, 95% confidence interval 1.43-11.13; P = 0.008) than individuals with 1-hour PG < 8.6 mmol/L, after correction for potential confounders. No association was observed between 1-hour PG and LS. Our data confirm that 1-hour PG ≥ 8.6 mmol/L is associated with higher signs of NAFLD, even among individuals with normal glucose tolerance, categorized as low risk by canonical diagnostic standards. TE is a safe low-impact approach that could be employed for stratifying the risk profile in these patients, with a high level of accuracy.

Sex-specific associations of the difference between 2-hour post-load and fasting plasma glucose with cardiovascular risk in a normoglycemic population

Abstract Background Elevated levels of fasting plasma glucose (FPG) and 2-hour post-load glucose (2hPG) have been established as individual risk factors for cardiovascular disease (CVD), coronary heart disease (CHD), and stroke. However, it is unclear whether the difference between 2hPG and FPG (2hPG-FPG) within normoglycemic influences the cardiovascular risk in women and men. Purpose To investigate the association between 2hPG-FPG and the incidence of CVD, CHD, and stroke among normoglycemic women and men in a large population-based cohort. Methods In this prospective cohort study, a total of 7224 participants with the normoglycemic state (mean age 37±11; women, 57.4%) that had baseline measurements of both FPG and 2hPG values and did not have prior CVD, CHD, or stroke were included and were followed for incidence of outcomes annually until March 2018. The normoglycemic range was defined as FPG&amp;lt; 5.55 and 2 h-PG&amp;lt; 7.77 mmol/L and not taking anti-diabetic medications. CHD was defined as either positive ECG findings and biomarkers, cardiac symptoms accompanied by either positive ECG or biomarker, or angiographic-proven CHD. Stroke was defined based on the WHO criteria. Also, CVD was defined as a composite of CHD and stroke. A Multivariable Cox­-regression model adjusted for age, body mass index, hypertension, hyperlipidemia, FPG, education level, and smoking status was used to assess the association between 2hPG-FPG and incident CVD, CHD, and stroke in women and men. We also used a cumulative incidence curve to illustrate the cumulative sex-specific incidence of CVD, CHD, and stroke during the follow-up time (Figure 1). Results During a median follow-up of 17.9 years (IQR: 13.75-18.46), 487 CVD (174 women), 427 CHD (140 women), and 76 stroke (37 women) events occurred. Among men, 2hPG-FPG was associated with an increased risk of CVD (hazard ratio [HR]:1.11, 95% confidence interval [CI]:1.01-1.22, p=0.03) and CHD (HR:1.11, 95% CI:1.00-1.22, p=0.04 ), but not stroke (HR:1.14, 95% CI:0.88-1.50, p= 0.33). No significant associations among women were found between 2hPG-FPG and the incidence of outcomes, with adjusted HRs of 1.02 (95% CI, 0.88-1.18, p=0.82), 1.00 (0.85-1.17, p=0.99), and 1.10 (0.80-1.52, p=0.54) for incident CVD, CHD, and stroke, respectively (Table 1). Conclusion A greater difference between 2hPG and FPG (2hPG-FPG) within the normoglycemic range was associated with an increased risk for incidence of CVD and CHD in men but not women. Further studies are warranted to explore the potential use of 2hPG-FPG for cardiovascular risk stratification, particularly among those with normal glucose parameters.Association of 2hPG-FPG with CV riskCumulative incidence of CVD, CHD, stroke

Circadian and post-glucose load changes in salivary testosterone concentration

Circadian and post-glucose load changes in salivary testosterone concentration

Correlation of Carotid Intima-Media Thickness with One-hour Postload Plasma Glucose (1h-PPG) in Overweight and Obese North Indian Adults

Background: Cardiovascular morbidities like arterial stiffness and atherosclerosis have a negative association with insulin resistance, which can be identified by carotid intima media thickness (CIMT) measurement. One-hour postload plasma glucose (1 h-PPG) is a novel marker for early identification of insulin resistance, but very few studies are available on its relationship with CIMT. Objective: To identify the correlation of CIMT with 1 h-PPG in overweight and obese adults without diabetes. Methods: Individuals not having known diabetes or other chronic illnesses were identified and subjected to the initial anthropometric analysis for body mass index (BMI) calculation. A standard oral glucose tolerance test was performed on individuals with a BMI of ≥25 kg/m2 for 1 h-PPG values, and a B-mode ultrasound scan of the neck was used for CIMT measurement. A Pearson’s correlation statistical test was applied for correlation identification. Results: A total of 94 nondiabetic individuals participated, of whom 55 (58.5%) were women. Mean age, BMI, and CIMT values of the study population were 38.8 (±8.09) years, 29.6 (±3.22) kg/m2, and 0.72 (±0.10) mm, respectively. Average 1 h-PPG levels were 150.7 (±21.11) mg/dl, and the Pearson’s coefficient ( r) value with CIMT was 0.5792 ( P &lt; 0.05). Further, correlation analysis demonstrated an r-value of −0.0029 for BMI, −0.1293 for waist-hip ratio, −0.0047 for waist-height ratio, 0.3862 for glycated hemoglobin (HbA1c), and −0.2930 for 2 h-PPG. Conclusion: In euglycemic adults, the early insulin resistance defining parameter, i.e., 1 h-PPG levels had a consistent positive correlation with CIMT, which is a marker of the initial stages of atherosclerosis.

THU245 Association Between Sleep Duration And Incident Diabetes Mellitus In Healthy Subjects: A 12-year Longitudinal Cohort Study

Abstract Disclosure: W. Kim: None. J. Huh: None. Objective: Previous studies demonstrated that inadequate sleep, including the deprivation of absolute sleep duration and poor sleep quality, was associated with a higher risk of type 2 diabetes mellitus (DM) and obesity. This study aimed to investigate whether sleep duration and/or quality is associated with incident DM. Methods: The study population consisted of participants in the ongoing Korean Genome and Epidemiology Study (KoGES)-Ansung and Ansan Cohort Study, a rural, community-based, prospective study. A total of 8,816 of 10,030 healthy participants were enrolled in a prospective cohort study. DM was diagnosed as fasting glucose ≥126 mg/dL or 2-h post-loading glucose ≥200 mg/dL. Sleep du-ration and quality questionnaires were completed. Sleep duration was classified into four groups: 6 &amp;lt;, 6-7, 8-9, 9 h/day. Sleep quality was assessed in participants with sleep duration of &amp;lt; 10 h/day using the Epworth Sleepiness Scale (ESS) which measures an excessive daytime sleepiness in individuals. Results: During the 14-year follow-up period, 18% (1630/8816) were diagnosed with DM. A U-shaped relationship was observed between sleep duration and incident DM, with the highest risk observed when sleep duration was 10 ≥ h/day (Hazard ratios (HR) 1.65 [1.25–2.17]). This group exhibited decreased insulin glycogenic index, a marker of insulin secretory function, during the study period. Among study participants who slept less than 10 h/day, the risk of incident DM increased when the ESS score was &amp;gt; 10. Conclusion: We found that the association between sleep duration and incident DM was U-shaped; both short (≤5 h) and long (≥10 h) sleep duration were associated with an increased risk for the occurrence of incident DM. When sleep duration was 10 h or longer per day, there was a tendency to develop DM due to decreased insulin secretory function. Even if the sleep duration is less than 10 h, the likelihood of developing diabetes is greater when the quality of sleep decreases. Presentation: Thursday, June 15, 2023

THU251 Diagnostic Performance For Predicting Hepatic And Peripheral Tissue Insulin Resistance In Young Adult Men Using 1Hour Post Load Serum Glucose And Insulin Levels A Pilot Study

Abstract Disclosure: A.J. Ledezma: None. C.F. Espinel Pachón: None. S.S. Perea: None. J.E. Caminos: None. Insulin resistance (RI) is a risk factor for prediabetes and DM2, and other non communicable diseases. Different studies have demonstrated that 1h post load serum glucose levels during an oral glucose test tolerance OGTT seem to be a better predictor of peripheral RI than 2h post load serum glucose among individuals without DM2. On the other hand, HOMA IR reflects primarily hepatic sensitivity/resistance, meanwhile, Matsuda index, may reflect both hepatic and peripheral tissue insulin sensitivity/resistance. Thus, this study aimed to evaluate the diagnostic performance, to identify hepatic and peripheral RI, of 1h post load serum glucose and insulin levels during an OGTT in young adult men, using ROC AUC analysis. This cross-sectional study was conducted on a total of 91 young adult men (18-31-year-olds), 47 healthy lean (BMI &amp;lt;25 kg/m2), and 44 obese nondiabetic subjects (BMI ≥30 kg/m2). Subjects underwent a standard 75g OGTT and blood samples were drawn at 0, 30, 60, and 120 min to obtain serum glucose and insulin levels. Clinical and anthropometric and biochemical variables were determined. Participants were classified as RI based on a predefined Matsuda index cutoff 4.3 value. Cut-offs, sensitivity, and specificity for glucose, insulin, and anthropometrics parameters were determined by AUC ROC analysis for predicting RI diagnosis, and Spearman´s correlation was established between biochemical variables and waist/height ratio and Delong test analysis. Our results showed that 1h post load glucose levels had higher sensitivity 84.1% vs 47.7% and AUC 83.9% [CI 95% 75.6; 92.1%] vs 72.4% [CI 95% 61.8%; 83.0%] than 2h post load during OGTT, however lower specificity was found 70.2% vs 89.4%. Additionally, 1h post load insulin levels had higher sensitivity 90.9% vs 77% and AUC 97.1% [CI 95% 94; 100%] vs 91.9% [CI 95% 86.3; 97.5%] than 2h post load during OGTT, without changes in specificity 97.9% vs 97.8%. It is important to highlight that waist/height ratio reached a 100% AUC 95% CI diagnostic performance for RI in our sample. Additionally, HOMA IR index 99.8% [CI 95% 99.1; 100%], 1/fasting insulin 100% [CI 95% 0.99; 100%], and fasting glucose/insulin ratio 99.7% [CI 95% 99.2; 100%], showed a high diagnostic performance for RI. In the Spearman correlation, Waist/height ratio presented a high correlation with respect to Matsuda -0.8672; p&amp;lt;0.01 G/I1H -0.7454; p&amp;lt;0.01, 1/I1H -0.7783; p&amp;lt; 0.01; Delong test, the best performance comparing 1H vs 2H, G1H/G2H with Z value 2.0668 and P 0.03 In conclusion, 1h post load glucose and insulin levels and the waist/height ratio show greater diagnostic performance than 2h post load for detecting peripheral tissue and hepatic RI in young men. Therefore, Cut-offs values of glucose and insulin levels 1h post load provide simple but useful test for early detection of different prevalent diseases related to RI. Presentation: Thursday, June 15, 2023

Different subtypes of gestational diabetes mellitus are associated with distinct perinatal outcomes in twin pregnancies

AimsTo determine whether different gestational diabetes mellitus (GDM) subtypes are associated with distinct perinatal outcomes in twin pregnancies. MaterialsThis retrospective cohort study enrolled women with twin pregnancies who gave birth at a tertiary hospital between January 2017 and December 2022. GDM was diagnosed by the IADPSG diagnostic criteria. Three subtypes of GDM were defined as only abnormal fasting glucose (OAFG) values, only abnormal post-load glucose (OAPG) values and abnormal combined fasting and post-load glucose (ACFPG) values. Logistic regression or generalized estimation equation models were used to test the correlation of subtypes of GDM and perinatal outcomes. ResultsGDM with OAPG had a slightly higher risk for preterm delivery (PTD) at <37 gestational weeks (aOR 1.22, 95 %CI 1.01–1.47) and neonatalintensivecareunit (NICU) admission (aOR 1.31, 95 %CI 1.09–1.57). GDM with ACFPG were associated with PTD at <37 gestational weeks (aOR 1.42, 95 %CI 1.06–1.89) and PTD at <34 gestational weeks (aOR 1.65, 95 % CI 1.14–2.39). GDM with OAFG had a lower risk of being small-for-gestational age (SGA) (aOR 0.48, 95 % CI 0.26–0.92). ConclusionsDifferent subtypes of GDM are associated with distinct perinatal outcomes. Only abnormal fasting glucose levels may be responsible for reduced the risk of SGA neonates.

Human Milk Oligosaccharides in Maternal Serum Respond to Oral Glucose Load and Are Associated with Insulin Sensitivity.

(1) Background: Pregnancy presents a challenge to maternal glucose homeostasis; suboptimal adaptations can lead to gestational diabetes mellitus (GDM). Human milk oligosaccharides (HMOs) circulate in maternal blood in pregnancy and are altered with GDM, suggesting influence of glucose homeostasis on HMOs. We thus assessed the HMO response to glucose load during an oral glucose tolerance test (OGTT) and investigated HMO associations with glucose tolerance/insulin sensitivity in healthy pregnant women. (2) Methods: Serum of 99 women, collected at 0 h, 1 h and 2 h during a 75 g OGTT at 24-28 gestational weeks was analyzed for HMOs (2'FL, 3'SLN, LDFT, 3'SL) by HPLC; plasma glucose, insulin and C-peptide were analyzed by standard biochemistry methods. (3) Results: Serum 3'SL concentrations significantly increased from fasting to 1 h after glucose load, while concentrations of the other HMOs were unaltered. Higher 3'SL at all OGTT time points was associated with a generally more diabetogenic profile, with higher hepatic insulin resistance (HOMA-IR), lower insulin sensitivity (Matsuda index) and higher insulin secretion (C-peptide index 1). (4) Conclusions: Rapid increase in serum 3'SL post-oral glucose load (fasted-fed transition) indicates utilization of plasma glucose, potentially for sialylation of lactose. Associations of sialylated HMOs with a more diabetogenic profile suggest sustained adaptations to impaired glucose homeostasis in pregnancy. Underlying mechanisms or potential consequences of observed HMO changes remain to be elucidated.