Single Point Insulin Sensitivity Estimator Research Articles

Association of single-point insulin sensitivity estimator index (SPISE) with future cardiovascular outcomes in patients with type 2 diabetes.

To investigate the association of single-point insulin sensitivity estimator (SPISE) index with future cardiovascular outcomes in patients with type 2 diabetes. SPISE index (= 600 × high-density lipoprotein cholesterol [mg/dL]0.185/triglycerides [mg/dL]0.2 × body mass index [kg/m2]1.338) was calculated in 10 190 participants. Cox proportional hazard regression models were applied to evaluate the association between SPISE index and future cardiovascular outcomes. Restricted cubic spline analyses and two-piecewise linear regression models were employed to explore the nonlinear association and to determine the threshold value. Subgroup and interaction analyses were conducted to test the robustness of the results. After fully adjusting for well-established metabolic confounders, higher SPISE index was significantly associated with lower risk of future cardiovascular outcomes in patients with type 2 diabetes (major adverse cardiovascular event [MACE]): hazard ratio [HR] 0.94, 95% confidence interval [CI] 0.90-0.98, p = 0.0026; overall mortality: HR 0.90, 95% CI 0.86-0.93, p < 0.0001; cardiovascular disease [CVD] mortality: HR 0.85, 95% CI 0.79-0.92, p < 0.0001; congestive heart failure (CHF): HR 0.72, 95% CI 0.67-0.78, p < 0.0001; major coronary events: HR 0.91, 95% CI 0.87-0.95, p < 0.0001. There was a nonlinear association between SPISE index and future cardiovascular outcomes (the threshold value was 5.68 for MACE, 5.71 for overall mortality, 4.64 for CVD mortality, 4.48 for CHF, and 6.09 for major coronary events, respectively). Higher SPISE index was independently associated with lower risk of future cardiovascular outcomes in type 2 diabetes patients after full adjustment for well-established metabolic confounders.

Telomere length as a modifier in the relationship between phthalate metabolites exposure and glucose homeostasis

Given the rising concern over the potential impact of environmental factors on metabolic heath, we conducted a cross-sectional analysis among 645 adults aged 20 and older in the National Health and Nutrition Examination Survey (NHANES), examining the association between nine phthalate metabolites (Mono-n-butyl phthalate (MBP), Mono-ethyl phthalate (MEP), Mono-(2-ethyl)-hexyl phthalate (MEHP), Mono-benzyl phthalate (MBzP), Mono-n-methyl phthalate (MnMP), Mono-(3-carboxy propyl) phthalate (MCPP), Mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), Mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP), Mono-isobutyl phthalate (MiBP)) and six glucose homeostasis indices (fasting glucose, fasting insulin, hemoglobin A1C (HbA1C), homeostatic model assessment of insulin resistance (HOMA-IR), single Point Insulin Sensitivity Estimator (SPISE), and HOMA-β). Latent Class Analysis identified three phthalate metabolites exposure patterns: high MEP-low MEOHP (n = 282), high MBzP-low MEHHP (n = 214), and high MEHHP, MEOHP (n = 149). The high MBzP-low MEHHP and high MEHHP, MEOHP, versus the high MEP-low MEOHP, exposure groups showed significantly higher levels of fasting insulin (β = 0.126, 95% CI: 0.023–0.228), SPISE (β = 0.091, 95% CI: 0.018–0.164), and HOMA-IR (β = 0.091, 95% CI: 0.018–0.164). In the shorter telomere length group, high MEHHP, MEOHP exposure showed an increase in SPISE levels (β = 0.153, 95% CI: 0.037–0.269), while in the overweight/obese subgroup, high MEHHP, MEOHP exposure was significantly positively associated with HOMA-IR (β = 0.392, 95% CI: 0.150–0.735). Bayesian kernel machine regression analyses showed positive associations between higher combined phthalate exposure and increased glucose homeostasis indices (fasting glucose, HbA1C, fasting insulin, SPISE, and HOMA-IR). The quantile of g-calculation analysis also supported the positive associations with HbA1C, HOMA-IR, and fasting insulin. Our findings indicate that phthalate exposure was positively associated with glucose homeostasis indices, which strengthen the call for proactive measures to reduce phthalate exposure and mitigate potential risks to glucose metabolism.

Altered Glucagon and GLP-1 Responses to Oral Glucose in Children and Adolescents With Obesity and Insulin Resistance.

Pediatric obesity is characterized by insulin resistance, yet it remains unclear whether insulin resistance contributes to abnormalities in glucagon and incretin secretion. To examine whether fasting and stimulated glucagon, glucagon-like peptide-1 (GLP-1), and glucose-dependent insulinotropic polypeptide (GIP) concentrations differ between children and adolescents with obesity and insulin resistance (OIR), obesity and normal insulin sensitivity (OIS), and controls with normal weight (NW). 80 (34 boys) children and adolescents, aged 7-17 years with OIR (n = 22), OIS (n = 22), and NW (n = 36) underwent an oral glucose tolerance test with measurements of serum insulin, plasma glucose, glucagon, total GLP-1, and total GIP. Homeostatic model assessment of insulin resistance (HOMA-IR), single point insulin sensitivity estimator (SPISE), Matsuda index, insulinogenic index (IGI), and oral disposition index (ODI) were calculated. Fasting concentrations of glucagon and GLP-1 were higher in the OIR group, with no significant differences for GIP. The OIR group had higher glucagon total area under the curve (tAUC0-120) and lower GLP-1 incremental AUC (iAUC0-120), with no significant differences in GIP iAUC0-120. Higher fasting glucagon was associated with higher HOMA-IR, lower Matsuda index, lower SPISE, higher IGI, and higher plasma alanine transaminase, whereas higher fasting GLP-1 was associated with higher HOMA-IR, lower Matsuda index, and lower ODI. Higher glucagon tAUC0-120 was associated lower SPISE and lower Matsuda index, whereas lower GLP-1 iAUC0-120 was associated with a higher HOMA-IR, lower Matsuda index, and lower ODI. Children and adolescents with OIR have elevated fasting concentrations of glucagon and GLP-1, higher glucagon and lower GLP-1 responses during an OGTT compared to those with OIS and NW. In contrast, individuals with OIS have similar hormone responses to those with NW.

ИНДЕКСЫ СУРРОГАТНОЙ ОЦЕНКИ ИНСУЛИНОРЕЗИСТЕНТНОСТИ У ДЕТЕЙ И ПОДРОСТКОВ С ОЖИРЕНИЕМ

Obesity is the most common reason for the insulin resistance (IR) though obesity in children is not always associated with IR. The markers based on fasting glucose and/or insulin levels and alternative parameters with conventional lipid-based indexes are used in assessing the IR in clinical practice. The purpose of the research was to assess the relationship between alternative IR surrogate biomarkers as follows: triglycerides (TG) to high-density lipoprotein cholesterol (HDL-C), TG/HDL-C ratio; single-point insulin sensitivity estimator (SPISE) index; triglyceride-glucose index (TyG), with generally accepted indices based on the insulin/glucose ratios, such as HOMA-IR, QUICKI, Caro, in a cohort of obese children and adolescents. Materials and methods used: a single-stage multicenter comparative study was conducted involving 127 patients aged 6 to 17 y/o with simple obesity of varying degrees. The following indices were calculated: HOMA-IR = fasting insulin (mU/ml) x fasting plasma glucose (FPG) (mmol/L) / 22.5; QUICKI = 1/Log (Fasting Insulin, µU/ml) + Log (Fasting Glucose, mg/dl); Caro = fasting plasma glucose (mmol/l) / fasting insulin (μU/ml); TG/HDL-C = TG (mmol/L) / HDL-C (mmol/L); triglyceride-glucose index TyG = Ln [fasting TG (mg/dl) x fasting plasma glucose (mg/dl)/2], where Ln is the logarithm; SPISE = 600 × HDL-C0.185/(TG0.2 x BMI1.338). Results: 75 (59%) boys and 52 (41%) girls were included in the study; the median age was 12.9 [10.4; 14.9] y/o. Pre-pubertal development was recorded in 25 (19.7%), pubertal - in 102 (80.3%). The prevalence of impaired glucose tolerance (IGT) was 5.5%. In children with IGT, the SPISE index was lower than in children with normal glucose tolerance (3.69 [3.49; 4.37] vs. 4.8 [3.99; 5.55], p=0.021) with no statistically significant differences between these groups in other markers. In the IGT subgroup, a high negative correlation was found between SDS BMI and SPISE (R=-0.97). In the general SDS group, BMI correlated with insulin (R=+0.24), TG (R=+0.2), HOMA (R=+0.24), Caro (R=-0.26), TG/HDL-C (R=+0.28) and SPISE (R=-0.65). The SPISE index was lower in girls than in boys (4.94 [3.63; 5.73] vs. 4.07 [3.59; 5.16], p = 0.045). No statistically significant differences were recorded for other gender-related markers. A negative correlation was also found between the obesity degree and SPISE in the subgroups of girls (R=-0.49) and boys (R=-0.70) as well as among pre-pubertal children of both genders (R=-0.61). The maximum correlation between SDS BMI and SPISE was recorded in the subgroup of teenagers of both genders (R=-0.88). In the general group, TyG was weakly correlated with HOMA-IR (R=+0.26) and QUICKI (R=-0.24), while SPISE showed a weak association with all studied insulin indices; no statistically significant correlation between insulin indices and TG/HDL-C was found. In the subgroup of girls, no significant relationships between the evaluated markers were found, in the subgroup of boys, TyG weakly correlated with HOMA-IR (R=+0.29) and QUICKI (R=-0.32). Stronger correlations were recorded in boys between SPISE and all studied insulin indices. In the subgroup of prepubertal patients, a correlation was found between TyG and QUICKI (R=-0.44), SPISE and Caro (R=+0.56), SPISE and HOMA-IR (R=-0.50). The TG/HDL-C ratio did not statistically significantly correlate with traditional IR markers. TyG showed weak correlations with HOMA-IR and QUICKI in the general group and the boys’ subgroup. In the prepubertal period, TyG only weakly correlated with QUICKI and did not show strong associations with insulin-based indices in pubertal children. The SPISE index showed correlations with insulin markers both in the main group and in individual subgroups. Conclusion: the SPISE index can be considered as a relatively simple and accessible method for assessing IR in obese children and adolescents.

The single point insulin sensitivity estimator (SPISE) index as a predictor of metabolic syndrome in Korean adults

PurposeRecently, the single-point insulin sensitivity estimator (SPISE) has been developed as a simple surrogate of insulin resistance based on BMI, triglycerides (TG), and HDL-C. However, no studies have focused on the predictive power of the SPISE index for identifying metabolic syndrome (MetSyn) in Korean adults. Here, this study aimed to estimate the predictive power of the SPISE index for determining MetSyn and to compare its predictive power with other insulin sensitivity/resistance indices in South Korean adults. MethodsA total of 7837 participants from the 2019 and 2020 Korean National Health and Nutrition Examination Surveys were analyzed in the present study. MetSyn was defined by the AHA/NCEP criteria. In addition, HOMA-IR, inverse insulin, TG/HDL, TyG index (triglyceride-glucose index), and SPISE index were calculated based on the previous literature. ResultsPredictive power of the SPISE index for determining MetSyn (ROC-AUC [95 % CI] = 0.90 [0.90–0.91], sensitivity = 83.4 %, specificity = 82.2 %, cut-off point = 6.14, p < .001) was higher than that of HOMA-IR (ROC-AUC: 0.81), inverse insulin (ROC-AUC: 0.76), TG/HDL-C (ROC-AUC: 0.87), and TyG index (ROC-AUC: 0.88), the P value for ROC-AUC comparison < .001. ConclusionSPISE index has demonstrated superior predictive value for diagnosing MetSyn regardless of sex and is strongly correlated with blood pressure compared with other surrogate indices of insulin resistance, attesting to its utility as a reliable indicator of insulin resistance and MetSyn in Korean adults.

A Single-Point Insulin Sensitivity Estimator (SPISE) of 5.4 is a good predictor of both metabolic syndrome and insulin resistance in adolescents with obesity.

The Single-Point Insulin Sensitivity Estimator (SPISE) is a biomarker of insulin sensitivity estimated using BMI and triglycerides and high-density lipoprotein cholesterol. We assessed the accuracy of SPISE to screen obesity-related cardiometabolic risk in children and adolescents. Cross-sectional validation study for a screening test in a sample of n=725 children and adolescents from an obesity clinic. Weight, height, waist circumference, blood arterial pressure, lipid profile, glucose, insulin and Tanner stage were measured. BMI, BMI for-age-and sex (BAZ), and HOMA-IR were estimated. HOMA-IR values ≥2.1 and ≥3.3 were considered IR in Tanner I-II, ≥3.3 for Tanner III-IV and ≥2.6 for Tanner V, respectively. Metabolic Syndrome (MetS) was diagnosed with the Cook phenotype. SPISE was estimated according to the following algorithm: [600* HDL^0.185/(TG^0.2* BMI^1.338)]. The optimal SPISE cut points for IR and MetS prediction were determined by ROC curve analysis. In prepubertal obese patients (9.2 ± 2.1y; 18.4% males), the prevalence of IR and MetS was 28.2% y 46.9%, respectively; 58% had severe obesity (BAZ ≥4 SD). In pubertal obese patients (12.6 ± 1.8y; 57% males), the prevalence of IR and MetS was 34.1% and 55.3%, respectively; 34% had severe obesity. In prepubertal children, a SPISE of 6.3 showed the highest sensitivity (73.2%) and specificity (80%) to screen individuals with IR (AUC: 0.80; LR +: 3.3). Likewise, a SPISE of 5.7 got the highest sensitivity (82.6%) and specificity (86.1%) to screen patients with MetS (AUC: 0.87; LR +: 5.4). In pubertal patients, a SPISE of 5.4 showed the highest sensitivity and specificity to screen children and adolescents with both IR (Sn: 76.1%; Sp: 77.5%; AUC: 0.8; LR +: 3.1) and MetS (Sn: 90.4%; Sp: 76.1%; AUC: 0.90; LR +: 3.5). In children and adolescents with obesity, SPISE has good or very good performance in predicting IR and MetS. SPISE may be considered a relatively simple and low-cost diagnosis tool that can be helpful to identify patients with greater biological risk. In adolescents with obesity, the same cut point allows identification of those at higher risk of both IR and MetS.

Sex-Specific Cut-Offs of Single Point Insulin Sensitivity Estimator (SPISE) in Predicting Metabolic Syndrome in the Arab Adolescents.

The Single Point Insulin Sensitivity Estimator (SPISE) is a novel surrogate marker for insulin sensitivity and was found comparable to the gold standard clamp test as well as for predicting the Metabolic Syndrome (MetS) in several populations. The present study aimed to assess for the first time, the validity of SPISE in predicting MetS among Arab adolescents. In this cross-sectional study, 951 Saudi adolescents aged 10−17 years were randomly recruited from different schools across Riyadh, Saudi Arabia. Anthropometrics were measured and fasting blood samples were collected for the assessment of glucose, lipid profile, adipokines, C-reactive protein and 25 hydroxyvitamin (OH) D. MetS was defined using the National Cholesterol Education Program’s (NCEP) criteria with age-specific thresholds for adolescents. The SPISE as well as insulin resistance (HOMA-IR) indices were calculated. The over-all prevalence of MetS was 8.6% (82 out of 951). SPISE index was significantly lower in MetS than non-MetS participants in both sexes (5.5 ± 2.5 vs. 9.4 ± 3.2, p < 0.001 in boys and 4.4 ± 1.4 vs. 8.6 ± 3.2, p < 0.001 in girls). The SPISE index showed a significant inverse correlation with resistin, leptin, and C-reactive protein, and a significant positive correlation with adiponectin and 25(OH) D. Areas under the curve (AUC) revealed fair and good accuracy for predicting MetS 84.1% and 90.3% in boys and girls, respectively. The sex-specific cut-off proposed was SPISE index ≤6.1 (sensitivity 72.2% and specificity 83.9%) for boys and ≤6.46 (sensitivity 96.3% and specificity 73.4%), for girls. This study suggests that the SPISE index is a simple and promising diagnostic marker of insulin sensitivity and MetS in Arab adolescents.

The Effect of Childhood Obesity or Sarcopenic Obesity on Metabolic Syndrome Risk in Adolescence: The Ewha Birth and Growth Study.

The prevalence of obesity and metabolic syndrome (MetS) in the pediatric population has increased globally. We evaluated the impact of childhood obesity and sarcopenic obesity on the risk of MetS in adolescence using the Ewha Birth and Growth Cohort study data. In this study, we analyzed data from 227 participants who were followed up at the ages of 7-9 and 13-15 years. Overweight and obesity were defined as a body mass index of the 85th percentile or higher based on national growth charts, and sarcopenic obesity was defined using body composition data. Metabolic diseases in adolescence were identified by calculating the pediatric simple metabolic syndrome score (PsiMS), continuous metabolic syndrome score (cMetS), and single-point insulin sensitivity estimator (SPISE) as MetS indices. The prevalence of overweight was approximately 15% at both 7-9 and 13-15 years old, and that of sarcopenic obesity (7-9 years old) was 19.5%. Boys aged 13-15 years had a significantly larger waist circumference (WC) and higher systolic blood pressure (SBP) than girls. The MetS indices (PsiMS, cMetS, and SPISE) showed no significant differences by gender. Overweight and sarcopenic obese people have a higher overall risk of MetS components than normal people. The overweight group had a significantly higher prevalence of PsiMS and cMetS than the normal group, while the SPISE was significantly lower and the MetS indicator was worse in the overweight group than in the normal group. Similar results were obtained in the group with sarcopenic obesity. Both overweight and sarcopenic obesity remained significantly associated with MetS indicators, even after adjusting for covariates. Furthermore, metabolic health assessed by the cMetS in adolescence was affected not only by childhood overweight but also by adolescence, which showed an interaction effect. The results of this study emphasize the importance and need for early detection of childhood obesity and effective public health interventions.

Single Point Insulin Sensitivity Estimator (SPISE) As a Prognostic Marker for Emerging Dysglycemia in Children with Overweight or Obesity.

The single point insulin sensitivity estimator (SPISE) is a recently developed fasting index for insulin sensitivity based on triglycerides, high density lipoprotein cholesterol, and body mass index. SPISE has been validated in juveniles and adults; still, its role during childhood remains unclear. To evaluate the age- and sex-specific distribution of SPISE, its correlation with established fasting indexes and its application as a prognostic marker for future dysglycemia during childhood and adolescence were assessed. We performed linear modeling and correlation analyses on a cross-sectional cohort of 2107 children and adolescents (age 5 to 18.4 years) with overweight or obesity. Furthermore, survival analyses were conducted upon a longitudinal cohort of 591 children with overweight/obesity (1712 observations) with a maximum follow-up time of nearly 20 years, targeting prediabetes/dysglycemia as the end point. The SPISE index decreased significantly with age (-0.34 units per year, p &lt; 0.001) among children and adolescents with overweight and obesity. Sex did not have an influence on SPISE. There was a modest correlation between SPISE and established fasting markers of insulin resistance (R = -0.49 for HOMA-IR, R = -0.55 for QUICKI-IR). SPISE is a better prognostic marker for future dysglycemia (hazard ratio (HR) 3.47, 95% confidence interval (CI) 1.60-7.51, p &lt; 0.01) than HOMA-IR and QUICKI-IR (HR 2.44, 95% CI 1.24-4.81, p &lt; 0.05). The SPISE index is a surrogate marker for insulin resistance predicting emerging dysglycemia in children with overweight or obesity, and could, therefore, be applied to pediatric cohorts that lack direct insulin assessment.

Triglyceride to high-density lipoprotein cholesterol ratio is an independent predictor of liver fibrosis among pediatrics non-alcoholic fatty liver disease.

Insulin resistance (IR), one of the key components of the metabolic syndrome, is recognized as the pathophysiological hallmark of non-alcoholic fatty liver disease (NAFLD). This study aims to investigate the relationship between surrogate markers of IR and the severity of NAFLD among overweight or obese children. A total of 56 consecutive children aged 6 to 18 years old were recruited from the pediatric obesity and type 2 diabetes mellitus (T2DM) clinic in University Malaya Medical Centre (UMMC) from 2016 to 2019. Data on anthropometric measurements, clinical components of metabolic syndrome and fasting serum insulin were collected. Triglyceride to high-density lipoprotein cholesterol ratio (TG: HDL-C), Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) and Single Point Insulin Sensitivity Estimator (SPISE) were calculated. Transient elastography was performed with hepatic steatosis and liver fibrosis assessed by controlled attenuation parameter (CAP) and liver stiffness measurement (LSM), respectively. A total of 44 children (78.6%) had liver steatosis and 35.7% had presence of significant liver fibrosis (stage F≥2). Majority (89.3%) are obese and 24 children (42.9%) were diagnosed with metabolic syndrome. Higher number of children with T2DM and significant liver fibrosis were associated with higher tertiles of TG: HDL-C ratio (p<0.05). Top tertile of TG: HDL-C ratio was an independent predictor of liver fibrosis (OR=8.14, 95%CI: 1.24-53.36, p=0.029). ROC analysis showed that the area under the curve (AUC) of HOMA-IR (0.77) and TG: HDL-C ratio (0.71) were greater than that of metabolic syndrome (0.70), T2DM (0.62) and SPISE (0.22). The optimal cut-off values of HOMA-IR and TG: HDL-C ratio for detecting liver fibrosis among children with NAFLD are 5.20 and 1.58, respectively. Children with NAFLD and higher TG: HDL-C ratio are more likely to have liver fibrosis. TG: HDL-C ratio is a promising tool to risk stratify those with NAFLD who are at risk of developing advanced liver disease.

An Insight Into the Association of Sclerostin With Insulin Sensitivity and Glycemic Parameters in Male Indian Prediabetic and Diabetic Population.

BackgroundType 2 diabetes (T2D) is increasing day by day and creating a huge financial and social burden on the Indian population. Insulin resistance results in hyperglycemia, a condition that eventually causes prediabetes and Type 2 diabetes. The etiopathogenesis of T2D is still not clearly defined. Wnt signaling pathway is involved in pancreas development, islet function, insulin production, and secretion. Recent studies show that sclerostin, a Wnt signaling inhibitor, is associated with diabetes. The sclerostin level is altered as a function of race and ethnicity. However, no study has been conducted to observe the sclerostin level in prediabetic and diabetic individuals in the Indian population.ObjectivesThe main objectives of the study are: to determine whether sclerostin is associated with glycemic parameters, serum insulin levels, insulin resistance/ sensitivity, beta-cell function, and adipose tissue insulin resistance (Adipo-IR).MethodsThis observational study was carried out at a tertiary care hospital, in Rishikesh, Uttarakhand, India. Individuals with T2D and prediabetes and healthy references were included in this study. Sclerostin and free fatty acids (FFA) were measured with the enzyme-linked immunosorbent assay (ELISA), and blood sugar, insulin, and glycated haemoglobin (HbA1c) were measured by the hexokinase, chemiluminescent, and chromatography methods, respectively. Messenger RNA (mRNA) was quantified by real-time polymerase chain reaction (PCR) using the SYBR Green protocol. Adipo-IR, homeostasis model assessment-estimated insulin resistance (HOMA-IR), homeostasis model assessment of β-cell function (HOMA-B), quantitative insulin sensitivity check index (QUICKI), and single point insulin sensitivity estimator (SPISE) indices were calculated.ResultsA total of 171 study participants were enrolled in type 2 diabetes, prediabetes, and controls groups, having 57 each in the group. There was a gradual increase in sclerostin levels from healthy [242.12(158.44)] to prediabetes [256.06(299.65)] and diabetes [465.76 (735.71)] with a significant (<0.001) difference from healthy reference. Sclerostin showed a significant positive correlation with fasting blood sugar (r=0.200; p=0.009), HbA1c (r=0.394; p<0.001) and free fatty acids (r=0.205; p=0.007) in total study participants. The SPISE index showed a significant positive correlation (r=0.269, p=0.043) in the prediabetic group. SOST, GLUT4, and insulin receptor (IR) mRNA expression all corroborate with the glycemic status.ConclusionSignificantly higher expression of sclerostin (both protein and gene) in newly diagnosed T2D and prediabetes male patients, as well as significant association with SPISE index, suggest that sclerostin might be an indicator of pathophysiology related to insulin resistance, which is a characteristic feature of diabetes mellitus. However, the identification of causal relationships would warrant a large-scale prospective cohort study.

Single Point Insulin Sensitivity Estimator in Pediatric Non-Alcoholic Fatty Liver Disease.

BackgroundAttenuated insulin-sensitivity (IS) is a central feature of pediatric non-alcoholic fatty liver disease (NAFLD). We recently developed a new index, single point insulin sensitivity estimator (SPISE), based on triglycerides, high-density-lipoprotein and body-mass-index (BMI), and validated by euglycemic-hyperinsulinemic clamp-test (EHCT) in adolescents. This study aims to assess the performance of SPISE as an estimation of hepatic insulin (in-)sensitivity. Our results introduce SPISE as a novel and inexpensive index of hepatic insulin resistance, superior to established indices in children and adolescents with obesity.Materials and MethodsNinety-nine pubertal subjects with obesity (13.5 ± 2.0 years, 59.6% males, overall mean BMI-SDS + 2.8 ± 0.6) were stratified by MRI (magnetic resonance imaging) into a NAFLD (>5% liver-fat-content; male n=41, female n=16) and non-NAFLD (≤5%; male n=18, female n=24) group. Obesity was defined according to WHO criteria (> 2 BMI-SDS). EHCT were used to determine IS in a subgroup (n=17). Receiver-operating-characteristic (ROC)-curve was performed for diagnostic ability of SPISE, HOMA-IR (homeostatic model assessment for insulin resistance), and HIRI (hepatic insulin resistance index), assuming null hypothesis of no difference in area-under-the-curve (AUC) at 0.5.ResultsSPISE was lower in NAFLD (male: 4.8 ± 1.2, female: 4.5 ± 1.1) than in non-NAFLD group (male 6.0 ± 1.6, female 5.6 ± 1.5; P< 0.05 {95% confidence interval [CI]: male NAFLD 4.5, 5.2; male non-NAFLD 5.2, 6.8; female NAFLD 4.0, 5.1, female non-NAFLD 5.0, 6.2}). In males, ROC-AUC was 0.71 for SPISE (P=0.006, 95% CI: 0.54, 0.87), 0.68 for HOMA-IR (P=0.038, 95% CI: 0.48, 0.88), and 0.50 for HIRI (P=0.543, 95% CI: 0.27, 0.74). In females, ROC-AUC was 0.74 for SPISE (P=0.006), 0.59 for HOMA-IR (P=0.214), and 0.68 for HIRI (P=0.072). The optimal cutoff-level for SPISE between NAFLD and non-NAFLD patients was 5.18 overall (Youden-index: 0.35; sensitivity 0.68%, specificity 0.67%).ConclusionSPISE is significantly lower in juvenile patients with obesity-associated NAFLD. Our results suggest that SPISE indicates hepatic IR in pediatric NAFLD patients with sensitivity and specificity superior to established indices of hepatic IR.

Single Point Insulin Sensitivity Estimator for predicting type 2 diabetes mellitus in obese adolescents.

PurposeThe prevalence of adolescents with type 2 diabetes mellitus (T2DM) has rapidly increased in Korea over the past few decades with the increase in the number of obese adolescents. The single point insulin sensitivity estimator (SPISE) was recently introduced as a surrogate marker for insulin sensitivity to predict T2DM in adults. We aimed to determine risk factors for T2DM in obese adolescents, including SPISE.MethodsThis retrospective study included 104 adolescents diagnosed with T2DM at Korea University Hospital between January 2010 and December 2020. We compared clinical and biochemical parameters and the SPISE of normoglycemic overweight and obese individuals with those of prediabetic and diabetic adolescents to determine risk factors for T2DM. Receiver operating characteristic analysis was performed with the Youden index to determine the cutoff point of SPISE.Results Frequency of fatty liver and family history of T2DM were significantly higher and SPISE level was significantly lower in patients with T2DM than in normoglycemic overweight/obese and prediabetic adolescents (P<0.01). A family history of T2DM, fatty liver, and SPISE value below the cutoff point (4.49) were identified as significant risk factors for T2DM in multiple logistic regression analysis after controlling for age, sex, and body mass index standard deviation score (P<0.01).ConclusionsFamily history of T2DM, fatty liver, and low SPISE (<4.49) are risk factors that can independently affect the occurrence of T2DM in obese adolescents. Among these risk factors, SPISE is a promising marker for predicting adolescent T2DM; careful monitoring of these individuals is needed to prevent progression to T2DM.

Single-Point Insulin Sensitivity Estimator (SPISE) as a Feasible Marker of Insulin Resistance in Adult Metabolic Syndrome: Evaluated in a Hospital Based Cross-Sectional Pilot Study at Tertiary Care Centre of Uttarakhand.

Insulin resistance (IR) plays an important role as a major determinant of Metabolic syndrome (MetS). Various methods are available for measuring insulin resistance but they are laborious, time-consuming, and costly. Therefore various surrogate markers and indices have been devised to simplify and improve the determination of insulin resistance. Recently, a new index, single point insulin sensitivity estimator (SPISE) was proposed in the European population and was found comparable to the gold standard test (hyperinsulinemic euglycemic glucose clamp).This study was planned to evaluate whether SPISE could be a useful potential low-cost indicator for predicting MetS with IR patients in Indian population. Eighty-three participants from outpatient careof AIIMS Rishikesh were evaluated after informed consent. They were divided into Metabolic syndrome (n = 56) and Non Metabolic Syndrome(n = 27), using South Asian Modified National Cholesterol Education Program- ATP-III criteria for metabolic syndrome. SPISE index, HOMA-IR, Insulin Resistance Index, Triglycerides to high-density lipoproteins cholesterol ratio (TG/HDL-C) were calculated for all the subjects. Receiver operating characteristic (ROC) curve was plotted to assess discriminatory ability of SPISE, HOMA-IR, TG/HDL-C ratio, IRI and hs-CRP to differentiate between IR(Metabolic syndrome) and non-IR (Non-Metabolic syndrome) subjects. SPISE has greater area under curve with better sensitivity and specificity compared to HOMA-IR, IRI, TG/HDL-C ratio and hs CRP. So, SPISE has better predictive ability than HOMA-IR, IRI, TG/HDL-C ratio and hs CRP to discriminate IR from non-IR cases. SPISE could be a useful potential low-cost indicator with high sensitivity and specificity for predicting IR in MetS patients.

The single-point insulin sensitivity estimator (SPISE) index is a strong predictor of abnormal glucose metabolism in overweight/obese children: a long-term follow-up study

PurposeTo investigate the relationship between the single-point insulin sensitivity estimator (SPISE) index, an insulin sensitivity indicator validated in adolescents and adults, and metabolic profile in overweight/obese children, and to evaluate whether basal SPISE is predictive of impaired glucose regulation (IGR) development later in life.MethodsThe SPISE index (= 600 × HDL0.185/Triglycerides0.2 × BMI1.338) was calculated in 909 overweight/obese children undergoing metabolic evaluations at University of Cagliari, Italy, and in 99 normal-weight, age-, sex-comparable children, selected as a reference group, together with other insulin-derived indicators of insulin sensitivity/resistance. 200 overweight/obese children were followed-up for 6.5 [3.5–10] years, data were used for longitudinal retrospective investigations.ResultsAt baseline, 96/909 (11%) overweight/obese children had IGR; in this subgroup, SPISE was significantly lower than in normo-glycaemic youths (6.3 ± 1.7 vs. 7 ± 1.6, p < 0.001). The SPISE index correlated positively with the insulin sensitivity index (ISI) and the disposition index (DI), negatively with age, blood pressure, HOMA-IR, basal and 120 min blood glucose and insulin (all p values < 0.001). A correlation between SPISE, HOMA-IR and ISI was also reported in normal-weight children. At the 6.5-year follow-up, lower basal SPISE—but not ISI or HOMA-IR—was an independent predictor of IGR development (OR = 3.89(1.65–9.13), p = 0.002; AUROC: 0.82(0.72–0.92), p < 0.001).ConclusionIn children, low SPISE index is significantly associated with metabolic abnormalities and predicts the development of IGR in life.

Undernutrition and suboptimal growth during the first year are associated with glycemia but not with insulin resistance in adulthood.

This study aimed to assess whether weight, length, and conditional growth during the first year are associated with glycemia and insulin resistance among young adults. A non-concurrent longitudinal design was used in the study. This is a population-based cohort study, composed of people aged from 22 to 28 years. We estimated z-scores from birth to the first year and the infants were classified as stunted, underweight, overweight, obese, wasted, and at risk of wasting, using cut-offs proposed by the World Health Organization (Child Growth Standards, 2006). Conditional weight and length gain variables were estimated. Glycemia, insulin, homeostasis model assessment of insulin resistance (HOMA-IR), and single point insulin sensitivity estimator (SPISE) were evaluated in adulthood. Multiple linear regressions that includes the variables associated with glycemia and insulin resistance were used. In total, 1,070 subjects were evaluated and glycemia in adulthood was higher among subjects who were wasted or at risk of wasting at 12 months (β coefficient = 2.77; 95%CI: 0.37; 5.21). In relation to normal weight, those subjects who were overweight at 12 months showed the lowest glycemia (β coefficient = -2.39; 95%CI: -4.32; -0.36). Conditional weight gain in the first year was negatively associated with glycemia in adulthood (β coefficient = -0.65; 95%CI: -1.23; -0.08). SPISE was higher among underweight subjects, and negatively associated with conditional relative weight gain and conditional linear growth in the first year. In conclusion, we found that undernutrition and suboptimal growth were associated with higher glycemia.

Cut-off Values and Clinical Utility of Surrogate Markers for Insulin Resistance and Beta-Cell Function to Identify Metabolic Syndrome and Its Components among Southern Indian Adults.

BackgroundInsulin resistance (IR) is a collective clinical entity that exacerbates metabolic syndrome (MetS). As the gold-standard test to quantify IR involves intravenous insulin loading and repeated blood glucose monitoring, many indices have been developed for IR assessment for convenience. This study tested the ideal cut-off values and clinical utility of IR indices in identifying MetS.MethodsWe recruited 150 subjects, 75 MetS patients and 75 healthy controls, then obtained written informed consent to participate in this study. We collected fasting blood samples for glucose and lipid profiles and calculated nineteen indices of IR and insulin secretion using validated formulae. We determined the precision of these IR indices using the area under the curve (AUC) in a receiver operating characteristic analysis.ResultsSubjects with MetS have significantly higher IR coupled with lower insulin sensitivity and beta-cell function than controls. Among the surrogate markers of IR tested, the homeostatic model assessment of insulin resistance (HOMA-IR), HOMA-adiponectin (HOMA-AD), triglyceride-glucose (TyG) index, HOMA-1%S (insulin sensitivity), quantitative insulin sensitivity check index (QUICKI), McAuley index, single-point insulin sensitivity estimator (SPISE), and HOMA-2%B (beta-cell function) showed the highest AUC values for detecting MetS.ConclusionOur study results suggest that the ideal cut-off and AUC values identified for HOMA-IR, HOMA-AD, the TyG index, HOMA-1%S, QUICKI, the McAuley index, SPISE, and HOMA-2%B offer a clinical approach to the early detection and risk stratification for MetS among people in southern India.

Urinary organophosphate esters metabolites, glucose homeostasis and prediabetes in adolescents

BackgroundEmerging experimental evidence indicates that organophosphate esters (OPEs) can trigger glucose metabolic disorders. However, human evidence, especially in adolescents, is unavailable. ObjectivesWe utilized data from the National Health and Nutrition Examination Survey 2011–2014 to evaluate whether urinary OPEs metabolites were associated with prediabetes and glucose homeostasis. MethodsA total of 349 adolescents (12-19-year old) who provided at least 8 h fasting blood samples, had urinary OPEs metabolites detected were included. Prediabetes was defined according to the levels of fasting plasma glucose (FPG), 2-h post oral plasma glucose (2 h-OGTT) and glycated hemoglobin A1c (HbA1c). The homeostatic model assessment (HOMA-IR) and the Single Point Insulin Sensitivity Estimator (SPISE) were used to assess insulin resistance and sensitivity, respectively. Multiple binary logistic and linear regressions were used to evaluate the associations with prediabetes and indices of glucose homeostasis. The least absolute shrinkage and selection operator (LASSO) regression was used to assess the associations in a multi-pollutant context. ResultsAfter adjusting for covariates, certain urinary OPEs metabolites were associated with prediabetes and indices of glucose homeostasis in all adolescents. Stratified analyses by sex revealed that such associations were largely sex-dependent. In females, the multiple pollutant models showed that bis(1,3–32 dichloro-2-propyl) phosphate (BDCIPP) was positively associated with prediabetes [odds ratio (OR) = 2.51, 95%CI:1.29, 4.89, for one scaled unit increase in exposure] and 2 h-OGTT (β = 0.07, 95%CI:0.01,0.12); bis(2-chloroethyl) phosphate (BCEP) was negatively associated with fasting insulin (β = −0.10, 95%CI: 0.19,-0.01) and HOMA-IR (β = −0.10, 95%CI: 0.19,-0.003); and detectable bis(1-choloro-2-propyl) phosphate (BCIPP) (>LOD vs < LOD) was inversely associated with 2 h-OGTT (β = −0.11, 95%CI: 0.21,-0.02). In males, consistent inverse associations were found for detectable di-n-butyl phosphate (DNBP) with prediabetes, FPG, 2 h-OGTT, fasting insulin and HOMA-IR. ConclusionUrinary OPEs metabolites were associated with prediabetes and indices of glucose homeostasis in adolescents. But such associations varied by sex. Future studies with multiple measurements of OPEs exposure are needed to confirm our findings.

Validity assessment of the single-point insulin sensitivity estimator (spise) for diagnosis of cardiometabolic risk in post-pubertal hispanic adolescents

Insulin measurements are not advised for cardiometabolic risk screening in large groups. Here we assessed the accuracy of the single-point insulin sensitivity estimator (SPISE) to diagnose cardiometabolic risk in Chilean adolescents. In 678 post-pubertal adolescents (52% males, M(SD) age = 16.8 (0.2) years), height, weight, waist circumference, blood lipids, glucose, insulin, and blood pressure were measured. BMI, HOMA-IR, and SPISE were estimated; HOMA-IR values ≥ 2.6 were considered insulin resistance (IR). Metabolic syndrome (MetS) was defined with the joint IDF/AHA/NHBLI standard. Using receiver operating characteristic curves, we obtained optimal SPISE cutpoints for IR and MetS diagnosis. The prevalence of MetS and IR was 8.2% and 17.1%, respectively. In males, the optimal cutoff for MetS diagnosis was 5.0 (sensitivity: 97%; specificity: 82%), and the optimal cutoff for IR diagnosis was 5.9 (sensitivity: 71%; specificity: 83%). In females, a SPISE of 6.0 had the highest sensitivity (90%) and specificity (74%) for MetS diagnosis. A SPISE of 6.4 was the optimal cutoff for IR diagnosis; however, sensitivity and specificity were 61% and 75%. In males and female post-pubertal adolescents, SPISE had a very good and good diagnostic performance, respectively, in predicting MetS. It was an accurate diagnostic tool for IR prediction in males, but not necessarily in females.

Could SCGF-Beta Levels Be Associated with Inflammation Markers and Insulin Resistance in Male Patients Suffering from Obesity-Related NAFLD?

One of the pathologic hallmarks of obesity is macrophage infiltration of adipose tissue that has been confirmed as source of multipotent adult stem cells. Stem cell growth factor-beta (SCGF-β) shows activity on granulocyte/macrophage progenitor cells in combination with granulocyte macrophage colony-stimulating factor (GM-CSF) and macrophage colony-stimulating factor (M-CSF). Obesity-associated inflammation induces insulin resistance (IR), which is central to nonalcoholic fatty liver disease (NAFLD) or hepatic steatosis (HS). We searched for relationship between levels of SCGF-β and those of C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor-β (TNF-β), interleukin-12p40 (IL-12p40), interleukin-10 (IL-10), ferritin, GM-CSF and M-CSF and between SCGF-β concentrations and IR in obese patients with HS. Eighty obese patients were retrospectively studied. Serum cytokines levels were appreciated by magnetic bead-based multiplex immunoassays. IR was evaluated by homeostatic model assessment (HOMA), HOMA-derived β-cell function (HOMA-B%), quantitative insulin sensitivity check Index (QUICKI) and single point insulin sensitivity estimator (SPISE). HS and spleen volume were assessed by ultrasonography (US). SCGF-β and IL-6 levels predicted HOMA values (p = 0.032 and 0.041, respectively) only in males. In male patients, CRP and IL-6 levels (p = 0.007) predicted SCGF-β concentrations (p = 0.03 and 0.007, respectively), which in turn predicted HS at US, p = 0.037. SCGF-β levels were linked to IR and HS severity with the mediation role of CRP. IL-10 levels negatively predicted SCGF-β concentrations (p = 0.033). M-CSF levels predicted serum concentration of both TNF-β and IL-12p40 (p = 0.00), but did not predict serum IL-10 (p = 0.30). Prediction of HOMA values by SCGF-β levels, likely mediated by markers of inflammation, characterizes this study, shedding some light on mechanisms inducing/worsening IR of male patients with obesity-related NAFLD.