Beyond Obesity and Overweight: The Clinical Assessment and Treatment of Excess Body Fat in Children : Part 1 - Insulin Resistance as the Root Cause of Pediatric Obesity.

PURPOSE OF REVIEW: Pediatric obesity and comorbidities related to insulin resistance continue to be a growing public health crisis. If lifestyle measures are unsuccessful, pharmacological and surgical interventions are offered. In this paper, we describe the driving force of the obesity crisis: hyperinsulinemia and the development of insulin resistance. We give historical background of key policy issues which have contributed to this pandemic as well as the physiologic mechanisms of insulin resistance. The prevalence of obesity will continue to rise unless the root cause of hyperinsulinemia is addressed. RECENT FINDINGS: Current research on insulin resistance demonstrates that a decreased consumption of carbohydrates is an effective first-line dietary intervention for the treatment of obesity and related metabolic diseases. Evidence shows it is safe and beneficial. A low-carbohydrate eating pattern can be helpful to address pediatric obesity. However, there must be policy guardrails in place to ensure that this is a sustainable and viable option for children and their families. There must be a change in the nutritional environment to help individuals battle the chronic disease of obesity.

Beyond Obesity and Overweight: the Clinical Assessment and Treatment of Excess Body Fat In Children : Part 2 - the Prescription of Low-Carbohydrate Eating as the First Approach.

PURPOSE OF REVIEW: Pediatric obesity and comorbidities related to insulin resistance continue to be a growing public health crisis. If lifestyle measures are unsuccessful, pharmacological and surgical interventions are offered. In this paper, we describe the driving force of the obesity crisis: hyperinsulinemia and the development of insulin resistance. We give historical background of key policy issues which have contributed to this pandemic as well as the physiologic mechanisms of insulin resistance. The prevalence of obesity will continue to rise unless the root cause of hyperinsulinemia is addressed. RECENT FINDINGS: Current research on insulin resistance demonstrates that a decreased consumption of carbohydrates is an effective first-line dietary intervention for the treatment of obesity and related metabolic diseases. Evidence shows it is safe and beneficial. A low-carbohydrate eating pattern can be helpful to address pediatric obesity. However, there must be policy guardrails in place to ensure that this is a sustainable and viable option for children and their families. There must be a change in the nutritional environment to help individuals battle the chronic disease of obesity.

Association between the homeostasis model assessment of insulin resistance and coronary artery calcification: a meta-analysis of observational studies.

Background: Insulin resistance (IR), a risk factor for cardiovascular diseases, has garnered significant attention in scientific research. Several studies have investigated the correlation between IR and coronary artery calcification (CAC), yielding varying results. In light of this, we conducted a systematic review to investigate the association between IR as evaluated by the homeostasis model assessment (HOMA-IR) and CAC. Methods: A comprehensive search was conducted to identify relevant studies in PubMed, Embase, Scopus, and Web of Science databases. In addition, preprint servers such as Research Square, BioRxiv, and MedRxiv were manually searched. The collected data were analyzed using either fixed or random effects models, depending on the heterogeneity observed among the studies. The assessment of the body of evidence was performed using the GRADE approach to determine its quality. Results: The current research incorporated 15 studies with 60,649 subjects. The analysis revealed that a higher category of HOMA-IR was associated with a greater prevalence of CAC in comparison to the lowest HOMA-IR category, with an OR of 1.13 (95% CI: 1.06-1.20, I2 = 29%, P < 0.001). A similar result was reached when HOMA-IR was analyzed as a continuous variable (OR: 1.27, 95% CI: 1.14-1.41, I2 = 54%, P < 0.001). In terms of CAC progression, a pooled analysis of two cohort studies disclosed a significant association between increased HOMA-IR levels and CAC progression, with an OR of 1.44 (95% CI: 1.04-2.01, I2 = 21%, P < 0.05). It is important to note that the strength of the evidence was rated as low for the prevalence of CAC and very low for the progression of CAC. Conclusion: There is evidence to suggest that a relatively high HOMA-IR may be linked with an increased prevalence and progression of CAC.

Developing a risk assessment tool for identifying individuals at high risk for developing insulin resistance in European adolescents: the HELENA-IR score.

OBJECTIVES: To develop and validate an easy-to-use screening tool for identifying adolescents at high-risk for insulin resistance (IR). METHODS: Α total of 1,053 adolescents (554 females), aged 12.5 to 17.5 years with complete data on glucose and insulin levels were included. Body mass index (BMI), fat mass index (FMI) and the homeostasis model assessment for insulin resistance (HOMA-IR) were calculated. VO2max was predicted using 20 m multi-stage fitness test. The population was randomly separated into two cohorts for the development (n=702) and validation (n=351) of the index, respectively. Factors associated with high HOMA-IR were identified by Spearman correlation in the development cohort; multiple logistic regression was performed for all identified independent factors to develop a score index. Finally, receiver operating characteristic (ROC) analysis was performed in the validation cohort and was used to define the cut-off values that could identify adolescents above the 75th and the 95th percentile for HOMA-IR. RESULTS: BMI and VO2max significantly identified high HOMA-IR in males; and FMI, TV watching and VO2max in females. The HELENA-IR index scores range from 0 to 29 for males and 0 to 43 for females. The Area Under the Curve, sensitivity and specificity for identifying males above the 75th and 95th of HOMA-IR percentiles were 0.635 (95%CI: 0.542-0.725), 0.513 and 0.735, and 0.714 (95%CI: 0.499-0.728), 0.625 and 0.905, respectively. For females, the corresponding values were 0.632 (95%CI: 0.538-0.725), 0.568 and 0.652, and 0.708 (95%CI: 0.559-0.725), 0.667 and 0.617, respectively. Simple algorithms were created using the index cut-off scores. CONCLUSIONS: Paediatricians or physical education teachers can use easy-to-obtain and non-invasive measures to apply the HELENA-IR score and identify adolescents at high risk for IR, who should be referred for further tests.

Model-Based Assessment of C-Peptide Secretion and Kinetics in Post Gastric Bypass Individuals Experiencing Postprandial Hyperinsulinemic Hypoglycemia.

Assessment of insulin secretion is key to diagnose postprandial hyperinsulinemic hypoglycemia (PHH), an increasingly recognized complication following bariatric surgery. To this end, the Oral C-peptide Minimal Model (OCMM) can be used. This usually requires fixing C-peptide (CP) kinetics to the ones derived from the Van Cauter population model (VCPM), which has never been validated in PHH individuals. The objective of this work was to test the validity of the OCMM coupled with the VCPM in PHH subjects and propose a method to overcome the observed limitations. Two cohorts of adults with PHH after gastric bypass (GB) underwent either a 75 g oral glucose (9F/3M; age=42±9 y; BMI=28.3±6.9 kg/m2) or a 60 g mixed-meal (7F/3M; age = 43 ± 11 y; BMI=27.5±4.2 kg/m2) tolerance test. The OCMM was identified on CP concentration data with CP kinetics fixed to VCPM (VC approach). In both groups, the VC approach underestimated CP-peak and overestimated CP-tail suggesting CP kinetics predicted by VCPM to be inaccurate in this population. Thus, the OCMM was identified using CP kinetics estimated from the data (DB approach) using a Bayesian Maximum a Posteriori estimator. CP data were well predicted in all the subjects using the DB approach, highlighting a significantly faster CP kinetics in patients with PHH compared to the one predicted by VCPM. Finally, a simulation study was used to validate the proposed approach. The present findings question the applicability of the VCPM in patients with PHH after GB and call for CP bolus experiments to develop a reliable CP kinetic model in this population.

Risk Assessment and Determination of Factors That Cause the Development of Hyperinsulinemia in School-Age Adolescents.

Background and Objectives: Hyperinsulinemia and insulin resistance are not synonymous; if the risk of developing insulin resistance in adolescents is monitored, they do not necessarily have hyperinsulinemia. It is considered a condition of pre-diabetes and represents a condition of increased risk of developing DM (diabetes mellitus); it can exist for many years without people having the appropriate symptoms. This study aims to determine the risk of developing hyperinsulinemia at an early age in adolescents by examining which factors are crucial for its occurrence. Materials and Methods: The cross-sectional study lasting from 2019 to 2021 (2 years) was realized at the school children's department in the Valjevo Health Center, which included a total of 822 respondents (392 male and 430 female) children and adolescents aged 12 to 17. All respondents underwent a regular, systematic examination scheduled for school children. BMI is a criterion according to which respondents are divided into three groups. Results: After summary analyzes of OGTT test respondents and calculated values of HOMA-IR (homeostatic model assessment for insulin resistance), the study showed that a large percentage of respondents, a total of 12.7%, are at risk for hyperinsulinemia. The research described in this paper aimed to use the most popular AI (artificial intelligence) model, ANN (artificial neural network), to show that 13.1% of adolescents are at risk, i.e., the risk is higher by 0.4%, which was shown by statistical tests as a significant difference. Conclusions: It is estimated that a model using three different ANN architectures, based on Taguchi's orthogonal vector plans, gives more precise and accurate results with much less error. In addition to monitoring changes in each individual's risk, the risk assessment of the entire monitored group is updated without having to analyze all data.

Temporal relationship between body mass index and triglyceride-glucose index and its impact on the incident of hypertension.

BACKGROUND AND AIMS: Obesity and insulin levels can influence each other by metabolism. However, their temporal sequences and influence on hypertension are generally unknown, especially in Chinese adults. Recently, some scholars have proposed that triglycerides-glucose index (TyG) is an important indicator of insulin resistance. The study aims to describe the relationship between body mass index (BMI) and TyG index and its impact on hypertension. METHODS AND RESULTS: A total of 4081 adults (56.33% women) without antihypertensive, hypoglycemic or lipid-lowering medications were selected for the present study. Measurements of BMI and TyG index were obtained twice from 2012 to 2017. Cross-lagged panel analysis was used to describe the temporal sequences between BMI and TyG index, and the effect of their temporal relationship patterns on hypertension was explored through mediation analysis. After adjusting for confounding factors (age, sex, ethnicity et al.), the cross-lagged path coefficient from baseline BMI to follow-up TyG (ρ2 = 0.135, P < 0.001) was significantly greater than the path coefficient from baseline TyG to follow-up BMI (ρ1 = 0.043, P < 0.001), and P < 0.001 for the difference between ρ1 and ρ2. Furthermore, the sensitivity analyses between women and men revealed identical findings. In addition, TyG index mediation effect on BMI-hypertension was estimated to be 38.45% (P < 0.001) in total population, 25.24% in women and 57.35% in men. CONCLUSION: These results provided evidence that the temporal relationship between BMI and insulin resistance is reciprocal and a higher BMI precedes hyperinsulinemia in Chinese adults. This relationship plays an essential role in the development of hypertension, while there is a difference between women and men.

Ex vivo model for the assessment of the cytotoxicity of biological materialfrom patients with carbohydrate metabolism disturbances.

BACKGROUND: Carbohydrate metabolism disturbances have long been considered the cause of civilisation diseases, such as type 2 diabetes, obesity, or cardiovascular diseases. Currently an increasing number of theses also link impaired glucose and/or insulin metabolism to neurodegenerative diseases, calling them neurometabolic diseases. AIM OF THE STUDY: Aim of the study was to assess the cytotoxic influence of multicompound biological material (blood serum) from people with different carbohydrate metabolism disturbances to the viability of PC12 cell line. MATERIAL AND METHODS: Undifferentiated PC12 cell line were incubated for 48 hours in standard conditions with the addition of human serum from individuals with diffrent (low and high) levels of hyperglycaemia (LGL and HGL) and hyperinsulinaemia (LIL and HIL). The cytotoxicity was estimated by the MTT test, and the viability percentage (SP%) was calculated in relation to control samples (cells incubated only with RPMI). RESULTS: The obtained results indicate cytotoxic activity and decreased viability of the PC12 cells after 48 hours of incubation with human serum with different degrees of hyperglycaemia and insulinaemia. Cell viability increased slightly with the increase in glucose level but decreased with the increase in insulin concentration in individual groups, but without statistical significance. CONCLUSIONS: Blood serum, as multicompound biological material, influences negatively PC12 cell line but in a variety of ways. Increasing hyperinsulinaemia has a higher cytotoxic effect on the cells than hyperglycaemia, which probably results from the fact that it is compensated by other components of biological material; however, further studies are necessary to obtain more detailed characteristics of these processes.

Assessment of mouse liver [1-13C]pyruvate metabolism by dynamic hyperpolarized MRS.

Hyperpolarized [1-13C]pyruvate magnetic resonance (MR) spectroscopy has the unique ability to detect real-time metabolic changes in vivo owing to its high sensitivity compared with thermal MR and high specificity compared with other metabolic imaging methods. The aim of this study was to explore the potential of hyperpolarized MR spectroscopy for quantification of liver pyruvate metabolism during a hyperinsulinemic-isoglycemic clamp in mice. Hyperpolarized [1-13C]pyruvate was used for in vivo MR spectroscopy of liver pyruvate metabolism in mice. Mice were divided into two groups: (i) non-stimulated 5-h fasted mice and (ii) hyperinsulinemic-isoglycemic clamped mice. During clamp conditions, insulin and donor blood were administered at a constant rate, whereas glucose was infused to maintain isoglycemia. When steady state was reached, insulin-stimulated mice were rapidly infused with hyperpolarized [1-13C]pyruvate for real-time tracking of the dynamic distribution of metabolic derivatives from pyruvate, such as [1-13C]lactate, [1-13C]alanine and [13C]bicarbonate. Isotopomer analysis of plasma glucose confirmed 13C-incorporation from [1-13C]pyruvate into glucose was increased in fasted mice compared with insulin-stimulated mice, demonstrating an increased gluconeogenesis in fasted mice. The AUC ratios for [1-13C]alanine/[1-13C]pyruvate (38.2%), [1-13C]lactate/[1-13C]pyruvate (41.8%) and [13C]bicarbonate/[1-13C]pyruvate (169%) all increased significantly during insulin stimulation. Hyperpolarized [1-13C]pyruvate can be used for in vivo MR spectroscopy of liver pyruvate metabolism during hyperinsulinemic-isoglycemic clamp conditions. Under these conditions, insulin decreased gluconeogenesis and increased [1-13C]alanine, [1-13C]lactate and [13C]bicarbonate after a [1-13C]pyruvate bolus. This application of in vivo spectroscopy has the potential to identify impairments in specific metabolic pathways in the liver associated with obesity, insulin resistance and nonalcoholic fatty liver disease.

[Effect of peripheral hyperinsulinemia on assessment of pharmacokinetics and pharmacodynamics of insulin preparations in euglycemic clamp].

Objective: To evaluate the effect of peripheral hyperinsulinemia on assessment of pharmacokinetics (PK) and pharmacodynamics (PD) of insulin preparations in euglycemic clamp. Method: A total of 40 healthy male volunteers aged 18-45 years old in West China Hospital between 2015 and 2017 were divided into euglycemic-hyperinsulinaemic clamp (A) group and euglycemic clamp (B) group. Humulin R (0.2 U/kg) was given subcutaneously at steady state of clamp after infusion of short-acting insulin in A group while in B group Humulin R was given subcutaneously without establishment of artificial hyperinsulinemia. The blood glucose was maintained within target range during the whole clamp. Result: Maximum insulin concentration [(667±141) pmol/L vs (267±68) pmol/L, P<0.01] and area under curve (AUC) of insulin concentration [(152±32) nmol·L(-1)·min vs (57±7) nmol·L(-1)·min, P<0.01] in A group were higher while maximum glucose infusion rate (GIR) [(3.70±0.70) mg·kg(-1)·min(-1) vs (7.66±2.11) mg·kg(-1)·min(-1), P<0.01] and AUC of GIR [(931±272) mg/kg vs (1 920±452) mg/kg, P<0.01] were lower compared to B group. The serum C-peptide levels were lower in both groups after administration of insulin compared with baseline. Conclusion: It is not necessary applying euglycemic-hyperinsulinaemic clamp to evaluate the PK/PD of insulin preparations, which may overestimate the PKparameters and underestimate the PD parameters of insulin preparations.

Incentive design to boost health for juveniles with Medicaid coverage: Evidence from a field experiment.

Augmenting incentives for juveniles with separate incentives for parents could boost juvenile efforts to reduce BMI. However, financing a parent incentive by reducing the incentives offered to adolescents could attenuate the juvenile response. In a field experiment, Medicaid-covered juveniles enrolled in a cardiac wellness program were randomly assigned to two groups: juveniles in the focused-incentive group received all earned points; juveniles in the split-incentive group split earned points with a parent. The focused-incentive group was 12.8 percentage points more likely to achieve their stipulated goals compared to the split-incentive group at the end of the 3-month active phase of the program. In contrast, members of the split-incentive group outperformed their peers in the focused-incentive group during the second quarter, and the two incentives structures were equally effective at the year-end session. Additional quasi-experimental data indicates that members of both incentivized groups significantly outperformed (focused-incentive group by 8.48 percentage points and split-incentive group by 11.0 percentage points) a pre-experiment (non-incentivized) set of juveniles enrolled in the same program at year-end.

Diabetes and Cancer: Cancer Should Be Screened in Routine Diabetes Assessment.

Cancer incidence appears to be increased in both type 1 and type 2 diabetes mellitus (DM). DM represents a risk factor for cancer, particularly hepatocellular, hepatobiliary, pancreas, breast, ovarian, endometrial, and gastrointestinal cancers. In addition, there is evidence showing that DM is associated with increased cancer mortality. Common risk factors such as age, obesity, physical inactivity and smoking may contribute to increased cancer risk in patients with DM. Although the mechanistic process that may link diabetes to cancer is not completely understood yet, biological mechanisms linking DM and cancer are hyperglycemia, hyperinsulinemia, increased bioactivity of insulin-like growth factor 1, oxidative stress, dysregulations of sex hormones, and chronic inflammation. However, cancer screening rate is significantly lower in people with DM than that in people without diabetes. Evidence from previous studies suggests that some medications used to treat DM are associated with either increased or reduced risk of cancer. However, there is no strong evidence supporting the association between the use of anti-hyperglycemic medication and specific cancer. In conclusion, all patients with DM should be undergo recommended age- and sex appropriate cancer screenings to promote primary prevention and early detection. Furthermore, cancer should be screened in routine diabetes assessment.

Transient neonatal hyperinsulinaemic hypoglycaemia: perinatal predictors of length and cost of stay.

Admission to neonatal care causes separation of infants from their parents, can adversely affect breast-feeding and is associated with painful procedures. Our aim was to identify perinatal factors and cost of care associated with transient neonatal hyperinsulinaemic hypoglycaemia (HH). Infants born after 35 weeks of gestation admitted because of hypoglycaemia were studied. The neonates were divided into two groups (HH and non-HH), and their length and cost of care were compared and perinatal factors predicting those outcomes explored. Forty of the 474 infants admitted with hypoglycaemia were diagnosed with HH. The HH group had a lower median (IQR) glucose level on admission compared to the non-HH group (p < 0.001). The median (IQR) cost of stay was higher in the HH group (p < 0.001). In the HH group, the GIRmax was significantly correlated with cost of stay (p < 0.001). GIRmax predicted a cost of stay > £9140 with an area under the ROC curve of 0.956. GIRmax > 13.9 mg/kg/min predicted admission cost > £9140 with 86% sensitivity and 93% specificity.Conclusion: Transient neonatal HH was associated with a higher length and cost of stay in infants admitted for hypoglycaemia. The GIRmax can predict the length and cost of stay. What is Known: • Neonatal hypoglycaemia is the leading cause of term and late preterm neonatal admissions. • Hyperinsulinism (HH) is the commonest cause of persistent hypoglycaemia, and delay in the diagnosis and management can have a detrimental impact on long-term development. What is New: • We have demonstrated prior to NICU admission that blood glucose concentrations were lower in infants with HH compared to those without. • The maximum GIR had a stronger correlation with total length and cost of hospital stay compared to insulin levels in HH infants.

Increased Energy Expenditure, Lipolysis and Hyperinsulinemia Confer Resistance to Central Obesity and Type 2 Diabetes in Mice Lacking Alpha2α-Adrenoceptors.

The alpha2A-adrenoceptors (α2A-ARs) are Gi-coupled receptors, which prejunctionally inhibit the release of norepinephrine (NE) and epinephrine (Epi), and postjunctionally inhibit insulin secretion and lipolysis. We have earlier shown that α2A-/- mice display sympathetic hyperactivity, hyperinsulinemia and improved glucose tolerance. Here we employed α2A-/- mice and placed the mice on a high-fat diet (HFD) to test the hypothesis that lack of α2A-ARs protects from diet-induced obesity and type 2 diabetes (T2D). In addition, a high-caloric diet was combined with running wheel exercise to test the interaction of diet and exercise. HFD was obesogenic in both genotypes, but α2A-/- mice accumulated less visceral fat than the wild-type controls, were protected from T2D, and their insulin secretion was unaltered by the diet. Lack of α2A-ARs is associated with an increased sympatho-adrenal tone, which resulted in increased energy expenditure and fat oxidation rate potentiated by HFD. Fittingly, α2A-/- mice displayed enhanced lipolytic responses to Epi, and increased faecal lipids suggesting altered fat mobilization and absorption. Subcutaneous white fat appeared to be thermogenically more active (measured as Ucp1 mRNA expression) in α2A-/- mice, and brown fat showed an increased response to NE. Exercise was effective in reducing total body adiposity and increasing lean mass in both genotypes, but there was a significant diet-genotype interaction, as even modestly increased physical activity combined with lack of α2A-AR signalling promoted weight loss more efficiently than exercise with normal α2A-AR function. These results suggest that blockade of α2A-ARs may be exploited to reduce visceral fat and to improve insulin secretion.

Assessment of hepatic insulin extraction from in vivo surrogate methods of insulin clearance measurement.

Hyperinsulinemia, accompanied by reduced first-pass hepatic insulin extraction (FPE) and increased secretion, is a primary response to insulin resistance. Different in vivo methods are used to estimate the clearance of insulin, which is assumed to reflect FPE. We compared two methodologically different but commonly used indirect estimates with directly measured FPE in healthy dogs ( n = 9). The indirect methods were 1) metabolic clearance rate of insulin (MCR) during the hyperinsulinemic-euglycemic clamp (EGC), a steady-state method, and 2) fractional clearance rate of insulin (FCR) during the frequently sampled intravenous glucose tolerance test (FSIGT), a dynamic method. MCR was calculated as the ratio of insulin infusion rate to steady-state plasma insulin. FCR was calculated as the exponential decay rate constant of the injected insulin. Directly measured FPE is based on the difference in insulin measurements during intraportal vs. peripheral vein insulin infusions. We found a strong correlation between indirect FCR (min-1) and FPE (%). In contrast, we observed a poor association between MCR (ml·min-1·kg-1) and FPE (%). Our findings in canines suggest that FCR measured during FSIGT can be used to estimate FPE. However, MCR calculated during EGC appears to be a poor surrogate for FPE.

Obviating much of the need for insulin therapy in type 2 diabetes mellitus: A re-assessment of insulin therapy's safety profile.

Current processes of care for diabetes mellitus (DM) were shaped during the era when insulin therapy was considered inexorable to the management of advanced stage type 2 (T2DM), though this no longer appears to be categorically true. There are also dashed hopes that insulin therapy can prevent or stall diabetes. While exogenous insulin remains a life-sparing tool for fully insulin-dependent DM, insulin therapy-induced hyperinsulinemia now appears to contribute to serious safety issues beyond hypoglycemia and weight gain. Iatrogenic and compensatory hyperinsulinemia are metabolic disruptors of ß-cells, liver, muscle, kidney, brain, heart and vasculature, inflammation, and lipid homeostasis, among other systems. This may compromise ß-cells, exacerbate insulin resistance (IR), and increase risk of cardiovascular (CV) disease. Striking associations between exogenous insulin and risks of CV events, cancer, and all-cause mortality in clinical trial and real-world cohorts caution that insulin may pose more harm than previously evidenced. At our disposal are numerous alternate tools that, alone or in combination, efficaciously manage hyperglycemia and glucolipotoxicity, and do so without inducing hypoglycemia, weight gain, or hyperinsulinemia. Moreover, these new tools support true precision therapy, as modern day drug classes can be aligned with the various mediating pathways of hyperglycemia at work in any given patient. Some also appear to promote ß-cell survival, with intriguing data being presented for newer agents, such as incretins. As such, we encourage preferential use of non-insulin antidiabetic agents to injected insulin for the management of non-insulin-dependent patients with T2DM, including in advanced stage T2DM. The goal of this article is to augment existing literature to 1) correct misconceptions on the rationale and necessity for insulin therapy in T2DM, 2) discuss emerging negative safety data with insulin therapy, and, 3) offer a practical means to reduce reliance on insulin through delayed initiation, minimized dose, and, drug switching to safer agents, and, potentially, reframes processes of care.

Assessment of Insulin Resistance in Subjects with Normal Glucose Tolerance, Hyperinsulinemia with Normal Blood Glucose Tolerance, Impaired Glucose Tolerance, and Newly Diagnosed Type 2 Diabetes (Prediabetes Insulin Resistance Research).

AIM: To evaluate the differences in insulin resistance (IR) among subjects with normal glucose tolerance (NGT), hyperinsulinemia with NGT (HINS), impaired glucose tolerance (IGT), and newly diagnosed type 2 diabetes mellitus (T2DM). METHODS: 5 NGT, 25 HINS, 25 IGT, and 25 T2DM subjects participated in this research. The hyperinsulinemic-euglycemic clamp technique (HECT) was performed in all of them to evaluate IR levels. The relative factors influencing IR were evaluated. The simple insulin sensitivity indices were calculated, and the correlation between each index and the M value was analyzed. RESULTS: The M values of NGT, HINS, IGT, and T2DM groups were 11.88 ± 2.93 mg · kg(-1) · min(-1), 6.23 ± 1.73 mg · kg(-1) · min(-1), 6.37 ± 2.12 mg · kg(-1) · min(-1), and 6.19 ± 1.89 mg · kg(-1) · min(-1), respectively. M values in HINS, IGT, and T2DM groups were lower than those in the NGT group (P = 0.005); however, the differences among the HINS, IGT, and T2DM groups were not statistically significant (P = 0.835). The independent factors influencing the M value were waistline and fasting insulin level (FINS). The simple insulin sensitivity indices, especially Matsuda and Gutt index, were significantly associated with the M value (P < 0.01). CONCLUSION: IR existed in the HINS, IGT, and T2DM groups, and IR levels were consistent in the three groups. The independent factors influencing IR were waistline and FINS.

Recognition, assessment and management of hypoglycaemia in childhood.

Hypoglycaemia is frequent in children and prompt management is required to prevent brain injury. In this article we will consider hypoglycaemia in children after the neonatal period. The most common causes are diabetes mellitus and idiopathic ketotic hypoglycaemia (IKH) but a number of endocrine disorders and inborn errors of metabolism (IEMs) need to be excluded. Elucidation of the diagnosis relies primarily on investigations during a hypoglycaemic episode but may also involve biochemical tests between episodes, dynamic endocrine tests and molecular genetics. Specific treatment such as cortisol replacement and pancreatic surgery may be required for endocrine causes of hypoglycaemia, such as adrenal insufficiency and congenital hyperinsulinism. In contrast, in IKH and most IEMs, hypoglycaemia is prevented by limiting the duration of fasting and maintaining a high glucose intake during illnesses.