Increased Insulin Resistance Research Articles

The effect of sun light exposure on prediabetic patients in tamil nadu population

This study examines the impact of sunlight exposure on metabolic health indicators in prediabetic individuals in Tamil Nadu, with a focus on its potential to reduce the risk of Type 2 diabetes mellitus (T2DM). Prediabetes, characterized by elevated glucose levels, is a major risk factor for both T2DM and cardiovascular diseases. With projections that diabetes will affect 380 million people globally by 2025, including 70 million in India, early intervention is critical. Vitamin D, synthesized through sunlight exposure, plays a role in insulin sensitivity and glucose regulation. Vitamin D deficiency has been linked to increased insulin resistance and higher HbA1c levels, particularly among those with obesity, a common risk factor in prediabetes. This retrospective study included 100 prediabetic patients, divided based on sunlight exposure, and followed over three years. Key anthropometric and metabolic parameters such as BMI, blood glucose, HbA1c, and lipid profiles were assessed. Results showed that the sunlight-exposed group had significant improvements in BMI, blood glucose, and HbA1c compared to those with low sunlight exposure, with blood pressure also improving, though HDL and LDL cholesterol changes were not statistically significant. These findings suggest that regular sunlight exposure may help delay or prevent diabetes progression by improving metabolic health, especially when combined with lifestyle modifications and Vitamin D supplementation. Further research is recommended to determine optimal sunlight exposure guidelines for high-risk groups.

Long-term health after Severe Acute Malnutrition in children and adults- the role of the Pancreas (SAMPA): Protocol

Background: Prenatal growth retardation may increase the risk of later chronic non-communicable diseases (NCDs), including diabetes; however, long-term effects of wasting malnutrition in childhood or adulthood are less studied. Pancreatic exocrine and endocrine functions, both critical for nutrition and NCD aetiology, may not fully recover following malnutrition. However, the evidence and mechanistic information is piecemeal. We hypothesise that wasting malnutrition at any age has long-term detrimental effects on endocrine and exocrine pancreatic structure and function. Methods: The SAMPA international research programme will assess pancreatic structure and function in 3700 participants from ongoing observational nutrition cohorts, two adolescent and four adult, in Zambia, Tanzania, Philippines, and India. Pancreas size, structure, and calcification will be assessed by ultrasound and computed tomography (CT) scan; exocrine function by faecal elastase and serum lipase; and endocrine function by haemoglobin A1c (HbA1c) and blood glucose, insulin and C-peptide concentrations during an oral glucose tolerance test (OGTT). In-depth hormonal analyses of incretins, glucagon, proinsulin and trypsinogen during OGTT and intravenous glucose tolerance tests will be done in subsets of adult participants. Pancreatic size and function outcomes will be compared between people with and without prior wasting malnutrition. Analyses will investigate effect modification by sex, current age, time since malnutrition, current body mass index and dietary patterns. Mathematical modelling of OGTT data will be used to estimate the relative contribution to glucose dysregulation of decreased insulin production, changes in insulin clearance and increased insulin resistance. Proinsulin/insulin ratio will be analysed in archived samples from the Tanzanian cohort using a nested case-control design to investigate whether abnormal values precede diabetes. Conclusions: SAMPA, a large-scale multi-centre research programme using data from people with or without prior wasting malnutrition to assess several aspects of pancreatic phenotype, will provide coherent evidence for future policies and programmes for malnutrition and diabetes.

The Role of STING in Liver Injury Is Both Stimulus- and Time-Dependent.

STING, Tmem173, is involved in liver injury caused by both infectious and sterile inflammatory models. Its role in toxic liver injury and non-alcoholic fatty liver disease (NAFLD), however, is less clear. While a few groups have investigated its role in NAFLD pathogenesis, results have been conflicting. The objective of this study was to clarify the exact role of STING in toxic liver injury and NAFLD models. Goldenticket mice (Tmem173gt), which lack STING protein, were subjected to either a toxic liver injury with tunicamycin (TM) or one of two dietary models of non-alcoholic fatty liver disease: high fructose feeding or Fructose-Palmitate-Cholesterol (FPC) feeding. Three days after TM injection, Tmem173gt mice demonstrated less liver injury (average ALT of 54 ± 5 IU/L) than control mice (average ALT 108 ± 24 IU/L). In contrast, no significant differences in liver injury were seen between WT and Tmem173gt mice fed either high fructose or FPC. Tmem173gt mice only distinguished themselves from WT mice in their increased insulin resistance. In conclusion, while STING appears to play a role in toxic liver injury mediated by TM, it plays little to no role in two dietary models of NAFLD. The exact role of STING appears to be stimulus-dependent.

The Correlation of Different Intensities Exercise on Telomere Length

Many studies have been conducted to establish the connection between exercise and telomere length, but still have varying results. Telomeres are reiterative DNA sequences (5'-TTAGGGn-3') which function to protect genomic DNA from enzymatic degradation. Telomere length can be used as a biomarker of aging because its repetitive structures are known to be highly relevant in the cellular aging process and the shortening of telomeres that occurs with increasing age is considered as an important contributor to aging in organisms. Several factors that affect telomere length are oxidative stress, chronic inflammation, BMI, lifestyle such as smoking, alcohol intake, stress, increased insulin resistance, and exercise. This study aims to determine the correlation of exercise at different intensities on telomere length. The method used in this study is internet search for journals and articles through several websites. The eligible criteria include studies in English language published between 2012 and 2022. The studies that report the correlation of different intensities exercise on telomere length were selected for the systematic literature review. As a result, the people who perform moderate to vigorous physical activity more in their leisure time, have longer leukocyte telomere length (LTL) and long-term resistance training may exert a protective effect on muscle telomere length in the elderly. Several studies have reported a correlation between prevention of leukocyte telomere length shortening and exercise at a certain intensity successfully.

210 Restricted Maternal Nutrition: Impacts on Fetal Development and Metabolism in Sheep

Abstract Adequate nutrition is important for proper growth and metabolism. This is even more important during gestation when insults to the fetus can negatively impact fetal growth and development with persistent effects into adulthood. Using a sheep model, we have demonstrated that maternal restricted feeding (60% of National Research Council requirements) during gestation reduced growth in offspring and muscle fiber cross-sectional area. These changes in growth are associated with reduced stem cell (satellite cells and mesenchymal stem cells) population and function. Offspring of restricted-fed mothers also displayed altered metabolism indicated by increased insulin resistance, leptin dysregulation, and reduced circulating metabolic and growth factors. Based on these persistent negative effects of maternal diet on offspring postnatal growth and metabolism, we evaluated the impacts during fetal growth on whole body and tissue-specific metabolism and the impact of maternal realimentation during gestation. Nutrient restriction caused changes in metabolic pathways in a tissue specific manner in muscle, liver, and blood demonstrating the ability of maternal diet to program offspring metabolism in highly metabolic tissues. Several pathways involved in amino acid, lipid, carbohydrate, and transsulfuration/methionine metabolism were altered in all 3 tissues, demonstrating the whole-body effects of maternal diet on offspring metabolism. Interestingly, realimentation alleviated some of the effects of nutrient restriction on offspring metabolic pathways. In summary, maternal nutrient restriction during gestation negatively affects offspring fetal growth with persistent effects into adulthood which may be caused by changes in stem cell function and key metabolic pathways during fetal development.

Cytokine system in the patients with type 2 diabetes mellitus non-infected with SARS-CoV-2

Diabetes mellitus (DM) is a common chronic non-communicable disease, being the most significant comorbidity in SARS-CoV-2 viral infection. The proportion of DM patients among those with COVID-19 is up to 25.0% in the Russian Federation. In presence of DM, clinical course of COVID-19 is characterized by greater severity and persistence of pulmonary damage, an increased need for immunosuppressive, glucocorticoid and combined antiviral therapy in COVID-19 patients, and with prolonged rehabilitation period. Pathogenetic effects of DM on severe course of the SARS-CoV-2 viral infection are being actively studied. The following factors were considered, e.g., negative impact of hyperglycemia on the course of infection; direct cytotoxic and indirect damage to pancreatic -cells with further activation of pro-inflammatory mechanisms; cumulation and progression of generalized inflammation common to DM and COVID-19 including impaired production of cytokines; influence of SARS-CoV-2 virus on the renin-angiotensin-aldosterone system causing inhibition of insulin secretion and increased insulin resistance. Chronic inflammation and impaired immune response may be among the main mechanisms of association between type 2 DM (T2DM) and COVID-19. It is important to identify systemic inflammatory disorders in patients with type 2 diabetes, which may be associated with greater disease severity, being of negative prognostic value. The aim of the present work was to investigate concentrations of some serum cytokines in the patients with type 2 diabetes not infected with SARS-CoV-2.
 The study included 20 patients with type 2 diabetes; the control group consisted of 11 clinically healthy volunteers. The serum concentration of 13 cytokines was assessed by multiplex analysis on a MAGPIX-100 immunoanalyzer using a Merck multiplex analysis kit (Germany), in accordance with the manufacturers instructions.
 Increased serum concentrations in T2DM patients were found, as compared with the control group for some key pro-inflammatory cytokines: CX3CL1, TNF, IFN, IL-8, IL-17A, MIP-1, and MIP-1. We have also revealed a decrease in serum concentrations of IL-4. Serum immunoregulatory cytokines in the T2DM were found to be changed in different directions: a decrease in IL-5, along with increase of IL-12p70 and IL- 17, whereas the serum contents of IL-2, IL-13 did not change.
 A comprehensive analysis of serum cytokine concentrations may increase clinical significance of assessing serum cytokine concentrations as prognostic and diagnostic markers, as well as therapeutic targets in type 2 DM, like as in SARS-CoV-2 infection.

Mitigation of Cadmium Toxicity through Modulation of the Frontline Cellular Stress Response

Cadmium (Cd) is an environmental toxicant of public health significance worldwide. Diet is the main Cd exposure source in the non-occupationally exposed and non-smoking populations. Metal transporters for iron (Fe), zinc (Zn), calcium (Ca), and manganese (Mn) are involved in the assimilation and distribution of Cd to cells throughout the body. Due to an extremely slow elimination rate, most Cd is retained by cells, where it exerts toxicity through its interaction with sulfur-containing ligands, notably the thiol (-SH) functional group of cysteine, glutathione, and many Zn-dependent enzymes and transcription factors. The simultaneous induction of heme oxygenase-1 and the metal-binding protein metallothionein by Cd adversely affected the cellular redox state and caused the dysregulation of Fe, Zn, and copper. Experimental data indicate that Cd causes mitochondrial dysfunction via disrupting the metal homeostasis of this organelle. The present review focuses on the adverse metabolic outcomes of chronic exposure to low-dose Cd. Current epidemiologic data indicate that chronic exposure to Cd raises the risk of type 2 diabetes by several mechanisms, such as increased oxidative stress, inflammation, adipose tissue dysfunction, increased insulin resistance, and dysregulated cellular intermediary metabolism. The cellular stress response mechanisms involving the catabolism of heme, mediated by heme oxygenase-1 and -2 (HO-1 and HO-2), may mitigate the cytotoxicity of Cd. The products of their physiologic heme degradation, bilirubin and carbon monoxide, have antioxidative, anti-inflammatory, and anti-apoptotic properties.

Eat Slowly to Beat Bowling

This mini–review article highlights the importance of ‘slow eating’ for human protection against metabolic disorders, namely diabetes, obesity, and associated complexities in today’s stressful times. Recent findings suggest that fast eating increases insulin resistance, metabolic syndrome, and weight gain.

Determinants of hyperglucagonemia in pediatric non-alcoholic fatty liver disease.

ObjectiveOver the years, non-alcoholic fatty liver (NAFLD) disease has progressed to become the most frequent chronic liver disease in children and adolescents. The full pathology is not yet known, but disease progression leads to cirrhosis and hepatocellular carcinoma. Risk factors included hypercaloric diet, obesity, insulin resistance and genetics. Hyperglucagonemia appears to be a pathophysiological consequence of hepatic steatosis, thus, the hypothesis of the study is that hepatic fat accumulation leads to increased insulin resistance and impaired glucagon metabolism leading to hyperglucagonemia in pediatric NAFLD.Methods132 children and adolescents between 10 and 18 years, with varying degrees of obesity, were included in the study. Using Magnetic Resonance Imaging (MRI) average liver fat was determined, and patients were stratified as NAFLD (>5% liver fat content) and non-NAFLD (<5%). All patients underwent a standardized oral glucose tolerance test (OGTT). Additionally, anthropometric parameters (height, weight, BMI, waist circumference, hip circumference) such as lab data including lipid profile (triglycerides, HDL, LDL), liver function parameters (ALT, AST), uric acid, glucose metabolism (fasting insulin and glucagon, HbA1c, glucose 120 min) and indices evaluating insulin resistance (HIRI, SPISE, HOMA-IR, WBISI) were measured.ResultsChildren and adolescents with NAFLD had significantly higher fasting glucagon values compared to the non-NAFLD cohort (p=0.0079). In the NAFLD cohort univariate analysis of fasting glucagon was associated with BMI-SDS (p<0.01), visceral adipose tissue volume (VAT) (p<0.001), average liver fat content (p<0.001), fasting insulin concentration (p<0.001), triglycerides (p<0.001) and HDL (p=0.034). This correlation equally applied to all insulin indices HOMA-IR, WBISI, HIRI (all p<0.001) and SPISE (p<0.002). Multivariate analysis (R² adjusted 0.509) for the same subgroup identified HIRI (p=0.003) and VAT volume (p=0.017) as the best predictors for hyperglucagonemia. Average liver fat content is predictive in pediatric overweight and obesity but not NAFLD.ConclusionsChildren and adolescents with NAFLD have significantly higher fasting plasma glucagon values, which were best predicted by hepatic insulin resistance and visceral adipose tissue, but not average liver fat content.

Diabetestechnologie in der Schwangerschaft

The use of diabetes technology in pregnant women with type 1 diabetes, as well as in gestational diabetes and type 2 diabetes is becoming increasingly important. In the phase of increasing insulin resistance, especially in the second trimester, the focus is to adjust insulin therapy based on continuous glucose monitoring (CGM) targets. This requires proper bolus management and aggressive injection–eating intervals. In addition, it is essential that counseling have a strong focus on women’s eating behaviors, due to the high potential in terms of glycemic control. Sensor-augmented insulin pump therapy is used without trial data (low suspend, predictive low-glucose suspend, hybrid closed loop) and a few studies are expected to be undertaken in the near future, leaving observation as the only viable option for now. Artificial pancreas systems are the future, both in terms of control and well-being.

Simple Method to Predict Insulin Resistance in Children Aged 6-12 Years by Using Machine Learning.

BackgroundDue to the increasing insulin resistance (IR) in childhood, rates of diabetes and cardiovascular disease may rise in the future and seriously threaten the healthy development of children. Finding an easy way to predict IR in children can help pediatricians to identify these children in time and intervene appropriately, which is particularly important for practitioners in primary health care.Patients and MethodsSeventeen features from 503 children 6–12 years old were collected. We defined IR by HOMA-IR greater than 3.0, thus classifying children with IR and those without IR. Data were preprocessed by multivariate imputation and oversampling to resolve missing values and data imbalances; then, recursive feature elimination was applied to further select features of interest, and 5 machine learning methods—namely, logistic regression (LR), support vector machine (SVM), random forest (RF), extreme gradient boosting (XGBoost), and gradient boosting with categorical features support (CatBoost)—were used for model training. We tested the trained models on an external test set containing information from 133 children, from which performance metrics were extracted and the optimal model was selected.ResultsAfter feature selection, the numbers of chosen features for the LR, SVM, RF, XGBoost, and CatBoost models were 6, 9, 10, 14, and 6, respectively. Among them, glucose, waist circumference, and age were chosen as predictors by most of the models. Finally, all 5 models achieved good performance on the external test set. Both XGBoost and CatBoost had the same AUC (0.85), which was highest among those of all models. Their accuracy, sensitivity, precision, and F1 scores were also close, but the specificity of XGBoost reached 0.79, which was significantly higher than that of CatBoost, so XGBoost was chosen as the optimal model.ConclusionThe model developed herein has a good predictive ability for IR in children 6–12 years old and can be clinically applied to help pediatricians identify children with IR in a simple and inexpensive way.

Extended Inter-Meal Interval Negatively Impacted the Glycemic and Insulinemic Responses after Both Lunch and Dinner in Healthy Subjects.

This study aimed to investigate the glycemic and insulinemic effects of lunch timing based on a fixed feeding window, and the effects of apple preload on postprandial glucose and insulin responses after nutrient-balanced lunch and the subsequent high-fat dinner in healthy participants. Twenty-six participants completed four randomized, crossover experimental trials: (1) early standardized lunch at 12:00 (12S); (2) apple preload to 12S (12A+S); (3) late standardized lunch at 14:00 (14S); and (4) apple preload to 14S (14A+S); wherein twenty participants’ blood samples were collected for insulin analysis following the lunch trails. In each experimental trial, each participant equipped with a continuous glucose monitor (CGM) was provided with a standardized breakfast and a high-fat dinner to be consumed at 8:00 and 18:00, respectively. The late lunch (14S) resulted in significantly elevated glucose peak, delayed insulin peak time, decreased insulin sensitivity, and increased insulin resistance following the lunch; also decreased glycemic response following the subsequent dinner and larger blood glucose fluctuation over the 24-h period compared with the 12S. The 14A+S significantly reduced the glucose peak, the insulin peak time and the glycemic variability following the lunch, also the 24-h glycemic variability compared with the 14S. The insulin sensitivity was significantly improved in the 12A+S, compared with that of the 12S. In conclusion, the present study found that an extra 2-h inter-meal fasting before and after lunch resulted in elevated glycemic response in both macronutrient-balanced meal and high-fat meal in healthy subjects. The negative impact of a late lunch could be partly reversed by the apple preload, without a trade-off of insulin secretion.

Abstract P076: Obesity Is Associated With Increased F2-isoprostanes And Il-6 In Black Women.

Obesity affects over 40% of the adult population and is a major risk factor for morbidity and mortality due to cardiovascular disease. Black women have one of the highest prevalence of obesity in the United States and approximately 80% are overweight or obese with increased insulin resistance, hypertension, and cardiovascular events. We previously found that isolevuglandins formed in the F2-isoprostane pathway of free radical–mediated lipid peroxidation contributes to IL-6 production in dendritic cells leading to inflammation and hypertension. Thus, we hypothesized that F2-isoprostanes contribute to increased inflammation and IL-6 production among obese Black women. We recruited 88 Black women of age 42.0±9.8 years, weight 102±16 kg, body mass index (BMI) 37.68±5.08, systolic blood pressure 124±14 mmHg, diastolic blood pressure 76.2±9.9 mmHg, and insulin 15.0±8.7 uU/ml. We measured plasma F2-isoprostane levels using gas chromatography/negative ion chemical ionization mass spectrometry (GC/NICI-MS) at the Eicosanoid Core at Vanderbilt University Medical Center. We also measured plasma cytokines including TNF-α 68±174, IL-1β 135±372, IL-6 1615±2769, IL-8 3536±1901, and IL-10 324±633 pg/mL. Using Pearson’s correlation analysis, we found that increased BMI correlated with increased plasma F2-isoprostane levels (Fig. 1A, R=0.23, p=0.037). Interestingly among all the inflammatory cytokines, elevated IL-6 correlated with increased F2-isoprostanes (Fig. 1B, R= 0.44, p=.0025). These results suggest that F2-isoprostanes may contribute to the obesity-induced cardiovascular risk in Black women by increasing production of inflammatory cytokine IL-6.

GLP-1 Agonist to Treat Obesity and Prevent Cardiovascular Disease: What Have We Achieved so Far?

To discuss evidence supporting the use of glucagon-like peptide 1 receptor agonists (GLP-1RA) to treat obesity and their role as a cardioprotective drug. Obesity is not just a hypertrophy of the adipose tissue because it may become dysfunctional and inflamed resulting in increased insulin resistance. Being overweight is associated with increased incidence of cardiovascular events and weight loss achieved through lifestyle changes lowers risk factors, but has no clear effect on cardiovascular outcomes. In contrast, treating obesity with GLP-1RA decreases cardiovascular risk and the possible mechanisms of cardioprotection achieved by this class of drugs are discussed. GLP-1RA were initially developed to treat type 2 diabetes patients, in whom the effects upon glycemia and, moreover, weight loss, especially with long-acting GLP-1RA, were evident. However, cardiovascular safety trials in type 2 diabetes patients, the majority presenting cardiovascular disease and excess weight, showed that GLP-1 receptor agonists were indeed capable of decreasing cardiovascular risk. Type 2 diabetes treatment with GLP-1RA liraglutide and semaglutide paved way to a ground-breaking therapy specific for obesity, as shown with the SCALE 3mg/day liraglutide program and the STEP 2.4mg/week semaglutide program. A novel molecule with superior performance is tirzepatide, a GLP-1 and GIP (Gastric Inhibitory Peptide) receptor agonist and recent results from the SURPASS and SURMOUNT programs are briefly described. Liraglutide was approved without a CVOT (Cardiovascular Outcome Trial) because authorities accepted the results from the LEADER study, designed for superiority. The SELECT study with semaglutide will report results only in 2023 and tirzepatide is being tested in patients with diabetes in the SURPASS-CVOT. Clinical studies highlight that GLP-1RA to treat obesity, alongside their concomitant cardioprotective effects, have become a hallmark in clinical science.

FAK-Mediated Signaling Controls Amyloid Beta Overload, Learning and Memory Deficits in a Mouse Model of Alzheimer's Disease.

The non-receptor focal adhesion kinase (FAK) is highly expressed in the central nervous system during development, where it regulates neurite outgrowth and axon guidance, but its role in the adult healthy and diseased brain, specifically in Alzheimer’s disease (AD), is largely unknown. Using the 3xTg-AD mouse model, which carries three mutations associated with familial Alzheimer’s disease (APP KM670/671NL Swedish, PSEN1 M146V, MAPT P301L) and develops age-related progressive neuropathology including amyloid plaques and Tau tangles, we describe here, for the first time, the in vivo role of FAK in AD pathology. Our data demonstrate that while site-specific knockdown in the hippocampi of 3xTg-AD mice has no effect on learning and memory, hippocampal overexpression of the protein leads to a significant decrease in learning and memory capabilities, which is accompanied by a significant increase in amyloid β (Aβ) load. Furthermore, neuronal morphology is altered following hippocampal overexpression of FAK in these mice. High-throughput proteomics analysis of total and phosphorylated proteins in the hippocampi of FAK overexpressing mice indicates that FAK controls AD-like phenotypes by inhibiting cytoskeletal remodeling in neurons which results in morphological changes, by increasing Tau hyperphosphorylation, and by blocking astrocyte differentiation. FAK activates cell cycle re-entry and consequent cell death while downregulating insulin signaling, thereby increasing insulin resistance and leading to oxidative stress. Our data provide an overview of the signaling networks by which FAK regulates AD pathology and identify FAK as a novel therapeutic target for treating AD.

Statin therapy is not associated with insulin resistance in children and adolescents with familial hypercholesterolaemia

Background and Aims : Statins are first line therapy for lowering atherogenic low-density lipoprotein cholesterol (LDL-C) in patients with familial hypercholesterolaemia (FH). Statins were associated with an increased insulin resistance and the risk for type 2 diabetes. We aimed to assess the effect of statins on insulin resistance in children.

Glucose metabolism in systemic juvenile idiopathic arthritis

BackgroundSystemic juvenile idiopathic arthritis (SJIA) is a chronic systemic inflammatory disease in children. Overproduction of inflammatory cytokines in SJIA resembles that in adult onset Still disease. Chronic inflammation causes insulin resistance and consequently leading to abnormal glucose metabolism. Adults with rheumatoid arthritis (RA) have increased risks of abnormal glucose metabolism and diabetes. To date, glucose metabolism in patients with SJIA has not been elucidated.MethodsPatients with SJIA aged 4–25 years were recruited. All patients underwent an oral glucose tolerance test (OGTT). Indices of insulin sensitivity [homeostasis model assessment for insulin resistance (HOMA-IR) and whole-body insulin sensitivity index (WBISI)] and β-cell function [insulinogenic index (IGI) and disposition index (DI)] were calculated. Obese children with normoglycemia who underwent the OGTT were served as a control group.ResultsA total of 39 patients with SJIA, aged 4–25 years, median (IQR) BMI SDS was 0.1 (-0.5 to 1.7). Patients were divided into 2 groups, overweight/obese (OW/OB) (n = 11) and lean (n = 28). Only one obese patient had prediabetes and none had diabetes. In comparison with sex- and age-matched OW/OB controls (n = 33), OW/OB patients with SJIA had higher insulin resistance [median (IQR) HOMA-IR: 2.6 (2.1–3.3) vs 1.5 (0.8–2.0), p = 0.001], lower insulin sensitivity [median (IQR) WBISI: 3.7 (2.7–5.9) vs 5.4 (4.5–8.7), p = 0.024], and higher insulin secretion [median (IQR) IGI: 2.5 (2.0–3.5) vs 1.0 (0.8–1.9), p = 0.001]. In lean patients with SJIA, insulin sensitivity indices seemed to be comparable with those of lean controls.ConclusionsOverweight/obese children with SJIA seemed to have increased insulin resistance and thus may have an increased risk for developing diabetes.

Molecular Mechanisms Underlying Intensive Care Unit-Acquired Weakness and Sarcopenia.

Skeletal muscle is a highly adaptable organ, and its amount declines under catabolic conditions such as critical illness. Aging is accompanied by a gradual loss of muscle, especially when physical activity decreases. Intensive care unit-acquired weakness is a common and highly serious neuromuscular complication in critically ill patients. It is a consequence of critical illness and is characterized by a systemic inflammatory response, leading to metabolic stress, that causes the development of multiple organ dysfunction. Muscle dysfunction is an important component of this syndrome, and the degree of catabolism corresponds to the severity of the condition. The population of critically ill is aging; thus, we face another negative effect—sarcopenia—the age-related decline of skeletal muscle mass and function. Low-grade inflammation gradually accumulates over time, inhibits proteosynthesis, worsens anabolic resistance, and increases insulin resistance. The cumulative consequence is a gradual decline in muscle recovery and muscle mass. The clinical manifestation for both of the above conditions is skeletal muscle weakness, with macromolecular damage, and a common mechanism—mitochondrial dysfunction. In this review, we compare the molecular mechanisms underlying the two types of muscle atrophy, and address questions regarding possible shared molecular mechanisms, and whether critical illness accelerates the aging process.

Statins and renal disease progression, ophthalmic manifestations, and neurological manifestations in veterans with diabetes: A retrospective cohort study

Statins increase insulin resistance, which may increase risk of diabetic microvascular complications. Little is known about the impact of statins on renal, ophthalmologic, and neurologic complications of diabetes in practice. The objective of this study was to examine the association of statins with renal disease progression, ophthalmic manifestations, and neurological manifestations in diabetes. This is a retrospective cohort study, new-user active comparator design, that included a national Veterans Health Administration (VA) patients with diabetes from 2003 to 2015. Patients were age 30 years or older and were regular users of the VA with data encompassing clinical encounters, demographics, vital signs, laboratory tests, and medications. Patients were divided into statin users or nonusers (active comparators). Statin users initiated statins and nonusers initiated H2-blockers or proton pump-inhibitors (H2-PPI) as an active comparator. Study outcomes were: 1) Composite renal disease progression outcome; 2) Incident diabetes with ophthalmic manifestations; and 3) Incident diabetes with neurological manifestations. Out of 705,774 eligible patients, we propensity score matched 81,146 pairs of statin users and active comparators. Over a mean (standard deviation) of follow up duration of 4.8 (3) years, renal disease progression occurred in 9.5% of statin users vs 8.3% of nonusers (odds ratio [OR]: 1.16; 95% confidence interval [95%CI]: 1.12-1.20), incident ophthalmic manifestations in 2.7% of statin users vs 2.0% of nonusers (OR: 1.35, 95%CI:1.27-1.44), and incident neurological manifestations in 6.7% of statin users vs 5.7% of nonusers (OR: 1.19, 95%CI:1.15-1.25). Secondary, sensitivity, and post-hoc analyses were consistent and demonstrated highest risks among the healthier subgroup and those with intensive lowering of LDL-cholesterol. Statin use in patients with diabetes was associated with modestly higher risk of renal disease progression, incident ophthalmic, and neurological manifestations. More research is needed to assess the overall harm/benefit balance for statins in the lower risk populations with diabetes and those who receive intensive statin therapy.

The spectrum of diabetes in acute and chronic pancreatitis.

To discuss the spectrum of diabetes related to acute and chronic pancreatitis (which are types of pancreatogenic diabetes) and its overlapping features with type 1 and type 2 diabetes. Patients with diabetes related to acute and chronic pancreatitis present clinically within a spectrum of overlapping features with other forms of diabetes. In this spectrum, glucose metabolism alterations range from increased insulin resistance following acute pancreatitis (resembling type 2 diabetes) towards a permanent loss of beta-cell function and impaired insulin secretion in end-stage chronic pancreatitis. Overlapping features with type 1 diabetes (beta cell autoantibodies) and type 2 diabetes (obesity, dyslipidemia, and hereditary/genetic factors) contribute to the heterogeneity of this spectrum. Pancreatogenic diabetes secondary to acute or chronic pancreatitis is a heterogeneous entity with a variable clinical presentation, including many cases that are misdiagnosed and treated as type 2 diabetes. This is problematic as pancreatogenic diabetes is associated with a poor prognosis and entails special considerations for management. Recent discoveries showing overlapping features with type 1 and type 2 diabetes along with an improved understanding of its pathophysiology are expected to improve the diagnosis and treatment of these and other forms of pancreatogenic diabetes.