Decreased Insulin Sensitivity Research Articles

Diet Compliance Analysis Towards Blood Sugar Levels For Diabetes Mellitus Patients

Background: People with diabetes mellitus are increasing in number. Controlling blood sugar levels is an action that must be taken to get normal and stable blood sugar levels. Self-control takes precedence over treatment. Compliance with diet is one of the important things in controlling blood sugar levels. Raflesia Room as one of the internal medicine inpatients in dr. SoedomoTrenggalek, received inpatient care for the majority of diabetes mellitus patients.
 Purpose : The purpose of this study was to analyze the relationship between diet adherence and blood sugar levels in people with diabetes mellitus.
 Methods : The research design used descriptive analytic with cross sectional approach. The population in this study were patients with diabetes mellitus in the Raflesia room of Dr. SoedomoTrenggalek Hospital in January 2017 with 30 patients. With a simple random sampling technique so that 29 samples were obtained.
 Result : The results showed that almost all respondents, namely 25 (86%) respondents, had abnormal blood sugar levels. Almost all respondents, 23 (79%) did not comply with the diet. Chi square test results obtained 0.004 which means there is a relationship between dietary compliance with blood sugar levels of diabetes mellitus patients in Raflesia room Dr. Soedomo Hospital Trenggalek in 2017.
 Conclusion : Old age is an age that is susceptible to a decrease in body function, especially hormonal causes of decreased pancreatic function resulting in a decrease in insulin sensitivity which causes high blood sugar levels. The level of education has an important role in diet compliance where patients are required to understand 3J "Types, Amounts and Schedules" so that the lower level of education causes lower diet compliance. Disobedience to diets causes sufferers to consume irregular foods which cause a pile of glucose and blood so that hyperglycemia occurs.

Cardiovascular and Metabolic Effects of Androgen-Deprivation Therapy for Prostate Cancer.

Androgen-deprivation therapy (ADT) entails lowering serum testosterone levels to castrate levels and forms a cornerstone of the management of hormone-sensitive advanced prostate cancer; however, the benefit of ADT is partially offset by its detrimental metabolic and cardiovascular adverse effects. ADT decreases insulin sensitivity while promoting dyslipidemia and sarcopenic obesity, which leads to an increased risk of cardiovascular morbidity and potentially mortality. The risk seems to be highest in elderly patients who have had recent cardiovascular events before starting ADT. It is prudent to engage in an individualized risk-benefit discussion and develop a cohesive multidisciplinary management plan to medically optimize and closely observe these patients before and during treatment with ADT.

Effects of probiotics, prebiotics or synbiotics on jawbone in obese-insulin resistant rats.

Chronic high-fat diet (HFD) consumption results in gut dysbiosis, systemic inflammation, obese-insulin resistance, and osteoporosis of the jawbones. The probiotics, prebiotics or synbiotics alleviated gut dysbiosis and the metabolic disturbance in HFD-induced obesity. However, the effects on jawbone properties have not been investigated. This study aimed to investigate the effects of probiotic Lactobacillus paracasei HII01, prebiotic xylooligosaccharide (XOS), and synbiotics on the jawbone properties along with metabolic parameters, gut and systemic inflammation in HFD-fed rats. Forty-eight male Wistar rats were fed with either a HFD or normal diet for 12weeks. Rats in each group were subdivided into four subgroups to be treated with either vehicle, probiotics, prebiotics, or synbiotics for the additional 12weeks. Blood samples, gut, bone marrows, and jawbones were collected to determine metabolic parameters, inflammation, and bone properties. The HFD-fed rats developed obese-insulin resistance, as indicated by increased body weight, dyslipidemia and decreased insulin sensitivity. Serum lipopolysaccharide levels and interleukin-6 mRNA expression in the ileum and bone marrows were elevated. Altered bone metabolism and the impaired jawbone properties were evident as indicated by decreased bone mineral density with increased trabecular separation. Reduced ultimate load and stiffness were observed in HFD-fed rats. Treatments with probiotics, prebiotics or synbiotics in HFD-fed rats improved metabolic parameters and reduced inflammation. However, no alterations in jawbone properties were found in all treatments. The osteoporosis of the jawbone occurred in obese-insulin resistance, and treatments with probiotics, prebiotics and synbiotics were not sufficient to improve the jawbone properties.

Impairment of bisphenol F on the glucose metabolism of zebrafish larvae

Bisphenol F (BPF) is a substitute of bisphenol A in the production of epoxy resin and polycarbonate. Its extensive use in consumer products leads to a wide human exposure at high levels. Although the adverse effects of BPF on animal health are of increasing public concern, its risks on systematic glucose metabolism and blood glucose concentrations still remain largely unknown. Using zebrafish larvae as the model animal, we investigated the disturbance of BPF exposure on glucose metabolism and the underlying mechanisms. Zebrafish larvae at 96 h post fertilization were exposed to 0.1, 1, 10, and 100 μg/L of BPF for 48 h. Compared with the control group, glucose levels of larvae increased significantly in the 10 and 100 μg/L exposure groups, which are associated with enhancement of gluconeogenesis and suppression of glycolysis induced by high doses of BPF. Additionally, both mRNA expressions and protein levels of insulin increased significantly in the 10 and 100 μg/L exposure groups, while transcription levels of genes encoding insulin receptor substrates decreased significantly in these groups, indicating a possibly decreased insulin sensitivity due to impairment of insulin signaling transduction downstream of insulin receptor. Further, compared with BPF alone, co-exposure of larvae to BPF and rosiglitazone, an insulin sensitizer, significantly attenuates increases in both glucose levels and mRNA expressions of a key gluconeogenesis enzyme. Our data therefore indicate impairing insulin signaling transduction may be the main mechanism through which BPF disrupts glucose metabolism and induces hyperglycemia. Results of the present study inform the health risk assessment of BPF and also suggest the use of zebrafish larvae in large-scale screening of chemicals with possible glucose metabolism disturbing effect.

Association of Vitamin D and Parathyroid Hormone with Insulin Sensitivity, Beta Cell Function and Gestational Diabetes in Pregnancy: A Cross-Sectional, Observational Study.

IntroductionVitamin D (25OHD) and parathyroid hormone (PTH) are associated with dysglycemia, and we investigated them in gestational diabetes mellitus (GDM).MethodsIn this cross-sectional, observational study, we included 75 pregnant women between 24 and 28 weeks of gestation. A fasting venous sample was collected for plasma glucose (FPG), insulin, PTH and 25OHD. Glucose and insulin samples were collected hourly after 75 g glucose load for 2 h. Insulin sensitivity was estimated by the Matsuda index (MI) and beta cell function by the insulin secretion sensitivity index (ISSI-2). The subjects were stratified into three groups and tertiles according to the 25OHD and PTH, respectively. Appropriate statistical tests were used to compare the MI, ISSI-2 and GDM among the groups.ResultsGDM was seen in 14/75, and of these patients, 2 were 25OHD deficient, 7 insufficient and 5 had sufficient 25OHD. MI and ISSI-2, though not correlated with the 25OHD, decreased from the lower to higher PTH tertile (P < 0.001). FPG, AUCgluc (area under the curve glucose) and prevalence of GDM increased from the lower to higher PTH tertile (P < 0.001).ConclusionIncreased PTH was associated with decreased insulin sensitivity, beta cell function and GDM in pregnancy, irrespective of the underlying 25OHD level.

Oral Glucose Tolerance is Associated with Neuroelectric Indices of Attention Among Adults with Overweight and Obesity.

This study aimed to elucidate the relationship between glucose levels and insulin resistance and sensitivity obtained from oral glucose tolerance tests and neurophysiological indices of attention among adults with overweight and obesity. Forty adults with overweight or obesity (BMI ≥ 25 kg/m2 ) underwent dual-energy x-ray absorptiometry to assess visceral adipose tissue. Repeated venous blood samples were collected during an oral glucose tolerance test to measure insulin resistance (homeostatic model assessment of insulin resistance) and indices of insulin sensitivity (Matsuda index and Stumvoll metabolic clearance rate). Attention was assessed using event-related brain potentials recorded during a visual oddball task. Amplitude and latency of the P3 wave form in a central-parietal region of interest were used to index attentional resource allocation and information processing speed. Following adjustment for visceral adipose tissue, reduced values of Matsuda index and Stumvoll metabolic clearance rate (indicating poor insulin sensitivity) were correlated with longer peak latency, whereas insulin area under the curve was positively related to peak latency, indicating slower information processing. Individuals with decreased insulin sensitivity (Matsuda index < 4.3) had significantly longer P3 latencies compared with individuals with normal insulin sensitivity. Higher fasting glucose, but not homeostatic model assessment of insulin resistance, and reduced indices of glucose sensivity are associated with decrements in attention characterized by slower reaction time and slower information processing speed among adults with overweight and obesity.

Sucralose decreases insulin sensitivity in healthy subjects: a randomized controlled trial

Recently, the absence of metabolic effects from nonnutritive sweeteners has been questioned. The aim of this study was to evaluate the effects of sucralose consumption on glucose metabolism variables. We performed a randomized controlled trial involving healthy subjects without comorbidities and with a low habitual consumption of nonnutritive sweeteners (n=33/group). The intervention consisted of sucralose consumption as 15% of Acceptable Daily Intake every day for 14 d using commercial sachets. The control group followed the same procedures without any intervention. The glucose metabolism variables (insulin sensitivity, acute insulin response to glucose, disposition index, and glucose effectiveness) were evaluated by using a 3-h modified intravenous-glucose-tolerance test before and after the intervention period. Individuals assigned to sucralose consumption showed a significant decrease in insulin sensitivity with a median (IQR) percentage change of -17.7% (-29.3% to -1.0%) in comparison to -2.8% (-30.7% to 40.6%) in the control group (P=0.04). An increased acute insulin response to glucose from 577 mU · L-1· min (350-1040 mU · L-1· min) to 671 mU · L-1· min (376-1010 mU · L-1· min) (P=0.04) was observed in the sucralose group for participants with adequate adherence. Sucralose may have effects on glucose metabolism, and our study complements findings previously reported in other trials. Further studies are needed to confirm the decrease in insulin sensitivity and to explore the mechanisms for these metabolic alterations. This trial was registered at www.clinicaltrials.gov as NCT02589002.

GPR55 deficiency is associated with increased adiposity and impaired insulin signaling in peripheral metabolic tissues.

Emerging evidence indicates that G-protein coupled receptor 55 (GPR55), a nonclassic receptor of the endocannabinoid system that is activated by L-α-lysophosphatidylinositol and various cannabinoid ligands, may regulate endocrine function and energy metabolism. We examined how GPR55 deficiency and modulation affects insulin signaling in skeletal muscle, adipose tissue, and liver alongside expression analysis of proteins implicated in insulin action and energy metabolism. We show that GPR55-null mice display decreased insulin sensitivity in these tissues, as evidenced by reduced phosphorylation of PKB/Akt and its downstream targets, concomitant with increased adiposity and reduced physical activity relative to wild-type counterparts. Impaired tissue insulin sensitivity coincided with reduced insulin receptor substrate-1 abundance in skeletal muscle, whereas in liver and epididymal fat it was associated with increased expression of the 3-phosphoinoistide lipid phosphatase, phosphatase and tensin homolog. In contrast, GPR55 activation enhanced insulin signaling in cultured skeletal muscle cells, adipocytes, and hepatocytes; this response was negated by receptor antagonists and GPR55 gene silencing in L6 myotubes. Sustained GPR55 antagonism in 3T3-L1 adipocytes enhanced expression of proteins implicated in lipogenesis and promoted triglyceride accumulation. Our findings identify GPR55 as a positive regulator of insulin action and adipogenesis and as a potential therapeutic target for countering obesity-induced metabolic dysfunction and insulin resistance.—Lipina, C., Walsh, S. K., Mitchell, S. E., Speakman, J. R., Wainwright, C. L., Hundal, H. S. GPR55 deficiency is associated with increased adiposity and impaired insulin signaling in peripheral metabolic tissues.

The usefulness of short-term high-fat/high salt diet as a model of metabolic syndrome in mice

Diabetic cardiomyopathy (DC) describes diabetes-associated changes in the structure and function of myocardium that are not directly linked to other factors such as hypertension. Currently there are some models of DC; however, they take a large time period to mimic key features. In the present study, we investigated the effects of a short-term high-fat/high salt diet (HFHS) treatment on myocardial function and structure, and vascular reactivity in C57BL/6 male mice. After 14 weeks HFHS induced hypertension (MAP = 144.95 ± 16.13 vs 92.90 ± 18.95 mm Hg), low glucose tolerance (AUC = 1049.01 ± 74.79 vs 710.50 ± 52.57 a.u.), decreased insulin sensitivity (AUC = 429.83 ± 35.22 vs 313.67 ± 19.55 a.u.) and increased adiposity (epididymal fat weight 0.96 ± 0.10 vs 0.59 ± 0.06 OW/BW × 102), aspects present in metabolic syndrome. Cardiac evaluation showed diastolic dysfunction (E/A ratio = 1.20 vs 1.90 u.a.) and cardiomyocyte hypertrophy (cardiomyocyte area = 502.82 ± 31.46 vs 385.58 ± 22.11 μm2). Lastly, vascular reactivity was impaired with higher contractile response (136.10 ± 3.49 vs 120.37 ± 5.43%) and lower response to endothelium-dependent vasorelaxation (74.01 ± 4.35 vs 104.84 ± 3.57%). In addition, the diet was able to induce an inward coronary remodeling (vascular total area: SCNS 6185 ± 800.6 vs HFHS 4085 ± 213.7 μm2). Therefore, we conclude that HFHS short-term treatment was able to induce metabolic syndrome-like state, cardiomyopathy and vascular injury working as an important tool to study cardiometabolic diseases.

Sodium butyrate ameliorates insulin resistance and renal failure in CKD rats by modulating intestinal permeability and mucin expression.

BackgroundThe associated increase in the lipopolysaccharide (LPS) levels and uremic toxins in chronic kidney disease (CKD) has shifted the way we focus on intestinal microbiota. This study shows that a disruption of the intestinal barrier in CKD promotes leakage of LPS from the gut, subsequently decreasing insulin sensitivity. Butyrate treatment improved the intestinal barrier function by increasing colonic mucin and tight junction (TJ) proteins. This modulation further ameliorated metabolic functions such as insulin intolerance and improved renal function.MethodsRenal failure was induced by 5/6th nephrectomy (Nx) in rats. A group of Nx and control rats received sodium butyrate in drinking water. The Nx groups were compared with sham-operated controls.ResultsThe Nx rats had significant increases in serum creatinine, urea and proteinuria. These animals had impaired glucose and insulin tolerance and increased gluconeogenesis, which corresponded with decreased glucagon-like peptide-1 (GLP-1) secretion. The Nx animals suffered significant loss of intestinal TJ proteins, colonic mucin and mucin 2 protein. This was associated with a significant increase in circulating LPS, suggesting a leaky gut phenomenon. 5′adenosine monophosphate-activated protein kinase (AMPK) phosphorylation, known to modulate epithelial TJs and glucose metabolism, was significantly reduced in the intestine of the Nx group. Anti-inflammatory cytokine, interleukin 10, anti-bacterial peptide and cathelicidin-related antimicrobial peptide were also lowered in the Nx cohort. Butyrate treatment increased AMPK phosphorylation, improved renal function and controlled hyperglycemia.ConclusionsButyrate improves AMPK phosphorylation, increases GLP-1 secretion and promotes colonic mucin and TJ proteins, which strengthen the gut wall. This decreases LPS leakage and inflammation. Taken together, butyrate improves metabolic parameters such as insulin resistance and markers of renal failure in CKD animals.

Adipose Tissue Transferrin and Insulin Resistance.

Excessive body iron stores are a risk factor for decreased insulin sensitivity (SI) and diabetes. We hypothesized that transcriptional dysregulation of genes involved in iron metabolism in adipocytes causes insulin resistance. To define the genetic regulation of iron metabolism and its role in SI, we used gene expression, genotype, and SI data from an African American cohort (N = 256). Replication studies were performed in independent European ancestry cohorts. In vitro studies in human adipocytes were performed to define the role of a selected gene in causing insulin resistance. Among 62 transcripts representing iron homeostasis genes, expression of 30 in adipose tissue were correlated with SI. Transferrin (TF) and ferritin heavy polypeptide were most positively and negatively associated with SI, respectively. These observations were replicated in two independent European ancestry adipose data sets. The strongest cis-regulatory variant for TF expression (rs6785596; P = 7.84 × 10-18) was identified in adipose but not muscle or liver tissue. Variants significantly affected the normal relationship of serum ferritin to insulin resistance. Knockdown of TF in differentiated Simpson-Golabi-Behmel syndrome adipocytes by short hairpin RNA decreased intracellular iron, reduced maximal insulin-stimulated glucose uptake, and reduced Akt phosphorylation. Knockdown of TF caused differential expression of 465 genes, including genes involved in glucose transport, mitochondrial function, Wnt-pathway/ SI, chemokine activity, and obesity. Iron chelation recapitulated key changes in the expression profile induced by TF knockdown. Genetic regulation of TF expression in adipose tissue plays a novel role in regulating SI.

Large-for-Gestational-Age May Be Associated With Lower Fetal Insulin Sensitivity and β-Cell Function Linked to Leptin.

Fetal overgrowth is associated with increased risk for type 2 diabetes in adulthood. It is unclear whether there are alterations in insulin sensitivity and β-cell function in early life. To determine whether large-for-gestational-age (LGA) (birth weight > 90th percentile), an indicator of fetal overgrowth, is associated with altered fetal insulin sensitivity and β-cell function. In the Design, Development, and Discover birth cohort in Canada, we studied 106 pairs of LGA and optimal-for-gestational-age (OGA; birth weight, 25th to 75th percentiles) infants matched by maternal ethnicity, smoking status, and gestational age. Cord plasma glucose-to-insulin ratio was used as an indicator of fetal insulin sensitivity, and proinsulin-to-insulin ratio was used as an indicator of β-cell function. Cord plasma leptin and high-molecular-weight (HMW) adiponectin concentrations were measured. Comparisons of infants who were born LGA vs OGA, adjusted for maternal and newborn characteristics, showed that cord blood insulin, proinsulin, and leptin concentrations were significantly higher, whereas HWM adiponectin concentrations were similar. Glucose-to-insulin ratios were significantly lower (15.4 ± 28.1 vs 22.0 ± 24.9; P = 0.004), and proinsulin-to-insulin ratios significantly higher (0.73 ± 0.82 vs 0.60 ± 0.78; P = 0.005) in LGA vs OGA newborns, indicating lower insulin sensitivity and β-cell function in LGA newborns. These significant differences were almost unchanged after further adjustment for cord blood adiponectin levels but disappeared upon additional adjustment for cord blood leptin levels. This study demonstrates that LGA may be associated with decreases in both fetal insulin sensitivity and β-cell function. The alterations appear to be linked to elevated leptin levels.

SLC6A4 5HTTLPR Polymorphism Affects Insulin Secretion in Patients with Polycystic Ovary Syndrome.

Purpose To investigate in a pilot study of genetic polymorphisms in serotonin system influencing basal- and glucose-stimulated insulin secretion in women with polycystic ovary syndrome (PCOS). Methods A cross-sectional study included 65 female patients with PCOS followed up at the endocrine outpatient clinic of the University Medical Center Ljubljana and a control group of 94 young healthy female blood donors. Oral glucose tolerance test was performed only in PCOS patients and basal- and glucose-stimulated blood glucose and insulin levels were measured. All the subjects were genotyped for 5HTR1A rs6295, 5HTR1B rs13212041, and SLC6A4 5HTTLPR polymorphisms in the serotonin system. Results Genotype distributions were in accordance with the Hardy-Weinberg equilibrium (HWE), except for 5HTR1A rs6295 in healthy controls and 5HTR1B rs13212041 in PCOS patients that were not consistent with HWE. SLC6A4 5HTTLPR polymorphism was significantly associated with insulin secretion (p = 0.030) and with the area under the curve of insulin blood levels during OGTT (p = 0.021). None of the investigated polymorphisms was significantly associated with basal- or glucose-stimulated blood glucose levels at any point in time during OGTT or with the basal insulin concentration. Conclusions Serotonin system may play a role in glucose-stimulated insulin secretion in patients with insulin resistance (IR) and decreased insulin sensitivity. Further studies are needed to conclude whether the observed effect is characteristic for PCOS-related metabolic disturbances or for the identified mutation in different high metabolic risk populations.

Circulating Chemerin Levels, Anthropometric Indices and Metabolic Profile in Morbid Obesity

Recent data suggest that chemerin could be important for the pathophysiology of obesity. However, its relation with clinical indices of obesity and metabolic parameters is controversial and less studied in metabolic healthy patients with morbid obesity. Our study demonstrated that circulating chemerin is related to anthropometric indices, it is an independent predictor for waist to hip circumference ratio as well as for decreased insulin sensitivity, but not for other metabolic changes. Chemerin/adiponectin ratio is also a useful parameter, but not superior to chemerin levels.

MiR-30a Remodels Subcutaneous Adipose Tissue Inflammation to Improve Insulin Sensitivity in Obesity.

Chronic inflammation accompanies obesity and limits subcutaneous white adipose tissue (WAT) expandability, accelerating the development of insulin resistance and type 2 diabetes mellitus. MicroRNAs (miRNAs) influence expression of many metabolic genes in fat cells, but physiological roles in WAT remain poorly characterized. Here, we report that expression of the miRNA miR-30a in subcutaneous WAT corresponds with insulin sensitivity in obese mice and humans. To examine the hypothesis that restoration of miR-30a expression in WAT improves insulin sensitivity, we injected adenovirus (Adv) expressing miR-30a into the subcutaneous fat pad of diabetic mice. Exogenous miR-30a expression in the subcutaneous WAT depot of obese mice coupled improved insulin sensitivity and increased energy expenditure with decreased ectopic fat deposition in the liver and reduced WAT inflammation. High-throughput proteomic profiling and RNA-Seq suggested that miR-30a targets the transcription factor STAT1 to limit the actions of the proinflammatory cytokine interferon-γ (IFN-γ) that would otherwise restrict WAT expansion and decrease insulin sensitivity. We further demonstrated that miR-30a opposes the actions of IFN-γ, suggesting an important role for miR-30a in defending adipocytes against proinflammatory cytokines that reduce peripheral insulin sensitivity. Together, our data identify a critical molecular signaling axis, elements of which are involved in uncoupling obesity from metabolic dysfunction.

Poor Sleep and Obesity: Concurrent Epidemics in Adolescent Youth

Poor sleep and obesity are both extraordinarily common in the US adolescent population and often occur simultaneously. This review explores the links between obesity and sleep, outlining what is known about the relationships between sleep characteristics, obesity, and cardiometabolic risk factors in youth. Sleep duration is less than optimal in teens, and decreases as age increases. This is detrimental to overall well-being and is associated with obesity in children, adolescents, and young adults. Accordingly, inadequate sleep duration is associated with poor diet quality, decreased insulin sensitivity, hyperglycemia, and prevalent cardiometabolic risk factors. Evidence suggests that poor sleep quality and altered circadian timing characterized by a preferred later sleep onset, known as “adolescent chronotype,” contributes to shortened sleep duration. Obstructive sleep apnea (OSA) occurs more frequently among youth with obesity, and is associated with autonomic nervous system activity promoting higher blood pressure, increased markers of cardiovascular disease risk, and insulin resistance. While there is a clear association between OSA and type 2 diabetes in adults, whether or not this association is prevalent in youth is unclear at this time. Interventions to improve both sleep duration and quality, and obesity in adolescents are scarce and more evidence is needed to determine if such interventions can improve obesity-related health outcomes.

Circadian misalignment induces fatty acid metabolism gene profiles and compromises insulin sensitivity in human skeletal muscle

Circadian misalignment, such as in shift work, has been associated with obesity and type 2 diabetes. However, direct effects of circadian misalignment on skeletal muscle insulin sensitivity and the muscle molecular circadian clock have never been studied in humans. Here, we investigated insulin sensitivity and muscle metabolism in 14 healthy young lean men [age 22.4 ± 2.8 years; body mass index (BMI) 22.3 ± 2.1 kg/m2 (mean ± SD)] after a 3-d control protocol and a 3.5-d misalignment protocol induced by a 12-h rapid shift of the behavioral cycle. We show that short-term circadian misalignment results in a significant decrease in muscle insulin sensitivity due to a reduced skeletal muscle nonoxidative glucose disposal (rate of disappearance: 23.7 ± 2.4 vs. 18.4 ± 1.4 mg/kg per minute; control vs. misalignment; P = 0.024). Fasting glucose and free fatty acid levels as well as sleeping metabolic rate were higher during circadian misalignment. Molecular analysis of skeletal muscle biopsies revealed that the molecular circadian clock was not aligned to the inverted behavioral cycle, and transcriptome analysis revealed the human PPAR pathway as a key player in the disturbed energy metabolism upon circadian misalignment. Our findings may provide a mechanism underlying the increased risk of type 2 diabetes among shift workers.

LDL and HDL lipoprotein subfractions in multiple sclerosis patients with decreased insulin sensitivity.

Increased metabolic and cardiovascular morbidity has been reported in multiple sclerosis (MS) patients. Previously, we have found decreased insulin sensitivity and hyperinsulinemia in a group of newly diagnosed MS patients. We hypothesize that these features may be associated with an altered lipid profile and low, intermediate, or high density lipoprotein (LDL, IDL, HDL) subclasses accelerating atherosclerosis and thus contributing to the cardiovascular risk increase in these patients. In a group of 19 newly diagnosed untreated MS patients with previously found hyperinsulinemia and insulin resistance and a matched group of 19 healthy controls, the lipoprotein subclasses profile was determined. Polyacrylamide gel electrophoresis was used to separate and measure the LDL (large LDL and small dense LDL), HDL (large, intermediate and small), and IDL (A, B and C) subclasses with the Lipoprint© System (Quantimetrix Corporation, Redondo Beach, CA, USA). No difference was found either in the conventional lipid or lipoprotein subclasses profile between the MS patients and healthy controls. We found an inverse association between the level of IDL-B with fasting insulin (r=-0.504, p=0.032), the insulin resistance estimated by homeo-static model assessment - insulin resistance (HOMA-IR) (r=-0.498, p=0.035), insulin response expressed as area under the curve (AUC; r=-0.519, p=0.027), and area above the baseline (AAB; r=-0.476, p=0.045) and positive association with insulin sensitivity estimated by insulin sensitivity index (ISI) Matsuda (r=0.470, 0.048) in MS patients, but not in healthy controls suggesting the first signs in lipoprotein subclasses profile change. Our data indicate that changes in lipoprotein profile and subclasses are preceded by insulin resistance and hyperinsulinemia in patients with newly diagnosed MS.

What Is the Role of Nutritional Supplements in Support of Total Hip Replacement and Total Knee Replacement Surgeries? A Systematic Review.

Nutritional supplements can influence outcomes for individuals undergoing major surgery, particularly in older persons whose functional reserve is limited. Accelerating recovery from total hip replacement (THR) and total knee replacement (TKR) may offer significant benefits. Therefore, we explored the role of nutritional supplements in improving recovery following THR and TKR. A systematic review was conducted to source randomized clinical trials that tested nutritional supplements in cohorts of THR or TKR patients. Our search yielded nine relevant trials. Intake of a carbohydrate-containing fluid is reported to improve insulin-like growth factor levels, reduce hunger, nausea, and length of stay, and attenuate the decrease in whole-body insulin sensitivity and endogenous glucose release. Amino acid supplementation is reported to reduce muscle atrophy and accelerate return of functional mobility. One paper reported a suppressive effect of beta-hydroxy beta-methylbutyrate, l-arginine, and l-glutamine supplementation on muscle strength loss following TKR. There is limited evidence for nutritional supplementation in THR and TKR pathways; however, the low risk profile and potential benefits to adjunctive treatment methods, such as exercise programs, suggest nutritional supplements may have a role. Optimizing nutritional status pre-operatively may help manage the surgical stress response, with a particular benefit for undernourished, frail, or elderly individuals.

Serum Creatinine Progressively Decreases with Obesity and Type 2 Diabetes in Nonhuman Primates

Low muscle mass has been associated with insulin resistance and the development of type 2 diabetes (T2DM). Serum creatinine is a metabolite of creatine present in the skeletal muscle. The creatinine concentration is stable and directly proportional to skeletal muscle mass. Low levels of creatinine have been shown to be associated with the development of T2DM. The underlying mechanism of low creatinine and its risk for the development of diabetes is not known. Nonhuman primates (NHPs), maintained on a healthy diet, frequently develop spontaneous middle-aged obesity, metabolic syndrome (MetSyn), and T2DM similar to humans. In the present study, longitudinal evaluation of the associations between creatinine and the development of obesity, MetSyn, and T2DM in 125 male rhesus monkeys were studied. In addition, 7 male monkeys with long term calorie-restriction (CR) to maintain a healthy lean mass were used as a comparison group. Creatinine decreased as age (r=-0.39, p\0.001), body fat percent (r=-0.27, p\0.001), HbA1c% (r=-32, p\0.001) increased. Decrease in insulin sensitivity was significantly (r=0.07, p\0.001) associated with a decrease in percent fat free mass. Creatinine also declined with decreasing insulin sensitivity (r=0.23, p\0.05) and fat free mass (FFM) (r=0.26, p\001) indicating that monkeys with higher lean muscle mass exhibited better insulin sensitivity. Creatinine was significantly decreased in monkeys with T2DM compared to both MetSyn and metabolically normal monkeys (p\0.001). Longitudinal data analysis showed progressive decline of creatinine with MetSyn and the development of T2DM. CR monkeys showed no significant change in creatinine throughout the lifelong duration of calorie restriction. Also unchanged during CR were fasting plasma glucose, body fat, FFM, or body weight. This is the first longitudinal study showing the association of creatinine with the development of T2DM. Serum creatinine levels declined with decrease in fat free mass and insulin sensitivity. Disclosure U.K. Chaudhari: None. J.D. Newcomb: None. B.C. Hansen: None.