Higher Serum Insulin Research Articles

Cellular Mechanisms of Saline Extract of Alligator Pepper (Zingiberaceae Aframomum melegueta) for Specific Protection against Fetal Macrosomia

Introduction: Aqueous extract of Alligator pepper is known to reduce gestational weight gain and litter size in Sprague Dawley rats. This study was done to determine the underlying hormonal and cellular mechanisms of action. Methods: We performed a controlled cross sectional intervention study with 45 female Sprague Dawley rats, which after acclimatization for two weeks, were allowed to mate with male rats for three days. Thereafter, these female rats were randomly allocated into three groups A, B and C with 15 female rats in each group. These three major groups were further randomly allocated into three subgroups so that each subgroup had 5 female rats. Pregnant female rats in Group A were injected with 2ml of normal saline intraperitoneally on day 4. Pregnant female rats in groups B and C were injected intraperitoneally with 6.7mg/Kg body weight and 13.3mg/ kg body weight of saline extract of Alligator Pepper respectively on day 4. Glucose levels were estimated with glucometer on days 7, 14, and 21. Blood was collected by intra-ventricular puncture and assayed for insulin levels. Observed differences between control and experimental groups were subjected to tests of significance. Results: Alligator pepper treated pregnant rats had significantly higher serum glucose levels than control group. Low dose and high dose Alligator pepper depressed serum insulin levels in the experimental group on day 7 and days 7 and 14 respectively Conclusion: Intraperitoneal injection of saline extract of Alligator pepper prevents first and second trimester hyper-insulinemia in pregnant Sprague Dawley rats.

Non-alcoholic fatty liver disease in patients with chronic viral hepatitis

Aim. To estimate the prevalence of non-acloholic fatty liver disease in patients with chronic hepatitis B, and the association of non-acloholic fatty liver disease with the biochemical, virological and metabolic faсtors. Methods. 53 patients with chronic hepatitis B observed in the regional hospital of infective diseases, Stavropol, at 2008-2012, were included. Patients were distributed to 2 groups according to the results of liver biopsies: group I - patients with hepatosteatosis (5%) and group II - no signs of steatosis (≤5%). Anthropometric, histological, biochemical, virological, and metabolic determinants were compared. Results. Of 53 patients, 18 (34%) liver biopsies had signs of steatosis. Patients with steatosis (group I), compared with group II, were older (43±13 vs 34.5±10.9 years, р=0.015), had higher body mass index (30±5.3 vs 22.9±4.3 kg/m 2, р=0.015), higher level of triglycerides (1.6±0.8 vs 1.06±0.7 mmol/l, р=0.014), higher level of cholesterol (5.6±0.7 vs 4.97±0.9 mmol/l, р=0.012), and higher serum insulin (13±7.9 vs 8.2±3 mkME/l, р=0.002) and leptin levels (16.2±15.6 vs 6.5±5.2 ng/ml, р=0.001). The values of HOMA (Homeostasis Model Assessment) and QUICKI (quantitative insulin sensitivity check index) indices corresponded to insulin resistance (НОМА 2.9±1.8 and 1.9±0.8, р=0.007; QUICKI 0.33±0.02 and 0.35±0.03, р=0.014). There were no differences in histological activity scores by Knodell and fibrosis scores by METAVIR scale between the groups. No reliable differences in virological parameters (viral load and HBeAg status) were obtained. Conclusion. Non-alcoholic fatty liver disease is observed in one-third of patients with hepatitis B and is associated with host metabolic factors, which correspond to the parameters of metabolic syndrome.

Antidiabetic Activity of Zinc Oxide and Silver Nanoparticles on Streptozotocin-Induced Diabetic Rats

The use of nanoparticles in medicine is an attractive proposition. In the present study, zinc oxide and silver nanoparticles were evaluated for their antidiabetic activity. Fifty male albino rats with weight 120 ± 20 and age 6 months were used. Animals were grouped as follows: control; did not receive any type of treatment, diabetic; received a single intraperitoneal dose of streptozotocin (100 mg/kg), diabetic + zinc oxide nanoparticles (ZnONPs), received single daily oral dose of 10 mg/kg ZnONPs in suspension, diabetic + silver nanoparticles (SNPs); received a single daily oral dose of SNP of 10 mg/kg in suspension and diabetic + insulin; received a single subcutaneous dose of 0.6 units/50 g body weight. Zinc oxide and silver nanoparticles induce a significant reduced blood glucose, higher serum insulin, higher glucokinase activity higher expression level of insulin, insulin receptor, GLUT-2 and glucokinase genes in diabetic rats treated with zinc oxide, silver nanoparticles and insulin. In conclusion, zinc oxide and sliver nanoparticles act as potent antidiabetic agents.

RETRACTED: Anti-diabetic activity of Swertia corymbosa (Griseb.) Wight ex C.B. Clarke aerial parts extract in streptozotocin induced diabetic rats

Swertia corymbosa locally called as Shirattakuchi have a long history of use in Ayurveda herbal preparations in Indian traditional system of medicine. It has been used in folklore medicine for the treatment of diabetes. The present study aimed to investigate the effect of the methanolic extract of Swertia corymbosa (SC) in diabetic and to analyze its chemical composition by HPLC-ESI/MS that may correlate with their pharmacological activities. The in vitro anti-diabetic activity of the extracts was measured by using α-glucosidase and α-amylase enzyme inhibitory activity. The methanolic extract of Swertia corymbosa were administered orally (125, 250 and 500 mg/kg, for 28 days) to streptozotocin-induced diabetic rats. Hypoglycemic effects, oral glucose tolerance test, change in body weight and lipid profile, biochemical analysis and histopathological examination were assessed. High-performance liquid chromatography-electrospray ionization/mass spectrometry (HPLC-ESI/MS) method was also developed to analyze the chemical composition. In vitro anti-dabetic study, the methanol extract of SC is found to be a potent inhibitor of α-glucosidase and α-amylase activity. Oral administration of SC and standard drug for 28 days caused a significant decrease in the concentrations of blood glucose level, total cholesterol (TC), serum triglycerides (TGs), low-density lipoprotein-cholesterol (LDL-C), malondialdehyde (MDA) and significant increase in the concentrations of high density lipoprotein-cholesterol (HDL-C), serum insulin and body weight. Furthermore, activities of antioxidative enzymes, including SOD, GPx, GSH and CAT were enhanced dosed dependently with SC. Histopathological studies of the pancreas showed the regeneration of the β-cells by extract which were earlier necrosed by streptozotocin. Ten major compounds such as loganic acid (1), swertiamarin (2), sweroside (3), gentiopicroside (4), isovitexin (5), amoroswertin (6), amarogentin (7), gentiacaulein (8), decussatin (9) and swertianin (10) were analyzed by HPLC-ESI/MS system. These results demonstrate that SC aerial parts of methanolic extract is an effective anti-diabetic and antioxidant activities which provides the scientific proof for the folklore medicine.

Zinc Oxide Nanoparticles Show Antidiabetic Activity in Streptozotocin-Induced Type 1 and 2 Diabetic Rats

The correlation of diabetes and an imbalance in zinc homeostasis makes zinc-based therapy an attractive proposition. In this study, zinc oxide nanoparticles were evaluated for antidiabetic effects and safety. Zinc oxide nanoparticles (1, 3 and 10 mg/kg) were tested for antidiabetic activity in streptozotocin-induced Type 1 and 2 diabetic rats. A single-dose pharmacokinetic study, cytotoxicity, hemolysis, acute and subacute toxicity tests, and mechanism-of-action studies were performed. Oral administration of zinc oxide nanoparticles resulted in significant antidiabetic effects--that is, improved glucose tolerance, higher serum insulin (70%), reduced blood glucose (29%), reduced nonesterified fatty acids (40%) and reduced triglycerides (48%). Nanoparticles were systemically absorbed resulting in elevated zinc levels in the liver, adipose tissue and pancreas. Increased insulin secretion and superoxide dismutase activity were also seen in rat insulinoma (RIN-5F) cells. Nanoparticles were safe up to a 300 mg/kg dose in rats. Zinc oxide nanoparticles are a promising antidiabetic agent warranting further studies.

Effects of Metformin on Thyroid Function in Patients of Subclinical Hypothyroidism

Background : To study the effect of metformin on thyroid function test (TFT) in patients of subclinical hypothyroidism (SCH). Methods: A total of 30 patients of SCH with TSH between 5 - 10 mIU/L were given 2, 000 mg/day of metformin for12 weeks. Patients were divided into two groups based on presence or absence of thyroid peroxidase antibody (TPO). Baseline anthropometric characteristics, fT3, fT4, TSH, serum insulin, HOMA-IR and quality of life were assessed at baseline and at 12 weeks. Results: A total of 23 patients (76.7%) who were TPO antibody negative (group 1) showed statistically significant decrease in TSH concentration at 12 weeks with no significant change in fT3 and fT4 in contrast to 7 patients (23.3%) who were TPO antibody positive (group 2). Patients in group 1 were significantly more obese, had higher serum insulin and HOMA-IR as compared to group 2. Body weight, waist circumference, BMI and percentage body fat decreases significantly in both the groups at 12 weeks as compared to baseline but on intergroup comparison this decrease was not significant statistically (P = 0.46). The HOMA-IR of group 1 was significantly higher than that of group 2 at baseline (P ? 0.02). Serum insulin and HOMA-IR decreased significantly in both the groups but again on intergroup comparison, no significant difference was observed. A positive correlation between serum TSH and serum insulin level and HOMA-IR level (r = 0.608, P ? 0.01 and r = 0.592, P ? 0.01 respectively) was observed in group 1. Conclusion: Metformin suppresses serum TSH levels without affecting fT3 and fT4 levels in SCH without any evidence of autoimmune thyroiditis. doi: http://dx.doi.org/10.4021/j em188 w

Association of TNF-1031T/C and clinical efficacy of insulin therapy in newly diagnosed type 2 diabetics

Tumor necrosis factor (TNF ) locus has been a long-standing type 2 diabetes (T2D) candidate gene. Few studies have been conducted on TNF SNP (single nucleotide polymorphism) as rs1799964 (T-1031C), rs1800630 (A-863C) and rs1799724 (C-857T) in T2D. The purpose of this study is to examine the association of TNF SNP and T2D in a case control study and further explore whether these SNPs influence the clinical efficacy of insulin therapy. A total of 109 newly diagnosed type 2 diabetics and 168 healthy individuals were recruited. Three tag SNPs (rs1799964 (T-1031C), rs1800630 (A-863C), rs1799724 (C-857T)) were selected across the TNF locus and polymerase chain reaction (PCR) directed sequencing was performed. The patients received Lispro 25 twice daily to achieve glycemic control and they were followed up for 1 year. Plasma glucose level, lipid profile, homeostatic model assessment for insulin resistance (HOMA-IR) and homeostatic model assessment for beta-cell function (HOMA-β) were compared among groups with different haplotypes of SNPs. Haplotype of TNF-1031C-863C-857C increased the risk of T2D (OR = 2.7, P < 0.05) . Comparing with homozygote of TNF-1031T-863C-857C diabetics (TCC), those carrying CCC allele had higher fasting serum insulin (16.1(12.0-20.3) mU/L) and HOMA-IR (lnHOMA-IR 1.8 ± 0.4) levels (TCC group: 10.6(8.1-14.3) mU/L and 1.42 ± 0.54 respectively, P < 0.05)). One-year insulin treatment decreased HbA1c effectively in both TCC and CCC groups (P < 0.05). However, higher HOMA-IR was still observed in CCC group than that of TCC after normoglycemia (lnHOMA-IR: 2.5(0.9-3.9) vs 1.1(0.8-1.8) respectively, P < 0.05) . Moreover HOMA-β showed no significant improvement in CCC group as it was in TCC group by the endpoint of follow-up. TNF-1031C-863C-857C is a risk haplotype for T2D. CCC carrying patients failed to achieve HOMA-β improvement. And it might be due to increased endogenous HbOMA-IR level comparing with TCC homozygote.

Insulin autoimmune syndrome (Hirata Disease) in European Caucasians taking α‐lipoic acid

Lipoic acid (LA) is a widely used nutritional supplement and is sometimes used as an adjuvant treatment for diabetic neuropathy and other conditions. Insulin autoimmune syndrome (IAS, Hirata disease) is a rare cause of spontaneous hypoglycaemia, extremely high serum insulin levels and high titres of autoantibodies against endogenous insulin despite no prior exposure to exogenous insulin. In Japanese individuals, IAS is associated with the human leucocyte antigen (HLA) HLA-DRB1*04:06 allele and often occurs upon exposure to sulphhydryl-containing compounds including LA. Only one case has been reported in Caucasians. We now report six Caucasian patients taking LA with IAS and describe a unique HLA subtype in these patients. Six Caucasian patients (M = 3; F = 3), median age 63 years, presented with spontaneous episodes of fasting and postabsorptive hypoglycaemia associated with mainly neuroglycopenic symptoms. No patient was treated with insulin or had an insulinoma. Hypoglycaemic symptoms appeared 30 and 120 days after taking lipoic acid (LA; 600 mg/day). Case histories and standard laboratory analyses were utilized. Discontinuation of LA resulted in a reduction in hypoglycaemic episodes. All patients were treated with oral or iv glucose and prednisone (12.5-25 mg/day). HLA analysis revealed the HLA-DRB1*04:03 allele in five patients, while the HLA-DRB1*04:06 allele was present in one patient. This is the first report of LA-related IAS in Caucasians who possess the HLA-DRB1*04:03 allele, implicating this allele in the genetic susceptibility to IAS in Caucasians. The greater occurrence of the HLA-DRB1*04:03 allele in Caucasian and other populations, combined with the growing use of LA in developed countries, may be a future predictor of additional cases of IAS.

Could mean platelet volume among complete blood count parameters be a surrogate marker of metabolic syndrome in pre-pubertal children?

Interest in childhood metabolic syndrome (MetS) has increased substantially due to the increasing prevalence of childhood obesity on a global scale. Early recognition of MetS is critical in order to delay the development of cardiovascular disease (CVD). In this study, we evaluated the relationship between complete blood count (CBC) parameters and MetS among pre-pubertal children which may provide evidence in support of using low cost, readily available clinical haematological parameters for the detection of MetS. A retrospective analysis was carried out on 330 (125 lean vs. 205 overweight) Turkish pre-pubertal children who attend to a paediatric outpatient clinic. Age, gender, puberty, body mass index, CBC parameters, cardiometabolic risk factors including lipid profiles, high sensitive serum reactive protein (hsCRP) and insulin resistance index calculated by homeostasis model assessment (HOMA-IR) were evaluated and compared among lean, overweight children and children with MetS. The mean age of the study population was 7.4 ± 1.9 years. In both gender, the mean values of mean corpuscular volume (MCV), mean corpuscular haemoglobin (MCH) and mean corpuscular haemoglobin concentration (MCHC) were significantly lower and red blood cell (RBC), platelet (PLT) counts were significantly higher in overweight children. Overall, 8.4% (n = 28) of patients met the criteria of MetS. Children with MetS had higher levels of PLT and lower levels of mean platelet volume (MPV). Of all the haematological parameters analysed, PLT was positively, whereas MPV was negatively correlated with MetS in girls. In addition, MPV was inversely correlated with fasting blood glucose, HOMA-IR, low density lipoprotein-cholesterol (LDL-C) and low density lipoprotein-cholesterol/high density lipoprotein-cholesterol (LDL-C/HDL-C) ratio in girls after adjusting for confounding factors. The risk analyses of MetS in terms of MPV quartiles showed that the adjusted OR (95% CI) for the lowest vs. the highest quartile was 7.71 (1.45–40.89) in girls. These data might suggest that MPV could be another feature of MetS in pre-pubertal girls and might be used as a surrogate marker for MetS in clinical settings.

Effect of exogenous leptin on thrombotic and metabolic profiles of FVB/B6 lipodystrophic mice

The adipokine leptin appears to play a pro‐thrombotic role in mice, a function that has not been examined in lipodystrophic animals. This study was designed to examine the thrombotic and metabolic effects of leptin administration in a mouse model of lipodystrophy. Eight‐week‐old, male FVB(AZIP/F1)/B6 mice (Transgenic, Tg and Wild‐type, Wt) received recombinant mouse leptin (Tg‐T, n=4; Wt‐T, n=4) or vehicle (Tg‐C, n=3; Wt‐C, n=5) via osmotic pumps over 12 days. Tg mice had a prolonged time to occlusive thrombosis compared to Wt mice (p&lt;0.05), and leptin therapy had no effect on this trait. At baseline/control, Tg mice were heavier than Wt mice (p&lt;0.05), had larger livers (p&lt;0.0001), higher serum insulin (p&lt;0.01) and plasma and liver triglyceride (p&lt;0.01 and p&lt;0.05, respectively), and undetectable leptin (p&lt;0.0001). Tg‐T mice lost weight (p&lt;0.05) and had smaller livers (p&lt;0.05), higher leptin levels (p=0.01) and reduced insulin levels (p&lt;0.05), compared to Tg‐C mice. Elevated HOMA‐IR scores in Tg‐C mice (p&lt;0.05) verified insulin resistance, ameliorated by leptin therapy. These findings confirm the hepatomegaly, insulin resistance and hyperlipidemia seen in lipodystrophic mice and the effectiveness of leptin therapy while also suggesting that lipodystrophy, at least in the AZIP/F1 mouse, exerts an anti‐thrombotic phenotype independent of the lack of leptin. Funding source: American Diabetes Association.

Plasminogen activator inhibitor-1 in children with central obesity: Effect on left ventricular function

Aim The aim of the study was to investigate the Plasminogen activator inhibitor-1 (PAI-1) expression in obese children and to clarify its role with respect to left ventricular (LV) function. Patients and methods This study included 69 obese children and adolescents, 40 lean healthy controls. Children were considered obese according to body mass index (BMI) percentile for age and sex curves of growth for our population. Each subject’s fat distribution was assessed by measuring waist hip ratio (WHR). Obese children with peripheral fat distribution were excluded. Exclusion criteria included hypertension, endocrine, cardiovascular, renal, insulin dependent or independent diabetes mellitus and smoking habits. Laboratory investigations included measurement of plasma PAI-1 antigen. Determination of total serum cholesterol, low density lipoprotein, high density lipoprotein, triglycerides, blood glucose and fasting serum insulin. Echocardiography study was obtained by two dimensionally guided M mode. Results BMI and WHR were significantly higher in obese compared to lean children (P 0.05). Plasma PAI-1 were significantly higher in obese compared to controls (P = 0.03). A significant direct correlation was revealed between PAI-1 in comparison to WHR, fasting insulin and LVM/H. Plasma PAI -1 and WHR were independent predictors of LVM/H. Conclusions Obese children with central fat distribution showed an increase in plasma PAI-1 antigen. Also PAI-1 contributes directly to the complication of obesity including type 2 diabetes and cardiovascular disease.

Glycemic variability in preterm infants receiving intermittent gastric tube feeding: Report of three cases

Late-onset hypoglycemia (day 12-16, blood glucose <50 mg/dL) was detected in three preterm infants (birthweight 998-1780 g; gestational age 27-30 weeks) by routine screening. All infants showed high serum insulin levels and extremely low ketone levels at the time of hypoglycemia. Continuous glucose monitoring was conducted at 31-34 weeks' postconceptual age when the infants were receiving intermittent gastric tube feeding with no intravenous glucose infusion. The continuous glucose monitoring results showed characteristic postprandial glucose increases and subsequent sharp deceases along with many hyper- and hypoglycemic events. This fluctuating pattern disappeared at 38-40 weeks' postconceptual age. These observations suggest that prolonged insulin oversecretion may be associated with early aggressive intravenous nutrition, and that large glycemic variability is a common feature of tube-fed preterm infants that can be explained by immature glucose homeostasis.

Metabolisches Syndrom und Prostatakarzinom

The relationship between metabolic syndrome (MS) and prostate cancer (PCA) is highly complex and harbors multiple facets not least because MS is not a single entity but represents a poorly defined inhomogeneous mixture of different diseases and conditions. Although numerous studies suggest a correlation between MS or components of MS and the development of prostate cancer, current evidence cannot be considered convincing. While diabetes appears to be inversely related to PCA, increased serum levels of triglycerides, cholesterol and insulin-like growth factor 1 (IGF-1) may be predictive for high grade disease. Further studies suggested that MS and high serum insulin levels are independent predictors of an unfavorable prognosis in patients with metastatic PCA. Early detection and improved therapeutic options have dramatically prolonged the course of the disease in advanced PCA through the last decades. As a consequence, development of MS in patients undergoing hormone therapy along with the cardiovascular risks has gained increasing relevance. Based on this evolution prevention, early detection and sustainable therapy represent an important clinical challenge to modern urologists active in urooncology.

Are higher serum IgE concentrations associated with adult cardiovascular disease?

The burden of cardiovascular disease (CVD) is high and likely to increase in future decades as a result of demographic and epidemiological transitions in populations. In the United States, CVD is responsible for 17% of national health expenditures. As the population ages, these costs are expected to continue to increase substantially [1]. Continuous identification of novel risk and protective contributors will play an important role in preventing and delaying the disease and therefore saving costs at all levels and prolonging life expectancy. Previous research studies have suggested that IgE-mediated events may play a role in the pathogenesis of CVD, involving platelet activation and arterial spasm [3]. In this context, it was aimed to determine the relationships between serum total and allergen-specific immunoglobulin E (IgE) and risk of CVD in a national population-based setting. As described elsewhere [2], United States National Health and Nutrition Examination Surveys is a national, population-based, multiyear, cross-sectional study. Information on demographics, lifestyle factors, and medical conditions including self-reported CVD with ever coronary heart disease, stroke, heart failure, heart attack, and anginawas obtainedbyhousehold interviewusingquestionnaires.Written informed consent was obtained for all subjects. In the 2005–2006 cohort, participants aged 1 year and older were tested for serum total IgE concentrations and people aged 6 and above were tested for additional allergen-specific IgE concentrations using the Pharmacia Diagnostics ImmunoCAP 1000 System (Kalamazoo,Michigan). A detailed description of the laboratorymethod can be found at NHANES 2005–2006web page (http://www.cdc.gov/nchs/data/nhanes/nhanes_05_06/al_ige_d.pdf). Since people aged 20 and over were asked in relation to cardiovascular disease conditions, participants aged 20 and above were eligible to be included in the current analysis. Effects of serum total (cutoff: 170 kU/L) and 19 allergen-specific (cutoff: 0.35 kU/L) IgE concentrations on risk of CVD were examined by t-test, generalized linear model, and logistic regression model, with Pb0.05 considered statistically significant. Total CVD was counted as having any of subtypes (binary: categorical variable) and was summed by all subtypes as number of CVD events (continuous variable). Covariates included age, sex, ethnicity, education (cutoff: high school), body mass index, high blood pressure (≥140 mm Hg for systolic blood pressure and ≥90 mm Hg for diastolic blood pressure), active smoking (cotinine as a proxy), serum insulin, serum LDL-cholesterol, and alcohol consumption (≥12 drinks in a year). Final models were also weighted. Statistical software STATAversion 12.0 (STATA, College Station, Texas, USA) was used to perform all the analyses. Since this study is secondary data analysis by extracting data from the NHANES website, no further ethics approval is required. Table 1 presents the characteristics of included participants (N=4979). Table 2 shows the effects of serum total IgE concentrations on the risk of CVD by subtypes. Apparently, people with any CVD type had higher levels of serum total IgE concentrations. In the multi-level regression modeling after full adjustments and being weighted, people with higher serum total IgE concentrationswere likely to have coronary heart disease (OR 2.02, 95%CI 1.001–4.08, P=0.05). Moreover, among all allergen-specific IgE concentrations, only serum shrimp IgE antibody was significantly associatedwith coronary heart disease (OR 2.96, 95%CI 1.06–8.28, P=0.04). However, serum shrimp antibody was not significantly associated with other CVD subtypes (Table 3). Although number of CVD events seemed to be related to higher serum shrimp IgE antibody, it did not reach significance. In the present study, the effects of serum total and seafood-specific IgE concentrations on risk of CVD subtypes and number of events were firstly examined in a national and population-based setting. It was observed that serum total IgE concentrations and serum shrimp IgE antibodywere significantlyassociatedwith an increased riskof coronary

Higher Serum Insulin Concentrations Positively Influence the Bone Mineral Density in African American Adolescents.

Puberty is a developmental stage of increased insulin resistance that also is a critical period for bone mass accrual. Historically, African Americans (AA) have lesser risk for osteoporotic fractures compared to European Americans (EA). AA also have higher incidence of insulin resistance. The possibility that bone health and insulin secretion or concentrations are linked has not been investigated. We aimed to examine the associations of bone mineral density (BMD) and bone mineral apparent density (BMAD) with insulin sensitivity and secretion in healthy adolescent girls and healthy female adults and to evaluate ethnic differences in these associations. Observational cohort design. University of Alabama at Birmingham, between January 2010 and September 2011. Healthy, female, non-smoking adolescents and young adults (14-55 years) were enrolled in this observational cohort study. Adolescents had significantly higher fasting insulin (P=0.0002), insulin area under the curve [AUC] (P= 0.0004) and lower insulin sensitivity (P=0.0005) compared to adults. Among adolescents, AA race was significantly associated with BMD (β=0.086, P=0.01) and BMAD (β=0.0075, P=0.002); however, adjusting for insulin AUC explained this difference. Insulin AUC (β=0.0006, P=0.029) and fasting insulin (β=0.0005, P=0.01) were positively associated with BMAD only in AA adolescents. Insulin AUC and fasting insulin were not significant predictors of BMD for adults. The higher insulin concentration among AA adolescents is associated with increased BMD and higher BMAD.

Effects of Metformin on Thyroid Function in Patients of Subclinical Hypothyroidism

Background : To study the effect of metformin on thyroid function test (TFT) in patients of subclinical hypothyroidism (SCH). Methods: A total of 30 patients of SCH with TSH between 5 - 10 mIU/L were given 2, 000 mg/day of metformin for12 weeks. Patients were divided into two groups based on presence or absence of thyroid peroxidase antibody (TPO). Baseline anthropometric characteristics, fT3, fT4, TSH, serum insulin, HOMA-IR and quality of life were assessed at baseline and at 12 weeks. Results: A total of 23 patients (76.7%) who were TPO antibody negative (group 1) showed statistically significant decrease in TSH concentration at 12 weeks with no significant change in fT3 and fT4 in contrast to 7 patients (23.3%) who were TPO antibody positive (group 2). Patients in group 1 were significantly more obese, had higher serum insulin and HOMA-IR as compared to group 2. Body weight, waist circumference, BMI and percentage body fat decreases significantly in both the groups at 12 weeks as compared to baseline but on intergroup comparison this decrease was not significant statistically (P = 0.46). The HOMA-IR of group 1 was significantly higher than that of group 2 at baseline (P &lt;= 0.02). Serum insulin and HOMA-IR decreased significantly in both the groups but again on intergroup comparison, no significant difference was observed. A positive correlation between serum TSH and serum insulin level and HOMA-IR level (r = 0.608, P &lt;= 0.01 and r = 0.592, P &lt;= 0.01 respectively) was observed in group 1. Conclusion: Metformin suppresses serum TSH levels without affecting fT3 and fT4 levels in SCH without any evidence of autoimmune thyroiditis. J Endocrinol Metab. 2013;3(4-5):105-110 doi: https://doi.org/10.4021/jem188w

A case of insulin antibody-induced glucose instability in an elderly woman with type 2 diabetes on hemodialysis, successfully ameliorated with liraglutide

We encountered a 68-year-old woman with type 2 diabetes who had frequent insulin-induced hypoglycemia in the morning. She had renal failure, and was on hemodialysis. The hypoglycemia in the morning was severe, induced by the small dosage of insulin, whilst she showed severe postprandial hyperglycemia. A blood test revealed high serum insulin and C-peptide levels, and a high binding rate of insulin antibody. Switching human insulin to an insulin analogue, glulisine, failed to avoid hypoglycemia. Scatchard plot analysis indicated that the high affinity site of the patient’s insulin antibody had a low affinity constant (K1) and a high binding capacity (R1) against all tested insulin, almost equivalent values reported in insulin autoimmune syndrome cases. Treatment with the glucagon-like peptide-1 analogue liraglutide ameliorated the postprandial hyperglycemia without hypoglycemia, resulting in improved glycemic stability. Furthermore, the continued use of liraglutide reduced both serum insulin level and binding rate of insulin antibody. This is the first case of using liraglutide in an insulin-antibody positive patient with renal failure on hemodialysis. Liraglutide could be an effective and safe remedy for patients with insulin antibody-related glucose instability, regardless of their renal function.

Tumor thrombus formation in two dogs with insulinomas

A 9-year-old sexually intact male Staffordshire Bull Terrier and a 9-year-old neutered male Boxer were evaluated for intermittent neurologic signs including muscle tremors, ataxia, episodic collapse, disorientation, and seizures. Both dogs had low blood glucose and high serum insulin concentrations. Results of abdominal ultrasonography were unremarkable for both dogs. Exploratory laparotomy revealed a mass that extended from the body of the pancreas into the pancreaticoduodenal vein in each dog. Marginal resection of pancreatic masses was performed, and tumor thrombi were removed via venotomy in both dogs. Histologic evaluation indicated the masses were pancreatic islet cell tumors with tumor thrombi. Clinical signs resolved following surgical resection of tumors and tumor thrombi, and the dogs were euglycemic during the follow-up period (17 and 45 months after surgery). Although gross tumor thrombus formation has been identified in humans with insulinomas, tumor thrombi have not been previously reported for dogs with insulinomas. Surgical removal of tumor thrombi via venotomy seemed to be well tolerated by the dogs. Tumor thrombus formation did not seem to adversely affect prognosis for the 2 dogs of this report.

Evaluation of a commercially available radioimmunoassay and species-specific ELISAs for measurement of high concentrations of insulin in equine serum

To evaluate a human radioimmunoassay (RIA) and equine and high-range porcine (hrp) species-specific ELISAs for the measurement of high serum insulin concentrations in ponies. Serum samples from 12 healthy nonobese ponies (7 clinically normal and 5 laminitis prone; 13 to 26 years of age; 11 mares and 1 gelding) before and after glucose, insulin, and dexamethasone administration. Intra-and interassay repeatability, freeze-thaw stability, dilutional parallelism, and assay agreement were assessed. Assay detection limits were as follows: RIA, < 389 μU/mL; equine ELISA, < 175 μU/mL; and hrp ELISA, 293 to 8,775 μU/mL. Mean ± SD intra- and interassay repeatability were respectively as follows: RIA, 6.5 ± 5.1 % and 74 ± 3.4%; equine ELISA, 10.6 ± 11.0% and 9.0 ± 4.6%; and hrp ELISA, 19.9 ± 172% and 173 ± 16.6%. Freezing and thawing affected measured concentrations. Dilutional parallelism in the RIA was only evident when insulin-depleted equine serum was used as a diluent (percentage recovery, 95.7 ± 274%); in the ELISAs, dilutional parallelism was observed when a zero calibrator was used. Agreement between RIA and equine ELISA results was good for samples containing concentrations < 175 μU of insulin/mL (bias, -18.5 ± 25.5 μU/mL; higher in RIA). At higher concentrations, assay agreement was poor between RIA and equine ELISA results (bias, -185.3 ± 98.7 μU/mL) and between RIA and hrp ELISA results (bias, 25.3 ± 183.0 μU/mL). Agreement among results of the 3 assays was variable, and dilutional parallelism was only evident with the RIA when insulin-depleted equine serum was tested. Caution is recommended when evaluating high insulin concentrations measured with the RIA or ELISAs.

Immune Regulatory Properties of Allogeneic Adipose-Derived Mesenchymal Stem Cells in the Treatment of Experimental Autoimmune Diabetes

Adipose-derived mesenchymal stem cells (ADMSCs) display immunosuppressive properties, suggesting a promising therapeutic application in several autoimmune diseases, but their role in type 1 diabetes (T1D) remains largely unexplored. The aim of this study was to investigate the immune regulatory properties of allogeneic ADMSC therapy in T cell–mediated autoimmune diabetes in NOD mice. ADMSC treatment reversed the hyperglycemia of early-onset diabetes in 78% of diabetic NOD mice, and this effect was associated with higher serum insulin, amylin, and glucagon-like peptide 1 levels compared with untreated controls. This improved outcome was associated with downregulation of the CD4+ Th1-biased immune response and expansion of regulatory T cells (Tregs) in the pancreatic lymph nodes. Within the pancreas, inflammatory cell infiltration and interferon-γ levels were reduced, while insulin, pancreatic duodenal homeobox-1, and active transforming growth factor-β1 expression were increased. In vitro, ADMSCs induced the expansion/proliferation of Tregs in a cell contact–dependent manner mediated by programmed death ligand 1. In summary, ADMSC therapy efficiently ameliorates autoimmune diabetes pathogenesis in diabetic NOD mice by attenuating the Th1 immune response concomitant with the expansion/proliferation of Tregs, thereby contributing to the maintenance of functional β-cells. Thus, this study may provide a new perspective for the development of ADMSC-based cellular therapies for T1D.