Genetic factors underlying tacrolimus intolerance after liver transplantation.

Background: Tacrolimus (FK506) is the cornerstone of immunosuppression after liver transplantation (LT), however, clinically, switching from FK506 to cyclosporine (SFTC) is common in LT patients with tacrolimus intolerance. The aim of this study was to investigate the genetic risk of patients with tacrolimus intolerance. Methods: A total of 114 LT patients were enrolled in this retrospective study. SNPs were genotyped using Infinium Human Exome-12 v1.2 BeadChip, and genome-wide gene expression levels were profiled using Agilent G4112F array. Results: SFTC was a potential risk factor of dyslipidemia (OR=4.774[1.122-20.311], p = 0.034) and insulin resistance (IR) (OR=6.25[1.451-26.916], p = 0.014), but did not affect the survival of LT patients. Differential expression analysis showed donor CYP3A5, CYP2C9, CFTR, and GSTP1, four important pharmacogenetic genes were significantly up-regulated in the tacrolimus intolerance group. Twelve SNPs of these four genes were screened to investigate the effects on tacrolimus intolerance. Regression analysis showed donor rs4646450 (OR=3.23 [1.22-8.60] per each A allele, p = 0.01), donor rs6977165 (OR=6.44 [1.09-37.87] per each C allele, p = 0.02), and donor rs776746 (OR=3.31 [1.25-8.81] per each A allele, p = 0.01) were independent risk factors of tacrolimus intolerance. Conclusions: These results suggested that SFTC was a potential risk factor for dyslipidemia and IR after LT. Besides, rs4646450, rs6977165, and rs776746 of CYP3A5 might be the underlying genetic risks of tacrolimus intolerance. This might help transplant surgeons make earlier clinical decisions about the use of immunosuppression.

Increased Insulin Concentrations During Growth Hormone Treatment in Girls With Turner Syndrome Are Ameliorated by Hormone Replacement Therapy.

Objective: Turner syndrome (TS) is characterized by complete or partial loss of one sex chromosome and is commonly associated with short stature, metabolic changes (such as central obesity, abnormal glucose tolerance and high triglycerides) and premature ovarian insufficiency (POI). Primary management of TS during childhood and adolescence comprises treatment with human growth hormone (hGH) and, in cases with early loss of ovarian function, hormone replacement therapy (HRT). Given that metabolic parameters are altered when HRT is applied during menopause, we analyzed whether metabolic changes might be positively or negatively affected within 10 years after HRT and/or hGH in girls with TS. Design: Observational study. Methods: Data were collected from the medical records of 31 girls with TS attending two endocrinologic centers in Germany between 2000 and 2020. Descriptive statistics are reported as the mean ± SEM or percentages. Results: The mean age at first presentation was 99.06 ± 8.07 months, the mean height was 115.8 ± 3.94 cm, and the mean BMI 19.0 ± 0.99 was kg/m2. Treatment with hGH was given to 96.8% of the girls, starting at an average age of 99.06 ± 8.70 months, and was continued for 67.53 ± 6.28 months. HRT was administered to 80.6% of all patients and was started at a mean age of 164.4 ± 4.54 months. During the follow-up, we did not observe any significant absolute changes in lipid parameters, but we detected beneficial effects of childhood hGH: significantly lower cholesterol (-0.206/month; p = 0.006), lower low density lipoprotein cholesterol (-0.216/month; p = 0.004), and higher high density lipoprotein cholesterol (+0.095/month; p = 0.048). Insulin concentrations, showed a significant increase attributable to hGH treatment (+0.206/month; p = 0.003), which was ameliorated by concomitant or subsequent HRT (-0.143/month; p = 0.039). Conclusion: Treatment with hGH and HRT is provided to most girls with TS. Metabolic effects are associated with both modalities. Monitoring of metabolic changes appears to be important to detect unfavorable effects, and could guide treatment adjustment and duration.

Blood pressure control in type 2 diabetes mellitus with arterial hypertension. The important ancillary role of SGLT2-inhibitors and GLP1-receptor agonists.

Type 2 diabetes mellitus and arterial hypertension are major cardiovascular risks factors which shares metabolic and haemodynamic abnormalities as well as pathophysiological mechanisms. The simultaneous presence of diabetes and arterial hypertension increases the risk of left ventricular hypertrophy, congestive heart failure, and stroke, as compared to either condition alone. A number of guidelines recommend lifestyle measures such as salt restriction, weight reduction and ideal body weight mainteinance, regular physical activity and smoking cessation, together with moderation of alcohol consumption and high intake of vegetables and fruits, as the basis for reduction of blood pressure and prevention of CV diseases. Despite the availability of multiple drugs effective for hypertension, BP targets are reached in only 50 % of patients, with even fewer individuals with T2DM-achieving goals. It is established that new emerging classes of type 2 diabetes mellitus treatment, SGLT2 inhibitors and GLP1-receptor agonists, are efficacious on glucose control, and safe in reducing HbA1c significantly, without increasing hypoglycemic episodes. Furthermore, in recent years, many CVOT trials have demonstrated, using GLP1-RA or SGLT2-inihibitors compared to placebo (in combination with the usual diabetes medications) important benefits on reducing MACE (cardio-cerebral vascular events) in the diabetic population. In this hypothesis-driven review, we have examined the anti-hypertensive effects of these novel molecules of the two different classes, in the diabetic population, and suggest that they could have an interesting ancillary role in controlling blood pressure in type 2 diabetic patients.

Ghrelin, resistin and insulin in obese diabetic women in Wad-Madani, Sudan.

BACKGROUND: Obesity in the Sudan is increasing at alarming rate with the tendency of reaching an epidemic proportion in women. It is commonly associated with type 2 diabetes (T2D). Some adipokine hormones such as resistin are associated with obesity. OBJECTIVES: To study how the levels of resistin, ghrelin and insulin are associated with obesity,fat distribution and (T2D) and to ascertain any interrelationships between them. SUBJECTS AND METHODS: 150 women, age ≥18 years old, resident in Wad-Madani town, Sudan were participated in the study. They were divided into 3 groups according to body mass index (BMI) value: I (normal weight), II (overweight) and III (obese diabetic). Fasting serum resistin and ghrelin concentrations were measured using ELISA method. Insulin levels were determined by radioimmunoassay(RIA). RESULTS: The mean±SD levels of resistin 5.80±4.91ng/mL,Ghrelin107.60±26.67pg/M and Insulin 11.92±8.54mLU/ml in obese diabetic were found to be greater than in normal or overweight women. In normal weight values were 3.07±2.15 ng/mL 83.30±13.38pg/mL, and 6.62±6.77mLU/ml for resistini, ghrelin and Insulin, respectively. Values for overweight women 3.64±2.63 pg/mL 90±17.35 pg/mL and 8.13±7.54 mLU/ml for resistin, ghrelin and insulin respectively. CONCLUSIONS AND RECOMMENDATIONS: Increased BMI, waist circumference (WC) and hormones (ghrelin and resistin) were associated with insulin resistance. Further studies are needed to accept or refute these findings.

High glucose inhibits myogenesis and induces insulin resistance by down-regulating AKT signaling.

BACKGROUND: A high glucose level is usually considered to be the factor that induces tissue and cell dysfunction and damage, commonly known as "glucose toxicity". OBJECTIVE: This study aimed to explore the effects and the potential molecular mechanisms of high glucose on myoblast differentiation and insulin sensitivity. MATERIALS AND METHODS: C2C12 cells were cultured in differentiation medium containing 25, 40, or 60 mM glucose for 1, 3, or 5 days. E-MHC positive area and GLUT4 fluorescence were evaluated through Immunofluorescence. The expression of Myf5, MyoD, myogenin were measured by performing western blot and qRT-PCR. The protein expression of GLUT4 on cell membrane and glucose uptake in C2C12 myotubes were measured through western blot and 2-NBDG assay. AKT activator SC79 and inhibitor MK2206 was utilized to reveal the important role of AKT signaling in myogenesis and insulin sensitivity inhibited by high glucose. RESULTS: 60 mM glucose inhibits myogenesis by decreasing the expression of MyoD and myogenin, and induces insulin resistance by reducing both basal and insulin-stimulated GLUT4 expressions and glucose uptakes. The influences of high glucose on myogenesis and IR was related to decreased AKT activation. SC79 rescued the inhibition of high glucose on myogenesis and attenuated IR. MK2206 inhibits the myogenic differentiation and induces IR. CONCLUSION: The present study reveals that high glucose inhibited myogenisis accompanied by inducing IR, through AKT signaling inhibition, which may help to further research for resisting degenerative muscular diseases caused by glucose metabolism disorders.

The Emerging Roles of Microparticles in Diabetic Nephropathy.

Microparticles (MPs) are a type of extracellular vesicles (EVs) shed from the outward budding of plasma membranes during cell apoptosis and/or activation. These microsized particles then release specific contents (e.g., lipids, proteins, microRNAs) which are active participants in a wide range of both physiological and pathological processes at the molecular level, e.g., coagulation and angiogenesis, inflammation, immune responses. Research limitations, such as confusing nomenclature and overlapping classification, have impeded our comprehension of these tiny molecules. Diabetic nephropathy (DN) is currently the greatest contributor to end-stage renal diseases (ESRD) worldwide, and its public health impact will continue to grow due to the persistent increase in the prevalence of diabetes mellitus (DM). MPs have recently been considered as potentially involved in DN onset and progression, and this review juxtaposes some of the research updates about the possible mechanisms from several relevant aspects and insights into the therapeutic perspectives of MPs in clinical management and pharmacological treatment of DN patients.

A Study Examining the Effect of a Short Bout of Postprandial Walking on the Glycemic Effect of a Meal: Type 1 Diabetes.

OBJECTIVE: The purpose of this pilot study was to determine whether 15 minutes of postprandial walking has an effect on the glycemic response to a breakfast beverage in individuals with type 1 diabetes (T1DM). METHODS: Seven participants, aged 22.3 ± 4.3 years, with T1DM using intensive insulin therapy completed 2 days of data collection. On day 1, participants measured baseline fasting blood glucose (BG) with a glucometer, consumed an 8-ounce Boost® beverage (41 grams carbohydrate), administered a bolus of insulin according to the carbohydrate load and fasting BG, and sat quietly, repeating BG measurements 15, 30, 60, 90, and 120 minutes after consumption. On day 2, participants repeated the protocol, but walked 15 minutes at 50% to 60% maximum heart rate immediately after beverage consumption. RESULTS: The difference between peak and baseline (peak - baseline) BG and incremental glucose area under the curve (iAUC) were lower in all but one participant on the walking compared to the sedentary day. Mean peak - baseline BG was significantly lower on the walking day compared to the sedentary day (6.4 ± 1.2 vs 14.4 ± 3.4 mmol/L, respectively, p = 0.016) as was the iAUC, (241.1 ± 155.8 vs 468.6 ± 94.5 mmol/L/120 min, respectively, p = 0.031). CONCLUSIONS: Fifteen minutes of postprandial walking can blunt the spike in BG and overall glycemic response to a breakfast beverage in young adults with T1DM and may be an effective and realistic component in the management of T1DM.

Effects of intermittent fasting on health markers in those with type 2 diabetes: A pilot study.

AIM: To determine the short-term biochemical effects and clinical tolerability of intermittent fasting (IF) in adults with type 2 diabetes mellitus (T2DM). METHODS: We describe a three-phase observational study (baseline 2 wk, intervention 2 wk, follow-up 2 wk) designed to determine the clinical, biochemical, and tolerability of IF in community-dwelling volunteer adults with T2DM. Biochemical, anthropometric, and physical activity measurements (using the Yale Physical Activity Survey) were taken at the end of each phase. Participants reported morning, afternoon and evening self-monitored blood glucose (SMBG) and fasting duration on a daily basis throughout all study stages, in addition to completing a remote food photography diary three times within each study phase. Fasting blood samples were collected on the final days of each study phase. RESULTS: At baseline, the ten participants had a confirmed diagnosis of T2DM and were all taking metformin, and on average were obese [mean body mass index (BMI) 36.90 kg/m2]. We report here that a short-term period of IF in a small group of individuals with T2DM led to significant group decreases in weight (-1.395 kg, P = 0.009), BMI (-0.517, P = 0.013), and at-target morning glucose (SMBG). Although not a study requirement, all participants preferentially chose eating hours starting in the midafternoon. There was a significant increase (P < 0.001) in daily hours fasted in the IF phase (+5.22 h), although few attained the 18-20 h fasting goal (mean 16.82 ± 1.18). The increased fasting duration improved at-goal (< 7.0 mmol/L) morning SMBG to 34.1%, from a baseline of 13.8%. Ordinal Logistic Regression models revealed a positive relationship between the increase in hours fasted and fasting glucose reaching target values (χ2 likelihood ratio = 8.36, P = 0.004) but not for afternoon or evening SMBG (all P > 0.1). Postprandial SMBGs were also improved during the IF phase, with 60.5% readings below 9.05 mmol/L, compared to 52.6% at baseline, and with less glucose variation. Neither insulin resistance (HOMA-IR), nor inflammatory markers (C-reactive protein) normalized during the IF phase. IF led to an overall spontaneous decrease in caloric intake as measured by food photography (Remote Food Photography Method). The data demonstrated discernable trends during IF for lower energy, carbohydrate, and fat intake when compared to baseline. Physical activity, collected by a standardized measurement tool (Yale Physical Activity Survey), increased during the intervention phase and subsequently decreased in the follow-up phase. IF was well tolerated in the majority of individuals with 6/10 participants stating they would continue with the IF regimen after the completion of the study, in a full or modified capacity (i.e., every other day or reduced fasting hours). CONCLUSION: The results from this pilot study indicate that short-term daily IF may be a safe, tolerable, dietary intervention in T2DM patients that may improve key outcomes including body weight, fasting glucose and postprandial variability. These findings should be viewed as exploratory, and a larger, longer study is necessary to corroborate these findings.

Effect of berberine on the ratio of high-molecular weight adiponectin to total adiponectin and adiponectin receptors expressions in high-fat diet fed rats.

OBJECTIVE: To assess the effects of berberine (BBR) on high-molecular weight (HMW) adiponectin and adiponectin receptors (adipoR1/adipoR2) expressions in high-fat (HF) diet fed rats. METHODS: Forty Wistar male rats were randomly assigned into a normal diet fed group and three HF diet (fat for 45% calories) fed groups (n=10 for each group). All rats underwent 12 weeks of feeding. After 4 weeks feeding, rats in the two of three HF diet fed groups were treated with 150 mg·kg-1·day-1 BBR (HF+LBBR group) and 380 mg·kg-1·day-1 BBR (HF+HBBR group) by gavage once a day respectively for the next 8 weeks while the rats in other groups treated with vehicle (NF+Veh and HF+Veh). Body weight and food intake were observed and recorded on daily basis. At the end of 12 weeks, the blood, liver, epididymal fat tissues and quadriceps femoris muscles were collected. Fasting insulin, plasma fasting glucose, serum free fatty acid (FFA), total adiponectin and HMW adiponectin levels were measured by enzyme linked immunosorbent assay method. Glucose tolerance test (GTT) and insulin tolerance test (ITT) were performed to determine the insulinsensitizing. Meanwhile the homeostasis model assessment (HOMA) method was used to determine insulin resistance (HOMA-IR). The expressions of adipoR1, adipoR2 and adenosine monophophate activated protein kinase (AMPK) phosphorylation level in skeletal muscle and liver tissue were detected by Western blot. Liver and kidney toxicity were evaluated during treatment. RESULTS: The body weight of rats in high- or low-dose BBR group reduced as well as HOMA-IR, FFA concentrations and fasting insulin levels decreased compared with HF+Veh group (P<0.05). BBR also increased the ratio of HMW to total adiponectin in high fat-fed rats compared with rats in the HF+Veh group. High- and low-dose BBR increased adipoR1 expression in skeletal muscle by over 6- and 2-fold (P<0.05), respectively, and high-dose BBR also increased adipoR2 expression in liver tissue by over 2-fold (P<0.05). BBR significantly increased AMPK phosphorylation in HF diet rats compared with normal diet rats (P<0.05). The ratio of HMW to total adiponectin was inversely correlated with HOMA-IR (r=-0.52, P=0.001). Meantime, no liver and kidney toxicity was found in high fat-fed rats that treated by BBR. CONCLUSION: Berberine may improve insulin resistance by increasing the expression of adiponectin receptors and the ratio of HMW to total adiponectin.

Polimorfismo GLY972ARG del Gen sustrato de receptor de insulina 1 en pre-púberes con riesgo cardiometabólico / GLY972ARG plymorphism in the insulin receptor substrate 1 Gene in prepubertal children with cardiometabolic risk

Introducción: El sustrato del receptor de insulina 1 (IRS1) es un componente importante de la cascada de transducción de señales de la insulina y podría estar relacionado con los trastornos metabólicos asociados al síndrome metabólico. Objetivo: Evaluar el papel del polimorfismo Gly972Arg del gen IRS1 con factores de riesgo cardiometabólicos en niños pre-púberes. Metodología: Se estudiaron 279 niños con edades comprendidas entre 2-12 años, clasificados según los parámetros antropométricos y bioquímicos en: a) niños obesos sin RI (n=135), b) niños obesos con RI (n=80) y c) niños controles sanos (n=64). A cada niño se le realizó una extracción de sangre en ayunas y una postprandial, para determinar glicemia e insulina basal y postprandial, triglicéridos, colesterol total y fraccionado y la frecuencia genotípica del SNP Gly972Arg. Resultados: Se observó que 37,5% de los niños presentó RI; 9,6% hiperglicemia en ayunas; 27,3% hipertrigliceridemia y 50,46% bajos niveles de HDL-c. La frecuencia genotípica fue 89% genotipo Gly/Gly y 11% genotipo Gly/Arg. Se encontró diferencia significativa en la distribución de los diferentes genotipos del gen de IRS1 en los niños con sobrepeso/obesidad sin RI y niños con sobrepeso/obesidad con RI con respecto al grupo control (OR= 4,47; IC 95%=0,96-16,92; p < 0,05) y (OR= 4,43; IC 95%=0,93-21,00; p < 0,05) respectivamente. Conclusión: Se observó una asociación entre la presencia del genotipo Gly/Arg del gen IRS1 con sobrepeso/obesidad (factor de riesgo cardiometabólico) en los niños del estudio, presentando estos niños 4 veces más riesgos a presentar sobrepeso/obesidad que los niños con el genotipo Gly/Gly.

Introduction: Insulin receptor substrate 1 (IRS-1) is an important component of the insulin signal transduction cascade and could be related with metabolic disorders associated with metabolic syndrome (MS). Aim: Evaluate the role of the Gly972Arg polymorphism in the IRS1 gene in prepubertal children with cardiometabolic risk factors. Methods: We studied 279 children between 2-12 years of age, divided in groups 3 groups: a) obese children without insulin resistance (IR) (n=135), b) obese children with IR (n=80) and c) healthy children as controls (n=64). Basal and postprandial glucose, insulin, triglycerides, total and fractionated cholesterol and genotype frequency of the Gly972Arg SNP were determined in fasting and postprandial samples in each child. Results: 37.5% of the children had IR; in the fasting state, 9.6% had hyperglycemia, 27.3% hypertriglyceridemia and 50.46 % low HDL-C. The genotypic frequency was 89% for the Gly / Gly genotype and 11% Gly / Arg genotype. Significant difference was found in the distribution of the different genotypes of the IRS1 gene in children with overweight/obesity without IR and children with overweight/obesity with IR compared to the control group (OR = 4.47;CI 95% = 0.96-16.92; p <0.05) and (OR = 4.43; CI 95%= 0.93 - 21.00, p <0.05) respectively. Conclusion: Association between the presence of Gly/Arg genotype of the IRS1 gene with overweight/obesity (cardiometabolic risk factor) was observed in the studied children. These children were four times more likely to be overweight/obese than children with Gly / Gly genotype.

Study on relationship of serum level of 25 hydroxyl vitamin D3 with insulin resistance and bone metabolism in diabetic patients with chronic kidney disease / 中国糖尿病杂志

Objective To investigate the relationship of serum level of 25 hydroxyl vitamin D3 [25(OH)D3 ] with insulin resistance (IR) and bone metabolism in diabetic patients with chronic kidney disease (CKD) . Methods From April 2012 to February 2014 ,200 diabetic patients with CKD were selected ,and they were divided into three groups according to eGFR:60 subjects in eGFR> 45 ~ 59 ml/(min?1.73 m2 ) group ,60 subjects in eGFR 30~44 ml/(min?1.73 m2 ) group and 80 subjects in eGFR 15~29 ml/(min?1.73 m2 ) group .Clinical features ,IR and indexes of bone metabolism among different groups were compared .Indexes of bone metabolism between two groups with different HOMA‐IR level were also compared . Results The difference of age ,gender ,BMI ,blood pressure and FPG among three groups had no statistical significance (P> 0 .05) .The difference of duration of diabetes mellitus ,duration of CKD ,urine protein ,blood lipid ,eGFR ,HbA1c ,FIns ,HOMA‐IR and indexes of bone metabolism had statistical significance (P< 0.05) .In 200 patients ,there were 129 patients (IR) with HOMA‐IR≥3.28 ,and 71 patients (non‐insulin resistance) with HOMA‐IR<3.28 .The difference of bone metabolism indexes between two groups had statistical significance (P<0.05) .The serum level of 25(OH)D3 was positively related to HOMA‐IR ,bone mineral density (BMD) at left proximal femur , BMD at lumbar ,P ,Ca and BSAP (P<0.05);while it was negatively related to osteoprotegerin and PTH (P<0 .05) . Conclusion The serum level of 25 (OH )D3 has relevance to IR and bone metabolism in diabetic patients with CKD .

Effects of the insulin sensitizer pioglitazone on menstrual irregularity, insulin resistance and hyperandrogenism in young women with polycystic ovary syndrome.

BACKGROUND: Polycystic ovary syndrome (PCOS) is the most common endocrine cause of menstrual irregularities, hirsutism and acne. Women with PCOS present elevated plasma insulin levels, both fasting and after a glucose load, as an indirect evidence of insulin resistance. PCOS women may also present hypertension, low levels of HDL cholesterol, hypertriglyceridemia, visceral obesity and a higher level of CRP and fibrinogen that can predict an atherosclerotic risk. METHODS: This study was carried out on 15 young women with PCOS selected according to the 2003 diagnostic criteria of The Rotterdam Consensus Statement and 15 Control women. PCOS women were treated with pioglitazone 30 mg/day and at the beginning and after 6 months of treatment were evaluated: menstrual cycle trend, hirsutism and acne, total cholesterolemia and HDL, triglyceridemia, fibrinogenemia, C-reactive protein, oral glucose tolerance test, glycated hemoglobin, FSH, LH, 17OH-progesterone, 17ß-estradiol, free and total testosterone, SHBG, DHEA-S, Δ4-androstenedione and adiponectin. RESULTS AND DISCUSSION: Treatment with pioglitazone improves the irregularities of menses and hirsutism. Six months of treatment modify other parameters linked with a higher risk of type 2 diabetes mellitus and cardiovascular diseases: adiponectin increased with reduction of insulin resistance while fibrinogen and CRP levels decreased.

Perioperative nutritional support.

The relationship between preoperative malnutrition and morbi-mortality has been documented for years. Despite the existence of tools that allow its detection, and therefore treat this entity, their introduction into clinical practice is not wide-spread. Both perioperative insulin resistance and hyperglycemia are associated with increased perioperative morbidity and length of hospital stay. The intake of carbohydrate-rich drinks 2-4h prior to surgery reduces insulin resistance. In the immediate postoperative period, the enteral route is safe and well tolerated and its early use reduces hospital stay and postoperative complications compared with parenteral nutritional support. Inmunonutrition has been proven effective to decrease postoperative complications and hospital stay. In view of these data we opted for the adoption of these measures replacing bowel rest and the indiscriminate use of postoperative parenteral nutrition.

Efeito do exercício físico sobre marcadores inflamatórios na resistência à insulina / Effect of exercise on inflammatory markers on insulin resistance

Obesidade e processos inflamatórios crônicos podem levar a um aumento dos níveis sanguíneos de algumas moléculas responsáveis por mediar a inflamação, denominadas citocinas. O aumento em até 3 vezes desses marcadores em relação ao valor normal, recebe o nome de inflamação crônica de baixo grau e tem sido considerada um dos principais fatores de risco para o desenvolvimento de patologias como a Resistência à Insulina, do Diabetes Mellitus tipo 2 (DM2) e da síndrome Metabólica. Medicamentos com efeito anti-inflamatório não estão autorizados para o tratamento de inflamações crônicas e o exercício físico vem sendo utilizado como tratamento alternativo com resultados positivos. O exercício físico estimula, através da contração muscular, a produção de interleucina-6 (IL-6), que promove um ambiente anti-inflamatório sendo capaz de melhorar a transmissão do sinal insulínico. O exercício também aumenta a quantidade de GLUT4, estimulando a captação de glicose. Portanto, o exercício físico é capaz de reduzir a produção e a ação de marcadores inflamatórios, melhorando um quadro de resistência insulínica, além de poder prevenir contra o desenvolvimento do DM2. É também uma ferramenta extremamente importante no tratamento do DM2, visto que promove um aumento da captação de glicose por vias independentes à da insulina

Obesity and chronic inflammatory processes may lead to increased blood levels of some molecules responsible for mediating inflammation, called cytokines. The increase in these markers up to 3 times compared to the normal value, is called low-grade chronic inflammation and has been considered one of the main risk factors for the development of pathologies such as Insulin Resistance, Type 2 Diabetes Mellitus (T2DM) and metabolic syndrome. Drugs with anti-inflammatory effect are not authorized for the treatment of chronic inflammation and exercise has been used as an alternative treatment with positive results. The exercise stimulates muscular contraction by the production of interleukin-6 (IL-6) promotes antiinflammatory environment being able to improve the transmission of the insulin signal. The exercise also increases the amount of GLUT4 by stimulating glucose uptake. Therefore, exercise can reduce the production and action of inflammatory markers, a framework for improving insulin resistance, and can prevent against the development of T2DM. It is also an extremely important tool for the treatment of type 2 diabetes, since it promotes an increased uptake of glucose by the independent pathways of insulin

Relationship between benign prostatic hyperplasia and insulin resistance in elderly men of different ages / 中华老年医学杂志

Objective To explore the relationship between insulin resistance (IR) and benign prostatic hyperplasia (BPH) in elderly men of different ages.Methods Totally 100 elderly outpatients with BPH in our hospital from January 2012 to June 2012 were recruited in this study.All patients were divided into 2 groups according to age:60-75 years(n =52) and 76-93 years (n=48).Fasting plasma glucose,fasting insulin (FINS) and prostate specific antigen (PSA) were assayed.Insulin resistance index (IRI) was calculated by using the homeostasis model assessment-insulin resistance (HOMA2-IR) software.The body height,body weight,waist circumference were measured and the body mass index (BMI) was calculated.Prostate volume (PV) was measured by abdominal ultrasound.Clinical data were compared between the two groups.Based on HOMA2-IR,patients were divided into insulin resistant group (IR＞ 1.7) and non insulin resistant group (IR＜ 1.7).Serum PSA,PV and waist circumference were compared between the two groups.Results The waist circumference and PV were significantly larger in insulin resistant group than in non-insulin resistant group [(96.6± 7.2) cm vs.(93.1±8.9) cm,(50.0±9.0) ml vs.(46.1±7.8) ml,respectively,P＜0.01,0.05].However,the PSA level was lower in insulin resistant group than in non-insulin resistant group [(1.44±1.08) μg/L vs.(2.1 ±2.0)μg/L,P＜0.05],and no correlation was found between HOMA-IR and PV.There was no correlation between serum PSA levels and PV in patients aged 76-93 years.In patients aged 60-75 years,PSA level was positively correlated with PV (r =0.52,P＜0.05) and negatively correlated with HOMA-IR (r=0.38,P＜0.05).Conclusions Serum PSA level is positively correlated with PV and negatively correlated with HOMA IR in BPH patients under 75 years old.

El sobrepeso y la obesidad como un problema de salud / Overweight and obesity as an universal health problem

Se destaca al sobrepeso y obesidad como el principal condicionante actual de patología crónica no transmisible. Se identifican y discuten las principales comorbilidades asociadas al sobrepeso y obesidad, analizando las evidencias que las apoyan. Se destaca el rol de la adiposidad en la etiopatogenia del síndrome metabólico y en forma muy especial de la DM. Se analiza la asociación entre indicadores de masa corporal y tejido adiposo y tasas de mortalidad, destacando un significativo incremento de la mortalidad a medida que la masa corporal o grasa se incrementa. Se destacan los rangos asociados a la menor mortalidad, nadires que fundamentan los rangos de peso normal. Se discute en forma separada la asociación entre sobrepeso yobesidad en la infancia y adolescencia y salud, en especial su posible rol en la incidencia de patologías crónicas al alcanzar la adultez.

The article highlights overweight and obesity as the main factor in some current chronic diseases. Also it identifies and discusses major co-morbidities associated with overweight and obesity, analyzing the evidence that support them. The role of adiposity in the pathogenesis of metabolic syndrome especially in the development of mellitus diabetes 2 is discussed. We analyze the association between indicators of body mass and adipose tissue and mortality, highlighting a significant increase in mortality as the fat body mass increases and shows the range associated with lower mortality, basing the normal weight ranges. Will be discussing separately the association between overweight and obesity in childhood and adolescence health, especially its possible role in the incidence of chronic diseases that will develop at adulthood.

Benefits of fixed-doses combination for type 2 diabetes / 中华内分泌代谢杂志

With consideration of optimizing treatment of type 2 diabetes,early combination therapy has been deeply explored, with fixed-doses combination therapy as a available preparation for easier administration. Avandamet ( rosiglitazone maleate and metformin HC1) is widely used in clinical treatment, providing comprehensive and sustained long-term efficacy and confirmed safety with lower hypoglycemia risk, and also high convenience and compliance. Combination of rosiglitazone and metformin improves the dual core defects of type 2 diabetes, targeting FPG and PPG reduction through decreasing hepatic glucose output, and improving peripheral insulin resistance, especially increasing skeletal muscle's utilization of glucose respectively. Large-scale clinical trials gave more confidence to Avandamet. Recently, RECORD study indicated that rosiglitazone in combination with metformin achieved long-term antihyperglycemic efficacy in 5 years period, superior to sulphanylureas plus metformin. Additionally, lower risk of hypoglycemia is another benefit of Avandamet. In conclusion,early use of Avandamet can yield much more benefits than monotherapy and late administration, in consistent with implication of evidence-based trial, guideline, and clinical experiences.

Recent advances in the study of lipocalin-2 / 复旦学报（医学版）

Lipocalin-2 is an adipocytokine secreted mainly by adipose tissue. Increasing lines of evidence suggest that lipocalin-2 is an inflammatory factor associated with insulin resistence, obesity and its complications. The precise mechanism of the development of obesity-related disorders induced by lipocalin-2 is not very clear, however, it may be a useful target in drug therapy for obesity-related metabolic and cardiovascular diseases.

Establishment of hyperinsulinemic euglycemic clamp technique and the reference value of insulin sensitivity index in Chinese / 中华临床营养杂志

Objective To establish the technique of hyperinsulinemic euglycemic clamp and to study the reference value of insulin sensitivity index in healthy Chinese. Methods According to the feedback mathematical model developed by DeFronzo, the technique of hyperinsulinemic euglycemic clamp was used in 90 healthy Chi- nese [ male:female =71 = 19; age; (28. 3±6. 1) years; body mass index (20. 9±1.5) kg/m2 ] to study die glu-cose metabolized rate. Blood samples were obtained at timed intervals in the fasting state and during the clamp for the measurement of glucose, insulin and C peptide. Results During the clamp tests, the blood glucose levels were con-trolled within 10% of target value. The coefficient of variation of glucose levels was 3. 8% 0.1%. In the steady state, the insulin sensitivity index (glucose metabolized rate, M value ) was (7.78±2.30) mg· kg-1 min-1, which was distributed normally. The lowest quartile of M value was 6. 286 mg·kg -1 min-1'. The coefficient of variation of M value was 9.4%±2.8%. Conclusion The technique of hyperinsulinemic euglycemic clamp and the reference value of insulin sensitivity index in healthy Chinese are successfully established in our center.

The effect of rosiglitazone on non-alcoholic fatty liver in experimental rats / 中国糖尿病杂志

Objective To investigate the effect of rosiglitazone on non-alcoholic fatty liver (NA and to explore the relationship between insulin resistance and NAFL. Methods Animal model of NAFL was established by feeding Sprague-Dawley rats a high-fat diet for 8 weeks. The model rats were then randomized into rosiglitazone-treated and untreated groups. The animals were sacrificed after being treated with rosiglitazone or vehicle for 4 weeks. The histological changes of liver were examined, and liver function, fasting plasma glucose, fasting serum insulin, serum lipid profile, leptin, and adiponectin were measured. Results As compared with untreated group, hepatic steatosis and liver function were significantly improved in rosiglitazone-treated group. Alanine aminotransferase (ALT) was 54±19 U/L vs 101±24 U/L, aspartic acid aminotransferase (AST) 151±37 U/L vs 198±48 U/L, and alkaline phosphatase (ALP) 87±16 U/L vs 115±39 U/L, respectively (P<0.01). Serum adiponectin level was higher, and serum leptin level and insulin resistance index (HOMA-IR) were lower in rosiglitazone-treated group than in untreated group. HOMA-IR was 6.9±1.8 vs 12.0±1.2 (P<0.01). Serum triglyceride, total cholesterol and low density lipoprotein-cholesterol level were significantly decreased in rosiglitazone-treated group as compared with untreated group (P<0.01). Conclusions Insulin resistance might play important role in the pathogenesis of NAFL. Rosiglitazone effectively reverses NAFL in animal model.