The Influence of the Pro12Ala Mutation of PPARγ2 Receptor Gene on β-cells Restoration and Insulin Resistance in Type 2 Diabetes with Hypertension

The aim of this investigation was to determine whether a PPAR72 Prol2Ala polymorphism was associated with insulin resistance, β-cellfunction and hypertension in Chinese populations. 289 unrelated Chinese subjects first diagnosed Type 2 diabetes （HbAC1〈6.0） were investigated, including 132 hypertensive diabetic （HTD） subjects, 157 normotensive diabetic （NTD） subjects. Blood pressure and anthropometric measurements were collected from all participants, as well as several venous blood samples during oral glucose tolerance test （OGTT）. Biochemical measurements （high-density lipoprotein （HDL） and low-density lipoprotein-cholesterol （LDL）, triglycerides） and PPARγ2 Pro12Ala genotype were also determined. And insulin resistance and β-cells function was assessed by HOMA-IR and HOMA-β respectively. The frequency of subjects bearing the Pro12Ala was lower in the hypertension group （3. 03 %） than in the non-hypertension group （5.7 %） （P〈0.05） after adjusted for age, BMI and gender. Hypertensive diabetic Pro12Ala subjects had lower fasting plasma glucose level （P=0. 0127）, and better glucose tolerance 60 min after oral glucose （P=0. 0361）. Moreover, plasma insulin concentrations at 60 min was lower than those without A variant （P = 0. 0275）, and both hypertensive Ala/Pro in HOMA-β （P ： 0. 0455） and AUC for insulin （P=0. 0473） were higher, and HOMA-IR was lower （P=0. 0375） as compared with hypertensive Pro/Pro subjects. No association was observed between Prol2Ala genotype and BMI, total cholesterol, HDL- cholesterol or triglycerides in either group. Our findings suggested that the Ala 12 allele of the PPARγ2 gene may improve insulin resistance and ameliorate β-cell function reserves in T2DM with hypertension, and protect patients from hypertension in T2DM. As an important thrifty gene, environment factors may exerts an effect of PPARγ2 on glucose homeostasis and insulin resistance.

Effect of Prepared Rhubarb on Insulin Resistance in Patients With Pregnancy Induced Hypertension

Objective: To investigate the effect of prepared rhubarb on insulin resistance in patients with pregnancy induced hypertension (PIH) and its mechanism. Methods: All the 92 patients accepted 75 g oral glucose tolerance test (OGTT) and insulin release test before and after treatment. These patients were divided into two groups (treated group and control group). Prepared rhubarb and nifedipine were given to the treated group, while nifedipine was given to the control group alone. Circulating endothelial cell (CEC), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) were measured and glucose area under curve (GAUC), insulin area under curve (IAUC), insulin sensitivity index (ISI) were calculated. And 30 normal pregnant women were selected as the healthy group. Results: CEC, TNF-a, IL-6, GAUC and IAUC of PIH patients were significantly higher than those of the normal healthy group; while ISI of PIH patients was significantly lower than that of the healthy group. ISI was significantly negatively correlated to CEC, TNF-a and IL-6. After treatment, CEC, TNF-α, IL-6, GAUC decreased and ISI increased significantly in the treated group; while in the control group, all above-mentioned parameters showed no change. Conclusion: Prepared rhubarb can improve insulin resistance of PIH by reducing vascular endothelial cell's damage.

Insulin Resistance and Hypertension

The insulin sensitivity in hypertensive patients with normal glucose tolerance(NGT) , impaired glucose tolerance (IGT) and type 2 diabetes m ellitus (DM) and the insulin resistance (IR) under the disorder of glucose metabolism and hypertension were studied. By glucose toler- ance test and insulin release test,insulin sensitivity index (ISI) and the ratio of area under glucose tolerance curve(AUCG) to area under insulin release curve(AU CI) were calculated and analyzed. The results showed that ISI was decreased to varying degrees in the patients with hypertension, the m ildest in the group of NGT with hypertension,followed by the group of IGT without hyper- tension,the group of IGT with hypertension and DM(P=0 ) .There was very significant differ- ence in the ratio of AUCG/ AUCI between the hypertensive patients with NGT and controls (P= 0 ) .It was concluded that a significant IR existed during the development of IGT both in hyperten- sion and nonhypertension.The increase of total insulin secretion (AUCI) was associated with non- hypertension sim ultaneously.IR of the hypertensive patients even existed in NGT and was wors- ened with the deterioration of glucose metabolism disorder,but the AUCI in the HT group changed slightly.A relative deficiency of insulin secretion or dysfunction ofβ- cell of isletexisted in IGT and DM of the hypertensive patients.

Relationship between insulin resistance and blood lipid and sport in patients with type II diabetes mellitus complicated with hypertension

Objective To study the relationship between insulin resistance and blood pressure and blood lipid in patients with type II diabetes mellitus complicated with hypertension.Methods The serum concentration of fasting glucose,insulin,lipids and the level of blood pressure were measured in 56 patients with type II diabetes mellitus complicated with hypertension.Results The insulin sensitivity index(ISI) decreased in patients with type II diabetes mellitus complicated with hypertension compared with the patients with type II diabetes mellitus with normal blood pressure(P< 0.05).A negative correlation with hypertension was found between ISI and SBP,DBP,TG,ApoB in patients with type II diabetes mellitus complicated with hypertension(P<0.05).There was a positive correlation between ISI and HDL in patients with type II diabetes mellitus complicated with hypertension(P<0.05).Conclusion Insulin resistance presents in patients of type II diabetes mellitus complicated with hypertension.Insulin resistance is the major cause of hypertension and lipid metabolic disturbance in patients with type II diabetes mellitus complicated with hypertension.

THE ROLE OF MAGNESIUM METABOLISM IN ESSENTIAL HYPERTENSION WITH INSULIN RESISTANCE

Objective To investigate the effects or magneslum metabollsm and other positive ions in pathogenesis of essential hypertension(EH) patients with insulin resistanceI1R). Methods The levels of Na+, K+, Ca2+, Mg2+ in erythrocyte and 24-hour urine samples were observed in 47 EH patients aud in 3o subjects with normal blood pressure. insulin sensitivity index was used to evaluate tke insulin sensitivity. Results in EH patients, the levels of K+ and Mg2+ in erythrocyte declined, but the levels or Na+ and Ca2+ in erythrocyte increased, and the 24-hour urinary excretion of Mg2+ reduced as compared to the subjects with normal blood pressure (P <o. o5). The levels of K+ and Mg2+ in erythrocyte of EH patients positively correlated witk insulin sensitivity index, and tke Mg2+ level in erythrocyte positively correlated with 24-hour urlnary excretion or Ca2+ and Mg2+, and tke K+ level in erythrocyte- Conclusion Abnormality or magnesium metabolism in EH patients may be the linking ractor for hypertension and insulin resistance, and may relate to inadequate intake of magnesium. Calcium and potassium may be involved in the occurrence of insulin resistance through affecting magnesium metabolism.

Research progress on mechanism of Chinese material medica in preventing and treating insulin resistance and type 2 diabetes mellitus

Insulin resistance(IR)is a significant feature and one of the basic links in the pathogenesis of type 2 diabetes mellitus(T2DM).Chinese material medica(CMM)has promoted the development of traditional Chinese medicine due to its definite clinical efficacy in the treatment of IR and T2DM.However,owing to the fact that the mechanism of CMM is characterized by“multiple components and multiple targets”,which has not been effectively interpreted,result in the scientificity of clinical efficacy with CMM is controversial.Therefore,this article summarized the mechanisms of CMM and its main active components in improving IR and preventing and treating T2DM,whose aim is to provide valuable reference for the research mechanism on the treatment of IR and T2DM.

Relationship between skin fold thickness and insulin resistance in the essential hypertensive patients in Vietnam

Background Previous studies reported a close relationship between obesity and insulin resistance in the essential hypertensive patients. Objective In this study, we examined the relationship between the skin fold thickness and insulin resistance then developed a formula to estimate the insulin resistance index according to the skin fold thickness in the essential hypertensive patients. Subjects and Methods Medical records of 80 patients (37 males, 43 females) were reviewed and the data were tabulated. Anthropometric indexes (including height, weight, waist circumference, hip circumference, and skins fold thickness at 5 fatty difference points on the Erdheim diagram), fasting plasma glucose and insulin concentration were recorded. The mean age was 57.0 ?9.2 years. The insulin resistance index was calculated following the Homeostasis Model Assessment (HOMA) formula. Results Compared with the group with BMI < 23 kg/m2, the group with BMI≥23 kg/m2 had higher fasting insulin concentration (8.85±4.97 pmol/L vs 15.60±8.70 pmol/L, P<0.001 ) and higher insulin resistance index in ( 2.15±1,24 vs 3.76±2.22, P<0.001). No significant difference in fasting plasma insulin concentration, insulin resistance index between male and female was observed (P > 0.05). There was a positive correlation between skin fold thickness and the fasting insulin concentration and insulin resistance index. The skin fold thickness at point A8 had the best coefficient correlated with fasting plasma insulin(r=0.79, P < 0.001) and insulin resistance index (r= 0.79, P < 0.001). A formula to estimate the insulin resistance index by skin fold thickness at point A8 as: Insulin resistance index = 0.12×[skin fold thickness at A8 point (mm)] - 1. Conclusion: In the essential hypertensive patients, the formula to estimate insulin resistance index as 0.12×[skin fold thickness at A8 point (mm)]-1 may predict accurately the level of insulin resistance. (J Geriatr Cardiol 2005; 2(4):228-232 )

What Are the Determinants of Insulin Resistance (IR) and How Effective Is the Sub-Saharan Africa-Specific Threshold of Abdominal Obesity (AO-SSA) Identifying IR in Congolese Black Hypertensive Patients?

Background: Hypertensive patients with insulin resistance (IR) are at greater risk of cardiovascular disease and may represent a particular subset of hypertension (HTN) requiring special medical attention. Quantitative measurements of the IR are not suitable for routine clinical practice. Met-abolic syndrome (MetS) or simply abdominal obesity (AO) is surrogate of IR. The performance of the recently proposed Sub-Saharan Africa cut-off point of abdominal obesity for identifying IR in hypertensive patients has never been evaluated. Aims: The main objective was to compare the performance of the newly proposed Sub-Saharan Africa specific threshold of abdominal obesity (AO-SSA) to that of IDF (AO-IDF) in identifying IR in Congolese Black Hypertensive Patients. Methods: A cross-sectional study was conducted at the Heart of Africa Cardiovascular Center, Lomo Medical Clinic, Kinshasa Limete, DR Congo, between January 2007 and January 2010. Homeostatic model assessment (HOMA) index was calculated to determine IR. Multivariate logistic regression analysis was used to assess the independent determinants of IR. The intrinsic (sensitivity and specificity) and extrinsic (positive predictive value and negative predictive value) characteristics of the AO-SSA, AO-IDF, AO-ATP III, MetS-SSA, MetS-IDF, and MetS-ATP III were calculated. The kappa statistic was determined for agreement between the ATPIII, IDF and SSA defined AO and MetS with HOMA-IR. Results: Men represented the majority of the enrolled patients: 105 (64.4%) and the mean age of all participants were 57 ± 11 years. Insulin resistance was found in 79.1% of the study population with 88.7, 79.3, 84.6, 71.4, 75.5, 91.1, 60.3 and 44.8 respectively among patient with MetS-ATP, MetS-IDF, MetS-SSA, AO-ATP III, AO-IDF, AO-SSA, diabetics and non-obese non-diabetic hypertensive patients. In multivariate analysis, the risk of IR was associated independently and significantly (p < 0.05) with cigarette smoking, low-HDL-C, hyperuricemia, and diastolic HTN, as shown in the following equation: Y = ﹣1.404 + 1.054 Cigarette Smoking + 0.872 low HDL-C + 0.983 hyperuricemia + 0.852 diastolic hypertension. The AO-SSA, with 87.7% sensitivity and 67.6% specificity, was the only surrogate who showed an acceptable agreement with the HOMA-IR index. Abdominal obesity defined according to other thresholds and the metabolic syndrome whatever the used diagnostic criteria have a slight agreement with the HOMA-IR index. Conclusion: IR was found to be prevalent in our study population. Cigarette smoking, low-HDL-C, hyperuricemia, and isolated diastolic HTN magnify IR. The AO-SSA is an easy and cost efficient method to diagnose IR in Congolese Black Hypertensive Patients. Further study in wider group is indicated to validate our findings.

Study of the Pathogenesis of Hypertension Associated with Non-Insulin Dependent Diabetes Mellitus

In order to study the pathogenesis of hypertension associated with noninsulin dependent diabetes mellitus (NIDDM), Plasma glucose, insulin levels at fasting and following an oral glucose load were measured. Na +K +pump and Ca 2+ pump activities of red blood cell membrane were also assessed. Hypertensive patients with normal or impaired glucose tolerance (NGT, or IGT) had hyperinsulinemia. Obese hypertensive patients also had hyperinsulinemia, while nonobese hypertensive patients had no hyperinsulinemia, but exhibited a delay in insulin response to oral glucose tolerance test (OGTT). In multivariate analysis, considering the factors of age, BMI and plasma glucose level, DBP were still positively related to both 30 min insulin level and IAUC, but negatively correlated to activities of Na +K +pump and Ca 2+ pump. These results demonstrated that a link between obesity, hpertension and NIDDM is the insulin resistance and/or hyperinsulinemia.

Effects of telmisartan on hypertensive patients with dyslipidemia and insulin resistance

Objective To investigate the effects of telmisartan on the blood glucose,blood lipid,blood insulin,and insulin resistance in the hypertensive patients with dyslipidemia,and also its effect on controlling blood pressure. Patients and Methods A total of 96 hypertensive patients(34 females,62 males) with dyslipidemia were included(mean age 51.2±9.6,range 42-65 years) . Patients were randomized to receive either telmisartan 80 mg/day(n=46) or enalapril 10 mg/day(n=50) for 6 months. The levels of blood pressure(BP) ,heart rate(HR) ,and biochemical data were measured before therapy and at the end of the 3-month treatment and 6-month treatment,respectively. Meanwhile,insulin resistance was evaluated by using a homeostasis model assessment of insulin resistance(HOMA-IR) and insulin sensitivity(HOMA-IS) . Results In the telmisartan group,the mean blood pressure was obviously lower than that of pre-therapy(P< 0.05) ,and the levels of triglyceride(TG) ,HOMA-IR,and HOMA-IS were all obviously lower than those of pre-therapy and of the enalapril group at the end of the 3-month-treatment period(P<0.05) . After 6 months of treatment,the levels of TG,HOMA-IR,and HOMA-IS in the telmisartan group were significantly lower in comparison with those of pre-therapy,the enalapril group(P<0.01) ,and 3-month-treatment(P<0.05) . Post-prandial12 hour blood glucose(P2HBG) in the telmisartan group decreased significantly after 6-month treatment compared with that of pre-therapy and the enalapril group(P<0.05) . The level of high density lipoprotein(HDL) cholesterol was significantly higher after 6-month treatment in the telmisartan group than with pre-therapy and the enalapril group(P<0.05) . Conclusions Telmisartan could not only control blood pressure steadily and effectively,but also decrease blood TG,increase HDL cholesterol and insulin sensitivity,and lower insulin resistance.

Effects of telmisartan on hypertensive patients with dyslipidemia and insulin resistance

The benefits of angiotensin converting enzyme inhibitor (ACEI) and angiotensin receptor blocker (ARB) beyond blood pressure reduction have been proven through many large studies (HOPE, LIFE) in high risk CVD patients;1 post hoc studies have shown reductions in new onset type 2 diabetes mellitus (DM). ……

Measurement of lumbar muscle glucose utilization rate can be as useful in estimating skeletal muscle insulin resistance as that of thigh muscle

Background: Skeletal muscle glucose utilization (SMGU) can be accessed by positron emission tomography (PET) and18F-FDG to characterize insulin resistance. The quantity of skeletal muscle in the lumbar is sufficient to indicate that SMGU in the lumbar (SMGU- lumbar) can be measured with18F-FDG PET of the chest instead of obtaining thigh muscle SMGU (SMGU-thigh). This would reduce PET scan time to avoid thigh muscle PET scan. This study was aimed to compare SMGU-lumbar and thigh muscle SMGU under insulin clamping to identify the validity of measurements of SMGU in the lumbar for studies of insulin resistance. Methods: Thirty-three patients underwent sequential dynamic18F-FDG PET of both the thoracic (37 min) and thigh region (22 min) during hyperinsulinemic euglycemic insulin clamping. Both SMGU-lumbar and SMGU-thigh were calculated by Patlak graphical analysis. Whole body insulin resistance was assessed by a whole body glucose disposal rate during hyperinsulinemic euglycemic insulin clamping. Input function was obtained from the time activity curve of the descending aorta and venous blood sampling as previously validated. Results: SMGU-thigh (0.0506 ± 0.0334 μmol/min/g) was comparable to SMGU-lumbar (0.0497 ± 0.0255 μmol/min/g). The Bland-Altman method of difference plot analysis showed a significant correlationship between SMGU- thigh and SMGU-lumbar (r = 0.506, p = 0.0028). There were seen very good significant correlationship between whole body glucose utilization rate in both thigh (r = 0.737, p = 0.0001) and lumbar (r = 0.772, p = 0.0001). Conclusion: These results support the validity of measuring SMGU-lumbar to estimate insulin resistance during PET imaging of the chest.

Functional imaging of skeletal muscle glucose metabolism by ¹⁸FDG PET to characterize insulin resistance in patients at high risk for coronary artery disease

Insulin resistance is associated with several coronary risk factors and is thought to play a critical role for the development of coronary artery disease. Insulin resistance has several causes, including an impaired skeletal muscle glucose utilization rate (SMGU), reduced peripheral blood flow, and altered fatty tissue metabolism, with SMGU being considered the most important. Nonetheless, insulin resistance has only been estimated by the glucose disposal rate (GDR) in previous studies. Methods: Skeletal muscle metabolic imaging with 18FDG and positron emission tomography (PET) was undertaken to measure SMGU during hyperinsulinemiceuglycemic clamping in 22 normotensive type-2 diabetics under no medications (T2- DM), 17 normotensive non-diabetic hypertriglyceridemics, 22 patients with hypertension, and 12 agematched controls. Whole body insulin resistance was assessed by the GDR during hyperinsulinemiceuglycemic insulin clamping. Results: The SMGU and GDR were significantly reduced in T2DM (32.1 ± 16.6 μmol/min/kg and 24.3 ± 13.0 μmol/min/kg, respectively), hypertriglyceridemics (36.5 ± 13.5 μmol/min/ kg and 22.7 ± 8.07 μmol/min/kg respectively) and patients with hypertension (35.4 ± 26.6 μmol/min/kg and 29.0 ± 9.90 μmol/min/kg, respectively) compared with controls (72.2 ± 44.1 μmol/min/kg and 43.0 ± 22.9 μmol/min/kg, p < 0.01, respectively). In all groups studied, SMGU was significantly correlated with GDR (r = 0.76, p < 0.01) and GDR (F = 13.9) was independently related to SMGU (r = 0.81, p < 0.01). Conclusion: Insulin resistance is significantly associated with SMGU to a similar degree among patients with T2DM, essential hypertension and hypertriglyceridemia. 18FDG PET functional imaging allows insulin resistance to be assessed.

Influence of Diet Behavior on Insulin Resistance in Hypertensive Black Sub-Saharan Africans: A Multicentric, Cross-Sectional Study

Background: Insulin resistance (IR) is the backbone of cardiovascular diseases (CVDs). The latter are the most common non-communicable diseases globally. Diet is an important determinant of CVDs. The link between diet and cardiovascular health could be explained by an association between diet pattern and IR. Aims: To investigate the association between salt and specific food consumption as well as different diet patterns (Mediterranean, westernized, and intermediate dietary patterns) with HOMAIR as a surrogate marker of IR, and fasting insulin in Black, sub-Saharan essential hypertensive patients. Methods: The multicentric, cross-sectional analysis involved 77 Congolese Black hypertensive participants with no history of cardiovascular disease. Daily sodium chloride intake (NaCl g/24h) was estimated from 24-hour urine collection. Dietary behaviours were evaluated through a semi-quantitative food frequency questionnaire (FFQ). Homeostatic model assessment of insulin resistance (HOMAIR) ≥ 2.5 was used as surrogate marker of IR. Results: A decrease in weekly consumption of fruits, vegetables and fish would significantly explain an increase of 29% (r = 0.292;p = 0.010), 24% (r = 0.242;p = 0.034) and 23% (r = 0.226;p = 0.048) of the value of HOMAIR respectively. In contrast, an increase in daily sodium chloride intake was associated with 28% (r = 0.283, p = 0.027) of the increase in HOMAIR. Also, a decrease in the average weekly consumption of fruit, vegetables and fish would significantly explain an increase of 25% (r = 0.247;p = 0.030), 30% (r = 0.302;p = 0.008) and 31% (r = 0.313;p = 0.006) of fasting insulin. In contrast, an increase in red meat consumption was associated with a 26% increase (r = 0.257, p = 0.024) in fasting insulin. In multivariable adjusted analysis 45% of variation in fasting insulin (R2 = 0.452;overall p = 0.005) were explained by fruits, vegetables and fish consumption. 38% of variation in HOMAIR (R2 = 0.379;overall p = 0.047) were explained by fruits and vegetable consumption and daily sodium chloride intake (NaCl g/24h). Conclusions: In hypertensive Black sub-Saharan Africans, Salt intake and westernized diet seem to promote insulin resistance whereas Mediterranean diet, fruits, vegetables and fish consumption enhance insulin sensitivity.

Study on Features of Insulin Resistance in Patients with Coronary Heart Disease

Objective Researching the features of insulin resistance in patients with coronary heart disease (CHD) . Methods The study included 20 healthy subjects (control group), 53 CHD patients without (Group A) and 24 with essential hypertension (Group B) . Oral glucose tolerance test was administered to all subjects. Venous blood samples were taken during fasting and at 30, 60, 120 and 180 min after the glucose load (100g). All samples were assayed for glucose, insulin and C - peptide. Results The glucose, insulin, and C - peptide curves were at a hierarchy of Group B > Group A > the control group. Insulin - sensitivity - index was at an inverse hierarchy (-4. 31±0.55, -4. 05±0.47, - 3. 82±0. 42, respectively) . The ratio of the area under the C - peptide to the insulin was at a hierarchy of control group (3. 84±0. 81)> Group A (2. 84±0. 93)> Group B (2.26±0. 67), P < 0. 01) . As to insulin and C - peptide releasing types, most subjects of the control group had common type, while the predominant response type was pure - high in Group A, delayed - and delayed - high in Group B. Conclusions There are insulin resistance, insulin - C - peptide separation and changes of insulin and C - peptide releasing types in CHD patients. Insulin resistance is more severe when with hypertension. The hyperinsulinemia in CHD might be due to the over - secretion of insulin, also due to slow clearance in the patients accompanied by hypertension.

Mechanism Analysis of Gui Jianyu in treating Hypertension complicated with Impaired Glucose Tolerance Based on Network Pharmacology and Molecular Docking

Objective To explore the mechanism of Gui Jianyu(Euonymus alatus(Thunb.)Sieb.)in treating hypertension(HT)complicated with impaired glucose tolerance(IGT)based on network pharmacology and molecular docking technology.Methods The main chemical components and targets of Gui Jianyu were obtained from TCMSP database.The Swiss Target Prediction platform was used to predict drug-related targets for supplement.Main disease targets of HT complicated with IGT were obtained from GenCards,OMIM and DrugBank databases.The intersection targets of drugs and two diseases were obtained by R and Veen Diagram was drawn.The protein-protein interaction(PPI)network model was constructed in STRING platform and visualized by Cytoscape tool.GO and KEGG analysis on Metascape platform were used to analyse the common targets.Network of main drug components-disease targets-pathways was established with Cytoscape tool.Finally,the molecular docking between the core regulatory active components of Gui Jianyu and the core targets were verified by Autodock vina.Results Eight active components and 357 corresponding targets were obtained.681 HT related targets and 727 IGT related targets,196 disease intersection targets,and 57 Gui Jianyu targets in the treatment of HT complicated with IGT were confirmed.20 GO and 19 KEGG main pathways were enriched.Molecular docking of 2 key active ingredients with 2 key targets showed that all results scores were less than-5.0 kcal·mol-1.Quercetin and kaempferol,the key active components,had good binding activity with AKT1 and TP53.Conclusion Gui Jianyu may play a key role in the treatment of HT complicated with IGT by reducing insulin resistance.This work explored the common pathogenesis of HT complicated with IGT,and also provided a reference for further pharmacological research and exploration the efficacy of Gui Jianyu for HT complicated with IGT.

Study on Insulin Resistance and Genetic Polymorphisms in Essential Hypertension Patients of Two Different Kinds of TCM Constitution

Objective： To investigate the relationship of insulin resistance and the polymorphisms of insulin receptor-related genes in essential hypertension patients of two different kinds of TCM constitution. Methods： Oral glucose tolerance test （OGTT） and insulin release test （InRT） were conducted in 217 essential hypertensive patients of either sluggish meticulous （SM） constitution （139 cases） or prosperous impetuous （PI） constitution （78 cases）, and the polymorphism of three genes, including insulin-like growth factor-1 receptor （IGF-1R）, insulin receptor substrate-1 （IRS-1） and 2 （IRS-2） genes were detected. Results： （1） OGTT, InRT and insulin resistance index （Homa-IR） were higher and insulin sensitive index （ISI） was lower in the patients of SM constitution than those in patients of PI constitution. （2） Significant difference of ISI and Homa-IR was shown in patients of both constitutions with genotype G of the 3 genes. Conclusion： Decrease of insulin sensitivity and increase of insulin resistance are more obvious in hypertensive patients with genotype G of the 3 genes of SM constitution than in those of PI constitution. Therefore, the difference in constitution might be one of the genetic characteristics for insulin resistance in hypertensive patients.

Mechanisms of developmental programming of the metabolic syndrome and related disorders

There is consistent epidemiological evidence linking low birth weight, preterm birth and adverse fetal growth to an elevated risk of the metabolic syndrome (obesity, raised blood pressure, raised serum triglycerides, lowered serum high-density lipoprotein cholesterol and impaired glucose tolerance or insulin resistance) and related disorders. This "fetal or developmental origins/programming of disease" concept is now well accepted but the "programming" mechanisms remain poorly understood. We reviewed the major evidence, implications and limitations of current hypotheses in interpreting developmental programming and discuss future research directions. Major current hypotheses to interpret developmental programming include: (1)thrifty phenotype; (2) postnatal accelerated or catchup growth; (3) glucocorticoid effects; (4) epigenetic changes; (5) oxidative stress; (6) prenatal hypoxia; (7) placental dysfunction; and (8) reduced stem cell number. Some hypothetical mechanisms (2, 4 and 8) could be driven by other upstream "driver" mechanisms. There is a lack of animal studies addressing multiple mechanisms simultaneously and a lack of strong evidence linking clinical outcomes to biomarkers of the proposed programming mechanisms in humans. There are needs for (1) experimental studies addressing multiple hypothetical mechanisms simultaneously; and (2) prospective pregnancy cohort studies linking biomarkers of the proposed mechanisms to clinical outcomes or surrogate biomarker endpoints. A better understanding of the programming mechanisms is a prerequisite for developing early life interventions to arrest the increasing epidemic of the metabolic syndrome, type 2 diabetes and other related disorders.

Gut microbiota and diabetes: From correlation to causality and mechanism

In this review,we summarize the recent microbiome studies related to diabetes disease and discuss the key findings that show the early emerging potential causal roles for diabetes.On a global scale,diabetes causes a significant negative impact to the health status of human populations.This review covers type 1 diabetes and type 2 diabetes.We examine promising studies which lead to a better understanding of the potential mechanism of microbiota in diabetes diseases.It appears that the human oral and gut microbiota are deeply interdigitated with diabetes.It is that simple.Recent studies of the human microbiome are capturing the attention of scientists and healthcare practitioners worldwide by focusing on the interplay of gut microbiome and diabetes.These studies focus on the role and the potential impact of intestinal microflora in diabetes.We paint a clear picture of how strongly microbes are linked and associated,both positively and negatively,with the fundamental and essential parts of diabetes in humans.The microflora seems to have an endless capacity to impact and transform diabetes.We conclude that there is clear and growing evidence of a close relationship between the microbiota and diabetes and this is worthy of future investments and research efforts.

Mechanism of immune attack in the progression of obesity-related type 2 diabetes

Obesity and overweight are widespread issues in adults,children,and adolescents globally,and have caused a noticeable rise in obesity-related complications such as type 2 diabetes mellitus(T2DM).Chronic low-grade inflammation is an important promotor of the pathogenesis of obesity-related T2DM.This proinflammatory activation occurs in multiple organs and tissues.Immune cellmediated systemic attack is considered to contribute strongly to impaired insulin secretion,insulin resistance,and other metabolic disorders.This review focused on highlighting recent advances and underlying mechanisms of immune cell infiltration and inflammatory responses in the gut,islet,and insulin-targeting organs(adipose tissue,liver,skeletal muscle)in obesity-related T2DM.There is current evidence that both the innate and adaptive immune systems contribute to the development of obesity and T2DM.