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In this study we performed Tissue Doppler Imaging (TDI), two-dimensional speckle tracking imaging (2D- STI) and three-dimensional speckle tracking imaging (3D-STI) on enrolled healthy, overweight and obese groups (34 subjects in each group), respectively, to analyze cardiac structure and its function. Compared with healthy group, global longitudinal strain (GLS), global circumferential strain (GCS), global area strain(GAS) and global radial strain (GRS) decreased progressively (P < 0.05). The ratio of early diastolic mitral inflow velocity to global early diastolic strain rate of left ventricle (E/e'sr) (r = 0.466, P < 0.001), GLS (r = 0.502, P < 0. 001), GCS (r = 0.426, P < 0.001), GAS (r = 0.535, P < 0.001) and GRS (r = -0.554, P < 0.001) were correlated with body mass index (BMI). E/e'sr (r = 0.37, P = 0.003), GLS (r = 0.455, P < 0.001), GCS (r = 0.282, P = 0.02), GAS (r = 0.412, P < 0.001) and GRS (r = -0.471, P < 0.001) were correlated with free fatty acid (FFA). Stepwise multiple linear regression revealed that BMI was independently correlated with E/e'sr, GLS, GCS, GAS and GRS. Waist to hip ratio (WHR) was independently correlated with GLS, GCS, GAS and GRS. FFA was independently correlated with E/e'sr (P < 0.05). The study showed that cardiac structure changed and impaired left ventricular global systolic and diastolic function in overweight and obes population. Moreover, BMI, WHR and FFA may be independent influence factors of cardiac function in overweight and obese population.
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Humans , Body Mass Index , Case-Control Studies , Echocardiography, Three-Dimensional , Heart , Heart Ventricles , Linear Models , Obesity , Overweight , Reproducibility of Results , Ventricular Function, LeftABSTRACT
The changes in hypothalamic-pituitary function in older people include the effects of aging per se on hypothalamic-pituitary physiology,such as age-related declines in GH-IFG-1 system and increased activity in CRH-ACTH axis,and the hormone hyposecretion due to anterior pituitary diseases in elderly,including fibrosis and vascular alterations.In considering changes in hypothalamic-pituitary function in older people,it is important to distinguish between what is age-related and what is disease-related.Symptoms associated with hypopituitarism are nonspecific and may be often attributed to normal aging and can be challenging in clinical practice.Furthermore,the benefits and safety of selective pituitary hormonal replacement,including growth hormone replacement,remain controversial in the elderly.The evidence for age-related changes in GH-IGF-1 system and CRH-ACTH axis and their clinical consequences are reviewed.The characteristics in the clinical approach to disease-related hypopituitarism in older person are also briefly discussed.
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Objective To investigate the clinical characteristics,peripheral insulin sensitivity,and β-cell function in patients with ketosis-prone diabetes(KPD).Methods Thirty-one patients with newly diagnosed ketosisprone diabetes were admitted to West China Hospital from January 2004 to December 2009.They were divided into 2 groups according to their body mass index (BMI):OB-KPD (BMI ≥ 25 kg/m2,n =22) and Lean-KPD (BMI ＜ 23 kg/m2,n =9).10 patients with newly-onset type 2 diabetes free from ketosis (OB-DM:BMI ≥ 25 kg/m2,n =10) were enlisted as control.Detailed assessments of medical history and symptoms of hyperglycemia were performed.The islet cell antibody (ICA),insulin autoantibody (IAA),anti-glutamic acid decarboxylase antibody (GAD-Ab),fasting plasma glucose,serum insulin,C-peptide and free fat acids concentrations were measured.All of the subjects underwent oral and intravenous glucose tolerance tests,euglycemic-hyperinsulinemia and hyperglycemia clamp test,to evaluate the insulin secretion and insulin sensitivity respectively.Insulin sensitivity was determined by glucose disposal rate (GDR) of steady state during euglycemic clamp and acute insulin secretion was calculated by insulin area under curve(AUCins 0-10 min) during IVGTT.Maximal insulin secretion was determined by glucose infusion rate (GIR) and serum insulin concentration of steady state during hyperglycemic clamp test.Results Age,sex,duration of diabetes were matched among groups.A family history of diabetes was strongly associated with those patients with obesity,compared with lean ketosis prone diabetes(16/22 vs 1/9).GDR was (4.91 ± 1.82) mg · kg 1 · min-1 in subjects with OB-KPD,being lower than that in Lean-KPD patients[(6.26 ± 1.89) mg · kg 1 · min-1] and OB-DM group[(6.78-± 1.69) mg · kg 1 · min-1,P＜0.01].Serum insulin and C-peptide in OB-KPD patients were higher than Lean-KPD patients.Area under the insulin curve [AUCins0-10min (183.86 ± 31.1) mIU/L] and GIR[(2.65 ±1.53) mg · kg-1 · min-1] in OB-KPD patients were lower than those in OB-DM group[(697.06-± 231.9) mIU/L,(6.53 ± 2.21)mg · kg 1 · min-1,P＜0.0 1],but slightly higher than the Lean-KPD group [AUCins0 10min (92.1 ±29.8) mUU/L,GIR (2.55 ± 1.49) mg · kg 1 · min-1,P＜0.05].Glucose disposal rate (GDR) was strongly associated with casual plasma glucose (r =-0.502,P＜0.01),HbA1C(r =-0.553,P＜0.0 1) and FFA eoneentrations (r=-0.504,P＜0.01) on admission.Conclusions Insulin resistance and β-cell dysfunction coexist in all KPD patients.OB-KPD patients exhibit more severe insulin resistance,while Lean-KPD patients have lower insulin secretion.KPD patients had severe hyperglycemia,hypertriglyceridemia,and high plasma FFA levels on admission,suggesting that hyperglycemia and elevated FFA levels could result in serious insulin resistance,β-cell dysfunction,and diabetic ketosis in patients with KPD.
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Pharmaceutical researchers at home and abroad have been working in pursuit of an effective, easy-to-use and safe way of non-injecting insulin administration. Oral insulin was considered to be one of the ideal administration ways for the treatment of diabetes mellitus. In this review, we introduce the clinical value and progress of oral insulin delivery in recent years. The mechanisms, therapeutic effect, limitations of oral insulin delivery, and the future perspectives in this research field are also discussed.
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Animals , Humans , Administration, Oral , Diabetes Mellitus , Drug Therapy , Drug Carriers , Drug Delivery Systems , InsulinABSTRACT
The effects of elevated levels of glucose and (or) free fatty acids on insulin secretion were studied in obese rats by intravenous glucose tolerance test and isolated pancreas perfusinn. The results showed that both glucose- and arginine-stimulated insulin secretions were severely impaired by glucolipotoxicity and the production of ketone was increased dramatically.
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Objective To evaluate the effects of elevated circulating free fatty acids (FFA) level on basal and glucose stimulated insulin secretion (GSIS) of islet β-cell and to explore the pathophysiological link between FFA and impaired β-cell dysfunction. Methods Male SD rats underwent infusions with normal saline (C group), intralipid+heparin (FFA group) and N-acetylcysteine+FFA (NAC group) for 2-4 days. Insulin secretion from pancreatic tissues was evaluated during intravenous glucose tolerance test and isolated pancreas perfasion test at the end of 2 and 4 days infusion. Results After 2 days infusion, the basal insulin secretion from isolated perfused pancreas was increased in FFA group [(55.5±19.4 vs 27.4±6.7) mU/L, P<0.01], but the response to 16.7 mmol/L glucose in isolated perfased pancreas was similar in FFA and C groups. The peak value during GSIS was inhibited by 4 days FFA infusion [(46.8±33.0 vs 214.7±27.4)mIU/L,P<0.05]. GSIS was also decreased in FFA group compared with C group in IVGTr. After interfered with NAC, GSIS was partly recovered [(165.4± 14.8)mIU/L, P<0.01]. Conclusion Elevated circulating FFA levels may contribute to the abnormality of pancreatic islet β-cell through oxidative stress.
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The relationship between elevated concentration of circulating free fatty acids (FFA) and insulin resistance wag studied,and the pathophysiological mechanism of insulin resistance,especially focused on oxidative stress,was explored.It was found that the elevated circulating FFA level led to insulin resistance in rats, which was partly caused by oxidative stress,and that antioxidative treatment was able to reverse the pathologic change.As a result of enhancing reactive oxygen species production[(886±105 vs 427±42)mmol/L,P<0.05] and disrupting antioxidant[(272±47 vs 561±36)μmol/L,P<0.05],elevated concentration of FFA may induce oxidative stress.
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Objective To compare the clinical efficacy and safety of domestic orlistat and imported orlistat in Chinese overweight and obese patients. Methods In a randomized, double-blinded and positive-controlled study, 228 adults (BMI 24-< 40 kg/m~2) evaluated at seven research centers were randomized to receive domestic orlistat or imported orlistat 120 mg 3 times a day with an energy-controlled diet for 24 weeks. Results After 24 weeks, domestic orlistat treated patients got significant weight-loss (5.0±3.7) kg, which was comparable with that of imported orlistat treated patients (4.5±3.5) kg (P=0.3922).Compared with the findings before treatment, there was significant decrease of systolic blood pressure (4.4±11.5)mm Hg (1 mm Hg=0.133 kPa) and serum levels of TC (0.54±0.79) mmol/L and LDL-C (0.32±0.64) mmol/L in the domestic orlistat treated group(compared with levels of baseline, P< 0. 0001). There was no significant difference between the two groups in the changes of blood pressure and lipid levels. Both groups had similar adverse event profiles, most of which were mild and transient gastrointestinal events. There were no serious adverse events in beth groups. Conclusions Domestic orlistat combined with a light low-energy diet promoted significant weight loss, which was comparable with that of imported orlistat after 24 weeks of treatment. There was also improvement in blood pressure and serum levels of TC and LDL-C. Domestic orlistat was as effective and safe as imported orlistat in the treatment of obesity.
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Objective To understand the variation of the motality and death causes for diabetic inpatients in West China Hospital(WCH) during 1996～2004. Methods First,the amount of diabetic inpatients(14670) and died persons (9597)were got each year by computer search system of our hospital from 1996 to 2004,and the case code of died diabetic subjects (842)were obtained.Then,those medical records were investigated and reviewed in details to get useful information.The motality,death causes and its constituent ratio of dead diabetic inpatients were analysed. Data input and analysis were conducted using the tool Epidate3.0,packages SPSS13 and SAS8.0. Results There were totally 14760 inpatients and 842 deaths who were suffered from DM during 1996-2004.The mortality rate was 5.74% and the standardized mortality rate was 5.37%.Tumor was the first cause of deaths (22.3%),followed by infection(15%),fatal cardiovascular events(14.4%),cerebrovascular events(12.3%).Diabetic nephropathy(DN)(6.3%) took the 6th place just after COPD(8%).There were 9269 deaths in the hospital in total(≥15 years old) during 1996-2004 while DM patients contributed 9.08% to them.The proportion of diabetic patients among the total deaths kept increasing every year(χ2=71.9070,P<0.01). Conclusions The mortality proportion of diabetic inpatients among the total deaths in West China Hospital from 1996 to 2004 is increasing every year.It needs to pay more attention to the main death cause of tumor in diabetic patients
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Insulin resistance(IR) is a independent risk factor of ichemic angiopathy .The abnormal state of thrombosis and fibrinolysis is a critical pathology component of IR,and play a vital role in initiating and developing cardiovasculer disease. Under IR state, the,inhancement of plasminogen-activator inhibitior-1(PAI-1)synthesis by adipose tissue and the reduced generation of nitric oxide with endothelial dysfunction contribute to the hypo-fibrinolytic/pro-thrombotic state and promote atherosclerotic. Accompanied with IR developing, when B cell function can't keep normal glycemia, the advanced glycosylation end products(AGEs) are increased as a result of hyperglycemia. AGEs can aggravate endothelial injury and accelerate the course of atherosclerotic. Fully comprehending the pathogenesis of thrombosis and fibrinolysis in IR and taking therapy for the pathology have clinical significance.
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Ketosis-prone diabetes mellitus(KPDM) may be a subtype of type 2 diabetes,characterized by fulminant onset,with diabetic ketoacidosis and usually obesity and over-weight,as well as a positive family history of diabetes,but lacking markers of autoimmunity observed in classic type 1 diabetes.Recovery of glucose homeostasis,accompanied by recovery of ?-cell function,follows intensive glycemic regulation by insulin.Because of the mixed features of type 1 and type 2 diabetes,there is no completely agreement on diagnostic criteria and classification according to clinic presentation,metabolic and immunologic features of the novel atypical diabetes.Additional pathophysiological and genetic insight is therefore needed to provide a better understanding of the mechanisms of partially reversible insulin secretary defect in such syndrome,which is critical for its clinical classification and the development of appropriate treatment strategies.
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Protein kinase C(PKC) is a serine/threonine kinase groups including a series of isoenzyme.Hyperglycemia and elevated free fatty acid can affect signal transduction pathway function,in particular activation of diacylglycerol (DG) and PKC,which occurs in the diabetic state. Activation of PKC lead to insulin resistance and diabetic vascular complications. PKC ? isoform selective inhibitor(LY 333531) and vitamin E have shown potential effect as therapies for diabetic vascular complication.
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Objective To investigate the associations between microalbuminuria and early atherosclerosis in type 2 diabetes.Methods We measured the combined intima-media thickness (IMT) of the common carotid arteries and the inner diameter (ID) of tibia artery with high resolution ultrasound in 30 type 2 diabetic patients,and compared with 13 age-matched non-diabetics as control.The diabetic patients were subgrouped into DM-A subjects whose urinary albumin excretion were normal,and DM-B subjects who were with microalbuminuria,and DM-C subjects who with macroalbuminuria.Results The results showed that the IMT values were greater in diabetic patients than in control subjects (0.65 ?0.12 mm vs 0.48?0.06mm, P
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ObjectiveTo investigate the associations between microalbuminuria and early atherosclerosis in type 2 diabetes.MethodsWe measured the combined intima-media thickness (IMT) of the common carotid arteries and the inner diameter (ID) of tibia artery with high resolution ultrasound in 30 type 2 diabetic patients,and compared with 13 age-matched non-diabetics as control.The diabetic patients were subgrouped into DM-A subjects whose urinary albumin excretion were normal,and DM-B subjects who were with microalbuminuria,and DM-C subjects who with macroalbuminuria.ResultsThe results showed that the IMT values were greater in diabetic patients than in control subjects(0.65±0.12 mm vs 0.48±0.06mm,P<0.001),and greater in group of DM-B and DM-C than in group of DM-A.The ID of tibia artery were smaller in diabetic subjects than in controls (1.98±0.49mm vs 2.45±0.30mm,P<0.01),and smaller in DM-B and DM-C group than DM-A.Besides,multiple linear regression analysis demonstrated that the risk factors for IMT and ID of tibia artery of type 2 diabetes were diabetic duration,total cholesterol levels,blood pressure and urinary albumin excretion.ConclusionIt can be concluded that microalbuminuria is related to atherosclerosis at early stage of the disease process.
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Objective To study the molecular genetic mechanism of a patient with 17? hydroxylase (CYP17) deficiency. Methods Genomic DNA were abstracted from the blood of the patient, her parents and healthy control. The 8 exons of CYP17 gene were amplified, using 5 pairs of designed primers, with polymerase chain reaction (PCR), and the 8 exons were sequenced by the dideoxy terminator method to determined the mutation sites. The corresponding exons of the parents of the patients were also amplified and sequenced to determine the zygosity of the patient and the source of the gene variances. Results The analysis revealed that the patient (46, XY) was a compound heterozygote carrying two different inherited mutations on CYP17 gene, one from mother containing a point mutation Arg 96 (C G G)→ Gln(C A G) and the other from father containing a nine base deletion (CACTCTTTC) at amino acid position 487～489 (Asp Ser Phe) near the carboxyl terminus of P450c17. Conclusion The CYP17 gene of the patient with 17? hydroxylase deficiency is a compound heterozygous mutation. The mutation changes the amino acid sequence of P450c17 enzyme, which in turn affected the enzymatic activity. Arg 96 is essential in P450c17 enzyme activity. Deletion of Asp 487 Ser 488 Phe 489 in exon 8 may be a prevalent mutation causing P450c17 deficiency in Southeast Asia.
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Observations were carried out in 10 moderately well controlled diabetic patients on their usual therapeutic regimens from 10Pm to 10Am on two days.On the control day,samples were obtained without intervention.On another day,nocturnal hypoglycemia was induced.Nocturnal hypoglycemia did not appear to cause clinically important fasting and postprandial hyperglycemia in diabetic patients.It is sug- gested that the morning hyperglycemia is not caused by Somogyi effect but dawn phenomenom.
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Objective To evaluate the relationship of the levels of serum oxide and antioxide with endothelium-dependent vasodilatation(EDV) in obese subjects and to explore the effect of oxidative stress on endothelial dysfunction in obese subjects. Methods 20 euglycemic obese males (Ob) and 13 age- matched normal controls (NC) underwent euglycemic hyperinsulinemia clamp study to evaluate the peripheral glucose disposal rate (GDR) in steady-state and brachial artery ultrasound studies to assess the endothelium-dependent vasodilatation (EDV). The serum levels of ROS, MDA, GSH-PX, GSH and free fatty acids (FFAs) were measured. Results The serum ROS, MDA and FFA concentrations were significantly higher in Ob group than in the controls (P
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Sixty diabetic patients and twenty normal controls were studied. The results showed that: 1) Counter-immuno-electrophoresis is a sensitive and simple test suitable for the detection and monitoring of diabetic microproteinuria; 2) The proteinuria in diabetic nephropathy is glomerular in origin which is supported by the finding of a marked increase in urinary albumin excretion and a normal level of urinary ?2-microglobulin; 3) The serum ?2-microglobulin appears to be a more sensitive index than serum creatinine and creatinine clearance rate for the detection of impairment of renal function in diabetic patients; 4) Diabetic nephropathy is related to glycemic control and duration of diabetes mellitus.