Central fat predicts deterioration of insulin secretion index and fasting glycaemia: 6-year follow-up of subjects at varying risk of Type 2 diabetes mellitus.

AIMS: To examine the relationships between body composition and changes in fasting glycaemia, and in indices of insulin secretion and insulin action over 6 years in females with a family history of Type 2 diabetes with or without prior gestational diabetes ('at risk' group, AR) and control females (control group, C). METHODS: At baseline and at follow-up, an oral glucose tolerance test and dual energy X-ray absorptiometry assessment of body composition were performed. Indices of insulin resistance (HOMA R') and insulin secretion (HOMA beta') were obtained from fasting insulin and glucose concentrations. RESULTS: At baseline, the groups were similar for age, body mass index, fasting levels of plasma glucose and insulin, HOMA R' and HOMA beta'. Despite similar total body fatness, AR had significantly greater waist circumference and central fat (both P < 0.02) compared with C. At follow-up there was a significant increase in central adiposity only in AR, and the fasting plasma glucose (FPG) level was higher in AR compared with C (5.0 +/- 0.2 vs. 4.3 +/- 0.2 mmol/l, P = 0.02). This rise in plasma glucose in AR was related to a decline in HOMA beta' (r = 0.45, P = 0.0065). Both the baseline and the increments in total and central abdominal fat mass were associated with the time-related decline in HOMA beta'. CONCLUSIONS: Six years after initial assessment, AR showed deterioration in FPG levels due predominantly to a decline in insulin secretion index without major change in insulin resistance index. Importantly, baseline body fatness (especially central adiposity), as well as increases in fatness with time, were the major predictors of the subsequent decline of insulin secretion index and the consequent rise in FPG.     

Comparison of the growth hormone, IGF-1 and insulin in cerebrospinal fluid and serum between patients with motor neuron disease and healthy controls

Neurotrophic effects of the growth hormone (GH), insulin-like growth factor-1 (IGF-1) and insulin on the central nervous system have become more apparent in the past decade. In this study, we measured serum and cerebrospinal fluid (CSF) concentrations of GH, IGF-1 and insulin in 35 patients with motor neuron disease (MND) [24 patients with definite amyotrophic lateral sclerosis (ALS) and 11 patients with progressive bulbar palsy] and in 40 healthy controls. Levels of serum concentrations of GH and IGF-1 did not significantly differ between the MND patient group and the healthy controls, while the level of insulin was significantly decreased ( P  = 0.0033) in the MND patient group. However, levels of all three examined parameters in CSF were significantly lower in the MND group than in the healthy controls with the statistical significance for IGF-1 and insulin of P  < 0.001. This finding has not been reported previously, and further investigations into its association with ALS should establish whether it can be used as an early marker of the disease, or whether it merely represents a consequence of ALS development.     

Novel enzyme immunoassay of anti-insulin igG in human serum

A novel enzyme immunoassay of anti-insulin IgG in human serum is described. A serum sample containing anti-insulin IgG was treated with dextran-charcoal at pH 6.0 to remove endogenous insulin and subsequently incubated with dinitrophenyl biotinyl nonspecific rabbit IgG-insulin conjugate. The reaction mixture was further incubated with a rabbit (antidinitrophenyl bovine serum albumin) IgG-coated polystyrene ball to trap the complex formed between anti-insulin IgG and the conjugate. After washing to eliminate nonspecific IgG in the test serum, the polystyrene ball was incubated with dinitrophenyl-L-lysine to elute the complex. The eluate was incubated with an avidin-coated polystyrene ball. Finally, the amount of human anti-insulin IgG in the complex trapped onto the avidin-coated polystyrene ball was measured by incubation with rabbit (antihuman IgG (γ-chain)) Fab'-peroxidase conjugate. This enzyme immunoassay was 1,000-fold more sensitive than the conventional enzyme immunoassay, in which an insulin-bovine serum albumin-coated polystyrene ball was incubated with a serum sample containing anti-insulin IgG and subsequently with rabbit (antihuman IgG (γ-chain)) Fab'-peroxidase conjugate. The principle of the novel enzyme immunoassay can be used to more sensitively measure antibodies for most kinds of haptens and antigens than the conventional enzyme immunoassay.     

Sequential metabolic studies of pancreas allograft function in type 1 diabetic recipients.

We have previously shown that the loss of acute first phase insulin secretion precedes pancreas allograft rejection and development of glucose intolerance in Type 1 diabetic patients. In order to examine whether there is a progressive loss of phases of insulin secretion and beta-cell function in technically successful pancreas transplants during the first year, we measured glucose, insulin, and C-peptide responses to physiological (mixed meal) and pharmacological (IV glucose and IV glucagon) stimulation in 27 glucose-tolerant, insulin-independent allograft recipients at 3, 6, and 12 months. Mean +/- SE fasting serum glucose levels were normalized throughout the study period. Postprandial serum glucose profiles tended to increase by 12 months compared to 3 and 6 months, although peak glucose levels were not statistically different. Following pancreas transplantation, basal serum insulin levels were high at 3 months (163 +/- 17 pM), 6 months (165 +/- 22 pM), and 12 months (248 +/- 54 pM, p = NS) in the Type 1 diabetic pancreas allograft recipients when compared to normal (25 +/- 3 pM). We observed slight elevations in postprandial insulin and C-peptide profiles at 12 months compared to 3 and 6 months. Following IV glucose and glucagon stimulation, serum insulin and C-peptide levels as well as phases of insulin release did not differ over the 12-month study period. Similarly, the glucose decay constant (KG) was nearly identical at 3, 6, and 12 months. In summary, 1 year following successful whole cadaveric, heterotopic pancreas transplantation in Type 1 diabetic recipients, fasting serum glucose remains normalized, while postprandial glucose tends to rise.(ABSTRACT TRUNCATED AT 250 WORDS)     

The pitfalls of the dexamethasone suppression test: A biological marker of endogenous depression?

In the past few years there have been numerous publications which have stressed the value of the dexamethasone suppression test (DST) as a diagnostic marker of endogenous depression. Our own studies in 333 psychiatric inpatients and 121 healthy subjects did not reveal a differential diagnostic use for the DST. This result is in good agreement with other results in the literature. Our data demonstrate that intervening variables such as severity of illness, weight loss, sleep disturbances, situational stress, drug and alcohol withdrawal, and the pharmacokinetics of dexamethasone have an important influence on DST results, regardless of the diagnostic classification.     

血钙水平与肾癌肿瘤大小、分期的相关性分析

目的分析肾细胞癌患者血钙水平和肿瘤大小与分期的相关性，从而进一步发现与病情相关的规律和了解病情。方法按照血钙水平将肿瘤大小／分期相应地分3组，即降低、正常和升高各3组。利用SPSS10．0软件，对3组不同的肿瘤大小／分期病例进行差异性分析和相关性研究。结果3组不同的肿瘤大小差异性分析（Kruskal-wallisH）显示，X^2=4．768，df=2，P=0．092；Spearman相关分析显示相关系数为．0．166，P=0．029。3组不同的肿瘤分期差异性分析（Kruskal-Wallis H）显示，X^2=4、277，df=2，P=0．118；Spearman相关系数为．0．157，P=-0．039。结论3组不同的肿瘤大小之间差异性无统计学意义，血钙水平与肿瘤大小间存在负相关；3组不同的肿瘤分期之间差异性无统计学意义，血钙水平与肿瘤分期间存在负相关。     

Short-term suppression of plasma free fatty acids fails to improve insulin sensitivity when intramyocellular lipid is elevated.

AIMS: Metabolic responses to manipulation of the plasma free fatty acid (FFA) concentration were assessed in six healthy men via cross-over design to determine whether FFAs independently influence insulin sensitivity. METHODS: Intramyocellular lipid (IMCL) was measured by proton magnetic resonance spectroscopy and insulin sensitivity via frequently sampled intravenous glucose tolerance test (IVGTT) after 67 h of two identical low carbohydrate/high fat (LC) diets which were used to elevate IMCL and plasma FFAs. To uncouple the influence of FFAs and IMCL on insulin sensitivity, FFAs were suppressed 30 min prior to and during IVGTT in one treatment [LC + nicotinic acid (NA)] by NA ingestion. RESULTS: Vastus lateralis IMCL was significantly elevated in LC (13.3 +/- 1.1 x 10(-3)) and LC + NA (13.5 +/- 1.1 x 10(-3)) (P < 0.01 for both), but was not different between conditions (P > 0.05). Plasma FFAs were raised in LC (0.79 +/- 0.08 mmol/l) and LC + NA (0.80 +/- 0.11 mmol/l) (P < 0.01 for both) and were significantly reduced by NA ingestion prior to (0.36 +/- 0.05 mmol/l, P < 0.01) and during IVGTT (P < 0.05) in LC + NA. Despite marked differences in plasma FFA availability, insulin sensitivity and glucose tolerance were not different between LC and LC + NA (P > 0.05 for both). CONCLUSIONS: Plasma FFAs appear to exert no immediate effect on insulin sensitivity/glucose tolerance independent of their action on intracellular lipid moieties. Further research is required to elucidate the duration of FFA suppression required to restore insulin sensitivity following lipid-induced insulin resistance.     

Effect of adiposity on plasma lipid transfer protein activities: a possible link between insulin resistance and high density lipoprotein metabolism

Abstract. The mechanisms responsible for the decreased high density lipoprotein (HDL) cholesterol levels associated with obesity and insulin resistance are not well understood. Lecithin: cholesterol acyltransferase (LCAT) and cholesterol ester transfer protein (CETP) are key factors in the esterification of cholesterol in HDL and the subsequent transfer of cholesteryl ester towards apolipoprotein B-containing lipoproteins. Phospholipid transfer protein (PLTP) may be involved in the regulation of HDL particle size. We therefore measured the activities of LCAT, CETP and PLTP using exogenous substrate assays, as well as lipids, lipoproteins, insulin and C-peptide in fasting plasma from eight healthy obese men (body mass index >27 kg m^-2) and 24 non-obese subjects. The obese men had lower levels of HDL cholesterol (P<0·05) and higher levels of plasma triglycerides (P<0·05), insulin (P<0·05) and C-peptide (P<0·01), as compared to the quartile of subjects with the lowest body mass index (BMI <22·4 kg m^-2). CETP and PLTP activities were elevated in the obese men by 35% (P<0·01) and by 15% (P<0·05), respectively. LCAT activity was comparable among the quartiles. Linear regression analysis showed that CETP activity was positively correlated with body mass index (P<0·02), fasting blood glucose (P7lt;0·05) and plasma C-peptide (P<0·05). PLTP activity was positively related to body mass index (P<0·01), waist to hip circumference ratio (P<0·001), as well as to fasting blood glucose (P<0·05) and plasma C-peptide (P<0·05) It is concluded that the activities of CETP and PLTP are influenced by adiposity and possibly by insulin resistance. Elevated lipid transfer protein activities may provide a mechanism that contributes to alterations in HDL in insulin resistant states.     

胰腺癌细胞的增殖同膜脂质饱和度,膜胰岛素受体的关系

外源性表皮生长因子(或生长抑素)能促进(或抑制)胰腺癌细胞的增殖。胰腺癌细胞增殖速率的高低与细胞膜脂质饱和度的降、升;与膜胰岛素受体数量的增减密切相关。测定细胞膜脂质饱和度和胰岛素受体数量,是判断胰腺癌增殖状态的灵敏指标,有一定临床价值。     

INTRAOPERATIVE BLEEDING IN ENDOSCOPIC SUBMUCOSAL DISSECTION IN THE STOMACH AND STRATEGY FOR PREVENTION AND TREATMENT

To control intraoperative bleeding is an important key to successful endoscopic submucosal dissection. The distribution of submucosal vessels encountered during the procedure differ in places in the stomach and are roughly categorized into three groups: those located in the antrum, those in the lesser curvature, and those on the anteroposterior corpus wall which consists of oblique muscle layers. Therefore, knowledge of a suitable setting of diathermy and adjusted depth of dissection in the submucosal layer for each site is imperative. The combination of utilizing the distal attachment forced or swift coagulation (trimming with coagulation mode) have enable the treatment with an insulation tipped knife safer.