Distribution of type V secretory phospholipase A2 expression in human hepatocytes damaged by liver disease

BACKGROUND AND AIM: Type V secretory phospholipase A2 (sPLA2-V) is a key enzyme in the arachidonate cascade. However, the distribution of sPLA2-V in human liver has not yet been investigated. In this study, the significance of sPLA2-V expression in human hepatocytes damaged by liver disease was investigated. METHODS: Samples of liver tissue from patients with chronic hepatitis B and C, hepatitis virus-related liver cirrhosis, and congestive hepatocyte injury were immunostained with antibodies against sPLA2-V, cyclooxygenase (COX)-2, hepatitis viral antigens, transforming growth factor (TGF)-beta1, interleukin (IL)-1beta and tumor necrosis factor (TNF)-alpha. RESULTS: In chronic hepatitis patients, sPLA2-V-positive hepatocytes were scattered in the liver lobules, while cyclooxygenase-2, IL-1beta, and TNF-alpha were diffusely expressed. Hepatocytes around necroinflammatory lesions were strongly positive for sPLA2-V. Some sPLA2-V-positive hepatocytes were also positive for viral antigens. TGF-beta1 was expressed only in fibrotic lesions. The pattern of distribution of these proteins in liver cirrhosis patients was similar to that in chronic hepatitis patients, but sPLA2-V expression tended to be more intense than in chronic hepatitis. In the congestive liver, sPLA2-V, COX-2, and the two cytokines were diffusely expressed in surviving hepatocytes. CONCLUSIONS: sPLA2-V expression in hepatocytes is induced by viral infection, fibrosis, and circulatory disturbance. Immunostaining using sPLA2-V antibody is useful for the detection of injured hepatocytes in patients with liver diseases.     

Gastroduodenal reflux induces group IIa secretory phospholipase A2 expression and activity in murine esophagus

Exposure of esophageal epithelium to gastric and duodenal contents results in the histologic changes of hyperproliferation and mucosal thickening. We have previously shown that presence of secretory phospholipase A₂ (sPLA₂) is necessary to produce these histologic changes in a murine model of gastroduodenal reflux. We sought to determine the influence of gastroduodenal reflux (GDR) on sPLA₂ protein and mRNA levels as well as enzyme activity in esophageal tissue. BALB/c (sPLA₂^+/+) mice (n= 28) underwent side‐to‐side surgical anastomosis of the first portion of the duodenum and GE junction (DGEA) resulting in continuous exposure of esophageal mucosa to mixed gastric and duodenal contents. Sham control mice (n= 14) underwent laparotomy, esophagotomy and closure. Real‐time RT PCR was used to quantitate the influence of GDR on group IIa sPLA₂ expression. Immunofluorescent staining was quantitated by digital microscopy using a specific antibody to identify and locate sPLA₂ protein. A colorimetric assay was used to quantify total sPLA₂ activity after standardization of protein levels. Statistical analysis was conducted using Student's t‐test. Group IIa sPLA₂ mRNA and protein levels were increased at 4 and 8 weeks compared with sham controls. This increase occurred in a time‐dependent manner and correlated with esophageal mucosal thickness. Furthermore, sPLA₂ enzyme activity was increased significantly at 4 and 8 weeks compared with untreated controls. The expression of group IIa sPLA₂ as well as sPLA₂ activity is induced by GDR. This novel finding indicates that sPLA₂ may play a role in the development of the histologic changes produced by GDR in esophageal mucosa.     

Transfusion prevents acute chest syndrome predicted by elevated secretory phospholipase A2

Acute pulmonary injury is known as acute chest syndrome (ACS) in patients with sickle cell disease (SCD). Secretory phospholipase A2 (sPLA2) was found to predict those at risk for ACS and a trial was designed to determine if red blood cell transfusion can be used to prevent ACS. Patients with an elevated sPLA2 were randomised to either receive a single transfusion or standard care. Five of the eight patients (63%) randomised to standard care developed ACS versus none of the seven patients randomised to the transfusion arm (P = 0.026, Odds ratio = 23.6, 95% confidence interval 1, 557). This study suggests that transfusion may prevent ACS.     

Metabolism of very low- and low-density lipoproteins isolated from normolipidaemic Type 2 (non-insulin-dependent) diabetic patients by human monocyte-derived macrophages

Summary The very low- and low-density lipoprotein fractions were isolated from 16 normolipidaemic Type 2 (non-insulin-dependent) diabetic patients in good to fair glycaemic control and from corresponding age-, sex-, and race-matched, non-diabetic control subjects. Rates of cholesteryl ester synthesis averaged 268±31 vs 289±40 pmol ¹⁴C-cholesteryl oleate·-mg cell protein^–1·20 h^–1 for very low- and 506±34 vs 556±51 pmol ¹⁴C-cholesteryl oleate·mg cell protein^–1·20 h^–1 for low-density lipoproteins isolated from the Type 2 diabetic patients and control subjects, respectively, when they were incubated with human macrophages. A group of approximately one-third of the patients was selected for separate analyses because very low-density lipoproteins isolated from these patients did stimulate more cholesteryl ester synthesis when incubated with macrophages. There were no significant differences in the lipid composition of the lipoproteins isolated from the three groups of subjects. The relative proportion of apoprotein C to apoprotein E was significantly decreased (p<0.002) in the very low-density lipoproteins from diabetic patients and was further decreased in samples from these selected diabetic patients. The apoprotein C-I content of very low-density lipoproteins isolated from diabetic patients was increased compared to control subjects and was further increased in samples from the selected diabetic patients (p<0.02). There were no significant differences in the proportions of apoproteins C-III-0, C-III-1, or C-III-2 among the three groups. These studies suggest that in normolipidaemic Type 2 diabetic patients, the apoprotein composition of VLDL is abnormal and this may alter VLDL macrophage interactions and thus contribute to the increased prevalence of atherosclerosis in diabetic patients.     

Synovial-type (group II) phospholipase A2 in serum of febrile patients with haematological malignancy

Abstract: Elevated concentrations of synovial-type (group II) phospholipase A2 (PLA2-II) in serum are associated with septic bacterial infections. We measured the concentrations of PLA2-II in serum in 24 fever episodes involving patients suffering from haematological malignancies and having fever after cytotoxic treatment. We applied a novel time-resolved fluoroimmunoassay using a polyclonal antibody raised against recombinant human synovial-type PLA2. The concentrations of PLA2-II in serum were 194.7 ± 204.4 μg/l (mean ± SD, median 141.9, range 4.6–931.5 μg/l). The concentrations of PLA2-II correlated well to the concentrations of C-reactive protein (CRP) in serum (r = 0.688, p<0.001). The PLA2-II concentrations increased faster than the corresponding CRP values and began to decrease 12 hours after the beginning of antimicrobial treatment. Inverse correlations were found between the concentrations of PLA2-II and blood neutrophil and platelet counts. No correlation was found between the concentrations of PLA2-II and the duration of the time interval from the onset of preceding cytotoxic and corticosteroid treatment to the first blood sample. The concentration of pancreatic PLA2 was within the reference interval in all samples. The present results indicate that PLA2-II resembles an acute-phase protein and is not of blood cell or pancreatic origin.     

The role of lipoprotein-associated phospholipase A(2) in the metabolic syndrome and diabetes

OBJECTIVES: Lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) is a novel inflammation marker. We investigated its association with other coronary risk factors and evaluated its role as a comprehensive marker of the metabolic syndrome in individuals with type 2 diabetes. METHODS: Our cross-sectional study evaluated 92 insulin-treated subjects with type 2 diabetes. Biochemical measurements of Lp-PLA(2), glycemic control, lipid profiles, and C-reactive protein were carried out. Seventy-seven subjects were diagnosed as having the metabolic syndrome, which was defined according to the American Heart Association/National Heart, Lung, and Blood Institute Scientific Statement. RESULTS: Lp-PLA(2) was significantly correlated with waist-hip ratio (r=.25), triglycerides (r=.50), high-density lipoprotein cholesterol (r=-.31), and low-density lipoprotein cholesterol (LDL-C; r=.27; all P<.02). In a multiple-regression model, triglycerides and LDL-C levels were the significant predictors of Lp-PLA(2). Lp-PLA(2) was significantly higher in subjects with the metabolic syndrome than in those without it (268+/-23.4 vs. 127+/-15.8 ng/ml, P<.001). There was a linear increase in Lp-PLA(2) with an increment of the number of the metabolic syndrome criteria (P(trend)=.041). Another multiple-regression model showed that the hypertriglyceridemia component was the only predictor of Lp-PLA(2). CONCLUSIONS: Our findings suggest that Lp-PLA(2) assay potentially facilitates a more comprehensive assessment of the metabolic syndrome in patients with type 2 diabetes on insulin.     

血清脂联素与新诊断2型糖尿病病人及代谢综合征患者的关系

目的对血清脂联素水平与新诊断2型糖尿病及代谢综合征患者的关系进行观察和分析。方法测定140例新诊断2型糖尿病患者与80例非糖尿病患者空腹血清脂联素及血糖、血脂、血压等指标，并分析各指标与脂联素的相关性。结果（1）新诊断2型糖尿病患者的血清脂联素水平显著降低。（2）随着代谢综合征指标的增多，脂联素含量呈下降趋势。（3）新诊断为糖尿病组中脂联素与代谢综合征、男性、体重指数呈负相关，与高密度脂蛋白胆固醇呈正相关。结论血清脂联素浓度与2型糖尿病及代谢综合征密切相关，低脂联素血症是糖尿病及代谢综合征的又一特征，在其发病中可能起重要的作用。     

血清尿酸水平对2型糖尿病一级亲属代谢综合征的预测价值

目的：观察2型糖尿病一级亲属中血清尿酸水平是否与代谢综合征（MS）的组成成分有关,明确在2型糖尿病一级亲属这一高危人群中尿酸能否成为预测MS的独立因子。方法招募年龄在40～70岁的2型糖尿病一级亲属322人,其中男性119人,女性203人,检测身高、体质量、血压、肝功、肾功、血脂以及口服糖耐量试验,计算体质量指数（BMI）。根据中华医学会糖尿病学分会关于MS的诊断标准（2004）诊断MS。结果在全部人群中,血清尿酸水平与身高、体质量、BMI、餐后2h血糖（2hPBG）、收缩压（SBP）、舒张压（DBP）、甘油三酯（TG）、高密度脂蛋白胆固醇（HDL-C）有关（r＝0.376、0.450、0.285、0.127、0.244、0.225、0.395、-0.184,P＜0.05）,尿酸水平为365～537μmol/L（男性）及283～411μmol/L（女性）的MS患病率（男性62.1%,女性32.7%）明显高于0～274,275～320μmol/L（男性,30.0%,26.7%）及0～188,189～230μmol/L（女性,7.8%,9.6%）,尿酸水平在MS人群中明显高于无MS人群[（315.83±83.97） vs （251.80±75.21）μmol/L,P＜0.01]。不论男性还是女性,尿酸平均水平随着MS组成个数的增加而增高（P＜0.05）。尿酸对MS的单因素logistic回归分析中,比值比（OR）及95%可信区间为男性1.008（1.002？1.013,P＝0.005）、女性1.010（1.004？1.016,P＝0.001）。多因素logistic回归分析尿酸对MS的作用则不显著。结论尿酸与MS大部分组成部分相关, MS患者有较高的尿酸水平,但尿酸可能不是预测MS独立因素。     

Increased mean carotid intima media thickness in type 2 diabetes mellitus patients with non-blood pressure component metabolic syndrome: A preliminary report

AIMS:

Patients with type-2 diabetes mellitus have greater carotid intima media thickness and they are at risk for generalized atherosclerosis. This study aimed to compare the thickness of carotid artery intima media in type-2 diabetes mellitus patients with and without nonblood pressure component metabolic syndrome.

SETTINGS AND DESIGN:

This was a comparative observational study conducted in the Departments of Pharmacology and Physiology in the College of Medicine, Al-Mustansiriyia University in cooperation with Baghdad Teaching Hospital.

MATERIALS AND METHODS:

Forty-six diabetic patients of both sexes with systolic blood pressure < 130 mm Hg and diastolic blood pressure < 85 mm Hg were subjected to high resolution B-mode ultrasonography of the common and internal carotid arteries. Patients were grouped into those without metabolic syndrome (Group I) and with nonblood pressure component metabolic syndrome (Group II).

STATISTICAL ANALYSIS:

The two-tailed unpaired Student''s t-test was used in this study.

RESULTS:

Significantly high mean thickness was observed in the common carotid intima media (0.824 ± 0.155 mm) but not in the internal carotid arteries in group II patients compared to group I patients (0.708 ± 0.113 mm). Group II also had a significant number of patients with increased lesion intima media thickness (≥ 1.1 mm).

Conclusion:

The greater carotid intima media thickness observed in type 2 diabetes mellitus patients is related to the metabolic syndrome even in the absence of the blood pressure component.     

Melatonin ameliorates SGLT2 inhibitor-induced diabetic ketoacidosis by inhibiting lipolysis and hepatic ketogenesis in type 2 diabetic mice

Sodium-glucose cotransporter-2 inhibitors (SGLT2i) are effective hypoglycemic agents that can induce glycosuria. However, there are increasing concerns that they might induce diabetic ketoacidosis. This study investigated the effect of melatonin on SGTL2i-induced ketoacidosis in insulin-deficient type 2 diabetic (T2D) mice. The SGLT2i dapagliflozin reduced blood glucose level and plasma insulin concentrations in T2D mice, but induced increases in the concentrations of plasma β-hydroxybutyrate, acetoacetate, and free fatty acid and a decrease in the concentration of plasma bicarbonate, resulting in ketoacidosis. Melatonin inhibited dapagliflozin-induced ketoacidosis without inducing any change in blood glucose level or plasma insulin concentration. In white adipose tissue, melatonin inhibited lipolysis and downregulated phosphorylation of PKA, HSL, and perilipin-1. In liver tissue, melatonin suppressed cellular cyclic AMP levels and downregulated phosphorylation of PKA, AMPK, and acetyl-CoA carboxylase (ACC). In addition, melatonin increased hepatic ACC activity, but decreased hepatic CPT1a activity and acetyl-CoA content. These effects of melatonin on lipolysis and hepatic ketogenesis were blocked by pretreatment with melatonin receptor antagonist or PKA activator. Collectively, these results suggest that melatonin can ameliorate SGLT2i-induced ketoacidosis by inhibiting lipolysis and hepatic ketogenesis though cyclic AMP/PKA signaling pathways in T2D mice. Thus, melatonin treatment may offer protection against SGLT2i-induced ketoacidosis.     

Apolipoprotein C in Type 2 (non-insulin-dependent) diabetic patients with hypertriglyceridaemia

Summary The composition of apolipoprotein C of the very low density lipoproteins (VLDL) was examined in 23 treated Type 2 (non-insulin-dependent) diabetic patients, who had elevated VLDL concentrations. Apolipoprotein C was separated by isoelectric focussing into apolipoprotein C-II which is known as the specific activator of lipoprotein lipase, and three apolipoprotein C-III fragments. A regulatory role has been ascribed to the ratio of apolipoprotein C-II to apolipoprotein C-III in the removal of plasma triglycerides. In our diabetic group, the composition of apolipoprotein C of the VLDL particles was not different from that of a healthy control group. In particular, the above apolipoprotein ratio and the relative amounts of apolipoprotein C-III fragments were normal. Hypertriglyceridaemia in these diabetic subjects does not seem to be related to alterations in the apolipoprotein C composition.     

急性冠脉综合征与脂蛋白相关磷脂酶A2的相关性

目的 探讨急性冠脉综合征患者血清脂蛋白相关磷脂酶A2（Lp-PLA2）的水平及其对预后的临床价值.方法 入选急性冠脉综合征（ACS）患者112例,分为不稳定型心绞痛（UA）组、急性心肌梗死（AMI）组和非ST段抬高型心肌梗死（NSTEMI）组,其中UA组根据危险度分层分为低危、中危和高危组;对照组78例.所有患者均行冠状动脉造影检查,采用Gensini积分方法对各支冠状动脉病变程度进行评定,用ELISA方法测定各组Lp-PLA2水平,进行对比分析.结果 ACS各组患者血清Lp-PLA2水平均显著高于对照组（P＜0.01）;AMI组Lp-PLA2水平显著高于UA组（P＜0.01）;高危、中危组Lp-PLA2水平均高于低危组（P＜0.01,P＜0.05）,且三组相对应的冠脉评分也随着危险度的升高而增加（P＜0.01）.结论 Lp-PLA2水平可作为预测ACS病情严重程度及预后的重要生化指标之一.     

急性冠状动脉综合征患者血清血栓调节蛋白和脂蛋白相关磷脂酶A2水平变化及临床意义

目的:检测急性冠状动脉综合征(ACS)患者血清血栓调节蛋白(TM)及脂蛋白相关磷脂酶A2(Lp-PLA2)水平变化及临床意义。方法:入选冠心病患者120例,分为ACS组69例和稳定性心绞痛(SAP)组51例。再将120例冠心病患者按病变血管支数分为单支病变组(45例)、双支病变组(38例)和3支病变组(37例)。采用Gensini评分系统评定冠状动脉血管病变狭窄程度,按Gensini积分分为轻度病变组(<26分)36例、中度病变组(26~54分)48例和重度病变组(>54分)36例。另选同期有胸痛症状CTA正常的患者20例为对照组。用酶联免疫吸附试验(ELISA)法分别检测血清TM、Lp-PLA2水平。结果:与对照组比较,SAP组、ACS组血清TM、Lp-PLA2水平均明显升高;与SAP组比较,ACS组血清TM、Lp-PLA2均明显升高。单支病变组、双支病变组及3支病变组血清TM、Lp-PLA2均差异无统计学意义。重度病变组血清TM水平明显高于中度病变组和轻度病变组(均P<0.05)。轻度病变组、中度病变组和重度病变组血清Lp-PLA2均差异无统计学意义(P>0.05)。ACS组患者血清TM和Lp-PLA2间呈正相关,而SAP组和对照组间无相关。结论:ACS患者血清TM和Lp-PLA2均升高,说明炎性反应及内皮功能损伤参与了ACS的发病过程,并且两者可能有协同作用。     

Role of group II secretory phospholipase A2 in atherosclerosis: 1. Increased atherogenesis and altered lipoproteins in transgenic mice expressing group IIa phospholipase A2.

Some observations have suggested that the extracellular group IIa phospholipase A2 (sPLA2), previously implicated in chronic inflammatory conditions such as arthritis, may contribute to atherosclerosis. We have examined this hypothesis by studying transgenic mice expressing the human enzyme. Compared with nontransgenic littermates, the transgenic mice exhibited dramatically increased atherosclerotic lesions when maintained on a high-fat, high-cholesterol diet. Surprisingly, the transgenic mice also exhibited significant atherosclerotic lesions when maintained on a low-fat chow diet. Immunohistochemical staining indicated that sPLA2 was present in the atherosclerotic lesions of the transgenic mice. On both chow and atherogenic diets, the transgenic mice exhibited decreased levels of HDLs and slightly increased levels of LDLs compared with nontransgenic littermates. These data indicate that group IIa sPLA2 may promote atherogenesis, in part, through its effects on lipoprotein levels. These data also provide a possible mechanism for the observation that there is an increased incidence of coronary artery disease in many chronic inflammatory diseases.     

Prediction of cardiovascular and total mortality in Chinese type 2 diabetic patients by the WHO definition for the metabolic syndrome

AIM: The aim of this study is to investigate the prevalence of metabolic syndrome (MES) in type 2 diabetic patients and the predictive values of the World Health Organization (WHO) and National Cholesterol Education Programme (NCEP) definitions and the individual components of the MES on total and cardiovascular mortality. METHODS: A prospective analysis of a consecutive cohort of 5202 Chinese type 2 diabetic patients recruited between July 1994 and April 2001. RESULTS: The prevalence of the MES was 49.2-58.1% depending on the use of various criteria. There were 189 deaths (men: 100 and women: 89) in these 5205 patients during a median (interquartile range) follow-up period of 2.1 (0.3-3.6 years). Of these, 164 (87%) were classified as cardiovascular deaths. Using the NCEP criterion, patients with MES had a death rate similar to those without (3.51 vs. 3.85%). By contrast, based on the WHO criteria, patients with MES had a higher mortality rate than those without (4.3 vs. 2.4%, p = 0.002). Compared to patients with neither NCEP- nor WHO-defined MES, only the group with MES defined by the WHO, but not NCEP, criterion had significantly higher mortality rate (2.6 vs. 6.8%, p < 0.001). Using Cox regression analysis, only age, duration of diabetes and smoking were identified as independent factors for cardiovascular or total death. Among the various components of MES, hypertension, low BMI and albuminuria were the key predictors for these adverse events. CONCLUSIONS: In Chinese type 2 diabetic patients, the WHO criterion has a better discriminative power over the NCEP criterion for predicting death. Among the various components of the MES defined either by WHO or NCEP, hypertension, albuminuria and low BMI were the main predictors of cardiovascular and total mortality.     

Low HDL‐cholesterol is common in European Type 2 diabetic patients receiving treatment for dyslipidaemia: data from a pan‐European survey

Aims To measure the prevalence of low high‐density lipoprotein (HDL)‐cholesterol (men < 1.03 mmol/l; women < 1.29 mmol/l) in European Type 2 diabetic patients receiving treatment for dyslipidaemia. Methods The pan‐European Survey of HDL‐cholesterol measured lipids and other cardiovascular risk factors in 3866 patients with Type 2 diabetes and 4436 non‐diabetic patients undergoing treatment for dyslipidaemia in 11 European countries. Results Diabetic patients were more likely to be obese or hypertensive than non‐diabetic patients. Most patients received lifestyle interventions (87%) and/or a statin (89%); treatment patterns were similar between groups. Diabetic patients had [means (SD)] lower HDL‐cholesterol [1.22 (0.37) vs. 1.35 mmol/l (0.44) vs. non‐diabetic patients, P < 0.001] and higher triglycerides [2.32 (2.10) vs. 1.85 mmol/l (1.60), P < 0.001]. More diabetic vs. non‐diabetic patients had low HDL‐cholesterol (45% vs. 30%), high triglycerides (≥ 1.7 mmol/l; 57% vs. 42%) or both (32% vs. 19%). HDL‐cholesterol < 0.9 mmol/l was observed in 18% of diabetic and 12% of non‐diabetic subjects. Differences between diabetic and non‐diabetic groups were slightly greater for women. LDL‐ and total cholesterol were lower in the diabetic group [3.02 (1.05) vs. 3.30 mmol/l (1.14) and 5.12 (1.32) vs. 5.38 mmol/l (1.34), respectively, P < 0.001 for each]. Conclusions Low HDL‐cholesterol is common in diabetes: one in two diabetic women has low HDL‐cholesterol and one diabetic man in four has very low HDL‐cholesterol. Management strategies should include correction of low HDL‐cholesterol to optimize cardiovascular risk in diabetes.     

Impact of metabolic syndrome risk factors in first-degree relatives of type 2 diabetic patients

OBJECTIVE: Family members of patients with an established diagnosis of type 2 diabetes mellitus (T2DM) are theoretically at risk of having the metabolic syndrome (MetS). A sample of these family members was studied from a population in a small township in Argentina, which has a high prevalence of T2DM. METHODS: We examined the clinical and metabolic characteristics of 132 first-degree relatives of T2DM patients (FDR) and 112 age-matched controls. The subjects were categorized according to the International Diabetes Federation (IDF) and National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATPIII) criteria for MetS. RESULTS: The prevalence of MetS in the FDR group was 34.8 (IDF) and 26.5% (NCEP-ATPIII) respectively, which was significantly different to the prevalence in controls (p < 0.025). According to IDF criteria, the most prevalent factors among FDR subjects with MetS were low HDL-cholesterol (87%) followed by hypertriglyceridemia (69.5%). In the MetS group, which ranged between 20-29 years old (36%), the major risk factor in women was a low HDL-cholesterol serum level. In the MetS group, which ranged between 30-39 years old (44.4%), the most important risk factor in men was hypertriglyceridemia. CONCLUSION: This study revealed that the prevalence of MetS is high in young FDR adults, who need urgent preventive treatment, including lifestyle changes. The risk of developing T2DM is five times higher in non-diabetic people with MetS than in those without the syndrome.     

Lipoprotein lipase activity and serum lipoproteins in untreated Type 2 (insulin-independent) diabetes associated with obesity

Summary Serum lipoproteins and the heparin-releasable lipoprotein lipase (LPL) activity of adipose tissue and skeletal muscle were measured in 36 untreated obese patients with Type 2 (insulin-independent) diabetes and the values were compared with those of non-diabetic subjects of similar age, sex and relative body weight. In diabetic men, the LPL activity of adipose tissue was significantly reduced when expressed per tissue weight or per fat cell (p<0.01). Diabetic females had slightly but not significantly lower LPL activity in adipose tissue than the non-diabetic females. The muscle LPL activity was similar in diabetic and non-diabetic subjects of both sexes. When the diabetic men were classified according to fasting blood glucose, the patients with high glucose levels had lower adipose tissue LPL activity than those with moderate hyperglycaemia. In both diabetic and non-diabetic subjects, there was a significant positive correlation between HDL cholesterol concentrations and adipose tissue LPL activity. It is concluded that Type 2 diabetes influences adipose tissue LPL activity and plasma lipoprotein concentrations and that this effect is superimposed on the similar changes produced by obesity alone.