Removing the men who have sex with men blood donation deferral: Informing risk models using Canadian public health surveillance data.

OBJECTIVE: Gay, bisexual and other men who have sex with men (gbMSM) were ineligible to donate blood in most countries since the 1980's. In Canada the deferral period has been incrementally decreased from lifetime to male-to-male sex in the last 3 months. Now a few countries have removed the deferral altogether. Risk models have been utilised to estimate the probability of an HIV positive donation being released into the blood supply and to inform incremental changes to the length of the deferral period. Here we use public health data to estimate the risk of HIV if the gbMSM deferral criteria were removed in Canada. MATERIAL AND METHODS: We calculate the risk reduction among heterosexuals based on responses to standard risk questions routinely asked of donors. We assume gbMSM will donate at the same rate as heterosexual males. We apply the same risk reduction principle to HIV incidence and prevalence among gbMSM in the general population to evaluate the HIV risk without gbMSM time deferral. We model three scenarios where risk reduction is varied by assumptions about incidence and compliance with deferral criteria. RESULTS: The estimates for all scenarios were not significantly different to the currently observed scenario which predicts a residual risk of 0.02 HIV positive per million donations (95% CI: 0.000006-0.09). CONCLUSION: The models predict that removing the gbMSM deferral criteria would result in HIV residual risk similar to currently observed.

Is high hemoglobin a hindrance factor for blood donation? A pilot observational study from the coastal region of India.

BACKGROUND: Blood donors with high Hb are often deferred for the presumed risk of polycythemia vera (PV). However, adequate data to substantiate or refute this hypothesis is lacking. METHODOLOGY: We conducted an observational study on blood donors found to have high hemoglobin (Hb≥18g/dL) during the pre-donation screening process using a portable hemoglobinometer at our blood center for four months. We adopted a cost effective methodology wherein a questionnaire was used to elicit the secondary causative factors of high hemoglobin and a complete blood count test to observe the blood cell parameters and JAK2V617F mutation test was performed in a subset of donors lacking secondary erythrocytosis (SE) history. RESULTS: Of the total 7076 donors enrolled, 112 male donors (1.58%) had high hemoglobin. The majority (70.4%) were repeat donors with mean age of 31.4 years. About 61% of the donors had attributable factors for SE like smoking, occupational exposure to carbon monoxide. The mean hemoglobin value of capillary and venous hemoglobin demonstrated a statistically significant difference (P<0.05) where 2.7% of donors had venous Hb<18g/dL. The hematological profile of all the donors showed increased RBC but normal platelet and WBC count. Of 24 donors included for the JAK2V617F test, none had a positive report. CONCLUSION: This study suggests high hemoglobin in blood donors is less likely due to PV. Hence, re-considering their deferral may help alleviate donor anxiety and allow donor return. However, multi-centric studies are required to develop consensus statements on PV risk status and blood donation eligibility.

Donor deferral policies for men who have sex with men: past, present and future.

We review the history and evolution of blood donor criteria for men who have sex with men (MSM). Deferral policies in many jurisdictions, including Australia, New Zealand, Canada, the United States, Brazil and many western European countries are based on a period of abstinence from MSM, often of 12 months duration. Several countries (Italy, Spain and Portugal) defer donors based on sexual behaviours considered to be at high risk, regardless of whether the partner is same sex or opposite sex. Compliance is a key determinant in the efficacy of any deferral policy. We summarize research themes and strategies discussed at a January 2017 meeting held in Toronto, Canada, to provide an evidence basis for future policy changes.

Donor attention to reading materials.

BACKGROUND AND OBJECTIVES: Mandatory predonation reading materials inform donors about risk factors for transmissible disease, possible complications of donation and changes to the donation process. We aimed to assess the attention to predonation reading materials and factors which may affect attention. MATERIALS AND METHODS: A national survey in 2008 of 18,108 blood donors asked about self-assessed attention to reading the materials. In face-to-face interviews, 441 donors completed additional questions about reading the materials and a literacy test. Qualitative interviews of 27 donors assessed their approach to reading. RESULTS: In the national survey, most of the first-time donors said they read all or most of the materials (90.9% first-time vs. 57.6% repeat donors, P < 0.001) and 66% vs. 23.1% reported reading them carefully (P < 0.001). In face-to-face interviews comparing those who read materials carefully, skimmed or did not read, most knew that donors are informed of positive transmissible disease test results (97.1%, 95.5, 98.0 P > 0.05), but fewer recalled seeing the definition of sex (77.2%, 56.9, 24.2 P < 0.001). Literacy was poor (30.5% frustration level, 60.3% instructional, 9.2% independent) but similar when those who read materials carefully, skimmed or did not read were compared (P > 0.05). Qualitative interviews showed that donors are reluctant to read any more than necessary and decide based on perceived importance or relevance. CONCLUSION: Attention to predonation reading materials tends to be better among first-time donors. The effectiveness is limited by low motivation to read, especially for repeat donors, as well as poor literacy.

The epidemiology of human T-cell lymphotropic virus types I and II in Canadian blood donors.

OBJECTIVES: Blood donors in Canada have been tested for Human T-Cell Lymphotropic Virus (HTLV) since 1990. We report the epidemiology, risk factors and lookback/traceback of HTLV-positive donors/recipients. METHODS: The annual HTLV rate was calculated from 1990 to 2010. Residual risk was estimated as the product of incidence and window period. Twenty-nine HTLV-positive donors and 116 matched controls (ratio 1 : 4) were interviewed about risk factors. For HTLV-positive donations, lookback investigations involved identification of all previous donations, and attempting to locate and test recipients. Traceback was initiated when transfusion transmission was queried for HTLV-positive blood recipients. All donors of products that the recipient received were identified, with an attempt to locate and test them. RESULTS: The HTLV rate decreased from 9.35 per 100,000 donations in 1990 to 1.11 in 2010. The residual risk of infection was 1 in 7.6 million donations. In logistic regression birth overseas (OR 18.7), history of sexually transmitted diseases (OR 32.9), sex with unknown background (OR 5.4) and blood transfusion (OR 8.9) were significant predictors. In the lookback study, of 109 HTLV-positive donors, 508 components were transfused, of whom 147 recipients were tested and 18 (12%) were positive. All were transfused prior to the implementation of donor testing. Twenty-three traceback investigations were requested involving 324 transfused untested products,of whom 219 (67.6%) of donors were tested and 13 (6%) were positive for HTLV. CONCLUSIONS: With testing of the blood supply, the risk from HTLV is very low and while most HTLV-positive donors have risk factors, deferrable risk is rare.

Donor motivation in Xi'an, China: comparison with Canadian donors.

BACKGROUND AND OBJECTIVES: In China, paid donation is prohibited by law. There is little literature assessing donor motivation in China, and comparison with western countries such as Canada is important in understanding the application of Western literature. We compared motivational factors in donors from the city of Xi'an, China, with Canadian donors matched for age, sex and donation status. MATERIALS AND METHODS: A total of 218 donors in Xi'an completed an interview about motivation as did 218 Canadian donors matched for age, sex and donation status. Frequencies and percentages of responses to questions were tabulated and compared using the Chi-squared test. RESULTS: Donors in Xi'an and Canada felt a personal responsibility to donate blood (81·2% vs. 78·0%, P = 0·2057), but Xi'an donors were more likely to consider blood donation a social responsibility (81·7% vs. 45·2%, P < 0·0001). Xi'an donors more often believed that society views donation as a normal activity (98·6% vs. 48·4%, P < 0·0001) and that the social atmosphere promotes donation (90·3% vs. 53·5%, P < 0·0001) and saw greater health benefit (52·3% vs. 12·5%, P < 0·0001). Most Xi'an donors believed in balance between their life force (Qi) and blood (86·7% vs. 49·8%, P < 0·0001) but did not believe blood lost from donating would affect this (0·5% vs. 3·8%, P = 0·01). CONCLUSION: While traditional Chinese beliefs may not be seen as a barrier among people in Xi'an who donate blood, blood donation is seen differently than by Canadian donors. There is a need for more research specific to China to tailor recruitment strategies.

The impact of increasing the upper age limit of donation on the eligible blood donor population in Canada.

OBJECTIVES: Using population prevalence data for deferrable diseases/conditions we estimated the Canadian population eligible to donate according to three upper-age limit scenarios. BACKGROUND: The donor selection criteria limit the number of potential blood donors but relaxing the upper age criteria could mitigate this. METHODS AND MATERIALS: Forty deferral criteria were identified and their corresponding prevalence data obtained to estimate the number of people excluded by the criteria. The eligible blood donor population was estimated from national census data taking the age limits, deferral criteria and deferral time-period into account. As more than one disease/condition may co-exist, the estimate was adjusted to avoid over-representation. RESULTS: Of about 33 million Canadians aged 17 (18 in Québec) to 65, 15·1 million (45·8%) are eligible to donate blood. This number increases to 15·7 million when including people up to 71 years and to 17·1 million in the absence of an upper age limit. CONCLUSION: As about 1·2 million units are collected from 600,000 donors annually, there are more than enough eligible people to meet the need. However, recruitment of donors is challenging and the absence of an upper age limit allows an additional 2 million people to donate. Other countries may wish to consider modification of the upper age criterion to address the effect of an aging population on the blood supply.

Current incidence and residual risk of HIV, HBV and HCV at Canadian Blood Services.

Estimates of the viral residual risk should be updated to reflect current incidence of infection in blood donors. Incidence rates were estimated for allogeneic whole-blood donations made to Canadian Blood Services from 2006 to 2009 based on transmissible disease conversions of repeat donations within a 3-year period. Residual risk was estimated as the incidence multiplied by the window period. The residual risk of HIV was 1 per 8 million donations, HCV 1 per 6·7 million donations and HBV 1 per 1·7 million donations. The residual risk remains low and has decreased for HCV since our previous estimates due to reduced incidence.

Evaluation of the confidential unit exclusion form: the Canadian Blood Services experience.

BACKGROUND: In the mid-1980s, confidential unit exclusion (CUE) was implemented to permit donors unwilling to admit risk factors in screening to exclude their donation from transfusion. With changes in donor behaviour, epidemiology of disease and improvements in testing, many blood establishments have stopped using it. We evaluated its benefit in Canada, and reported its utility in predicting transmissible-disease (TD) and high-risk behaviour. STUDY DESIGN AND METHODS: TD-positive donations and incident cases between 2004 and 2008 were analyzed in CUE-safe and CUE-unsafe designated donations. An anonymous survey of 40,000 donors asked about CUE use and risk factors. RESULTS: There were 7104 (0.15%) donations designated CUE-unsafe of 4,775,044 donations. Most TD-positive donations were designated CUE-safe (1023/1030, 99.32%) with only seven (0.68%) designated CUE-unsafe. Of 95 incident cases, all were designated CUE-safe including three NAT-yield cases (1 HIV and 2 HCV). In the survey, some donors found the CUE difficult to understand [10.5% (first-time), 3.2% (repeat)], only half thought that the blood would still be tested [48.9% (first-time), 45.9% (repeat)], and about a fifth believed that collection site staff could see their designation. No survey respondents who used the CUE admitted to risk behaviour, but about 1% of donors who designated CUE-safe had high-risk behaviours. CONCLUSION: The data do not provide any indication of a safety benefit from CUE, but CUE use results in a small but constant loss of apparently safe donations.

Understanding non-disclosure of deferrable risk: a study of blood donors with a history of intravenous drug use.

Non-disclosure of deferrable risk has received little attention in the literature. We examined deferrable risk (history of intravenous drug use [IVDU]) and donor attitudes towards truthfulness, the screening process and interpretation of the screening question as well as risk profile. Donors negative for all markers with a self-reported history of IVDU (N = 30) and matched controls were identified from an anonymous mail-out survey. In a separate survey, hepatitis C virus (HCV)-positive donors participated in a telephone interview, from which all those with IVDU history (N = 29) were selected plus matched controls (combined total 59 IVDU, 236 controls). IVDU donors, when compared with matched controls, tended to believe that it is OK not to answer truthfully if one believes that her/his blood is safe (18.6% vs. 4.7%) and that some questions are a little too personal (35.6% vs. 21.7%). IVDU donors were more likely than controls to say they failed to acknowledge screening questions appropriately (23% vs. 2.2%) or to agree that IVDU questions are mainly about recent drug taking or sharing needles (29% vs. 11%) even though the screening question asked about IVDU ever without any such qualifiers. IVDU donors were also more likely to have other lifestyle/risk factors such as history of sex with IVDU (45.5% vs. 1.7%). Donors with deferrable IVDU history may rationalise that revealing their status is not necessary and may misinterpret the question. Failure to acknowledge risk behaviour is complex, and some degree of non-disclosure may be an inherent part of pre-donation screening.

Donor's understanding of the definition of sex as applied to predonation screening questions.

BACKGROUND AND OBJECTIVES: Predonation screening questions about sexual risk factors should provide an extra layer of safety from recently acquired infections that may be too early to be detected by testing. Donors are required to read a definition of sex as it applies to predonation screening questions each time they come to donate, but how well donors apply such definitions has not been evaluated. We aimed to determine how donors define sex when answering screening questions. MATERIALS AND METHODS: In total, 1297 whole blood donors were asked in a private interview to select from a list of sexual activities which ones they believed were being asked about in sexual background questions. Donors' definitions were coded as under-inclusive, correct or over-inclusive in relation to the blood services' definition. Qualitative interviews were carried out with 21 donors to understand reasoning behind definitions. RESULTS: Most donors had an over-inclusive definition (58.7%) or the correct definition (31.9%). Of the 9.4% of donors who had an under-inclusive definition, 95% included both vaginal and anal sex, but not oral sex. About 9% in each group were first-time donors (P > 0.05) who had never read the definition. The qualitative interviews indicated that donors reason their definition based on their own concept of transmissible disease risk. CONCLUSION: Donors apply a range of definitions of sex when answering questions about their sexual background. This may be due to different concepts of risk activities, and required reading of the definition has little impact.

Protection of vascular wall function in insulin-resistant rats from copper oxidative stress.

The effects of oxidative stress on vascular function in the insulin-resistant state were assessed in mesenteric resistance arteries of obese, insulin-resistant (cp/cp) and lean, normal (+/?) JCR : LA-cp rats. Nitric oxide-mediated relaxation of noradrenaline-contracted arteries in response to acetylcholine was impaired after 2 h of incubation with Cu(2+) in both genotypes, with or without the continuing presence of Cu(2+). Relaxation was enhanced on initial exposure to Cu(2+), and post-incubation removal of the Cu(2+) resulted in a greater impairment of relaxation. Arteries from cp/cp rats were less impaired in function by Cu(2+) incubation than were those of +/? controls. Sodium nitroprusside-mediated relaxation was impaired by exposure to Cu(2+), with an accompanying increase in EC(50). The impairment in acetylcholine-mediated relaxation in the arteries from both cp/cp and +/? rats was completely inhibited by co-incubation with copper-zinc superoxide dismutase and catalase, confirming that the impairment associated with Cu(2+) incubation was due to oxidative stress. The impairment appears to involve both smooth muscle and the endothelium. The cp/cp rats showed greater resistance to the effects of oxidative stress on arterial function, possibly due to an adaptation to oxidative stress on arterial function associated with the insulin-resistant state.

Beneficial insulin-sensitizing and vascular effects of S15261 in the insulin-resistant JCR:LA-cp rat.

S15261, a compound developed for the oral treatment of type II diabetes, is cleaved by esterases to the fragments Y415 and S15511. The aim was to define the insulin-sensitizing effects of S15261, the cleavage products, and troglitazone and metformin in the JCR:LA-cp rat, an animal model of the obesity/insulin resistance syndrome that exhibits an associated vasculopathy and cardiovascular disease. Treatment of the animals from 8 to 12 weeks of age with S15261 or S15511 resulted in reductions in food intake and body weights, whereas Y415 had no effect. Troglitazone caused a small increase in food intake (P <.05). Treatment with S15261 or S15511 decreased plasma insulin levels in fed rats and prevented the postprandial peak in insulin levels in a meal tolerance test. Y415 had no effect on insulin levels. Troglitazone halved the insulin response to the test meal, but metformin gave no improvement. S15261 decreased the expression of phosphoenolpyruvate carboxykinase and glucose-6-phosphatase and stimulated the expression of acetyl-CoA carboxylase and acyl-CoA synthase. S15261 also reduced the expression of carnitine palmitoyltransferase I and hydroxymethyl-glutaryl-CoA synthase. S15261, but not troglitazone, reduced the exaggerated contractile response of mesenteric resistance vessels to norepinephrine, and increased the maximal nitric oxide-mediated relaxation. S15261, through S15511, increased insulin sensitivity, decreased insulin levels, and reduced the vasculopathy of the JCR:LA-cp rat. S15261 may thus offer effective treatment for the insulin resistance syndrome and its associated vascular complications.

Vascular wall function in insulin-resistant JCR:LA-cp rats: role of male and female sex.

Vascular wall function was assessed in obese insulin-resistant (cp/cp) and lean normal (+/?), male and female, JCR:LA-cp rats. Both male and female cp/cp rats showed enhanced maximum contractility in response to norepinephrine; impaired smooth muscle in response to sodium nitroprusside, a nitric oxide (NO) donor; and impaired relaxation in response to acetylcholine (ACh), compared with their lean counterparts. The abnormalities were similar in male and female cp/cp rats. The NO synthase inhibitor, Nomega-nitro-L-arginine methyl ester (L-NAME), inhibited ACh-mediated relaxation significantly in male rats, both cp/cp and +/?. The inhibition of ACh-mediated relaxation by L-NAME in +/? females was less, with no reduction in maximal relaxation, and was absent in cp/cp females. These effects suggest that the relative importance of NO in the endothelial modulation of smooth muscle contractility is greater in male rats. The results are consistent with a decreased role for endothelial NO in the cp/cp rats of both sexes and a reduction in NO-independent cholinergic relaxation in the male cp/cp rat. This NO-independent mechanism is not affected in the female cp/cp rats. The relatively small differences between males and females in smooth muscle cell and vascular function may contribute to sex-related differences in the atherogenesis, vasospasm, and ischemic damage associated with the obese insulin-resistant state.

Chelation therapy in the JCR:LA-cp rat: experimental assessment of a putative antiatherosclerotic treatment.

OBJECTIVE: To test the efficacy of chelation therapy, an alternative medical treatment, as an antiatherosclerotic procedure, using an animal model of insulin resistance and vascular disease. DESIGN: A prospective animal experiment with procedures modelled on human chelation treatments. SUBJECTS: The JCR:LA-cp rat, a strain that, if homozygous for the autosomal recessive cp gene, becomes obese and insulin resistant, with marked hyperinsulinemia and hypertriglyceridemia, and is unique in the spontaneous development of atherosclerosis and ischemic myocardial lesions. EXPERIMENTAL PROTOCOL: Eight-month-old, obese, male JCR:LA-cp rats were fitted with indwelling venous cannulae and infused over 4 weeks with ethylenediaminetetraacetic acid (EDTA) 5 days a week at a daily dose of 40 mg/kg body weight. At the end of the treatment period, samples were taken for assay of blood parameters and for mineral content of bone. The rats were sacrificed and perfusion-fixed for scanning electron microscopy of the aortic arch. RESULTS: Plasma cholesterol concentrations were not changed by the EDTA treatment. In contrast, plasma triglyceride concentrations were raised significantly (74%, p < 0.05). Lean control rats showed minimal abnormality of the aortic arch, whereas the obese control rats had raised intimal lesions, frequent adherent macrophages and endothelial damage. The frequency of these vascular abnormalities in the EDTA-treated rats was not different from that seen in the obese controls. The bone contents of calcium and magnesium were not significantly reduced. CONCLUSIONS: Chelation therapy using intravenous EDTA has no beneficial effects on the arterial lesions in the atherosclerotic JCR:LA-cp rat. The increase in plasma triglyceride concentrations would be grounds for concern in human patients.

Vascular wall dysfunction in JCR:LA-cp rats: effects of age and insulin resistance.

We tested the hypothesis that aging and insulin resistance interact to increase vascular dysfunction by comparing the function of isolated mesenteric resistance arteries in obese, insulin-resistant JCR:LA-cp rats and lean, insulin-sensitive rats of the same strain at 3, 6, 9, and 12 mo of age. The peak constrictor responses to norepinephrine, phenylephrine, and high potassium were elevated in arteries from obese rats. Responses to these agents increased with age in both obese and lean rats. An eicosanoid constrictor contributed substantially to vasoconstriction in the arteries from both lean and obese animals. Inhibition of nitric oxide synthase increased the vasoconstrictor response to norepinephrine in both obese and lean rats. This effect increased with age in lean rats only. Vascular relaxation in response to acetylcholine and sodium nitroprusside was impaired in the obese rats and did not alter with age. The results suggest that obese JCR:LA-cp rats have enhanced maximal constriction, which originates in the arterial smooth muscle and increases with age. There is evidence that the ability of the arteries to compensate for the enhanced contractility is impaired in obese rats, particularly with advanced age.

Modulation of vasomotion in resistance arteries of JCR:LA-cp rats: a model of insulin resistance.

Obesity and insulin resistance are strongly associated with an increased risk of vascular disease. Vasomotion is the cyclic variation in the diameter of arteries and is a general feature of the vasculature that may have important physiological consequences. We tested the hypothesis that obesity - insulin resistance is associated with abnormal vasomotion by comparing obese, insulin-resistant JCR:LA-cp rats, known to develop vasculopathy, atherosclerosis, and ischemic lesions of the heart, with lean insulin-sensitive animals from the same strain. Vasomotion was assessed using isolated mesenteric arteries on a myograph system after preconstriction to 50% of maximal constriction with norepinephrine. The amplitude of vasomotion was enhanced by the presence of meclofenamate, a prostaglandin H synthase inhibitor, and was diminished by N(G)-nitro-L-arginine methyl ester (L-NAME), a nitric oxide synthase inhibitor. Removal of the endothelium essentially abolished vasomotion, and meclofenamate had no effect on de-endothelialized arteries. Frequency was not altered by either L-NAME or meclofenamate. Although pharmacological inhibition of nitric oxide and eicosanoid production clearly altered vasomotion, there was no difference in the amplitude or frequency of vasomotion in arteries from obese rats compared with lean rats. These results indicate that the endothelium plays a central role in modulating vasomotion, involving both enhancing and inhibiting effects, and that vasomotion is similar between obese, insulin-resistant and lean, insulin-sensitive rats.

Vascular wall reactivity in conductance and resistance arteries: differential effects of insulin resistance.

Insulin resistance is associated with an increased risk of cardiovascular disease that is probably related to abnormalities of vascular wall function. The JCR:LA-cp rat is a unique animal model of human vascular disease that exhibits a profound insulin resistance, vasculopathy, and cardiovascular disease, and allows study of the relationships between insulin resistance and vascular function. Conductance and resistance arteries serve different functions, thus vascular disease may affect these types of artery differently. Concentration-response curves to norepinephrine, phenylephrine, and acetylcholine were studied in conductance vessels (aortic rings) and resistance vessels (mesenteric arteries) from 12-week-old male obese and lean JCR:LA-cp rats. The aortic rings and mesenteric arteries from obese rats showed increased maximal response to phenylephrine compared with those from lean rats, whereas only the mesenteric arteries from obese rats showed increased maximal response to norepinephrine. In aortic rings, relaxation to acetylcholine was similar for both genotypes, but the mesenteric arteries of obese rats showed impaired relaxation to acetylcholine. We conclude that the sensitivity to vasoconstriction is enhanced in aortic rings and mesenteric arteries of obese male JCR:LA-cp rats, but endothelial function is impaired only in the mesenteric resistance arteries of these animals. Hence functional aberrations in the obese, insulin-resistant state are more pronounced in mesenteric resistance arteries than in a major conductance artery.

Low-density lipoprotein size, high-density lipoprotein concentration, and endothelial dysfunction in non-insulin-dependent diabetes.

We examined endothelial function (nitric-oxide mediated) in 29 men with diet-treated non-insulin-dependent (Type 2) diabetes mellitus (NIDDM) and 18 male age-matched controls. Forearm blood flow was measured by venous occlusive plethysmography during intra-arterial administration of acetylcholine (ACh, 7.5 and 15 microg min(-1)) and sodium nitroprusside (SNP, 3 and 10 microg min(-1)). LDL particle size was estimated by non-denaturing gel electrophoresis. Serum lipids, blood pressure, and glycated haemoglobin were also measured. LDL particle size was smaller (p = 0.048) in the diabetic patients than controls. In the diabetic patients, LDL particle size was a significant positive predictor (p = 0.01) of the area under the dose-response curve for ACh, after adjusting for age, HbA1c, systolic BP, and cholesterol (R2 0.20). In stepwise regression including serum lipid and lipoprotein concentrations and LDL particle size, decreased HDL cholesterol was the best predictor of an impaired vasodilatory response to ACh. Vasodilatory responses to sodium nitroprusside were not significantly correlated with LDL particle size or serum lipid and lipoprotein concentrations. We conclude that in men with NIDDM, small, dense LDL particle size is associated with abnormal endogenous release of nitric oxide. The contribution of small, dense LDL particles to the development of endothelial dysfunction and early diabetic vasculopathy may not, however, be as great as decreased HDL cholesterol.