Ethnic comparison of the association of undiagnosed diabetes with obesity.

OBJECTIVE: The aim of the study was to investigate the crude prevalence and estimated probability of undiagnosed diabetes in different ethnic groups, given the same level of obesity. DESIGN AND SUBJECTS: Cross-sectional data from 24 515 men and 29 952 women, aged >or=30 years, and free of previously diagnosed diabetes were included. Baseline body mass index (BMI) and waist circumference were measured. Diabetes was defined according to both fasting and 2-h 75-g glucose criteria. RESULTS: Prevalence of undiagnosed diabetes was the highest in Asian Indians, the lowest in Europeans and intermediate in others, given the same BMI or waist circumference category across the BMI or waist circumference ranges (P<0.001 for all BMI or waist categories). beta-Coefficients corresponding to a 1 s.d. increase in BMI were 0.34/0.28, 0.41/0.43, 0.42/0.61, 0.36/0.59 and 0.33/0.49 for the Asian Indians, Chinese, Japanese, Mauritian Indians and European men/women (homogeneity test: P>0.05 in men and P<0.001 in women), and in waist: 0.31/0.31, 0.30/0.46, 0.22/0.57 and 0.38/0.58 for the Asian Indians, Chinese, Mauritian Indians and Europeans, respectively (homogeneity test: P>0.05 in men and P<0.001 in women). CONCLUSION: Prevalence of undiagnosed diabetes increased with an increasing BMI or waist circumference to a similar degree in men in all ethnic groups but to a lesser degree in Asian Indian women than in others, regardless of the higher prevalence in Asian Indians than in others at the same BMI (or) waist circumference levels.

Does abnormal insulin action or insulin secretion explain the increase in prevalence of impaired glucose metabolism with age in populations of different ethnicities?

BACKGROUND: Age is associated with both impaired glucose and insulin metabolism. To what extent the age-related changes in insulin resistance (IR) and beta-cell function contribute to the increase in prevalence of impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) is less known, and this is investigated in this study. METHODS: This study included 6610 men and 7664 women of different ethnic groups aged 30-69 years. IR and beta-cell function were examined by the homeostasis model assessment of insulin resistance (HOMA-IR) and homeostasis model assessment of beta-cell function (HOMA-B). Odds ratios (ORs) and 95% confidence intervals (95% CIs) were estimated using logistic regression analysis adjusting for body mass index and study. RESULTS: In Chinese men, the ORs (95% CIs) for IFG were 2.69 (1.70, 4.26), 2.51 (1.49, 4.21) and 2.89 (1.68, 4.97), respectively, in age groups of 40-49, 50-59 and 60-69 years compared with 30-39 years (p < 0.001 for trend); the corresponding figures for IGT were 1.73 (1.25, 2.38), 2.54 (1.78, 3.63) and 3.57 (2.46, 5.19) (p < 0.001 for trend). Similar trends for IGT were observed also in Chinese women and other ethnic groups, but not for IFG in Mauritius Indian and Creole men. Adjustment for HOMA-IR and HOMA-B reduced the ORs in all age groups of all ethnicities for both IFG and IGT, but the risk gradient between age groups remained particularly for the IGT. CONCLUSIONS: The age-related increase in glucose intolerance may not be fully explained by the defect in HOMA-IR and HOMA-B. As HOMA-IR and HOMA-B are only surrogate measures of insulin sensitivity and insulin secretion, the results need to be further investigated.

Blood lipid levels in relation to glucose status in seven populations of Asian origin without a prior history of diabetes: the DECODA study.

BACKGROUND: Dyslipidaemia commonly coexists with diabetes. We investigated the association of lipid profiles with glucose levels in populations of Asian origin without a prior history of diabetes. METHODS: Cross-sectional data of 10,374 men and 12,552 women aged 30-74 years from 14 cohorts, representing seven populations of Asian origin were jointly analysed. Multivariable adjusted linear regression analyses with standardized regression coefficients (beta) were performed to estimate relationships between lipids and plasma glucose. RESULTS: Within each glucose category, fasting plasma glucose (FPG) levels were correlated with increasing levels of triglycerides (TGs), total cholesterol (TC), TC to high-density lipoprotein (HDL) ratio and non-HDL cholesterol (non-HDL-C) (p < 0.05 in most of the ethnic groups) and inversely associated with HDL-C (p < 0.05 in some, but not all, of the populations). The association of lipids with 2-h plasma glucose (2hPG) followed a similar pattern as that for the FPG, except that an inverse relationship between HDL-C and glucose was more commonly observed for 2hPG than for FPG among different ethnic groups. CONCLUSIONS: Hyperglycaemia is associated with adverse lipid profiles in Asians without a prior history of diabetes. The 2hPG appears to be more closely associated with lipid profiles than does FPG. When assessing the risk of cardiovascular disease, the association of the dyslipidaemia with intermediate hyperglycaemia needs to be considered.

A socio-historical hypothesis for the diabetes epidemic in Chinese--preliminary observations from Hong Kong as a natural experiment.

It has been hypothesized that the emerging epidemic of diabetes in economically transitioning or recently transitioned populations is due to mismatch between developmental and mature environments. We took advantage of migration within an ethnically homogenous population to investigate this hypothesis, and the potentially modifying role of postnatal growth conditions, proxied by greater height. We used multivariable logistic regression in a population-based cross-sectional study from 1994 to 1996 of 2,341 long-term Hong Kong residents aged 25-74 years, either born in contemporaneously developed Hong Kong or migrants from economically undeveloped Guangdong. Migrant status was not associated with clinically diagnosed diabetes, odds ratio 1.05 (95% confidence interval 0.69-1.58) in adult migrants compared to Hong Kong-born natives and 1.22 (0.83-1.80) in preadult migrants, adjusted for age, sex, socio-economic position, and lifestyle. However, the association of diabetes with migrant status varied with height, suggesting a potentially complex relationship between indicators of prenatal and postnatal nutritional exposures. Compared to tall Hong Kong-born natives, the odds ratio of diabetes was 2.36 (1.20-4.61) in tall migrants, 1.94 (1.07-3.53) in short Hong Kong-born natives, but 1.04 (0.48-2.23) in short adult migrants. Additionally adjusting for body mass index and waist-hip ratio had little effect, apart from attenuating the association between short height and diabetes prevalence in Hong Kong-born natives. Whether the current epidemic of diabetes is a long-standing effect of such mismatch or a "first-generation through effect" generated by rapid economic development causing disproportionate growth remains to be determined.

GooD4Mum: A general practice-based quality improvement collaborative for diabetes prevention in women with previous gestational diabetes.

AIMS: Gestational diabetes (GDM) and Type 2 diabetes pose tremendous health and economic burdens as worldwide incidence increases. Primary care-based systematic diabetes screening and prevention programs could be effective in women with previous GDM. GooD4Mum aimed to determine whether a Quality Improvement Collaborative (QIC) would improve postpartum diabetes screening and prevention planning in women with previous GDM in general practice. METHODS: Fifteen general practices within Victoria (Australia) participated in a 12-month QIC, consisting of baseline and four quarterly audits, guideline-led workshops and Plan-Do-Study-Act feedback cycles after each audit. The primary outcome measures were the proportion of women on local GDM registers completing a diabetes screening test and a diabetes prevention planning consultation within the previous 15 months. RESULTS: Diabetes screening increased with rates more than doubled from 26% to 61% and postpartum screening increased from 43%-60%. Diabetes prevention planning consultations did not show the same level of increase (0%-10%). The recording of body mass index improved overall (51%-69%) but the number of women with normal body mass index did not. CONCLUSIONS: GooD4Mum supported increased diabetes screening and the monitoring of high risk women with previous GDM in general practice.

Prevalence, detection and drug treatment of hypertension in a rural Australian population: the Greater Green Triangle risk factor study 2004-2006.

BACKGROUND: Hypertension is an important risk factor for cardiovascular disease; however, limited findings are available on its detection and management in rural Australia. AIM: To assess the prevalence, awareness and treatment of hypertension in a rural South-East Australian population. METHODS: Three cross-sectional surveys in Limestone Coast, Corangamite Shire and Wimmera regions during 2004-2006 using a random population sample (n = 3320, participation rate 49%) aged 25-74 years. Blood pressure was measured by trained nurses. Information on history of hypertension and medication was obtained by questionnaires. Hypertension was defined as systolic blood pressure >or=140 mmHg and/or diastolic blood pressure >or=90 mmHg and/or on antihypertensive drug treatment. RESULTS: Overall, one-third of participants had hypertension; of these, two-thirds, 54% (95% confidence interval (CI) 47-60) of men and 71% (95% CI 65-77) of women, were aware of their condition. Half of the participants with hypertension were treated and nearly half of these were controlled. Both treatment and control were more common in women (60%, 95% CI 54-67 and 55%, 95% CI 47-64) compared with men (42%, 95% CI 36-49 and 35%, 95% CI 26-44). Monotherapy was used by 55% (95% CI 48-61) of treated hypertensives. Angiotensin-converting enzyme inhibitors were the most frequently used class of antihypertensive drugs in men, whereas angiotensin-converting enzyme inhibitors, angiotensin receptor antagonists and diuretics were all widely used among women. CONCLUSION: This study emphasizes suboptimal detection and treatment of hypertension, especially in men, in rural Australia.

Apolipoprotein E2-Christchurch (136 Arg----Ser). New variant of human apolipoprotein E in a patient with type III hyperlipoproteinemia.

The primary structure of apolipoprotein E (apo E) was investigated in seven type III hyperlipoproteinemic patients with the apo E-2/2 phenotype. Six of the patients had identical two-dimensional tryptic peptide maps. These differed from the normal apo E3 map by the altered mobility of a single peptide. Amino acid analysis and sequencing showed that apo E2 in these patients had a substitution of 158 Arg----Cys. The presence of this mutation in six of the seven type III patients confirms that this is the most common form of apo E2. The seventh type III patient had a unique map with a new peptide resulting from a substitution of 136 Arg----Ser. He was heterozygous for this and for the more common apo E2 (158 Arg----Cys) variant. His very low-density lipoprotein contained approximately five times more apo E2 (136 Arg----Ser) than apo E2 (158 Arg----Cys), as determined by cysteamine treatment and peptide mapping. This new apo E2 mutant thus appears to contribute significantly to the patient's hyperlipidemia.

Is a single definition of the metabolic syndrome appropriate?--A comparative study of the USA and Asia.

The metabolic syndrome has been identified as an increasingly important precursor to cardiovascular diseases in many Asian populations. Our objective was to compare the contribution of component risk factors to the diagnosis of the metabolic syndrome, as defined by the Third report of the National Cholesterol Education Program Expert Panel Adult Treatment Panel (NCEP-ATPIII), in the US and selected Asian populations. Nationally representative survey data from Hong Kong, Taiwan, Thailand and the US were used. Analyses were restricted to men and women aged > or = 35 years. The age-standardized prevalence of the NCEP-ATPIII defined metabolic syndrome was highest in the US (31% in men, 35% in women), and lowest in Taiwan (11% in men, 12% in women). The component risk factors that defined the presence of the metabolic syndrome varied between countries. As expected, abnormal waist circumference was considerably more prevalent among individuals with the metabolic syndrome in the US (72% in men, 94% in women) compared with their Asian counterparts, but substantial variation was also observed between the Asian populations (13-22% in men, 38-63% in women). Furthermore, the relative contribution of other risk factors to the metabolic syndrome was also substantially different between countries. The NCEP-ATPIII definition identifies a heterogeneous group of individuals with the metabolic syndrome in different populations.

Increased plasma apolipoprotein(a) levels in IDDM patients with microalbuminuria.

Patients with insulin-dependent diabetes mellitus (IDDM) have a significantly increased risk of macrovascular disease, particularly if they have persistent proteinuria. To determine whether altered levels of apolipoprotein(a) [apo(a)], the plasminogenlike glycoprotein of the potentially atherogenic lipoprotein(a); contribute to the increased risk of atherosclerosis, apo(a) levels were measured in 107 patients with IDDM and compared with nondiabetic control subjects and male elective coronary artery graft patients. Apo(a) levels were increased in diabetic patients with microalbuminuria (geometric mean 245 U/L, 95% confidence interval [CI] 142-427, n = 30) and albuminuria (mean 196 U/L, 95% CI 97-397, n = 18) with levels comparable to patients with coronary artery disease (mean 193 U/L, 95% CI 126-298, n = 40), which were higher than in the control group (mean 107 U/L, 95% CI 85-134, n = 140; P = 0.016). Apo(a) levels in diabetic patients without microalbuminuria (mean 86 U/L, 95% CI 63-116, n = 59) were comparable with the control population and less than in those with microalbuminuria (P less than 0.001) and albuminuria (P = 0.014). The elevated apo(a) levels found in patients with IDDM and increased urinary albumin loss may contribute to their heightened risk of macrovascular disease.

Frequency distributions of apolipoprotein(a) kringle IV repeat alleles and their effects on lipoprotein(a) levels in Caucasian, Asian, and African populations: the distribution of null alleles is non-random.

A size polymorphism (K IV VNTR) and largely unknown sequence variation in the apolipoprotein(a) [apo(a)] gene on chromosome 6q26-q27 together determine most of the extreme variation in apo(a) glycoprotein expression and lipoprotein(a) [Lp(a)] plasma concentration in Caucasians. We have determined Lp(a) plasma concentrations, the number of kringle IV (K IV) repeats in the apo(a) gene and the expression of the apo(a) glycoprotein in four ethnic groups (Khoi San, South African Blacks, Hong Kong Chinese and Caucasians from the Tyrol, total n = 788). The distributions of Lp(a) concentrations, the frequencies of expressed and non-expressed apo(a) K IV alleles, and the impact of the size polymorphism on Lp(a) concentrations were all heterogeneous across populations. In contrast, the effect of the K IV repeat alleles appeared homogeneous. Lp(a) concentrations were higher in Africans and Chinese than in Caucasians, but this was not explained by differences in K IV repeat allele frequencies among populations. Lp(a) concentrations were highest in Khoi San, suggesting that high Lp(a) is an old African trait. When expressed as Spearman rank correlations the impact of the size polymorphism was smallest in African Blacks (R = -0.386) and largest in the Chinese (R = -0.692). In all four populations, the distribution of non-expressed apo(a) alleles was non-random. Rather they were significantly associated with distinct size alleles and overall positively with high K IV repeat numbers. The negative correlation of K IV repeat length with Lp(a) concentration was non-linear in Khoi San and the average apo(a)-size-allele-associated Lp(a) concentrations were markedly different between all populations. We conclude that besides the apo(a) size variation, other factors affect Lp(a) concentrations to different degrees in the study populations. Most likely, this is sequence variation in apo(a) which is not the same in the different ethnic groups.

In vitro synthesis of M and Z forms of human alpha 1-antitrypsin.

mRNA was prepared from autopsy liver samples from a homozygote for alpha 1-antitrypsin deficiency (PiZZ) and from a normal (PiMM) subject. Both preparations gave equivalent synthesis of alpha 1-antitrypsin in a wheat germ cell-free system. This suggests that the deficiency of plasma alpha 1-antitrypsin associated with the Z variant is due to a failure of processing and secretion of the protein rather than of its synthesis. It is likely that it is the resultant intracellular accumulation of the Z protein rather than a deficiency of protease inhibitor that is the primary cause of the liver pathology associated with this variant.

Apolipoprotein E phenotypes in hyperlipidaemic patients and their implications for treatment.

Apolipoprotein E phenotypes were determined on 417 consecutive lipid clinic patients using an isoelectric focussing technique. Of the 15 patients with phenotype E2/2, 13 (3.1%) had type III hyperlipoproteinaemia and 2 obese identical twins had type V. A further 20 patients (4.8%) had similar plasma and lipoprotein lipid levels but were E2 heterozygotes (14 E3/2 and 6 E4/2). They displayed a widened pre-beta-band almost confluent with the beta-band rather than the broad beta-band shown in classical E2/2 type III patients. In view of the similarities between these heterozygotes and the classical homozygous (E2/2) type III patients and their occurrence in the same families we suggest the nomenclature homozygous and heterozygous type III. In a subsequent comparison between 30 E2/2, 22 E3/2 and 8 E4/2 type III individuals the only significant difference in plasma and lipoprotein lipid parameters was a lower VLDL cholesterol to triglyceride ratio of 0.85 in E3/2 patients than that of 1.24 in E2/2 patients (P less than 0.01). Both homozygous and heterozygous patients showed premature ischaemic heart disease and both responded dramatically and similarly to treatment with clofibrate. These observations indicate that apo E phenotyping is worthwhile in all patients with combined hyperlipidaemia and that homozygous and heterozygous type III hyperlipoproteinaemia is not uncommon.

Growth hormone therapy transiently increases apolipoprotein(a) in short beta-thalassaemia major children with normal growth hormone reserve.

Recombinant human growth hormone (rhGH) is now available for treatment of short stature due to growth hormone (GH) deficiency. It's potential use in other causes of short stature raises concerns about adverse effects of long term treatment on carbohydrate and lipoprotein metabolism. We describe the serial changes in lipids, lipoproteins and apolipoproteins, including apo(a) in 12 children with beta-thalassaemia major undergoing rhGH treatment for 24-36 months. All showed satisfactory increases in height and weight. A significantly higher mean plasma apo(a) was observed at 3 months (102.6 U/l) versus baseline (71.4 U/l, P < 0.01, geometric means). Subsequently apo(a) levels gradually decreased returning to pretreatment levels after 36 months of rhGH treatment. There were parallel rises and falls in the apo(a) isoforms of different sizes during treatment. There were only minimal changes in the other lipid related parameters. All children had markedly reduced cholesterol levels (3.0 +/- 0.49 mmol/l, mean +/- S.D.) characteristic of their underlying disease. In conclusion the elevation of apo(a) by GH is only transient, there is no differential effect of rhGH on the large and small isoforms of apo(a) and there are no clinically significant adverse effects of rhGH treatment on lipoprotein metabolism.

LDL subfractions in acromegaly: relation to growth hormone and insulin-like growth factor-I.

Acromegaly is associated with changes in lipoprotein metabolism and an excess in cardiovascular mortality. We have examined low density lipoprotein (LDL) subfraction distribution in 24 patients with active acromegaly and in controls matched for age, sex and body mass index. LDL was subfractionated by density gradient ultracentrifugation. The concentration of small dense LDL-III was significantly higher in the acromegalic patients compared to the controls (94.2 +/- 44.9 versus 67.2 +/- 30.4 mg/dl, P < 0.05) and there was a concomitant reduction in the intermediate subfraction LDL-II (124.8 +/- 31.3 versus 149.9 +/- 30.0 mg/dl, P < 0.05). Univariate analysis showed that both growth hormone (GH) and insulin-like growth factor (IGF)-I correlated with LDL-III and inversely with LDL-II. Acromegalic patients were found to have lower hepatic lipase (HL) and lipoprotein lipase (LPL) activities than controls (HL: 13.29 +/- 6.56 versus 21.58 +/- 7.27 micromol FFA released/ml/h, P < 0.001: LPL: 7.22 +/- 3.04 versus 11.53 +/- 7.85 micromol FFA released/ml/h, P < 0.05) whereas plasma cholesteryl ester transfer protein (CETP) activity was significantly increased (8.15 +/- 1.81 versus 5.54 +/- 1.86 pmol/microl/h, P < 0.001). Both GH and IGF-I were significantly associated with HL, LPL and CETP activities. Multivariate analysis on this relatively small sample size showed that in normal subjects, triglyceride and HL activity were the major determinants of LDL-III. In contrast, GH and HDL were the main determinants in acromegaly, accounting for 32 and 24% in the variability of LDL-III respectively. In conclusion, GH excess has a direct effect on LDL subfraction distribution.

Serum apolipoprotein(a) correlates with growth hormone levels in Chinese patients with acromegaly.

Untreated acromegaly is associated with an increased cardiovascular morbidity and mortality. The contribution of altered lipid metabolism remains unclear. We investigated the relationship between serum apolipoprotein(a) (apo(a)) and growth hormone (GH) levels in 15 patients with acromegaly before and during treatment with octreotide, a long-acting somatostatin analogue, 288-600 micrograms/day s.c., for 6 months. Before treatment serum apo(a) was significantly elevated in acromegalic patients (geometric mean being 323 U/l vs. 142 U/l in controls (n = 92; P < 0.01)). Octreotide treatment resulted in significant reductions in serum apo(a) concentration (F = 7.22; P < 0.01; geometric mean being 232 U/l and 248 U/l at 3 months and 6 months respectively) and apo(a) concentrations on treatment were not significantly different from control values. There were significant reductions in serum GH (F = 7.30; P < 0.01), insulin growth factor 1 (IGF1) (F = 31.4, P < 0.001) and insulin (F = 4.57; P < 0.05) concentrations. Plasma glycosylated haemoglobin levels were unchanged. Apo(a) levels correlated with serum GH (r = 0.450; P < 0.01) but showed no correlation with basal insulin concentrations. Serum HDL cholesterol increased on treatment (F = 4.29; P < 0.05). Triglycerides were reduced only in the 12 patients without diabetes mellitus (F = 4.75; P < 0.05). No significant change in LDL cholesterol occurred. Our findings suggest that apo(a) may constitute another cardiovascular risk factor in untreated acromegaly and that GH may be involved in the regulation of circulating apo(a) concentration.

Fibrinogen, angina and coronary heart disease in a Chinese population.

Although fibrinogen is an established risk factor of coronary heart disease (CHD), whether fibrinogen is associated with CHD in Chinese is not clear. This population-based cross-sectional study aimed to analyse this relationship in Hong Kong Chinese. Fibrinogen was measured by the Clauss method in 1348 men and 1385 women aged 25-74 years. Severity of CHD was defined as most serious if the subjects had medically diagnosed CHD, as less serious if they had angina only, and as normal if they had neither. The prevalence of angina and CHD was respectively 2.4% and 2.2% in men and 3.2% and 2.7% in women. In men the age-adjusted mean fibrinogen concentration was 2.47 (95% confidence interval (CI) 2.43-2.51) g/l in the normal group, 2.65 (95% CI 2.45-2.85) g/l in the angina group, and 2.78 (95% CI 2.56-3. 00) g/l in the CHD cases (P<0.01); in women it was respectively 2.61 (95% CI 2.59-2.63), 2.66 (95% CI 2.50-2.82), 2.90 (95% CI 2.72-3.08) g/l (P<0.01). The differences were significant after adjustment of other significant risk factors. We conclude that fibrinogen should be considered as a risk factor in Chinese.

The relationship between fibrinogen and other coronary heart disease risk factors in a Chinese population.

Few studies have examined fibrinogen in Chinese populations in which the incidence of coronary heart disease (CHD) is lower than that in the West. This study aimed to examine the relationship between fibrinogen and other CHD risk factors in Hong Kong Chinese. Fibrinogen was measured by the Clauss method in 1359 men and 1405 women aged 25-74 years, randomly selected from the Hong Kong population. Mean fibrinogen level increased with age, from 2.22 g/l in those aged 25-34 years to 2.76 g/l in 65-74 years in men, and from 2.42 to 2.94 g/l respectively in women. The most important factors associated with fibrinogen were age, obesity and blood lipid levels in both genders. In men, smoking was associated with higher fibrinogen levels and cessation of smoking with lower levels. Prospective studies are needed to examine the role of fibrinogen in CHD in Chinese and other Asian populations.

Homozygous Tangier disease and cardiovascular disease.

Decreased levels of plasma high density lipoprotein (HDL) cholesterol have been associated with premature cardiovascular disease (CVD). Tangier disease is an autosomal co-dominant disorder in which homozygotes have a marked deficiency of HDL cholesterol and apolipoprotein (apo) A-I levels (both < 10 mg/dl), decreased low density lipoprotein (LDL) cholesterol levels (about 40% of normal), and mild hypertriglyceridemia. Homozygotes develop cholesterol ester deposition in tonsils (orange tonsils), liver, spleen, gastrointestinal tract, lymph nodes, bone marrow, and Schwann cells. Our purpose was to assess the prevalence of CVD in Tangier disease. We reviewed published clinical information on 51 cases of homozygous Tangier disease, report 3 new cases and provide autopsy information on 3 cases. Mean (+/- S.D.) lipid values of all cases were as follows: total cholesterol 68 +/- 30 mg/dl (32% of normal), triglycerides 201 +/- 118 mg/dl (162% of normal), HDL cholesterol 3 +/- 3 mg/dl (6% of normal) and LDL cholesterol 50 +/- 38 mg/dl (37% of normal). The most common clinical finding in these subjects (n = 54) was peripheral neuropathy which was observed in 54% of cases versus < 1% of control subjects (n = 3130). CVD was observed in 20% of Tangier patients versus 5% of controls (P < 0.05), and in those that were between 35 and 65 years of age, 44% (11 of 25) had evidence of CVD (either angina, myocardial infarction or stroke) versus 6.5% in 1533 male controls and 3.2% in 1597 female controls in this age group (P < 0.01). In 9 patients who died, 2 died prior to age 20 of probable infectious diseases, 3 of documented coronary heart disease at ages 48, 64, and 72, 2 of stroke at ages 56 and 69, one of valvular heart disease, and 1 of cancer. In three autopsy cases, significant diffuse atherosclerosis was observed in one at age 64, moderate atherosclerosis and cerebral infarction in another at age 56, but no atherosclerosis was noted in the third case who died of lymphoma at age 62. In one patient with established coronary heart disease, none of the lipid lowering agents used (niacin, gemfibrozil, estrogen or lovastatin) raised HDL cholesterol levels above 5 mg/dl. However, these agents did have significant effects on lowering triglyceride and LDL cholesterol levels. Our data indicate that there may be heterogeneity in these patients with regard to CVD risk, that peripheral neuropathy is a major problem in many patients, and that CVD is a significant clinical problem in middle aged and elderly Tangier homozygotes.(ABSTRACT TRUNCATED AT 400 WORDS)

Effects of fluvastatin on prothrombotic and fibrinolytic factors in type 2 diabetes mellitus.

The effects of fluvastatin therapy on parameters of coagulation and fibrinolysis were evaluated in patients with diabetic dyslipidemia in a randomized, placebo-controlled study. Fluvastatin therapy was associated with a small reduction in factor VII coagulant activity, von Willebrand factor, and in plasminogen activator inhibitor 1 and tissue plasminogen activator antigens, but the effects of fluvastatin on hemostatic factors were much less marked than its effects on plasma lipids.

Vesicoureteric reflux: segregation analysis.

Complex segregation analysis was applied to data from 88 families containing at least one person with vesicoureteric reflux. Analysis showed that a single major locus was the most important causal factor in this condition, with the mutant allele being dominant to the normal allele and having a gene frequency of about 0.16%. Forty-five percent of gene carriers will have vesicoureteric reflux and/or reflux nephropathy as adults and 15% will develop renal failure, compared to 0.05% and 0.001%, respectively, for those not carrying the gene. This analysis confirms the importance of screening close relatives of persons with proven vesicoureteric reflux or reflux nephropathy.