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Aims To investigate the usefulness of the additional measurement of HbA1c, compared with performing only the oral glucose tolerance test ( OGTT), in identifying participants at increased cardiometabolic risk, in an urban Chinese population. Methods All participants from the fourth visit of the population-based Hong Kong Cardiovascular Risk Factors Prevalence Study, without known diabetes, were included. All had their glycaemic status assessed by OGTT and HbA1c, according to American Diabetic Association 2010 criteria. Results Based on OGTT criteria alone, 3.5% of the study cohort ( N = 1300) had diabetes and 19.2% had prediabetes. Based on HbA1c criteria only, 6.2% had diabetes and 61.2% had prediabetes. The measurement of HbA1c, in addition to the OGTT, increased the proportion of participants with diabetes to 7.8% and with prediabetes to 65.3%. Subjects with prediabetes having raised HbA1c but normal glycaemia ( N = 600) had waist circumference, systolic blood pressure, fasting glucose, insulin resistance index ( HOMA- IR), Gutt Index and Framingham 10-year cardiovascular risk scores intermediate between those with both normal HbA1c and glycaemia ( N = 350), and those with impaired fasting glucose and/or impaired glucose tolerance ( N = 249; all P < 0.01). Conclusion The measurement of HbA1c in our population, in addition to the OGTT, results in the detection of a large number of participants with prediabetes having raised HbA1c but normal glycaemia who have a cardiometabolic risk profile intermediate between impaired fasting glucose and/or impaired glucose tolerance and normal participants, and would benefit from early lifestyle intervention. [ABSTRACT FROM AUTHOR]

A 51-year-old man was referred for evaluation of gradual increase in body fat over bilateral arms, chest and abdomen for 6 months. He was a non-smoker and he drank at least four bottles of beer daily since the age of 18. There was no significant past medical history or any family history of obesity or endocrine diseases. Physical examination showed localized large bulk of fat over the neck, both arms and mammary regions, abdomen, and back (Figs and ). The lower limbs and buttock were relatively spared. There was telangiectasia over the face and chest wall, but no palmar erythema nor finger clubbing. The liver span was normal, and the spleen tip was palpated 2 cm below the costal margin. Examination of the cardiovascular, respiratory and neurological system was normal. [ABSTRACT FROM AUTHOR]

Adipose tissue is a highly dynamic endocrine organ, secreting a number of bioactive substances (adipokines) regulating insulin sensitivity, energy metabolism and vascular homeostasis. Dysfunctional adipose tissue is a key mediator that links obesity with insulin resistance, hypertension and cardiovascular disease. Obese adipose tissue is characterized by adipocyte hypertrophy and infiltration of inflammatory macrophages and lymphocytes, leading to the augmented production of pro-inflammatory adipokines and vasoconstrictors that induce endothelial dysfunction and vascular inflammation through their paracrine and endocrine actions. By contrast, the secretion of adiponectin, an adipokine with insulin sensitizing and anti-inflammatory activities, is decreased in obesity and its related pathologies. Emerging evidence suggests that adiponectin is protective against vascular dysfunction induced by obesity and diabetes, through its multiple favourable effects on glucose and lipid metabolism as well as on vascular function. Adiponectin improves insulin sensitivity and metabolic profiles, thus reducing the classical risk factors for cardiovascular disease. Furthermore, adiponectin protects the vasculature through its pleiotropic actions on endothelial cells, endothelial progenitor cells, smooth muscle cells and macrophages. Data from both animal and human investigations demonstrate that adiponectin is an important component of the adipo-vascular axis that mediates the cross-talk between adipose tissue and vasculature. This review highlights recent work on the vascular protective activities of adiponectin and discusses the molecular pathways underlying the vascular actions of this adipokine. [ABSTRACT FROM AUTHOR]

Androgen deficiency in the ageing male (ADAM) was proposed to characterize a symptom cluster of decrease in sexual function and strength, dysphoria and osteopenia in ageing men with decreased levels of androgens. Unlike menopause, literature on the topic is scarce and focuses mainly on the physiological aspects of the problem. However, men with ADAM also face a milieu of psychosocial stressors which may adversely affect their mental health. It is pertinent to examine ADAM within a psychological context. This study aims to determine the prevalence of symptoms of ADAM among Chinese men, and to examine their relationship with psychological distress and quality of life. A cross-sectional design was employed with standardized questionnaires to assess symptoms of ADAM and related psychological factors. The ADAM questionnaire, Hospital Anxiety and Depression Scale, Perceived Stress Scale, General Health Questionnaire and Short Form Health Survey-12 were administered to a community sample of 311 Chinese men (aged 40–80) attending a family medicine clinic in Hong Kong. Demographic information was also collected. A total of 87.8% of the sample was screened ADAM positive using the ADAM questionnaire. Age, duration of marriage, occupation, household income and physical health were found to be significantly associated with ADAM status. ADAM positive individuals were found to have higher anxiety and depression scores, higher stress level, higher psychiatric morbidity and poorer physical and mental quality of life compared with their ADAM negative counterparts. Symptoms of ADAM are prevalent among the Chinese. ADAM positivity as measured by the ADAM questionnaire is associated with poorer psychological well-being and quality of life in the ageing population. Further research and clinical attention to the psychological needs of this population is warranted. [ABSTRACT FROM AUTHOR]

Objectives. F11 receptor, also known as junctional adhesion molecule-1, in the autonomic nervous system is implicated in the development of hypertension in spontaneous hypertensive rats. We investigated the association of single nucleotide polymorphisms (SNPs) in the F11 receptor gene ( F11R) with hypertension and central obesity in Hong Kong Chinese. Methods. Seven tagging SNPs were identified in the HapMap database. Genotyping was performed using Sequenom MassArray in 263 hypertensive subjects and 393 normotensive controls, of whom 263 matched the cases in age and sex. Results. When subjects on anti-hypertensive medication were excluded, rs790056 and rs2774276 were associated with lower systolic blood pressure (TT:124.8 ± 18.3 mmHg vs. TC + CC: 120.2 ± 15.5 mmHg, P = 0.004 and CC: 124.7 ± 18.5 mmHg vs. CG+GG: 120.5 ± 15.1 mmHg, P = 0.007 respectively). Comparing 213 subjects with central obesity with 213 controls matched for sex and age, rs2481084 and rs3737787 were associated with lower odds of central obesity (odds ratio = 0.516, P = 0.002 and odds ratio = 0.540, P = 0.005 respectively). All these associations remained significant after correction for multiple testing. Analysis of statistically similar SNPs suggested that the causative variants for systolic blood pressure were located in F11R, whilst those for central obesity could be due to causative variants in the transcription factor 1 gene immediately upstream. Conclusions. F11 receptor plays a role in blood pressure regulation, not only in rats but also in man. The link between F11 receptor and central obesity merits further investigation. [ABSTRACT FROM AUTHOR]

Background Postprandial changes in remnant-like lipoprotein particles (RLP) contribute to the severity of coronary heart disease in type 2 diabetes. Since the determinants of postprandial response in RLP are not well understood, this study investigated the roles of fasting triglyceride, apolipoprotein (apo) E polymorphism and insulin resistance in a group of overweight/obese Chinese type 2 diabetic subjects. Methods Postprandial triglyceride (TG) and RLP-cholesterol (RLP-C) were determined after a mixed meal containing 70-g fat at 2-h intervals for 8 h in 32 normotriglyceridemic (NTG) and 31 hypertriglyceridemic (HTG) subjects. RLP-C was measured using an immunoseparation assay and apo E genotypes using polymerase chain reaction and restriction mapping. Insulin resistance was defined as homeostasis model assessment index (HOMA-IR). Results The HTG subjects had greater postprandial increase in TG and RLP-C than NTG ( p < 0.001), but there were no significant differences in HOMA-IR and apo E allele frequencies. Subjects who were non-E3-carriers had the largest postprandial increment in TG and RLP-C. On stepwise linear regression analysis, log(HOMA-IR) was only an independent determinant of fasting TG but not postprandial TG or RLP-C. The major determinants of fasting and postprandial RLP-C were fasting TG and apo E genotype, accounting for 53 and 6% of the variance of fasting RLP-C ( p < 0.01) and 31 and 13% of the variance of postprandial RLP-C respectively ( p < 0.01). Conclusions Insulin resistance is mainly a determinant of fasting triglyceride in Chinese type 2 diabetic subjects, whereas apo E genotype is a better predictor of both fasting and postprandial concentrations of RLP. Copyright © 2004 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Summary objective Multiple endocrine neoplasia type 1 (MEN1) is characterized by a triad of neoplasia affecting the parathyroid glands, enteropancreatic endocrine tissue and the anterior pituitary gland. design In order to define the prevalence of MEN1 germ-line mutations in Southern Chinese patients with MEN1 syndrome, we performed direct sequencing of the entire open reading frame of the MEN1 gene for 12 index patients and their first-degree relatives. results Six patients had familial MEN1 syndrome and six had apparently sporadic disease. Nine different germ-line mutations at the MEN1 gene were identified, including three novel mutations [248–249delTT in exon 2, K559X(AAG → TAG) in exon 10 and IVS 2nt + 2(G → T) in intron 2]. All patients with familial MEN1 syndrome were heterozygous carriers of a germ-line mutation and MEN1-related disorders were only evident in their first-degree relatives who also carried the mutation. All patients with an enteropancreatic lesion were mutation carriers and the absence of mutation in three apparently sporadic MEN1 patients with only hyperparathyroidism and pituitary microadenoma might represent the presence of MEN1 phenocopy. conclusions The finding of MEN1 germ-line mutation in all patients with familial MEN1 syndrome suggests that genetic screening should be useful in our population to identify affected individuals within a kindred and allow early detection of MEN1-related tumours. [ABSTRACT FROM AUTHOR]

Abstract Aims Post-prandial lipaemia is prolonged and exaggerated in patients with Type 2 diabetes mellitus, with an accumulation of atherogenic triglyceride-rich lipoprotein remnants. We postulate that orlistat, a gastrointestinal lipase inhibitor, may cause changes in post-prandial lipoprotein metabolism by reducing dietary triglyceride absorption. Methods The acute effect of a single dose of 120 mg orlistat on post-prandial glucose, lipids, remnant lipoproteins and free fatty acids (FFA) was evaluated in a randomized, double-blind, placebo-controlled cross-over study of 63 overweight patients with Type 2 diabetes mellitus (body mass index 30.4 ± 3.8 kg/m2 ). Either a single dose of orlistat or placebo was given before a standard mixed meal containing 70 g of fat and plasma triglyceride (TG), remnant-like particles cholesterol (RLP-C) and FFA were sampled at 2-h intervals for 8 h. RLP-C was measured by an immunoseparation assay and FFA by an enzymatic colorimetric method. Results The concentrations of plasma TG (P < 0.0001), RLP-C (P = 0.003), and FFA (P < 0.0001) were significantly lower at 2 h after orlistat compared with placebo. Both plasma RLP-C (P = 0.04) and FFA (P < 0.0001) remained lower after orlistat than placebo at 4 h. The incremental area under the curve (iAUC) above baseline fasting level for both TG and RLP-C was significantly more reduced after orlistat than placebo (iAUC-TG 5.8 (3.7–8.2) mmol/l × h-1 vs. 5.7 (4.1–10.9), respectively, P = 0.04; iAUC-RLP-C: 0.53 (0.23–1.04) mmol/l × h-1 vs. 0.56 (0.35–1.40), respectively, P = 0.02). The test meal was well tolerated by all subjects, with only three subjects reporting faecal urgency after orlistat. Conclusions Orlistat has a beneficial effect on post-prandial lipaemia in overweight Type 2 diabetic patients and lowers plasma TG, RLP-C and FFA in the early post-prandial period. Diabet. Med. 19, 944–948 (2002). [ABSTRACT FROM AUTHOR]

Background Hyperhomocysteinemia has been shown to adversely affect vascular function. The aim of this study was to determine whether hyperhomocysteinemia was independently associated with changes in endothelium-dependent and -independent vasomotor functions in patients with type 2 diabetes mellitus. Materials and methods Fasting homocysteine (tHcy) was measured in 123 patients with type 2 diabetes and in 61 nondiabetic controls. Endothelium-dependent and -independent vasodilation was measured using high-resolution vascular ultrasound. Results Plasma tHcy concentration was increased in the diabetic patients (11.1 ± 3.7 µmol L[sup -1] vs. 9·8 ± 2·9, P < 0·05). The prevalence of hyperhomocysteinemia (defined as tHcy > 15 µmol L[sup -1]) was higher in the diabetic patients (P < 0·05). Within group comparisons showed that both the abnormalities in endothelium-dependent and -independent vasodilation were significantly more severe in diabetic patients with tHcy 10-15 (P<0·05) and tHcy> 15 µmolL[sup -1] (P<0·05) than in those patients with tHcy < 10 µmol L[sup -1]. When compared with nondiabetic controls matched for tHcy levels, impairment of endothelium-dependent and -independent vasodilation were already evident, even in patients with normal tHcy levels (P<0.01). Despite significant univariate relationships between tHcy and endothelium-dependent (r = -0·24, P < 0·01) and -independent vasodilation (r=-0·33, P<0·01) in patients with diabetes, only the relationship between tHcy and endothelium-independent vasodilation remained significant after adjusting for other cardiovascular risk factors in multiple regression analysis. Conclusions Impairment of endothelium-dependent and -independent vasodilation was already present in diabetic patients with normal tHcy levels, and these abnormalities became more severe with increasing tHcy levels. Only the association between... [ABSTRACT FROM AUTHOR]

OBJECTIVESSleep apnoea has been reported to occur in subjects with acromegaly. This study evaluates the relationship among biochemical activity, sleep apnoeic activity and upper airway anatomic profile in acromegaly, and the effect of Sandostatin® LAR®, a long-acting somatostatin analogue, on these parameters. PATIENTSFourteen subjects with acromegaly were recruited. MEASUREMENTSSubjects were assessed at baseline and those with apnoea-hypopnoea index (AHI) ≥ 5 were reassessed after 6 months of treatment with Sandostatin® LAR® 20–30 mg IMI 4-weekly. Biochemical activity was assessed with levels of GH and IGF-1. Sleep disordered breathing was assessed with overnight polysomnography. Upper airway anatomic profile was defined with computerized tomographic cephalometry. RESULTSOf 14 subjects (age 42·0 ± 8·1 years, mean ± SD; 11 men) at baseline, there was a positive correlation between GH and tongue length (VT; P = 0·004), and between AHI and cephalometric indices: length of soft palate (PMU; P = 0·002); mandibular plane-hyoid bone distance (MPH; P = 0·017), maximum thickness of soft palate (Max-SP; P = 0·018) and VT (P = 0·027). Eight patients had sleep disordered breathing (AHI ≥ 5) which was predominantly obstructive in nature (AHI = 29·4 ± 22·6). After treatment, there were significant improvements in hormonal profile: GH, mU/l (before, 51·5 ± 27·8; after, 8·0 ± 7·4; P = 0·017) and IGF-1, nmol/l (before, 95·5 ± 23·4; after, 35·0 ± 12·4; P = 0·012); sleep-disordered breathing: AHI (before, 29·4 ± 22·6; after, 13·4 ± 11·12; P = 0·025), snoring episodes (before, 486 ± 240; after, 165 ± 170; P = 0·05); cephalometric indices, mm: MPH (before, 18·8 ± 12·1; after, 14·8 ±... [ABSTRACT FROM AUTHOR]

Serum leptin levels are decreased in patients with acromegaly and rise after GH is normalized by surgical treatment. We have evaluated the effect of Sandostatin® LAR® on leptin levels in acromegalic patients since there are recent data to suggest that somatostatin, in addition to its GH lowering effect, also reduces serum leptin levels in humans. Nineteen patients with active acromegaly were studied. Eleven patients received monthly injection of Sandostatin® LAR® and eight patients underwent transsphenoidal surgery. Serum concen-trations of leptin, GH, IGF-1 and insulin were measured before and after treatment. Serum leptin concentrations were lower in patients with active acromegaly than controls matched for age, sex and body mass index (BMI) [2·79 µg/l (2·60) vs. 4·41 µg/l (5·07); median (inter-quartile range); P < 0·01]. A positive correlation between serum leptin concentrations and BMI was observed in the controls (r = 0·46, P < 0·05) but not in the acromegalic patients before treatment (r = 0·32, ns). In the group of patients treated with Sandostatin® LAR®, a marked reduction in GH and IGF-1 was achieved by week 8 and GH and IGF-1 remained suppressed throughout the 6 months of treatment. There was no change in BMI. A significant increase in leptin levels only became evident after 6 months of treatment [2·99 µg/l (2·60) vs. 4·21 µg/l (3·84), P < 0·05]. Leptin levels also significantly increased after transsphenoidal surgery [3·05 µg/l (5·73) vs. 5·19 µg/l (4·93), P < 0·05]. The positive correlation between serum leptin concentrations and BMI was restored in acromegalic patients both after treatment with Sandostatin® LAR® (r = 0·62, P < 0·05) and after surgery (r = 0·81, P < 0·05). Leptin concentrations were decreased in patients with active acromegaly and lowering GH by either Sandostatin® LAR® or transsphenoidal surgery led to an increase in leptin concentrations. [ABSTRACT FROM AUTHOR]

SUMMARY Aims To determine the prevalence of Type 2 diabetes mellitus and impaired glucose tolerance (IGT) and their relationships to fibrinogen and other cardiovascular risk factors in Hong Kong Chinese. Methods A probability sample of 1316 men and 1348 women aged 25–74 years were examined in a population-based cross-sectional study. Results A total of 3.0% (95% confidence interval 2.1–3.9) of men had previously diagnosed (known) and 6.4% (5.0–7.8) newly diagnosed (unknown) diabetes, 14.4% (12.4–16.5) had IGT and 79.2% were normal by 1985 WHO diagnostic criteria; corresponding prevalences in women were 3.7% (2.7–4.7), 5.9% (4.6–7.2), 17% (14.8–19.2) and 73.4%. The age-standardized prevalence of Type 2 diabetes for the 35–64 age group was 9.5% (7.5–11.6) in men and 10.2% (8.0–12.4) in women. Age-adjusted mean fibrinogen levels in these four groups (normal/IGT/unknown diabetes/known diabetes) with decreasing degrees of glucose tolerance (diabetes status) were 2.80, 2.57, 2.51 and 2.47 g/l (P = 0.003) in men, and 2.86, 2.72, 2.67, 2.61 g/l (P = 0.005) in women. Age, obesity, systolic blood pressure and triglycerides were significantly associated with diabetes status in both sexes, fibrinogen in men only and high density lipoprotein cholesterol negatively in women. Conclusions The prevalence of Type 2 diabetes mellitus was very high especially in older subjects, and fibrinogen was associated with increasing glucose intolerance in men but not in women. The detection and better control of cardiovascular risk factors, particularly hypertension in this developed Chinese community with a high prevalence of diabetes and glucose intolerance, is particularly important. [ABSTRACT FROM AUTHOR]

SUMMARY Aims While the American Diabetes Association (ADA) 1997 diagnostic criteria advocate the use of fasting plasma glucose only, the World Health Organization (WHO) criteria retain the use of the standard oral glucose tolerance test (OGTT). The present study evaluated the relative merit of the respective diagnostic criteria in Chinese. Methods Data collected for the Hong Kong Cardiovascular Risk Factor Prevalence Study was analysed. This was a representative population-based study, conducted from 1995 to 1996 among 2900 Chinese subjects aged 25–74 years using a 75-g OGTT. Results The prevalence of diabetes (known plus unknown) was 6.2% (95% confidence interval 5.3–7.1%), 9.2% (8.1–10.3%), and 9.8% (8.7–10.9%) based on ADA 1997, WHO 1985 and WHO 1998 criteria, respectively, with a very high prevalence in older subjects. The 2451 subjects classified as normal under ADA 1997 criteria were heterogenous: 15.3% had impaired glucose tolerance; 2.1% had diabetes under WHO 1998 criteria. These latter two smaller groups had cardiovascular risk profiles comparable to that found among the impaired fasting glucose subjects (under ADA), but worse than that among the concordant normal glucose tolerance subjects. Conclusions The ADA criteria underestimate both diabetes prevalence and cardiovascular risk in this population. Hence fasting glucose alone is an inadequate approach and OGTT should be retained to identify at-risk individuals in both clinical diagnosis and epidemiological studies. [ABSTRACT FROM AUTHOR]

1The pharmacokinetics and pharmacodynamics of intranasal (IN) and oral 1-deamino-8-d-arginine vasopressin (DDAVP) were compared in 10 Chinese adults with central diabetes insipidus previously controlled on IN DDAVP. This was followed by comparison of the acute pharmacodynamics of commonly used oral preparations (containing 100, 200 and 400 μg per tablet) and a 1 year prospective evaluation of the long-term safety and efficacy of oral DDAVP. 2Following 20 μg IN and 200 μg orally, respective plasma DDAVP concentrations peaked after 45.6±7.3 and 93.3±3.3 (mean±s.e.mean) min, reaching 24.1±4.7 and 15.1±3.2 pmol l−1 and respective terminal half-lives were 2.2±0.1 and 2.0±0.1 h. Based on the area under the concentration-time-curve, the bioequivalent IN/oral ratio was 1:16. 3As judged by changes in urine flow rate and osmolality after IN or oral (100, 200 or 400 μg) DDAVP, antidiuretic activity increased rapidly during the second hour and peaked at 4 h. The antidiuresis duration and magnitude correlated with the oral dose ( P<0.001 and <0.05 respectively), and was least following 100 μg ( P<0.01 vs 200 or 400 μg). Increasing the dose from 200 to 400 μg did not increase maximal antidiuretic activity significantly, but there was a trend towards a longer duration of action ( P=0.076). 4During the 1-year prospective study with oral DDAVP 300-600 μg per day in two to three doses, stable and satisfactory antidiuresis (comparable with that on previous IN therapy) was maintained; tablets were well-tolerated and no side-effect warranted drug withdrawal. 5These findings suggest that the 100 and 200 μg preparations of oral DDAVP are adequate for the long-term control of central diabetes insipidus in our population, and that the 400 μg preparation may have a role if the frequency of administration is to be reduced. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "Nonalcoholic Fatty Liver Disease in Morbidly Obese Patients and the Effect of Bariatric Surgery," by R. J. De Ridder and colleagues in the previous issue.

Acromegaly patients are known to have an increased risk of malignancies, especially colonic adenocarcinoma. This may be as a result of the growth-stimulating effect of growth hormone (GH). The clustering of leukaemia in children treated with GH has also caused concern. There have been a few reports of leukaemia in acromegaly patients. We report two patients with acute lymphoblastic leukaemia and one patient with acute myeloid leukaemia among 106 acromegaly patients treated over a 15-year period. Two of the cases received radiotherapy as part of their treatment. Adjusted for age and follow-up years, the incidence of leukaemia in this cohort is significantly higher than the general population. The incidence is also higher than would be expected as a result of radiotherapy alone, suggesting that GH may play a synergistic role. [ABSTRACT FROM AUTHOR]