Zinc-α2-glycoprotein is associated with non-albuminuric chronic kidney disease progression in type 2 diabetes: a retrospective study with 4-year follow-up.

AIM: To investigate the association between baseline plasma zinc-α2-glycoprotein and non-albuminuric chronic kidney disease progression in type 2 diabetes. METHODS: Adults with normoalbuminuria at entry (n=341; age 57±10 years, 52% men) were analysed. Chronic kidney disease progression was defined as a decrease in chronic kidney disease stage and a decline of ≥25% in estimated GFR from baseline. Baseline plasma zinc-α2-glycoprotein levels were quantified by immunoassay, and analysed either as a continuous variable or by tertiles in Cox proportional hazards models. Model discrimination was assessed using Harrell's C-index. A sensitivity analysis was performed on a subset of individuals who maintained normoalbuminuria during follow-up. RESULTS: Chronic kidney disease progression occurred in 54 participants (16%). Zinc-α2-glycoprotein levels were elevated in chronic kidney disease progressors (P = 0.011), and more progressors were assigned to the higher zinc-α2-glycoprotein tertile than non-progressors. In the unadjusted Cox model, zinc-α2-glycoprotein, both as a continuous variable (hazard ratio 1.72, 95% CI 1.08-2.75) and tertile 3 (vs tertile 1; hazard ratio 2.14, 95% CI 1.10-4.17), predicted chronic kidney disease progression. The association persisted after multivariable adjustment. The C-index of the Cox model increased significantly after incorporation of zinc-α2-glycoprotein into a base model comprising renin-angiotensin system antagonist usage. Sensitivity analysis showed that zinc-α2-glycoprotein independently predicted chronic kidney disease progression among individuals who maintained normoalbuminuria during follow-up. CONCLUSIONS: Plasma zinc-α2-glycoprotein is associated with chronic kidney disease progression, and may serve as a useful early biomarker for predicting non-albuminuric chronic kidney disease progression in type 2 diabetes.

Ethnic disparities in risk of cardiovascular disease, end-stage renal disease and all-cause mortality: a prospective study among Asian people with Type 2 diabetes.

AIM: To study prospectively the ethnic-specific risks of cardiovascular disease, end-stage renal disease and all-cause mortality in patients with Type 2 diabetes mellitus among native Asian subpopulations. METHODS: A total of 2337 subjects with Type 2 diabetes (70% Chinese, 17% Malay and 13% Asian Indian) were followed for a median of 4.0 years. Time-to-event analysis was used to study the association of ethnicity with adverse outcomes. RESULTS: Age- and gender-adjusted hazard ratios for cardiovascular disease in ethnic Malay and Asian Indian subjects were 2.01 (1.40-2.88; P<0.0001) and 1.60 (1.07-2.41; P=0.022) as compared with Chinese subjects. Adjustment for conventional cardiovascular disease risk factors, including HbA1c , blood pressure and lipid profile, slightly attenuated the hazards in Malay (1.82, 1.23-2.71; P=0.003) and Asian Indian subjects (1.47, 0.95-2.30; P=0.086); However, further adjustment for baseline renal function (estimated GFR) and albuminuria weakened the cardiovascular disease risks in Malay (1.48, 0.98-2.26; P=0.065) but strengthened that in Asian Indian subjects (1.81, 1.14-2.87; P=0.012). Competing-risk regression showed that the age- and gender-adjusted sub-distribution hazard ratio for end-stage renal disease was 1.87 (1.27-2.73; P=0.001) in Malay and 0.39 (0.18-0.83; P=0.015) in Asian Indian subjects. Notably, the difference in end-stage renal disease risk among the three ethnic groups was abolished after further adjustment for baseline estimated GFR and albuminuria. There was no significant difference in risk of all-cause mortality among the three ethnic groups. CONCLUSIONS: Risks of cardiovascular and end-stage renal diseases in native Asian subjects with Type 2 diabetes vary substantially among different ethnic groups. Differences in prevalence of diabetic kidney disease may partially explain the ethnic disparities.

High normal albuminuria is independently associated with aortic stiffness in patients with Type 2 diabetes.

BACKGROUND: High normal albuminuria is associated with higher cardiovascular risk in patients with diabetes. Increased aortic stiffness is an established risk factor of vascular events. However, the relationship between albuminuria within the normal range (0-30 mg/g) and aortic stiffness in patients with Type 2 diabetes is unknown. METHODS: A total of 614 normoalbuminuric subjects with Type 2 diabetes with spot urinary albumin:creatinine ratio ≤ 30 mg/g and estimated glomerular filtration rate ≥ 60 ml min⁻¹ 1.73 m⁻² were included in the study. Aortic stiffness was assessed by carotid-femoral pulse wave velocity. RESULTS: Pulse wave velocity increased progressively with the increase of albumin:creatinine ratio within the normoalbuminuric range (0-30 mg/g). Only 2.6% of the subjects with an albumin:creatinine ratio in the lowest quartile (0.7-3.4 mg/g) were classified as having aortic stiffness (pulse wave velocity ≥12 m/s). In contrast, the proportion of subjects with aortic stiffness increased significantly with the increase of albumin:creatinine ratio level (11.0%, 10.4% and 13.6% in albumin:creatinine ratio quartiles 2, 3 and 4, respectively, P = 0.008). A logistic regression model revealed that the odds of having aortic stiffness were increased by 56% with a 1-SD increase of log albumin:creatinine ratio after adjustment for age, gender, duration of diabetes, HbA1c , blood pressure, HDL and LDL cholesterol, estimated glomerular filtration rate, BMI, usage of renin-angiotensin system antagonists, statins and insulin. CONCLUSIONS: High normal albuminuria is associated with aortic stiffness in patients with Type 2 diabetes, which may in part explain their increased cardiovascular risk.

Associations between pigment epithelium-derived factor, insulin resistance and high density lipoprotein.

AIMS: To measure serum pigment epithelium-derived factor in control subjects with normal fasting glucose, and in subjects with impaired fasting glucose and those with newly diagnosed Type 2 diabetes, before treatment initiation, and to measure pigment epithelium-derived factor prospectively in patients being treated with HDL-raising therapy, niacin. METHODS: We enrolled 89 individuals attending an institutional health screen. Biochemical indices including lipids, homeostasis model assessment-insulin resistance, high-sensitivity C-reactive protein and pigment epithelium-derived factor were analysed in fasting blood. To validate the association between HDL and pigment epithelium-derived factor, we analysed samples from a separate study cohort with low HDL, followed up for 12-weeks while on niacin treatment. Secreted pigment epithelium-derived factor from 3T3-L1 adipocytes, after HDL treatment (24-h), was measured using Western blot analysis. RESULTS: Mean (± sd) serum pigment epithelium-derived factor was significantly higher in subjects with impaired fasting glucose [13.99 (± 3.06) µg/ml] and Type 2 diabetes [12.94 (± 2.61)] µg/ml, compared with control subjects [11.83 (± 2.85) µg/ml (P = 0.014)]. In multivariate analyses, serum pigment epithelium-derived factor concentration was associated with BMI (ß = 0.32, 0.007), homeostasis model assessment-insulin resistance (ß = 0.33, P = 0.01) and HDL (ß = -0.24, P = 0.05), after adjustment for age, gender and high-sensitivity C-reactive protein. In the niacin study, on-treatment HDL was an independent determinant of pigment epithelium-derived factor (ß = -0.439, P = 0.033), after adjusting for age, homeostasis model assessment-insulin resistance and treatment. Adipocytes treated with HDL were found to have reduced pigment epithelium-derived factor secretion [24.8% (50 µg/ml), 28.4% (100 µg/ml) HDL; P < 0.05)], compared with the control samples. CONCLUSION: Serum pigment epithelium-derived factor is positively associated with homeostasis model assessment-insulin resistance and negatively associated with HDL. Further studies are needed to understand the mechanism of low HDL and raised pigment epithelium-derived factor and to determine if they are causally related to the pathobiology of insulin resistance.

Predictors of decrease in ankle-brachial index among patients with diabetes mellitus.

AIM: Screening for peripheral arterial disease, a complication among patients with diabetes, is performed by periodic assessment of ankle-brachial index. We aimed to study the degree of ankle-brachial index change over time and factors associated with significant change. METHOD: We assessed difference between two ankle-brachial index measurements over time in a consecutive series of 82 patients with Type 2 diabetes. All patients had ankle-brachial index > 0.9 but ≤ 1.3 for the first measurement, and significant ankle-brachial index decrease was defined as a decrease of > 0.1 in the follow-up measurement compared with the baseline. RESULTS: The mean follow-up duration was 27.6 (median 30.0) months. Significant ankle-brachial index decrease was seen in 20.7% of patients, including 5% with follow-up ankle-brachial index of ≤ 0.9, consistent with the diagnosis of peripheral arterial disease. After adjusting for age and gender, higher baseline HbA(1c) and serum creatinine levels, increase in follow-up serum LDL cholesterol levels compared with baseline and history of retinopathy were predictors of significant ankle-brachial index decrease. CONCLUSIONS: Our study suggests that, within two years, one in five patients with diabetes and a normal ankle-brachial index may have significant progression of peripheral arterial disease. Annual ankle-brachial index assessment and better control of hyperlipidaemia may thus be required for at-risk patients with poor glycaemic control, renal impairment and retinopathy.

Adipocytokine zinc α2 glycoprotein (ZAG) as a novel urinary biomarker for normo-albuminuric diabetic nephropathy.

OBJECTIVE: A substantial proportion of diabetic nephropathy individuals are non-albuminuric. Using a proteomic approach, we searched for novel urinary biomarkers. METHODS: We studied three groups (n = 6 per group) of males with Type 2 diabetes: (1) normal renal function; (2) classical diabetic nephropathy (urinary albumin-creatinine ratio > 1000 mg/g and glomerular filtration rate < 60 ml/min.1.73 m(2) ) and (3) non-albuminuric diabetic nephropathy (glomerular filtration rate < 60 ml/min.1.73 m(2) and urinary albumin-creatinine ratio < 30 mg/g). We used two-dimensional fluorescence differential gel electrophoresis, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry peptide identification and western blot validation in the study. RESULTS: Sixty protein spots were differentially abundant between the non-albuminuric and macro-albuminuric subjects (> 2.5-fold, P < 0.05). In the non-albuminuric subjects, in addition to previously reported α(1) -microglobulin, the next most interesting spot (upregulated 3.44-fold, P = 0.0026) was human zinc-α(2) -glycoprotein, a novel adipose-cytokine associated with glomerular injury. This was confirmed by western blot and replicated in female diabetic nephropathy subjects. CONCLUSIONS: From our preliminary results, human zinc-α(2) -glycoprotein may be a novel urinary biomarker for non-albuminuric diabetic nephropathy.

Associations of young onset age and genetic risk of beta cell dysfunction with glycaemic progression in individuals with type 2 diabetes.

AIM: To study the relationship between genetic risk of beta cell dysfunction, young onset age and glycaemic progression in individuals with type 2 diabetes (T2D). MATERIALS AND METHODS: 1385 T2D outpatients were included in cross-sectional sub-study and 730 insulin-naïve outpatients were followed for 3 years in prospective sub-study. Genetic risk score (GRS) was derived from 24 beta cell dysfunction-related single nucleotide polymorphisms, with lower and upper 25 percentiles defined as low and high genetic risk. Glycaemic progression was defined as requirement for sustained insulin therapy. RESULTS: 388 participants in cross-sectional and 128 in prospective sub-study experienced glycaemic progression. Young onset age (T2D diagnosis below 40 year-old) was associated with high risk of glycaemic progression as compared to usual-onset counterparts (adjusted OR 1.64 [95% CI 1.14-2.36], and 2.92 [95% CI 1.76-4.87] in cross-sectional and prospective sub-study, respectively). As compared to those with intermediate risk, a low GRS was associated with lower risk for glycaemic progression (adjusted OR 0.72 [95% CI 0.49-1.06], and 0.51 [95% CI 0.29-0.90]) whereas a high GRS was not significantly associated with glycaemic progression. Notably, the association of young-onset T2D with high risk of glycaemic progression was independent of known clinical risk factors and beta cell dysfunction GRS (P interaction > 0.10). CONCLUSION: Young onset age and low genetic risk of beta cell dysfunction are independently associated with risk of glycaemic progression. Our data do not support that genetic risk modulates the risk of glycaemic progression in individuals with young-onset T2D.

Microarray analysis of multiple candidate genes and associated plasma proteins for nephropathy secondary to type 2 diabetes among Chinese individuals.

AIMS/HYPOTHESIS: Evolving research suggests that common and rare alleles jointly constitute the genetic landscape of complex disease. We studied the association between 43 pathway-related candidate genes with 'intermediate phenotype' (i.e. corresponding plasma protein) and diabetic nephropathy in a customised microarray of 1,536 SNPs. METHODS: In this case-control study of type 2 diabetic Chinese individuals with and without diabetic nephropathy, cases (n = 545) were defined on the basis of a spot urinary albumin/creatinine ratio (ACR) > 113 mg/mmol; the value for controls (n = 503) was ACR < 3.3 mg/mmol. Genotyping was performed using Illumina GoldenGate assay. RESULTS: No single nucleotide polymorphism (SNP) remained significant in single locus analysis after correction for multiple testing. Therefore, we explored the best approximately 1% SNPs. Of these 13 SNPs, four clustered to a 5' end NADPH oxidase homologue 4 (NOX4) haplotype (GGCC frequency = 0.776) with estimated OR for diabetic nephropathy of 2.05 (95% CI 1.04-4.06) (heterozygous) and 2.48 (1.27-4.83) (homozygous) (p = 0.0055). The haplotype was correlated with plasma Cu/Zn superoxide dismutase (SOD) concentration, suggesting increased oxidative burden. Endothelin-1 SNP (rs1476046G>A, frequency = 0.252) was correlated with plasma C-terminal pro-endothelin-1 concentrations with an estimated OR for diabetic nephropathy of (heterozygous) 1.26 (0.96-1.66) and (homozygous) 1.87 (1.13-3.12) (p = 0.0072). Nitric oxide synthase 1 (NOS1) 5' haplotype (TGTC frequency = 0.38) also revealed a suggestive association with diabetic nephropathy: heterozygous 1.26 (0.95-1.67), homozygous 1.57 (1.04-2.35) (p = 0.0073). A rare NADPH oxidase homologue 1 (NOX1)-coding non-synonymous SNP (Arg315His, frequency = 0.006) was found exclusively among cases. CONCLUSIONS/INTERPRETATION: Our preliminary observations suggest that common haplotypes from NOX4 and endothelin-1 SNP correlated with plasma Cu/Zn SOD and C-terminal pro-endothelin-1 concentrations, respectively, and might have conferred diabetic nephropathy susceptibility. Common NOS1 and rare NOX1 variants also revealed a suggestive association with diabetic nephropathy. Future studies to validate our observation are needed.

Niacin affects cell adhesion molecules and plasminogen activator inhibitor-1 in HepG2 cells.

BACKGROUND: Beyond lipid-modifying actions, niacin lowers the risk of atherothrombotic events by lowering prothrombotic factors like fibrinogen. Plasminogen activator inhibitor type 1 (PAI-1) is a potential factor for atherogenesis and thrombosis, increased in acute myocardial infarctions and restenosis after angioplasty. Cell adhesion molecules (CAM) mediate adhesion, recruitment and migration of white blood cells through vascular surfaces, an essential process in atherogenesis. ICAM-1 is a significant predictor of future coronary events. Whether niacin affects ICAM-1 expression is unknown. We studied the effects of niacin on PAI-1 and CAM using HepG2 cells. METHODS: HepG2 cells were cultured in DMEM until 90% confluent. After serum starvation, cells were exposed to DME/F12 containing niacin. Transforming growth factor-beta (TGF-beta) was added directly to cell media. Cell lysate and conditioned media were collected for measurement of PAI-1 by ELISA. For measurement of ICAM, cells were treated with tumor necrosis factor-alpha (TNF-alpha) instead. The effect of niacin on mRNA expression of ICAM-1 was studied using RT-PCR. RESULTS: Niacin reduced the TGF-beta-induced rise by 30% to 55% (p=0.002). The differences in degree of PAI-1 reduction, between different niacin concentrations, were not statistically significant. Niacin reduced TNF-alpha-induced rise in ICAM-1 levels by 66% to 89% (p<0.0001), but did not significantly affect TNF-alpha-induced rise in PECAM-1. Semiquantitative RT-PCR analysis showed that reduced TNF-alpha-induced rise in ICAM-1 mRNA expression significantly by 17% (p=0.001). CONCLUSIONS: Treatment with niacin suppressed PAI-1 and ICAM-1 levels in HepG2 cells. Further studies to understand the mechanistic pathways of this suppression, could further explain benefits of niacin in prevention of atherosclerotic disease, and offer therapeutic avenues against the rising burden of atherothrombotic disease.

Patients with low levels of high-density lipoprotein cholesterol: to treat or not to treat?

Clinical evidence indicates that a low level of high-density lipoprotein cholesterol (HDL-C) is a major risk of atherosclerosis. Raising HDL-C reduces this risk significantly, making HDL-C levels an important target of treatment for dyslipidaemia, especially in pre-existent atherosclerosis. HDL-C is protective against atherosclerosis, largely due to its function of reverse cholesterol transport. Additionally, some important roles include fibrinolysis, antioxidant functions, and reduction of platelet aggregability. A number of agents potentially modify HDL favourably. Niacin is the most potent HDL-C raising agent currently available in clinical practice, followed by fibrates. CETP inhibitors show greater HDL-C rising, but are still used in trial settings only. HDL mimetic agents are another group of agents that offer much promise. Clinical outcome data are awaited for these newer therapeutic agents.

The effect of a 5-month supervised program of physical activity on anthropometric indices, fat-free mass, and resting energy expenditure in obese male military recruits.

Studies using mainly dietary restriction have shown that weight loss is associated with a decrease in fat-free mass (FFM) and resting energy expenditure (REE). The aim of this study was to investigate the effects of a weight-loss program relying solely on increased physical activity on FFM and REE. Forty-two overweight male military recruits (12 with initial body mass index [BMI] between 25.0 and 29.9 kg/m2, group 1; 14 with BMI between 30.0 and 34.9 kg/m2, group 2; and 16 with BMI of at least 35 kg/m2, group 3) completed a 5-month program of supervised physical activity that included both aerobic and muscle-strengthening components. All subjects lost significant amounts of weight (group 1, 8.6 kg; group 2, 15.7 kg; group 3, 22.0 kg). This weight loss was accompanied by a significant reduction in the waist to hip ratio (WHR) in all groups. FFM was maintained in all groups. REE tended to decline in all groups (group 1, from 1,595.0 +/- 46.9 to 1,511.7 +/- 53.2 kcal/d; group 2, from 1,751.4 +/- 56.0 to 1,680.0 +/- 63.1 kcal/d; group 3, from 1,901.9 +/- 93.7 to 1,740.0 +/- 67.3 kcal/d), but this decline reached statistical significance only when all 42 subjects were considered. REE normalized for FFM did not decrease except in group 1. Furthermore, differences between the slopes and intercepts of the regression lines relating REE with FFM before and at completion of the 5-month program were not statistically significant, suggesting that the relationship between REE and FFM was maintained after weight loss.(ABSTRACT TRUNCATED AT 250 WORDS)

The impact of metformin therapy on hepatic glucose production and skeletal muscle glycogen synthase activity in overweight type II diabetic patients.

The effect of metformin therapy on glucose metabolism was examined in eight overweight newly presenting untreated type II diabetic patients (five males, three females). Patients were treated for 12 weeks with either metformin (850 mg x 3) or matching placebo using a double-blind crossover study design; patients were studied at presentation and at the end of each treatment period. Insulin action was assessed by measuring activation of skeletal muscle glycogen synthase (GS) before and during a 4-hour hyperinsulinemic euglycemic clamp (100 mU.kg-1 x h-1). Metformin therapy was associated with a significant decrease in fasting blood glucose (6.8 +/- 0.6 v 8.3 +/- 0.9 mmol.L-1, P < .01) and glycosylated hemoglobin ([HbA1] 7.7% +/- 0.4% v 8.5% +/- 0.5%, P < .01) levels. Fasting hepatic glucose production (HGP) was also significantly decreased following metformin therapy (1.98 +/- 0.13 v 2.41 +/- 0.20 mg.kg-1 x min-1, P < .02), whereas fasting insulin and C-peptide concentrations remained unaltered. The decrease in basal HGP correlated closely with the decrease in fasting blood glucose concentration (r = .92, P < .001). Insulin-stimulated glucose uptake was assessed using the hyperinsulinemic euglycemic clamp technique and was increased post-metformin (3.8 +/- 0.6 v 3.1 +/- 0.7 mg.kg-1 x min-1, P < .05). This was primarily the result of increased nonoxidative glucose metabolism (1.1 +/- 0.6 v 0.4 +/- 0.6 mg.kg-1 x min-1, P < .05); oxidative glucose metabolism did not change. Metformin had no measurable effect on insulin activation of skeletal muscle GS, the rate-limiting enzyme controlling muscle glucose storage.(ABSTRACT TRUNCATED AT 250 WORDS)

Management of newly diagnosed non-insulin-dependent (type 2) diabetes mellitus: a retrospective audit.

A retrospective survey of the case records of 130 patients with newly diagnosed non-insulin-dependent diabetes mellitus (NIDDM) was performed to assess the effect of 1 year of clinical attendance on blood glucose control, body weight, lipid profile and blood pressure. The mean age of these patients was 63 +/- (SE) 0.1 years and 45% were 65 years or older. Body mass index (BMI) was 28.3 +/- 0.49 kg m-2 and 72% were overweight or obese. Sixty-seven percent of the patients were hypertensive (WHO criteria). Serum cholesterol was 6.0 +/- 0.2 mmol/l, HDL cholesterol 1.0 +/- 0.0 mmol/l and triglycerides 3.14 +/- 0.29 mmol/l (non-fasting). Seventy-two percent of the patients were managed on diet alone and 23% by diet plus sulphonylurea. The remaining 5% were treated by metformin or a combination of metformin plus sulphonylurea. After one year, glycated haemoglobin (HbA1) decreased from 10.7 +/- 0.3% to 8.2 +/- 0.2% (P less than 0.01; normal less than 7.5%). The sulphonylurea groups showed similar decreases in HbA1. Overall there was a small but significant fall in BMI (-0.5 +/- 0.2 kg m-2; P less than 0.05). However, the diet treated patients showed a significant decrease in BMI (-0.8 +/- 0.3 kg m-2; P less than 0.01) whilst BMI increased in the sulphonylurea treated group (+0.7 +/- 0.2 kg m-2; P less than 0.01). Serum lipid concentrations remained unchanged in both groups. The proportion of patients with hypertension remained the same. Hence after one year of clinical attendance, HbA1 improved but there was minimal change in the associated cardiovascular risk factors.(ABSTRACT TRUNCATED AT 250 WORDS)

Overnight (1 mg) dexamethasone suppression testing reliably distinguishes non-cushingoid obesity from Cushing's syndrome.

To determine the sensitivity of the overnight 1-mg dexamethasone suppression test in diagnosing Cushing's syndrome, we evaluated the cortisol responses of 55 subjects (25 non-obese individuals with body mass index less than 25 kg/m2, 20 obese individuals with body mass index greater than 30 kg/m2, and 10 patients with surgically proven Cushing's syndrome) following ingestion of 1 mg dexamethasone at midnight. The basal 8 AM plasma cortisol levels among non-obese and obese individuals and patients with Cushing's syndrome were 310 +/- 85, 377 +/- 91, and 813 +/- 270 nmol/L, respectively. Following 1 mg of dexamethasone, Cushing's syndrome patients showed minimal suppression of cortisol to 609 +/- 180 nmol/L (P = 0.79). Non-obese and obese individuals suppressed to 18.7 +/- 6.0 nmol/L (P less than 0.001) and 22 +/- 7.1 nmol/L (P = 0.003), respectively. The results demonstrated similar cortisol responses to overnight dexamethasone suppression in obese and non-obese groups, and clearly distinguished these subjects from those with Cushing's syndrome. Obesity is not a confounding factor in the 1-mg dexamethasone suppression test.

Management of thyroid disease in pregnancy.

Thyroid disease occurs in pregnant at the rate of 0.2-0.6%. Graves' disease is the most common thyroid disorder in our pregnant patients. Thyroid disease is suspected if a significant goitre is detected during pregnancy. Confirmation by thyroid function tests is necessary but their interpretation requires an understanding of changes in the maternal thyroid physiology. Pharmacotherapy with the thionamides is the treatment of choice. Changes in dosage are influenced by the effect of pregnancy on the disease and the optimal level of control for the mother and the foetus. The dose is best titrated against the free thyroxine index or free thyroxine level. The outcome of pregnancy depends on early diagnosis and skillful manipulation of antithyroid drugs.

Management of hyperlipidaemia.

Recent community-based studies have shown that hypercholesterolaemia is common in Singapore. High low-density lipoprotein (LDL) cholesterol, low high-density lipoprotein (HDL) cholesterol as well as hypertriglyceridaemia are associated with higher prevalence of cardiovascular disease. The aim of this article is to discuss the clinical management of adult patients with hyperlipidaemia. For practical purposes, the hyperlipidaemias can be divided into four patterns: 1) hypercholesterolaemia with normal triglyceride, 2) moderate hypertriglyceridaemia with normal cholesterol, 3) combined moderate hypercholesterolaemia and hypertriglyceridaemia, and 4) severe hypertriglyceridaemia with moderate hypercholesterolaemia. Each pattern can be attributed primarily to genetic conditions or secondarily to common diseases. It is important to attempt aetiopathogenetic diagnosis for each hyperlipidaemic patient as treatment of an underlying condition may sometimes reverse the hyperlipidaemia eg hypothyroidism and hypercholesterolaemia. In general, a low cholesterol and low fat (particularly saturated fat) diet is useful in patients with all four patterns of hyperlipidaemia. Patients with severe hypertriglyceridaemia and moderate hypercholesterolaemia may benefit from a further drastic reduction in fat intake. Pharmacological therapy is required for patients who do not achieve target lipid levels after diet modification. The choice of drug therapy is, to a large extent, dependent on the pattern of hyperlipidaemia. In some situations, combination drug therapy may be required. Caution is required in combining hypolipidaemic drugs as the side-effects of individual drugs may be potentiated when used in combination.

Epidemiology of diabetes mellitus in the Asia-Pacific region.

The complex interaction between genetic and environmental factors in the causation of diabetes mellitus is well illustrated by the epidemiology of diabetes in the Asia-Pacific region. Among the Chinese, the prevalence of diabetes is uniformly higher among Chinese living outside China than in the Chinese in The People's Republic of China. Similarly among the Indians, the prevalence of diabetes is universally higher in those who have settled outside India than in Indians in India. In the Pacific populations, diabetes is much commoner among the Nauruans and Fiji Indians. Throughout the Asia-Pacific countries, economic progress and urbanisation have a uniformly deleterious effect on diabetes. A better understanding of the hereditary and environmental factors in the causation of diabetes is required to halt and reverse the rising prevalence of diabetes in the Asia-Pacific region.

A study of non-toxic goitre.

A population study showed a prevalence of 2.8% for nontoxic goitres. The clinical significance of non-toxic goitres were not previously defined. This study examined 64 patients with non-toxic goitres which were classified clinically as diffuse (gp1), lobular (gp2) and nodular (gp3). They were studied in terms of thyroid antibodies, radioisotope scanning, ultrasonography and fine-needle aspiration cytology. The goitres were mainly nodular (69%), the rest were diffuse and lobular in equal numbers. Seventy percent of the nodular goitres had 1 nodule. One case of diffuse goitre and half the lobular goitres had multinodularity demonstrated on imaging. Antithyroid antibodies were detected in 20% of gp2, 7% of gp3 and none in gp1. Malignancy was found in 2% of gp2, 11% of gp3 and nil in gp1. A management strategy for non-toxic goitre was discussed.

Metabolic abnormalities in young non-obese males with hypertension.

Essential hypertension has been shown by various studies to be an insulin-resistant state. However, most of these studies have included obese and elderly patients. We were interested to know the extent of insulin resistance in a group of young, non-obese patients with hypertension. A total of 59 male patients with essential hypertension and 31 controls matched for age, sex and body mass index were studied. All the subjects were under 35 years old and had a body mass index of less than 27 kg/m2. Our results showed that such patients with hypertension had significantly higher fasting insulin, total insulin after glucose challenge, insulin/glucose ratio and higher triglycerides than the control subjects.

Hyperinsulinaemia in non-obese subjects with hypertriglyceridaemia: a preliminary report.

It has been known for some time that hyperinsulinaemia is associated with hypertriglyceridaemia. However, previous studies looking at the relationship between hyperinsulinaemia and hypertriglyceridaemia have included overweight subjects. The effect of obesity on the insulin status of hypertriglyceridaemic patients is uncertain. We investigated the insulin status of hypertriglyceridaemic subjects in the absence of confounding factors such as obesity, hypertension and diabetes mellitus. Our results demonstrate that basal insulin levels as well as the insulin response after an intravenous glucose challenge are higher in moderately hypertriglyceridaemic patients when compared to age and body mass index matched controls. Hyperinsulinaemia may have pathogenetic significance for hypertriglyceridaemia as well as other features of a constellation of metabolic derangements such as obesity, hypertension and glucose intolerance.