K. S. L. Lam

The prevalence of diabetes, association with cardiovascular risk factors and implications of diagnostic criteria (ADA 1997 and WHO 1998) in a 1996 community-based population study in Hong Kong Chinese

SUMMARY

Development of Diabetes in Chinese With the Metabolic Syndrome A 6-year prospective study

OBJECTIVE—We investigated the association of the metabolic syndrome with new-onset diabetes in the Hong Kong Cardiovascular Risk Factor Prevalence Study cohort. RESEARCH DESIGN AND METHODS—We followed up on 1,679 subjects without diabetes at baseline. Those with a previous diagnosis of diabetes or those who were receiving drug treatment were considered to be diabetic. The remaining subjects underwent a 75-g oral glucose tolerance test (OGTT). Diabetes was defined by plasma glucose ≥7.0 mmol/l with fasting and/or ≥11.1 mmol/l at 2 h. RESULTS—The prevalences of the metabolic syndrome at baseline were 14.5 and 11.4%, respectively, according to U.S. National Cholesterol Education Program (NCEP) and International Diabetes Federation (IDF) criteria. After a median of 6.4 years, there were 66 and 54 new cases of diabetes in men and women, respectively. The metabolic syndrome at baseline predicted incident diabetes. Hazard ratios (HRs) for the NCEP and IDF definitions of the syndrome were 4.1 [95% CI 2.8–6.0] and 3.5 [2.3–5.2], respectively. HRs for fasting plasma glucose (FPG) ≥6.1 or 5.6 mmol/l were 6.9 [4.1–11.5] and 4.1 [2.8–6.0], respectively. The NCEP and IDF criteria had 41.9 and 31.7% sensitivity and 87.5 and 90.2% specificity, respectively. Their positive predictive values were low, ∼20%, but their negative predictive values were ∼95%. CONCLUSIONS—The metabolic syndrome, particularly its component, elevated FPG, predicts diabetes in Chinese. An individual without the metabolic syndrome is unlikely to develop diabetes, but one who has it should practice therapeutic lifestyle changes and have periodic FPG measurements to detect new-onset diabetes.

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.

Central obesity predicts the worsening of glycemia in southern Chinese

AIMS: The association between obesity and type 2 diabetes has been found to be consistent across different ethnic populations. Our aim was to study the contribution of obesity to the development of type 2 diabetes in a non-obese Chinese population with a high prevalence of diabetes (9.8% in 1995–1996).METHODS: Six-hundred and forty-four non-diabetic subjects were recruited from the Hong Kong Cardiovascular Risk Factor Prevalence Study (1995–1996). This was a community-based population study which involved the use of a 75 g oral glucose tolerance test and 1985 World Health Organization diagnostic criteria. Their glycemic status was reassessed at 2 y.RESULTS: In subjects with impaired glucose tolerance (n=322), the annual progression rate to diabetes (4.8%; 95% CI 2.5–7.1%), was 8-fold that in control subjects (0.6%; 95% CI 0.0–1.4%; P<0.001). Baseline waist–hip ratio (WHR; OR per unit increase=1.05; 95% CI 1.02–1.07, P=0.0003) and post-load 2 h plasma glucose (OR per unit increase=2.02; 95% CI 1.76–2.34, P<0.0001) were significantly associated with glycemic status at 2 y in stepwise polytomous logistic regression analysis. Subjects with high baseline waist circumference or WHR (≥median) were more likely to have worsening of glucose tolerance at 2 y than those with low waist circumference (<median; conversion to diabetes, OR 3.8, P=0.001) or WHR (<median; conversion to diabetes, OR 2.8, P=0.019).CONCLUSION: Abdominal obesity, readily assessed by the measurement of WHR or waist circumference, was for the first time shown prospectively to be independently associated with the deterioration of glucose tolerance in a Chinese population.

Acarbose in NIDDM patients with poor control on conventional oral agents: a 24-week placebo-controlled study

OBJECTIVE To determine the efficacy of acarbose, compared with placebo, on the metabolic control of NIDDM patients inadequately controlled on maximal doses of conventional oral agents. RESEARCH DESIGN AND METHODS In this three-center double-blind study, 90 Chinese NIDDM patients with persistent poor glycemic control despite maximal doses of sulfonylurea and metformin were randomly assigned to receive additional treatment with acarbose 100 mg thrice daily or placebo for 24 weeks, after 6 weeks of dietary reinforcement. Efficacy was assessed by changes in HbA1c, fasting and 1-h postprandial plasma glucose and insulin levels, and fasting lipid levels. RESULTS Acarbose treatment was associated with significantly greater reductions in HbA1c (−0.5 ± 0.2% vs. placebo 0.1 ± 0.2% [means ± SEM], P = 0.038), 1-h postprandial glucose (−2.3 ± 0.4 mmol/1 vs. placebo 0.7 ± 0.4 mmol/1, P < 0.001) and body weight (−0.54 ± 0.32 kg vs. placebo 0.42 ± 0.29 kg, P < 0.05). There was no significant difference between the two groups regarding changes in fasting plasma glucose and lipids or fasting and postprandial insulin levels. Flatulence was the most common side effect (acarbose vs. placebo: 28/45 vs. 11/44, P < 0.05). One patient on acarbose had asymptomatic elevations in serum transaminases that normalized in 4 weeks after acarbose withdrawal. Another patient on acarbose developed severe hypoglycemia; glycemic control was subsequently maintained on half the baseline dosage of sulfonylurea. CONCLUSIONS In NIDDM patients inadequately controlled on conventional oral agents, acarbose in moderate doses resulted in beneficial effects on glycemic control, especially postprandial glycemia, and mean body weight. Additional use of acarbose can be considered as a useful alternative in such patients if they are reluctant to accept insulin therapy.

Acute effect of orlistat on post-prandial lipaemia and free fatty acids in overweight patients with Type 2 diabetes mellitus.

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.

Fibrinogen, other cardiovascular risk factors and diabetes mellitus in Hong Kong: a community with high prevalence of Type 2 diabetes mellitus and impaired glucose tolerance

SUMMARY

C-reactive protein as a predictor of hypertension in the Hong Kong Cardiovascular Risk Factor Prevalence Study (CRISPS) cohort

Inflammation contributes to the development of hypertension. Whether C-reactive protein (CRP) has a causal role in hypertension remains unknown. We studied the relationship between circulating CRP levels and hypertension. The role of single-nucleotide polymorphisms (SNPs) in the CRP gene as determinants of its plasma levels and the propensity to develop hypertension was investigated. Plasma CRP and genotypes of nine SNPs were determined in 1925 unrelated subjects from the Hong Kong Cardiovascular Risk Factor Prevalence Study-2 (CRISPS-2) in 2000–2004. Among 1378 subjects normotensive in CRISPS-2, 1115 subjects had been followed up in CRISPS-3 after a median interval of 5.3 years, 236 of whom had developed hypertension. Plasma CRP was independently associated with the development of hypertension in CRISPS-3 (odds ratio per quartile=1.26, P=0.010). Six SNPs were associated with plasma CRP (all P<0.001). However, none of the SNPs was significantly associated with blood pressure, prevalent or incident hypertension, or change in blood pressure. In conclusion, plasma CRP predicts the development of hypertension. Genetic variants in the CRP gene are significantly associated with plasma CRP but not with hypertension. The future risk of hypertension is therefore more related to plasma CRP than SNPs in the CRP gene in this population.

Genetic variants associated with persistent central obesity and the metabolic syndrome in a 12-year longitudinal study

OBJECTIVE Central obesity predisposes to various cardiometabolic diseases and is a key component of the metabolic syndrome (MetS). We have previously demonstrated that three obesity-susceptible single nucleotide polymorphisms (SNPs), rs10938397 (GNPDA2), rs8050136 (FTO) and rs17782313 (MC4R), were associated with obesity and waist circumference in cross-sectional studies in the Chinese population. In this study, we investigate whether these SNPs could also predict the persistence of central obesity and MetS in subjects from the Hong Kong Cardiovascular Risk Factors Prevalence Study (CRISPS) cohort. DESIGN AND METHODS We genotyped these SNPs in i) 354 subjects with and 994 subjects without central obesity at both baseline and a 12-year follow-up, ii) 2214 subjects (816 cases and 1398 controls) in an MetS cross-sectional case-control study and iii) 225 subjects with and 1221 subjects without MetS at both baseline and the 12-year follow-up. RESULTS Both FTO rs8050136 (P(age, sex-adjusted)=0.019; odds ratio (OR) (95% confidence intervals (CI)): 1.35 (1.05, 1.73)) and GNPDA2 rs10938397 (P(age, sex-adjusted)=3 × 10(-3); OR (95% CI): 1.34 (1.11, 1.63)) were significantly associated with persistent central obesity. GNPDA2 rs10938397 was also significantly associated with MetS (P(age, sex-adjusted)=0.011, OR (95% CI): 1.20 (1.04, 1.38)) in the case-control study. However, none of these SNPs showed an individual association with persistent MetS. In the combined genetic risk analyses for persistent central obesity and persistent MetS, the combined genetic risk score of the three SNPs showed an OR of 1.25 (95% CI: 1.10, 1.42; P(age, sex-adjusted)=4.92 × 10(-3)) and 1.19 (95% CI: 1.03, 1.38; P(age, sex-adjusted)=0.019) for each additional risk allele respectively. CONCLUSION This study demonstrated that FTO and GNPDA2 variants predicted persistent central obesity in the Chinese population, further supporting their importance as obesity-susceptible genes.

Diabetic nephropathy is associated with the 5¢-end dinucleotide repeat polymorphism of the aldose reductase gene in Chinese subjects with Type 2 diabetes

Aims We investigated whether the promoter dinucleotide repeat polymorphism of the aldose reductase gene (5′‐ALR2), implicated in the development of nephropathy in Type 1 diabetes, was associated with diabetic nephropathy in Type 2 diabetes.