The effects of diet and orlistat on body weight and lipid profiles in high risk Chinese patients with coronary artery disease, obesity and hypercholesterolemia.

BACKGROUND: Orlistat is a gastrointestinal lipase inhibitor approved for use in obesity. So far, no evidence has been reported on the use of orlistat in obese patients with coronary artery disease (CAD). AIM: To investigate the effect of orlistat on body weight and lipid profiles in obese patients with CAD and hypercholesterolemia. METHODS: Thirty non-diabetic patients with CAD, body mass index (BMI) > or = 25 kg/m(2) and low-density lipoprotein cholesterol (LDL-C) > or = 2.6 and < 4.1 mmol/L were put on diet for 12 weeks. Those still having a BMI > or = 25 kg/m(2) received orlistat 120 mg thrice daily for another 24 weeks. RESULTS: BMI was significantly reduced by 1.7% after 12 weeks of dietary treatment. The 24-week orlistat treatment resulted in further significant reduction in BMI (-2.8%) and LDL-C (-7.0%). CONCLUSION: Diet and orlistat treatment significantly reduced BMI and improved LDL-C in obese patients with CAD and hypercholesterolemia.

Association of smoking with increasing vascular involvement in type 2 diabetic Chinese patients.

PURPOSE: To identify the relationship between smoking and the metabolic profile and existing vascular disease in Chinese type 2 diabetic patients. METHODS: 1710 diabetic patients were screened for complications, and biochemical and anthropometric vascular risk factors. As most smokers were male, differences were only compared between male current (n = 196) and never smoking patients (n = 300). RESULTS: The smokers had higher glycosylated haemoglobin levels (8.2 +/- 2.0 vs. 7.6 +/- 1.8%, p < 0.001) than never smokers, despite a greater proportion receiving hypoglycaemic agents (87.5 vs. 79.6%, p = 0.003). Male smokers compared to never smokers had lower HDL-cholesterol levels (1.12 +/- 0.31 vs. 1.20 +/- 0.30 mmol/L, p = 0.006), and elevated albumin-to-creatinine ratio (3.57 [2.68-4.75] vs. 2.47 [1.99-3.05] mg/mmol, p = 0.040). However, diastolic blood pressure was lower in the smoking group (78 +/- 12 vs. 82 +/- 12 mmHg, p = 0.001) even though they received less blood pressure-lowering treatments (23.8 vs. 33.2%, p = 0.034). The prevalence of peripheral vascular disease was increased in the diabetic patients who smoked compared to nonsmokers (7.1 vs. 2.8%, p = 0.039). CONCLUSIONS: Smoking was associated with a more adverse metabolic profile and peripheral vascular disease. As mainland China undergoes rapid modernisation and urbanisation, the observed effects of smoking means tobacco control becomes increasingly important to prevent or minimise potential health impacts and chronic disease.

MicroAlbuminuria Prevalence Study (MAPS) in hypertensive type 2 diabetic patients in Hong Kong.

OBJECTIVES: To assess the prevalence of macroalbuminuria and microalbuminuria, and the level of blood pressure control in patients with type 2 diabetes and hypertension in Hong Kong. DESIGN: Cross-sectional clinic-based epidemiological study. SETTING: Six medical centres (including two public hospital diabetes centres) in Hong Kong. PATIENTS: Recruited from the medical centres from April to November 2002, after excluding those with bacteriuria and haematuria. MAIN OUTCOME MEASURES: Body mass index; blood pressure; levels of blood glucose, macroalbuminuria, and microalbuminuria; treatments for hypertension and diabetes. RESULTS: The as per-protocol recruited population of 437 hypertensive type 2 diabetic patients had a mean age of 61.7 (standard error, 0.5) years. Overall, the prevalence of diabetic nephropathy in this population was high; 18.3% had macroalbuminuria (95% confidence interval, 16.5-20.2%) and 24.9% had microalbuminuria (95% confidence interval, 22.9-27.0%). Predictive factors were advanced age, male sex, poor blood pressure control, and existing cardiovascular complications. Whilst almost all patients (96.1%) were receiving treatment for hypertension, only 25.6% had systolic/diastolic blood pressures below the 130/85 mm Hg target. CONCLUSIONS: In Hong Kong, the prevalence of microalbuminuria and macroalbuminuria is high in type 2 diabetic patients with hypertension, particularly in males and those with poorly controlled systolic blood pressure. Tight glycaemic control, antihypertensive therapy, and use of renin-angiotensin system inhibitors/blockers are necessary to retard the progression of nephropathy to advanced renal disease.

Metabolic syndrome by the international diabetes federation definition in Hong Kong Chinese.

In this report, we aimed to examine the impact of the new International Diabetes Federation (IDF) definition on the prevalence and clinical characteristics of subjects with metabolic syndrome (MES). Data were obtained from a prevalence survey for cardiovascular risk factors in a Hong Kong Chinese working population. There were 1513 subjects well representing all occupational groups from managers to general laborers [910 (60.1%) men and 603 (39.9%) women (mean age 37.5+/-9.2, median 37.0, range 18-66 years)]. The crude prevalence of MES defined by the IDF criterion was 7.4% (compared to other criteria: NCEP, 9.6%; WHO, 13.4% and EGIR, 8.9%). The age-standardized prevalence of MES by the IDF criterion was 8.8% in women and 7.3% in men. Subjects with MES defined by IDF criterion had higher body mass index and waist compared to those with MES defined by NCEP or WHO criteria, and lower triglyceride compared to those with MES defined by NCEP criterion after adjustment for age, gender and smoking. Non-MES subjects defined by IDF criterion had higher 2h glucose and insulin resistance compared to non-MES subjects defined by WHO. In conclusion, the new IDF criterion for MES is easy to implement in clinical practice. It may be potentially more 'specific' in identifying subjects with MES although compared to the NCEP criterion, it may have missed a proportion of subjects, especially men, who have metabolic derangement. Prospective and interventional studies are needed to validate the prognostic values of this new definition in comparison with other existing definitions.

Inter-relationships between DNA damage, ascorbic acid and glycaemic control in Type 2 diabetes mellitus.

AIMS: The onset of complications in Type 2 diabetes mellitus (DM) patients cannot be predicted in individuals. Evidence suggests a link between complications and hyperglycaemia, oxidative stress and antioxidants, but causality is unclear. This study investigated baseline (entry) fasting plasma ascorbic acid, lymphocytic DNA damage and glycaemic control in Type 2 DM as part of a long-term study, the aim of which is to explore a biomarker profiling approach to identify and improve outcome in high-risk subjects. METHODS: A cross-sectional study, in which DNA damage, glycated haemoglobin (HbA(1c)), fasting plasma glucose (FPG) and ascorbic acid (AA) were measured on fasting blood samples collected from 427 Type 2 DM subjects. RESULTS: DNA damage was significantly (P < 0.0001) and directly correlated to both FPG (r = 0.540) and HbA(1c) (r = 0.282), and was significantly (P < 0.0001), independently and inversely correlated to plasma AA (r = -0.449). In those subjects with both poor glycaemic control and low AA (< 48 microm, the overall mean value for the study group), DNA damage was significantly (P < 0.005) higher compared with those subjects with a similar degree of hyperglycaemia but with AA above the mean. CONCLUSIONS: The novel finding of a significant inverse relationship between plasma AA and DNA damage in Type 2 DM indicates that poorly controlled diabetic subjects might benefit from increased dietary vitamin C. The data also have important implications for biomarker profiling to identify those subjects who might benefit most from intensive therapy. Longer-term follow-up is underway.

An alarmingly high prevalence of diabetic nephropathy in Asian type 2 diabetic patients: the MicroAlbuminuria Prevalence (MAP) Study.

AIM/HYPOTHESIS: Microalbuminuria represents the earliest clinical evidence of diabetic nephropathy and is a marker of increased cardiovascular morbidity and mortality. Its early detection allows the implementation of individualised and aggressive intervention programmes to reduce cardiovascular risk factors. There is limited information on the prevalence of microalbuminuria among hypertensive type 2 diabetic patients in Asia. METHODS: This cross-sectional epidemiological study aimed to assess the prevalence of microalbuminuria and macroalbuminuria among consecutively screened hypertensive type 2 diabetic adult patients in 103 centres in 10 Asian countries or regions. Predictive factors for microalbuminuria and macroalbuminuria were characterised using a stepwise logistic regression model. RESULTS: A total of 6,801 patients were enrolled and 5,549 patients constituted the per-protocol population (patients with bacteriuria and haematuria were excluded). The prevalence of microalbuminuria was 39.8% (39.2-40.5; 95% CI) and the prevalence of macroalbuminuria was 18.8% (18.2-19.3; 95% CI). Only 11.6% of the patients had systolic and diastolic blood pressure below the 130/80 mm Hg target. In the multivariate analyses, the predictive factors for the presence of microalbuminuria were age, BMI, systolic blood pressure and ethnic origin. The highlighted predictive factors for the presence of macroalbuminuria were age, sex, ethnic origin, BMI, duration of diabetes, presence of diabetic complications, intake of diuretics, intake of calcium channel blockers, diastolic and systolic blood pressure. CONCLUSIONS/INTERPRETATION: The high prevalence (58.6%) of micro or macroalbuminuria observed in these patients is alarming and indicates an impending pandemic of diabetic cardiovascular and renal diseases in Asia with its potential economic consequences.

Triglyceride, albuminuria and blood pressure are the major associations of non-fatal cardiovascular disease in Chinese type 2 diabetes.

Diabetes is associated with an increased risk of cardiovascular disease (CVD). We studied risk factors for CVD in a cohort of Chinese type 2 diabetic patients recruited between July 1994 and August 1998. Ischemic heart disease (IHD) was defined as a history of: (i) confirmed coronary artery disease (with typical electrocardiographic changes or a positive exercise tolerance test) in patients under care of a cardiologist; (ii) documented myocardial infarction; or (iii) coronary interventions such as angioplasty or coronary artery bypass graft. Cerebrovascular accident (CVA) was defined as any definite cerebral vascular event with or without residual neurological deficit. CVD was defined as a history of IHD or CVA. The study enrolled 3333 patients, including 1370 men (41.1%) and 1963 women (58.9%) of mean age 55.9+/-13.3 years (range, 16-91 years; median, 57 years). A total of 279 patients (8.4%) had CVD (including 4.1% with CVA, 4.9% with IHD, and 0.6% with both CVA and IHD). Men had an overall higher rate of CVD than women (10.1% vs. 7.1%, p=0.002). All cardiovascular diseases showed a progressive increase in prevalence with increasing age with the peak among those aged

A low socio-economic status is an additional risk factor for glucose intolerance in high risk Hong Kong Chinese.

To examine whether a low socio-economic status (SES) is an additional risk factor for glucose intolerance in Hong Kong Chinese with known risk factors for glucose intolerance, a total of 2847 Chinese subjects (473 men and 2374 women) were recruited from the community for assessment. They had known risk factors for glucose intolerance including a previous history of gestational diabetes, positive family history of diabetes in first degree relatives and equivocal fasting plasma glucose concentrations between 7 and 8 mmol/l or random plasma glucose concentrations between 8 and 11 mmol/l. The 2847 subjects were classified according to their education levels and occupations: education group 1 = high school or university, group 2 = middle school, group 3 = illiterate or up to elementary school; occupational group 1 = professional or managerial, group 2 = non-manual, group 3 = manual, group 4 = unskilled, group 5 = housewife or unemployed. Different socio-economic groups were well represented in this selected population. The distribution of educational groups in this study was similar to that recorded in the 1991 Hong Kong Census. When analysed according to education levels and after adjustment for age, women in the lowest social class had the highest prevalence of diabetes, body mass index, blood pressure and plasma glucose concentrations. Men with the lowest education level had the highest prevalence of diabetes after age adjustment. The age-adjusted odds ratio (95% confidence intervals) of having diabetes was 2.3 (1.3. 4.3) in female subjects and 2.5 (1.2, 5.4) in male subjects with the lowest SES compared to subjects with the highest SES. When categorised according to occupation and after adjustment for age, women in the lowest social class had the highest prevalence of diabetes and glycaemic indexes. The age-adjusted odds ratio of having diabetes was 4.5 (1.9, 10.9) in female subjects with the lowest SES compared to those with the highest SES. The corresponding age-adjusted odds ratio in male subjects was 1.9 (0.9, 3.9) but this was not statistically significant. In conclusion, a lower socio-economic class, categorised either by occupational or educational level, was an additional risk factor for diabetes in Hong Kong Chinese who had known risk factors for glucose intolerance. These subjects should have increased priority for health education and regular diabetes screening. Our findings further emphasise the complex relationships between societal affluence, personal income and educational level.

A young male patient with persistent fever due to tuberculous peritonitis.

Tuberculous peritonitis is an uncommon disease in Hong Kong. We report a case of tuberculous peritonitis in a young male. The patient presented with persistent fever and intermittent cough for 1 month, but had no gastrointestinal symptoms. It was only through detection of slight abdominal ascites that subsequent abdominal paracentesis and laparoscopic biopsy confirmed the diagnosis. Appropriate antituberculous treatment was prescribed. Progress was complicated by persistent fever and liver function derangement, successfully managed by careful titration of antituberculous medications.

Factors predicting the age when type 2 diabetes is diagnosed in Hong Kong Chinese subjects.

OBJECTIVE: To examine the factors predicting age at diagnosis of type 2 diabetes in Hong Kong Chinese. RESEARCH DESIGN AND METHODS: The relationships between age at diagnosis and parental history of diabetes as well as an array of clinical and metabolic factors were examined using a hospital clinic-based diabetes registry involving 3,414 index patients with type 2 diabetes Patterns of age at diagnosis in successive generations were also examined using 21 affected child-parent pairs and 7 affected child-parent-grandparent trios. RESULTS: Approximately 29% of the index patients were diagnosed with type 2 diabetes at < or = 35 years of age (hereby defined as early-onset). Compared with the patients diagnosed at >35 years of age (hereby defined as late-onset) the early-onset patients had higher rates of positive paternal (16 vs. 5%) and maternal (22 vs. 12%) history of diabetes (both at P < 0.01) and had poorer metabolic profiles. In the overall index patients, male sex, higher HbA1c waist-to-hip ratio (WHR), and systolic blood pressure (sBP); lower HDL cholesterol level; and a positive paternal was well as maternal history of diabetes predicted younger age at diagnosis. More senior age and higher BMI and diastolic blood pressure predicted olderq age at diagnosis. Predictors for younger age at diagnosis in the male patients were higher HbA1c and sBP and a positive paternal history of diabetes Predictors for younger age at diagnosis in the female patients were higher HbA1c WHR, and sBP and a paternal as well as maternal history of diabetes. In the affected child parent pairs and clild-parent-grandparent trios there was a decrease in age at diagnosis in successive generations. CONCLUSIONS: Our data indicate that both familial (possibly genetic) and metabolic factors affect the age of onset of type 2 diabetes in the Chinese population. The results also suggest an onset and progression pattern of the disease that is compatible with the phenomenon of anticipation.

HLA typing and immunological characterization of young-onset diabetes mellitus in a Hong Kong Chinese population.

AIMS: A study of the Hong Kong Chinese showed that the majority of subjects with young-onset diabetes (age of diagnosis < 35 years) present with a phenotype suggestive of Type 2 diabetes mellitus, although up to 50% subsequently need insulin treatment. The aim of this study was to use a combination of clinical, genetic and immunological markers to characterize the disease phenotype further in such individuals and to determine whether the requirement for insulin is the result of autoimmune disease. METHODS: One hundred and thirty-seven Hong Kong Chinese with young-onset diabetes were studied, irrespective of their mode of presentation. The subjects were typed for alleles of the HLA-DR and -DQ genes and investigated for the presence of autoantibodies to glutamic acid decarboxylase (GAD). Plasma C-peptide concentration and requirement for insulin were also determined. RESULTS: One hundred and three subjects presented with a syndrome resembling Type 2 diabetes, while 34 presented with Type 1 diabetes. Of the former group, 35 patients (34.0%) were insulin-deficient, 16 (15.5%) were insulin-treated and seven (6.9%) were positive for GAD autoantibodies. Among the GAD-positive subjects presenting with Type 2 diabetes, the HLA-DRB1*03 allele may be a marker of early progression to insulin therapy. CONCLUSIONS: Seven subjects with Type 2 diabetes at presentation had autoantibodies to GAD. Causes other than GAD autoimmunity, however, must be sought to explain the high prevalence of insulin deficiency observed in the Chinese patients. This study highlights the heterogeneity of the pathogenic processes leading to the diabetic phenotype.

Treatment of Chinese acromegaly with a combination of bromocriptine and octreotide.

BACKGROUND: Good results have been reported with combined use of octreotide and bromocriptine in acromegalic Caucasians. Data concerning the efficacy and tolerability of this combination treatment in Chinese acromegalic patients are scanty. AIM: The aim of this study was to assess the efficacy and tolerability of combined therapy using bromocriptine and octreotide in the treatment of acromegaly in Chinese patients and to compare the cost-effectiveness of various regimes. METHODS: Sixteen Chinese acromegalic patients with growth hormone (GH) concentration not suppressible to below 5 mU/L (2 microg/L) during an extended OGTT were recruited to undergo four phases of the study. During the study period, the patients were given bromocriptine alone, bromocriptine and low dose octreotide, bromocriptine and medium dose octreotide, and medium dose octreotide alone. Plasma concentrations of GH and insulin-like growth factor-1 (IGF-1) were measured before and after the completion of each phase. RESULTS: The number of patients reaching target GH concentrations was significantly higher when treated with octreotide compared to baseline (p<0.05). Bromocriptine alone had a significant effect but not to the extent of octreotide alone. A combination of low dose octreotide and bromocriptine is as efficacious in the treatment of acromegaly as high dose octreotide. None of the patients suffered from serious adverse effects. CONCLUSION: The results confirmed the usefulness and tolerability of bromocriptine and octreotide in Chinese acromegalics. The most cost-effective regime in this study was a combination of low dose octreotide and bromocriptine.

Outcomes of screening for diabetes in high-risk Hong Kong Chinese subjects.

OBJECTIVE: To examine the significance of individual risk factors on the development of diabetes in subjects who underwent screening for diabetes. RESEARCH DESIGN AND METHODS: A total of 1,649 Chinese subjects underwent screening for diabetes. They were asymptomatic but had known risk factors for diabetes, including a positive family history of diabetes, a past history of gestational diabetes, obesity, hypertension, and/or dyslipidemia. Another 799 age-matched subjects from the community who had no risk factors for diabetes were used as the comparison group. RESULTS: Of the 1,649 subjects who underwent screening, 241 (14.6%) had diabetes. In these subjects, 989 (60.0%) had 1 risk factor, 502 (30.4%) had 2 risk factors, 141 (8.6%) had 3 risk factors, and 17 (1.0%) had 4 or 5 risk factors for diabetes. Of the 799 control subjects, 29 (3.6%) had diabetes. Compared with the comparison group, the odds ratio (95% CI) of having diabetes after adjustment for age was 5.2 (3.5-7.7) in the 1,649 subjects with known risk factors. The odds ratio of having diabetes increased from 3.7 in subjects with 1 risk factor to 28.4 in subjects with 4 or 5 risk factors. CONCLUSIONS: In men, age, BMI, family history of diabetes, and dyslipidemia, and in women, age, BMI, hypertension, dyslipidemia, total cholesterol, and history of gestational diabetes are associated with increased odds of developing diabetes. These risk factors have additive effects on the odds of having diabetes. Early and regular screening for diabetes and other cardiovascular risk factors is essential in these high-risk individuals.

Diabetes in Hong Kong Chinese: evidence for familial clustering and parental effects.

OBJECTIVE: To investigate transmission patterns of diabetes and their relationships with clinical characteristics in Hong Kong Chinese patients with late-onset (age > or =35 years) type 2 diabetes. RESEARCH DESIGN AND METHODS: This study involved 2,310 patients consecutively selected from a hospital clinic-based diabetes registry. These patients all reported the diabetes status of their parents as well as siblings. RESULTS: Approximately 36% of the 2,310 patients reported at least 1 affected parent or sibling (25 and 21% reported at least 1 diabetic parent and sibling, respectively). These patients, irrespective of their sex, were more likely to have a diabetic mother than a diabetic father (17 vs. 13% of the male patients and 18 vs. 9% of the female patients, P<0.01). The male patients were more likely than the female patients to have a diabetic father (13 vs. 9%, P<0.01). The female patients with a diabetic mother were found to have higher levels of plasma total cholesterol compared with the female patients with a diabetic father in multiple comparisons with adjustment for significance (5.56+/-1.30 vs. 5.09+/-0.95 mmol/l, P<0.05). In 2-group comparisons, there was also evidence that the male patients with a diabetic father had higher BMI values than the male patients with a diabetic mother (25.9+/-3.5 vs. 25.0+/-3.5 kg/m2, P<0.05). CONCLUSIONS: We found familial clustering of diabetes in the Hong Kong Chinese population as well as a significant maternal influence and a male sex-specific paternal effect. We suggest that both maternal and paternal factors may be implicated in the development of type 2 diabetes in the Chinese population.

Mitochondrial DNA A3243G mutation in patients with early- or late-onset type 2 diabetes mellitus in Hong Kong Chinese.

BACKGROUND AND OBJECTIVES: The mitochondrial DNA A to G mutation at nucleotide 3243 (mt3243) is associated with a subtype of diabetes characterized by maternal transmission and deafness. We have previously reported a 2.7% prevalence of this mutation in a cohort of young patients with either type 1 or type 2 diabetes. In this study, we aimed to confirm this finding by examining for the prevalence of this mutation in a large-scale study. SUBJECTS AND METHODS: Nine hundred and six unrelated Chinese patients with type 2 diabetes and 213 nondiabetic controls were studied. The presence of mt3243 mutation was determined by polymerase chain reaction amplification and ApaI digestion. RESULTS: This mutation was found in four of 133 (3.0%) patients with early onset ( 40 years) diabetes and no family history. Basal pancreatic beta-cell function, as assessed by fasting plasma C-peptide, was variable amongst mutation carriers, and did not correlate with the level of heteroplasmy of mutation. CONCLUSIONS: In agreement with most studies, our results suggest that despite the high prevalence of positive maternal family history of diabetes amongst our type 2 diabetic patients, mt3243 mutation was not a major cause of diabetes in either early- or late-onset diabetic patients in Hong Kong. The role of other genetic, environmental and intrauterine factors needs further investigation.

Glycaemic control in type 2 diabetes: the impact of body weight, beta-cell function and patient education.

We examined the determinants of glycaemic control in a consecutive cohort of 562 newly-referred Chinese type 2 diabetic patients (57% women) during a 12-month period. All patients underwent a structured assessment with documentation of clinical and biochemical characteristics. Pancreatic beta-cell function was assessed by fasting plasma C-peptide concentration. Insulin deficiency was defined as fasting plasma C-peptide <0.2 pmol/ml. Insulin resistance (IR) was calculated using the homeostasis model assessment (HOMA) based on a product of fasting plasma glucose and insulin concentrations. Treatment was considered appropriate when insulin-deficient patients were treated with insulin and non-insulin-deficient patients were treated with oral agents or diet. Mean (+/-SD) age was 54.3+/-13.8 years (range 17-87 years) and disease duration was 5.0+/-5.9 years. At the time of referral, 70.5% (n=396) were on drug therapy (9% on insulin and 62.8% on oral agents), 20.6% (n=116) were on diet and 9% (n=50) had not received any form of treatment. The mean HbA(lc) was 8.4+/-2.3%. The geometric mean (x// antilog SD) of IR was 4.62x//2.51 (range 0. 63-162.7) and correlated only with waist : hip ratio (WHR, p=0.008). The geometric mean of plasma C peptide was 0.47x//2.89 nmol/l and correlated with BMI (p<0.001). Glycated haemoglobin was correlated positively with age (p=0.013), disease duration (p<0.001), IR (p<0. 001) and negatively with BMI (p<0.001). Glycated haemoglobin was lower in patients who had seen a dietitian (7.9% vs. 8.7%, p<0.001) or diabetes nurse (7.8% vs. 8.7%, p<0.001) or who performed self blood glucose monitoring (7.9% vs. 8.6%, p=0.001) and higher among smokers (8.9% vs. 8.2%, p=0.003). Compared to insulin-deficient patients (n=118), non-insulin-deficient patients (n=413) had features resembling that of the Metabolic Syndrome with increased WHR (p=0.005), blood pressure (p<0.001), BMI (p=0.001) and were older (p=0.04). Amongst the insulin-deficient patients, 27% were treated with oral agents or diet. Patients receiving appropriate therapy (n=362) had a lower HbA(lc) than those treated inappropriately (n=173) (8.2% vs. 8.7%, p=0.02). On multivariate analysis, short disease duration (p<0.001), low IR (p<0.001), high BMI (p=0.001), diabetes education (p<0.001), lack of smoking (p=0. 014) and choice of appropriate treatment (p=0.009) were the independent determinants of good glycaemic control.