Dual blockade of the renin-angiotensin-aldosterone system is safe and effective in reducing albuminuria in Asian type 2 diabetic patients with nephropathy.

INTRODUCTION: Blockade of the renin-angiotensin-aldosterone system (RAAS) by either the angiotensin converting enzyme inhibitor (ACE-I) or the angiotensin II receptor blocker (ARB) has been shown to reduce albuminuria and delay the progression of diabetic nephropathy. This study evaluated the effect of dual blockade of the RAAS by adding an ACEI or an ARB to the administration of either drug alone on albuminuria in Asian type 2 diabetic patients with nephropathy. METHODS: 34 patients were randomly assigned to receive either enalapril 20 mg or losartan 100 mg once daily for eight weeks. Following this, all patients received a combination of enalapril 10 mg and losartan 50 mg daily for eight weeks, followed by enalapril 20 mg and losartan 100 mg daily for another eight weeks. The blood pressure and 24-hour urinary albumin excretion (UAE) were monitored. RESULTS: Following monotherapy with enalapril, there was a mean and standard error (SE) reduction in the UAE and mean arterial pressure (MAP) of 9.8 (SE 6.8) percent (p-value is 0.061) and 5.3 (SE 2.2) mmHg (p-value is 0.026), respectively; the reduction in UAE and MAP following monotherapy with losartan was by 10.9 (SE 14.1) percent (p-value is 0.053) and 4.5 (SE 1.9) mmHg (p-value is 0.034), respectively. Combination therapy with enalapril and losartan further reduced the UAE (11.2 [SE 8.7] percent, p-value is 0.009] despite there being no significant change in the MAP (-1.2 [SE 1.47] mmHg, p-value is 0.42). The adverse effects included dry cough (seven [19.4 percent] patients, resulting in the withdrawal of medication in two patients), and transient hyperkalaemia (two [six percent] patients). CONCLUSION: Dual blockade of the RAAS is safe and effective in reducing albuminuria in Asian type 2 diabetic patients with nephropathy.

Analysis of the contribution to type 2 diabetes susceptibility of sequence variation in the gene encoding stearoyl-CoA desaturase, a key regulator of lipid and carbohydrate metabolism.

AIMS/HYPOTHESIS: Stearoyl-CoA desaturase (SCD) is emerging as a key regulator of lipid and carbohydrate metabolism. Scd-null mice display a beneficial metabolic phenotype characterised by resistance to obesity, diabetes and hyperlipidaemia. The human homologue, SCD, maps to a region of chromosome 10 linked to type 2 diabetes, and SCD activity correlates with insulin sensitivity. Given this strong positional and biological candidacy, the present study sought to establish whether sequence variation in SCD influences susceptibility to type 2 diabetes and related traits. METHODS: The SCD gene was resequenced in 23 diabetic subjects. Six variants within coding and adjacent sequence, including a non-synonymous SNP in exon 5 (M224L), were selected for genotyping in a primary set of 608 diabetic subjects and 600 control subjects. RESULTS: There was no association (at the allele, genotype or haplotype level) with type 2 diabetes, although genotype frequencies at the +14301 A>C SNP in the 3' untranslated region showed borderline association (p~0.06) when evidence for linkage was taken into account. However, replication studies (350 young-onset diabetic patients; 747 controls) failed to confirm any relationship with diabetes for this variant. No significant associations were seen for diabetes-related traits including BMI and waist-to-hip ratio. CONCLUSIONS/INTERPRETATION: The present study, the first reported analysis of this gene, indicates that the SCD variants typed do not explain chromosome-10-encoded susceptibility to type 2 diabetes. Although this study provided no evidence that SCD sequence variation influences diabetes susceptibility or related traits, SCD remains a major target for pharmaceutical and/or environmental manipulation.

Hereditary spherocytosis, a pitfall in the assessment of glycaemic control.

The use of glycosylated haemoglobin in the assessment of diabetic control is ubiquitous. Hereditary spherocytosis is a haemolytic anaemia with shortened red blood cell lifespan, which can interfere with the methods of glycosylated haemoglobin measurement. We report a case of hereditary spherocytosis in a young man with type 1 diabetes, and illustrate the discrepancy in the measurements of glycosylated haemoglobin, which were inconsistent with the blood glucose profiles. Fructosamine, an alternative time-averaged indicator of blood glucose level, was advantageous in this particular situation. The awareness of the limitations of glycosylated haemoglobin is essential in the clinical care of patients with diabetes, which is a major health problem in Singapore.

Lean, nondiabetic Asian Indians have decreased insulin sensitivity and insulin clearance, and raised leptin compared to Caucasians and Chinese subjects.

OBJECTIVE: To study and compare the insulin sensitivity of healthy, nondiabetic Asian Indians with that of two other ethnic groups (Caucasian and Chinese) living in Singapore. DESIGN: Study of insulin sensitivity using euglycaemic hyperinsulinaemic glucose clamp. SUBJECTS: A total of 10 healthy, lean, young male subjects of each ethnic group, matched for age, body mass index (BMI) and physical activity. They all had normal glucose tolerance and had no family history of diabetes. MEASUREMENTS: Anthropometric parameters (BMI, waist-hip ratio (WHR) and percentage body fat (PBF)), fasting lipid profile and leptin concentration, insulin sensitivity index, and insulin clearance. RESULTS: Healthy lean (BMI 22.1+/-1.5 kg/m(2) (mean+/-s.d.)) Indians had significantly higher fasting serum leptin (5.1+/-2.5 vs Chinese 1.0+/-0.9 vs Caucasian 2.3+/-1.2 ng/ml; P<0.001), lower insulin sensitivity index (9.9+/-3.3 vs Chinese 14.1+/-3.5 vs Caucasian 18.8+/-9.2 mg/min kg fat-free mass/microU/ml; P<0.002), and lower insulin clearance (461.4+/-54.8 vs Chinese 621.0+/-99.3 vs Caucasian 646.9+/-49.2 ml/min m(2); P<0.001). Indians also had a higher PBF (26.5+/-5.2 vs Chinese 19.5+/-2.2 vs Caucasians 22.9+/-1.4%; P<0.001), diastolic blood pressure (P=0.036), fasting insulin (P<0.006) and fasting triglyceride (P=0.022). Stepwise regression analysis showed that ethnicity was the only significant independent determinant variable for the differences in insulin sensitivity index (P=0.008). CONCLUSION: Healthy lean nondiabetic Indians were more insulin resistant compared to other ethnic groups despite the similarity in living environment. These findings may warrant preventive health-care strategies for type II diabetes and coronary artery disease to target Indians at an earlier stage compared to other ethnic groups.

Frictional resistance to sliding archwires with repeated displacement.

Fictional resistance between a length of stainless steel archwire and a single bracket was calculated, and the effects of cyclical displacement forces on frictional resistance were tested. With the application of repeated displacement forces to the archwire, the force required to slide the wire through the bracket was substantially reduced. The percentage reduction in the force required to slide the wire was dependent on the size of the displacement force applied to the archwire. Frictional resistance in the mouth may not be satisfactorily reflected by steady mode laboratory models. The clinical implications for different types of orthodontic brackets remain unresolved.