Prevalence of albuminuria and cardiovascular risk profile in a referred cohort of patients with type 2 diabetes: an Asian perspective.

BACKGROUND: Microalbuminuria (MA) is a risk marker for diabetic nephropathy and cardiovascular (CV) disease (CVD) in patients with diabetes. This study aimed to describe the prevalence of albuminuria, CV risk factors, and treatments for renal and CV protection in an Asian population with type 2 diabetes. METHODS: This cross-sectional study conducted in eight Asian countries enrolled normotensive/hypertensive adults with type 2 diabetes without known proteinuria and/or non-diabetic kidney disease. Exclusion criteria were type 1 diabetes, menstruation, pregnancy, and acute fever. A single random urinary albumin/creatinine test was carried out in all patients. RESULTS: Of 8,561 patients, 14% had diabetic retinopathy, and 17% and 21% had history of CV disease and smoking, respectively. Normoalbuminuria was seen in 44%, MA in 44%, and macroalbuminuria in 12%. Target glycosylated hemoglobin (HbA1c) (<7%) was reached in only 37% of 3,834 patients with available values. Diabetes was managed by diet alone in 6%, while others received oral hypoglycemic drugs and/or insulin. In total, 75% did not reach target blood pressure (BP) of

Adding biphasic insulin aspart 30 once or twice daily is more efficacious than optimizing oral antidiabetic treatment in patients with type 2 diabetes.

AIM: To evaluate the efficacy and safety of adding biphasic insulin aspart 30 (BIAsp30; NovoMix 30) to existing oral antidiabetic agents (OADs) vs. optimizing OADs in a subgroup of Western Pacific patients with type 2 diabetes inadequately controlled on oral monotherapy or oral combination therapy. METHODS: This 26-week, multi-centre, open-labelled, randomized, two-arm parallel trial consisted of a 2-week screening period, followed by 24 weeks of treatment. Subjects randomized to BIAsp30 treatment (n = 129) received BIAsp30 once daily (o.d.) at dinnertime between Week 2 and Week 14, and those not reaching treatment targets were switched to twice daily (b.i.d.) BIAsp30 at Week 14 (n = 50). Subjects randomized to the OAD-only arm (n = 63) continued with their previous OAD treatment and, in an attempt to reach treatment goals, the dose was optimized (but OAD unchanged) in accordance to local treatment practice and labelling. RESULTS: Significantly greater reductions in HbA(1c) over Weeks 0-13 with BIAsp30 (o.d.) vs. OAD-only treatment (1.16 vs. 0.58%; p < 0.001), and over Weeks 0-26, with BIAsp30 (o.d.) and BIAsp30 (b.i.d.) treatments vs. OAD-only treatment (1.24 vs. 1.34 vs. 0.67%; p < 0.01). Hypoglycaemic episodes were reported in 54% of the patients in BIAsp30 (o.d. and b.i.d. pooled) and 30% of the patients in OAD-only group. All episodes were minor or symptomatic, except for one in each treatment group, which was major. CONCLUSIONS: Initiating BIAsp30 treatment is a safe and more effective way to improve glycaemic control in Western Pacific patients with type 2 diabetes inadequately controlled with oral monotherapy or oral combination therapy compared with optimizing oral combination therapy alone. In patients not reaching treatment target on BIAsp30 (o.d.), treatment with BIAsp30 (b.i.d.) should be considered.

Two common and three novel PDS mutations in Thai patients with Pendred syndrome.

Pendred syndrome is an autosomal recessive disorder characterized by congenital sensorineural deafness, goiter, and impaired iodide organification. It is caused by mutations in the PDS gene. Most published mutation studies of Pendred syndrome have dealt with Western populations. In this study, we examined clinical and molecular characteristics of 16 affected individuals in 6 unrelated Thai families. Of all the affected, 100% (16/16) had bilateral deafness, 68.8% (11/16) goiters, and 25% (4/16) hypothyroidism. Follicular thyroid carcinoma and Hürthle cell adenoma were found in affected members of a family, raising the possibility of an increased risk of thyroid carcinoma in Pendred syndrome patients. Sequence analysis of the entire coding region of the PDS gene successfully identified all 12 mutant alleles in these 6 families. The 12 identified mutant alleles constituted 6 distinct mutations including 3 splice site mutations (IVS4-1G>A, IVS7-2A>G, IVS9- 1G>A), one frame shift mutation (1548insC) and 2 missense mutations (T67S, H723R). Eight mutations out of 12 were constituted by IVS7- 2A>G and 1548insC, each one being present in 4 distinct alleles in our studied group. The identification of these two frequent PDS mutations will facilitate the molecular diagnosis of Pendred syndrome in Thai populations. In addition, three newly identified mutations, T67S, IVS4-1G>A, and IVS9-1G>A, were not observed in 50 unrelated healthy Thai controls.

Glimepiride in type 2 diabetes mellitus Thai patients.

This study aimed to confirm the efficacy of glimepiride given once daily in the treatment of Thai type 2 diabetic patients and to find out the optimum dosage for Thai patients. The patients were enrolled at the diabetic clinics of 5 hospitals (Rajavithi, Chulalongkorn, Pramongkutklao, Siriraj and Theptarin Hospitals). All patients started glimepiride 1 mg once daily and escalated to 2, 3, 4 and until 6 mg every 4 weeks if fasting plasma glucose (FPG) exceeded 140 mg/dL. Subjects were 60 females and 29 males with an average age of 52.2 +/- 10.0 years. Mean BMI was 25.5 +/- 3.8 kg/m2. Fifty seven patients (64.0%) were drug naïve and thirty two patients (36.0%) had been previously treated with oral hypoglycemic agents. Seventy three per cent of the drug naïve and 37 per cent of the previously treated patients could be controlled with 1-2 mg of glimepiride once daily. At the twelfth week of treatment, mean fasting plasma glucose decreased from 224.6 to 156.6 mg/dL (30% reduction) and mean HbA1c decreased from 10.0 to 7.5 per cent (25% reduction). At the end of the study 49.4 per cent of the patients had HbA1c < 7.0 per cent, 21.3 per cent had HbA1c 7.0-8.0 per cent and 29.3 per cent had HbA1c > 8.0 per cent. Adverse events that were probably or possibly related to the drug were reported in 5 patients (5.6%). Three of them were hypoglycemia and two patients had skin rash. All hypoglycemic episodes were mild. Glimepiride was indicated to be safe. There were no clinically significant changes in clinical laboratory values, physical examinations and vital signs. In conclusion, glimepiride was efficacious and safe in type 2 diabetes Thai patients and 1-2 mg of glimepiride appeared to be a sufficient dose for most newly diagnosed type 2 diabetic patients.

Site selectivity of osteoblast gene expression response to thyroid hormone localized by in situ hybridization.

We have previously reported that thyroid-stimulating hormone (TSH)-suppressive doses of L-thyroxine (L-T4) decrease femoral, but not vertebral, bone mineral density (BMD) in rats. L-T4-induced decreases in BMD were associated with increased expression of genes, reflecting osteoblast activity in mRNA extracted from whole femurs but not from vertebrae. To document that this skeletal selectivity reflected altered osteoblast activity, we studied gene expression by in situ hybridization in 8-wk-old rats treated with L-T4 (20 microg x 100 g body wt(-1) x day(-1)) for 4 wk. TSH-suppressive doses of L-T4 were associated with decreased femoral (0.299 +/- 0.005 vs. 0.273 +/- 0.005 g/cm2, P < 0.01), but not vertebral (0.222 +/- 0.004 vs. 0.218 +/- 0.003 g/cm2), BMD. In situ hybridization documented that L-T4 administration for 4 wk increased expression of osteocalcin and alkaline phosphatase mRNA in femoral, but not vertebral, osteoblasts. This study demonstrates a differential gene expression response of vertebral and femoral osteoblasts to L-T4. This altered degree of gene expression markers of osteoblast activity documented by in situ hybridization may in part explain the apparent clinical differences in the effect of L-T4 on femoral and vertebral BMD.

Differential responses of femoral and vertebral bones to long-term excessive L-thyroxine administration in adult rats.

Recent studies suggest that thyroid-stimulating hormone suppressive doses of thyroid hormone decrease bone mass in humans and growing rats. To determine the long-term effects of excessive L-thyroxine administration on the femur and vertebrae in an adult rat model, 20 male Sprague-Dawley rats (20 weeks old) were randomized into two groups. Group 1 received L-thyroxine (20 micrograms/100 g body weight ip daily), and group 2 received normal saline ip daily for 20 weeks. Femoral and lumbar vertebral bone mineral density measurements were performed at 0, 6, 15, 18 and 20 weeks of treatment. After 20 weeks of treatment, total RNA was isolated from both femoral and lumbar bones. Northern hybridization was performed with 32P-labeled DNA probes for osteocalcin, osteopontin, alkaline phosphatase and tartrate-resistant acid phosphatase. Significant decreases in bone mineral density in the femur of L-thyroxine-treated rats were observed after 15 weeks (p < 0.03). Lumbar bone mineral density was not affected. Both osteoblast (osteocalcin, osteopontin, alkaline phosphatase) and osteoclast (tartrate-resistant acid phosphatase) gene expression markers were increased significantly in the femoral bone (p < 0.001), but not in the lumbar vertebrae of the L-thyroxine-treated rats. We conclude that long-term administration of excessive doses of L-thyroxine to the adult rat preferentially affects femoral but not vertebral bone. This is manifested by decreased bone mineral density as well as increased gene expression markers for osteoblast and osteoclast activity in the femur.

Phospholipid and glutamic acid decarboxylase autoantibodies in diabetic neuropathy.

OBJECTIVE: To determine the prevalence and significance of phospholipid autoantibodies (PLAs) and glutamic acid decarboxylase (GAD) autoantibodies in the circulation of normal patients and diabetic patients with and without neuropathy. RESEARCH DESIGN AND METHODS: We measured PLAs in a total of 78 patients (a diabetic group with somatic or autonomic neuropathy [n = 40] another group without neuropathy [n = 38]), and GAD autoantibodies in a subset of 22 patients. RESULTS: PLAs are found in 2% of the general population. We found PLAs in 32% of the diabetic population without neuropathy, in 88% of those with neuropathy, in 55% of those with retinopathy, and in 25% of those with established nephropathy. The frequencies of immunoglobulins in the neuropathic group were: IgG = 78%, IgM = 33%, and IgA = 23%. There was no correlation between PLAs and microalbuminuria, macrovascular disease, fibrinogen, duration of diabetes, or neuropathy, but there was a strong correlation with total neuropathy score. Sera with high PLA IgG titers bound to the surface of neuroblastoma cells and inhibited cell growth. Antibodies to GAD65 were present in 32% and to GAD67 in 0% of patients. No titers of GAD65, GAD67, or the GAD65 ratio were associated with the degree of neuropathy of the presence of PLAs. CONCLUSIONS: PLAs occur frequently in the sera of patients with diabetes and correlate with the extent of neuropathy, suggesting a role for PLAs in the etiology thereof. The measurement of PLAs may constitute a marker for ongoing damage to nerves.

Quantitative measurement of cutaneous perception in diabetic neuropathy.

To determine the diagnostic value of various cutaneous sensory modalities in diabetic neuropathy, we studied cutaneous perception at the dominant hallux of 113 subjects (32 normal healthy controls and 81 diabetic subjects). The cutaneous sensory perception tests included warm and cold thermal perception, vibration, touch-pressure sensation, and current perception testing (CPT). The sensitivity of each modality when specificity is held greater than 90% was as follows: warm = 78%, cold = 77%, vibration = 88%, tactile-pressure = 77%, 5-Hz CPT = 52%, 250-Hz CPT = 48%, and 2000-Hz CPT = 56%. Combination thermal and vibratory gave optimum sensitivity (92-95%) and specificity (77-86%). We conclude that vibratory and thermal testing should be the primary screening tests for diabetic peripheral neuropathy. Other modalities may be of use only in specific situations.