Askandar Tjokroprawiro

Disturbance of B-vitamin status in people with type 2 diabetes in Indonesia—Link to renal status, glycemic control and vascular inflammation

BACKGROUND Diabetes is associated with mishandling of thiamine in the kidney and development of diabetic nephropathy. The aim of this study is to assess the disturbance of thiamine and other B-vitamin status of patients with type 2 diabetes in Indonesia. METHODS One hundred and fifteen patients with type 2 diabetes with and without microalbuminuria or albuminuria and 39 healthy people were recruited. After a 2-month washout period for B-vitamin supplementation, markers of vitamins B(1), B(6), B(9) and B(12), were determined. RESULTS Fractional excretion of thiamine (22.8 versus 33.5%; P<0.05) and urinary excretion of the vitamin B(6) degradation product 4-pyridoxic acid (0.081 versus 0.133 μmol/g creatinine, P<0.001) was increased in patients with type 2 diabetes with respect to healthy controls. There was also increased total plasma cobalamin (398 versus 547 pmol/l, P<0.001) and holotranscobalamin (74 versus 97 pmol/l, P<0.001) in patients with type 2 diabetes. In multiple regression analysis these were linked to HbA1c, duration of diabetes and systolic blood pressure, and fasting plasma glucose, folate and C-reactive protein, respectively. CONCLUSIONS There was renal mishandling of thiamine, increased degradation of vitamin B(6) and cytosolic metabolic resistance to vitamin B(12) in patients with type 2 diabetes in Indonesia.

The GIANT study, a cluster-randomised controlled trial of efficacy of education of doctors about type 2 diabetes mellitus management guidelines in primary care practice

OBJECTIVES Primary aim: does general practitioner (GP) education on type 2 diabetes treatment improve HbA1c? Secondary aim: cardiovascular risk factors, hypoglycaemia, treatment intensification, health service utilisation, treatment barriers. METHODS 99 Asia-Pacific GPs were cluster-randomised to be educated on regional diabetes management guidelines (intervention) or continue standard care (control). The intervention employed meetings, reminders, medical record summary sheets and patient result cards. Each GP recruited four type 2 diabetic patients, assessed at baseline, 6 and 12 months. The primary outcome was mean change in HbA1c from 0 to 6 months in patients with baseline HbA1c≥6.5%. RESULTS 361 patients (93%) completed 6 month follow-up. The primary HbA1c outcome was -0.11% (95% CI -0.27, 0.05) with intervention and -0.22% (95% CI -0.39, -0.05) in the control group (p=0.340). The groups did not differ in control of other glycaemic indices, blood pressure or lipids after 6 or 12 months. In those with HbA1c≥9.0%, approximately 50% received intensified treatment by 6 months, and 30% in the final 6 months. GPs identified treatment costs and patient reluctance to use insulin as management barriers. CONCLUSIONS/INTERPRETATION A structured GP education programme did not improve HbA1c in patients with type 2 diabetes.

Safety, tolerability, and efficacy of metformin extended-release oral antidiabetic therapy in patients with type 2 diabetes: An observational trial in Asia

Background:  The aim of the present prospective observational study was to assess the tolerability and antihyperglycemic efficacy of metformin extended‐release (MXR) in the routine treatment of patients with type 2 diabetes mellitus (T2DM) from six Asian countries.

High frequency of autonomic as well as peripheral neuropathy in patients with malnutrition-related diabetes mellitus.

We assessed peripheral and autonomic nerve function in 27 diabetics. Ten had malnutrition-related diabetes mellitus (MRDM), eight insulin-dependent diabetes mellitus (IDDM), and nine non-insulin-dependent diabetes mellitus (NIDDM). The frequency of peripheral neuropathy was 70, 78 and 13% in MRDM, NIDDM and IDDM respectively. Furthermore, the frequency of abnormality in cardiac beat-to-beat variation was 50 and 38% in MRDM and IDDM respectively, whereas our NIDDM patients did not show this abnormality. The patients with MRDM thus revealed a high frequency of not only peripheral but also autonomic neuropathy. Autonomic dysfunction appears to be a new characteristic of MRDM, not mentioned by the WHO study group.

DLBS3233, a combined bioactive fraction of Cinnamomum burmanii and Lagerstroemia speciosa, in type-2 diabetes mellitus patients inadequately controlled by metformin and other oral antidiabetic agents.

Abstract Background DLBS3233, a combined bioactive fraction of Cinnamomum burmanii and Lagerstroemia speciosa, has preclinically demonstrated its beneficial effects on glucose and lipid metabolism through the upregulation of insulin-signal transduction. This study evaluated the clinical efficacy of an add-on therapy with DLBS3233 in type-2 diabetes mellitus subjects inadequately controlled by metformin and other oral antidiabetes. Methods This was an open and prospective clinical study for 12 weeks of therapy, involving type-2 diabetes mellitus patients who had been treated with two oral antidiabetic agents for at least 3 months prior to screening, yet, with HbA1c level was still beyond 7.0 %. DLBS3233 was given orally at the dose of 100 mg once daily in addition to their baseline oral antidiabetes medication. The primary end point was the reduction of HbA1c level; and the secondary end points were changes of fasting and 1-h postprandial glucose, homeostatic model assessment-insulin resistance, adiponectin, and lipid profile, from their respective baseline. Results After 12 weeks of treatment, the HbA1c level was reduced by 0.65±1.58 % (p=0.001) from baseline (9.67±2.11 %); while the 1-h-PG level was reduced by –1.45±3.89 mmol/L (p=0.021) from baseline (15.29±4.49 mmol/L). Insulin sensitivity, lipid profile and adiponectin level were improved to a considerable extent. DLBS3233 did not adversely affect body weight, liver, and renal function. Most adverse events observed were tolerably mild and they all had been resolved by the end of the study. Conclusions The add-on oral antidiabetes therapy with DLBS3233 at the dose of 100 mg once daily helped type-2 diabetes mellitus patients to improve their glycemic control, enhance insulin sensitivity, lipid profile, and adiponectin level. In addition, DLBS3233 treatment concomitantly with other oral antidiabetic agents was proven safe and tolerable in type-2 diabetes subjects.

The Role of Creb in Adipogenesis through Mammalian Target of Rapamycin of Complex 1 (mTORC1) Pathyway

One of the tissues taking the biggest part in the pathogenesis of obesity is adipose tissue mainly formed by white fat cells. Recently, the processes adipogenesis become a treatment target for obesity. One of the pathway that allegedly participated in the process of adipogenesis is activated via CREB. The upstream pathway is by means of protein of mammalian targets of rapamycin (mTOR). This study was aimed to determine the role of CREB in adipogenesis through the activation of p70S6K1 by mTORC1. This was an experimental study. Subjects were primary cultured preadipocytes taken from visceral fat of white rats (Rattus norvegicus). Cell cultures were classified into 4 groups: (K) Control of adipogenesis: without rapamycin and RNAi CREB, (A): was given rapamycin 10 nM, (B): was given RNAi CREB 100 nM, (C): was given rapamycin 10 nM and RNAi CREB 100 nM. p70S6K1, CREB activation, and expression of C/EBPδ measured on day 2, 4, and 6, and the morphology of adipocytes on day 6. Data were analyzed with Anova test, LSD test, and Pearson correlation test with 95% confidence level. The data showed that rapamycin activated p70S6K1 and caused lower CREB compared with control group during adipogenesis. These results indicated that adipogenesis was blocked, which resulted from the inhibition of p70S6K1 and CREB activation by rapamycin and RNAi CREB. The inhibition was stronger in rapamycin + RNAi CREB group. Statistically, there was significant correlation between p70S6K1 and CREB; and between CREB and C/EBPδ. It was concluded that the role of CREB in adipogenesis was mediated by the activation of p706K1 by mTORC1.