Shireene Ratna Vethakkan

Potential Biomarkers of Insulin Resistance and Atherosclerosis in Type 2 Diabetes Mellitus Patients with Coronary Artery Disease

Type 2 diabetes mellitus patients with coronary artery disease have become a major public health concern. The occurrence of insulin resistance accompanied with endothelial dysfunction worsens the state of atherosclerosis in type 2 diabetes mellitus patients. The combination of insulin resistance and endothelial dysfunction leads to coronary artery disease and ischemic heart disease complications. A recognized biological marker, high-sensitivity C-reactive protein, has been used widely to assess the progression of atherosclerosis and inflammation. Along with coronary arterial damage and inflammatory processes, high-sensitivity C-reactive protein is considered as an essential atherosclerosis marker in patients with cardiovascular disease, but not as an insulin resistance marker in type 2 diabetes mellitus patients. A new biological marker that can act as a reliable indicator of both the exact state of insulin resistance and atherosclerosis is required to facilitate optimal health management of diabetic patients. Malfunctioning of insulin mechanism and endothelial dysfunction leads to innate immune activation and released several biological markers into circulation. This review examines potential biological markers, YKL-40, alpha-hydroxybutyrate, soluble CD36, leptin, resistin, interleukin-18, retinol binding protein-4, and chemerin, as they may play significant roles in insulin resistance and atherosclerosis in type 2 diabetes mellitus patients with coronary artery disease.

Non‐alcoholic fatty liver disease in diabetics – prevalence and predictive factors in a multiracial hospital clinic population in Malaysia

There is currently no published study comparing prevalence of non‐alcoholic fatty liver disease (NAFLD) and associated factors among diabetics of different ethnicity in the Asia‐Pacific region.

Why do some people with type 2 diabetes who are using insulin have poor glycaemic control? A qualitative study

Objective To explore factors influencing poor glycaemic control in people with type 2 diabetes using insulin. Research design A qualitative method comprising in-depth individual interviews. A semistructured interview guide was used. The interviews were audiorecorded, transcribed verbatim and analysed using a thematic approach. Participants Seventeen people with type 2 diabetes using insulin with glycated haemoglobin (HbA1c) ≥9% for >1 year. Setting The Primary Care Clinic and Diabetes Clinic in the University of Malaya Medical Centre (UMMC), Malaysia. Results Data analysis uncovered four themes: lifestyle challenges in adhering to medical recommendations; psychosocial and emotional hurdles; treatment-related factors; lack of knowledge about and self-efficacy in diabetes self-care. Conclusions Factors that explain the poor glycaemic control in people with type 2 diabetes using insulin were identified. Healthcare providers could use these findings to address patients’ concerns during consultations and help to improve glycaemic control.

Relationship between ultrasonographic nerve morphology and severity of diabetic sensorimotor polyneuropathy.

In the current study, the aim was to characterize the nerve ultrasound cross‐sectional areas (CSAs) of type 2 diabetic patients with diabetic sensorimotor polyneuropathy (DSP) of different severities.

Genetic markers predicting sulphonylurea treatment outcomes in type 2 diabetes patients: current evidence and challenges for clinical implementation

The clinical response to sulphonylurea, an oral antidiabetic agent often used in combination with metformin to control blood glucose in type 2 diabetes (T2DM) patients, has been widely associated with a number of gene polymorphisms, particularly those involved in insulin release. We have reviewed the genetic markers of CYP2C9, ABCC8, KCNJ11, TCF7L2 (transcription factor 7-like 2), IRS-1 (insulin receptor substrate-1), CDKAL1, CDKN2A/2B, KCNQ1 and NOS1AP (nitric oxide synthase 1 adaptor protein) genes that predict treatment outcomes of sulphonylurea therapy. A convincing pattern for poor sulphonylurea response was observed in Caucasian T2DM patients with rs7903146 and rs1801278 polymorphisms of the TCF7L2 and IRS-1 genes, respectively. However, limitations in evaluating the available studies including dissimilarities in study design, definitions of clinical end points, sample sizes and types and doses of sulphonylureas used as well as ethnic variability make the clinical applications challenging. Future studies need to address these limitations to develop personalized sulphonylurea medicine for T2DM management.

Genetic polymorphisms associated with overweight and obesity in uncontrolled Type 2 diabetes mellitus

Generally, obese and overweight individuals display higher free fatty acid levels, which stimulate insulin resistance. The combination of overweight or obesity with insulin resistance can trigger Type 2 diabetes mellitus (T2DM) and are primary contributing factors to the development of uncontrolled T2DM. Genetic polymorphisms also play an important role as they can impact a populations susceptibility to becoming overweight or obese and developing related chronic complications, such as uncontrolled T2DM. This review specifically examines the genetic polymorphisms associated with overweight and obesity in patients with uncontrolled T2DM. Particularly, gene polymorphisms in ADIPOQ (rs1501299 and rs17300539), LepR (rs1137101 and rs1045895), IRS2 (rs1805092), GRB14 (rs10195252 and rs3923113) and PPARG (rs1801282) have been associated with overweight and obesity in uncontrolled T2DM.

Clinical and genetic predictors of dipeptidyl peptidase-4 inhibitor treatment response in Type 2 diabetes mellitus

AIM To determine the clinical and genetic predictors of the dipeptidyl peptidase-4 (DPP-4) inhibitor treatment response in Type 2 diabetes mellitus (T2DM) patients. PATIENTS & METHODS DPP4, WFS1 and KCNJ11 gene polymorphisms were genotyped in a cohort study of 662 T2DM patients treated with DPP-4 inhibitors sitagliptin, vildagliptin or linagliptin. Genotyping was performed by Applied Biosystems TaqMan SNP genotyping assay. RESULTS Patients with triglyceride levels less than 1.7 mmol/l (odds ratio [OR]: 2.2.; 95% CI: 1.031-4.723), diastolic blood pressure (DBP) less than 90 mmHg (OR: 1.7; 95% CI: 1.009-2.892) and KCNJ11 rs2285676 (genotype CC) (OR: 2.0; 95% CI: 1.025-3.767) were more likely to response to DPP-4 inhibitor treatment compared with other patients, as measured by HbA1c levels. CONCLUSION Triglycerides, DBP and KCNJ11 rs2285676 are predictors of the DPP-4 inhibitor treatment response in T2DM patients.

Sliding-scale versus basal-bolus insulin in the management of severe or acute hyperglycemia in type 2 diabetes patients: a retrospective study.

Sliding-scale and basal-bolus insulin regimens are two options available for the treatment of severe or acute hyperglycemia in type 2 diabetes mellitus patients. Although its use is not recommended, sliding-scale insulin therapy is still being used widely. The aims of the study were to compare the glycemic control achieved by using sliding-scale or basal-bolus regimens for the management of severe or acute hyperglycemia in patients with type 2 diabetes and to analyze factors associated with the types of insulin therapy used in the management of severe or acute hyperglycemia. This retrospective study was conducted using the medical records of patients with acute or severe hyperglycemia admitted to a hospital in Malaysia from January 2008 to December 2012. A total of 202 patients and 247 admissions were included. Patients treated with the basal-bolus insulin regimen attained lower fasting blood glucose (10.8±2.3 versus 11.6±3.5 mmol/L; p = 0.028) and mean glucose levels throughout severe/acute hyperglycemia (12.3±1.9 versus 12.8±2.2; p = 0.021) compared with sliding-scale insulin regimens. Diabetic ketoacidosis (p = 0.043), cardiovascular diseases (p = 0.005), acute exacerbation of bronchial asthma (p = 0.010), and the use of corticosteroids (p = 0.037) and loop diuretics (p = 0.016) were significantly associated with the type of insulin regimen used. In conclusion, type 2 diabetes patients with severe and acute hyperglycemia achieved better glycemic control with the basal-bolus regimen than with sliding-scale insulin, and factors associated with the insulin regimen used could be identified.

Ultrasonography-diagnosed non-alcoholic fatty liver disease is not associated with prevalent ischemic heart disease among diabetics in a multiracial Asian hospital clinic population.

BACKGROUND Non-alcoholic fatty liver disease (NAFLD) and cardiovascular diseases are both common among patients with diabetes mellitus. OBJECTIVE The aim of this study is to determine if ultrasonography-diagnosed NAFLD is associated with prevalent ischemic heart disease (IHD) among patients with diabetes mellitus. METHODS This is a cross-sectional study on consecutive patients seen at the Diabetic Clinic, University of Malaya Medical Centre. The medical record for each patient was reviewed for documented IHD. Patients without documented IHD but had symptoms and/or electrocardiographic changes suggestive of IHD were referred for cardiac evaluation. RESULTS Data for 399 patients were analyzed. Mean age was 62.8±10.5 years with 43.1% male. NAFLD and IHD were present in 49.6 and 26.6%, respectively. The prevalence of IHD among patients with and without NAFLD was 24.7 and 28.4%, respectively (P=0.414). The prevalence of IHD was highest among the Indians (34.1%) followed by the Malays (29.2%) and the Chinese (20.1%). No association was found between NAFLD and IHD when analyzed according to ethnicity. On multivariate analysis, independent factors associated with IHD were older age, lower levels of physical activity, greater waist circumference and higher serum glycated hemoglobin level. CONCLUSIONS Ultrasonography-diagnosed NAFLD was not associated with prevalent IHD among patients with diabetes mellitus in a multiracial Asian hospital clinic population.

Asymmetrical bone loss in a patient with poliomyelitis: an indication for anti-osteoporotic therapy.

BACKGROUND Poliomyelitis survivors suffer from post-myelitic complications including osteoporosis that are often overlooked. METHODS We report a case of a 49-year-old lady with history of poliomyelitis with resultant flaccid paralysis of the involved limb. RESULTS The bone mineral density revealed asymmetrical severe osteoporosis in the poliomyelitic limb. Given the risk of falls and fractures, she was commenced on oral bisphosphonate therapy. CONCLUSION Poliomyelitis is an important acquired risk factor for regional osteoporosis. This condition should be detected and treated in this cohort of patients who are clearly at higher risk of fractures.