Objectives To evaluate the effect of the sodium-glucose cotransporter 2 inhibitor (SGLT2-I) dapagliflozin on endothelial function in patients with high-risk type 2 diabetes mellitus (T2DM). Methods This was a prospective, double-blind, randomized, placebo-controlled, clinical trial of patients with T2DM with underlying ischemic heart disease who were receiving metformin and insulin therapy (n = 81). After 12-weeks of additional therapy with either dapagliflozin (n = 40) or placebo (n = 41), systemic endothelial function was evaluated by change in flow-mediated dilation (ΔFMD), change in nitroglycerin-mediated dilation (ΔNMD) and surrogate markers including intercellular adhesion molecule 1 (ICAM-1), endothelial nitric oxide synthase (eNOS), high-sensitivity C-reactive protein (hs-CRP), and lipoprotein(a) (Lp[a]). Glycemic and lipid profiles were also measured. Results The dapagliflozin group demonstrated significant reductions of hemoglobin A1c (HbA1c) and fasting blood glucose (FBG) compared to the placebo group (ΔHbA1c –0.83 ± 1.47% vs –0.16 ± 1.25%, P = 0.042 and ΔFBG vs –0.73 ± 4.55 mmol/L vs –1.90 ± 4.40 mmol/L, P = 0.015, respectively). The placebo group showed worsening of ΔFMD while the dapagliflozin group maintained similar measurements pre- and posttherapy (P = not significant). There was a reduction in ICAM-1 levels in the dapagliflozin group (–83.9 ± 205.9 ng/mL, P < 0.02), which remained unchanged in the placebo group (–11.0 ± 169.1 ng/mL, P = 0.699). Univariate correlation analysis revealed a significant negative correlation between HbA1c and ΔFMD within the active group. Conclusion A 12-week therapy with dapagliflozin, in addition to insulin and metformin therapies, in high-risk patients resulted in significant reductions in HbA1c, FBG, and surrogate markers of the endothelial function. Although the dapagliflozin group demonstrated a significant association between reduction in HbA1c and improvement in FMD, there was no significant difference in FMD between the 2 groups.
Introduction: The latest revised version of the World Health Organization's dengue classification was released in 2009. A handful of studies have taken initiatives to evaluate the old and revised guidelines to determine early signs and symptoms of severe dengue. This retrospective study aimed to compare the classification of dengue using both the 1997 and 2009 guidelines in a selected cohort of dengue patients from Peninsular Malaysia between 2008 and 2012. Methodology: Adult dengue patients were recruited from tertiary hospitals in two different states, Selangor and Kelantan, in Peninsular Malaysia. Their clinical manifestations were assessed. Results: A total of 281 confirmed dengue patients were enrolled; the mean duration of illness at admission was five days. Of these, 88.6%, 10.7%, and 0.7% were classified according to the 1997 guidelines as having dengue fever (DF), dengue hemorrhagic fever (DHF), and dengue shock syndrome (DSS), respectively. When the WHO 2009 guidelines were applied, 17.1%, 78.3%, and 4.6% were classified as dengue without warning signs, dengue with warning signs, and severe dengue, respectively. Conclusions: Our data suggests that the revised WHO 2009 guidelines stratify a much larger proportion of patients into a category that requires a higher level of medical and nursing care.
Introduction There is limited data on the effects of low carbohydrate diets on renal outcomes particularly in patients with underlying diabetic kidney disease. Therefore, this study determined the safety and effects of very low carbohydrate (VLCBD) in addition to low protein diet (LPD) on renal outcomes, anthropometric, metabolic and inflammatory parameters in patients with T2DM and underlying mild to moderate kidney disease (DKD). Materials and methods This was an investigator-initiated, single-center, randomized, controlled, clinical trial in patients with T2DM and DKD, comparing 12-weeks of low carbohydrate diet (<20g daily intake) versus standard low protein (0.8g/kg/day) and low salt diet. Patients in the VLCBD group underwent 2-weekly monitoring including their 3-day food diaries. In addition, Dual-energy x-ray absorptiometry (DEXA) was performed to estimate body fat percentages. Results The study population (n = 30) had a median age of 57 years old and a BMI of 30.68kg/m2. Both groups showed similar total calorie intake, i.e. 739.33 (IQR288.48) vs 789.92 (IQR522.4) kcal, by the end of the study. The VLCBD group showed significantly lower daily carbohydrate intake 27 (IQR25) g vs 89.33 (IQR77.4) g, p<0.001, significantly higher protein intake per day 44.08 (IQR21.98) g vs 29.63 (IQR16.35) g, p<0.05 and no difference in in daily fat intake. Both groups showed no worsening of serum creatinine at study end, with consistent declines in HbA1c (1.3(1.1) vs 0.7(1.25) %) and fasting blood glucose (1.5(3.37) vs 1.3(5.7) mmol/L). The VLCBD group showed significant reductions in total daily insulin dose (39(22) vs 0 IU, p<0.001), increased LDL-C and HDL-C, decline in IL-6 levels; with contrasting results in the control group. This was associated with significant weight reduction (-4.0(3.9) vs 0.2(4.2) kg, p = <0.001) and improvements in body fat percentages. WC was significantly reduced in the VLCBD group, even after adjustments to age, HbA1c, weight and creatinine changes. Both dietary interventions were well received with no reported adverse events. Conclusion This study demonstrated that dietary intervention of very low carbohydrate diet in patients with underlying diabetic kidney disease was safe and associated with significant improvements in glycemic control, anthropometric measurements including weight, abdominal adiposity and IL-6. Renal outcomes remained unchanged. These findings would strengthen the importance of this dietary intervention as part of the management of patients with diabetic kidney disease.
Introduction Insulinoma is a functioning pancreatic neuroendocrine tumor primarily leading due to hypoglycemia due to hypersecretion of insulin. This case illustrates the real challenges faced in the detection of an occult insulinoma, which resulted in a protracted course of the disease. Case presentation A 33-year-old female presented with recurrent hypoglycemia. Endogenous hyperinsulinemia was confirmed by a prolonged fast, however serial imaging was negative. Incidental finding of an ovarian mass gave rise to the suspicion of an insulin-producing ovarian tumor. Subsequent multimodality pancreatic imaging remained negative, requiring more invasive investigations. The tumor was localized by specialized arteriography using calcium stimulation to support the diagnosis of an insulinoma. However, repeated negative imaging led to further delays in definitive management, with worsening hypoglycemia. The surgery was finally performed three years after the initial presentation with successful removal of the tumor using intra-operative ultrasound. Clinical discussion It is important to emphasize that preoperative radiological imaging is useful to localize pancreatic lesions. However, most insulinomas could only be detected intraoperatively. The absence of suggestive radiological evidence should not deter surgeons from proceeding with definitive surgical intervention. Conclusion The case highlights the importance of a multidisciplinary approach in the management of a complicated case.
A 48-year-old female with long-standing type 2 diabetes mellitus presented with acute onset of bilateral lower limb weakness. She had been previously well and denied any constitutional symptoms. Physical examinations revealed generalized lower limb weakness with bilateral lower limb hypotonia, power of 0 over 5, reduced deep tendon reflexes, and loss of peripheral sensations up to the level of T10. Upper limb functions were normal. Rectal examination showed a lax anal tone and reduced anal grip. Blood investigations showed elevated serum alkaline phosphatase, corrected serum calcium, and parathyroid hormone. Magnetic resonance imaging of the spine revealed an expansile mass at the posterior element of the ninth thoracic vertebrae, causing spinal compression with possible impingement of the right T9 exiting spinal nerve. An urgent surgical decompression and tissue biopsy were performed for stabilization of the spine. Intraoperative findings included spinal cord compression secondary to an epidural tumour mass extending from T9 to T10 disc levels. Histopathological analysis showed a giant cell tumour of the spine. A 99mTc Sestamibi-SPECT parathyroid scintigraphy showed an ectopic parathyroid adenoma at the left suprasternal region. A diagnosis of Brown tumour secondary to ectopic parathyroid adenoma was made. She underwent an exploratory parathyroidectomy procedure with removal of the ectopic parathyroid gland, which resulted in a normalization of the serum calcium and parathyroid hormone. Unfortunately, her lower limb functions did not return to normal, and she remained paraplegic at 6 months postoperatively.
Introduction Obesity is strongly linked to the development of diabetic kidney disease. Very low carbohydrate diets (VLCBD) were associated with a reduction in weight but there is little evidence of its effects on diabetic kidney disease (DKD) patients. The aim of the randomized controlled trial study is to determine the metabolic effects of VLCBD in addition to low protein diet (LPD) in DKD patients. Materials and Methods 30 patients with type 2 diabetes aged 40-75 years and a HbA1c 7-10.5% were randomly allocated to receive VLCBD (<20g daily intake) versus standard low protein (0.8g/kg/day) diet. The patients received consultations every two weeks for 12 weeks. Metabolic profiles, glycemic control, inflammatory markers and visceral adipose tissue mass effects of the dietary interventions were compared. Result: The VLCBD group demonstrated significant reductions in weight (-4. 0 IQR 3.9 vs 0.2 IQR4.2 kg, p=<0. 001) and BMI (-1.5 IQR 1.18 vs 0. 074 IQR 1.54, p=<0. 001) in comparison to LPD group. There was reduction in waist circumference within both groups (- 4. 0 IQR 5.25, p= 0. 003 and -2. 0 IQR 3.6, p=0. 009) respectively. Estimated visceral adipose tissue mass and volume were significantly reduce in VLCBD group. There was significant reduction in ALT and GGT in both group. However, there is no significant changes in improvement in liver US in both groups. However, both group also showed significant reduction in HbA1c (-1.3 IQR 1.1% vs -0.7 IQR1.25%, respectively, p=NS). There is significant increment in LDL in VLCBD group which not present in LPD group. The VLCBD group showed a significant reduction in IL-6 levels with a contrasting rise within the LPD group (-1.53 IQR3.35 vs 0.46 IQR 1.95, p= 0. 028). Patients in VLCBD appeared to have improvement in physical activity score in comparison to LPD group. Conclusion After short term intensive VLCBD intervention in DKD patients, improvement were observed in metabolic markers, diabetes status and inflammatory markers with improvement of physical activity score. Presentation: No date and time listed
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