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  1. Awang MH, Hatta SFWM, Mohamad AF, Ghani RA
    J Med Case Rep, 2023 Mar 02;17(1):73.
    PMID: 36859300 DOI: 10.1186/s13256-023-03764-w
    BACKGROUND: Denosumab is known to cause abnormalities in calcium homeostasis. Most of such cases have been described in patients with underlying chronic kidney disease or severe vitamin D deficiency. Previous bariatric surgery could also contribute to hypocalcemia and deterioration in bone health.

    CASE PRESENTATION: We present a case of a 61-year-old Malay female with worsening bilateral limb weakness, paresthesia, and severe carpopedal spasm a week after receiving subcutaneous denosumab for osteoporosis. She had a history of gastric bypass surgery 20 years ago. Post gastric bypass surgery, she was advised and initiated on lifelong calcium, vitamin D, and iron supplementations that she unfortunately stopped taking 5 years after surgery. Her last serum blood tests, prior to initiation on denosumab, were conducted in a different center, and she was told that she had a low calcium level; hence, she was advised to restart her vitamin and mineral supplements. Laboratory workup revealed severe hypocalcemia (adjusted serum calcium of 1.33 mmol/L) and mild hypophosphatemia (0.65 mmol/L), with normal magnesium and renal function. Electrocardiogram showed a prolonged QTc interval. She required four bolus courses of intravenous calcium gluconate, and three courses of continuous infusions due to retractable severe hypocalcemia (total of 29 vials of 10 mL of 10% calcium gluconate intravenously). In view of her low vitamin D level of 33 nmol/L, she was initiated on a loading dose of cholecalciferol of 50,000 IU per week for 8 weeks. However, despite a loading dose of cholecalciferol, multiple bolus courses, and infusions of calcium gluconate, her serum calcium hovered around only 1.8 mmol/L. After 8 days of continuous intravenous infusions of calcium gluconate, high doses of calcitriol 1.5 μg twice daily, and 1 g calcium carbonate three times daily, her serum calcium stabilized at approximately 2.0 mmol/L. She remained on these high doses for over 2 months, before they were gradually titrated down to ensure sustainability of a safe calcium level.

    CONCLUSION: This case report highlights the importance of screening for risk factors for iatrogenic hypocalcemia and ensuring normal levels before initiating denosumab. The patient history of bariatric surgery could have worsened the hypocalcemia, resulting in a more severe presentation and protracted response to oral calcium and vitamin D supplementation.

  2. Ghani RA, Shyam S, Arshad F, Wahab NA, Chinna K, Safii NS, et al.
    Nutr Diabetes, 2014;4:e107.
    PMID: 24535618 DOI: 10.1038/nutd.2014.5
    Post-gestational diabetes mellitus (GDM) women are recommended weight loss to manage increased cardio-metabolic risks. We investigated the effects of lowering diet glycaemic index (GI) on fasting blood glucose (FBG), serum lipids, body weight and composition of post-GDM women with varying fasting insulin levels (INS). Seventy-seven Asian, non-diabetic women with previous GDM (aged 20-40 years, mean BMI: 26.4±4.6 kg m(-2)) were recruited. At baseline, 20 subjects with INS <2 μIU ml(-1) and 18 with INS 2 μIU ml(-1) received conventional dietary recommendations (CHDR) only. CHDR emphasised energy and fat intake restriction and encouraged increase in dietary fibre intakes. Twenty-four subjects with INS <2 μIU ml(-1) and 15 with INS 2 μIU ml(-1), in addition to CHDR, received low-GI education (LGI). Changes in FBG, serum lipids, body weight and body composition were evaluated. Subjects with INS <2 μIU ml(-1) had similar outcomes with both diets. After 1 year, subjects with INS 2 μIU ml(-1) who received LGI education had reductions in FBG and triglycerides. Subjects who received CHDR observed increase in both FBG and triglycerides (P<0.05). Among all subjects, diet GI was lower and dietary fibre intakes were higher in LGI compared with CHDR subjects (all P<0.05). Thus, in Asian post-GDM women with normal/higher INS, adding low-GI education to CHDR improved management of FBG and triglycerides.
  3. Zulkifli KK, Mohamed Shah FZ, Ismail AI, Abdul Rahman TH, Ghani RA
    Chron Respir Dis, 2021;18:14799731211056348.
    PMID: 34797178 DOI: 10.1177/14799731211056348
    OBJECTIVES: Dysglycemia is known to be a common comorbidity of chronic obstructive pulmonary disease (COPD). However, undiagnosed dysglycemia and the associated factors remain under-reported. This study aimed to determine the prevalence and the associated factors of dysglycemia among COPD patients.

    METHODS: This was a cross-sectional, single-center study involving adults with established COPD (n = 186) divided into those with or without hospital admissions for acute exacerbation. Oral glucose tolerance test (OGTT) was performed in patients with no known history of dysglycemia.

    RESULTS: There were 16 patients who had overt diabetes, and 32 had prediabetes following the OGTT. Forty percent had histories of hospital admissions for COPD exacerbations. Both groups demonstrated similar 2-h post prandial glucose, glycated hemoglobin (HbA1c) and fasting blood glucose. The incidences of newly diagnosed dysglycemia were higher in both groups (40.8% vs 34.6%, p = 0.57). Cumulative days of admission (≥6 days/year) and weight (≥65 kg) were identified as predictors for dysglycemia within the study population.

    DISCUSSION: This study demonstrated a high number of overt and newly diagnosed dysglycemia among COPD patients who had no previous history of abnormal glucose. Recent acute exacerbations of COPD could have a negative impact on glycemia, although the results did not attain statistical significance. However, there is a need for adequate screening for dysglycemia, particularly among those with frequent acute exacerbations of their condition.

  4. Ghani RA, Bin Yaakob I, Wahab NA, Zainudin S, Mustafa N, Sukor N, et al.
    J Clin Lipidol, 2013 Sep-Oct;7(5):446-53.
    PMID: 24079286 DOI: 10.1016/j.jacl.2013.04.004
    BACKGROUND: Type 2 diabetes is associated with early development of endothelial dysfunction. Patients present with typical dyslipidemia (predominantly high levels of triglycerides [TG] and low levels of high-density lipoprotein cholesterol [HDL-C]) or mixed hypercholesterolemia (high levels of low-density lipoprotein cholesterol [LDL-C] and TG with low HDL-C). Normal levels include LDL-C < 100 mg/dL, TG < 135 mg/dL, and HDL-C > 40 mg/dL for men and >50 mg/dL for women.
    OBJECTIVE: To determine the effects of 8 weeks' administration of fenofibrate on inflammatory markers, metabolic parameters, and endothelial dysfunction.
    METHODS: We administered micronized fenofibrate (Laboratories Fourneir S.A Dijon, France) daily for 8 weeks to 40 dyslipidemic, type 2 diabetes patients with equal numbers in each arm of the typical or mixed dyslipidemia groups. Noninvasive endothelial function assessments were performed and serum inflammatory markers obtained before and after treatment.
    RESULTS: The typical group demonstrated significantly greater TG reduction and HDL-C increment, ie, 56% vs, 21.3% (P < .005) and 21% vs. 7.6% (P = .001), respectively, compared with the mixed group. There was greater LDL-C reduction within the mixed group compared with the typical group 21.0% vs. 2.2% (P < .05). Endothelial dysfunction was present in both groups at baseline. After treatment, the typical group demonstrated significant improvement in resting brachial diameter (3.9 mm [interquartile range {IQR} 3.3-4.7] to 4.2 mm [IQR 3.4-4.8], P = .001) compared with no change within the mixed group (3.6 mm [IQR 3.1-5.4] to 3.7 mm [IQR 3.1-5.3], P = .26). Flow-mediated diameter improved significantly in both groups. The mixed group had significantly greater levels of hs-CRP at baseline but no changes throughout the study. The mixed group demonstrated an increase in vascular adhesion molecule-1 from 706 ng/mL (IQR 566-1195) to 845 ng/mL (637-1653; P = .01), a reduction of tumor necrosis factor-α from 7.0 pg/mL (IQR 1.0-43.5) to 2.5 pg/mL (IQR 1.5-13.5; P = .04) throughout the study.
    CONCLUSIONS: We effectively compared 8 weeks of fenofibrate therapy in type 2 diabetics with contrasting lipid abnormalities. The typical dyslipidemia group showed significantly greater lipid improvements compared with the mixed dyslipidemia group. Both groups had improvements in endothelial functions that were independent of the lipid levels. We concluded that fibrate therapy in type 2 diabetics is beneficial, especially those with typical dyslipidemia and extends beyond its lipid lowering properties.
    KEYWORDS: Endothelial dysfunction; Fenofibrate; High-density lipoprotein cholesterol; Low density lipoprotein; Noninvasive endothelial function assessments; Triglyceride; Vascular cell adhesion molecule-1; hsCRP
  5. Ghani RA, Zainudin S, Ctkong N, Rahman AF, Wafa SR, Mohamad M, et al.
    Nephrology (Carlton), 2006 Oct;11(5):386-93.
    PMID: 17014550
    Sepsis is characterized by an uncontrolled release of pro-inflammatory and anti-inflammatory mediators leading to immunoparalysis, cellular and humoral dysfunction, multiorgan dysfunction and death. This study evaluated the efficacy of high-volume haemofiltration (HVHF) compared with continuous venovenous haemofiltration (CVVH) in removing these inflammatory mediators. Clinical responses were assessed with the sequential organ failure assessment (SOFA) score.
  6. Ahmed IA, Mikail MA, Bin Ibrahim M, Bin Hazali N, Rasad MS, Ghani RA, et al.
    Food Chem, 2015 Apr 1;172:778-87.
    PMID: 25442620 DOI: 10.1016/j.foodchem.2014.09.122
    Baccaurea angulata is an underutilised tropical fruit of Borneo Island of Malaysia. The effect of solvents was examined on yield, total phenolic (TPC), total flavonoids (TFC), total carotene content (TCC), free radical scavenging activities and lipid peroxidation inhibition activities. The results indicated that the pulp (edible portion) had the highest yield, while methanol extracts were significantly (p < 0.01) found to contain higher TPC, TFC and TCC than phosphate buffered saline (PBS) extracts for all the fruits parts. The methanol extracts also showed remarkable antiradical activity and significant lipid peroxidation inhibition activities, with their IC50 results highly comparable to that of commercial blueberry. The variations in the results among the extracts suggest different interactions, such as negative or antagonistic (interference), additive and synergistic effect interactions. The study indicated that B. angulata like other underutilised tropical fruits contained remarkable primary antioxidants. Thus, the fruit has the potential to be sources of antioxidant components.
  7. Omar N, Koshy M, Hanafiah M, Hatta SFWM, Shah FZM, Johari B, et al.
    J Res Med Sci, 2020;25:64.
    PMID: 33088301 DOI: 10.4103/jrms.JRMS_560_17
    Background: Nonalcoholic fatty liver disease (NAFLD) has become one of the major diseases plaguing worldwide. Several studies reported its association with ischemic heart disease (IHD). This study aims to determine the relationships between severity of steatosis with glycemic control and carotid intima-media thickness (CIMT) among a high-risk population of type 2 diabetes mellitus (T2DM) with proven IHD.

    Materials and Methods: This was a cross-sectional study involving patients aged between 18 and 65 years diagnosed with T2DM with IHD (n = 150). Ultrasonography of the abdomen to determine NAFLD severity category and CIMT measurements was performed by two independent radiologists. NAFLD was graded according to the severity of steatosis (NAFLD-3, NAFLD-2, NAFLD-1, and NAFLD-0). Comparison between different stages of NAFLD (NAFLD-3, NAFLD-2, NAFLD-1, and NAFLD-0) was analyzed using Chi-square and analysis of variance tests for categorical and continuous variables, respectively.

    Results: The prevalence of NAFLD was 71% (n = 107). NAFLD-1 was detected in 39% of the patients, 32% had NAFLD-2, no patients with NAFLD-3, and 29% had non-NAFLD. There were no patients with NAFLD-2 having higher systolic and diastolic blood pressure, weight, body mass index, waist circumference, total cholesterol, triglycerides, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol. Glycated hemoglobin (HbA1c) concentration was highest within the NAFLD-2. NAFLD-2 showed higher mean CIMT. Every 1% rise in HbA1c for patients with NAFLD significantly increases the CIMT by 0.03 mm (95% CI: 0.009, 0.052, P = 0.006).

    Conclusion: These findings suggest additional atherosclerotic risks within the NAFLD-2 group with significantly higher HbA1c and CIMT compared to the NAFLD-1 and NAFLD-0 groups. It is, therefore, vital to incorporate stricter glycemic control among patients with T2DM and IHD with moderate NAFLD as part of atherosclerotic risk management strategy.

  8. Lim LL, Hussein Z, Noor NM, Raof ASA, Mustafa N, Bidin MBL, et al.
    PLoS One, 2024;19(1):e0296298.
    PMID: 38166049 DOI: 10.1371/journal.pone.0296298
    AIM: Given a lack of data on diabetes care performance in Malaysia, we conducted a cross-sectional study to understand the clinical characteristics, control of cardiometabolic risk factors, and patterns of use of guideline-directed medical therapy (GDMT) among patients with type 2 diabetes (T2D), who were managed at publicly-funded hospitals between December 2021 and June 2022.

    METHODS: Patients aged ≥18 years with T2D from eight publicly-funded hospitals in the Greater Kuala Lumpur region, who had ≥2 outpatient visits within the preceding year and irrespective of treatment regimen, were eligible. The primary outcome was ≥2 treatment target attainment (defined as either HbA1c <7.0%, blood pressure [BP] <130/80 mmHg, or low-density lipoprotein cholesterol [LDL-C] <1.8 mmol/L). The secondary outcomes were the individual treatment target, a combination of all three treatment targets, and patterns of GDMT use. To assess for potential heterogeneity of study findings, all outcomes were stratified according to prespecified baseline characteristics namely 1) history of atherosclerotic cardiovascular disease (ASCVD; yes/no) and 2) clinic type (Diabetes specialist versus General medicine).

    RESULTS: Among 5094 patients (mean±SD age 59.0±13.2 years; T2D duration 14.8±9.2 years; HbA1c 8.2±1.9% (66±21 mmol/mol); BMI 29.6±6.2 kg/m2; 45.6% men), 99% were at high/very high cardiorenal risk. Attainment of ≥2 treatment targets was at 18%, being higher in General medicine than in Diabetes specialist clinics (20.8% versus 17.5%; p = 0.039). The overall statin coverage was 90%. More patients with prior ASCVD attained LDL-C <1.4 mmol/L than those without (13.5% versus 8.4%; p<0.001). Use of sodium-glucose cotransporter-2 (SGLT2) inhibitors (13.2% versus 43.2%), glucagon-like peptide-1 receptor agonists (GLP1-RAs) (1.0% versus 6.2%), and insulin (27.7% versus 58.1%) were lower in General medicine than in Diabetes specialist clinics.

    CONCLUSIONS: Among high-risk patients with T2D, treatment target attainment and use of GDMT were suboptimal.

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