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.
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.
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.