A 57-year-old man with symptoms of fatigue, joint pains and insomnia was found to have hypercalca... more A 57-year-old man with symptoms of fatigue, joint pains and insomnia was found to have hypercalcaemia secondary to hyperparathyroidism with a corrected calcium of 2.61 mmol/L (2.2-2.6 mmol/L) and a serum parathyroid hormone (PTH) of 86 pg/mL (10-65 pg/mL). Preoperative workup demonstrated a parathyroid adenoma in the right upper position and he proceeded to surgery. Postoperatively, however, his symptoms remained unchanged and the corrected calcium remained elevated at 2.87 mmol/L with a PTH of 59 pg/mL. He had no family history of hypercalcaemia. Further investigations revealed low 24 h urinary calcium level and a low urine calcium to creatinine ratio. Genetic testing revealed a mutation in exon 4 of the calcium sensing receptor (CaSR) confirming a diagnosis of familial hypocalciuric hyercalcaemia (FHH). The case is an example of a rare phenomenon when a parathyroid adenoma develops in patients with FHH.
Type 1 diabetes mellitus (TIDM) classically presents with symptomatic hyperglycemia and many pati... more Type 1 diabetes mellitus (TIDM) classically presents with symptomatic hyperglycemia and many patients develop diabetic ketoacidosis prior to their diagnosis. However, non-classical presentation or co-presentation with associated diseases may delay diagnosis or lead to challenges in acute, clinical management. An 18-yr-old girl presented to hospital with severe, symptomatic hypoglycemia. Clinical history and serum electrolyte concentrations suggested a diagnosis of adrenal insufficiency. She remained hypoglycemic until glucocorticoid replacement was commenced, at which point she developed persistent hyperglycemia requiring insulin therapy. Subsequent follow up confirmed the diagnosis of Addison's disease (AD), the treatment of which unmasked co-existing type 1 diabetes. Autoimmune diseases often cluster together in affected patients and first-degree relatives. Approximately 1 in 200 patients with T1DM develop AD. However, months or more commonly years usually elapse between the presentation of different autoimmune conditions. The co-diagnosis T1DM and AD in the acute setting is rare. Moreover, the first presentation of T1DM with severe hypoglycemia is even more exceptional. This case highlights the need for vigilance during the acute, emergency management of patients with autoimmune conditions and, in particular, to consider the possibility of concurrent antibody-mediated diseases which may need to be addressed during resuscitation.
An increase in serum osteoprotegerin (OPG) is associated with type 2 diabetes mellitus, the sever... more An increase in serum osteoprotegerin (OPG) is associated with type 2 diabetes mellitus, the severity of vascular calcification, and coronary artery disease. Obesity is a risk factor for diabetes and cardiovascular disease, but little is known about the relationship between OPG and obesity. The purpose of this study was to determine if changes in body mass index (BMI) and insulin sensitivity influence circulating OPG in healthy subjects. A total of 100 subjects (36 lean, 41 overweight, and 23 obese) with normal glucose tolerance, blood pressure, and electrocardiogram stress test result volunteered for this study. Insulin sensitivity was estimated using a 2-hour oral glucose tolerance test with oral glucose insulin sensitivity analysis. Osteoprotegerin, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL),soluble receptor activator of nuclear factor-κβ ligand (sRANKL), and adiponectin were analyzed using commercially available enzyme-linked immunosorbent assays. Osteoprotegerin (P < .01) and adiponectin (P < .001) were significantly decreased in the obese compared with lean subjects. There was no significant difference between BMI categories for TRAIL or sRANKL. Controlling for age and sex, there was a significant correlation between OPG and adiponectin (r = 0.391, P < .001), BMI (r = -0.331, P < .001), waist circumference (r = -0.268, P < .01), homeostasis model assessment of insulin resistance (r = -0.222, P < .05), and oral glucose insulin sensitivity (r = 0.221, P < .05). Both OPG and adiponectin were negatively correlated with body weight, BMI, waist circumference, and fasting plasma insulin while being positively correlated with insulin sensitivity (P < .05). Controlling for age, sex, and BMI, TRAIL was positively related to fat mass (r = 0.373, P < .001) and waist circumference (r = 0.257, P < .05). In contrast to patients with type 2 diabetes mellitus, circulating OPG is lower in…
Insulin resistance (IR) is associated with low adiponectin and elevated high sensitivity C-reacti... more Insulin resistance (IR) is associated with low adiponectin and elevated high sensitivity C-reactive protein (hsCRP). Osteoprotegerin (OPG) has been shown to be elevated in type 2 diabetes, but whether it reflects underlying IR is unclear. We aimed to compare the ability of serum OPG with adiponectin and hsCRP to act as a marker for IR in individuals with normal and abnormal glucose tolerance. 115 men underwent a 75 g oral glucose tolerance test. OPG, hsCRP and adiponectin were measured using ELISA. IR was assessed using the homeostasis model assessment of insulin resistance (HOMA-IR). Men with abnormal glucose tolerance (n=38) were older (58.3±11.2 vs 47.3±11.4 years, P<.001), had higher body mass index (BMI) (31.1±2.9 vs 27.9±3.2 kg/m(2), P<.001) and were more insulin resistant (median (I.Q.) HOMA-IR 5.88 (3.38) vs 1.13 (1.14), P<.001) than those with normal glucose tolerance (n=77). After adjustment for age and BMI, OPG (6.28 (2.32) vs 5.16 (1.86) pmol/L, P<.001) and hsCRP (2.07 (5.47) vs 0.78 (1.05) mg/L, P<.001) were higher and adiponectin (3.02±1.17 vs 4.78±2.38 μg/mL, P<.001) was lower in those with AGT. After adjustment for age and BMI, adiponectin (r=-0.317, P<.001) and hsCRP (r=0.318, P<.001), but not OPG (r=0.126, P=.196) correlated with HOMA-IR. On multiple linear regression analysis, adiponectin and hsCRP but not OPG were independent predictors of HOMA-IR. OPG is higher in individuals with abnormal glucose tolerance,…
A 57-year-old man with symptoms of fatigue, joint pains and insomnia was found to have hypercalca... more A 57-year-old man with symptoms of fatigue, joint pains and insomnia was found to have hypercalcaemia secondary to hyperparathyroidism with a corrected calcium of 2.61 mmol/L (2.2-2.6 mmol/L) and a serum parathyroid hormone (PTH) of 86 pg/mL (10-65 pg/mL). Preoperative workup demonstrated a parathyroid adenoma in the right upper position and he proceeded to surgery. Postoperatively, however, his symptoms remained unchanged and the corrected calcium remained elevated at 2.87 mmol/L with a PTH of 59 pg/mL. He had no family history of hypercalcaemia. Further investigations revealed low 24 h urinary calcium level and a low urine calcium to creatinine ratio. Genetic testing revealed a mutation in exon 4 of the calcium sensing receptor (CaSR) confirming a diagnosis of familial hypocalciuric hyercalcaemia (FHH). The case is an example of a rare phenomenon when a parathyroid adenoma develops in patients with FHH.
Type 1 diabetes mellitus (TIDM) classically presents with symptomatic hyperglycemia and many pati... more Type 1 diabetes mellitus (TIDM) classically presents with symptomatic hyperglycemia and many patients develop diabetic ketoacidosis prior to their diagnosis. However, non-classical presentation or co-presentation with associated diseases may delay diagnosis or lead to challenges in acute, clinical management. An 18-yr-old girl presented to hospital with severe, symptomatic hypoglycemia. Clinical history and serum electrolyte concentrations suggested a diagnosis of adrenal insufficiency. She remained hypoglycemic until glucocorticoid replacement was commenced, at which point she developed persistent hyperglycemia requiring insulin therapy. Subsequent follow up confirmed the diagnosis of Addison's disease (AD), the treatment of which unmasked co-existing type 1 diabetes. Autoimmune diseases often cluster together in affected patients and first-degree relatives. Approximately 1 in 200 patients with T1DM develop AD. However, months or more commonly years usually elapse between the presentation of different autoimmune conditions. The co-diagnosis T1DM and AD in the acute setting is rare. Moreover, the first presentation of T1DM with severe hypoglycemia is even more exceptional. This case highlights the need for vigilance during the acute, emergency management of patients with autoimmune conditions and, in particular, to consider the possibility of concurrent antibody-mediated diseases which may need to be addressed during resuscitation.
An increase in serum osteoprotegerin (OPG) is associated with type 2 diabetes mellitus, the sever... more An increase in serum osteoprotegerin (OPG) is associated with type 2 diabetes mellitus, the severity of vascular calcification, and coronary artery disease. Obesity is a risk factor for diabetes and cardiovascular disease, but little is known about the relationship between OPG and obesity. The purpose of this study was to determine if changes in body mass index (BMI) and insulin sensitivity influence circulating OPG in healthy subjects. A total of 100 subjects (36 lean, 41 overweight, and 23 obese) with normal glucose tolerance, blood pressure, and electrocardiogram stress test result volunteered for this study. Insulin sensitivity was estimated using a 2-hour oral glucose tolerance test with oral glucose insulin sensitivity analysis. Osteoprotegerin, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL),soluble receptor activator of nuclear factor-κβ ligand (sRANKL), and adiponectin were analyzed using commercially available enzyme-linked immunosorbent assays. Osteoprotegerin (P < .01) and adiponectin (P < .001) were significantly decreased in the obese compared with lean subjects. There was no significant difference between BMI categories for TRAIL or sRANKL. Controlling for age and sex, there was a significant correlation between OPG and adiponectin (r = 0.391, P < .001), BMI (r = -0.331, P < .001), waist circumference (r = -0.268, P < .01), homeostasis model assessment of insulin resistance (r = -0.222, P < .05), and oral glucose insulin sensitivity (r = 0.221, P < .05). Both OPG and adiponectin were negatively correlated with body weight, BMI, waist circumference, and fasting plasma insulin while being positively correlated with insulin sensitivity (P < .05). Controlling for age, sex, and BMI, TRAIL was positively related to fat mass (r = 0.373, P < .001) and waist circumference (r = 0.257, P < .05). In contrast to patients with type 2 diabetes mellitus, circulating OPG is lower in…
Insulin resistance (IR) is associated with low adiponectin and elevated high sensitivity C-reacti... more Insulin resistance (IR) is associated with low adiponectin and elevated high sensitivity C-reactive protein (hsCRP). Osteoprotegerin (OPG) has been shown to be elevated in type 2 diabetes, but whether it reflects underlying IR is unclear. We aimed to compare the ability of serum OPG with adiponectin and hsCRP to act as a marker for IR in individuals with normal and abnormal glucose tolerance. 115 men underwent a 75 g oral glucose tolerance test. OPG, hsCRP and adiponectin were measured using ELISA. IR was assessed using the homeostasis model assessment of insulin resistance (HOMA-IR). Men with abnormal glucose tolerance (n=38) were older (58.3±11.2 vs 47.3±11.4 years, P<.001), had higher body mass index (BMI) (31.1±2.9 vs 27.9±3.2 kg/m(2), P<.001) and were more insulin resistant (median (I.Q.) HOMA-IR 5.88 (3.38) vs 1.13 (1.14), P<.001) than those with normal glucose tolerance (n=77). After adjustment for age and BMI, OPG (6.28 (2.32) vs 5.16 (1.86) pmol/L, P<.001) and hsCRP (2.07 (5.47) vs 0.78 (1.05) mg/L, P<.001) were higher and adiponectin (3.02±1.17 vs 4.78±2.38 μg/mL, P<.001) was lower in those with AGT. After adjustment for age and BMI, adiponectin (r=-0.317, P<.001) and hsCRP (r=0.318, P<.001), but not OPG (r=0.126, P=.196) correlated with HOMA-IR. On multiple linear regression analysis, adiponectin and hsCRP but not OPG were independent predictors of HOMA-IR. OPG is higher in individuals with abnormal glucose tolerance,…
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Papers by Diarmuid Smith