Association between Sleep Disruption and Levels of Lipids in Caucasians with Type 2 Diabetes

Aim. To investigate the association between sleep quality and duration with lipid and glycaemic control in Caucasian subjects with type 2 diabetes. Methods. Sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI) in 114 type 2 diabetes (T2DM) subjects. Comparisons were made between subjects with different sleep quality and sleep duration. Hierarchical multiple regression analyses were used to determine contributors to metabolic parameters. Results. Subjects with poor sleep quality (PQ; PSQI ≥ 6) had higher systolic blood pressure, glycated haemoglobin, urine albumin : creatinine ratio (UAC), total cholesterol (TC), and triglycerides (TG) ( for all) compared to those with good sleep quality (GQ; PSQI ≤ 5). Long sleep duration (LSD) subjects had higher TC and short sleep duration (SSD) subjects had higher TG compared to those with medium sleep duration. Sleep duration and PSQI score were independent predictors of TC and low-density lipoprotein cholesterol (LDL), contributing to 14.0% and 6.1% of the total variance, respectively. Conclusions. In this Caucasian T2DM population, PQ is associated with adverse cardiovascular risk markers, and long and short sleep disruptions have an independent negative impact on lipids. Sleep assessment should be included as part of a diabetes clinic review

A case of pembrolizumab-induced severe DKA and hypothyroidism in a patient with metastatic melanoma

Immune checkpoint inhibitors (ICIs) have revolutionised cancer therapy and improved outcomes for patients with advanced disease. Pembrolizumab, a monoclonal antibody that acts as a programmed cell death 1 (PD-1(PDCD1)) inhibitor, has been approved for the treatment of advanced melanoma and other solid tumours. Immune-related adverse events (irAEs) including endocrinopathies have been well described with this and other PD-1 inhibitors. While hypothyroidism and hyperthyroidism, and less commonly hypophysitis, are the most common endocrinopathies occurring in patients treated with pembrolizumab, the incidence of type 1 diabetes mellitus (T1DM) was low in clinical trials. We report a case of pembrolizumab-induced primary hypothyroidism and T1DM presenting with severe diabetic ketoacidosis (DKA). A 52-year-old male patient was treated with pembrolizumab for metastatic melanoma. He presented to the emergency department with a 1-day history of nausea and vomiting 2 weeks after his seventh dose of pembrolizumab, having complained of polyuria and polydipsia for 2 months before presentation. He had been diagnosed with thyroid peroxidase (TPO) antibody-negative hypothyroidism, requiring thyroxine replacement, shortly after his fifth dose. Testing revealed a severe DKA (pH: 6.99, glucose: 38.6 mmol/L, capillary ketones: 4.9 and anion gap: 34.7). He was treated in the intensive care unit as per the institutional protocol, and subsequently transitioned to subcutaneous basal-bolus insulin. After his diabetes and thyroid stabilised, pembrolizumab was recommenced to treat his advanced melanoma given his excellent response. This case highlights the importance of blood glucose monitoring as an integral part of cancer treatment protocols composed of pembrolizumab and other ICIs

The importance of night-time systolic blood pressure in diabetic patients

Objective: Diabetic patients exhibit a higher cardiovascular risk compared to people without diabetes. The use of ambulatory blood pressure monitoring (ABPM) is gaining popularity in this population. Night-time SBP has consistently been shown to be a potent predictor of cardiovascular risk in the normal population. We studied the predictive value of night-time ABPM in a cohort of diabetic patients. Research design and methods: At baseline, when not on antihypertensive medication, 11 291 patients (5326 men, mean age 54.6 years) underwent ABPM. Using a computerized national registry of death, mortality outcome was ascertained. Among 859 diabetic patients with a mean follow-up of 5.3 years, there were 74 deaths. Results: Compared to people without diabetes, those with diabetes had daytime and night-time SBP of 146.4 vs. 145.1 (P = NS) and 131.2 vs. 126.4 mmHg (P < 0.0001), respectively. As a consequence, more diabetic patients had a non-dipping night-time SBP profile (47.4 vs. 35.5%; P = < 0.0001). In a Cox proportional-hazards model, night-time SBP was an independent predictor of cardiovascular mortality in diabetic patients after adjustment for sex, age, smoking history, previous cardiovascular events, BMI and daytime SBP. The resultant hazard ratio for a 10-mmHg increase in night-time SBP for total cardiovascular, stroke and cardiac mortality was 1.32 (1.12–1.69), 1.95 (1.18–3.20) and 1.24 (0.99–1.56), respectively. Conclusion: Night-time SBP is a significant predictor of cardiovascular mortality in patients with diabetes

Acute diabetic neuropathy following improved glycaemic control: a case series and review

We present three cases of acute diabetic neuropathy and highlight a potentially underappreciated link between tightening of glycaemic control and acute neuropathies in patients with diabetes. Case 1: A 56-year-old male with poorly controlled type 2 diabetes (T2DM) was commenced on basal-bolus insulin. He presented 6 weeks later with a diffuse painful sensory neuropathy and postural hypotension. He was diagnosed with treatment-induced neuropathy (TIN, insulin neuritis) and obtained symptomatic relief from pregabalin. Case 2: A 67-year-old male with T2DM and chronic hyperglycaemia presented with left lower limb pain, weakness and weight loss shortly after achieving target glycaemia with oral antihyperglycaemics. Neurological examination and neuro-electrophysiological studies suggested diabetic lumbosacral radiculo-plexus neuropathy (DLPRN, diabetic amyotrophy). Pain and weakness resolved over time. Case 3: A 58-year-old male was admitted with blurred vision diplopia and complete ptosis of the right eye, with intact pupillary reflexes, shortly after intensification of glucose-lowering treatment with an SGLT2 inhibitor as adjunct to metformin. He was diagnosed with a pupil-sparing third nerve palsy secondary to diabetic mononeuritis which improved over time. While all three acute neuropathies have been previously well described, all are rare and require a high index of clinical suspicion as they are essentially a diagnosis of exclusion. Interestingly, all three of our cases are linked by the development of acute neuropathy following a significant improvement in glycaemic control. This phenomenon is well described in TIN, but not previously highlighted in other acute neuropathies

Obesity and Insulin Resistance Are the Main Determinants of Postprandial Lipoprotein Dysmetabolism in Polycystic Ovary Syndrome

Postprandial dyslipidaemia may be a plausible mechanism by which polycystic ovary syndrome (PCOS) increases cardiovascular risk. We sought to investigate whether the postprandial glucose and insulin and lipid and lipoprotein responses, including that of apolipoprotein B-48 (apoB-48) containing chylomicrons, to a mixed meal are different in obese PCOS women when compared to obese control subjects and whether differences, if any, are related to obesity, insulin resistance (IR), hyperandrogenaemia, or PCOS status. 26 women with PCOS (age 30.4±1.2 years (mean ± SEM), body mass index (BMI) 36.8±1.5 kg/m2) and 26 non-PCOS subjects (age 34.1±0.9 years, BMI 31.5±1.0 kg/m2) were studied before and up to 8 hours following a standard mixed meal. AUC-triglyceride (AUC-TG) was higher and AUC-high-density lipoprotein (AUC-HDL) lower in PCOS women. These differences were not apparent when BMI was accounted for. Insulin sensitivity (SI), AUC-apoB-48, and AUC-apolipoprotein B (AUC-apoB) were found to be independent predictors of AUC-TG, accounting for 55% of the variance. Only AUC-insulin remained significantly elevated following adjustment for BMI. Obesity related IR explains postprandial hypertriglyceridaemia and hyperinsulinaemic responses. Management of obesity in premenopausal women with PCOS is likely to reduce their cardiovascular risk burden

Association between Sleep Disruption and Levels of Lipids in Caucasians with Type 2 Diabetes

Aim. To investigate the association between sleep quality and duration with lipid and glycaemic control in Caucasian subjects with type 2 diabetes. Methods. Sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI) in 114 type 2 diabetes (T2DM) subjects. Comparisons were made between subjects with different sleep quality and sleep duration. Hierarchical multiple regression analyses were used to determine contributors to metabolic parameters. Results. Subjects with poor sleep quality (PQ; PSQI ≥ 6) had higher systolic blood pressure, glycated haemoglobin, urine albumin : creatinine ratio (UAC), total cholesterol (TC), and triglycerides (TG) ( &lt; 0.05 for all) compared to those with good sleep quality (GQ; PSQI ≤ 5). Long sleep duration (LSD) subjects had higher TC and short sleep duration (SSD) subjects had higher TG compared to those with medium sleep duration. Sleep duration and PSQI score were independent predictors of TC and low-density lipoprotein cholesterol (LDL), contributing to 14.0% and 6.1% of the total variance, respectively. Conclusions. In this Caucasian T2DM population, PQ is associated with adverse cardiovascular risk markers, and long and short sleep disruptions have an independent negative impact on lipids. Sleep assessment should be included as part of a diabetes clinic review

A case of pembrolizumab-induced severe DKA and hypothyroidism in a patient with metastatic melanoma.

Immune checkpoint inhibitors (ICIs) have revolutionised cancer therapy and improved outcomes for patients with advanced disease. Pembrolizumab, a monoclonal antibody that acts as a programmed cell death 1 (PD-1(PDCD1)) inhibitor, has been approved for the treatment of advanced melanoma and other solid tumours. Immune-related adverse events (irAEs) including endocrinopathies have been well described with this and other PD-1 inhibitors. While hypothyroidism and hyperthyroidism, and less commonly hypophysitis, are the most common endocrinopathies occurring in patients treated with pembrolizumab, the incidence of type 1 diabetes mellitus (T1DM) was low in clinical trials. We report a case of pembrolizumab-induced primary hypothyroidism and T1DM presenting with severe diabetic ketoacidosis (DKA). A 52-year-old male patient was treated with pembrolizumab for metastatic melanoma. He presented to the emergency department with a 1-day history of nausea and vomiting 2 weeks after his seventh dose of pembrolizumab, having complained of polyuria and polydipsia for 2 months before presentation. He had been diagnosed with thyroid peroxidase (TPO) antibody-negative hypothyroidism, requiring thyroxine replacement, shortly after his fifth dose. Testing revealed a severe DKA (pH: 6.99, glucose: 38.6 mmol/L, capillary ketones: 4.9 and anion gap: 34.7). He was treated in the intensive care unit as per the institutional protocol, and subsequently transitioned to subcutaneous basal-bolus insulin. After his diabetes and thyroid stabilised, pembrolizumab was recommenced to treat his advanced melanoma given his excellent response. This case highlights the importance of blood glucose monitoring as an integral part of cancer treatment protocols composed of pembrolizumab and other ICIs. Learning points: The incidence of T1DM with pembrolizumab treatment is being increasingly recognised and reported, and DKA is a common initial presentation. Physicians should counsel patients about this potential irAE and educate them about the symptoms of hyperglycaemia and DKA. The ESMO guidelines recommend regular monitoring of blood glucose in patients treated with ICIs, a recommendation needs to be incorporated into cancer treatment protocols for pembrolizumab and other ICIs in order to detect hyperglycaemia early and prevent DKA.</p

Marked hyperandrogenicity in a 60-year-old woman

Markedly elevated androgen levels can lead to clinical virilization in females. Clinical features of virilization in a female patient, in association with biochemical hyperandrogenism, should prompt a search for an androgen-producing tumor, especially of ovarian or adrenal origin. We herein report the case of a 60-year-old woman of Pakistani origin who presented with the incidental finding of male pattern baldness and hirsutism. Her serum testosterone level was markedly elevated at 21 nmol/L (normal range: 0.4–1.7 nmol/L), while her DHEAS level was normal, indicating a likely ovarian source of her elevated testosterone. Subsequently, a CT abdomen-pelvis was performed, which revealed a bulky right ovary, confirmed on MRI of the pelvis as an enlarged right ovary, measuring 2.9 × 2.2 cm transaxially. A laparoscopic bilateral salpingo-oophorectomy was performed, and histopathological examination and immunohistochemistry confirmed the diagnosis of a Leydig cell tumor, a rare tumor accounting for 0.1% of ovarian tumors. Surgical resection led to normalization of testosterone levels