Sex Differences in Response to Treatment with Glucagon-like Peptide 1 Receptor Agonists: Opportunities for a Tailored Approach to Diabetes and Obesity Care.

The available data suggest differences in the course of type 2 diabetes mellitus (T2DM) between men and women, influenced by the distinguishing features of the sex. Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) are a relatively new class of antidiabetic drugs that act by mimicking the function of endogenous glucagon-like peptide 1. They constitute valuable agents for the management of T2DM as, in addition to exerting a strong hypoglycemic action, they present cardiorenal protective properties, promote weight loss, and have a good safety profile, particularly with respect to the risk of hypoglycemia. Due to the precedent of studies having identified sexual dimorphic elements regarding the action of other antidiabetic agents, ongoing research has attempted to examine whether this is also the case for GLP-1 RAs. Until now, sex differences have been observed in the impact of GLP1-RAs on glycemic control, weight reduction, and frequency of adverse events. On the contrary, the question of whether these drugs differentially affect the two sexes with respect to cardiovascular risk and incidence of major adverse cardiovascular events remains under investigation. Knowledge of the potential sex-specific effects of these medications is extremely useful for the implementation of individualized therapeutic plans in the treatment of T2DM. This narrative review aims to present the available data regarding the sex-specific action of GLP-1 RAs as well as to discuss the potential pathophysiologic mechanisms explaining these dissimilarities.

The effect of vitamin D supplementation on glycemic status of elderly people with prediabetes: a 12-month open-label, randomized-controlled study.

BACKGROUND: Data on the efficacy of vitamin D in improving the glycemic status of elderly people with prediabetes are scarce. This open-label, randomized-controlled trial investigated the effect of vitamin D supplementation on glycemic markers of Greek people with prediabetes aged 60 years or above, over 12 months. RESEARCH DESIGN AND METHODS: Participants were randomized to a weekly vitamin D3 dose of 25,000 IU (n = 45) or nothing (n = 45), on top of lifestyle measures. Anthropometric and glycemic markers were assessed at baseline, 3, 6, and 12 months. RESULTS: Supplemented participants demonstrated a significant increase in 25(OH)D concentrations at 3,      6,      and 12 months     compared to baseline    . In the intervention group, fasting glucose was decreased at 6 months compared to baseline (96.12 ± 5.51 vs 103.40 ± 12.05 mg/dl, p < 0.01) and glycated hemoglobin was significantly lower at 6 and 12 months compared to baseline [5.82 ± 0.21% vs 5.87 ± 0.21%, p = 0.004 and 5.80 ± 0.23% vs 5.87 ± 0.21%, p < 0.001, respectively]. CONCLUSIONS: Vitamin D could be complementary to lifestyle change strategy for the management of prediabetes in the elderly. CLINICAL TRIAL REGISTRATION: ISRCTN51643592.

Clinical and Genetic Predictors of Glycemic Control and Weight Loss Response to Liraglutide in Patients with Type 2 Diabetes.

Background: Evidence suggests a heterogeneous response to therapy with glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in patients with type 2 diabetes mellitus (T2DM). The aim of this study is to identify the genetic and clinical factors that relate to glycemic control and weight loss response to liraglutide among patients with T2DM. Methods: The medical records of 116 adults with T2DM (51% female, mean body mass index 35.4 ± 6.4 kg/m2), who had been on treatment with liraglutide for at least 6 months and were genotyped for CTRB1/2 rs7202877 (T > G) polymorphism, were evaluated. Clinical and laboratory parameters were measured at baseline, 3, and 6 months after initiating liraglutide treatment. The good glycemic response was defined as one of the following: (i) achievement of glycated hemoglobin (HbA1c) < 7% (ii) reduction of the baseline HbA1c by ≥1%, and (iii) maintenance of HbA1c < 7% that a patient already had before switching to liraglutide. Weight loss responders were defined as subjects who lost ≥3% of their baseline weight. Results: Minor allele frequency was 16%. Individuals were classified as glycemic control and weight loss responders (81 (70%) and 77 (66%), respectively). Carriers of the rs7202877 polymorphic allele had similar responses to liraglutide treatment in terms of glycemic control (odds ratio (OR): 1.25, 95% confidence interval (CI): 0.4, 3.8, p = 0.69) and weight loss (OR: 1.12, 95% CI: 0.4, 3.2, p = 0.84). In the multivariable analysis, higher baseline HbA1c (adjusted OR: 1.45, 95% CI: 1.05, 2.1, p = 0.04) and lower baseline weight (adjusted OR: 0.97, 95% CI: 0.94, 0.99, p = 0.01) were associated with better glycemic response to liraglutide, while higher baseline weight was associated with worse weight response (adjusted OR: 0.97, 95% CI: 0.95, 0.99, p = 0.02). Conclusions: Specific patient features can predict glycemic and weight loss response to liraglutide in individuals with T2DM.

Vitamin D Alleviates Anxiety and Depression in Elderly People with Prediabetes: A Randomized Controlled Study.

Older people are prone to frailness, present poor adherence to pharmacotherapy, and often have adverse drug effects. Therefore, it is important to develop effective and safe interventions to mitigate the burden of anxiety and depression disorders in this population. The aim of this study was to investigate the effect of vitamin D supplementation on the anxiety and depression status of elderly people with prediabetes. Participants were randomly assigned a weekly dose of vitamin D3 of 25,000 IU (n = 45, mean age 73.10 ± 7.16 years) or nothing (n = 45, mean age 74.03 ± 7.64 years), in addition to suggested lifestyle measures. The State-Trait Anxiety Inventory subscales (STAI-T and STAI-S) and the Patient Health Questionnaire-9 (PHQ-9) were used to evaluate anxiety and depression levels, respectively, at baseline, 6, and 12 months. A total of 92.68% of the participants in the vitamin D group and 97.14% of the controls exhibited vitamin D deficiency (<20 ng/mL) at baseline. Mean STAI-T scores were lower in supplemented individuals than in the control group at 6 (38.02 ± 9.03 vs. 43.91 ± 7.18, p = 0.003) and 12 months (32.35 ± 7.77 vs. 44.97 ± 7.78, p < 0.001). The same pattern was evident for STAI-S scores at 6 (37.11 ± 7.88 vs. 43.20 ± 9.33, p = 0.003) and 12 months (32.59 ± 6.45 vs. 44.60 ± 9.53, p < 0.001). Supplemented participants demonstrated lower mean PHQ-9 scores compared to controls at 6 (15.69 ± 6.15 vs. 19.77 ± 8.96, p = 0.021) and 12 months (13.52 ± 5.01 vs. 20.20 ± 8.67, p < 0.001). Participants with deficiency and insufficiency at baseline experienced equal benefits of supplementation in terms of anxiety and depression scores. In conclusion, in a high-risk population, a weekly vitamin D supplementation scheme was effective in alleviating anxiety and depression symptoms. More studies are needed to elucidate the relevant mechanisms.

Type 2 diabetes management in people aged over seventy-five years: targets and treatment strategies.

Older people (those aged 65 years or more) with diabetes comprise a heterogenous group of patients with special needs and features; this is particularly true for those aged 75 years or more. It is important that individualized glycemic targets be adopted in this population, after considering life expectancy, presence of diabetic complications and other comorbidities. In general, less rigorous targets and avoidance of overtreatment seems to be a reasonable strategy in daily clinical settings. There is a paucity of data regarding the efficacy and safety of various hypoglycemic agents, especially for those aged over 75. The evidence suggests that sulfonylureas and insulin regimens should be used with caution due to a high risk of hypoglycemia. Dipeptidyl peptidase-4 inhibitors are a good choice for the management of diabetes in older age groups, although a warning against the use of specific agents in people with heart failure is valid. There are insufficient data to decide whether the cardiorenal protective properties of sodium-glucose co-transporter 2 inhibitors outweigh the risks associated with these drugs. The use of glucagon-like peptide-1 receptor agonists by older patients is supported not only by their good safety and efficacy profiles, but also by their potential to improve glucose-independent outcomes, through their pleiotropic actions. The aim of this narrative review is to summarize the evidence on glycemic targets and optimal therapeutic approaches for older patients with type 2 diabetes and discuss the risk-benefit balance of various therapeutic approaches in this group.

Metformin: Is it Still the First Line in Type 2 Diabetes Management Algorithm?

Type 2 diabetes mellitus (T2DM) has an ever-growing prevalence worldwide, affecting 1 in 11 adults. It continues to significantly impact patients in terms of morbidity and mortality, in addition to impairing quality of life while adding to the spiralling healthcare costs. Metformin was first used over half a century ago, and for the past two decades, it has been considered first-line oral therapy to treat patients with T2DM, in whom lifestyle measures failed to improve glycaemic control. Early landmark studies supported a glycaemic benefit with metformin use with a relatively safe adverse effect profile, particularly with avoidance of hypoglycaemia. Moreover, studies have indicated other potential beneficial role for metformin on organs typically affected by diabetes complications. However, more recently, with the discovery of newer hypoglycaemic agents and the wealth of data provided by large-scale cardiovascular safety studies, algorithms for the treatment of patients with T2DM have become increasingly complex. Indeed, recent guidelines challenge current thinking and advocate the use of agents other than metformin as first-line agents in those with higher cardiovascular risk, potentially unseating metformin from its long-held throne. This narrative review aims to summarize the background and origins of metformin, assess its role in the current management of patients with T2DM, highlighting the clinical efficacy and safety profile of this agent. Also, the position of metformin in the clinical algorithms is discussed in light of the most recent evidence in the field, helping with an ever-increasing shift towards individualized patient care to maximize benefits and minimize risks.

The role of vitamin D in the pathogenesis and treatment of diabetes mellitus: a narrative review.

Diabetes mellitus, a metabolic disorder associated with chronic complications, is traditionally classified into two main subtypes. Type 1 diabetes mellitus (T1DM) results from gradual pancreatic islet ß cell autoimmune destruction, extending over months or years. Type 2 diabetes mellitus (T2DM) is a heterogeneous disorder, with both insulin resistance and impairment in insulin secretion contributing to its pathogenesis. Vitamin D is a fat-soluble vitamin with an established role in calcium metabolism. Recently, several studies have provided evidence suggesting a role for it in various non-skeletal metabolic conditions, including both types of diabetes mellitus. Preclinical studies of vitamin D action on insulin secretion, insulin action, inflammatory processes, and immune regulation, along with evidence of an increase of hypovitaminosis D worldwide, have prompted several epidemiological, observational, and supplementation clinical studies investigating a potential biological interaction between hypovitaminosis D and diabetes. This narrative review aims to summarize current knowledge on the effect of vitamin D on T1DM and T2DM pathogenesis, prevention, and treatment, as well as on micro- and macrovascular complications of the disease. Furthermore, on the basis of current existing evidence, we aim to highlight areas for potential future research.

Emerging incretin hormones actions: focus on bone metabolism.

Incretin hormones, namely glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) are gastro-intestinal hormones released from different enteroendocrine cells after nutrient intake. Incretins exert their actions though binding to and activation of specific GIP and GLP-1 receptors which are present in several target tissues. Incretin receptor activation in the pancreas leads to the incretin effect and other significant non-insulinotropic effects. Extra-pancreatic effects of incretin hormones in several other target tissues, such as their role in the pathophysiology of obesity and their potential relation with cardiovascular function, cognitive function, triglyceride storage in adipose tissue and bone metabolism, have attracted scientific interest. In the current review we intend to summarize existing knowledge on specific effects of GIP and GLP-1 in bone cells and bone metabolism. Starting from the identification of GIP receptor and GLP-1 receptor in animal and human bone cells, continuing with the skeletal effects of incretin deficiency or overexpression in animals, ending to the latest data on incretin and incretin agonists administration in cells, animals and humans, incretins play a significant yet complex role in the pathophysiology of bone metabolism affecting both formation and resorption. Although existing evidence seem strong and concrete, there is still a long way to go until their possible therapeutic or adjuvant use as bone modulating drugs can be considered.

The Relationship between Primary Hyperparathyroidism and Thrombotic Events: Report of Three Cases and a Review of Potential Mechanisms.

We have described three uncommon cases of patients who presented with clinical thrombotic events (stroke, pulmonary embolism and deep venous thrombosis) during the course of a hypercalcemia-induced hypercoagulable state. After thorough investigation, the diagnosis of primary hyperparathyroidism - due to a parathyroid adenoma - was established in all cases. The association between hypercalcemia and venous or arterial thrombosis has been previously described; however, relevant data are still insufficient. The existing evidence in the field was reviewed and the interesting underlying pathophysiologic mechanisms were also discussed. Further studies are required to shed more light on the unusual, still intriguing relationship between calcium and thrombosis.

The role of telenursing in the management of Diabetes Type 1: A randomized controlled trial.

BACKGROUND: Diabetes Mellitus type 1 (T1DM) is a chronic disease that requires patients' self-monitoring and self-management to achieve glucose targets and prevent complications. Telenursing implicates technology in the interaction of a specialized nurse with patients with chronic diseases in order to provide personalized care and support. OBJECTIVE: To evaluate the effect of telenursing on T1DM patients' compliance with glucose self-monitoring and glycemic control. DESIGN: Randomized controlled study. SETTINGS: Outpatient Department of Diabetes, Endocrinology and Metabolism of a University Hospital in Northern Greece. METHODS: Ninety-four T1DM patients were recruited and randomized in two groups by a random number generator. The intervention group (N = 48) was provided with telenursing services. A specialized nurse made a weekly contact via telephone motivating patients to frequently measure blood glucose and adopt a healthy lifestyle. The control group (N = 46) received standard diabetes advice and care in the clinic. The primary outcome was the effect of the intervention in glucose control and glucose variability. The secondary outcome was the effect on frequency of self-monitoring. SPSS 20.0 was used for data analysis. RESULTS: The two groups did not differ in age, sex, physical activity or initial HbA1c. In the intervention group, blood glucose significantly decreased at the end of the study in all predefined measurements, compared to control group: morning (93.18 ±â€¯13.30 mg/dl vs. 105.17 ±â€¯13.74 mg/dl, p < 0.005), pre-prandial (114.76 ±â€¯9.54 mg/dl vs. 120.84 ±â€¯4.05 mg/dl, p < 0.005), post-prandial (193.35 ±â€¯25.36 mg/dl vs. 207.84 ±â€¯18.80 mg/dl, p < 0.005), and HbA1c decreased significantly over time in the intervention group (8.3 ±â€¯0.6% at the beginning of the study vs. 7.8 ±â€¯1% at the end of the study, p = 0.03). In the intervention group there were also fewer omitted glucose measurements than in the control group. CONCLUSIONS: Patients in the intervention group achieved better glucose control and more frequent self-monitoring than patients in routine care in the clinic. The findings of our study indicate that telenursing can motivate T1DM patients to better control their disease.

Expression of microRNAs that regulate bone turnover in the serum of postmenopausal women with low bone mass and vertebral fractures.

BACKGROUND: Circulating microRNAs (miRs) are currently being investigated as novel biomarkers for osteoporosis and osteoporotic fractures. AIM: The aim of this study was to investigate serum levels of specific microRNAs, known regulators of bone metabolism, in postmenopausal women with low bone mass and with or without vertebral fractures (VFs). METHODS: For the analysis, 14 miRs were isolated from the serum of 35 postmenopausal women with low bone mass and with at least one moderate VF and 35 postmenopausal women with low bone mass without fractures. Thirty postmenopausal women with normal BMD values and no history of fractures served as controls. Main outcome parameters were changes in the expression of selected miRs in the serum of patient population and compared with controls. RESULTS: From the 14 miRs that were selected, we identified 5 miRs, namely miR-21-5p, miR-23a, miR-29a-3p, miR-124-3p and miR-2861 that were significantly deregulated in the serum of patients with low bone mass compared with controls. Serum miR-124 and miR-2861 were significantly higher, whereas miR-21, miR-23 and miR-29 were lower in patients compared with controls. In a sub-group analysis of the patient population, the expression of miR-21-5p was significantly lower among osteoporotic/osteopenic women with VFs, showing 66% sensitivity and 77% specificity in distinguishing women with a vertebral fracture. CONCLUSION: This study identifies a differential expression pattern of miR-21-5p in the serum of women with low BMD and VFs.

Somatostatin Analogue Treatment of a TSH-Secreting Adenoma Presenting With Accelerated Bone Metabolism and a Pericardial Effusion: A Case Report.

Increased bone turnover and other less frequent comorbidities of hyperthyroidism, such as heart failure, have only rarely been reported in association with central hyperthyroidism due to a thyrotropin (TSH)-secreting pituitary adenoma (TSHoma). Treatment is highly empirical and relies on eliminating the tumor and the hyperthyroid state.We report here an unusual case of a 39-year-old man who was initially admitted for management of pleuritic chest pain and fever of unknown origin. Diagnostic work up confirmed pericarditis and pleural effusion both refractory to treatment. The patient had a previous history of persistently elevated levels of alkaline phosphatase (ALP), indicative of increased bone turnover. He had also initially been treated with thyroxine supplementation due to elevated TSH levels. During the diagnostic process a TSHoma was revealed. Thyroxine was discontinued, and resection of the pituitary tumor followed by treatment with a somatostatin analog led to complete recession of the effusions, normalization of ALP, and shrinkage of pituitary tumor.Accelerated bone metabolism and pericardial and pleural effusions attributed to a TSHoma may resolve after successful treatment of the tumor. The unexpected clinical course of this case highlights the need for careful long-term surveillance in patients with these rare pituitary adenomas.

Patient With Severe Hyponatremia Caused by Adrenal Insufficiency Due to Ectopic Posterior Pituitary Lobe and Miscommunication Between Hypothalamus and Pituitary: A Case Report.

Hyponatremia may be one of the clinical manifestations of adrenal insufficiency (AI) and during the diagnostic workup of hyponatremic patients investigation of AI should be included.We report the case of an 82-year-old patient who was admitted to our hospital with clinical symptoms and laboratory findings of hyponatremia. Following the diagnostic algorithm of hyponatremia we reached the diagnosis of AI. Clinician's attention must focus on the underlying cause of AI which in this case was hidden in a miscommunication between hypothalamus and pituitary due to an ectopic posterior pituitary lobe and became apparent by a pituitary magnetic resonance imaging (MRI) scan. Treatment with oral hydrocortisone resulted in full clinical recovery and electrolyte balance, which was maintained after 7 months of follow-up.Secondary AI is related with hyponatremia through increased ADH secretion. Although a hyponatremic episode may be the first presentation of AI, clinical suspicion is of high importance in order to place the right diagnosis. Disruption of communication between hypothalamus and pituitary is a rare but considerable cause of AI.