Longitudinal analysis of atherosclerotic cardiovascular disease risk and healthcare costs in newly diagnosed type 2 diabetes in a real-world setting.

AIMS: To assess longitudinal risk for atherosclerotic cardiovascular disease (ASCVD) and cost of healthcare resource utilization over 9 years in patients with or without newly diagnosed type 2 diabetes (T2DM) who had no ASCVD at baseline. METHODS: This retrospective, longitudinal analysis of a large, nationwide US administrative claims database compared adults with newly diagnosed T2DM (n = 22,468) and a propensity score matched non-T2DM cohort (n = 22,468). Longitudinal risk of ASCVD and total annual healthcare costs were determined. Subgroup analysis was conducted for 3 age categories: 18-44, 45-64, and 65+ years. RESULTS: From 2006 to 2015, ASCVD was identified in a significantly greater percentage of patients in the T2DM versus non-T2DM cohort (43.2% vs 32.3%; Hazard ratio [HR] = 1.45, P < 0.001). Total annual healthcare cost was markedly higher in T2DM versus non-T2DM cohorts (48.4% higher at year 9). The differences between cohorts were most pronounced in patients aged 18-44 years. CONCLUSIONS: This 9-year claims-based retrospective, longitudinal analysis showed a higher risk of ASCVD and higher healthcare costs in newly diagnosed T2DM patients versus those without T2DM, with highest relative risk and cost differences observed in younger patients.

LEADER 5: prevalence and cardiometabolic impact of obesity in cardiovascular high-risk patients with type 2 diabetes mellitus: baseline global data from the LEADER trial.

BACKGROUND: Epidemiological data on obesity are needed, particularly in patients with type 2 diabetes mellitus (T2DM) and high cardiovascular (CV) risk. We used the baseline data of liraglutide effect and action in diabetes: evaluation of CV outcome results-A long term Evaluation (LEADER) (a clinical trial to assess the CV safety of liraglutide) to investigate: (i) prevalence of overweight and obesity; (ii) relationship of the major cardiometabolic risk factors with anthropometric measures of adiposity [body mass index (BMI) and waist circumference (WC)]; and (iii) cardiometabolic treatment intensity in relation to BMI and WC. METHODS: LEADER enrolled two distinct populations of high-risk patients with T2DM in 32 countries: (1) aged ≥50 years with prior CV disease; (2) aged ≥60 years with one or more CV risk factors. Associations of metabolic variables, demographic variables and treatment intensity with anthropometric measurements (BMI and WC) were explored using regression models (ClinicalTrials.gov identifier: NCT01179048). RESULTS: Mean BMI was 32.5 ± 6.3 kg/m(2) and only 9.1 % had BMI <25 kg/m(2). The prevalence of healthy WC was also extremely low (6.4 % according to International Joint Interim Statement for the Harmonization of the Metabolic Syndrome criteria). Obesity was associated with being younger, female, previous smoker, Caucasian, American, with shorter diabetes duration, uncontrolled blood pressure (BP), antihypertensive agents, insulin plus oral antihyperglycaemic treatment, higher levels of triglycerides and lower levels of high-density lipoprotein cholesterol. CONCLUSIONS: Overweight and obesity are prevalent in high CV risk patients with T2DM. BMI and WC are related to the major cardiometabolic risk factors. Furthermore, treatment intensity, such as insulin, statins or oral antihypertensive drugs, is higher in those who are overweight or obese; while BP and lipid control in these patients are remarkably suboptimal. LEADER confers a unique opportunity to explore the longitudinal effect of weight on CV risk factors and hard endpoints.

PACAP-containing intrapineal nerve fibers originate predominantly in the trigeminal ganglion: a combined retrograde tracing- and immunohistochemical study of the rat.

Pituitary adenylate-cyclase activating polypeptide (PACAP) is a neuropeptide originally isolated from the hypothalamus and located in many neuronal systems in both the central and peripheral nervous system. PACAP is also found in nerve fibers innervating the pineal gland, where it stimulates the secretion of the pineal hormone, melatonin, by binding to specific PACAP-receptors located on the cell membrane of the pinealocyte. In this study we have investigated the origin of PACAP-containing nerve fibers innervating the rat pineal gland by combined retrograde tracing with Fluorogold and immunohistochemistry for PACAP. A solution of 2% Fluorogold was injected iontophoretically into the superficial pineal gland of Wistar rats, and the animals were allowed to survive for 1 week. After perfusion fixation of the rats, the location of the tracer was investigated in the brain and the sphenopalatine, otic, and trigeminal ganglia. The tracer was found in all the investigated ganglia. However, colocalization with PACAP was predominantly found in the trigeminal ganglion and only occasionally in the sphenopalatine and otic ganglia. Due to the stimulatory function of PACAP on pineal melatonin secretion, the PACAP-containing neurons of this ganglion could be considered a subset of the parasympathetic nervous system. The presence of neurons with a parasympathetic function in a ganglion that has been considered a purely sensory ganglion, is a new concept in neuroanatomy.