Summary Objective Serum adiponectin levels are affected by gender, body fat mass, several pathological factors or therapeutic interventions and it might be also affected by age. This study aimed to investigate the relationship between serum adiponectin levels and age in several physiological states. Design, Patients and Measurements The study was carried out in 21 100 healthy subjects (12 363 men and 8737 women) and 1833 patients with type 2 diabetes (1233 men and 600 women). Physical and demographic characteristics were recorded, and blood samples were collected to measure serum adiponectin levels. Using these data, we determined the relationships between serum adiponectin levels and various parameters, including age. Results Serum adiponectin levels increased with increasing age of healthy subjects and in patients with diabetes, in both men and women. Serum adiponectin levels were positively correlated with age in healthy subjects and patients with diabetes, in both men and women. In stepwise multiple regression analysis with serum adiponectin levels as the dependent variable and physiological characteristics as explanatory variables, age was significantly and independently associated with serum adiponectin levels in each of these groups of subjects. Conclusions Serum adiponectin levels are significantly and positively associated with age in healthy subjects and in patients with diabetes. This association is independent of renal function, body fat status, glucose metabolism and lipid profiles.
With the increasing prevalence of diseases related to obesity, metabolic syndrome and its key player adiponectin are now attracting considerable attention. Hypoadiponectinaemia is reported to be a risk factor for hypertension and associated with endothelial dysfunction, which is closely related to complications of obesity such as hypertension. As there is limited information regarding serum adiponectin levels in normotensive people, we undertook the large-scale study to determine the association of adiponectin with blood pressure (BP) in mainly normotensive people.In 21 100 Japanese adults (12 363 men and 8737 women) who had no apparent diseases, we examined the relationship between the serum adiponectin concentration and BP by performing a questionnaire survey, physical measurements and measurement of laboratory parameters including the serum adiponectin level.Subjects with hypoadiponectinaemia had higher systolic and diastolic BPs as already reported. And interestingly, subjects with higher adiponectin had lower systolic and diastolic BP. According to linear regression analysis, adiponectin showed a significant negative correlation with systolic and diastolic BP independently of the other variables. Analysis of covariance according to adiponectin quintiles showed that systolic and diastolic BP in highest adiponectin quintile was significantly lower than in other quintiles.This study revealed that there were significant trends toward lower systolic and diastolic BP with higher adiponectin not only in hypertensive people but also in normotensive people.
Abstract Background Ectopic fat is fat that accumulates in or around specific organs or compartments of the body including myocardium. The clinical features of type 2 diabetes patients with high fat accumulation in the myocardium remain unknown. Moreover, little is known about the influence of myocardial fat accumulation in type 2 diabetes on coronary artery disease and cardiac dysfunction. We aimed to clarify the clinical features, including cardiac functions, of type 2 diabetes patients with myocardial fat accumulation. Methods We retrospectively enrolled type 2 diabetes patients who underwent ECG-gated coronary computed tomography angiography (CCTA) and abdominal computed tomography (CT) scan examinations within 1 year of CCTA from January 2000 to March 2021. High fat accumulation in the myocardium was defined as the low mean myocardial CT value of three regions of interest, and the associations between CT values and clinical characteristics or cardiac functions were assessed. Results In total, 124 patients were enrolled (72 males and 52 females). The mean age was 66.6 years, the mean BMI was 26.2 kg/m 2 , the mean ejection fraction (EF) was 67.6%, and the mean myocardial CT value was 47.7 Hounsfield unit. A significant positive correlation was found between myocardial CT value and EF (r = 0.3644, p = 0.0004). The multiple regression analyses also showed that myocardial CT value was independently associated with EF (estimate, 0.304; 95% confidence interval (CI) 0.092 to 0.517; p = 0.0056). Myocardial CT value showed significant negative correlations with BMI, visceral fat area and subcutaneous fat area (r = − 0.1923, − 0.2654, and -0.3569, respectively, p < 0.05). In patients who were ≥ 65 years or female, myocardial CT value showed significant positive correlations with not only EF (r = 0.3542 and 0.4085, respectively, p < 0.01) but also early lateral annular tissue Doppler velocity (Lat e’) (r = 0.5148 and 0.5361, respectively, p < 0.05). The multiple regression analyses showed that myocardial CT value was independently associated with EF and Lat e’ in these subgroups (p < 0.05). Conclusions Patients with type 2 diabetes, especially in elderly or female patients, who had more myocardial fat had more severe left ventricular systolic and diastolic dysfunctions. Reducing myocardial fat accumulation may be a therapeutic target for type 2 diabetes patients.
Low serum adiponectin (Ad) level is an important risk factor for the development of type 2 diabetes mellitus (T2DM).To determine whether the changes in Ad in subjects with low baseline serum Ad levels can reduce the rate of development of T2DM.We performed a large-scale longitudinal study of 7052 healthy Japanese men who underwent general health checkups more than twice between April 2007 and May 2015 at the Physical Check up Center, Sumitomo Hospital. The participants were divided into quartile groups according to baseline Ad level. Subjects of the lowest baseline Ad group (≤5.2 μg/mL) were subdivided into quartile subgroups according to the percent change in Ad (%ΔAd) and into two subgroups according to endpoint Ad (>5.2 and ≤5.2 μg/mL).The cumulative incidence rate of T2DM.The cumulative incidence rate of T2DM of the lowest baseline Ad group (≤5.2 μg/mL) was significantly higher than the other quartile groups. The cumulative incidence rates of T2DM were significantly lower in the largest (≥21.5%) and the second largest (9.3% to 21.4%) %ΔAd-increased subgroups compared with the %ΔAd-decreased subgroup (P < 0.001 and P = 0.005, respectively). The cumulative incidence rates of T2DM were significantly lower in the endpoint Ad >5.2 μg/mL subgroup than in the ≤5.2 μg/mL subgroup (P < 0.001).Increases in serum Ad levels of at least ~10% or >5.2 μg/mL can potentially reduce the risk of development of T2DM in Japanese men with low baseline Ad levels who are at a high risk of developing T2DM.
The aim of this study was to determine the effective waist circumference (WC) reduction rate in avoiding the development of type 2 diabetes mellitus (T2DM) in <55 years and ≥55 years Japanese men with abdominal obesity. The study subjects were 795 men with WC ≥85 cm, fasting plasma glucose <126 mg/dL, 2-hr plasma glucose on 75 g of oral glucose tolerance test <200 mg/dL, and HbA1c 5.6-6.4 % (38-40 mmol/mol) at baseline who underwent general health checkups more than twice between April 2007 and May 2015. They were divided into 5 groups based on the change in WC during the observation period (WC gain group, and four groups stratified according the rate of WC loss). The subjects were also divided into the <55 years and ≥55 years (at baseline) subgroups. The cumulative incidence rate of T2DM was analyzed and compared among the groups. The cumulative incidence rates of the largest WC loss quartile (≥5.45 %) in all age, of the largest WC loss quartile (≥5.60 %) and second largest WC loss quartile (3.44-5.59 %) in the <55 years subgroup, and of the largest WC loss quartile (≥5.37 %) in the ≥55 years subgroup were significantly lower than that of the gain group (p<0.001, p=0.009, 0.012, and 0.012, respectively). WC reduction rate of at least about 3 % in the younger (<55 years) and at least about 5 % in the older (≥55 years) non-diabetic Japanese men with abdominal obesity can effectively reduce the chance of development of T2DM.
A 40-year-old man presented with Cushing's syndrome due to bilateral adrenal hyperplasia with multiple nodules. Computed tomography scan results were atypical demonstrating an enlargement of the bilateral adrenal glands harboring multiple small nodules, but the lesion was clinically diagnosed to be primary pigmented nodular adrenocortical disease (PPNAD) based on both endocrinological test results and his family history. We performed bilateral adrenalectomy and confirmed the diagnosis histologically. An analysis of the patient and his mother's genomic DNA identified a novel mutation in the type Iα regulatory subunit of protein kinase A (PRKAR1A) gene; p.E17X (c.49G>T). This confirmed the diagnosis of PPNAD which is associated with Carney Complex.
Maturity‐onset diabetes of the young (MODY) is a monogenic form of type 2 diabetes mellitus that is characterized by impairment of glucose‐stimulated insulin secretion from pancreatic β‐cells. We previously reported that heterozygous mutations of the hepatocyte nuclear factor (HNF)‐1α gene cause a form of MODY (MODY3). We have subsequently found that collectrin, a recently cloned kidney‐specific gene of unknown function, is a novel target of HNF‐1α in pancreatic β‐cells. In addition, we have demonstrated that collectrin forms a complex with the soluble N‐ethylmaleimide‐sensitive factor attachment protein receptor (SNARE) complex by direct interaction with snapin, a protein that is thought to be involved in neurotransmission by binding to synaptosomal‐associated protein, 25 KD (SNAP25). Collectrin favours the formation of SNARE complexes and controls insulin exocytosis.
