Key points Sound information is transmitted by different subtypes of spiral ganglion neurons (SGN) from the ear to the brain. Selective damage of SGN peripheral synapses (cochlear synaptopathy) is widely recognized as one of the primary mechanisms of hearing loss, whereas the mechanisms at the SGN central synapses remain unclear. We report that different subtypes of SGN central synapses converge at different ratios onto individual target cochlear nucleus neurons with distinct physiological properties, and show biased morphological and physiological changes during age‐related hearing loss (ARHL). The results reveal a new dimension in cochlear nucleus neural circuitry that systematically reassembles and processes auditory information from different SGN subtypes, which is altered during ageing and probably contributes to the development of ARHL. In addition to known cochlear synaptopathy, the present study shows that SGN central synapses are also pathologically changed during ageing, which collectively helps us better understand the structure and function of SGNs during ARHL. Abstract Sound information is transmitted from the cochlea to the brain by different subtypes of spiral ganglion neurons (SGN), which show varying degrees of vulnerability under pathological conditions. Selective cochlear synaptopathy, the preferential damage of certain subtypes of SGN peripheral synapses, has been recognized as one of the main mechanisms of hearing loss. The organization and function of the auditory nerve (AN) central synapses from different subtypes of SGNs remain unclear, including how different AN synapses reassemble onto individual neurons in the cochlear nucleus, as well as how they differentially change during hearing loss. Combining immunohistochemistry with electrophysiology, we investigated the convergence pattern and subtype‐specific synaptopathy of AN synapses at the endbulb of Held, as well as the response properties of their postsynaptic bushy neurons in CBA/CaJ mice of either sex under normal hearing and age‐related hearing loss (ARHL). We found that calretinin‐expressing (type Ia) and non‐calretinin‐expressing (type Ib/Ic) endbulbs converged along a continuum of different ratios onto individual bushy neurons with varying physiological properties. Endbulbs degenerated during ageing in parallel with ARHL. Furthermore, the degeneration was more severe in non‐calretinin‐expressing synapses, which correlated with a gradual decrease in bushy neuron subpopulation predominantly innervated by these inputs. These synaptic and cellular changes were profound in middle‐aged mice when their hearing thresholds were still relatively normal and prior to severe ARHL. Our findings suggest that biased AN central synaptopathy and the correlated shift in cochlear nucleus neuronal composition play significant roles in weakened auditory input and altered central auditory processing during ARHL.

Objective. To investigate changes in the glycated hemoglobin A1c (A1c) level and those in β cell function and insulin resistance in newly diagnosed and drug naive type 2 diabetes patients and to evaluate the relationship between them. Design and Methods. A total of 818 newly diagnosed diabetic individuals who were ≥40 years of age were recruited. The subjects were grouped by A1c values (<6.5%, 6.5–7%, 7-8%, 8-9%, and ≥9%). The homeostasis model assessment (HOMA) was used to evaluate pancreatic β cell function (HOMA-β) and insulin resistance (HOMA-IR). ANOVA, t-tests, and binary logistic regression analysis were used for data analysis. Results. Compared with subjects with A1c values <6.5%, individuals with an A1c of 6.5–7% exhibited an increased HOMA-β index. However, the HOMA-β index was significantly decreased at A1c values ≥7% and further decreased by 9.3% and by 23.7%, respectively, at A1c values of 7-8% and 8-9%. As A1c increased to ≥9%, a 62% reduction in β cell function was observed, independently of age, gender, body mass index (BMI), blood pressure (BP), blood lipids, and hepatic enzyme levels. Meanwhile, insulin resistance was significantly increased with an increase in A1c values. Conclusions. Elevated A1c values (≥7%) were associated with substantial reductions in β cell function.

Background Cardiovascular and cerebrovascular diseases have become leading causes of death in China as the economy develop and lifestyles change. This study aimed to estimate the relationship of the age, gender, and glucose metabolism with the serum lipid and lipoprotein levels of middle-aged and elderly Chinese men and women in Shandong Province. Methods We conducted a cross-sectional study in Shandong Province that included 10,028 adults aged ≥40 years. Fasting serum total, low-density lipoprotein (LDL), high-density lipoprotein (HDL) cholesterol and triglycerides were measured by standard methods. Results The estimates of total, LDL, and HDL cholesterol and triglycerides were as follows: 5.35, 3.18, 1.51, and 1.34 mmol/L in the middle-aged and elderly Chinese adult population; 5.14, 3.08, 1.42, and 1.33 mmol/L in male subjects; 5.46, 3.24, 1.56, and 1.34 mmol/L in females; 5.27, 3.11, 1.54, and 1.24 mmol/L in the normal glucose tolerance population, 5.49, 3.27, 1.50, and 1.41 mmol/L in the population with pre-diabetes, and 5.39, 3.23, 1.43, and 1.58 mmol/L in the population with diabetes, respectively. Moreover, 36.92 and 19.10% of the adults had borderline-high and high total cholesterol. The population estimates for borderline-high, high LDL and low HDL cholesterol levels were 25.24, 13.39, and 5.64%, respectively. Meanwhile, borderline high and high triglyceride levels accounted for 16.7 and 17.47% of the population, respectively. Conclusions Serum total and LDL cholesterol levels were high in the ≥40 years old population of Shandong Province. Age, gender, glucose metabolism status, body mass index (BMI) and glycosylated hemoglobin (HbA1c) can affect serum lipid and lipoprotein levels.

ObjectiveTo investigate how the glucose variability between fasting and a 2-h postload glucose state (2-h postload plasma glucose [2hPG]-fasting plasma glucose [FPG]) is associated with chronic kidney disease (CKD) in middle-aged and elderly Chinese patients previously diagnosed with type 2 diabetes.Design and MethodsThis cross-sectional study included 1054 previously diagnosed type 2 diabetes patients who were 40 years of age and older. First, the subjects were divided into two groups based on a glycated hemoglobin (HbA1c) value of 7%. Each group was divided into two subgroups, with or without CKD. The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation was used to estimate the glomerular filtration rate (GFR). CKD was defined as eGFR<60 mL/min/1.73 m2. Multiple linear regression analysis was used to estimate the association between the 2hPG-FPG and eGFR. The 2hPG-FPG value was divided into four groups increasing in increments of 36 mg/dl (2.0 mmol/L): 0–72, 72–108, 108–144 and ≥144 mg/dl, based on the quartiles of patients with HbA1c levels ≥7%; then, binary logistic regression analysis was used to investigate the association between 2hPG-FPG and the risk of CKD.ResultsIn the patients with HbA1c levels ≥7%, the 2hPG-FPG was significantly associated with decreased eGFR and an increased risk of CKD independent of age, gender, body mass index (BMI), systolic blood pressure (BP), diastolic BP, smoking, and drinking, as well as fasting insulin, cholesterol, triglyceride, and HbA1c levels. The patients with 2hPG-FPG values ≥144 mg/dl showed an increased odds ratio (OR) of 2.640 (P = 0.033). Additionally, HbA1c was associated with an increased risk of CKD in patients with HbA1c values ≥7%.ConclusionsThe short-term glucose variability expressed by 2hPG-FPG is closely associated with decreased eGFR and an increased risk of CKD in patients with poor glycemic control (HbA1c≥7%).

ObjectiveTo investigate the relationship between lipid profiles [including total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C)] and a mild decline in the estimated glomerular filtration rate (eGFR) in subjects with normal serum lipid levels.Design and MethodsIn this study, we included 2647 participants who were ≥40 years old and had normal serum lipid levels. The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation was used to estimate the GFR. A mildly reduced eGFR was defined as 60–90 mL/min/1.73 m2. First, multiple linear regression analysis was used to estimate the association of lipid profiles with the eGFR. Then, the levels of each lipid component were divided into four groups, using the 25th, 50th and 75th percentiles as cut-off points. Finally, multiple logistic regression analysis was used to investigate the association of different lipid components with the risk of mildly reduced eGFR.ResultsIn the group with a mildly reduced eGFR, TG and LDL-C levels were significantly increased, but HDL-C levels were significantly decreased. After adjusting for age, gender, body mass index (BMI), systolic blood pressure (SBP), glycated hemoglobin (HbA1c), smoking and drinking, only TC and TG were independently related to the eGFR. Additionally, only TG showed a linear relationship with an increased risk of a mildly reduced eGFR, with the highest quartile group (TG: 108–150 mg/dl [1.22–1.70 mmol/L]) having a significantly increased risk after adjusting for the above factors.ConclusionsTriglyceride levels are closely associated with a mildly reduced eGFR in subjects with normal serum lipid levels. Dyslipidemia with lower TG levels could be used as new diagnostic criteria for subjects with mildly reduced renal function.