CD28null T cells in aging and diseases: From biology to assessment and intervention.

CD28null T cells, an atypical subset characterized by the loss of CD28 costimulatory molecule expression, exhibit functional variants and progressively expand with age. Moreover, T cells with these phenotypes are found in both typical and atypical humoral immune responses. Consequently, they accumulate during infectious diseases, autoimmune disorders, cardiovascular conditions, and neurodegenerative ailments. To provide an in-depth review of the current knowledge regarding CD28null T cells, we specifically focus on their phenotypic and functional characteristics as well as their physiological roles in aging and diseases. While uncertainties regarding the clinical utility remains, we will review the following two crucial research perspectives to explore clinical translational applications of the research on this specific T cell subset: 1) addressing the potential utility of CD28null T cells as immunological markers for prognosis and adverse outcomes in both aging and disease, and 2) speculating on the potential of targeting CD28null T cells as an interventional strategy for preventing or delaying immune aging processes and disease progression.

Vascular Aging: Assessment and Intervention.

Vascular aging represents a collection of structural and functional changes in a blood vessel with advancing age, including increased stiffness, vascular wall remodeling, loss of angiogenic ability, and endothelium-dependent vasodilation dysfunction. These age-related alterations may occur earlier in those who are at risk for or have cardiovascular diseases, therefore, are defined as early or premature vascular aging. Vascular aging contributes independently to cardio-cerebral vascular diseases (CCVDs). Thus, early diagnosis and interventions targeting vascular aging are of paramount importance in the delay or prevention of CCVDs. Here, we review the direct assessment of vascular aging by examining parameters that reflect changes in structure, function, or their compliance with age including arterial wall thickness and lumen diameter, endothelium-dependent vasodilation, arterial stiffness as well as indirect assessment through pathological studies of biomarkers including endothelial progenitor cell, lymphocytic telomeres, advanced glycation end-products, and C-reactive protein. Further, we evaluate how different types of interventions including lifestyle mediation, such as caloric restriction and salt intake, and treatments for hypertension, diabetes, and hyperlipidemia affect age-related vascular changes. As a single parameter or intervention targets only a certain vascular physiological change, it is recommended to use multiple parameters to evaluate and design intervention approaches accordingly to prevent systemic vascular aging in clinical practices or population-based studies.

[Insulin requirement profiles and related factors of type 2 diabetics with insulin pump therapy].

OBJECTIVE: To explore the insulin requirement profiles and analyze the related factors of type 2 diabetics on insulin pump therapy. METHODS: A total of 296 patients were admitted to hospital for 1-2 weeks of insulin pump therapy and received a diet of 25-30 kcal/kg ideal body weight per day. Insulin infusion was adjusted to achieve normoglycemia. It was defined as fasting capillary blood glucose of no more than 7.0 mmol/L and capillary blood glucose at 2 hours after each of three meals of no more than 10.0 mmol/L. After goal-reaching for 3 days, the insulin requirement profiles and related factors were analyzed. RESULTS: The average time of achieving normoglycemia was (5.1 ± 2.9) days. The total daily insulin dose per kilogram was (0.80 ± 0.27) U/kg and the ratio of total basal insulin dose to total bolus insulin dose 40%: 60%. Patients with central obesity needed a higher ratio of total basal insulin dose to total daily insulin dose (P < 0.05). Associations existed between the ratio of total basal insulin dose to total daily insulin dose and disease duration, waist circumference and ratio of 2 hour-postprandial C-peptide to fasting C-peptide (r = 0.169, 0.143, -0.107, all P < 0.05). Multivariate linear regression analyses showed that waist circumference, disease duration and ratio of 2 hour-postprandial C-peptide to fasting C-peptide were independently related with the ratio of total basal insulin dose to total daily insulin dose. Also waist circumference, fasting plasma glucose and hemoglobin A1c levels were independently associated with total daily insulin dose per kilogram. CONCLUSION: The ratio of total basal insulin dose to total bolus insulin dose is 40%: 60% in Chinese type 2 diabetics with insulin pump therapy. And it is associated with central obesity level and ß-cell function. Parameters indicating glycemic control and central obesity should be taken into consideration for total insulin requirements.

Secondary diabetic ketoacidosis and severe hypoglycaemia in patients with established type 1 diabetes mellitus in China: a multicentre registration study.

BACKGROUND: Diabetic ketoacidosis (DKA) and severe hypoglycaemia are common acute complications of type 1 diabetes mellitus (T1DM). This study aimed to determine the incidence of, and risk factors for, these complications in Chinese patients with established T1DM. METHODS: This cross-sectional study recruited patients with established T1DM from 16 centres in Guangdong Province, China. Incidence rates were expressed as episodes/100 patient-years. Regression models identified risk factors for the occurrence and recurrence of secondary DKA and severe hypoglycaemia. RESULTS: A total of 611 patients with established T1DM (53.7% women) were recruited. The incidence of secondary DKA and severe hypoglycaemia was 26.4 (22.4, 31.0) and 68.8 (62.2, 76.0)/100 patient-years, respectively. Significant risk factors for secondary DKA were female gender [relative risk (RR) = 2.12], medical reimbursement rate <50% (RR = 1.84), uncontrolled diet (RR = 1.76), smoking (RR = 2.18) and poor glycaemic control [glycated haemoglobin A1c (HbA1c)/1.0% increase; RR = 1.15]. Overweight/obesity was a protective factor (RR = 0.57). Significant risk factors for severe hypoglycaemia included male gender (RR = 1.71), medical reimbursement rate < 50% (RR = 1.36), longer duration of T1DM (per 5-year increase, RR = 1.22), underweight (RR = 1.44), uncontrolled diet ('never controlled' or 'sometimes controlled' vs. 'usually controlled', RR = 2.09 or 2.02, respectively), exercise <150 min/week (RR = 1.66), presence of neuropathy (RR = 1.89), smoking (RR = 1.48) and lower HbA1c values (per 1.0% decrease, RR = 1.46). Overweight/obesity was a protective factor (RR = 0.62). Additionally, 34.4% of secondary DKA and 81.1% of severe hypoglycaemia episodes occurred in 3.8% and 16.2% patients with recurrent events (≥two episodes), respectively. CONCLUSIONS: The results indicate that secondary DKA and severe hypoglycaemia occur at high rates in Chinese patients with established T1DM and that recurrence is likely to occur in high-risk patients. Comprehensive management of T1DM should include recommendations to control modifiable risk factors.