“The Times They Are A-Changin’” at Diabetes Care

Every five years or so, the editorial team leading Diabetes Care turns over with the appointment of new leadership. This issue of volume 46 represents the first of a new editorial team, making it the tenth group to be responsible for the scientific content of the journal. Starting in 1978 with Jay Skyler as its first editor, Diabetes Care has gone from strength to strength with new initiatives and a steady increase in its influence. This impact has been in line with the charge given at the journal’s founding by the then president of the American Diabetes Association Norbert Freinkel when he wrote, “The new journal is designed to promote better patient care by serving the expanded needs of all health professionals committed to the care of patients with diabetes.

The relative associations of β-cell function and insulin sensitivity with glycemic status and incident glycemic progression in migrant Asian Indians in the United States: The MASALA study

AIMS: We assessed the relative associations of β-cell dysfunction and insulin sensitivity with baseline glycemic status and incident glycemic progression among Asian Indians in the United States. METHODS: A 5-sample oral glucose tolerance test was obtained at baseline. Normoglycemia, impaired fasting glucose (IFG), impaired glucose tolerance (IGT), and type 2 diabetes (T2DM) were defined by ADA criteria. The Matsuda Index (ISI(M)) estimated insulin sensitivity, and the Disposition Index (DI(o)) estimated β-cell function. Visceral fat was measured by abdominal CT. After 2.5 years, participants underwent a 2-sample oral glucose tolerance test. Standardized polytomous logistic regression was used to examine associations with prevalent and incident glycemia. RESULTS: Mean age was 57±8 years and BMI 26.1±4.6 kg/m(2). Log ISI(M) and log DI(o) were associated with prediabetes and T2DM after adjusting for age, sex, BMI, family history of diabetes, hypertension, and smoking. After adjusting for visceral fat, only DI(o) remained associated with prediabetes (OR per SD 0.17, 95% CI: 0.70, 0.41) and T2DM (OR 0.003, 95% CI: 0.0001, 0.03). Incidence rates (per 1,000 person-year) were: normoglycemia to IGT: 82.0, 95% CI (40, 150); to IFG: 8.4, 95% CI (0, 41); to T2DM: 8.6, 95% CI (0, 42); IGT to T2DM: 55.0, 95% CI (17, 132); IFG to T2DM: 64.0, 95% CI (3, 316). The interaction between sex and the change in waist circumference (OR 1.8, per SD 95% CI: 1.22, 2.70) and the change in log HOMA-β(OR 0.37, per SD 95% CI: 0.17, 0.81) were associated with glycemic progression. CONCLUSIONS: The association of DI(o) with baseline glycemia after accounting for visceral fat as well as the association of the change in log HOMA-β with incident glycemic progression implies innate β-cell susceptibility in Asian Indians for glucose intolerance or dysglycemia

Antigen-driven EGR2 expression is required for exhausted CD8(+) T cell stability and maintenance

Chronic stimulation of CD8⁺ T cells triggers exhaustion, a distinct differentiation state with diminished effector function. Exhausted cells exist in multiple differentiation states, from stem-like progenitors that are the key mediators of the response to checkpoint blockade, through to terminally exhausted cells. Due to its clinical relevance, there is substantial interest in defining the pathways that control differentiation and maintenance of these subsets. Here, we show that chronic antigen induces the anergy-associated transcription factor EGR2 selectively within progenitor exhausted cells in both chronic LCMV and tumours. EGR2 enables terminal exhaustion and stabilizes the exhausted transcriptional state by both direct EGR2-dependent control of key exhaustion-associated genes, and indirect maintenance of the exhausted epigenetic state. We show that EGR2 is a regulator of exhaustion that epigenetically and transcriptionally maintains the differentiation competency of progenitor exhausted cells.Mayura V. Wagle, Stephin J. Vervoort, Madison J. Kelly, Willem Van Der Byl, Timothy J. Peters, Ben P. Martin ... et al

Relationship between alanine aminotransferase levels and metabolic syndrome in nonalcoholic fatty liver disease

Objective: To investigate the relationship between alanine aminotransferase (ALT) levels and metabolic syndrome (MS) in nonalcoholic fatty liver disease (NAFLD). Methods: A total of 26527 subjects who received medical health checkup in our hospital from January 2005 to July 2007 were enrolled in the study. The diagnosis of fatty liver was based on ultrasound imaging. MS was defined according to the criteria of the Adult Treatment Panel III. ALT, triglyceride (TG), high density lipoprotein cholesterol (HDL-c), fasting plasma glucose (FPG), height, weight, waist circumference (WC), systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured in each subject to analyze the relationship between MS and ALT activity. Results: (1) The prevalence of NAFLD in men (30.94%) was significantly higher than that in women (15.65%); (2) The incidence of MS in NAFLD (33.83%) was significantly greater than that in non-NAFLD (10.62%); (3) Of the 6470 subjects with NAFLD, in the age-adjusted partial correlation analysis, there were statistically significant correlations between the ALT levels and most metabolic risk factors in each sex (P<0.01), except that ALT levels had no correlation with HDL-c in women. Moreover, in the multiple stepwise regression analysis, SBP lost its significance, and WC, body mass index (BMI), age, DBP, TG and FPG were independently associated with ALT levels in both sexes (P<0.05). HDL-c remained significant and was independently related to ALT levels in men; (4) ALT levels were significantly higher in subjects with MS compared to those without MS (P<0.001). Mean ALT levels increased with the number of MS components in each sex (P<0.05 for trend). Conclusion: We found a strong relationship between ALT levels and MS in NAFLD and revealed that the cluster of MS components might be the predictor for ALT elevations