Background/Aims: Glucocorticoids are associated with a number of side effects including the development of new-onset hyperglycemia or diabetes. The diagnosis and treatment of glucocorticoid-induced hyperglycemia are surprisingly undervalued by many health-care professionals, probably due to the lack of quality studies that assess specific reasons for and prevention of hyperglycemia. The aim of this meta-analysis was to evaluate the long-term incidence of glucocorticoid-induced hyperglycemia and diabetes in nondiabetic patients who received glucocorticoid treatment. Methods: We searched Medline, Embase, and the Cochrane Library (Central) until January 2014 for studies in which subjects received systematic glucocorticoid treatment and which evaluated whether subjects developed hyperglycemia or were diagnosed with diabetes following treatment. The primary outcome for this analysis was the incidence of hyperglycemia and the secondary outcome was the frequency of diabetes. Results: We identified 13 studies that met our inclusion criteria; 12 of the studies were retrospective or observational in design. We found that the rate at which patients developed glucocorticoid-induced hyperglycemia or diabetes was 32.3% (p = 0.003) and 18.6% (p = 0.002), respectively. Conclusions: Our meta-analysis indicated that glucocorticoid-induced hyperglycemia occurs fairly frequently and points to the need for the design of prospective, randomized, controlled studies to further investigate and better understand this medical problem.

Preclinical studies show that GABA exerts anti-diabetic effects in rodent models of type 1 diabetes. Because little is known about its absorption and effects in humans, we investigated the pharmacokinetics and pharmacodynamics of GABA in healthy volunteers. Twelve subjects were subjected to an open-labeled, three-period trial involving sequential oral administration of placebo, 2g GABA once, and 2g GABA three times/day for seven days, with a 7-day washout between each period. GABA was rapidly absorbed (Tmax: 0.5~1 h) with the half-life (t1/2) of 5 h. No accumulation was observed after repeated oral GABA administration for 7 days. Remarkably, GABA significantly increased circulating insulin levels in the subjects under either fasting (1.6-fold, single dose; 2.0-fold, repeated dose; p<0.01) or fed conditions (1.4-fold, single dose; 1.6-fold, repeated dose; p<0.01). GABA also increased glucagon levels only under fasting conditions (1.3-fold, single dose, p<0.05; 1.5-fold, repeated dose, p<0.01). However, there were no significant differences in the insulin-to-glucagon ratio and no significant change in glucose levels in these healthy subjects during the study period. Importantly, GABA significantly decreased glycated albumin levels in the repeated dosing period. Subjects with repeated dosing showed an elevated incidence of minor adverse events in comparison to placebo or the single dosing period, most notably transitional discomforts such as dizziness and sore throat. However, there were no serious adverse events observed throughout the study. Our data show that GABA is rapidly absorbed and tolerated in human beings; its endocrine effects, exemplified by increasing islet hormonal secretion, suggest potential therapeutic benefits for diabetes.

IL-10-producing B cells (B10 cells) have been shown to play a suppressive role in the peripheral blood of humans, with their numbers and function altered in several autoimmune diseases. However, the role of B10 cells in Graves’ disease (GD) remains unknown. In this study, we demonstrated that B10 cells in human peripheral blood belonged to a CD24^hiCD27⁺ B cell subpopulation. The proportion of B10 cells along with the CD19⁺CD24^hiCD27⁺ B cell subset was significantly lower in new-onset patients compared with healthy individuals. In recovered patients, these proportions were restored to levels similar to those seen in healthy individuals. Additionally, we found that CD19⁺CD24^hiCD27⁺ B cells from healthy individuals inhibited proliferation and TNF-α production of CD4⁺ T cells via an IL-10–independent pathway. They also inhibited IFN-γ production by CD4⁺ T cells, through an IL-10–dependent pathway. In contrast, their suppressive function on CD4⁺ T cell proliferation and cytokine production was impaired in new-onset and recovered patients compared with healthy individuals. Our study provides evidence that CD19⁺CD24^hiCD27⁺ B cells may possess the capacity to downregulate immune responses, partially by production of IL-10 in human peripheral blood. Impairment of their immunosuppressive function may contribute to GD pathogenesis and relapse.

There are two different types of fat present in mammals: white adipose tissue, the primary site of energy storage, and brown adipose tissue, which is specializes in energy expenditure. Factors that specify the developmental fate and function of brown fat are poorly understood. Bone morphogenic proteins (BMPs) play an important role in adipogenesis. While BMP4 is capable of triggering commitment of stem cells to the white adipocyte lineage, BMP7 triggers commitment of progenitor cells to a brown adipocyte lineage and activates brown adipogenesis. To investigate the differential effects of BMPs on the development of adipocytes, C3H10T1/2 pluripotent cells were pretreated with BMP4 and BMP7, followed by different adipogenic induction cocktails. Both BMP4 and BMP7 unexpectedly activated a full program of brown adipogenesis, including induction of the brown fat-defining marker uncoupling protein-1 (UCP1), increasing the expression of early regulators of brown fat fate PRDM16 (PR domain-containing 16) and induction of mitochondrial biogenesis and function. Implantation of BMP4-pretreated C3H10T1/2 cells into nude mice resulted in the development of adipose tissue depots containing UCP1-positive brown adipocytes. Interestingly, BMP4 could also induce brown fat-like adipocytes in both white and brown preadipocytes, thereby decreasing the classical brown adipocyte marker Zic1 and increasing the recently identified beige adipocyte marker TMEM26. The data indicate an important role for BMP4 in promoting brown adipocyte differentiation and thermogenesis in vivo and in vitro and offers a potentially new therapeutic approach for the treatment of obesity.

Aims/Introduction: The aim of the present study was to use the sudomotor function test, Sudoscan, as a screening method for the evaluation of asymptomatic diabetic distal symmetric polyneuropathy in Chinese type 2 diabetes patients. As a result, more attention could be paid to those asymptomatic patients who could be easily neglected and underdiagnosed in everyday clinic.Materials and Methods: A total of 394 Chinese type 2 diabetes patients were enrolled and tested for symptoms and clinical signs of neuropathy using the Neurological Symptom Score, Neuropathy Disability Score, and vibration perception threshold. Sudoscan was carried out, and the results were collected as the measurement of the electrochemical skin conductance of both hands and feet.Results: In the present study, we found that the abnormal rate of Sudoscan results in patients with asymptomatic neuropathy was higher than those without neuropathy and those with symptomatic neuropathy. This study also showed that lower electrochemical skin conductance at the feet was significantly associated with increasing symptoms, Neurological Symptom Score (r = −0.124, P < 0.05), Neuropathy Disability Score (r = −0.3, P < 0.01) and vibration perception threshold value (r = −0.18, P < 0.05). Logistic analysis showed that age (odds ratio 1.042, 95% confidence interval 1.014−1.071, P < 0.05) and feet electrochemical skin conductance levels (odds ratio 0.98, 95% confidence interval 0.962–0.993, P < 0.01) were independently associated with diabetic distal symmetric polyneuropathy.Conclusions: Sudoscan might be a promising tool to screen asymptomatic diabetic distal symmetric polyneuropathy in Chinese patients with type 2 diabetes mellitus.