空腹血糖受损人群自然转归及其影响因素的观察

目的 探讨开滦研究中IFG人群的自然转归及其影响因素。方法采用前瞻性队列研究,对FPG6．1～7．0mmol／L且无糖尿病史的IFG人群,随访2年。结果（1）最终共纳入IFG者5562例,随访2年后2985例（53．7％）血糖降至正常,1305例（23．5％）仍为IFG,1272例（22．90A）诊断为糖尿病;（2）分别以血糖转为正常或进展为糖尿病为因变量,以各危险因素作为自变量行多因素Logistic回归分析,结果显示年龄、BMI、WHR、SBP、LDL-C水平是进展为糖尿病的危险因素。结论IFG人群约22．9％进展为糖尿病。年龄、BMI、WHR、LDL-C水平是进展为糖尿病的危险因素。     

维生素D受体基因多态性与青少年代谢综合征空腹血糖受损的关系研究

目的探讨维生素D受体(VDR)基因多态性与青少年代谢综合征(MS)空腹血糖受损(IFG)的关系。方法选取2017年3月至2019年8月在上海市松江区中心医院接受治疗的青少年代谢综合征患者(MS组)242例和体检中心健康检查的青少年(NC组)200例作为研究对象。MS组按照是否出现空腹血糖受损分为IFG亚组和Non-IFG亚组,分析维生素D受体基因ApaⅠ位点多态性及与相关临床资料的关系。结果三组研究对象VDR基因ApaⅠ基因型及等位基因分布频率比较差异具有统计学意义,且aa基因型频率、a等位基因频率均在IFG亚组中最高,在NC组中最低(χ2值分别为36.954、31.501,均P<0.01);不同基因型患者空腹血糖(FPG)、糖化血红蛋白(HbA1c)、空腹胰岛素(Fins)、高密度脂蛋白胆固醇(HDL-C)、1,25-二羟基维生素D3[1,25-(OH)2D3]比较差异有统计学意义,且aa基因型患者的FPG、HbA1c、Fins水平更高,HDL-C、1,25-(OH)2D3水平更低(F值分别为6.278、5.536、9.663、6.012、11.547,均P<0.05);Logistic回归分析结果显示,体质指数(BMI)、FPG、HbA1c、稳态模型胰岛素抵抗指数(HOMA-IR)、aa基因型及a等位基因为MS患者空腹血糖受损的危险因素,HDL-C及1,25-(OH)2D3为MS患者空腹血糖受损的保护因素,其OR值及95%CI分别为2.416(1.397~6.222)、2.978(1.694~8.996)、1.896(1.207~7.554)、2.021(1.832~7.449)、2.142(1.214~8.094)、2.423(1.353~7.939)、0.421(0.384~0.852)、0.527(0.436~0.847),均P<0.05。结论维生素D受体基因ApaⅠ位点多态性与MS患者空腹血糖受损存在一定相关性,其可能通过降低维生素D受体水平引起MS空腹血糖受损。     

Can sulphonylurea addition to lifestyle changes help to delay diabetes development in subjects with impaired fasting glucose? The Nepi ANtidiabetes StudY (NANSY)

The Nepi ANtidiabetes StudY (NANSY) is a 5-year randomized, double-blind, placebo-controlled trial in Swedish primary care, examining whether the development of type 2 diabetes (T2D) and retinopathy (separately reported) would be delayed in 40- to 70-year-old subjects with impaired fasting glucose (IFG) who, in addition to lifestyle changes, were treated with either placebo or low-dosage sulphonylurea (SU) (1-mg glimepiride; Amaryl). Of 274 subjects (163 men, 111 women), 138 were allocated to placebo (46.0% men, 56.8% women) and 136 to glimepiride (54.0% men, 43.2% women). The primary endpoint was conversion to diabetes. Average follow-up time was 3.71 years; 96 subjects converted to diabetes, 55 allocated to placebo and 41 to glimepiride (absolute difference 9.8%; p = 0.072). In conclusion, the study failed to support the notion that low-dose SU added to lifestyle changes in IFG subjects would help to delay the conversion to diabetes.     

Interaction between α-synuclein and tau in Parkinson's disease comment on Wills et al.: elevated tauopathy and α-synuclein pathology in postmortem Parkinson's disease brains with and without dementia. Exp Neurol 2010; 225: 210-218

Recent neurochemical studies in postmortem brains of patients with Parkinson's disease (PD), PD with dementia (PDD) and age-matched controls revealed significant decrease of tyrosine hydroxylase (TH) and dopamine transporter (DAT) in striatum, confirming previous studies indicating substantial loss of dopaminergic neurons and terminals. Insoluble α-synuclein (αSyn) was significantly increased in both striata and inferior frontal gyrus (IFG), more severe in PDD, probably related to Lewy body (LB) burden discussed as one cause of dementia in PD. Parkin levels frequently related to recessive and young-onset PD were unchanged, suggesting no link to sporadic PD. Novel and most interesting data showed elevated tauopathy in striata of both PD and PDD, associated with increased levels of phosphorylated GSK-3β and reduced 20S proteasomal subunits but – despite increased cortical αSyn – unchanged pTau in IFG, related to increased pGSK-3β and decreased 19S proteasome subunits. These data, recently confirmed in PDGF-αSyn transgenic mice (Haggerty et al., submitted) suggest tauopathy in PD and PDD restricted to the dopaminergic nigrostriatal system and in various animal models of PD show topographic differences from a global tauopathy in Alzheimer's disease (AD) (and other tauopathies). Although some of these data are at variance to current neuropathologic findings in PD and PDD, they confirm frequently discussed correlations/overlaps between AD and PD/PDD and synergistic effects of αSyn, pTau, β-amyloid, and other pathologic proteins, suggesting a dualism or triad of neurodegeneration, the basic molecular pathogenesis remains to be elucidated.     

Nerve growth factor/p38 signaling increases intraepidermal nerve fiber densities in painful neuropathy of type 2 diabetes

Painful diabetic neuropathy (PDN) is a common, yet devastating complication of type 2 diabetes. At this time, there is no objective test for diagnosing PDN. In the current study, we measured the peptidergic intraepidermal nerve fiber densities (IENFD) from hind paws of the db/db mouse, an animal model for type 2 diabetes, during the period of mechanical allodynia from 6 to 12 weeks of age. Intraepidermal nerve fibers (IENF) of the hind footpads were identified by protein gene product (PGP) 9.5 immunohistochemistry. The peptidergic IENF were determined by double immunofluorescence using anti-PGP9.5 and antibodies against tropomyosin-receptor-kinase (Trk) A. We observed a significant increase in PGP9.5-positive IENFD at 8 and 10 weeks of age. Similarly, Trk A-positive peptidergic IENF, which also express substance P and calcitonin gene related peptide in db/db mice, were observed to be elevated from 1.5 to 2 fold over controls. This upregulation ended at 16 weeks of age, in accordance with the reduction of mechanical allodynia. Anti-NGF treatment significantly inhibited the upregulation of peptidergic IENFD during the period of mechanical allodynia, suggesting that increased neurotrophism may mediate this phenomenon. In addition, SB203580, an inhibitor of p38, blocked the increase in peptidergic IENFD in db/db mice. The current results suggest that peptidergic IENFD could be a potential diagnostic indicator for PDN in type 2 diabetes. Furthermore, the inhibition of NGF-p38 signaling could be a potential therapeutic strategy for treating this painful condition.     

Neural correlates of blink suppression and the buildup of a natural bodily urge

Neuroimaging studies have elucidated some of the underlying physiology of spontaneous and voluntary eye blinking; however, the neural networks involved in eye blink suppression remain poorly understood. Here we investigated blink suppression by analyzing fMRI data in a block design and event-related manner, and employed a novel hypothetical time-varying neural response model to detect brain activations associated with the buildup of urge. Blinks were found to activate visual cortices while our block design analysis revealed activations limited to the middle occipital gyri and deactivations in medial occipital, posterior cingulate and precuneus areas. Our model for urge, however, revealed a widespread network of activations including right greater than left insular cortex, right ventrolateral prefrontal cortex, middle cingulate cortex, and bilateral temporo-parietal cortices, primary and secondary face motor regions, and visual cortices. Subsequent inspection of BOLD time-series in an extensive ROI analysis showed that activity in the bilateral insular cortex, right ventrolateral prefrontal cortex, and bilateral STG and MTG showed strong correlations with our hypothetical model for urge suggesting these areas play a prominent role in the buildup of urge. The involvement of the insular cortex in particular, along with its function in interoceptive processing, helps support a key role for this structure in the buildup of urge during blink suppression. The right ventrolateral prefrontal cortex findings in conjunction with its known involvement in inhibitory control suggest a role for this structure in maintaining volitional suppression of an increasing sense of urge. The consistency of our urge model findings with prior studies investigating the suppression of blinking and other bodily urges, thoughts, and behaviors suggests that a similar investigative approach may have utility in fMRI studies of disorders associated with abnormal urge suppression such as Tourette syndrome and obsessive-compulsive disorder.     

Cannabis cue-elicited craving and the reward neurocircuitry

Cue-elicited craving or the intense desire to consume a substance following exposure to a conditioned drug cue is one of the primary behavioral symptoms of substance use disorders (SUDs). While the concept of cue-elicited craving is well characterized in alcohol and other substances of abuse, only recently has it been described in cannabis. A review of the extant literature has established that cue-elicited craving is a powerful reinforcer that contributes to drug-seeking for cannabis. Further, emergent research has begun to identify the neurobiological systems and neural mechanisms associated with this behavior. What research shows is that while theories of THC's effects on the dopaminergic-reward system remain divergent, cannabis cues elicit neural activation in the brain's reward network.     

The importance of different immunosuppressive regimens in the development of posttransplant diabetes mellitus

Solid-organ transplantation is the optimal long-term treatment for most patients with end-stage organ failure. After solid-organ transplantation, short-term graft survival significantly improved (1). However, due to chronic allograft nephropathy and death with functioning graft, long-term survival has not prolonged remarkably (2). Posttransplant immunosuppressive medications consist of one of the calcineurin inhibitors in combination with mycophenolate mofetil (MMF) or azathioprine (Aza) and steroids. All of them have different adverse effects, among which posttransplant diabetes mellitus (PTDM) is an independent risk factor for cardiovascular (CV) events and infections causing the death of many transplant patients and it may directly contribute to graft failure (3). According to the criteria of the American Diabetes Association (4), diabetes mellitus (DM) is defined by symptoms of diabetes (polyuria and polydipsia and weight loss) plus casual plasma glucose concentration ≥ 11.1 mmol/L or fasting plasma glucose (FPG) ≥ 7.0 mmol/L or 2-h plasma glucose level ≥ 11.1 mmol/L following oral glucose tolerance test (OGTT). This metabolic disorder occurring as a complication of organ transplantation has been recognized for many years. PTDM, which is a combination of decreased insulin secretion and increased insulin resistance, develops in 4.9/15.9% of liver transplant patients, in 4.7/11.5% of kidney recipients, and in 15/17.5% of heart and lung transplants [cyclosporine A (CyA)/tacrolimus (Tac)-based regimen, respectively] (5). Risk factors of PTDM can be divided into non-modifiable and modifiable ones (6), among which the most prominent is the immunosuppressive therapy being responsible for 74% of PTDM development (7). Emphasizing the importance of the PTDM, numerous studies have determined the long-term outcome. On the basis of these studies, graft and patient survival is tendentiously (8) or significantly (9, 10) decreased for those developing PTDM.     

Spatiotemporal dynamics of auditory and picture naming-related high-gamma modulations: A study of Japanese-speaking patients

ObjectiveTo characterize the spatiotemporal dynamics of auditory and picture naming-related cortical activation in Japanese-speaking patients.MethodsTen patients were assigned auditory naming and picture naming tasks during extraoperative intracranial EEG recording in a tertiary epilepsy center. Time-frequency analysis determined at what electrode sites and at what time windows during each task the amplitude of high-gamma activity (65–95 Hz) was modulated.ResultsThe superior-temporal gyrus on each hemisphere showed high-gamma augmentation during sentence listening, whereas the left middle-temporal and inferior-frontal gyri showed high-gamma augmentation peaking around stimulus offset. Auditory naming-specific high-gamma augmentation was noted in the bilateral superior-temporal gyri as well as left frontal-parietal-temporal perisylvian network regions, whereas picture naming-specific augmentation was noted in the occipital-fusiform regions, bilaterally. The inferior pre- and postcentral gyri on each hemisphere showed modality-common high-gamma augmentation time-locked to overt responses.ConclusionsThe spatiotemporal dynamics of auditory and picture naming-related high-gamma augmentation in Japanese-speaking patients were qualitatively similar to those previously reported in studies of English-speaking patients.SignificanceThe cortical dynamics for auditory sentence recognition are at least partly shared by cohorts speaking two distinct languages. Multicenter studies regarding the clinical utility of high-gamma language mapping across Eastern and Western hemispheres may be feasible.