2型糖尿病一级亲属代谢相关指标分布规律的研究

为了研究2型糖尿病(DM)家系一级亲属的代谢相关指标变化规律,选择55个2型糖尿病家系中糖尿病患者的一级亲属为研究对象,按照糖耐量试验结果分组,比较组间血压、血糖、血脂、C肽、胰岛素等指标。结果显示,2型糖尿病家系一级亲属各组血脂水平的变化差异无显著性,而血糖、胰岛素抵抗等指标差异有显著性。由此得出结论,2型DM家系一级亲属血脂、血糖、血压、胰岛素等指标均有一定程度的异常,且各组间的血糖、血压、胰岛素抵抗等差异显著于血脂水平的变化。     

Unlocking the Energy Dynamics of Executive Functioning: Linking Executive Functioning to Brain Glycogen

ABSTRACT— Past work suggests that executive functioning relies on glucose as a depletable energy, such that executive functioning uses a relatively large amount of glucose and is impaired when glucose is low. Glucose from the bloodstream is one energy source for the brain, and glucose stored in the brain as glycogen is another. A review of the literature on glycogen suggests that executive functioning uses it in much the same way as glucose, such that executive functioning uses glycogen and is impaired when glycogen is low. Findings on stress, physical persistence, glucose tolerance, diabetes, sleep, heat, and other topics provide general support for this view.     

Does diabetes protect or provoke Alzheimer's disease? Insights into the pathobiology and future treatment of Alzheimer's disease

Diabetes mellitus has long been considered a risk factor for the development of vascular dementia. Epidemiologic evidence has suggested that diabetes mellitus significantly increases risk for the development of Alzheimer's disease, independent of vascular risk factors. As insulin's role as a neuromodulator in the brain has been described, its significance for AD has also emerged. Insulin dysregulation may contribute to AD pathology through several mechanisms including decreased cortical glucose utilization particularly in the hippocampus and entorhinal cortex; increased oxidative stress through the formation of advanced glycation end-products; increased Tau phosphorylation and neurofibrillary tangle formation; increased b-amyloid aggregation through inhibition of insulin-degrading enzyme. Future treatment of AD might involve pharmacologic and dietary manipulations of insulin and glucose regulation.     

Implications of Psychosocial Factors for Diabetes Outcomes among Children with Type 1 Diabetes: A Review

We adopt a risk and resistance framework to review the literature on the psychosocial factors that influence diabetes outcomes—specifically self‐care behavior (blood glucose monitoring, diet, exercise, insulin administration) and glycemic control. We examine both personal and social/environmental risk and resistance factors. We conclude by suggesting conceptual and methodological directions for future research. Conceptually, we suggest that researchers examine the synergy among variables that cut across domains, mechanisms linking psychosocial factors to diabetes outcomes, and the impact of goals on health. Methodologically, we suggest that researchers examine age, gender, and race as moderator variables; utilize momentary data collection technology; and employ more sophisticated longitudinal analyses.     

从2型糖尿病的发病机制谈糖尿病治疗的新策略

2型糖尿病的发病机制主要为胰岛素抵抗与胰岛β细胞分泌功能受损,二者相互依存、相互作用。2型糖尿病的治疗应以减轻胰岛素的抵抗和保护胰岛β细胞为主,以生活方式干预加二甲双胍作为基础治疗,根据不同个体在不同阶段所侧重的不同发病机制,采用联合、综合管理。     

Plasma BDNF is reduced among middle-aged and elderly women with impaired insulin function: Evidence of a compensatory mechanism

Brain-derived neurotrophic factor (BDNF) plays a regulatory role in neuronal differentiation and synaptic plasticity and has been linked to glucose regulation and cognition. Associations among plasma BDNF, cognition, and insulin function were explored. Forty-one participants with impaired insulin function (IIF), ranging from insulin resistance to type 2 diabetes mellitus (T2DM), were matched with 41 healthy controls on gender, age, education, and IQ. Participants received complete medical, neurological, psychiatric, and neuropsychological evaluations. IIF individuals had significantly lower plasma BDNF levels than controls, particularly females, and higher BDNF levels were associated with poorer explicit memory in IIF females, suggesting that higher levels within this group may reflect the body’s efforts to respond to damage. After accounting for age, education, and HbA1c, BDNF significantly predicted 13.1–23.5% of the variance in explicit memory in IIF women. These findings suggest that BDNF elevations within diseased groups may not always be a marker of health.     

Hippocampal memory processes are modulated by insulin and high-fat-induced insulin resistance

Insulin regulates glucose uptake and storage in peripheral tissues, and has been shown to act within the hypothalamus to acutely regulate food intake and metabolism. The machinery for transduction of insulin signaling is also present in other brain areas, particularly in the hippocampus, but a physiological role for brain insulin outside the hypothalamus has not been established. Recent studies suggest that insulin may be able to modulate cognitive functions including memory. Here we report that local delivery of insulin to the rat hippocampus enhances spatial memory, in a PI-3-kinase dependent manner, and that intrahippocampal insulin also increases local glycolytic metabolism. Selective blockade of endogenous intrahippocampal insulin signaling impairs memory performance. Further, a rodent model of type 2 diabetes mellitus produced by a high-fat diet impairs basal cognitive function and attenuates both cognitive and metabolic responses to hippocampal insulin administration. Our data demonstrate that insulin is required for optimal hippocampal memory processing. Insulin resistance within the telencephalon may underlie the cognitive deficits commonly reported to accompany type 2 diabetes.     

An evaluation of recollection and familiarity in Alzheimer’s disease and mild cognitive impairment using receiver operating characteristics

There is a need to investigate exactly how memory breaks down in the course of Alzheimer’s disease (AD). Examining what aspects of memorial processing remain relatively intact early in the disease process will allow us to develop behavioral interventions and possible drug therapies focused on these intact processes. Several recent studies have worked to understand the processes of recollection and familiarity in patients with mild cognitive impairment (MCI) and very mild AD. Although there is general agreement that these patient groups are relatively unable to use recollection to support veridical recognition decisions, there has been some question as to how well these patients can use familiarity. The current study used receiver operating characteristic (ROC) curves and a depth of processing manipulation to understand the effect of MCI and AD on the estimates of recollection and familiarity. Results showed that patients with MCI and AD were impaired in both recollection and familiarity, regardless of the depth of encoding. These results are discussed in relation to disease pathology and in the context of recent conflicting evidence as to whether familiarity remains intact in patients with MCI. The authors highlight differences in stimuli type and task difficulty as possibly modulating the ability of these patients to successfully use familiarity in support of memorial decisions.     

Sex differences in the relation of depressive symptoms, hostility, and anger expression to indices of glucose metabolism in nondiabetic adults.

This study examined the relation of depressive symptomatology, hostility, and anger expression to indices of glucose metabolism and tested whether gender moderates these associations in a sample of 135 healthy, nondiabetic adults (75 men, 60 women). The severity of depressive symptoms, hostility, and anger expression was positively associated with estimated insulin resistance (IR) and insulin in women but not in men. Anger expression was positively associated with glucose in women only. A summary score of depressive symptoms, hostility, and anger expression was positively associated with estimated IR, insulin, and glucose in women but not in men. Hence, in women, IR and elevated levels of fasting insulin and glucose may be one pathophysiological mechanism mediating the increased risk of cardiovascular disease and Type 2 diabetes associated with these psychological attributes.     

The relationship of diabetes knowledge to regimen compliance and metabolic control during pregnancy

Abstract

The relationship of diabetes knowledge to regimen compliance and metabolic control was examined in a sample of pregnant women with preexisting insulin-dependent and noninsulin-dependent diabetes mellitus (N = 27) and women who developed gestational diabetes during pregnancy (N = 45). Subjects completed self-report measures of diabetes knowledge and compliance with their diabetic regimen and blood glucose levels were monitored. Knowledge was positively, although modestly, related to dietary compliance, compliance with insulin administration and insulin reaction management recommendations, as well as fasting blood glucose levels. Findings suggest that among pregnant women, efforts to increase knowledge of diabetes specific to pregnancy may result in some improvement in selected aspects of the diabetic regimen.     

Cognitive and affective Theory of Mind in mild to moderate Alzheimer's disease

Theory of Mind (ToM) allows one's own and others' cognitive and emotional mental states to be inferred. Although many patients with Alzheimer's disease (AD) display impaired social functioning as their disease progresses, very few studies have investigated ToM in AD. Those that have done so suggest that patients' ToM deficits are the consequence of other cognitive impairments. The aim of this study was thus to investigate changes in both the cognitive and the affective dimensions of ToM in AD, using tasks designed to circumvent the patients' comprehension difficulties. Sixteen mild to moderate AD patients and 15 healthy controls matched on age, sex and education level underwent cognitive (preference judgment and first‐ and second‐order false belief) and affective (Reading the Mind in the Eyes) ToM assessments. Comprehension of false belief stories was verified and an additional neuropsychological examination was undergone. We observed impaired performances by AD patients on all the ToM tasks. While working memory and executive functioning impairments contributed to the deterioration in the more complex aspects of cognitive ToM abilities as highlighted by a correlation analysis, we failed to observe any comprehension difficulties in patients who performed poorly on simple cognitive ToM tasks, which suggests that AD truly affects cognitive ToM.     

The Impairment of Retention Induced by Insulin in Mice May Be Mediated by a Reduction in Central Cholinergic Activity

Immediate posttraining intraperitoneal injection of nonconvulsive doses of insulin (2-20 IU/kg) significantly impaired retention of male Swiss mice tested 24 h after training in a one-trial step-through inhibitory avoidance task. The dose-response curve showed a U-shaped form. However, of the doses tested, only 8 IU/kg was effective. Insulin did not affect response latencies in mice not given the footshock on the training trial, indicating that the actions of insulin on retention performance were not due to nonspecific proactive effects on response latencies. The impairing effects of insulin (8 IU/kg) on retention were time-dependent, which suggests that insulin impaired memory storage. The simultaneous administration of glucose (10-1000 mg/kg) antagonized, in a dose-related manner, the actions of insulin (8 IU/kg) on retention, suggesting that the hormone may have produced a hypoglycemic response leading to a decrease in CNS glucose availability with a subsequent memory impairment. Low subeffective doses of atropine (0.5 mg/kg) or mecamylamine (5 mg/kg), but not methylatropine (0.5 mg/kg) or hexamethonium (5 mg/kg), given immediately after training but 10 min before an ineffective dose of insulin (4 IU/kg), interacted with and impaired retention. The central anticholinesterase physostigmine (35 or 70 μg/kg), but not its quaternary analog neostigmine (35 or 70 μg/kg), prevented the memory impairment induced by insulin (8 IU/kg). Considered together, these findings are consistent with the view that a decrease in the CNS glucose availability impairs the synthesis and/or release of acetylcholine in brain regions critically involved in memory storage.     

The free and cued selective reminding test for predicting progression to Alzheimer's disease in patients with mild cognitive impairment: A prospective longitudinal study

Amnestic mild cognitive impairment (aMCI) patients carry a greater risk of conversion to Alzheimer's disease (AD). Therefore, the International Working Group (IWG) on AD aims to consider some cases of aMCI as symptomatic prodromal AD. The core diagnostic marker of AD is a significant and progressive memory deficit, and the Free and Cued Selective Reminding Test (FCSRT) was recommended by the IWG to test memory in cases of possible prodromal AD. This study aims to investigate whether the performance on the FCSRT would enhance the ability to predict conversion to AD in an aMCI group. A longitudinal study was conducted on 88 aMCI patients, and neuropsychological tests were analysed on the relative risk of conversion to AD. During follow‐up (23.82 months), 33% of the aMCI population converted to AD. An impaired FCSRT TR was significantly associated with the risk of conversion to dementia, with a mean time to conversion of 25 months. The FCSRT demonstrates utility for detecting AD at its prodromal stage, thus supporting its use as a valid clinical marker.     

Memory for Music in Alzheimer’s Disease: Unforgettable?

The notion that memory for music can be preserved in patients with Alzheimer’s Disease (AD) has been raised by a number of case studies. In this paper, we review the current research examining musical memory in patients with AD. In keeping with models of memory described in the non-musical domain, we propose that various forms of musical memory exist, and may be differentially impaired in AD, reflecting the pattern of neuropathological changes associated with the condition. Our synthesis of this literature reveals a dissociation between explicit and implicit musical memory functions. Implicit, specifically procedural musical memory, or the ability to play a musical instrument, can be spared in musicians with AD. In contrast, explicit musical memory, or the recognition of familiar or unfamiliar melodies, is typically impaired. Thus, the notion that music is unforgettable in AD is not wholly supported. Rather, it appears that the ability to play a musical instrument may be unforgettable in some musicians with AD.     

Reprint of: 'Brain insulin signaling: A key component of cognitive processes and a potential basis for cognitive impairment in type 2 diabetes'

Understanding of the role of insulin in the brain has gradually expanded, from initial conceptions of the brain as insulin-insensitive through identification of a role in regulation of feeding, to recent demonstration of insulin as a key component of hippocampal memory processes. Conversely, systemic insulin resistance such as that seen in type 2 diabetes is associated with a range of cognitive and neural deficits. Here we review the evidence for insulin as a cognitive and neural modulator, including potential effector mechanisms, and examine the impact that type 2 diabetes has on these mechanisms in order to identify likely bases for the cognitive impairments seen in type 2 diabetic patients.     

Effects of combined treatment with vitamins C and E on passive avoidance learning and memory in diabetic rats

Learning and memory deficits occur in diabetes mellitus. Although the pathogenesis of cognitive impairment in diabetes has not been fully elucidated, factors such as metabolic impairments, vascular complications and oxidative stress are thought to play possible roles. Here we investigated the effect of chronic treatment with vitamin C (50 mg/kg, p.o), vitamin E (100 mg/kg, p.o) and both together on passive avoidance learning (PAL) and memory in male Wistar control and diabetic rats. Treatments were begun at the onset of hyperglycemia. Passive avoidance learning was assessed 30 days later. Retention was tested 24 h after training. At the end, animals were weighed and blood samples were drawn for plasma glucose measurement. Diabetes caused impairment in acquisition and retrieval processes of PAL and memory. The combination of vitamin C and E improved learning and memory in controls and reversed learning and memory deficits in diabetic rats. Combined treatment also affected the body weight and plasma glucose level of diabetic treated animals compared to untreated diabetic animals. Hypoglycemic effects and antioxidant properties of the vitamins may be involved in the nootropic effect of such treatment. These results show that combined treatment with vitamins C and E improved PAL and memory of control rats. In addition, combined vitamins administration to rats for 30 days from onset of diabetes alleviated the negative influence of diabetes on learning and memory. Therefore, combined vitamins treatment may provide a new potential alternative for prevention of impaired cognitive functions associated with diabetes and may warrant further clinical study.     

2型糖尿病大血管病变机理和糖尿病治疗

2型糖尿病大血管病变与代谢综合征密切相关.现代医学认为两者的根本原因是胰岛素抵抗,导致糖耐量下降,血脂紊乱,高胰岛素血症,高血压和高凝状态等.从系统论的观点阐述了代谢综合征的相互关系和2型糖尿病大血管病变发病机理,并进一步从该观点阐明2型糖尿病的防治策略.     

Brain insulin signaling: a key component of cognitive processes and a potential basis for cognitive impairment in type 2 diabetes

Understanding of the role of insulin in the brain has gradually expanded, from initial conceptions of the brain as insulin-insensitive through identification of a role in regulation of feeding, to recent demonstration of insulin as a key component of hippocampal memory processes. Conversely, systemic insulin resistance such as that seen in type 2 diabetes is associated with a range of cognitive and neural deficits. Here we review the evidence for insulin as a cognitive and neural modulator, including potential effector mechanisms, and examine the impact that type 2 diabetes has on these mechanisms in order to identify likely bases for the cognitive impairments seen in type 2 diabetic patients.     

Functional decline in the early stages of Alzheimer's disease

At present most reports of functional decline in patients with Alzheimer's Disease (AD) are anecdotal, and few studies have objectively documented the course of the disease. This is a report of a 2-year follow-up of 15 AD patients characterized by mild functional impairment, and 22 age-, sex-, and education-matched control subjects. In a previous cross-sectional study of these 37 subjects and 16 AD patients with moderate functional impairment, we found that measures of memory and attention deficits accounted for much of the impairment observed in functional competence. The current longitudinal study found that these same initial assessments could be used to predict functional decline in the 15 mildly impaired patients. These patients were observed to decline to levels similar to those of the 16 moderate patients. In contrast, the control subjects exhibited little decline during the same period. These results both affirm that it is possible to diagnose AD in its mild form and demonstrate the validity of the initial diagnosis.     

Glucose metabolism,hippocampal subfields and cognition in first-episode and never-treated schizophrenia

BackgroundPrevious studies have indicated that glucose metabolism and altered hippocampal structure and function play a pivotal role in cognitive deficits in schizophrenia (SZ). This study was designed to explore the inter-relationship between glucose metabolism, hippocampal subfield volume, and cognitive function in the antipsychotics-naive first episode (ANFE) SZ patients.MethodsWe chose the fasting insulin, glucose, and insulin resistance (HOMA-IR) index as biomarkers of glucose metabolism. Cognitive function was assessed by the MATRICS Consensus Cognitive Battery (MCCB). The hippocampal subfield volume, glucose metabolism biomarkers, and cognitive function were evaluated in 43 ANFE SZ and 29 healthy controls (HCs).ResultsCompared with HCs, SZ patients had higher fasting blood glucose and insulin levels and HOMA-IR (all p < 0.05). Correlation analysis revealed that category fluency performance was positively associated with fasting glucose level. Fasting insulin or HOMA-IR was positively associated with the hippocampal subfield volume in patients (all p<0.05). Moreover, the spatial span index score was associated with the volume of the right presubiculum, subiculum, and right hippocampal tail. In addition, multiple regression analysis found that the interaction effects of insulin × right fimbria or insulin × left fimbria were independent predictors of the MCCB total score.ConclusionsOur findings suggest that abnormal glucose metabolism and cognitive decline occur in the early stage of SZ. The interaction between abnormal glucose metabolism and hippocampal subfields was associated with cognitive functions in SZ.