Diabetes mellitus and the β cell: the last ten years

Diabetes is a major global problem. During the past decade, the genetic basis of various monogenic forms of the disease, and their underlying molecular mechanisms, have been elucidated. Many genes that increase type 2 diabetes (T2DM) risk have also been identified, but how they do so remains enigmatic. Nevertheless, defective insulin secretion emerges as the main culprit in both monogenic and polygenic diabetes, with environmental and lifestyle factors, via obesity, accounting for the current dramatic increase in T2DM. There also have been significant advances in therapy, particularly for some monogenic disorders. We review here what ails the β cell and how its function may be restored.     

Polymorphic Variants of the Renin–Angiotensin System Genes in the Polymetabolic Syndrome and Non-Insulin-Dependent Diabetes Mellitus

Polymorphisms of the genes for angiotensin-converting enzyme (ACE) and angiotensinogen, the proteins of the renin–angiotensin system (RAS), were tested for association with the polymetabolic syndrome (PMS) and non-insulin-dependent diabetes mellitus (NIDDM) in the Moscow population. The insertional (I) allele and the IIgenotypeof the ACE gene proved to be associated with PMS. A significant difference in allele and genotype frequency distributions of the (CA) _n microsatellite of the 3"-untranslated exon of the angiotensinogen gene was revealed between randomly sampled individuals and patients with PMS and IDDM from the Moscow population.     

Cadmium Exposure and Incidence of Diabetes Mellitus - Results from the Malm? Diet and Cancer Study

Background

Cadmium is a pollutant with multiple adverse health effects: renal dysfunction, osteoporosis and fractures, cancer, and probably cardiovascular disease. Some studies have reported associations between cadmium and impaired fasting glucose and diabetes. However, this relationship is controversial and there is a lack of longitudinal studies.

Objectives

To examine prospectively whether cadmium in blood is associated with incidence of diabetes mellitus.

Methods

The study population consists of 4585 subjects without history of diabetes (aged 46 to 67 years, 60% women), who participated in the Malmö Diet and Cancer study during 1991–1994. Blood cadmium levels were estimated from hematocrit and cadmium concentrations in erythrocytes. Incident cases of diabetes were identified from national and local diabetes registers.

Results

Cadmium concentrations in blood were not associated with blood glucose and insulin levels at the baseline examination. However, cadmium was positively associated with HbA1c in former smokers and current smokers. During a mean follow-up of 15.2±4.2 years, 622 (299 men and 323 women) were diagnosed with new-onset of diabetes. The incidence of diabetes was not significantly associated with blood cadmium level at baseline, neither in men or women. The hazard ratio (4^th vs 1^st quartile) was 1.11 (95% confidence interval 0.82–1.49), when adjusted for potential confounders.

Conclusions

Elevated blood cadmium levels are not associated with increased incidence of diabetes. The positive association between HbA1c and blood cadmium levels has a likely explanation in mechanisms related to erythrocyte turnover and smoking.     

Diabetes Mellitus and the Risk of Alzheimer’s Disease: A Nationwide Population-Based Study

Objectives

Possible association between diabetes mellitus (DM) and Alzheimer’s disease (AD) has been controversial. This study used a nationwide population-based dataset to investigate the relationship between DM and subsequent AD incidence.

Methods

Data were collected from Taiwan’s National Health Insurance Research Database, which released a cohort dataset of 1,000,000 randomly sampled people and confirmed it to be representative of the Taiwanese population. We identified 71,433 patients newly diagnosed with diabetes (age 58.74±14.02 years) since January 1997. Using propensity score, we matched them with 71,311 non-diabetic subjects by time of enrollment, age, gender, hypertension, hyperlipidemia, and previous stroke history. All the patients were followed up to December 31, 2007. The endpoint of the study was occurrence of AD.

Results

Over a maximum 11 years of follow-up, diabetic patients experienced a higher incidence of AD than non-diabetic subjects (0.48% vs. 0.37%, p<0.001). After Cox proportional hazard regression model analysis, DM (hazard ratio [HR], 1.76; 95% confidence interval [CI], 1.50–2.07, p<0.001), age (HR, 1.11; 95% CI, 1.10–1.12, p<0.001), female gender (HR, 1.24; 95% CI, 1.06–1.46, p = 0.008), hypertension (HR, 1.30; 95% CI, 1.07–1.59, p = 0.01), previous stroke history (HR, 1.79; 95% CI, 1.28–2.50, p<0.001), and urbanization status (metropolis, HR, 1.32; 95% CI, 1.07–1.63, p = 0.009) were independently associated with the increased risk of AD. Neither monotherapy nor combination therapy with oral antidiabetic medications were associated with the risk of AD after adjusting for underlying risk factors and the duration of DM since diagnosis. However, combination therapy with insulin was found to be associated with greater risk of AD (HR, 2.17; 95% CI, 1.04–4.52, p = 0.039).

Conclusion

Newly diagnosed DM was associated with increased risk of AD. Use of hypoglycemic agents did not ameliorate the risk.     

《Palaeoanthropology and Paleolithic archaeology in the people's republic of China》

This excellent volume fills a much needed gap in making available to western scholarsmany of the important developments in paleoanthropology in the People's Republic of China.Discoveries in other parts of the world such as Europe and particularly Africa have often over-shadowed the valuable contributions stemming from work in China since the end of the CulturalRevolution.The editors of this volume must be congratulated for their efforts and particularlyfor providing in Chapter 1,a review chapter,an extensive and very useful bibliography.     

Attack on the East-the status and management of biological invasions in China

正WANG F,JIANG M,ZHAN A. Biological Invasions and Its Management in China. VolumeⅠ,Springer Nature,Singapore,2017,366 pp.=C 72.79 ISBN 978-94-024-0946-8WANG F,JIANG M,ZHAN A. Biological Invasions and Its Management in China. VolumeⅡ,Springer Nature,Singapore,2017,252 pp.=C 72.79 ISBN 978-981-10-3426-8Decades after ecologist realized the negative effects of species alien to local floras and faunas,and started investigating the effects of them,particularly those that cause invasions,governments started accepting the importance of this issue and biological invasions became a well-known environmental problem. In     

Ten-Year Mortality and Cardiovascular Morbidity in the Finnish Diabetes Prevention Study—Secondary Analysis of the Randomized Trial

Background

The Finnish Diabetes Prevention Study (DPS) was a randomized controlled trial, which showed that it is possible to prevent type 2 diabetes by lifestyle changes. The aim of the present study was to examine whether the lifestyle intervention had an effect on the ten-year mortality and cardiovascular morbidity in the DPS participants originally randomized either into an intervention or control group. Furthermore, we compared these results with a population-based cohort comprising individuals of varying glucose tolerance states.

Methods and Findings

Middle-aged, overweight people with IGT (n = 522) were randomized into intensive intervention (including physical activity, weight reduction and dietary counseling), or control “mini-intervention” group. Median length of the intervention period was 4 years and the mean follow-up was 10.6 years. The population-based reference study cohort included 1881 individuals (1570 with normal glucose tolerance, 183 with IGT, 59 with screen-detected type 2 diabetes, 69 with previously known type 2 diabetes) with the mean follow-up of 13.8 years. Mortality and cardiovascular morbidity data were collected from the national Hospital Discharge Register and Causes of Death Register. Among the DPS participants who consented for register linkage (n = 505), total mortality (2.2 vs. 3.8 per 1000 person years, hazard ratio HR = 0.57, 95% CI 0.21–1.58) and cardiovascular morbidity (22.9 vs. 22.0 per 1000 person years, HR = 1.04, 95% CI 0.72–1.51) did not differ significantly between the intervention and control groups. Compared with the population-based cohort with impaired glucose tolerance, adjusted HRs were 0.21 (95% CI 0.09–0.52) and 0.39 (95% CI 0.20–0.79) for total mortality, and 0.89 (95% CI 0.62–1.27) and 0.87 (0.60–1.27) for cardiovascular morbidity in the intervention and control groups of the DPS, respectively. The risk of death in DPS combined cohort was markedly lower than in FINRISK IGT cohort (adjusted HR 0.30, 95% CI 0.17–0.54), but there was no significant difference in the risk of CVD (adjusted HR 0.88, 95% CI 0.64–1.21).

Conclusions

Lifestyle intervention among persons with IGT did not decrease cardiovascular morbidity during the first 10 years of follow-up. However, the statistical power may not be sufficient to detect small differences between the intervention and control groups. Low total mortality among participants of the DPS compared with individuals with IGT in the general population could be ascribed to a lower cardiovascular risk profile at baseline and regular follow-up.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00518167","term_id":"NCT00518167"}}NCT00518167     

Association of Pulmonary Tuberculosis and Diabetes in Mexico: Analysis of the National Tuberculosis Registry 2000–2012

Background

Tuberculosis (TB) remains a public health problem in Mexico while the incidence of diabetes mellitus type 2 (DM) has increased rapidly in recent years.

Objective

To describe the trends of incidence rates of pulmonary TB associated with DM and not associated with DM and to compare the results of treatment outcomes in patients with and without DM.

Materials and Methods

We analysed the National Tuberculosis Registry from 2000 to 2012 including patients with pulmonary TB among individuals older than 20 years of age. The association between DM and treatment failure was analysed using logistic regression, accounting for clustering due to regional distribution.

Results

In Mexico from 2000 to 2012, the incidence rates of pulmonary TB associated to DM increased by 82.64%, (p <0.001) in contrast to rates of pulmonary TB rate without DM, which decreased by 26.77%, (p <0.001). Patients with a prior diagnosis of DM had a greater likelihood of failing treatment (adjusted odds ratio, 1.34 (1.11–1.61) p <0.002) compared with patients who did not have DM. There was statistical evidence of interaction between DM and sex. The odds of treatment failure were increased in both sexes.

Conclusion

Our data suggest that the growing DM epidemic has an impact on the rates of pulmonary TB. In addition, patients who suffer from both diseases have a greater probability of treatment failure.     

The Islands in the South China Sea: How Does Their Presence Limit the Extent of the High Seas and the Area and the Maritime Zones of the Mainland Coasts?

A number of small islands (the Paracel Islands, Pratas Island, the Spratly Islands, and Scarborough Reef) may have a considerable influence on the extent of maritime zones in the South China Sea. The maritime zones of these islands can limit the extent of the high seas and the Area in the South China Sea and the extent of the maritime zones of the mainland coasts. To assess the impact of the islands, it is necessary to establish whether they can generate the full suite of maritime zones. Under international law, some islands do not have an entitlement to an exclusive economic zone and continental shelf. Where islands can generate these maritime zones, a second issue arises, namely, how to delimit these zones with those of the mainland coasts bordering the South China Sea.     

Diabetes and Cognitive Decline: Are Steroids the Missing Link?

Although elevated cortisol levels may be found in diabetes, cortisol's role in diabetes-associated cognitive impairment is unclear. A recent study (Stranahan et al., 2008) shows that reducing glucocorticoid levels in rodent diabetes models prevents cognitive deficits and enhances neurogenesis and synaptic plasticity. The clinical relevance of these intriguing findings remains undetermined.     

Deregulation of Pancreas-Specific Oxidoreductin ERO1β in the Pathogenesis of Diabetes Mellitus

A growing body of evidence has underlined the significance of endoplasmic reticulum (ER) stress in the pathogenesis of diabetes mellitus. ER oxidoreductin 1β (ERO1β) is a pancreas-specific disulfide oxidase that is known to be upregulated in response to ER stress and to promote protein folding in pancreatic β cells. It has recently been demonstrated that ERO1β promotes insulin biogenesis in β cells and thus contributes to physiological glucose homeostasis, though it is unknown if ERO1β is involved in the pathogenesis of diabetes mellitus. Here we show that in diabetic model mice, ERO1β expression is paradoxically decreased in β cells despite the indications of increased ER stress. However, overexpression of ERO1β in β cells led to the upregulation of unfolded protein response genes and markedly enlarged ER lumens, indicating that ERO1β overexpression caused ER stress in the β cells. Insulin contents were decreased in the β cells that overexpressed ERO1β, leading to impaired insulin secretion in response to glucose stimulation. These data indicate the importance of the fine-tuning of the ER redox state, the disturbance of which would compromise the function of β cells in insulin synthesis and thus contribute to the pathogenesis of diabetes mellitus.     

Quantitative classification and carbon density of the forest vegetation in Lüliang Mountains of China

Forests play a major role in global carbon (C) cycle, and the carbon density (CD) could reflect its ecological function of C sequestration. Study on the CD of different forest types on a community scale is crucial to characterize in depth the capacity of forest C sequestration. In this study, based on the forest inventory data of 168 field plots in the study area (E 111°30′–113°50′, N 37°30′–39°40′), the forest vegetation was classified by using quantitative method (TWINSPAN); the living biomass of trees was estimated using the volume-derived method; the CD of different forest types was estimated from the biomass of their tree species; and the effects of biotic and abiotic factors on CD were studied using a multiple linear regression analysis. The results show that the forest vegetation in this region could be classified into 9 forest formations. The average CD of the 9 forest formations was 32.09 Mg ha⁻¹ in 2000 and 33.86 Mg ha⁻¹ in 2005. Form. Picea meyeri had the highest CD (56.48 Mg ha⁻¹), and Form. Quercus liaotungensis + Acer mono had the lowest CD (16.14 Mg ha⁻¹). Pre-mature forests and mature forests were very important stages in C sequestration among four age classes in these formations. Forest densities, average age of forest stand, and elevation had positive relationships with forest CD, while slope location had negative correlation with forest CD.     

A New Genus and Species—Cycadostrobilus paleozoicus Zhu of Cycadaceae from the Permian of China

This paper describes a new microstrobilus of palaeozoic Cycadaceae collected from the upper part of Lower Shihezi Formation, Dongshan Mine, Taiyuan, Shanxi, China and named it as Cycadostrobilus paleozoicus Zhu, gen. et sp. nov. This new cycad is the oldest microstrobilus to our knowlege of cycads. In the same locality and layer, there are Primocycas chinensis Zhu et Du, Sphenophyllum emarginatum Brongn. , S. costae Sterz. , S. verticallatum (Schloth.) Brongn. , S. oblongifolium (Germ. et Kaulf. ) Ung. , Tingia carbonica (Schenk.) Halle, T. hamaguchii Kon’no, Macrostachys huttoniformis Halle, Sphenopteris norinii Halle, S. firmata Sze, S. gothanii Halle, Sphenopteridium pseudogermanicum (Halle) Gu et Zhi, Pecopteris feminaeformis (Schloth.) Sterz. , P. wongii Halle, P. tuberculata Halle, P. unita Brongn. , P. taiyuanensis Halle, Emplectopteris triangularis Halle, Taeniopteris norinii Halle, T. spp. , Cordaites principalis (Germ.) Gein. , Cornucarpus patulus Halle, Radicites spp. and a few taxa unknown to palaeobotanical data. The authors consider that Cycadostrobilus paleozoicus is the same species as Primocycas chinensis, and its veg.etative leaves are similar to those of the genus Taeniopteris, e.g.T. norinii Halle.     

Plants of Leptostrobus Heer （Czekanowskiales） from the Early Cretaceous and Late Triassic of China, with Discussion of the Genus

Investigation of the Mesozoic seed plant Leptostrobus Heer from the Yangcaogou Formation of the Late Triassic and the Yixian Formation of the Early Cretaceous, Liaoning Province, China, provides new Insight Into Its general morphology and geographical distribution. The materials of L. cancer from the Yixian Formation described herein are later than all the past findings of this species and add to the record of L. cancer during the Early Cretaceous. Based on well-preserved specimens, the specific diagnosis Is slightly emended and the reconstructlon of L. cancer Is perfected. The materials from the Yangcaogou Formation of the Late Triassic are placed in L. spheericus, in addition, we review the history of investigation of the genus Leptostrobus since its establishment in 1876 and discuss the main characteristics of each species.     

Diabetes and the heart: could the diabetic myocardium be protected by preconditioning?

Both type 1 and type 2 diabetes (insulin-dependent and non-insulin dependent diabetes, respectively) are associated with increased risk for microvascular and macrovascular complications including retinopathy, neuropathy, nephropathy and atherosclerosis. Type 2 diabetes markedly increases the risk for cardiovascular morbidity and mortality, which has major public health implications. In this review, molecular mechanisms pertaining to diabetes-induced heart pathology are addressed.     

The Effect of Experimental Diabetes on the Twenty‐Four‐Hour Pattern of the Vasodilator Responses to Acetylcholine and Isoprenaline ın the Rat Aorta

The aim of this study was to investigate whether time‐dependent variations in the relaxant effect of acetylcholine, an endothelium‐dependent vasorelaxant via muscarinic receptors, and isoprenaline, a nonselective β‐adrenoceptor agonist in rat aorta, are influenced by streptozotocin (STZ)‐induced experimental diabetes. Adult male rats were divided randomly into two groups: control and STZ‐induced (STZ, 55 mg/kg, intraperitoneal) diabetes. The animals were synchronized to a 12∶12 h light‐dark cycle (lights on 08∶00 h) and sacrificed at six different times of day (1, 5, 9, 13, 17, and 21 hours after lights on; HALO) eight weeks after STZ injection. The in vitro responsiveness of thoracic aorta rings obtained from control and diabetic rats to acetylcholine (10^?9–10^?5 M) and isoprenaline (10^?10–10^?3 M) was determined in six different times. EC₅₀ (the concentration inducing half of the maximum response) values and maximum responses were calculated from cumulative concentration‐response curves of the agonists and were analyzed with respect to time and STZ treatment. Treatment, time, and interactions between treatment and time were tested by two‐way analysis of variance (ANOVA). To analyze differences due to biological time, one‐way ANOVA was used. STZ treatment did not significantly change EC₅₀ values or maximum responses for both agonists. There were statistically significant time‐dependent variations in the EC₅₀ values for isoprenaline and maximum responses for both acetylcholine and isoprenaline in control groups by one‐way ANOVA, but significant time‐dependent variations disappeared in the aortas isolated from STZ‐induced diabetic rats. The vasodilator responses to acetylcholine and isoprenaline failed to show any significant interaction (treatment×time of study) between STZ treatment and time of sacrifice in both EC₅₀ values and maximum responses by two‐way ANOVA. These results indicate there is a basic temporal pattern in the responses to acetylcholine and isoprenaline in rat aorta which continues in diabetes. It is shown for the first time that experimental diabetes does not change the 24 h pattern of responses to acetylcholine and isoprenaline, and that time‐dependent variations in the responses to these agonists disappear in diabetic animals. Although further studies are required to define the underlying mechanism(s) of these findings, results suggest that experimental diabetes can modify the time‐dependent vasorelaxant responses of rat aorta. This may help to understand the circadian rhythms in cardiovascular physiology and pathology or in drug effects in diabetes.     

Who Will Manage American Patients With Diabetes? Residents’ Career Preferences and Perceptions of Diabetes Care

ObjectiveTo identify the factors that encourage or discourage internal medicine and pediatric residents regarding specializing in endocrinology with a focus on diabetes.MethodsWe conducted an electronic survey of internal medicine and pediatric residents using a $10 participation incentive. A total of 653 residents responded to the survey (estimated response rate of 9.2%)—626 from residency programs that were contacted for our survey and 27 from referrals.ResultsAmong internal medicine and pediatric residents surveyed, 39 respondents (6.0%) planned to specialize in endocrinology, and 27 of these (4.1% of total respondents) planned to focus on diabetes. “Intellectual satisfaction, ” “emotional satisfaction, ” and “work-life balance” were identified by respondents as the most important factors in their choice of a specialty, with ratings of 5.5, 5.4, and 5.3 on a 6-point Likert scale. Among these factors identified as most important to a medical career, endocrinology with a focus on diabetes scored poorly with regard to intellectual and emotional satisfaction but received high ranking with regard to lifestyle. With regard to other factors, endocrinology was rated negatively on “compensation, ” “number of procedures, ” and “patient adherence to prescribed treatment.” Exposure to diabetes during training had no major influence on the decision to enter endocrinology.ConclusionEndocrinology with a focus on diabetes care is not an attractive specialty for most internal medicine and pediatric residents. Therefore, new strategies to attract residents to the field of diabetes care are needed. (Endocr Pract. 2011;17:235-239)