Methodological and physiological test–retest reliability of 13C‐MRS glycogen measurements in liver and in skeletal muscle of patients with type 1 diabetes and matched healthy controls

Glycogen is a major substrate in energy metabolism and particularly important to prevent hypoglycemia in pathologies of glucose homeostasis such as type 1 diabetes mellitus (T1DM). ¹³C‐MRS is increasingly used to determine glycogen in skeletal muscle and liver non‐invasively; however, the low signal‐to‐noise ratio leads to long acquisition times, particularly when glycogen levels are determined before and after interventions. In order to ease the requirements for the subjects and to avoid systematic effects of the lengthy examination, we evaluated if a standardized preparation period would allow us to shift the baseline (pre‐intervention) experiments to a preceding day. Based on natural abundance ¹³C‐MRS on a clinical 3 T MR system the present study investigated the test–retest reliability of glycogen measurements in patients with T1DM and matched controls (n = 10 each group) in quadriceps muscle and liver. Prior to the MR examination, participants followed a standardized diet and avoided strenuous exercise for two days. The average coefficient of variation (CV) of myocellular glycogen levels was 9.7% in patients with T1DM compared with 6.6% in controls after a 2 week period, while hepatic glycogen variability was 13.3% in patients with T1DM and 14.6% in controls. For comparison, a single‐session test–retest variability in four healthy volunteers resulted in 9.5% for skeletal muscle and 14.3% for liver. Glycogen levels in muscle and liver were not statistically different between test and retest, except for hepatic glycogen, which decreased in T1DM patients in the retest examination, but without an increase of the group distribution. Since the CVs of glycogen levels determined in a “single session” versus “within weeks” are comparable, we conclude that the major source of uncertainty is the methodological error and that physiological variations can be minimized by a pre‐study standardization. For hepatic glycogen examinations, familiarization sessions (MR and potentially strenuous interventions) are recommended. Copyright © 2016 John Wiley & Sons, Ltd.     

Dietary knowledge,attitude and practice among type 2 diabetes mellitus patients in Sudan: a hospital-based cross-sectional study

BackgroundIn Sudan, the prevalence of diabetes in adults was estimated at 19.1% in 2015. This study assessed dietary knowledge, attitude, and practices (KAP) of type 2 diabetes mellitus (T2DM) patients in Sudan.MethodsWe randomly selected 238 T2DM patients from a list of 2460 patients from the Jabber Abulizz Hospital. We interviewed them face-to-face using a structured questionnaire. Multivariate logistic regression analyses were performed to investigate the determinants of KAP regarding the recommended diets for T2DM patients.ResultsMajority of the patients demonstrated good knowledge (54.6%), positive attitude (79%); and good practice (58%). The result revealed that patients with formal education had 3.0 (95% CI: 1.6–5.7) times higher odds of having good diabetic dietary knowledge than those with informal education. While patients who had good knowledge and a positive attitude were respectively 4.7 (95% CI: 2.4–8.9) and 3.2 (95% CI: 1.5–6.7) times more likely to follow dietary recommendations than the patients with poor knowledge and negative attitudes.ConclusionIrrespective of the socio-demographic position, the good knowledge and the positive attitude towards the recommended diet, all the T2DM patients complied with the dietary recommendations. These findings highlight the need for improving knowledge and promoting positive attitudes towards the recommended diet among T2DM patients.     

Management of type 2 diabetes with multiple oral hypoglycaemic agents or insulin in primary care: retrospective cohort study

BACKGROUND: Intensive glycaemic control can reduce the risk of microvascular complications in people with type 2 diabetes. AIM: To examine the extent of monitoring and glycaemic control of patients with type 2 diabetes prescribed oral agents and/or insulin, and to investigate transition to insulin. DESIGN OF STUDY: Retrospective cohort study. SETTING: A total of 154 general practices in the UK contributing to the DIN-LINK database between 1995 and 2005. METHOD: People with type 2 diabetes were identified using Read codes and prescribing data. Outcome measures were: glycaemic monitoring and control on multiple oral agents and/or insulin, and transition to insulin. RESULTS: A total of 14 824 people with type 2 diabetes were prescribed multiple oral agents concurrently, of whom 5064 (34.16%) had haemoglobin A(1c) (HbA(1c)) assessments 6 months before and following initiation of their last oral therapy. Mean HbA(1c) before therapy was 9.07%, which dropped to 8.16% following therapy (mean difference 0.91%, 95% confidence interval [CI] = 0.86 to 0.95, P <0.0001). Of the patients with HbA(1c) assessments, 3153 (62.26%) had evidence of poor glycaemic control following therapy. Median time to insulin for patients prescribed multiple oral agents was 7.7 years (95% CI = 7.4 to 8.5 years); 1513 people began insulin during the study and had HbA(1c) assessments 6 months before and following insulin. Mean HbA(1c) before insulin was 9.85% (standard deviation [SD] 1.96%) which decreased by 1.34%, (95% CI = 1.24% to 1.44%) following therapy, but 1110 people (73.36%) still had HbA(1c) > or =7.5%. CONCLUSION: Many people with type 2 diabetes received inadequate monitoring and had poor glycaemic control. Intensive management is required to reduce the risk of microvascular complications.     

Metabolic bariatric surgery and type 2 diabetes mellitus: an endocrinologist's perspective

Traditional treatment of T2DM consisting of modification of diet, an exercise regimen, and pharmacotherapy has problems of poor lifestyle modifications and fail tend of treatment over time, now bariatric surgery is recommended for treatment of obese patients with T2DM because its great improvements on weight loss and metabolic. In this article, effects of bariatric surgery on diabetes and diabetes-related complications are reviewed.     

神经源分化因子基因多态性与2型糖尿病的关联性研究

目的　探讨神经源分化因子 (neurogenic differentiation factor 1,Neuro D)基因多态性与 2型糖尿病发生的关联性。方法　运用错配聚合酶链反应 -限制性片段长度多态性方法检测了中国湖北地区汉族 32 4例 2型糖尿病 (其中以发病年龄 40岁为界 ,分为早发及晚发两组 )及 12 4名正常对照者 ,Neuro D基因第 45位密码子碱基变异 (GCC→ ACC)。结果　 Neuro D基因在所测人群中未发现有纯合变异者。在早发 2型糖尿病组 ,其 AT基因型频率为 2 6 .8% ,与正常对照组 (10 .5 % )及晚发 2型糖尿病组 (11.6 % )比较 ,差异有显著性 (分别为χ2 =7.85 ,P=0 .0 0 5 ;χ2 =8.81,P=0 .0 0 3) ;Thr45等位基因频率在早发 2型糖尿病组及正常对照组、晚发 2型糖尿病组分别为 13.4%、5 .2 %和 5 .8% ,差异亦有显著性 (χ2 =7.15 ,P=0 .0 0 8;χ2 =8.13,P=0 .0 0 4) ;晚发 2型糖尿病组与正常对照组比较 ,Ala45 Thr基因型频率 (11.6 % vs10 .5 % ,P>0 .0 5 )及等位基因频率 (5 .8% vs 5 .2 % ,P>0 .0 5 )差异不明显 ,Thr45等位基因与早发 2型糖尿病发生相关 (OR=2 .5 2 ,95 % CI:1.42～ 4.49) ;基因型为 AT型的 2型糖尿病患者其空腹血浆 C肽水平较 AA型患者低 ,差异有显著性 (P<0 .0 5 )。结论　 Neuro D基因多态性与早发 2型糖尿     

Crystallization of oral fluid components in patients with type 2 diabetes mellitus

Crystal aggregations of oral fluid from normal subjects and patients with type 2 diabetes mellitus were examined. Morphological signs characterizing crystal aggregations of salivary pools from patients with type 2 diabetes mellitus are described and classified. Translated fromByulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 138, No. 9, pp. 345–347, September, 2004     

Crystallization of oral fluid components in patients with type 2 diabetes mellitus

Crystal aggregations of oral fluid from normal subjects and patients with type 2 diabetes mellitus were examined. Morphological signs characterizing crystal aggregations of salivary pools from patients with type 2 diabetes mellitus are described and classified.Translated from Byulleten Eksperimentalnoi Biologii i Meditsiny, Vol. 138, No. 9, pp. 345–347, September, 2004     

Association of toll‐like receptor 4 polymorphisms with type 2 diabetes mellitus

Toll‐like receptor 4 (TLR4) plays important roles in modulating innate immunity. Type 2 diabetes mellitus (T2DM) is a chronic and complex disease that is characterized by impaired insulin resistance and dysregulated immune response. In the current study, we investigated whether TLR4 polymorphisms were correlated with susceptibility to T2DM in the Chinese population. Four TLR4 polymorphisms (?2431T/C, Asp299Gly, Thr399Il3, and +3725G/C) were genotyped in 936 T2DM patients and 978 healthy controls. Results showed that the prevalence of TLR4 +3725GC and CC genotypes was significantly decreased in T2DM cases than those in controls [odds ratio (OR) = 0.68, 95% confidence interval (CI) = 0.55–0.84, p = 0.0003, and OR=0.46, 95% CI = 0.32–0.67, p = 3.71 × 10^?5, respectively). Also, the frequency of TLR4 +3725C allele was significantly lower in T2DM patients (p = 2.50 × 10^?8). The ?2431T/C did not reveal any significant differences between cases and controls. We did not detect Asp299Gly and Thr399Il3 polymorphisms in our study group. Stratification analysis of the clinical features in the patients demonstrated that frequency of +3725CC genotype was lower in patients older than 50 years old (p = 0.047). In conclusion, these results indicate that TLR4 +3725G/C polymorphism may be a novel protective factor against T2DM in the Chinese population.     

Enlarged PLIN5-uncoated lipid droplets in inner regions of skeletal muscle type II fibers associate with type 2 diabetes

Skeletal muscle physiology remains of paramount importance in understanding insulin resistance. Due to its high lipid turnover rates, regulation of intramyocellular lipid droplets (LDs) is a key factor. Perilipin 5 (PLIN5) is one of the most critical agents in such regulation, being often referred as a protector against lipotoxicity and consequent skeletal muscle insulin resistance. We examined area fraction, size, subcellular localization and PLIN5 association of LDs in two fiber types of type 2 diabetic (T2D), obese (OB) and healthy (HC) individuals by means of fluorescence microscopy and image analysis. We found that T2D type II fibers have a significant sub-population of large and internalized LDs, uncoated by PLIN5. Based on this novel result, additional hypotheses for the pathophysiology of skeletal muscle insulin resistance are formulated, together with future research directions.     

对氧磷酶2基因C311S多态性与2型糖尿病合并缺血性脑卒中的相关性

目的 探讨对氧磷酶2(paraoxonase 2，PON2)基因多态性与2型糖尿病(type 2 diabetes mellitus，T2DM)患者合并缺血性脑卒中(ischemic stroke，IS)的关系。方法 用聚合酶链反应—限制性片段长度多态性分析法探查PON2基因C311S多态性在T2DM合并IS组、T2DM无IS组以及正常对照组的基因频率。结果 发现中国人存在PON2基因C311S多态性，C／S等位基因频率为0．145／0．855。T2DM合并IS组患者PON2基因的C等位基因频率显著高于T2DM无IS组和正常对照组，差异有显著性(P＜0．05)。结论 中国人2型糖尿病患者PON2基因第311位密码子的多态性与并发缺血性脑卒中有关，C等位基因是2型糖尿病并发缺血性脑卒中的危险因素之一。     

Association of hypoadiponectinemia with hypoglutathionemia in NAFLD subjects with and without type 2 diabetes

Objective: The aim of this study is to measure the extent of oxidative stress and to see whether it has any correlation to changes in adiponectin levels in NAFLD subjects with and without Type 2 diabetes. Methods: Subjects recruited from the Chennai Urban Rural Epidemiology Study comprise of 1: Normal Glucose Tolerance (NGT) subjects without NAFLD; 2: NGT with NAFLD; 3: Type 2 Diabetic patients [T2DM] without NAFLD and 4: T2DM with NAFLD. Thiobarbituric acid reactive substances (TBARS), protein carbonyl (PCO), glutathione and adiponectin levels were measured by standard methods. Ultrasound of the liver was used to diagnose NAFLD. Results: T2DM subjects with NAFLD had significantly (p < 0.001) higher levels of thiobarbituric acid reactive substances (TBARS) and protein carbonyls (PCO) but lower (p < 0.001) GSH/GSSG ratio and adiponectin levels compared to other three groups. The association of hypoadiponectinemia withNAFLD/Type 2 diabetes was significant even after adjusting for age, gender and BMI, but lost when adjusted for parameters of oxidative stress. While palmitate significantly reduced GSH/GSSG ratio in hepatocytes, addition of exogenous recombinant adiponectin restored the GSH/GSSG ratio comparable to those of untreated cells. Conclusion: There exists an association of hypoglutathionemia and hypoadiponectinemia in subjects with NAFLD and/or T2DM. In addition to the known beneficial effects, out study also exposes the antioxidant nature of adiponectin.     

2型糖尿病易感位点的功能性L1逆转录转座子的研究

目的通过一种新的策略寻找2型糖尿病的易感基因.方法应用美国生物技术信息中心提供的BLAST(basic local alignment search tool)检索工具,对已报道的2型糖尿病易感位点的核酸序列进行检索分析,发现功能性L1逆转录转座子可能是易感基因.然后应用逆转录-聚合酶链反应检测25例2型糖尿病患者和22名正常对照的L1逆转录转座子表达水平,用SPSS10.0软件包进行统计学分析,并对6例患者和4名正常人的L1逆转录转座子进行定位克隆、基因组序列测定.结果对人类基因组及GenBank数据库进行全面搜索分析发现L1逆转录转座子分布在除19号、21号和Y染色体外的其它染色体上.这种分布情况与已报道的易感位点在染色体上的分布情况有相似性.功能性L1逆转录转座子在2型糖尿病患者组的表达水平明显低于正常对照组(P＜0.001).L1逆转录转座子在2型糖尿病患者有不同程度的缺失和(或)无意义突变,而在正常对照无突变.结论功能性L1逆转录转座子可能是2型糖尿病的某一易感基因或者是其易感基因的重要调节因子之一.功能性L1逆转录转座子表达水平的高低可能可以作为筛选2型糖尿病的一个生物学指标.     

Reproducibility of single- and multi-voxel 1H MRS measurements of intramyocellular lipid in overweight and lean subjects under conditions of controlled dietary calorie and fat intake

The reproducibility of repeated single-voxel 1H MRS (SV-MRS) and spectroscopic imaging (MRSI) measurements of intramyocellular lipid (IMCL) in the tibialis anterior muscle of five lean and five overweight female Caucasians, during 7 days of controlled dietary fat and calorie intake, was assessed at 1.5 T. Duplicate measures of IMCL relative to total muscle creatine (IMCL/tCr) obtained 3 days apart by both SV-MRS and MRSI correlated well (r = 0.65 and r = 0.95, respectively, P < 0.05). The coefficients of variation for repeated measures of IMCL/tCr by SV-MRS and MRSI were 24.4% and 10.7%, respectively. IMCL/tCr measured by MRSI was higher in overweight subjects than in lean subjects (8.3 +/- 3.8 vs 4.3 +/- 2.4, P < 0.05). Although both methods achieved good reproducibility in measuring IMCL in vivo, MRSI was found to offer greater flexibility and reliability, and higher sensitivity to IMCL differences, whereas SV-MRS was advantageous with respect to shorter scan time and ease of implementation.     

Autonomic and sensory ganglionopathy occurring in a patient with fulminant type 1 diabetes mellitus

A 63‐year‐old male with a previous infection was admitted to our hospital because of acute pancreatitis. Although he had no history of diabetes mellitus, laboratory examinations revealed marked hyperglycemia on admission, and intensive insulin treatment was required. After 2 weeks, he developed severe pandysautonomia and sensory impairment, and eventually died from colonic perforation caused by paralytic ileus at 1 year after onset. Autopsy findings showed a complete loss of pancreatic islet beta cells with mild fibrosis of the exocrine pancreas. Neuropathological examination showed myelin loss of the dorsal fasciculus at all levels of the spinal cord and ganglionopathy of the dorsal root and sympathetic truncus, revealing degeneration of ganglion cells and a decrease in their number with the formation of Nageotte nodules. On the basis of this clinicopathological evidence, fulminant type 1 diabetes mellitus (T1DM) and idiopathic immune‐mediated autonomic neuropathy were suspected. Here, we suggest a close etiological relationship between both diseases.     

Patient reactions to a web-based cardiovascular risk calculator in type 2 diabetes: a qualitative study in primary care

Background

Use of risk calculators for specific diseases is increasing, with an underlying assumption that they promote risk reduction as users become better informed and motivated to take preventive action. Empirical data to support this are, however, sparse and contradictory.

Aim

To explore user reactions to a cardiovascular risk calculator for people with type 2 diabetes. Objectives were to identify cognitive and emotional reactions to the presentation of risk, with a view to understanding whether and how such a calculator could help motivate users to adopt healthier behaviours and/or improve adherence to medication.

Design and setting

Qualitative study combining data from focus groups and individual user experience. Adults with type 2 diabetes were recruited through website advertisements and posters displayed at local GP practices and diabetes groups.

Method

Participants used a risk calculator that provided individualised estimates of cardiovascular risk. Estimates were based on UK Prospective Diabetes Study (UKPDS) data, supplemented with data from trials and systematic reviews. Risk information was presented using natural frequencies, visual displays, and a range of formats. Data were recorded and transcribed, then analysed by a multidisciplinary group.

Results

Thirty-six participants contributed data. Users demonstrated a range of complex cognitive and emotional responses, which might explain the lack of change in health behaviours demonstrated in the literature.

Conclusion

Cardiovascular risk calculators for people with diabetes may best be used in conjunction with health professionals who can guide the user through the calculator and help them use the resulting risk information as a source of motivation and encouragement.     

A cluster randomised controlled trial of the effect of a treatment algorithm for hypertension in patients with type 2 diabetes

BACKGROUND: Good blood pressure (BP) control reduces the risk of complications in people with type 2 diabetes, yet many do not achieve this. Guidelines for managing hypertension recommend increasing antihypertensive medications until control is achieved, but the effect of such recommendations in routine primary care is unknown. AIM: To evaluate the effectiveness of a BP treatment algorithm in primary care patients with type 2 diabetes. DESIGN OF STUDY: A cluster randomised controlled trial of 1534 patients with type 2 diabetes. SETTING: Forty-two practices in Nottingham, UK. METHOD: Practices were randomised to continue usual care or to use a treatment algorithm designed so that practice nurses and GPs would increase antihypertensive treatment in steps until the target of 140/80 mmHg was reached. Participants were assessed by a clinical interview and case note review at recruitment and at 1 year. The primary outcome measure was the proportion of participants achieving target BP at 1 year. RESULTS: At 1 year there was no difference between the proportions of participants with well controlled BP in the intervention and control arms (36.6% versus 34.3%; P = 0.27). Mean systolic and diastolic blood pressures were identical in the two arms (143/78 mmHg). There was some evidence that participants in the intervention arm were more likely to be receiving higher doses of their antihypertensive drugs, although there was no significant difference in the number of different antihypertensive drugs prescribed. Participants in the intervention arm had a higher rate of primary care BP-related consultations over 12 months than those receiving usual care (rate ratio = 1.55, 95% confidence interval [CI] = 1.26 to 1.88, P<0.001). CONCLUSION: Despite increased monitoring and possibly higher doses of medication there was no improvement in blood pressure control. Improvements achieved by specialist nurse-led clinics in secondary care may not translate to people with type 2 diabetes in primary care settings.     

雌激素替代治疗对2型糖尿病围绝经期妇女血糖的影响

目的:分析激素替代治疗对2型糖尿病围绝经期妇女血糖的影响.方法:随机选取2014年6月至2016年6月于石家庄市第二医院就诊的2型糖尿病围绝经期患者82例,随机分为观察组(n=41)与对照组(n=41),两组均给予降血糖等常规治疗,观察组给予替勃龙治疗,对照组给予复合维生素B进行安慰剂治疗,对比两组患者的临床疗效、血糖水平、胰岛素抵抗相关指标水平.结果:观察组治疗总有效率为97.56％,对照组为80.48％,两组疗效比较差异有统计学意义(x2=6.116,P=0.013);治疗前E2,FPG,2hPG,HbAlc,HOMA-IR,resistin,TNF-α和CRP等水平两组比较,差异无统计学意义(P＞0.05);治疗后观察组FPG,2hPG,HbAlc,HOMA-IR,resistin,TNF-α和CRP水平明显下降,与治疗前比较,差异有统计学意义(P＜0.05);E2水平有所升高,但与治疗前比较,差异无统计学意义(P＞0.05);对照组治疗后上述指标变化不明显,与观察组治疗后相关指标比较,差异有统计学意义(P＜0.05).结论:采用替勃龙治疗2型糖尿病围绝经期患者,能够显著降低患者的血糖水平,治疗效果良好.