Diabetes mellitus and the risk of non-vertebral fractures: the Tromsø study

We wanted to determine the risk of non-vertebral fracture associated with type and duration of diabetes mellitus, adjusting for other known risk factors. This is a population-based 6-year follow-up of 27,159 subjects from the municipality of Tromsø, followed from 1994 until 2001. The age range was 25–98 years. Self-reported diabetes cases were validated by review of the medical records. All non-vertebral fractures were registered by computerized search in radiographic archives. A total of 1,249 non-vertebral fractures was registered, and 455 validated cases of diabetes were identified. Men with type I diabetes had an increased risk of all non-vertebral [relative risk (RR) 3.1 (95% CI 1.3–7.4)] and hip fractures [RR 17.8 (95% CI 5.6–56.8)]. Diabetic women, regardless of type of diabetes, had significantly increased hip fracture risk [RR 8.9 (95% CI 1.2–64.4) and RR 2.0 (95% CI 1.2–3.6)] for type I and type II diabetes, respectively. Diabetic men and women using insulin had increased hip fracture risk. Duration of disease did not alter hip fracture risk. An increased risk of all non-vertebral fractures and, especially, hip fractures was associated with diabetes mellitus, especially type I. Type II diabetes was associated with increased hip fracture risk in women only.     

Current understandings of the pathogenesis of type 1 diabetes:Genetics to environment

Type 1 diabetes(T1D) is an autoimmune disease that usually strikes early in life,but can affect individuals at almost any age. It is caused by autoreactive T cells that destroy insulin-producing beta cells in the pancreas. Epidemiological studies estimate a prevalence of 1 in 300 children in the United States with an increasing incidence of 2%-5% annually worldwide. The daily responsibility, clinical management, and vigilance required to maintain blood sugar levels within normal range and avoid acute complications(hypoglycemic episodes and diabetic ketoacidosis) and long term micro-and macro-vascular complications significantly affects quality of life and public health care costs. Given the expansive impact of T1D, research work has accelerated and T1D has been intensively investigated with the focus to better understand, manage and cure this condition. Many advances have been made in the past decades in this regard,but key questions remain as to why certain people develop T1D, but not others,with the glaring example of discordant disease incidence among monozygotic twins. In this review, we discuss the field's current understanding of its pathophysiology and the role of genetics and environment on the development of T1D. We examine the potential implications of these findings with an emphasis on T1D inheritance patterns, twin studies, and disease prevention. Through a better understanding of this process, interventions can be developed to prevent or halt it at early stages.     

A comparative study of pancreas transplantation between type 1 and 2 diabetes mellitus

BackgroundPancreas transplantation remains the best long-term treatment option to achieve physiological euglycemia and insulin independence in patients with labile diabetes mellitus (DM). It is widely accepted as an optimal procedure for type 1 DM (T1DM), but its application in type 2 DM (T2DM) is not unanimously acknowledged.MethodsIn total, 146 diabetes patients undergoing pancreas transplantation were included in this study. Clinical data and outcomes were compared between the T1DM and T2DM groups.ResultsMajority (93%) of the pancreas transplantations in T2DM were for uremic recipients. Complications occurred in 106 (73%) patients, including 70 (48%) with early complications before discharge and 79 (54%) with late complications during follow-up period. Overall, rejection of pancreas graft occurred in 37 (25%) patients. Total rejection rate in T2DM recipients was significantly lower than that in T1DM. The short- and long-term outcomes for endocrine function in terms of fasting blood sugar and hemoglobin A1c levels and graft survival rates are comparable between the T2DM and T1DM groups.ConclusionsT2DM is not inferior to T1DM after pancreas transplantation in terms of surgical risks, immunological and endocrine outcomes, and graft survival rates. Therefore, pancreas transplantation could be an effective option to treat selected uremic T2DM patients without significant insulin resistance.     

WJD 5~(th) Anniversary Special Issues(3): Type 1 diabetes Distinct clinical and laboratory characteristics of latent autoimmune diabetes in adults in relation to type 1 and type 2 diabetes mellitus

Ever since its first appearance among the multiple forms of diabetes,latent autoimmune diabetes in adults(LADA),has been the focus of endless discussions concerning mainly its existence as a special type of diabetes.In this mini-review,through browsing important peer-reviewed publications,(original articles and reviews),we will attempt to refresh our knowledge regarding LADA hoping to enhance our understanding of this controversial diabetes entity.A unique combination of immunological,clinical and metabolic characteristics has been identified in this group of patients,namely persistent islet cell antibodies,high frequency of thyroid and gastric autoimmunity,DR3 and DR4 human leukocyte antigen haplotypes,progressive loss of beta cells,adult disease onset,normal weight,defective glycaemic control,and without tendency to ketoacidosis.Although anthropomorphic measurements are useful as a first line screening,the detection of C-peptide levels and the presence of glutamic acid decarboxylase(GAD)autoantibodies is undoubtedly the sine qua non condi-tion for a confirmatory LADA diagnosis.In point of fact,GAD autoantibodies are far from being solely a biomarker and the specific role of these autoantibodies in disease pathogenesis is still to be thoroughly studied.Nevertheless,the lack of diagnostic criteria and guidelines still puzzle the physicians,who struggle between early diagnosis and correct timing for insulin treatment.     

有氧运动联合褪黑素对二型糖尿病大鼠骨质疏松影响的实验研究

目的观察有氧运动和褪黑素对二型糖尿病大鼠骨质疏松的影响。方法成年雌性SD大鼠80只,6周龄,随机分为安静对照组(N)、糖尿病对照组(D)、正常有氧运动组(E)、糖尿病有氧运动组(DE)、正常褪黑素组(M)、糖尿病褪黑素组(DM)、正常有氧运动褪黑素组(EM)、糖尿病有氧运动褪黑素组(DEM),观察各组大鼠体重、脊椎骨以及左右股骨骨密度(BMD)、观察大鼠血糖、血清丙二醛(MDA)、超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)、血清总钙(Ca)、无机磷(P)和甲状旁腺素(PTH)的变化。结果与N组相比,E、M和EM组大鼠体重、血糖、血Ca、血P和血PTH无明显变化(P0.05),血清SOD、GSH-Px水平、腰椎和左右股骨BMD显著升高(P0.05),血清MDA水平显著降低(P0.05),D组大鼠体重、血清SOD、GSH-Px水平、血Ca、腰椎和左右股骨BMD显著降低(P0.05),血糖、血清MDA和血PTH水平显著升高(P0.05),血P无明显变化(P0.05);与D组比较,DE、DM组大鼠体重、血清SOD、GSH-Px水平、血Ca、腰椎和左右股骨BMD显著升高(P0.05),血糖、血清MDA和血PTH水平显著降低(P0.05),血P无明显变化(P0.05),有氧运动和褪黑素同时干预效果更好。结论有氧运动和褪黑素均能改善糖尿病骨质疏松,且两者联合干预的效果更加显著,其可能与通过提高糖尿病大鼠的抗氧化应激能力,调节糖的代谢从而有效地的降低血钙和PTH,改善BMD来缓解骨质疏松有关。     

25 羟维生素D3与糖尿病骨质疏松患者的相关性研究

目的 观察 2 型糖尿病(T2DM)患者骨质疏松与25 羟维生素D3(25-OH-D3)的关系? 方法 测定186 例2 型糖尿病(T2DM)患者及65例年龄?性别相匹配健康对照者血(Ca) ?磷(P),采用酶联免疫法测定各组血清骨特异性碱性磷酸酶(ALP)?血清骨钙素(BGP)? (25-OH-D3)的浓度? 结果 2型糖尿病组BGP?25-OH-D3浓度低于对照组,差异显著(P<0.05),血清Ca?P?血浆ALP浓度与对照组之间无显著差异(P>0.05)? 女型糖尿病患者骨质疏松症的发病率高于男性,女性OP组BGP?25-OH-D3的浓度显著低于男性OP组(P<0.05)? 结论 2 型糖尿病患者 25-OH-D3的减少可影响钙?磷代谢,从而导致骨质疏松,因此对于 2 型糖尿病患者应早期适量补充钙剂及维生素D3?     

Glycaemic control,treatment satisfaction and quality of life in type 2 diabetes patients in Greece: The PANORAMA study Greek results

AIM: To provide an update on glycaemic control inEuropean patients with type 2 diabetes mellitus(T2DM). We present the Greek population data of the study. METHODS: An observational multicenter, cross-sectional study evaluating glycaemic control and a range of other clinical and biological measures as well as quality of life(Qo L) and treatment satisfaction in 375 patients with T2 DM enrolled by 25 primary care sites from Greece. RESULTS: The mean age of the patients was 63.5 years and the male/female ratio 48.9%/51.1%. 79.7% of the patients exerted none or light physical activity, 82.4% were overweight or obese and 32.9% did not meet Hb A1 c target of less than 7.0%(53 mmol/mol). Patients reported high satisfaction to continue with treatment, high satisfaction with administered treatment and increased willingness to recommend treatment to others(mean Diabetes Treatment Satisfaction Questionnaire score 29.1 ± 5.6). However, 80% of the patients reported that their Qo L would be better without diabetes. Finally, the most challenging parameter reported was the lack of freedom to eat and drink. CONCLUSION: This analysis of the Greek Panorama study results showed that a considerable percentage of T2 DM patients in Greece do not achieve glycaemic target levels, despite the favourably reported patient satisfaction from administered therapy. Additionally, the majority of primary care T2 DM patients in Greece depict the negative effect of the disease in their Qo L.     

25-(OH)VD与2型糖尿病患者的糖尿病肾病相关性研究

目的 探讨25-(OH)VD与2型糖尿病患者的糖尿病肾病相关性。方法 收集937例未接受维生素D补充治疗的2型糖尿病患者,测定各临床指标以分析糖尿病肾病的相关因素。结果 与正常尿微量白蛋白组患者相比,微量或大量尿白蛋白组患者的25-(OH)VD 水平较低且具有显著统计学差异。相关性分析显示,用性别和BMI作为校正指数,年龄、糖尿病病程、高血压病程、收缩压、糖化血红蛋白、肌酐、尿素氮与尿微量白蛋白呈正相关,而25-(OH)VD 水平与尿微量白蛋白呈负相关。结论 25-(OH)VD 水平与2型糖尿病患者的尿微量白蛋白呈显著负相关。     

糖尿病肾病患者骨密度及骨代谢标志物的临床研究

目的探讨2型糖尿病(T2DM)不同阶段糖尿病肾病(DN)患者的骨密度(BMD)及骨代谢标志物的变化。方法检测T2DM正常白蛋白尿患者(51例)与DN患者(微量白蛋白尿组40例,临床白蛋白尿组28例,肾功不全组20例)的BMD及骨代谢指标。结果 25羟维生素D3(25-OH-D3)在正常白蛋白尿组最高,在DN各组间随着肾功能的恶化逐渐降低(P0.05)。DN各组血清骨钙素(BGP)及血清总I型胶原氨基端延长肽(T-PINP)均低于正常白蛋白尿组(P0.05)。DN各组I型胶原羧基端肽β特殊序列(βCTX)均高于正常白蛋白尿组(P0.05)。肾功不全组血清甲状旁腺激素(PTH)明显高于其他3组(P0.05),其他各组间差异无显著性(P0.05)。大量白蛋白尿组及肾功不全组各部位BMD值均低于正常白蛋白尿组(P0.05)。多元相关分析表明腰椎BMD及股骨颈BMD与年龄、血Cr、BUN、尿MA/Cr、βCTX、PTH成负相关,与血Ca、25-OHD3、BGP、T-PINP成正相关,女性患者腰椎BMD及股骨颈BMD与绝经年限成负相关。结论随着T2DM患者肾功能逐渐下降,其骨量减少的程度逐渐加重,T-PINP、BGP、βCTX、25-OH-D3等骨代谢指标较BMD更敏感地反映DN早期骨代谢的变化。DN患者的BMD与年龄、绝经年限、尿MA/Cr、25-OH-D3等因素相关。     

Age of onset of diabetes and all-cause mortality

Diabetes mellitus continues to present a large social, financial and health system burden across the world. The relationship between age of onset of the different types of diabetes and all-cause mortality is uncertain. In this review paper, the relationship between age of onset of the different types of diabetes and all-cause mortality will be reviewed and an update of the current evidence will be presented. There is strong evidence of the relationship between age of onset of type 2 diabetes mellitus (T2DM) and all-cause mortality, good evidence of the relationship between age of onset of T1DM and all-cause mortality and no evidence of the relationship between age of onset of gestational diabetes or prediabetes and all-cause mortality. Further research is needed to look at whether aggressive management of earlier onset of T2DM can help to reduce premature mortality.     

Insulin independence and normalization of oral glucose tolerance test after islet cell allotransplantation

To achieve permanent normoglycemia in patients with type I diabetes, it is necessary to renew the insulin-producing β-cells by transplantation of either a vascularized pancreatic graft or isolated islets of Langerhans. Presently, about 10 % of patients with type I diabetes undergoing islet allotransplantation achieve insulin independence; however, glucose intolerance remains in the majority of cases. We report a case of long-term insulin independence after islet allotransplantation in a type I diabetic patient. Three years after islet transplantation, the patient remains insulin-independent with a normal oral glucose tolerance test (OGTT). The patient therefore no longer meets the World Health Organization criteria for the diagnosis of diabetes mellitus and demonstrates that islet transplantation can cure diabetes in type I diabetic patients. Received: 28 December 1999 Revised: 18 August 2000 Accepted: 24 April 2001     

Toxic stress,inflammation and symptomatology of chronic complications in diabetes

Diabetes affects at least 382 million people worldwide and the incidence is expected to reach 592 million by 2035.The incidence of diabetes in youth is skyrocketing as evidenced by a 21% increase in type 1 diabetes and a 30.5% increase in type 2 diabetes in the United States between 2001 and 2009.The effects of toxic stress,the culmination of biological and environmental interactions,on the development of diabetes complications is gaining attention.Stress impacts the hypothalamus-pituitaryadrenal axis and contributes to inflammation,a keybiological contributor to the pathogenesis of diabetes and its associated complications.This review provides an overview of common diabetic complications such as neuropathy,cognitive decline,depression,nephropathy and cardiovascular disease.The review also provides a discussion of the role of inflammation and stress in the development and progression of chronic complications of diabetes,associated symptomatology and importance of early identification of symptoms of depression,fatigue,exercise intolerance and pain.     

Distinct clinical and laboratory characteristics of latent autoimmune diabetes in adults in relation to type 1 and type 2 diabetes mellitus

Ever since its first appearance among the multiple forms of diabetes, latent autoimmune diabetes in adults (LADA), has been the focus of endless discussions concerning mainly its existence as a special type of diabetes. In this mini-review, through browsing important peer-reviewed publications, (original articles and reviews), we will attempt to refresh our knowledge regarding LADA hoping to enhance our understanding of this controversial diabetes entity. A unique combination of immunological, clinical and metabolic characteristics has been identified in this group of patients, namely persistent islet cell antibodies, high frequency of thyroid and gastric autoimmunity, DR3 and DR4 human leukocyte antigen haplotypes, progressive loss of beta cells, adult disease onset, normal weight, defective glycaemic control, and without tendency to ketoacidosis. Although anthropomorphic measurements are useful as a first line screening, the detection of C-peptide levels and the presence of glutamic acid decarboxylase (GAD) autoantibodies is undoubtedly the sine qua non condition for a confirmatory LADA diagnosis. In point of fact, GAD autoantibodies are far from being solely a biomarker and the specific role of these autoantibodies in disease pathogenesis is still to be thoroughly studied. Nevertheless, the lack of diagnostic criteria and guidelines still puzzle the physicians, who struggle between early diagnosis and correct timing for insulin treatment.     

Evaluation of the Finnish Diabetes Risk Score to predict type 2 diabetes mellitus in a Colombian population: A longitudinal observational study

AIM: To assess the performance of the Finnish Diabetes Risk Score(FINDRISC) questionnaire for detecting and predicting type 2 diabetes mellitus(DM2) in a Colombian population.METHODS: This is a longitudinal observational study conducted in Floridablanca, Colombia. Adult subjects(age ≥ 35 years) without known diabetes, were included. A modified version of FINDRISC was completed, and the glycemia values from all the subjects were collected from the hospital's database. Firstly, a cross-sectional analysis was performed and then, the subsample of prediabetic participants was followed for diabetes incidence. RESULTS: A total of 772 subjects were suitable for the study. The overall prevalence of undiagnosed DM2 was 2.59%, and the incidence of DM2 among the prediabetic participants was 7.5 per 100 person-years after a total of 265257 person-years follow-up. The FINDRISC at baseline was significantly associated with undiagnosed and incident DM2. The area under receiver operating characteristics curve of the FINDRISC score for detecting undiagnosed DM2 in both men and women was 0.7477 and 0.7175, respectively; and for predicting the incidence of DM2 among prediabetics was 71.99% in men and 67.74% in women. CONCLUSION: The FINDRISC questionnaire is a useful screening tool to identify cross-sectionally unknown DM2 and to predict the incidence of DM2 among prediabetics in the Colombian population.     

Molecular and biochemical trajectories from diabetes to Alzheimer&rsquo;s disease: A critical appraisal

Diabetes mellitus (DM), a metabolic disorder is a major orchestra influencing brain and behavioral responses via direct or indirect mechanisms. Many lines of evidence suggest that diabetic patients apparently face severe brain complications, but the story is far from being fully understood. Type 2 diabetes, an ever increasing epidemic and its chronic brain complications are implicated in the development of Alzheimer’s disease (AD). Evidences from clinical and experimental studies suggest that insulin draws a clear trajectory from the peripheral system to the central nervous system. This review is a spot light on striking pathological, biochemical, molecular and behavioral commonalities of AD and DM. Incidence of cognitive decline in diabetic patients and diabetic symptoms in AD patients has brought the concept of brain diabetes to attention. Brain diabetes reflects insulin resistant brain state with oxidative stress, cognitive impairment, activation of various inflammatory cascade and mitochondrial vulnerability as a shared footprint of AD and DM. It has become extremely important for the investigators to understand the patho-physiology of brain complications in diabetes and put intensive pursuits for therapeutic interventions. Although, decades of research have yielded a range of molecules with potential beneficial effects, but they are yet to meet the expectations.     

Latent autoimmune diabetes in adults: A distinct but heterogeneous clinical entity

Latent autoimmune diabetes in adults (LADA) accounts for 2%-12% of all cases of diabetes. Patients are typically diagnosed after 35 years of age and are often misdiagnosed as type II Diabetes Mellitus (DM). Glycemic control is initially achieved with sulfonylureas but patients eventually become insulin dependent more rapidly than with type II DM patients. Although they have a type II DM phenotype, patients have circulating beta (β) cell autoantibodies, a hallmark of type I DM. Alternative terms that have been used to describe this condition include type 1.5 diabetes, latent type I diabetes, slowly progressive Insulin Dependent Diabetes Mellitus, or youth onset diabetes of maturity. With regards to its autoimmune basis and rapid requirement for insulin, it has been suggested that LADA is a slowly progressive form of type I DM. However, recent work has revealed genetic and immunological differences between LADA and type I DM. The heterogeneity of LADA has also led to the proposal of criteria for its diagnosis by the Immunology of Diabetes Society. Although many workers have advocated a clinically oriented approach for screening of LADA, there are no universally accepted criteria for autoantibody testing in adult onset diabetes. Following recent advances in immunomodulatory therapies in type I DM, the same strategy is being explored in LADA. This review deals with the contribution of the genetic, immunological and metabolic components involved in the pathophysiology of LADA and recent approaches in screening of this distinct but heterogeneous clinical entity.     

不同骨密度检测方法在2型糖尿病骨质疏松患者中的应用

目的 探讨2型糖尿病患者骨质疏松的相关指标,为早期诊断和治疗提供理论依据.方法 选取2011年3月～11月在某院已确诊为2型糖尿病的住院患者60例为病例组,同期健康体检者52例为正常对照组,分别采用跟骨超声骨密度检测仪(QUS)、双能X线(DEXA)、周围骨定量CT(pQCT)进行骨密度检测.结果 用QUS、DEXA及pQCT测定60例2型糖尿病患者提示骨质疏松者分别占45 %、51.7%、46.8%.而与对照组比较,2型糖尿病患者骨密度显著低于正常对照组(P＜0.05),2型糖尿病患者骨质疏松相关指标异常者占51.7%;在2型糖尿病患者中,女性2型糖尿病患者骨质疏松相关指标显著低于男性(P＜0.05).结论 2型糖尿病患者容易并发骨质疏松,其中女性2型糖尿病患者的患病率更高.     

高龄住院老年人中2型糖尿病与老年性骨折呈负相关-病例对照研究

目的：采用病例对照法初步分析2型糖尿病与老年性骨折的关系。方法根据纳入和排除标准筛选大于60周岁的住院糖尿病和非糖尿病病人,收集其人口学特征、病史和治疗情况,采用SAS 9.2软件建立logistic多元回归模型分析调整多种因素后2型糖尿病与老年性骨折的关系。结果共纳入150例病例,平均年龄82.39岁。女性（ OR：3.314,95％CI 1.191～9.218）和年龄（每增加5岁OR：1.399,95％CI 1.010～1.939）是老年性骨折的危险因素;调整年龄和性别等混杂因素的影响之后,患2型糖尿病和血管性痴呆的患者发生老年性骨折的风险更低,OR值分别为0.237（95％CI 0.072～0.787）和0.091（95％CI 0.015～0.742）。结论本研究提示在高龄住院老年人中2型糖尿病与老年性骨折呈负相关,其原因有待更大样本量的研究进行分析。