Dipeptidyl-peptidase-4 (DPP-4) inhibitors are a new class of anti-diabetic agents that reduce blood glucose by preventing the degradation of the endogenous incretin hormones, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). The protection of DPP-4 inhibitors on β-cell function has been demonstrated in patients with type 2 diabetes (T2D). Because DPP-4 is an enzyme widely expressed in humans, DPP-4 inhibitors are speculated to be multi-target agents. However, the other potential therapeutic value of DPP-4 inhibitors remains unknown. Recently, some therapeutic effects of DPP-4 inhibitors, such as immune regulation, cardiovascular protection and anti-inflammatory effect have been gradually observed. This article provides a systematic and comprehensive review of current researches on the newly-found effect and mechanism of DPP-4 inhibitors in therapy.
In the present study, we evaluated the incidence of heart failure (HF) in diabetic foot ulcer (DFU) patients, investigated clinical characteristics and its relationship to prognosis in such a population.
Clinical characteristics of 330 consecutive Chinese subjects (137 males and 193 females) hospitalized for diabetic foot ulcers were collected. Clinical characteristics were assessed to determine the effects about the presence of HF on DFU. All the subjects were followed up for 3 months. Rates of healing, new ulcers, amputations and mortality were calculated at the end of the follow-up to analyze the effect of heart failure on the prognosis of diabetic foot ulcer.
HF accounted for 64.3% of the patients with ulcers, and the rate would increase from Wagner 1 to Wagner 5 ( 42.4% vs.59.1%vs. 64.7% vs. 73.3% vs. 87.0%), higher than 33.6% for diabetes(Wagner 0). Factors associated with high risk for HF were plasma albumin level, creatine clearance rate, NYHA grade, and neutrophil count. And HF conferred a greater increase in relative risk of worse prognosis when compared with non-HF. The 3-month healing rates of diabetic foot ulcer were 60.3% vs. 75.7% between HF and non-HF patients. More frequent recurrences and amputations were detected in HF when compared with non-HF counterparts (13.2% vs. 7.5%, 28.6% vs. 20.0%, respectively, P<0.05). All-cause mortality occurred in 14 of 126 HF subjects compared with 3 of 70 non-HF subjects (11.1% vs. 4.3%, P<0.05).
The prevalence of HF was high in Chinese inpatient with DFU, and the presence of HF indicated a worse prognosis.
Ever since the DCCT (1) confirmed that tight glycemic control can prevent long term diabetic complications, the goal of diabetes care has been to normalize blood sugar without causing hypoglycemia. Unfortunately, achieving this otherwise laudable goal requires huge amounts of patient and physician resources. For patients, management is onerous since it requires constant attentiveness to the volume of carbohydrates consumed, the testing of capillary blood sugar 4 times per day, the calculation of insulin doses, and either the injection of 2 different types of insulin up to 5 times per day or use of a continuously worn insulin pump. The current insulin pump, while functioning as a calculator to help determine the prandial insulin bolus, still requires vigilance on the part of the wearer regarding the appropriateness of the dose which it computes as well as the insertion of the pump subcutaneous insulin infusion system every 2-3 days. In addition, some patients elect to use a subcutaneous sensor to monitor glucose trends which does not, however, obviate the need for glucose testing 4 times per day testing while still requiring the wearing of a second device and subcutaneous reinsertion every 7 days. Finally, all of this necessitates the supervision by a physician or certified diabetic educator (CDE), usually with visits at 3 month intervals. Given the burden imposed by such a program, it would seem very desirable to eliminate the human input and to develop a “closed-loop system” wherein a glucose sensing device records the blood sugar level and automatically sends the information to an insulin delivery device. But given the currently available technology as well as the biology of blood glucose homeostasis, the question is whether the fantasy of this “artificial pancreas” can be transformed into reality in the near future.
]]>Glucagon-like peptide-1(GLP-1) analogues are emerged as insulin secretagogues and widely used in type 2 diabetic patients. GLP-1 analogues also demonstrate a promotion of beta cell proliferation and reduction of apoptosis in rodents.In the present study, we investigated the protection of pancreatic beta cells by early use (at age of 2 weeks) of GLP-1 analogue, Liraglutide in GK rats and explored the underlying mechanisms.
Effects of Liraglutide on glucose tolerance were evaluated by intraperitoneal glucose tolerance test (IPGTT) and insulin release tests (IRT). Ki67 and TUNEL immunostaining, Western blots and real-time PCR were applied to evaluate cell proliferation, apoptosis and related gene expressions.
Our results demonstrated that early use of Liraglutide improved glucose tolerance during Liraglutide treatment in GK rats. Liraglutide increased pancreatic insulin contents and markedly reduced beta cell apoptosis. Liraglutide also downregulated pro-apoptotic gene expressions and reduced intra-islet macrophage infiltration.
This experiment reported for the first time that early use of Liraglutide could protect beta cell failure in pre-diabetic GK rats through reduction of beta cell apoptosis and ameliorating islet inflammation.
Early use of Liraglutide could protect beta cells through reduction of beta cell apoptosis and ameliorating islet inflammation.
Liraglutide could protect beta cell failure and delay diabetes progression in pre-diabetic GK rats through reduction of beta cell apoptosis and ameliorating islet inflammation.
Statins, beyond their lipid lowering effects, exert their cardiovascular effects through their pleiotropic actions.1 We undertook this study to determine the potential differences in intensity and timing of the anti-inflammatory effects of statins between patients with and without diabetes mellitus (DM) so as to detect the particular traits associated with cardiovascular risk as well as benefits from statins in patients with DM, a known state of chronic inflammation and high oxidative stress and an independent risk factor for CVD.2 Both patient groups were recruited amongst patients with end-stage renal disease (ESRD) on chronic hemodialysis (HD), a subpopulation already at chronic inflammation and oxidative stress and, thus, undergoing accelerated atherogenetic process,3 in anticipation that these patients are more amenable to measurable short-term effects from the treatment.
]]>The prevention of cardiovascular disease is among our highest priorities in managing patients with diabetes. The concerns that arose from the association between rosiglitazone use and the incidence of myocardial infarction have led drug regulation authorities to mandate evidence of cardiovascular safety before a new anti-hyperglycaemic agent can be approved. For the di-peptidyl peptidase-4 (DPP4) inhibitors, the availability and analysis of these data have to date not only shown apparent safety but have also raised the tantalising possibility of cardiovascular protection. There are, however, numerous caveats to such analyses and their interpretation. Foremost, the trials are primarily designed to determine the glucose lowering properties of these agents and not their effects on cardiovascular outcomes, which are instead captured as adverse events. In addition, the majority of these studies are of short duration, have relatively few patients and mostly do not focus on subjects with pre-existing heart disease or at high risk of developing it. These limitations notwithstanding, some interesting findings are evident.
]]>Hyperglycemia of inpatients will increase the incidence of complications, mortality and medical cost, meanwhile prolong the hospitalized course. A consensus on hyperglycemia management target in adult inpatients is proposed by experts of Chinese Society of Endocrinology in order to control hyperglycemia of inpatients safely and effectively. Individualization is emphasized in this consensus. Different stratified glycemic targets should be established according to different patients and conditions. Target blood glucose control is unnecessary for diabetic patients during hospital stay. Glycemic decrement should generally not be quick. Hypoglycemia should be avoided as much as possible, and for overweight and obesity individuals weight gain should be avoided as much as possible also. At the same time, the risks of infection and hyperglycemic crisis must also be avoided due to loose glycemic control.
Diabetes and cancer are both heterogeneous and multifactorial diseases with tremendous impact on health worldwide. Epidemiologic evidence suggests that certain malignancies may be associated with diabetes, as well as with diabetes risk factors and, perhaps, with certain diabetes treatments. A number of biological mechanisms could account for these relationships. Insulin-like growth factor (IGF)-1 and 2, type 1 IGF receptors, and insulin and its receptor play roles in the development and progression of cancers. Although randomised controlled trial evidence does not support or refute associations of diabetes and its treatments with either increased or reduced risk of cancer incidence or prognosis, consideration of malignancy incidence rates and the magnitude of the trials that would be required to address these issues explains why such studies may not be readily undertaken.
Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease in Western countries, affecting 20-33% of the general population. Large population-based surveys in China indicated an approximately 15-30% prevalence. The NAFLD prevalence has increased rapidly in parallel with the regional trends of obesity, type2 diabetes and metabolic syndrome. In addition, NAFLD has remarkably contributed to the increased overall as well as cardiovascular and liver-related mortality in the general population. In view of the fact that the research on NAFLD has been advancing rapidly in recent years, the current consensus provides a brief update to the progress of the field, and suggests preferred approaches to a comprehensive management of NAFLD and its related metabolic diseases.
Diabetes mellitus (DM) is a common cause of polyneuropathy. The aim of the study is to evaluate the two point discrimination (TPD) in comparison to nerve conduction studies in early period of DM.
48 patients with early diagnosed (<5 years) Type 2 DM and 17 healthy controls were included in this study. Twenty-six had neuropathic pain and 22 patients with DM were asymptomatic. Medical history, clinical and biochemical assessments, neurological examination for polyneuropathy, LANSS (Leeds Assessment of Neuropathy Symptoms and Signs) score, TPD, and electrophysiological evaluations were conducted in all subjects.
Nerve conduction studies of patients showed both demyelination and axonal damage related findings. The patients with neuropathic pain had higher TPD value on plantar surface of foot and both groups had higher TPD values on outer lateral malleolus in comparison to controls (p<0.05). There was a correlation between TPD and axonal damage in these patients (p<0.05). In the patients without neuropathic pain, distal latencies of motor or sensory nerves correlated with TPD values (p<0.05). In controls, only 3rd digit TPD value related to distal motor latency of median nerve (p<0.05).
TPD method is less painful, practical, cost-effective, more easily applicable, and was completed in less time. Higher TPD value in lower extremities shows nerve damage in the patients. These findings suggest that elevation of the TPD value can easily determine neuropathy which has been started in early period diabetes patients.
Type 2 diabetes mellitus is a progressive disease characterized by worsening insulin resistance and a decline in β-cell function. Achieving good glycemic control becomes more challenging as β-cell function continues to deteriorate throughout the disease process. The traditional management paradigm emphasizes a stepwise approach and insulin has generally been reserved as a final armament. However, mounting evidences showed short term intensive insulin therapy used at the early stage of type 2 diabetes could improve β-cell function and result in better glucose control and more extended glycemic remission than oral anti-diabetic agents. Improvement of insulin sensitivity and lipid profile were also observed after early initiation of short term intensive insulin therapy. Thus, administrating short term intensive insulin therapy in patients with newly diagnosed type 2 diabetes has a potential in delaying the natural process of this disease, and should be considered when clinicians initiate treatment. Although early use of insulin is advocated by some guidelines, the optimal time to initiate insulin therapy is not clearly defined or easily recognized, and there was a lack of pragmatic approach. In this review, we summarized the current understanding of the early intensive insulin therapeutic approach in patients with newly diagnosed type 2 diabetes, focusing on its clinical benefit and problems, possible biological mechanisms of action, and discussed our perspective.
Disparities in diabetic foot ulcer treatment outcomes have been well described. Few studies identify risk factors that contribute to disparate healing and amputation rates. In a unique academic center serving urban public, private, and veterans, we investigated the amputation and healing rates as well as specific risk factors for disparate treatment outcomes.
A retrospective chart review of diabetic patients with a new diagnosis of a foot ulcer at geographically adjacent, but independent public, private, and Veterans Administration (VA) hospitals was conducted. Healing and lower extremity amputation outcomes were assessed.
234 patients met inclusion criteria at all three hospitals. VA patients were older (mean = 72.5 years, p<0.001) and had gangrenous ulcers (mean = 14.1%, p <0.001) compared to the private and public hospitals. Public hospital patients were mostly Hispanic (mean =54%, p< 0.001) with a shorter duration of diabetes (mean= 12.8yrs, p=0.02), but were more poorly controlled than VA and private hospital patients (p=<0.001). Prior amputation (OR =1.97, p=0.016), and non-Caucasian race (OR=2.42, p=0.004) increased risk of amputation on multivariate analysis. Presence of osteomyelitis (p=0.0371) and gangrene (p< 0.001) are independent risk factors for amputation. 42.3% of all patients were treated by amputation (6.8% private, 12% public and 23.5% VA, p< 0.001).
In a single triumvirate health care system, where the patient population is stratified primarily by insurance, VA patients have significantly higher amputation rates compared to the adjacent private and public hospital. VA patients are largely racial minorities with advanced DFU progression to gangrenous ulcers.
The aims of this study were to determine the frequency of delayed gastric emptying in children and adolescents with Type 1 diabetes mellitus (T1DM); and to investigate the relationship between gastric emptying rate and other contributing factors, such as serum HbA1c levels, duration of diabetes and micro-albuminuria, in these patients.
This was a clinical trial evaluating the rate of gastric emptying of solid meals in 33 children and adolescents with T1DM and in 26 healthy peers, by radionuclide method. Three consecutive overnight urine collections were used to calculate albumin excretion rate (AER).
There was no significant difference in the gastric half-emptying time (GE t1/2) (151.66 ±154.46 min vs. 109.76 ± 60.52 min, P=0.885) and the frequency of delayed gastric emptying (36.4% vs. 30.8%, P=0.433) between patients and controls. There was a moderately positive correlation with the GE t1/2 and duration of diabetes in the patients (r=0.380, P=0.029). The GE t1/2 did not correlate with the microalbumin levels in the patients. In these patients, the Body Mass Index Standard Deviation Scores (BMISDS) were significantly lower than in patients with normal gastric emptying (-0.13±0.87 vs. 0.7±1.23, P=0.044).
Progression of delayed gastric emptying is more likely to be related to a longer duration of diabetes rather than glycemic control in children and adolescents with T1DM. Patients with delayed gastric emptying are thinner compared to patients with a normal rate of gastric emptying; they may also be asymptomatic.
Type 1 diabetic children with delayed gastric emptying are frequently asymptomatic and thin. There were no correlations between delayed gastric emptying and borderline micro-albuminuria and metabolic control. This study adds that the rate of gastric emptying can be investigated in thin children with T1DM with long disease duration, although they may be asymptomatic.
This short review summarizes and updates clinical experience with two classes of drugs introduced in the management of type 2 diabetes mellitus (T2DM) over the past 8 years: the glucagon-like peptide (GLP)-1 receptor agonists, and the dipeptidyl peptidase(DPP)-4 inhibitors. Both classes of agents address the so called “incretin defect” in patients with T2DM.Discovery of the incretin effectIn 1964 Elrick et al1 described that oral glucose administration leads to greater insulin response than when glucose is delivered intravenously. That enhanced effect was called the “incretin” effect. Clearly, the difference between oral administration of glucose and its delivery by intravenous route was the presence of nutrient in the gastrointestinal track. Actually, the observation that factors released by the duodenum could stimulate insulin production predates discovery of insulin by 15 years. Moore, Edie and Abram2 stated then: “…the internal secretion of the pancreas might be stimulated and initiated (similarly to the external secretion) by a substance of the nature of a hormone or secretin yielded by the duodenal mucous membrane…” And it was La Barre who in 1932 coined the term “incrétine” when he described a substance produced in the small intestine with the capacity to cause hypoglycemia without stimulating exocrine pancreatic secretion3. This idea was replicated in 1986 by the work of Nauck et al.4. By definition, incretin hormones are secreted after nutrient ingestion and stimulate insulin secretion at the concentration that is reached by the ingestion. Some time elapsed before a number of hormones, released from specific cells of the small intestine, were identified.
]]>Self-efficacy plays a critical role in diabetes self-care. This study explored factors contributing to decreased insulin therapy self-efficacy in insulin-naïve patients with type 2 diabetes mellitus (T2DM) initiating and managing insulin therapy over 36 weeks.
This study was conducted within an international, randomized clinical trial comparing two insulin therapies administered by insulin pen in patients with T2DM inadequately controlled with oral anti-hyperglycemic medications. Patients completed the Self-Efficacy about Insulin Therapy Questionnaire (SEITQ) at baseline and endpoint. In addition, patients completed patient-reported measures assessing expectations about insulin therapy at baseline and perceptions about insulin therapy and insulin delivery system (IDS) satisfaction at endpoint. Baseline and endpoint SEITQ scores were compared. Using pre-specified criteria, patients were classified as having decreased or no change/improved insulin self-efficacy. Demographic, clinical, and patient-reported variables were entered into a logistic regression model with decreased insulin self-efficacy (yes/no) as the dependent variable.
Baseline and endpoint SEITQ data were available for 450 insulin-naïve patients with T2DM (mean age=59 years; 53% female; 57% Caucasian; mean baseline hemoglobin A1C=9.4%; 79 mmol/mol). Insulin therapy self-efficacy improved from baseline to endpoint (74.0 vs. 77.5; p<0.001). Logistic regression analysis indicated lower IDS satisfaction (p<0.0001), lower IDS social acceptability (p=0.004), and more positive expectations of insulin therapy (p<0.0001) were associated with decreased insulin self-efficacy. No demographic or clinical variables were significantly associated with decreased insulin self-efficacy.
A candid discussion between clinicians and their insulin-naïve patients with T2DM about the benefits/challenges of insulin therapy may prevent unrealistic expectations that could potentially undermine insulin self-efficacy.
To examine the relationship between major depression and insulin resistance by gender and race/ethnicity among young adults without diabetes mellitus.
Secondary analyses of cross-sectional data from the National Health and Nutrition Examination Survey 1999-2008 were performed (n = 2265). Major depression was measured by the Composite International Diagnostic Interview and the Patient Health Questionnaire 9. Insulin resistance was measured by the homeostasis model assessment for insulin resistance. Multivariate logistic regression analyses adjusted for risk factors of insulin resistance were conducted.
There was a significant negative association between major depression and insulin resistance among men (body mass index [BMI]: OR = 0.297, 95% CI = [0.132-0.671]; waist circumference [WC]: OR = 0.295, 95% CI= [0.130-0.666]). For women, no significant association was found (BMI: OR = 1.774, 95% CI = [0.643-4.898]; WC: OR = 1.654, 95% CI = [0.690-3.965]). There was no significant interaction between race/ethnicity and major depression on insulin resistance (Wald χ2 = 4.2927,p=.2315). Body mass index and waist circumference were significantly associated with insulin resistance among men (BMI: OR = 1.255, 95% CI = [1.195-1.318]; WC: OR = 1.095, 95% CI = [1.076-1.115]) and women (BMI: OR = 1.220, 95% CI = [1.182-1.260]; WC: OR = 1.084, 95% CI = [1.064-1.105]), respectively).
There are gender differences in the relationship between major depression and insulin resistance among adults aged 20-39 years. No evidence was found to support the role of race/ethnicity in the relationship. Health care professionals should be aware of risk factors for insulin resistance and develop interventions to help prevent the progression of insulin resistance to type 2 diabetes mellitus.
Current literature regarding the effect of selenium supplementation on risk of diabetes is inconclusive. Hence a longitudinal study was conducted to investigate the effect of selenium supplementation on serum glucose levels in elderly men.
Data were obtained from 699 men participating in a randomized, double-blind, placebo-controlled Phase 3 clinical trial investigating the effect of two doses of selenium (200 and 400 μg/day) compared to placebo on incidence of prostate cancer. Subjects were followed every six months for up to five years. Serum glucose levels were obtained every six months. Mixed effects regression models were used to assess if rate of change of serum glucose levels was significantly different in the selenium supplemented groups as compared to placebo. Sensitivity analyses were performed to assess the robustness of findings and to minimize the possibility of residual bias due to fasting status.
Of the total 2893 glucose measurements, 734 were carried out when the subject had been fasting for ≥ 8 hours. The changes in serum glucose levels during the course of the trial were not statistically significantly different as compared to placebo for the selenium 200 μg/day (p = 0.98) or selenium 400 μg/day (p = 0.81) treatment groups. Sensitivity analyses demonstrated comparable results for models using the total population and models restricted to subjects with only fasting glucose data.
These results do not support a relationship between selenium supplementation and risk of diabetes. Hence recommendations regarding selenium supplementation based on increased risk of diabetes seem premature.
So far, studies on the association between glucose transporter 1 (GLUT1) rs841853 polymorphism and type 2 diabetes mellitus (T2DM) risk have generated considerable controversy. The current study was performed to clarify the association of this genetic variation and T2DM.
A comprehensive literature search of electronic databases was conducted to obtain articles focused on the relationship between GLUT1 rs841853 polymorphism and T2DM, followed by a systemic meta-analysis.
Fourteen articles and nineteen individual studies were included finally. Main analyses revealed extreme heterogeneity and random effect pooled ORs were weakly significant in allele contrast [OR=1.28, CI (1.01, 1.63), p=0.04] and dominant model [OR=1.52, CI (1.19, 1.94), p=0.0008] for allele T. Subgroup analyses for Caucasians showed marginal positive results in dominant model. However, analyses for Asians yielded obvious relationship to T2DM risk in all genetic models. Interestingly, allele T even seemed to be a protective factor for developing T2DM for Blacks in allele contrast. Sensitivity analyses did not alter materially for most comparisons and no publication bias was found in this meta-analysis.
The results of current meta-analysis provided evidence that GLUT1 rs841853 polymorphism may confer increased susceptibility to T2DM in Asians. However, no strong evidence currently available supports the association between this genetic variation and T2DM in Caucasians, Blacks or overall population.
Population-based (PB) registries of type 1 diabetes (T1D) in children have been essential in determining the geographic, racial and temporal patterns of the disease. There is a paucity of PB data on the prevalence of type 1 and type 2 diabetes (T2D) in youth.
Prevalence of diabetes in children was determined using a PB survey of the 628 schools in Philadelphia. Data obtained included type of diabetes, DOB, race, gender, date of diagnosis, diabetes treatment, and most recent height and weight.
The survey was completed by nurses at 510 schools (81% of schools) representing 252,896 children (70% of children in Philadelphia). Prevalence (per 1000) was computed assuming data were missing at random. The survey identified 492 school children with diabetes (355 T1D, 88 T2D, 49 type unknown). Overall prevalence of T1D was 1.58 (0.73 W, 0.56 AA, 0.50 H) and T2D was 0.35 (0.03 W, 0.28 AA, 0.05 H). Mean age of diagnosis was T1D= 8.6 yr, T2D= 11.9 yr. T1D was greater in males, T2D in females. Of children with T2D, 25% were treated with insulin. BMI was >95th % in 20% of children weighed; 10% of T1D, 57% of T2D.
Although the Philadelphia Pediatric Diabetes Registry is the longest ongoing US incidence registry of its kind, these are the first PB prevalence data of children with diabetes in Philadelphia, PB studies in schools are able to capture children with diabetes who are diagnosed and treated in a variety of settings.
The Philadelphia data demonstrate that T1DM is 4.5 times more prevalent than T2DM in children. Although there has been a marked increase of T2DM, it is critical to recognize that T1DM continues to be a much greater risk for children.
Few studies have examined the prevalence of diabetes in youth because of inherent difficulties in case ascertainment. These data are among the few derived from a population based prevalence study of type 1 and type 2 diabetes in youth.
Maturity-onset diabetes of young (MODY) is a heterogeneous group of monogenic diabetes subtypes characterized by onset before age 25, residual β-cell function and autosomal dominant inheritance. In addition to diabetes, HNF1β-MODY (hepatocyte nuclear factor1β, formerly MODY5) exhibits a phenotype of structural renal abnormalities, abnormal liver function tests, hyperuricemia and abnormalities of the pancreas, genital tract and gastrointestinal system1,2. In contrast to HNF1α- and HNF4α-MODY patients who are sensitive to sulfonylureas, HNF1β-MODY patients usually require insulin3. There is no report of successful use of metformin or insulin sensitizers in this setting.
]]>To assess baseline characteristics, glycemic control and treatment with oral antidiabetic drugs (OAD) in type 2 diabetes mellitus (T2DM) patients.
This multinational, observational study comprised: 1) cross-sectional survey; 2) longitudinal phase evaluating 6-month follow-up of sulfonylurea (SU)-treated patients. Inclusion criteria: patients ≥21 years, newly diagnosed/treated with OAD monotherapy for <6 months but inadequately controlled. Data collected for cross-sectional study were demographics, medical history, diabetic complications and co-morbidities, OAD treatment, glycosylated hemoglobin (HbA1c), fasting blood glucose (FBG), absenteeism and hospitalization. For longitudinal phase, additional data were collected on achievement of HbA1c target, reasons for not achieving HbA1c target, and patient compliance.
Cross-sectional survey (N=1487):- newly diagnosed: 75.9%; males: 46.7%; mean age: 52.0±11.6 years; mean body mass index: 25.8±4.4 kg/m2; central obesity: 73.3%; hypertension: 43.8%; dyslipidemia: 60.5%; mean diabetes duration: 1.1 years; mean HbA1c: 9.8±2.4%; mean FBG: 11.3±4.3 mmol/L; previously received OAD: 21.8% (SU: 58.3%, biguanide: 47.2%). Longitudinal phase:- at baseline (T0, N=1066) and 6-month (T6, N=830) visits, 99.8% and 97.1% patients received SU, respectively. There was decrease in mean HbA1c (T0 10.2% vs. T6 7.3%, p<0.0001), and mean FBG (T0 11.9 mmol/L vs. T6 4.2 mmol/L, p<0.0001). Patients with HbA1c<7% increased from 4.5% at T0 to 46.8% at T6. Reasons for not achieving target HbA1c: poor diabetes education 50.7%, non-compliance to OADs 21.4%, fear of hypoglycemia 19.7%.
In T2DM patients managed with OADs, marked reductions in HbA1c and FBG are achievable. However, patient education and compliance are important for achieving and maintaining treatment targets.
To identify the optimal threshold of HbA1c and to evaluate the predictive performance of HbA1c levels in diagnosing diabetes and prediabetes in a middle-aged and elderly Han Chinese population from northwest China.
A total of 3354 participants aged 40 years or older with no history of diabetes from northwest China were enrolled in this cross-sectional study. All subjects underwent a 75g OGTT and HbA1c test. HbA1c thresholds for diagnosing diabetes and prediabetes were identified by highest sum of sensitivity and specificity of each cutoff points and the receiver operating characteristic curve was used to evaluate the diagnostic accuracy of the HbA1c threshold.
The mean (±SD) age of the participants was 57±8 years, and 70.75% were women. According to OGTT, a total of 1347 (40.16%) subjects had impaired fasting glucose and/or impaired glucose tolerance, 725 (21.62%) had diabetes. The area under the receiver operating characteristics curve for detecting undiagnosed diabetes and prediabetes by HbA1c levels were 0.810 (95%CI: 0.796-0.823) and 0.732 (95%CI: 0.717-0.747), respectively. HbA1c threshold of 6.4% and 6.1% produced the highest sum of sensitivity (60.00% and 61.49%) and specificity (87.33% and 73.24%) for diagnosing diabetes and prediabetes, respectively.
HbA1c is an effective and convenient method for diagnosing diabetes and prediabetes. The HbA1c threshold of 6.4% and 6.1% may be used as diagnostic criteria for diabetes and prediabetes, respectively, in Han Chinese population living in northwest China.
The main finding of this study is that the optimal threshold for diagnosing diabetes and prediabetes were 6.4% and 6.1%, respectively, in Han Chinese living in northwest China.
To our knowledge, it is the first time that HbA1c was tested and the optimal threshold for diagnosing diabetes and prediabetes in such a large Han Chinese population in Northwest China.
Various ocular conditions which leadto vision loss in different degrees such as cataract, ischemic optic neuropathy and retinopathy are closely related to diabetes mellitus. 1-3 Diabetic patients may also suffer from transient or permanent changes in refraction. 4-5 We describe here an extreme case of transient hyperopia in a newly diagnosed diabetic patient following intense blood glucose control.
]]>To determine if the addition of nurse case managers (NCMs) trained in motivational interviewing (MI) to usual care would result in improved outcomes in high risk type 2 diabetes patients.
A 2-year randomized controlled pragmatic trial randomized 545 patients to usual care control (n=313) or those who received the intervention (n= 232) with additional practice embedded NCM care, including MI-guided behavior change counseling. NCMs received intensive MI training with ongoing fidelity assessment.
Systolic BP was better in the intervention group (131±15.9 vs. 135±18.2, p < 0.05). HbA1c, LDL, and diastolic BP improved in both groups: HbA1c (control group 9.1% to 8.0%, intervention group 8.8% to 7.8%), LDL (control group 127 to 100 mg/dL, intervention group 128 to 102 mg/dL), diastolic BP (control group 78 to 74 mm Hg, intervention group 80 to 74 mm Hg). Depression symptom scores were better in the intervention group. The reduction in diabetes-related distress approached statistical significance.
NCMs and MI improved systolic BP and complications screening. The large decrease in HbA1C and LDL in the control group may have obscured any further intervention effect. Although nurses prompted providers for medication titration, strategies to reduce provider clinical inertia might also be needed.
In patients with type 2 diabetes, an intervention with nurse case management and motivational interviewing improves systolic blood pressure, depression, and screening for complications.
First study to look at the benefit of the addition of motivational interviewing to nurse case management in the care of the high-risk adult with type 2 diabetes. Particular attention was given to ensuring fidelity to the motivational interviewing approach.
Genetic variants of PPP1R3B, a gene encoding a critical protein involved in hepatic glycogen metabolism were recently reported to be associated with plasma levels of lipids and C-reactive protein (CRP) among populations of mostly European descent. This study aimed to examine whether the PPP1R3B variants are associated with plasma levels of lipids and inflammation factors in Chinese Hans with different circulating profiles of these two phenotypes.
In this study, five SNPs of PPP1R3B gene were genotyped and their associations with plasma lipids and CRP were determined in 1,636 Chinese Hans.
Three SNPs, namely rs2126259, rs9987289 and rs19334 were significantly associated with plasma levels of low-density lipoprotein cholesterol (LDL-C), and rs2126259 and rs9987289 were also significantly associated with total cholesterol. Moreover, the other two SNPs (rs189798 and rs330919) were significantly associated with plasma CRP level, but not with plasma lipid levels.
PPP1R3B genetic polymorphisms may contribute to the variations of plasma lipid and CRP levels among Chinese Hans.
revealed that the genetic polymorphisms of PPP1R3B might influence the levels of circulating lipids and CRP levels among Chinese Hans.
the associations of PPP1R3B gene polymorphism with cardiovascular disease risk factors in Chinese population.
The forkhead box O subfamily has four members including FoxO1, FoxO3, FoxO4 and FoxO6. Unlike other three FoxO members, FoxO6 has garnered considerably less attention due to earlier reports that FoxO6 is limited to the brain. Recent data indicate that FoxO6 is produced in the liver of both rodent and human origins. Hepatic FoxO6 activity, which remains at low basal levels in fed states, is markedly induced in fasted mice. FoxO6 activity becomes abnormally higher in the liver of mice with dietary obesity or type 2 diabetes. Genetically engineered mice with elevated FoxO6 activity in the liver exhibit pre-diabetes, culminating in the development of glucose intolerance, fasting hyperglycemia and hyperinsulinemia. Conversely, inhibition of FoxO6 activity in insulin-resistant liver results in the reduction of fasting hyperglycemia, contributing to the amelioration of hyperinsulinemia in type 2 diabetic mice. These new data suggest that FoxO6 is an important regulator of hepatic glucose metabolism in response to insulin or physiological cues. Insulin inhibits FoxO6 activity by promoting its phosphorylation and disabling its activity in the nucleus without altering its subcellular distribution via a mechanism that is distinct from other members of the FoxO subfamily. In this article, we will provide a comprehensive review on the role of FoxO6 in glucose metabolism in health and disease. We will also address whether FoxO6 dysregulation is a contributing factor for the pathogenesis of fasting hyperglycemia and discuss whether FoxO6 is a potential therapeutic target for improving fasting hyperglycemia in type 2 diabetes.
Based on increasing evidence from animal and human studies, vitamin D deficiency is now regarded as a potential risk factor for type 2 diabetes (T2D). Vitamin D is involved in the pathogenesis of pancreatic β-cell dysfunction, insulin resistance and systemic inflammation, conditions that contribute to the development of T2D. Vitamin D can affect the progress of this disease directly through the activation of its own receptor and indirectly via the regulation of calcium (Ca) homeostasis. Observational studies have revealed an inverse association between vitamin D deficiency and incident T2D. More double-blind randomized control studies that investigate the effects of vitamin D supplementation on insulin sensitivity, insulin secretion and the occurrence of T2D are needed.
© 2013 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and Wiley Publishing Asia Pty Ltd
With the recent knowledge of the possible involvement of 1,25-dihydroxyvitamin D in the pathogenesis of Type 1 Diabetes (T1D) and the results of its administration in animal models, we conducted a clinical trial by treating high-risk children, positive in autoantibodies for T1D, with oral calcitriol.
This prospective trial included 12 children aged 1.5-13 yrs at presentation, who were investigated for the potential risk for T1D because of the already diagnosed association of celiac disease and autoimmune thyroiditis (4 girls), autoimmune thyroiditis at a very young age (2 girls, 2 boys), diagnosis of T1D in their siblings (2 boys) and impaired glucose tolerance (1 boy, 1 girl). Serum levels of autoantibodies (ICA, anti-GAD65, IAA, anti-IA2) and calcium metabolism (Ca, P, PTH, ALP, total 25(OH)vitamin D and Ca/Cr in 2-hr morning urine sample) were evaluated prior and at 6 month intervals after initiating 0.25 μg daily calcitriol for 1 to 3 yrs.
In all children included persistent negativation of the anti-GAD65 (7 children) and IAA autoantibodies (6 children) was observed within 0.4-2.1 yrs. Of the two children with IGT the boy proved to have MODY 2 and the girl normalized her glycaemic profile.
Despite the small number of subjects and the absence of a control group, 0.25 μg of daily calcitriol is effective in negativation of the anti-GAD65 and IAA autoantibodies at a median time of 6 months. This simple, safe and of low cost strategy may prove effective in prevention of T1D in the future.
© 2013 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and Wiley Publishing Asia Pty Ltd
The insulinotropic activity of the combined root and stem of Gongronema latifolium (Asclepiadaceae) was evaluated to justify its African ethnomedicinal use in the management of diabetes.
A methanolic extract of the combined root and stem and its vacuum liquid chromatographic fractions (A1-A6) were tested for glucose reducing and in vitro insulin stimulating abilities using glucose loaded rats and INS-1 cells, respectively. In vivo insulin releasing activities for the significantly (p < 0.05) active anti-hyperglycaemic A5 and A6 were determined, using glucose loaded rats. In vitro insulin stimulating potential of column chromatographic fraction C1 and its isolated constituents were also determined.
The extract (100 mg/kg) had higher in vivo anti-hyperglycaemic activity than the individual fractions A1-A6, indicating a synergistic effect of the plant constituents. Higher in vivo insulin release given by A5 (100 mg/kg) than that of A6 agreed with their in vivo anti-hyperglycaemic activities and confirmed insulin release as a hitherto unreported mechanism of action of the plant. Compared to 5.6 mM glucose (negative control), the extract, A3, A6 and C1 (100.0 μg/mL) elicited significantly (p < 0.05) higher in vitro insulin release that was similar (p > 0.05) to glibenclamide (1.0 μg/ml). Fraction C1 yielded a 1:1 mixture of α-amyrin and β-amyrin cinnamates (1a/1b), lupenyl cinnamate (2), lupenyl acetate (3) as well as two unidentified triterpenoids, Y and Z. The 1a/1b (100.0 μg/mL) demonstrated the highest insulinotropic activity comparable (p > 0.05) to that of glibenclamide (1.0 μg/ml).
The results confirmed pancreatic activity as a mechanism of antidiabetic action for G. latifolium and justified its ethnomedical use.
© 2012 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and Wiley Publishing Asia Pty Ltd
To investigate the association of arch type and gender to the plantar pressure distribution in subjects without diabetes mellitus and diabetics without peripheral neuropathy.
Plantar pressures of 62 type 2 diabetes subjects (aged 63.6 ± 7.6 years; BMI 24.3 ± 2.9; duration of diabetes 7 ± 2.5 years) with no peripheral neuropathy and 63 non diabetic adults (aged 62.5 ± 8.5 years; BMI 22.4 ± 2.5) were recorded in static stance using a foot analyzer. Data was collected from both feet and were analyzed for their association with disease, arch type and gender using ‘Mann Whitney U test’ and ‘Chi square test’ respectively.
A significant difference was noted between the plantar pressures of left and right feet in diabetic subjects of both gender and their metatarsal heads were over-loaded in terms of magnitude. This increased over-load noted in the plantar pressures correlated poorly with the type of the foot arch and gender of all the diabetic subjects. However, there was no difference noted between the pressures at different zones amongst the diabetic and non-diabetic groups.
No difference in plantar pressures was identified between the non-diabetic subjects and the diabetics without peripheral neuropathy. No significant correlation was found between plantar pressures in diabetic subjects and their arch type or gender. There was however significant difference in plantar pressures between right and left feet
© 2012 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and Wiley Publishing Asia Pty Ltd
To examine the association between antidepressant use, diagnosed depression, and new onset diabetes among elderly Medicare beneficiaries.
Longitudinal data from merged survey and claims from the nationally representative Medicare Current Beneficiary Survey(MCBS) from 1999-2005 were used. Diabetes incidence was extracted from claims and survey data over a 3-year period. Depression and antidepressant use data were obtained over time. Multivariable logistic regressions were used to examine association between antidepressant use, depression, and new onset diabetes, adjusted for demographic, socioeconomic, and lifestyle risk factors. Analyses accounted for complex design of MCBS.
Incident diabetes rate was 4.8% for those “without depression and without antidepressants” and 9.5% for those with any antidepressant use in all 3-years and diagnosed depression. Compared to Medicare beneficiaries who did not report any antidepressant use, beneficiaries reporting antidepressant use in all 3-years were 50% more likely to have new onset diabetes. However, when diagnosed depression was entered in the model, we did not observe a statistically significant association between long-term antidepressant use and new onset diabetes. Medicare beneficiaries with any depression were twice as likely as those without depression to develop diabetes(AOR = 2.04, [1.51, 2.75).
Depression could independently increase risk of developing diabetes, while there is no evidence of association between antidepressants and new onset diabetes. If replicated, these results have significant clinical implications.
We found increased diabetes risk among Medicare beneficiaries with depression.
Long-term use of antidepressants in the absence of depression increases risk of diabetes.
© 2012 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and Wiley Publishing Asia Pty Ltd
The objective of the current study was to compare the efficacy of two different insulin formulations, insulin aspart (IAsp) and regular human insulin (RHI), for prandial insulin coverage with neutral protamine Hagedorn (NPH) insulin as basal insulin using a meta-analysis approach. The primary endpoint was change in A1c over time. Secondary endpoints included incidence of hypoglycemia and postprandial glycemic control.
Clinical trials (Type 1 and Type 2 diabetes) complying with Good Clinical Practice, and with individual patient data, were included in the meta-analysis. Trials were randomized, consisting of (at least) two treatment arms and had a minimum duration of 12 weeks. Estimates were calculated using fixed-effects and random-effects models. Heterogeneity was assessed for each analysis. The effect of baseline parameters on A1c was analyzed in extended simultaneous models.
The mean difference in A1c was 0.1% (95% confidence interval [CI] [−0.15; −0.04], P < 0.001) in favor of IAsp. Higher accumulated dose of IAsp, higher age and increased rates of hypoglycemia were associated with improved A1c outcome. Fasting plasma glucose was not significantly different between regimens. Postprandial glucose was significantly lower after treatment with IAsp compared with RHI, but the analysis did present a significant level of heterogeneity (P < 0.001). The overall rate of hypoglycemia was the same with both regimens, but nocturnal hypoglycemia was significantly lower with IAsp.
A basal–bolus regimen with IAsp as bolus insulin provided minimal, but statistically significant, improvement in overall glycemic control with a lower rate of nocturnal hypoglycemic episodes, compared with a corresponding regimen with bolus RHI.
Type 2 diabetes (T2D) is one of the most common diseases, affecting 5–10% of the population in most countries; the progression of its prevalence has been constant over the past 50 years in all countries worldwide, creating a major public health problem in terms of disease management and financial burden. Although the pathophysiology of T2D has been attributed for decades to insulin resistance and decreased insulin secretion, particularly in response to glucose, the contributing role of glucagon in hyperglycemia has been highlighted since the early 1970s by demonstrating its glycogenolytic, gluconeogenic and ketogenic properties. More recently, the importance of glucagon in diabetes has been highlighted in a model of streptozotocin-induced diabetic mice becoming euglycemic in the absence of glucagon receptors and without insulin treatment. Understanding the dysregulation of α-cells in diabetes will be critical to better define the pathophysiology of diabetes and develop new antidiabetic treatment.
2型糖尿病是最常见的疾病之一，在大部分国家5%–10%的人群受其影响；在过去的50年时间里，全世界所有国家的糖尿病患病率都在不断增加，由于疾病管理与财政负担，糖尿病已经成为一个主要的公共健康问题。虽然近几十年以来2型糖尿病的病理生理已经被归因于胰岛素抵抗与胰岛素分泌减少，特别是对葡萄糖的反应，从20世纪70年代初以来已经证实了胰升糖素具有分解糖原、葡萄糖异生以及生酮作用，并强调了其在高血糖中所起的作用。近期，在一个链脲霉素诱导的糖尿病小鼠模型中，敲除胰升糖素受体后即使不使用胰岛素治疗小鼠的血糖仍正常，这凸显了胰高血糖素在糖尿病中的重要性。为了更好地解释糖尿病的病理生理以及研制新型的降糖治疗药物，了解糖尿病的α细胞功能失调至关重要。
Several classes of antidiabetic agents have been introduced into the market place over the past dozen years. As our understanding of the underlying pathophysiology of type 2 diabetes has advanced, attempts have been made to address these defects specifically. This brief review focuses on our experience with two such pharmacological approaches: (i) a synthetic amylin analog addressing amylin deficiency; and (ii) a dopaminergic agonist, focused on enhancing the lowered dopaminergic tone in patients with type 2 diabetes. Importantly, the use of these agents is not associated with hypoglycemia or weight gain.
在过去的十几年里有几类降糖药物已经被推向了市场。随着我们对2型糖尿病潜在病理生理学的理解日益深入，我们已经在尝试研制特别针对这些缺陷的药物。这篇简要的综述关注于我们对以下两个药物的使用经验：（i）一种合成的胰淀素类似物，用来解决胰淀素缺乏的问题；以及（ii）一种多巴胺受体激动剂，用来增强2型糖尿病患者降低的多巴胺效应。重要的是，使用这些药物与低血糖或者体重增加都没有关系。
Latent autoimmune diabetes in adults (LADA) is a form of autoimmune diabetes with features of both type 1 and type 2 diabetes and in the middle of the diabetes spectrum. Scientists clash on the question of whether this type of diabetes is a unique diabetes subtype. Multicenter studies have been performed in different countries, including the Korea National Diabetes Program (KNDP) collaboratory group, the Ehime study in Japan, the Not Insulin-Requiring Autoimmune Diabetes (NIRAD) study in Italy, the Nord-Trøndelag Health (HUNT) study in Norway, the UK Prospective Diabetes Study (UKPDS) in the UK, the Action LADA study in Europe and the LADA China study in China. These studies found universal immunogenetic effects associated with LADA, but with some ethnic differences. Herein we summarize those multicenter studies and compare the ethnic similarities and differences between East and West from epidemiological, clinical, immune, and genetic viewpoints.
成人隐匿性自身免疫糖尿病（LADA）是自身免疫糖尿病的一种亚型，处于糖尿病连续疾病谱的中间，兼具1型糖尿病和2型糖尿病的特征。目前对于这类糖尿病究竟是否为一种独立的糖尿病亚型仍有分歧。已有多项关于LADA的多中心研究在不同国家开展，其中包括：韩国国家糖尿病计划(KNDP) 协作组、日本Ehime研究、意大利NIRAD研究、挪威HUNT研究、英国UKPDS研究、欧洲Action LADA研究以及中国LADA China研究。上述研究发现LADA具有普遍的免疫遗传特征, 但仍存在种族差异。因此，我们从流行病学、临床特点、免疫遗传学等多个方面总结上述多中心研究，比较东西方LADA之间的种族差异。
This open-label, single-period study assessed the pharmacokinetics, safety, tolerability, and pharmacodynamics of exenatide once weekly (q.w.), following single and multiple weekly subcutaneous (s.c.) injections in native Chinese patients with type 2 diabetes (T2D).
Patients (n = 25; mean [±SD] age 51.3 ± 8.2 years; body mass index 25.6 ± 2.4 kg/m2; HbA1c 7.4 ± 1.2%; duration of diabetes 3.1 ± 3.1 years) previously treated with diet modification and exercise alone or incombination with stable metformin doses were enrolled in the study. Twenty-five patients received weekly doses of 2 mg, s.c., exenatide q.w. for 10 weeks, followed by 10 weeks observation. Pharmacokinetic parameters of exenatide, fasting plasma glucose (FPG), HbA1c, and body weight were summarized using descriptive statistics.
Steady state plasma exenatide concentrations (299 pg/mL) were attained within 8 weeks. Exenatide q.w. was generally well tolerated, and the majority of adverse events reported were mild in severity. The most frequent study drug-related adverse events were diarrhea and vomiting. Decreases were observed from baseline to 10 weeks in FPG (~3.0 mmol/L), HbA1c (~1.0%), and body weight (~3.8 kg).
This is the first clinical trial of exenatide q.w. in native Chinese patients with T2D. The results suggest that exenatide q.w. has a pharmacokinetic profile in this patient population similar to that observed in other ethnic and racial populations, and appears to be safe and generally well tolerated, with the potential to improve glycemic control and decrease body weight without increasing the risk of hypoglycemia.
考察了对中国本土2型糖尿病患者给予单次和多次皮下注射艾塞那肽周制剂的药代动力学、药效动力学、安全性和耐受性。研究设计为开放性、单周期。
入选对象为仅靠饮食控制和锻炼或联合使用稳定剂量的二甲双胍控制血糖的患者（n=25人，平均年龄51.3±8.2岁，BMI 25.6±2.4 kg/m2，HbA1c 7.4%±1.2%，糖尿病病程3.1±3.1年）。25名患者接受每周皮下注射艾塞那肽周制剂，剂量为2mg，共10周，并在停药后随访10周。对艾塞那肽的药代动力学参数、空腹血糖FBG、HbA1c和体重进行描述性统计。
给药8周时艾塞那肽达到稳态血药浓度（299 pg/mL）。艾塞那肽周制剂耐受性良好，绝大多数报告的不良事件均为轻度。与研究药物相关的最常见的不良事件是腹泻和呕吐。与基线相比给药10周后FBG降低最多达3.0 mmol/L，HbA1c降低最多达1.0%，体重降低最多达3.8 kg。
这是艾塞那肽周制剂首次用于中国本土2型糖尿病患者的临床试验。研究结果显示，艾塞那肽周制剂在中国糖尿病患者中的药代动力学特性和在其他种族中相似。该药物是安全的，耐受性良好，可以改善血糖控制和降低体重，同时不会增加低血糖风险。
Genetic determinations are important in type 2 diabetes (T2DM) pathology. We investigated associations between genetic variants of 17 diabetes-related genes/loci, T2DM and diabetic complications in Chinese She subjects.
A comprehensive gene-based association study was conducted using 17 single nucleotide polymorphisms in Chinese She subjects with normal glucose tolerance (n = 1119), impaired glucose regulation (n = 1767), and T2DM (n = 443). We applied major abnormal Minnesota Code findings to predict cardiovascular risk and estimated glomerular filtration rate to assess kidney function.
Nine variants in FTO rs8050136, WFS1 rs10010131, CDKN2A/B rs10811661, KCNJ11 rs5219, CDC123/CAMK1D rs12779790, JAZF1 rs864745, SLC30A8 rs13266634, CDKAL1 rs10946398, and HHEX/IDE rs5015480 were significantly associated with T2DM (P < 0.05). Single nucleotide polymorphisms in WFS1 rs10010131, CDKN2A/B rs10811661, CDC123/CAMK1D rs12779790, JAZF1 rs864745, FTO rs8050136, and HHEX/IDE rs5015480 were associated with T2DM and impaired glucose regulation. Risk alleles in WFS1 rs10010131, IGF2BP2 rs4402960, CDKAL1 rs10946398, FTO rs8050136, KCNQ1 rs2237897, and ADAMTS9 rs4607103 were significantly associated with decreased homeostatic model assessment (HOMA)-β (P < 0.05). After adjusting for age, gender and body mass index, genetic variants JAZF1 rs864745, FTO rs8050136, and HHEX/IDE rs5015480 were significantly related to reduced estimated glomerular filtration rate (P < 0.05). Genetic variants in WFS1 rs10010131, CDKN2A/B rs10811661, CDC123/CAMID rs12779790, JAZF1 rs864745, FTO rs80501360, CDKAL1 rs10946398, and HHEX/IDE rs5015480 correlated with abnormal major Minnesota Code findings (P < 0.05).
Variants in WFS1, CDKN2A/B, KCNJ11, CDC123/CAMK1D, JAZF1, SLC30A8, FTO, CDKAL1, and HHEX/IDE genes are significantly associated with T2DM in She Chinese subjects. JAZF1, FTO, CDKAL1, and HHEX/IDE are associated with diabetic nephropathy. WFS1, CDKN2A/B, CDC123/CAMK1D, JAZF1, FTO, CDKAL1, and HHEX/IDE are associated with cardiovascular risk.
遗传是决定2型糖尿病发病的重要因素。我们分析了中国畲族人群17个糖尿病相关基因位点的遗传变异与2型糖尿病及并发症之间的相关性。
一项全面的以基因为基础的相关性研究，评估了中国畲族人群的糖耐量正常者（n=1119）、糖耐量异常者（n=1767）和2型糖尿病患者（n=443）的17个基因的单核苷酸多态性（SNP）。以主要的明尼苏达编码异常预测心血管风险，用估算肾小球滤过率评估肾功能。
FTO rs8050136，WFS1 rs10010131，CDKN2A/B rs10811661，KCNJ11 rs5219，CDC123/CAMK1D rs12779790，JAZF1 rs864745，SLC30A8 rs13266634，CDKAL1 rs10946398，和HHEX/IDE rs5015480等9个基因位点变异与2型糖尿病显著相关 （P<0.05）。WFS1 rs10010131，CDKN2A/B rs10811661，CDC123/CAMK1D rs12779790，JAZF1 rs864745，FTO rs8050136和HHEX/IDE rs5015480等的SNP与2型糖尿病和糖耐量异常相关。WFS1 rs10010131，IGF2BP2 rs4402960，CDKAL1 rs10946398，FTO rs8050136，KCNQ1 rs2237897和 ADAMTS9 rs4607103等的风险等位基因与HOMA-β指数降低显著相关（P<0.05）。校正年龄、性别和体重指数后，JAZF1 rs864745，FTO rs8050136和 HHEX/IDE rs5015480的基因变异与估算肾小球滤过率下降显著相关（P<0.05）。WFS1 rs10010131，CDKN2A/B rs10811661，CDC123/CAMID rs12779790，JAZF1 rs864745，FTO rs80501360， CDKAL1 rs10946398和HHEX/IDE rs5015480 等的基因变异与主要的明尼苏达编码异常显著相关（P< 0.05）。
WFS1，CDKN2A/B，KCNJ11，CDC123/CAMK1D，JAZF1，SLC30A8，FTO，CDKAL1和 HHEX/IDE等的基因变异与中国畲族人群的2型糖尿病显著相关。JAZF1，FTO，CDKAL1和 HHEX/IDE等的基因变异与糖尿病肾病相关。WFS1， CDKN2A/B，CDC123/CAMK1D，JAZF1，FTO，CDKAL1和 HHEX/IDE等的基因变异与心血管风险相关。
Background: Diabetic oxidative stress coexists with a reduction in the antioxidant status, which can further increase the deleterious effects of free radicals. Zinc is an essential trace element with significant antidiabetic activity. However, the acceptance of zinc compounds as promising therapeutic antidiabetic agents has been slowed due to concerns regarding chronic toxicity. Recently, we have designed, synthesized and characterized a novel zinc–flavonol complex and evaluated its antidiabetic efficacy in streptozotocin (STZ)-diabetic rats. The aim of the present study was to evaluate the role of the zinc–flavonol complex in the antioxidant status of diabetic rats.
Methods: Diabetes was induced in rats by i.p. injection of STZ. Diabetic rats were then treated with the zinc–flavonol complex (5 mg/kg, p.o.) for 30 days. The extent of oxidative stress was assessed by determining lipid peroxide levels, pancreatic tissue antioxidant enzyme activities and plasma concentrations of non-enzymatic antioxidants. In addition, nuclear levels of nuclear factor (NF)-κB p65, pancreatic nitric oxide (NO), and plasma levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6 were determined. Pancreatic tissues were examined histologically.
Results: Oral treatment with the zinc–flavonol complex significantly improved antioxidant levels and alleviated levels of oxidative stress markers. Furthermore, significant increases were seen in NF-κB p65, NO, TNF-α, IL-1β and IL-6 levels. Histological observations revealed that the zinc–flavonol complex effectively protects pancreatic β-cells against oxidative damage.
Conclusion: The results of the present study indicate that the zinc–flavonol complex has an antioxidative and anti-inflammatory role in the diabetic milieu.
背景： 糖尿病的氧化应激与抗氧化能力下降同时存在，进一步增加了自由基的损害作用。锌是一种人体必需的微量元素，它具有显著的抗糖尿病活性。然而，因为担心导致慢性中毒，所以将锌化合物作为有前途的抗糖尿病治疗药物目前还未能被人们接受。最近，我们设计、合成了一种具有特征性的新型锌黄酮醇复合物，并且在链脲霉素（STZ）-糖尿病大鼠中评估了它的抗糖尿病疗效。本研究的目的是评估锌黄酮醇复合物在糖尿病大鼠中的抗氧化能力。
方法： 大鼠通过腹腔内注射STZ诱导出糖尿病。接着对糖尿病大鼠使用锌黄酮醇复合物（5 mg/kg，口服）治疗30天。通过测定过氧化的脂质水平、胰腺组织抗氧化物酶活性以及血浆中的非酶类抗氧化物浓度来评估氧化应激的程度。另外，还测定了核因子（NF）-ΚB p65的细胞核水平，胰腺一氧化氮（NO），TNF-α、IL-1β以及IL-6的血浆水平。对胰腺组织进行组织学检查。
结果： 口服锌黄酮醇复合物可显著地改善抗氧化物的水平，同时减少氧化应激标志物的水平。此外，还可以看到NF-KB p65、NO、TNF-a、IL-1β以及IL-6水平显著升高。组织学观察结果显示锌黄酮醇复合物能够有效地保护胰腺β细胞免受氧化损伤。
结论： 本研究结果表明，在糖尿病环境中锌黄酮醇复合物具有抗氧化以及抗炎的作用。
Background: To evaluate the effects of a nutritional education program on cardiovascular risk among elderly patients with type 2 diabetes (T2D).
Methods: Ninety-seven elderly patients with T2D were enrolled in the present randomized controlled educational trial study. Patients were divided into intervention and control groups. The Belief, Attitude, Subjective Norm, Enabling Factors (BASNEF) educational model was used to design the educational intervention. Patients in the control group received their usual care during the study. Anthropometric data, lipid profiles and blood pressure measurements were collected at baseline and Week 12 in each group.
Results: Significant declines were observed in the intervention compared with control group in terms of body weight (−1.3 ± 1.1 vs 0.11 ± 0.58 kg, respectively), body mass index (−0.48 ± 0.37 vs 0.05 ± 0.22 kg/m2, respectively), serum triglyceride levels (−18.25 ± 32.15 vs −3.67 ± 22.61 mg/dL, respectively; P < 0.05 for all), and the waist-to-hip ratio (P = 0.03). There were no significant differences between the intervention and control groups in terms of high-density lipoprotein–cholesterol (−1.02 ± 4.35 vs −1.10 ± 6.93 mg/dL, respectively; P = 0.9) or low-density lipoprotein–cholesterol (−4.04 ± 11.64 vs −1.08 ± 4.35 mg/dL, respectively; P = 0.2).
Conclusions: Short-term nutritional education based on the BASNEF educational model improves serum triglyceride levels and anthropometric indices in elderly patients with T2D.
背景： 评估营养教育计划对老年2型糖尿病患者心血管风险的影响。
方法： 本随机对照教育试验入组了97名老年2型糖尿病患者。患者被分为干预组与对照组。采用信仰、态度、主观规范、促成因素（BASNEF）教育模型来设计教育干预计划。研究期间对照组的患者接受常规护理。收集患者在基线与第12周时的人体测量数据、脂质特征以及血压测量结果。
结果： 与对照组相比，可以观察到干预组患者的体重（分别为-1.3±1.1 kg与0.11±0.58kg）、体重指数（分别为-0.48±0.37 kg/m2与0.05±0.22 kg/m2）、血清甘油三酯水平（分别为-18.25±32.15与-3.67±22.61mg/dL）（所有的P<0.05）以及腰-臀比（P=0.03）均显著下降。干预组与对照组之间的高密度脂蛋白胆固醇（分别为-1.02±4.35 mg/dL与-1.10±6.93 mg/dL；P=0.9）或者低密度脂蛋白胆固醇（分别为-4.04±11.64与-1.08±4.35 mg/dL；P=0.2）没有显著差异。
结论： 基于BASNEF教育模型的短期营养教育可以改善老年2型糖尿病患者的血清甘油三酯水平以及人体测量指标。
Background: In addition to its glucoregulatory actions, exendin-4, a stable glucagon-like peptide-1 receptor agonist, exhibits protective effects in the pancreas and anti-obesity effects. Suitable combination treatment with other anti-obesity or pancreas protective agents would be an effective approach to optimize these additional effects. In the present study, we investigated the effects of the addition of omeprazole, a proton pump inhibitor, to exendin-4 in db/db mice, an experimental model of obesity and type 2 diabetes.
Methods: The effects repeated dose treatment for 14 days with exendin-4 (8 μg/kg, s.c.) and omeprazole (30 mg/kg, s.c.) on glycemic control, food intake, and body weight were determined in obese and hyperglycemic db/db mice. The effects of these treatments on plasma gastrin, ghrelin, and leptin levels were determined, along with effects on nausea-like symptoms. The pancreatic effects of the repeated dose treatment were assessed by measuring %HbA1c in the circulation as well as pancreatic insulin and glucagon content and glucokinase activity.
Results: Combination treatment resulted in significant decreases in plasma leptin and ghrelin levels after repeated dosing. Omeprazole improved the anorectic and body weight-lowering effects and reversed the inhibitory effect of exendin-4 on gastrin levels after repeated dose treatment. The 14-day combination treatment significantly reduced glucose excursion and improved insulin levels, with a concomitant decrease in %HbA1c levels. It also improved glucokinase activity and pancreatic insulin content, with a significant decrease in glucagon content.
Conclusions: Combined treatment with omeprazole with exendin-4 reduces food intake and body weight gain, most likely through changes in plasma ghrelin and leptin levels, and improves pancreatic insulin and glucagon content by improving glucokinase activity.
背景： 除了具有葡萄糖调节作用之外，唾液素-4，一种稳定的胰升糖素样肽-1受体激动剂，还具有胰腺保护作用与减肥作用。为了使这些额外的疗效最佳化，适当地联合使用其他的减肥或者胰腺保护药物将是一个有效的方法。在本研究中，我们考察了唾液素-4联合质子泵抑制剂奥美拉唑对一种2型糖尿病且肥胖的实验模型db/db小鼠的影响。
方法： 在肥胖的高血糖db/db小鼠中使用唾液素-4（8 μg/kg，皮下注射）与奥美拉唑（30 mg/kg，皮下注射）重复治疗14天后测定其对血糖控制、食物摄入以及体重的影响。测定该治疗对血浆胃泌素、胃促生长素以及瘦素水平的影响，以及它们对恶心样症状的影响。通过测定循环中的%HbA1c、胰腺内的胰岛素与胰升糖素含量以及葡萄糖激酶活性来评估重复治疗对胰腺的影响。
结果： 重复给药后，联合治疗可导致血浆瘦素与胃促生长素水平显著下降。奥美拉唑可以改善厌食与体重减轻作用，并且逆转唾液素-4对胃泌素水平的抑制作用。14天的联合治疗显著减少血糖波动，胰岛素水平也有改善，并伴随着%HbA1c水平的下降。它还改善了葡萄糖激酶的活性以及胰腺内的胰岛素含量，胰升糖素的含量则显著减少。
结论： 联合使用奥美拉唑与唾液素-4治疗后可减少食物摄入以及减少体重增加，最有可能的机制是通过改变血浆中的胃促生长素与瘦素水平，以及通过增加葡萄糖激酶的活性来改善胰腺内的胰岛素与胰升糖素含量。
To determine the prevalence of diabetic retinopathy (DR) in patients with newly diagnosed type 2 diabetes mellitus (T2DM) in Jordan, as well as the factors associated with DR.
A cross-sectional study was conducted among 127 consecutive newly diagnosed (within the past 6 months) patients with T2DM attending one of two diabetic care centers. Complete ocular examinations were performed by an ophthalmologist and relevant data were collected. A fundus examination was performed using slit lamp indirect ophthalmoscopy after pupillary dilation with 1% tropicamide drops, with DR defined and classified according to the scale developed by the Global Diabetic Retinopathy Project Group.
Of all the patients examined, 7.9% had DR. Of those with DR, 40% already had clinically significant macular edema necessitating laser photocoagulation or intravitreal injections. Multivariate analysis revealed that age and HbA1c were significantly associated with DR. The odds of DR increased by 11% for each 1 year increase in age (odds ratio [OR] 1.11; 95% confidence interval [CI] 1.02–1.20). For each 1% increase in HbA1c, the odds of DR increased by 43% (OR 1.43; 95% CI 1.09–1.88).
Fewer than one-tenth of newly diagnosed Jordanian patients with T2DM had DR, but more than one-third of these patients had significant maculopathy. Therefore, early screening is strongly recommended for all newly diagnosed T2DM patients. Increased age and HbA1c values are associated with increased odds of DR. A study with a larger sample size is needed to elucidate the risk factors for DR in newly diagnosed T2DM.
测定约旦新诊断的2型糖尿病患者出现糖尿病视网膜病变的患病率，以及与糖尿病视网膜病变相关的因素。
在就诊于两个糖尿病保健中心之一的连续的127名新诊断（在过去的6个月以内）的2型糖尿病患者中进行的横向研究。由一名眼科医师进行完整的眼部检查，并收集相关的数据。利用1%的托品酰胺滴剂散瞳后使用裂隙灯间接眼底镜检查法进行一次眼底检查，糖尿病视网膜病变的定义与分类依照全球糖尿病视网膜病变项目组制定的量表。
在所有被检查的患者中，7.9%有糖尿病视网膜病变。在那些有糖尿病视网膜病变的患者中，40%在临床上已经出现显著的黄斑水肿，他们急需进行激光凝固治疗或者玻璃体内注射治疗。多元分析结果表明，年龄以及HbA1c均与糖尿病视网膜病变显著相关。年龄每增加1岁，出现糖尿病视网膜病变的几率增加11%（OR：1.11；95%Cl：1.02-1.20）。HbA1c每增加1%，出现糖尿病视网膜病变的几率增加43%（OR：1.43；95% CI：1.09-1.88）。
约旦新诊断的2型糖尿病患者出现糖尿病视网膜病变的几率小于十分之一，但是出现糖尿病视网膜病变的患者中有显著黄斑病变的比例大于三分之一。因此，强烈推荐对所有新诊断的2型糖尿病患者进行早期筛查。年龄以及HbA1c值的增加均与糖尿病视网膜病变几率增加有关。需要进行一项更大样本量的研究来阐明新诊断的2型糖尿病患者出现糖尿病视网膜病变的危险因素。
The aim of the present study was to determine whether the administration of Diamel, marketed as a food supplement by Catalysis Laboratories (Madrid, Spain) could improve any of the components of metabolic syndrome (MS), as well as insulin resistance and sensitivity.
In all, 100 patients with MS (19–70 years of age) who satisfied the World Health Organization criteria for MS were included in the study. Participants were randomly assigned to receive either oral Diamel or a placebo (while maintaining a diet appropriate to their weight and physical activity) at a dose of two capsules before each of the three main meals each day for 1 year. Anthropometric indices, blood pressure, fasting plasma glucose, lipid profile, insulin, creatinine, and uric acid (UA) were determined. Insulin resistance (IR) was assessed and three indirect indices were used to calculate insulin sensitivity (IS).
Compared with placebo, Diamel improved fasting insulin concentrations, IS, and IR and reduced UA concentrations from 6 months until the end of treatment (P < 0.05 for all). In addition, after 12 months treatment with Diamel, significant changes from baseline were seen for mean fasting insulin (P < 0.05), UA (P < 0.05), IR (P < 0.001), and IS (P < 0.001), whereas no such changes were seen in the placebo-treated group. Improvements were noted in body mass index, IR, and IS in both groups.
Long-term Diamel treatment, combined with lifestyle changes, was beneficial for IR and IS, and reduced serum UA levels in patients with MS.
本研究的目的是明确服用Diamel（一种由西班牙马德里的Catalysis实验室推出的膳食补充剂）后是否能够改善代谢综合征（MS）的任何组成部分，以及是否能够改善胰岛素抵抗与敏感性。
共有100名满足世界卫生组织诊断标准的MS患者（年龄为19-70岁）入组这项研究。参与者被随机分组，口服Diamel或者安慰剂（同时给予能够维持他们的体重和体力活动的适当饮食）进行治疗，在每天三次的主餐前服用两个胶囊的剂量，共1年。测定了人体测量指标、血压、空腹血糖、血脂谱、胰岛素、肌酐以及尿酸水平。评估了胰岛素抵抗，使用三个间接的指标来计算胰岛素敏感性。
与安慰剂相比，从第6个月开始，Diamel可改善患者的空腹胰岛素浓度、胰岛素敏感性以及胰岛素抵抗，并降低尿酸浓度（所有P<0.05）直至治疗末期。经过12个月的Diamel治疗以后，与基线相比有显著变化的指标为平均空腹胰岛素（P<0.05）、尿酸（P<0.05）、胰岛素抵抗（P<0.001）以及胰岛素敏感性（P<0.001），然而在安慰剂治疗组中没有看到这种变化。两组患者的体重指数、胰岛素抵抗以及胰岛素敏感性都有所改善。
MS患者长期使用Diamel治疗，同时改变生活方式，对胰岛素抵抗与胰岛素敏感性均有益，并可减少他们的血清尿酸水平。
Point-of-care (POC) HbA1c testing allows for timely treatment changes, improved glycemic control, and patient and provider satisfaction. Substantial variation between POC and laboratory HbA1c results has been reported. At our university hospital diabetes clinic, we observed significant negative bias in HbA1c with the DCA Vantage™ (Siemens Healthcare Diagnostics, Tarrytown, NY, USA) compared with the Tosoh G8 HPLC laboratory analyzer (Tosoh Bioscience, San Francisco, CA, USA). This led us to systematically analyze the bias with the goal of recalibrating the DCA to minimize bias.
We analyzed 45 patient samples, with HbA1c ranging between 5% and 10.8%, concurrently on two DCA analyzers and on the Tosoh G8 machine. The bias for each sample was the difference between the value on the DCA and the Tosoh G8 analyzer. Based on regression equations derived from the data, a correction factor for each DCA analyzer was calculated. The analyzers were recalibrated and retested for bias.
At baseline, the mean bias (range) was −0.5229 (+0.1 to −1.3) for Analyzer 1 and −0.5348 (0.0 to −1.6) for Analyzer 2. After recalibration, the mean bias (range) was 0.000 (+0.6 to −0.6) and 0.0003 (+0.5 to −0.5) for Analyzers 1 and 2, respectively, and the systematic negative bias seen prior to the calibration was almost eliminated.
We recommend periodic recalibration of POC analyzers to eliminate systematic unidirectional bias and to harmonize results between the POC and central laboratory analyzers within a healthcare system. Calibration may need to be repeated with any change in the reagent lot.
床边（POC）HbA1c检验有助于及时改变治疗方案，改善血糖控制以及患者与检验员的满意度。目前已经报告了HbA1c的POC与实验室结果之间的主要变异。在我们的大学医院糖尿病门诊中观察后发现，与使用东曹G8高效液相色谱实验分析仪（东曹生命科学公司, 圣弗兰西斯科，加利福尼亚州，美国）所检测的HbA1c结果相比较，使用DCA Vantage™（西门子医疗诊断公司，塔里敦，纽约，美国）所检测的HbA1c结果有显著的负偏移。这促使我们对偏倚进行系统分析，目的是重新校准DCA以使偏倚最小化。
我们分析了45名患者的样本，同时使用两台DCA分析仪以及东曹G8机器进行检验，他们的HbA1c范围在5%-10.8%之间。使用DCA和东曹G8分析仪检测，每个样本的检测值的偏移都不相同。根据这些数据得来的回归方程，可以计算出每台DCA分析仪的校正因子。重新校准分析仪后再次检验这些偏移。
在基线时，第1台分析仪的平均偏移（范围）为-0.5229（+0.1至-1.3），第2台分析仪为-0.5348（0.0至-1.6）。经过重新校准后，第1台与第2台分析仪的平均偏移（范围）分别为0.000（+0.6至-0.6）与0.0003（+0.5至-0.5），在校准之前看到的系统性负偏移基本上被消除了。
我们推荐定期重新校准POC分析仪以排除系统性的单向偏移，并且在同一个医疗保健系统内使POC的结果与中心实验室分析仪的结果保持一致。一旦试剂批号出现任何变化可能需要重复校准。
Diabetes differentially affects the vascular system in males and females. Although various results have been reported, very few studies have focused on responses in females. In the present study, we investigated contractile responses to norepinephrine in aortas of alloxan-diabetic female rats and evaluated endothelial modulation of these responses.
Concentration–response curves were constructed to norepinephrine in the absence or presence of NG-nitro-l-arginine methyl ester (l-NAME), indomethacin, losartan, tezosentan, and calphostin C; pre-pro-endothelin mRNA expression was evaluated; and norepinephrine-stimulated expression of phosphorylated (p-) Akt Ser473, p-endothelial nitric oxide synthase (eNOS) Ser1177, and p-eNOS Ser633 was determined in endothelial cells incubated in the presence of low (5 mmol/L) or high (25 mmol/L) glucose concentrations.
Similar maximal responses (Rmax) to norepinephrine were seen in control and diabetic endothelium-intact aortas; however, Rmax was reduced in diabetic endothelium-denuded aortas. Incubation of endothelium-intact aortas with 100 μmol/L l-NAME increased Rmax in the control group only. Inhibition of cyclo-oxygenase (10 μmol/L indomethacin) and blockade of angiotensin II receptors (10 μmol/L losartan) reduced Rmax in endothelium-intact aortas in both the control and diabetic groups. Blockade of endothelin receptors (0.1 μmol/L tezosentan) and inhibition of protein kinase C (PKC; 0.1 μmol/L calphostin C) reduced Rmax only in endothelium-intact aortas from diabetic rats. Pre-pro-endothelin mRNA expression was increased in aortas from diabetic female rats. Finally, p-Akt Ser473, p-eNOS Ser1177, and p-eNOS Ser633 levels were enhanced after norepinephrine stimulation only in low glucose-treated endothelial cells.
In aortas of diabetic female rats, reductions in smooth muscle contractile responses to norepinephrine are counterbalanced by the endothelium via reduced eNOS activation and increased endothelin release and PKC activation.
糖尿病对男性与女性血管系统造成的影响有所不同。虽然已经有了各种结果报告，但是很少有研究重点观察糖尿病对女性的影响。在本研究中，我们调查了四氧嘧啶-糖尿病雌性大鼠主动脉对去甲肾上腺素的收缩反应，评估了这些反应的内皮调节作用。
在缺乏或者存在NG-硝基- L -精氨酸甲酯（L-NAME）、吲哚美辛、氯沙坦、替唑生坦以及钙感光蛋白C的情况下分别构建了去甲肾上腺素的浓度-反应曲线；评估了前内皮素原mRNA的表达情况；并且在低（5mmol/L）或者高（25 mmol/L）浓度的葡萄糖孵养基中测定了去甲肾上腺素刺激后内皮细胞的磷酸化（p-）Akt Ser473、p-内皮一氧化氮合成酶（eNOS）Ser1177以及p-eNOS Ser633的表达情况。
在对照组以及糖尿病组中的内皮完整的主动脉对去甲肾上腺素的最大反应（Rmax）相似；然而，糖尿病大鼠血管内皮裸露的主动脉的Rmax下降。内皮完整的主动脉孵育在100 μmol/L L-NAME中只增加对照组的Rmax。在对照组与糖尿病组中，抑制环氧合酶（10 μmol/L吲哚美辛）以及阻断血管紧张素Ⅱ受体（10 μmol/L氯沙坦）都可以减少内皮完整的主动脉的Rmax。阻断内皮素受体（0.1 μmol/L替唑生坦）以及抑制蛋白激酶C（PKC；0.1 μmol/L钙感光蛋白C）只减少糖尿病大鼠内皮完整的主动脉的Rmax。来自糖尿病雌性大鼠的主动脉前内皮素原mRNA表达增加。最后，经过去甲肾上腺素刺激后，只有低浓度葡萄糖孵育的内皮细胞的p-Akt Ser473、p-eNOS Ser1177以及p-eNOS Ser633水平升高。
在糖尿病雌性大鼠主动脉中，平滑肌对去甲肾上腺素的收缩反应下降被内皮细胞通过减少eNOS活性以及增加内皮素释放与增强PKC活性所抵消。
Peripheral neuropathy is a serious complication of diabetes and several conditions that may lead to the loss of lower extremity function and even amputations. Since the introduction of statins, their use has increased markedly. Recent reports suggest a role for statins in the development of peripheral neuropathy. The aims of the present study were to assess the association between statin use and peripheral neuropathy, and to determine whether this association varied by diabetes status.
Data from the lower extremity examination supplement of the 1999–2004 National Health and Nutrition Examination Survey were used.
The overall prevalence of statin use was 15% and the prevalence of peripheral neuropathy was 14.9%. The prevalence of peripheral neuropathy was significantly higher among those who used statins compared with those who did not (23.5% vs 13.5%, respectively; P < 0.01). Multivariate logistic regression revealed that statin use (adjusted odds ratio 1.3; 95% confidence interval 1.1–1.6; Wald P = 0.04) was significantly associated with peripheral neuropathy, controlling for diabetes status, age, gender, race, height, weight, blood lead levels, poverty, glycohemoglobin, use of vitamin B12, alcohol abuse, hypertension, and non-high-density lipoprotein–cholesterol. Diabetes status, age, gender, height, weight, blood lead levels, poverty, and glycohemoglobin were also significantly associated with peripheral neuropathy. We found no effect modification between statin use and diabetes status, race, gender, age, vitamin B12, blood lead levels, or alcohol abuse.
In the present cross-sectional study, we found a modest association between peripheral neuropathy and statin use. Prospective studies are required to determine the causal direction.
周围神经病变是一种严重的糖尿病并发症，在某些情况下可导致下肢丧失功能甚至截肢。自从他汀类药物问世以来，其使用日益增加。最近的报告表明他汀类药物可以影响周围神经病变的发展。本研究的目的是评估他汀的使用情况与周围神经病变之间的关系，并且明确这种关系是否会随着糖尿病状态的转变而有所不同。
所使用的数据来源于1999-2004年全国健康与营养调查研究的下肢检查附录部分。
全体人员的他汀使用率为15%，周围神经病变患病率为14.9%。与不使用他汀的患者相比较，使用他汀类药物的患者的周围神经病变的患病率显著更高（分别为23.5%与13.5%；P<0.01）。多元对数回归分析结果显示他汀的使用与周围神经病变显著相关（校正后OR，1.3；95%CI，1.1-1.6；Wald检验P=0.04），控制变量为糖尿病状态、年龄、性别、种族、身高、体重、血铅水平、贫穷、糖化血红蛋白、维生素B12的使用、酗酒、高血压以及非高密度脂蛋白胆固醇。糖尿病状态、年龄、性别、身高、体重、血铅水平、贫穷以及糖化血红蛋白也与周围神经病变显著相关。我们没有发现糖尿病状态、种族、性别、年龄、维生素B12、血铅水平或者酗酒对他汀的使用有影响。
在当前这项横向研究中，我们发现周围神经病变与他汀的使用之间具有适度的相关性。需要进行前瞻性的研究以明确因果关系。
To compare characteristics of autoantibody (aAb)-positive and -negative cases of type 1 diabetes (T1D) <18 years old in the T1D Exchange clinic registry.
An aAb-positive status (n = 6239) required at least one of the aAbs to be positive; an aAb-negative status (n = 485) required negative results on testing of at least two different aAbs.
The percentage of males was higher (58% vs 51%; P = 0.002) and total daily insulin dose lower (P = 0.003) in aAb-negative compared with aAb-positive groups, but both groups had similar distributions of race–ethnicity, diagnosis age, family history of T1D, ketoacidosis at diagnosis, body mass index at diagnosis and at most recent office visit, and current HbA1c.
Male gender and lower total daily insulin dose were more likely in aAb-negative than aAb-positive children with T1D, but no other distinguishing characteristics were identified. Further examination of characteristics of aAb-negative cases may help characterize the heterogeneous nature of T1D.
在1型糖尿病（T1D）交流中心临床登记的年龄小于18岁的T1D病例中，比较自身抗体（aAb）阳性与自身抗体阴性的患者的特征。
aAb阳性状态（n=6239）要求至少有一种aAbs为阳性；aAb阴性状态（n=485）要求至少有两种不同的aAbs检测结果为阴性。
与aAb阳性组相比较，aAb阴性组中男性的比例更高（58% vs 51%；P=0.002），总的每日胰岛素剂量更低（P=0.003），但是两组的种族-族裔分布、诊断年龄、T1D家族史、诊断时有酮症酸中毒、诊断时的体重指数、最近一次随访时的体重指数以及当前的HbA1c都相类似。
与aAb阳性的T1D儿童相比较，aAb阴性组中男性儿童更多且总的每日胰岛素剂量更低，但是没有发现其他有差异的特征。进一步检查aAb阴性病例的特征可能有助于明确T1D的异质性。