Volume 06 · Issue 04 · 2014

Diabetic neuropathy is one of the most common chronic complications of diabetes^[1,2,3]。 The disease can involve any part from the central nervous system to the neuromuscular junction, and can be damaged in multiple parts at the same time, resulting in the diversity of clinical manifestations of patients with diabetic neuropathy, which brings great difficulties to clinical diagnosis^[4]。 There are many screening methods for diabetic neuropathy^[5,6,7,8]Commonly used screening methods for diabetic peripheral neuropathy (DPN) include ankle reflex, pressure sensation, vibration sensation, acupuncture sensation, temperature sensation, Toronto neuropathy screening, plantar pressure measurement, electrophysiological examination, etc.^[9,10]。 Therefore, among the numerous methods of diabetic neuropathy examination, it is important to choose different screening methods for different lesions.

Diabetic painful neuropathy (PDN) is a clinically common sensory peripheral neuropathy, the most common cause of which is distal symmetric polyneuropathy (DSPN). The prevalence of PDN in diabetic patients is 16%, and 39% of them are untreated^[1]。 The pathogenesis of PDN is complex and the clinical manifestations are diverse. It is characterized by symmetrical pain in the distal limb and nocturnal aggravation, which seriously affects the quality of life of patients. The treatment of this disease is mainly to control pain, and there are many clinical trials to study this. Knowing the clinical characteristics of the disease and giving effective drug treatment can help to relieve the symptoms and improve the quality of life.

Diabetic neuropathy (DN) is one of the most common complications of diabetes, in which 1/4 of patients have symptoms, about half of patients have objective signs, and 95% of patients can find objective evidence of peripheral nerve damage after detailed neurological examination. Unfortunately, clinicians lack awareness of this pathological state, and the diagnosis rate is less than 1/3 even in patients with symptomatic DN^[1]。

Diabetic peripheral neuropathy is an earlier and most common chronic complication in diabetic patients. Among them, diabetic autonomic neuropathy can involve cardiovascular, gastrointestinal tract and genitourinary system tissues and organs. Diabetic cardiac autonomic neuropathy (DCAN) can cause abnormalities in heart rate control and vascular hemodynamics, significantly increasing the risk of arrhythmias and sudden death in diabetic patients^[1], is one of the most serious chronic complications in patients with type 2 diabetes. However, due to the insidious onset and no obvious clinical symptoms in the early stage, it is often ignored. In recent years, with the improvement of people's understanding of DCAN, objective detection methods make it possible to detect cardiac autonomic dysfunction early, so as to achieve the goal of early intervention or even reversal of DCAN.

Diabetic peripheral neuropathy (DPN) is one of the main complications of diabetes mellitus, of which distal symmetric polyneuropathy (DSPN) is the most typical and the most important. The prevalence rate in diabetic population is about 30%^[1]。 DPN involves sensory and motor nerves, and has a variety of manifestations. Patients often have a weakened or absent protective sensation that greatly increases the risk of developing diabetic foot, or pain or paresthesia seriously affects the quality of life. There is no doubt about the importance of DPN, but its prevention and treatment has always been a difficult point in clinical practice. This article will review the current treatment of DPN from the perspective of evidence-based medicine, especially the current treatment status of DPN pathological progression.

To evaluate the efficacy and clinical value of the neuropathy symptom score/neuropathy disability score (NSS/NDS) compared with nerve conduction velocities (NCV) in the diagnosis of diabetic peripheral neuropathy (DPN).

Observational study of 679 patients diagnosed with type 2 diabetes mellitus (404 males and 275 females, the average age was (59±11) years) was performed using the standard NSS/NDS and NCV criteria for the diagnosis of DPN. Taking NCV as the gold standard, we compared NCV against NSS/NDS using the following parameters: sensitivity, specificity, positive and negative predictive values, Youden index, Kappa value and correlation. Correlation analysis was done by using Spearman correlation and multivariate logistic regression.

The sensitivity, specificity, positive and negative predictive values, Youden index, Kappa value and correlation of NSS/NDS compared with NCV was 68.0%, 77.2%, 86.5%, 53.5%, 71.0%, 45.2%, 0.405, 0.424, respectively. The abnormal rate of NCV of patients was more remarkable when NSS score ≥5 or NDS score ≥6 (77.8%-100%). NSS and NDS demonstrated an obvious positive association with NCV(r=0.292, 0.358, both P<0.01). The NCV values for each nerve showed a negative correlation with the severity of symptoms and signs. Logistic regression analysis showed that the risk factors of DPN were disease duration, age and urinary albumin-to-creatinine ratio when NSS/NDS were considered as the diagnostic criteria(odds rations(OR)=1.085, 1.051, 1.002, all P<0.01). A similar result was observed with NCV.

NSS/NDS demonstrates a positive association with NCV, especially when neurological symptoms and neurological signs became more serious. NSS/NDS analysis is a simple, rapid, cheap and powerful screening tool for the diagnosis of DPN.

To investigate the impacts of lisinopril on the microcirculation of peripheral nerve as well as nerve function and structure in diabetic rats.

Diabetic rat model was prepared by injecting streptozotocin into the tail veins of 25 six-week-old healthy male Wistar rats. The rats models were randomly divided into diabetic group and lisinopril treatment group(20 mg·kg^-1·d^-1, 8 weeks), 10 healthy rats were set as normal controls. Sciatic nerve conduction velocity and ultrastructure were observed 8 weeks after intervene. The plasma nitric oxide(NO), nerve tissue superoxide dismutase(SOD), malondialdehyde(MDA) levels by were detected by chemocolorimetry. The 6-keto-prostaglandin F1α(6-keto-PGF1α) levels were measured by radioimmunoassay, and plasminogen activator inhibitor(PAI-1), tissue-type plasminogen activator(t-PA) were assayed by enzyme linked immunosorbent assay(ELISA), capillary density of sciatic endoneurium was evaluated by immunohistochemistry of CD34. Single factor analysis of variance was used to compare the differences among groups.

Compared with those in normal control group, the motor and sensory nerve conduction velocity of diabetic rats slowed down(t=8.952, 9.642, both P<0.05) and the ultrastructure of the sciatic nerve was abnormal; Plasma NO, 6-keto-PGF1α, t-PA, SOD levels decreased and PAI-1, MDA increased in diabetic rats(t=3.535-8.054, all P<0.05). The motor and sensory nerve conduction velocity of sciatic nerve in lisinopril treatment group improved significantly than those in diabetic rats(t=6.774, 7.058, both P<0.05), and the extenuated atrophy and degeneration of axon and myelin, and ameliorated stenosis and occlusion of capillary of sciatic nerve were all improved. Moreover, the plasma levels of NO, 6-keto-PGF1α, t-PA and SOD levels increased and PAI-1 and MDA levels decreased significantly in lisinopril treatment group than those in diabetic rats(t=2.611-6.544, all P<0.05), and the angiogenesis of endoneurium was improved(t=6.868, P<0.05).

Lisinopril provides protective effects on early diabetic peripheral neuropathy, it may relate to its improvement of nerve microcirculation and nerve perfusion in diabetic rats.

To evaluate the glucose-lowering effect and safety of benazepril in Chinese patients with diabetes mellitus (DM).

We searched PubMed, EMBASE, Chinese Biomedical Literature Database (CBM), the Cochrane Library and China National Knowledge Infrastructure (CNKI) databases from January 1989 to August 2011 for randomized controlled trials (RCTs) conducted in Chinese patients with diabetes mellitus treated by benazepril. Two investigators identified studies independently according to predefined inclusion and exclusion criteria, and data was extracted. Statistical analysis was performed using the Stata 11 software.

Total of 1 326 candidate articles were identified, of which 22 enrolling 1 633 Chinese DM patients met the selection criteria. The dosage of benazepril is from 5 mg to 30 mg once daily. In addition to glucose-lowering treatment, benazepril treatment resulted in a 0.8 mmol/L reduction in change of fasting plasma glucose (FPG) from baseline (P<0.05) and 3.0 mmol/L reduction in 2-hour postprandial plasma glucose (2 hPG) (P<0.05), compared with blank control group. Compared with angiotensin Ⅱ receptor blockers(ARB), there was no significant difference in change of FPG, 2 hPG or HbA1c from baseline(allP>0.05). Benazepril was found not effective on change of fasting plasma insulin and 2 hours plasma insulin from baseline. Cough was the most common side effect in patients after benazepril treatment, with anOR of 5.39 (95%CI: 2.02-14.40) compared with other active control drugs. Other side effects were rare. Clinical heterogeneity was the main heterogeneity (I²>25% in most studies).

Benazepril may be efficacious on lowering fasting and 2 hours plasma glucose in Chinese DM patients, while not effective in lowering HbA1c or insulin. Generally the safety is acceptable except for a higher incidence of cough. However, the results may be biased by the quality of included studies.

To investigate the correlation between glomerular filtration rate (estimated glomerular filtration rate, eGFR) and serum total bilirubin (TBIL), direct bilirubin (DBIL), indirect bilirubin(IBIL) in patients with type 2 diabetes mellitus.

According to eGFR level, 523 cases of type 2 diabetic inpatients from October 2011 to September 2012 in Department of Diabetic Nephropathy, Metabolic Diseases Hospital, Tianjin Medical University were divided into four groups: glomerular hyperfiltration group (n=133), normal renal function group (n=194), mild renal dysfunction group (n=125), moderate and severe renal dysfunction group (n=171). The differences of TBIL, DBIL and IBIL levels among the four groups were compared. The related factors analysis of eGFR was perfor, med. Variance analysis was used to analysize mulitiple groups of data.

The bilirubin levels of glomerular hyperfiltration group was significantly lower than normal renal function group (P<0.05). TBIL level was (10.9±4.0) vs (12.5±4.5) μmol/L, DBIL level was (3.8±1.6) vs (4.4±1.7) μmol/L, IBIL level was (7.1±2.8) vs (8.0±3.1) μmol/L. The levels of TBIL, DBIL and IBIL in moderate and severe renal dysfunction group significantly reduced than those of other three groups (F=15.296, 15.024, 11.609, all P<0.05). In the patients with eGFR<130 ml/min, correlation analysis results indicate: eGFR was negatively correlated with age, the course of diabetes, total cholesterol, low-density lipoprotein cholesterol (r=-0.307, -0.203, -0.149, -0.111, all P<0.05), and was positively correlated with TBIL, DBIL and IBIL (r=0.291, 0.275, 0.254, all P<0.05).

Serum bilirubin levels are associated with glomerular filtration rate in patients with type 2 diabetes.

To explore the effect and safety of laparoscopic gastric bypass surgery in patients with type 2 diabetes mellitus and body mass index (BMI)<28 kg/m².

Twenty-seven consecutively selected diabetic patients with BMI <28 kg/m ² underwent gastric bypass in a tertiary-care hospital from January, 2008 to December, 2012 were retrospectively studied and followed up with telephone interview. Postoperative changes in BMI, waist circumference, glycaemic control, lipid levels, blood pressure, surgery related complications, diet habits and degree of satisfaction were recorded.

Totally 21 patients (77.8%) were successfully followed. Mean follow-up time was (2.7±1.1) years. There was no mortality, but 2 anastomotic ulcer, postoperatively. The fasting plasma glucose (FPG) and glycated hemoglobin A1c(HbA1c) decreased significantly after surgery (FPG: (6.4±1.5)vs(8.2±3.2)mmol/L, t=2.787; HbA1c: (6.6±1.2)%vs(7.8±1.9)%, t=2.473, both P<0.05). And there were statistical difference in weight and BMI before and after operation (weight(77±10)vs(65±12) kg,t=4.474, BMI(25.1±2.3)vs(22.8±4.6)kg/m², t=2.756, both P<0.05). So was the change of waist circumference ((93.3±11.7) vs (83.3±7.6) cm,t=3.133, P<0.05). Diabetes remission occurred in 61.9% of cases (13/21), with glycemic improvement in 23.8% (5/21), and failure in 14.3% (3/21). Compared with the patients with diabetes improved and failed, the preoperative characteristics of diabetes remission group had no significant difference. Rate of hypertension and dyslipidemia remission were 54.5% and 66.7%, respectively. And the average satisfaction for all patients was (83±17)%.

Gastric bypass surgery somehow safely and effectively ameliorated diabetes and associated comorbidities, in patients with a BMI of <28 kg/m ^2, independent with weight loss. But the validity still need more research to confirm.

To investigate the changes in plasma very long chain fatty acids (VLCFAs) in polycystic ovary syndrome (PCOS) patients, and further to explore its relationship with obesity and insulin resistance.

Two hundred and five PCOS patients were screened out according to the diagnostic criteria of Rotterdam conference (2003), aged 18-40 years. A group of 117 healthy infertile women of corresponding period was taken as control. These women were chosen randomly from reproductive center due to the problems of uterine tube or males. The plasma hormone levels were examined. Ten kinds of plasma VLCFAs were detected by gas chromatography-mass spectrometry (GC-MS). Data between two groups analysis was performed by t test. Multiple stepwise regression analysis was used to analysize multiple factors of measurement data.

Compared with normal individuals, plasma VLCFAs levels was disorder in PCOS patients. There is a lower C20: 4n-6/C20: 3n-6 in VLCFAs of PCOS patients, and a higher C20: 1n-9, C20: 2n-7, C20: 3n-6, C22: 4n-6, C20: 5n-3, C22: 5n-3 and C22: 6n-3, compared with the control group(t=0.539-6.155, all P<0.05). In the PCOS group, compared with non-obese patients, obese patients had a higher C20: 0, and lower C20: 3n-6 and C20: 2n-7 (t=-0.927, 2.452, 0.767, both P<0.05). Compared with non insulin resistance group, patients with insulin resistance had a higher C20: 0 and lower C20: 2n-7 and C22: 5n-3 levels (t=-2.064, 2.195, 2.183, both P<0.05). Multiple stepwise regression analysis showed that C20: 2n-7 and C20: 0 were independent risk factors of obesity and insulin resistance, respectively.

Disturbance metabolism of VLCFA existed in the PCOS patients. The decrease of C20: 2n-7 was probably an influence factor of obesity in PCOS patients and the increase of C20: 0 was probably an influence factor of insulin resistance in PCOS patients.

To investigate the effect of calcitriol on the expression of interleukin-17(IL-17) in kidney of diabetic rats.

A total of forty-five healthy eight-week-old male SD rats were treated with streptozotocin(STZ). The STZ-induced diabetic rats were randomly divided into 3 groups: diabetic group, low-dose calcitriol (group L) and high-dose calcitriol (group H). Another 10 healthy SD rats were considered as normal control(NC) group. After 12 weeks, body weight, blood glucose(BG), blood urea nitrogen(BUN), serum creatinine(Scr), serum IL-17 and 24-hour urine albumin(UAlb) were detected. Kidney weight/body weight ratio(KI) of rats was calculated. The expressions of IL-17, tumor necrosis factor-α(TNF-α) and transforming growth factor-β1(TGF-β1) in kidney cortex were detected by immunohistochemistry. Pathological changes in kidneys were observed by light microscope. One-way ANOVA was used for data analysis.

(1)The serum BUN, Scr and UAlb were significantly higher in diabetic group than those in NC group ((16.1±1.6) mmol/L vs (6.9±1.8) mmol/L, (75±11) vs (46±9) μmol/L, (1.14±0.13) vs (0.45±0.11) mg/24 h, t=12.627, 7.534, 12.762, respectively, all P<0.05), and those in group L and group H were decreased compared with model group (the serum BUN, Scr and UAlb in group L were (12.1±1.5) mmol/L, (58±8) μmol/L and (0.86±0.10) mg/24 h, respectively). (2)The serum IL-17, expressions of IL-17 in kidney cortex were significantly higher in model group than those in NC group((510±47) vs(133±22)ng/L, (164±9) vs (82±4),t=17.244, 20.757, respectively, all P<0.05), and those in group H((253±27)ng/L, 119±5) were significantly lower than in group L((324±35)ng/L, 132±5,t=3.379, 3.615, respectively, all P<0.05). (3)Observation by light microscope showed renal tissue of rats from NC group was almost normal, the pathological changes of rats from model group were demonstrated by the increasing of mesangial cells and matrix area in renal glomerulus, vacuolar degeneration of renal tubular epithelial cells. Pathological changes in kidneys were improved in Group L and Group H.

Calcitriol is effective in improving the reduction of the serum IL-17 and expressions of IL-17 in kidney cortex in diabetic rats. It suggests that calcitriol may protect the kidneys of diabetic rats via regulating expression of IL-17.

In the spring of March, Beijing, the capital, has a little warmth. On March 15th, 2014, the "Xingzhi Lecture Hall" activity jointly sponsored by the Editorial Committee of Chinese Diabetes Journal and the Youth Committee of Diabetes Branch of Chinese Medical Association and supported by AstraZeneca officially kicked off.

On March 6, 2014, the Chinese Diabetes Journal "Yikai Cup" Diabetes Physician Salon was successfully held in Beijing. This salon was hosted by Professor Pan Changyu, a senior consultant of Chinese Diabetes Journal and a famous endocrinologist, and Director Yang Ying of the editorial department of Chinese Diabetes Journal. The case discussion process was hosted by Professor Yu Miao of Peking Union Medical College Hospital and Professor Yang Guoqing of PLA General Hospital respectively. A total of nearly 60 young doctors from the field of diabetes in Beijing attended this salon. The doctors in the salon spoke enthusiastically, and the atmosphere was warm. Through this way of brainstorming and knowledge stirring, everyone's clinical diagnosis and treatment thinking was expanded. The salon continues to be co-organized by Changzhou Qianhong Pharmaceutical Co., Ltd.

Turner syndrome is a condition with the most common clinical features, including reduced final height, gonadal dysgenesis, and so on. In addition, an increased risk of autoimmune disease has been observed among the patients with Turner syndrome. Here we present a unique case of Turner syndrome with a group of autoimmune diseases, including type 1 diabetes and Hashimoto thyroiditis, whose islet function recovered partly after treatment with humanized anti CD20 monoclonal antibody(rituximab). On the base of this case report and relevant papers, we infer that: as individuals with Turner syndrome are prone to develop autoimmune conditions, the risk of endocrine autoimmune diseases should be paid more attention during the clinical process of diagnosis and treatment. The Turner patients should be observed with multiple auto-antibodies during the long-term follow up, clinical intervene should be implemented even before the irreversible immune disturbance.

A 42 year old woman who complained of dry mouth, polydipsia for 12 years, vomiting and diarrhea for 2 days was clinically diagnosed as Turner syndrome. She was diagnosed as hypothyroidism 2 years ago. We completed systemic examinations for the patient. The type B ultrasound test of uterus and ovaries showed that her uterus was infantilism and the bilateral ovarian didn't imaging. The glycated hemoglobin(HbA1c) level was 12.66%, the results of oral glucose tolerance tests(OGTT) met the diagnostic criteria for diabetes mellitus. Bone mineral density: lumbar osteoporosis (T value: -3.25, Z value: -3.01). Chromosomal inspection showed a 45, X/46, XX karyotype. Adrenal cortex function was normal. The patient was finally diagnosed as Turner syndrome(mosaictype type) and accompanied by diabetes, hypothyroidism and osteoporosis. This showed we should take a systematic inspection for a patient with diabetes and congenital defects sexuality in order to confirm the diagnosis of Turner syndrome and its complications as soon as possible, and to give an appropriate treatment.

Hypoxia exists in the occurrence and development of diabetes mellitus and its chronic complications^[1,2,3]The possible reasons include: (1) due to poor blood sugar control, increased secretion of glucagon, growth hormone and epinephrine, gluconeogenesis, free fatty acid oxidation, increased protein conversion rate and other factors in diabetic patients, the basal metabolic rate is significantly increased and oxygen consumption is increased; (2) Hyperglycemia reduces the level of 2,3-diphosphoglycerate in erythrocytes and reduces the oxygen carrying capacity of erythrocytes; (3) The increase of glycosylated hemoglobin (HbA1c) in diabetic patients can cause the oxygen separation curve to shift left, which reduces the oxygen release of hemoglobin, while the hypercoagulable state of blood can cause poor, stasis or even blockage of microcirculation blood flow, further aggravating hypoxia; (4) Diabetes mellitus complicated with cardiomyopathy, cardiac autonomic nerve dysfunction and myocardial microcirculation lesions can lead to decreased cardiovascular function, and these factors can aggravate tissue hypoxia. At present, more and more studies have shown that hypoxia is the pathogenesis of chronic complications of diabetes. Because nerve cells are particularly sensitive to hypoxia, hypoxia can seriously affect the occurrence and development of diabetic peripheral neuropathy. Hypoxia-inducible factor 1 α (HIF-1 α) is one of the key factors that regulate intracellular oxygen metabolism. It is also the only transcription factor discovered so far that can exert activity under specific hypoxia, and plays a protective role in the occurrence and development of diabetes mellitus and its complications^[4,5]。 This paper reviews the role of HIF-1 α in diabetic peripheral neuropathy and its related mechanisms.

Postprandial hypotension (PPH) is a common geriatric condition defined by a decrease in systolic blood pressure of 20 mmHg (1 mmHg =0.133 kPa) after a meal or a decrease in systolic blood pressure from ≥100 mmHg before a meal to<90 mmHg^[1], or when symptoms such as dizziness or even syncope occur after a meal, even if the blood pressure drop does not meet the above criteria, PPH can be diagnosed. PPH is common in diabetic patients, and the incidence of PPH in diabetic patients is 37%^[2]。 In diabetic patients, blood pressure fluctuations correlate with urinary albumin excretion rate^[3], blood pressure variability rate as a risk factor for the progression of diabetic nephropathy^[4], is an independent predictor of macrovascular and microvascular lesions in diabetic patients^[5]Therefore, the prevention and treatment of PPH is of great significance to reduce complications in diabetic patients. Therefore, endocrinologists should pay attention to screening PPH when diagnosing and treating diabetic patients, and whether their hypotension is related to eating for those with blood pressure fluctuations. However, there is little literature on the relationship between PPH and diabetes, and four cases of Hoeldtke were first reported in 1986^[6]。 This article will review this.

Healthy diet, regular exercise and rational drug treatment are the most critical parts of the overall management of diabetes, but for the majority of diabetes specialists, diet treatment is the most difficult evidence-based part of the whole program. The American Diabetes Association (ADA) put forward the "Recommended Principles of Nutrition and Diet for Diabetic Patients" for the first time in the world since 1974, and regularly updates the recommended contents with the continuous improvement of evidence-based evidence. Since the 21st century, updated "nutritional therapy recommendations" (referred to as "recommendations") were introduced in 2004 and 2008. ADA has gradually positioned nutritional therapy as an indispensable part of overall diabetes management, requiring every diabetic patient to actively participate in individualized diet management^[1]。 However, data from a survey of 18,404 diabetic patients in the United States showed that only 9.1% of patients had received individualized nutritional guidance from a registered dietitian once or more in nine years^[2]。 Many patients and medical institutions are unaware that nutrition counseling or treatment services should be provided. Therefore, this evidence-based nutrition recommendation in 2013 "recommends"^[3]It provides practical basis for medical staff in various medical institutions.

Sexual dysfunction, especially erectile dysfunction, is more common in men with type 2 diabetes, and its incidence can reach 75%. The incidence of hypogonadism is higher in men with type 2 diabetes, and low testosterone levels are associated with sexual dysfunction and low responsiveness to oral medication of erections.

At present, most studies are about the influence of type 2 diabetes on the risk of non-alcoholic fatty liver disease, and in turn, whether non-alcoholic fatty liver disease has an influence on the risk of type 2 diabetes is unclear. To this end, Park et al. from Sungkyunkwan University in South Korea conducted a 5-year prospective cohort study.

There are many causes of cognitive dysfunction and dementia in patients with type 2 diabetes. Studies have reported the effects of hypoglycemic episodes on cognitive function. Investigators from Taiwan, China, randomly selected a sample of 1 000 000 cases from the Taiwanese National Health Care Database to investigate the risk of dementia in patients with type 2 diabetes with or without prior episodes of hypoglycemia.

Closed negative pressure drainage (VAC) is a new method of wound treatment, which reduces wound healing time by generating local negative pressure, improving tissue perfusion and aspirating local exudate. Researchers from Mashhad University in Iran evaluated the efficacy of VAC on diabetic foot ulcers.

Women suffering from preeclampsia (PEC) and gestational hypertension (GH), regardless of whether they are obese or have impaired glucose tolerance, present with insulin resistance (IR) during pregnancy. In addition to gestational diabetes mellitus (GDM), does PEC/GH also increase the risk of postpartum diabetes in women? If yes, is there a synergistic effect between PEC/GH and GDM on the long-term diabetes risk? This question has not been answered yet.