Volume 09 · Issue 08 · 2017

The ultimate goal of diabetes treatment is to prevent and reduce complications and reduce deaths. Because diabetic nephropathy can lead to renal insufficiency-uremia, need to rely on dialysis treatment to maintain life, seriously affect the quality of life of patients, diabetic nephropathy is also the most feared complication of diabetic patients. Foreign research data show that the incidence of end stage renal disease (ESRD) in patients with diabetic nephropathy with a course of more than 20 years is 40.8/1,000 person-years, and they need renal replacement therapy such as dialysis or transplantation^[1]。 During the past 20 years, new onset hemodialysis patients due to diabetic nephropathy have increased significantly with the number of people with diabetes. In the dialysis population in the United States, diabetes has occupied the first place in its underlying disease.

The striking similarity between the eye and the kidney in terms of structure, development, and genetics suggests that kidney disease and eye disease may be closely linked. A growing number of studies have found that chronic kidney disease is associated with diabetic retinopathy, age-related macular degeneration, glaucoma, and cataracts. Furthermore, retinal microvascular parameters have been shown to predict chronic kidney disease. This article starts with the scientific research idea of exploring the diagnosis of kidney disease in diabetic ophthalmopathy, and combines the work of our team to introduce it to colleagues.

The American Diabetes Association (ADA) Independently Released 2016 Position Statement on Physical Activity for People with Diabetes^[1](hereinafter referred to as the 2016 ADA Position Statement) discussed 10 aspects: (1) diagnosis of diabetes and prediabetes and types of exercise and physical activity; (2) benefits from exercise and physical activity; (3) Benefits and recommendations for reducing sedentary time; (4) Physical activity and type 2 diabetes; (5) Physical activity and type 1 diabetes; (6) Suggestions for diabetic patients to participate in physical activity; (7) Physical activity, pregnancy, and diabetes; (8) Reduce adverse events during exercise in diabetic patients; (9) managing physical activity and patient complications and concomitant diseases; (10) Promotion and maintenance of physical activity.

To investigate the efficacy and safety of linagliptin, one dipeptidyl peptidase Ⅳ (DPP-4) inhibitor, in type 2 diabetes mellitus (T2DM) patients with hypertension and microalbuminuria.

In eight completed (before October 2015) phase Ⅲ clinical trials which were designed to evaluate the efficacy of linagliptin (alone or combined with other oral antidiabetic drugs), all the T2DM patients with hypertension and microalbuminuria at baseline were included in this pooled analysis. The included patients could be drug-naïve, with metformin monotherapy or metformin combined with sulfonylureas dual therapy at baseline. In each clinical trial, participants were randomized to receiving linagliptin 5mg daily or placebo for 24weeks. Efficacy was assessed by the change from baseline in glycated hemoglobin (HbA_1c) and fasting plasma glucose (FPG) after 24 weeks of treatment. Safety endpoint was evaluated by frequency of adverse events. Efficacy endpoints were analyzed with the analysis of covariance. Safety data were analyzed using descriptive statistics.

A total of 532 T2DM patients were included (placebo group 152, linagliptin group 380). At baseline the mean age was 60 years, mean HbA_1c was 8.2% and mean FPG was 169 mg/dl (1 mg/dl=0.056 mmol/L) . After 24 weeks of treatment, placebo-corrected mean change in HbA_1c and FPG were-0.57%(95% CI:-0.74%--0.39%, P<0.000 1) and-24 mg/dl [95%CI: (15~32) mg/dl, P<0.000 1], respectively. The incidence of any adverse events (both for 63.2%) was the same between placebo group and linagliptin group. Also, the changes of blood pressure and serum lipid concentration were similar between the two groups.

Linagliptin may significantly improve glycemic control and be well tolerated in T2DM patients with hypertension and microalbuminuria.

To compare urinary microalbumin levels and prevalence of microalbuminuria in subjects with normal glucose tolerance (NGT) and prediabetes including various types of impaired glucose regulation.

During 2007-2008, subjects (n=47 325), aged ≥20 years, including 18 976 males and 28 349 females, from 152 city blocks and 112 villages in China, were recruited using stratified and multi-staged sampling methods. According to the results of 75 g oral glucose tolerance test (OGTT), participants were divided to NGT group, isolated impaired fasting glucose (i-IFG) group, isolated impaired glucose tolerance (i-IGT) and impaired fasting glucose with impaired glucose tolerance group (IGT/IFG). Abnormal urinary microalbumin was defined if its level was above 30 mg/L. The urinary microalbumin levels and the prevalence of abnormal microalbuminuria were compared and analyzed among groups. Analysis of variance, rank sum test and multiple linear regression were applied for statistical analysis.

The urinary microalbumin level [media (upper-lower quantiles)] in IGT/IFG group was 16(8~37) mg/L and that in i-IGT group was 13(7-30) mg/L. Both were higher than that in NGT group [10(6-21) mg/L](allP<0.01); but there was no significant difference between NGT group and i-IFG group [11(6-24) mg/L]. The prevalence of abnormal urinary microalbumin was 31.5% in IGT/IFG group, 25.0% in i-IGT group, 20.2% in i-IFG group and 17.6% in NGT group.

The prevalence of abnormal microalbuminuria is already increased even at the pre-diabetic stage. That suggests we should manage risk factors for microalbuminuria of these patients as early as possible.

To investigate the prevalence and clinical features of normoalbuminuric diabetic kidney disease (NA-DKD) in patients with type 2 diabetes.

A total of 3 813 outpatients with type 2 diabetes and complete records of serum creatinine (Cr) and urinary albumin/creatinine ratio (ACR) were collected from January 2015 to December 2016. The distribution of different eGFR and albuminuria and the age-specific prevalence of different types of DKD were calculated using one-way analysis of variance. Patients were stratified according to gender, mean arterial pressure, glycosylated hemoglobin (HbA_1c)≥7% and low density lipoprotein cholesterol (LDL-C)≥2.6 mmol/L and Multivariate Logistic regression analyses were performed to determine odds ratios and 95% confidence interval(CI) of patients with normoalbuminuric and eGFR< 60 ml·min^-1· (1.73 m²) ^-1 (NA-DKD) .

The prevalence of NA-DKD was significantly higher than that of albuminuric eGFR< 60 ml·min^-1· (1.73 m²) ^-1 DKD [971/3 813(25.47%) vs 376/3 813(9.86%)] while that of albuminuric eGFR ≥60 ml·min^-1· (1.73 m²) ^-1 type DKD was in between. The prevalence of all types of DKD rose with age, NA-DKD had the highest prevalence in those 61-70 years old which was much older than other two types. In NA-DKD group, the prevalence was lower in male than in female, poorly controlled blood glucose associated with a decreased OR[OR= 0.91, 95%CI (0.88-0.95) ], while poorly controlled blood pressure and LDL-C resulted showed the opposite[OR= 1.31, 95%CI (1.15-1.46) , OR=1.14, 95%CI (0.98-1.25)].

Compared with albuminuric DKD, the prevalence of NA-DKD was much higher in patients with type 2 diabetes. NA-DKD was more common in women, senior citizen, patients with well controlled glycemia and patients with poorly controlled blood pressure and LDL-C.

To investigate the relationship between serum irisin and carotid atherosclerosis (CAS) in type 2 diabetes.

A total of 30 patients with type 2 diabetes (T2DM) complicated with CAS and another 30 gender-, age-matched T2DM patients without CAS were enrolled from June 2014 to December 2015; over the same period, 30 gender-, age-matched healthy participants were included as the normal control (NC). Fasting plasma glucose, blood lipid, glycosylated hemoglobin A_1c, fasting insulin were measured; serum irisin level was determined by enzyme-linked immunosorbent assay. Analysis of covariance, nonparametric test, Spearman correlation analysis and Logistic regression analysis were used for data analysis.

The serum irisin levels decreased significantly in T2DM with CAS and without CAS groups when compared with that in NC group 3.3(2.7, 3.7), 4.0(3.7,4.3), 4.5(3.7, 5.3) mg/L, respectively, Z=-3.150,-2.197, both P<0.05), and it was obviously lower in the CAS group than that in the T2DM without CAS group (Z=-2.263, P<0.05). The irisin level was negatively correlated with homeostasis model assessment of insulin resistance, duration of diabetes (r=-0.312,-0.321, both P<0.05), and was positively correlated with high density lipoprotein-cholesterol (HDL-C), diastolic blood pressure (r=0.321, 0.285, both P<0.05). Irisin and HDL-C were the independent protective factors for CAS (B=-1.225,-4.332, both P<0.05).

Irisin may be associated with the occurrence and development of T2DM; depressed serum irisin level may be one of the causes of occurrence and development of macroangiopathy in patients with T2DM.

To explore the clinical characteristics of ketosis in patients with gestational diabetes mellitus (GDM).

It was an observational retrospective study. Based on the testing result of urine ketone body and blood β-hydroxybutyric acid, 77 cases with gestational diabetes mellitus from January 2015 to April 2016 treated in the Clinical Nutrition Department of Beijing Anzhen Hospital were allocated into two groups: GDM with diabetic ketosis as the observation group ( n=37) and GDM without diabetic ketosis as the control group (n=40). Family history, past medical history and treatment record, blood pressure, glycosylated hemoglobin, total protein (TP), serum albumin (ALB), urea, creatinine, hemoglobin and other indexes were collected. Blood glucose was recorded by the continuous glucose monitoring system. The data of two groups was statistically compared by using χ ² test and t test.

The daily average blood glucose, fasting blood glucose, 2-hour after dinner blood glucose, hyperglycemia events, hyperglycemic duration and minimal blood glucose in the observation group were all significantly lower than those in the control group (t=-4.156--0.745, all P<0.05). The level of TP in the observation group was lower than that of the control group [(58.4±3.7) vs (67.0±2.9) g/L, t=-0.796, P=0.034]. The incidence rate of hypoproteinemia and percentage of patients who had decreased ALB in the observation group were both significantly higher than those of the control group [100%(37/37) vs 25.0%(10/40), 100%(37/37) vs 80.0%(32/40), χ ²=45.463, 8.258, both P<0.05]. Total calorie intake, carbohydrate intake and energy contribution in the observation group were all significantly lower than those in the control group [(1 846±229) vs (2 119±186) g, (230±45) vs (300±36)g, 50.2%±4.1% vs 57.5%±3.6%, t=-5.780,-7.568,-8.363, all P<0.05].

Ketosis in GDM patients is mainly starvation ketosis. Compared with patients without ketosis, total calorie intake, especially carbohydrate intake in GDM with ketosis are more insufficient. On the premise of diet control in GDM patient, it is suggested to ensure total calorie intake, and high quality protein intake should be appropriately increased, so as to attain the qualified blood glucose meanwhile reducing the risk of ketosis.

Nod-like receptor family pyrin domain containing 3 (NLRP3) and interleukin-1β (IL-1β) were detected for exploring the interactive mechanism between type 2 diabetes mellitus (T2DM) and chronic periodontitis (CP).

Hospitalized T2DM patients,aged 20-80 years old were divided into T2DM+CP group (n=70), T2DM group (n=40), CP group (n=30) and healthy control group (n=35). The concentration of IL-1β protein were tested by ELISA assays and the expression of NLRP3 mRNA were detected by RT-PCR. The differences of the concentrations of IL-1β and the levels of the NLRP3 inflammasomemRNA were compared by ANOVA (analysis of variance) ,the relationships between 4 groups were evaluated by pearson test or spearman test.

The up-regulation of serum IL-1β concentrations was detected in the T2DM+CP group compared with the healthy group, the CP group and the T2DM group[ (41±10) , (28±6) , (34±8) , (31±7) ng/L,F=23.092, P<0.05]. The expression of NLRP3 mRNA of the T2DM+CP group was higher compared with the healthy group, the CP group and the T2DM group (1.9±0.5, 1.0, 1.4±0.6, 1.4±0.5, F=33.076, P<0.05) . The expression of ASCmRNA of the CP group, the T2DM group and the T2DM+CP group was higher compared with the healthy group (3.0±1.2, 2.9±1.9, 2.7±0.9, 1.0, F=23.756, P<0.05) . The expression of caspase-1 mRNA of the CP group and the T2DM+CP group was higher compared with the healthy group (1.5±0.4, 1.4±0.6, 1.0, F=19.155, P<0.05) .The expression of NLRP3 mRNA and caspase-1 mRNA were correlated positively with the serum IL-1β concentrations (r=0.343, 0.227, all P<0.05) .

The increased serum IL-1β concentration and NLRP3 mRNA expression may promote the chronic inflammatory response and aggravate the progression of the disease in patients with T2DM and CP.

To investigate the role of phosphatase and tensin homologue deleted on chromosome ten (PTEN) regulated Janus kinase2/signal transducer and activator of transcription 3(JAK2/STAT3) signaling pathway in the sensitivity of ischemic postconditioning (IPO) to diabetic hearts.

Healthy male SD rats, weighing 220-280 g, were used in this study. Type 1 diabetic rat models were induced by a single intraperitoneal injection of streptozotocin (60 mg/kg), and 8 weeks after, sixty diabetic rats were randomly divided into 5 groups (n=12 each): sham group (S group), ischemia reperfusion group (I/R group), ischemic postconditioning group (IPO group), PTEN inhibitor BpV+I/R group (BpV+I/R group) and BpV+IPO group. Myocardial I/R was induced by occlusion of the anterior descending branch of left coronary artery for 30 min followed by 120 min of reperfusion. IPO was induced by 3 cycles of 10 second reperfusion and ischemia at the onset of reperfusion. Sham group was performed all the steps only not to draw the suture. Bpv (1 mg/kg) was given as intravenous injections 1 hour before ischemia, and the equal volume of normal saline was given in untreated control groups. At 2 hours of reperfusion, the serum and heart tissue of diabetic rats were collected for determination of the level of serum creatine kinase-myocardial band isoenzyme (CK-MB), infarct size (IS), apoptosis index (AI) and PTEN activity, as well as the expression of PTEN, phosphorylated JAK2(p-JAK2), phosphorylated STAT3(p-STAT3) and apoptosis related protein caspase-3. One-way analysis of variance was used when data were compared among multiple groups, paired t test was applied to compare between two groups.

Compared with S group, the level of CK-MB, PTEN activity were significantly increased, the expression of PTEN and cleaved caspase-3 were up-regulated in both I/R and IPO groups (t=2.997-7.702, all P<0.05). Compared with IPO group, the level of CK-MB, IS and AI, as well as PTEN activity were significantly decreased, and the expression of p-JAK2, p-STAT3 were up-regulated, the expression of cleaved caspase-3 was down-regulated in BpV+IPO group[3 003±613 vs 1 247±440, 42%±8% vs 53%±6%, 21%±3% vs 33%±6%,(584±78) vs (918±136) pmol, 1.73±0.29 vs 1.06±0.24, 1.75±0.19 vs 1.01±0.16, 1.6±0.4 vs 2.2±0.5, t=2.837-9.249, all P<0.05]. There was no significant difference in the parameters mentioned above between I/R and IPO groups, and between BpV+I/R and I/R groups.

Inhibition of PTEN restores IPO-induced cardioprotection in diabetic reperfusion heart possibly by activating JAK2/STAT3 signaling pathway.

The incidence of abnormal glucose metabolism in patients with acute coronary syndrome (ACS) is much higher than that in the general population. A 2015 Swedish study showed that the overall incidence of abnormal glucose metabolism in ACS patients was 72%^[1]； In 2005, the China Heart Survey Group conducted a survey of ACS patients in 52 hospital coronary care units (CCU) in 7 cities in China, and found that the proportion of abnormal blood glucose metabolism reached 67%^[2]。 Global Registry of Acute Coronary Events (GRACE) risk score is currently the main indicator for judging the prognosis of ACS. It can accurately and quickly reflect the risk degree of ACS patients, accurately predict the mortality rate of patients and suggest the prognosis. At present, there are many studies on the blood glucose of ACS patients in China, but there are few studies on the relationship between the immediate blood glucose level of ACS patients and the GRACE risk score, and the relationship between the immediate blood glucose of ACS patients with abnormal glucose metabolism and the GRACE risk score. Therefore, this study was designed.

insulin autoimmune syndrome (IAS) was developed in 1970 by Japanese scholar Hirata et al.^[1]First reported, also known as Hirata disease, the classic concept is severe spontaneous hypoglycemia caused by non-exogenous insulin in the blood inducing the production of high concentrations of immunoactive insulin and high-titer insulin autoantibodies (IAA)^[2]。 Since the first report of this disease, about 400 cases have been reported worldwide, most of which come from Japan. It is the third cause of spontaneous hypoglycemia in Japan besides insulinoma and giant extrapancreatic tumors. First reported in China since 1985^[3]At present, about 100 cases have been reported. The first case of IAS caused by alpha-lipoic acid was reported in Japan in 2006^[4], after which South Korea^[5]Europe^[6]Similar cases have been reported, but no lipoic acid-induced IAS has been reported in China.

With the increasing incidence of diabetes mellitus, diabetic nephropathy (DKD) has become one of the main causes of chronic kidney injury^[1,2]。 In European and American countries, DKD has become the leading cause of end-stage renal disease (ESRD), accounting for about 45% of ESRD^[3]Bringing serious socio-economic burden. According to the pathophysiological characteristics of DKD, interventional therapy in stages 1 and 2 of diabetic renal injury can reverse the renal injury^[4,5]Therefore, early identification of mild kidney injury caused by diabetes has become the focus of clinical attention. At present, pathological biopsy is recognized as the diagnostic gold standard of DKD, which can clarify kidney injury and assess the degree of injury. However, pathological biopsy is an invasive examination, and the ability to detect kidney lesions and assess the prognosis of kidney disease remains to be confirmed^[6]。 In 2014, the American Diabetes Association and the American Nephrology Foundation reached a consensus to define DKD as an estimated glomerular filtration rate (eGFR) less than 60 ml/ (min · 1.73 m²) or urinary albumin/creatinine above 30 mg/g for more than 3 months^[7,8,9]； Since then, the Chinese DKD prevention and treatment guidelines have also recommended the use of urinary albumin excretion (UAE) and eGFR to assess kidney function in diabetic patients^[9]。 However, in recent years, a large number of studies have found that the use of UAE to diagnose DKD lacks sensitivity and specificity^[6,10]When eGFR is reduced, irreversible damage usually occurs in the kidney, so finding markers with higher sensitivity, specificity and excellence has become a new direction for clinical and laboratory joint efforts. In recent years, a new risk scoring system for chronic kidney disease (CKD), CKD273, has emerged, which can be used to diagnose chronic kidney injury specifically, and its application in DKD has also attracted people's attention. This paper mainly summarizes CKD273 and its application in DKD.

diabetic gastroparesis (diabetic gastroparesis) is one of the common complications of diabetic patients, which exists in 27% to 58% of type 1 diabetes and 30% of type 2 diabetes^[1]。 Presented as gastric emptying dysfunction caused by non-mechanical obstruction, characterized by delayed emptying of gastric contents accompanied by early satiety, and symptoms such as nausea, vomiting, abdominal pain in the patient^[2]Abdominal distension and vomiting were the most common^[3]。 Gastric emptying dysfunction will affect the absorption and metabolism of food and hypoglycemic drugs, and seriously affect the quality of life of patients^[4]。 However, due to the lack of specificity of its clinical symptoms, imaging and other methods to detect gastric emptying have been important objective indicators for diagnosing gastric emptying and evaluating its therapeutic effect since gastroparesis was named^[5]。 This article mainly reviews the pathogenesis of diabetic gastroparesis and some existing detection methods.

At present, the efficacy of berberine in the treatment of diabetes has been confirmed by extensive clinical and animal experiments. Its mechanism of action is generally considered to improve insulin resistance, protect β cell function, anti-inflammatory and anti-oxidative stress, and other mechanisms such as promoting glycolysis and inhibiting gluconeogenesis. However, pharmacological studies have found that the bioavailability of oral berberine is very low, and the absorption rate of intestinal tract is only 5% ~10%^[1]The maximum plasma concentration after a single oral dose of berberine 400 mg in adults was only 0.4 μ g/L^[2]It is difficult to explain the hypoglycemic mechanism of berberine by classical pharmacokinetic theory. It was found that the effect of berberine has dual kinetic characteristics, namely, plasma kinetics (the drug is absorbed into the blood, mainly exerting anti-arrhythmia and hypertension effects) and gastrointestinal kinetics (the drug is not absorbed into the blood, mainly exerting antibacterial effects). A deep understanding of these two pharmacokinetic characteristics of berberine can reduce the blindness of formulation design and provide scientific basis for formulation development. Due to the poor absorption of oral berberine, in order to give full play to the hypoglycemic effect of berberine, many scholars have devoted themselves to improving the dosage form of oral berberine and studying how to improve the bioavailability of berberine^[3,4]。 Berberine has many hypoglycemic mechanisms in the gastrointestinal tract, and it has hypoglycemic effect without being absorbed into the blood. This review provides a new direction for the study of pharmacological mechanism of berberine and similar drugs.

Macrovascular lesions and microvascular lesions are major complications of type 2 diabetes mellitus (T2DM). About 35% of diabetic patients develop kidney disease, and the mortality rate of these patients is increased^[1]。 Therefore, reducing the occurrence and delaying the progression of kidney disease is one of the important contents of diabetes management.