Volume 06 · Issue 11 · 2014

At the 2014 Annual Meeting of the American Diabetes Society (ADA), the Banting Award winner was Professor Daniel Drucker of the University of Toronto, Canada, one of the founders of incretin research. His award-winning speech "Decoding Intestinal Metabolic Information and Promoting Treatment Innovation" once again focused the attention of the diabetes field on incretin. Cardiovascular disease is the main complication of type 2 diabetes. On the basis of good control of blood sugar, comprehensively improving cardiovascular risk factors and reducing the morbidity and mortality of cardiovascular disease are the main goals of treatment of type 2 diabetes. Glucagon-like peptide 1 receptor agonists (GLP-1RA) and dipeptidyl peptidase IV (DPP-4) inhibitors enrich the treatment of diabetes^[1]While the extrapancreatic effects based on incretin therapy are also attracting increasing attention, basic and clinical research helps us to understand the cardiovascular protective effects based on incretin therapy.

Lower extremity atherosclerotic lesions (LEAD), as an important component of multi-site arterial diseases, and cardiovascular and cerebrovascular diseases such as coronary heart disease and stroke are involved in a series of subacute and non-infectious inflammatory processes involved in inflammatory cells and inflammatory factors^[1]Therefore, the clinical significance of LEAD lies not only in its own clinical symptoms (intermittent claudication, resting pain) and its serious consequences (amputation). Studies have shown that the incidence of cardiovascular and cerebrovascular events in patients 1 year after the diagnosis of LEAD is as high as 21.14%^[2]Therefore, its predictive value for cardiovascular and cerebrovascular diseases cannot be ignored. As an early marker disease of systemic arteriosclerosis, LEAD can indirectly understand the systemic vascular lesions of diabetic patients by screening LEAD, and then strengthen the early management of related vascular lesions, which has higher health and economic benefits.

The relationship between diabetes and its drug therapy and macrovascular disease has been a hot topic in the field of diabetes and cardiovascular disease (CVD) in recent decades. The University Collaborative Group for Diabetes Research (UGDP) in the 1970s was the first large-scale study to assess the effect of different hypoglycemic drugs on macrovascular complications in adults with non-insulin-dependent diabetes^[1]。 The results showed that insulin therapy was not superior to simple dietary control for cardiovascular complications; Both tolbutamide and phenformin were prematurely terminated due to more all-cause and cardiovascular deaths. The announcement of UGDP results has caused great controversy in the medical field, and many scholars have questioned its research design and results. The UGDP has triggered a series of studies on the interrelationship between diabetes therapy and macrovascular disease. The purpose of this paper is to synthesize the results of multiple evidence-based studies and analyze the possible influencing factors of different results, so as to provide evidence for the treatment and prevention of diabetes.

Diabetic nephropathy is one of the most important microvascular complications of diabetes mellitus, and it is currently the leading cause of end-stage renal disease (ESRD)^[1]。 Foreign research data show that the incidence of developing 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^[2]。 The prevalence of diabetic nephropathy in China is also increasing rapidly. From 2009 to 2012, the prevalence of diabetic nephropathy in type 2 diabetic patients in China is 30% ~50% among community patients^[3,4], about 40% of hospitalized patients^[5]。 The onset of diabetic nephropathy is hidden, and once it enters the stage of massive proteinuria, the rate of progression to ESRD is about 14 times that of other kidney lesions. Therefore, early diagnosis, prevention and delay of the occurrence and development of diabetic nephropathy are of great significance to improve the survival rate and quality of life of diabetic patients. In order to standardize the diagnosis and treatment of diabetic nephropathy, the Microvascular Complications Group of Diabetes Branch of Chinese Medical Association organized domestic experts in the field of endocrinology and nephrology to jointly formulate this consensus.

To investigate the relationship between serum osteocalcin(BGP) and peripheral arterial disease in type 2 diabetic patients among Uygur and Han people.

Total of 477 type 2 diabetic patients aged ≥50 years, including 262 Uighur and 215 Han patients, were selected in People 's Hospital of Xinjiang Uygur Autonomous Region from January 2012 to April 2013, and were divided into different groups by gender further: male and postmenopausal women. The general clinical data of patients were recorded. Fasting plasma glucose(FPG), fasting insulin(FINS), glycated hemoglobin A1c (HbA1c), triglyceride(TG), total cholesterol(TC), low- density lipoprotein cholesterol(LDL- C), high- density lipoprotein cholesterol(HDL- C), BGP, serum creatinin(SCr), high- sensitivity C- reactive protein(hs- CRP), ankle brachial index(ABI), body mass index(BMI), homeostasis model assessment of insulin resistance (HOMA- IR) and homeostasis model beta cell function index(HOMA- β) of patients were recorded and compared between groups. Regression analysis was applied to explore the relationship between BGP and peripheral arterial disease in men and postmenopausal women.

Compared between male and postmenopausal female patients in same nationality, the differences of age, HDL-C, SCr, BGP were significant; the t values in Han nationality were- 3.330, - 3.515, 8.164, - 3.588, and in Uygur nationality were -2.545, 0.251, 11.367, -3.413; there was statistical difference in the use of hypotensive drugs, the χ ² value was 5.641 in Han nationality and 6.903 in Uygur nationality; all P<0.05. Compared in same gender between Han and Uygur nationality, the differences of age, BMI, HbA1c, TG, hs-CRP, BGP were significant; the t values in men were 2.143, - 9.210, - 2.399, - 4.084, - 3.700, - 2.406, and in postmenopausal women were 3.524, - 6.004, - 6.414, - 2.896, - 5.809, - 2.246; there were significant difference in HOMA-IR between two nationalities in both gender, the Z values in Han nationality was -2.649 and -3.208 in Uygur nationality; there were statistical defferences in the hypoglycemic drug and hypotensive drug use too, the χ ² value in Han nationality were 5.225, 4.492 and 11.160, 4.017 in Uygur nationality; all P<0.05. Serum osteocalcin was significantly and negatively related to peripheral arterial disease in Uygur male patients with logistic regression analysis after adjusted for other indices (B=- 0.153, P<0.05).

In type 2 diabetic Uygur male patients, the decrease of serum osteocalcin levels may be a better clinical predictor of peripheral arterial disease.

To investigate the glycemic control and macrovascular complications risk factors in early onset type 2 diabetes mellitus(EDM).

This cross-sectional study included three groups: (1) EDM group, adults diagnosed with type 2 diabetes at 18-40 yeas of age (n=219). (2) Usual onset diabetes mellitus group as control DM group, adults diagnosed with type 2 diabetes older than 40 years (n= 1 036). (3) Age matched non- diabetic group (n=478). Body mass index(BMI), blood pressure, fasting glucose, glycated hemoglobin A1c(HbA1c), fasting insulin, high- density lipoprotein cholesterol(HDL- C), triglycerides and low- density lipoprotein cholesterol(LDL- C) were measured. For patients with diabetes mellitus, the complications were also examined. The t test and multivariate logistic regression analysis were used for statistical analysis.

(1) The systolic and diastolic blood pressure was higher in EDM group than those in usual onset DM group ( t=2.685,2.560, all P <0.05). There were significantly higher smoking rate (χ ²=5.439, P <0.05) and higher rate of insulin therapy (χ ²=15.725, P<0.05) in EDM group than in control DM group.(2) In EDM group, 14.2% of them had HbA1c<7%. The prevalence rates of atherosclerotic plaque in arteries, diabetic retinopathy, neuropathy and positive micro-albuminuria were 50.7%, 52.5%, 53.4% and 53.0%, respectively. After adjusted age and gender, there were higher HbA1c levels (F=3.733, P <0.05) and lower HbA1c control rate (χ ²=8.508, P <0.05) of EDM group than control DM group. (3) Compared with the age matched non- diabetes group, the EDM group had higher levels of BMI ( t=3.623, P<0.05) , blood pressure (SBP t=16.392, P<0.001; DBP t=7.056, P<0.05) and LDL- C ( t=4.112, P<0.05). (4) In EDM group, women had a higher risk for arterial atherosclerosis than man ( OR=3.218, 95% CI: 1.527- 6.781). The postprandial 2 hour glucose and systolic blood pressure were also the risk factors for arterial atherosclerosis in EDM group ( OR=1.04, 95% CI: 1.016-1.072; OR=1.013, 95% CI:1.003-1.029 respectively).

Only 14.2% patients with early-onset diabetes meet the HbA1c control target and more than 50% patients already have macrovascular complications. In EDM patients, female, systolic blood pressure and postprandial 2 hour blood glucose are related with macrovascular complications.

To assess the efficacy and safety of adding basal insulin to current oral antidiabetic drugs (OADs)regime in poorly controlled elderly patients with type 2 diabetes compared to increasing the OADs.

In this retrospective study, we observed 746 elderly outpatients (mean age 69 yrs, glycated hemoglobin A1c(HbA1c) 7.5%- 11.0% and fasting blood glucose(FBG)>7.5 mmol/L) who were inadequately controlled with OADs for enrollment from our hospital specialist clinics from January 2004 to December 2011. All enrolled patients were divided into 2 groups according to either adding basal insulin to current therapy or increasing OADs. The changes of glucose control, OADs therapy, body weight and the incidence of hypoglycemic events were assessed and compared between the 2 groups during the 24- week observation period.

A total of 286 patients were included in the final analysis, 176 in the adding basal insulin group (Group A) and 110 in the increasing OADs group (Group B). During the 24-week observation period, the reduction of HbA1c and FBG in the Group A were significantly larger than that in the Group B (2.5 mmol/L vs 2.1 mmol/L, 2.0% vs 1.7%, t=-5.86,-3.93, both P<0.01). HbA1c level<7.0% was achieved by 78.4% patients (138/176) and 54.5% patients (60/110) in the groups A and B, respectively (χ²= 18.1, P<0.01). The group A had fewer total hypoglycemic events compared with group B(31.5%(56/176) vs 52% (57/110) , χ ²=12.0, P<0.01). The patients in the group A had lower doses and number of oral antidiabetic drugs compared with the group B. There was no difference regarding weight gain between the 2 groups.

The addition of basal insulin to current OADs therapy may be an effective and safe option for poorly controlled elderly patients with type 2 diabetes.

To assess the correlation between obstructive sleep apnea-hypopnea syndrome(OSAHS) and diabetic microangiopathy.

Total of 239 patients were recruited casually from Department of Endocrinology, Henan Provincial People's Hospital. Diabetic peripheral neuropathy (DPN) was diagnosed using the Michigan Neuropathy Screening Instrument and neurophysiological methods. Diabetic nephropathy(DN) was diagnosed using urine albumin/creatinine ratio. Diabetic retinopathy(DR) was diagnosed using fundus fluorescein angiography. Patients were divided into DPN group(97) and non- DPN group(142), DN group(74) and non-DN group(165), DR group(87) and non-DR group(152). 3-nitrotyrosine (3- NT) was measured by enzyme- lirked immunosorbent assay. The Studentt test, Chi- square test and multivariate logistic regression were used.

Diabetes duration, glycosylated hemoglobin, OSAHS were independent risk factors of DPN (OR =1.12,2.93,3.54,P<0.05). Diabetes duration, glycosylated hemoglobin, systolic pressure, OSAHS were independent risk factors of DN (OR=1.11,3.23,1.67,9.58,P< 0.05). Diabetes duration, glycosylated hemoglobin, OSAHS were independent risk factors of DR (OR=1.17, 2.89,2.54,P<0.05). 3- NT levels were higher in patients with OSAHS compared with those without ((121.6± 9.3) vs (87.5±9.1) nmol/L,t=4.36,P<0.05).

OSAHS is independently associated with diabetic microangiopathy in type 2 diabetic patients.

To explore the nutritional status of patients with type 2 diabetes in urban community of Yangpu district in Shanghai.

Diet status of 400 patients with type 2 diabetes were investigated by the way of 24-hour dietary recall method for 3 consecutive days, and assess their dietary nutrients. The t test or χ² test was applied in data comparisons among the groups.

The dietary energy intake of patients with type 2 diabetes was low, only reach to 62.8% of the recommended standard of adult diet nutrients (male 72.4%; female 56.5%). The energy ratio provided by protein, fat and carbohydrate was 14.4%, 33.9% and 51.7%, respectively, and the fat intake was relatively higher. The energy ratio provided by breakfast, lunch and supper dinner was 23.4%, 38.0% and 38.6%, respectively, and the breakfast was relatively lower, supper dinner was relatively higher. The ratio reach to the recommended standard of adult diet of vitamin E, Ferrum, Niacin, Manganese, phosphorus and cholesterol were 149.6%, 138.1%,137.1%, 132.5%, 127.5% and 122.0%, respectively. But the ratio reach to the recommended standard of protein, fat, carbohydrate, dietary fiber, Calcium, Zinc, Cuprum, Magnesium, Potassium, vitamin A, vitamin B1, vitamin B2 and vitamin C were 77.87%, 90.31%, 57.06%, 50.69%, 49.28%, 81.43%, 75.67%, 75.69%, 77.50%, 77.03%, 55.05%, 58.17% and 67.63%, respectively.

The energy provided by diet in patients with type 2 diabetes was low, and some dietary nutrients intake of these patients was unreasonable. Education and instruction of diet and nutrition should be enforced in these patients.

To observe the effects of the ketogenic diet and exercises in the diabetic rats and discuss the mechanism.

Fifty SD rats (weight (190±20) g) were divided into normal control group (NC group,n=10) and diabetes model group (n=40). Diabetes was induced by highcarbohydrate and high- fat diet plus intraperitoneal injection of streptozotocin(STZ), and 26 diabetic rats were subdivided into diabetes model group (DM group,n=13) and ketogenic diet treatment group (MT,n=13) randomly. After treating for 14 weeks, The metabolic index were measured such as serum glucose, glycosylated hemoglobin A1c(HbA1c), serum triglyceride, et al. The morphologic change of livers and pancreas were also observed by hematoxylin-eosin staining. Finally, the expression level of glycometabolism-related genes were detected in rat livers via RT-PCR, Western blotting and histochemistry. The results were analyzed with one-way anova.

(1)After 14 weeks, 2 rats died, 1 rat was found with liver tumor in DM group( n=10). Compared with the DM group, the serum glucose((10.8±5.5) vs(26.7±3.3) mmol/L), urea nitrogen((5.9±1.1 )vs (8.9±1.6) mmol/L), serum triglyceride((0.42±0.40)vs(2.07±1.63)mmol/L) and HbA1c (4.3±0.7)% vs (6.5±0.3)% were all declined in MT group ( t=8.361, 4.876, 3.035, 2.142, all P<0.05). No significant difference showed between MT group and NC group (all P>0.05). (2) Under the histomorphology of pancreas were recovered compared with DM group: the pancreatic cell alignment became tighter with less necrosis in MT group. (3)The transcriptional level of glucokinase (GCK)(50.86±3.96,1.03±0.31; t=21.71)and pyruvate kinase isozymes L/R (Pklr)(3.04±0.27,1.00±0.04; t=13.053)in livers of MT group significant increased than DM group (P<0.001). Whereas, the transcriptional level of phosphoenolpyruvate carboxykinase 1 (PCK-1) (0.51±0.03,1.01±0.15; t=5.548)in livers of MT group significant decreased than DM group (P<0.01). These results was also consistent with WB and histochemistry data.

Ketogenic diet and exercises treatment could reduce serum glucose and lipid in diabetic rats, partially through modulating the expression of GCK, Pklr and PCK-1 in livers.

microvesicles (MVs) are small vesicle-like substances formed by cell activation or apoptosis under certain physiological or pathological conditions, and budding and shedding directly from the surface of cell membrane. Various risk factors for macrovascular lesions in type 2 diabetes mellitus (T2DM) can stimulate MVs formation, and MVs levels are significantly elevated in T2DM and cardiovascular disease. MVs can participate in the development of diabetic macrovascular disease by mediating pathological processes such as endothelial cell injury, thrombosis, plaque rupture and collateral circulation disorder. Current research believes that MVs is expected to be a potential biomarker for the diagnosis, prognosis and efficacy judgment of T2DM macrovascular disease. The research progress of MVs and T2DM macrovascular disease is summarized as follows.

Diabetes is one of the chronic non-communicable epidemic diseases that seriously endanger human health. More than 70% of diabetic patients die of cardiovascular diseases, which is 2~3 times the mortality rate of cardiovascular diseases in non-diabetic people^[1]。 At present, most studies mainly focus on coronary atherosclerotic heart disease caused by macrovascular disease, while there are few studies on diffuse myocardial disease caused by microvascular disease, autonomic neuropathy, and abnormal myocardial metabolism. In recent years, researchers have put forward the concept of diabetic cardiomyopathy (DCM), and gradually realized that DCM is one of the main cardiac complications of diabetic patients and the main cause of heart failure in diabetic patients.

It is rare to have significant hyperinsulinemia in adult patients with occult autoimmune diabetes mellitus (LADA) with a long course of disease. We admitted one such patient and unexpectedly found that the accompanying hyperinsulinemia was completely relieved during high-dose hormone use in the treatment of nephrotic syndrome, and blood sugar fluctuations were controlled, which is now reported below.

According to recent data, only about 10% of China's nearly 100 million diabetic patients have achieved blood sugar control standards^[1]。 2011 Ji et al.^[2]The mean glycosylated hemoglobin (HbA1c) was 7.85% in the survey of 238 639 patients with type 2 diabetes. All these data suggest that the blood glucose control of Chinese diabetic patients is not ideal. How to better control blood sugar is a topic worth exploring.

Acetaldehyde dehydrogenase 1 (ALDH1) is a marker of human stem cells that regulates cell differentiation by catalyzing the conversion of retinaldehyde to retinoic acid (RAs). However, there are few data on the expression level and function of ALDH1 in human fetal pancreatic development. Li et al., Institute of Child Health, University of Western Ontario, Canada, studied the expression pattern of ALDH1 and its functional role in islet cell differentiation.

Beta cells rapidly secrete insulin in response to a sharp increase in blood glucose, but with further sustained exposure to glucose, insulin secretion gradually decreases. Although this mechanism is unclear, this regulatory pattern suggests the existence of a time-dependent glucose receptor system (TDGS) that temporarily reduces insulin secretion. Interestingly, early beta cell dysfunction is often characterized by excessive basal (e.g. fasting) insulin secretion, suggesting impairment of these related mechanisms. Since sweet receptors (STRs) on beta cells are related to the regulation of insulin secretion, and glucose is the real ligand of STRs, Kyriazis et al. from Sanford-Burnham Medical Research Institute in the United States observed whether STRs mediate the glucose reception mechanism and participate in the regulation of basal insulin secretion.

Early in the onset of type 2 diabetes mellitus (T2DM), abnormal glucagon secretion by islet alpha cells precedes impaired insulin secretion (GSIS) after beta cells receive glucose stimulation. However, whether hyperglucagonemia is causally related to beta cell dysfunction remains unknown. Glucagon stimulates hepatic glucose production via the cyclic adenosine phosphate-protein kinase A (cAMP-PKA) pathway by binding to receptors on the surface of hepatocytes, causing a hyperglycemic state. Although hyperglycemia stimulates insulin secretion from beta cells, transgenic mice with upregulated hepatocyte PKA activity show increased hepatic glucose production and elevated blood glucose, but GSIS are abnormally impaired.

Decreased beta cell mass due to apoptosis is an important defect in type 2 diabetes. Islet amyloid, formed by the aggregation of human islet amyloid polypeptide (hIAPP), promotes beta cell death in islet grafts of patients with type 2 diabetes and type 1 diabetes. Park et al. from the University of British Columbia, Canada, used human pancreatic islets and mouse pancreatic islets expressing hIAPP and removing caspase-8 from β cells to explore the role of caspase-8 in amyloid-induced apoptosis of pancreatic islet β cells, and observed whether inhibition of caspase-8 could protect β cells under the toxic effect of amyloid.

Most Maf transcription factors such as MafA and MafB are expressed in a spatiotemporal-specific manner in pancreatic islet cells of rodents. Studies in mice with Mafa- / -and pancreas-specific Mafa Δ PANC deletion mutations have shown that Mafa plays a major role in adult beta cell activation, while MafB plays an important role in embryonic beta cell activity. Hang et al. from Vanderbilt School of Medicine in the United States used whole pancreatic MafA deletion mutant mice to conduct research to clarify when MafA has significant significance on β cell function and how MafB produced in a short time after birth affects this, and identify the genes regulated by MafA in this period.