Volume 07 · Issue 05 · 2015

Diabetes is spreading rapidly around the world. According to the International Diabetes Federation (IDF) data in 2013, 8.3% of adults (382 million people) have diabetes^[1]It is estimated that the number of diabetes patients will exceed 592 million within 25 years. At the same time, changes in lifestyle, competitive pressure in the workplace, physical and mental illnesses make people's sleep status change, and the number of sleep disorders is increasing day by day. According to a 2013 survey by the National Sleep Foundation in the United States, 21% of Americans sleep less than 6 hours on weekdays, and sleep disorders are common among Chinese people. There is a temporal consistency between sleep disorders and diabetes prevalence. Is there a correlation between them? In recent years, studies on sleep disorders and diabetes have found that sleep structure, sleep time and sleep-related diseases may affect the occurrence and development of diabetes. Sleep medicine has become a discipline closely related to endocrine and metabolic diseases.

To evaluate the status of obstructive sleep apnea hypopnea syndrome (OSAHS) in patients with type 2 diabetes, and to investigate the association with neurotransmitter levels in cerebral tissue.

The status of OSAHS was evaluated using portable sleep apnea monitor in 328 patients with type 2 diabetes who was hospitalized from September 2012 to September 2014 in Department of Endocrinology, Shanghai East Hospital, of which brain proton magnetic resonance spectroscopy was performed in 132 patients to detect neurotransmitter levels in the left hippocampus and left brainstem area. Patients were divided into T2DM without OSAHS group (125 cases) and T2DM with OSAHS group (203 cases) according hypopnea index (AHI). Measurement data between two groups were compared by using t test, count data rate were compared by using χ ² test.

The prevalence of OSAHS was 61.9% (203/328) in patients with type 2 diabetes mellitus. There were significant differences in age, body mass index (BMI), waist circumference, hip circumference, Cho/Cr level in the left hippocampus and Cho/NAA level in the left brainstem area and prevalence rate of hypertension in patients with OSAHS compared that with non–OSAHS (t=– 2.038,– 3.391,– 2.577,– 2.576, Z=– 1.923、– 2.06, χ²=5.746, all P<0.05). There were significant differences in diabetes duration, body mass index, prevalence rate of hypertension in patients with severe OSAHS compared that with mild OSAHS (t = – 2.074,– 3.923,χ²=4.524, all P< 0.05). Logistic regression analysis showed that age (OR1.03, 95% CI 1.01– 1.05, P<0.05), body mass index(OR=1.14, 95% CI 1.07– 1.23, P<0.05), NAA/Cr (OR=1.563,95% CI 1.02–2.438, P<0.05) and Cho/Cr level(OR=0.506,95% CI 0.263– 0.976, P<0.05) in the left hippocampus were independent risk factors of OSAHS.

There is higher prevalence of OSAHS in patients with type 2 diabetes. BMI and age are the risk factors of OSAHS. There are abnormal metabolic changes in neurotransmitter levels in the left hippocampus and left brainstem area in diabetic patients with OSAHS.

To study the changes of glucagon–like peptide–1(GLP–1) and effects of GLP–1 analogues on sleep – disordered breathing in the type 2 diabetic patients with obstructive sleep apnea – hypopnea syndrome(OSAHS).

One hundred sixty–nine patients were enrolled as research subjects from in–patients and normal control from October 2012 to September 2014. Based on oral glucose tolerance test (OGTT) and polysomnography (PSG), patients were divided into the OSAHS–T2DM group (45), the OSAHS group (42), the T2DM group (47) and the control group (40). Fasting and postprandial GLP – 1 and 3 – nitrotyrosine were determined by enzyme linked immunosorbent assay (ELISA). The levels of GLP – 1 amongfour groups were compared by one–way ANOVA analysis. Patients with OSAHS and T2DM were treated with GLP–1 analogues or conventional oral hypoglycemic drugs. Independent sample t test and ANOVA test were used to analyze the data between two groups and among multiple groups, respectively. Multiple logistic regression was used to assess whether the treatment of GLP–1 analogues was independently associated with the improvement of sleep–disordered breathing.

Compared with the control group, OSAHS group and T2DM group, the levels of fasting and post prandial GLP- 1 and △ GLP- 1 decreased in the OSAHS–T2DM group ((2.9±1.4),(6.4±2.7), (5.5±3.1), (3.6±1.4) μg/L, F=26.78, P<0.05). This research found the change of body weight and treatment of GLP–1 analogues was independently associated with the improvement of sleep–disordered breathing by binarylogistic regression (OR=1.27, 95% CI 1.13–1.72; OR=3.52, 95% CI 1.82- 9.74). Compared with patients treated with conventional oral hypoglycemic drugs, the level of blood flow velocity increased(t=5.86, P<0.05) and the level of 3–nitrotyrosine decreased in the patients treated with GLP-1 analogues (t=- 12.32, P<0.05).

The level of GLP- Idecrease in the patients with OSAHS and T2DM.The treatment of GLP – 1 analogues can improve sleep – disordered breathing in the patients with OSAHS and T2DM.

To investigate the effect of obstructive sleep apnea– hypopnea syndrome (OSAHS) on serum 3–nitrotyrosine (3–NT) level and insulin resistance in individuals with type 2 diabetes mellitus (T2DM).

Total of 199 hospitalized patients with T2DM in the Department of Endocrinology from February 2012 to January 2014 were selected as subjects, and 41 healthy individuals underwent health check were set as control(NC). All subjects underwent overnight polysomnography while hospitalized. The subjects were then stratified by the presence or absence of OSAHS: group OM included 81 patients with both T2DM and OSAHS, group SDM included 118 patients with T2DM but without OSAHS. Apnea- hypopnea index (AHI), time spent in saturation of pulse oxygen below 90% (TST90), nocturnal lowest saturation of pulse oxygen(LPO₂) and mean saturation of pulse oxygen(MPO₂) were evaluated. Serum 3 – NT level and insulin resistance, as assessed by homeostasis model assessment C–peptide(HOMA–C) were compared across the three groups. Differences in measurement data were compared with one–way analysis of variance among 3 groups, and SNK-q test was used when data were compared between 2 groups.

The body mass index(BMI), HOMA–C and waist circumference(WC), systolic blood pressure(SBP), diastolic pressure (DBP), glycosylated hemoglobin A_1c(HbA_1c), triglyceride(TG), uric acid (UA) and serum 3–NT were all significantly higher in group OM when compared with those in group SDM and NC(F=5.591–73.427, all P<0.01), whele high density lipoprotein cholesterol(HDL– C) was significantly lower(F=51.209,P<0.05). The serum 3- NT levels had a positive association with AHI and total sleep time with TST90(r=0.425, 0.409, both P<0.05) and a negative association with LPO₂ and MPO₂(r=- 0.222,- 0.280, both P<0.01). Similarly, HOMA – C had a positive association with AHI and TST90 (r=0.324, 0.421, both P<0.01) and a negative association with LPO₂ and MPO₂(r=-0.183,–0.200, both P<0.01). After adjusted for BMI, WC, blood pressure, fasting blood glucose (FBG), TG and other factors, AHI, TST90 and MPO₂ were also impact factors of serum 3–NT (OR= 1.025,1.031 and 0.891, all P<0.05); and AHI and TST90 were also influencing factors of HOMA-C (OR= 1.026 and 1.022, both P<0.05). The prevalence of coronary disease and stroke, diabetic nephropathy, diabetic retinopathy and diabetic peripheral neuropathy were all significantly higher in the group OM than those in the group SDM (χ²=9.866, 7.508, 5.341, 4.484, all P<0.05). In the group OM, serum 3–NT level was significantly higher in those with diabetes complications than that in those without complications (t=–2.536, P<0.05).

Compared with those without OSAHS, patients with both T2DM and OSAHS have higher levels of 3- NT as well as worse bodyweight, blood pressure, uric acid levels, lipid profiles, insulin resistance, and incidence of diabetes complications.

To investigate the association between ambulatory blood pressure rhythm and urinary albumin excretion rate (UAER) in type 2 diabetes with sleep disorder patients.

Three hundred and seventy three in–patients with type 2 diabetes treated from May 2012 to May 2014 in Metabolic Disease Hospital of Tianjin Medical Universitywere divided into two groups according to Pittsburgh Sleep Quality Index(PSQI): patients without sleep disorder (267) and patients with sleep disorder (106). The groups were further divided into normoalbuminuria group, microalbuminuria group and macroalbuminuria group by UAER. The changes of the average blood pressure, the circadian rhythm of blood pressure, the smoothness index of blood pressure and blood pressure variation were analyzed between the two groups and each subgroup. The regression analysis were performed between sleep disorder as well as UAER and other indicators. One–way ANOVA was used to analyze data among multiple groups. LSD-t test was used to analyze data between two groups.

(1) The average blood pressure as well as coefficient variations of blood pressure was significant higher and the decreasing percentage of blood pressure at night and smoothness index of blood pressure was significant lower in patients with sleep disorder than those in patients without sleep disorder(t=2.9924- 5.3979, all P<0.05). (2) The average blood pressure and coefficient variation of blood pressure increased and the decreasing percentage of blood pressure at night and smoothness index of blood pressure decreased in all with and without sleep disorder subgroup patients with the increasing UAER. Significant changes of the above indicators were in sleep disorder subgroup(t=2.0073-4.0395, all P<0.05). (3) sleep disorder was positively related to 24 h systolic blood pressure, systolic blood pressure at night and UAER,whereas was negatively related to the decreasing percentage of systolic blood pressure at night(Wald= 4.192,4.590,6.019,5.910, all P<0.05).UAER was positively related to PSQI score, diastolic blood pressure at night and systolic blood pressure at night, whereas was negatively related to the decreasing percentage of systolic blood pressure at night(β=0.224, 0.251, 0.287, – 0.242, allP<0.05).

Abnormal circadian rhythm of blood pressure in type 2 diabetes patients with sleep disorder may be related to UAER.

To explore the interaction between family history of diabetes and sleep duration on prevalence of type 2 diabetes mellitus (T2DM).

A cohort study was conducted among permanent residents aged from 18 to 75 years in Xuzhou in May 2013. On the basis of this, a followed–up study of five years was conducted among a collection of participants without T2DM, and the interaction between family history of diabetes and sleep duration on prevalence of T2DM in followed–up participants was evaluated. Non–conditional logistic regression analysis was used to analyse the association between family history of diabetes and sleep duration on prevalence of T2DM.

Total of 15 939 participants were involved inthe followed–up study, and after five years, finally 11 842 participants were still in the cohort. The average sleep duration of total participants was (7.2±1.1) hours per night. The accumulative rate of T2DM among the followed- up participants was 3.10%. After adjusting for the confounding factors, compared with that participants with sleep duration of 6–8 h/night, individuals with sleep duration<6 hours per night had a higher prevalence of T2DM (RR=1.54,95% CI: 1.21–2.13, P<0.01), and the risk of T2DM did not increase in individuals with sleep duration>8 hours per night (RR=1.31,95% CI: 0.96–1.74, P>0.05). Individuals with family history of diabetes were more likely to suffer from T2DM than those without(RR=4.35,95% CI:2.01- 7.14, P<0.01). After adjusted for potential confounding factors, individuals withfamily history of diabetes and sleep duration <6 hours per night had significantly increased risk prevalence of T2DM (RR=7.98,95% CI: 3.86–12.95, P<0.01) and the risk of T2DM in participants with the family history of diabetesand sleep duration>8 hours per night didn't increase significantly(RR=1.12,95% CI: 0.88 – 1.59, P>0.05) when compared with participants with sleep duration of 6- 8 hours per night without family history of diabetes. After adjusted for potential confounding factors, values of the relative excess risk of interaction (RERI),the attributable proportion(AP), and the synergy index(S) for the additive interaction betweenthe family history of diabetes and sleep duration<6 hours per night were 3.51(1.41- 6.77), 0.46(0.26-0.62) and 1.98(1.24-3.13) respectively, while 0.07(- 0.18-0.31)、0.02(- 0.15-0.10)and 0.95(- 0.04-2.01) for the additive interaction between the family history of diabetes and sleep duration>8 hours per night.

Additive interactions exist between family history of diabetes and sleep duration<6 hours per night. There is not combined interaction to the increased risk of T2DM when family history of diabetes and sleep duration>8 hours per night at the same time.

To investigate insulin sensitivity in Chinese adult patients with type 1 diabetes mellitus through hyperinsulinemic–euglycemic clamp technique.

Adult patients with type 1 diabetes mellitus (n=10, group T1DM) and age, sex, body mass index, waist and waist-hip ratio matched normal glucose tolerance subjects (n=10, group NGT) were recruited from the third affiliated hospital of Sun Yat–sen University between June 2011 and June 2013. There were 5 male and 5 female in each group. The average age was (27±5) and (27±8) yrs in each group, respectively. Hyperinsulinemic-euglycemic clamp were performed to measure glucose disposal rate as insulin sensitivity. Differences between groups were analyzed by Student'st test.

No significant differences were found in age, waist, waist-hip ratio, body mass index, systolic blood pressure, diastolic blood pressure, triglyceride, low – density lipoprotein–cholesterol, high–density lipoprotein–cholesterol and uric acid between type 1 diabetes mellitus group and normal glucose tolerance group (t=- 1.248- 0.973, all P>0.05), except for glycated hemoglobin A_1c ((7.5± 0.8)% vs (5.2± 0.3)%,t=- 6.318, P<0.001). Glucose disposal rate in type 1 diabetes mellitus and normal glucose tolerance groups were (7.8±1.9) mg·kg^-1·min^–1 and (14.0±1.7) mg·kg^–1·min^–1 (t=7.769, P<0.001), respectively.

Insulin resistance may be present in Chinese patients with adult type 1 diabetes mellitus.

To evaluate the efficacy and safety of platelet–rich gel(PRG) in the treatment of the refractory diabetic foot ulcers.

A total of Sixty-two patients with refractory diabetic foot ulcer were recruited, from June 1, 2013 to September 1, 2014. All patients were randomly assigned into the conventional group(n=31) and PRG group(n=31) by the method of random number generator. Both groups were treated with general support and wound managed as usual. Wound treatments were same for two groups such as off–loading, debridement, dressing change, improvement of blood perfusion and anti–infection if necessary. The wounds of PRG group were treated with PRG according to wound volume to extract blood,and then covered with petrolatum gauze,after completely cleaning and regular treatment. Wounds were observed 3 days after enrollment, and every week until healed completely or in the end of 12 weeks observing period. The t,u and χ ² tests were used for comparing baseline data and healing efficacy. Kaplan–Meier survival analysis was used for comparing cumulative ulcer healing rate over time between two groups, Cox regression analysis was used for screening the factors influencing healing.

The healing efficacy (including poor, better, good and completely healing) in PRG group is better than conventional group(u=- 3.081, P< 0.05). The total effective rate (percentage of good and completely healing) (96.8% vs 71.0%, χ²=9.226, P< 0.05)and completely healing rate (93.5% vs 61.3%, χ²=7.631, P<0.05) of PRG group were significantly higher than those of conventional group. The comparison of Kaplan–Meier healing time curve between PRG group and conventional group was statistically significant (P<0.05). Compared with conventional group, median of healing time was shorter in PRG group (26(21–35) vs 60(43–84) d,Z=- 5.073, P<0.05). Cox regression analysis of these two groups showed that the PRG treatment, ABI, baseline ulcer volume were statistically different(B=2.552,2.982,– 0.343, RR=12.836,19.725,– 0.343,all P<0.05). The hospital stay and medical cost between PRG group and conventional group were no statistically significant(allP>0.05). During the observation period, there was no serious adverse events associated with PRG treatment.

PRG treatment is effective, safe in treating the refractory diabetic foot ulcers, and significantly promotes ulcer healing without increasing economic burden in hospital.

To evaluate the changes of health–related quality of life (HRQoL) in Chinese patients with type 2 diabetes (T2DM) after starting with, or switching to, biphasic insulin aspart 30 (BIAsp 30).

From November 2008 to March 2011, eligible T2DM patients, initiating or switching to premix (BIAsp 30), basal (insulin detemir), and meal-time (insulin aspart) insulin analogs, were recruited from 130 hospitals in China. HRQoL was evaluated by European Quality of Life-5 Dimensions (EQ-5D) questionnaire at baseline and 24 weeks. This study reported how HRQoL changed in Chinese people with T2DM after starting with, or switching to, BIAsp 30. Subgroup analyses were conducted. The paired t test, and Chi–square test were conducted for statistical analysis.

The reported HRQoL measured by EQ- 5D visual analogue scale score in total cohort, subgroup switching from oral anti–diabetic drugs (OADs) and subgroup switching from human premix insulin increased by 6.2 (from 75.8 to 82.0), 5.9(from 75.7 to 81.6) and 6.6(from 75.0 to 81.6) respectively; and the EQ–5D index score over 24 weeks increased by 0.018 (from 0.875 to 0.893), 0.019(from 0.876 to 0.894) and 0.034(from 0.845 to 0.879), respectively; all the changes were statically significant (t=28.10, 19.80, 10.90, 5.90, 4.30, 3.90, all P<0.05). The percentage of patients reporting no problems in the mobility, pain/discomfort, and anxiety/depression dimensions of EQ–5D increased to some extent too.

BIAsp 30 treatment is associated with improved HRQoL in patients with T2DM in China.

To investigate the protective roles of bone marrow-derived mesenchymal stem cells in glucolipotoxicity–induced INS–1 cell damage and the possible mechanisms involved.

INS–1 cells were divided into three groups according to different treatment, control group, high glucose group/ PA group and high glucose/PA with BMSCs co–culture group. INS–1 cells in high glucose/PA with BMSCs co-culture group were exposured to the culture medium containing 16.7 mmol/L glucose and 0.4 mmol/L palmitic acid (PA) for 48 hours, and then co–cultured with BMSCs for another 24 hours. The viability of INS- 1 cells was assessed by CCK8 assay. The expression of Cleaved cysteine asparate pro–tease- 3 (Caspase–3) were detected by western blot. The cell apoptosis incidence was measured using Annexin V/propidium iodinate (PI) staining by a flow cytometer. The insulin secretion of INS–1 cells were measured using a Ratio Immunity Assay (RIA) kit. The mitochondrial membrane potential (MMP) was detected with JC–1 probe by a flow cytometer. Intracellular reactive oxygen species (ROS) production was detected using dichlorofluoresceindiacetate (DCFH – DA) and quantified by a flow cytometer. Comparisons between two groups were measured using Student'st – test.

Compared with control group, there were a significant decrease of INS–1 cell viability((100.0%±0.8%) vs (71.9%±3.2%),t=8.46, P<0.01), upregulated expression of Cleaved Caspase- 3 (0.25±0.03 vs 1.01±0.07,t=10.28, P<0.01) and an increase of apoptosis incidence ((6.9%±0.4%)vs (16.4%±1.2%),t=17.38, P<0.01), combined with reduced basal insulin secretion (BIS) and glucose stimulated insulin secretion (GSIS) (t=5.745,13.559, P<0.01) in high glucose/ PA group. BMSCs co – culture improved the viability of INS – 1 cells, down – regulated the expression of Cleaved Caspase–3, reduced the apoptosis incidencet=3.98,5.16,13.08, P<0.05), and significantly increased the BIS((80.743±0.012) vs (109.67±1.058) ng/mg,t=5.674, P<0.05)and GSIS ((120.0±1.3) vs (231.2±1.6)ng/mg protein,t=10.148, P<0.01), compared with chronic high glucose/PA–treated INS – 1 cells. Additionally, mitochondrial function was impaired according to the glucolipotoxicity–induced mitochondrial depolarization (95.7±8.5 vs 45.9±4.2,t=5.239, P<0.05) and considerable ROS accumulation ((13.3%±0.9%)vs(34.2% ± 0.8%),t=17.38, P<0.01). However, compared with chronic high glucose/PA- treated INS- 1 cells, BMSCs treatment effectively reversed glucolipotoxicity–induced depolarization (46±4vs 87±14,t=2.822, P<0.05) and reduced the cellular ROS level ((34.3%±0.8%) vs (22.5%±0.4%),t=13.08, P<0.01), indicating that BMSCs could recover the injury of the mitochondrial function.

BMSCs played an important cyto-protective role in glucolipotoxicity–induced INS–1 cell damage, and the possible mechanism underlying this effect might be associated with the improvement of mitochondrial function.

To investigate the characteristics of components of metabolic syndrome in young men with hypogonadotropic hypogonadism (HH).

A total of 35 treatment–naïve male patients (19.3±5.0) yrs) with HH were included in the HH group, and 22 healthy young men of similar age and body mass index (BMI) were recruited in the control group from June 2013 to September 2014. Serum sex hormones, follicle – stimulating hormone (FSH), luteinizing hormone (LH) and serum lipids levels were measured in fasting blood samples. Plasma glucose and insulin levels were taken during oral glucose tolerance test(OGTT) test. Areas under the curves of glucose (AUCG) and insulin (AUCI), homeostasis model assessment of insulin resistance (HOMA–IR), and other metabolic parameters were calculated respectively. Data between two groups were analyzed by Student'st test.

No significant differences were showed in age((19.3±5.0)vs (21.0±2.4) yrs) and BMI ((23.0±4.2) vs (22.2±1.6) kg/m²,t=1.691,1.020, both P>0.05). Compared with the control group, triglyceride(TG) were significantly higher ((0.9±0.3)vs (1.4±0.7) mmol/L,t= 3.527, both P<0.05) and high density lipoprotein-cholesterol (HDL-C) in blood was lower ((1.25±0.23)vs (1.07±0.27 mmol/L),t=2.547, P<0.05) in the HH group; Compared with the control group, homeostasis model assessment–insulin resistance was significantly higher (3.1±1.4 vs 1.6±0.3,t=5.773, P<0.05) while insulin sensitivity index was lower (95±50 vs 247±66,t=9.648, P<0.05) in the HH group. 2 h postprandial plasma glucose (2 h PG) and 3 h PG) levels were higher (t=2.334, 2.913, both P < 0.05) and the insulin levels at 0 min, 1 h, 2 h and 3 h all significantly increased in the HH group ( t=2.420- 5.800, all P <0.05). The maximal insulin excretion time was at 2 h after glucose loading in the HH group.

Hypogonadotropic hypogonadal young male patients are more likely to develop insulin resistance, higher WC and serum lipids levels compared with healthy men at the same age.

Clinical studies have shown that AFABP can significantly predict the progression of blood glucose levels and is an independent predictor of T2DM and T2DM with macrovascular complications^[7,8,9]and with lipid metabolism disorders^[11]arteriosclerosis^[12]The occurrence and development are closely related. However, there is little research evidence about AFABP in the pathogenesis of GDM, and the changes of serum AFABP levels in Chinese GDM patients have not been reported. This study showed that AFABP levels were significantly increased in the GDM group compared with the NGT group, and the difference was statistically significant even after adjustment for age and FINS. Kralisch et al.^[13]It was first reported in 2009 that serum AFABP was significantly higher in patients with GDM [gestational (200 ± 30) days] than in normal pregnant women, and it was considered that the risk of GDM was independently related to AFABP. In 2011, Ortega – Senovilla et al^[14]The study found that there were differences in AFABP levels between GDM patients and NGT patients in the third trimester of pregnancy (>37 weeks), but there was no statistically significant difference in AFABP levels between the two groups after adjusting for pre-pregnancy BMI and FINS. Analyzing the data of this study, the BMI of NGT and GDM subjects before pregnancy was overweight or even obese, while AFABP level itself was positively correlated with obesity and the severity of metabolic diseases^[15]。 In addition, unlike the GDM diagnostic criteria adopted in this study, this study adopted the 2010 IADPSG new diagnostic criteria for GDM^[10], the new diagnostic criteria blood glucose cut-off point is down-regulated, which is helpful for early screening of pregnant women with abnormal glucose metabolism during pregnancy. Moreover, this study observed Chinese GDM patients, and the results of the study were different from the Ortega-Senovilla study because of different ethnic genetic background, different BMI, different pregnancy study stage, and different diagnostic criteria for GDM.

sleep apnea hypopnea syndrome (SAHS) and type 2 diabetes mellitus (T2DM) often exist in the same individual and belong to comorbid diseases. The prevalence of SAHS in diabetic patients is significantly higher than that in the general population. Domestic studies have shown that the prevalence of SAHS in T2DM patients is over 60%. The prevalence of T2DM in SAHS patients is also significantly higher than that in normal people. The prevalence of SAHS in obese T2DM patients is as high as 86%^[1]。 In order to raise awareness of the relationship between SAHS and T2DM, the International Diabetes Federation Epidemiology and Prevention Group issued a consensus on the issue in 2008^[2]In 2010, the Sleep Division and Diabetes Division of the Respiratory Disease Branch of the Chinese Medical Association in China also reached a further consensus on this issue^[3]。

Type 2 diabetes (T2DM) is a chronic non-communicable disease that affects human health. The latest survey in China shows that the prevalence of T2DM among adults is as high as 11.6%, about 114 million people^[1]。 Long-term diabetes and its resulting microvascular and macrovascular complications not only seriously affect health, but also bring a heavy economic burden to families and society. Diabetic nephropathy is one of the main microvascular complications of diabetes, and about 20% ~30% of diabetic patients develop diabetic nephropathy. In addition, diabetic nephropathy is also closely related to the morbidity and mortality of cardiovascular diseases. However, the current prevention and treatment measures cannot completely stop the progression of diabetic nephropathy, and new drugs need to be developed. In the past decade, glucagon-like peptide 1 (GLP-1) receptor agonists and dipeptidyl peptidase IV (DPP-4) inhibitors have been used to treat T2DM. This incretin-based treatment has effects on multiple organ systems in addition to blood glucose control. This review focuses on the protective effects of incretin on the renal system and its possible mechanisms.

The relationship between hypoglycemic drugs and cardiovascular adverse events has been increasingly concerned in recent years^[1,2]。 The U.S. Food and Drug Administration (FDA) officially issued relevant guidelines in 2008, requiring all new hypoglycemic drugs to be evaluated for their cardiovascular safety. Therefore, a variety of novel hypoglycemic dipeptide kininase IV (DPP-4) inhibitors have carried out clinical trials of cardiovascular outcomes. The results of two large-scale clinical trials-"Comparison of the Effect of Alogliptin and Standard Therapy on Cardiovascular Safety of Patients with Type 2 Diabetes Mellitus (T2DM) with Recent Acute Coronary Syndrome (ACS)" (EXAMINE study, NCT00968708) and "Evaluation of Cardiovascular Outcomes with Saxagliptin in Patients with T2DM" (SAVOR study, NCT01107886) were first published in 2013. This article mainly discusses the cardiovascular safety of DPP-4 inhibitors by interpreting large-scale clinical studies of cardiovascular outcomes.