Volume 12 · Issue 06 · 2020

The risk of osteoporosis and fracture in diabetic patients is significantly higher than that in non-diabetic patients. So far, there is still a lack of related research on the prevalence and characteristics of osteoporosis in the elderly with diabetes in China. The effective prevention and control of diabetes, osteoporosis and osteoporotic fractures still faces great challenges. Elderly diabetic patients with osteoporosis should be given reasonable intervention treatment on the basis of individualized comprehensive evaluation.

The basic principles of severity, preventability and treatment of diabetic foot and reduction of diabetic amputation rate are emphasized. This paper introduces the history and main work of the International Diabetic Foot Working Group and the International Diabetic Foot Congress, especially the process and basic contents of formulating the international clinical guidelines for diabetic foot, and the importance of implementing the clinical guidelines for standardizing the clinical diagnosis, treatment and research of diabetic foot.

Among the diseases that place a heavy burden on patients and society in the world, diabetic foot ranks tenth, and 30% of diabetic patients will develop diabetic foot ulcers throughout their lives. Clinicians need to give the right patient the right treatment at the right time. A change in perception and greater attention to diabetic foot disease comes at an opportune time. Medical staff need to further master the knowledge of diabetic foot in order to reduce the burden caused by diabetic foot on patients and society.

After a systematic review of the literature forming the basis of the IWGDF guidelines, the International Working Group on Diabetic Foot (IWGDF) has defined a series of definitions, standards and terminology explanations about diabetic foot, and recommended that they should always be applied in clinical practice and research to facilitate communication and exchange between different professionals. The author translates and interprets these definitions, standards and explanations of terms, aiming at providing help and reference for clinical workers.

Patients with type 2 diabetes mellitus (T2DM) are at risk of developing atherosclerotic cardiovascular disease (ASCVD) and chronic kidney disease (CKD), which are important causes of disabling and death in these patients. For the prevention and management of both ASCVD and CKD, cardiovascular risk factors should be systematically evaluated, and ASCVD and CKD should be screened in patients with T2DM. In this consensus, it is recommended that metformin is the first-line hypoglycemic agent for patients with T2DM and established ASCVD or very high cardiovascular risk, heart failure (HF), or CKD, and it should be remaining in the treatment regimen unless contraindicated or intolerable. In patients with T2DM and established ASCVD or very high cardiovascular risk, addition of glucagon-like peptide 1 receptor agonist (GLP-1RA) or sodium-glucose cotransporter 2 inhibitor (SGLT2i) with proven cardiovascular benefit should be considered whatever the level of glycated hemoglobin (HbA_1c). SGLT2i should be preferably added on the therapies of patients with T2DM and HF. In patients with T2DM and CKD, SGLT2i should be preferred for the combination therapy, and GLP-1RA with proven renal benefit would be alternative if SGLT2i is contraindicated. The prevention of hypoglycemia and management of multiple risk factors, including lifestyle modification, antihypertensive, lipid-lowering and antiplatelet therapies, should be kept in mind in treating patients with T2DM and ASCVD, HF or CKD.

To investigate the effects of Sitagliptin on blood glucose control, insulin sensitivity and pancreatic α-and β-cell function in drug-naïve type 2 diabetes mellitus (T2DM).

Eighty four drug-naïve patients with duration of diabetes less than 3 years were treated with Sitagliptin for 12 weeks. Hyperinsulinemic-euglycemic clamp technique was used to evaluate insulin sensitivity, the glucose infusion rate (GIR), before and after Sitagliptin treatment. The early-phase insulin secretion and glucagon secretion after a standard meal were used to estimate β-and α-cell function. Paired t test or rank sum test were used to compare the differences before and after treatment, and multivariate regression analysis was used to evaluate the correlation.

After Sitagliptin treatment for 12 weeks, HbA_1c decreased from (7.70±1.22) % to (6.63±0.58) %, decreased by (1.08±0.13) % in T2DM patients (t=-8.12, P<0.01). Accordingly, the fasting plasma glucose (FPG) and 2-h postprandial plasma glucose (2 h PG) levels were also significantly reduced ［(6.33±0.92) and (7.71±1.70) mmol/L, (8.44±1.62) and (13.27±2.74) mmol/L,P<0.01］. The GIR increased from 4.39 to 5.71 mg·kg^-1·min^-1 without significant weight reduction(P<0.01). The early-phase insulin secretion index (ΔI₃₀/ΔG₃₀) increased from 2.42(1.09, 4.42) to 5.17(3.44, 8.56) mU/mmol (P<0.05). The insulin-AUC was also significantly improved (P<0.01), but there was no significant change in glucagon-AUC (P>0.05). Multivariate regression analysis showed that baseline insulin sensitivity (β=-0.070, P=0.03) and HbA_1c (β=0.192, P=0.001) were positively associated with the HbA_1cafter treatment.

A 12-week sitagliptin treatment reduced HbA_1c by more than 1.0% in T2DM patients, and not only significantly improved pancreatic β-cell function, but also significantly improved insulin sensitivity.

To study the features of metabolic profile and chronic complications in early-onset type 2 diabetes mellitus (T2DM) patients and further investigate their prognosis.

Clinical data of diabetes patients (n=3 628) admitted to the Department of Endocrinology Nanjing Drum Tower Hospital from January 2015 to September 2018 were collected. The patients were divided into two groups: early- and late-onset groups which were defined as diagnosis at <40 years old ( n=768) and ≥40 years old (n=2 860). The average age of the early-onset group was (41±11) years, of which 71.1% were male (546 cases), and the average age of the late-onset group was (63±10) years, of which 59.1% were male (1 690 cases). Medical history and physical examination data were collected, including course of disease, body mass index, family history of diabetes, etc. Fasting plasma glucose (FPG) and glycated hemoglobin A_1cwere also measured. Independent sample t-test, chi-square test, Mann-Whitney U test and binary logistic regression were used to analyze the clinical characteristics of the patients with early-onset T2DM and related risk factors of chronic complications. Additive models were used to analyze the interaction between early onset T2DM and diabetes duration on chronic complications. We further compared the change of their metabolic index between early and late-onset groups in newly-diagnosed patients (diabetes duration<1 year).

Compared with the late-onset T2DM group, the proportion of patients with a family history of diabetes was higher in the early-onset group, and body mass index was higher (both P<0.01). The early-onset group had higher glycated hemoglobin A_1c(9.2%±2.1%vs 8.7%±2.2%,t=-4.454, P<0.01) and more patients with microvascular complications [38.8% (298/768) vs 29.4% (841/2 860), χ²=24.819, P<0.01]. Early-onset T2DM and diabetes duration more than 10 years had an interaction effect on microvascular complications. Further adjustment of age, duration of diabetes, family history of diabetes, conventional cardiovascular risk factors and treatment regimen, the risk of diabetic kidney disease was still higher than that of the late-onset group (odds ratio1.66，95% confidence interval: 1.01-2.71, P<0.05). For newly diagnosed T2DM patients, after a median follow-up of 373 days, fasting blood glucose (FPG) decreased more in the early-onset group (ΔFPG_{early-onset group}-ΔFPG_{late-onset group}=-0.62 mmol/L, 95% confidence interval: -1.18 mmol/L, -0.05 mmol/L).

Metabolic profiles of early-onset T2DM is poorer with higher prevalence of diabetic complications. Early intervention for early-onset T2DM should be emphasized.

To evaluate the effect of onset age of diabetes on metabolic control in adult patients with type 1 diabetes mellitus (T1DM).

Adults with T1DM from Guangdong type 1 diabetes translational study between Janurary 2011 to December 2017 were enrolled in this cross-over survey. Patients were eligible if they were aged ≥18 years with diabetes duration longer than 1 years. Demographic data, glycated hemoglobin A_1c (HbA_1c), body mass index（BMI）, lipid level, blood pressure (BP) and other metabolic indicators were collected. Insulin resistance in adults with T1DM was evaluated by estimate glucose disposal rate (eGDR) model calculation. The effects of onset age of diabetes on metabolic control and insulin resistance in adult patients with T1DM were evaluated. Partial correlation analysis was used to analyze the correlation between the onset age of diabetes and HbA_1c or insulin resistance after eliminating the influence of the course of diabetes.

(1) A total of 872 T1DM adults including 508 (58.3%) female patients with disease duration over 1 year were enrolled. The mean age was (33±11) years old，the mean onset age was (27±12) years and the mean diabetic duration was (8±6) years. (2) The overall mean HbA_1c level for all patients was (8.9±2.6)%, and 23.8% (n=208) of them had HbA_1c <7%. The mean BMI for all patients was (20.8±2.8) kg/m ², and 89.7% (n=782) of them had BMI 18.5 to 23.9 kg/m². 26.3% (n=61) patients were dyslipidemia (TG≥1.7 mmol/L or HDL-C<1.04 mmol/L). The mean BP for all patients was (116±15)/(73±9) mmHg (1 mmHg=0.133 kPa), and 88.4% (n=691) of them achieved the recommended BP control target. Only 26 patients (3.0%) reached the control standard in blood glucose, body weight, blood pressure and blood lipids. The overall eGDR was 8.84 (6.84,10.79) mg·kg^－1·min^－1. (3) Children and adolescent onset patients had a higher mean HbA_1c（F=4.863，P<0.05） and a severer insulin resistance (F=3.177，P<0.05) compared with adult onset diabetic patients. The control rate of HbA_1c and serum lipid in children onset patients were lower compared with those in the other two groups (F=2.943 and 3.404, all P<0.05).

Earlier onset age of diabetes is associated with poor metabolic control and insulin resistance in T1DM adult patients in China Guangdong province. Individual management should take the diabetes onset age into account.

To investigate the association of serum osteocalcin with femoral artery intima-media thickness (FIMT) and lower extremity atherosclerotic plaque in middle-aged male type 2 diabetes mellitus (T2DM) with different lipid status.

Newly diagnosed male T2DM patients aged (52.0±6.0) years in the Second Department of Endocrinology of Tangshan Gongren Hospital from January 2017 to January 2019 were selected as the objects of study by random number method. The subjects were divided into two groups: the dyslipidemia group (156 cases) and the normal lipid group (148 cases). Fasting plasma glucose (FPG), fasting insulin, glycated hemoglobin A_1c (HbA_1c), total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), hypersensitive C-reactive protein (hs-CRP) and osteocalcin were detected, and the homeostasis model assessment of insulin resistance (HOMA-IR) was calculated to evaluate insulin resistance. The FIMT and plaques in lower limb arteries were measured by ultrasonography measurements. The relationship between serum osteocalcin and FIMT as well as lower extremity atherosclerotic plaque were evaluated. The t test, rank sum test and χ² test were used for comparison between groups. Pearson and Spearman correlation analysis and multivariate logistic regression analysis were used for correlation analysis.

The osteocalcin level in the normal lipid group was significantly higher than that in the dyslipidemia group [(17.84±6.71) vs (16.36±6.25) ng/ml, t=1.993, P=0.047]. Osteocalcin was inversely associated with age, FPG, HbA_1c, HOMA-IR, TC, TG, LDL-C and hs-CRP by correlation analysis (r=-0.172--0.137, all P<0.05). In multivariate linear regression analysis, osteocalcin was negatively associated with FIMT in the dyslipidemia group (β=-0.184,P<0.05). The low osteocalcin level was independent risk factors for lower extremity atherosclerotic plaque in the overall population using Logistic regression analysis after adjusting other factors (odds ratio: 0.946, 95% confidence interval: 0.908-0.985,P<0.01). In multivariate logistic regression analysis, the low osteocalcin level still significantly increased the risk of lower extremity atherosclerotic plaque in the dyslipidemia group (odds ratio: 0.935, 95% confidence interval: 0.880-0.993,P=0.028), while the low osteocalcin level didn’t increase the risk of lower extremity atherosclerotic plaque in the normal group (odds ratio: 0.956, 95% confidence interval: 0.901-1.015, P>0.05).

Osteocalcin is correlated negatively with FIMT in newly diagnosed middle-aged male T2DM patients with dyslipidemia, and the low osteocalcin level was independent risk factor for the occurrence of lower extremity atherosclerotic plaque in these patients.

To explore the effects of glycine on myocardial caveolin-3/endothelial nitric oxide synthase (eNOS) signal and oxidative stress in diabetic myocardium of rats.

According to random number table method, 30 adult male SD rats at 8 weeks of age were randomly divided into 3 groups (10 in each group): the control group (C), diabetes mellitus group (D, diabetes model induced by single intraperitoneal streptozotocin injection), diabetes+glycine treatment group (D+Gly, after the success of the diabetes model, treated by 1% glycine aqueous solution instead of drinking water treatment for 8 weeks). The H9C2 cells were exposed to 30 mmol/L glucose and 140 μmol/L glycine context and cultured for 48 hours. The contents of super oxide dismutase (SOD), malondialdehyde (MDA), lactate dehydrogenase (LDH) and total protein and CCK-8 test were detected using commercial assay kits. HE staining was used to detect the pathological changes of diabetic myocardium, and the expression of caveolin-3 and p-eNOS were detected by Western blot. One-way analysis of variance was used for comparison between groups, and Tukey test was used for pairwise comparison.

(1) The MDA content of myocardial tissue were significantly higher in rats of diabetes group than that in control group (q=6.57, P<0.05). The SOD content of myocardial tissue and the expression levels of caveolin-3 and p-eNOS were significantly lower in rats of diabetes group than that in control group (q=15.72, 11.84,15.18, all P<0.05). (2) The MDA content of myocardial tissue were significantly lower in diabetic rats treated with glycine than that in untreated diabetic rats [(4.81±0.94) vs (6.06±0.85) nmol/mg prot,q=4.51, P<0.05]. The SOD content of myocardial tissue and the expression of caveolin-3 and p-eNOS were significantly higher in diabetic rats treated with glycine than that in untreated diabetic rats [(73.17±11.83) vs (42.01±10.35) U/mg prot, 0.78±0.08 vs 0.55±0.14, 0.83±0.13 vs 0.50±0.12,q=9.17,6.05,10.02, all P<0.05]. (3) The SOD content, caveolin-3 and p-eNOS expression were significantly decrease in H9C2 cardiomyocytes in high glucose group than that in low glucose group (q=10.04,10.20,18.25, all P<0.05), while the MDA content was significantly higher than low glucose group (q=18.98, P<0.05). (4) The SOD content, caveolin-3, p-eNOS protein expression were significantly higher in high glucose-exposed H9C2 cardiomyocytes with versus without glycine treatment [(11.35±1.64) vs (7.61±1.02) U/mg prot, 0.91±0.06 vs 0.77±0.05, 0.74±0.04 vs 0.62±0.06,q=4.21, 6.21,5.77, all P<0.05], while MDA content was significantly lower than untreated group [(1.42±0.08) vs (2.07±0.15) nmol/mg prot,q=10.82, P<0.05].

Glycine exerted diabetic myocardial protection may through regulating caveolin-3/eNOS signal and alleviating oxidative stress injury.

To study the effects of fibroblast growth factor 1 (FGF1) and its mutant (FGF1^ΔHBS) on blood glucose of type 2 diabetic mice induced by streptozotocin.

The model of type 2 diabetic mice was established using streptozotocin (STZ). Mice were randomly divided into model group, FGF1 treatment group, FGF1^ΔHBS treatment group (low, medium and high dose) and control group. The model group and control group were given the same amount of saline. The acute effect study was given by single intraperitoneal injection （the FGF1 group was given a single intraperitoneal injection at 0.5 mg/kg, and FGF1^ΔHBS was given a single intraperitoneal injection at low, medium, and high does）, while the chronic effect study was given by intraperitoneal injection every other day for 28 consecutive days (after the acute effect study, mice in each group were injected intraperitoneally at the above dose the next day). Observe and record the living conditions of mice, monitored the blood glucose changes of mice.Observe the effect of FGF1 and its mutants on the changes of serum insulin and liver glycogen in mice. Comparison of the proliferation effects of FGF1 and FGF1^ΔHBS on the mice embryonic fibroblasts. One-way analysis of variance was used for comparison between groups, and LSD-t test was used for pantwise comparison between groups.

Compared with the normal group, the body weight, blood glucose, serum insulin and liver glycogen content increased significantly（t=9.347，20.321，12.723，4.545，all P<0.05）. Compared with the model group, the blood glucose of FGF1 and FGF1^ΔHBS treatment group （low，medium and high doses） was decreased significantly (t=15.650, 15.513, 16.261, 16.929, all P<0.05), and the single effect lasted for 24 hours. Serum insulin[（0.41±0.14）,（0.46±0.06）,（0.40±0.06） and （0.37±0.06） vs （0.90±0.12）ng/ml，t=10.509,9.282,10.616,11.256, all P<0.05] decreased significantly，and the liver glycogen content [（24.38±6.8）,（26.5±3.43）,（27.2±3.15） and （28.45±2.23） vs （15.16±3.66） mg/g，t=3.372,6.391,7.049,8.762, all P<0.05] increased further. There was no significant difference from the low, medium and high doses groups of FGF1^ΔHBS (P>0.05). Compared with FGF1, the absorbance of FGF1^ΔHBS （0.42±0.01 vs 0.65±0.04，t=14.067，P<0.05）decreased，so the proliferation effect of FGF1^ΔHBS was significantly lower than that of FGF1.

FGF1^ΔHBS lost the ability of promoting cell division basically, but its effect of decreasing blood glucose is similar to FGF1. The mechanism may be to increase the content of glycogen in liver by changing insulin sensitivity. FGF1^ΔHBS has the potential to be further developed as a drug for diabetes.

Young women, with the onset of "gestational diabetes", are thin in size, have a family history of diabetes in both maternal and paternal lines, and their mother's hearing is impaired. Islet function test showed good insulin sensitivity and absolute lack of insulin secretion function, and hearing test showed sensorineural deafness. The mtDNA A3243G mutation was found by mitochondrial gene detection in blood samples, which has the clinical characteristics of mitochondrial diabetes. The genetic detection of blood samples confirmed the diagnosis of mitochondrial diabetes.

As the largest endocrine organ of human body, the role of gastrointestinal tract in the regulation of blood glucose homeostasis and the treatment of diabetes is increasingly prominent. Proglucagon-derived peptides (PGDPs) produced by the intestine, namely glucagon-like peptide-1 (GLP-1), GLP-2, gastric acid regulator, intestinal glucagon, etc., participate in the regulation of blood glucose homeostasis by regulating food intake, gastric emptying rate, insulin and glucagon release and other pathways. Drugs based on intestinal PGDPs can correct a variety of pathophysiological defects in the pathogenesis of type 2 diabetes and effectively improve blood sugar, which has become a research hotspot in the field of diabetes.

At the end of 2019, the American Diabetes Association released the 2020 version of the diabetes diagnosis and treatment guidelines. Based on new research evidence, the guidelines have been updated for the diagnosis and treatment of diabetic nephropathy. New staging methods for chronic kidney disease were introduced, and recommendations for screening, monitoring and treatment of patients with diabetic nephropathy were updated; Improving the position of sodium-glucose cotransporter 2 inhibitor in the prevention and treatment of diabetic nephropathy; Updated the research evidence of angiotensin converting enzyme inhibitors and angiotensin II receptor antagonists for the primary prevention of diabetic nephropathy; Added attention to nutritional therapy for acute kidney injury and diabetic nephropathy. At the same time, the progress of clinical treatment of diabetic nephropathy is briefly introduced.

Patients with type 1 diabetes mellitus (T1DM) have a significantly increased risk of fracture, decreased bone strength, and bone damage is considered one of its chronic complications. Osteopenia and bone mass decrease are the pathological basis of bone damage in T1DM, and low bone turnover is its characteristic manifestation. The mechanisms of T1DM-related bone damage are diverse, involving metabolism, hormones, nutrition, immunity, etc., which have not been fully elucidated. A mild decrease in bone mineral density in patients with T1DM does not match a significant increase in fracture risk, and it is necessary to evaluate their bone strength in a combination of multiple ways. There are no standard recommendations and procedures for the screening and treatment of T1DM skeletal damage, and further research is needed.