Volume 13 · Issue 08 · 2021

Based on my organization, translation and review of the 2019 edition of the International Clinical Guidelines for Diabetic Foot issued by the International Diabetic Foot Working Group (IWGDF) and related literatures, combined with my experience in participating in the compilation of the Guidelines for Prevention and Treatment of Diabetic Foot in China (2019 edition), and the practice of clinical medical treatment and professional training of diabetic foot for many years, this paper expounds the problems that need attention in the prevention and treatment of diabetic foot, including diagnosis and differential diagnosis, multidisciplinary cooperative team, wound healing, amputation, basic treatment and local treatment, standardized treatment and auxiliary treatment, emphasis on psychological disorders and doctor-patient communication, etc. Emphasize the importance of implementing clinical guidelines and standardized diagnosis and treatment of diabetic foot in the prevention and treatment of diabetic foot.

Type 2 diabetes mellitus (T2DM) is one of the rapidly growing metabolic diseases in the world. The human gut flora (GM) plays an important role in metabolism and immune regulation. Abnormal gut microbiota metabolism in patients with T2DM promotes the entry of gut bacteria and their harmful metabolites into the circulatory system, causing damage to multiple organs by interfering with insulin sensitivity, glucose metabolism, and immune homeostasis. Starting from the application of metabolomics in T2DM, the author mainly expounds the dysregulation of GM in T2DM, the mechanism of metabolomics explaining the metabolic regulation of GM on T2DM, and the treatment of T2DM based on GM metabolism.

In recent years, many important advances have been made in the research of diabetic nephropathy (DKD) at home and abroad, and more evidence-based medical evidence has been obtained. The Microvascular Complications Group of Diabetes Branch of Chinese Medical Association organized relevant experts in the field of endocrinology and nephrology across the country to compile this guideline, aiming to convey the latest and important progress and further standardize the management of DKD. The guidelines cover the definition, screening, diagnosis, staging, assessment and prevention of DKD. Highlight early screening, emphasize the importance of standardized comprehensive management, and pay attention to the role of new antihyperglycemic drugs in the treatment of DKD; Emphasize the integrated diagnosis and treatment mode of "diagnosis-staging-evaluation-prevention and treatment", and formulate a diagnosis and treatment flow chart to highlight clinical practicality. The guidelines will help clinicians standardize the management of DKD patients and work to improve the prognosis of DKD patients.

To investigate the clinical characteristics and risk factors of subclinical cardiovascular disease (CVD) in type 1 diabetes mellitus (T1DM).

A total of 257 patients who registered in Department of Endocrinology, the First Affiliated Hospital with Nanjing Medical University between January 2017 and December 2020 were selected into the analysis. Data regarding medical history, anthropometrics and laboratory data were collected. Patients with T1DM without the use of hypolipidemic or antiplatelet drugs and CVD were divided into subclinical CVD group [carotid intima-media thickness (cIMT)≥1.0 mm or brachial ankle pulse wave velocity (baPWV) ≥1 400 mm/s, 73 cases] and non-subclinical cardiovascular disease group (cIMT<1.0 mm and baPWV<1 400 mm/s, 158 cases). Systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured, triglycerides (TG), low-density lipoprotein-cholesterol (LDL-C), non-high-density lipoprotein-cholesterol (non-HDL-C), glycated hemoglobin A_1c (HbA_1c) were detected, coefficient of variation (CV), insulin sensitivity, neutrophil-to-lymphocyte-ratio (NLR), urinary albumin-to-creatinine ratio (UACR), estimated glomerular filtration rate (eGFR) were calculated. The t test, t′ test, χ² test and nonparametric test were used for comparison between the two groups. Multivariable logistic regression models assessed the association between subclinical complications and risk factors.

The incidence of CVD in T1DM was 7.4% (19/257), and the incidence of subclinical CVD was 31.6% (73/231). Compared with the non-subclinical CVD group, the subclinical CVD group had higher age, diabetes duration, age at diagnosis, body mass index, SBP, DBP, TG, LDL-C, non-HDL-C, NLR, UACR, CV and the prevalence of diabetic nephropathy and diabetic peripheral neuropathy, while had lower insulin sensitivity, insulin pump utilization rate and eGFR (P<0.05). Logistic regression analysis showed that increasing the prevalence of diabetic peripheral neuropathy [odds ratio (OR)=3.97,P=0.012], and increasing non-HDL-C (OR=1.57, P=0.035), HbA_1c (OR=1.23, P=0.007), DBP (OR=1.07, P=0.002), SBP (OR=1.04, P=0.005) and UACR (OR=1.01, P=0.046) and decreasing insulin sensitivity (OR=0.09, P=0.022) were associated with increased risk for subclinical CVD after age and diabetic duration were adjusted.

Diabetic peripheral neuropathy, dyslipidemia, chronic hyperglycemia, hypertension, albuminuria and insulin sensitivity are important risk factors of subclinical CVD in T1DM.

To investigate the relationship between serum selenoprotein S (SelS) and obesity in patients with type 2 diabetes mellitus (T2DM).

Two hundred and nine T2DM patients who were managed by the National Metabolic Management Center (MMC) of the First Affiliated Hospital of Dalian Medical University from November 2017 to November 2019 and 55 healthy people as controls in the health examination center of our hospital were enrolled in the retrospective cross-sectional study. The general condition, biochemical indexes and obesity evaluation parameters were recorded. According to the serum SelS quartile, T2DM patients were divided into Q1 group: ≤95.10 ng/dl (53 cases), Q2 group: 95.12 to 111.62 ng/dl (52 cases), Q3 group: 112.46 to 130.97 ng/dl (52 cases), Q4 group: ≥131.33 ng/dl (52 cases). Analysis of variances, rank sum test and Chi-square test were used for comparison between groups. Multiple stepwise regression was used to analyze the influencing factors of obesity evaluation index.

There was statistically significant difference in visceral fat index (VAI) among T2DM abdominal obesity group, non-abdominal obesity group and healthy control group (H=36.679, P<0.01), but there was no statistically significant difference in serum SelS. There was statistically significant difference in serum amyloid A (SAA) level among the SelS quartile groups (H=3.560, P<0.01), but there was no statistically significant difference in visceral fat area (VFA), subcutaneous fat area (SFA), visceral fat area to subcutaneous fat area ratio (VSR) and VAI. Serum SelS was positively correlated with VFA, VSR, VAI and SAA (r=0.158 to 0.448, all P<0.05). Serum SelS was an independent risk factor for VFA (β=0.172,P=0.003), VSR (β=0.001, P=0.01) and VAI (β=0.009, P=0.038).

Serum SelS level in T2DM patients is positively correlated with VFA, VSR and VAI, which is an independent risk factor for abdominal obesity.

To investigate the characteristics of bone metabolism in postmenopausal women with type 2 diabetes mellitus (T2DM) and its relationship with blood glucose fluctuation.

From June 2018 to December 2020, 211 postmenopausal women with T2DM who hospitalized in the Department of Endocrinology of Hefei Second People′s Hospital were enrolled in this study. The age, menopausal years, body mass index (BMI) and other general data of all the subjects were collected. The levels of blood sugar, blood lipid serum uric acid (UA), thyroid function, calcium, phosphorus, alkaline phosphatase, 25-hydroxyvitamin D (25-VitD), osteocalcin, β-carboxyl terminal peptide (β-CTX) and other biochemical indexes were measured. The data of mean amplitude of glycemic excursions (MAGE), coefficient of variation (CV), standard deviation of blood glucose (SDBG), mean of daily differences (MODD), time in range (TIR) and time above range (TAR) were obtained by continuous glucose monitoring system. Bone mineral density (BMD) was measured by dual energy X-ray absorptiometry for the diagnosis of osteoporosis. The patients were divided into osteoporosis group (OP) and the non-osteoporosis group (NOP) based on BMD results. The clinical data, biochemical indexes and related indexes of blood glucose fluctuation were compared between the two groups. Multivariate logistic regression analysis was used to analyze the relationship between osteoporosis and blood glucose fluctuation in postmenopausal women with T2DM.

There were 104 cases in OP group and 107 cases in NOP group. The prevalence of osteoporosis in postmenopausal women with T2DM was about 49.29% (104/211). There were significant differences in age, menopause, BMI, UA, free triiodothyronine, blood phosphorus, 25-VitD between the OP and NOP group (all P<0.05). The level of osteocalcin in the OP group was lower than that in the NOP group, and the β-CTX were significantly higher than that in NOP group (P<0.05). The related indexes of blood glucose fluctuation such as MAGE, CV, SDBG, MODD, TIR and TAR were significant different between the OP and NOP group. All the risk factors were included in the multivariate logistic regression equation. The results of multivariate logistic regression analysis indicated that age, menopausal years and MAGE were risk factors for osteoporosis while BMI and 25-VitD were protective factors.

Bone metabolism in postmenopausal women with T2DM is characterized by reduced bone formation and enhanced bone resorption. BMI and 25-VitD are protective factors while age, menopause years and MAGE are risk factors. To careful control of glucose, especially the within-day blood glucose fluctuation, is beneficial to the early prevention and treatment of osteoporosis in postmenopausal women with T2DM.

To analyze the relationship between serum uric acid (UA) and retinal vessel calibers in patients with type 2 diabetes mellitus (T2DM).

T2DM patients aged between 18 and 70 years old who were hospitalized in the Department of Endocrinology of First Affiliated Hospital of Air Force Military Medical University from January 2011 to August 2016 were enrolled. Height, weight, body mass index (BMI), systolic blood pressure, diastolic blood pressure, serum UA, glycated hemoglobin A_1c (HbA_1c), total cholesterol (TC), triglyceride (TG), high-density lipoprotein-cholesterol (HDL-C) and low-density lipoprotein-cholesterol (LDL-C), and estimated glomerular filtration rate (eGFR) were recorded. The retinal vascular parameters in the whole fundus range were measured by automatic computer image analysis software, which were central arteriole caliber (aCtr), middle arteriole caliber (aMdl), peripheral arteriole caliber (aPeri), central arteriole caliber (vCtr), middle arteriole caliber (vMdl) and peripheral arteriole caliber (vPeri). Mann-Whitney U test or t test was used for comparison between two groups, Kruskal-Wallis H test was used for comparisons among multiple groups, and ordered logistic regression analysis was used to evaluate the correlation between serum UA level and retinal vascular diameter in different genders.

A total of 1 660 patients with T2DM were enrolled, including 1 171 men and 489 women. There were statistically significant differences in serum UA, aCtr, aMdl, aPeri, vCtr, vMdl and vPeri levels among different genders (P<0.05). Ordered logistic regression analysis showed that elevated serum UA was a risk factor for widened aCtr and vPeri in males (odds ratios were 1.461 and 1.411, respectively, bothP<0.05). In women, elevated serum UA was a risk factor for aPeri narrowing and for vPeri widening (odds ratios of 2.161 and 1.592, respectively, bothP<0.05).

Serum uric acid level is closely associated with retinal vessel calibers in patients with T2DM. In men, elevated serum UA level was an independent risk factor for the widening of aCtr and vPeri, while in women, elevated serum uric acid level was an independent risk factor for the narrowing of aPeri and the widening of vPeri.

To explore the clinical application of high-frequency ultrasound in the screening of lipohypertrophy (LH).

This was a cross-section study. A total of 548 diabetic patients who received insulin injection more than six months were recruited from November 2016 to September 2020 in the First Affiliated Hospital of Nanjing Medical University. Clinical data and insulin injection duration of patients were collected, the patients were examined through visual and palpation and ultrasound. The t-test, nonparametric test or Chi square test was used to compare the count data between groups.

Of the 548 patients, 418 patients were found to have LH detected by clinical examination, 478 patients by ultrasound, 390 patients both by clinical examination and ultrasound. The detectable rate of LH by high-frequency ultrasound was higher than that by the clinical examination [76.3% (418/548) vs. 87.2% (478/548), χ²=59.998, P<0.01]. Compared with those detected by ultrasound only, the mean depth, median length, median width and median area of LH detected both by clinical examination and ultrasound examination were higher, with a statistically significant difference in the width diameter (P<0.05). The imaging features of LH included three types ( hyperechoic, isoechoic, hypoechoic) and five subtypes. Among them, the most common type was hyperechoic type, which had no blood flow, no capsule, and uniform mass with unclear boundary, accounting for 65.9% (315/478). Compared with LH detected by high-ultrasound only, the mean deep diameter, length diameter, width diameter and area of LH detected both by clinical examination and ultrasound examination were all increased, and the difference of width diameter was statistically significant [8.67 (7.66, 13.21) mm vs. 13.47 (8.70, 18.22) mm,Z=-2.135, P<0.05].

In addition to the traditional clinical examination (visualization and palpation), high-frequency ultrasound can be used as an important supplement to the examination of insulin injection site in diabatic patients.

To investigate the effect of cyclophilin D (CypD) on the apoptosis of mouse pancreatic islet β cell MIN6 induced by palmitic acid and its mechanism.

Stable CypD-overexpressing (OE) and CypD knockdown (KD) cell line was established in MIN6 cells by lentiviral transfection. The experiment wasgrouped as follows: control group [(untransfected virus without palmitic acid treatment (PA)], OE-control (ctrl) group, OE-ctrl+PA group, OE-CypD group (transfected CypD overexpression virus without PA treatment), OE-CypD+PA group, KD-ctrl group (transfected knockdown control virus without PA treatment), KD-ctrl+PA group, KD-CypD group (transfected with CypD knockdown virus without PA treatment), KD-CypD+PA group. Flow cytometry was used to detect the apoptosis rate of each group. The quantitative real-time polymerase chain reaction and Western blot were used to detect the effect of PA treatment on the expression of CypD. Western blot was used to detect the expression of apoptosis-related proteins Bcl-2 associated X protein (Bax), B cell lymphoma-2 (Bcl-2), Caspase3, cytochrome c (Cyt-c), and apoptotic protease activating factor (Apaf-1). Intracellular calcium ion fluorescence was detected via confocal microscopy. Thet-test was used for comparison between the two groups, and the one-way analysis of variance was used for the comparison among multiple groups.

Compared with the control group, with the increase of PA concentration, the apoptosis rate of MIN6 cells increased significantly (P<0.01), CypD mRNA (1.00±0.04 vs. 1.88±0.02, respectively) and CypD protein expression (0.049±0.004 vs. 0.577±0.006, respectively) were significantly increased, and the difference was statistically significant (P<0.01). Compared with the OE-ctrl+PA group, the apoptosis rate of the OE-CypD+PA group increased [(31.33±2.72) % vs. (24.95±0.94) %, respectively,P<0.05], and the intracellular calcium ion fluorescence signal increased (27.62±0.74 vs. 24.61±0.15,P<0.01), the levels of apoptosis-related proteins Bax, Caspase3, Cyt-c, and Apaf-1 increased (P<0.01), and the level of cell survival protein Bcl-2 decreased (P<0.01). Compared with the KD-ctrl+PA group, the apoptosis rate of the KD-CypD+PA group decreased [(22.87±0.34) % vs. (26.91±0.93) %, respectively,P<0.05], and the intracellular calcium ion fluorescence signal decreased (23.26±0.65 vs. 27.82±0.86, respectively,P<0.01). The levels of apoptosis proteins Bax, Caspase3, mitochondrial-associated apoptosis proteins Cyt-c, Apaf-1 decreased (P<0.01), and Bcl-2 levels increased (P<0.01).

CypD aggravates PA-induced lipotoxic injury in MIN6 cells, which might be related to mitochondrial dysfunction. Knockdown of CypD has a protective effect on MIN6 cells under lipotoxicity.

A young female patient with a history of diabetes mellitus for 14 years, left foot ulceration for 1 year, cataract in both eyes 6 years ago, hypertriglyceridemia, heterogeneous fatty liver and multiple atherosclerosis were reported after admission. The patient had a "bird-like appearance", gray hair, high-profile and hoarse voice, slender limbs, thin skin, and deep bone ulcers were visible on the dorsal side of the first metatarsal bone and the lateral malleolus of the left foot. Oral swab samples were collected and genomic DNA was extracted for whole exon high-throughput sequencing. Two heterozygous mutations (c.1270-1G>A and c.3475A>T) in the patient's WRN gene were detected, and Werner syndrome was diagnosed. In clinical work, differential diagnosis should be paid attention to patients with diabetic foot ulcer.

This article reports three patients with Wolfram syndrome who had "type 1 diabetes" as the first symptom, followed by papillary atrophy, diabetes insipidus or hearing loss, who were admitted from April 2019 to October 2020. The genetic tests all carried WFS1 homozygous mutation, and the family members were verified to confirm the diagnosis. Taking "Wolfram syndrome" as the keyword, searched in CNKI, Wanfang database and Pubmed, and screened out 48 Chinese patients (including 3 cases in this article) reported at home and abroad, of which only 14 cases underwent genetic testing. Summary analysis found that Wolfram syndrome involves multiple systems. Diabetes and optic atrophy mostly appear within 10 years old, while the diagnosis age is mostly 11-20 years old. The onset age is earlier, and the rate of misdiagnosis and missed diagnosis is high. Therefore, clinically, children and adolescents with any two or more symptoms should be screened as much as possible for early diagnosis.

Continuous glucose monitoring (CGM), as a new technology for blood glucose monitoring, can help improve overall blood glucose control and improve long-term management in diabetic patients. However, new technologies are generally accompanied by high costs, so it is necessary to evaluate them from the perspective of health economics. This paper summarizes the health economics research on CGM in recent years.

Type 2 diabetes mellitus (T2DM) is a risk factor for osteoporosis, and the effects of T2DM and various hypoglycemic drugs on bone metabolism have attracted more and more attention. Sodium-glucose cotransporter 2 inhibitor (SGLT2i) inhibits renal tubular reabsorption of sodium-glucose, promotes urinary glucose excretion, lowers blood glucose levels, reduces body weight, and improves the prognosis of cardiovascular and diabetic nephropathy. In this paper, the mechanism of SGLT2i on bone mineral ion metabolism was expounded, which may cause imbalance of calcium and phosphorus homeostasis, increase of fibroblast growth factor 23 and parathyroid hormone levels, which may affect bone metabolism, and its effects on bone mineral density, bone microstructure and bone turnover were discussed. The effect of SGLT2i on bone mineral density and fracture risk is still controversial, and evidence of larger clinical trials is awaited. For patients with T2DM with high fracture risk, the advantages and disadvantages should be fully weighed when applying, and the bone mineral density and fracture risk should be monitored and evaluated regularly.

As an essential trace element of the body, iron is very important for maintaining the health of the body. Excessive iron ions can promote the production of reactive oxygen species, thus causing damage to cells and tissues. With the introduction of the concept of ferroptosis, an iron-dependent cell death mode, more and more studies have focused on ferroptosis. Recent studies have confirmed the relationship between iron overload and iron death and metabolic diseases, which brings a dawn for the prevention and treatment of metabolism-related fatty liver disease and other diseases. This article reviews the latest research progress of iron overload, iron death and metabolism-related fatty liver disease at home and abroad, aiming to provide reference for targeted inhibition of iron death to prevent and treat metabolic diseases.