Establishment and Reliability Evaluation of Prognostic Models in Diabetic Foot.

Purpose: To study the risk factors affecting amputation and survival in patients with diabetic foot (DF) and to construct a predictive model using the machine learning technique for DF foot amputation and survival and evaluate its effectiveness. Materials and Methods: A total of 200 patients with DF hospitalized in the First Affiliated Hospital of Shantou University Medical College in China were selected via cluster analysis screening, Kaplan-Meier survival calculation, amputation rate and Cox proportional hazards model investigation of risk factors associated with amputation and death. In addition, we constructed various models, including Cox proportional hazards regression analysis, the deep learning method convolution neural network (CNN) model, backpropagation (BP) neural network model, and backpropagation neural network prediction model after optimizing the genetic algorithm. The accuracy of the 4 prediction models for survival and amputation was assessed, and we evaluated the reliability of these computational models based on the size of the area under the ROC curve (AUC), sensitivity and specificity. Results: We found that the 1-year survival rate in patients with DF was 88.5%, and the 1-year amputation rate was 12.5%. Wagner's Classification of Diabetic Foot Ulcers grade, ankle-brachial index (ABI), low-density lipoprotein (LDL), and percutaneous oxygen partial pressure (TcPO2) were independent risk factors for amputation in patients with DF, while cerebrovascular disease, Sudoscan sweat gland function score, glycated hemoglobin (HbA1c) and peripheral artery disease (PAD) were independent risk factors for death in patients with DF. In addition, our results showed that in the case of amputation, the COX regression predictive model revealed an AUC of 0.788, sensitivity of 74.1% and specificity of 83.6%. The BP neural network predictive model identified an AUC of 0.874, sensitivity of 87.0% and specificity of 87.7%. An AUC of 0.909, sensitivity of 90.7% and specificity of 91.1% were found after optimizing the BP neural network prediction model via genetic algorithm. In the deep learning CNN model, the AUC, sensitivity and specificity were 0.939, 92.6%, and 95.2%, respectively. In the analysis of risk factors for death, the COX regression predictive model identified the AUC, sensitivity and specificity as 0.800, 74.1% and 85.9%, respectively. The BP neural network predictive model revealed an AUC, sensitivity and specificity of 0.937, 93.1% and 94.4%, respectively. Genetic algorithm-based optimization of the BP neural network predictive model identified an AUC, sensitivity and specificity of 0.932, 91.4% and 95.1%, respectively. The deep learning CNN model found the AUC, sensitivity and specificity to be 0.861, 82.8% and 89.4%, respectively. Conclusion: To identify risk factors for death, the BP neural network predictive model and genetic algorithm-based optimizing BP neural network predictive model have higher sensitivity and specificity than the deep learning method CNN predictive model and COX regression analysis.

[Effects of glucagon on plasma ghrelin level in type 2 diabetes mellitus].

OBJECTIVE: To investigate the effect of glucagon on ghrelin secretion in type 2 diabetes mellitus (T2DM) patients. METHODS: Circulating ghrelin and C-peptide were measured during glucagon stimulation test in 38 cases with T2DM and 30 cases in normal controls (NC) at the 1st Affiliated Hospital of Shantou University from May 2006 to December 2007. RESULTS: (1) There was no significant difference in the fasting C-peptide and fasting ghrelin levels of the NC group were (1.3 +/- 0.6) microg/L and (3.0 +/- 1.0) ng/ml respectively, both not significantly different from those of the T2DM group [(1.2 +/- 0.4) microg/L and (2.7 +/- 0.8) microg/L respectively, P > 0.05 and P > 0.05]; six minutes after the injection of glucagon, the C-peptide level of the T2DM group increased to (2.0 +/- 0.8) microg/L (P < 0.01), and that of the NC group increased to (3.0 +/- 0.8) microg/L (P < 0.01), and the C-peptide level 6 min after of the T2DM group was significantly lower than that of the NC group (P < 0.01). The ghrelin level 6 min after the injection of glucagon of the NC group was (2.3 +/- 0.7) microg/L, significantly lower than that before the injection (P < 0.01). But the ghrelin level 6 min after the injection of glucagon of the T2DM group was (2.9 +/- 0.9) microg/L, NOT significantly different from that before the injection (P > 0.05). (2) Fasting ghrelin level was significantly negatively correlated with the waist circumference (r = -0.343, P < 0.05). CONCLUSION: In healthy subjects exogenous glucagon decreases the ghrelin level. Ghrelin may be associated with the beta-cell hypofunction and first-phase insulin secretion defects in T2DM. Insulin, glucagon, and ghrelin secreted influence each other to regulate glucose homeostasis.

[A multicenter survey on the diabetic foot and its neuropathy in China].

OBJECTIVE: To investigate the characteristics of diabetic foot with neuropathy and its related factors. METHODS: 530 out- and in-patients in 14 grade A class 3 comprehensive hospitals in China with foot problems were surveyed. 337 of the 500 patients (63.58%) suffered from neuropathy, 172 (32.45%) with diabetic foot with simple neuropathy and 165 (31.13%) with simple neuropathy combined with peripheral artery disease (PAD). 193 of the 500 patients (36.42%) suffered from peripheral artery disease (PAD). 77.7% of ulcer were caused by physical factors. Questionnaire survey was conducted to collect the demographic data, present and past history, history of the hyperglycemia and lipid disorders, classification and phases of the foot ulcers based on Wagner' system and Texas system, characteristics of neuropathy and other diabetic complications, and relative risk factors. Detailed physical examination was performed, including 10 g nylon filament sensation examination. RESULTS: The duration of diabetic foot of the patients with simple neuropathy was 3 (1, 60) months, significantly shorter than that of the diabetic foot patients with PAD [5 (1, 96) months, P < 0.001]. The Wagner degree of ulcer was related to the duration of diabetes, economic income, foot deformity, nerve reflection, diapason vibration sensation of foot, sensation point of 10 g nylon filament, ankle/brachial index (ABI), foot artery pulse, fasting blood sugar (FBS) and glycated hemoglobin (HbA1c). Stepwise regression analysis revealed that ABI of left posterior tibial artery, vibration detection threshold and economic income were the most significant influencing factors of the degree of ulcer. CONCLUSION: Neuropathy ulcer is common in diabetic foot patients. The prognosis of healing in diabetic foot with neuropathy is prior to that of diabetic foot with PAD. The neuropathy and PAD of foot influence each other and aggravate the condition of diabetic foot. The examinations of diapason vibration sensation of foot, sensation point of 10 g nylon filament, and Achilles tendon reflex are simple and practical, and are worth recommending.

Different effect of handle region peptide on ß-cell function in different sexes of rats neonatally treated with sodium L-glutamate.

BACKGROUND The (pro)renin receptor ((P)RR) was reported to be expressed in various tissues including the pancreas, and handle region peptide (HRP) is believed to block the function of (P)RR. This study aimed to investigate the effect of HRP on the glucose tolerance status and ß-cell function of female rats, neonatally treated with sodium L-glutamate (MSG) and to compare with the previously reported HRP effect on male rats. MATERIAL AND METHODS Female MSG rats aged 8 weeks were divided into MSG control group and HRP treated group and the normal SD rats served as control. The MSG rats were treated with HRP by osmotic minipumps with dose of 1 mg/kg per day for total 28 days. Glucose tolerance status was evaluated at the end of the study. Islets α-cell and ß-cell were marked with insulin antibody and glucagon antibody respectively. The proliferation of islet cells and expression of subunit of NADPH oxidase P22phox were marked by PCNA and P22phox antibody. Picrosirius red staining was performed for evaluating fibrosis of islets. RESULTS HRP improved the glucose status tolerance with decreasing α-cell mass, islets PCNA-positive cells, expression of P22phox and picrosirius red stained areas, and increasing ß-cell mass in female MSG rats. The indexes with obviously interacted effect of sexes and HRP for the MSG rats were the AUC of blood glucose concentration (P<0.01), α-cell mass (P<0.05), proliferation of islet cells (P<0.01) and area of picrosirius red staining (P<0.01). CONCLUSIONS HRP improved the glucose tolerance status in the females although it was previously reported to worsen the glucose tolerance in male MSG rats. Different levels of sex hormones may partly account for the disparate effects observed for HRP in different sexes.

Handle Region Peptide Ameliorating Insulin Resistance but Not ß Cell Functions in Male Rats Neonatally Treated with Sodium L-Glutamate.

Handle region peptide (HRP), which was recognized as a blocker of (pro)renin receptor ((P)RR), may block the function of (P)RR. The aim of this study was to investigate the effect of HRP with a large dose of 1 mg/kg/d on glucose status in the rats treated neonatally with monosodium L-glutamate (MSG). At the age of 8 weeks, the MSG rats were randomly divided into MSG control group, HRP treated group with minipump (MSG-HRP group), losartan treated group (MSG-L group), and HRP and losartan cotreated group (MSG-HRP-L group) and fed with high-fat diet for 4 weeks. Losartan but not HRP increased the levels of insulin releasing and ameliorate glucose status although both losartan and HRP improved insulin sensitivity. On the one hand, both losartan and HRP decreased levels of pancreatic local Ang-II and NADPH oxidase activity as well as its subunits P(22phox). On the other hand, losartan but not HRP decreased α -cell mass and number of PCNA-positive cells located periphery of the islets and decreased picrosirius red stained area in islets. HRP ameliorating insulin resistance but not ß -cell functions leads to hyperglycemia in the end in male MSG rats, and the dual characters of HRP may partly account for the phenomenon.