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Background The current surveillance system only focuses on notifiable infectious diseases in China. The arrival of the big-data era provides us a chance to elaborate on the full spectrum of infectious diseases. Methods In this population-based observational study, we used multiple health-related data extracted from the Shandong Multi-Center Healthcare Big Data Platform from January 2013 to June 2017 to estimate the incidence density and describe the epidemiological characteristics and dynamics of various infectious diseases in a population of 3,987,573 individuals in Shandong province, China. Results In total, 106,289 cases of 130 infectious diseases were diagnosed among the population, with an incidence density (ID) of 694.86 per 100,000 person-years. Besides 73,801 cases of 35 notifiable infectious diseases, 32,488 cases of 95 non-notifiable infectious diseases were identified. The overall ID continuously increased from 364.81 per 100,000 person-years in 2013 to 1071.80 per 100,000 person-years in 2017 (χ2 test for trend, P P Conclusions Infectious diseases remain a substantial public health problem, and non-notifiable diseases should not be neglected. Multi-source-based big data are beneficial to better understand the profile and dynamics of infectious diseases.

Background: Insulin therapy is essential for type 1 and inadequately controlled type 2 diabetic patients. Insulin allergies have become less common since the introduction of highly purified human recombinant insulin. There are rare reports of severe insulin allergic reactions after percutaneous transluminal coronary angioplasty (PTCA) in patients with type 2 diabetes who had no previous allergic reactions. To better understand the causes and presentation of this rare acute reaction, we present the following observed case. Case summary: A 63-year-old Chinese man (height, 172 cm; weight, 68.5 kg) with a 17-year history of type 2 diabetes and hypertension was first admitted to the West China Hospital, Sichuan University, Sichuan, People's Republic of China, for uncontrolled type 2 diabetes. He used regular human insulin, neutral protamine Hagedorn insulin, or premixed insulin without any allergic reactions. Four months later, PTCA was performed because of an acute myocardial infarction. The patient was administered 50 mg of protamine after active abdominal bleeding due to a right external iliac artery rupture. Three months later, recurrent raised, pruritic erythema occurred at the insulin injection site immediately after injection. Four weeks later, he experienced an attack of generalized urticaria at multiple previous injection sites (abdomen, upper arms, thighs) after injecting premixed insulin. It was accompanied by dizziness and palpitations. During the following 3 months, the symptoms recurred 3 times; one time, the patient reported losing consciousness for 2 to 3 minutes. The results of a skin prick test found that he was allergic to human recombinant insulin and insulin lispro. The allergy was resolved by changing his treatment regimen from insulin to oral hypoglycemic agents. A Naranjo score of 10 suggested a definite relationship (score ≥9) between the adverse drug reaction and the insulin administration. Conclusions: We present a definite case of allergy associated with insulin and insulin lispro administration. The patient had not experienced anaphylactic reactions prior to PTCA and protamine administration.

The aim of this preliminary study is to investigate contributions of basal glucose (BG) and postprandial glucose (PPG) increments to overall hyperglycemia in newly diagnosed patients with type 2 diabetes mellitus (T2DM).We evaluated the relative contributions of BG and PPG to overall hyperglycemia in 59 newly diagnosed T2DM patients according to BG baseline value of 6.1 mmol/L and 24-h glucose profiles of normal glucose tolerance (NGT) subjects obtained by continuous glucose monitoring as baseline, respectively.When the baseline was 24-h glucose profiles of the NGT subjects, the relative contributions of PPG in the T2DM patients with hemoglobin A1c (HbA1c) levels of ≤ 7.0%, 7.0-9.0%, and9.0% were 57.58%, 44.69%, and 21.56%, respectively. When the baseline value was equal to 6.1 mmol/L, the relative contributions of PPG in the T2DM patients with HbA1c levels of ≤ 7.0%, 7.0-9.0%, and9.0% were 77.23%, 53.43%, and 22.78%, respectively. Compared with the 24-h glucose profiles of the NGT subjects as the baseline, the relative contribution of PPG was overestimated by about 10-20% in the T2DM patients with HbA1c levels of ≤ 9.0% when 6.1 mmol/L was chosen as the baseline.In the newly diagnosed T2DM patients with mild hyperglycemia, PPG is a predominant contributor, whereas the relative contributions of BG gradually increase from mild to severe hyperglycemia and obviously exceed PPG in the T2DM patients with HbA1c levels of9.0%. This finding implies that the initial pharmacotherapy may target PPG in those patients with mild hyperglycemia and target BG in those patients with severe hyperglycemia.

The variability of postprandial plasma glucose is an independent risk factor for diabetes. The type and amount of carbohydrate may be important determinants of glycemic control. The aim of the study was to compare the effects of different proportions of carbohydrate in breakfast on postprandial blood glucose fluctuations in impaired glucose regulation (IGR) and normal glucose tolerance (NGT) subjects.This is a cross-sectional study of two groups including 55 subjects with IGR and 78 individuals with NGT. Their recorded breakfast was sorted into low-carbohydrate (LC) (carbohydrate45%), medium-carbohydrate (MC) (carbohydrate 45-65%), and high-carbohydrate (HC) (carbohydrate65%) meals according to the proportion of carbohydrate. Glucose concentrations were continuously measured with a continuous glucose monitoring system, and parameters such as the incremental area under the curve (iAUC) of glucose and postprandial glucose excursion (PPGE) were calculated to evaluate postprandial glucose fluctuations.The postprandial fluctuations of glucose increased gradually with increased proportions of carbohydrate in breakfast in both IGR and NGT subjects. For the MC and HC meals, iAUC, PPGE, postprandial glucose spike (PGS), and mean blood glucose were significantly greater than those in the NGT group (P0.05), respectively. The median time to PGS and the time period in which glucose concentrations decreased to baseline after the MC and HC meals in the IGR group were significantly longer than those in the NGT group (P0.01), respectively. Compared with the NGT subjects for the HC meal, the IGR subjects consuming the MC meal had greater PGS, range of glucose concentrations, SD, and PPGE (P0.05).The proportion of carbohydrate in breakfast contributes to glucose excursions in the NGT and IGR subjects. In the IGR subjects, a HC meal should be avoided and a LC meal should be recommended to prevent development of diabetes.

To investigate the dynamic changes of matrix metalloproteinase-1,-9 (MMP-1, MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1 ) in the refractory diabetic dermal ulcers treated with autologous platelet-rich gel (APG).86 patients with nonhealing diabetic dermal ulcers were randomly assigned to two groups treated with standard procedures and APG (standard care plus topic application of autologous platelet-rich gel). The granulation tissues were collected at d0, d3, d6, d9, and d15 in patients in the APG group and at d0, d6, d15 in patients in the standard care group. The areas of ulcers were measured. The protein levels of MMP-1, MMP-9 and TIMP-1 in the tissues were determined with ELISA. The ratio of MMP-9/TIMP-1 and its relationship with the areas of ulcers were examined.The areas of ulcers of patients in the APG group decreased significantely (vs. do, P0.05). The concentrations of MMP-1 in the granulation tissues of patients treated with APG fluctuated and reached the lowest level at d15 (vs. d6, P0.05). The concentrations of MMP-9 in the patients treated with AGP decreased from d3 to d15, but without statistical significance compared with d0 (P0.05). The concentrations of TIMP-1 in the patients treated with AGP increased from d3 and reached the peak at d6 (P0.05). The ratio of MMP-9/TIMP-1 at both d6 and d15 decreased significantly compared with d0 (P0.05) in the patients treated with AGP. The areas of ulcers in the patients with standard care decreased significantly at d15 (vs. d6, P0.05). The concentrations of MMP-1 reached the peak at d6 (P0.05) and then decreased in the patients with standard care but was still higher than the patients treated with APG (P0.05). The concentrations of MMP-9 decreased significantly at d15 compared with d0 in the patients treated with standard care (P0.05), but the change of TIMP-1 was not significant. The ratio of MMP-9/TIMP-1 in the patients with standard care decreased at d15 compared with the d0 (P0.05). The ratio of MMP-9/TIMP-1 was positively correlated with the areas of ulcers (r = 0.353, P0.05).Topical application of APG might redress the proteolytic imbalance of refractory diabetic dermal ulcers by decreasing the concentration of MMPs and increasing that of TIMPs in granulation tissues. The ratio of MMP-9/TIMP-1 is a predictor of poor healing of refractory diabetic dermal ulcers.

To investigate the relationship between blood glucose fluctuations and carotid intima-media thickness (CIMT) in type 2 diabetic patients.64 patients with type 2 diabetes mellitus (T2DM) in the Department of Endocrinology and Metabolism, West China Hospital from July 2009 to March 2012 were recruited in this study. The CIMT were measured bilaterally with high-resolution ultrasonography. The glucose excursions were assessed by the following parameters obtained from the continuous glucose monitoring system (CGMS) for 72 h: mean blood glucose (MBG) and its standard deviation (SD), mean amplitude of glycemic excursion (MAGE), mean of daily differences (MODD). Glycosylated hemoglobin (HbAlc), triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-c), and low-density lipoprotein cholesterol (LDL-c) of the participants were also determined. According to the levels of CIMT, 64 diabetic patients were classified into two groups: diabetes mellitus without atherosclerosis (A group, n = 37) and diabetes mellitus with atherosclerosis (B group, n = 27). The relationship between the parameters of glycaemic variability and CIMT was examined.(1) There were no differences between A group and B group with regard to gender composition, course of diabetes, body mass index (BMI), diabetic chronic complications, family history of diabetes, smoking, alcohol drinking, diastolic blood pressure (DBP), TG, TC, HDL-c, SD and MAGE (P0.05). A group had younger age and lower levels of systolic blood pressure (SBP), LN(LDL-c) and LN (MODD) than B group (P0.05). (2) Pearson correlation analyses showed that CIMT was positively correlated with age (r = 0.370, P = 0.005), LN (LDL-c) (r = 0.325, P = 0.009), SD (r = 0.251, P = 0.045) and LN (MODD) (r = 0.346, P = 0.005). (3) Age, smoking, LN (LDL-c) and LN (MODD) were identified as predictors for CIMT in the multiple linear regression analysis.Glucose excursions may contribute to the development of atherosclerosis in patients with type 2 diabetes, which is independent from HbA1c levels.

To examine the association of the Thr394Thr polymorphism of PPARGC1A gene with type 2 diabetes (T2DM), insulin resistance (IR) and other metabolic disorders in a Chinese population.Three hundred and seven subjects including 151 T2DM patients and 156 normal glucose tolerant controls (NC) were enrolled in this study. The Thr394Thr G/A polymorphism was genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Glucose, insulin, lipids levels were determined in all subjects. Body mass index (BMI), waist circumferences, index of homeostasis model assessment-insulin resistance (HOMA-IR) and blood pressure were also measured.The diabetic subjects had higher levels of BMI, waist circumferences, blood systolic pressure, triglycerides and lower levels of high density lipoprotein-cholesterol (HDL-C) compared with those of control subjects (P0.05). About 43.7% (66/151) of the T2DM subjects had the AG genotype, while 37.2% (58/156) in the NC group. The frequency of the A allele was 0.225 in T2DM, and 0.186 in the NC subjects. There were no significant differences either in genotype or allelic distribution of G/A polymorphism between the two groups. In the T2DM group, subjects with AA and GA genotypes had significantly higher levels of HOMA-IR, waist circumferences and lower levels of HDL-C (P0.05) than those carrying GG genotype. HOMA-IR in subjects with AA and AG were significantly higher than those with GG genotype in both groups.The A allele of the Thr394Thr (G--A) polymorphism of the PPARGC1A gene was associated with insulin resistance, and may be related to central obesity and decreased HDL-C levels in Chinese population. The relationship between this polymorphism and T2DM needs further investigation.

To explore the epidemiological status of abnormal glucose metabolism and its influential factors among middle and aged population with hypertension in Chengdu area.In 2008, after adopting the methods of stratified cluster sampling, the authors investigated 4685 subjects of the middle and aged population between the age of 40 - 79 in Chengdu urban and rural area by checking blood pressure and oral glucose tolerance test (OGTT). Patients with previously known diabetes mellitus (DM) were only asked to perform fasting glucose and to carry out a questionnaire. Comparison of the prevalence rates of abnormal glucose metabolism in hypertensive and non-hypertensive subjects was carried out. The prevalence rates of isolated impaired glucose tolerance (I-IGT) and isolated postprandial hyperglycemia (IPH) among middle and aged subjects with hypertension were acquired and the influential factors of abnormal glucose metabolism among middle and aged subjects with hypertension were analyzed.The prevalence rate of abnormal glucose metabolism in the hypertensive subjects was obviously higher than that in the non-hypertensive subjects; without using OGTT, 72.9% of the pre-diabetic and 54.4% of the new diagnosed DM patients would remain undiagnosed if fasting plasma glucose detection was used alone. Age, diabetic history of first degree relatives, overweight or obesity were the risk factors for the development of abnormal glucose metabolism among middle and aged male subjects with hypertension in Chengdu area. Exercise training and high education level were the protective factors. Age, diabetic history of first degree relatives, abdominal obesity and hypertriglyceridemia were the risk factors for the development of abnormal glucose metabolism among middle and aged female subjects with hypertension in Chengdu area.More than 50% of middle and aged subjects with hypertension in Chengdu area has accompanying abnormal glucose metabolism. OGTT easily discloses the abnormal status and should be a routine procedure in the diagnosis of pre-diabetes or DM in such population. Appropriate exercise, learning diabetes-related knowledge to take reasonable lifestyle, and intervention of metabolic factors such as overweight or obesity are advised. Abdominal obesity and hypertriglyceridemia play important roles in leading to abnormal glucose metabolism among middle and aged population with hypertension.

To develop the evaluation tool for the risk level of abnormal glucose metabolism morbidity in the middle-aged and elder populations.By the stratified cluster sampling method, a survey was conducted in middle-aged and elder populations aged 40 - 70 years old in urban and rural areas of Chengdu during April-November 2008. The parameters included blood pressure, fasting blood glucose, blood glucose after oral administration of 75 g glucose, blood lipid, blood uric acid, height, body weight and waistline, etc. A total of 5205 valid copies of questionnaires were obtained. A discriminant analysis and a multifactorial logistic regression analysis were conducted. The quantitative scoring system was established and the ROC analysis conducted to screen the boundary point of the quantitative scoring system. The discriminant performance of simple scoring model was conducted in 336 subjects for physical examination.The accuracies of discriminant analysis in male and female models were 79.04% and 81.35% respectively. The simple male scoring mode included the following eight parameters: age, physical work intensity, parental history of diabetes mellitus, sibling's history of diabetes mellitus, BMI index, existing abdominal obesity and history of hypertension. The simple female scoring mode included the following eight parameters: age, physical work intensity, physical training, parental history of diabetes mellitus, sibling's history of diabetes mellitus, BMI index, existing abdominal obesity, history of hypertension, number of parturition and history of gestational diabetes mellitus. The ROC AUCs were 0.701 and 0.728 in male and female models respectively. During applications in other populations, the sensitivity and specificity of the male model were 86.86% and 65.12% while those of female model 88.89% and 72.97% respectively.The newly developed evaluation tool for the risk level of abnormal glucose metabolism morbidity in middle-aged and elder populations is both simple and practical. With an excellent practicability; it may be used to screen abnormal glucose metabolism in middle-aged and elder populations.

To find out the clinical characteristic elements as parameters and detect the polymorphism at PvU II endonuclease site and Arg(140) Trp mutation of the CD38 gene of LADA patients in the Chengdu area.The clinical parameters, islet cell-specific autoantibodies, C-peptide levels, genetic and mutation frequency of the CD38 gene in 44 patients with LADA and 67 patients with T2DM were investigated and compared with those in 25 normal controls.The patients of 30-50 years of age had higher prevalence of LADA. A number of LADA patients were obese or over-obese. The positivity of GAD-Ab, ICA and IAA declined with the increase of age. Both LADA and T2DM patients had the polymorphisms of B/B and A/B of the CD38 gene, but the healthy controls did not have such polymorphisms. Arg1140 Trp mutation was not found in both patients and healthy controls.This research revealed no relationship between the on-set of LADA and the CD38 polymorphism and CD38 Arg(140) Trp mutation.

To evaluate the effects of sibutramine on body weight, body fat mass, metabolism of plasma glucose and serum lipids, and insulin resistance (IR) in primary obesity patients.A double-blind, double-placebo, randomized controlled, multi-center clinical trial was conducted. 359 voluntary obese subjects, whose body mass index (BMI)or = 27 kg/m(2), without hypertension and diabetes, were enrolled. They were randomly divided into group A, B and C respectively. Sibutramine tablets or capsules were administered 10-20 mg/day for 24 weeks to the test groups and placebo to a control group. CT scan was used to measure the intra or subcutaneous-abdominal fat areas (IAFA, SAFA) at L(4)-L(5) level. Dual energy X-ray absorptiometry (DEXA) was used to measure total body fat mass (TBFM).315 subjects continued to be followed for 24 weeks. After opening the blind, it was shown that group A received sibutramine tablet (n = 107), group B placebo (n = 104) and group C was capsule (n = 104). In group A and C body weight loss was 4.86 kg (6.42%) and 4.68 kg (6.38%), TBFM reduction was 4.07 kg (13.94%) and 4.09 kg (15.02%), SAFA decreased 7.30% and 7.45%, IAFA decreased 19.21% and 16. 98% respectively. Fasting plasma glucose decreased from 5.69 to 4.83 mmol/L and from 5.38 to 4.69 mmol/L in group A and C respectively. Fasting serum insulin decreased from 20.98 to 14.75 mU/L and from 21.11 to 14.68 mU/L, 2 h insulin decreased from 70.91 to 44.11 mU/L and from 73.13 to 41.93 mU/L in group A and C respectively. Serum triglyceride decreased from 1.98 to 1.73 mmol/L and 1.84 to 1.67 mmol/L, total cholesterol decreased from 5.08 to 4.75 mmol/L and from 5.06 to 4.46 mmol/L, high-density lipoprotein cholesterol increased from 1.13 to 1.28 mmol/L and 1.10 to 1.31 mmol/L in group A and C respectively, HOMA-IR index decreased from 5.32 to 3.32, and from 5.09 to 3.12 respectively in group A and C. Adverse drug reaction was 32.41%, 13.47% and 31.20% in group A, B and C.Sibutramine tablet or capsule decreases comparably body weight and TBFM, especially IAFA regulates plasma glucose and serum lipid metabolism and also decreases IR. Sibutramine is well tolerated in most of the subjects.

A 63-year-old woman was admitted with fatigue, general malaise, paraesthesiae, muscle cramping and weakness of the limbs. Since the age of 13, she had suffered from a transient lower extremities paralysis 3 times. Past history was unremarkable. There was no family history of disease. In addition, she denied any form of self-medication, surreptitious diuretic and laxative abuse, persistent vomiting and diarrhea. The blood pressure was 120/70 mmHg, BMI = 23.0 kg/m2, WHR = 0.84. A little anxious. The results of physical examinations were unnoticeable. The cranial-nerve functions were intact. Manual muscle tests revealed her extremities in normal condition. Sensation was normal in all modalities. The deep tendon reflexes were present but decreased mildly.Laboratory tests showed moderate to severe hypokalemia with a serum potassium concentration of 2.77 to 3.17 mmol/L, hypomagnesemia (0.31-0.35 mmol/L), hypocalcaemia (1.79-1.99 mmol/L), hypocalciuria (0.12-1.10 mmol/24 h), and metabolic alkalosis. The patient had elevated plasma renin activity and normoaldosteronism; her parathyroid hormone level was normal. Urinary calcium to creatinine ratio was (5.17-23.57) x 10(-3) mg/mg Cr. The renal clearance studies in this patient using furosemide or hydrochlorothiazide disclosed that urine volume and chloride clearance (CCL) were increased after furosemide administration, but there was no obvious change after the administration of hydrochlorothiazide. Furthermore, the distal fractional chloride reabsorption [CH2O/(CH2O+CCI)] was dramatically decreased by furosemide administration, whereas thiazide had little effect on it. These findings pointed to the presence of a non-functional thiazide-sensitive sodium/chloride cotransporter in the distal convoluted tubule, so the diagnosis of Gitelman's syndrome (GS) was made.The patient was treated with indomethacin 50 mg, tid; after 3 days, the potassium increased, but calcium and magnesium serum levels failed to improve. So triamterene 50 mg, tid was also administrated. After 4 days, the serum levels of potassium, calcium were normalized, and the serum levels of magnesium increased from 0.35 mmol/L to 0.52 mmol/L; weakness and fatigue improved markedly, the clinical symptoms disappeared. The 18-month-follow-up study found the magnesium serum level normal.GS may be present with severe hypocalcaemia and hypokalemic periodic paralysis; the renal clearance studies by diuretic administration may be of help in diagnosing Gitelman's syndrome, and the combined use of indomethacin with triamterene has good therapeutic effect.

To investigate the distribution of body fat and analyze its characteristics and relationship with metabolic variables in obese Chinese.In this observational, cross sectional study, the total body fat mass was measured using body mass index (BMI), and as an index of intra-abdominal fat accumulation, the ratio of the visceral (VA) to abdominal subcutaneous (SA) adipose area (VSR) was determined using a computed tomography (CT) scans made at the level of L4/L5 in 309 obese human subjects (male 88; female 221). Blood pressure (BP), fasting serum lipids such as triglycerides (TG), total cholesterol (TC), high density lipoprotein(HDL-c), low density lipoprotein (LDL-c), and serum uric acid (UA) were also determined.(1) There were no differences between the male and the female subjects in regard to age, BMI, SBP, LDL-c and HDL-c. SA was significantly greater in women, whereas VA and VSR were significantly greater in men; DBP, UA, TC and TG were significantly higher in men than in women. (2) In both men and women, VSR was significantly higher in obese Chinese than in obese European and Americans. Age, TG and LDL-c were higher in subjects with visceral fat obesity (VFO) than in those with subcutaneous fat obesity (SFO). In males, TC,UA were significantly higher in VFO than in SFO. (3) 57 paired cases of male and female subjects matched for VSR were studied, and significant higher levels of serum UA and TG were noted in the male than in the female subjects. (4) After being adjusted for age and BMI, the analyses of partial correlation showed that in both men and women, VSR was positively correlated with TG and LDL-c, and SA was negatively correlated with LDL-c. In men, VA was positively correlated with SBP, and SA was negatively correlated with TG. In women, VA was positively correlated with TG, LDL-c; SA was negatively with LDL-c, but it was positively correlated with HDL-c and UA. (5) Stepwise multiple regression analysis showed that SA, VA, VSR were independent predictor for TG and LDL-c, SBP, and TC respectively (adjusting R2=0.079, 0.193, 0.122, 0.072, P=0.005, 0.000, 0.001, 0.007, respectively) in males. In females. VSR was an independent predictor for TG and LDL-c (adjusting R2=0.024, 0.113, P=0.012, 0.000 respectively); both BMI and SA were important predictors for UA and HDL-c, and SA was an important predictor for SBP.The above data suggest that in obese Chinese, the body fat distribution is characterized by central obesity, the cardiovascular risk factors are not only associated with general obesity but more closely associated with regional body fat distribution (VFO), and the relationships between regional body fat distribution and metabolic variables vary with gender.

To explore novel pathogenic mutation in the mitochondrial DNA gene in diabetic pedigree.Twenty-eight suspected mitochondrial DNA diabetic families were recruited. The gene fragment was produced by PCR, and mutation was detected by direct sequencing.In one pedigree, the proband and her mother were found carrying the most common nt3243 A --G mutation and another 16S rRNA 3205C --T mutation. But only 3205C --T was found in her affected brother. All the two patients were deaf and developed diabetes in early age, characterized by impaired beta cell function and low body mass index (BMI). The proband had relatively higher lactic acid concentration than normal individuals. A novel ND1 gene 3434 A --G(TAT --TGT) mutation was explored in another proband with deafness and her affected family members.16SrRNA 3205C --T mutation was found in a mitochondrial diabetes mellitus pedigree, implying its potential pathogenic role in diabetes. Another novel ND1 3434 A --G mutation was found in another diabetic pedigree. Because this mutation causes amino acid change (Tyr --Cys) and is co-segregated with diabetes, it may be diabetogenic.