OBJECTIVES: Patients with classical type 1 diabetes mellitus (T1DM) require lifelong dependence on exogenous insulin therapy due to pancreatic beta-cell destruction and absolute insulin deficiency. T1DM accounts for about 90% of children with diabetes in China, with a rapid increase in incidence and a younger-age trend. Epidemiological studies have shown that the overall glycated haemoglobin (HbA1c) and compliance rate are low in Chinese children with T1DM. Optimal glucose control is the key for diabetes treatment, and maintaining blood glucose within the target range can prevent or delay chronic vascular complications in patients with T1DM. Therefore, this study aims to investigate the glycemic control of children with T1DM from Hunan and Henan Province with flash glucose monitoring system (FGMS), and to explore factors associated with glycemic variability. METHODS: A total of 215 children with T1DM under 14 years old were enrolled continuously in 16 hospitals from August 2017 to August 2020. All subjects wore a FGMS device to collect glucose data. Correlation of HbA1c, duration of diabetes, or glucose scan rates with glycemic variability was analyzed. Glucose variability was compared according to the duration of diabetes, HbA1c, glucose scan rates and insulin schema. RESULTS: HbA1c and duration of diabetes were positively correlated with mean blood glucose, standard deviation of glucose, mean amplitude of glucose excursions (MAGE), and coefficient of variation (CV) of glucose (all P<0.01). The glucose scan rates during FGMS wearing was significantly positively correlated with time in range (TIR) (P=0.001) and negatively correlated with MAGE and mean duration of hypoglycemia (all P<0.01). Children with duration ≤1 year had lower time below range (TBR) and MAGE when compared with those with duration >1 year (all P<0.05). TIR and TBR in patients with HbA1c ≤7.5% were higher (TIR: 65% vs 45%, TBR: 5% vs 4%, P<0.05), MAGE was lower (7.0 mmol/L vs 9.4 mmol/L, P<0.001) than those in HbA1c >7.5% group. Compared to the multiple daily insulin injections group, TIR was higher (60% vs 52%, P=0.006), MAGE was lower (P=0.006) in the continuous subcutaneous insulin infusion group. HbA1c was lower in the high scan rates (≥14 times/d) group (7.4% vs 8.0%, P=0.046), TIR was significantly higher (58% vs 47%, P<0.001), and MAGE was lower (P<0.001) than those in the low scan rate (<14 times/d) group. CONCLUSIONS The overall glycemic control of T1DM patients under 14 years old in Hunan and Henan Province is under a high risk of hypoglycemia and great glycemic variability. Shorter duration of diabetes, targeted HbA1c, higher glucose scan rates, and CSII are associated with less glycemic variability.
Adolescent ; Blood Glucose ; Blood Glucose Self-Monitoring ; Child ; Diabetes Mellitus, Type 1/drug therapy* ; Glucose ; Glycated Hemoglobin A/analysis* ; Humans ; Hypoglycemia/prevention & control* ; Hypoglycemic Agents/therapeutic use* ; Insulin/therapeutic use*

Eight terpenoids were isolated from the fruits of Amomum villosum by silica gel, Sephadex LH-20, Rp-C_(18), MCI GEL CHP20 P column chromatography, preparative TLC, and HPLC. Their structures were identified by HR-ESI-MS, ~1H and ~(13)C-NMR, IR, UV, [α]_D, and ECD spectroscopic data as kravanhin A 3-O-β-D-glucopyranoside(1), kravanhin B(2), 6-eudesmene-1β,4β-diol(3), oplodiol(4), vicodiol(5),(1R,2S,4R,7S)-vicodiol 9-O-β-D-glucopyranoside(6),(1R,2S,4S,5R)-angelicoidenol 2-O-β-D-glucopyranoside(7), and(1S,2S,4R,6S)-bornane-2,6-diol 2-O-β-D-glucopyranoside(8). Compound 1 was a new compound, and compounds 2-5 were isolated from A. villosum for the first time. Their hypoglycemic activity was tested based on STC-1 cell model and two enzymatic models(GPa and PTP1 B). The results showed that compounds 1, 7, and 8 could stimulate GLP-1 with the secretion rates of 692.8%, 398.6%, and 483.3% at 25.0 μmol·L~(-1), and compound 6 showed inhibitory activity against GPa with an IC_(50) value of 78.6 μmol·L~(-1).
Fruit/chemistry* ; Terpenes/analysis* ; Amomum ; Hypoglycemic Agents/analysis* ; Chromatography, High Pressure Liquid

Blood Glucose ; China ; Diabetes Mellitus, Type 2/drug therapy* ; Glycated Hemoglobin A/analysis* ; Glycemic Control ; Humans ; Hypoglycemic Agents/therapeutic use*

INTRODUCTIONWe aimed to evaluate the effectiveness and safety of canagliflozin as compared to sitagliptin in a real-world setting among multiethnic patients with Type 2 diabetes mellitus (T2DM) in Singapore.

METHODSThis was a new-user, active-comparator, single-centre retrospective cohort study. Patients aged 18-69 years with T2DM and estimated glomerular filtration rate ≥ 60 mL/min/1.73 m were eligible for inclusion if they were initiated and maintained on a steady daily dose of canagliflozin 300 mg or sitagliptin 100 mg between 1 May and 31 December 2014, and followed up for 24 weeks.

RESULTSIn total, 57 patients (canagliflozin 300 mg, n = 22; sitagliptin 100 mg, n = 35) were included. The baseline patient characteristics in the two groups were similar, with overall mean glycated haemoglobin (HbA1c) of 9.4% ± 1.4%. The use of canagliflozin 300 mg was associated with greater reductions in HbA1c (least squares [LS] mean change -1.6% vs. -0.4%; p < 0.001), body weight (LS mean change -3.0 kg vs. 0.2 kg; p < 0.001) and systolic blood pressure (LS mean change: -9.7 mmHg vs. 0.4 mmHg; p < 0.001), as compared with sitagliptin 100 mg. About half of the patients on canagliflozin 300 mg reported mild osmotic diuresis-related side effects that did not lead to drug discontinuation.

CONCLUSIONOur findings suggest that canagliflozin was more effective than sitagliptin in reducing HbA1c, body weight and systolic blood pressure in patients with T2DM, although its use was associated with an increased incidence of mild osmotic diuresis-related side effects.

Adolescent ; Adult ; Aged ; Blood Glucose ; drug effects ; Blood Pressure ; Body Mass Index ; Body Weight ; Canagliflozin ; administration & dosage ; Diabetes Mellitus, Type 2 ; drug therapy ; Female ; Glomerular Filtration Rate ; Hemoglobins ; analysis ; Humans ; Hypoglycemic Agents ; administration & dosage ; Least-Squares Analysis ; Male ; Middle Aged ; Osmosis ; Retrospective Studies ; Singapore ; Sitagliptin Phosphate ; administration & dosage ; Systole ; Treatment Outcome ; Young Adult

Catalpol, a major bioactive component from Rehmannia glutinosa, which has been used to treat diabetes. The present study was designed to elucidate the anti-diabetic effect and mechanism of action for catalpol in db/db mice. The db/db mice were randomly divided into six groups (10/group) according to their blood glucose levels: db/db control, metformin (positive control), and four dose levels of catalpol treatment (25, 50, 100, and 200 mg·kg), and 10 db/m mice were used as the normal control. All the groups were administered orally for 8 weeks. The levels of fasting blood glucose (FBG), random blood glucose (RBG), glucose tolerance, insulin tolerance, and glycated serum protein (GSP) and the globe gene expression in liver tissues were analyzed. Our results showed that catalpol treatment obviously reduced water intake and food intake in a dose-dependent manner. Catalpol treatment also remarkably reduce fasting blood glucose (FBG) and random blood glucose (RBG) in a dose-dependent manner. The RBG-lowering effect of catalpol was better than that of metformin. Furthermore, catalpol significantly improved glucose tolerance and insulin tolerance via increasing insulin sensitivity. Catalpol treatment significantly decreased GSP level. The comparisons of gene expression in liver tissues among normal control mice, db/db mice and catalpol treated mice (200 and 100 mg·kg) indicated that there were significant increases in the expressions of 287 genes, whichwere mainly involved in lipid metabolism, response to stress, energy metabolism, and cellular processes, and significant decreases in the expressions of 520 genes, which were mainly involved in cell growth, death, immune system, and response to stress. Four genes expressed differentially were linked to glucose metabolism or insulin signaling pathways, including Irs1 (insulin receptor substrate 1), Idh2 (isocitrate dehydrogenase 2 (NADP), mitochondrial), G6pd2 (glucose-6-phosphate dehydrogenase 2), and SOCS3 (suppressor of cytokine signaling 3). In conclusion, catalpol ecerted significant hypoglycemic effect and remarkable therapeutic effect in db/db mice via modulating various gene expressions.
Animals ; Blood Glucose ; metabolism ; Diabetes Mellitus, Experimental ; drug therapy ; genetics ; metabolism ; Disease Models, Animal ; Dose-Response Relationship, Drug ; Drugs, Chinese Herbal ; administration & dosage ; analysis ; Gene Expression ; drug effects ; Glucosephosphate Dehydrogenase ; genetics ; metabolism ; Humans ; Hypoglycemic Agents ; administration & dosage ; Insulin ; metabolism ; Insulin Receptor Substrate Proteins ; genetics ; metabolism ; Iridoid Glucosides ; administration & dosage ; analysis ; Isocitrate Dehydrogenase ; genetics ; metabolism ; Liver ; drug effects ; metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Rehmannia ; chemistry ; Suppressor of Cytokine Signaling 3 Protein ; genetics ; metabolism

To investigate the effect of berberine on glycemia regulation in rats with diabetes and the related mechanisms.Diabetic-like rat model was successfully induced by intraperitoneal injection of streptozotocin in 50 out of 60 male SD rats, which were then randomly divided into 5 groups with 10 rats in each:control group (received vehicle only), positive drug control group (sitagliptin 10 mg·kg·d), low-dose berberine group (30 mg·kg·d), moderate-dose berberine group (60 mg·kg·d), and high-dose berberine group (120 mg·kg·d). All animals were fed for 3 d, and fasting blood sampling was performed on day 3 of administration. Rats were given glucose (2 g/kg) by gavage 30 min after the last dose. Blood and intestinal samples were obtained 2 h after glucose loading. Fasting blood glucose (FBG) and 2-h postprandial plasma glucose (2h-PPG) were detected by using biochemical analyzer, and insulin, glucagon-like peptide-1 (GLP-1) and dipeptidyl peptidase-Ⅳ(DPP-Ⅳ) were measured by using ELISA kit.No significant difference in FBG and serum DPP-Ⅳ level were found between berberine groups and control group (all>0.05). Compared with control group, serum levels of GLP-1 and insulin were increased in high-and moderate-dose berberine groups, while 2h-PPG was decreased (all<0.05); GLP-1 levels in the intestinal samples were increased, while DPP-Ⅳ levels were decreased in all berberine groups (all<0.05).Short-term berberine administration can decrease 2h-PPG level in streptozotocin-induced diabetic rat model through local inhibition of intestinal DPP-Ⅳ. The efficacy of DPP-Ⅳ inhibitor may be associated with its intestinal pharmacokinetics.
Animals ; Berberine ; pharmacokinetics ; pharmacology ; Blood Glucose ; drug effects ; Diabetes Mellitus, Experimental ; chemically induced ; drug therapy ; Dipeptidyl Peptidase 4 ; analysis ; drug effects ; pharmacokinetics ; Dipeptidyl-Peptidase IV Inhibitors ; Dose-Response Relationship, Drug ; Glucagon-Like Peptide 1 ; analysis ; blood ; Hypoglycemic Agents ; Insulin ; blood ; Intestines ; chemistry ; drug effects ; Male ; Rats ; Rats, Sprague-Dawley ; Sitagliptin Phosphate

Sleep has important effects on physical and mental health, and sleep disorders are associated with increased mortality and morbidity. This study was conducted to evaluate the relationship between sleep duration or sleep quality and the risk of type 2 diabetes. The FACTS (FAmily CohorT Study in primary care) was established to investigate the relations between familial environment and health which was conducted at 22 family medicine outpatient clinics in general hospitals. Total 563 patients without diabetes who received > or =1 year follow-up examination were included in the analysis. We used the Pittsburgh Sleep Quality Index to determine sleep quality, and a score of > or =5 was considered to define poor sleep quality. Patients taking oral hypoglycemic agents, having a fasting glucose level of >126 mg/dL, or diagnosed with diabetes by physicians were classified as having diabetes. The median follow-up period was 2.5 years. Poor sleep quality was associated with a higher risk of diabetes after adjusting for age, sex, body mass index, income, physical activity, and family history of diabetes (relative risk=2.64; 95% confidence interval, 1.03-6.78). As a risk factor for the development of diabetes, poor sleep quality may independently increase the incidence of diabetes.
Aged ; Blood Glucose/analysis ; Body Mass Index ; Cohort Studies ; Demography ; Diabetes Mellitus, Type 2/complications/*diagnosis/drug therapy ; Female ; Follow-Up Studies ; Humans ; Hypoglycemic Agents/therapeutic use ; Male ; Middle Aged ; Obesity/complications ; Primary Health Care ; Risk Factors ; *Sleep ; Surveys and Questionnaires

Although various basal-bolus insulin therapy (BBIT) protocols have been used in the clinical environment, safer and more effective BBIT protocols are required for glucose control in hospitalized patients with type 2 diabetes (T2D). Modeling approaches could provide an evaluation environment for developing the optimal BBIT protocol prior to clinical trials at low cost and without risk of danger. In this study, an in-silico model was proposed to evaluate subcutaneous BBIT protocols in hospitalized patients with T2D. The proposed model was validated by comparing the BBIT protocol and sliding-scale insulin therapy (SSIT) protocol. The model was utilized for in-silico trials to compare the protocols of adjusting basal-insulin dose (BBIT1) versus adjusting total-daily-insulin dose (BBIT2). The model was also used to evaluate two different initial total-daily-insulin doses for various levels of renal function. The BBIT outcomes were superior to those of SSIT, which is consistent with earlier studies. BBIT2 also outperformed BBIT1, producing a decreased daily mean glucose level and longer time-in-target-range. Moreover, with a standard dose, the overall daily mean glucose levels reached the target range faster than with a reduced-dose for all degrees of renal function. The in-silico studies demonstrated several significant findings, including that the adjustment of total-daily-insulin dose is more effective than changes to basal-insulin dose alone. This research represents a first step toward the eventual development of an advanced model for evaluating various BBIT protocols.
Blood Glucose/analysis ; Diabetes Mellitus, Type 2/*drug therapy ; Hospitalization ; Humans ; Hypoglycemic Agents/*therapeutic use ; Insulin/*therapeutic use ; Models, Theoretical

OBJECTIVE: To evaluate the relationship between type 2 diabetes mellitus (DM) and oncological outcomes in early stage cervical cancer patients who underwent radical surgical resection. METHODS: Patients with early stage cervical cancer diagnosed between 2001 and 2014 were retrospectively enrolled. We assessed the outcomes of 402 non-DM and 42 DM patients with cervical cancer. We tested the prognostic value of DM via Cox proportional hazard modeling. RESULTS: Patients with DM were more likely to be older and overweight. In the DM group, 20 and 22 patients were and were not taking metformin, respectively. The 5-year recurrence-free survival (RFS) and 5-year overall survival (OS) rate for the whole study population were 88.49% and 96.34%, respectively. In the DM group, there was no evidence that metformin affected the RFS (p=0.553) or the OS (p=0.429). In multivariate analysis, age (p=0.007), histology (p=0.006), and deep stromal invasion (p=0.007) were independent adverse prognostic factors for RFS. There was a borderline significant association of increased RFS with DM (p=0.051). However, a time-varying-effect Cox model revealed that the DM was associated with a worse RFS (hazard ratio, 11.15; 95% CI, 2.00 to 62.08, p=0.022) after 5 years. DM (p=0.008), age (p=0.009), and node status (p=0.001) were the only 3 independent prognostic factors for OS. CONCLUSION: Early stage cervical cancer patients with type 2 DM have a poorer oncological outcome than patients without DM.
Adult ; Age Factors ; Diabetes Mellitus, Type 2/*complications/drug therapy ; Female ; Humans ; Hypoglycemic Agents/therapeutic use ; *Hysterectomy ; Metformin/therapeutic use ; Middle Aged ; Prognosis ; Proportional Hazards Models ; Retrospective Studies ; Survival Analysis ; Uterine Cervical Neoplasms/*complications/diagnosis/surgery

BACKGROUND: Glycated albumin (GA) is a better marker of short-term glycemic control than glycated hemoglobin (A1c). Dyslipidemia is the main cause of cardiovascular complications in diabetes mellitus (DM). Studies on the correlation of GA with lipid indices are sparse. We investigated the diagnostic utility of GA for DM and its relationship with serum lipid profiles compared with that of A1c. METHODS: The GA enzymatic method was used to determine the diagnostic utility of GA for DM by using samples from 163 normal subjects (group 1) and 102 patients newly diagnosed with type 2 DM (T2DM; group 2). To analyze the lipid profiles, 263 patients with T2DM receiving treatment (group 3) were recruited. RESULTS: GA correlated with A1c (r=0.934, P<0.0001). Linear regression analysis indicated that GA levels were about 2.48 folds those of A1c. In the ROC analysis for GA to diagnose DM, the areas under the curve (0.988, 95% confidence interval 0.972-1.004) was excellent. HDL levels were significantly lower in groups 2 and 3. In group 1, positive correlations were observed between A1c and triglyceride (TG), total cholesterol (TC), LDL, TG/HDL, TC/HDL, and LDL/HDL levels. A negative correlation was observed between HDL and A1c levels. In group 3, HDL levels (P=0.0124 and P=0.0141, respectively) were significantly higher and LDL levels tended to be lower, not statistically significant, in the well-controlled group categorized using the A1c and GA cut-off values. CONCLUSIONS: GA is a potential diagnostic tool for DM. Compared with A1c, GA seems less relevant to dyslipidemia.
Adult ; Area Under Curve ; Blood Glucose/analysis ; Cholesterol, HDL/blood ; Cholesterol, LDL/blood ; Chromatography, High Pressure Liquid ; Diabetes Mellitus, Type 2/complications/*diagnosis/drug therapy ; Female ; Humans ; Hyperlipidemias/complications/*diagnosis ; Hypoglycemic Agents/therapeutic use ; Linear Models ; Lipids/blood ; Male ; Middle Aged ; ROC Curve ; Serum Albumin/*analysis