Effect of electroacupuncture on liver Akt/FoxO1 signaling pathway in rats with diabetic fatty / 中国针灸

OBJECTIVE@#To observe the effect of electroacupuncture (EA) on liver protein kinase B (Akt)/forkhead box transcription factor 1 (FoxO1) signaling pathway in Zucker diabetic fatty (ZDF) rats, and to explore the possible mechanism of EA on improving liver insulin resistance of type 2 diabetes mellitus.@*METHODS@#Twelve male 2-month-old ZDF rats were fed with high-fat diet for 4 weeks to establish diabetes model. After modeling, the rats were randomly divided into a model group and an EA group, with 6 rats in each group. In addition, six male Zucker lean (ZL) rats were used as the blank group. The rats in the EA group were treated with EA at bilateral "Zusanli" (ST 36), "Sanyinjiao" (SP 6), "Weiwanxiashu" (EX-B 3), and "Pishu" (BL 20). The ipsilateral "Zusanli" (ST 36) and "Weiwanxiashu" (EX-B 3) were connected to EA device, continuous wave, frequency of 15 Hz, 20 min each time, once a day, six times a week, for a total of 4 weeks. The fasting blood glucose (FBG) in each group was compared before modeling, before intervention and after intervention; the serum levels of insulin (INS) and C-peptide were measured by radioimmunoassay method, and the insulin resistance index (HOMA-IR) was calculated; HE staining method was used to observe the liver tissue morphology; Western blot method was used to detect the protein expression of Akt, FoxO1 and phosphoenolpyruvate carboxykinase (PEPCK) in the liver.@*RESULTS@#Before intervention, compared with the blank group, FBG was increased in the model group and the EA group (P<0.01); after intervention, compared with the model group, FBG in the EA group was decreased (P<0.01). Compared with the blank group, the serum levels of INS and C-peptide, HOMA-IR, and the protein expression of hepatic FoxO1 and PEPCK were increased (P<0.01), while the protein expression of hepatic Akt was decreased (P<0.01) in the model group. Compared with the model group, the serum levels of INS and C-peptide, HOMA-IR, and the protein expression of hepatic FoxO1 and PEPCK were decreased (P<0.01), while the protein expression of hepatic Akt was increased (P<0.01) in the EA group. In the model group, the hepatocytes were structurally disordered and randomly arranged, with a large number of lipid vacuoles in the cytoplasm. In the EA group, the morphology of hepatocytes tended to be normal and lipid vacuoles were decreased.@*CONCLUSION@#EA could reduce FBG and HOMA-IR in ZDF rats, improve liver insulin resistance, which may be related to regulating Akt/FoxO1 signaling pathway.

A cross-sectional study to assess beta-cell function in individuals with recently diagnosed young-onset type 2 diabetes mellitus and its’ complications / Journal of the ASEAN Federation of Endocrine Societies

Objective@#The primary objective was to assess beta-cell function of recently-diagnosed young-onset type 2 diabetes mellitus (T2DM) individuals using basal and stimulated C-peptide levels. The secondary objective was to examine the association between C-peptide with metabolic factors and diabetes complications.@*Methodology@#A cross-sectional study was conducted for young-onset T2DM individuals aged 18-35 years with a disease duration of not more than 5 years. Plasma C-peptide was measured before and after intravenous glucagon injection. Demographic data, medical history and complications were obtained from medical records and clinical assessment. Continuous data were expressed as median and interquartile range (IQR). Categorical variables were described as frequency or percentage. Multivariable linear regression analysis was used to determine factors associated with C-peptide levels.@*Results@#113 participants with young-onset T2DM with a median (IQR) age of 29.0 (9.5) years and 24 (36) months were included in this study. The median (IQR) basal and stimulated C-peptide was 619 (655) pmol/L and 1231 (1024) pmol/L. Adequate beta-cell function was present in 78-86% of the participants based on the basal and stimulated C-peptide levels. We found hypertension, obesity and diabetic kidney disease (DKD) to be independently associated with higher C–peptide levels. In contrast, females, smokers, those on insulin therapy and with longer duration of disease had lower C–peptide levels.@*Conclusion@#Most recently diagnosed young-onset T2DM have adequate beta-cell function. Elevated C-peptide levels associated with obesity, hypertension and diabetic kidney disease suggest insulin resistance as the key driving factor for complications.

When do we need to suspect maturity onset diabetes of the young in patients with type 2 diabetes mellitus?

ABSTRACT Objetivo: Maturity onset diabetes of the young (MODY) patients have clinical heterogeneity as shown by many studies. Thus, often it is misdiagnosed to type 1 or type 2 diabetes(T2DM). The aim of this study is to evaluate MODY mutations in adult T2DM patients suspicious in terms of MODY, and to show clinical and laboratory differences between these two situations. Subjects and methods: In this study, we analyzed 72 type 2 diabetic patients and their relatives (35F/37M) who had been suspected for MODY and referred to genetic department for mutation analysis. The gene mutations for MODY have been assessed in the laboratory of Marmara University genetics. Totally 67 (32F/35M; median age 36.1) diabetic patients were analyzed for 7 MODY mutations. Twelve patients who have uncertain mutation (VUS) were excluded from study for further evaluation. MODY(+) (n:30) patients and T2DM patients (n:25) were compared for clinical and laboratory parameters. Results: In MODY(+) subjects, mutations in GCK (MODY 2) (n:12; 40%) were the most common followed by HNF4A (MODY 1) (n:4; 13.3%). Diabetes diagnosis age was younger in MODY(+) group but not statistically significant. Sixty-six percent of MODY(+) subjects had diabetes history at 3-consecutive generations in their family compared with 28% of T2DM patients statistically significant (p:0.006). Gender, BMI, C-peptide, HbA1c, lipid parameters, creatinine, GFR, microalbuminuria, vitamin D and calcium were not statistically different between the groups. Conclusion: According to present study results, MODY mutation positivity is most probable in young autoantibody (-) diabetic patients diagnosed before 30 years of age, who have first degree family history of diabetes.

Recurrent hypoglycemic coma and diabetic ketoacidosis caused by insulin antibody: a rare case of type 1 diabetes mellitus / Hipoglicemia hiperinsulinémica causada por anticuerpos antiinsulina: informe de un caso

ABSTRACT Insulin antibodies (IAs) induced by exogenous insulin rarely cause hypoglycemia. However, insulin autoantibodies (IAAs) in insulin autoimmune syndrome (IAS) can cause hypoglycemia. The typical manifestations of IAS are fasting or postprandial hypoglycemia, elevated insulin level, decreased C-peptide levels, and positive IAA. We report a 45-year-old male with type 1 diabetes mellitus (T1DM) treated with insulin analogues suffering from recurrent hypoglycemic coma and diabetic ketoacidosis (DKA). His symptoms were caused by exogenous insulin and were similar to IAS. A possible reason was that exogenous insulin induced IA. IA titers were 61.95% (normal: 300 mU/L and < 0.02 nmol/L when hypoglycemia occurred. Based on his clinical symptoms and other examinations, he was diagnosed with hyperinsulinemic hypoglycemia caused by IA. His symptoms improved after changing insulin regimens from insulin lispro plus insulin detemir to recombinant human insulin (Gensulin R) and starting prednisone.

Los anticuerpos contra la insulina (AI) inducidos por la insulina exógena raramente causan hipoglucemia. No obstante, los autoanticuerpos contra la insulina (AIA) en el síndrome autoinmune de insulina (SAI) pueden causar hipoglucemia. Las manifestaciones típicas del SAI son la hipoglucemia en ayunas o posprandial, niveles elevados de insulina, la disminución del nivel de péptido C y AIA positivos. Presentamos un paciente hombre de 45 años con diabetes mellitus de tipo 1 (DMT1) tratado con análogos de insulina, que sufría comas hipoglucémicos recurrentes y cetoacidosis diabética (CAD). Sus síntomas fueron causados por la insulina exógena y fueron similares al SAI. La posible razón fue que la insulina exógena indujo AI. El título de AI era del 61,95% (Normal: 300 mU/L y < 0,02 nmol/L cuando se producía la hipoglucemia. Basados en sus síntomas clínicos y otros exámenes, se le diagnosticó hipoglucemia hiperinsulinémica causada por la AI. Sus síntomas mejoraron después de cambiar el régimen de insulina de lispro más insulina detemir a insulina humana recombinante (Gensulin R) y de empezar a tomar prednisona.

Análisis comparativo de respuesta glicémica y de péptido C, tras la ingesta de estevia y D-tagatosa, según habitualidad de consumo de edulcorantes no nutritivos y preferencias alimentarias reportadas por mujeres con resistencia a la insulina / Comparative analysis of glicemic response and c peptide, after comsumption of stevia and d tagatosa, according to regular compsumtion of not nutritive sweeteners andnourish preferences reported by woman with insuline resistance

INTRODUCCIÓN: El consumo de edulcorantes no nutritivos (ENN) ha ido en aumento. A pesar de ello, se desconoce el efecto entre el consumo habitual de ENN y las preferencias alimentarias con parámetros bioquímicos en pacientes con resistencia a la insulina. OBJETIVO: Comparar la respuesta glicémica y de péptido C, según habitualidad de consumo de edulcorantes y preferencias alimentarias reportados por mujeres con resistencia a la insulina tras la ingesta de estevia y D-tagatosa. MÉTODOS: Treinta y tres mujeres con RI se sometieron a una encuesta de opción múltiple sobre preferencias alimentarias y ETCC modificada de edulcorantes. Aleatoriamente recibieron una precarga de control o experimental (estevia y D-tagatosa) donde se midió glicemia y péptido C en los tiempos -10, 30, 60, 90, 120, 180. RESULTADOS: Se encontró un ABC de péptido C más alto después de la ingesta de D-tagatosa (p = 0,02) en pacientes que prefieren alimentos ricos en proteínas en comparación con aquellos que prefieren alimentos ricos en grasas o en carbohidratos simples. Se observó un mayor ABC de péptido C (p = 0,04) para la prueba control en quienes prefieren el sabor salado y consumen menor cantidad de ENN, sin diferencias significativas entre quienes prefirieron sabor dulce. CONCLUSIONES: Al comparar las respuestas glicémicas e insulinémicas entre habitualidad de consumo de edulcorantes y preferencias alimentarias reportados por las pacientes tras la ingesta de agua, estevia y D-Tagatosa, no se obtuvieron diferencias significativas. Salvo en quienes preferían alimentos ricos en proteínas tras la ingesta de D- tagatosa y quienes preferían sabor salado con menor consumo habitual de ENN tras ingesta control.

INTRODUCTION: The consumption of non-nutritive sweeteners (NNS) has been increasing. Despite this, the effect between the habitual consumption of ENN and food preferences with biochemical parameters in patients with insulin resistance is unknown. OBJECTIVE: To compare the glycemic and C-peptide response, according to the habitual consumption of sweeteners and food preferences reported by women with insulin resistance after ingesting stevia and D-tagatose. METHODS: Thirty-three women with IR underwent a multiple choice survey on food preferences and modified ETCC for sweeteners. They randomly received a control or experimental preload (stevia and D-tagatose) where glycemia and peptide C were measured at times -10, 30, 60, 90, 120, 180. RESULTS: A higher C-peptide AUC was found after ingestion of D-tagatose (p = 0.02) in patients who prefer foods rich in protein compared to those who prefer foods rich in fat or simple carbohydrates. A higher AUC of peptide C (p = 0.04) is performed for the control test in those who prefer a salty taste and consume a lower amount of ENN, without significant differences between those who prefer a sweet taste. CONCLUSION: When comparing the glycerol and insulin responses between the habitual consumption of sweeteners and the food preferences reported by the patients after the ingestion of water, stevia and D-Tagatose, no significant differences were obtained. Except in those who prefer foods rich in protein after ingesting D-tagatose and those who prefer salty taste with less habitual consumption of NNS after control intake.

C-peptide level as predictor of type 2 diabetes remission and body composition changes in non-diabetic and diabetic patients after Roux-en-Y gastric bypass

OBJECTIVES: Several predictors of type 2 diabetes mellitus (T2DM) remission after metabolic surgery have been proposed and used to develop predictive scores. These scores may not be reproducible in diverse geographic regions with different baseline characteristics. This study aimed to identify predictive factors associated with T2DM remission after Roux-en-Y gastric bypass (RYGB) in patients with severe obesity. We hypothesized that the body composition alterations induced by bariatric surgery could also contribute to diabetes remission. METHODS: We retrospectively evaluated 100 patients with severe obesity and T2DM who underwent RYGB between 2014 and 2016 for preoperative factors (age, diabetes duration, insulin use, HbA1c, C-peptide plasma level, and basal insulinemia) to identify predictors of T2DM remission (glycemia<126 mg/dL and/or HbA1c<6.5%) at 3 years postoperatively. The potential preoperative predictors were prospectively applied to 20 other patients with obesity and T2DM who underwent RYGB for validation. In addition, 81 patients with severe obesity (33 with T2DM) underwent body composition evaluations by bioelectrical impedance analysis (InBody 770®) 1 year after RYGB for comparison of body composition changes between patients with and those without T2DM. RESULTS: The retrospective analysis identified only a C-peptide level >3 ng/dL as a positive predictor of 3-year postoperative diabetes remission, which was validated in the prospective phase. There was a significant difference in the postoperative body composition changes between non-diabetic and diabetic patients only in trunk mass. CONCLUSION: Preoperative C-peptide levels can be useful for predicting T2DM remission after RYGB. Trunk mass is the most important difference in postoperative body composition changes between non-diabetic and diabetic patients.

Low rate of latent autoimmune diabetes in adults (LADA) in patients followed for type 2 diabetes: A single centers experience in Turkey

ABSTRACT Objective In this study, we aimed to determine the frequency of and the clinical and metabolic features of patients with latent autoimmune diabetes in adults (LADA) at a single center in Turkey. Subjects and methods Patients over 30 years of age diagnosed with type 2 diabetes who did not require insulin for a minimum of 6 months following diagnosis were included. Data from 324 patients (163 women; 161 men), with a mean age of 54.97 ± 7.53 years, were analyzed in the study. Levels of antibodies to glutamate decarboxylase (anti-GAD) were measured in all patients, and LADA was diagnosed in patients testing positive for anti-GAD antibodies. Results Anti-GAD positivity was identified in 5 patients (1.5%). Family history of diabetes, body mass index (BMI), age, sex distribution, insulin resistance, serum triglycerides, high-density lipoprotein, and low-density lipoprotein were similar in the LADA and type 2 diabetes patients. Median HbA1c was significantly higher (10.8% vs. 7.38%, p = 0.002) and fasting C-peptide was lower (0.75 ng/mL vs. 2.82 ng/mL, p = 0.009) in patients with LADA compared to in those with type 2 diabetes. Among the 5 patients with LADA, 4 were positive for antithyroid peroxidase antibodies. The median disease duration was relatively shorter among patients with LADA (4 years vs. 7 years, p = 0.105). Conclusion We observed a LADA frequency of 1.5% among Turkish patients followed for type 2 diabetes. The presence of obesity and metabolic syndrome did not exclude LADA, and patients with LADA had worse glycemic control than patients with type 2 diabetes did.

Effect of High β-glucan Barley on Postprandial Blood Glucose and Insulin Levels in Type 2 Diabetic Patients

Factors Related to Blood Intact Incretin Levels in Patients with Type 2 Diabetes Mellitus

BACKGROUND: We performed this study to identify factors related to intact incretin levels in patients with type 2 diabetes mellitus (T2DM). METHODS: We cross-sectionally analyzed 336 patients with T2DM. Intact glucagon-like peptide 1 (iGLP-1) and intact glucose-dependent insulinotropic polypeptide (iGIP) levels were measured in a fasted state and 30 minutes after ingestion of a standard mixed meal. The differences between 30 and 0 minute iGLP-1 and iGIP levels were indicated as ΔiGLP-1 and ΔiGIP. RESULTS: In simple correlation analyses, fasting iGLP-1 was positively correlated with glucose, C-peptide, creatinine, and triglyceride levels, and negatively correlated with estimated glomerular filtration rate. ΔiGLP-1 was positively correlated only with ΔC-peptide levels. Fasting iGIP showed positive correlations with glycosylated hemoglobin (HbA1c) and fasting glucose levels, and negative correlations with ΔC-peptide levels. ΔiGIP was negatively correlated with diabetes duration and HbA1c levels, and positively correlated with Δglucose and ΔC-peptide levels. In multivariate analyses adjusting for age, sex, and covariates, fasting iGLP-1 levels were significantly related to fasting glucose levels, ΔiGLP-1 levels were positively related to ΔC-peptide levels, fasting iGIP levels were related to fasting C-peptide levels, and ΔiGIP levels were positively related to ΔC-peptide and Δglucose levels. CONCLUSION: Taken together, intact incretin levels are primarily related to C-peptide and glucose levels. This result suggests that glycemia and insulin secretion are the main factors associated with intact incretin levels in T2DM patients.

Serum R-Spondin 1 Is a New Surrogate Marker for Obesity and Insulin Resistance

BACKGROUND: Recent in vivo studies indicated that R-spondin 1 (RSPO1) regulates food intake and increases insulin secretion, but its role in humans remains unknown. This study investigated the association between serum levels of RSPO1 and diverse metabolic parameters in humans. METHODS: The study population consisted of 43 subjects with newly diagnosed diabetes mellitus, and 79 non-diabetic participants. Serum levels of RSPO1 were measured using the enzyme-linked immunosorbent assay. The relationships between circulating RSPO1 and diverse metabolic parameters were analyzed. RESULTS: Circulating RSPO1 levels increased to a greater extent in the obese group than in the lean group. Moreover, serum levels of RSPO1 were higher in the insulin-resistant group than in the insulin-sensitive group. Serum levels of RSPO1 were significantly correlated with a range of metabolic parameters including body mass index, fasting C-peptide, homeostasis model assessment of insulin resistance index, and lipid profile. Moreover, levels were significantly associated with insulin resistance and obesity in non-diabetic subjects. CONCLUSION: This study demonstrated the association between serum levels of RSPO1 and a range of metabolic parameters in humans. Serum levels of RSPO1 are significantly related to obesity and insulin resistance, although the precise mechanisms remain unknown.

Favorable Glycemic Control with Once-Daily Insulin Degludec/Insulin Aspart after Changing from Basal Insulin in Adults with Type 2 Diabetes

BACKGROUND: Conflicting results have been reported on the efficacy of insulin degludec/insulin aspart (IDegAsp) compared to basal insulin in type 2 diabetes. We investigated the effects of changing basal insulin to IDegAsp on glycemic control and sought to identify factors related to those effects.METHODS: In this retrospective study of patients from three referral hospitals, patients with type 2 diabetes using basal insulin with hemoglobin A1c (HbA1c) levels less than 11.0% were enrolled. Basal insulin was replaced with IDegAsp, and data were analyzed from 3 months before to 3 months after the replacement.RESULTS: Eighty patients were recruited (52.5% male; mean age, 67.0±9.8 years; mean duration of diabetes, 18.9±8.5 years; mean HbA1c, 8.7%±1.0%). HbA1c levels increased during 3 months of basal insulin use, but significantly decreased after changing to IDegAsp (8.28%±1.10%, P=0.0001). The reduction was significant at 6 months in 35 patients whose longer-term data were available. Patients with a measured fasting plasma glucose (m-FPG) lower than their predicted FPG (p-FPG) by regression from HbA1c showed a significant HbA1c reduction caused by the change to IDegAsp, even without a significantly increased insulin dose. However, patients whose m-FPG was higher than their p-FPG did not experience a significant HbA1c reduction, despite a significantly increased insulin dose. Furthermore, the HbA1c reduction caused by IDegAsp was significant in patients with low fasting C-peptide levels and high insulin doses.CONCLUSION: We observed a significant glucose-lowering effect by replacing basal insulin with IDegAsp, especially in patients with a lower m-FPG than p-FPG.

Early Assessment of the Risk for Gestational Diabetes Mellitus: Can Fasting Parameters of Glucose Metabolism Contribute to Risk Prediction?

BACKGROUND: An early identification of the risk groups might be beneficial in reducing morbidities in patients with gestational diabetes mellitus (GDM). Therefore, this study aimed to assess the biochemical predictors of glycemic conditions, in addition to fasting indices of glucose disposal, to predict the development of GDM in later stage and the need of glucose-lowering medication.METHODS: A total of 574 pregnant females (103 with GDM and 471 with normal glucose tolerance [NGT]) were included. A metabolic characterization was performed before 15+6 weeks of gestation by assessing fasting plasma glucose (FPG), fasting insulin (FI), fasting C-peptide (FCP), and glycosylated hemoglobin (HbA1c). Thereafter, the patients were followed-up until the delivery.RESULTS: Females with NGT had lower levels of FPG, FI, FCP, or HbA1c at the early stage of pregnancy, and therefore, showed an improved insulin action as compared to that in females who developed GDM. Higher fasting levels of FPG and FCP were associated with a higher risk of developing GDM. Moreover, the predictive accuracy of this metabolic profiling was also good to distinguish the patients who required glucose-lowering medications. Indices of glucose disposal based on C-peptide improved the predictive accuracy compared to that based on insulin. A modified quantitative insulin sensitivity check index (QUICKIc) showed the best differentiation in terms of predicting GDM (area under the receiver operating characteristics curve [ROC-AUC], 72.1%) or need for pharmacotherapy (ROC-AUC, 83.7%).CONCLUSION: Fasting measurements of glucose and C-peptide as well as the surrogate indices of glycemic condition could be used for stratifying pregnant females with higher risk of GDM at the beginning of pregnancy.

Clinical features for hospitalized type 1 diabetic patients with different ages of onset / 中南大学学报(医学版)

To explore the clinical features and complications of 545 hospitalized type 1 diabetic patients.
 Methods: All data of 545 patients with typical type 1 diabetes (T1DM) who were hospitalized in the Department of Endocrinology, the Second Xiangya Hospital, Central South University were collected. The data were analyzed retrospectively to explore the clinical features and complications. Clinical and biochemical characteristics were analyzed through comparison between different subgroups according to the onset age (≤13 years old, 14-29 years old, ≥30 years old).
 Results: The median onset age of T1DM patients was 27.0 (15.0, 40.0) years, and the middle-onset was 42.1%. Among the 3 groups, the proportion of female (58.0%) was the highest in the ≤13 years old group, concomitant with the lowest SBP and serum creatinine levels as well as the lowest incidence of all microvascular complications (21.0% of diabetic nephropathy, 23.3% of diabetic retinopathy, 34.1% of diabetic peripheral neuropathy; all P<0.05). Moreover, the fasting C peptide and peak C peptide levels were the lowest in ≥30 years old group compared with the other two groups, and the incidence of ketosis (33.5%) and all macrovascular complications were the highest among the three groups (all P<0.05).
 Conclusion: There are about half of the hospitalized patients with T1DM whose onset ages are ≥30 years. The incidence of ketosis at the onset and the risk for various microvascular and macrovascular complications after onset are higher than those with the onset age <30 years.

Long-limb Roux-en-Y Reconstruction after Subtotal Gastrectomy to Treat Severe Diabetic Gastroparesis

The role of surgical intervention in patients with diabetic gastroparesis is unclear. We report a case of a 37-year-old man with a history of recurrent episodes of vomiting and long-standing type 2 diabetes mellitus. Esophagogastroduodenoscopy did not reveal any findings of reflux esophagitis or obstructive lesions. A gastric emptying time scan showed prolonged gastric emptying half-time (344 minutes) indicating delayed gastric emptying. Laboratory tests revealed elevated fasting serum glucose and glycosylated hemoglobin (HbA1c, 12.9%) and normal fasting C-peptide and insulin levels. We performed Roux-en-Y reconstruction after subtotal gastrectomy to treat gastroparesis and improve glycemic control, and the patient showed complete resolution of gastrointestinal symptoms postoperatively. Barium swallow test and gastric emptying time scan performed at follow-up revealed regular progression of barium and normal gastric emptying. Three months postoperatively, his fasting serum glucose level was within normal limits without the administration of insulin or oral antidiabetic drugs with a reduced HbA1c level (6.9%). Long-limb Roux-en-Y reconstruction after subtotal gastrectomy may be useful to treat severe diabetic gastroparesis by improving gastric emptying and glycemic control.

Efficacies of Stem Cell Therapies for Functional Improvement of the β Cell in Patients with Diabetes: A Systematic Review of Controlled Clinical Trials

BACKGROUND AND OBJECTIVES: This study was performed to investigate whether stem cell therapy enhances β cell function by meta-analysis with proper consideration of variability of outcome measurements in controlled trial of type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM) patients. METHODS: A systematic search was performed from inception to January 2018 in PubMed, EMBASE, and Cochrane databases. β cell function was assessed by stimulated C-peptide, fasting C-peptide, normal glycosylated hemoglobin levels (HbA1C), and exogenous insulin dose patterns. The quality of the studies were assessed by both the Cochrane Collaboration's Risk of Bias (ROB) for Randomized controlled trials and the Risk of Bias in Non-randomized Studies of Interventions (ROBINS-I) for non-randomized controlled trials. RESULTS: From the selected final 15 articles, total of 16 trials were analyzed. There were 6 T1DM trials (total 153 cases) and 10 T2DM trials (total 457 cases). In T2DM patients, the changes in stimulated C-peptide, HbA1c, and exogenous insulin dose versus baseline showed a favorable pattern with a significant heterogeneity in stem cell therapy. In T1DM, there was no significant difference between control group and stem cell therapy group in three indicators except for HbA1c. Most of the studies were rated as having high risk of bias in the quality assessment. CONCLUSIONS: The stem cell therapy for DM patients is not effective in T1DM but seems to be effective in improving the β cell function in T2DM. However the observed effect should be interpreted with caution due to the significant heterogeneity and high risk of bias within the studies. Further verification through a rigorously designed study is warranted.

Importance of Adherence to Personalized Diet Intervention in Obesity Related Metabolic Improvement in Overweight and Obese Korean Adults

We investigated weight loss effect of personalized diet education in overweight/obese Korean adults. Overweight/obese Korean adults (body mass index [BMI] ≥ 23 kg/m2 or waist circumference [WC] ≥ 90 cm for men, ≥ 85 cm for women) were recruited, and 40 participants who completed the 10-week intervention were finally included in the analyses. At first visit, study participants (small group with individual counseling) were educated for optimal diet by clinical dietitian, and checked for their compliance through telephone/text message every 1–2 week during the intervention. Anthropometric and biochemical parameters and dietary intake were investigated. Body weight, BMI, WC, and body fat mass were significantly reduced in whole participants. Hemoglobin A1c, insulin, and low-density lipoprotein cholesterol were also significantly decreased after the intervention. Total energy intake (EI) during the intervention was not significantly decreased compared to the baseline value, but the proportions of energy derived from macronutrients were within the ranges recommended by 2015 Dietary Reference Intake for Koreans. Based on actual EI, participants were classified into high-adherence (HA) (prescribed EI ± 25%, n = 29), low-adherence I (LA-I) ( 125% of prescribed EI, n = 4). Only HA group showed significant improvements in anthropometric parameters, glycemic control and lipid profile. Interestingly, LA-I group showed significant increases in glucose, insulin, C-peptide and insulin resistance. In conclusion, a shift from overweight/obesity to healthy weight can be accomplished by high adherence to personalized diet modification, not by EI reduction.

The role of C-peptide in the attenuation of outcomes of diabetic kidney disease: a systematic review and meta-analysis / Emprego do peptídeo C na atenuação dos desfechos da doença renal do diabetes: uma revisão sistemática e meta-análise

ABSTRACT Introduction: Preclinical trials have shown that C-peptide may contribute to the treatment of diabetic kidney disease (DKD). This systematic review and meta-analysis aimed to assess the use of C-peptide in attenuating the outcomes of DKD. Methods: Searches were made on databases PubMed, Web of Science, and Scielo for in vivo clinical and preclinical trials written in English, Portuguese or Spanish that looked into the use of C-peptide in the attenuation of the outcomes of DKD. Results: Twelve papers were included in this review, one clinical and eleven preclinical trials. In the clinical trial, DKD patients given C-peptide had lower levels of albuminuria than the subjects in the control group, but glomerular filtration rates were not significantly different. The main parameters assessed in the preclinical trials were glomerular filtration rate (six trials) and albuminuria (five trials); three trials described less hyperfiltration and three reported lower levels of albuminuria in the groups offered C-peptide. The meta-analysis revealed that the animals given C-peptide had lower glomerular volumes and lower urine potassium levels than the groups not given C-peptide. Conclusion: The results of the studies included in the systematic review diverged. However, the meta-analysis showed that the animals given C-peptide had lower glomerular volumes and lower urine potassium levels.

RESUMO Introdução: Estudos pré-clínicos demonstraram que o peptídeo C pode contribuir para a terapia da doença renal do diabetes (DRD). Esta revisão sistemática e meta-análise teve como objetivo avaliar a utilidade do peptídeo C na atenuação dos desfechos da DRD. Métodos: Foram utilizadas as bases de dados PubMed, Web of Science e Scielo, e definidos como critérios de elegilibilidade ensaios clínicos e pré-clínicos in vivo, redigidos em inglês, português ou espanhol, que avaliaram a utilidade do peptídeo C na atenuação dos desfechos da DRD. Resultados: Doze artigos foram incluídos nesta revisão: onze ensaios pré-clínicos e um ensaio clínico. No ensaio clínico, os pacientes com DRD que receberam peptídeo C apresentaram menor albuminúria do que os do grupo controle, contudo não houve diferença significativa em relação à taxa de filtração glomerular. Os principais parâmetros avaliados pelos estudos pré-clínicos foram taxa de filtração glomerular (seis estudos) e albuminúria (cinco estudos), dos quais três encontraram menor hiperfiltração e três verificaram menor albuminúria no grupo que recebeu peptídeo C. A meta-análise demonstrou que os animais que receberam peptídeo C apresentaram menor volume glomerular e menor excreção urinária de potássio em comparação com aqueles que não o receberam. Conclusão: Os resultados dos estudos incluídos nesta revisão sistemática foram divergentes. Contudo, a meta-análise demonstrou que a administração do peptídeo C em animais resultou em menor volume glomerular e menor excreção urinária de potássio.

The characteristics of blood glucose fluctuations in patients with fulminant type 1 diabetes mellitus in the stable stage

ABSTRACT Objective: The aim was to characterize blood glucose fluctuations in patients with fulminant type 1 diabetes (FT1DM) at the stable stage using continuous blood glucose monitoring systems (CGMSs). Subjects and methods: Ten patients with FT1DM and 20 patients with classic type 1 diabetes mellitus (T1DM) (the control group) were monitored using CGMSs for 72 hours. Results: The CGMS data showed that the mean blood glucose (MBG), the standard deviation of the blood glucose (SDBG), the mean amplitude glycemic excursions (MAGE), the blood glucose areas and the percentages of blood glucose levels below 13.9 mmol/L were similar between the two groups. However, the percentage of blood glucose levels below 3.9 mmol/L was significantly higher in the FT1DM group compared to the T1DM group (p < 0.05). The minimum (Min) blood glucose level in the FT1DM group was significantly lower than that of the T1DM group (p < 0.05). Patients with FT1DM had severe dysfunction of the islet beta cells and alpha cells compared to patients with T1DM, as indicated by lower C-peptide values and higher glucagon/C-peptide values. Conclusion: In conclusion, patients with FT1DM at the stable stage were more prone to hypoglycemic episodes as recorded by CGMSs, and they had a greater association with severe dysfunction of both the beta and alpha islet cells compared to patients with T1DM.

Etiologia da hiperglicemia em crianças críticas e o impacto da disfunção de órgãos / Etiology of hyperglycemia in critically ill children and the impact of organ dysfunction

RESUMO Objetivo: Verificar a incidência da hiperglicemia de estresse em crianças em condição grave e investigar a etiologia da hiperglicemia com base em um modelo de avaliação da homeostasia. Métodos: Estudo prospectivo de coorte, conduzido em uma unidade de terapia intensiva pediátrica da Cairo University, que incluiu 60 crianças com doença grave e 21 controles saudáveis. Utilizaram-se os níveis séricos de glicose, insulina e peptídeo C, avaliados em até 24 horas após a admissão. O modelo de avaliação da homeostasia foi utilizado para analisar a função das células beta e a sensibilidade à insulina. Resultados: A hiperglicemia foi estimada em 70% dos pacientes. Valores de glicemia ≥ 180mg/dL se associaram com desfechos piores. Os níveis de glicemia se correlacionaram de forma positiva com o Pediatric Risk for Mortality (PRISM III) e o número de órgãos com disfunção (p = 0,019 e p = 0,022, respectivamente), enquanto os níveis de insulina se correlacionaram de forma negativa com o número de órgãos com disfunção (r = -0,33; p = 0,01). O modelo de avaliação da homeostasia revelou que 26 (43,3%) das crianças em condições graves tinham baixa função de células beta e 18 (30%) baixa sensibilidade à insulina. Detectou-se patologia combinada em apenas dois (3,3%) pacientes. Baixa função de células beta se associou de forma significante com a presença de disfunção de múltiplos órgãos, disfunção respiratória, cardiovascular e hematológica, e presença de sepse. Conclusões: A disfunção de células beta pareceu ser prevalente em nossa coorte e se associou com disfunção de múltiplos órgãos.

ABSTRACT Objective: This study aimed to study the incidence of stress hyperglycemia in critically ill children and to investigate the etiological basis of the hyperglycemia based on homeostasis model assessment. Methods: This was a prospective cohort study in one of the pediatric intensive care units of Cairo University, including 60 critically ill children and 21 healthy controls. Serum blood glucose, insulin, and C-peptide levels were measured within 24 hours of admission. Homeostasis model assessment was used to assess β-cell function and insulin sensitivity. Results: Hyperglycemia was estimated in 70% of patients. Blood glucose values ≥ 180mg/dL were associated with a poor outcome. Blood glucose levels were positively correlated with Pediatric Risk for Mortality (PRISM III) score and number of organ dysfunctions (p = 0.019 and p = 0.022, respectively), while insulin levels were negatively correlated with number of organ dysfunctions (r = −0.33, p = 0.01). Homeostasis model assessment revealed that 26 (43.3%) of the critically ill patients had low β-cell function, and 18 (30%) had low insulin sensitivity. Combined pathology was detected in 2 (3.3%) patients only. Low β-cell function was significantly associated with the presence of multi-organ dysfunction; respiratory, cardiovascular, and hematological dysfunctions; and the presence of sepsis. Conclusions: β-Cell dysfunction appeared to be prevalent in our cohort and was associated with multi-organ dysfunction.

Serum Soluble Epidermal Growth Factor Receptor Level Increase in Patients Newly Diagnosed with Type 2 Diabetes Mellitus

We analyzed circulating soluble epidermal growth factor receptor (sEGFR) levels in humans. Serum sEGFR levels were higher in subjects with newly diagnosed type 2 diabetes mellitus compared with controls. Serum sEGFR was positively correlated with glycosylated hemoglobin and serum glucose and negatively correlated with serum insulin and C-peptide levels.