Insulin resistance is a hallmark of type 2 diabetes and obesity while the mechanism remains unclear. Current therapy to treat type 2 diabetes is metformin, the 5'-monopho sphate-activated protein kinase (AMPK) activator, owing to the ability to augment peripheral glucose uptake. However, metformin also displays limitations, as AMPK activation remains intact and regular in most type 2 diabetes and metformin does not seem to facilitate peripheral insulin resistance. Evidence has shown that PI3K-Akt/PKB pathway could be induced via insulin and act as an important effector. Akt/PKB is capable of inducing a great number of downstream molecules, such as translocating glucose transporters GLUTs to the cell membrane thus increase glucose uptake. Hence, any defect in Akt/PKB pathway along with the downstream molecules could lead to insulin resistance. Inositol pyrophosphates, synthesized by inositol hexakisphosphate (IP6) kinase 1 (IP6K1) and competitive with 3,4,5-bisphosphate (PIP3) to bind the PH domain of Akt/PKB, demonstrate the ability to inhibit Akt signaling. In addition, IP6K1 knockout mice present increased insulin sensitivity and obesity resistance, indicating a novel therapeutic target in confronting insulin resistance. Taken together, we conclude that Akt activation is another potential strategy to ameliorate insulin resistance. (C) 2017 Published by Elsevier Ireland Ltd.
This meta-analysis of randomized controlled trials (RCTs) aims to investigate how to perform better interventions targeting modifiable risk factors of diabetic retinopathy (DR) to prevent and control DR in patients with type 2 diabetes by comparing different intervention types and follow-up intervals. Literature published before June 1st, 2019 were searched on Pubmed, Embase and ScienceDirect. RCTs targeting modifiable risk factors of DR (including blood glucose, blood pressure, lipid, dietary, physical activity and smoking) were selected by two reviewers and double checked for accuracy. Random effects models were estimated to calculate pooled Odds Ratios (OR). Twenty-two RCTs (n = 22,511) were included. In general, interventions targeting modifiable risk factor of DR reduced the risk of developing DR (I-2 = 26.7%; OR = 0.60; 95% CI 0.45 to 0.79) and DR worsening (I-2 = 0.0%; OR = 0.62; 95% CI 0.47 to 0.80; P < 0.001). Multifactorial interventions had better effect on reducing the risk of development and progression of DR in comparison with other interventions, while only blood-pressure-control interventions showed significant effect on slowing down DR worsening. Additionally, interventions with follow-up >5 years had better effect on reduction of DR development, and interventions with follow-up >2 years had better effect on reducing the risk of DR worsening. (C) 2019 The Authors. Published by Elsevier B.V. This is an open access article under the CC BYNC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Aim: Circadian rhythm controls a wide variety of physiological processes in the body. Disruption of the circadian clock in metabolic tissues may increase the risk of diabetes, obesity, and metabolic syndrome. The following study investigated whether the expression of clock genes of peripheral blood cells is impaired in type 2 diabetes (DT2) and whether inflammatory markers are associated with circadian clock gene expression in DT2 patients. Materials and methods: Blood samples were obtained from 36 DT2 patients and 14 nondiabetic volunteers. Transcript levels of circadian clock genes were analyzed using real-time quantitative PCR; plasma inflammatory markers were measured by ELISA or clinical laboratory test. Results: The CLOCK, BMAL1, PER1, CRY1 and CRY2 mRNA levels were decreased in the diabetic patients. In addition, HbA1c levels were negatively correlated with BMAL1, PER1 and CRY1 mRNA levels. The levels of IL-6, TNF-alpha and CRP were higher in diabetic subjects compared to control subjects. Impaired expression of circadian clock gene was interrelated with the elevated levels of plasma IL-6 and TNF. Moreover, amultiple linear regression showed that plasma IL-6 level was correlated with impaired expression of circadian clock gene. Conclusions: Circadian clock genes are reduced in peripheral leucocytes of DT2 patients. Furthermore, impaired expression of circadian clock gene are interrelatedwith the elevated levels of plasma inflammatory markers. (C) 2019 Published by Elsevier B.V.
Background: The role of chronic inflammation initiated by persistent hyperglycemia in podocyte injury has attracted increasing attention. The advanced glycation end products (RAGE) receptor-nuclear factor-kappa B (NF-kappa B) signaling pathway is involved in the occurrence of inflammation. We speculate that treatment with human umbilical cord mesenchymal stem cells (hUCMSCs) combined with resveratrol can block this signaling pathway and protect podocyte function. Methods: Non obesity diabetes(NOD) mice were randomly divided into 5 groups: NOD-T1DM, Res, hUCMSCs, hUCMSCs + Res and insulin (INS)groups. Mice without diabetes were classified as NOD control group(NOD group). Blood glucose(BG), blood urea nitrogen(BUN), serum creatinine(SCr), 24-h urine albumin excretion rate (UAER) were measured. The expression of nephrin, WT1 and RAGE, MCP-1 in renal tissues were detected by Western blot, expression of NF-kappa B protein(P65) was determined by immunohistochemistry. Results: The combined treatment of hUCMSCs and Resveratrol can reduce BG, BUN, SCr, 24h UAER, and the expression of the inflammatory factors MCP-1, RAGE and NF-kappa B; increase the number of podocytes and the expression of the podocyte-related proteins nephrin and WT1 in type 1 diabetes mellitus, and improve renal pathological structure. Conclusions: Combining of hUCMSCs and resveratrol can better protect renal podocyte function, and the effects on the reduction of blood glucose and renal injury are better than those obtained by insulin treatment. This indicated that the combination of Res and hUCMSCs may be a novel therapeutic method for the treatment of DN. (C) 2019 Published by Elsevier B.V.
Background: Diabetes mellitus (DM) is a growing public health concern globally, including Ethiopia. Although numerous studies have been published from different parts of Ethiopia, no attempt ismade so far to estimate the burden of DM at the national level. This study aims to estimate the pooled prevalence of DM and its association with hypertension in Ethiopia. Methods: A systematic search was conducted in major databases. Two authors extracted the necessary data and analysis was conducted using STATA version 14. Heterogeneity across the studies was evaluated by Cochran's Q test and I-2 statistics. Results: Eighteen studies with a total of 45,284 participants were included in this review. The pooled prevalence of DM was 4.99% (95% CI: 3.86%, 6.11%). Hypertension was significantly associated with DM (OR: 8.32; 95% CI: 3.05, 22.71). Conclusion: The burden of DM in Ethiopia is considerable, and the association between diabetes and hypertension is significant. Based on the evidence, this review recommends establishing the coordinated national programs that counteract the increasing burden of DM in the country is very essential. In addition, Early hypertension screening should be done in diabetic patients to control co-morbidity and further complications. (C) 2019 Elsevier B.V. All rights reserved.
Objective: Growth differentiation factor 15 (GDF15) has been demonstrated to increase in diabetes as a protective factor. However, studies assessing relationships between GDF15 levels and gestational diabetes mellitus (GDM) are limited. In this study, we aimed to investigate whether GDF15 levels are related to GDM in Chinese subjects. Methods: We included 200 GDM patients and 200 matched normal controls in the second trimester as well as 130 GDM patients and 130 matched normal controls in the third trimester. Serum GDF15 levels of all participants were determined using an enzyme-linked immunosorbent assay (ELISA). Then, according to GDF15 levels, we equally divided the participants in the second and third trimesters into four subgroups respectively. The relationships of serum GDF15 levels with glucolipid metabolism indicators were analyzed. Results: In the third trimester, GDF15 levels were significantly higher in the GDM patients than in the normal controls (P < 0.001). Additionally, fasting blood glucose (FBG), 1-h postprandial glucose (1h-PG), 2-h postprandial glucose (2h-PG), hemoglobin A1C (HbA1c) and area under curve of glucose (AUCG) from the 75-g oral glucose tolerance test (OGTT) were positively associated with GDF15 levels (P < 0.05), even after adjusting for age, pregestational BMI, changes of BMI until the third trimester, gestational age, twin and family history of diabetes. Moreover, GDF15 levels were higher in the third trimester than in the second trimester (P < 0.001). No significant relationships were found between GDF15 levels and glucolipid metabolism in the second trimester (P > 0.05). Conclusions: Serum GDF15 levels were positively correlated with glucose metabolism in the third trimester in Chinese pregnant women. (C) 2019 Elsevier B.V. All rights reserved.
Aims: To determine the prevalence of low faecal elastase-1 (FE-1) (<= 200 mu/g) in type 2 diabetes (T2DM), and to test the hypothesis that pancreatic enzyme replacement therapy (PERT) would reduce postprandial glycaemia after a high-fat, high-carbohydrate meal in T2DM subjects with low FE-1. Methods: Of 109 community-based patients who submitted stool samples, 10 had low FE-1 and 8 were recruited (6 male, 2 female, 67.8 +/- 3.0 years). Participants were given a high-fat, high-carbohydrate meal (718 kcal) with either pancrelipase (50,000 units) or placebo in a randomised, double-blind, crossover fashion. The primary outcome was the difference in postprandial glycaemia following PERT vs placebo, as evaluated by the incremental area under the postprandial plasma glucose curve (iAUC). Secondary outcomes included differences in gastric half-emptying time (T50) measured using scintigraphy, and C-peptide iAUC. Results: The prevalence of low FE-1 in T2DM was 9.2% (95% CI 3.8-14.6%). There was no difference in postprandial glycaemia iAUC (P = 0.38), gastric emptying T50 (P = 0.69) or C-peptide iAUC (P = 0.25) after PERT compared to placebo. Conclusions: Decreased FE-1 has a relatively low prevalence in community-based patients with T2DM, and PERT does not reduce postprandial glycaemia in these patients. Clinical Trial Registration Number: ACTRN12617000349347. (C) 2019 Elsevier B.V. All rights reserved.
Aims: To analyze the trends on diabetes mellitus (DM) healthcare management in Spain. Methods: Retrospective observational study between January 1st 2007 and 31th December 2015 with DM as the principal diagnosis. The main clinical outcome measures were all-cause, in-hospital mortality and 30-day readmissions. We also analyze three Prevention Quality Indicators (PQI) for DM. Results: The number of hospitalization episodes decreased significantly as well as the frequentation rate and average length of stay (Incidence Rate Ratio [IRR] = 0.963, p < 0.001; 0.91, p < 0.001 and 0.986, p < 0.001, respectively). Crude in-hospital mortality and readmissions rates and risk-standardized in-hospital mortality rates (RSMR), however, remained stable (IRR = 0.988, p = 0.073; IRR = 1.003, p = 0.334 and IRR = 0.997, p = 0.116, respectively). A relevant variability in RSMR, both at hospital (Median Odds Ratio 1.49) and regional level, was found. High volume hospitals (>= 105 DM discharges at year) showed better outcomes. High variability was also found in PQI indicators al regional level. Conclusion: The present analysis shows an improvement in hospitalizations related to DM in Spain in the period 2007-2015. There was also a decrease in the frequentation rate and in the average length of stay. These findings are probably explained by quality improvements in the healthcare management of the DM at the ambulatory level. However, there were important differences in the management of diabetic inpatients both at the hospital and the regional level. (C) 2019 Elsevier B.V. All rights reserved.
Aims: Because collagen is fundamental to wound healing and skin formation, collagen-containing dressing materials might be beneficial in treating diabetic foot ulcers (DFU), but supporting evidence is needed. Here, we examined the effectiveness and safety of collagen dressing material in DFU treatment. Methods: This prospective, randomized, placebo-controlled, single-center study included patients with type 1 or 2 diabetes and palpable foot pulse who had Wagner grade 1 or 2 ulcers >= 1.0 cm(2) with no signs of healing for >= 6 weeks. Patients were treated with foam dressing alone (control group) or with a porcine type I collagen dressing material (collagen group). Complete ulcer healing rate was the primary endpoint, and healing velocity and time to 50% size reduction were secondary endpoints. Results: Thirty patients were included (collagen group: 17, control group: 13). There were no significant differences in demographic factors or baseline DFU characteristics. Compared to the control group, the collagen group presented a higher rate of complete healing [82.4% vs. 38.5%, P = .022], faster healing velocity (P < .05), and shorter median time to 50% size reduction (21 versus 42 days; hazard ratio = 1.94, P < .05). Conclusions: Wound management using collagen materials in DFUs showed faster and complete healing rate. (C) 2019 Elsevier B.V. All rights reserved.
Aims: To analyse the correlation of cardiac autonomic neuropathy (CAN), sympathetic and parasympathetic dysfunction with the different diagnostic tools for large and small peripheral nerve fibres in type 2 diabetes mellitus (T2DM). Methods: We included 153 T2DM subjects (92 men) with mean age of 64.4 years. CAN, as well as sympathetic and parasympathetic dysfunction were diagnosed by the Ewing's cardiovascular reflex tests. Vibration perception threshold (VPT), monofilament, Ipswich Touch test, automated sural nerve conduction study and neuropathy disability score (NDS) evaluated large and small peripheral nerve fibre function. Results: CAN (adjusted odds ratio [aOR]: 44.57), parasympathetic (aOR: 18.40) and sympathetic dysfunction (aOR: 5.50) correlated with measures of small fibre function evaluated by pinprick sensation and temperature perception. Among tools for large nerve fibres, positive correlation was shown between: (1) CAN and abnormal VPT (aOR: 16.78), (2) parasympathetic dysfunction and abnormal VPT (aOR: 39.47). Conclusions: CAN and parasympathetic dysfunction correlate with peripheral neuropathy, especially when the latter is assessed through VPT and measures of small fibre function as evaluated by pinprick sensation and temperature perception. The latter additionally correlate with sympathetic nervous system impairment. (C) 2019 Elsevier B.V. All rights reserved.
Aims: To explore the information-seeking experiences of patients with Type 2 diabetes and how these influenced self-management behaviours. Methods: We interviewed 18 patients with Type 2 Diabetes attending outpatient diabetes centers in South Western Sydney. Data were analyzed thematically. Results: Patients described a number of challenges they faced when seeking information about diabetes self-management. One major challenge was receiving inconsistent and insufficient information from healthcare professionals, which consequently undermined patients' ability to self-manage diabetes. This became a disincentive in carrying out self-management tasks, and led to confusion and mistrust regarding the veracity of information received. Participants also described finding reliable information, and difficulty understanding and accessing relevant information as challenges. Medical jargon and lack of comprehensive explanations exacerbated knowledge deficits compounded by the complex maze of internet resources that some patients accessed. In response to what they perceived as confusing or inconsistent information, some patients followed "their own way" of managing their diabetes. Conclusions: Inconsistent information not tailored to the needs of patients adversely affects self-management. Taking time to provide simple explanations and assisting patients in navigating reliable web resources is becoming a vital role of healthcare professionals to reduce knowledge gaps in patients with low health literacy. Crown Copyright (C) 2019 Published by Elsevier B.V. All rights reserved.
Aim: To validate the Diabetes Medication Adherence Scale (DMAS-7), determine its concordance with another validated scales and to assess factors affecting medication adherence. Methods: A cross-sectional study was conducted on a sample of Lebanese patients with diabetes using a questionnaire. The level of adherence was measured using the DMAS-7 and the Lebanese Medication Adherence Scale (LMAS-14). Bivariate and multivariate analyses were conducted, and the scale was validated in terms of reliability, predictive ability, and construct validity using SPSS version 19. Results: Out of 300 eligible patients, the rate of adherence was 33.7%. Measures of validity showed good reliability (Cronbach alpha = 0.627), and good construct validity with LMAS-14 (Spearman's rho = 0.846; Cohen's kappa = 0.711). DMAS-7 was found to be both correlated with LMAS-14 (ICC average measure = 0.675; p-value <0.001) in addition to possessing a better predictive value. Thus, DMAS-7 showed to have good concordance and increased validity compared to LMAS-14. Having an optimal glycated hemoglobin (HbA1C) (OR = 0.779; p = 0.001) and performing regular physical activity (OR 2.328; p = 0.002) increased medication adherence. Conclusion: The DMAS-7 showed to be reliable and valid instrument superior to LMAS-14 in predicting adherence levels to oral anti-diabetic medications, and thus can be used to achieve better glycemic outcomes. (C) 2019 Elsevier B.V. All rights reserved.
Aims: Dipeptidyl peptidase 4 inhibitors (DPP4Is) can increase sympathetic activity. We aimed to evaluate the direct association between serum DPP4 activity and sympathetic activity in humans. Methods: Fasting serum DPP4 activity and plasma levels of catecholamines and their metabolites were measured in 211 patients with type 2 diabetes mellitus (T2DM) treated with DPP4I (n = 146) or non-DPP4I therapy (n = 65) and in healthy control subjects (n = 30). Results: Although there were no differences in plasma levels of catecholamines and their metabolites between the DPP4I and non-DPP4I groups, the levels in both of these groups were lower than those in the healthy control group. In DPP4I-treated patients, serum DPP4 activity showed an inverse correlation with plasma levels of norepinephrine (NE) (r = -0.339, p < 0.01), metanephrine (MET) (r = -0.251, p < 0.01) and normetanephrine (r = -0.312, p < 0.001). In addition, plasma MET level showed a weak inverse correlation with serum DPP4 activity in the combined T2DM group. In DPP4I-treated patients, the inverse correlation between DPP4 activity and plasma NE remained significant even after multiple adjustments. Conclusions: Our results suggest that although sympathetic activity is lower in patients with T2DM, the greater the suppression of DPP4 activity by DPP4I therapy, the greater the increase in sympathetic activity is, which may have clinical implications in high risk T2DM patients. (C) 2019 Elsevier B.V. All rights reserved.
Better knowledge on incidence, prevalence and clinical manifestations is needed for planning diabetes care in Sub Saharan Africa. Aims: To find a crude incidence/prevalence of diabetes in children and young adults in a low resource setting, classify the diabetes and audit the health record keeping. Methods: A retrospective observational study based on medical recordings 2010-2016. Target population was children and adolescent registered in Changing Diabetes in Children (CDiC) or Life for a Child (LFAC) programs for children with T1DM and diagnosed at 5 diabetes clinics in three geographical regions of Tanzania. 604 patients' files were available from five hospitals. Results: 336/604 files covered patients <15 years of age at diagnosis. The prevalence of diabetes <15 years of age ranged from 10.1 to 11.9 per 100,000 children and the annual incidence 1.8-1.9/100,000 children, with peak incidence at 10-14 years. A lot of data were missing. The great majority of the patients presented with typical signs and symptoms of T1D, 83.7% with plausible ketoacidosis (DKA). Conclusions: Diabetes incidence and prevalence is still low. T1D seems to dominate with very high frequency of DKA at diagnosis. Increased awareness of diabetes both in health care and community is needed. (C) 2019 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).