Metabolite profiling and biochemical investigation of the antidiabetic potential of Loranthus pulverulentus Wall n-butanol fraction in diabetic animal models.

ETHNOPHARMACOLOGICAL RELEVANCE: Globally, 537 million individuals are estimated to have diabetes. The traditional use of herbs for ameliorating diabetes symptoms is a common practice in Pakistan and use of Loranthus pulverulentus Wall (L. pulverulentus) by local people in Azad Jammu and Kashmir has been reported. AIM OF THE STUDY: In the present study, the antidiabetic potential of standardized n-butanol fraction of leaves of L. pulverulentus Wall, which is a parasite of Dalbergia sisso Roxb was assessed in both alloxan (ALX) and streptozotocin (STZ) diabetic animal models. MATERIALS AND METHODS: Chemical characterization of BF was performed using HPLC, GCMS and UHPLC-MS. The effect of the fraction (250 mg/kg) on insulin, plasma free fatty acids, L-lactate, pyruvate, MDA, HbA1c and glycogen levels in ALX and STZ animal models was determined. Liver and renal profiles were analyzed in the STZ model. Toxicological studies were performed by hemolytic, Ames mutagenicity, DNA protection, and thrombolytic assays. Histopathological analysis of the pancreas, liver, and kidney was performed. RESULTS: BF demonstrated highly significant (p < 0.001) antidiabetic potential in both diabetic models. BF significantly (p < 0.05) improved OGTT results in alloxanized diabetic mice and blocked the absorption of glucose from the gut. A significant (p < 0.001) increase in insulin levels and glycogen content in liver tissue and a decrease in plasma FFA, MDA, HbA1c, L-lactate, and pyruvate levels in STZ-diabetic mice were recorded. GC-MS and chromatographic analysis showed the presence of catechin, eugenol, longifolene, caryophyllene, Ar-tumerone and Geranyl-alpha-terpinene. Various metabolites with antidiabetic potential, including 4-hydroxycinnamyl alcohol 4-D-glucoside, zingerone glucoside, trans-trismethoxy resveratrol-d4, epigallocatechin 3-O-cinnamate, and ß-glucogallin, were identified using UHPLC-MS. Animals treated with BF showed marked improvements in cellular structures of the pancreas, liver and kidneys. This fraction is non-mutagenic and protects the DNA. CONCLUSION: The experimental fraction contained potential antidiabetic bioactive compounds responsible for alleviating diabetes-associated biochemical dysregulation. The fraction increased insulin levels and enhanced glycogen storage in muscles and the liver. It blocked glucose absorption from the intestine and substantially decreased HbA1c, lactate, pyruvate, free fatty acids, lipid, liver and kidney damage. Therefore, the use of BF for the treatment of type-2 diabetes may be beneficial.

Implementing Innovative Approaches to Improve Health Care Delivery Systems for Integrating Communicable and Non-Communicable Diseases Using Tuberculosis and Diabetes as a Model in Tanzania.

Background: Many evidence-based health interventions, particularly in low-income settings, have failed to deliver the expected impact. We designed an Adaptive Diseases Control Expert Programme in Tanzania (ADEPT) to address systemic challenges in health care delivery and examined the feasibility, acceptability and effectiveness of the model using tuberculosis (TB) and diabetes mellitus (DM) as a prototype. Methods: This was an effectiveness-implementation hybrid type-3 design that was implemented in Dar es Salaam, Iringa and Kilimanjaro regions. The strategy included a stepwise training approach with web-based platforms adapting the Gibbs' reflective cycle. Health facilities with TB services were supplemented with DM diagnostics, including glycated haemoglobin A1c (HbA1c). The clinical audit was deployed as a measure of fidelity. Retrospective and cross-sectional designs were used to assess the fidelity, acceptability and feasibility of the model. Results: From 2019-2021, the clinical audit showed that ADEPT intervention health facilities more often identified median 8 (IQR 6-19) individuals with dual TB and DM, compared with control health facilities, median of 1 (IQR 0-3) (p = 0.02). Likewise, the clinical utility of HbA1c on intervention sites was 63% (IQR:35-75%) in TB/DM individuals compared to none in the control sites at all levels, whereas other components of the standard of clinical management of patients with dual TB and DM did not significantly differ. The health facilities showed no difference in screening for additional comorbidities such as hypertension and malnutrition. The stepwise training enrolled a total of 46 nurse officers and medical doctors/specialists for web-based training and 40 (87%) attended the workshop. Thirty-one (67%), 18 nurse officers and 13 medical doctors/specialists, implemented the second step of training others and yielded a total of 519 additional front-line health care workers trained: 371 nurses and 148 clinicians. Overall, the ADEPT model was scored as feasible by metrics applied to both front-line health care providers and health facilities. Conclusions: It was feasible to use a stepwise training and clinical audit to support the integration of TB and DM management and it was largely acceptable and effective in differing regions within Tanzania. When adapted in the Tanzania health system context, the model will likely improve quality of services.

Factors associated with higher hemoglobin A1c and type 2 diabetes-related costs: Secondary data analysis of adults 18 to 64 in Texas with commercial insurance.

OBJECTIVE: This study will identify factors associated with higher hemoglobin A1c (A1c) values and diabetes-related costs among commercially insured adults in Texas diagnosed with type 2 diabetes. RESEARCH DESIGN AND METHODS: This secondary data analysis was based on claims data from commercially insured individuals 18-64 years of age residing in Texas with diagnosed type 2 diabetes during the 2018-2019 study period. The final analysis sample after all the exclusions consisted of 34,992 individuals. Measures included hemoglobin A1c, diabetes-related costs, Charlson Comorbidity Index, diabetes-related complications, rurality and other socioeconomic characteristics. Longitudinal A1c measurements were modeled using age, sex, rurality, comorbidity, and diabetes-related complications in generalized linear longitudinal regression models adjusting the observation time, which was one of the 8 quarters in 2018 and 2019. The diabetes-related costs were similarly modeled in both univariable and multivariable generalized linear longitudinal regression models adjusting the observation time by calendar quarters and covariates. RESULTS: The median A1c value was 7, and the median quarterly diabetes-related cost was $120. A positive statistically significant relationship (p = < .0001) was found between A1c levels and diabetes-related costs, although this trend slowed down as A1c levels exceeded 8.0%. Higher A1c values were associated with being male, having diabetes-related complications, and living in rural areas. Higher costs were associated with higher A1c values, older age, and higher Charlson Comorbidity Index scores. CONCLUSION: The study adds updated analyses of the interrelationships among demographic and geographic factors, clinical indicators, and health-related costs, reinforcing the role of higher A1c values and complications as diabetes-related cost drivers.

The Effect of Residual Gastric Volume on Body Mass Index, Excess Weight Loss Rate and Metabolic Response after Sleeve Gastrectomy.

BACKGROUND/AIM: To investigate the metabolic response and body mass index reduction according to the remaining stomach volume between 6-12 months after the operation in patients who underwent sleeve gastrectomy surgery for obesity and to determine the relationship between the remaining stomach volume and metabolic improvement. Materials and Methods: Patients underwent sleeve gastrectomy in a single center by the same team and with the same standardized method. Residual gastric volumes were calculated from three-dimensional computed tomography images obtained 6-12 months postoperatively. BMI, excess weight loss (EWL), total cholesterol, low density lipoprotein (LDL), high density lipoprotein (HDL), very low density lipoprotein (VLDL), triglyceride, hemoglobin A1c (HbA1c), total protein, albumin values were recorded preoperatively and at the time of residual volume measurement. Results: There were 49 subjects with a mean SD preoperative BMI of 47.26+-6.21 kg/m2 and mean age 37.51+-10.88 years. Mean residual volume was 155.36+-56.71 cc. Residual volume was associated with postoperative mean BMI (28.44+-3.23 kg/m2; p 0.001) and postperative mean EWL%(29.27+-7.66; p=0.001). Residual gastric volume was also negative correlated with postoperative mean HbA1c (p=0.004). HbA1c (p=0.828), LDL (p=0.661), HDL (p=0.848), triglycerides (p=0.641), VLDL (p=0.794), total protein relation (p=0.539) and albumin (p=0.824) were analyzed before and after surgery and were not correlated with residual gastric volume. CONCLUSION: The smaller the residual gastric volume after laparoscopic sleeve gastrectomy, the higher the %EWL and the greater the decrease in HbA1c. This study show that laparoscopic sleeve gastrectomy is an effective surgical procedure in patients with Type 2 diabetes mellitus.

Effect of Health Literacy Intervention on Glycemic Control and Renal Function Among Thai Older Adults at Risk of Type 2 Diabetes Mellitus.

Purpose: Diabetes patients with low health literacy often have poor health and clinical outcomes. The study aimed to assess the effectiveness of a health literacy intervention on glycemic control and renal function among Thai older adults at risk of type 2 diabetes mellitus (T2DM). Methods: A quasi-experimental study was carried out in rural areas of Phayao Province in northern Thailand. The participants were older adults with T2DM who recorded blood glucose levels ranging from 140 to 180 mg/dL and who were not receiving prescribed medication. The intervention lasted 12 weeks, and data were collected at three points: baseline, post-intervention, and at 3 months' follow-up. The study outcomes included the measurement of fasting blood sugar (FBS), hemoglobin A1C (HbA1c), and glomerular filtration rate (eGFR) levels after the intervention. A linear mixed model and generalized estimating equations model were used to assess the intervention effect for continuous and binary outcomes, respectively. Results: From baseline to post-intervention, FBS and HbA1c decreased more in the intervention group than in the control group by 8.2 mg/dL (p < 0.001) and 0.1% (p = 0.029), respectively, whereas eGFR increased by 8.0 mL/min/1.73m2 (p < 0.001). The absolute effect of the intervention at follow-up was -9.8 units for FBS, -0.4 units for HbA1c, and 14.0 units for eGFR. Abnormal HbA1c level (≥6.5%) of the intervention group was reported as 70.3% at baseline, 31.3% at post-intervention, and 9.4% at follow-up. Compared to baseline levels, the T2DM patients who received the intervention were 0.31 times less likely to have abnormal HbA1c levels than the control subjects at follow-up (p = 0.003) who received no intervention. Conclusion: Our findings suggest that this intervention may potentially improve diabetes self-management and prevention behaviors, thereby reducing the diabetes burden in rural communities in northern Thailand.

The sGC Activator Runcaciguat Has Kidney Protective Effects and Prevents a Decline of Kidney Function in ZSF1 Rats.

Chronic kidney disease (CKD) progression is associated with persisting oxidative stress, which impairs the NO-sGC-cGMP signaling cascade through the formation of oxidized and heme-free apo-sGC that cannot be activated by NO. Runcaciguat (BAY 1101042) is a novel, potent, and selective sGC activator that binds and activates oxidized and heme-free sGC and thereby restores NO-sGC-cGMP signaling under oxidative stress. Therefore, runcaciguat might represent a very effective treatment option for CKD/DKD. The potential kidney-protective effects of runcaciguat were investigated in ZSF1 rats as a model of CKD/DKD, characterized by hypertension, hyperglycemia, obesity, and insulin resistance. ZSF1 rats were treated daily orally for up to 12 weeks with runcaciguat (1, 3, 10 mg/kg/bid) or placebo. The study endpoints were proteinuria, kidney histopathology, plasma, urinary biomarkers of kidney damage, and gene expression profiling to gain information about relevant pathways affected by runcaciguat. Furthermore, oxidative stress was compared in the ZSF1 rat kidney with kidney samples from DKD patients. Within the duration of the 12-week treatment study, kidney function was significantly decreased in obese ZSF1 rats, indicated by a 20-fold increase in proteinuria, compared to lean ZSF1 rats. Runcaciguat dose-dependently and significantly attenuated the development of proteinuria in ZSF1 rats with reduced uPCR at the end of the study by -19%, -54%, and -70% at 1, 3, and 10 mg/kg/bid, respectively, compared to placebo treatment. Additionally, average blood glucose levels measured as HbA1C, triglycerides, and cholesterol were increased by five times, twenty times, and four times, respectively, in obese ZSF1 compared to lean rats. In obese ZSF1 rats, runcaciguat reduced HbA1c levels by -8%, -34%, and -76%, triglycerides by -42%, -55%, and -71%, and cholesterol by -16%, -17%, and -34%, at 1, 3, and 10 mg/kg/bid, respectively, compared to placebo. Concomitantly, runcaciguat also reduced kidney weights, morphological kidney damage, and urinary and plasma biomarkers of kidney damage. Beneficial effects were accompanied by changes in gene expression that indicate reduced fibrosis and inflammation and suggest improved endothelial stabilization. In summary, the sGC activator runcaciguat significantly prevented a decline in kidney function in a DKD rat model that mimics common comorbidities and conditions of oxidative stress of CKD patients. Thus, runcaciguat represents a promising treatment option for CKD patients, which is in line with recent phase 2 clinical study data, where runcaciguat showed promising efficacy in CKD patients (NCT04507061).

Changes in Branched-Chain Amino Acids One Year after Sleeve Gastrectomy in Youth with Obesity and Their Association with Changes in Insulin Resistance.

Adults with obesity have a reduction in branched-chain amino acid (BCAA) levels following metabolic and bariatric surgery (MBS), which is hypothesized to contribute to the metabolic advantages of MBS. We examined this relationship in 62 youth 13-24 years old with severe obesity (47 female) over 12 months. Thirty had sleeve gastrectomy (SG) and 32 were non-surgical controls (NS). We measured fasting insulin, glucose, glycated hemoglobin (HbA1c), isoleucine, leucine, and valine concentrations, and post-prandial insulin and glucose, following a mixed meal tolerance test. Twenty-four-hour food recalls were collected. At baseline, groups did not differ in the intake or the serum levels of BCAAs, HbA1C, HOMA-IR, Matsuda index, insulinogenic index, or oral Disposition index (oDI). Over 12 months, SG vs. NS had greater reductions in serum BCAAs, and SG had significant reductions in BCAA intake. SG vs. NS had greater reductions in HbA1c and HOMA-IR, with increases in the Matsuda index and oDI. In SG, baseline leucine and total BCAA concentrations were negatively correlated with the baseline Matsuda index. Reductions in serum leucine were positively associated with the reductions in HOMA-IR over 12 months. These associations suggest a potential role of BCAA in regulating metabolic health. Reducing dietary intake and serum BCAA concentrations may reduce insulin resistance.

Ethnicity/race, parent educational attainment, and obesity associated with prediabetes in children.

BACKGROUND/OBJECTIVES: Obesity and other predictors of type 2 diabetes disproportionally affect Hispanic and Black children in the US compared to non-Hispanic White (NHW) children. Yet, the prevalence of prediabetes in children remains unestablished, and guidelines for screening young children are lacking. This study examined the relationships between demographic factors and prediabetes in vulnerable youth in central Texas. SUBJECTS/METHODS: This is a cross-sectional analysis of baseline data from 976 3rd-5th graders (7-12 years) who participated in TX Sprouts, a school-based gardening, nutrition, and cooking trial in 16 elementary schools serving mainly children from minority backgrounds and lower-income households. Measures collected included age, sex, ethnicity, free/reduced-priced school lunch (FRL) status, parent educational attainment (questionnaires), BMI from height (stadiometer) and weight (TANITA scale), and prediabetes status from fasting plasma glucose (FPG) and HbA1c. Regressions examined cross-sectional associations between demographics and FPG, HbA1c, and prediabetes. RESULTS: Children were 47% male, 67% Hispanic, and 10% Black, with a mean age of 9.3 years; 71% received FRL, 50% had overweight/obesity, and 26% had prediabetes. Prediabetes rates were 2.8 and 4.8 times higher in Hispanic and Black children compared to NHW children, respectively (p ≤ 0.001), and 1.5 times higher in children with obesity versus normal BMI (p = 0.02). Children of parents with only an 8th-grade education, some high school education, or a high school degree had 3.1, 2.7, and 2.2 times higher odds of having prediabetes compared to children of college graduates, respectively (p ≤ 0.004). Analyses with FPG and HbA1c yielded similar results. CONCLUSION: These findings suggest a potential need for earlier screening, more comprehensive testing guidelines, and prevention programs tailored toward minority children, children with obesity, and children of parents with low educational attainment. Future research should explore this finding in a larger, nationally representative sample.

The outcome of medical nutrition therapy on glycemic control among type 2 diabetic patients.

Introduction: the global prevalence of type 2 diabetes in adults is estimated to be 6.4%. The current prevalence of type 2 diabetes in Egyptians aged 20 to 79 is approximately 15.6%. The objective of medical nutrition therapy (MNT) is to optimize the management of the "ABC" for diabetes control, glycated hemoglobin, blood pressure, and cholesterol. Our study aimed to assess the effect of MNT on glycemic control in patients with type 2 diabetes attending the family practice clinic. Methods: a quasi-experimental intervention trial was conducted with 40 diabetic patients seeking medical service in the Suez Canal University Hospital family practice clinic. The participants were over 20 years old and had uncontrolled type 2 diabetes. Patients were surveyed using El-Gilany questionnaire to evaluate the socio-demographic traits, physical examination data, and laboratory investigations at baseline and after 12 weeks. Results: medical nutrition therapy (MNT) significantly reduced glycated hemoglobin level (p<0.001); the median level of glycated hemoglobin was 10% with a minimum level of 7.5% vs. a maximum of 14% in the pre-intervention phase. In comparison, the median glycated hemoglobin level was 9.5%, with a minimum level of 5.6% vs. a maximum of 13.5% in the post-intervention phase. In addition, there was a significant improvement in blood pressure, weight, body mass index, fasting plasma glucose, and lipid profile. Conclusion: there is evidence that MNT is a crucial component of type 2 diabetes therapy.

Metabolic, renal, and hematological changes in chronic hepatitis C patients achieving rapid virologic response after 12 weeks of direct-acting antiviral treatment: A prospective cohort study.

The impact of direct-acting antivirals (DAA) therapy on lipid and glucose metabolism and kidney function in patients with hepatitis C virus (HCV) infection, along with its side effects on blood cells, remains controversial. Therefore, we conducted a study that enrolled 280 patients with HCV infection who achieved sustained virologic response after treatment with DAA therapy without ribavirin to evaluate the metabolic changes, renal function, and anemia risk based on real-world data. This study was an observational prospective study with a follow-up period of 12 weeks after the initiation of DAA therapy. Data on biochemical tests, renal function, blood counts, viral load, and host genomics were recorded before treatment and after 12 weeks of treatment with DAAs. DAA therapy reduced fibrosis-4 scores and improved liver function, with significant reductions in aspartate transaminase, alanine aminotransferase, and total bilirubin levels. However, DAA therapy slightly increased uric acid, cholesterol, and low-density lipoprotein cholesterol levels. It significantly reduced fasting blood glucose levels and hemoglobin A1C index (HbA1C) in the study group, while hemoglobin (Hb) and hematocrit (HCT) concentrations decreased significantly (4.78 ± 21.79 g/L and 0.09% ± 0.11%, respectively). The estimated glomerular filtration rate (eGFR) decreased by 12.89 ± 39.04 mL/min/1.73m2. Most variations were not related to the genotype, except for Hb, HCT, and HbA1C. Anemia incidence increased from 23.58% before treatment to 30.72% after treatment. Patients with HCV-1 genotype had a higher rate of anemia than did patients with genotype 6 (36.23% vs. 24.62%). Multivariate analysis showed that the risk of anemia was related to female sex, cirrhosis status, fibrosis-4 score, pretreatment eGFR, and pretreatment Hb level. The results of our study can provide helpful information to clinicians for the prognosis and treatment of HCV infection.

Analysis of risk factors of neonatal hypoglycemia and its correlation with blood glucose control of gestational diabetes mellitus: A retrospective study.

This study aimed to investigate the risk factors associated with neonatal hypoglycemia and its correlation with blood glucose control in patients with gestational diabetes mellitus (GDM). This study was a retrospective study. 880 pregnant women with GDM and their newborns were hospitalized from January 2018 to December 2022 in our hospital. The clinical information of GDM pregnant women and their newborns were reviewed and the hemoglobin A1c (HbA1c) values measured within 1 week before delivery were collected. According to the occurrence of neonatal hypoglycemia, which was divided into the control and observation groups. Logistic regression model was used to estimate the potential factors associated with neonatal hypoglycemia. The association between HbA1c of pregnant women before delivery and abnormal glucose metabolism in newborns was examined using spearman correlation analysis. A total of 104 cases of hypoglycemia occurred in neonates delivered by 880 GDM women and the incidence of neonatal hypoglycemia was 11.82%. There were significant differences in pre-pregnancy overweight or obesity, delivery mode, maternal blood sugar control effect and neonatal feeding standard between the 2 groups of GDM women (P < .05). Pre-pregnancy overweight or obesity, poor blood sugar control in GDM women, and improper neonatal feeding were risk factors for neonatal hypoglycemia. The results of logistic regression analysis showed that abnormal glucose metabolism in newborn (odds ratio [OR]: 2.43, 95% confidence interval [CI]: 1.12-4.73) and neonatal hypoglycemia (OR: 3.04, 95% CI: 1.33-5.79) were a risk factor. We also conducted the logistic analysis to evaluate the correlation between HbA1c before delivery and abnormal glucose metabolism in newborns of pregnant women with GDM through adjusting some potential factors. The results were still significant in the abnormal glucose metabolism in newborn (OR: 2.84, 95% CI: 1.23-6.63) and neonatal hypoglycemia (OR: 3.64, 95% CI: 1.46-8.18). Overweight or obesity of GDM parturient before pregnancy, poor blood glucose control of GDM parturient and improper feeding of newborns are all risk factors for neonatal hypoglycemia. HbA1c before delivery has a certain predictive value for abnormal glucose metabolism in newborns.

Association between serum asprosin and diabetic peripheral neuropathy in patients with type 2 diabetes mellitus in the community.

OBJECTIVE: This study aimed to investigate the relationship between serum asprosin level and diabetic peripheral neuropathy (DPN) in community patients with type 2 diabetes mellitus (T2DM). PATIENTS AND METHODS: A total of 498 patients with T2DM were recruited from Zhuoma Community Health Service Station and Chengbei West Street Community Health Service Center in Changzhi City of Shanxi Province between November 2019 and July 2021. Their height, weight, and body mass index (BMI), as well as fasting plasma glucose (FPG), glycosylated hemoglobin (HbA1c), triglyceride (TG), and serum asprosin levels, were analyzed. Patients were divided into the DPN group (n = 329) and the non-DPN group (n = 169) according to the presence or absence of DPN. The t-test, Mann-Whitney U test, and χ² test were used to compare the indicators between the two groups. Pearson or Spearman correlation analysis was used to evaluate the correlation between serum asprosin and other clinical data. Multivariate logistic regression analysis was used to analyze the influencing factors of DPN. RESULTS: Compared with the non-DPN group, the DPN group had higher serum asprosin (p < 0.05). The prevalence of DPN gradually increased according to the tertiles of asprosin (56%, 67%, and 75%; p < 0.05). Multivariate logistic regression analysis showed that after adjustment for covariates, patients with asprosin concentrations between 295.4-367.0 pg/ml and concentrations > 367.0 pg/ml had a higher risk of diabetic neuropathy compared than those with asprosin levels < 295.4 pg/ml (p < 0.05). CONCLUSIONS: Serum asprosin was found to be positively correlated with DPN, and it resulted as an influencing factor for DPN in patients with T2DM in the community. With the increase of asprosin, the risk of DPN also increased.

Positive Effects of Physical Activity on Prescription on Glycemic Control, Fitness, and Quality of Life in Newly Diagnosed Type 2 Diabetic Patients.

The aim was to investigate the effects of physical activity on prescription (PAP) compared with standard care (SC) in adult drug-naïve T2D patients. A randomized control trial was conducted with drug-naïve T2D patients attending an out-patient clinic Vietnam. Participants were randomly assigned to the PAP group (n+=+44) or the SC group (n+=+43). The PAP group received individualized recommendations for PA, intensive face-to-face training every two weeks. The SC group received the standard recommendations according to WHO guidelines. The mean HbA1c level change was larger (-10.6±6.4 mmol/mol) in the PAP group than in the SC group (-2.4±5.8 mmol/mol) (p<0.001). A one thousand step counts per day increase was significantly associated with a decrease of -2.43 mmol/mol in HbA1c [ß=-2.43, 95%CI: (-2.94, -1.92]) in the PAP group. The fasting plasma glucose levels of the PAP group decreased significantly compared with the SC group. The VO2-max increased significantly more in the PAP group than in the SC group. PAP had clear positive effects on health-related Quality of Life [mean between group difference: 9.54 (95%CI 5.84,13.23)]. Insulin resistance, BMI, waist circumference, total cholesterol, LDL cholesterol and triglycerides were significantly more decreased in the PAP group than in the control group. In conclusion, the fact that even a small change in mean step counts over three months had a beneficial effect on health-related outcomes in drug-naïve T2D patients can have large implications for treatment and management practices, not least in a middle-income country like Vietnam.

Elevated HbA1c level associated with disease severity and surgical extension in diabetic foot patients.

BACKGROUND: Diabetic foot is a complex syndrome that is associated with other diabetic complications, such as peripheral arte-rial disease and peripheral neuropathy. Optimization of plasma glucose and glycated hemoglobin (HbA1c) is one of the main principles of standard care and treatment approaches in individuals with diabetes mellitus (DM). In this study, the relationship of HbA1c level at the time of diagnosis was evaluated with diabetic foot disease severity score and surgical extension in patients with Type 2 DM. METHODS: This study included 301 consecutive patients who were diagnosed with diabetic foot in the general surgery diabetic foot clinic and were hospitalized for surgery. The relationships between the HbA1c levels of the patients with the Wagner and PEDIS (Perfusion, Extent, Dept, Infection, Sensation) classification system grades, and the surgical procedures performed were analyzed and the treatment outcomes were evaluated. RESULTS: It was determined that there was a 90% statistically significant relationship between HbA1c values of ≥10.1% and the de-velopment of Wagner Grade 4 diabetic foot ulcer (DFU) (P=0.037). A strong statistically significant relationship at the rate of 85% was determined between HbA1c values of ≥10.1% and the development of PEDIS Grade 3 ulcers. As the HbA1c values increased, so there was determined to be a statistically significant relationship with the development of PEDIS Grade 3 ulcer (P=0.003). In the comparison of the HbA1c values according to the type of surgery performed, a weak relationship was determined at the rate of 26%, and it was determined that as the HbA1c values increased, so there could be an increase in the amputation level. CONCLUSION: The results of this study showed that as HbA1c values at diagnosis increased in patients with diabetic foot; Wagner/PEDIS grades, disease severity, surgical extension, amputation level, and tissue loss increased. To reduce the severity of diabetic foot disease and prevent amputation, compliance with diabetic treatment and glycemic control should be increased.

Serum sclerostin level is positively associated with endothelial dysfunction measured by digital thermal monitoring in patients with type 2 diabetes: A prospective cross-sectional study.

Sclerostin and dickkopf-1 (DKK1), extracellular inhibitors of the canonical Wnt/ß-catenin signaling pathway, have been associated with vascular aging and atherosclerosis. This study aimed to assess the correlation of sclerostin and DKK1 concentrations with endothelial function measured using vascular reactivity index (VRI) in patients with type 2 diabetes mellitus (T2DM). Fasting blood samples were collected from 100 patients with T2DM. Endothelial function and VRI were measured using digital thermal monitoring and circulating sclerostin and DKK1 levels by enzyme-linked immunosorbent assays. VRI values < 1.0, 1.0-1.9, and > 2.0 indicated poor, intermediate, and good vascular reactivity, respectively. Overall, 30, 38, and 32 patients had poor, intermediate, and good vascular reactivity, respectively. Older age, higher serum glycated hemoglobulin, urinary albumin-to-creatinine ratio, and sclerostin as well as lower hypertension prevalence, systolic blood pressure, and diastolic blood pressure (DBP) were associated with poor VRI. Multivariable forward stepwise linear regression analysis showed that DBP (ß = 0.294, adjusted R2 change = 0.098, P < .001), log-glycated hemoglobin (ß = -0.235, adjusted R2 change = 0.050, P = .002), log-urine albumin-to-creatinine ratio (ß = -0.342, adjusted R2 change = 0.227, P < .001), and log-sclerostin level (ß = -0.327, adjusted R2 change = 0.101, P < .001) were independently associated with VRI. Serum sclerostin, along with glycated hemoglobin and albumin-to-creatinine ratio, exhibited a negative correlation with VRI, while DBP showed a positive correlation with VRI. These factors can independently predict endothelial dysfunction in patients with T2DM.

Secondary analysis of a randomized trial testing community health educator interventions for diabetes prevention among refugees with depression: effects on nutrition, physical activity and sleep.

BACKGROUND: Refugees have high levels of psychological distress that hamper lifestyle change efforts. We previously reported that community health educator (CHE) diabetes prevention interventions decreased HbA1c and depressive symptoms among Cambodian-American refugees with depression; this paper reports health behavior outcomes of those interventions. METHODS: Participants were aged 35-75, Khmer speaking, at risk for diabetes, and met study criteria for likely depression by either a) antidepressant medication and/or b) prolonged elevated depressive symptoms. Participants were randomized to one of three CHE interventions: 1) lifestyle intervention called Eat, Walk, Sleep (EWS), 2) EWS plus medication therapy management with a pharmacist/CHE team (EWS + MTM), or, 3) social services (SS; control). Physical activity and sleep were measured with 7 days of actigraphy. Nutrition was measured as carbohydrates as reported in a culturally tailored food frequency questionnaire. Assessments were at baseline, end point (12 months), and follow-up (15 months). RESULTS: The n = 188 participants were 78% female, average age of 55 years, half had a household income < $20,000, and modal education was 7.0 years. Individuals in the two treatment groups that received the EWS intervention significantly increased their brown rice consumption (p < .001, Cohen's d = 0.76) and their moderate-to-vigorous activity (p = .039, d = 0.32). No intervention changed sleep duration, timing, efficiency or wake after sleep onset. Across groups, individuals who increased brown rice consumption, increased vigorous activity and decreased total sleep time variability showed decreased HbA1c, with small effect sizes. CONCLUSIONS: CHEs may improve nutrition and physical activity in refugees with depression but more intensive interventions may be required to impact sleep. Improvements in all three behaviors appear to be associated with HbA1c lowering TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT02502929.

Identification and characterisation of diabetes in Uganda: protocol for the nested, population-based 'Diabetes in low-resource Populations' (DOP) Study.

INTRODUCTION: Sub-Saharan Africa is experiencing an increasing burden of diabetes, but there are little reliable data, particularly at the community level, on the true prevalence or why this condition affects young and relatively lean individuals. Moreover, the detection of diabetes in Africa remains poor, not only due to a lack of resources but because the performance of available diagnostic tests is unclear. METHODS: This research aims to (1) determine the prevalence and risk factors of diabetes in a rural Ugandan population, (2) use clinical and biochemical markers to define different diabetes phenotypes and (3) study the progression of diabetes in this population. We will also assess the utility of the widely used tests (glycated haemoglobin (HbA1c), oral glucose tolerance test (OGTT) and fasting glucose) in diagnosing diabetes. DESIGN: This is a population-based study nested within the longstanding general population cohort in southwestern Uganda. We will undertake a population survey to identify individuals with diabetes based on fasting glucose, HbA1c, OGTT results or history of pre-existing diabetes. PARTICIPANTS: The study intends to enrol up to 11 700 individuals aged 18 years and above, residing within the study area and not pregnant or within 6 months post-delivery date. All participants will have detailed biophysical and biochemical/metabolic measurements. Individuals identified to have diabetes and a random selection of controls will have repeat tests to test reproducibility before referral and enrolment into a diabetic clinic. Participants will then be followed up for 1 year to assess the course of the disease, including response to therapy and diabetes-related complications. CONCLUSIONS: These data will improve our understanding of the burden of diabetes in Uganda, the risk factors that drive it and underlying pathophysiological mechanisms, as well as better ways to detect this condition. This will inform new approaches to improve the prevention and management of diabetes. ETHICS AND DISSEMINATION: This study protocol was approved by the Uganda Virus Research Institute Research Ethics Committee (REC) (number: G.C./127/21/09/858), the London School of Hygiene and Tropical Medicine REC (number: 26638) and the Uganda National Council for Science and Technology (protocol number: HS1791ES). Written informed consent will be obtained from all participants before being enrolled on to the study and conducting study-related procedures. Research findings will be disseminated in policy briefs, seminars, local and international conferences and publications in peer-reviewed open-access journals. As part of the dissemination plans, findings will also be disseminated to patient care groups and to clinicians. TRIAL REGISTRATION NUMBER: NCT05487079.

Association between body mass index and hemoglobin A1c with serum prostate-specific antigen level: A retrospective cohort study.

OBJECTIVES: To assess the association between body mass index (BMI) and hemoglobin A1c (HbA1c) with serum prostate-specific antigen (PSA) level. METHODS: A retrospective cohort study was carried out at King Faisal Specialist Hospital and Research Centre in Riyadh, Saudi Arabia, from January 2016 to December 2021. Data were collected from the medical records of patients who visited the family medicine clinics, including demographics, smoking status, BMI value, index PSA level, testosterone level, digital rectal exam findings, prostate biopsy status, fasting blood glucose (FBG), HbA1c, diabetes duration, chronic comorbidities (namely, hypertension, dyslipidemia, or chronic kidney disease), and medication history. RESULTS: The mean PSA level was 1.89±4.02 ng/dL and mean HbA1c was 6.59±2.69%. Of the participants, 41.8% were overweight, 54.3% were non-diabetics, and 85.3% were nonsmokers. Only 11 (1.6%) participants had undergone a prostate biopsy after taking a PSA test. There was a positive correlation between PSA level and age, a negative correlation between PSA level and BMI, and no correlation between PSA level and HbA1c or FBG. CONCLUSION: Prostate-specific antigen levels were higher in older people and those with low BMIs. No correlations were found between PSA levels and HbA1c or FBG, even after adjusting for other variables. Moreover, no correlations were found between PSA levels and other comorbidities such as dyslipidemia, chronic kidney disease, and hypertension.

A Case of Acute-Onset Type 1 Diabetes Mellitus with Diabetic Ketoacidosis Triggered by COVID-19.

BACKGROUND It is well known that diabetes mellitus contributes to COVID-19 severity. Recently, there have been reports of an increase in the number of children with type 1 diabetes after the COVID-19 pandemic. CASE REPORT A 52-year-old woman presented to the Emergency Department with disturbance of consciousness, accompanied by a 1-day history of thirst, a fever of 38°C, and breathlessness. She had a positive coronavirus antigen test. Her initial vital signs assessment showed a heart rate of 120 beats per minute, blood pressure 90/50 mmHg, temperature 37.3°C, and respiratory rate 30 breaths/minute with an oxygen saturation of 100% with 10 L oxygen inhalation. Her initial laboratory test results showed a blood glucose level of 1507 mg/dl, HbA1c of 10.1%, ketone 2+, and blood gas pH 7.113. The patient was diagnosed with diabetic ketoacidosis (DKA). There were mild inflammatory findings with blood CRP 0.14 mg/dl and a white cell count of 12 400/µL, but no pneumonia on a chest CT scan. Therefore, the patient was diagnosed with COVID-19 and DKA. The patient was positive for anti-glutamic acid decarboxylase (anti-GAD antibody) and had markedly low levels 24-h urine C-peptide (CPR). She was diagnosed with acute-onset type 1 diabetes mellitus, as her blood examination showed a postprandial blood glucose level of 100 mg/dl and HbA1c of 5.7% 2 months before admission. After admission, fluid replacement and continuous intravenous insulin infusion therapy were started, and blood glucose and blood gas pH improved over 10 h. CONCLUSIONS There have been reports of cases of type 1 diabetes consequences of COVID-19, but the mechanism has not been elucidated.

Effects of continuous positive airway pressure therapy on glucose metabolism in patients with obstructive sleep apnoea and type 2 diabetes: a systematic review and meta-analysis.

Obstructive sleep apnoea is a highly prevalent chronic disorder and has been shown to be associated with disturbed glucose metabolism and type 2 diabetes. However, the evidence from individual clinical trials on the effect of continuous positive airway pressure (CPAP) treatment on glycaemic control in patients with co-existing obstructive sleep apnoea and type 2 diabetes remains controversial. A systematic review of randomised controlled trials assessing the effect of CPAP on glycaemic control in patients with obstructive sleep apnoea and type 2 diabetes was conducted using the databases MEDLINE, Embase, Cochrane and Scopus up to December 2022. Meta-analysis using a random-effect model was performed for outcomes that were reported in at least two randomised controlled trials. From 3031 records screened, 11 RCTs with a total of 964 patients were included for analysis. CPAP treatment led to a significant reduction in haemoglobin A1c (HbA1c) (mean difference -0.24%, 95% CI -0.43- -0.06%, p=0.001) compared to inactive control groups. Meta-regression showed a significant association between reduction in HbA1c and hours of nightly CPAP usage. CPAP therapy seems to significantly improve HbA1c and thus long-term glycaemic control in patients with type 2 diabetes and obstructive sleep apnoea. The amount of improvement is dependent on the hours of usage of CPAP and thus optimal adherence to CPAP should be a primary goal in these patients.