Human Diabetes Mellitus Research Articles

Thyroid disorders and the incidence of type 2 diabetes: insights from a 10-year cohort study in Germany.

Thyroid dysfunctions, such as hypothyroidism, hyperthyroidism, are known to influence metabolism, but their long-term impact on the development of type 2 diabetes mellitus (T2D) in humans remains elusive. Thus, this study aimed to assess the cumulative incidence and association between thyroid disorders and T2D development. We conducted a retrospective cohort study using data from the Disease Analyzer database (IQVIA™) from 2005 to 2022. The study included 158,674 patients with thyroid disorder and an equal number of matched patients without thyroid disorder. Propensity score matching was performed to balance age, sex, co-diagnoses between the cohorts. Kaplan-Meier curves and Cox regression models were used to assess the cumulative incidence and hazard ratios (HR) for new-onset T2D. After a 10-year follow-up period, the cumulative incidence of T2D was higher in patients with thyroid disorder compared to the non-thyroid disorder cohort (p<0.001). The HRs for T2D were 1.34 (95% CI: 1.28-1.39) for hypothyroidism and 1.30 (95% CI: 1.21-1.39) for hyperthyroidism. The strongest associations were observed in younger age groups for both hypothyroidism and hyperthyroidism. Thyroid disorders, including hypothyroidism and hyperthyroidism, are associated with an increased incidence of new-onset T2D. These findings suggest the need for proactive screening and management of glucose metabolism in patients with thyroid dysfunctions, particularly in younger individuals, independent of metabolic risk factors.

Detection of Some Heavy Metals (Mercury and Lead) Pollutants and their Association with Type 2 Diabetes Mellitus (T2DM) in Baghdad, Iraq

Due to the increased use of products carrying heavy metals caused by human factors in the streets of the city of Baghdad and their direct impact on the air, water quality and soil pollution, heavy metals pollution is one of the important environmental problems. As heavy metals cannot be degraded, they accumulate biologically, and, therefore, can directly threaten higher organisms including humans. The current study focused on detecting heavy metals (mercury and lead) to determine the adverse effects and risk of developing type 2 diabetes mellitus (T2DM) in humans. One hundred total blood samples were collected from healthy people and the patients of both sexes who were suffering from T2DM, with mean age of 31 to 75 years, after 8 to 12 hours of fasting. The first group - G1 the control group consisted of 20 health people (6 males and 14 females). The second group - G2 included 40 patients (20 males and 20 females) who had T2DM and were not exposed to any pollutants. The third group - G3 included 40 males with T2DM and also who were exposed to smoke from local electricity generators, as these samples were collected from workers or living near generators and were exposed to air pollution for a long time. Blood samples were collected from each individual by drawing blood from a vein to evaluate each of the biochemical tests, as well as detecting of some heavy metals such as mercury and lead. The results showed that there was a highly significant increase (p≤0.01) when both fasting blood sugar (FBS) and HbA1c were analysed. As for the results of the analysis of the types of lipid profile, there is no significant difference in cholesterol, while there was a significant increase (p≤0.05) in both low-density lipoprotein (LDL) cholestrol and very low density lipoprotein (VLDL) cholestrol and a highly significant increase (p≤0.01) for both triglyceride and high density lipoporotein cholesterol (HDL) cholestrol. The results of the liver function analysis showed that there was no significant difference in the results of the enzyme serum glutamic oxaloacetic transaminase (SGOT) as well as total bilirubin, while there was a significant increase (p≤0.05) in serum glutamate pyruvate transaminase (SGPT). Significant increase (p≤0.01) was detected in the alkaline phosphatase (ALP) enzyme for each of the studied groups. The results of the detection of the presence of heavy metals using the atomic absorption spectrophotometer showed that there was a significant increase (p≤0.01) in lead, and as for mercury, no significant difference was noticed.

The impact of bisphenol AF on skeletal muscle function and differentiation in vitro

Various environmental chemicals have been identified as contributors to metabolic diseases. Bisphenol AF (BPAF), a substitute for bisphenol A, has been associated with changes in glucose metabolism and incidence of type 2 diabetes mellitus in humans. However, its mode of action remains unclear. Considering that skeletal muscle is the primary tissue for glucose utilization and the development of insulin resistance, yet largely neglected in toxicological assessments, we investigated the impact of BPAF on skeletal muscle function and differentiation.We examined the effects of BPAF (0.01–10 μM) on glucose uptake, response to insulin, production of reactive oxygen species (ROS), intracellular calcium, and myocyte differentiation, during hyperglycemia, insulin stimulation, and muscle contraction. We used the rat myoblast cell line L6 differentiated into myotubes, and murine primary isolated muscle fibers.In myotubes and contracting adult fibers, BPAF increased mitochondrial ROS. Basal glucose uptake was increased in myotubes while cells' ability to respond to insulin was decreased. Additionally, in developing myotubes, differentiation markers were downregulated with BPAF, along with impaired formation of tube structures. These effects were primarily observed at 10 μM concentration, which is markedly higher than reported human exposure concentrations.The results provide an insight into potential hazards associated with BPAF in terms of metabolic disruption in skeletal muscle. The developed in vitro methods show promise for future usage in assessments of new chemicals and their mixtures.

Prospective clinical surveillance for severe acute respiratory illness and COVID-19 vaccine effectiveness in Kenyan hospitals during the COVID-19 pandemic.

There are limited data from sub-Saharan Africa describing the demographic characteristics, clinical features and outcome of patients admitted to public hospitals with severe acute respiratory infections during the COVID-19 pandemic. We conducted a prospective longitudinal hospital-based sentinel surveillance between May 2020 and December 2022 at 16 public hospitals in Kenya. All patients aged above 18 years admitted to adult medical wards in the participating hospitals were included. We collected data on demographic and clinical characteristics, SARS-CoV-2 infection and COVID-19 vaccination status and, admission episode outcomes. We determined COVID-19 vaccine effectiveness (VE) against admission with SARS-CoV-2 positive severe acute respiratory illness (SARI) (i.e., COVID-19) andprogression to inpatient mortality among patients admitted with SARI, using a test-negative case control design. Of the 52,636 patients included in the study, 17,950 (34.1%) were admitted with SARI. The median age was 50 years. Patients were equally distributed across sexes. Pneumonia was the most common diagnosis at discharge. Hypertension, Human Immunodeficiency Virus (HIV) infection and Diabetes Mellitus were the most common chronic comorbidities. SARS-CoV-2 test results were positive in 2,364 (27.9%) of the 8,471 patients that underwent testing. After adjusting for age, sex and presence of a chronic comorbidity, SARI patients were more likely to progress to inpatient mortality compared to non-SARI patients regardless of their SARS-CoV-2 infection status (adjusted odds ratio (aOR) for SARI and SARS-CoV-2 negative patients 1.22, 95% CI 1.10-1.37; and aOR for SARI and SARS-CoV-2 positive patients 1.32, 95% CI 1.24-1.40). After adjusting for age, sex and presence of a chronic comorbidity, COVID-19 VE against progression to inpatient mortality following admission with SARI for those with a confirmed vaccination status was 0.59 (95% CI 0.27-0.77). We have provided a comprehensive description of the demographic and clinical pattern of admissions with SARI in Kenyan hospitals during the COVID-19 pandemic period as well as the COVID-19 VE for these patients. These data were useful in providing situational awareness during the first three years of the pandemic in Kenya and informing national response measures.

Fenitrothion induces glucose metabolism disorders in rat liver BRL cells by inhibiting AMPKα and IRS1/PI3K/AKT signaling pathway

Fenitrothion (FNT) is a common organophosphorus pesticide that is widely used in both agricultural and domestic pest control. FNT has been frequently detected in various environmental media, including the human body, and is a notable contaminant. Epidemiological investigations have recently shown the implications of exposure to FNT in the incidence of various metabolic diseases, such as diabetes mellitus in humans, indicating that FNT may be a potential endocrine disruptor. However, the effects of FNT exposure on glucose homeostasis and their underlying mechanisms in model organisms remain largely unknown, which may limit our understanding of the health risks of FNT. In this study, FNT (4 5, 90, 180, and 4 50 μM) exposure model of rat hepatocytes (Buffalo Rat Liver, BRL cells) was established to investigate the effects and potential mechanisms of its toxicity on glucose metabolism. Several key processes of glucose metabolism were detected in this study. The results showed significantly increased glucose levels in the culture medium and decreased glycogen content in the FNT-exposed BRL cells. The results of quantitative real-time PCR and enzymology showed the abnormal expression of genes and activity/content of glucose metabolic enzymes involved in glucose metabolism, which might promote gluconeogenesis and inhibit glucose uptake, glycolysis, and glycogenesis. Furthermore, gluconeogenesis and glycolytic were carried out in the mitochondrial membrane. The abnormal of mitochondrial membrane potential may be a potential mechanism underlying FNT-induced glucose metabolism disorder. In addition, the mRNA and protein expression implicated that FNT may disrupt glucose metabolism by inhibiting the AMPKα and IRS1/PI3K/AKT signaling pathways. In conclusion, results provide in vitro evidence that FNT can cause glucose metabolism disorder, which emphasizes the potential health risks of exposure to FNT in inducing diabetes mellitus.

Effect of Hafnia alvei on Morphophysiologic Parameters and Gut Microbiota of Mice with Inherited Type 2 Diabetes Mellitus.

Inbred mouse strains KK.Cg-a/a and KK.Cg-Ay/a known as genetic models of type 2 diabetes mellitus significantly surpassed the control strain C57BL/6J in the body weight, relative weight of extractable fat, and basal blood glucose levels. Real-timePCR of fecal samples from KK.Cg-a/a and KK.Cg-Ay/a mice revealed dysbiosis typical of type 2 diabetes mellitus in humans and animals. Long-term intragastric administration of a suspension of Hafnia alvei bacteria had no effect on the above morphometric and biochemical parameters. At the same time, recovery of the Bacteroides spp. population in KK.Cg-Ay/a mice and a decrease in the number of Bifidobacterium spp. in KK.Cg-a/a mice were observed. The possibility of therapeutic use of the probiotic based on H. alvei is discussed.

Prevalence of renal insufficiency and factors associated among selected cancer patients on chemotherapy at Ocean Road Cancer Institute in Tanzania: a cross-sectional study

BackgroundCancer is among the leading cause of death worldwide. Chemotherapy is commonly used in cancer management and among the challenges in managing cancer patients is renal insufficiency (RI), which can be due to cancer or anticancer treatment and can be potentiated by different factors. Data regarding the prevalence of RI and associated factors in Tanzania is scanty. This study aims to assess the prevalence of RI and associated factors among selected cancer patients on chemotherapy.MethodsThis analytical cross-sectional study was conducted at Ocean Road Cancer Institute (ORCI) in Dar es Salaam, Tanzania, from March to May 2023. The study included cancer patients on chemotherapy. Data was collected using semi-structured questionnaires whereby socio-demographics, clinical and laboratory data were recorded. Data was analyzed by using STATA version 15. Categorical data was presented as frequencies and percentages, and continuous data was summarized using means. A modified Poisson regression model was used to assess factors associated with RI. The p-values ≤ 0.05 was considered statistically significant.ResultsOut of 354 patients, the majority (76.6%) were female. The enrolled patients’ mean age was 53 ± 13.19 years. The proportion of cancer patients with RI was 62.2% with most (60%) having stage 2 and stage 3 (37.7%). Age, hypertension (HTN), human immunodeficiency virus (HIV), diabetes mellitus (DM) and non-steroidal anti-inflammatory drugs (NSAIDs) use were significantly associated with increased risk of RI (p ≤ 0.05).ConclusionThis study showed that RI is common among cancer patients on chemotherapy. Age, HTN, DM, HIV and NSAIDS use were associated with RI. Close monitoring of kidney function is necessary for cancer patients with other factors associated with RI. Use of creatinine clearance (CrCl) rather than serum creatinine in estimating kidney function is important.

Correlation Between Blood Urea Nitrogen and Short- and Long-Term Glycemic Variability in Elderly Patients with Type 2 Diabetes Mellitus Who Were hospitalized:A Retrospective Study.

Type 2 diabetes mellitus (T2DM) is a metabolic disease characterized by insulin resistance and progressively impaired insulin secretion resulting in dynamic fluctuations in glucose levels.High blood urea nitrogen (BUN) levels have been linked to decreased insulin sensitivity, suppressed insulin synthesis and increased risk of incident diabetes mellitus in humans as well as insulin use in patients with T2DM.This study characterize the association between BUN levels and short-term and long-term glycemic variability(GV) in the elderly patients with T2DM who were hospitalized. A total of 927 elderly patients with T2DM were included in the study. The short-term GV was quantified using parameters such as standard deviation (SD), coefficient of variation (CV), time in range (TIR), and mean amplitude of glycemic excursions (MAGE), based on multi-point fingertip blood glucose monitoring. The long-term GV was quantified using parameters such as SD, CV, variation independent of the mean (VIM), and average successive variability (ARV), based on fasting blood glucose(FPG). The relationship between BUN levels and short-term and long-term GV in elderly T2DM who were hospitalized was explored using methods such as Spearman correlation coefficient, linear regression analysis, logistic regression analysis, and interaction tests. In elderly patients with T2DM were hospitalized, there is a significant correlation between BUN levels and both short-term and long-term GV. BUN is negatively correlated with the GV parameter TIR (r=-0.12, P=0.000), and positively correlated with SD (r=0.12, P=0.000), CV (r=0.07, P=0.026), MAGE (r=0.11, P=0.001), FPG-SD (r=0.08, P=0.013), and FPG-CV (r=0.08, P=0.014).Furthermore, the association remains consistent across different age, gender, BMI, and haemoglobin A1c (HbA1c) subgroups (P interaction > 0.05). In elderly patients with T2DM were hospitalized, BUN levels were positively associated with GV.Therefore, monitoring BUN levels were beneficial in assessing the degree of GV.

Human gestational diabetes mellitus–derived exosomes impair glucose homeostasis in pregnant mice and stimulate functional maturation of offspring-islets

AimsPancreatic islets undergo critical development and functional maturation during the perinatal period when they are highly sensitive to microenvironment. We aim to determine the effects and mechanisms of gestational diabetes mellitus (GDM) hypermetabolic stress on glucose homeostasis in pregnant mice and functional maturation of the islets of their offspring. Main methodsExosomes were extracted from the umbilical vein blood of individuals with or without GDM for administration to pregnant mice. The blood glucose, serum insulin, glycosylated hemoglobin, and lipopolysaccharide levels were measured in pregnant mice. The expression and localization of insulin, glucagon, PC1/3, PDX1, and p-S6 in the islets of neonatal rats were continuously monitored using immunofluorescence to evaluate their functional status. Primary islet cells were cultured and treated with GDM exosomes and exendin to determine the expression of GLP-1R, AKT, p-AKT, and p-S6 via western blotting. Key findingsGDM exosomes induced remarkable oral glucose intolerance, hyperinsulinemia, and metabolic inflammation in pregnant mice. The islets of GDM offspring exhibited high insulin, glucagon, PC1/3, PDX1, and p-S6 expression at and after birth, and activation of the local GLP-1/GLP-1R axis. The functional maturation of normal-offspring islets did not commence until after birth, while it was activated prior to birth in GDM offspring, seriously disrupting the whole process. GDM exosomes activated the GLP-1/GLP-1R axis between α and β cells, and stimulated functional maturation of β cells via the Akt–mTORC1–pS6 pathway. SignificanceThese findings provide preliminary insights into the mechanisms underlying the high incidence of diabetes in the offspring of mothers with GDM.

Dapagliflozin Does Not Protect against Adriamycin-Induced Kidney Injury in Mice

Introduction: Sodium-glucose cotransporter 2 (SGLT2) inhibitors target SGLT2 in renal proximal tubules and promote glycosuria in type 2 diabetes mellitus in humans and animal models, resulting in reduced blood glucose levels. Although clinical trials have shown that SGLT2 inhibitors attenuate the progression of chronic kidney disease, there have been concerns regarding SGLT2-induced acute kidney injury. In this study, we investigated the effect of SGLT2 inhibitors on adriamycin-induced kidney injury in mice. Methods: Seven-week-old balb/c mice were injected with adriamycin 11.5 mg/kg via the tail vein. Additionally, dapagliflozin was administered via gavage for 2 weeks. The mice were divided into five groups: vehicle, dapagliflozin 3 mg/kg, adriamycin, adriamycin plus dapagliflozin 1 mg/kg, and adriamycin plus dapagliflozin 3 mg/kg. Results: Adriamycin injection reduced the body weight and food and water intakes. Dapagliflozin also decreased the body weight and food and water intakes. Fasting blood glucose and urine volume were not altered by either adriamycin or dapagliflozin. Once adriamycin-induced kidney injury had developed, there were no differences in systolic blood pressure among the groups. Dapagliflozin did not alleviate proteinuria in adriamycin-induced kidney injury. Adriamycin induced significant glomerular and interstitial injury, but dapagliflozin did not attenuate these changes in renal injury. Interestingly, SGLT2 expressions were different between the cortex and medulla of kidneys by dapagliflozin treatment. Dapagliflozin increased SGLT2 expression in medulla, not in cortex. Conclusion: Dapagliflozin had no effect on proteinuria or inflammatory changes such as glomerular and tubular damages in adriamycin-induced kidney injury. Our study suggests that dapagliflozin does not protect against adriamycin-induced kidney injury. More experimental studies regarding the effects of SGLT2 inhibitors on various kidney diseases are needed to clarify the underlying mechanisms.

RFX6 Maintains Gene Expression and Function of Adult Human Islet α-Cells.

Mutations in the gene encoding the transcription factor regulatory factor X-box binding 6 (RFX6) are associated with human diabetes. Within pancreatic islets, RFX6 expression is most abundant in islet α-cells, and α-cell RFX6 expression is altered in diabetes. However, the roles of RFX6 in regulating gene expression, glucagon output, and other crucial human adult α-cell functions are not yet understood. We developed a method for selective genetic targeting of human α-cells and assessed RFX6-dependent α-cell function. RFX6 suppression with RNA interference led to impaired α-cell exocytosis and dysregulated glucagon secretion in vitro and in vivo. By contrast, these phenotypes were not observed with RFX6 suppression across all islet cells. Transcriptomics in α-cells revealed RFX6-dependent expression of genes governing nutrient sensing, hormone processing, and secretion, with some of these exclusively expressed in human α-cells. Mapping of RFX6 DNA-binding sites in primary human islet cells identified a subset of direct RFX6 target genes. Together, these data unveil RFX6-dependent genetic targets and mechanisms crucial for regulating adult human α-cell function. Article Highlights

A RETROSPECTIVE REVIEW OF THE BACTERIOLOGY OF HAND SEPSIS AT A TERTIARY HOSPITAL IN GAUTENG

The aim of this investigation is to firstly quantify the burden of disease, and secondly qualify the organisms being cultured during debridement to establish their sensitivities to available antibiotics. This study will also look at the concomitant burden of Human Immunodeficiency Virus (HIV) and Diabetes Mellitus (DM) in cases of hand sepsis, to establish whether these two disease processes require special consideration and treatment tailoring.The method employed to collect the data will be retrospective collection of patient information, using random sampling. Included patients will be adult patients who undergo debridement and have a sample registered on the National Health Laboratory System (NHLS). The daily intake sheet will be used to collect patients details and these details will then be used to collect results of intra-operative specimens using the NHLS. These patient details will also be used to check patients’ HIV results and HBA1c (Glycated Haemoglobin A1c) results.Majority of the specimens revealed Methicillin Sensitive Staphylococcus Aureus (MSSA), with a reassuringly low rate of Methicillin Resistant Staphylococcus Aureus (MRSA) when compared to international data. The yield of patients tested for HIV or DM was lower than expected, despite this being the standard of care.The projected impact of this study will be assessment of the current burden of disease and then clarification of our current management strategy, in order to assess if it would be possible to change to a more cost-effective antibiotic with a narrower spectrum of bacteria coverage. The potential exists to not only implement cost saving measures, but also promote antibiotic stewardship by decreasing the practice of empiric broad-spectrum antibiotic use.

SGLT2 and SGLT1 inhibitors suppress the activities of the RVLM neurons in newborn Wistar rats.

Hypertension is well-known to often coexist with diabetes mellitus (DM) in humans. Treatment with sodium-glucose cotransporter 2 (SGLT2) inhibitors has been shown to decrease both the blood glucose and the blood pressure (BP) in such patients. Some reports show that SGLT2 inhibitors improve the BP by decreasing the activities of the sympathetic nervous system. Therefore, we hypothesized that SGLT2 inhibitors might alleviate hypertension via attenuating sympathetic nervous activity. Combined SGLT2/SGLT1 inhibitor therapy is also reported as being rather effective for decreasing the BP. In this study, we examined the effects of SGLT2 and SGLT1 inhibitors on the bulbospinal neurons of the rostral ventrolateral medulla (RVLM). To investigate whether bulbospinal RVLM neurons are sensitive to SGLT2 and SGLT1 inhibitors, we examined the changes in the neuronal membrane potentials (MPs) of these neurons using the whole-cell patch-clamp technique during superfusion of the cells with the SGLT2 and SGLT1 inhibitors. A brainstem-spinal cord preparation was used for the experiments. Our results showed that superfusion of the RVLM neurons with SGLT2 and SGLT1 inhibitor solutions induced hyperpolarization of the neurons. Histological examination revealed the presence of SGLT2s and SGLT1s in the RVLM neurons, and also colocalization of SGLT2s with SGLT1s. These results suggest the involvement of SGLT2s and SGLT1s in regulating the activities of the RVLM neurons, so that SGLT2 and SGLT1 inhibitors may inactivate the RVLM neurons hyperpolarized by empagliflozin. SGLT2 and SGLT1 inhibitors suppressed the activities of the bulbospinal RVLM neurons in the brainstem-spinal preparations, suggesting the possibilities of lowering BP by decreasing the sympathetic nerve activities. RVLM, rostral ventrolateral medulla. IML, intralateral cell column. aCSF, artificial cerebrospinal fluid.

Effect of vinpocetine alone and in combination with enalapril in experimental model of diabetic cardiomyopathy in rats: possible involvement of PDE-1/TGF-β/ Smad 2/3 signalling pathways.

Diabetic cardiomyopathy (DC) is one of the severe secondary complications of diabetes mellitus in humans. Vinpocetine is an alkaloid having pleiotropic pharmacological effects. The present study is designed to investigate the effect of vinpocetine in DC in rats. Rats were fed a high-fat diet for nine weeks along with single dose of streptozotocin after the second week to induce DC. The haemodynamic evaluation was performed to assess the functional status of rats using the Biopac system. Cardiac echocardiography, biochemical, oxidative stress parameters and inflammatory cytokine level were analysed in addition to haematoxylin-eosin and Masson's trichome staining to study histological changes, cardiomyocyte diameter and fibrosis, respectively. Phosphodiesterase-1 (PDE-1), transforming growth factor-β (TGF-β) and p-Smad 2/3 expression in cardiac tissues were quantified using western blot/RT-PCR. Vinpocetine treatment and its combination with enalapril decreased the glucose levels compared to diabetic rats. Vinpocetine improved the echocardiographic parameters and cardiac functional status of rats. Vinpocetine decreased the cardiac biochemical parameters, oxidative stress, inflammatory cytokine levels, cardiomyocyte diameter and fibrosis in rats. Interestingly, expressions of PDE-1, TGF-β and p-Smad 2/3 were ameliorated by vinpocetine alone and in combination with enalapril. Vinpocetine is a well-known inhibitor of PDE-1 and the protective effect of vinpocetine in DC is exerted by inhibition of PDE-1 and subsequent inhibition of the expression of TGF-β/Smad 2/3.

RELATIONSHIP OF FASTING PLASMA ADIPONECTIN WITH FASTING PLASMA INSULIN IN YOUNG NON DIABETIC INDIVIDUALS

Introduction: Adiponectin is a hormone secreted by the adipose tissue into blood circulation. Blood levels of adiponectin were found to be reduced in obesity and type 2 diabetes mellitus in humans. Adiponectin has also been linked to insulin resistance associated with high fat diet and obesity. Aim: To evaluate the relationship between fasting plasmaadiponectin and fastinginsulin with each other, and with family history of diabetes mellitus in young non diabetic males and females. Materials and methods: The present cross sectional study was conducted at the Department of Biochemistry, Amala Institute of Medical Sciences, Thrissur, Kerala. Clinically healthy males and females between 18 and 25 years of age, were included in the study. Participants were asked to fill out a questionnaire with personal information, family history of type 2 diabetes mellitus and other relevant information. Blood samples were collected and fasting serum glucose, serum insulin and serum adiponectin were estimated. Results and Discussion: The relationship between adiponectin and fasting insulin were evaluated. Fasting adiponectin was found to be significantly and negatively correlating with fasting insulin and glucose in young non diabetic individuals between 18 – 25 years of age. Adiponectin also showed a negative relationship with factors that were directly related to insulin, such as fasting glucose, family history of type 2 diabetes mellitus. Conclusion: Higher level of adiponectin and lower level of insulin seen in young non diabetic individuals show that plasma adiponectin levels have a strong genetic predisposition.

Eugenia polyantha leaf extract as an antidiabetic alternative medicine on Rattus norvegicus

The public does not yet know the potential of Eugenia polyantha as an alternative medicine for diabetes mellitus. In fact, the content of chemical compounds such as flavonoids in Eugenia polyantha can minimize damage to the pancreas. This study aimed to determine the antidiabetic activity of the ethanolic extract of Eugenia polyantha leaf against streptozotocin-induced Wistar rats. The sample for this study were male white rats of the Wistar strain, consisting of 30 rats. It was divided into 6 test groups, group P1 was negative control (aqua dest), group P2 was positive control (glibenclamide), and group P3, P4, and P5 was treated with 70% ethanol extract of Eugenia polyantha leaf with doses of 312.5, 625 and 1250 mg/kg respectively. The blood glucose level on the 11th day was tested by ANOVA which is then tested by Duncan. The results showed Eugenia polyantha leaf extract has an effect on reducing blood glucose in Wistar rats (Rattus norvegicus) with doses 312.5, 625, and 1250 mg/kg body weight. The most effective dose of 70% ethanol extract of Eugenia polyantha leaf for reducing blood glucose is 1250 mg/kg body weight. Furthermore, the findings of this study can be tested in more depth so that it can be recommended to the public as an alternative medicine for diabetes mellitus in humans.

Associations of estrogen therapy and non-estrogen anti-resorptive therapy with diabetes mellitus risk: A classical and Bayesian meta-analysis.

Anti-resorptive therapy (AT) increases insulin resistance and decrease insulin secretion through reduced undercarboxylated osteocalcin in mice. However, there are inconsistent findings regarding the impact of AT use on the risk of diabetes mellitus in humans. We examined the association between AT and incident diabetes mellitus using classical and Bayesian meta-analysis. We searched Pubmed, Medline, Embase, Web of Science, Cochrane, and Google Scholar for studies listed from database inception to 25 February 2022. Randomized controlled trials (RCTs) and cohort studies reporting associations of estrogen therapy (ET) and non-estrogen anti-resorptive therapy (NEAT) with incident diabetes mellitus were included. Two reviewers independently extracted research data such as ET and NEAT, diabetes mellitus, risk ratios (RRs), and 95% confidence intervals (CIs) for incident diabetes mellitus associated with ET and NEAT from individual studies. This meta-analysis included data from nineteen original studies, consisting of fourteen ET and five NEAT studies. ET was associated with reduced risk of diabetes mellitus in the classical meta-analysis (RR: 0.90; 95% CI: 0.81-0.99). Slightly stronger results were found in the meta-analysis of RCTs (RR: 0.83; 95% CI: 0.77-0.89). The probability that RR<1.0 was 95% in the overall analysis and 99% in RCTs under weakly informative prior. Although NEAT was associated with reduced risk of diabetes mellitus overall (RR: 0.80; 95% CI: 0.67-0.97), this was not found in the RCT meta-analysis (RR: 0.90; 95% CI: 0.75-1.10). Under weakly informative prior, the probabilities that NEAT reduces diabetes mellitus by >0% were 99%, and 73% in the overall and RCT meta-analysis, respectively. In conclusion, meta-analysis provided consistent evidence against the hypothesis that AT increases diabetes risk. ET may reduce the risk of diabetes mellitus. Whether NEAT reduces the risk of diabetes mellitus is uncertain and requires additional evidence from RCTs.

Research Progress on Animal Models of Diabetes Mellitus

Diabetes Mellitus (DM) is a complicated metabolic illness defined by hyperglycemia due to faulty insulin production or activity, and it is one of the world’s fastest-growing public health concerns. The construction of a good diabetes mellitus model is crucial for diabetes mellitus pathophysiology research, diabetic mellitus prevention, and the development of effective therapeutic therapy. Diabetes mellitus models are now chemically induced, spontaneous, and genetically created. The models were created using the chemical induction of streptozotocin and alloxan, and the spontaneous type of diabetes mellitus animal models are appropriate for T1DM, T2DM, and related phenotypes, including obesity and insulin resistance. Genetically engineered animal models are much more closely related to human diabetes mellitus, including gene knockout animal models. They can be used to explain the cause of diabetes mellitus in terms of molecular mechanisms and to study the effects of individual genes on insulin secretion and insulin resistance faultlessly. This research provides a detailed description of T1DM and T2DM animal models, illustrating the importance of diabetes mellitus.

White-skinned sweet potato (Ipomoea batatas L.) acutely suppresses postprandial blood glucose elevation by improving insulin sensitivity in normal rats

Long-term administration of Ipomoea batatas L. (white-skinned sweet potato, WSSP) has been reported to help manage type 2 diabetes mellitus (T2DM) in humans and animals; however, the mechanisms of blood glucose regulation by WSSP remain unclear. Therefore, we aimed to investigate the acute effects of WSSP on blood glucose homeostasis under normal conditions and the underlying mechanisms. Three fractions of WSSP (≤10, 10–50, and >50 kDa) were obtained via ultracentrifugation. Rats were subjected to an oral glucose tolerance test (OGTT) after a single administration of WSSP. The insulin tolerance test (ITT) and pyruvate tolerance test (PTT) were performed to evaluate insulin sensitivity and gluconeogenesis, respectively. Single WSSP administration markedly reduced blood glucose levels as revealed by the OGTT. Serum insulin levels were not increased by WSSP treatment. Blood glucose levels during ITT were significantly reduced due to WSSP treatment. WSSP treatment activated the phosphorylation of Akt, thereby activating insulin signaling in the skeletal muscles and liver. The ≤10 kDa fraction considerably reduced blood glucose levels per the OGTT and ITT. In contrast, gluconeogenesis in PTT and the expression of key enzymes in hepatocytes were suppressed by the >50 kDa fraction. This study demonstrated that WSSP acutely reduced postprandial blood glucose levels by improving insulin sensitivity in skeletal muscles in normal rats, which was attributed to constituents with a molecular weight of ≤10 kDa. Moreover, WSSP treatment suppressed gluconeogenesis in the liver, for which constituents of >50 kDa were responsible. Thus, WSSP can acutely regulate blood glucose homeostasis via multiple mechanisms. Since postprandial hyperglycemia leads to the onset of T2DM, WSSP, as a functional food, may possess potential active compounds that prevent T2DM.

Mammalian models of diabetes mellitus, with a focus on type 2 diabetes mellitus.

Although no single animal model replicates all aspects of diabetes mellitus in humans, animal models are essential for the study of energy balance and metabolism control as well as to investigate the reasons for their imbalance that could eventually lead to overt metabolic diseases such as type 2 diabetes mellitus. The most frequently used animal models in diabetes mellitus research are small rodents that harbour spontaneous genetic mutations or that can be manipulated genetically or by other means to influence their nutrient metabolism and nutrient handling. Non-rodent species, including pigs, cats and dogs, are also useful models in diabetes mellitus research. This Review will outline the advantages and disadvantages of selected animal models of diabetes mellitus to build a basis for their most appropriate use in biomedical research.