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Background: Changes in vascular function are closely associated with the development of cardiovascular disease (CVD). Pulse wave velocity (PWV) is a potential indicator of vascular dysfunction; it allows noninvasive assessment of arterial stiffness. Currently, evidence for the effects of different classes of antidiabetic drugs on arterial stiffness remains limited. In this study, a network meta‐analysis (NMA) was performed to explore the associations between changes in arterial stiffness and first‐line antidiabetic drugs by evaluating PWV in patients with different metabolic abnormalities. Methods: We systematically searched several electronic databases for randomized controlled trials (RCTs) published from inception until 25 August 2022, without language restrictions. The primary outcome was the change in PWV (ΔPWV) in all included studies; subgroup analysis was performed for patients with abnormal glucose metabolism, including prediabetes and diabetes mellitus. NMA was performed to calculate the mean differences (MDs) with 95% confidence intervals (CIs) as effect sizes to evaluate the ΔPWV. Results: Among the 2257 candidate articles identified in the initial search, 18 RCTs were eventually included in the analysis. In all studies, two classes of new antidiabetic drugs, glucagon‐like peptide‐1 receptor (GLP‐1R) agonists and sSodium‐glucose co‐transporter 2 (SGLT‐2) inhibitors, improved arterial stiffness by decreasing PWV compared with placebo (MD = −1.11, 95% CI: −1.94 to 0.28) and (MD = −0.76, 95% CI: −1.45 to −0.08). A conventional antidiabetic drug, metformin, also showed similar efficacy compared with placebo (MD = −0.73, 95% CI: −1.33 to −0.12). Finally, in subgroup studies of patients with abnormal glucose metabolism diseases, GLP‐1R agonists (MD = −1.06, 95% CI: −2.05 to −0.10) significantly decreased PWV compared with placebo. Conclusion: Three classes of antidiabetic drugs—GLP‐1R agonists, SGLT‐2 inhibitors, and metformin—have the potential to improve arterial stiffness. Among the six classes of antidiabetic drugs analyzed, GLP‐1R agonists constitute the only class of drugs that improves arterial stiffness in patients with abnormal glucose metabolism diseases. [ABSTRACT FROM AUTHOR]

Diabetes is associated with a plethora of metabolic changes which may underlie the propensity to development of stroke (Figure 1).1 Insulin resistance has multiple drivers, is inextricably linked to type 2 diabetes, and is associated with coronary artery2 and cerebrovascular3 atherosclerosis. The long-term degree of hyperglycemia correlates with stroke likelihood, although there is no evidence that intensive glycemic treatment reduces stroke. Similarly, it appears that acute hyperglycemia at the time of stroke is associated with worse outcome, although there is no evidence that intensive glycemic treatment at the time of stroke improves outcome. Diabetes treatment approaches with evidence of pre-stroke prevention might play roles in post-stroke protection. [Extracted from the article]

Fish are good for your health in more ways than you may expect. For one, eating fish is a common dietary recommendation for a healthy diet. However, fish have much more to provide than omega‐3 fatty acids to your circulatory system. Some fish species now serve as important and innovative model systems for diabetes research, providing novel and unique advantages compared with classical research models. Not surprisingly, the largest share of diabetes research in fish occurs in the laboratory workhorse among fish, the zebrafish (Danio rerio). Established as a genetic model system to study development, these small cyprinid fish have eventually conquered almost every scientific discipline and, over the past decade, have emerged as an important model system for metabolic diseases, including diabetes mellitus. In this review we highlight the practicability of using zebrafish to study diabetes and hyperglycemia, and summarize some of the recent research and breakthroughs made using this model. Equally exciting is the appearance of another emerging discipline, one that is taking advantage of evolution by studying cases of naturally occurring insulin resistance in fish species. We briefly discuss two such models in this review, namely the rainbow trout (Oncorhynchus mykiss) and the cavefish (Astyanax mexicanus). HighlightsDifferent fish species are becoming increasingly attractive as models for the study of hyperglycemia and diabetes due to the ease of generating and maintaining large numbers of animals.Some fish species exhibit unique physiological and evolutionary features that could be used to gain further insights into vertebrate glucose homeostasis and dysregulation. [ABSTRACT FROM AUTHOR]

Background Glucagon-like peptide-1 receptor agonists provide effective hyperglycemia management in patients with type 2 diabetes. In a randomized head-to-head trial, liraglutide 1.8 mg q.d. led to greater reductions in HbA1c than exenatide 10 μg b.i.d. There are no direct comparisons of liraglutide 1.2 mg q.d. and exenatide b.i.d.; therefore, in the present study, an indirect comparison and meta-analysis were undertaken. Methods A systematic literature search was performed for randomized controlled trials of liraglutide 1.2 mg q.d. or exenatide b.i.d. with HbA1c as an outcome and ≥25 subjects. Key data were extracted and analyzed. A random-effects model was used to incorporate heterogeneity between studies. Results Three liraglutide 1.2 mg q.d. (n = 1060) and 10 exenatide b.i.d. (n = 2609) placebo-controlled studies were identified, allowing indirect comparison with placebo as the common arm. Baseline characteristics were mean age ~55 years, disease duration ~7 years, HbA1c ~8%, and body mass index ~32 kg/m2. Compared with exenatide b.i.d., liraglutide 1.2 mg was associated with significantly greater reductions from baseline in HbA1c (-0.29%; 95% confidence interval [CI] -0.53, -0.05) and fasting plasma glucose (-0.92 mmol/L; 95% CI -1.43, -0.41), with shorter duration of nausea (3 vs 14 days; P = 0.002) and fewer withdrawals (odds ratio 0.34; 95% CI 0.22, 0.52). The incidence of adverse events (including nausea) and withdrawals because of adverse events were similar between treatments. Conclusions Liraglutide 1.2 mg provided a significantly greater reduction in HbA1c than exenatide 10 μg b.i.d. The significantly shorter duration of nausea with liraglutide than exenatide may be appreciated by patients. [ABSTRACT FROM AUTHOR]

Gestational diabetes mellitus (GDM) is a global health concern, not only because its prevalence is high and on the increase, but also because of the potential implications for the health of mothers and their offspring. Unfortunately, there is considerable controversy in the literature surrounding the diagnosis and treatment of GDM, as well as the possible long-term consequences for the offspring. As a result, worldwide there is a lack of uniformly accepted diagnostic criteria and the advice regarding the treatment of GDM, including diet, insulin therapy, and the use of oral blood glucose-lowering agents, is highly variable. In this review we provide an overview of the important issues in the field of GDM, including diagnostic criteria, different treatment regimens available, and the long-term consequences of GDM in the offspring. [ABSTRACT FROM AUTHOR]

The article focuses on topics at the 76th Scientific conference sessions organized by nonprofit organization American Diabetes Association, on issues of major adverse cardiac events (MACE), primary endpoint cardiovascular death and non-fatal myocardial infraction. Other topics include drug effectiveness of liraglutide in reduction of diabetes, reduction in progression to macroalbuminuria and effectiveness of fasting plasma glucose.

Background Self-monitoring of blood glucose ( SMBG) is used as a means to detect and prevent hypoglycemia in patients with diabetes. However, information on the longitudinal measures (trajectory) of SMBG-based pre- and postprandial glucose fluctuations over time in relation to hypoglycemia is limited. Among patients treated with exenatide once weekly ( EQW) or insulin glargine ( IG), this study compared SMBG profiles over 52 weeks between patients who did and did not experience hypoglycemia. Methods Pooled patient-level 52-week longitudinal data of treatment with EQW ( n = 531) or IG ( n = 219) from three controlled trials were analyzed. Results The proportion of patients with at least one episode of hypoglycemia in the EQW and IG groups was 23% and 54%, respectively. The preprandial glucose measures from SMBG were significantly lower among patients who experienced hypoglycemia in both treatment groups compared with those who did not. In patients who experienced hypoglycemia, the average preprandial glucose levels over 52 weeks were lower by 0.64 and 0.66 mmol/L in the EQW and IG groups, respectively ( P < 0.01 in both cases) compared with those without hypoglycemia. The average postprandial levels were not significantly different between patients who did and did not experience hypoglycemia in both treatment groups. Among patients with hypoglycemia, the average prebreakfast glucose trajectory was higher by 0.48 mmol/L in the EQW compared with the IG group. Conclusions This study has revealed differential trajectories of pre- and postprandial glucose profiles between patients with and without hypoglycemia. However, the SMBG trajectories were similar between patients treated with EQW and IG. [ABSTRACT FROM AUTHOR]

Background Saudi Arabia is a community thrilled by sudden social and economical changes, leading to a sharp increase in the prevalence of abnormal glucose metabolism. Age-specific diabetes and impaired fasting glucose prevalence is the focus of this study with the expected risk factors. Methods A nationwide, household, randomized, population based cohort of 18 034 participants aged ≥30 years was selected to test for abnormal glucose metabolism using fasting plasma glucose ( FPG) according to American Diabetes Association ( ADA) criteria. Results The prevalence of diabetes was 25.4% with 40.3% being unaware of their disease, while impaired fasting glucose ( IFG) affected 25.5% of the total sample. IFG to diabetes ratio was one in this study, decreasing with age and increasing with body weight. Age ≥45 years, hypertension, history of gestational diabetes mellitus ( GDM), and high triglycerides are the strongest risk factors in diabetic patients, while history of GDM, dyslipidemia, obesity, and high triglycerides are the most significant risk factors in IFG participants. Conclusions Abnormal glucose metabolism has reached an epidemic level in this society, where half of adults and older are affected. Risk factors are behind this epidemic and the quick shift from IFG to diabetes in this society. [ABSTRACT FROM AUTHOR]

Background An estimated 2% of all deaths in Tajikistan can be attributed to diabetes but reliable data are scarce for the country and across Central Asia. We assessed the prevalence of impaired glucose tolerance and diabetes and associated predictors among residents aged ≥45 years in two districts in southern Tajikistan. Methods A population-representative survey following the WHO STEPwise approach to surveillance and including a two-stage cluster sampling was conducted. Enrolled participants were asked about risk factors for diabetes, and blood pressure, height and weight were measured. The blood glucose level was determined after overnight fasting, and the 2 h oral glucose tolerance test was performed if indicated. Results Complete datasets were available for 584 out of 672 study participants. One third of the cohort was male and half were 45-54 years old. Overall, 21.2% of the participants were found to be diabetic, 5.1% had impaired glucose tolerance and 4.3% impaired fasting glucose. An elevated body mass index ≥25 was observed in 61.5% of the cohort and an elevated blood pressure in 45.6% (systolic, cut-off 140 mm Hg) and 52.3% (diastolic, cut-off 90 mm Hg) respectively. Half of the participants classified as diabetic were aware of their status. Conclusions Impaired glucose tolerance and overweight are common among elderly residents of southern Tajikistan. Primary health care services should be strengthened to improve early detection and ensure adequate treatment of diabetes and quality of care. Community-based awareness rising about available peripheral services is crucial. [ABSTRACT FROM AUTHOR]

Background This study examined the prevalence and characteristics of type 2 diabetes in non-obese subjects to compare their cardiometabolic markers to those without diabetes. Methods Data were used from 17 098 men and 17 199 women from a voluntary health checkup program between 1998 and 2006 conducted in Japan. The prevalence of diabetes (fasting plasma glucose ≥ 7.0 mmol/L, hemoglobin A1c ≥ 6.5%, or known diabetes) was calculated in each subgroup of body mass index (group 1, <22; group 2, 22-25; group3, 25-27.5; and group 4, ≥27.5). The effect of diabetes and obesity on risk of an abnormal level of cardiometabolic marker was evaluated with a logistic regression model. Results In men, the prevalence of diabetes was 9.5% in total, 6.4%, 9.4%, 11.3% and 16.2% in group1 through 4, respectively. In women, it accounted for 4.3% in total, 2.4%, 4.5%, 8.7% and 12.3% per group, respectively. Non-obese diabetic subjects (in group 1 and 2) accounted for 60.8% and 62.0% of all the diabetic subjects in men and women, respectively. Non-obese population accounted for 71.2% and 83.6% of all men and women, respectively. Levels of cardiometabolic markers were higher in diabetic subjects than in non-diabetic subjects in each subgroup. Diabetes was associated with each abnormal level of cardiometabolic marker independent of obesity. Conclusion Over 60% of the diabetic subjects in this Japanese population were not obese. Non-obese diabetes is not widely addressed and should be considered for increased public attention. The elevated levels of cardiometabolic markers may contribute to an increased risk of cardiovascular disease in non-obese diabetes. [ABSTRACT FROM AUTHOR]

Background The aim of the present study was to investigate the relationship between mid-trimester ultrasound fetal liver length ( FLL) and gestational diabetes mellitus ( GDM) in a high-risk population. Methods A prospective study was performed in 331 women with singleton pregnancies who were at high risk of GDM and were undergoing a mid-trimester ultrasound examination. The ultrasound scan at 23 weeks gestation was followed by a 100-g oral glucose tolerance test ( OGTT) at 24 weeks gestation. Correlations between FLL and OGTT results at different time points were tested. Receiver operating characteristic ( ROC) analysis of FLL as a potential prognostic factor for GDM was also performed. Results In GDM patients, there was a significant positive correlation ( P < 0.01) between FLL and OGTT glycemia immediately before and 60, 120, and 180 min after glucose intake. Mean FLL in GDM was significantly higher than in healthy subjects (41.04 vs 31.09 mm, respectively; P < 0.001). When tested as a potential prognostic factor for GDM, fetal liver measurements showed excellent diagnostic performance. The ROC analysis established a cut-off value of FLL of 39 mm for the prediction GDM, with sensitivity of 71.76%, specificity 97.56%, positive predictive value 91.0%, and negative predictive value 90.9%. The usefulness of FLL measurements was supported by a high area under the ROC curve (90.5%). Conclusion In conclusion, there is a strong correlation between FLL and OGTT results, with FLL possibly serving as a valid marker for the prediction of GDM in high-risk populations. [ABSTRACT FROM AUTHOR]

Background Toll-like receptor 4 ( TLR4) plays an important role in innate immunity. Activation of innate immune response and subsequent chronic low-grade inflammation are thought to be involved in the pathogenesis of type 2 diabetes. In this study, we aimed to investigate the association of TLR4 variants with type 2 diabetes in the Chinese population. Methods Seven tag single nucleotide polymorphisms ( SNPs) of TLR4 based on HapMap Chinese data were genotyped in the Shanghai Chinese, including 3404 type 2 diabetes patients and 3401 controls. The controls were extensively phenotyped for the traits related to glucose metabolism and insulin secretion. Results In total participants, we identified that rs10759932 and rs1927911 were associated with type 2 diabetes (odds ratio 1.106, P = 0.009 for rs10759532, odds ratio 1.092, P = 0.013 for rs1927911). rs11536889 showed a trend association with type 2 diabetes (odds ratio 0.957, P = 0.057). This SNP was also associated with 2-h plasma glucose ( P = 0.033) and high-density lipoprotein-cholesterol ( P = 0.031). In female participants, rs10759932, rs1927911 and rs11536889 were associated with type 2 diabetes (odds ratio 1.176, P = 0.002 for rs10759932, odds ratio 1.136, P = 0.009 for rs1927911, odds ratio 0.882, P = 0.024 for rs11536889). Besides, rs11536889 was significantly associated with 2-h plasma glucose ( P = 0.050) and HOMA- B ( P = 0.046) with adjusting for age and body mass index in female normal subjects. Conclusions We conclude that genetic variants of TLR4 are associated with type 2 diabetes in the Chinese population, especially in female subjects. [ABSTRACT FROM AUTHOR]

Background The sensitivity of HbA1c is not optimal for the screening of patients with latent diabetes. We hypothesize that simple healthcare information could improve accuracy. Methods We retrospectively analyzed data, including HbA1c, from multiple years from the National Health and Nutrition Examination Survey ( NHANES) database (2005-2010). The data were used to create a logistic regression classification model for screening purposes. Results The study evaluated data for 5381 participants, including 404 with undiagnosed diabetes. The HbA1c screening data were supplemented with information about age, waist circumference, and physical activity in the HbA1c+ model. Alone, HbA1c alone had a receiver operating characteristics ( ROC) curve for the area under the curve ( AUC) of 0.808 (95% confidence interval [ CI] 0.792-0.834). The HbA1c+ model had an ROC AUC of 0.851 (95% CI 0.843-0.872). There was a significant difference in the AUC between our model and using HbA1c without supplementary information ( P < 0.05). Conclusions We have developed a novel screening model that could help improve screening for type 2 diabetes with HbA1c. It seems beneficial to systematically add additional patient healthcare information in the process of screening with HbA1c. [ABSTRACT FROM AUTHOR]

Background Syphilis, a sexually transmitted disease, is commonly referred to as the 'great imitator' because of its wide-ranging clinical presentations. Recently, we noticed that patients with neurosyphilis ( NS) seemed to be more susceptible to complications of diabetes mellitus ( DM). This is an interesting phenomenon, but it also puzzles clinicians because of scant knowledge about this situation. Methods A case-control study was conducted to explore the association between NS and DM. Clinical data and the prevalence of DM among NS patients, patients with syphilis but not NS (syphilis/non- NS), non-syphilis patients, and healthy controls were analyzed. In addition, we explored the time of occurrence of NS and DM. Results Fasting plasma glucose and HbA1c levels in NS patients were significantly higher than in syphilis/non- NS patients, non-syphilis patients, and healthy controls ( P < 0.05). In all, 45 of 149 NS patients (30.2%) were diagnosed with DM. The prevalence of DM in NS patients was significantly higher than in the other three groups ( P < 0.05). There was no relationship between the prevalence of DM and the type of NS (e.g. asymptomatic NS, syphilitic meningitis, meningovascular NS, general paresis, and tabes dosalis). In the study population, 57.8% of NS patients were diagnosed with DM at the same time, whereas 80.0% were diagnosed with DM within 5 years of their diagnosis of NS. Conclusions Based on the results of the present study, DM is not merely an occasional chance occurrence in NS patients. There is an association between NS and DM. [ABSTRACT FROM AUTHOR]

Background There is a growing interest in using the 2010 US Census data for age adjustment after the Census data are officially released. This report discusses the rationale, procedures, demonstrations, and caveats of age adjustment using the 2010 US Census data. Methods Empirical data from the Behavioral Risk Factor Surveillance System and the 2010 US Census age composition were used in demonstrations of computing the age-adjusted prevalence of diagnosed diabetes by race/ethnicity, across various geographic regions, and over time. Results The use of the 2010 US Census data yielded higher age-adjusted prevalence of diagnosed diabetes than using the 2000 projected US population data. The differences persisted across geographic regions, among racial/ethnic groups, and over time. Sixteen age compositions were generated to facilitate the use of the 2010 Census data in age adjustment. The SAS survey procedures and SUDAAN software programs yielded similar age-adjusted prevalence estimates of diagnosed diabetes. Conclusions Using the 2010 US Census data tends to yield a higher age-adjusted measure than using the 2000 projected US population data. Consistent use of a standard population and age composition is recommended once they are chosen for age adjustment. [ABSTRACT FROM AUTHOR]

The forkhead box O ( FoxO) subfamily has four members, namely FoxO1, FoxO3, FoxO4, and FoxO6. Unlike the other three members of the FoxO family, FoxO6 has garnered considerably less attention because of earlier reports that FoxO6 expression was limited to the brain. Recent data indicate that FoxO6 is produced in the liver of both rodents and humans. Hepatic FoxO6 activity, which remains at low basal levels in fed states, is markedly induced in fasted mice. FoxO6 activity becomes abnormally higher in the liver of mice with dietary obesity or type 2 diabetes ( T2D). Genetically engineered mice with elevated FoxO6 activity in the liver exhibit prediabetes, culminating in the development of glucose intolerance, fasting hyperglycemia, and hyperinsulinemia. Conversely, inhibition of FoxO6 activity in the insulin-resistant liver results in a reduction in fasting hyperglycemia, contributing to the amelioration of hyperinsulinemia in T2D mice. These new data suggest that FoxO6 is an important regulator of hepatic glucose metabolism in response to insulin or physiological cues. Insulin inhibits FoxO6 activity by promoting its phosphorylation and disabling its activity in the nucleus without altering its subcellular distribution via a mechanism that is distinct from other members of the FoxO subfamily. In this article, we comprehensively review the role of FoxO6 in glucose metabolism in health and disease. We also address whether FoxO6 dysregulation is a contributing factor for the pathogenesis of fasting hyperglycemia and discuss whether FoxO6 is a potential therapeutic target for improving fasting hyperglycemia in T2D. [ABSTRACT FROM AUTHOR]

The article discusses the role of glucagon in the treatment of diabetes. Studies suggest that glucagon suppression may be considered by increased insulin with hyperglycemia, and glucagon stimulation by reduction in insulin with hypoglycemia. There are studies which also suggest that glucagon action may extend beyond glycemia to include effects on weight and lipid homeostasis.

Background Clinical and epidemiological findings point to an association between type 2 diabetes ( T2D) and low birth weight. However, the nature of the relationship is largely unknown. The aim of this study was to identify novel single nucleotide polymorphisms ( SNPs) in T2D and birth weight, and their pleiotropic loci. Methods A pleiotropy-informed conditional false discovery rate (c FDR) method was applied to two independent genome-wide association studies ( GWAS) summary statistics of T2D ( n = 149 821) and birth weight ( n = 26 836). Results A conditional Q- Q plot showed strong enrichment of genetic variants in T2D conditioned on different levels of association with birth weight. 133 T2D-associated SNPs, including 120 novel SNPs, were identified with a significance threshold of c FDR < 0.05; 13 significant birth weight-associated SNPs, including 12 novel SNPs (c FDR < 0.05) were identified. Conjunctional c FDR (cc FDR) analysis identified nine pleiotropic loci, including seven novel loci, shared by both T2D and birth weight (cc FDR < 0.05). Two novel SNPs located at the CDK5 regulatory subunit-associated protein 1-like 1 ( CDKAL1; rs1012635; c FDR < 0.05) and adenylate cyclase 5 ( ADCY5; rs4677887; c FDR < 0.05) genes are of note. These two genes increase the risk of T2D and low birth weight through the pathway of the 'fetal insulin hypothesis.' Conclusion Several pleiotropic loci were identified between T2D and birth weight by leveraging GWAS results. The results make it possible to explain a greater proportion of trait heritability and improve our understanding of the shared pathophysiology between T2D and birth weight. [ABSTRACT FROM AUTHOR]

The author comments on the effectiveness of glycemic control in treating diabetes of patients. The author states glycemic control has long been used and proven to control the cardiovascular disease (CVD) of patients. Moreover, he said that the use of glycemic control needs long-term intervention if utilized in treating diabetes.