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Background and aims: Colorectal cancer (CRC) is a significant global health concern, with studies estimating a rise in new cases to 2.5 million by 2035. Type 2 diabetes (T2D) is also a growing issue, with an estimated 642 million adults affected by 2040. However, the relationship between T2D, its medications, and CRC remains unclear. Materials and methods: This case-control study includes 810 controls without CRC and 684 cases with CRC admitted to Rasoul-Akram and Firouzgar Hospitals from September 2019 to 2023. Adjusted and unadjusted odds ratios (OR) were calculated to investigate the effect of T2D and sulfonylurea consumption on the chance of CRC development, using univariate and multivariate logistic regression analyses. The relationship between T2D and the clinicopathological features of the tumor was investigated. Results: The results show that the effect of T2D on CRC is significant based on unadjusted OR (OR = 1.39, CI = 1.07, 1.81) and insignificant in adjusted OR (OR = 0.67, CI = 0.37, 1.20). The effect of sulfonylurea consumption on CRC was significant in both unadjusted (OR = 2.39, CI = 1.40, 4.09) and adjusted ORs (OR = 2.35, CI = 1.12, 4.91). All analyses related to the relationship between T2D and tumor clinicopathological characteristics were insignificant. Conclusion: This study found an insignificant association between type 2 diabetes and the chance of CRC development in an adjusted state. Sulfonylurea consumption was also associated with a higher chance of CRC development among patients with T2D. These findings have implications for clinical practice and public health strategies in CRC prevention for patients with T2D. [ABSTRACT FROM AUTHOR]

Background: Previous studies have assessed the association between antidiabetic drugs and stroke risk, but the results are inconsistent. Mendelian randomization (MR) was used to assess effects of antidiabetic drugs on stroke risk. Methods: We selected blood glucose-lowering variants in genes encoding antidiabetic drugs targets from genome-wide association studies (GWAS). A two-sample MR and Colocalization analyses were applied to examine associations between antidiabetic drugs and the risk of stroke. For antidiabetic agents that had effect on stroke risk, an independent blood glucose GWAS summary data was used for further verification. Results: Genetic proxies for sulfonylureas targets were associated with reduced risk of any stroke (OR=0.062, 95% CI 0.013-0.295, P=4.65×10－4) and any ischemic stroke (OR=0.055, 95% CI 0.010-0.289, P=6.25×10－4), but not with intracranial hemorrhage. Colocalization supported shared casual variants for blood glucose with any stroke and any ischemic stroke within the encoding genes for sulfonylureas targets (KCNJ11 and ABCC8) (posterior probability>0.7). Furthermore, genetic variants in the targets of insulin/insulin analogues, glucagon-like peptide-1 analogues, thiazolidinediones, and metformin were not associated with the risk of any stroke, any ischemic stroke and intracranial hemorrhage. The association was consistent in the analysis of sulfonylureas with stroke risk using an independent blood glucose GWAS summary data. Conclusions: Our findings showed that genetic proxies for sulfonylureas targets by lowering blood glucose were associated with a lower risk of any stroke and any ischemic stroke. The study might be of great significance to guide the selection of glucose-lowering drugs in individuals at high risk of stroke. [ABSTRACT FROM AUTHOR]

Background: Hip fracture is a major health problem that occurs more often in the elderly, especially in diabetic patients. Some studies have been conducted regarding the effect of anti- diabetic drugs on fractures. But so far, no meta-analysis study has been conducted to investigate the effect of diabetic drugs on hip fractures. Therefore, this study investigated the relationship between anti-diabetic drugs (Metformin, Sulfonylurea, and insulin) with hip fractures. Methods: In this systematic review and meta analysis study, PubMed, Scopus, Google Scholar, and Web of Science databases were searched with specific keywords to find relevant studies. Two researchers included related studies after screening based on the title and full text. Cochran's Q and I2 tests were used to assess heterogeneity between studies. Publication bias between studies was evaluated for each drug using Egger's test. A 95% confidence interval was used for effect size significance. Overall, 49 studies, including 6,631,297 participants, were reviewed. Results: The results showed that metformin significantly reduced the risk of hip fracture (HR: 0.833, 95% CI: 0.759, 0.914, P:0.001). Consumption of sulfonylurea compounds was significantly associated with an increased risk of hip fracture. (HR: 1.175, 95% CI:1.068,1.293, P:0.001), The risk of hip fracture in patients receiving insulin was significantly higher than in diabetic patients who did not receive insulin. (HR:1.366, 95% CI:1.226,1.522, P:0.001). Conclusion: The results of this study showed that taking metformin reduces the risk of hip fracture, and insulin and Sulfonylurea increase the risk of hip fracture. [ABSTRACT FROM AUTHOR]

Background: Biguanides and sulfonylurea are two classes of anti-diabetic medications that have commonly been prescribed all around the world. Diagnosis of biguanide and sulfonylurea exposures is based on history taking and physical examination; thus, physicians might misdiagnose these two different clinical settings. We aimed to conduct a study to develop a model based on decision tree analysis to help physicians better diagnose these poisoning cases. Methods: The National Poison Data System was used for this six-year retrospective cohort study.The decision tree model, common machine learning models multi layers perceptron, stochastic gradient descent (SGD), Adaboosting classiefier, linear support vector machine and ensembling methods including bagging, voting and stacking methods were used. The confusion matrix, precision, recall, specificity, f1-score, and accuracy were reported to evaluate the model's performance. Results: Of 6183 participants, 3336 patients (54.0%) were identified as biguanides exposures, and the remaining were those with sulfonylureas exposures. The decision tree model showed that the most important clinical findings defining biguanide and sulfonylurea exposures were hypoglycemia, abdominal pain, acidosis, diaphoresis, tremor, vomiting, diarrhea, age, and reasons for exposure. The specificity, precision, recall, f1-score, and accuracy of all models were greater than 86%, 89%, 88%, and 88%, respectively. The lowest values belong to SGD model. The decision tree model has a sensitivity (recall) of 93.3%, specificity of 92.8%, precision of 93.4%, f1_score of 93.3%, and accuracy of 93.3%. Conclusion: Our results indicated that machine learning methods including decision tree and ensembling methods provide a precise prediction model to diagnose biguanides and sulfonylureas exposure. [ABSTRACT FROM AUTHOR]

Background: Safety of sulfonylurea drugs in the treatment of Type 2 Diabetes is still under debate. The aim of this study was to compare the all-cause mortality and cardiovascular adverse events of sulfonylureas and drugs with a low risk for hypoglycaemia in adults with type 2 diabetes. Methods: Systematic review and meta-analysis of randomised controlled trials. Data sources: MEDLINE (PubMed, OVID), Embase, Cochrane Central Register of Controlled Trials, CINAHL, WOS and Lilacs. Study selection: Randomised controlled head-to-head trials that compared sulfonylureas with active control with low hypoglycaemic potential in adults (≥ 18 years old) with type 2 diabetes published up to August 2015. The drug classes involved in the analysis were metformin, dipeptidyl peptidase-4 (DPP-4) inhibitors, sodium-glucose co-transporter-2 (SGLT-2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists. Outcomes: The primary endpoint was all-cause mortality. The secondary endpoints were MACE, cardiovascular events and severe hypoglycaemia. Synthesis of results: Two reviewers checked study eligibility, independently extracted data and assessed quality with disagreements resolved through discussion. We assessed the risk of bias of the included studies using the Cochrane risk of bias tool for randomized trials v2. Pooled odds ratios (ORs) were estimated by using fixed effects model. The study is registered on PROSPERO (26/05/2016 CRD42016038780). Results: Our final analysis comprised 31 studies (26,204 patients, 11,711 patients given sulfonylureas and 14,493 given comparator drugs). In comparison to drugs with low hypoglycaemic potential, sulfonylureas had higher odds for all-cause mortality (OR 1.32, 95% CI 1.00-1.75), MACE (OR 1.32, 95% CI 1.07–1.61), myocardial infarction (fatal and non-fatal) (OR 1.67, 95% CI 1.17–2.38) and hypoglycaemia (OR 5.24, 95% CI 4.20–6.55). Subsequent sensitivity analysis revealed differences in the effect of sulfonylureas, with an increased risk of all-cause mortality with glipizide but not the other molecules. Conclusion: Our meta-analysis raises concern about the safety of SUs compared to alternative drugs involved in current analysis. Important differences may exist within the drug class, and glimepiride seems to have best safety profile. [ABSTRACT FROM AUTHOR]

Background: An increasing body of evidence implicates the resident gut microbiota as playing a critical role in type 2 diabetes (T2D) pathogenesis. We previously reported significant improvement in postprandial glucose control in human participants with T2D following 12-week administration of a 5-strain novel probiotic formulation ('WBF-011') in a double-blind, randomized, placebo controlled setting (NCT03893422). While the clinical endpoints were encouraging, additional exploratory measurements were needed in order to link the motivating mechanistic hypothesis - increased short-chain fatty acids - with markers of disease. Results: Here we report targeted and untargeted metabolomic measurements on fasting plasma (n = 104) collected at baseline and end of intervention. Butyrate and ursodeoxycholate increased among participants randomized to WBF-011, along with compelling trends between butyrate and glycated haemoglobin (HbA1c). In vitro monoculture experiments demonstrated that the formulation's C. butyricum strain efficiently synthesizes ursodeoxycholate from the primary bile acid chenodeoxycholate during butyrogenic growth. Untargeted metabolomics also revealed coordinated decreases in intermediates of fatty acid oxidation and bilirubin, potential secondary signatures for metabolic improvement. Finally, improvement in HbA1c was limited almost entirely to participants not using sulfonylurea drugs. We show that these drugs can inhibit growth of formulation strains in vitro. Conclusion: To our knowledge, this is the first description of an increase in circulating butyrate or ursodeoxycholate following a probiotic intervention in humans with T2D, adding support for the possibility of a targeted microbiome-based approach to assist in the management of T2D. The efficient synthesis of UDCA by C. butyricum is also likely of interest to investigators of its use as a probiotic in other disease settings. The potential for inhibitory interaction between sulfonylurea drugs and gut microbiota should be considered carefully in the design of future studies. [ABSTRACT FROM AUTHOR]

Background: Current evidence about the cardiovascular safety of glucagon-like peptide-1 receptor agonist (GLP-1ra) possesses limited generalizability to real-world patients with type 2 diabetes (T2D) in usual practice. This study aimed to investigate the comparative cardiovascular safety of GLP-1ra in comparisons with dipeptidyl peptidase-4 inhibitor (DPP-4i), sulfonylurea (SU), and insulin in a real-world population with T2D. Methods: Adults with newly-diagnosed T2D were identified from Taiwan's National Health Insurance Research Database in 2003–2014. A prevalent new-user cohort design was adopted to include a broad representation of real-world T2D patients being treated with GLP-1ra. The between-group comparability of baseline patient characteristics was achieved by matching on (1) initiation time of study drugs, (2) prior exposure to glucose-lowering agents, and (3) diabetes severity and complications, comorbidities, and concomitant cardiovascular medications using propensity scores. The primary outcome was a composite of cardiovascular disease (CVD) events and assessed up to the end of 2015. Cox modeling was employed to assess the association between study drugs and outcomes. Results: A total of 3195 GLP-1ra stable users was identified in 2011-2014. 1893, 1829, and 1367 GLP-1ra stable users were 1:1 matched to DPP-4i, SU and insulin users, respectively. Compared to DPP-4i, SU and insulin, the use of GLP-1ra was associated with a lower risk of composite CVD events [hazard ratio (95% confidence interval) 0.73 (0.57–0.96), 0.76 (0.57–1.00), and 0.81 (0.62–1.07), respectively]. Subgroup analyses revealed that GLP-1ra versus DPP-4i yielded a greater cardiovascular benefit in those without established CVD versus those with established CVD. Conclusions: This comparison study extends the supporting evidence for the cardiovascular safety of GLP-1ra to a broad spectrum of real-world T2D patients using GLP-1ra. [ABSTRACT FROM AUTHOR]

Background: Acetolactate synthase (ALS)-inhibiting herbicides from the chemical families of sulfonylureas and imidazolinones are used worldwide. However, drift or sprayer contamination from some sulfonylurea herbicides causes a high level of male sterility in cruciferous species, especially oilseed rape (OSR). In this paper, we evaluated the gametocidal effects of 27 ALS-inhibiting herbicides that were sprayed on OSR plants at the bolting stage. Results: OSR anther development was very sensitive to sublethal exposure to most ALS-inhibiting herbicides. The application of 18 out of the 20 tested sulfonylureas (except ethametsulfuron and ethoxysulfuron), two imidazolinones (imazethapyr and imazamox), and one sulfonylamino-carbonyltriazolinone (flucarbazone-sodium) at suitable rates could induce male sterility. Eight of the herbicides, including chlorsulfuron (at application rates of 60–120 mg/ha), halosulfuron-methyl (300–600 mg/ha), sulfosulfuron (400–600 mg/ha), triflusulfuron-methyl (500–750 mg/ha), pyrazosulfuron-ethyl (150–225 mg/ha), nicosulfuron (200–300 mg/ha), imazethapyr (750–1125 mg/ha), and imazamox (400–800 mg/ha), could induce over 90% male sterility and over 60% relative outcrossed seed set in six cultivars with different origins. These eight chemicals could be used as new gametocides for hybrid seed production. This study also examined the possibility of external application of these gametocides on several unstable Polima cytoplasmic male sterile and thermosensitive genic male sterile lines. Although the outcrossed seed set of the treated lines was slightly reduced, the gametocide application significantly increased the seed purity of the resulting hybrid. Conclusion: The finding of the gametocidal effects of most sulfonylureas and imidazolinones are of great importance for developing new functions for ALS-inhibiting herbicides. The application of gametocides will also greatly promote the safe utilization of environment-sensitive male sterility in hybrid seed production. Unexpectedly, the application of three triazolopyrimidines (florasulam, flumetsulam, and penoxsulam) and one pyrimidinylthiobenzoate (bispyribac-sodium) did not cause male sterility, although these herbicides obviously inhibited the activity of ALS and plant growth. This result suggests that inhibition of ALS activity does not always lead to male sterility in plants, and these gametocides may also inhibit other biological functions vital for microspore development. [ABSTRACT FROM AUTHOR]

Background: Type 2 diabetes (T2D) is a worldwide epidemic with considerable health and economic consequences. Sulfonylureas are widely used drugs for the treatment of patients with T2D. KCNJ11 and ABCC8 encode the Kir6.2 (pore-forming subunit) and SUR1 (regulatory subunit that binds to sulfonylurea) of pancreatic β cell KATP channel respectively with a critical role in insulin secretion and glucose homeostasis. TCF7L2 encodes a transcription factor expressed in pancreatic β cells that regulates insulin production and processing. Because mutations of these genes could affect insulin secretion stimulated by sulfonylureas, the aim of this study is to assess associations between molecular variants of KCNJ11, ABCC8 and TCF7L2 genes and response to sulfonylurea treatment and to predict their potential functional effects. Methods: Based on a comprehensive literature search, we found 13 pharmacogenetic studies showing that single nucleotide polymorphisms (SNPs) located in KCNJ11: rs5219 (E23K), ABCC8: rs757110 (A1369S), rs1799854 (intron 15, exon 16 -3C/T), rs1799859 (R1273R), and TCF7L2: rs7903146 (intron 4) were significantly associated with responses to sulfonylureas. For in silico bioinformatics analysis, SIFT, PolyPhen-2, PANTHER, MutPred, and SNPs3D were applied for functional predictions of 36 coding (KCNJ11: 10, ABCC8: 24, and TCF7L2: 2; all are missense), and HaploReg v4.1, RegulomeDB, and Ensembl's VEP were used to predict functions of 7 non-coding (KCNJ11: 1, ABCC8: 1, and TCF7L2: 5) SNPs, respectively. Results: Based on various in silico tools, 8 KCNJ11 missense SNPs, 23 ABCC8 missense SNPs, and 2 TCF7L2 missense SNPs could affect protein functions. Of them, previous studies showed that mutant alleles of 4 KCNJ11 missense SNPs and 5 ABCC8 missense SNPs can be successfully rescued by sulfonylurea treatments. Further, 3 TCF7L2 non-coding SNPs (rs7903146, rs11196205 and rs12255372), can change motif(s) based on HaploReg v4.1 and are predicted as risk factors by Ensembl's VEP. Conclusions: Our study indicates that a personalized medicine approach by tailoring sulfonylurea therapy of T2D patients according to their genotypes of KCNJ11, ABCC8, and TCF7L2 could attain an optimal treatment efficacy. [ABSTRACT FROM AUTHOR]

Background: For most cruciferous plants, which are known as important crops and a number of weeds, hybrid breeding is hampered by the unavailability of a pollination control system. Male sterility induced by a gametocide can be useful for the utilization of plant heterosis. Results: The gametocidal effect of sulfonylurea herbicide tribenuron-methyl was tested across seventeen cruciferous species or subspecies including Brassica juncea, B. carinata, B. oleracea ssp. capitata, B. oleracea ssp. acephala, B. rapa ssp. pekinensis, B. rapa ssp. chinensis, B. rapa ssp. parachinensis, B. nigra, Orychophragmus violaceus, Matthiola incana, Raphanus sativa, Sisymbrium altissimum, Eruca sativa, Sinapis alba, Sinapis arvensis, Capsella bursa-pastoris and Camelina sativa. The plants of 23 cultivars in these species or subspecies were foliar sprayed with 10 ml of 0.2 or 0.4 mg/L of tribenuron-methyl before the vacuolated microspore formed in the largest flower buds; the application was repeated ten to twelve days afterwards. Tribenuron-methyl exposure significantly changed the flowering phenology and reproductive function. The treated plants demonstrated a one to four day delay in flowering time and a shortened duration of flowering, as well as other slight phytotoxic effects including a reduction in plant height and floral organ size. Approximately 80% to 100% male sterility, which was estimated by both pollen staining and selfing seed-set rate, was induced in the plants. As a result, plants were rendered functionally able to out-cross, with an average 87% and 54% manually pollinated seed-set rate compared to the corresponding controls at the 0.2 mg/L and 0.4 mg/L doses, respectively. Conclusions: The results suggested that male reproductive function was much more sensitive to tribenuron-methyl exposure than female function. This sulfonylurea herbicide has a promising use as the gametocide for hybrid production in cruciferous plants. [ABSTRACT FROM AUTHOR]

Background: There have only been a few reports about use of dipeptidyl peptidase 4 (DPP-4) inhibitors in elderly patients with type 2 diabetes mellitus (T2DM), suggesting that the safety of these agents has not been sufficiently demonstrated. We performed a comparative review of the efficacy and safety of sitagliptin for Japanese patients with T2DM managed in the real-world clinical setting. Methods: An age-stratified analysis was performed of 831 patients who were treated with sitagliptin for 2 years. Parameters assessed included the hemoglobin A1c (HbA1c), body weight, serum creatinine, and adverse events. HbA1c and the incidence of hypoglycemia were also evaluated in patients treated with sitagliptin and a sulfonylurea (SU), who were divided into three age groups (<65 years, 65-74 years, and ≥75 years). Results: Comparison of glycemic control parameters, laboratory values, and adverse events revealed significant improvement of HbA1c, casual postprandial plasma glucose, and fasting plasma glucose in each age group with no change in body weight. Serum creatinine increased significantly in all age groups. Hypoglycemia only occurred in patients who received combined treatment with an SU and sitagliptin, and there was no age-related difference in its incidence. Conclusions: HbA1c was improved by 2 years of sitagliptin therapy in all three age groups, and age did not seem to influence the incidence of hypoglycemic events. These results confirm the efficacy and safety of sitagliptin in patients ≥ 75 years old, suggesting that it is also useful for treating elderly patients with T2DM. [ABSTRACT FROM AUTHOR]

Background: Sulfonylureas (SUs) are commonly used in the treatment of type 2 diabetes (T2DM), usually as second-line treatment after the failure of metformin. However, SUs are associated with poor durability, hypoglycemia and weight gain. Empagliflozin is a sodium glucose cotransporter 2 (SGLT2) inhibitor in development for the treatment of T2DM. In Phase II/III trials, empagliflozin reduced hyperglycemia, body weight and blood pressure, with a low incidence of hypoglycemia. The aim of this Phase III study is to compare the effects of empagliflozin and the SU glimepiride as second-line therapy in patients with T2DM inadequately controlled with metformin immediate release (IR) and diet/exercise. Method: After a 2-week placebo run-in, patients were randomized to receive empagliflozin 25 mg once daily (qd) or glimepiride 1-4 mg qd double-blind for 2 years, in addition to metformin IR. Patients who participate in the initial 2- year randomization period will be eligible for a 2-year double-blind extension. The primary endpoint is change from baseline in HbA1c. Secondary endpoints are change from baseline in body weight, the incidence of confirmed hypoglycemia and changes in systolic and diastolic blood pressure. Exploratory endpoints include markers of insulin secretion, body composition and responder analyses. Safety endpoints include the incidence of adverse events (AEs) (including macro- and microvascular adverse events) and changes from baseline in clinical laboratory parameters. Results: Between August 2010 and June 2011, 1549 patients were randomized and 1545 patients were treated. At baseline, mean (SD) age was 55.9 (10.4) years, HbA1c was 7.92 (0.84)%, body mass index was 30.11 (5.59) kg/m2, systolic blood pressure was 133.5 (15.9) mmHg and diastolic blood pressure was 79.5 (9.4) mmHg. Discussion: This is the largest study to compare the efficacy and safety of an SGLT2 inhibitor with an SU in patients with T2DM inadequately controlled on metformin to date. In addition to determining the effects of these treatments on glycemic control over the long term, this study will investigate effects on beta-cell function, cardiovascular risk factors and markers of renal function/damage. The results will help to inform the choice of second-line treatment in patients with T2DM who have failed on metformin. [ABSTRACT FROM AUTHOR]

Background: In-hospital observation is typically recommended for patients who present to the emergency department with symptomatic hypoglycemia who are taking oral diabetes medications or long acting insulin. Individuals considered to be at low risk of further hypoglycemic episodes by treating providers are however on occasion discharged to home when a low suspicion of recurrence and close observation is available. We describe the frequency of hypoglycemia recurrence requiring further emergency department evaluation who have been recently discharged from the emergency department and are taking oral diabetes medications or long-acting insulin., Methods: A retrospective chart review was performed over a 2-year period of time at a large community-based academic emergency department for patients with an ICD-9 diagnosis of hypoglycemia who were taking oral or injectable diabetes medications. Patients were included with symptomatic blood sugar readings less than 55 mg/dL measured by prehospital or hospital providers. For those discharged from the emergency department, medical records from the study hospital and nearby health care facilities, Emergency Medical Service reports, and county death records were reviewed to determine recurrence of symptoms requiring care., Results: There were 196 patients discharged over the study period with 10 (5.1%) patients returning to the emergency department within 48 h with recurrent hypoglycemia. Return visits occurred in 4 of 144 taking insulin alone; 2.8% (CI 1.1-6.9%), in 3 of 19 patients taking oral agents alone; 15.8% (CI 5.5-37.5%), and in 3 of 33 patients taking both insulin and oral medications; 9.1% (CI 3.1-23.6%). Frequency of hypoglycemia recurrence requiring repeat ED visits was more common in those taking oral agents compared to individuals taking insulin alone (p = 0.04). All 7 individuals with recurrent hypoglycemia who were taking insulin were taking long-acting insulin preparations. No discharged patients were identified on Emergency Medical Service refusal of care reports or county death records., Conclusion: Individuals discharged from the emergency department following hypoglycemic episodes who were taking oral diabetes medications are at a greater risk than individuals taking insulin alone of a return emergency department visit within 48 h for recurrent hypoglycemia.

Background: Almost 20 years ago, the frequencies of severe hypoglycemia requiring emergency medical treatment were reported in people with types 1 and 2 diabetes in the Tayside region of Scotland. With subsequent improvements in the treatment of diabetes, concurrent with changes in the provision of emergency medical care, a decline in the frequency of severe hypoglycemia could be anticipated. The present population-based data-linkage cohort study aimed to ascertain whether a temporal change has occurred in the incidence rates of hypoglycemia requiring emergency medical services in people with types 1 and 2 diabetes., Methods: The study population comprised all people with diabetes in Tayside, Scotland over the period 1 January 2011 to 31 December 2012. Patients' data from different healthcare sources were linked anonymously to measure the incidence rates of hypoglycemia requiring emergency medical services that include treatment by ambulance staff and in hospital emergency departments, and necessitated hospital admission. These were compared with data recorded in 1997-1998 in the same region., Results: In January 2011 to December 2012, 2029 people in Tayside had type 1 diabetes and 21,734 had type 2 diabetes, compared to 977 and 7678, respectively, in June 1997 to May 1998. In people with type 2 diabetes, the proportion treated with sulfonylureas had declined from 36.8 to 22.4% ( p  < 0.001), while insulin-treatment had increased from 11.7 to 18.7% ( p  < 0.001). The incidence rate of hypoglycemia requiring emergency medical treatment had significantly fallen from 0.115 (95% CI: 0.094-0.136) to 0.082 (0.073-0.092) events per person per year in type 1 diabetes ( p  < 0.001), and from 0.118 (0.095-0.141) to 0.037 (0.003-0.041) in insulin-treated type 2 diabetes ( p  = 0.008). However, the absolute annual number of hypoglycemia events requiring emergency treatment was 1.4-fold higher., Conclusions: Although from 1998 to 2012 the incidences of hypoglycemia requiring emergency medical services appeared to have declined by a third in type 1 diabetes and by two thirds in insulin-treated type 2 diabetes, because the prevalence of diabetes was higher (2.7 fold), the number of severe hypoglycemia events requiring emergency medical treatment was greater.

Background: Type 2 diabetes (T2D) is a worldwide epidemic with considerable health and economic consequences. Sulfonylureas are widely used drugs for the treatment of patients with T2D. KCNJ11 and ABCC8 encode the K ir 6.2 (pore-forming subunit) and SUR1 (regulatory subunit that binds to sulfonylurea) of pancreatic β cell K ATP channel respectively with a critical role in insulin secretion and glucose homeostasis. TCF7L2 encodes a transcription factor expressed in pancreatic β cells that regulates insulin production and processing. Because mutations of these genes could affect insulin secretion stimulated by sulfonylureas, the aim of this study is to assess associations between molecular variants of KCNJ11, ABCC8 and TCF7L2 genes and response to sulfonylurea treatment and to predict their potential functional effects., Methods: Based on a comprehensive literature search, we found 13 pharmacogenetic studies showing that single nucleotide polymorphisms (SNPs) located in KCNJ11: rs5219 (E23K), ABCC8: rs757110 (A1369S), rs1799854 (intron 15, exon 16 -3C/T), rs1799859 (R1273R), and TCF7L2: rs7903146 (intron 4) were significantly associated with responses to sulfonylureas. For in silico bioinformatics analysis, SIFT, PolyPhen-2, PANTHER, MutPred, and SNPs3D were applied for functional predictions of 36 coding (KCNJ11: 10, ABCC8: 24, and TCF7L2: 2; all are missense), and HaploReg v4.1, RegulomeDB, and Ensembl's VEP were used to predict functions of 7 non-coding (KCNJ11: 1, ABCC8: 1, and TCF7L2: 5) SNPs, respectively., Results: Based on various in silico tools, 8 KCNJ11 missense SNPs, 23 ABCC8 missense SNPs, and 2 TCF7L2 missense SNPs could affect protein functions. Of them, previous studies showed that mutant alleles of 4 KCNJ11 missense SNPs and 5 ABCC8 missense SNPs can be successfully rescued by sulfonylurea treatments. Further, 3 TCF7L2 non-coding SNPs (rs7903146, rs11196205 and rs12255372), can change motif(s) based on HaploReg v4.1 and are predicted as risk factors by Ensembl's VEP., Conclusions: Our study indicates that a personalized medicine approach by tailoring sulfonylurea therapy of T2D patients according to their genotypes of KCNJ11, ABCC8, and TCF7L2 could attain an optimal treatment efficacy.

Background: For most cruciferous plants, which are known as important crops and a number of weeds, hybrid breeding is hampered by the unavailability of a pollination control system. Male sterility induced by a gametocide can be useful for the utilization of plant heterosis., Results: The gametocidal effect of sulfonylurea herbicide tribenuron-methyl was tested across seventeen cruciferous species or subspecies including Brassica juncea, B. carinata, B. oleracea ssp. capitata, B. oleracea ssp. acephala, B. rapa ssp. pekinensis, B. rapa ssp. chinensis, B. rapa ssp. parachinensis, B. nigra, Orychophragmus violaceus, Matthiola incana, Raphanus sativa, Sisymbrium altissimum, Eruca sativa, Sinapis alba, Sinapis arvensis, Capsella bursa-pastoris and Camelina sativa. The plants of 23 cultivars in these species or subspecies were foliar sprayed with 10 ml of 0.2 or 0.4 mg/L of tribenuron-methyl before the vacuolated microspore formed in the largest flower buds; the application was repeated ten to twelve days afterwards. Tribenuron-methyl exposure significantly changed the flowering phenology and reproductive function. The treated plants demonstrated a one to four day delay in flowering time and a shortened duration of flowering, as well as other slight phytotoxic effects including a reduction in plant height and floral organ size. Approximately 80% to 100% male sterility, which was estimated by both pollen staining and selfing seed-set rate, was induced in the plants. As a result, plants were rendered functionally able to out-cross, with an average 87% and 54% manually pollinated seed-set rate compared to the corresponding controls at the 0.2 mg/L and 0.4 mg/L doses, respectively., Conclusions: The results suggested that male reproductive function was much more sensitive to tribenuron-methyl exposure than female function. This sulfonylurea herbicide has a promising use as the gametocide for hybrid production in cruciferous plants.