Associations among diabetes medication use, serum magnesium, and insulin resistance in a cohort of older Puerto Rican adults.

BACKGROUND: Hypomagnesemia is commonly observed in individuals with diabetes, but how diabetes medications alter magnesium (Mg) status remains unclear. OBJECTIVES: We aimed to examine the association between diabetes medication and hypomagnesemia and evaluate whether serum Mg mediates the association between diabetes medication and Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) in a prospective cohort. METHODS: Adults from the Boston Puerto Rican Health Study were included (n = 1106). Multivariable logistic regression models were used to estimate odds ratio (OR) and 95% confidence interval (CI) for cross-sectional association between diabetes medication and hypomagnesemia (serum Mg <0.75 mmol/L). Longitudinal mediation analysis was performed to evaluate the direct and indirect (via serum Mg) associations between diabetes medication and 4-y HOMA-IR in 341 participants with baseline hemoglobin A1c (HbA1c) of ≥6.5%. RESULTS: Mean age at baseline was 59.0 ± 7.6 y, with 28.0% male and 45.8% with hypomagnesemia. Use of metformin [OR (95% CI) = 3.72 (2.53, 5.48)], sulfonylureas [OR (95% CI) = 1.68 (1.00, 2.83)], and glitazones [OR (95% CI) = 2.09 (1.10, 3.95)], but not insulin, was associated with higher odds of hypomagnesemia. Use of multiple diabetes medications and longer duration of use were associated with higher odds of hypomagnesemia. Serum Mg partially mediated the association between metformin and HOMA-IR [indirect association: ß (95% CI) = 1.11 (0.15, 2.07)], which weakened the direct association [ß (95% CI) = -5.16 (-9.02, -1.30)] by 22% [total association: ß (95% CI) = -4.05 (-7.59, -0.51)]. Similarly, serum Mg mediated 17% of the association between sulfonylureas and elevated HOMA-IR. However, the mediation by serum Mg was weak for insulin and glitazones. CONCLUSIONS: Diabetes medication, especially metformin, was associated with elevated odds of hypomagnesemia, which may weaken the association between metformin and lowering of HOMA-IR. The causal inference needs to be confirmed in further studies.

Effects of Remote Ischemic Preconditioning on Decreasing Troponin Release in Patients Not Taking Sulfonylureas After Cardiac Surgery - A Meta-Analysis.

INTRODUCTION: Remote ischemic preconditioning (RIPC) is a new noninvasive myocardial protection strategy that uses blood pressure cuf inflation to simulate transient non-fatal ischemia to protect the myocardium and reduce ischemia-reperfusion injury. Sulfonylureas may mask the effects of RIPC due to their cardioprotec-tive effect. This meta-analysis aimed to evaluate whether RIPC, in the absence of sulfonylureas, reduces troponin release in patients undergoing cardiac surgery. METHODS: We conducted a meta-analysis of randomized controlled clinical trials to determine whether RIPC can reduce postoperative troponin release in cardiac surgery patients undergoing cardiopulmonary bypass without treatment with sulfonylureas. The data were normalized to equivalent units prior to the analysis. A random-effects model was used to provide more conservative estimate of the effects in the presence of known or unknown heterogeneity. RESULTS: Six studies with a total of 570 participants were included. The analysis showed that troponin release was lower in the RIPC group than in the control group at six hours (test of standardized mean differences = 0, Z=3.64, P<0.001) and 48 hours (Z=2.72, P=0.007) postoperatively. When the mean of cross-clamping time was > 60 minutes, RIPC reduced troponin release at six hours (Z=2.84, P=0.005), 24 hours (Z=2.64, P=0.008), and 48 hours (Z=2.87, P=0.004) postoperatively. CONCLUSION: In cardiac surgery patients who are not taking sulfonylureas, RIPC can reduce troponin release at six and 48 hours postoperatively; hence, RIPC may serve significant benefits in certain cardiac surgery patients.

Effects of Remote Ischemic Preconditioning on Decreasing Troponin Release in Patients Not Taking Sulfonylureas After Cardiac Surgery - A Meta-Analysis

ABSTRACT Introduction: Remote ischemic preconditioning (RIPC) is a new noninvasive myocardial protection strategy that uses blood pressure cuf inflation to simulate transient non-fatal ischemia to protect the myocardium and reduce ischemia-reperfusion injury. Sulfonylureas may mask the effects of RIPC due to their cardioprotec-tive effect. This meta-analysis aimed to evaluate whether RIPC, in the absence of sulfonylureas, reduces troponin release in patients undergoing cardiac surgery. Methods: We conducted a meta-analysis of randomized controlled clinical trials to determine whether RIPC can reduce postoperative troponin release in cardiac surgery patients undergoing cardiopulmonary bypass without treatment with sulfonylureas. The data were normalized to equivalent units prior to the analysis. A random-effects model was used to provide more conservative estimate of the effects in the presence of known or unknown heterogeneity. Results: Six studies with a total of 570 participants were included. The analysis showed that troponin release was lower in the RIPC group than in the control group at six hours (test of standardized mean differences = 0, Z=3.64, P<0.001) and 48 hours (Z=2.72, P=0.007) postoperatively. When the mean of cross-clamping time was > 60 minutes, RIPC reduced troponin release at six hours (Z=2.84, P=0.005), 24 hours (Z=2.64, P=0.008), and 48 hours (Z=2.87, P=0.004) postoperatively. Conclusion: In cardiac surgery patients who are not taking sulfonylureas, RIPC can reduce troponin release at six and 48 hours postoperatively; hence, RIPC may serve significant benefits in certain cardiac surgery patients.

A Target-Site Mutation Confers Cross-Resistance to ALS-Inhibiting Herbicides in Erigeron sumatrensis from Brazil.

Cases of weed resistant to herbicides have changed the dynamics of agricultural areas in Brazil, and in recent years, Erigeron species have caused major problems to farmers in the country, mainly in relation to the ineffectiveness of herbicide treatments used. The objective of this study was to confirm the cross-resistance to ALS inhibitors in populations of Erigeron sumatrensis as well as to investigate the existence of mutations in the site of action of ALS-inhibiting herbicides. To do this, 30 populations collected in the 2016/2017 crop season were grown in a greenhouse. Dose-response (chlorimuron-ethyl and cloransulam-methyl), inhibition of cytochrome P-450 with malathion, and ALS gene sequencing experiments were carried out in the F1 generations of two fleabane populations. The results proved the cross-resistance to chlorimuron-ethyl and cloransulam-methyl herbicides applied in the post-emergence of the resistant population of E. sumatrensis. The higher activity of P450 enzymes is unlikely responsible for the resistance of the population studied. The resistance mechanism found in R was the target site mutation Pro197Ser at the ALS gene. This is the first study in Brazil to identify a target-site change as a survival mechanism in E. sumatrensis for the resistance to ALS-inhibiting herbicides.

The Use of Oral Hypoglycemic Agents during Pregnancy: An Alternative to Insulin?

OBJECTIVE: Gestational Diabetes Mellitus (GDM) and Type 2 Diabetes Mellitus (DM2) are metabolic disorders characterized by increased insulin resistance. Although insulin is the treatment of choice in pregnant patients with DM, the prescription of oral hypoglycemic agents (OHA) has been increasing among practitioners. This study aimed to evaluate the maternal and neonatal outcomes when oral hypoglycemic agents were used in diabetic pregnant women. METHODS: Medical records from the Maternal-Infant Care Unit Clinics SoM-UPR (n=149) were reviewed. Patients that were treated with metformin, sulfonylurea or insulin were included. Maternal and neonatal outcomes were compared between groups. RESULTS: Patient's mean age was 28 ± 6 years. The majority had GDM (91%). The most common comorbidity was hypertension (9.9%). Lifestyle modification was used as treatment in 77% of patients during the second trimester, but its use decreased to 33% during the third trimester. Insulin was the treatment of choice. Among the OHA, sulfonylurea was preferred. Postprandial glucose levels were lower in patients who used insulin as compared to those without medications. CONCLUSION: No significant differences were found in maternal outcomes such as C-section, induction of labor, episiotomy or preterm labor, or neonatal outcomes such as macrosomia, neonatal hypoglycemia or congenital abnormalities among treatment groups. OHA can be considered as an alternative to insulin for the treatment of DM during pregnancy in selected cases.

Pregnancy Complicated by the Most Frequent Forms of Maturity Onset Diabetes of the Young: A Narrative Review on Its Pharmacological Implications.

BACKGROUND: Monogenic Diabetes (MFD) represents close to 2% of all the cases of diabetes diagnosed in people younger than 45 years old. Maturity-Onset Diabetes of the Young (MODY), neonatal diabetes, and several syndromic forms of diabetes are included among the most accounts for about typical forms of MDF. MODY is the most frequent type of MFD, with MODY 1, 2, 3, and 5 being the most prevalent forms. The aim of this narrative review is to describe pregnancy associated changes in the pharmacological profile of the antidiabetic drugs used in women with the most frequent MODY subtypes. METHODS: A comprehensive literature search was carried out to identify eligible studies from MEDLINE/ PubMed, EMBASE, and SCIELO databases from 1970 to 2019 first semester. RESULTS: Pregnancy introduces changes in the pharmacodynamic and pharmacokinetic profile of some of the treatments used in MODY. MODY 3 (also known as HNF1-A MODY) is the most frequent MDF. MODY 3 patients are highly sensitive to Sulfonylureas (SU). This is also the case for MODY pregnant women. This high sensitivity to SU is also registered in patients with MODY 1 (HNF4-A MODY). Pharmacodynamic changes have been proposed to explain this behavior (Epac2 hyperactivity). However, changes in expression/activity of the metabolizing CYP2C9 cytochrome and/or alterations in the drug transporters oatp1 (Slc21a1), Lst-1 (Slc21a6), OATPD (SLC21A11), and oat2 may better explain, at least in part, this phenomenon by an increase in the concentration of the active drug. CONCLUSION: The impact of changes in the pharmacological behavior of drugs like SU and other metabolized/transported by mechanisms altered in a pregnancy complicated by MODY is unknown. However, switching-to-insulin recommendation formulated for MODY 1 and 3 seems to be justified. Further research in this field is needed for a better understanding of changes in drug activity associated with this particular subset of patients with MFD.

Synthesis and characterization of a molecularly imprinted polymer (MIP) for solid-phase extraction of the antidiabetic gliclazide from human plasma.

Gliclazide is a sulfonylurea frequently prescribed for the management of type 2 diabetes mellitus in elderly patients and for patients with chronic renal or hepatic diseases. Even though it is considered a safer alternative, the drug can provoke side effects in some patients, especially hypoglycemia, due to the high interindividual variability. Therefore, the quantification of gliclazide in biological samples is usually recommended in order to assure efficacy and safety of the pharmacotherapy. However, due to the complexity of biological matrices, therapeutic monitoring can be very challenging, especially in the sample preparation step. For that reason, the synthesis and characterization of a novel and selective molecularly imprinted polymer (MIP) was proposed to be employed as sorbent for the extraction of gliclazide from human plasma samples by a molecularly imprinted solid-phase extraction (MISPE) procedure. Synthesis conditions were optimized (monomer, crosslinker and porogen) and the polymer was characterized for its morphological, physicochemical and stability properties. The influence of drug concentration, solvent composition and pH on the coefficient of distribution (Kd) and imprinting factor (IF) were studied, as well as repeatability between batches and selectivity. A bioanalytical method was developed applying the developed MIP as sorbent in solid phase extraction and liquid chromatography using a Poroshell 120 C18 (100 × 4.6 mm, 4 µm) column, acetonitrile and 10 mM potassium phosphate buffer pH 3.0 (50:50) at a flow-rate of 1.2 mL/min as mobile phase, temperature of 30 °C, injection volume of 40 µL and detection at 230 nm. The best reaction yield, extraction capacity, and selectivity was obtained using 2-hydroxyethyl methacrylate (2-HEMA), ethyleneglycol dimethacrylate (EGDMA) and acetonitrile. The optimized MIP showed coefficient of distribution (Kd) of 59.85 µg/g, imprinting factor (IF) of 1.60, and selectivity for gliclazide and other sulfonylureas compared to possible concurrent drugs. The developed method by MISPE-HPLC-UV showed to be appropriate to determine gliclazide in human plasma samples.

Effect of Ahasl1-1 and Ahasl1-4 alleles on herbicide resistance and its associated dominance in sunflower.

BACKGROUND: Acetohydroxyacid synthase large subunit 1 (Ahasl1) is a multiallelic locus involved in herbicide resistance in sunflower. Ahasl1-1 and Ahasl1-4 alleles harbor different point mutations that lead to different amino acid substitutions (Ala205Val and Trp574Leu, respectively). The objectives of this work were to evaluate the effect of these alleles at the enzymatic and whole-plant levels, and to determine the dominance relationships for imazapyr and metsulfuron-methyl herbicides. RESULTS: Resistant near-isogenic lines showed significantly lower specific AHAS activity than susceptible near-isoline. However, kinetic studies indicated that mutations did not change AHAS pyruvate affinity. Dose-response for six near-isolines carrying different combinations of Ahasl1-1 and Ahasl1-4 alleles and two herbicides (imazapyr and metsulfuron-methyl) were evaluated at whole-plant and enzymatic levels. Ahasl1-1 allele conferred moderate resistance to imazapyr and low resistance to metsulfuron-methyl. Conversely, Ahasl1-4 allele endowed high levels of resistance for both herbicides. Dominance of resistance at whole-plant level showed a semi-dominant behavior among the alleles for both herbicides. CONCLUSION: Ahasl1-4 allele confers higher resistance levels than Ahasl1-1 when evaluated with imazapyr and metsulfuron-methyl. Dominance estimations suggested that both parental lines should carry a resistance trait when developing hybrids. © 2018 Society of Chemical Industry.

Prevalence of hypoglycemia among a sample of sulfonylurea-treated patients with Type 2 diabetes mellitus in Argentina: The real-life effectiveness and care patterns of diabetes management (RECAP-DM) study.

AIM: Strict blood glucose control in the treatment of diabetes can sometimes lead to hypoglycemia. The main aim of this study was to assess the prevalence of hypoglycemia among patients receiving sulfonylureas alone, or in combination with metformin, for the treatment of Type 2 Diabetes Mellitus (T2DM) in Argentina. METHODS: This is a real life, multi-center, retrospective, and cross-sectional study based on clinical chart reviews including cross-sectional data, and evaluation of patient questionnaires of T2DM patients (>30 years), treated with sulfonylureas alone or in combination with metformin, during a routine clinic visit in 16 medical centers across Argentina. Socio-demographic and clinical parameters were collected from medical records, as well as hypoglycemic events from both the medical records and the patient questionnaires. The glycated hemoglobin (HbA1c) levels were obtained from medical records as well as a blood test. RESULTS: The study included a total of 397 patients with a mean age of 62.5 years, diagnosed for 9.9 years, and 54.2% male. Mean HbA1c levels were 8.1%, (65mmol/mol) at enrolment, with 36.4% being in control (HbA1c<7%, (53mmol/mol). Patients with HbA1c<7%, (53mmol/mol) were significantly older, diagnosed at older age, and had lower triglyceride levels. Almost 50% reported hypoglycemic episodes that were mostly mild, and with women more likely to report them. The large majority (86%) were on combined metformin and sulfonylureas, most commonly Glibenclamide (48.6%). Patients on combined therapy were significantly younger and more likely to have uncontrolled diabetes. CONCLUSIONS: This study demonstrated that out of a sample of 397 patients with T2DM treated with sulfonylureas alone or in combination with metformin in Argentina, around 50% of them reported symptoms of hypoglycemia induced by sulfonylureas, and one third of them achieved target HbA1c<7% levels.

Genotypic and Phenotypic Factors Influencing Drug Response in Mexican Patients With Type 2 Diabetes Mellitus.

The treatment of Type 2 Diabetes Mellitus (T2DM) consists primarily of oral antidiabetic drugs (OADs) that stimulate insulin secretion, such as sulfonylureas (SUs) and reduce hepatic glucose production (e.g., biguanides), among others. The marked inter-individual differences among T2DM patients' response to these drugs have become an issue on prescribing and dosing efficiently. In this study, fourteen polymorphisms selected from Genome-wide association studies (GWAS) were screened in 495 T2DM Mexican patients previously treated with OADs to find the relationship between the presence of these polymorphisms and response to the OADs. Then, a novel association screening method, based on global probabilities, was used to globally characterize important relationships between the drug response to OADs and genetic and clinical parameters, including polymorphisms, patient information, and type of treatment. Two polymorphisms, ABCC8-Ala1369Ser and KCNJ11-Glu23Lys, showed a significant impact on response to SUs. Heterozygous ABCC8-Ala1369Ser variant (A/C) carriers exhibited a higher response to SUs compared to homozygous ABCC8-Ala1369Ser variant (A/A) carriers (p-value = 0.029) and to homozygous wild-type genotypes (C/C) (p-value = 0.012). The homozygous KCNJ11-Glu23Lys variant (C/C) and wild-type (T/T) genotypes had a lower response to SUs compared to heterozygous (C/T) carriers (p-value = 0.039). The screening of OADs response related genetic and clinical factors could help improve the prescribing and dosing of OADs for T2DM patients and thus contribute to the design of personalized treatments.

Mechanism of Action of Novel Glibenclamide Derivatives on Potassium and Calcium Channels for Insulin Secretion.

Glibenclamide is widely used and remains a cornerstone and an effective antihyperglycemic drug. After the casual discovery of its hypoglycemic potential, this compound was introduced for diabetes treatment. However, the long-term side effects reveal that glibenclamide should be replaced by new molecules able to maintain the health of ß-cells, protecting them from hyperstimulation/hyperexcitability, hyperinsulinemia, functional failure and cell death. The aim of this review was to highlight the main mechanism of action of glibenclamide and the influence of its derivatives, such as acylhydrazones, sulfonamides and sulfonylthioureas on ß-cells potassium and calcium channels for insulin secretion as well as the contribution of these new compounds to restore glucose homeostasis. Furthermore, the role of glibenclamide-based novel structures that promise less excitability of ß-cell in a long-term treatment with effectiveness and safety for diabetes therapy was discussed.

Contrasts among origins of corn hybrids in relation to their susceptibility to nicosulfuron and isoxaflutole herbicides / Contrastes entre procedências de híbridos de milho em relação à suscetibilidade aos herbicidas nicosulfuron e isoxaflutole

Herbicide selectivity is the basis for successfull weed chemical control in agricultural production, as it is considered as a measurement of the difeerential response of different plant species to a certain herbicide. The objective of this work was to evaluate the effect of the origin of corn hybrid in relation to its susceptibility to the herbicides nicosulfuron and isoxaflutole. The research was conducted in greenhouse conditions and comprised two experiments, being the first one with nicosulfuron (09/09/2005 to 10/24/2005) and another one with isoxaflutole (10/09/04 to 11/10/04). Both experiments were run in a randomized blocks design, in a factorial scheme 33x3 for nicosulfuron and 23x3 for isoxaflutole, with four replicates. The first factor was constituted by corn hybrids and the second one by herbicide rates. After herbicide spraying, shoot dry biomass was evaluated. It was concluded that origins of corn hybrids affects the susceptibility to the herbicides nicosulfuron and isoxaflutole. In average, Balu and Codetec hybrids were the most sensitive to nicosulfuron. For isoxaflutole applied at 120 g ha-1 Balu hybrids were more tolerant than Embrapa hybrids.

A seletividade de herbicidas é a base para o sucesso do controle químico de plantas daninhas na produção agrícola, sendo considerada uma medida da resposta diferencial de diversas espécies de plantas a um determinado herbicida. Objetivou-se neste trabalho avaliar o efeito da procedência de híbridos de milho em relação à suscetibilidade aos herbicidas nicosulfuron e isoxaflutole. O estudo envolveu dois experimentos, um com nicosulfuron no período de 09/09/05 a 24/10/05 e outro com isoxaflutole no período de 09/10/04 a 10/11/04, ambos realizados em casa-de-vegetação. Os experimentos foram conduzidos no delineamento de blocos ao acaso, em arranjo fatorial de 33x3 para o nicosulfuron e 23x3 para o isoxaflutole, com quatro repetições, sendo que o primeiro fator constituído por híbridos de milho e o segundo por dosagens dos herbicidas. Após a aplicação do herbicida, avaliou-se a massa seca de parte aérea das plantas. Existem diferenças de tolerância entre procedências de híbridos de milho em relação à suscetibilidade aos herbicidas nicosulfuron e isoxaflutole. Constatou-se que, em média, as procedências Balu e Coodetec foram mais sensíveis ao nicosulfuron do que as demais procedências. Na dosagem de 120 g ha-1 de isoxaflutole, em média, a procedência Balu mostrou-se mais tolerante que a Embrapa.

Contrasts among origins of corn hybrids in relation to their susceptibility to nicosulfuron and isoxaflutole herbicides / Contrastes entre procedências de híbridos de milho em relação à suscetibilidade aos herbicidas nicosulfuron e isoxaflutole

Herbicide selectivity is the basis for successfull weed chemical control in agricultural production, as it is considered as a measurement of the difeerential response of different plant species to a certain herbicide. The objective of this work was to evaluate the effect of the origin of corn hybrid in relation to its susceptibility to the herbicides nicosulfuron and isoxaflutole. The research was conducted in greenhouse conditions and comprised two experiments, being the first one with nicosulfuron (09/09/2005 to 10/24/2005) and another one with isoxaflutole (10/09/04 to 11/10/04). Both experiments were run in a randomized blocks design, in a factorial scheme 33x3 for nicosulfuron and 23x3 for isoxaflutole, with four replicates. The first factor was constituted by corn hybrids and the second one by herbicide rates. After herbicide spraying, shoot dry biomass was evaluated. It was concluded that origins of corn hybrids affects the susceptibility to the herbicides nicosulfuron and isoxaflutole. In average, Balu and Codetec hybrids were the most sensitive to nicosulfuron. For isoxaflutole applied at 120 g ha-1 Balu hybrids were more tolerant than Embrapa hybrids.

A seletividade de herbicidas é a base para o sucesso do controle químico de plantas daninhas na produção agrícola, sendo considerada uma medida da resposta diferencial de diversas espécies de plantas a um determinado herbicida. Objetivou-se neste trabalho avaliar o efeito da procedência de híbridos de milho em relação à suscetibilidade aos herbicidas nicosulfuron e isoxaflutole. O estudo envolveu dois experimentos, um com nicosulfuron no período de 09/09/05 a 24/10/05 e outro com isoxaflutole no período de 09/10/04 a 10/11/04, ambos realizados em casa-de-vegetação. Os experimentos foram conduzidos no delineamento de blocos ao acaso, em arranjo fatorial de 33x3 para o nicosulfuron e 23x3 para o isoxaflutole, com quatro repetições, sendo que o primeiro fator constituído por híbridos de milho e o segundo por dosagens dos herbicidas. Após a aplicação do herbicida, avaliou-se a massa seca de parte aérea das plantas. Existem diferenças de tolerância entre procedências de híbridos de milho em relação à suscetibilidade aos herbicidas nicosulfuron e isoxaflutole. Constatou-se que, em média, as procedências Balu e Coodetec foram mais sensíveis ao nicosulfuron do que as demais procedências. Na dosagem de 120 g ha-1 de isoxaflutole, em média, a procedência Balu mostrou-se mais tolerante que a Embrapa.

Management of maturity-onset diabetes of the young (MODY)

La diabetes de tipo MODY (maturity-onset diabetes of the young) afecta entre 1 y 5% de los pacientes con diabetes en los Estados Unidos y otras naciones industrializadas. Las tres características más importantes de esta entidad son: desarrollo de diabetes antes de la edad de 25 a 30 años en ausencia de autoanticuerpos pancreáticos, transmisión genética autosómica dominante y evidencia de secreción residual de insulina. Existen seis subtipos de MODY de los cuales, el tipo 2 (mutación de la glucoquinasa-GKS) y el tipo 3 (mutación del factor nuclear hepático 1 alfa (HNF-1-alfa) son los más prevalentes (70% de todos los casos de diabetes de tipo MODY). Las sulfonilureas son la medicación de primera línea tanto en los niños como en los adultos, cuando la terapia dietética no es suficiente para normalizar la glicemia. Aunque los pacientes con subtipos 1, 3, y 4 usualmente responden bien a la terapia oral con sulfonilureas, un porcentaje significativo de pacientes con los subtipos 1 y 3 necesitan terapia con insulina debido a un deterioro progresivo de las células beta del páncreas. El mantenimiento de un estilo de vida activo y un peso normal, son recomendaciones esenciales en todos los pacientes con diabetes de tipo MODY.

Maturity-Onset Diabetes of the Young (MODY) affects 1-5% of people with diabetes in the USA and other industrialized countries. The three main features of MODY include: Development of diabetes before the age of 25 to 30 in absence of pancreatic antibodies, autosomal dominant inheritance, and evidence of residual insulin secretion. There are six subtypes of MODY of which, MODY2 (GCK mutation) and MODY3 (HNF1-alphaƒnmutation) are the most prevalent, accounting for more than 70% of cases. Sulfonylureas (SUs) remain the medication of first choice in children and adults when dietary therapy is insufficient to maintain normoglycemia. Although patients with MODY1, 3, and 4 usually respond very well to oral SUs, due to progressive beta-cell failure, a significant proportion of MODY1 and MODY3 patients may eventually require insulin therapy. Leading an active lifestyle and maintaining a normal weight are essential recommendations for all MODY patients.