ABSTRACT
Neonatal diabetes mellitus is considered when there is hyperglycaemia requiring insulin therapy. Phenotypically NDM is classified into three types-transient, permanent and syndromic forms. Permanent NDM-may start in new-born life and is mainly due single gene mutations-KCNJ11 and ABCC8. This mutation is almost 90% manageable with oral sulphonyl ureas. We report a case of Permanent NDM with KCNJ11 mutation who presented in diabetic Ketoacidosis at 4 months of age. Clinical genome sequencing revealed a heterozygous missense variation in exon 1 of the KCNJ11 gene (chr11: g.17387491G>A) that results in the amino acid substitution of cysteine for arginine at codon 201. She was initially treated with insulin for which she had poor glycaemic control. She responded well following the switch over to sulphonylureas with good compliance and has normal development.
ABSTRACT
Resumen La diabetes mellitus tipo 2 es una de las enfermedades metabólicas que afecta a diferentes órganos, uno en el cual es el riñón. Una de las principales complicaciones microvasculares es la nefropatía diabética, siendo la principal causa de insuficiencia renal crónica a nivel mundial. De ahí la importancia de las recomendaciones en la utilización o no de los fármacos antihiperglicemiantes, basadas en sus efectos beneficiosos a nivel de la función renal en relación con la tasa de filtración glomerular estimada y la relación albumina/creatinina en pacientes con diabetes mellitus tipo 2 y enfermedad renal. En estudios recientes se han evaluado antihiperglicemiantes con un impacto beneficioso a nivel de desenlaces cardiovascular y renal. En el presente artículo se revisan las acciones y los efectos de los diferentes grupos de medicamentos como la metformina, los inhibidores de la dipeptidil peptidasa 4, los agonistas de la GLP-1, tiazolidinedionas, sulfonilureas, inhibidores del cotransportador de sodio-glucosa tipo 2 e insulinas en la función renal en cuanto a las dosis de cada fármaco, tanto el uso de dosis establecidas, disminución de la dosis o el no uso del medicamento con base en el empeoramiento de la tasa de filtración glomerular estimada. Con respecto a la metodología aplicada para el desarrollo del artículo, se seleccionó artículos a partir de palabras claves como diabetes mellitus tipo 2, antihiperglicemiantes en la función renal, tasa de filtración glomerular estimada y relación albumina/creatinina; se emplearon artículos de revistas reconocidas que no superaran 5 años en su publicación, sin embargo, se utilizaron artículos que superaran este tiempo, dado que aportaban datos importantes para el artículo de revisión.
Abstract Type 2 diabetes mellitus is one of the metabolic diseases that affects different organs, one of which is the kidney. One of the main microvascular complications is diabetic nephropathy, being the main cause of chronic renal failure worldwide. Hence the importance of recommendations on the use or non-use of antihyperglycemic drugs based on their beneficial effects on kidney function, expressed by the estimated glomerular filtration rate and the albumin / creatinine ratio in patients with type 2 diabetes mellitus and kidney disease. Recent studies have shown antihyperglycemic agents with beneficial impact in cardiovascular and renal endpoints. In the present article we will review the actions and effects of different groups of drugs such as metformin, inhibitors of dipeptidyl peptidase 4, GLP-1 agonists, thiazolidinediones, sulfonylureas, SGLT-2 inhibitors and insulins in renal function in relation to the doses of each drug, both the use of established doses, reduction of the dose or non-use of the drug based on the worsening of the estimated glomerular filtration rate. With respect to the methodology applied for the development of the article, a selection of articles was made based on key words such as type 2 diabetes mellitus, antihyperglycemic agents in renal function, estimated glomerular filtration rate and albumin/ creatinine ratio. Prestigious journal articles were used with less than 5 years since its publication, however articles that exceed this time were used as they provided important data in the review article.
Subject(s)
Humans , Blood Glucose/analysis , Diabetes Mellitus, Type 2/drug therapy , Renal Insufficiency, Chronic/complications , Metformin/antagonists & inhibitorsABSTRACT
Diabetes is a chronic metabolic disorder with high mortality rate and with defects in multiple biological systems. Two major types of diabetes are recognized, type 1 and 2 with type 2 diabetes (T2D) being by far the more prevalent type. As diabetes affects multiple biological functions, the use of multiple drug classes having different mode of actions is required in order to optimize therapy in diabetic patients. Five major classes of oral antidiabetic agents (OHA) have traditionally been used for the management of patients with T2D. These include the sulphonylureas, meglitinides, biguanides, thiazolidinediones and the alpha-glucosidase inhibitors. Several newer classes of agents have also been introduced recently in the pharmacotherapy of T2D, including the incretin mimetics, the dipeptidy peptidase 4 (DPP-4) inhibitors, the sodium glucose co-transporter 2 (SGLT 2) inhibitors and more recently, the dual peroxisome proliferator-activated receptor (PPAR) agonists. Each of these agents has been shown in various experimental and clinical settings to be efficacious in T2D, but each is also associated with a number of adverse effects. Despite the vastarray of drugs introduced, metformin, a biguanide, largely remains the first choice mono therapy in T2D patients but several combination options are also available in poly pharmacy when mono therapy fails to produce the required glycemic control. The increasing number of drugs, together with numerous combination options in poly pharmacy, presents with the clinician an increasing complexity of therapeutic options. The likely pathogenetic mechanism of diabetes operating in the patient, as well as the mode of action, efficacy and safety of the drugs are some of the major considerations in the choice of any given agent or its combinations. This review therefore focuses on the mode of action, pharmacokinetics, indications, efficacy and adverse effects of the OHA used in T2D.
ABSTRACT
Adenosine triphosphate (ATP)-sensitive potassium (KATP) channels in pancreatic beta-cells play a crucial role in insulin secretion and glucose homeostasis. These channels are composed of two subunits: a pore-forming subunit (Kir6.2) and a regulatory subunit (sulphonylurea receptor-1). Recent studies identified large number of gain of function mutations in the regulatory subunit of the channel which cause neonatal diabetes. Majority of mutations cause neonatal diabetes alone, however some lead to a severe form of neonatal diabetes with associated neurological complications. This review focuses on the functional effects of these mutations as well as the implications for treatment.
Subject(s)
Adenosine Triphosphate , Glucose , Homeostasis , Insulin , KATP Channels , Polyphosphates , PotassiumABSTRACT
Objective: To study the common single nucleotide polymorphism (SNPs) of sulphonylurea receptor 1 (SUR1) gene (16-3c/t and S1369A) and its relationship with the glucose-reducing effect of gliclazide. Methods: A total of 115 patients with type 2 diabetes were enrolled in this 8-week, open-label, cohort study. All patients were required to take gliclazide for 8 weeks. FPG, HbA1c and insulin were assayed before and after therapy and HOMA-B and HOMA-IR indices were calculated to assess the therapeutic effects of gliclazide. The gene polymorphism of SUR1 was analyzed by Taq-Man technology and the effects of gliclazide were compared between patients with different phenotypes. Results: (1) The study was completed in 101 of the 115 patients and the frequencies of c and t alleles were 0.54 and 0.44, A and S were 0.58 and 0.42, respectively. (2) FPG, HbA1c and HOMA-B indices were significantly improved after therapy in patients with all kinds of genotypes (P0.05). (3) The changes of HbA1c and HOMA-B indices of t/t group were more obvious than those of c/c and c/t groups (P0.05). Conclusion: The polymorphism of SUR1 can influence the glucose-reducing effect of gliclazide and this influence might be associated with loci of SNPs.
ABSTRACT
Ion channels present in the plasma membrane and intracellular organelles of all cells, play an important role in maintaining cellular integrity, smooth muscle contraction, secretion of hormones and neurotransmitters. Among the ion channels, potassium channels (K+) are the most abundant having important role in cardiac repolarization, smooth muscle relaxation and insulin release. These are also involved in the regulation of physiological functions like gastrointestinal peristalsis. These channels are the most diverse of all ion channels and are coded by at least 75 genes. Moreover, these have different subunits which co-assemble to form diverse functional channels. Abnormalities in K+ channels are associated with diseases like long QT syndrome, Anderson Tawil syndrome, epilepsy, type 2 diabetes mellitus, etc. A number of naturally occurring as well as synthetic compounds have been identified that modulate the opening and closure of KATP Channels. Some of the currently available K+ channel modulators like sulphonylureas, minoxidil, amiodarone, etc. lack tissue selectivity and have adverse effects. Hence, the success of KATP channel modulators depend on their tissue selectivity. Molecular level studies are needed to understand the type of K+ channels as this can lead to the development of newer drugs with tissue selectivity for various diseases.
Subject(s)
Animals , Brain/physiology , Diabetes Mellitus, Type 2/physiopathology , Heart/physiology , Heart Diseases/physiopathology , Humans , Potassium Channel Blockers/therapeutic use , Potassium Channels/antagonists & inhibitors , Potassium Channels/genetics , Potassium Channels/physiologyABSTRACT
Objective In order to explore the effective dosage of insulin and its correlated elements in sulphonylureas failure in type 2 diabetes mellitus.Methods 61 cases of type 2 diabetics were separated into two groups,one group (group 1) is the first time using insulin and the other group (group 2) is in the use of insulin in the past.Results The effective insulin dosage of group 2 is significantly higher than that of group 1 (36.2?10.6 IU/d vs 30.1?10.5IU/d, P