Diabetes mellitus por mutación en el gen de glucokinasa: caso clínico / Diabetes mellitus caused by a mutation of glucokinase gene: report of an affected family

Maturity-Onset Diabetes of the Young (MODY) refers to a heterogeneous group of monogenic diabetes. Unlike other types of MODY characterized by genetic defects in transcription factors, MODY 2 is triggered by metabolic alterations caused by mutations of glucokinase (GCK), the first enzyme of the glycolytic pathway. We report a three-generation Chilean family with multiple cases affected with this disease. The index case is a patient who presented severe neonatal hyperglycemia (831 mg/dl, without ketosis) requiring continuous infusion of insulin, which was suspended after 48 hours with normalization of blood glucose. Subsequently, continuous glucose monitoring at 4 months of age revealed 47% of tissue glucose levels above 140 mg/dl, with fasting glucose levels between 120 and 166 mg/dl. The genetic analysis revealed a previously reported mutation in heterozygous state of the GCK gene (c.148C>T; p.His50Tyr). This mutation was also identified in more than one affected relative in the last two generations, with a transmission pattern suggestive of dominant inheritance. GCK gene sequencing led to a correct molecular diagnosis of MODY 2 while bioinformatic analysis indicated the possible molecular causes of the enzyme dysfunction. The knowledge of the molecular diagnosis allowed an adequate medical treatment for this disease.

Diabetes autoinmune (latente) del adulto / Latent autoimmune diabetes in adults

Backgroud: Latent Autoimmune Diabetes in Adults (LADA) is the term used to describe adults who have a slowly progressive form of diabetes mellitus (DM) of autoimmune etiology, but that may be treated initially without insulin. Although it shares some immunological and genetic aspects with type 1 DM, it affects an age group that is typically affected by type 2 DM. Therefore, it could be considered an intermediate type. Diagnosis is based on clinical and laboratory criteria: age of onset, initial response to oral hypoglycemic agents and the presence of specific antibodies for diabetes. Although the definitive treatment is insulin, glitazones may be useful in early stages of the disease. Currently, its management represents a challenge for the physician, including specialists, and it is a form of DM to keep in mind.

Determinación del índice de resistencia insulínica mediante HOMA en una población de la Región Metropolitana de Chile / Measurement of insulin resistance using the homeostasis model

Background: Insulin resistance is defined as an inappropriate high level of plasma insulin required to maintain metabolic homeostasis. It is associated with type 2 diabetes and cardiovascular diseases. The glucose clamp technique is the standard method for the measurement of insulin resistance. However, this method is laborious, expensive and impractical to perform in epidemiological investigations. The homeostasis model assessment (HOMA) has been proposed to assess insulin resistance and secretion, using fasting glucose and insulin concentrations. Aim: To measure insulin resistance using HOMA (HOMAir) in a population sample from the Metropolitan Region in Chile. Material and Methods: One hundred twenty subjects (59 female) with a normal body mass index and fasting blood glucose were studied. Fasting plasma glucose was measured by a glucose oxidase method and serum insulin was measured by radio immunoassay. Results: Fasting blood glucose was 81.6ñ9.4 mg/dl and serum insulin was 9.7ñ2.4 µU/ml. Mean HOMA insulin resistance was 1.96ñ0.57 (range 0.5 and 3.0). Conclusions: These HOMA values can be used as reference for Chilean non obese individuals

Indicadores de riesgo de aterosclerosis: evaluación mediante coronariografía en hombres no diabéticos con colesterol total igual o menor a 240 mg/dl / Index of atherosclerosis risk: evaluation by coronariography in non diabetic males with total cholesterol same or less than 240 mg/dl

We studied 90 male non diabetic patients aged between 40 and 65 years old with a total cholesterol of less than 240 mg/dl and not receiving cholesterol reducing drugs, that were subjected to elective coronary arteriography. Weight, height, blood pressure and smoking habits were recorded and a fsting blood sample was drawn to mesure total and HDL cholesterol, triglycerides, apoproteins A! and B, Lipoprotein(a) and plasma cholesteryl ester transfer activity. Arteriography disclosed coronary lesions in 54 patients. Compared to patients without lesions, the former had lower HDL cholesterol (34 ñ 9.8 vs 40.2 ñ 11.6 mg/dl) and higher total cholesterol/HDL, cholesterol and apoB/apoA1 ratios. No differences were found for lipoprotein(a) and plasma cholesteryl ester transfer activity. Unvariate analysis showed that low HDL cholesterol had the best predictive capacity for atherosclerosis