[Analysis of 4,164 type 1 diabetes antibody profiles in a Chilean health centre]. / Marcadores inmunológicos de diabetes tipo 1: análisis de 4.164 perfiles en un centro de salud de Chile.

BACKGROUND: Previous studies have assessed the role of Type 1 diabetes (DM1) antibodies as predictors of the natural history of disease. AIM: To determine the frequency and combinations of positivity for DM1 antibodies in patients with DM1 and the relationship between antibody positivity and the age of the patient. To explore the relationship between history of insulin therapy or diabetic ketoacidosis (DKA) at the onset of the disease with antibody positivity in a subsample. MATERIAL AND METHODS: Data was gathered from every sample processed for DM1 antibodies in our laboratory between January 2015 and September 2019. Medical records from 84 patients who tested positive for at least one antibody were revised to study the relationship between insulin therapy or DKA at the onset of the disease with antibody positivity. RESULTS: Forty percent of DM1 antibody tests were positive. Among positive tests, 1, 2, 3 or 4 DM1 antibodies were detected in 48%, 33%, 17% and 3% of cases, respectively. The likelihood of testing positive was inversely related with age for ICA, GAD, IA-2, ZnT8 and directlyproportionalforIAA (p= -0,012; -0,013; -0,014; -0,009; 0,005 respectively). An association between DKA at the onset of the disease and IA-2 positivity was observed (Odds ratio (OR) 5.38 95% confidence intervals (CI) 1.79 - 16.16, P < 0.01). No association was found between IAA positivity and history of insulin therapy (OR 2.25 95%CI 0.63 - 7.90, P = 0.2403). The results obtained from this study represent a novel local profile of DM1 antibody data, highlighting a relationship between antibody positivity and age.

Marcadores inmunológicos de diabetes tipo 1: análisis de 4.164 perfiles en un centro de salud de Chile / Analysis of 4, 164 type 1 diabetes antibody profiles in a Chilean health centre

Background: Previous studies have assessed the role of Type 1 diabetes (DM1) antibodies as predictors of the natural history of disease. Aim: To determine the frequency and combinations of positivity for DM1 antibodies in patients with DM1 and the relationship between antibody positivity and the age of the patient. To explore the relationship between history of insulin therapy or diabetic ketoacidosis (DKA) at the onset of the disease with antibody positivity in a subsample. Material and Methods: Data was gathered from every sample processed for DM1 antibodies in our laboratory between January 2015 and September 2019. Medical records from 84 patients who tested positive for at least one antibody were revised to study the relationship between insulin therapy or DKA at the onset of the disease with antibody positivity. Results: Forty percent of DM1 antibody tests were positive. Among positive tests, 1, 2, 3 or 4 DM1 antibodies were detected in 48%, 33%, 17% and 3% of cases, respectively. The likelihood of testing positive was inversely related with age for ICA, GAD, IA-2, ZnT8 and directlyproportionalforIAA (p= −0,012; −0,013; −0,014; −0,009; 0,005 respectively). An association between DKA at the onset of the disease and IA-2 positivity was observed (Odds ratio (OR) 5.38 95% confidence intervals (CI) 1.79 − 16.16, P < 0.01). No association was found between IAA positivity and history of insulin therapy (OR 2.25 95%CI 0.63 − 7.90, P = 0.2403). The results obtained from this study represent a novel local profile of DM1 antibody data, highlighting a relationship between antibody positivity and age.

[Second Consensus of the Chilean Society of Endocrinology and Diabetes about insulin resistance]. / II Consenso de la Sociedad Chilena de Endocrinología y Diabetes sobre resistencia a la insulina.

Insulin resistance is a prevalent condition commonly associated with unhealthy lifestyles. It affects several metabolic pathways, increasing risk of abnormalities at different organ levels. Thus, diverse medical specialties should be involved in its diagnosis and treatment. With the purpose of unifying criteria about this condition, a scientific-based consensus was elaborated. A questionnaire including the most important topics such as cardio-metabolic risk, non-alcoholic fatty liver disease and polycystic ovary syndrome, was designed and sent to national experts. When no agreement among them was achieved, the Delphi methodology was applied. The main conclusions reached are that clinical findings are critical for the diagnosis of insulin resistance, not being necessary blood testing. Acquisition of a healthy lifestyle is the most important therapeutic tool. Insulin-sensitizing drugs should be prescribed to individuals at high risk of disease according to clinically validated outcomes. There are specific recommendations for pregnant women, children, adolescents and older people.

II Consenso de la Sociedad Chilena de Endocrinología y Diabetes sobre resistencia a la insulina

Insulin resistance is a prevalent condition commonly associated with unhealthy lifestyles. It affects several metabolic pathways, increasing risk of abnormalities at different organ levels. Thus, diverse medical specialties should be involved in its diagnosis and treatment. With the purpose of unifying criteria about this condition, a scientific-based consensus was elaborated. A questionnaire including the most important topics such as cardio-metabolic risk, non-alcoholic fatty liver disease and polycystic ovary syndrome, was designed and sent to national experts. When no agreement among them was achieved, the Delphi methodology was applied. The main conclusions reached are that clinical findings are critical for the diagnosis of insulin resistance, not being necessary blood testing. Acquisition of a healthy lifestyle is the most important therapeutic tool. Insulin-sensitizing drugs should be prescribed to individuals at high risk of disease according to clinically validated outcomes. There are specific recommendations for pregnant women, children, adolescents and older people.

[Evaluation of serum insulin levels after an oral glucose load for the diagnosis of insulin resistance]. / Evaluación de la insulinemia post carga oral de glucosa como método diagnóstico de resistencia a la insulina.

BACKGROUND: In our country, the assessment of insulin resistance (IR) measuring serum insulin levels at 60 and 120 minutes after a 75 g oral glucose tolerance test (OGTT), is usual. However, there is no information about the distribution of serum insulin levels in the Chilean population. AIM: To assess the distribution of serum insulin levels at 60 and 120 minutes during OGTTs and suggest a statistical cut-off point to estimate the degree of IR. MATERIAL AND METHODS: Retrospective analysis of 1815 OGTTs performed in non-diabetic subjects aged between 18 and 75 years, at a university medical center. HOMA-IR (Homeostasis Model Assessment), insulin sensitivity index of Matsuda (ISI-Composite), and their correlation with serum insulin levels at 60 and 120 minutes were calculated. RESULTS: The 75th percentiles for serum insulin levels at 60 and 120 minutes were 127 and 81 µU/mL, respectively. There was a high correlation between HOMA-IR and ISI-Composite (r = -089, p < 0.001). There was a weaker although significant correlation between HOMA-IR and ISI-Composite and insulin levels at 60 (r = 0.56 and -0.79 respectively, p < 0,001) and 120 minutes (r = 0.54 and -0.75 respectively, p < 0,001). CONCLUSIONS: We propose 60 and 120 min serum insulin levels of 130 and 80 µU/mL respectively, as cut-off values for normality during OGTT in Chilean normoglycemic individuals.

Evaluación de la insulinemia post carga oral de glucosa como método diagnóstico de resistencia a la insulina / Evaluation of serum insulin levels after an oral glucose load for the diagnosis of insulin resistance

Background: In our country, the assessment of insulin resistance (IR) measuring serum insulin levels at 60 and 120 minutes after a 75 g oral glucose tolerance test (OGTT), is usual. However, there is no information about the distribution of serum insulin levels in the Chilean population. Aim: To assess the distribution of serum insulin levels at 60 and 120 minutes during OGTTs and suggest a statistical cut-off point to estimate the degree of IR. Material and Methods: Retrospective analysis of 1815 OGTTs performed in non-diabetic subjects aged between 18 and 75 years, at a university medical center. HOMA-IR (Homeostasis Model Assessment), insulin sensitivity index of Matsuda (ISI-Composite), and their correlation with serum insulin levels at 60 and 120 minutes were calculated. Results: The 75th percentiles for serum insulin levels at 60 and 120 minutes were 127 and 81 µU/mL, respectively. There was a high correlation between HOMA-IR and ISI-Composite (r = -089, p < 0.001). There was a weaker although significant correlation between HOMA-IR and ISI-Composite and insulin levels at 60 (r = 0.56 and -0.79 respectively, p < 0,001) and 120 minutes (r = 0.54 and -0.75 respectively, p < 0,001). Conclusions: We propose 60 and 120 min serum insulin levels of 130 and 80 µU/mL respectively, as cut-off values for normality during OGTT in Chilean normoglycemic individuals.

Acarbose improves hypoglycaemia following gastric bypass surgery without increasing glucagon-like peptide 1 levels.

BACKGROUND: Postprandial hypoglycaemia is a severe complication of Roux-en-Y gastric bypass (RYGBP). Acarbose, an α-glucosidase inhibitor (AGI), is employed in its treatment. Several studies have shown that AGIs increase the postprandial levels of glucagon-like peptide 1 (GLP-1). However, an excessive level of GLP-1 is one of the factors involved in the physiopathology of this condition. We analysed the effect of acarbose oral administration in eight RYBGP patients with clinically significant hypoglycaemia or dumping syndrome. METHODS: Glucose, insulin and GLP-1 plasma levels in fasting and after ingestion of a standard meal (Ensure Plus®; 13 g protein, 50 g carbohydrate, 11 g fat) were measured. The test was repeated the following week with the oral administration of 100 mg of acarbose 15 min prior to the meal. RESULTS: Five patients developed asymptomatic hypoglycaemia during the test (glucose level <50 mg/dl) with inappropriately high insulin levels and exaggerated GLP-1 response. Acarbose ingestion avoided hypoglycaemia in all of the patients and increased the lowest plasma glucose level (46.4 ± 4.8 vs. 59.0 ± 2.6 mg/dl, p < 0.01). Acarbose ingestion decreased the area under the curve for serum insulin and GLP-1 levels at 15 min after the meal. CONCLUSIONS: Acarbose avoided postprandial hypoglycaemia following RYGBP by decreasing the hyperinsulinemic response. This was associated with a decrease in early GLP-1 secretion, in contrast to that observed in non-surgical subjects. This finding could be explained by the reduction of glucose load in the jejunum produced by the α-glucosidase inhibition, which is the main stimulus for GLP-1 secretion.

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

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.

[Clinical and metabolic features of subjects with glucose intolerance and high fasting glucose levels]. / Características clínicas y metabólicas de los estados de intolerancia a la glucosa y glicemia de ayuno alteradas.

BACKGROUND: Subjects with glucose intolerance or high fasting glucose levels have a higher cardiovascular risk and frequently become diabetic. AIM: To assess clinical and metabolic characteristics of patients with glucose intolerance or high fasting glucose levels. MATERIAL AND METHODS: Fasting and post glucose load serum glucose and insulin levels were measured in 1404 people, aged 42,0 +/- 14,2 years (81% women) with high diabetic risk. We categorized subjects in different alterations of blood glucose, according to 2006 American Diabetes Association categories. Insulin resistance (RI), insulin secretion (beta %) and insulin disposition (ID), were calculated using fasting blood glucose and insulin levels, using the homeostasis model assessment (HOMA I and II). RESULTS: Sixty percent of studied subjects had first grade relatives with diabetes mellitus and 1097 (78%) were categorized as normal (N), 45 (3%) as Diabetes Mellitus (DM), 161 (11%) as high fasting glucose levels (GAA) and 103 (7%) as glucose intolerant (ITG). Fifty three of the 106 subjects with GAA (50%), were also glucose intolerant. Subjects with GAA had similar insulin sensitivity and lower beta cell function than N (insulin disposition 58 +/- 12 and 111 +/- 32%, respectively p < 0.01). ITG had less insulin sensitivity than N (HOMA-IR 2.6 +/- 1.50 +/- and 2.0 +/- 1.30, respectively) and only a mild decrease in beta cell function (insulin disposition 96 +/- 26 and 111 +/- 32% respectively, p < 0.01). Patients GAA plus ITG had similar alterations than those with DM (HOMA-IR 3.8 +/- 2.2 and 4.4 +/- 3.7 respectively; insulin disposition 57 +/- 10 and 56.0 +/- 26% respectively. CONCLUSIONS: Patients with higher fasting glucose levels behave differently from those with glucose intolerance. High fasting glucose levels are highly prevalent in subjects with high risk of DM and must be considered as risk indicator in preventive programs for diabetes mellitus.

Características clínicas y metabólicas de los estados de intolerancia a la glucosa y glicemia de ayuno alteradas / Clinical and metabolic features of subjects with glucose intolerance and high fasting glucose levels

Background: Subjects with glucose intolerance or high fasting glucose levels have a higher cardiovascular risk and frequently become diabetic. Aim: Toassess clinical and metabolic characteristics of patients with glucose intolerance or high fasting glucose levels. Material and methods: Fasting and post glucose load serum glucoseand insulin levels were measured in 1404 people, aged 42,0 ± 14,2 years (81% women) with high diabetic risk. We categorized subjects in different alterations of blood glucose, accordingto 2006 American Diabetes Association categories. Insulin resistance (RI), insulin secretion (ß %) and insulin disposition (ID), were calculated using fasting blood glucose and insulin levels, using the homeostasis model assessment (HOMA I and II). Results: Sixty percent of studied subjects had first grade relatives with diabetes mellitus and 1097 (78%) were categorized as normal (N), 45 (3%) as Diabetes Mellitus (DM), 161 (11%) as high fasting glucose levels (GAA) and 103 (7%) as glucose intolerant (ITG). Fifty three of the 106 subjects with GAA (50%), were also glucose intolerant. Subjects with GAA had similar insulinsensitivity and lower ß cell function than N (insulin disposition 58 ± 12 and 111 ± 32%, respectively, p <0.01). ITG had less insulin sensitivity than N (HOMA-IR 2.6 ± 1.50 ± and 2.0 ± 1.30, respectively) and only a mild decrease in ß cell function (insulin disposition 96 ± 26 and 111 ± 32% respectively, p < 0.01). Patients GAA plus ITG had similar alterations than those with DM (HOMA-IR 3.8 ± 2.2 and 4.4 ± 3.7 respectively; insulin disposition 57 ± 10 and 56.0 ± 26% respectively. Conclusions: Patients with higher fasting glucose levels behavedifferently from those with glucose intolerance. High fasting glucose levels are highly prevalent in subjects with high risk of DM and must be considered as risk indicator in preventive programs for diabetes mellitus.

[Determination of the insulin resistance index by the Homeostasis Model Assessment in a population of Metropolitan Region in Chile]. / Determinación del índice de resistencia insulínica mediante HOMA en una población de la región metropolitana de Chile.

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 81.6 +/- 9.4 mg/dl and serum insulin was 9.7 +/- 2.4 microU/ml. Mean HOMA insulin resistance was 1.96 +/- 0.57 (range 0.5 and 3.0). CONCLUSIONS: These HOMA values can be used as reference for Chilean non obese individuals.