Association between insulin resistance and the development of cardiovascular disease.

For many years, cardiovascular disease (CVD) has been the leading cause of death around the world. Often associated with CVD are comorbidities such as obesity, abnormal lipid profiles and insulin resistance. Insulin is a key hormone that functions as a regulator of cellular metabolism in many tissues in the human body. Insulin resistance is defined as a decrease in tissue response to insulin stimulation thus insulin resistance is characterized by defects in uptake and oxidation of glucose, a decrease in glycogen synthesis, and, to a lesser extent, the ability to suppress lipid oxidation. Literature widely suggests that free fatty acids are the predominant substrate used in the adult myocardium for ATP production, however, the cardiac metabolic network is highly flexible and can use other substrates, such as glucose, lactate or amino acids. During insulin resistance, several metabolic alterations induce the development of cardiovascular disease. For instance, insulin resistance can induce an imbalance in glucose metabolism that generates chronic hyperglycemia, which in turn triggers oxidative stress and causes an inflammatory response that leads to cell damage. Insulin resistance can also alter systemic lipid metabolism which then leads to the development of dyslipidemia and the well-known lipid triad: (1) high levels of plasma triglycerides, (2) low levels of high-density lipoprotein, and (3) the appearance of small dense low-density lipoproteins. This triad, along with endothelial dysfunction, which can also be induced by aberrant insulin signaling, contribute to atherosclerotic plaque formation. Regarding the systemic consequences associated with insulin resistance and the metabolic cardiac alterations, it can be concluded that insulin resistance in the myocardium generates damage by at least three different mechanisms: (1) signal transduction alteration, (2) impaired regulation of substrate metabolism, and (3) altered delivery of substrates to the myocardium. The aim of this review is to discuss the mechanisms associated with insulin resistance and the development of CVD. New therapies focused on decreasing insulin resistance may contribute to a decrease in both CVD and atherosclerotic plaque generation.

A Colombian diabetes risk score for detecting undiagnosed diabetes and impaired glucose regulation.

AIMS: (i) To develop a diabetes mellitus risk score model for the Colombian population (ColDRISC); and (ii) to evaluate the accuracy of the ColDRISC unknown Type 2 diabetes mellitus METHODS: Cross-sectional screening study of the 18-74 years-old population of a health-care insurance company (n=2060) in northern Colombia. Lifestyle habits and risk factors for diabetes mellitus were assessed by an interview using a questionnaire consisting of information regarding sociodemographic factors, history of diabetes mellitus, tobacco consumption, hypertension, nutritional and physical activity habits. Anthropometric measurements and an oral glucose tolerance test were taken. The sensitivity and the specificity, receiver-operating characteristic (ROC) curves, were calculated for the ColDRISC and FINDRISC. RESULTS: The area under the ROC curve for unknown Type 2 diabetes mellitus was 0.74 (95% CI: 0.70-0.79) for the ColDRISC and 0.73 for the FINDRISC (95% confidence intervals [CI] 0.69-0.78). Using the risk score cutoff value of 4 in the ColDRISC to detect Type 2 diabetes mellitus resulted in a sensitivity of 73% and specificity of 67%. CONCLUSIONS: The characteristics of the ColDRISC show that it can be used as a simple, safe, and inexpensive test to identify people at high risk for Type 2 diabetes mellitus in Colombia.

Glucose Metabolism Disorder Is Associated with Pulmonary Tuberculosis in Individuals with Respiratory Symptoms from Brazil.

BACKGROUND: Diabetes mellitus (DM) has been associated with increased risk for pulmonary tuberculosis (PTB) in endemic settings but it is unknown whether PTB risk is also increased by pre-DM. Here, we prospectively examined the association between glucose metabolism disorder (GMD) and PTB in patients with respiratory symptoms at a tuberculosis primary care reference center in Brazil. METHODS: Oral glucose tolerance test was performed and levels of fasting plasma glucose and glycohemoglobin (HbA1c) were measured in a cohort of 892 individuals presenting with respiratory symptoms of more than two weeks duration. Patients were also tested for PTB with sputum cultures. Prevalence of pre-DM and DM (based on HbA1c) was estimated and tested for association with incident PTB. Other TB risk factors including smoking history were analyzed. RESULTS: The majority of the study population (63.1%) exhibited GMD based on HbA1c ≥5.7%. Patients with GMD had higher prevalence of PTB compared to normoglycemic patients. Individuals with DM exhibited increased frequency of TB-related symptoms and detection of acid-fast bacilli in sputum smears. Among patients with previous DM diagnosis, sustained hyperglycemia (HbA1c ≥7.0%) was associated with increased TB prevalence. Smoking history alone was not significantly associated with TB in our study population but the combination of smoking and HbA1c ≥7.0% was associated with 6 times higher odds for PTB. CONCLUSIONS: Sustained hyperglycemia and pre-DM are independently associated with active PTB. This evidence raises the question whether improving glycemic control in diabetic TB patients would reduce the risk of TB transmission and simultaneously reduce the clinical burden of disease. A better understanding of mechanisms underlying these associations, especially those suggesting that pre-DM may be a factor driving susceptibility to TB is warranted.

Diet, physical activity and mental health status are associated with dysglycaemia in pregnancy: the Healthy Start Study.

AIMS: To examine the association between dysglycaemia and multiple modifiable factors measured during pregnancy. METHODS: The Healthy Start Study collected self-reported data on modifiable factors in early and mid-pregnancy (median 17 and 27 weeks gestation, respectively) from 832 women. Women received one point for each modifiable factor for which they had optimum scores: diet quality (Healthy Eating Index score ≥64), physical activity level (estimated energy expenditure ≥170 metabolic equivalent task-h/week), and mental health status (Perceived Stress Scale score <6 and Edinburgh Postnatal Depression Scale score <13). Dysglycaemia during pregnancy was defined as an abnormal glucose challenge result, ≥1 abnormal results on an oral glucose tolerance test, or a clinical diagnosis of gestational diabetes. Logistic regression models estimated odds ratios for dysglycaemia as a function of each factor and the total score, adjusted for age, race/ethnicity, pre-pregnancy BMI, history of gestational diabetes, and family history of Type 2 diabetes. RESULTS: In individual analyses, only physical activity was significantly associated with a reduced risk of dysglycaemia (adjusted odds ratio 0.67, 95% CI 0.44-1.00). We observed a significant, dose-response association between increasing numbers of optimal factors and odds of dysglycaemia (adjusted P=0.01). Compared with having no optimal modifiable factors, having all three was associated with a 73% reduced risk of dysglycaemia (adjusted odds ratio 0.27, 95% CI 0.08-0.95). CONCLUSIONS: An increasing number of positive modifiable factors in pregnancy was associated with a dose-response reduction in risk of dysglycaemia. Our results support the hypothesis that modifiable factors in pregnancy are associated with the risk of prenatal dysglycaemia.

Serum uric acid and disorders of glucose metabolism: the role of glycosuria

Hyperuricemia has been associated with hypertension, diabetes mellitus, and metabolic syndrome. We studied the association between hyperuricemia and glycemic status in a nonrandomized sample of primary care patients. This was a cross-sectional study of adults ≥20 years old who were members of a community-based health care program. Hyperuricemia was defined as a value >7.0 mg/dL for men and >6.0 mg/dL for women. The sample comprised 720 participants including controls (n=257) and patients who were hypertensive and euglycemic (n=118), prediabetic (n=222), or diabetic (n=123). The mean age was 42.4±12.5 years, 45% were male, and 30% were white. The prevalence of hyperuricemia increased from controls (3.9%) to euglycemic hypertension (7.6%) and prediabetic state (14.0%), with values in prediabetic patients being statistically different from controls. Overall, diabetic patients had an 11.4% prevalence of hyperuricemia, which was also statistically different from controls. Of note, diabetic subjects with glycosuria, who represented 24% of the diabetic participants, had a null prevalence of hyperuricemia, and statistically higher values for fractional excretion of uric acid, Na excretion index, and prevalence of microalbuminuria than those without glycosuria. Participants who were prediabetic or diabetic but without glycosuria had a similarly elevated prevalence of hyperuricemia. In contrast, diabetic patients with glycosuria had a null prevalence of hyperuricemia and excreted more uric acid and Na than diabetic subjects without glycosuria. The findings can be explained by enhanced proximal tubule reabsorption early in the course of dysglycemia that decreases with the ensuing glycosuria at the late stage of the disorder.

Subjects with impaired fasting glucose: evolution in a period of 6 years.

AIM: To study the evolution of impaired fasting glucose (IFG), considering glucose and HbA1c levels and risk factors associated, in a period of 6 years. METHODS: We studied 94 subjects with impaired fasting glucose (IFG) that were diagnosed in 2005 and followed up to 2012. Glucose and HbA1c levels were determined. A descriptive analysis of contingence charts was performed in order to study the evolution in the development of type-2 diabetes mellitus (T2DM). RESULTS: Twenty-eight of ninety-four subjects became T2DM; 51/94 remained with IFG; and 20/94 presented normal fasting glucose. From the 28 diabetic subjects, 9 had already developed diabetes and were under treatment with oral hypoglycemic agents; 5 were diagnosed with plasma glucose < 126 mg/dL, but with HbA1c over 6.5%. In those who developed diabetes, 15/28 had a family history of T2DM in first relative degree. Also, diabetic subjects had a BMI significantly higher than nodiabetics (t test: P < 0.01). The individuals that in 2005 had the highest BMI are those who currently have diabetes. CONCLUSION: The IFG constitutes a condition of high risk of developing T2DM in a few years, especially over 110 mg/dL and in obesity patients.

Serum uric acid and disorders of glucose metabolism: the role of glycosuria.

Hyperuricemia has been associated with hypertension, diabetes mellitus, and metabolic syndrome. We studied the association between hyperuricemia and glycemic status in a nonrandomized sample of primary care patients. This was a cross-sectional study of adults ≥ 20 years old who were members of a community-based health care program. Hyperuricemia was defined as a value >7.0 mg/dL for men and >6.0 mg/dL for women. The sample comprised 720 participants including controls (n=257) and patients who were hypertensive and euglycemic (n=118), prediabetic (n=222), or diabetic (n=123). The mean age was 42.4 ± 12.5 years, 45% were male, and 30% were white. The prevalence of hyperuricemia increased from controls (3.9%) to euglycemic hypertension (7.6%) and prediabetic state (14.0%), with values in prediabetic patients being statistically different from controls. Overall, diabetic patients had an 11.4% prevalence of hyperuricemia, which was also statistically different from controls. Of note, diabetic subjects with glycosuria, who represented 24% of the diabetic participants, had a null prevalence of hyperuricemia, and statistically higher values for fractional excretion of uric acid, Na excretion index, and prevalence of microalbuminuria than those without glycosuria. Participants who were prediabetic or diabetic but without glycosuria had a similarly elevated prevalence of hyperuricemia. In contrast, diabetic patients with glycosuria had a null prevalence of hyperuricemia and excreted more uric acid and Na than diabetic subjects without glycosuria. The findings can be explained by enhanced proximal tubule reabsorption early in the course of dysglycemia that decreases with the ensuing glycosuria at the late stage of the disorder.

Adiposity indices in the prediction of insulin resistance in prepubertal Colombian children.

OBJECTIVE: To compare BMI with abdominal skinfold thickness (ASF), waist circumference and waist-to-height ratio in the prediction of insulin resistance (IR) in prepubertal Colombian children. DESIGN: We calculated age- and sex-specific Z-scores for BMI, ASF, waist circumference, waist-to-height ratio and three other skinfold-thickness sites. Logistic regression with stepwise selection (P = 0·80 for entry and P = 0·05 for retention) was performed to identify predictors of IR and extreme IR, which were determined by age- and sex-specific Z-scores to identify the ≥ 90th and ≥ 95th percentile of homeostasis model assessment (HOMAIR), respectively. We used receiver operating characteristic curves to compare the area under the curve between models. SETTING: Bucaramanga, Colombia. SUBJECTS: Children (n 1261) aged 6-10 years in Tanner stage 1 from a population-based study. RESULTS: A total of 127 children (seventy girls and fifty-seven boys) were classified with IR, including sixty-three children (thirty-three girls and thirty boys) classified with extreme IR. Only ASF and BMI Z-scores were retained as predictors of IR by stepwise selection. Adding ASF Z-score to BMI Z-score improved the area under the curve from 0·794 (95 % CI 0·752, 0·837) to 0·811 (95 % CI 0·770, 0·851; P for contrast = 0·01). In predicting extreme IR, the addition of ASF Z-score to BMI Z-score improved the area under the curve from 0·837 (95 % CI 0·790, 0·884) to 0·864 (95 % CI 0·823, 0·905; P for contrast = 0·01). CONCLUSIONS: ASF Z-score predicted IR independent of BMI Z-score in our population of prepubertal children. ASF and BMI Z-scores together improved IR risk stratification compared with BMI Z-score alone, opening new perspectives in the prediction of cardiometabolic risk in prepubertal children.

[Glycemic dysfunction prevalence post acute pancreatitis. A prospective study]. / Prevalencia de disfunción glucémica post pancreatitis aguda. Estudio prospectivo.

OBJECTIVE: To estimate the prevalence of altered metabolism of carbohydrates in patients with mild acute pancreatitis. METHODS: We included 85 patients diagnosed with pancreatitis. We used to evaluate prognosis Balthazar and Ranson criteria. All patients were interviewed and examined. Was performed routine laboratory and Oral glucose tolerance test (OGTT) We excluded patients with previous diagnosis of diabetes mellitus, alcoholic pancreatitis, severe hypertriglyceridemia and recurrent/ severe pancreatitis. RESULTS: 30 women and 27 men. After performing the OGTT were classified into three groups. Group 1 (n: 19): normal OGTT; Group 2 (n: 33): GAA, IHC, or both, and Group 3 (n = 5): with diabetes mellitus. Patients in group 3 had a higher average age (p = 0.02), and higher diastolic blood pressure (DBP) (p = 0.048). We observe a significant difference in fasting glucose values (p = 0.0001) and 120 minutes post-OGTT in all groups (p = 0.0001). HOMA was found higher (p = 0.031) in group 2. CONCLUSIONS: This study showing a link between mild acute pancreatitis and dysfunction of glucose metabolism, which found older patients, DBP and those with metabolic syndrome, had a higher prevalence of 65.66% of Pre diabetes and diabetes.

Factors associated with poor glycemic control in older Mexican American diabetics aged 75 years and older.

OBJECTIVE: This study examines the prevalence and correlates of poor glycemic control in Mexican Americans aged 75 years and older with diabetes. METHODS: Data are from the 5(th) wave (2004-05) of the Hispanic Established Population for the Epidemiological Study of the Elderly (H-EPESE). A total of 2,069 Mexican Americans aged 75 and over were interviewed. Six hundred eighty nine subjects (33.5%) reported having been diagnosed with diabetes and 209 (30.3%) subjects agreed to a blood test of their HbA(1)c level. RESULTS: Of the 209 diabetic subjects with an HbA(1)c test, 73 (34.9%) had good glycemic control (HbA(1)c <7%) and 136 (65.1%) had poor glycemic control (HbA(1)c >7%). Bivariate analysis revealed that subjects with poor control had longer disease duration, had lower education, used the glucometer more frequently, and had more diabetes-complications when compared to those in the good glycemic control group. Multivariable logistic regression analysis found the following factors associated with poor glycemic control: <8 years of education, foreign-born, smoking, obesity, longer disease duration, daily glucometer use, and having macro-complications. DISCUSSION: Prevalence of poor glycemic control is very high in this population with very high and rising prevalence of diabetes. Further studies are needed to explore the effect of these and other characteristics on glycemic control among older Mexican Americans and to develop appropriate interventions to improve diabetes outcomes and increase life-expectancy.

The prevalence and clinical characteristics of glucose metabolism disorders in patients with liver cirrhosis. A prospective study.

AIMS: To define the prevalence and clinical characteristics of glucose metabolism disorders (GMD) in patients with compensated liver cirrhosis (LC). MATERIAL AND METHODS: Fasting plasma glucose (FPG) levels were measured to 130 patients with clinically stable LC. Oral glucose tolerance tests (OGTT) and fasting plasma insulin determinations were performed to patients with normal FPG. Insulin resistance (IR) was calculated with HOMA2-IR index. GMD were classified according to FPG and OGTT tests results and to the chronologic relation between diagnosis of diabetes mellitus (DM) and LC as follows: type-2 DM (T2DM), hepatogenous diabetes (HD) and impaired glucose tolerance. Patients from all groups were compared. RESULTS: The prevalence of GMD were as follows: T2DM in 25 patients (19.2%, 95% CI 12.5-25.9), HD in 28 (21.5%, 95% CI 14.5-28.5) and IGT in 36 (38.5%, 95% CI 30.1-46.7). The total of patients with GMD was 79.2% (95% CI 72.3-86.1). In 41% of cases GMD were subclinical and 48.7% of patients had IR. Patients with T2DM had a higher number of variables with significant differences compared with the other groups (more marked compared to the patients without GMD). The only differences between the patients with T2DM and HD were hypercreatininemia: 1.14 ± 0.53 vs. 0.84 ± 0.22 mg/dL (p = 0.005) and family history of DM: 8 (32%) vs. 2 (7%) (p = 0.02). CONCLUSION: Almost 80% of patients with compensated LC had GMD. Half of them were subclinical. The patients with T2DM had marked clinical differences compared to patients from the other groups, particularly renal impairment.

Glucose levels are associated with cardiovascular disease and death in an international cohort of normal glycaemic and dysglycaemic men and women: the EpiDREAM cohort study.

AIMS: In an international prospective cohort study we assessed the relationship between glucose levels and incident cardiovascular events and death. METHODS AND RESULTS: 18,990 men and women were screened for entry into the DREAM clinical trial from 21 different countries. All had clinical and biochemical information collected at baseline, including an oral glucose tolerance test (OGTT), and were prospectively followed over a median (IQR) of 3.5 (3.0-4.0) years for incident cardiovascular (CV) events including coronary artery disease (CAD), stroke, congestive heart failure (CHF) requiring hospitalization, and death. After OGTT screening, 8000 subjects were classified as normoglycaemic, 8427 had impaired fasting glucose (IFG) or impaired glucose tolerance (IGT), and 2563 subjects had newly diagnosed type 2 diabetes mellitus (DM). There were incident events in 491 individuals: 282 CAD, 54 strokes, 19 CHF, and 164 died. The annualized CV or death event rate was 0.79/100 person-years in the overall cohort, 0.51/100 person-years in normoglycaemics, 0.92/100 person-years among subjects with IFG and/or IGT at baseline, and 1.27/100 person-years among those with DM (p for trend <0.0001). Among all subjects, a 1 mmol/l increase in fasting plasma glucose (FPG) or a 2.52 mmol/l increase in the 2-h post-OGTT glucose was associated with a hazard ratio increase in the risk of CV events or death of 1.17 (95% CI 1.13-1.22). CONCLUSIONS: In this large multiethnic cohort, the risk of CV events or death increased progressively among individuals who were normoglycaemic, IFG or IGT, and newly diagnosed diabetics. A 1 mmol/l increase in FPG was associated with a 17% increase in the risk of future CV events or death. Therapeutic or behavioural interventions designed to either prevent glucose levels from rising, or lower glucose among individuals with dysglycaemia should be evaluated.

Metabolic syndrome: an all or none or a continuum load of risk?

OBJECTIVE: The aim of this study was to determine if an increasing number of traits of metabolic syndrome was associated with an increased severity of each of the traits. METHODS: A cohort of otherwise healthy 387 Latin-American subjects was evaluated for traits of metabolic syndrome according to National Cholesterol Education Program Adult Treatment Panel III (NECP ATP III) guidelines. Waist cricumference and triglyceride, high-density lipoprotein cholesterol (HDL-C), and blood pressure (BP) levels were measured. Glucose and insulin levels were obtained after 75 g of oral glucose. RESULTS: The prevalence of subjects with no traits and 1, 2, 3, and 4-5 traits was 10.1%, 27.1%, 36.7%, 20.9%, and 5.1%, respectively. Low HDL-C accounted for 55.2% and larger waist circumference for 30.5% of all cases with one trait. High BP and high glucose contributed mainly as the 4th or 5th trait. Higher values for obesity, abdominal obesity, dyslipidemia, BP, hyperglycemia, and hyperinsulinemia were observed as the number of traits increased from 0 to 4-5 traits. More traits meant more severe traits, even after adjusting by age. Subjects with metabolic syndrome but with 4-5 traits had a much higher risk load than those with 3 traits, due to more traits and more severe traits. CONCLUSIONS: We found that with an increasing number of traits of the metabolic syndrome that the severity of each trait increased. A gradual increase in risk load defined by trait clustering and severity was observed when moving from no traits to fully blown metabolic syndrome. Such a continuum of risk was also observed among subjects with metabolic syndrome, implying that subjects diagnosed with the syndrome may be at quite different risk load.

Trastornos metabólicos asociados con la evolución hacia la diabetes mellitus tipo 2 en una población en riesgo / Metabolic disorders associated with the evolution to type 2 diabetes mellitus in a risk group

INTRODUCCIÓN: el estado clínico y metabólico de la población en riesgo de padecer diabetes mellitus tipo 2 (DM2) es muy heterogéneo. OBJETIVO: identificar los factores que influyen en la progresión hacia la diabetes en los subgrupos de pacientes con distintos tipos y gravedad de los trastornos metabólicos. MÉTODOS: se realizó un estudio prospectivo en 209 sujetos en alto riesgo de progresión hacia la diabetes mellitus tipo 2 (antecedentes de trastornos de la tolerancia a la glucosa sin hiperglucemia en ayunas) para examinar los trastornos metabólicos que se asocian con la progresión hacia la diabetes. Se estudió la tolerancia a la glucosa, la secreción de insulina y la sensibilidad a la insulina al inicio del estudio y 2 años después. RESULTADOS: se encontró que el riesgo de desarrollo de diabetes mellitus dependía significativamente del grado de deterioro de la tolerancia a la glucosa presente en el estudio inicial (tolerancia a la glucosa normal, 10 por ciento; tolerancia a la glucosa alterada, 14,6 por ciento; tolerancia a la glucosa alterada + glucemia en ayunas alterada, 56,7 por ciento). En el grupo con tolerancia a la glucosa normal el factor predictivo fundamental de evolución hacia la diabetes mellitus era la deficiencia de la respuesta insulinosecretora inicial (OR: 8,13; IC de 95 por ciento; 1,83 a 36,0). En los sujetos con tolerancia a la glucosa alterada con glucemia en ayunas alterada y sin esta, el factor determinante era la glucemia en ayunas (OR: 5,41; IC de 95 por ciento; 2,15 a 13,6). La resistencia a la insulina no fue un factor predictivo significativo en ninguno de los subgrupos estudiados. CONCLUSIONES: los trastornos de la glucemia posprandial en las etapas iniciales de la evolución de la diabetes mellitus tipo 2 son inconstantes o reversibles, y no son suficientes para basar su diagnóstico precoz y las actividades preventivas o terapéuticas. La aparición de glucemia en ayunas alterada marca el inicio de una etapa de progresión acelerada hacia la diabetes mellitus tipo 2, por lo que en este grupo es necesario intensificar las medidas para revertir o enlentecer el deterioro metabólico. En el grupo con alto riesgo de diabetes y tolerancia a la glucosa normal, el único factor metabólico identificado como marcador pronóstico de la progresión hacia la diabetes es la baja respuesta insulínica. Se recomienda incorporar la evaluación de la capacidad funcional de la célula beta para la detección precoz de personas en riesgo de padecer diabetes(AU)

INTRODUCTION: The clinical and metabolic state of persons in risk of suffer type 2 diabetes mellitus (DM2) is very heterogeneous. Objetive: to identify the factors influencing in progression to diabetes in subgroups of patients with different types and the severity of metabolic disorders. A prospective study was conducted in 209 subjects in high risk of progression to type 2 diabetes mellitus (backgrounds of disorders related to glucose tolerance without fasting hyperglycemia) to examine the metabolic disorders associating with progression to diabetes. Glucose tolerance, insulin secretion and insulin sensitivity were studied at onset and two years later. RESULTS: we found that the risk to develop diabetes mellitus was in a significant dependence of the deterioration degree of glucose tolerance present in the initial study (normal glucose tolerance, 10 percent; altered glucose tolerance, 14,6 percent; altered glucose tolerance + altered fasting glycemia, 56,7 percent). In the group with a normal glucose tolerance the fundamental predictive factor of evolution to diabetes mellitus was the failure of initial insulin secretory response (OR: 8,13; 95 percent CI; 1,83 to 36,0). In the subjects with altered glucose tolerance with fasting altered glycemia and without it, determinant factor was the fasting glycemia (OR: 5,41; 95 percent CI; 2,15 to 13,6). The insulin resistance was not a significant predictive factor in any study subgroups. CONCLUSIONS: postprandial glycemia disorders in early stages of evolution to type 2 diabetes mellitus are changeable or reversible and insufficient to base its early diagnosis and the preventive or therapeutical activities. Appearance of an altered fasting glycemia is the onset of an accelerated progression stage to type 2 diabetes mellitus, thus, in this group it is necessary to intensify the measures to revert or slow the metabolic deterioration. In group with a high risk of diabetes and a normal glucose tolerance the only metabolic factor identified as a prognostic marker of progression to diabetes is the poor insulin-response. It is recommended to add the assessment of the functional ability of Beta-cell for the early detection of persons in risk of diabetes(AU)

Glucose tolerance, insulin secretion, and insulin sensitivity in children and adolescents with cystic fibrosis and no prior history of diabetes.

OBJECTIVE: To determine the prevalence of abnormalities of glucose metabolism in pediatric outpatients with cystic fibrosis (CF). STUDY DESIGN: Children and adolescents (n = 73, mean age 15.0 +/- 3.7 years) with CF not previously diagnosed with diabetes underwent 3-hour oral glucose tolerance testing. All subjects with CF were clinically stable and were not being treated for active infection. A reference group of young lean adults was used for comparison. Subjects were classified as having normal glucose tolerance (NGT) or abnormal glucose metabolism (AGM), including impaired glucose tolerance (IGT), impaired fasting glucose (IFG), or diabetes, by standard criteria. The insulinogenic index was calculated as a measure of beta-cell function, and insulin resistance was estimated with the homeostatic model assessment. RESULTS: The reference group was significantly older than the patients with CF, but in the control subjects, the AGM and NGT were comparable in body mass index z-scores (-0.8 +/- 1.3, -0.6 +/- 1.1, -0.21 +/- 0.9 kg/m2). Thirty-eight percent of subjects with CF had AGM: 43% IGT, 29% IFG, 14% IGT/IFG, and 14% diabetes. In spite of distinct differences in glycemic response, the subjects with NGT and AGM had marked abnormalities of insulin secretion relative to the control subjects (Insulinogenic index 5.8 +/- 1.0, 5.3 +/- 0.8, and 53.5 +/- 10.0 uU/mL/mmol/L, respectively; P < .0001). Insulin sensitivity did not differ among the 3 groups, although there was a trend toward greater insulin resistance in the subjects with AGM (homeostatic model assessment: CF-NGT 1.5 +/- 0.2, CF-AGM 1.9 +/- 0.3, REF 1.3 +/- 0.1, P = NS). CONCLUSION: Abnormalities in glucose metabolism are frequent in young patients with CF without a prior diagnosis of diabetes and are associated with marked defects in insulin secretion. Given the poor beta-cell function in patients with CF, even small reductions in insulin sensitivity may be an important determinant of AGM.