Post-acute pancreatitis diabetes: A complication waiting for more recognition and understanding.

Post-acute pancreatitis diabetes (PAPD) is the second most common type of diabetes below type 2 diabetes mellitus. Due to the boom in research on this entity carried out during the last decade, its recognition has increased. However, much of the medical community still does not recognize it as a medium and long-term complication of acute pancreatitis (AP). Recent prospective cohort studies show that its incidence is about 23% globally and 34.5% in patients with severe AP. With the overall increase in the incidence of AP this complication will be certainly seen more frequently. Due to its high morbidity, mortality and difficult control, early detection and treatment are essential. However, its risk factors and pathophysiological mechanisms are not clearly defined. Its diagnosis should be made excluding pre-existing diabetes and applying the criteria of the American Diabetes Association after 90 d of resolution of one or more AP episodes. This review will show the evidence published so far on the incidence and prevalence, risk factors, possible pathophysiological mechanisms, clinical outcomes, clinical characteristics and preventive and corrective management of PAPD. Some important gaps needing to be clarified in forthcoming studies will also be discussed.

Algorithm for Screening of Adrenal Function in Stable Patients with Cirrhosis.

INTRODUCTION AND AIMS: Adrenal insufficiency (AI) is common in patients with cirrhosis. We aimed to assess the presence of AI in stable patients with cirrhosis using the gold-standard insulin tolerance test (ITT) and to propose an algorithm for screening AI in these patients. MATERIAL AND METHODS: We studied 40 stable patients with cirrhosis. We determined the basal total (BTC) and peak cortisol (PTC) levels. Using the ITT, we defined AI as a serum PTC < 18 µg/dL at 30 min after insulin-induced hypoglycemia. We assessed the diagnostic accuracy of BTC in different stages of liver disease to discriminate between those with NAF and AI. RESULTS: Of the 40 patients, 24 (60%) presented with AI. Child-Pugh and MELD scores differed between the NAF and AI groups (Child-Pugh: NAF 7.2 ± 1.7 vs. AI 8.8 ± 2.4, p = 0.024 and MELD: NAF 9.9 ± 2.5 vs. AI 14.9 ± 6.3, p = 0.001). The BTC level was lower in patients with AI than in those with NAF (7.2 ± 2.4 vs. 12.5 ± 5.2, p < 0.001). A BTC value ≤ 10.0 µg/dL had a 96% sensitivity (negative predictive value: 90%) for identifying AI. This cutoff value (BTC ≤ 10.0 µg/dL) provided 100% specificity (positive predictive value: 100%) in patients with advanced liver disease (Child-Pugh ≥ 9 or MELD ≥ 12). CONCLUSION: An algorithm including the use of BTC and the severity of liver disease may be a useful and simple method for assessing adrenal function in stable patients with cirrhosis.

Comparison of statin eligibility according to the Adult Treatment Panel III, ACC/AHA blood cholesterol guideline, and presence of carotid plaque by ultrasound in Mexican mestizo patients with rheumatoid arthritis.

Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of death in rheumatoid arthritis (RA) patients. Guidelines of the American College of Cardiology and the American Heart Association (ACC/AHA) 2013 and the Adult Treatment Panel III (ATP-III) differ in their strategies to recommend initiation of statin therapy. The presence of carotid plaque (CP) by carotid ultrasound is an indication to begin statin therapy. We aimed to compare the recommendation to initiate statin therapy according to the ACC/AHA 2013 guidelines, ATP-III guidelines, and CP by carotid ultrasound. We then carried out an observational, cross-sectional study of 62 statin-naive Mexican mestizo RA patients, aged 40 to 75, who fulfilled the 1987 or 2010 ACR/European League Against Rheumatism (EULAR) classification criteria. CP was evaluated with B-mode ultrasound. Cohen's kappa (k) was used to assess agreement between ACC/AHA 2013 guidelines, ATP-III guidelines, and the presence of CP, considering a p < 0.05 as statistically significant. Agreement was classified as slight (0.01-0.20), fair (0.21-0.40), moderate (0.41-0.60), substantial (0.61-0.80), and an almost perfect agreement (0.81-1.00). Slight agreement (k = 0.096) was found when comparing statin recommendation between CP and ATP-III. Fair agreement (k = 0.242) was revealed between ACC/AHA 2013 and ATP-III. Comparison between ACC/AHA 2013 and CP showed moderate agreement (k = 0.438). ACC/AHA 2013 guidelines could be an adequate and cost-effective tool to evaluate the need of statin therapy in Mexican mestizo RA patients, with moderate agreement with the presence of CP by ultrasound.

Adding Multiple Adipokines into the Model do not Improve Weight Gain Prediction by Leptin Levels in Newborns.

OBJECTIVE: Most adipose tissue programming is realized in early life. Also, the postnatal three months, rather than the later phases of infancy, may be more relevant in the development of an adverse cardiometabolic risk profile. The adipokines phenotype, as a predictor of early-life weight gain, has been recently explored in cord blood. To determine whether in addition to leptin levels in cord samples, adiponectin, interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), resistin, plasminogen activator inhibitor-1 (PAI-1), and tumor necrosis factor alpha (TNF-α) levels improve weight gain prediction during the first three months of life. METHODS: Adiponectin, IL-6, MCP-1, leptin, resistin, PAI-1, and TNF-α were measured by multiplex immunoassay in a subsample of 86 healthy term newborns. RESULTS: Leptin levels significantly predicted weight gain at 3 months of follow-up (r2=0.09, p=0.006). In the multivariate analysis, including additional adipokines in the model, stepwise or all at once, did not increase the prediction of weight gain after the first three months of life. CONCLUSION: Adding adiponectin, IL-6, MCP-1, resistin, PAI-1, and TNF-α to the prediction model of weight gain in healthy newborns did not prove to be useful. It is probable that their relative contribution to weight gain is not important. Only leptin was relevant as a predictor of weight gain at the 3-month endpoint.

Measurement of Leptin by RIA Versus MIA in a Population of Healthy Newborns.

BACKGROUND: Assays based on multiplex immunoassay (MIA) technology have demonstrated advantages over enzyme-linked immunosorbent assay (ELISA) and radioimmunoassay (RIA). Its acceptance depends on how well it performs in comparison to older techniques. The aim is to compare the results of leptin using RIA versus MIA. METHODS: We analyzed 81 samples of umbilical cord blood of healthy term newborns by RIA and MIA. RESULTS: The concordance correlation coefficient was 0.158 (95% CI 0.10-0.21). Pearson's correlation coefficient was 0.6651 (95% CI 0.52-0.77; P < 0.0001). In the Bland-Altman plot, concordance is acceptable because most of the measurements are within a mean of ±1.96 SD. CONCLUSIONS: As shown by the Bland-Altman plot, there is concordance by both methods, but with a weak correlation.

Plasma cytokine levels imbalance in cirrhotic patients with impaired glucose tolerance and diabetes mellitus. A prospective study.

AIMS: To define if there is an imbalance in plasma levels of proinflammatory, fibrogenic and antifibrogenic cytokines in patients with liver cirrhosis (LC) and impaired glucose tolerance (IGT) or diabetes mellitus (DM). MATERIAL AND METHODS: We randomly selected 54 out of 100 patients with LC who had normal fasting plasma glucose (FPG) levels. Three groups were formed based on an oral glucose tolerance test (OGTT) results: 18 patients were normal, 18 had IGT, and 18 had DM. Plasma levels of cytokines were measured: TNF- α, soluble tumor necrosis factor receptor 1 (sTNF-R1), leptin, TGF-ß1, and hepatocyte growth factor (HGF). Also, fasting plasma insulin (FPI) levels were determined and HOMA2-IR was calculated. Results were compared with those of a control group of 18 patients without liver disease nor DM. Intergroup comparison was performed using non parametric tests. RESULTS: Significantly higher sTNF-R1 and lower TGF-ß1 were found in patients with IGT and DM compared to controls. Leptin, HGF, and TNF-α levels showed no significant differences. According to Child-Pugh classification all cytokines levels were impaired in groups B or C as compared to group A. Positive correlations between sTNF-R1 and HOMA2-IR and between leptin and HOMA2-IR were found. CONCLUSIONS: IGT and DM were associated with abnormalities of sTNF-R1 and TGF-ß1 compared to non cirrhotic controls. Among cirrhotic patients impairment of all cytokines were more marked in advanced liver disease. Finally, sTNF-R1 and leptin correlated with IR. These findings suggest that IGT and DM may be causally implicated with liver inflammation process.

[Diabetes in liver cirrhosis]. / La diabetes en la cirrosis hepática.

The prevalence of overt diabetes mellitus (DM) in liver cirrhosis is about 30%. However, DM or impaired glucose tolerance can be observed in 90% after an oral glucose tolerance test in patients with normal fasting plasma glucose. Type 2 DM may produce cirrhosis, whereas DM may be a complication of cirrhosis. The latter is known as «hepatogenous diabetes¼. Overt and subclinical DM is associated with liver complications and death in cirrhotic patients. Treating diabetes is difficult in cirrhotic patients because of the metabolic impairments due to liver disease and because the most appropriate pharmacologic treatment has not been defined. It is also unknown if glycemic control with hypoglycemic agents has any impact on the course of the liver disease.

Impact of an exercise program on acylcarnitines in obesity: a prospective controlled study.

BACKGROUND: Acylcarnitine (AC) transport dysfunction into the mitochondrial matrix is one of the pathophysiological mechanisms of type 2 diabetes mellitus (DM). The effect of an aerobic exercise (AE) program on this condition in obese subjects without DM is unclear. METHODS: A prospective, randomized, longitudinal, interventional study in a University Research Center involved a 10-week AE program in 32 women without DM and a body mass index (BMI) greater than 27 kg/m2. (Cases n = 17; Controls n = 15). The primary objective was to evaluate the influence of a controlled AE program on beta-oxidation according to modifications in short, medium, and long-chain ACs. Secondary objectives were to define the behavior of amino acids, and the correlation between these modifications with metabolic and anthropometric markers. RESULTS: The proportion of dropouts was 17% and 6% in controls and cases, respectively. In cases there was a significant reduction in total carnitine (30.40 [95% CI 28.2 to 35.6]) vs. (29.4 [CI 95% 25.1 to 31.7]) p = 0.0008 and long-chain AC C14 (0.06 [95% CI 0.05 to 0.08]) vs. (0.05 [95% CI 0.05 to 0.09]) p = 0.005 and in C18 (0.31 [95% CI 0.27 to 0.45]) vs. (0.28 [95% CI 0.22 to 0.32]) p = 0.03. Free fatty acid levels remained without change during the study in both groups. CONCLUSION: In conclusion, a controlled 10-week AE program improved beta-oxidation by reducing long-chain ACs. This finding highlights the importance that AE might have in avoiding or reverting lipotoxicity, and in consequence, improving insulin sensitivity and pancreatic beta cell functional reserve.

Association between umbilical cord leptin and weight gain according to feeding type in the early postnatal period, a brief report.

BACKGROUND: Weight gain in infancy depends on in utero nutritional status, with postnatal growth also dependent on feeding practices, culture, food accessibility and parents' education. OBJECTIVE: To evaluate the relationship between umbilical cord blood leptin levels and feeding mode (breast-fed vs. formula) on weight gain at three months of life. MATERIAL AND METHODS: Ninety-nine full-term newborns (male, n = 48; female, n = 51) were included in two groups according to feeding type: breast-fed (n = 49) and formula-fed (n = 50). Leptin was measured in blood obtained from the umbilical cord vein. RESULTS: Umbilical cord leptin levels and weight gain at three months had a significant inverse correlation in formula-fed infants (r = -0.294, P = 0.038). This finding was not reflected in breast-fed infants (r = -0.212, P = 0.144). CONCLUSIONS: In our Mexican breastfeeding cohort, umbilical cord leptin levels were a significant predictor of weight gain in formula-fed infants.

Typical leptin fall is mitigated by breastfeeding in female infants.

BACKGROUND AND AIMS: Programming of the nutritional and hormonal status of offspring occurs mostly during the gestational and breastfeeding periods. Several studies have reported that breastfed children are more protected from developing obesity in adult life; however, the mechanism that explains this phenomenon is not clear. We undertook this study to evaluate if weight, gender or feeding mode (breastfed or formula-fed) affects leptin levels (during the first 3 months after birth) in a cohort of term newborns, the Breastfeeding Cohort. METHODS: A cohort of 99 term newborns divided into four groups according to gender and feeding type: breastfed female, formula-fed female, breastfed male and formula-fed male were studied. Feeding mode was freely chosen by the parents. Blood sampling for glucose, insulin and leptin was performed at birth and after 3 months. RESULTS: No differences were found among the groups for maternal age, marital status, educational and socioeconomic level, maternal occupation, and prenatal care. No statistically significant differences were found for weight, length or body mass index at birth among the four groups. There were differences in leptin with a higher level in girls (0.907 ± 0.332) than boys (0.663 ± 0.351; p <0.001) at birth and at 3 months (0.618 ± 0.225, 0.464 ± 0.195; p <0.0001). A decrease in leptin levels from birth to 3 months was observed in all groups with the exception of breastfed females (0.849 ± 0.352-0.672 ± 0.222, p = NS). CONCLUSIONS: In our study, breastfed females were protected from this fall in serum leptin levels. Our findings support further studies on the long-term effects of breastfeeding.

[Expand newborn screening using tandem mass spectrometry: two years' experience in Nuevo León, Mexico]. / Tamiz metabólico neonatal por espectrometría de masas en tándem: dos años de experiencia en Nuevo León, México.

OBJECTIVE: To initiate a statewide expanded metabolic screening program in neonates with the purpose of identifying the most common inborn errors of metabolism. MATERIAL AND METHODS: From March 2002 through February 2004, a blood sample was obtained between 24 and 48 hours after delivery from every consecutive child born in public hospitals in Nuevo León. It was spotted on filter paper and analyzed by tandem mass spectrometry for expanded metabolic screening. RESULTS: A total of 42 264 samples were analyzed. Were obtained seven positive results, one for each disorder: homocystinuria, hyperphenylalaninemia, citrulinemia, transient tyrosinemia, 3-methylcrotonyl CoA carboxylase deficiency, 3-hydroxy-3-methylglutaryl CoA deficiency, and classic galactosemia. CONCLUSIONS: The estimated incidence of inborn errors of metabolism is 1:5 000, with a false positive rate of 0.22%. The program permitted the identification of metabolic disorders in the newborn, allowing an early intervention and prevention of life-threatening events and permanent neurological damage.

Tamiz metabólico neonatal por espectrometría de masas en tándem: dos años de experiencia en Nuevo León, México / Expand newborn screening using tandem mass spectrometry: two years' experience in Nuevo León, Mexico

OBJETIVO: Instituir un programa estatal de tamizaje neonatal ampliado para identificar errores innatos del metabolismo y determinar su prevalencia en la población de recién nacidos del estado de Nuevo León. MATERIAL Y MÉTODOS: Entre marzo de 2002 y febrero de 2004 se incluyeron neonatos consecutivos nacidos en hospitales públicos del estado. Se colectaron muestras de sangre en papel filtro entre las 24 y 48 horas de vida y se las sometió a tamiz metabólico mediante espectrometría de masas en tándem. RESULTADOS: Se analizaron 42 264 primeras muestras y se detectaron siete casos, uno de cada padecimiento: homocistinuria, fenilcetonuria, citrulinemia, tirosinemia/transitoria, deficiencia de 3-metilcrotonil-CoA carboxilasa, deficiencia de 3-hidroxi-3-metilglutaril-CoA liasa y galactosemia típica. CONCLUSIONES: La incidencia acumulada de defectos metabólicos en la población fue de 1:5 000 con 0.22 por ciento de casos falso-positivos. El programa permitió identificar y tratar con oportunidad los trastornos metabólicos al nacimiento con una efectiva prevención secundaria del retraso mental.

OBJECTIVE: To initiate a statewide expanded metabolic screening program in neonates with the purpose of identifying the most common inborn errors of metabolism. MATERIAL AND METHODS: From March 2002 through February 2004, a blood sample was obtained between 24 and 48 hours after delivery from every consecutive child born in public hospitals in Nuevo León. It was spotted on filter paper and analyzed by tandem mass spectrometry for expanded metabolic screening. RESULTS: A total of 42 264 samples were analyzed. Were obtained seven positive results, one for each disorder: homocystinuria, hyperphenylalaninemia, citrulinemia, transient tyrosinemia, 3-methylcrotonyl CoA carboxylase deficiency, 3-hydroxy-3-methylglutaryl CoA deficiency, and classic galactosemia. CONCLUSIONS: The estimated incidence of inborn errors of metabolism is 1:5 000, with a false positive rate of 0.22 percent. The program permitted the identification of metabolic disorders in the newborn, allowing an early intervention and prevention of life-threatening events and permanent neurological damage.

Cross-sectional observations of thyroid function in geriatric Mexican outpatients with and without dementia.

UNLABELLED: This work was aimed at determining and comparing the frequency of abnormal levels of thyroid stimulating hormone (TSH) in geriatric outpatients with and without dementia. This cross-sectional study enrolled patients, aged 60 years and older with or without dementia (established on the basis of DSM-IV-R), from geriatric outpatient unit with third level of medical care. Comparisons were between 33 (34%) patients without dementia versus 26 (58%) with dementia; both among 142 (24%) randomly selected sample (RSS) from unit's register; and the 101 (89%) in the memory-clinic case series (MCCS) of dementia were contrasted with the former. MEASUREMENTS: TSH, total/free thyroxine, mini-mental-state examination (MMSE), geriatric depression scale (GDS), Hachinski ischemic-score (HIS), and clinical data from the patients' charts. In the above order, high TSH was found in 9 (27.3%, confidence interval (CI)=12.1-42.5%), 6 (23.1%, CI=6.9-46.5%), and 30 (29.7%, CI=20.8-38.6%), respectively. Low-normal free thyroxine levels accompanied 76% of individuals with elevated TSH; in contrast of Gaussian distribution of free thyroxine in those with TSH in normal range. In conclusion, the high frequency found of hypothyroidism in patients with and without dementia warrants further studies. Treatment is only being recommended for patients with below range thyroxin levels; while treatment of subclinical hypothyroidism in the presence of cognitive decline will be addressed in the forthcoming studies.

Índice de Hachinski e imagen cerebral en el estudio ambulatorio de la demencia en ancianos / The Hachinski Index and brain imaging in ambulatory study of dementia in the elderly

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Gestational diabetes: Validity of ADA and WHO diagnostic criteria using NDDG as the reference test.

OBJECTIVE: Evidence is provided to clinicians and decision makers on the validity of ADA and WHO tests based on NDDG criteria for gestational diabetes. MATERIALS AND METHODS: During 18 months, all pregnant women attending a University Hospital underwent a 50-g, 1-h NDDG GCT for universal screening (n = 1092). The following appointment consisted of a 75-g, 2-h GTT (WHO test), independently of the prior result. Women with an abnormal 50-g and/or an abnormal 75-g, received a 100-g, 3-h GTT; subjects with only one abnormal 3-h GTT value were not included in the accuracy analysis. Women whose diagnosis followed NDDG criteria received treatment. Obstetricians were not aware of ADA/WHO results. RESULTS: ADA sensitivity was 100% (95%CI 98.6, 100) and specificity, 98.1% (95%CI 97.6, 98.6), whereas WHO sensitivity was 57.6% (95%CI 55.9, 59.2) and specificity, 85.1% (95%CI 84.7, 85.6). ADA results remained similar independently of obesity and age, but performed better with a family history of diabetes. Accuracy of WHO improved under selective screening, still the false negative rate ranged 40-56%. CONCLUSIONS: We recommend replicating this validation process in other health service settings. Although WHO test is easier and less expensive than NDDG or ADA, caution is needed before deciding employment of such criteria in pregnant women.

Efecto de la administración semanal de ácido fólico sobre los valores sanguíneos / The effect of weekly administration of folic acid on folic acid blood levels

Objetivo. Evaluar el efecto de la administración de 5 mg por semana de ácido fólico sobre los valores sanguíneos. Material y métodos. Estudio de comparación concurrente realizado en zonas urbanas y rurales del estado de Nuevo León, México, en 1998, a 74 mujeres, 39 de ellas con antecedente de un producto con defecto de cierre del tubo neural y 35 sin dicho antecedente. La muestra sólo incluyó a mujeres que parieron durante 1997. Las mujeres recibieron 5 mg de ácido fólico por semana durante tres meses. El AF sanguíneo fue determinado por radioinmunoanálisis (RIA), al inicio y una semana después de la última tableta. Se calcularon promedios y desviaciones estándar. Resultados. El 90 por ciento de las mujeres aumentó significativamente los valores sanguíneos. El ácido fólico intraeritrocitario se incrementó de 150.49 ñ 31.17 ng/ml a 184.21 ñ 35.53 ng/ml (p<0.005) y el plasmático de 5.93 ñ 1.98 ng/ml a 7.03 ñ 2.5 ng/ml (p<0.05). El 82 por ciento alcanzó cifras mayores de 160 ng/ml. Conclusiones. La administración semanal de 5 mg de ácido fólico puede ser una estrategia adecuada y costo eficiente para la suplementación con esta vitamina a la población de escasos recursos. El texto completo en inglés de este artículo está disponible en: http://www.insp.mx/salud/index.html