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AIMS: To evaluate the performance of the WATCH-DM risk score, a clinical risk score for heart failure (HF), in patients with dysglycaemia and in combination with natriuretic peptides (NPs). METHODS AND RESULTS: Adults with diabetes/pre-diabetes free of HF at baseline from four cohort studies (ARIC, CHS, FHS, and MESA) were included. The machine learning- [WATCH-DM(ml)] and integer-based [WATCH-DM(i)] scores were used to estimate the 5-year risk of incident HF. Discrimination was assessed by Harrells concordance index (C-index) and calibration by the Greenwood-Nam-DAgostino (GND) statistic. Improvement in model performance with the addition of NP levels was assessed by C-index and continuous net reclassification improvement (NRI). Of the 8938 participants included, 3554 (39.8%) had diabetes and 432 (4.8%) developed HF within 5 years. The WATCH-DM(ml) and WATCH-DM(i) scores demonstrated high discrimination for predicting HF risk among individuals with dysglycaemia (C-indices = 0.80 and 0.71, respectively), with no evidence of miscalibration (GND P ≥0.10). The C-index of elevated NP levels alone for predicting incident HF among individuals with dysglycaemia was significantly higher among participants with low/intermediate (<13) vs. high (≥13) WATCH-DM(i) scores [0.71 (95% confidence interval 0.68-0.74) vs. 0.64 (95% confidence interval 0.61-0.66)]. When NP levels were combined with the WATCH-DM(i) score, HF risk discrimination improvement and NRI varied across the spectrum of risk with greater improvement observed at low/intermediate risk [WATCH-DM(i) <13] vs. high risk [WATCH-DM(i) ≥13] (C-index = 0.73 vs. 0.71; NRI = 0.45 vs. 0.17). CONCLUSION: The WATCH-DM risk score can accurately predict incident HF risk in community-based individuals with dysglycaemia. The addition of NP levels is associated with greater improvement in the HF risk prediction performance among individuals with low/intermediate risk than those with high risk.

Background Patients with refractory nephrotic syndrome (NS) are at high risk of medication-induced glucose metabolism disorders, because of their long-term use of diabetogenic medications, particularly glucocorticoids and calcineurin inhibitors (CNIs). However, there have been no comprehensive evaluations of glucose metabolism disorders in pediatric patients with refractory NS. Moreover, glucocorticoids and CNIs could not be discontinued in these patients until the effectiveness of rituximab on refractory NS was shown, and therefore, there has been limited opportunity to evaluate glucose metabolism disorders after discontinuation of these medications. Methods Consecutive pediatric patients who started rituximab treatment for refractory NS were enrolled. Their glucose metabolism conditions were evaluated using the oral glucose tolerance tests (OGTT) and HbA1c levels at the initiation of rituximab treatment. Patients with glucose metabolism disorders at the first evaluation were reevaluated after approximately 2 years. Results Overall, 57% (20/35) of study patients had glucose metabolism disorders, and 40% (8/20) of these patients were detected only by their 2-h OGTT blood glucose levels and not by their fasting blood glucose or HbA1c levels. Non-obese/non-overweight patients had significantly more glucose metabolism disorders than obese/overweight patients (p = 0.019). In addition, glucose metabolism disorders in 71% (10/14) of patients persisted after the discontinuation of glucocorticoids and CNIs. Conclusions Whether the patient is obese/overweight or not, patients with refractory NS are at high risk of developing glucose metabolism disorders, even in childhood. Non-obese/non-overweight patients who are at high risk of diabetes need extra vigilance.

Background Patients with refractory nephrotic syndrome (NS) are at high risk of medication-induced glucose metabolism disorders, because of their long-term use of diabetogenic medications, particularly glucocorticoids and calcineurin inhibitors (CNIs). However, there have been no comprehensive evaluations of glucose metabolism disorders in pediatric patients with refractory NS. Moreover, glucocorticoids and CNIs could not be discontinued in these patients until the effectiveness of rituximab on refractory NS was shown, and therefore, there has been limited opportunity to evaluate glucose metabolism disorders after discontinuation of these medications. Methods Consecutive pediatric patients who started rituximab treatment for refractory NS were enrolled. Their glucose metabolism conditions were evaluated using the oral glucose tolerance tests (OGTT) and HbA1c levels at the initiation of rituximab treatment. Patients with glucose metabolism disorders at the first evaluation were reevaluated after approximately 2 years. Results Overall, 57% (20/35) of study patients had glucose metabolism disorders, and 40% (8/20) of these patients were detected only by their 2-h OGTT blood glucose levels and not by their fasting blood glucose or HbA1c levels. Non-obese/non-overweight patients had significantly more glucose metabolism disorders than obese/overweight patients (p = 0.019). In addition, glucose metabolism disorders in 71% (10/14) of patients persisted after the discontinuation of glucocorticoids and CNIs. Conclusions Whether the patient is obese/overweight or not, patients with refractory NS are at high risk of developing glucose metabolism disorders, even in childhood. Non-obese/non-overweight patients who are at high risk of diabetes need extra vigilance.

Background Patients with refractory nephrotic syndrome (NS) are at high risk of medication-induced glucose metabolism disorders, because of their long-term use of diabetogenic medications, particularly glucocorticoids and calcineurin inhibitors (CNIs). However, there have been no comprehensive evaluations of glucose metabolism disorders in pediatric patients with refractory NS. Moreover, glucocorticoids and CNIs could not be discontinued in these patients until the effectiveness of rituximab on refractory NS was shown, and therefore, there has been limited opportunity to evaluate glucose metabolism disorders after discontinuation of these medications. Methods Consecutive pediatric patients who started rituximab treatment for refractory NS were enrolled. Their glucose metabolism conditions were evaluated using the oral glucose tolerance tests (OGTT) and HbA1c levels at the initiation of rituximab treatment. Patients with glucose metabolism disorders at the first evaluation were reevaluated after approximately 2 years. Results Overall, 57% (20/35) of study patients had glucose metabolism disorders, and 40% (8/20) of these patients were detected only by their 2-h OGTT blood glucose levels and not by their fasting blood glucose or HbA1c levels. Non-obese/non-overweight patients had significantly more glucose metabolism disorders than obese/overweight patients (p = 0.019). In addition, glucose metabolism disorders in 71% (10/14) of patients persisted after the discontinuation of glucocorticoids and CNIs. Conclusions Whether the patient is obese/overweight or not, patients with refractory NS are at high risk of developing glucose metabolism disorders, even in childhood. Non-obese/non-overweight patients who are at high risk of diabetes need extra vigilance.

Recently, the Paleolithic diet became popular due to its possible health benefits. Several, albeit not all, studies suggested that the consumption of the Paleolithic diet might improve glucose tolerance, decrease insulin secretion, and increase insulin sensitivity. Therefore, the aim of this meta-analysis was to compare the effect of the Paleolithic diet with other types of diets on glucose and insulin homeostasis in subjects with altered glucose metabolism. Four databases (PubMed, Web of Sciences, Scopus, and the Cochrane Library) were searched to select studies in which the effects of the Paleolithic diet on fasting glucose and insulin levels, glycated hemoglobin (HbA1c), homeostasis model assessment of insulin resistance (HOMA-IR), and area under the curve (AUC 0–120) for glucose and insulin during the oral glucose tolerance test were assessed. In total, four studies with 98 subjects which compared the effect of the Paleolithic diet with other types of diets (the Mediterranean diet, diabetes diet, and a diet recommended by the Dutch Health Council) were included in this meta-analysis. The Paleolithic diet did not differ from other types of diets with regard to its effect on fasting glucose (standardized mean difference (SMD): −0.343, 95% confidence interval (CI): −0.867, 0.181, p = 0.200) and insulin (SMD: −0.141; 95% CI: −0.599, 0.318; p = 0.548) levels. In addition, there were no differences between the Paleolithic diet and other types of diets in HOMA-IR (SMD: −0.151; 95% CI: −0.610, 0.309; p = 0.521), HbA1c (SMD: −0.380; 95% CI: −0.870, 0.110; p = 0.129), AUC 0–120 glucose (SMD: −0.558; 95% CI: −1.380, 0.264; p = 0.183), and AUC 0–120 insulin (SMD: −0.068; 95% CI: −0.526, 0.390; p = 0.772). In conclusion, the Paleolithic diet did not differ from other types of diets commonly perceived as healthy with regard to effects on glucose and insulin homeostasis in subjects with altered glucose metabolism., Peer Reviewed

Background Patients with refractory nephrotic syndrome (NS) are at high risk of medication-induced glucose metabolism disorders, because of their long-term use of diabetogenic medications, particularly glucocorticoids and calcineurin inhibitors (CNIs). However, there have been no comprehensive evaluations of glucose metabolism disorders in pediatric patients with refractory NS. Moreover, glucocorticoids and CNIs could not be discontinued in these patients until the effectiveness of rituximab on refractory NS was shown, and therefore, there has been limited opportunity to evaluate glucose metabolism disorders after discontinuation of these medications. Methods Consecutive pediatric patients who started rituximab treatment for refractory NS were enrolled. Their glucose metabolism conditions were evaluated using the oral glucose tolerance tests (OGTT) and HbA1c levels at the initiation of rituximab treatment. Patients with glucose metabolism disorders at the first evaluation were reevaluated after approximately 2 years. Results Overall, 57% (20/35) of study patients had glucose metabolism disorders, and 40% (8/20) of these patients were detected only by their 2-h OGTT blood glucose levels and not by their fasting blood glucose or HbA1c levels. Non-obese/non-overweight patients had significantly more glucose metabolism disorders than obese/overweight patients (p = 0.019). In addition, glucose metabolism disorders in 71% (10/14) of patients persisted after the discontinuation of glucocorticoids and CNIs. Conclusions Whether the patient is obese/overweight or not, patients with refractory NS are at high risk of developing glucose metabolism disorders, even in childhood. Non-obese/non-overweight patients who are at high risk of diabetes need extra vigilance.

Recently, the Paleolithic diet became popular due to its possible health benefits. Several, albeit not all, studies suggested that the consumption of the Paleolithic diet might improve glucose tolerance, decrease insulin secretion, and increase insulin sensitivity. Therefore, the aim of this meta-analysis was to compare the effect of the Paleolithic diet with other types of diets on glucose and insulin homeostasis in subjects with altered glucose metabolism. Four databases (PubMed, Web of Sciences, Scopus, and the Cochrane Library) were searched to select studies in which the effects of the Paleolithic diet on fasting glucose and insulin levels, glycated hemoglobin (HbA1c), homeostasis model assessment of insulin resistance (HOMA-IR), and area under the curve (AUC 0–120) for glucose and insulin during the oral glucose tolerance test were assessed. In total, four studies with 98 subjects which compared the effect of the Paleolithic diet with other types of diets (the Mediterranean diet, diabetes diet, and a diet recommended by the Dutch Health Council) were included in this meta-analysis. The Paleolithic diet did not differ from other types of diets with regard to its effect on fasting glucose (standardized mean difference (SMD): −0.343, 95% confidence interval (CI): −0.867, 0.181, p = 0.200) and insulin (SMD: −0.141; 95% CI: −0.599, 0.318; p = 0.548) levels. In addition, there were no differences between the Paleolithic diet and other types of diets in HOMA-IR (SMD: −0.151; 95% CI: −0.610, 0.309; p = 0.521), HbA1c (SMD: −0.380; 95% CI: −0.870, 0.110; p = 0.129), AUC 0–120 glucose (SMD: −0.558; 95% CI: −1.380, 0.264; p = 0.183), and AUC 0–120 insulin (SMD: −0.068; 95% CI: −0.526, 0.390; p = 0.772). In conclusion, the Paleolithic diet did not differ from other types of diets commonly perceived as healthy with regard to effects on glucose and insulin homeostasis in subjects with altered glucose metabolism., Peer Reviewed

Prediabetes (intermediate hyperglycemia) consists of two abnormalities, impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) detected by a standardized 75-gram oral glucose tolerance test (OGTT). Individuals with isolated IGT or combined IFG and IGT have increased risk for developing type 2 diabetes (T2D) and cardiovascular disease (CVD). Diagnosing prediabetes early and accurately is critical in order to refer high-risk individuals for intensive lifestyle modification. However, there is currently no international consensus for diagnosing prediabetes with HbA1c or glucose measurements based upon American Diabetes Association (ADA) and the World Health Organization (WHO) criteria that identify different populations at risk for progressing to diabetes. Various caveats affecting the accuracy of interpreting the HbA1c including genetics complicate this further. This review describes established methods for detecting glucose disorders based upon glucose and HbA1c parameters as well as novel approaches including the 1-hour plasma glucose (1-h PG), glucose challenge test (GCT), shape of the glucose curve, genetics, continuous glucose monitoring (CGM), measures of insulin secretion and sensitivity, metabolomics, and ancillary tools such as fructosamine, glycated albumin (GA), 1,5- anhydroglucitol (1,5-AG). Of the approaches considered, the 1-h PG has considerable potential as a biomarker for detecting glucose disorders if confirmed by additional data including health economic analysis. Whether the 1-h OGTT is superior to genetics and omics in providing greater precision for individualized treatment requires further investigation. These methods will need to demonstrate substantially superiority to simpler tools for detecting glucose disorders to justify their cost and complexity.

Free sugars overconsumption is associated with an increased prevalence of risk factors for metabolic diseases such as the alteration of the blood lipid levels. Natural fruit juices have a free sugar composition quite similar to that of sugar-sweetened beverages. Thus, could fruit juice consumption lead to the same adverse effects on health as sweetened beverages? We attempted to answer this question by reviewing the available evidence on the health effects of both sugar-sweetened beverages and natural fruit juices. We determined that, despite the similarity of fruits juices to sugar-sweetened beverages in terms of free sugars content, it remains unclear whether they lead to the same metabolic consequences if consumed in equal dose. Important discrepancies between studies, such as type of fruit juice, dose, duration, study design, and measured outcomes, make it impossible to provide evidence-based public recommendations as to whether the consumption of fruit juices alters the blood lipid profile. More randomized controlled trials comparing the metabolic effects of fruit juice and sugar-sweetened beverage consumption are needed to shape accurate public health guidelines on the variety and quantity of free sugars in our diet that would help to prevent the development of obesity and related health problems.

The worldwide obesity epidemic has emerged as a major cause of insulin resistance and Type 2 diabetes. Chronic tissue inflammation is a well-recognized feature of obesity, and the field of immunometabolism has witnessed many advances in recent years. Here, we review the major features of our current understanding with respect to chronic obesity-related inflammation in metabolic tissues and focus on how these inflammatory changes affect insulin sensitivity, insulin secretion, food intake, and glucose homeostasis. There is a growing appreciation of the varied and sometimes integrated crosstalk between cells within a tissue (intraorgan) and tissues within an organism (interorgan) that supports inflammation in the context of metabolic dysregulation. Understanding these pathways and modes of communication has implications for translational studies. We also briefly summarize the state of this field with respect to potential current and developing therapeutics.

The discovery of RNAs (for example, messenger RNAs, non-coding RNAs) in sperm has opened the possibility that sperm may function by delivering additional paternal information aside from solely providing the DNA 1 . Increasing evidence now suggests that sperm small non-coding RNAs (sncRNAs) can mediate intergenerational transmission of paternally acquired phenotypes, including mental stress2,3 and metabolic disorders4-6. How sperm sncRNAs encode paternal information remains unclear, but the mechanism may involve RNA modifications. Here we show that deletion of a mouse tRNA methyltransferase, DNMT2, abolished sperm sncRNA-mediated transmission of high-fat-diet-induced metabolic disorders to offspring. Dnmt2 deletion prevented the elevation of RNA modifications (m5C, m2G) in sperm 30-40 nt RNA fractions that are induced by a high-fat diet. Also, Dnmt2 deletion altered the sperm small RNA expression profile, including levels of tRNA-derived small RNAs and rRNA-derived small RNAs, which might be essential in composing a sperm RNA 'coding signature' that is needed for paternal epigenetic memory. Finally, we show that Dnmt2-mediated m5C contributes to the secondary structure and biological properties of sncRNAs, implicating sperm RNA modifications as an additional layer of paternal hereditary information.

The discovery of RNAs (for example, messenger RNAs, non-coding RNAs) in sperm has opened the possibility that sperm may function by delivering additional paternal information aside from solely providing the DNA 1 . Increasing evidence now suggests that sperm small non-coding RNAs (sncRNAs) can mediate intergenerational transmission of paternally acquired phenotypes, including mental stress2,3 and metabolic disorders4-6. How sperm sncRNAs encode paternal information remains unclear, but the mechanism may involve RNA modifications. Here we show that deletion of a mouse tRNA methyltransferase, DNMT2, abolished sperm sncRNA-mediated transmission of high-fat-diet-induced metabolic disorders to offspring. Dnmt2 deletion prevented the elevation of RNA modifications (m5C, m2G) in sperm 30-40 nt RNA fractions that are induced by a high-fat diet. Also, Dnmt2 deletion altered the sperm small RNA expression profile, including levels of tRNA-derived small RNAs and rRNA-derived small RNAs, which might be essential in composing a sperm RNA 'coding signature' that is needed for paternal epigenetic memory. Finally, we show that Dnmt2-mediated m5C contributes to the secondary structure and biological properties of sncRNAs, implicating sperm RNA modifications as an additional layer of paternal hereditary information.

OBJECTIVE: Treatment with antipsychotic drugs is widely associated with metabolic side effects such as weight gain and disturbed glucose metabolism, but the pathophysiologic mechanisms are unclear.METHOD: Fifty nondiabetic (fasting plasma glucose ≤ 7.0 mmol/L), antipsychotic-treated male patients (ICD-10 diagnosis code F20, F21, F22, F25, F28, or F60; mean ± SD age = 33.0 ± 6.7 years; body mass index [BMI; kg/m²] = 26.0 ± 4.7; waist circumference = 95.9 ± 13.3 cm; glycated hemoglobin A1c [HbA1c] = 5.7% ± 0.3%) and 93 age- and waist circumference-matched healthy male controls (age = 33 ± 7.3 years; BMI = 26.1 ± 3.9; waist circumference = 94.6 ± 11.9 cm; HbA1c = 5.7% ± 0.3%) participated in this cross-sectional study. Blood was sampled in the fasting state and 90 minutes after ingestion of a standardized liquid meal (2,268 kJ). The primary outcomes were glucometabolic hormones and cardiovascular risk markers. Data were collected between March 2008 and February 2010.RESULTS: Compared to healthy controls, patients were characterized by elevated fasting levels of proinsulin, C-peptide, and glucose-dependent insulinotropic polypeptide (GIP) (P < .05) and higher postprandial levels of insulin, proinsulin, C-peptide, and GIP (P ≤ .02). Also, patients exhibited elevated plasma levels of C-reactive protein and signs of dyslipidemia. Fasting plasma levels of insulin, glucagon, glucagon-like peptide-1 (GLP-1), ghrelin, leptin, adiponectin, tumor necrosis factor-α, plasminogen activator inhibitor-1, and interleukin-6 and postprandial levels of glucagon, GLP-1, ghrelin, leptin, and adiponectin did not differ between groups.CONCLUSIONS: Presenting with an insulin resistant-like pattern, including beta cell hypersecretion and elevated GIP levels, nondiabetic antipsychotic-treated patients display emerging signs of dysmetabolism and a compromised cardiovascular risk profile. The appetite-regulating hormones GLP-1 and ghrelin appear not to be influenced by

Subclinical hypothyroidism may contribute to development of cardiovascular disease and has been shown that TSH >2.5uUI/mL is associated with endothelial dysfunction. Objectives: To determine carotid intima media thickness (CIMT), presence of carotid artery plaque and metabolic profile in asymptomatic middle-aged women with TSH ≥2.5 uUI/mL, and compare them with those with levels <2.5 uUI/mL. Design: Analytical and cross-sectional study. Setting: Dos de Mayo Hospital and Institute of Clinical Research, Universidad Nacional Mayor de San Marcos, Lima, Peru. Participants: Women with no history of thyroid disease, cardiovascular disease or diabetes. Interventions: Total cholesterol, HDL cholesterol, triglycerides, oral glucose tolerance test (OGTT), fasting insulin (F-Ins), body mass index (BMI), waist circumference and blood pressure were assessed in 60 women with no history of thyroid disease, cardiovascular disease or diabetes with mean age 53,8 ± 5,8 years. HOMA-IR index and LDL cholesterol were also determined. CIMT was measured by Doppler ultrasound. Main outcome measures: TSH ≥ 2.5 uUI/mL and metabolic profile, and association with CIMT. Results: From 60 women 38.3% had TSH ≥2.5 and 61.7% TSH <2.5 uUI/mL; 56% of women with TSH ≥2.5 and 65% with TSH <2.5 uUI/mL were hypertensive with no statistical difference. Lipid profile, fasting glucose, F-ins and index HOMA-IR were similar in both groups. Higher levels of BMI, glucose at 120 minutes, left CIMT and maximal CIMT were observed in women with TSH ≥2.5 uUI/mL (p=0.03, p=0.01, p=0.008 and p=0.02 respectively). The presence of plaques in the left carotid artery and in at least one of the carotid arteries was significantly more frequent in women with TSH ≥2.5 uUI/mL. Conclusions: TSH levels ≥2.5 uUI/mL in middle-aged women predispose to altered glucose metabolism and subclinical atherosclerosis, El hipotiroidismo subclínico puede contribuir al desarrollo de patologías cardiovasculares y se ha demostrado que a partir de niveles de TSH >2,5uUI/mL se desarrolla disfunción endotelial. Objetivos: Determinar el grosor de la íntima media carotídea (GIMC), la presencia de placas en carótidas y el perfil metabólico en mujeres de edad media asintomáticas con TSH ≥2,5 uUI/mL y compararlas con aquellas con niveles <2,5 uUI/mL. Diseño: Estudio transversal y analítico. Lugar: Hospital Nacional Dos de Mayo e Instituto de Investigaciones Clínicas, Universidad Nacional Mayor de San Marcos, Lima, Perú. Participantes: Mujeres sin historia de enfermedad tiroidea, cardiovascular o diabetes. Intervenciones: En 60 mujeres sin historia de enfermedad tiroidea, cardiovascular o diabetes, con edad promedio de 53,8 ± 5,8 años, se determinó la tirotropina (TSH), colesterol total (CT), colesterol de densidad alta (HDL), triglicéridos (Tg), glucosa (G) basal y a los 120 minutos (TTGO), insulina basal (Ins-B); se calculó las fracciones de colesterol de densidad baja (LDL), el nivel de insulinorresistencia (HOMA-IR), la presión arterial, perímetro de cintura abdominal, el índice de masa corporal (IMC) y el GIMC mediante ecoDoppler. Principales medidas de resultados: TSH ≥2,5 uUI/mL, perfil metabólico y su relación con GIMC. Resultados: El 38,3% presentó TSH ≥2,5 y 61,7% TSH <2,5 uUI/mL. El 56% de mujeres con TSH ≥2,5 y 65% con TSH <2,5 uUI/ml fueron hipertensas, sin diferencia estadística. El perfil lipídico, G basal, Ins-B e índice HOMA-IR fueron semejantes en ambos grupos. Se observó niveles significativamente más altos del IMC, G a los 120 minutos, el GIMC en carótida izquierda y el mayor entre ambas carótidas en las mujeres con TSH ≥2,5 uUI/mL (p=0,03, p=0,01, p=0,008 y p=0,02, respectivamente). La presencia de placas en la carótida izquierda y en al menos una de las carótidas fue significativamente más frecuente entre aquellas con TSH ≥2,5 uUI/mL. Conclusiones: Los niveles de TSH ≥2,5

Introduction: Under normal physiological normal conditions, high altitude inhabitants have lower blood sugar levels compared with persons living at sea level. These lower blood sugar values in high altitude are probably due to insulin. The explanation for the major glucose uptake in high altitude is not known yet. Objective: To evaluate the response to oral glucose tolerance test in healthy inhabitants of extremely high altitude areas compared to that of healthy persons living in high altitude places. To compare sensitivity to insulin using the oral glucose tolerance test in health persons living in extremely high altitude areas compared to that of healthy persons living in high altitude places. Materials and methods: This is a longitudinal, prospective and analytical study. The study group consisted in 40 healthy males living in a high altitude city (Puno, 3826 meters above sea level) and a control group including 35 healthy males living in an extremely high place for more than 5 years (Rinconada community, 5200 meters above sea level), and every subject underwent an oral glucose tolerance test. Results: Baseline blood glucose in the study group was 57.33 ± 6.08 (mg/dl); blood sugar levels after 1 hour were 82.33 ± 8.04; blood sugar values after 2 hours were 66.33 ± 4.62, and blood sugar after 3 hours was 80.75 ± 10.95 (mg/dl). In the control group, baseline blood sugar was 91.5 ± 12.11; blood sugar after 1 hour was 103.75 ± 10.5; blood sugar after 2 hours was 124.25 ± 13.1; and blood sugar after 3 hours was 80.75 ± 10.95. Conclusions: People living in extremely high altitude show blood glucose levels far below normal values, showing a differently shaped oral glucose tolerance curve compared to normal curves described in the literature., Introducción: En condiciones fisiológicas normales el habitante de la altura tiene una glicemia más baja en comparación con el habitante del nivel del mar. Esta menor glicemia basal en la altura probablemente sea debida a la insulina. La explicación para la mayor captación de glucosa en la altura aun se desconoce. Objetivos: Evaluar la respuesta al test de tolerancia oral a la glucosa en habitantes sanos de extrema altura en comparación a personas sanas residentes de gran altura. Comparar la sensibilidad a la insulina mediante el test de tolerancia oral a la glucosa de habitantes sanos de extrema altura y de gran altura. Materiales y métodos: El presente es un estudio longitudinal, prospectivo y analítico. El estudio incluyó a un grupo de estudio conformado por 40 varones sanos voluntarios residentes a gran altura (Puno, 3826 m.s.n.m.) y un grupo control conformado por 35 varones residentes de extrema altura por mas de 5 años (Centro poblado menor de Rinconada, 5200 m.s.n.m.), en los cuales se aplicó el test de tolerancia oral a la glucosa. Resultados: En el Grupo de Estudio la Glicemia basal fue de 57,33 ± 6,08; la Glicemia a 1h fue de 82,33 ± 8,04; la Glicemia a 2h fue de 66,33 ± 4,62; la Glicemia a las 3 horas fue de 80,75 ± 10,95 (en mg/dl). En el Grupo Control la Glicemia basal fue de 91,5 ± 12,11; la Glicemia a 1h fue de 103,75 ± 10,5; la Glicemia a 2h fue de 124,25 ± 13,1; la Glicemia a las 3 horas fue de 80,75 ± 10,95 (en mg/dl). Conclusiones: El residente de extrema altura muestra niveles de glicemia muy por debajo de los valores normales, mostrando una curva distinta a las curvas de normalidad establecidas en la bibliografía clásica.

Introduction: Under normal physiological normal conditions, high altitude inhabitants have lower blood sugar levels compared with persons living at sea level. These lower blood sugar values in high altitude are probably due to insulin. The explanation for the major glucose uptake in high altitude is not known yet. Objective: To evaluate the response to oral glucose tolerance test in healthy inhabitants of extremely high altitude areas compared to that of healthy persons living in high altitude places. To compare sensitivity to insulin using the oral glucose tolerance test in health persons living in extremely high altitude areas compared to that of healthy persons living in high altitude places. Materials and methods: This is a longitudinal, prospective and analytical study. The study group consisted in 40 healthy males living in a high altitude city (Puno, 3826 meters above sea level) and a control group including 35 healthy males living in an extremely high place for more than 5 years (Rinconada community, 5200 meters above sea level), and every subject underwent an oral glucose tolerance test. Results: Baseline blood glucose in the study group was 57.33 ± 6.08 (mg/dl); blood sugar levels after 1 hour were 82.33 ± 8.04; blood sugar values after 2 hours were 66.33 ± 4.62, and blood sugar after 3 hours was 80.75 ± 10.95 (mg/dl). In the control group, baseline blood sugar was 91.5 ± 12.11; blood sugar after 1 hour was 103.75 ± 10.5; blood sugar after 2 hours was 124.25 ± 13.1; and blood sugar after 3 hours was 80.75 ± 10.95. Conclusions: People living in extremely high altitude show blood glucose levels far below normal values, showing a differently shaped oral glucose tolerance curve compared to normal curves described in the literature., Introducción: En condiciones fisiológicas normales el habitante de la altura tiene una glicemia más baja en comparación con el habitante del nivel del mar. Esta menor glicemia basal en la altura probablemente sea debida a la insulina. La explicación para la mayor captación de glucosa en la altura aun se desconoce. Objetivos: Evaluar la respuesta al test de tolerancia oral a la glucosa en habitantes sanos de extrema altura en comparación a personas sanas residentes de gran altura. Comparar la sensibilidad a la insulina mediante el test de tolerancia oral a la glucosa de habitantes sanos de extrema altura y de gran altura. Materiales y métodos: El presente es un estudio longitudinal, prospectivo y analítico. El estudio incluyó a un grupo de estudio conformado por 40 varones sanos voluntarios residentes a gran altura (Puno, 3826 m.s.n.m.) y un grupo control conformado por 35 varones residentes de extrema altura por mas de 5 años (Centro poblado menor de Rinconada, 5200 m.s.n.m.), en los cuales se aplicó el test de tolerancia oral a la glucosa. Resultados: En el Grupo de Estudio la Glicemia basal fue de 57,33 ± 6,08; la Glicemia a 1h fue de 82,33 ± 8,04; la Glicemia a 2h fue de 66,33 ± 4,62; la Glicemia a las 3 horas fue de 80,75 ± 10,95 (en mg/dl). En el Grupo Control la Glicemia basal fue de 91,5 ± 12,11; la Glicemia a 1h fue de 103,75 ± 10,5; la Glicemia a 2h fue de 124,25 ± 13,1; la Glicemia a las 3 horas fue de 80,75 ± 10,95 (en mg/dl). Conclusiones: El residente de extrema altura muestra niveles de glicemia muy por debajo de los valores normales, mostrando una curva distinta a las curvas de normalidad establecidas en la bibliografía clásica.

Reduced circulating and tissue carnitine levels, possibly leading to impaired mitochondrial function, have been postulated to be involved in the pathogenesis of insulin resistance. However, whether L-carnitine administration may improve insulin sensitivity in patients with impaired fasting glucose (IFG) or type 2 diabetes mellitus (DM-2) is still controversial. The aim of the study was to explore the role of L-carnitine supplementation in influencing insulin sensitivity.

Primary hyperparathyroidism (pHPT), characterized by elevated serum levels of calcium and parathyroid hormone (PTH), is associated with a number of metabolic derangements causing secondary manifestations. These include osteoporosis and increased risk of fractures, but also risk factors for cardiovascular morbidity and mortality. These risk factors include impaired glucose tolerance (IGT), dyslipidemia, increased body mass index and hypertension. While the skeletal abnormalities are mainly due to elevated PTH, the latter disturbances are still unexplained. Non-insulin dependent diabetes mellitus (NIDDM), IGT, dyslipidemia and hypertension are all included in the metabolic syndrome, also associated with morbidity and mortality in cardiovascular diseases. In this thesis, decreased bone mineral density (BMD) and variables of the metabolic syndrome are explored in patients with mild and normocalcemic pHPT before and after parathyroidectomy. To further investigate the relationship between insulin sensitivity and calcium, a community-based cohort was investigated. In two different patient cohorts of pHPT, lipoprotein alterations with decreased levels of HDL-cholesterol and elevated triglycerides were found in association with a high frequency of IGT, NIDDM and decreased insulin sensitivity. Parathyroidectomy had effects on the dyslipidemia and in part on the glucose metabolism. The disturbed glucose metabolism in pHPT was substantiated by results from the general population by a negative association between insulin sensitivity, measured by hyperinsulinemic clamp, and serum calcium. In conclusion, normocalcemic, mild and overt pHPT are associated with a range of risk factors for cardiovascular diseases, development of NIDDM and decreased BMD in cortical as well as trabecular bone. These findings explain, at least in part, the elevated morbidity and mortality from cardiovascular disease as well as fractures, reported in pHPT patients. Moreover, in the general population, ser

Primary hyperparathyroidism (pHPT), characterized by elevated serum levels of calcium and parathyroid hormone (PTH), is associated with a number of metabolic derangements causing secondary manifestations. These include osteoporosis and increased risk of fractures, but also risk factors for cardiovascular morbidity and mortality. These risk factors include impaired glucose tolerance (IGT), dyslipidemia, increased body mass index and hypertension. While the skeletal abnormalities are mainly due to elevated PTH, the latter disturbances are still unexplained. Non-insulin dependent diabetes mellitus (NIDDM), IGT, dyslipidemia and hypertension are all included in the metabolic syndrome, also associated with morbidity and mortality in cardiovascular diseases. In this thesis, decreased bone mineral density (BMD) and variables of the metabolic syndrome are explored in patients with mild and normocalcemic pHPT before and after parathyroidectomy. To further investigate the relationship between insulin sensitivity and calcium, a community-based cohort was investigated. In two different patient cohorts of pHPT, lipoprotein alterations with decreased levels of HDL-cholesterol and elevated triglycerides were found in association with a high frequency of IGT, NIDDM and decreased insulin sensitivity. Parathyroidectomy had effects on the dyslipidemia and in part on the glucose metabolism. The disturbed glucose metabolism in pHPT was substantiated by results from the general population by a negative association between insulin sensitivity, measured by hyperinsulinemic clamp, and serum calcium. In conclusion, normocalcemic, mild and overt pHPT are associated with a range of risk factors for cardiovascular diseases, development of NIDDM and decreased BMD in cortical as well as trabecular bone. These findings explain, at least in part, the elevated morbidity and mortality from cardiovascular disease as well as fractures, reported in pHPT patients. Moreover, in the general population, ser

Primary hyperparathyroidism (pHPT), characterized by elevated serum levels of calcium and parathyroid hormone (PTH), is associated with a number of metabolic derangements causing secondary manifestations. These include osteoporosis and increased risk of fractures, but also risk factors for cardiovascular morbidity and mortality. These risk factors include impaired glucose tolerance (IGT), dyslipidemia, increased body mass index and hypertension. While the skeletal abnormalities are mainly due to elevated PTH, the latter disturbances are still unexplained. Non-insulin dependent diabetes mellitus (NIDDM), IGT, dyslipidemia and hypertension are all included in the metabolic syndrome, also associated with morbidity and mortality in cardiovascular diseases. In this thesis, decreased bone mineral density (BMD) and variables of the metabolic syndrome are explored in patients with mild and normocalcemic pHPT before and after parathyroidectomy. To further investigate the relationship between insulin sensitivity and calcium, a community-based cohort was investigated. In two different patient cohorts of pHPT, lipoprotein alterations with decreased levels of HDL-cholesterol and elevated triglycerides were found in association with a high frequency of IGT, NIDDM and decreased insulin sensitivity. Parathyroidectomy had effects on the dyslipidemia and in part on the glucose metabolism. The disturbed glucose metabolism in pHPT was substantiated by results from the general population by a negative association between insulin sensitivity, measured by hyperinsulinemic clamp, and serum calcium. In conclusion, normocalcemic, mild and overt pHPT are associated with a range of risk factors for cardiovascular diseases, development of NIDDM and decreased BMD in cortical as well as trabecular bone. These findings explain, at least in part, the elevated morbidity and mortality from cardiovascular disease as well as fractures, reported in pHPT patients. Moreover, in the general population, ser

Primary hyperparathyroidism (pHPT), characterized by elevated serum levels of calcium and parathyroid hormone (PTH), is associated with a number of metabolic derangements causing secondary manifestations. These include osteoporosis and increased risk of fractures, but also risk factors for cardiovascular morbidity and mortality. These risk factors include impaired glucose tolerance (IGT), dyslipidemia, increased body mass index and hypertension. While the skeletal abnormalities are mainly due to elevated PTH, the latter disturbances are still unexplained. Non-insulin dependent diabetes mellitus (NIDDM), IGT, dyslipidemia and hypertension are all included in the metabolic syndrome, also associated with morbidity and mortality in cardiovascular diseases. In this thesis, decreased bone mineral density (BMD) and variables of the metabolic syndrome are explored in patients with mild and normocalcemic pHPT before and after parathyroidectomy. To further investigate the relationship between insulin sensitivity and calcium, a community-based cohort was investigated. In two different patient cohorts of pHPT, lipoprotein alterations with decreased levels of HDL-cholesterol and elevated triglycerides were found in association with a high frequency of IGT, NIDDM and decreased insulin sensitivity. Parathyroidectomy had effects on the dyslipidemia and in part on the glucose metabolism. The disturbed glucose metabolism in pHPT was substantiated by results from the general population by a negative association between insulin sensitivity, measured by hyperinsulinemic clamp, and serum calcium. In conclusion, normocalcemic, mild and overt pHPT are associated with a range of risk factors for cardiovascular diseases, development of NIDDM and decreased BMD in cortical as well as trabecular bone. These findings explain, at least in part, the elevated morbidity and mortality from cardiovascular disease as well as fractures, reported in pHPT patients. Moreover, in the general population, ser