Prediabetes is more than a pre-disease: additional evidences supporting the importance of its early diagnosis and appropriate treatment.

AIM: To identify Prediabetes (PreD) as early and serious diabetes step using clinical-biochemical characteristics in the population of the Primary Prevention Diabetes Buenos Aires (PPDBA) study. METHODS: PPDBA Study evaluated benefits of adopting healthy lifestyles to prevent T2D. It recruited people 45-75 years of age with PreD (impaired fasting glycaemia [IFG], impaired glucose tolerance [IGT] or both, American Diabetes Association criteria), using an opportunistic approach. They completed a FINDRISC questionnaire, and those with a score ≥13 points were invited to participate. When they accepted, we performed an oral glucose tolerance test (OGTT) with a complete lipid profile and HbA1c while physicians completed a clinical history. We recruited 367 persons, and depending on OGTT results, the sample was divided into normals (NGT), PreD, or with diabetes (last one was excluded in our analysis). Data were statistically analyzed using parametric and nonparametric tests and logistic regression to identify parameters associated with PreD. RESULTS: From the recruited (n = 367) 47.7% have NGT, 48.5% PreD and 3.8% unknown T2D (excluded). People with PreD were significantly older, with a higher percentage of overweight/obesity, BMI, and larger waist circumference than NGT. They also showed significantly higher fasting and 2 h post glucose load, HbA1c, and triglyceride levels. No significant differences were recorded in the blood pressure, lipid profile though both groups had abnormally high LDL-c values. They also had a larger percentage of TG/HDL-c ratios (insulin resistance indicator) (55% vs. 37.5%). Logistic regression analysis showed that PreD was significant associated with age, waist circumference, and triglyceride above target values. CONCLUSION: Our findings showed that clinical and biochemical parameters were significantly different between people with PreD and those with NGT. This evidence supports the concept that PreD is a serious dysfunction, which should be early diagnosed and treated properly to prevent its transition to T2D and its complications.

Actividad física y factores de riesgo cardiovascular: evidencia de su interrelación a nivel nacional / Physical activity and cardiovascular risk factors: evidence of their interrelation nationwide

RESUMEN Antecedentes: En nuestro país la prevalencia de diabetes tipo 2 (DT2) y de factores de riesgo cardiovascular (FRCV) aumenta continuamente. Aunque el fenómeno se acompaña de adopción de estilos de vida no saludable que facilitan dicho crecimiento, es escasa la implementación de estrategias que puedan modificar la situación. Objetivo: Revisar la evidencia disponible sobre la magnitud del problema de la diabetes y los FRCV en nuestro país, su posible relación con la práctica de actividad física y potencial mecanismo de acción. Metodología: Evaluación de datos de la tercera Encuesta Nacional de Factores de Riesgo (ENFR) e información referida a factores que contribuyen al crecimiento de la prevalencia de DT2. Igualmente estrategias exitosas utilizadas a nivel mundial para su prevención. Resultados: El índice de masa corporal registrado en la población estudiada muestra un aumento del porcentaje de personas con sobrepeso/obesidad inverso a la práctica de actividad física. Igualmente los resultados de las pruebas de tolerancia a la glucosa oral muestran que sus alteraciones (prediabetes/diabetes) son menores entre quienes realizaban actividad física. El porcentaje de personas con valores de presión arterial dentro del rango normal al igual que de colesterol circulante (según valores meta de guías internacionales), es también significativamente menor entre quienes practicaban actividad física. Conclusión: La evidencia presentada demuestra objetivamente la necesidad/ventajas de implementar un programa de prevención primaria de diabetes a gran escala a nivel nacional para disminuir su crecimiento y la pertinencia de incluir la práctica de actividad física como estrategia de prevención tal como propone el PPDBA.

ABSTRACT Background: In our country, the prevalence of type 2 diabetes (DT2) and cardiovascular risk factors (CVRF) increases continuously. Although the phenomenon is accompanied by the adoption of unhealthy lifestyles that facilitate such growth, there is little implementation of strategies that can modify the situation. Objective: To review the available evidence on the magnitude of the problem of diabetes and CVRF in our country, its possible relationship with the practice of physical activity and potential mechanism of action. Methodology: Evaluation of data from the Third National Survey of Risk Factors (ENFR) and information referred to factors that promote the prevalence growth of T2D. Additionally, successful strategies have been used worldwide for its prevention. Results: The body mass index registered in the studied population shows an increase in the percentage of people with overweight/obesity inverse to the practice of physical activity. Likewise, the results of the oral glucose tolerance tests show that their alterations (prediabetes/ diabetes) are lower among those who performed physical activity. The percentage of people with blood pressure values within the normal range as well as circulating cholesterol (according to target values of international guidelines), is also significantly lower among those who practiced physical activity. Conclusion: The presented evidence objectively demonstrates the need/advantages of implementing a large-scale diabetes primary prevention program at the national level to.

PROPAT: a study to improve the quality and reduce the cost of diabetes care.

OBJECTIVE: In PROPAT we implemented an integrated approach to diabetes care designed to improve the quality and reduce the cost of care. STUDY DESIGN AND METHODS: PROPAT was a case-control study matching patients by age and gender (diabetes:control ratio 1:2) within IOMA, a public employment-based health maintenance organization (HMO) of the Province of Buenos Aires, Argentina. Costs were evaluated using prevalence data from an HMO perspective. We currently report clinical and biochemical data and costs from the first 297 patients enrolled who completed 1 year in PROPAT, and compare them with those derived from control patients. RESULTS: All recommended practices recorded as care provided at baseline increased significantly 1 year after implementing PROPAT, with a parallel significant improvement in several clinical and biochemical parameters, and markedly lower total annual per capita costs. CONCLUSIONS: These results demonstrate that the implementation of a comprehensive diabetes care program can simultaneously improve quality while reducing costs.

Hospitalization and re-hospitalization of people with and without diabetes in La Plata, Argentina: comparison of their clinical characteristics and costs.

OBJECTIVE: To examine the prevalence, characteristics, and costs of hospitalization and re-hospitalization of diabetic and non-diabetic patients in La Plata, Argentina, and to compare the data with those of developed countries. RESEARCH DESIGN AND METHODS: We studied all in-hospital registries of diabetic patients enrolled in a health maintenance organization of the Province of Buenos Aires (IOMA, November 1996). For each diabetic patient (127 persons), the characteristics of two other hospitalized non-diabetic patients matched by age and gender were simultaneously recorded. RESULTS: Of the 2200 recorded hospitalizations, 5.8% were for diabetic patients, accounting for 10.5% of the hospitalization cost. Cardiovascular diseases were the major cause of hospitalization in both groups. The per capita hospitalization cost of diabetic patients was significantly higher: 1628.5+/-1754.0 US dollars versus 833+/-842 US dollars; P=0.00002. Percent re-hospitalizations were five and a half times higher in diabetic patients (P=0.0001), and significantly associated with history of severe episodes of acute (odds ratio: 3.61; 95% CI: 1.11-11.70; P=0.03) and chronic (odds ratio: 4.26; 95% CI: 1.60-11.29; P=0.004) complications. CONCLUSIONS: The combination of higher and longer hospitalization rates and frequent re-hospitalizations resulted in increased costs for our diabetic population. Implementation of care programs based on education (for physicians and patients) could effectively decrease current and future costs of the disease.

A model educational program for people with type 2 diabetes: a cooperative Latin American implementation study (PEDNID-LA).

OBJECTIVE: To implement an educational program in 10 Latin American countries and to evaluate its effect on the clinical, biochemical, and therapeutic aspects as well as the economic cost of diabetes. RESEARCH DESIGN AND METHODS: Educators from each participating country were previously trained to implement the educational model. The patient population included 446 individuals with type 2 diabetes; all patients were <65 years of age, did not require insulin for metabolic control, did not have severe complications of diabetes or life-limiting illnesses, and had not previously participated in diabetes education courses. Clinical and therapeutic data and the cost of their pharmacological treatment were collected 6 months before participation in the educational program (-6 months), on entry into the program (time 0), and at 4, 8, and 12 months after initiation of the program. RESULTS: All parameters measured had improved significantly (P < 0.001) by 1 year: fasting blood glucose (mean +/- SD) 10.6 +/- 3.5 vs. 8.7 +/- 3.0 mmol/l; HbA(1c) 9.0 +/- 2.0 vs. 7.8 +/- 1.6%; body weight 84.6 +/- 14.7 vs. 81.2 +/- 15.2 kg; systolic blood pressure 149.6 +/- 33.6 vs. 142.9 +/- 18.8 mmHg; total cholesterol 6.1 +/- 1.1 vs. 5.4 +/- 1.0 mmol/l; and triglycerides 2.7 +/- 1.8 vs. 2.1 +/- 1.2 mmol/l. At 12 months, the decrease in pharmacotherapy required for control of diabetes, hypertension, and hyperlipidemia represented a 62% decrease in the annual cost of treatment ($107,939.99 vs. $41,106.30 [U.S.]). After deducting the additional cost of glucosuria monitoring ($30,604), there was still a 34% annual savings. CONCLUSIONS: The beneficial results of this educational model, implemented in 10 Latin American countries, reinforce the value of patient education as an essential part of diabetes care. They also suggest that an educational approach promoting healthy lifestyle habits and patient empowerment is an effective strategy with the potential to decrease the development of complications related to diabetes as well as the socioeconomic costs of the disease.

[Gestational diabetes. Determination of relative importance of risk factors]. / Diabetes gestacional. Determinación del peso relativo de sus factores de riesgo.

The aim of this study was to determine the relative importance of gestational diabetes (GD) risk factors to identify populations at risk. A total of 400 pregnant patients were studied, 200 with confirmed GD diagnosis and 200 controls with risk factors. They regularly attended health-care units belonging to the Ministry of Health of the Province of Buenos Aires, in the context of the Program for the Prevention, Care and Treatment of People with Diabetes of the Province of Buenos Aires (PRODIABA). The following risk factors were evaluated: GD in previous pregnancies, history of diabetes in first degree relatives, age > or = 30 years, BMI > 26, history of fetal macrosomy, perinatal mortality and hypertension during pregnancy. Data analysis was performed with the Program of Statistics in Public Health Epilnfo 6. The association between GD development as a dependent variable and the presence of different risk factors (independent variables) was analyzed with a multiple logistic regression model, determining the logistic probability to develop GD. Results showed that the incidence of risk factors to develop GD is not the same; therefore, they do not have the same predictive value. Overweight or obesity played a key central role, not only for its frequency, but also for its contribution to GD development. Our findings reinforce the importance of multi causal studies as the basis to design and implement prevention strategies for diabetes.

Diabetes gestacional. Determinación del peso relativo de sus factores de riesgo. / [Gestational diabetes. Determination of relative importance of risk factors]

The aim of this study was to determine the relative importance of gestational diabetes (GD) risk factors to identify populations at risk. A total of 400 pregnant patients were studied, 200 with confirmed GD diagnosis and 200 controls with risk factors. They regularly attended health-care units belonging to the Ministry of Health of the Province of Buenos Aires, in the context of the Program for the Prevention, Care and Treatment of People with Diabetes of the Province of Buenos Aires (PRODIABA). The following risk factors were evaluated: GD in previous pregnancies, history of diabetes in first degree relatives, age > or = 30 years, BMI > 26, history of fetal macrosomy, perinatal mortality and hypertension during pregnancy. Data analysis was performed with the Program of Statistics in Public Health Epilnfo 6. The association between GD development as a dependent variable and the presence of different risk factors (independent variables) was analyzed with a multiple logistic regression model, determining the logistic probability to develop GD. Results showed that the incidence of risk factors to develop GD is not the same; therefore, they do not have the same predictive value. Overweight or obesity played a key central role, not only for its frequency, but also for its contribution to GD development. Our findings reinforce the importance of multi causal studies as the basis to design and implement prevention strategies for diabetes.

[Evaluation and cost of the health care process of diabetic patients]. / Evaluación y costos del proceso de atención de pacientes diabéticos.

The aim of this randomized trial o evaluate the quality and cost of health care provided to people with diabetes in a Public Employment-Based Health Insurance program in La Plata, Argentina. Consequently, 1590 diabetic patients were interviewed and the data obtained were analyzed using univariate and multiple logistic regression. Patients treated without insulin (48%) were significantly older and reported obesity, hypertension, and macroangiopathy more frequently than those treated with insulin. Hospitalization rates were significantly higher in insulin-treated patients. These rates were comparable in people without complications or microangiopathy alone, but increased significantly in patients with macroangiopathy. Many recommended practices were not performed during the preceding year: foot exams (20-30%), referral to ophthalmologist (21-29%), and HbA1c test (60-78%). In contrast, the rate of medical testing and visits was high, even in uncomplicated patients, resulting in an estimated cost of the care 22.7% higher than it would have been if the tests and procedures had been performed as recommended by international guidelines. We conclude that the current care for diabetes is inefficient and expensive; the implementation of data-based guidelines would result in a more effective allocation of resources, thus improving the quality of diabetes care and overall quality of life.

Evaluación y costos del proceso de atención de pacientes diabéticos. / [Evaluation and cost of the health care process of diabetic patients]

The aim of this randomized trial o evaluate the quality and cost of health care provided to people with diabetes in a Public Employment-Based Health Insurance program in La Plata, Argentina. Consequently, 1590 diabetic patients were interviewed and the data obtained were analyzed using univariate and multiple logistic regression. Patients treated without insulin (48

) were significantly older and reported obesity, hypertension, and macroangiopathy more frequently than those treated with insulin. Hospitalization rates were significantly higher in insulin-treated patients. These rates were comparable in people without complications or microangiopathy alone, but increased significantly in patients with macroangiopathy. Many recommended practices were not performed during the preceding year: foot exams (20-30

), referral to ophthalmologist (21-29

), and HbA1c test (60-78

). In contrast, the rate of medical testing and visits was high, even in uncomplicated patients, resulting in an estimated cost of the care 22.7

higher than it would have been if the tests and procedures had been performed as recommended by international guidelines. We conclude that the current care for diabetes is inefficient and expensive; the implementation of data-based guidelines would result in a more effective allocation of resources, thus improving the quality of diabetes care and overall quality of life.

Effect of 2-hydroxyoestradiol on insulin secretion in normal rat pancreatic islets.

The possible action of 2-hydroxyoestradiol (2-OHE2) on glucose-induced insulin secretion was evaluated in pancreatic islets isolated from normal rats by collagenase digestion and incubated in KRB buffer. Insulin output in response to either 3.3 or 16.6 mM glucose was measured by radioimmunoassay in the absence or presence of different concentrations of 2-OHE2, norepinephrine (NE), or oestradiol. Islets were also incubated with 2-OHE2, NE, or oestradiol plus a fixed concentration (1 microM) of the alpha 2-adrenergic-receptor blocking agent yohimbine. The results showed that 2-OHE2, oestradiol and NE within a range of 0.1 to 20 microM inhibited glucose-induced insulin secretion in a dose-dependent manner: Ki (microM): 0.04 +/- 0.0001, 0.04 +/- 0.0002, and 0.01 +/- 9.1 E-6 respectively. This suppression was significantly reversed by yohimbine. Contrary to NE and 2-OHE2, oestradiol at lower concentrations (increasing within a range of 0.001 to 0.05 microM) in incubation medium in the same experimental conditions had a significant stimulatory effect on insulin secretion. Thus, it would appear that catecholoestrogens suppress islet insulin release via alpha 2-adrenergic receptors, which suggests that oestrogens may exert a dual modulatory effect on insulin secretion by enhancing release via direct interaction with the cytosolic-oestrogen receptor and inhibiting release after their local hydroxylation and the interaction of their new catechol moiety with alpha 2-adrenergic receptors. Our results suggest that these compounds may play a complementary role to CAs as negative modulators, and they also provide a broader scope for understanding the effect of oestrogens and/or their metabolites in the control of endocrine functions other than those related to reproduction.

Changes induced by sex steroids in the kinetic properties of hypothalamic GABA uptake.

The aim of this study was to determine the changes induced by sex steroids in the kinetic properties of hypothalamic GABA uptake. For this purpose, we measured [3H]-GABA uptake by crude hypothalamic synaptosomal fractions obtained from intact female and male rats, orchidectomized and ovariectomized rats, and female rats treated neonatally with estrogens ("virilized" female rats) in the absence or presence of increasing concentrations of unlabelled GABA. Kinetic analysis of the uptake was performed through Eadie Hofstee plots. The specific [3H]-GABA uptake by hypothalamic crude synaptosomes varied according to the sex of the animals and the endogenous level of sex steroids. It was higher in male than in female rats. Gonadectomy resulted in a three-fold increase of the GABA uptake in both groups. Estradiol administration to ovariectomized rats reverted the high values recorded in these animals to levels below the range observed in intact rats. [3H]-GABA uptake was higher in "virilized" than in female rats. The kinetic analysis of the dose-dependent inhibition of [3H]-GABA uptake by unlabelled GABA showed the existence of both high and low affinity uptake systems in female rats and a single uptake system in male rats. Ovariectomy induced an increase in the Vmax value whereas orchidectomy resulted in a lower Km and a higher Vmax compared to intact rats. In conclusion, our results show that [3H]-GABA uptake by crude synaptosomes is sexually dimorphic and depends on the hypothalamic levels of endogenous sex steroids after gonadectomy.

Effect of catecholestrogens on [3H]-GABA uptake by hypothalamic crude synaptosomes.

Catecholestrogens (CE), 2-hydroxyestradiol, 2-hydroxyestrone and primary estrogens, estradiol and estrone were tested in their ability to compete for the high affinity uptake of [3H]-GABA into crude synaptosomal fractions. Aliquots of the crude synaptosomal fraction obtained from normal rats were incubated for 10 min at 37 degrees C with [3H]-GABA in the presence, or absence, of estrogens and catecholestrogens. Neither estradiol nor estrone modified the specific [3H]-GABA uptake into crude synaptosomal fractions. On the contrary, CE significantly affected the specific [3H]-GABA uptake in a dose-dependent manner: low concentrations of CE enhanced the uptake; this effect disappeared with high concentrations of the compounds. The stimulatory effect of CE on [3H]-GABA uptake was blocked when samples were coincubated with nipecotic acid, thus suggesting that this effect is specific rather than the result of non-specific interactions of CE with the hypothalamic membrane.

Sex and gonadal activity modify the effect of 2-hydroxyestradiol on hypothalamic GABA uptake in the rat.

The aim of this study was to determine the changes induced by sex and sexual steroids on the effect of the catecholestrogen 2-hydroxyestradiol (2OHE2) upon hypothalamic GABA uptake. For this purpose we have measured [3H]-GABA uptake by crude synaptosomal fractions obtained from normal female and male rats and from ovariectomized and virilized female rats in the presence or absence of increasing concentrations (0.1 to 100 microM) of 20HE2. The results presented in this paper demonstrate that the effect of the catecholestrogen varied according to sex: it potentiated the specific [3H]-GABA uptake in female rats, whereas it clearly inhibited the uptake in male and virilized rats. The enhancing effect of the catecholestrogen was not affected by ovariectomy, but a higher specific GABA uptake was observed in the ovariectomized animals. The present study provides the first evidence that the effect of 2OHE2 on hypothalamic GABA uptake depends on sex, thus suggesting the existence of a sexual dimorphism. Further studies in this field are required to elucidate the physiological significance and the underlying mechanism of the mentioned effect.

Assessment of cardiovascular risk factors in menopausal Argentinian women.

The cardiovascular risk factor profile was assessed in a population sample consisting of 60 nonmenopausal (control) and 100 menopausal women from different cities in Buenos Aires Province, Argentina. Each subject was individually interviewed and asked to complete a specially designed questionnaire aimed at identifying cardiovascular risk factors. A clinical general and gynecological examination including blood pressure and anthropometric measurements as well as a Papanicolaou smear were performed. The most prevalent risk factor in the menopausal group was low physical activity (87% of the subjects), followed by nervous complaints (67%), obesity (64%), familial antecedents of cardiovascular disease (CVD; 38%) and hypertension (33%). Other risk factors assessed showed a level of prevalence below 10%. In the control group, a tobacco smoking habit was the CVD risk factor with the highest prevalence (47%). Nervous complaints also showed a high prevalence (48%). Most menopausal patients (77%) had a cardiovascular risk index (RI) level between 1.5 and 4.0, whereas 17% of these subjects had an RI greater than 4.0 (high-risk patients). The present study reveals that, in the studied community, the menopause is associated with increased levels of both estrogen-dependent and psychosocial risk factors for CVD.

Involvement of 5-lipoxygenase pathway in norepinephrine stimulation of rat pineal melatonin synthesis.

The effect of lipoxygenase inhibition, leukotriene agonists and antagonists, and 5-hydroxy-6,8,11,14-eicosatetraenoic acid (5-HETE) was examined in the rat pineal gland in organ culture. To study melatonin secretion pineal explants were incubated for 6 h in tissue culture medium 199 with the different drugs. Melatonin concentration in the pineal gland and the medium was measured by RIA. Exposure of explants to norepinephrine (NE) brought about a 2- to 5-fold increase in both parameters, an effect that was reduced but not abolished, by the lipoxygenase inhibitor nordihydroguaiaretic acid (NDGA; 10(-5) M). Lilly 171883 (10(-5) M) or FPL 55712 (10(-5) M; both antagonists of leukotrienes) reduced NE-induced melatonin production. Neither NDGA nor Lilly 171883 affected melatonin production in the absence of NE. Leukotrienes C4 and D4 increased melatonin release to the media at all concentrations tested (1-1,000 nM) with a maximum effect at 1 nM (leukotriene C4) and 10 nM (leukotriene D4). Significantly higher tissue melatonin concentrations as compared to controls were observed after exposure of pineal explants to 1 and 100 nM of leukotriene C4, or 100 nM of leukotriene D4. Another 5-lipoxygenase metabolite, 5-HETE, increased pineal melatonin content at concentrations of 1, 10 and 100 nM whereas only 1,000 nM stimulated melatonin release. These results suggest that the 5-lipoxygenase pathway plays a significant role in NE-stimulated melatonin production by the rat pineal gland.

In vitro effect of neuropeptide Y on melatonin and norepinephrine release in rat pineal gland.

1. To study neuropeptide Y (NPY) effect on melatonin production, rat pineal explants were incubated for 6 hr with 10-1,000 nM NPY in the presence or absence of 10 microM norepinephrine (NE). Melatonin content in the pineal gland and media was measured by radioimmunoassay (RIA). 2. NPY (10-1,000 nM) increased melatonin production and, at 10 or 100 nM concentrations (but not 1,000 nM), enhanced NE stimulation of melatonin production. 3. NPY (1,000 nM) impaired 3H-labeled transmitter release induced by a K+ depolarizing stimulus in rat pineals incubated with 3H-NE. 4. These results suggest that NPY affects both pre- and postsynaptic pineal mechanisms.

In vitro effects of adenohypophysial hormones on rat pineal melatonin content and release.

The effect of adenohypophysial hormones on rat pineal melatonin content and release was examined in vitro. Medium concentration of radioimmunoassayable melatonin decreased after a 6 h exposure to 1-100 ng/ml FSH; pineal levels of melatonin were only decreased by 100 ng/ml FSH. LH (1-100 ng/ml) augmented significantly medium melatonin concentration, tissue levels being increased at 10 ng/ml LH. Parallel increases of explant and medium melatonin content were found after exposure to 1-100 ng/ml TSH. At the smallest concentration employed (1 ng/ml) prolactin increased melatonin content and release while at 100 ng/ml a significant depression of both parameters was found. Growth hormone (1-10 ng/ml) augmented melatonin levels in medium but failed to modify them at 100 ng/ml, although at this concentration tissue melatonin levels increased. ACTH did not modify pineal melatonin synthesis in vitro.