Utilidad del trabecular bone score en sujetos adultos con osteogénesis imperfecta / Usefulness of the trabecular bone score in adult subjects with osteogenesis imperfecta

Objetivo: Analizar la utilidad del trabecular bone score (TBS) en adultos con osteogénesis imperfecta (OI) y su relación con variables clínicas, antropométricas y densitométricas, especialmente con la presencia de fracturas y la severidad de la enfermedad.Material y métodos: Estudio transversal realizado en 31 pacientes adultos con OI (edad 40.5±15.2 años, 68% mujeres, 87% tipo I). Se analizaron las características clínicas de los pacientes (fracturas, tipo de OI, IMC y tratamiento), la densidad mineral ósea (DMO) (mediante DXA), valorando la presencia de osteoporosis densitométrica, y los valores de TBS (TBS iNsight), estimando la presencia de microarquitectura degradada (valores <1.230). Los resultados se compararon entre los diferentes tipos de OI (I y III-IV) y con los de un grupo control de sujetos sanos.Resultados: La mayoría de los pacientes (29/31, 94%) tenían antecedentes de fracturas y el 29% recibía tratamiento antiosteoporótico. El 61% tenía una osteoporosis densitométrica y el 19% tenían una microarquitectura degradada. No se observaron diferencias en los valores del TBS según la gravedad de la OI (OI tipo I vs. III-IV: 1.297 vs. 1.339, p=n.s.); ningún paciente con OI tipo III-IV tenía TBS<1.230. Los valores de TBS se relacionaron con la edad (r=-0.6, p<0.01), la DMO lumbar (r=0.4, p=0.03) y el IMC (r=-0.5, p=0.01). Los pacientes con OI tenían valores más bajos de TBS y DMO que el grupo control en todas las localizaciones analizadas.Conclusión: El TBS es poco sensible en la valoración de la calidad ósea en la OI, pues ninguno de los pacientes con OI grave tenía una microarquitectura degradada y ésta sólo se observó en el 19% de los pacientes con OI a pesar de presentar una alta prevalencia de fracturas. (AU)

Continuous Variable Entanglement in an Optical Parametric Oscillator Based on a Nondegenerate Four Wave Mixing Process in Hot Alkali Atoms.

We present the measurement of entanglement between twin beams generated with a doubly resonant optical parameter oscillator (OPO) based on four-wave mixing in hot ^{85}Rb vapor above threshold. This is the first measurement of entanglement in an OPO with a χ^{(3)} media above threshold. We reconstruct the covariance matrix for several configurations and based on a full picture of the four side band mode state, we study entanglement between all possible bipartitions. We show a robust generation of entanglement with stronger generation for a specific pair of modes. For this system, we show that atomic density is a determinant factor for the generation and loss of quantum correlations. The generation of entangled fields with an atomic OPO operating close to atomic resonance of alkali atoms enables a natural integration into quantum networks.

Low serum osteocalcin levels are associated with diabetes mellitus in glucocorticoid treated patients.

Bone turnover markers are decreased in GC-treated subjects with DM. Decreased OC levels in GC-treated patients were associated with an increased risk of DM. These results suggest the involvement of OC in glucose homeostasis regulation in DM. INTRODUCTION: Osteocalcin (OC) is involved in the regulation of glucose homeostasis. Glucocorticoid (GC) treatment is associated with impaired osteoblast function, decreased OC levels, and the development and/or worsening of pre-existing diabetes mellitus (DM). Whether decreased OC levels in GC-treated subjects contribute to DM is not well known. The aim of this study was to analyse whether OC levels in GC-treated patients are associated with the presence of DM. METHODS: One hundred twenty-seven patients (aged 61.5 ± 17.9 years) on GC treatment were included. GC dose, treatment duration, presence of DM and bone formation (OC, bone ALP, PINP) and resorption markers (urinary NTX, serum CTX) were analysed. The cut-offs of each bone turnover marker (BTM) for the presence of DM were evaluated and optimised with the Youden index and included in the logistic regression analysis. RESULTS: Among the patients, 17.3% presented DM. No differences were observed in GC dose or duration or the presence of fractures. Diabetics showed lower levels of OC (7.57 ± 1.01 vs. 11.56 ± 1; p < 0.001), PINP (21.48 ± 1.01 vs. 28.39 ± 1; p = 0.0048), NTX (24.91 ± 1.01 vs. 31.7 ± 1; p = 0.036) and CTX (0.2 ± 1.01 vs. 0.3 ± 1; p = 0.0016). The discriminating BTM cut-offs for DM presence were < 9.25 ng/mL for OC, < 24 ng/mL for PINP, < 27.5 nMol/mM for NTX and < 0.25 ng/mL for CTX. In a multivariate logistic regression model adjusted for GC dose, BMI, age and the above four BTMs, only OC remained independently associated with DM presence. Thus, in a model adjusted for GC dose, BMI and age, OC was significantly associated with DM (OR: 6.1; 95%CI 1.87-19.89; p = 0.001). CONCLUSION: Decreased OC levels in GC-treated patients are associated with increased odds of DM, and only OC was independently associated with DM in a model including four BTMs.

Long-term effects of lifestyle and metformin interventions in DPP on bone density.

In the Diabetes Prevention Program Outcome Study (DPPOS), a cohort at high risk of diabetes, randomization to intensive lifestyle intervention or metformin, both associated with weight loss, did not have long-term negative effects on BMD compared with the placebo group. Potential positive effects of metformin on bone warrant further investigation. INTRODUCTION: Randomization to lifestyle intervention (ILS) or metformin in the Diabetes Prevention Program (DPP) resulted in weight loss and reduced progression to diabetes. Weight loss is associated with reduced bone mineral density (BMD), but the long-term effects of these interventions on BMD are unknown. In the DPP Outcome Study (DPPOS), we determined if randomization to ILS or metformin, compared with placebo, was associated with differences in BMD approximately 16 years later. METHODS: Of 3234 DPP participants, 2779 continued in DPPOS and were offered ILS in group format. Those randomized to metformin were offered unmasked metformin. At DPPOS year 12, 1367 participants had dual-energy X-ray absorptiometry scans. BMD in metformin and ILS groups was compared to placebo using sex-specific linear regression models, adjusted for age, race/ethnicity, and weight and weight-bearing activity at DPP baseline. RESULTS: At DPPOS year 12, mean age was 66.5 (±9.5) years. Femoral neck BMD was similar in the ILS and placebo groups in men (difference = -0.021 g/cm2, 95%CI (-0.063, 0.021)) and in women (+0.014 g/cm2, 95%CI (-0.014, 0.042)). Femoral neck BMD was higher in the metformin compared to placebo group although not statistically different in men (+0.017 g/cm2, 95% CI (-0.023, 0.058)) and in women (+0.019 g/cm2, 95% CI (-0.009, 0.047)). Prevalence of osteoporosis was low and similar across treatment groups in men (0.9%; p=0.745) and women (2.4%; p=0.466). CONCLUSION: In a cohort at high risk of diabetes, lifestyle intervention or metformin did not appear to have long-term negative effects on BMD. Potential positive effects of metformin on bone warrant further research.

Vertebral fractures are increased in rheumatoid arthritis despite recent therapeutic advances: a case-control study.

Prevalence and risk factors of vertebral fractures in postmenopausal RA women were assessed in 323 patients and compared with 660 age-matched women. Of patients, 24.15% had at least one vertebral fracture vs.16.06% of controls. Age, glucocorticoids and falls were the main fracture risks. Vertebral fractures were associated with disease severity. INTRODUCTION: There is little quality data on the updated prevalence of fractures in rheumatoid arthritis (RA) that may have changed due to advances in the therapeutic strategy in recent years. This study was aimed at analysing the prevalence and risk factors of vertebral fractures in postmenopausal women with RA and comparing it with that of the general population. METHODS: We included 323 postmenopausal women diagnosed with RA from 19 Spanish Rheumatology Departments, randomly selected and recruited in 2018. Lateral radiographs of the thoracic and lumbar spine were obtained to evaluate morphometric vertebral fractures and the spinal deformity index. We analysed subject characteristics, factors related to RA, and fracture risk factors. The control group consisted of 660 age-matched Spanish postmenopausal women from the population-based Camargo cohort. RESULTS: Seventy-eight (24.15%) RA patients had at least one vertebral fracture. RA patients had increased fracture risk compared with controls (106 of 660, 16.06%) (p = 0.02). Logistic regression analysis showed that age (OR 2.17; 95% CI 1.27-4.00), glucocorticoids (OR 3.83; 95% CI 1.32-14.09) and falls (OR 3.57; 95% CI 1.91-6.86) were the independent predictors of vertebral fractures in RA patients. The subgroup with vertebral fractures had higher disease activity (DAS28: 3.15 vs. 2.78, p = 0.038) and disability (HAQ: 0.96 vs. 0.63, p = 0.049), as compared with those without vertebral fractures. CONCLUSION: The risk of vertebral fracture in RA is still high in recent years, when compared with the general population. The key determinants of fracture risk are age, glucocorticoids and falls. Patients with vertebral fractures have a more severe RA.

Quantum Noise Correlations of an Optical Parametric Oscillator Based on a Nondegenerate Four Wave Mixing Process in Hot Alkali Atoms.

We present the first measurement of two-mode squeezing between the twin beams produced by a doubly resonant optical parameter oscillator (OPO) in an above threshold operation based on parametric amplification by nondegenerate four wave mixing with rubidium (^{85}Rb). We demonstrate a maximum intensity difference squeezing of -2.7 dB (-3.5 dB corrected for losses) with a pump power of 285 mW and an output power of 12 mW for each beam, operating close to the D1 line of Rb atoms. The use of open cavities combined with the high gain media can provide a strong level of noise compression and the access to new operation regimes that could not be explored by crystal based OPOs. The spectral bandwidth of the squeezed light is broadened by the cavity dynamics, and the squeezing level is robust for strong pump powers. Stable operation was obtained up to 4 times above the threshold. Moreover, operation of the OPO close to the atomic resonances of alkali atoms allows a natural integration into quantum networks, including structures such as quantum memories.

The Association of Frailty with Hospitalizations and Mortality among Community Dwelling Older Adults with Diabetes.

BACKGROUND: Diabetes (DM) is associated with an accelerated aging that promotes frailty, a state of vulnerability to stressors, characterized by multisystem decline that results in diminished intrinsic reserve and is associated with morbidity, mortality and utilization. Research suggests a bidirectional relationship between frailty and diabetes. Frailty is associated with mortality in patients with diabetes, but its prevalence and impact on hospitalizations are not well known. OBJECTIVES: Determine the association of frailty with all-cause hospitalizations and mortality in older Veterans with diabetes. DESIGN: Retrospective cohort. SETTING: Outpatient. PARTICIPANTS: Veterans 65 years and older with diabetes who were identified as frail through calculation of a 44-item frailty index. MEASUREMENTS: The FI was constructed as a proportion of healthcare variables (demographics, comorbidities, medications, laboratory tests, and ADLs) at the time of the screening. At the end of follow up, data was aggregated on all-cause hospitalizations and mortality and compared non-frail (robust, FI≤ .10 and prefrail FI=>.10, <.21) and frail (FI≥.21) patients. After adjusting for age, race, ethnicity, median income, history of hospitalizations, comorbidities, duration of DM and glycemic control, the association of frailty with all-cause hospitalizations was carried out according to the Andersen-Gill model, accounting for repeated hospitalizations and the association with all-cause mortality using a multivariate Cox proportional hazards regression model. RESULTS: We identified 763 patients with diabetes, mean age 72.9 (SD=6.8) years, 50.5% were frail. After a median follow-up of 561 days (IQR=172), 37.0% they had 673 hospitalizations. After adjustment for covariates, frailty was associated with higher all-cause hospitalizations, hazard ratio (HR)=1.71 (95%CI:1.31-2.24), p<.0001, and greater mortality, HR=2.05 (95%CI:1.16-3.64), p=.014. CONCLUSIONS: Frailty was independently associated with all-cause hospitalizations and mortality in older Veterans with diabetes. Interventions to reduce the burden of frailty may be helpful to improve outcomes in older patients with diabetes.

Analysis of previous training with simulated models on the success rate of ultrasound-guided supraclavicular block. Prospective cohort study. / Análisis del entrenamiento previo con modelos simulados en el porcentaje de éxito del bloqueo supraclavicular guiado por ultrasonido. Estudio de cohorte prospectivo.

INTRODUCTION: The teaching based on simulation and acquisition of skills is changing the paradigm of education and restructuring the clinical residences, with the aim of acquiring better skills, increasing procedural success, reducing complications, as well as providing safe, effective, and efficient and focused care of the patient. Peripheral nerve blocks have advanced as techniques for anatomical repairs, use of neurostimulator, and ultrasound. The posgraduate anaesthesiology program implemented a teaching program that included phases of theoretical teaching, training with simulated models, and application in real scenarios. OBJECTIVE: To analyse the success, the management of the ultrasound equipment and the incidence of complications of ultrasound-guided supraclavicular blocks (BSE) in the clinical scenario, performed by residents of anaesthesiology previously trained with a theoretical and simulated model. METHODS: Prospective cohort study among residents of anaesthesiology (R1, R2, R3, R4), who received previous theoretical-practical training on simulated models. The evaluation was performed by expert anaesthesiologists, with video analysis of the ultrasound screen performed at the time of BSE initiation. RESULTS: The evaluation included 16 residents, who performed 156 BSE. None had previous experience in ultrasound-guided blocks. The success of the block was 96.15%. The team management was excellent (from 86% to 95%), with no significant differences among the residents. (P=.61) The incidence of complications was 0.64%, corresponding to arterial puncture. CONCLUSIONS: In BSE, previous training with a theoretical and simulated model could increase the probability of success and reduce complications. With adequate training, first year residents managed to successfully carry out the procedure.

Rosiglitazone treatment and cardiovascular disease in the Veterans Affairs Diabetes Trial.

AIMS: To evaluate the relationship between patterns of rosiglitazone use and cardiovascular (CV) outcomes in the Veterans Affairs Diabetes Trial (VADT). METHODS: Time-dependent survival analyses, case-control and 1 : 1 propensity matching approaches were used to examine the relationship between patterns of rosiglitazone use and CV outcomes in the VADT, a randomized controlled study that assessed the effect of intensive glycaemic control on CV outcomes in 1791 patients with type 2 diabetes (T2D) whose mean age was 60.4 ± 9 years. Participants were recruited between 1 December 2000 and 31 May 2003, and were followed for 5-7.5 years (median 5.6) with a final visit by 31 May 2008. Rosiglitazone (4 mg and 8 mg daily) was initiated per protocol in both the intensive-therapy and standard-therapy groups. Main outcomes included a composite CV outcome, CV death and myocardial infarction (MI). RESULTS: Both daily doses of rosiglitazone were associated with lower risk for the primary composite CV outcome [4 mg: hazard ratio (HR) 0.63, 95% confidence interval (CI) 0.49-0.81 and 8 mg: HR 0.60, 95% CI 0.49-0.75] after adjusting for demographic and clinical covariates. A reduction in CV death was also observed (HR 0.25, p < 0.001, for both 4 and 8 mg/day rosiglitazone); however, the effect on MI was less evident for 8 mg/day and not significant for 4 mg/day. CONCLUSIONS: In older patients with T2D the use of rosiglitazone was associated with decreased risk of the primary CV composite outcome and CV death. Rosiglitazone use did not lead to a higher risk of MI.

Pharmacological treatment of diabetes in older people.

The pharmacological management of diabetes in older people is complex and challenging. It requires a comprehensive understanding of the individual beyond the diabetes itself. Through the ageing years, the older individual presents with diabetes-related and non-related comorbidities and complications, develops functional limitations and psychological issues, and may lack social support and access to care. A disturbance in these categories, known as the four geriatric domains, will negatively affect diabetes self-management and self-efficacy, leading to poor outcomes and complications. Furthermore, older people with diabetes may be more interested in the management of other chronic conditions such as pain or impaired mobility, and diabetes may be lower in their list of priorities. Proper education must be provided to the older individual and caregivers, with continuous monitoring and counselling, especially when pharmacological interventions offer risks of side effects, adverse reactions and interactions with other medications. Informed shared medical decisions will help to improve adherence to the regimen; however, such discussions ought to be based on the best evidence available, which is unfortunately limited in this age group. We performed a review focused on pharmacological agents and summarize current evidence on their use for the treatment of diabetes in older people. We encourage clinicians to investigate and incorporate the four geriatrics domains in the selection and monitoring of these agents.

Impact of diagnosis of diabetes on health-related quality of life among high risk individuals: the Diabetes Prevention Program outcomes study.

PURPOSE: The purpose of this study is to assess if diagnosis of type 2 diabetes affected health-related quality of life (HRQoL) among participants in the Diabetes Prevention Program/Diabetes Prevention Program Outcome Study and changes with treatment or diabetes duration. METHODS: 3,210 participants with pre-diabetes were randomized to metformin (MET), intensive lifestyle intervention (ILS), or placebo (PLB). HRQoL was assessed using the SF-36 including: (1) 8 SF-36 subscales; (2) the physical component (PCS) and mental component summary (MCS) scores; and (3) the SF-6D. The sample was categorized by diabetes free versus diagnosed. For diagnosed subgroup, mean scores in the diabetes-free period, at 6 months, 2, 4 and 6 years post-diagnosis, were compared. RESULTS: PCS and SF-6D scores declined in all participants in all treatment arms (P < .001). MCS scores did not change significantly in any treatment arm regardless of diagnosis. ILS participants reported a greater decrease in PCS scores at 6 months post-diagnosis (P < .001) and a more rapid decline immediately post-diagnosis in SF-6D scores (P = .003) than the MET or PLB arms. ILS participants reported a significant decrease in the social functioning subscale at 6 months (P < .001) and two years (P < .001) post-diagnosis. CONCLUSIONS: Participants reported a decline in measures of overall health state (SF-6D) and overall physical HRQoL, whether or not they were diagnosed with diabetes during the study. There was no change in overall mental HRQoL. Participants in the ILS arm with diabetes reported a more significant decline in some HRQoL measures than those in the MET and PLB arms that developed diabetes.

Metabolic syndrome components and their response to lifestyle and metformin interventions are associated with differences in diabetes risk in persons with impaired glucose tolerance.

AIMS: To determine the association of metabolic syndrome (MetS) and its components with diabetes risk in participants with impaired glucose tolerance (IGT), and whether intervention-related changes in MetS lead to differences in diabetes incidence. METHODS: We used the National Cholesterol Education Program/Adult Treatment Panel III (NCEP/ATP III) revised MetS definition at baseline and intervention-related changes of its components to predict incident diabetes using Cox models in 3234 Diabetes Prevention Program (DPP) participants with IGT over an average follow-up of 3.2 years. RESULTS: In an intention-to-treat analysis, the demographic-adjusted hazard ratios (95% confidence interval) for diabetes in those with MetS (vs. no MetS) at baseline were 1.7 (1.3-2.3), 1.7 (1.2-2.3) and 2.0 (1.3-3.0) for placebo, metformin and lifestyle groups, respectively. Higher levels of fasting plasma glucose and triglycerides at baseline were independently associated with increased risk of diabetes. Greater waist circumference (WC) was associated with higher risk in placebo and lifestyle groups, but not in the metformin group. In a multivariate model, favourable changes in WC (placebo and lifestyle) and high-density lipoprotein cholesterol (placebo and metformin) contributed to reduced diabetes risk. CONCLUSIONS: MetS and some of its components are associated with increased diabetes incidence in persons with IGT in a manner that differed according to DPP intervention. After hyperglycaemia, the most predictive factors for diabetes were baseline hypertriglyceridaemia and both baseline and lifestyle-associated changes in WC. Targeting these cardiometabolic risk factors may help to assess the benefits of interventions that reduce diabetes incidence.

Physical interpretation for the correlation spectra of electromagnetically-induced-transparency resonances.

The phenomenon called Electromagnetically Induced Transparency (EIT) may induce different types of correlation between two optical fields interacting with an ensemble of atoms. It is presently well known, for example, that in the vicinity of an EIT resonance the dominant correlations at low powers turn into anti-correlations as power increases. Such correlation spectra present striking power-broadening-independent features, with the best condition for measuring the characteristic linewidth occurring at the highest powers. In the present work we investigate the physical mechanisms responsible for this set of observations. Our approach is first to reproduce these effects in a better controlled experimental setup: a cold atomic ensemble, obtained from a magneto-optical trap. The results from this conceptually simpler system were then compared to a correspondingly simpler theory, which clearly relates the observed features to the interplay between two key aspects of EIT: the transparency itself and the steep normal dispersion near two-photon resonance.

Women relatives of Hispanic patients with type 2 diabetes are more prone to exhibit metabolic disturbances.

Hyperinsulinemia and impaired insulin action are familial and predictive of Type 2 diabetes onset. Since high levels of insulin are characteristic of our general (venezuelan)hispanic population, the purpose of this investigation was to identify early metabolic defects in a group of healthy first degree relatives of Type 2 diabetic patients. We studied 46 (29 women and 17 men; ages ranging 18-66 y) first degree relatives of Type 2 diabetic patients comparing them with 22 (12 women and 10 men; ages ranging 22-60 y) subjects who had no family history of diabetes. All subjects underwent resting blood pressure and anthropometric measurements; a 75 g oral glucose tolerance test with determination of glucose and insulin and a fasting lipid profile. The relatives of Type 2 diabetic patients had higher tricipital (TC) and subscapular (SC) skinfolds, and elevated DBP in relation to the control group. The skinfolds elevation was more evident in women, while in men the elevation in DBP predominates. None of the relatives had glucose intolerance, however, the glucose-stimulated insulin response was elevated at all points in men as well as in women. No difference was observed in the HOMA values for IR and beta cell function, or in the delta I30/delta G30 ratio. The lipid profile showed a marked elevation in TG levels in men as well as in women, with low HDL-C values in men. No other lipid abnormalities were observed. Correlation analysis revealed strong association between BMI and WHR with skinfolds and several parameters of the carbohydrate metabolism in women, but not in men. IR in women was possitively associated with skinfolds, SBP and lipid parameters and beta cell function with VLDL-C. Adult relatives of Type 2 diabetic venezuelan patients from hispanic origin had, early in their lives, several parameters of the metabolic syndrome as hyperinsulinemia, obesity, dyslipidemia and high blood pressure. These alterations were more prominent in women, group in which the association among BMI, WHR and IR were statistically significant respect to SBP, DBP, basal insulin, insulin/glucose ratio, TG and HDL-C.

[Gender differences and diabetic status in the relationship of blood apolipoprotein C-III, free fatty acids and triglycerides in subjects at risk for glucose intolerance]. / Diferencias según sexo y estado diabético en la relación entre apolipoproteína C-III y ácidos grasos libres con los triglicéridos séricos en sujetos a riesgo para intolerancia a la glucosa.

Insulin resistance and hyperinsulinemia can induce overproduction of triglyceride (TG) rich VLDL in the liver by increasing the availability of free fatty acids (FFA). Conversely, apolipoprotein C-III (apoC-III) is an inhibitor of the catabolism of TG-rich lipoproteins. To explore the relationship among FFA, apo C-III and TG in hyperinsulinemic subjects, we studied 103 individuals (63 women and 40 men) with a body mass index (BMI) 25 Kg/m2: 59 subjects with normal glucose tolerance (NGT), and 44 with newly diagnosed type 2 diabetes. After adjustment for age, BMI, fasting insulin and TG, FFA were significantly higher in women than in men and in subjects with diabetes compared with NGT. Subjects with diabetes had higher apo C-III levels compared to NGT, adjusted for age, sex and BMI, and that was largely accounted for by differences in insulin and TG levels. In addition, regression analysis in subjects with diabetes showed that TG were strongly associated with apo C-III in both men and women (r = 0.90 and 0.79, respectively; p < 0.001), while the association tended to be smaller between TG and FFA (r = 0.48, p < 0.05 in men and r = 0.45, p = 0.06 in women). Conversely, in individuals with NGT fasting TG was strongly associated with apo C-III in men (r = 0.83, p < 0.01) but not with FFA, while in women TG was associated with FFA (r = 0.39, p < 0.05) but not with apo C-III. In summary, elevated apo C-III was a predominant factor associated with elevated TG levels in NGT men and all subjects with type 2 diabetes, while FFA were more closely related with TG levels in NGT women.

Improved triglyceride control with low glycaemic index-high carbohydrate modified-lipid diet in a hypertriglyceridaemic child.

This study reports a 7-y-old boy with severe hypertriglyceridaemia who was successfully treated for 6 y with a low glycaemic index-high carbohydrate modified-lipid diet that produced beneficial changes in triglyceride and total cholesterol levels. It is suggested that a selection of a complex digestible carbohydrate and an adequate ratio between polyunsaturated and monounsaturated fat may, in the long term, favourably improve the lipid profile.

[Steps toward the primary prevention of type II diabetes mellitus. Various epidemiological considerations]. / Pasos hacia la prevención primaria de la diabetes mellitus tipo II. Algunas consideraciones epidemiológicas.

Non-insulin-dependent diabetes mellitus (NIDDM), or type II diabetes is rapidly becoming one of the most common chronic disease in the United States and worldwide, with more than 7% of the adult population affected. NIDDM is even more common in the elderly and in minority population including Hispanic Americans, African Americans, Asian and Pacific Island Americans, and Native Americans. In these populations, NIDDM may be present in 10% to as much as 50% of the adult population. However diagnosed NIDDM is only the tip of the iceberg of an epidemic of glucose intolerance. Impaired glucose intolerance (IGT) is even more prevalent that NIDDM; and in addition to be a major risk factor for the development of NIDDM, IGT is associated with an increased risk of macrovascular disease. Recent advances in research into the etiology and natural history of diabetes have increased the knowledge to such an extent that primary prevention of NIDDM is becoming a reality. This primary prevention can be implemented a) through a population strategy, i.e. changing the lifestyle and environmental determinants that are known to be risk factors for diabetes, and b) through high-risk strategy, i.e. targeting preventive measures only at those specific individuals or groups that are at high risk for the future development of NIDDM. The latter is the strategy of the Diabetes Prevention Program (DDP), a clinical study sponsored by the National Institute of Diabetes and Digestive and Kidney Disease in USA. Twenty five centers were selected to participate in this program. The purpose of DPP is prevent or delay the development of NIDDM in those persons who are at high risk because they have IGT. DPP will also evaluate if the interventions selected to prevent the development of NIDDM can decrease the frequency of cardiovascular events and the occurrence and magnitude of the cardiovascular risk factors that accompany NIDDM and IGT. Four thousand volunteers will be recruited from populations known to be at particular high risk fo IGT and NIDDM including the following: elderly, overweight individuals, persons with family history of NIDDM, women with history of gestational diabetes, and minority populations. In order to be eligible, persons who are older than 25 years will have to demonstrate IGT with plasma glucose levels 100-139 mg/dl fasting and 140-199 mg/dL two hours after a 75 g OGTT. Three study intervention were selected based on their potential efficacy in ameliorating abnormal glucose metabolism in IGT and on their safety and tolerable profile of side-effects. The interventions include: intensive lifestyle intervention which focuses on a healthy diet to achieve and maintain at least a 7% loss of body weight and an increase in caloric expenditure of at least 700 kcal per week. The drug therapy interventions include the biguanide metformin and the thiazolidinedione troglizatone. Standard life-style recommendations, which include conventional instructions regarding diet and exercise, will be provided to all participants, including a placebo treated group which will serve as the control group for the study. After randomization, participants will have quarterly evaluations and have, in addition, a fasting plasma glucose at semi-annual visits and a 75 g OGTT at annual visits. All participants will be followed for three years after the study-wide closing date for recruitment, resulting in 3 to 6 years of participant follow-up. The primary outcome is the development of NIDDM according to WHO criteria (fasting plasma glucose level 140 mg/dL or 2-hour plasma glucose 200 mg/dL after a 75 g OGTT). Secondary outcome will focus en cardiovascular disease and its risk factors and change of glycemia, insulin secretion and sensitivity, obesity, physical activity and nutrient intake, quality of life, and the occurrence of adverse events.