Microdialysis measurements of lamellar perfusion and energy metabolism during the development of laminitis in the oligofructose model.

REASONS FOR PERFORMING STUDY: Failure of lamellar energy metabolism, with or without ischaemia, may be important in the pathophysiology of sepsis-associated laminitis. OBJECTIVES: To examine lamellar perfusion and energy balance during laminitis development in the oligofructose model using tissue microdialysis. STUDY DESIGN: In vivo experiment. METHODS: Six Standardbred horses underwent laminitis induction using the oligofructose model (OFT group) and 6 horses were untreated controls (CON group). Microdialysis probes were placed in the lamellar tissue of one forelimb (all horses) as well as the skin dermis of the tail in OFT horses. Dialysate and plasma samples were collected every 2 h for 24 h and concentrations of energy metabolites (glucose, lactate, pyruvate) and standard indices of energy metabolism (lactate to glucose ratio [L:G] and lactate to pyruvate ratio [L:P]) determined. Microdialysis urea clearance was used to estimate changes in tissue perfusion. Data were analysed nonparametrically. RESULTS: Median glucose concentration decreased to <30% of baseline by 8 h in OFT lamellar (P = <0.01) and skin (P<0.01) dialysate. Lactate increased mildly in skin dialysate (P = 0.04) and plasma (P = 0.05) but not lamellar dialysate in OFT horses. Median pyruvate concentration decreased to <50% of baseline in OFT lamellar dialysate (P = 0.03). A >5-fold increase in median L:G compared with baseline occurred in OFT lamellar and skin dialysate (P<0.03). From a baseline of <20, median L:P increased to a peak of 80 in OFT skin and 38.7 in OFT lamellar dialysates (P<0.02); however, OFT lamellar dialysate L:P was not significantly different from CON. Urea concentration decreased significantly in OFT lamellar dialysate (increased urea clearance) but not in OFT skin or CON lamellar dialysate. CONCLUSIONS: Increased lamellar perfusion occurred during the development of sepsis-associated laminitis in the oligofructose model. Glucose concentrations in the lamellar interstitium decreased, suggesting increased glucose consumption but there was no definitive evidence of lamellar energy failure.

The effect of weightbearing and limb load cycling on equine lamellar perfusion and energy metabolism measured using tissue microdialysis.

REASONS FOR PERFORMING STUDY: Lamellar perfusion is thought to be affected by weightbearing and limb load cycling; this may be critical in the development of supporting limb laminitis. OBJECTIVES: To document the effects of unilateral weightbearing and altered limb load cycling on lamellar energy metabolism and perfusion. STUDY DESIGN: Randomised, controlled (within subject), experimental trial. METHODS: Nine Standardbred horses were instrumented with microdialysis probes in the foot lamellar tissue and skin (over the tail base). Urea (20 mmol/l) was added to the perfusate. Samples were collected every 15 min for a 1 h control period, then during periods of unilateral weightbearing (opposite limb held off the ground for 1 h); enhanced static limb load cycling (instrumented limb lifted every 10 s for 30 min); reduced limb load cycling activity (i.v. detomidine sedation) and continuous walking (30 min). Dialysate concentrations of glucose, lactate, pyruvate and urea were measured and lactate:glucose (L:G) and lactate:pyruvate (L:P) ratios were calculated. For each intervention, values were compared with baseline using nonparametric statistical testing. RESULTS: Lamellar dialysate glucose increased and L:G decreased significantly during enhanced static limb load cycling. Glucose and pyruvate increased, and L:G, L:P and urea decreased significantly during walking. Simultaneous skin dialysate values did not change significantly. There were no significant dialysate changes during unilateral weightbearing or after detomidine administration, but only the latter resulted in a significant decrease in limb load cycling frequency. CONCLUSIONS: Increases in limb load cycling frequency (particularly walking) caused dialysate changes consistent with increased lamellar perfusion. Unilateral weightbearing (1 h) and a sedation-induced reduction in limb load cycling frequency did not have a detectable effect on lamellar perfusion. More research is needed to confirm the role of hypoperfusion in supporting limb laminitis, but strategies to increase limb load cycling may be important for prevention.

Microdialysis measurements of equine lamellar perfusion and energy metabolism in response to physical and pharmacological manipulations of blood flow.

REASONS FOR PERFORMING STUDY: A suitable method for evaluating lamellar perfusion changes and their metabolic consequences is currently lacking. OBJECTIVES: To examine perfusion changes in lamellar tissue using serial microdialysis measurements of urea clearance and energy metabolites. STUDY DESIGN: Randomised, controlled (within subject) experimental trial. METHODS: Nine Standardbred horses were instrumented with microdialysis probes in the foot lamellar tissue and skin (over the tail base). Urea (20 mmol/l) was added to the perfusate and its clearance was used to estimate local perfusion. Samples were collected every 15 min for a 1 h control period, then during application of a distal limb tourniquet, during periods when norepinephrine or potassium chloride (KCl) were included in both skin and lamellar perfusates, and after systemic (intravenous) acetylpromazine. Dialysate concentrations of glucose, lactate, pyruvate and urea were measured and lactate:glucose (L:G) and lactate:pyruvate (L:P) ratios calculated. Values were compared with pre-intervention baseline and also between simultaneous skin and lamellar samples using nonparametric statistical methods. RESULTS: Lamellar glucose decreased and lactate, urea, L:G and L:P increased significantly with tourniquet application, without significant changes in skin dialysate values. Lamellar and skin glucose decreased and L:G increased significantly during norepinephrine infusion, but mild increases in urea were not significant at either site. KCl caused significant decreases in lamellar and skin L:G, and an increase in skin glucose, but did not affect urea clearance. Acetylpromazine caused profound decreases in lamellar glucose and L:P, with increased L:G and pyruvate, but did not affect urea clearance or any skin dialysate values. CONCLUSIONS: Significant changes in microdialysis urea clearance only occurred with severe lamellar hypoperfusion. However, changes in dialysate metabolite concentrations reflected less profound fluctuations in perfusion. This method may be useful for examining lamellar perfusion and energy balance during laminitis development and for the evaluation of vasoactive therapeutics.

Equine lamellar energy metabolism studied using tissue microdialysis.

Failure of lamellar energy metabolism may contribute to the pathophysiology of equine laminitis. Tissue microdialysis has the potential to dynamically monitor lamellar energy balance over time. The objectives of this study were to develop a minimally invasive lamellar microdialysis technique and use it to measure normal lamellar energy metabolite concentrations over 24 h. Microdialysis probes were placed (through the white line) into either the lamellar dermis (LAM) (n = 6) or the sublamellar dermis (SUBLAM) (n = 6) and perfused continuously over a 24 h study period. Probes were placed in the skin dermis (SKIN) for simultaneous comparison to LAM (n = 6). Samples were collected every 2 h and analysed for glucose, lactate, pyruvate, urea and glycerol concentrations. LAM was further compared with SUBLAM by simultaneous placement and sampling in four feet from two horses over 4 h. Horses were monitored for lameness, and either clinically evaluated for 1 month after probe removal (n = 4) or subjected to histological evaluation of the probe site (n = 10). There were no deleterious clinical effects of probe placement and the histological response was mild. Sample fluid recovery and metabolite concentrations were stable for 24 h. Glucose was lower (and lactate:glucose ratio higher) in LAM compared with SUBLAM and SKIN (P < 0.05). Pyruvate was lower in SUBLAM than SKIN and urea was lower in LAM than SKIN (P < 0.05). These differences suggest lower perfusion and increased glucose consumption in LAM compared with SUBLAM and SKIN. In conclusion, lamellar tissue microdialysis was well tolerated and may be useful for determining the contribution of energy failure in laminitis pathogenesis.

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.

[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.

Frecuencia y características de las infecciones urinarias en personas con diabetes mellitus / Frequency and characteristics of urinary infections in people with diabetes

El objetivo del estudio fue determinar la frecuencia y características clínicas y microbiológicas de las infecciones del tracto urinario (ITU) en pacientes diabéticos (DM) y no diabéticos (NoDM) ambulatorios. Los pacientes se evaluaron a través del análisis de urocultivos (UC) y de una encuesta individual relevada en el momento del análisis. Los UC se efectuaron en tres laboratorios microbiológicos con metodología estandarizada y la encuesta se registró en un formulario ad hoc. Se incluyeron 2.379 pacientes, de los cuales 208 eran DM(8.7). El porcentaje de UC positivos fue significativamente mayor en los DM (34.1) que en los NoDM (20.7; X² p=0.000001). La presencia de UC positivo fue mayor en mujeres DM (35.7) que en las NoDM (20.4;X²p=0.002). En pacientes con UC positivo el antecedente de ITU fue mas frecuente en los DM (62) que en los NoDM(44). No hubo diferencias significativas con respecto a la presencia de síntomas en ambos grupos, siendo la disuria el síntoma más frecuente. No hubo diferencias significativas en la frecuencia y tipo de microorganismos aislados en ambos grupos. El análisis de la sensibilidad de los antimicrobianos mostró alta resistencia a aminopenicilina (AMN) y trimetoprima-sulfametoxazol(TMS) y una actividad aceptable de la cefalexina(CEF). Estos resultados confirman la mayor frecuencia de ITU en los DM, especialmente en mujeres,y su mayor recurrencia. La AMN y la TMS no deberían utilizarse como tratamiento empírico de las ITU ambulatorias por su baja actividad, siendo la CEF una buena elección. Las fluorquinolonas presentaron el menor índice de resistencia, aunque mayor al descripto

Frecuencia y características de las infecciones urinarias en personas con diabetes mellitus / Frequency and characteristics of urinary infections in people with diabetes

El objetivo del estudio fue determinar la frecuencia y características clínicas y microbiológicas de las infecciones del tracto urinario (ITU) en pacientes diabéticos (DM) y no diabéticos (NoDM) ambulatorios. Los pacientes se evaluaron a través del análisis de urocultivos (UC) y de una encuesta individual relevada en el momento del análisis. Los UC se efectuaron en tres laboratorios microbiológicos con metodología estandarizada y la encuesta se registró en un formulario ad hoc. Se incluyeron 2.379 pacientes, de los cuales 208 eran DM(8.7). El porcentaje de UC positivos fue significativamente mayor en los DM (34.1) que en los NoDM (20.7; X² p=0.000001). La presencia de UC positivo fue mayor en mujeres DM (35.7) que en las NoDM (20.4;X²p=0.002). En pacientes con UC positivo el antecedente de ITU fue mas frecuente en los DM (62) que en los NoDM(44). No hubo diferencias significativas con respecto a la presencia de síntomas en ambos grupos, siendo la disuria el síntoma más frecuente. No hubo diferencias significativas en la frecuencia y tipo de microorganismos aislados en ambos grupos. El análisis de la sensibilidad de los antimicrobianos mostró alta resistencia a aminopenicilina (AMN) y trimetoprima-sulfametoxazol(TMS) y una actividad aceptable de la cefalexina(CEF). Estos resultados confirman la mayor frecuencia de ITU en los DM, especialmente en mujeres,y su mayor recurrencia. La AMN y la TMS no deberían utilizarse como tratamiento empírico de las ITU ambulatorias por su baja actividad, siendo la CEF una buena elección. Las fluorquinolonas presentaron el menor índice de resistencia, aunque mayor al descripto(AU)

Characteristics, clinical course, and in-hospital mortality of non-insulin-dependent diabetic and nondiabetic patients with acute myocardial infarction in Argentina.

The characteristics and clinical course of 1040 cases of acute myocardial infarction (AMI) among non-insulin-dependent diabetics (146) and nondiabetics (894) were compared. Patients with non-insulin-dependent diabetes mellitus (NIDDM) historically showed a greater percentage of AMI, angina, and risk factors than nondiabetic patients. Although the degree of left-ventricular function upon admission (according to the Killip and Kimball scores) was similar in both the diabetic and nondiabetic groups, the prevalence of hypertension and hypercholesterolemia was significantly higher in the NIDDM patients. All told, NIDDM cases were 1.73 [relative risk (RR)] times more likely to die of AMI than nondiabetic patients. The age factor and the presence of shock of any type also significantly increased the case-fatality rate. Diabetic patients showed signs of successful reperfusion less often than control subjects, an event that was closely associated with their case-fatality rate. In the NIDDM group, both the age and gender factor as well as a history of either casual or in-hospital clinical events such as cardiogenic shock, reinfarction, unsuccessful reperfusion, and incidence of anterior AMI along with either pain or previous angina were clear prognosticators of poor outcome from AMI. In the nondiabetic group, cardiogenic shock and hypertension were indicators of poor prognosis. These results would suggest that an improvement in the incidence of successful reperfusion in NIDDM patients, particularly in the face of clinical indicators of poor AMI prognosis, could decrease the high AMI mortality currently observed in these patients.

[Current situation of diabetic patients in hemodialysis in Buenos Aires]. / Estado actual de los pacientes diabéticos en hemodiálisis en Buenos Aires.

The aim of this study was to evaluate the clinical and biochemical characteristics and the different types of treatment of diabetic patients in hemodialysis (HD) due to their end-stage renal disease (ESRD). The protocol was organized as a multicentric, case-control study and comprised twenty-nine HD centres from the city and province of Buenos Aires (PRODIHEM). The population sample included all diabetic patients in HD (n = 103) and the non diabetic patients hemodialyzed in the morning hours (n = 230) as controls. In this sample, the recorded prevalence for diabetes mellitus was 12%. Among diabetic patients, 61% were non insulin dependent, 23% were insulin dependent and 16% were of the non insulin dependent type treated with insulin (Fig. 1). The results obtained in this study show that the current situation of diabetic patients in HD is far from being satisfactory: they require HD treatment at an early age; the disease is commonly associated with various comorbid factors not always appropriately treated; they show a fast deleterious progress towards ESRD, and they have a short halflife period in HD. The results also showed that there are no defined and common criteria for the treatment and control of these patients; thus, due to their poor clinical performance, only a small percentage reach a priority for a renal transplant.

[Diabetes mellitus and hypertension, clinical and epidemiological aspects in the population of La Plata]. / Diabetes mellitus e hipertensión arterial. Aspectos clínicos y epidemiológicos en la población de La Plata.

The purpose of this study was to determine socio-demographic characteristics, habits, most frequent morbid associations and degree of compliance with the control and treatment of their illness in a population of diabetic and hypertense patients of the La Plata area. A representative sample (890 people) was selected through a home survey (413 housing units). The results obtained show that diabetic and hypertense people a) are in average older than the general population and that the percentage of sedentary habits among them is also higher; b) show multiple typical symptoms of the illness but do not identify them as such and consequently diagnosis is frequently haphazardous; c) have a higher frequency of association with other risk factors, intercurrencies and hospitalization; d) are treated mainly by giving priority to drugs over changes in their detrimental habits; e) tend to ignore those indications that prescribe a change in their habits and f) control their illness at an inadequate periodicity. Consequently, it would be advisable to emphasize the incorporation of education strategies into the treatment of these patients in order to give more importance to preventive and health promoting actions. Education programmes should include not only patients and their families but also members of the health team and the community in general.

Diabetes mellitus e hipertensión arterial. Aspectos clínicos y epidemiológicos en la población de La Plata. / [Diabetes mellitus and hypertension, clinical and epidemiological aspects in the population of La Plata]

The purpose of this study was to determine socio-demographic characteristics, habits, most frequent morbid associations and degree of compliance with the control and treatment of their illness in a population of diabetic and hypertense patients of the La Plata area. A representative sample (890 people) was selected through a home survey (413 housing units). The results obtained show that diabetic and hypertense people a) are in average older than the general population and that the percentage of sedentary habits among them is also higher; b) show multiple typical symptoms of the illness but do not identify them as such and consequently diagnosis is frequently haphazardous; c) have a higher frequency of association with other risk factors, intercurrencies and hospitalization; d) are treated mainly by giving priority to drugs over changes in their detrimental habits; e) tend to ignore those indications that prescribe a change in their habits and f) control their illness at an inadequate periodicity. Consequently, it would be advisable to emphasize the incorporation of education strategies into the treatment of these patients in order to give more importance to preventive and health promoting actions. Education programmes should include not only patients and their families but also members of the health team and the community in general.

A simple economic evaluation model for selecting diabetes health care strategies.

The aim of this work was to develop a simple model to evaluate the health care cost of diabetes in order to help decision-makers in selecting strategies for the prevention, control, and treatment of the disease. The model assesses the cost of full coverage of health care of diabetic patients free of chronic complications and in comparison with those of the treatment of acute and chronic complications. For that purpose, standardized cost figures were obtained from both annual control and treatment of uncomplicated diabetic patients and the treatment of one episode of ketoacidosis, acute myocardial infarction, and amputation of two toes. The treatment/prevention cost ratio obtained showed that prevention of a single episode of any of these late-complication-related events would provide enough funds to cover either the total or partial annual cost of control and treatment of several uncomplicated diabetic patients. These facts would favour the allocation of funds in such a way as to allow adequate control and treatment of diabetic patients to keep them free of the chronic complications of the disease. This would be a wise investment of funds, which would result in a reduction in the socioeconomic cost of the disease and in a better quality of life for the diabetic patients and their families.

Costs of temporary and permanent disability induced by diabetes.

OBJECTIVE: To evaluate the indirect costs of diabetes and show their relationship to the chronic complications of diabetes. RESEARCH DESIGN AND METHODS: The cost of temporary and permanent disability for diabetic patients was studied in a group of La Plata University employees and in a second group at the government institutions of the Buenos Aires Province during 3 consecutive yr (1984-1986). RESULTS: Absences due to temporary disability were similar for the diabetic group without chronic complications and an age- and sex-matched nondiabetic control group. Conversely, diabetic patients with chronic complications had major increases in absences compared with the control subjects. Diabetes mellitus was the third leading cause of permanent disability mainly due to macrovascular and retinal lesions. This disability resulted in an average of 11 yr of work production loss per patient. CONCLUSIONS: These results suggest that diabetic individuals without complications incur few additional costs compared with nondiabetic individuals. However, once complications appear, the indirect costs are very high, suggesting that secondary preventions of the diabetic complications might be an optimal approach for reducing the health-care burden of diabetes.