Deterioration of cardiac autonomic function over a period of one year in relation to cardiovascular and somatic neuropathy complications in type 2 diabetes mellitus.

AIMS: Progression of cardiac autonomic dysfunction (CADF) in relation to severity of diabetic autonomic neuropathy is well documented. But its progression while coexisting with somatic neuropathy (PNP) and cardiovascular disease (CVD) is less described. We monitored CADF over a period of one year in relation to PNP and CVD in patients with type 2 diabetes mellitus. METHODS: Cardiac autonomic function was assessed in 104 type 2 diabetics. Based on complications study subjects were divided into four subgroups: Group A (No complications); Group B (with CVD); Group C (with PNP); Group D (with CVD and PNP). The parameters measured were: Expiratory:Inspiratory ratio (E:I ratio) and standard deviation of all the N-N intervals (SDNN). These parameters were measured at the baseline and at follow-up. Data analysis was done by employing suitable statistical tests. RESULTS: In Group B: SDNN declined (p<0.001); E:I ratio did not change. In Group C: E:I ratio declined (p<0.01); SDNN did not change. In Group D: SDNN and E:I ratio declined significantly (p<0.001). CONCLUSION: CADF coexisting with PNP and CVD deteriorates with time. E:I ratio and SDNN are suitable markers in monitoring CADF coexisting with PNP and CVD respectively in type 2 diabetes mellitus.

Influencing factors of QTc among the clinical characteristics in type 2 diabetes mellitus.

AIMS: Although the clinical implications of prolonged Q-T interval have been described, the clinical determinants of Q-T interval in type 2 diabetes mellitus are not clear. We examined the influencing factors of QTc in type 2 diabetes mellitus. METHODS: This study involved 207 patients with type 2 diabetes mellitus and 141 healthy controls. QTc was estimated from resting lead II electrocardiogram. Data analysis was done using unpaired Student's 't' and Pearson correlation tests. RESULTS: Only female diabetics with somatic neuropathy had longer QTc compared to controls (p<0.01). Only in male diabetics negative correlation was found between QTc and heart rate response to deep breathing (p<0.01). Male and female study subjects with diabetic retinopathy had longer QTc compared to controls (p<0.01, 0.05). Only male diabetics with hypertension had longer QTc compared to controls (p<0.05). CONCLUSION: QTc prolongation is associated with diabetic neuropathy with sex difference in its manifestation. It is influenced by diabetic retinopathy in male and female diabetics. It is influenced by hypertension in male type 2 diabetics.

Effect of diaphragmatic breathing on heart rate variability in ischemic heart disease with diabetes.

BACKGROUND: Reduced heart rate variability is associated with an unfavorable prognosis in patients with ischemic heart disease and diabetes. Whether change in breathing pattern can modify the risk factor in these patients has not been definitely proved. OBJECTIVE: To evaluate the effect of diaphragmatic breathing on heart rate variability (HRV) in ischemic heart disease patients with diabetes. METHODS: Study population consisted of 145 randomly selected male patients of which 45 had ischemic heart disease (IHD), 52 had IHD and diabetes (IHD-DM) and the remaining 48 had IHD and diabetic neuropathy (IHD-DN). HRV was assessed by 5 minute-electrocardiogram using the time domain method. The intervention group was divided into compliant and non-compliant groups and follow-up recording was carried out after three months and one year. RESULTS: Baseline recordings showed a significant decrease in HRV in ischemic heart disease (IHD) patients with or without diabetes (p<0.01). IHD patients had higher HRV than IHD patients with diabetes (p<0.01) or diabetic neuropathy (p<0.01). Increase in HRV was observed in patients who practiced diaphragmatic breathing for three months (IHD-DM: p<0.01; IHD-DN: p<0.05) and for one year (IHD-DM: p<0.01; IHD-DN: p<0.01). The HRV significantly decreased after one year in non-compliant patients. The regular practice of diaphragmatic breathing also improved the glycemic index in these patients. CONCLUSION: The regular practice of diaphragmatic breathing significantly improves heart rate variability with a favorable prognostic picture in ischemic heart disease patients who have diabetes. These effects seem to be potentially beneficial in the management of IHD patients with diabetes.

Efeito da respiração diafragmática sobre a variabilidade da frequência cardíaca na doença cardíaca isquêmica com diabete / Efecto de la respiración diafragmática sobre la variabilidad de la frecuencia cardiaca en la enfermedad cardiaca isquémica con diabetes / Effect of diaphragmatic breathing on heart rate variability in ischemic heart disease with diabetes

FUNDAMENTO: A diminuição da variabilidade da frequência cardíaca (VFC) está associada com um prognóstico desfavorável em pacientes com doença cardíaca isquêmica (DCI) e diabete. Ainda não foi provado em definitivo se a mudança no padrão respiratório pode modificar o fator de risco nesses pacientes. OBJETIVO: Avaliar o efeito da respiração diafragmática sobre a VFC em pacientes diabéticos com DCI. MÉTODOS: A população do estudo consistiu em 145 pacientes do sexo masculino selecionados ao acaso, dos quais 45 apresentavam DCI, 52 apresentavam DCI e diabete (DCI-DM) e 48 apresentavam DCI e neuropatia diabética (DCI-ND). A VFC foi avaliada através de ECG de 5 minutos usando o método de domínio de tempo. O grupo de intervenção foi dividido em grupo aderente e não-aderente e o seguimento foi registrado após três meses e um ano. RESULTADOS:A avaliação basal mostrou uma diminuição significante em VFC nos pacientes com doença cardíaca isquêmica com ou sem diabete (p<0,01). Os pacientes com DCI apresentavam VFC mais alta do que os pacientes com DCI-DM (p<0,01) e DCI-ND (p<0,01). Um aumento na VFC foi observado em pacientes que praticaram respiração diafragmática por três meses (DCI-DM: p<0,01; DCI-ND: p<0,05) e por um ano (DCI-DM: p<0,01; DCI-ND: p<0,01). A VFC diminuiu significantemente após um ano em pacientes não-aderentes. A prática regular de respiração diafragmática também melhorou o índice glicêmico nesses pacientes. CONCLUSÃO: A prática regular de respiração diafragmática melhora de forma significante a VFC em uma direção prognosticamente favorável em pacientes com DCI e diabete. Esses efeitos parecem ser potencialmente benéficos no manejo desses pacientes.

BACKGROUND: Reduced heart rate variability is associated with an unfavorable prognosis in patients with ischemic heart disease and diabetes. Whether change in breathing pattern can modify the risk factor in these patients has not been definitely proved. OBJECTIVE: To evaluate the effect of diaphragmatic breathing on heart rate variability (HRV) in ischemic heart disease patients with diabetes. METHODS: Study population consisted of 145 randomly selected male patients of which 45 had ischemic heart disease (IHD), 52 had IHD and diabetes (IHD-DM) and the remaining 48 had IHD and diabetic neuropathy (IHD-DN). HRV was assessed by 5 minute-electrocardiogram using the time domain method. The intervention group was divided into compliant and non-compliant groups and follow-up recording was carried out after three months and one year. RESULTS: Baseline recordings showed a significant decrease in HRV in ischemic heart disease (IHD) patients with or without diabetes (p<0.01). IHD patients had higher HRV than IHD patients with diabetes (p<0.01) or diabetic neuropathy (p<0.01). Increase in HRV was observed in patients who practiced diaphragmatic breathing for three months (IHD-DM: p<0.01; IHD-DN: p<0.05) and for one year (IHD-DM: p<0.01; IHD-DN: p<0.01). The HRV significantly decreased after one year in non-compliant patients. The regular practice of diaphragmatic breathing also improved the glycemic index in these patients. CONCLUSION: The regular practice of diaphragmatic breathing significantly improves heart rate variability with a favorable prognostic picture in ischemic heart disease patients who have diabetes. These effects seem to be potentially beneficial in the management of IHD patients with diabetes.

FUNDAMENTO: La disminución de la variabilidad de la frecuencia cardiaca (VFC) está asociada a un pronóstico desfavorable en pacientes con enfermedades cardiaca isquémica (DCI) y diabetes. Todavía no se aprobó en definitivo si el cambio en el estándar respiratorio puede modificar el factor de riesgo en esos pacientes. OBJETIVO: Evaluar el efecto de la respiración diafragmática sobre la VFC en pacientes diabéticos con DCI. MÉTODOS: La población del estudio consistió en 145 pacientes del sexo masculino seleccionados al azar, de los cuales 45 presentaban DCI, 52 presentaban DCI y diabetes (DCI-DM) y 48 presentaban DCI y neuropatía diabética (DCI-ND). La VFC se evaluó a través de ECG de 5 minutos con el empleo del método de dominio de tiempo. El grupo de intervención se dividió en grupo adherente y no-adherente y se registró el seguimiento tras tres meses y un año. RESULTADOS: La evaluación basal reveló una disminución significante en VFC en los pacientes con enfermedades cardiaca isquémica con o sin diabetes (p<0,01). Los pacientes con DCI presentaban VFC más alta que los pacientes con DCI-DM (p<0,01) y DCI-ND (p<0,01). Un aumento en la VFC se observó en pacientes que practicaron respiración diafragmática por tres meses (DCI-DM: p<0,01; DCI-ND: p<0,05) y por un año (DCI-DM: p<0,01; DCI-ND: p<0,01). La VFC disminuyó significantemente tras un año en pacientes no-adherentes. La práctica regular de respiración diafragmática también mejoró el índice glucémico en esos pacientes. CONCLUSIÓN: La práctica regular de respiración diafragmática mejora de forma significante la VFC en una dirección pronósticamente favorable en pacientes con DCI y diabetes. Esos efectos parecen ser potencialmente benéficos en el manejo de esos pacientes.

Independent predictors of cardiac parasympathetic dysfunction in type 2 diabetes mellitus.

INTRODUCTION: Although the clinical implications of diabetic autonomic neuropathy have been described, the clinical determinants of parasympathetic dysfunction in type 2 diabetes mellitus are not clear. We investigated the clinical determinants of heart rate response to deep breathing in type 2 diabetes mellitus. METHODS: This study involved 207 randomly selected patients with type 2 diabetes mellitus and 141 healthy controls. Heart rate response to deep breathing was measured in all the subjects. Heart rate response to Valsalva manoeuvre and active standing was measured in lesser numbers. Data analysis was done using unpaired Student's t-test, Pearson's correlation test and multiple regression. RESULTS: Heart rate response to deep breathing, Valsalva manoeuvre and active standing was lower in patients with diabetes mellitus than in controls (p-value is less than 0.0001, 0.01 and 0.01, respectively). Age, female gender and presence of somatic neuropathy were the independent predictors of reduced heart rate response to deep breathing (p-value is 0.001). Independent positive correlation was found between resting heart rate and heart response to deep breathing (p-value is 0.02). Factors associated with depressed heart rate response to deep breathing, but not independently predictive, were duration of diabetes mellitus, presence of hypertension, coronary artery disease, foot ulcer and retinopathy. Mean heart rate response to deep breathing of 47 patients with diabetes mellitus free of all complications was lower compared to controls (p-value is less than 0.01). CONCLUSION: Our data suggests that parasympathetic dysfunction mainly coexists with somatic neuropathy. It may be isolated, or precede detection of other complications. Age and female gender are the other predictors of reduced heart rate response to deep breathing in type 2 diabetes mellitus.

Forced swimming stress induced alterations in ingestive behavior in rats.

The effects of forced swimming stress (15 minutes per day) on body weight, food intake, blood sugar, water intake, and urine output were studied in adult male Wistar rats on the first, seventh, fourteenth and 21st days in different subgroups. There was a significant initial decrease in the body weight up to 14 days followed by a regain in the body weight, which was sustained until 21 days. Though there was no change in the food intake initially for 7 days, after 14 days a significant increase in the food intake was observed. A significant hypoglycemia was observed throughout the entire period of stress. More significant fall in the blood sugar level was observed in the initial period of exposure of stress (1-7 days). There was a significant reduction in the water intake in the stressed animals. Urine output decreased significantly up to 7 days of stress, though it got marginally increased later. Thus, repeated stress may produce a reduction in body weight only initially, which is accompanied with an initial decrease in food and water intake also. The peak response to stress was seen after 7 days of stress exposure. There was a gradual recovery back to normal in the body weight, food intake, and water intake and urine output when stress period was prolonged to 14-21 days. This is suggestive of the adaptation of the organism to repeated exposure of similar kind of stress.

Effect of acute and chronic conditions of over-crowding on free choice ethanol intake in rats.

Male albino rats of Wistar strain were exposed to overcrowding stress in two different groups for a period of seven days. One group of rats was kept under stress for six hours per day (acute stressed group) and the other group rats was kept under stress continuously (chronic stressed group). The effect of these acute and chronic stresses on voluntary alcohol (2% w/v) intake was monitored during the 7 days of stress exposure, and ethanol preference and total ethanol intake in terms of g/kg body weight were also studied. A significant increase in ethanol preference and ethanol intake was observed in one-day and 7 days chronic stressed group. No significant increase in ethanol intake was observed in acute stress. Thus a short lasting stressor may not increase ethanol-drinking behavior, whereas when animals were exposed to more intense stressor continuously for 7 days, an increase in voluntary drinking behavior may be seen.

Voluntary alcohol drinking & caloric intake in rats exposed to crowding stress.

BACKGROUND & OBJECTIVES: Alcohol intake in animals is regulated in much the same way as intake of food. The effect of alcohol on feeding behaviour is not well documented. The objective of this study was to test whether alcohol was ingested as a source of calories after crowding stress in rats. METHODS: Male albino rats were exposed to crowding stress continuously for two weeks and the effect of stress on the body weight, food intake, voluntary alcohol consumption and caloric intake in terms of food and alcohol was studied. RESULTS: A significant decrease in the body weight was seen after one (P < 0.05), 7 and 14 days (P < 0.01) of stress compared to controls. Food intake decreased significantly (P < 0.01) after one day of stress and there was recovery after 7 days stress. Absolute alcohol intake (g/kg body weight) increased significantly (P < 0.001) after one day of stress. Prolonged stress for two weeks significantly (P < 0.01) increased the alcohol consumption. Total caloric intake in stressed rats decreased significantly (P < 0.001) after acute stress. After 14 days, stressed rats showed significant (P < 0.001) increase in total caloric intake compared to day one. INTERPRETATION & CONCLUSION: Crowding stress decreased the body weight gain throughout the period of stress. Chronic stress for two weeks increased the voluntary alcohol consumption and total caloric intake. Food intake alone seemed insufficient to provide the extra demand of energy due to prolonged stress and hence, the rats may be drinking increasing amounts of alcohol (when provided) to supply the extra energy required to combat stress.

Effect of basolateral amygdala & ventromedial hypothalamic lesions on ingestion & taste preference in rat.

BACKGROUND & OBJECTIVES: Amygdaloid nuclei and the hypothalamic structures are known to have intimate functional relationships. But to date the nature of this relationship has not been completely understood. In the present study, this relationship was evaluated. METHODS: Lesions were performed in basolateral nucleus of amygdala (BLA) and the ventromedial hypothalamus (VMH) in the same rats sequentially to evaluate both the individual, as well as combined effects of lesions of these two centres. Food intake, water intake and the body weight were studied before and after the lesions. RESULTS: The first lesion of BLA or VMH increased the food and water intake significantly (P < 0.01). But in the VMH lesioned rats, further lesioning of BLA, reduced the intensity of the hyperphagia. This suggested a kind of interrelationship between these centres, pointing out that intact BLA was instrumental in the development of VMH induced hyperphagia. To further assess the interactions of these two centres, three bottle free choice taste preference tests were undertaken by using sweet, salty solution along with tap water. The lesion of the BLA increased the intake of sweet tasting saccharin solution. This preference was retained even after the lesion of the VMH in the same rats. INTERPRETATION & CONCLUSION: Therefore it appeared as if the VMH neurons might not be involved in the sweet taste preference following BLA lesion, suggesting involvement of some other pathway for taste selection responses. But the development of full fledged VMH lesion induced hyperphagia could occur only in the presence of intact BLA.

Increased sweet taste preference following the lesion of basolateral nucleus of amygdala (BLA) in rat.

A study of gustatory preference was carried out in Wistar strain albino rats by electrolytically lesioning the basolateral nucleus of amygdala. The intake of sweet tasting saccharin (Sn-0.1% soln w/v), NaCl solutions (1% Soln w/v) and tap water, were tested in single bottle, 2 bottle choice and 3 bottle choice situations. The consumption of fluids both before and after the stereotaxic surgery was recorded and statistically analysed. Lesion of BLA increased the intake of all fluids in the single bottle tests (P < 0.01). But the increase in the group provided with saccharin was more than that in other two groups. When taste preference was tested using 2-bottle and 3-bottle choice situations, the lesioned rats were seeking Sn solution. In our previous study, we found that the lesion of BLA increased fluid intake in rats. The intake, in the present study was more in those animals provided with Sn solution. When choice was given, the rats shifted their preference from water to the Sn following the lesion. Thus this study confirms that BLA is involved in the preference for sweet tasting solution over the NaCl or plain water.

Influence of different types of stress on selected cardiovascular parameters in rats.

Wistar strain male albino rats were exposed to different types of stressors like isolation, immobilization, overcrowding and forced swimming, for a duration of one day, 7 days, 15 days and 30 days and the effect on heart weight, adrenal weight, heart rate, P-R interval and serum transaminase levels were studied. There was a significant increase in the heart weight and adrenal weight in most of the stress subgroups. Tachycardia was seen in all the types of stress upto 7 days, except in the case of overcrowding stress. Serum transaminase level increased significantly in all the types of stress. Among the different types of stress, immobilization and forced swimming had greater effect on the heart weight and heart rate. Increase in the heart rate and heart weight was observed only in the initial period of exposure to a stressor and when the animals were exposed to a prolonged stressor like 15 days and 30 days, there was no further increase in the heart weight and heart rate which may be due to the adaptation of the animal to a chronic stressor.

FORCED SWIMMING STRESS-INDUCED CHANGES IN THE PHYSIOLOGICAL AND BIOCHEMICAL PARAMETERS IN ALBINO RATS.

The effects of fresh water swimming and cold water swimming for one day, 7 days and 15 days were studied on the total body weight, weight of the heart, kidney, adrenals, blood sugar level, serum cholesterol level, total leucocyte count, absolute neutrophil count and absolute eosinophil count in albino rats. The stress session in each day lasted for 45 min. Though the body weight of the animals decreased significantly during the initial period, when the stress period was prolonged, there was recovery in the body weight. There was a significant increase in the weight of the heart, kidney and adrenal glands after both types of stress. A significant leucopenia, eosinopenia and neutropenia along with significant hypoglycemia and hypocholesterolemia was observed in all the subgroups. A maximum stress response was seen upto a period of 7 days and the stress response decreased when the stress period was prolonged to 15 days in the physiological parameters studied. This could be due to the adaptation or habituation for the continued stress. There was no sign of adaptation in the case of biochemical parameters studied. A statistically significant physiological and biochemical changes were observed even after one day of forced swimming stress.

Involvement of basolateral nucleus & central nucleus of amygdala in the regulation of ingestive behaviour in rat.

Wistar albino rats were subjected to bilateral lesions of the basolateral nucleus of amygdala (BLA) and central nucleus of amygdala (CEA), individually and sequentially. The lesions of BLA increased the food and water intake significantly and that of CEA decreased the intake in rats. Sequential lesions of BLA and CEA (BLA-CEA & CEA-BLA), predominantly showed the lesion effects of BLA while the effects of lesion of CEA were masked in such animals. Thus it is concluded that BLA exerts an inhibitory influence while CEA exerts an excitatory influence on the ingestive behaviour and also that these centres interact with each other.

Methanol-induced monoamine changes in hypothalamus and striatum of albino rats.

This paper suggests that like ethanol, methanol also produces certain changes in the steady state level of monoamines in hypothalamus and striatum of albino rats. Though, the toxic manifestations of methanol are attributed to the metabolic end product of methanol viz. formic acid by several workers, we report here that the methanol-induced brain monoamine changes, at least, could be attributed to the direct action of methanol rather than to its metabolic end products like formaldehyde or formate. Studies in the steady state level of rat brain monoamines have shown that after methanol administration (3 g/kg), there is severe depletion of dopamine level in striatum but a significant increase in the level of dopamine, serotonin and 5-hydroxy indole acetic acid in hypothalamus. At the same time, norepinephrine and epinephrine levels are reduced in hypothalamus as well as in striatum. These effects do not seem to be induced by metabolic acidosis. The changes in monoamine levels are very well correlated with the blood and brain level of methanol as evidenced by maintaining a higher methanol level either by simultaneous administration of ethanol or by blocking methanol metabolism by pretreatment with 4-methyl pyrazole and 3-amino-1,2,4-triazole. It is thus postulated that monoamine changes induced by methanol appear to be the direct effect of methanol per se on the monoaminergic neuronal membranes.

Brain biogenic amine levels after methanol administration: possible mechanism of action on central monoaminergic neurons in discrete areas of brain in Wistar rat.

Alterations in the steady state level of rat brain biogenic amines - dopamine, nor-epinephrine, epinephrine, serotonin and 5-hydroxy indole acetic acid, in response to intraperitoneal administration of methanol (3g/kg b.w.) were studied in discrete areas of the rat brain. The monoamine changes induced by methanol were quite different from those induced by ethanol consumption. They were also region-specific; hypothalamus being more vulnerable for methanol-induced monoamine changes. The effects produced by methanol were correlated with the blood and brain level of methanol at the given time, suggesting that the effects were dependent upon the local concentration of methanol in different brain regions. Acidosis induced by ammonium chloride and sodium formate administration did not alter the monoamine levels and therefore, the effects of methanol were not possibly due to acidosis. Blocking or delaying the metabolism of methanol either by 4-Methyl Pyrazole and 3-Amino 1,2,4-Triazole or by simultaneous administration of ethanol resulted in the potentiation of methanol effect. Therefore, it was concluded that methanol induced changes in brain biogenic amines were due to methanol per se and not due to metabolic end products viz. formaldehyde or formic acid.

Methanol induced biogenic amine changes in discrete areas of rat brain: role of simultaneous ethanol administration.

Alteration in the steady state level of brain biogenic amines produced by methanol differ considerably in rats when compared to the effects produced by ethanol. When ethanol and methanol were administered simultaneously in identical concentration, the effects produced by methanol were much more pronounced in the presence of ethanol. This could be attributed to the delay in the metabolism of methanol as ethanol competes with methanol for alcohol dehydrogenase enzyme activity. Hence, it is presumed that the effects produced by methanol seem to be primarily due to the direct action of methanol itself and not due to metabolic end products of methanol. It is also inferred that if methanol per se is going to produce any permanent damage in the central nervous system due to abnormal neurotransmitter behaviour, they cannot be prevented by treatment with ethanol.

The effect of methanol on rat brain monoamine levels.

The variations in brain monoamine levels after methanol administration were studied in discrete areas of rat brain. Acute methanol administration (2 g/kg and 4 g/kg) significantly decreased Dopamine (DA) level in striatum and increased it in hypothalamus. Nor-Epinephrine (NE) and Epinephrine (E) levels were reduced in most of the areas studied. Serotonin (5HT) level was increased in hypothalamus, midbrain and cortex with corresponding increase in 5 Hydroxy Indole Acetic Acid (5 HIAA) level. It was concluded that central monoaminergic neurons were specifically influenced either directly or indirectly after methanol administration and that the effect of methanol differed according to the brain area and its action on different monoaminergic systems were quite different.

Effects of ethanol and methanol on spontaneous electromyographic signals and neuromuscular latency.

The effect of alcohols (ethanol and methanol) on rat electromyogram (E.M.G.) and neuromuscular latency were studied in thiopentone anesthetized albino rats. Both alcohols were given intraperitoneally (100 mg/100 g of body weight) to the respective groups and the controls received saline. Electromyographic signals were recorded from gastrocnemius muscle. For latency studies both the alcohols were given intravenously (iv) at a dose of 20 mg/100 g of body weight, and response to in situ sciatic nerve stimulation was studied before and after alcohol administration. Our results show that both ethanol and methanol induce spontaneous electromyographic signals and in addition produce changes in the latent period and the amplitude of the response.