Risk factors for coronary heart disease mortality among persons with diabetes

Although synovial lining cells (SLC) have been implicated in the production of hyaluronan (HA), which is found at particularly high concentrations in synovial fluid, the degree to which individual cells within the synovium are adapted to this particular function remains to be elucidated. Uridine diphosphoglucose dehydrogenase (UDPGD) activity is the irreversible, rate-limiting step in the production of UDP-glucuronate, an essential monosaccharide in the synthesis of HA. We have assessed the UDPGD activity, microdensitometrically, in individual lining cells of normal and rheumatoid (RA) synovium, using a modified quantitative cytochemical method. In normal synovium, high activity was confined to the cells of the lining with negligible activity in the deeper subintima. The mean UDPGD activity/cell in lining cells of rheumatoid synovium was significantly lower than the activity in normal SLC. In some samples of RA and normal synovium, a bimodal distribution of cells was evident in the lining on the basis of UDPGD activity, a zone of cells in the basal layers with high UDPGD activity and a separate population of cells in more superficial layers with relatively low UDPGD activity. The results suggest that a particular population of cells is present, consistently in normal and more variably in RA synovial lining, which have high UDPGD activity/cell and may be involved in the production of HA. Furthermore, in RA synovium both the UDPGD activity/cell and the relative proportion of these cells within the lining appear to be decreased.     

Peripheral osteopenia in adult patients with insulin-dependent diabetes mellitus

Alterations in bone metabolism in diabetes mellitus is a topic of special interest. Bone blood flow is increased in the distal limb of diabetic patients, which is believed to increase osteoclastic activity. We measure bone mineral density using dual-photon absorptiometry in the distal lower limb, the femoral neck, and the lumbar spine in 41 IDDM patients and in 30 control persons. In the diabetic group there was a 10% reduction of bone mineral density in the femoral neck (p < 0.01) and a 12% reduction in the distal limb (p < 0.001) compared with the control group. No significant difference was found in the lumbar spine (p = 0.22). Our data yield incidence for peripheral osteopenia in IDDM-patients, independent of any systemic bone disease such as osteoporosis. A link between decreased bone mineral density and diabetic neuropathy has been observed for the femoral neck (p < 0.001), but not for the distal limb or axial skeleton. Whether there is a common aetiological link or a casual connection between diabetic neuropathy and bone mineral density has still to be determined.     

Products with high glycemic indices as factors in the metabolic stress of patients with insulin-dependent diabetes mellitus

Fifty-five patients aged 15-35 years with insulin-dependent diabetes mellitus lasting 3.8 +/- 1.2 years underwent carbohydrate food loading. Within 2 hours after the meal, at 15-min intervals measurements were made of glycemia, C-peptide, insulin, glucagon, hydrocortisone, blood STH levels. Contrary to foodstuffs with low glycemia indices (GI), i.e. vermicelli, buckwheat, the intake of fast absorbed products with high GI (potatoes, hardtack, bread) stimulates glycemia and residual secretion of the islet cells. Enhanced entrance of gastrointestinal glucose into the systemic blood flow and growing insulinemia aroused glucagon secretion depression. The body responses to the above processes, assessed as metabolic stress, with increasing blood hydrocortisone and STH concentrations.     

Insulin resistance precedes microalbuminuria in patients with insulin-dependent diabetes mellitus

BACKGROUND: Insulin resistance has been associated with hypertension and with renal complications in patients with type 1 diabetes mellitus. Causal relationships have not been fully explained. METHODS: We investigated whether insulin resistance precedes microalbuminuria by measuring insulin resistance with a euglycaemic clamp in combination with indirect calorimetry in 16 uncomplicated type 1 diabetic patients and in six healthy control subjects. The patients had over 10 year duration of diabetes, and were expected to experience either a complication-free or complicated disease course within the next few years. They have thereafter been followed for the development of microalbuminuria for 3 years. RESULTS: In a euglycaemic insulin clamp glucose disposal was lower in diabetic patients compared with control subjects (7.5 +/- 2.9 and 12.6 +/- 2.0 mg/kg LBM/min; P<0.002), mainly due to impaired glucose storage (4.3 +/- 2.3 vs 8.6 +/- 1.6 mg/kg LBM/min; P<0.001). Three years later seven IDDM patients had albumin excretion rate over 30 mg/24 h; glucose disposal (5.5 +/- 2.1 vs 9.0 +/- 2.2 mg/kg LBM/min; P<0.01) had been lower in patients who developed microalbuminuria compared with those who remained normoalbuminuric. CONCLUSIONS: Insulin resistance predicts the increment in urinary albumin excretion. Insulin resistance depends mainly on impaired glucose storage in uncomplicated IDDM.     

Glycemic control and cardiopulmonary function in patients with insulin-dependent diabetes mellitus

BACKGROUND: We studied cardiopulmonary function during exercise in young subjects with long-standing insulin-dependent diabetes mellitus (IDDM) who have no clinical cardiopulmonary disease to determine the relationships of aerobic capacity, gas exchange, ventilatory power requirement, and cardiac output to chronic glycemic control. METHODS: Eighteen subjects with IDDM and 14 normal control subjects were studied. Nine diabetic subjects received twice daily insulin injections and had chronically elevated levels of glycosylated hemoglobin (hyperglycemic group); 9 other diabetic subjects received insulin via continuous infusion pumps and maintained chronic near-normal levels of glycosylated hemoglobin (normoglycemic group). At the end of at least 7 years of regular follow-up, aerobic capacity was determined by cycle ergometry. Lung volume, diffusing capacity, and cardiac output during exercise were measured by a rebreathing technique. Ventilatory power was measured by the esophageal balloon technique. RESULTS: Maximal work load and oxygen uptake were markedly impaired in chronically hyperglycemic diabetic patients associated with significant restrictions of lung volume, lung diffusing capacity, and stroke index during exercise. Membrane diffusing capacity was significantly reduced at a given cardiac index. The normoglycemic patients consistently showed less impairment than the hyperglycemic patients. CONCLUSION: Physiologically significant cardiopulmonary dysfunction develops in asymptomatic patients with long-standing IDDM. Chronic maintenance of near-normoglycemia is associated with improved cardiopulmonary function.     

Risk factors for mortality among hospitalized children with persistent diarrhoea in Pakistan

We evaluated factors associated with mortality among a cohort of malnourished children with persistent diarrhoea (PD) admitted for nutritional rehabilitation with a defined rice-lentil (Khitchri) and yoghurt diet. Of 302 children consecutively admitted with PD, 13 (4 per cent) died, mostly (62 per cent) within 72 h of admission. Univariate analysis of risk factors at admission associated with mortality indicated significantly increased risk of death with severe stunting [relative risk (RR) 3.1, 95 per cent confidence interval (CI) 1.1-9.0], hypoalbuminaemia (RR 4.3, 95 per cent CI 1.5-12.3), stool frequency > 12/day (RR 6.0, 96 per cent CI 2.0-17.6), stool volume > 100 g/kg/day (RR 10.7, 95 per cent CI 3.0-37.6) and severe dehydration (RR 7.5, 95 per cent CI 2.6-21.8). Children who died also had comparatively shorter duration of diarrhoea at admission, and were also associated with higher rate of bacteremia at admission (Fisher's exact test P < 0.01). The logistic regression model evaluating multivariate risk of mortality identified weight-for-age z-score and sepsis as significant risk factors. Our data suggest that severe malnutrition and sepsis are associated with significantly increased risk of mortality in children with PD. Stringent screening for infections and recognition of subgroups with severe malnutrition and severe diarrhoea may improve screening and case management strategies for this disorder.     

Risk factors for perinatal and postnatal mortality in lambs

Factors associated with preweaning mortality in lambs were identified by developing risk profiles with logistic regressions for perinatal and postnatal mortality. Compared with heavy lambs, lambs of low birth weight had almost twice the risk of perinatal mortality (odds ratio [OR] = 1.9) and lambs of average weight had a slightly lower risk (OR = 0.7). Two of four lambing location categories affected perinatal mortality, with lambs born at unmonitored areas at greatest risk (OR = 2.7). Multiple births increased the risk of perinatal mortality (OR = 1.5), especially among Targhee lambs (OR = 4.0). Breed variations in perinatal mortality were significant in Suffolk lambs (OR = 1.9) and Booroola Rambouillet lambs (OR = 2.1). Lambs born weak had an increased risk of postnatal mortality while strong lambs had a decreased risk (OR = 3.7 and 0.6, respectively) if the dam had an adequate milk supply. Poor milk supply increased the risk of postnatal mortality for lambs of average vigour (OR = 3.3), but did not change the risk for weak or strong lambs. Male lambs castrated at 30 days of age were at less risk of postnatal mortality (OR = 0.3) than females. There were slight increases in the risk of postnatal mortality for intact males (OR = 1.3), low birth weight lambs (OR = 1.6), and lambs born in sheds (OR = 1.3). Suffolk lambs (OR = 1.8) and Targhee lambs (OR = 1.6) had a higher risk of postweaning mortality.     

Risk factors for above-knee amputations in diabetes mellitus

BACKGROUND: Above-knee amputation (AKA) is a common complication in diabetics, mostly after one or more lower level amputations (LEAs) have been done. The aim of this study was to identify risk factors for AKAs among diabetics. METHODS: We abstracted 1,800 medical records of hospitalizations for LEA. Kaplan's comorbidity classification was used to rank disease severity. We used both univariate and multivariate models to identify risk factors for AKA. RESULTS: Of the 1,043 diabetic amputees in this study, 22% had AKA. Variables associated with AKA were locomotor impairment, severe anemia, history of lower extremity bypass surgery, body mass index (BMI) < 20 kg/m2, female sex, cerebrovascular disease, cardiovascular disease, and SGOT > 40 U/L. CONCLUSIONS: Most of these risk factors represent end-stage processes and do not have good treatment alternatives. Perhaps one of the practical applications of these data is not to describe risk of proximal amputations but instead to look more closely at candidates who should be considered for distal procedures.     

Hypertension in insulin-dependent diabetes

Hypertension is seen in approximately 85% of IDDM patients with diabetic nephropathy and blood pressure elevation is an early event in the development of this complication. In IDDM patients with clinical nephropathy, a positive correlation has been demonstrated between the blood pressure and the urinary albumin excretion and reduction of blood pressure reduces albuminuria as well as the rate of decline in glomerular filtration rate. Also extrarenal abnormalities such as retinopathy, cardiovascular diseases and signs of endothelial dysfunction, sometimes seen in non-diabetics with severe and/or prolonged hypertension, are frequently demonstrated in IDDM patients with clinical nephropathy. The aim of the present study was to provide circumstantial evidence for the thesis that hypertension in IDDM patients with nephropathy is secondary to the kidney involvement and not the cause of the kidney disease. Furthermore, by familial and physiological studies the review also aimed to contribute to the understanding of the pathogenesis of hypertension in patients with clinical nephropathy. Finally the question of optimal pharmacological antihypertensive treatment was discussed. It was demonstrated that in IDDM patients with elevated urinary albumin excretion above normal level the prevalence of hypertension is 60%, whereas in patients without signs of renal impairment hypertension is not more prevalent as in the age and sex-matched background population (about 4% in both groups). Based upon the observation, that some of these IDDM patients with hypertension but normal UAE were hypertensive for many years, we designated this group as IDDM patients with essential hypertension for further studies. In this group, we had the opportunity to study the association between blood pressure and the development of extrarenal complications in patients with IDDM. The group with essential hypertension and IDDM showed to have less retinopathy compared with diabetics with similar blood pressure but elevated UAE. In contrast to the hypertensive patients with nephropathy, a normal transcapillary escape rate of albumin and normal plasma levels of von Willebrand factor, of angiotensin-converting-enzyme and of inactive renin were demonstrated in the former group of patients. Thus, the extrarenal abnormalities found in IDDM patients with hypertension are more closely associated to the presence of albuminuria than to the elevation of blood pressure, indirectly supporting the hypothesis that hypertension per se is not the cause of these abnormalities in the IDDM patients with nephropathy. Furthermore, the present study does not disclose a genetic disposition to hypertension in IDDM patients with elevated UAE.     

Trends in mortality of childhood-onset insulin-dependent diabetes mellitus in Leicestershire: 1940-1991

The relative risk of death by calendar date of diagnosis was investigated in a population-based incident cohort of 845 (463 males:382 females) IDDM diagnosed in Leicestershire before the age of 17 years between 1940 and 1989. The mortality status of 844 (99.9%) patients was determined as of the 31 December 1991, representing 14,346 person-years of risk. Trends in relative risk of death were investigated using Cox proportional hazards modelling for within cohort comparisons and age/sex and calendar time adjusted standardized mortality ratios (SMR) using generalized linear modelling for external comparisons. Median age at diagnosis was 10 years (range 3 months to 16 years); median duration of diabetes 15 years (range 1-51 years). Forty-four patients had died (5.2%; median age at death 31 years, range 11-51 years). A further four patients died at presentation (within 24 h) from ketoacidosis and are excluded from all analyses. Calendar date of diagnosis was found to be an important predictor of mortality. Adjusting for attained age there was evidence of a decline in relative risk of death with calendar date of diagnosis of 3.4% (95% CI, 0.005-6.9%) per annum, equivalent to a 32% fall per decade (95% CI, 5-51%), or 84% (95% CI, 21-97) from 1940 to 1989. The data are consistent with a large fall in mortality between the 1940s and 1950s representing over 50% of the total reduction in mortality between 1940 and 1991. Neither sex nor age at diagnosis were significant predictors of mortality. Over the study period 1940-89 the SMR (male and female combined) fell from 981 (541-1556) to 238 (60-953) relative to the general population. This population-based study shows that the prognosis for Type 1 (insulin-dependent) diabetes mellitus has improved markedly over the period 1940-1991.     

Parasympathetic neuropathy associated with left ventricular diastolic dysfunction in patients with insulin-dependent diabetes mellitus

BACKGROUND: As extracorporeal shock wave lithotripsy (ESWL) is frequently carried out on an outpatient basis, it is crucial to choose an adequate analgesic with less adverse effect. This study evaluated the use of three different intravenous agents: fentanyl, tramadol HCl and tenoxicam in ESWL. METHODS: One hundred and twenty patients undergoing lithotripsy were randomly assigned to receive either intravenous fentanyl 1 microgram/kg, tramadol HCl 1.5 mg/kg or tenoxicam 0.3 mg/kg before lithotripsy. Pain intensity was recorded using verbal rating pain scales (VRPS). Cases without adequate analgesia (VRPS > 4) or could not tolerate the pain, additional bolus of fentanyl 25 micrograms were given until adequate analgesia was achieved. Side effects were recorded as well. RESULTS: No significant differences were found among groups in demographic data, VRPS, number of total shock waves, cases with supplementary fentanyl, mean dose of supplementary fentanyl or the incidence of dizziness. However, the incidence of nausea or vomiting was significantly higher in fentanyl and tramadol groups comparing with tenoxicam group (15.0% and 25.0% vs. 0.0%). Oxygen saturation in fentanyl group was also significantly lower than the other two groups (p < 0.01). In addition, VRPS had a significant correlation with voltage intensities (p < 0.05). CONCLUSIONS: Lithotripsy can be satisfactorily performed by employing fentanyl, tramadol or tenoxicam for analgesia; tenoxicam apparently offers a better analgesic quality with less side effect. Furthermore, the need for stronger analgesia during larger voltage intensity should be tailored to the needs of the individuals.     

Reproducibility of data in a study of the risk factors for insulin-dependent diabetes mellitus

The reliability of information about mothers' and fathers' education, weight and height at birth, history of diarrhoea, duration of exclusive breast feeding and age of introduction of cows' milk products, selected from a structured questionnaire used in home interviewers was examined in a sample of 38 cases and 38 controls from a study related to the risk factors of insulin-dependent diabetes mellitus. The repetition of the questions was done by telephone. The agreement between the answers of both interviewers was verified using the kappa statistic (categorical variables) and the intra-class correlation coefficient (quantitative variables). The results enable one to conclude that the information is reproducible.     

Beneficial effect of the ACE inhibitor captopril in normotensive patients with insulin-dependent diabetes

The increase of glomerular filtration can often be observed in patients with insulin dependent diabetes mellitus, even in the early stage of the disease and it does not require the presence of microalbuminuria. This phenomenon can be explained by vasoconstriction occurring in the efferent arterioles. Eighteen normotensive, diabetic patients (aged: 28-42) who developed increased glomerular filtration were recruited in this study. The specific objectives were: 1. to study the beneficial effect of angiotensin converting enzyme inhibitor on the glomerular filtration, 2. to evaluate the effect of this treatment on blood pressure and hemodynamic parameters in normotensive, diabetic subjects. After a placebo period of one week, patients were treated orally a daily dose of 3 x 6.25 mg of captopril for twelve weeks. Glomerular filtration was assessed by the isotopic clearance method and blood pressure recordings were taken every 30 minutes throughout a day using an automatic programmable device. Preload, afterload and linear ejection fraction were estimated by echocardiograph, whereas cardiac index was measured by isotopic first pass technique. At the end of the treatment period a significant decrease of glomerular filtration was observed (from 141.9 +/- 10 ml/min to 98.9 +/- 12 ml/min; p < 0.01. Similarly, the afterload exhibited a significant drop due to drug treatment (45.6 +/- 5.8 x 10(3) dyn/cm2 vs. 55.4 +/- 4.7 x 10(3) dyn/cm2 at the end of the placebo period (p < 0.01). However, preload, linear ejection fraction, and cardiac index did not significantly change during the treatment. According to the results obtained from this study a beneficial effect of captopril on the early development of the glomerular hyperfiltration was demonstrated in normotensive diabetic patients who did not develop microalbuminuria. This issue needs to be investigated further in a large scale clinical trial.     

Neuropsychological changes in adolescents with insulin-dependent diabetes.

Assessed the neurobehavioral status of 40 12–19 yr olds with a long history (at least 3 yrs) of insulin-dependent diabetes mellitus and of 40 demographically similar nondiabetic adolescents. A detailed social and medical history was obtained from parents, and the degree of recent metabolic control was determined by examining the glycosolated hemoglobin values of diabetic Ss. Ss under age 16 yrs were given 7 subtests of the WISC—R; Ss aged 16 yrs and older were given the same subtests from the WAIS. Ss also completed tests that assessed associative learning and memory; visuospatial ability; speed, dexterity, and visuomotor integration; CFF; and self-concept. Results show that diabetics performed within normal limits on all tests, although significant between-groups differences did appear on measures of verbal intelligence, visuomotor coordination, and CFF. Although it could be argued that these results are indicative of structural brain damage, the possibility is discussed that the differences observed may be a function of transient metabolic abnormalities at the time of testing or, alternately, may be a reflection of the behavioral changes associated with having a life-threatening illness. (46 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Neuropsychological profiles in men with insulin-dependent diabetes.

Assessed 27 18–35 yr old males with insulin-dependent diabetes mellitus on a variety of intellectual, achievement, and neuropsychological measures. The 8 Ss in poor metabolic control (glycosylated hemoglobin?>?11%) obtained lower scores on the Wechsler Adult Intelligence Scale (WAIS) Information and Vocabulary subtests than did a demographically matched group in good metabolic control. Ss in poor control evidenced disrupted attention on a simple reaction time (RT) measure. The combination of earlier disease onset (before age 13 yrs) and poor control was associated with lower WAIS Similarities test scores, although performance was still within the average range. Results suggest that poor metabolic control is associated with a variety of mild performance decrements. Underlying attentional mechanisms that may be related to poor disease control and poorer test performance are discussed. (25 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Otoneurologic abnormalities in insulin-dependent diabetes

The Authors discuss the role of plasma prolactin concentration as a marker to discriminate epileptic and non epileptic seizures. In 40 children was determined prolactin during the first seizure (30 feverish and 10 non feverish seizures). The analysis of the results shows that during non feverish seizures prolactin concentration in higher, but we don't know if the same seizures are the beginning of epilepsy. So plasma prolactin concentration is a parameter of moderate interest in diagnosis and prognosis in childhood paroxismal disorders.