Relationship between diabetes control and pulmonary function in insulin-dependent diabetes mellitus

PURPOSE: To evaluate the effect of different levels of glycemic control on the pulmonary function of subjects with type I insulin-dependent diabetes mellitus. PATIENTS AND METHODS: Eighteen subjects with type I insulin-dependent diabetes mellitus with no history or physical findings of respiratory disease. Patients were given insulin therapy with a standard twice-daily insulin injection regimen (standard treatment group) or a subcutaneous insulin infusion device (insulin pump) (intensive treatment group). Glycosylated hemoglobin (HbA1c) levels were determined at quarterly intervals in both groups of patients (standard treatment group, n = 10; intensive treatment group, n = 8). Pulmonary function and diffusing capacity for carbon monoxide (DLCO) were measured after 6 years of continuous follow-up. RESULTS: The average HbA1c in the standard treatment group was significantly higher than that of the intensive treatment group throughout the 6 years of follow-up (p less than 0.001). The forced vital capacity of the standard treatment group was 85 +/- 3% of predicted as compared with 106 +/- 4% of predicted in the intensive treatment group (p less than 0.001). The DLCO was also significantly diminished in the standard treatment group as compared with that in the intensive treatment group (65 +/- 2% versus 87 +/- 4% of predicted) (p less than 0.001). CONCLUSION: These data confirm previous reports of abnormal respiratory function in subjects with insulin-dependent diabetes mellitus and suggest that long-term near-normoglycemia may be beneficial in preventing the deterioration of pulmonary function associated with diabetes mellitus.     

Cross-section study of pulmonary function in patients with insulin-dependent diabetes mellitus

In this study, we attempted to establish the prevalence and nature of pulmonary dysfunction in a cross section of a diabetic population and the relationship of pulmonary dysfunction to diabetic factors and complications. Forty insulin-dependent diabetic patients, 15 to 60 yr of age, and 40 healthy reference subjects, matched for age, sex, and race, were studied. All subjects were lifelong nonsmokers and had no clinical evidence of past or present respiratory disease. Lung function was assessed from the flow-volume curve, single-breath nitrogen washout, static lung elastic recoil, and pulmonary diffusing capacity (DLCO/VA) and its components: membrane diffusing capacity (Dm/VA) and pulmonary capillary blood volume (Qc/VA). The diabetic patients had an increased value for Kst(L) and in Kst(L), the exponential shape constant of the pressure-volume curve compared with that of the reference subjects (Kst(L), 0.184 +/- 0.011 versus 0.135 +/- 0.005; p less than 0.005, mean +/- SEM). The DL/VA was lower in the diabetic subjects (4.62 = 0.12 versus 5.31 +/- 0.10 ml/min/mm Hg/L; p less than 0.001), and this was due to a lower Qc/VA (9.45 +/- 0.43 versus 11.75 +/- 0.35 ml/min; p less than 0.001). The Kst(L) and Qc/VA were correlated with the duration of diabetes. The In Kst(L) was negatively correlated with both DL/VA (r = -0.32, p less than 0.05) and Qc/VA (r = -0.36, p less than 0.05). There was no association between abnormal pulmonary function and the presence of other diabetic complications. It is concluded that there are mild, duration-related abnormalities of lung elastic recoil and pulmonary diffusing capacity and a reduction in pulmonary capillary blood volume in insulin-dependent diabetes mellitus.     

Antibody-dependent killer-cell function in insulin-dependent diabetes mellitus

Antibody-dependent killer-cell activity (ADCC) was determined in 36 insulin-dependent diabetics (IDD) and 32 controls. The medians of cytotoxic indices obtained by using either antibody coated chicken red blood or HeLa cells as targets were statistically significantly reduced in the diabetics (P less than 0.05 for both systems). However, due to the wide range and considerable overlap of the cytotoxic indices observed in patients and controls, the biological significance of these mathematical differences remains to be determined. The duration of the disease did not have any influence on killer (K) cell function and only a slight tendency for decreased ADCC during episodes of poor metabolic control was noted. Further analysis of the influence of diabetes-associated factors did not reveal any definite correlation between the functional K cell deficit, the insulin dosage administered, the insulin antibody titers, the blood glucose at the time of sampling, the 24 hour glucosuria and IDD-associated immunogenetic factors.     

Elevated muscle tissue oxygen tension in short-term insulin-dependent diabetes mellitus

In order to assess hemodynamic changes in early phases of insulin-dependent diabetes mellitus, muscle tissue oxygen tensions were determined in 7 newly diagnosed insulin-dependent diabetic patients and in 6 healthy control subjects matched for sex, age and weight. Muscle tissue oxygen tension was measured by polarrographic needle probes while breathing ambient air and oxygen enriched air with an oxygen concentration of 40 per cent as well. Three times during the experiment, heart rates, blood pressures, blood glucose concentrations, and capillary oxygen tensions were obtained. Heart rate, blood pressure, peripheral and autonomic nerve functions did not differ between the 2 groups studied. While breathing ambient air, muscle tissue oxygen tensions were significantly (p = 0.025) higher in the diabetic patients than in the control subjects. In contrast to the control subjects, diabetic patients did not increase muscle tissue oxygen tensions after inhalation of oxygen enriched air despite of an equal increase in capillary oxygen tensions (2p less than 0.05). Local tissue hypoxia does not seem to be a leading cause of hemodynamic abnormalities in the early phases of diabetes.     

Pulmonary function in insulin-dependent diabetes mellitus with limited joint mobility

Patients with insulin dependent diabetes mellitus (IDDM) and limited joint mobility (LJM) were studied to determine if altered respiratory mechanics were another manifestation of a generalized disturbance in collagen metabolism. Lung volumes and maximal expiratory flow volume curves were measured in 23 patients with IDDM. Patients were divided into 2 groups: (1) 11 without LJM, and (2) 12 with severe LJM. The groups were matched for age, sex, and glycemic control but not for duration of IDDM. In patients with severe LJM, forced vital capacity (FVC) and forced expiratory volume in one second (FEV1) were significantly decreased (p less than 0.05). Total lung capacity (TLC), thoracic gas volume (TGV) at functional residual capacity (FRC) and residual volume (RV) were also significantly lower (p less than 0.05) in the severe LJM group. There was no evidence of air-flow obstruction in either group. Our results demonstrate an association between severe LJM and a significant decrease in lung volumes. This could be due to decreased lung compliance or restriction of chest wall expansion.     

Magnesium and insulin-dependent diabetes mellitus

There is accumulating evidence that the changes which occur in the metabolism of some micronutrients in diabetes mellitus might have a specific role in the pathogenesis and complications of this disease. Magnesium deficiency is the most evident disturbance of metal metabolism in insulin-dependent diabetes mellitus. Hypomagnesemia has been linked both to the acute metabolic and late chronic complication of diabetes. Of particular concern, is the association between hypomagnesemia and ischemic heart disease and severe retinopathy in humans with diabetes mellitus. Appropriate magnesium supplementation might prove beneficial in normalizing the low plasma and tissue magnesium levels and prevent or retard the development of vascular complications in diabetic patients. However, well designed and documented experiments need to be performed before the rationales for such therapy are well established.     

Altered adrenal and thyroid function in children with insulin-dependent diabetes mellitus

In 129 children, aged 12.6±3.8 years, affected by type 1 diabetes mellitus, the levels of dehydroepiandrosterone sulfate (DHEAS), cortisol, T₃, fT₃, T4, fT4, rT₃, TSH, cholesterol, and triglycerides were evaluated and compared with those of a control group of 458 healthy age-matched children. The results were also correlated with hemoglobin HbA_1C. The DHEAS-standard deviation score (DHEAS-SDS; –0.36±0.77) was significantly different from zero in diabetic children, while the cortisol serum level was higher than in control subjects (485±94 vs 359±132 nmol/l). Moreover, the DHEAS-SDS and DHEAS-SDS/cortisol ratio correlated negatively with HbA_1c. Diabetic patients also showed lower T₃ values (2.22 ± 0.4 vs 2.32±0.3 nmol/l) and a higher rT₃/T₃ ratio (0.17±0.09 vs 0.15±0.05) than controls. There was a negative correlation between T₃ and HbA_1C. Cholesterol (4.77±1.08 vs 4.51±0.76 mmol/l) and triglycerides (0.82 ±0.53 vs 0.63±0.37 g/L) levels were higher in diabetic children and positively correlated with HbA_1c, but not with DHEAS-SDS. We can therefore conclude that diabetes, particularly if poorly controlled, tends to induce a dissociation of cortisol and DHEAS secretion and a low T₃ syndrome, similar to that seen in other illnesses.     

Improved diabetes control reduces skeletal muscle capillary basement membrane width in insulin-dependent diabetes mellitus

We studied the relationship between the control of blood glucose and the width of skeletal muscle capillary basement membrane in 54 insulin-dependent diabetic patients. After initial measurement of levels of glycosylated hemoglobin and the width of skeletal muscle capillary basement membrane, the patients were divided into two groups: an intensive treatment group of 30 patients who were treated with continuous subcutaneous insulin infusion and a control group of 24 patients who continued to receive conventional treatment, usually two daily injections of insulin. Both groups have been followed prospectively for periods of time up to 4 years. Within 1 year the intensive treatment group had a significant decrease in glycosylated hemoglobin levels as compared to baseline values reflecting improved control of blood glucose. This level of glycosylated hemoglobin was stable over the remainder of the follow-up period. This group also had a significant reduction in the width of skeletal muscle capillary basement membrane within 1 year and it persisted for the 4 years of observation. The control group of patients had no significant change in their level of glycosylated hemoglobin and the width of the skeletal muscle capillary basement membrane tended to increase with time. It this result in skeletal muscle capillaries applies to those of retinal and renal tissue, meticulous diabetic control for a prolonged period of time may be beneficial in preventing the progression of the microvascular complications of diabetes mellitus.     

Exocrine pancreatic function in children and adolescents with insulin-dependent diabetes mellitus.

Exocrine pancreatic function was evaluated in 21 diabetic children on the basis of a p-aminobenzoic acid (PABA) test and a determination of fasting serum amylase, pancreatic isoamylase, lipase, trypsin and elastase levels. Fecal chymotrypsin was also measured. Compared to the controls, the diabetic children had significantly lower levels of trypsin (P less than 0.001) and elastase (P less than 0.02). Fecal chymotrypsin appeared to be significantly lower (P less than 0.01) in diabetic children than in controls but in all patients fecal chymotrypsin values registered above the limit considered to be normal. No significant correlation was observed between pancreatic enzyme concentrations, serum and urinary PABA values, and chronologic age, HbA1 and insulin requirement. Only for serum PABA a significant negative correlation with duration of disease (P less than 0.01) has been observed. These data show that exocrine pancreatic function may be abnormal in children with IDDM.     

Vascular function and carotid intimal-medial thickness in children with insulin-dependent diabetes mellitus

OBJECTIVES: The objective of this study was to evaluate endothelium-dependent vasodilation and carotid intimal-medial thickness (IMT) in children with insulin-dependent diabetes mellitus. BACKGROUND: Diabetes mellitus is an established risk factor for atherosclerosis. Vascular complications of diabetes are not clinically evident in diabetic children. However, preclinical atherosclerosis is more common in young subjects exposed to cardiovascular risk factors. Endothelial function and carotid IMT, known to be abnormal in preclinical atherosclerosis, have not been studied concurrently in a pediatric population exposed to a risk factor for atherosclerosis. METHODS: We studied 31 diabetic teenagers (age 15.0 +/- 2.4 years; duration of diabetes 6.8 +/- 3.9 years) and 35 age-matched healthy children (age 15.7 +/- 2.7 years). Using high-resolution vascular ultrasound, we compared carotid IMT and brachial artery responses to reactive hyperemia (endothelium-dependent vasodilation) and to sublingual nitroglycerin (endothelium-independent vasodilation). RESULTS: There was no difference in baseline brachial artery diameter between the two groups. Endothelium-dependent vasodilation was significantly lower in diabetic children compared with healthy children (4.2 +/- 3.8% vs. 8.2 +/- 4.2%, p < 0.001). There was no difference in endothelium-independent vasodilation (17 +/- 6% vs. 18 +/- 6%, p = NS) or mean carotid IMT between the groups (0.33 +/- 0.05 vs. 0.32 +/- 0.08 mm, p = NS). Endothelium-dependent brachial vasodilation correlated with blood glucose levels (r = 0.58, p = 0.001) and was weakly and inversely related to the duration of diabetes (r = -0.4, p = 0.02), total cholesterol, and low-density lipoprotein cholesterol levels. CONCLUSIONS: Endothelial function is impaired in children with diabetes mellitus within the first decade of its onset and precedes an increase in carotid IMT. The relative timing of these events is important in the evaluation of strategies to prevent progression of atherosclerosis and other vascular complications in this patient population.     

Celiac disease and insulin-dependent diabetes mellitus

We screened for celiac disease, by means of IgA class anti-endomysium antibodies (EmA), 383 consecutive adults with insulin-dependent diabetes mellitus (IDDM). Two control populations entered the study as well: 151 adults with biopsy proven celiac disease, as true positives; and 520 controls (healthy and diseased) as true negatives. IgA-EmA positivity was found in 145 of 151 (96%) celiac disease patients but in none of the controls (100% specificity). EmA were positive in 12 of 383 (3.13%) IDDM patients: 10 of these positives underwent intestinal biopsy, which showed either partial or total villous atrophy. Only one patient presented with gastrointestinal complaints, but severe iron deficiency was found in all. The IDDM celiac patients were started on a gluten-free diet: four refused both the diet and the follow-up protocol. Approximately one year after gluten withdrawal no significant change in the degree of diabetes control was observed, while an increased requirement for insulin was observed in three of four patients who strictly complied with the diet. The prevalence of biopsy-proven celiac disease among adult IDDM patients (1:38), eight times higher than that recently estimated for the general Italian population and the absence, except in one case, of gastrointestinal symptoms emphasizes the benefit of screening programs on populations at risk.     

Pathogenesis of insulin-dependent diabetes mellitus

Insulin-dependent and independent types of diabetes mellitus differ not only in clinical traits but also in some other peculiarities: a different degree of disorder of insulin secretion, relationship with the HLA system, the presence of antibodies to pancreatic islets. The latter antibodies are typical of insulin-dependent diabetes mellitus whereas in insulin-independent diabetes mellitus they are absent. Autoimmune mechanisms of the pathogenesis of diabetes mellitus are confirmed by the presence of different antibodies to pancreatic islets, including cytoplasmic, cell-bound, cytotoxic and immunoprecipitating antibodies. The above autoantibodies were characterized, and a hypothetical mechanism of the development of insulin-dependent diabetes mellitus was proposed.     

Thyroid function and autoimmune manifestations in insulin-dependent diabetes mellitus during and after pregnancy

Insulin-dependent diabetes is associated with other autoimmune diseases and subclinical hypothyroidism has been reported in pregnant diabetic women. We studied the thyroid function of 85 women with diabetes during pregnancy and after delivery, as well as various autoantibodies. During pregnancy, thyroid microsomal antibodies were present in 17/85, antibodies against thyroid peroxidase in 16/85, thyroglobulin antibodies in 2/85, parietal cell antibodies in 23/85, adrenal antibodies in 4/77, rheumatoid factor in 15/85, and thyroid-stimulating antibodies in 43/85. Presence of antibodies was not combined with thyroid dysfunction, but TSH and HbA1c was increased (p less than 0.005) in women with thyroid antibodies. The gestational age of the infants was lower (p less than 0.01) in women with positive thyroid-stimulating antibody titre, whereas the ponderal index was only lower in those with peroxidase antibodies (p less than 0.05). After delivery, microsomal and peroxidase antibodies were positive in 10 (17.5%) of 57 patients followed. Six women developed postpartum thyroiditis (10.5%), of whom 5 were positive for both microsomal and peroxidase antibodies; two of those showing a hyperthyroid phase also had positive thyroid-stimulating antibody titre. We conclude that autoantibodies occur with increased incidence in pregnant diabetic women. Thyroid antibodies are related to a slightly reduced thyroid capacity and involve a high risk of postpartum thyroiditis. Further, thyroid antibodies seem to influence the nutritional status of the infant.     

Left ventricular performance and autonomic dysfunction in patients with long-term insulin-dependent diabetes mellitus

Cardiac autonomic neuropathy (CAN) is a very frequent complication of insulin-dependent mellitus type 1, affecting the sympathetic or parasympathetic sections or both. The different impairment in the two sections might modify left ventricular function early. To evaluate this relationship, we studied 61 patients (mean age 39.6±7 years) with type 1 diabetes for more than 10 years, without coronary artery disease (CAD; negative ergometric stress test) and without other pathologies that could interfere with ventricular function. All patients underwent MONO-, 2-dimensional and Doppler echocardiographic examination and radionuclide angiography with⁹⁹Tc (RNA). According to the outcome of the Ewing tests, patients were divided into two groups: group A with two or more tests altered (26 patients with CAN) and group B with one or no tests altered (35 patients without CAN). No significant differences between the two groups were found in the systolic function parameters with either technique. In contrast, a pattern of abnormal relaxation was found for the diastolic function parameters: in group A a decrease in E-wave velocity and its time-velocity integral and an increase in A-wave and its time-velocity integral were detected with echocardiography. Moreover, RNA showed a reduced peak filling rate and an increased isovolumic relaxation time. When compared with normal values, an abnormal diastolic filling, defined as two independent echocardiography plus one RNA variable impairment, was found in 15 patients (57.6%) in group A and in only 4 patients (11.4%) in group B (P<0.001). Our findings suggest an early involvement of diastolic function in patients with CAN.     

Heart function (angioscintigraphic evaluation) and sympathetic tone in insulin-dependent diabetes mellitus

Cardiac failure is a frequent feature in diabetic patients and it often causes their death. But how and when cardiac disease begins in this kind of patient is still debatable. For example, cardiac failure can be present even in the absence of atherosclerotic involvement of coronary arteries in young diabetics. The aims of our study were to evaluate the cardiac function and sympathetic tone of 16 young type 1 diabetic patients (8 M and 8 F, mean age: 27 years, SD +/- 5) in comparison with 10 normal subjects (4 M and 6 F, mean age: 30 years, SD +/- 7). Diabetic patients were choose from a large population because of the following features young age, absence of clinical and instrumental evidence of micro- or macroangiopathy, clinical evidence of diabetic autonomic neuropathy, proteinuria or arterial hypertension. They were in good metabolic control on daily insulin therapy of two or three administrations. Cardiac function was evaluated at rest and during submaximal exercise on a cycloergometer in supine position using radionuclide ventriculography with technetium 99m. Sympathetic tone was checked using the five clinical tests according to Ewing and the plasmatic level of catecholamines at rest was evaluated using high pressure chromatography. The ejection fraction, cardiac output, stroke volume of diabetics were comparable with those of normal subjects even in the presence of comparable systemic vascular resistance. The increase in ejection fraction during effort was normal. Only in one diabetic patient (incidentally the oldest one) did ejection fraction decrease (7%) during effort. The peak ejection and filling rates were significantly higher (p less than 0.001) in diabetic patients compared to those of normal subjects.(ABSTRACT TRUNCATED AT 250 WORDS)