Maria Donatelli

Circulating endothelin-1 levels in type 2 diabetic patients with ischaemic heart disease

To investigate whether circulating endothelin-1 (Et-1) may be related to the increased incidence and severity of ischaemic heart disease in type 2 diabetes mellitus, we compared the concentrations in type 2 diabetic patients and in non-diabetic patients with coronary artery disease (CAD) angiographically documented. Plasma levels of Et-1 were determined in 34 type 2 diabetic patients with CAD (16 with stable angina, 6 with unstable angina, 12 with previous myocardial infarction) and in 19 non-diabetic patients with CAD (4 with stable angina, 5 with unstable angina, 10 with previous myocardial infarction). Fifteen diabetic patients without CAD and 9 healthy volunteers served as control subjects. In the type 2 diabetic patients, the mean Et-1 levels were 3.19±1.61 pmol/l in those with stable angina, 3.58±1.92 pmol/l in those with unstable angina, 4.24±2.53 pmol/l in those with myocardial infarction. These values were not significantly different one another, nor from the values obtained from type 2 diabetic controls (3.64±2.13 pmol/l). In the non-diabetic patients, the mean Et-1 levels were 3.92±0.73 pmol/l in those with stable angina, 4.35±1.67 pmol/l in those with unstable angina, 4.33±1.66 pmol/l in those with myocardial infarction. These values were not significantly different one another, but significantly higher than those obtained from healthy controls (2.07±0.67 pmol/l;P<0.001). No significant differences were found in Et-1 levels between diabetic and non-diabetic patients with stable, unstable angina and previous myocardial infarction. In contrast, a statistically significant difference was found in Et-1 levels between diabetic and non-diabetic control subjects (P<0.05). In conclusion, similar raised concentrations of Et-1 in diabetic and non-diabetic patients with stable, unstable angina and previous myocardial infarction do not support the hypothesis that higher levels of Et-1 in diabetic patients are responsible for the increased incidence of CAD in diabetes mellitus. However, the raised Et-1 levels found in diabetic patients in the absence of CAD strongly suggest that a generalised endothelial dysfunction, documented in our study by increased levels of Et-1, most probably precedes subsequent cardiovascular diseases.

The influence of high dose intravenous immunoglobulins on immunological and metabolic pattern in newly diagnosed type I diabetic patients

In autoimmune disease the functional deficiency of T suppressor cells, also described in Type I diabetes, may be restored through immunoglobulin (Ig) infusion, which increases antigen phagocytosis, NK activity, cell clones and antibody anti-idiotype responses. Sixteen Type I diabetic patients were studied: eight were treated soon after the initial correction of disease-onset glycemic deterioration with intensive intravenous (i.v.) 7S Ig treatment (0.4 g/kg/BW) for 1 week and once per week for 6 months, whilst the remaining patients constituted the control group. All patients were evaluated during the study for metabolic and immunological parameters. A reduction in insulin requirement compared to conventionally treated patients was observed at the third (0.17 +/- 0.06 vs 0.44 +/- 0.08 IU/kg/BW; P less than 0.02) and at the sixth month of therapy (0.19 +/- 0.07 vs 0.54 +/- 0.07 IU/kg/BW; P less than 0.005). Two patients ceased to require insulin therapy within the BW; P less than 0.005). Two patients ceased to require insulin therapy within the first month, showing a prolonged restoration of B-cell function. Serum C-peptide values were also significantly higher in the Ig-treated group compared to the control group after 3 and 6 months. As regards immunological parameters, patients showed a decrease in insulin antibody levels and a reduction in TAC+ cells. Intravenous Ig therapy seems able to affect positively the first phases of metabolic and immunological deterioration of Type I diabetes.

Placental lactogen, progesterone, total estriol and prolactin plasma levels in pregnant women with insulin-dependent diabetes mellitus

Fifteen insulin-dependent diabetic (Whites class B-C) and 10 healthy pregnant women were examined from the 12th to the 36th wk. Every 4 wk, a blood sample was drawn to determine total estriol, progesterone, placental lactogen and prolactin. Throughout the pregnancy, total estriol and progesterone in diabetic and non-diabetic women are very similar. On the contrary, the PRL levels are constantly lower in diabetic pregnant women, even though the difference is statistically significant only for the 24th wk determination. The hPL level is instead significantly lower in diabetic pregnant women at the 12th, 20th, 24th, 32nd and 36th wk. A negative correlation exists between the hPL value and the mean blood glucose level, performed the same day as the hormonal test. This correlation is statistically significant at the 12th, 16th, 20th, 28th and 36th wk. No significant difference is found between the two groups examined for the delivery week, the placental weight, the birth weight and the fetal body weight index. To conclude, while estriol and progesterone are not affected by the higher variability of glucose levels during pregnancy in diabetics, compared to normals, hPL and perhaps also PRL may be influenced by the mild hyperglycemia consequent to diabetes.

Insulin resistance and endogenous digoxin-like factor in obese hypertensive patients with glucose intolerance.

Hypertensive obese subjects with glucose intolerance have hyperinsulinaemia, insulin resistance and intracellular cation imbalance resulting in increased sodium content. The aim of our study was to assess in these patients plasma levels of endogenous digoxin-like factor (EDLF), an inhibitor of the sodium-pump mechanism. We studied 14 hypertensive and 12 normotensive subjects with obesity and glucose intolerance for fasting blood glucose, and plasma insulin, C-peptide and EDLF levels: the two groups were matched for age and BMI and were studied after a 2-week wash-out period from hypotensive drugs. Compared with normotensives, hypertensive subjects had higher plasma insulin levels, a greater immunoreactive insulin/C-peptide ratio, a lower glucose/insulin ratio and higher plasma EDLF levels. Our results confirm that among obese people with glucose intolerance, hypertensives are more hyperinsulinaemic and insulin-resistant than normotensives and indicate that the intracellular cation imbalance in these patients may be attributable, at least in part, to EDLF.

Study of pituitary secretion in relation to retinopathy in patients with juvenile diabetes mellitus

SummaryFifteen juvenile diabetic patients with normal eye fundus, 6 with non proliferative retinopathy, 5 with proliferative retinopathy and 5 healthy control subjects were studied in order to investigate pituitary function in relation to diabetic retinopathy. ACTH values at 0800 and 1800, hPRL and TSH secretion in response to 200 μg TRH i.v., and GH secretion in response to 500 mg oral L-dopa were evaluated. In all diabetic subjects, 0800 ACTH levels were lower than in controls. Basal hPRL, TSH and GH values of the diabetics did not differ from those of the controls. No significant differences were found in hPRL levels in response to TRH, whereas significantly lower TSH responses were found in the diabetics. L-dopa caused a significantly different response of GH in the diabetic subjects compared to controls. There is thus a considerable derangement in pituitary hormone secretion in juvenile diabetes mellitus.

A low reported energy intake is associated with metabolic syndrome.

Background and aims: Metabolic syndrome (MS) may be associated with the presence of an energy-sparing metabolism that predisposes to the excess accumulation of body fat. This study examined the relationship between reported energy intake and obesity in individuals with and without MS. Methods and results: Ninety consecutive non-diabetic obese subjects were divided into 2 groups based on the presence (MS+: no.=50) or absence (MS−: no.=40) of MS. The study design was cross-sectional. The 3-day food record method was used to assess the subjects’ usual energy intake and the Diet Readiness Test (DRT) was also administered. Compared to the MS− group, the MS+ group had a significantly higher body weight, body mass index (mean±SEM: 39.1 ±1.3 vs 31.5±0.9, p<0.001) and fat mass. The absolute energy intake of the MS+ group (8629±331 kJ/24h) did not differ from that of the MS− group (8571±515 kJ/24h; p=ns). The daily energy intake normalized for the fat-free mass (FFM) size was higher in the MS− group (163±8 kJ/kg-FFM·24h) than in the MS+ group (138±4 kJ/kg-FFM·24h; p<0.03). The DRT test results were similar in both groups except that section 6 (exercise patterns and attitudes) score was lower in the MS+ group (10.0±0.5) than in the MS− group (11.9±0.5; p<0.01). Conclusion: The results of this study support the hypothesis that subjects with MS have an energy-sparing metabolism.

Toxic adenoma and papillary thyroid carcinoma in a patient with Graves' disease.

A case of a very rare association of toxic adenoma and papillary carcinoma with Graves’ disease is presented. A 34-year-old woman developed Graves’ disease with mild ophthalmopathy. An ultrasound revealed diffuse thyroid enlargement with a hypoechoic pattern and a hypoechoic nodule with regular edges of 1.6 cm in diameter at the lower pole of the left lobe. A thyroid 131I scintiscan showed a diffuse and homogeneous 131I distribution. The 131I uptake (RAIU) was elevated. One year later, while still on a low dose of methimazole, the patient had a recurrence of hyperthyroidism following an iodine load from a contrast agent. A further thyroid ultrasound confirmed the previously described pattern but showed a new hypoechoic nodule of 1.1 cm with irregular edges in the left lobe. A thyroid 131I scintiscan this time demonstrated a hyperactive area localised in the larger nodule and a lower diffuse uptake of the remaining tissue. Because of the worsening of the symptoms of hyperthyroidism, the patient had a left lobectomy. On histological examination, the larger nodule was well encapsulated and showed the characteristics of a hyperfunctioning follicular adenoma. The smaller nodule was a typically unencapsulated papillary carcinoma. Several other microfoci of papillary carcinoma were also found in the adjacent tissue. Completion of thyroidectomy was therefore performed, followed by 131I ablative therapy and thyroxine suppressive treatment. This observation suggests that the chronic abnormal stimulation of the thyroid gland by the thyroid-stimulating antibody (TSAb) may facilitate the neoplastic transformation of the thyrocytes in individuals with a critical genetic background.

Effects of dynamic exercise and metabolic control on left ventricular performance in insulin-dependent diabetes mellitus.

SummaryIn subclinical diabetic cardiomyopathy, previous reports did not positively correlate the altered cardiac performance with metabolic parameters. Fifteen insulin-dependent diabetic subjects, without any clinical or instrumental evidence of heart diseases, were studied. Signs of diabetic microangiopathy were absent. Systolic time intervals, metabolic and hormonal parameters (blood glucose, free fatty acids, blood lactate and plasma norepinephrine) were evaluated at rest and after dynamic exercise during poor (MAGE 6.36±0.72 mmol/l) and good (MAGE 3.46±0.66 mmol/l) metabolic control, obtained by means of insulin therapy. Rest values of systolic time intervals were normal during poor and good metabolic control. After exercise, pre-ejection period/left ventricular ejection time ratio increased mainly during poor control as a result of an increased pre-ejection period: conversely, a smaller increase in pre-ejection period/left ventricular ejection time ratio occurred during good metabolic control. The exercise-induced free fatty acids utilization did not occur during poor control as it occurred during good control. The percentage of increments in blood lactate was virtually identical in ketotic and non-ketotic patients and in normal subjects. High norepinephrine plasma levels were observed both at rest and during dynamic exercise in poorly controlled diabetic patients. Conclusively, testing of systolic time intervals after exercise might be useful in the detection of preclinical diabetic cardiomyopathy. The decreased cardiac functional reserve observed during poor control might be related to an altered energetic fuel utilization.

Study on maternal, fetal and amniotic prolactin in gestational diabetic women, at term

SummaryIn order to determine whether prolactin secretion was affected in diabetic pregnancy, maternal, fetal and amniotic fluid prolactin (PRL) concentrations were measured in gestational non treated diabetic women at parturition. Amniotic fluid PRL levels, though higher than those in maternal and fetal serum, were significantly lower than those of the controls (p<0.005); no case of respiratory distress syndrome or congenital malformation was found at birth.

Evaluation of B-cell secretion and peripheral insulin resistance during pregnancy and after delivery in gestational diabetes mellitus with obesity

SummaryNine pregnant women with gestational diabetes mellitus (GDM) were studied. Six normal pregnant women and six normal nonpregnant women were evaluated as control groups. All the women underwent oral glucose tolerance test and glucose clamp during the third trimester of pregnancy and two months after delivery. During OGTT, glucose, C-peptide and insulin plasma levels were determined. C-peptide and insulin values in the late phase of OGTT were higher during pregancy than after delivery in both groups. In gestational diabetic women, the M-value in the second steady-state during glucose clamp was lower than in controls, both during pregnancy and after delivery. Nevertheless, in both groups the M-value during pregnancy was lower than after delivery. Moreover, in gestational diabetic women there was an inverse correlation between M-value in the second steady-state and ponderal excess index after delivery. In conclusion, the impaired peripheral glucose utilization and the pancreatic pattern of gestational diabetic women compared to normals suggested altered B-cell secretion response, increased peripheral resistance and overweight to be the main changes in GDM.