Ma-Pi 2 macrobiotic diet and type 2 diabetes mellitus: pooled analysis of short-term intervention studies.

The macrobiotic, Ma-Pi 2 diet (12% protein, 18% fat and 70% carbohydrate), has shown benefit in adults with type 2 diabetes mellitus (T2DM). This pooled analysis aims to confirm results from four, 21-day intervention studies with the Ma-Pi 2 diet, carried out in Cuba, China, Ghana and Italy. Baseline and end of study biochemical, body composition and blood pressure data, were compared using multivariate statistical methods and assessment of the Cohen effect size (d). Results showed that all measured indicators demonstrated significant changes (p < 0.001); most of them with a very high (d ≥ 1.30), or high (d = 0.80-1.29) effect size. The global effect size of the diet was Italy (1.96), China (1.79), Cuba (1.38) and Ghana (0.98). The magnitude of the individual effect on each variable by country, and the global effect by country, was independent of the sample size (p > 0.05). Similarly, glycemia and glycemic profiles in all four studies were independent of the sample size (p = 0.237). The Ma-Pi diet 2 significantly reduced glycemia, serum lipids, uremia and cardiovascular risk in adults with T2DM. These results suggest that the Ma-Pi 2 diet could be a valid alternative treatment for patients with T2DM and point to the need for further clinical studies. Mechanisms related to its benefits as a functional diet are discussed.

Anti-inflammatory effect of exercise training in subjects with type 2 diabetes and the metabolic syndrome is dependent on exercise modalities and independent of weight loss.

BACKGROUND AND AIMS: We investigated the effect of different exercise modalities on high sensitivity-C reactive protein (hs-CRP) and other inflammatory markers in patients with type 2 diabetes and the metabolic syndrome. METHODS AND RESULTS: Eighty-two patients were randomized into 4 groups: sedentary control (A); receiving counseling to perform low-intensity physical activity (B); performing prescribed and supervised high-intensity aerobic (C) or aerobic+resistance (D) exercise (with the same caloric expenditure) for 12 months. Evaluation of leisure-time physical activity and assessment of physical fitness, cardiovascular risk factors and inflammatory biomarkers was performed at baseline and every 3 months. Volume of physical activity increased and HbA(1c) decreased in Groups B-D. VO(2max), HOMA-IR index, HDL-cholesterol, waist circumference and albuminuria improved in Groups C and D, whereas strength and flexibility improved only in Group D. Levels of hs-CRP decreased in all three exercising groups, but the reduction was significant only in Groups C and D, and particularly in Group D. Changes in VO(2max) and the exercise modalities were strong predictors of hs-CRP reduction, independent of body weight. Leptin, resistin and interleukin-6 decreased, whereas adiponectin increased in Groups C and D. Interleukin-1ß, tumor necrosis factor-α and interferon-γ decreased, whereas anti-inflammatory interleukin-4 and 10 increased only in Group D. CONCLUSION: Physical exercise in type 2 diabetic patients with the metabolic syndrome is associated with a significant reduction of hs-CRP and other inflammatory and insulin resistance biomarkers, independent of weight loss. Long-term high-intensity (preferably mixed) training, in addition to daytime physical activity, is required to obtain a significant anti-inflammatory effect.

Physical activity/exercise training in type 2 diabetes. The role of the Italian Diabetes and Exercise Study.

Cardiorespiratory fitness is inversely related to the development of type 2 diabetes and cardiovascular morbidity and mortality. Trials in individuals with impaired glucose tolerance have highlighted the role of physical activity/exercise in the prevention of type 2 diabetes. Moreover, physical activity and exercise training have been recognized as treatment options for patients with type 2 diabetes. Both aerobic and resistance training were shown to produce beneficial effects by reducing HbA(1c), inducing weight loss and improving fat distribution, lipid profile and blood pressure in patients with type 2 diabetes. Mixed aerobic and resistance training was recently shown to be more effective than either one alone in ameliorating HbA(1c). However, further research is needed to establish the volume, intensity and type of exercise that are required to reduce cardiovascular burden and particularly to define the best strategy for promoting long-term compliance and durable lifestyle changes in individuals with type 2 diabetes. The Italian Diabetes Exercise Study (IDES) is a prospective Italian multicentre randomized controlled trial, of larger size and longer duration than previously published trials. It has been designed to assess the combined effect of structured counselling and supervised mixed (aerobic plus resistance) exercise training, as compared with counselling alone, on HbA(1c) and other cardiovascular risk factors as well as fitness parameters in individuals with type 2 diabetes and the metabolic syndrome. This study was also aimed at testing a sustainable strategy for promoting and maintaining a sufficient level of physical activity among individuals with type 2 diabetes to be implemented at the population level.

Self glucose monitoring and physical exercise in diabetes.

Cardiorespiratory fitness, which is determined mainly by the level of physical activity, is inversely related to mortality in the general population as well as in subjects with diabetes, the incidence of which is also increased by low exercise capacity. Exercise is capable of promoting glucose utilization in normal subjects as well as in insulin-deficient or insulin-resistant diabetic individuals. In diabetic subjects treated with insulin or insulin secretagogues, exercise may also result in complications, with too much insulin causing hypoglycaemia and not enough insulin leading to hyperglycaemia and possibly ketoacidosis; both complications may also occur several hours after exercise. Therefore, self-monitoring of blood glucose before, during (for exercise duration of more than 1 h) and after physical exercise is highly recommended, and also carbohydrate supplementation may be required. In the Italian Diabetes Exercise Study (IDES), measurement of blood glucose and systolic and diastolic blood pressure levels before and after supervised sessions of combined (aerobic + resistance) exercise in type 2 diabetic subjects with the metabolic syndrome showed significant reductions of these parameters, though no major hypoglycaemic or hypotensive episode was detected. The extent of reduction of blood glucose was related to baseline values but not to energy expenditure and was higher in subjects treated with insulin than in those on diet or oral hypoglycaemic agents (OHA). Thus, supervised exercise training associated with blood glucose monitoring is an effective and safe intervention to decrease blood glucose levels in type 2 diabetic subjects.

Plasma levels of adrenomedullin, a vasoactive peptide, in type 2 diabetic patients with and without retinopathy.

AIM: The aim of this study was to investigate whether adrenomedullin (AM) secretion is modified in type 2 diabetic patients with and without retinopathy. METHODS: The study was performed on 92 patients with type 2 diabetes, 65 of whom had uncomplicated diabetes, 27 had retinopathy, and 40 had mild to moderate hypertension. Patients with serum creatinine levels >1.2 mg/dL, were excluded. Circulating AM was assayed using a specific radioimmunoassay. RESULTS: AM concentrations were significantly higher in type 2 diabetic patients (25+/-2.1 pg/mL) than in the 31 normal subjects (11+/-0.8 pg/mL) (P<0.001). Type 2 diabetic patients with retinopathy had significantly greater AM levels (30.8+/-3.4 pg/mL) than both controls (P<0.001) and type 2 diabetic patients without retinopathy (25.2+/-2 pg/mL same as previous value) (P<0.001). No statistical difference was found between diabetic patients with pre-proliferative retinopathy (27.3+/-4.7 pg/mL) and proliferative retinopathy (24+/-3.1 pg/mL) (P=0.543). In type 2 diabetic patients, a significant correlation between plasma AM levels and HbA1c values (r=0.467; P<0.01) was found. CONCLUSION: Our findings indicate that circulating AM is increased in type 2 diabetic patients and that increase correlates with poor glucose metabolic control and presence of retinopathy.

A 6-month follow-up study of the randomized controlled Ma-Pi macrobiotic dietary intervention (MADIAB trial) in type 2 diabetes.

BACKGROUND: In the MADIAB trial (a 21-day randomized, controlled trial in patients with type 2 diabetes (T2D)), intervention with the Ma-Pi 2 macrobiotic diet resulted in significantly greater improvements in metabolic control compared with a standard recommended diet for patients with T2D. We report on a 6-month follow-up study, which investigated, whether these benefits extended beyond the 21-day intensive dietary intervention, in real-world conditions. SUBJECTS: At the end of the MADIAB trial (baseline of this follow-up study), all participants continued their assigned diet (Ma-Pi or control) for 6 months. The Ma-Pi 2 group followed the Ma-Pi 4 diet during this follow-up study. Forty of the original 51 subjects (78.4%) participated in the follow-up (body mass index, 27-45 kg m(-2); age, 40-75 years). Primary outcome was percentage change from baseline in HbA1c; secondary outcomes were anthropometric data and lipid panel. RESULTS: A significantly greater median percentage reduction was observed for HbA1c in the Ma-Pi group (-11.27% (95% confidence interval (CI): -10.17; -12.36)) compared with the control group (-5.88% (95% CI: -3.79; -7.98)) (P < 0.001). Total and low-density lipoprotein (LDL) cholesterol increased in both groups with no differences between groups (P=0.331 and P=0.082, respectively). After correcting for age and gender, the Ma-Pi diet was associated with a higher percentage reduction in HbA1c (95% CI: 2.56; 7.61) and body weight (95% CI: 0.40; 3.99), and a higher percentage increase in LDL cholesterol (95% CI: -1.52; -33.16). However, all participants' total and LDL cholesterol levels remained within recommended ranges (<200 mg dl(-1) and <100 mg dl(-1), respectively). The Ma-Pi diet group achieved the target median HbA1c value (<5.7% (39 mmol mol(-1))) at 6 months. CONCLUSIONS: Both the Ma-Pi and control diets maintained their benefits beyond the 21-day intensive monitored intervention over a 6-month follow-up in real-world conditions. The Ma-Pi diet resulted in greater improvement in glycemic control.

Inhibition of glucagon secretion in the human newborn by glucose infusion.

Plasma glucagon, serum insulin, and blood glucose responses during a 30-min glucose (1 g/kg body wt) or saline infusion were reported in 37 full-term and 35 preterm infants. They were studied either on the first day of life before feeding was initiated or during the first week of life. Glucose infusion promptly suppressed glucagon secretion in all infants even from the initial hours of extrauterine life. The mean maximal decrement in percentage in the full-term infants on the day of birth and older was 54 +/- 4% and 61 +/- 6%, respectively, while the maximal decrement in the preterm infants on day of birth and older was significantly lower (44 +/- 3% and 38 +/- 4%, respectively). The insulin response to glucose was variable in all infants and most of them showed a delayed rise of serum insulin. No change in plasma glucagon, blood glucose, and serum insulin was observed during and after saline infusion.

A lower level of entropy in circadian rhythm of the sinus R-R intervals suggests a prevalence of the cardiac sympathetic regulation in early physiological pregnancy.

The study estimates the unpredictable disorder (chaos) within the 24 h pattern of sinus R-R intervals (SRRI) in clinically healthy pregnant women (CHPW) and clinically healthy non-pregnant women (CHNPW), in order to evaluate the early gestational changes in neurovegetative cardiac pacing. SRRI were provided by the 24-h Holter ECG of 10 CHPW and 10 CHNPW. SRRI were investigated by descriptive conventional statistics by means of the Time and Frequency Domain Analysis, and subsequently, in their chaotic component by means of entropy analysis. Both the SRRI and entropy were tested via the Cosinor method to better decipher whether or not the periodic disorder in heart rate variability is modified in pregnancy as a result of a gestational tonic resetting of the cardiac sympatho-vagal regulation. Cosinor analysis documented that the circadian rhythm of both the SRRI and entropy were preserved in CHNPW and CHPW. However, the circadian rhythm of SRRI and entropy in CHPW exhibited a significantly decreased 24 h mean. Via the analysis of the rhythmicity of entropy, this study has documented that the chaos in the 24 h pattern of SRRI is less prominent in CHPW than in CHNPW. Such a reduction of level in the deterministic periodic chaos of heart rate variability provides evidence that, in early pregnancy, a tonic elevation of the sympathetic activity regulates cardiac pacing.

Analysis of the chaotic component of the sinusal R-R intervals as a tool for detecting a silent cardiac dysautonomia in type 2 diabetes mellitus.

This study explores the heart rate (HR) variability (V) in order to detect whether the chaotic component of the sinusal R-R intervals (SRRI) can be interpreted as an early indicator of a silent cardiac neurovegetative dysautonomia in apparently uncomplicated Type 2 diabetic patients (DP). The SRRI were provided by the 24-h Holter ECG of 10 Type 2 DP (5 M and 5 F, mean age = 41 +/- 5 years). Control data were obtained by the 24-h Holter ECG of 10 clinically healthy subjects (CHS, 5 M and 5 F, mean age = 38 +/- 6 years). The chaotic component of HRV was investigated via the correlation dimension (CD) analysis (A) of the SRRI, performed per each hour of the ECG recording. The hourly-qualified series of SRRI, HR and CD index (I) were, in turn, analyzed via methods of conventional statistics and chronobiology, the latter ones for assessing the circadian rhythm (CR). The CDI CR was found to peak during the night in CHS, and to be unphysiologically rotated to the diurnal hours of the day in Type 2 DP. The diurnal inversion of the CDI CR in Type 2 DP suggests that the chaotic component of HRV shows an abnormal rhythnic pattern over the day-night period. Considering that the investigated Type 2 DP were lacking of documentable signs of cardiac neuropathy, it is hypothesized that the diurnal phase of shift CDI CR might be a potential indicator of a silent autonomic cardiac dysfunction in Type 2 DP. Such a hypothesis waits for further confirmations.

Amniotic fluid insulin and C peptide levels in diabetic and nondiabetic women during early pregnancy.

Thanks to the widespread use of amniocentesis, glucose, insulin, and C peptide have often been measured in amniotic fluid (AF) during late gestation, but little is known about their concentrations during early pregnancy. To better understand early fetal beta-cell function under normal conditions and in the presence of maternal diabetes, we measured glucose, insulin, and C peptide in the AF collected during weeks 15-22 in 77 healthy and 9 diabetic women undergoing amniocentesis for clinical indications and compared the results with those obtained during late pregnancy (weeks 34-36). The AF C peptide concentration was higher in diabetic women (102 +/- 53 vs. 38 +/- 2 pmol/L), in the women with a family history of diabetes (41 +/- 6 vs. 35 +/- 2 pmol/L), after the 19th week of gestation (46 +/- 5 vs. 35 +/- 2 pmol/L; in the presence of lower glucose concentrations), and in the presence of maternal plasma glucose levels greater than 5.56 mmol/L (42 +/- 3.5 vs. 34 +/- 2 pmol/L). The comparison between early and late gestation showed decreasing glucose and increasing C peptide concentrations in both healthy and diabetic women (in the latter, C peptide values were always 3 times higher), whereas the insulin concentration was increased in late gestation only in diabetic women. The AF C peptide/insulin molar ratio increased throughout pregnancy in both healthy (from 0.97 +/- 0.06 to 4.3 +/- 1.2) and diabetic (from 2.9 +/- 1.1 to 13.2 +/- 1.6) women. These parallel changes suggest that the fetal clearance and/or degradation of insulin and C peptide may greatly change during both normal and diabetic gestation.

Two polyclonal antisera detect different AGE epitopes in human plasma samples.

Advanced glycation end products (AGEs), involved in the pathogenesis of diabetic complications, comprise a series of related chemical structures which might possess dissimilar immunogenic characteristics. In this study the levels of AGE in plasma samples from normal subjects (N=41) and diabetic patients (N=44) were measured by ELISA using two polyclonal antisera (named CF5 and CF199, respectively, and immunologically characterized) raised using two different immunogens and immunization techniques. Age levels were significantly higher in diabetic than in normal plasma samples (P<0.0001) with both antisera. However, CF199 detected higher AGE levels than CF5 both in normal (P<0.0001) and diabetic (P<0.005) samples. Pre-incubation with AGE-bovine serum albumin (BSA) caused the loss of most the reactivity of both antisera. Pre-incubation with carboxy-methyl-lysine-BSA (an oxidation-derived AGE) induced the loss of nearly all CF5 reactivity while CF199 retained a significant amount of activity against AGE antigens. Moreover, CF5 lost over 90% of its reactivity against BSA incubated with high glucose under non-oxidative conditions, suggesting its recognition of mainly oxidation-derived AGE epitopes. The different AGE levels measured by the two antisera suggests, therefore, that one single antiserum is unable to recognize all the various AGE epitopes which might be present, at any time, in tissues and body fluids in health and disease.

Plasma met-enkephalin in type I diabetes.

Physiological and pathological evidence suggests that opioid peptides may play a role in glucose homeostasis. We measured plasma levels of beta-endorphin (beta-END) and met-enkephalin (met-ENK) in 22 type I diabetic patients and 15 healthy women (control group). No differences were observed in plasma beta-END levels, whereas plasma met-ENK levels were significantly higher (Student's t test, P less than .005) in diabetics than in controls before (68 +/- 3 pg/mL v 32 +/- 7 pg/mL) and 1 hour after, a standard meal and administration of insulin therapy (81 +/- 9 pg/mL v 32 +/- 7 pg/mL). This is the first report of met-ENK levels in insulin-dependent diabetes mellitus (IDDM), and an impaired feedback of insulin/met-ENK is suggested.

Glucagon and growth hormone secretion in insulin-treated diabetics: effects of added sulfonylureas.

Eleven insulin-dependent ketosis-prone diabetics were given glibenclamide (5 mg/day) in addition to their usual insulin treatment for a period of 1 or 6 mo. There was significant reduction in arginine-induced IRG and hGH secretion and no change in blood glucose levels after either 1 or 6 mo of treatment. During that time no change in weight or insulin requirement was observed. The importance of the duration of treatment and the fact that in this type of patient the effects on IRG and hGH secretion could not be mediated by the influence on insulin secretion are stressed.

Sorbitol malabsorption and nonspecific abdominal symptoms in type II diabetes.

Some data suggest that sorbitol intake may be responsible for diarrhea in diabetic patients. One hundred thirteen hydrogen breath tests were performed in type II diabetics (72) and normal controls (41) after oral loads of sorbitol ranging from 2.5 to 20 g in iso-osmolar solutions to assess the role of malabsorption of this compound in the genesis of abdominal symptoms. The prevalence of sorbitol malabsorption and abdominal symptoms, peak (Cmax H2) and total (Ctot H2) hydrogen production, and mouth to cecum transit time (MCTT) did not differ in type II diabetics and controls. Malabsorption was observed more frequently with the highest doses of sorbitol (10% of patients at a dose of 2.5 g and approximately 75% at 20 g). Symptoms, usually consisting of mild discomfort and abdominal distension, were observed only after sorbitol loads of 10 and 20 g in 27.2% of the diabetics and in 36.3% of the controls. Diarrhea was present in three subjects (two diabetics and one control) only at a dose of 20 g. These data indicate that it is highly unlikely for sorbitol to play a role in inducing diabetes diarrhea. A moderate (up to 10 g) sorbitol intake is not contraindicated in type II diabetics.

Plasma met-enkephalin levels in diabetic patients: influence of autonomic neuropathy.

The presence of opioid peptides within pancreatic islets in several animal species and in humans suggests that these peptides could play a role in pancreatic endocrine secretion, influencing glucose metabolism. We measured plasma met-enkephalin (met-Enk) levels in eight neuropathic (four with insulin-dependent diabetes mellitus [IDDM] and four with non-insulin-dependent diabetes mellitus [NIDDM]) and eight nonneuropathic (four IDDM and four NIDDM) diabetic patients to study met-Enk secretion in diabetic patients with asymptomatic autonomic neuropathy. Plasma met-Enk levels were significantly lower in neuropathic compared with nonneuropathic patients both in the IDDM group (28.7 +/- 4.8 v 61.6 +/- 4.1 pg/mL, P < .0025) and in the NIDDM group (26.5 +/- 3.6 v 44.3 +/- 4.6 pg/mL, P < .0125). This study suggests that the presence of neuropathy in diabetic patients, even if asymptomatic, is associated with a significant decrease of plasma met-Enk levels, thus contributing to a worsening of metabolic control under stress conditions.

Fetal pancreatic function in infants of diabetic and rhesus-isoimmunized women.

OBJECTIVE: To measure insulin and glucagon concentrations in amniotic fluid (AF) collected near term in basal conditions and after an arginine test in diabetic, rhesus-isoimmunized, and control pregnant women. METHODS: At baseline, AF was collected from 44 diabetic, 32 rhesus-isoimmunized, and 27 control pregnant women in late pregnancy. Fifty-two diabetic, six rhesus-isoimmunized, and nine control pregnant women had amniocentesis 2 hours after arginine infusion (30 g intravenous/30 minutes) at 33-36 weeks. RESULTS: Baseline AF glucose concentrations were significantly greater in diabetic women than the other conditions, and they related to the gestational age in the women with hemolytic disease of the newborn. Insulin and glucagon AF content of isoimmunized pregnancies overlapped controls, whereas insulin and insulin/glucagon molar ratios were significantly higher, and glucagon values lower, in diabetic pregnancies compared with isoimmunized and control pregnancies. In isoimmunized pregnancies, the AF concentrations of glucose, insulin, and glucagon were correlated with gestational age (less than 34, 34 weeks or more). The samples collected after arginine infusion, compared with those collected at baseline, showed significantly greater insulin and insulin/glucagon molar ratio values in diabetic (28 +/- 5 versus 11 +/- 1 microU/mL, P = .001; 29.4 +/- 1.7 versus 12.0 +/- 2.8, P = .001) and in Rh pregnant women (18 +/- 6 versus 7.7 +/- 0.7 microU/mL, P = .001; 30 +/- 9 versus 3.4 +/- 0.4 I/G, P = .001), whereas no significant difference was observed in the controls. CONCLUSION: Basal islet hormone concentrations in AF are modified by maternal diabetes and further influenced by arginine administration. Arginine produces an AF response that is similar in pregnancies complicated by diabetes mellitus and rhesus-isoimmunization, despite different (hyperglycemia and euglycemia) maternal blood glucose levels.

Influence of maternal metabolic control and insulin antibodies on neonatal complications and B cell function in infants of diabetic mothers.

Circulating insulin antibodies at birth and the degree of maternal metabolic control were measured in 68 infants of insulin-treated diabetic mothers. Their correlation with neonatal B cell function and with the clinical features of the infants was evaluated in order to better understand their influence on fetal outcome. Maternal metabolic control was assessed on the basis of blood glucose levels, glycosuria and the occurrence of hypoglycemia and/or ketonuria. All infants were clinically evaluated for gestational age, macrosomia, hypoglycemia, hyperbilirubinemia, hypocalcemia, and respiratory distress syndrome. Cord blood plasma glucose, C peptide, and IgG insulin antibodies were also measured. It was shown that poor maternal metabolic control was associated with a higher prevalence of fetal morbidity as well as with signs of B cell hyperfunction. Also the presence of circulating insulin antibodies correlated well with higher C peptide levels and with several neonatal complications. B cell hyperfunction, indicated by high C peptide levels in the infants of diabetic mothers, may possibly play a causal role in the pathogenesis of fetal morbidity. In conclusion, a good fetal outcome in insulin-treated diabetic pregnancies was associated with and may have depended upon: (1) good maternal metabolic control, and (2) absence or low levels of circulating insulin antibodies.

Transplantation of irradiated heterotopic segmental human pancreas.

The results of three irradiated segmental pancreatic autotransplantations in patients with cancer of the pancreatic head are presented. The grafts with ligated ducts were irradiated with 5000 or 2000 rad. Following irradiation, the pancreatic tails that were tumor-free at the section line were autotransplanted by anastomosing the splenic vessels to the common femoral vessels. The first graft (5000 rad) that was necrotic, was removed on the 15th postoperative day and the patient was placed on insulin therapy. The second and third patient (2000 rad) are both alive with functioning grafts without exocrine secretion and with normal carbohydrate metabolism, 7 months and 1 month after transplantation, respectively. Technically, irradiated pancreas transplantation is a feasible procedure, which could be applicable to patients with cancer of the pancreatic head to avoid secondary complications of diabetes after total pancreatectomy, and to patients with juvenile or chronic pancreatitis. It is possible that high-dose irradiation can completely destroy eventual multicenter tumor foci in the pancreatic tail.

Diabetes mellitus: lessons from patient education.

The education of diabetic patients, proposed as an essential therapeutic tool since the early 1920s and accepted as such by official medicine only in the 1970s, has generated great enthusiasm over the last decade, with increasing concern for greater effectiveness by improved motivation of both patients and doctors. Structured education depends on the precise definition of agreed, short-term objectives, whose attainment shall be verified. Educational objectives may be set at different levels: knowledge of the disease, skills required for treatment, capacity to integrate therapy in everyday life,... The most relevant objectives however are the therapeutic goals of each individual patient, i.e. most often, prevention of acute complications, near-normoglycemia to prevent late complications and foot care to prevent disabling consequences of the latter. This can only be attained through a global approach to the patient, at once medical, educational and psychological. Medical science has definitively confirmed the importance of near- normoglycemia and proposes more effective insulin regimens and new recommendations for diet and exercise. Education demands a lot from health care providers: specific training, teaching skills, good communication, supportive attitude, readiness to listen and to negotiate. Patients' motivation to learn and adhere to treatment is also greatly influenced by individual factors, both psychological and environmental, that need to be taken into account.

Activated T cells in normal pregnant women and neonates.

The phenotyping of T-cell subsets and T cells at different stages of activation was performed using a panel of monoclonal antibodies in samples from normal pregnant women at different stages of gestation and in the cord blood of neonates. The data obtained from pregnant women showed a slight decrease in the total number of T cells at the beginning of pregnancy, whereas there was a clear increase in 4F2-positive lymphocytes after a few months of gestation. No significant increase in Class II-positive lymphocytes was observed in normal pregnant women in comparison with adult healthy women. The data from neonates revealed a clear decrease of OKT3- and OKT4-positive cells and an increase of 4F2-positive cells in comparison with control subjects. These data indicate that alerted, but not fully activated, lymphocytes are present in the circulation of both the mother, after the first months of pregnancy, and the neonate. This finding reinforces the concept that during pregnancy there is an activation of certain immune components rather than a general depression of the immune system.