Review of general suggestions on physical activity to prevent and treat gestational and pre-existing diabetes during pregnancy and in postpartum.

The aim of this review is to provide general suggestions on physical activity (PA) in pre-gestational and gestational diabetes mellitus (GDM) and encourage women to take part in safe and effective activities throughout pregnancy, in the absence of other contraindications. PA before and during pregnancy and in postpartum has many positive effects on the mother, as it could reduce the risk of GDM, excessive weight gain and lower back pain and also prevents, in the postpartum, diabetes mellitus. It may also reduce the duration of labour and complications at childbirth, fatigue, stress, anxiety and depression, thereby leading to an improved sense of wellbeing. Clinically, it is thought to help prevent preeclampsia and premature birth even though RCTs provide conflicting evidence with regard to the prevention of GDM. The main reason for this rests on the fact that the majority of clinical trials have not been able to replicate the preventive effect of PA on the onset of GDM, such as the different adherence of the patient to PA. Herein, we survey the literature regarding exercise and PA on GDM prevention and treatment as well as on clinical outcomes in pre-GDM in pregnancy. On the basis of the current literature, we also present a series of general recommendations and suggestions on PA and exercise training in pregnancy among both diabetic patients and those at risk for GDM.

Effects of myo-inositol on glucose variability in women with gestational diabetes.

OBJECTIVE: Myo-inositol supplementation prevents gestational diabetes (GDM) in women at risk and reduces insulin resistance in women with GDM. No data are available about its effect on glucose variability. The aim of this study was to evaluate the effects of a supplementation of myo-inositol on glucose variability in women with GDM. PATIENTS AND METHODS: Myo-inositol effect on glucose variability was studied in a pilot case-control study involving 12 consecutive pregnant women (median age 34 years, 25.0% insulin-treated) with GDM. Six women received myo-inositol 2 g plus 200 mg folic acid twice a day, the others received only folic acid. Information on side effects was collected. A continuous glucose monitoring system was wore before and at the beginning of the supplementation. Mean amplitude of glucose excursion (MAGE), standard deviation (SD) and variability coefficient were the indexes of glucose variability. RESULTS: Myo-inositol lowered glucose levels in the first days after the treatment was started. However, pre-post supplementation overall mean glucose difference was similar between groups (-4.8 vs. 5.0 mg/dL for controls and treated, respectively; p = 0.79). Pre-post differences in SD (13.7 vs. 6.0; p < 0.001), MAGE (3.5 vs.-1.5; p < 0.001) and variability coefficient (0.14 vs. 0.02; p < 0.001) were improved in myo-inositol group. No side effects were recorded. CONCLUSIONS: Myo-inositol is effective in reducing glucose variability in women with GDM. It could be a useful strategy for treating GDM.

Clinical and metabolic outcomes in pregnant women at risk for gestational diabetes mellitus supplemented with myo-inositol: a secondary analysis from 3 RCTs.

BACKGROUND: Gestational diabetes mellitus is defined as carbohydrate intolerance that begins or is first recognized during pregnancy. Insulin sensitizing substances such as myo-inositol have been considered for the prevention of gestational diabetes mellitus and related complications. OBJECTIVE: Because previous studies failed to show a clear reduction of gestational diabetes mellitus complications, the aim of this study was to evaluate clinical and metabolic outcomes in women who are at risk for gestational diabetes mellitus supplemented with myo-inositol since the first trimester. STUDY DESIGN: A secondary analysis of databases from 3 randomized, controlled trials (595 women enrolled) in which women who were at risk for gestational diabetes mellitus (a parent with type 2 diabetes mellitus, obese, or overweight) were supplemented with myo-inositol (4 g/d) throughout pregnancy. Main measures were the rate of adverse clinical outcomes: macrosomia (birthweight, ≥4000 g), large-for-gestational-age babies (fetal growth, ≥90 percentile), fetal growth restriction (fetal growth, ≤3 percentile), preterm birth (delivery before week 37 since the last menstruation), gestational hypertension, and gestational diabetes mellitus. RESULTS: A significant reduction was observed for preterm birth (10/291 [3.4%] vs 23/304 [7.6%]; P=.03), macrosomia (6/291 [2.1%] vs 16/304 [5.3%]; P=.04), Large-for-gestational-age babies (14/291 [4.8%] vs 27/304 [8.9%]; P=.04) with only a trend to significance for gestational hypertension (4/291 [1.4%] vs 12/304 [3.9%]; P=.07). Gestational diabetes mellitus diagnosis was also decreased when compared with the control group (32/291 [11.0%] vs 77/304 [25.3%]; P<.001). At univariate logistic regression analysis, myo-inositol treatment reduced the risk for preterm birth (odds ratio, 0.44; 95% confidence interval, 0.20-0.93), macrosomia (odds ratio, 0.38; 95% confidence interval, 0.14-0.98), and gestational diabetes mellitus diagnosis (odds ratio, 0.36; 95% confidence interval, 0.23-0.57). CONCLUSION: Myo-inositol treatment in early pregnancy is associated with a reduction in the rate of gestational diabetes mellitus and in the risk of preterm birth and macrosomia in women who are at risk for gestational diabetes mellitus.

Hypertensive disorders during pregnancy and 3 years after delivery in women with gestational hyperglycemia.

AIMS: Women with gestational hyperglycemia commonly experience hypertensive disorders during pregnancy. More information is needed about how hypertension develops in these patients over time. We investigated the prevalence of hypertension during and 3 years after pregnancy in Caucasian women with gestational hyperglycemia. We also investigated metabolic syndrome presence, glucose tolerance status, insulin sensitivity and insulin secretion levels in the follow-up period. METHODS: In a prospective longitudinal study with a 3-year follow-up, we assessed hypertension status and clinical-related characteristics of 103 consecutive women with gestational hyperglycemia sub-grouped according to their hypertensive status during and after pregnancy. RESULTS: Overall, 29 (28.1%) women had hypertension during pregnancy (24 gestational hypertension; 4 chronic hypertension; 1 preeclampsia). At follow-up 16 (15.5%) women were diagnosed as having hypertension (11 with hypertension in pregnancy; 5 with a normotensive pregnancy). Women with hypertension after pregnancy had higher BMI, metabolic syndrome rate and worse insulin resistance indexes than normotensive women. Weight increase at follow-up (OR 1.17, 95% CI 1.00-1.35) and hypertension in pregnancy (OR 6.72, 95% CI 1.17-38.64) were associated with hypertension after pregnancy. CONCLUSIONS: Women with gestational hyperglycemia should undergo regular monitoring during and after pregnancy to detect metabolic and clinical impairments and to prevent cardiovascular harm.

Long-acting Insulin Analogs Effect on gh/igf Axis of Children with Type 1 Diabetes: a Randomized, Open-label, Two-period, Cross-over Trial.

BACKGROUND: Growth hormone (GH) secretion is increased in pre-pubertal children with type 1 diabetes and GH excess produces insulin resistance. Early-morning insulinopenia contributes to lower insulin-like growth factor (IGF-I) levels and to GH hypersecretion. OBJECTIVE: To evaluate differences in GH/IGF-I axis of pre-pubertal children with type 1 diabetes treated with glargine or detemir as long-acting insulin analogues, which was the main outcome measure, and to compare insulin effects in obtaining good metabolic control. SUBJECTS: Children with type 1 diabetes. METHODS: This was a 32-week, randomized, open-label, two-period, cross-over comparison between bedtime glargine and twice-daily detemir insulin, involving pre-pubertal children in care at a diabetes pediatric centre. After a 8-week-run-in period subjects were randomized to bedtime glargine or twice-daily detemir insulin administration. After a 12-week period treatments were inverted and continued for additional 12 weeks. RESULTS: Overall, 15 pre-pubertal children (53.3% males, mean age 8.6±1.5 years, duration of diabetes 4.2±1.5 years) completed the study. Groups did not differ for GH/IGF axis and HbA1c levels. Treatment with glargine was associated with lower fasting glucose values than treatment with detemir (8.1±1.5 vs. 8.2±1.7 mmol/L, p=0.01). Incidence rate of hypoglycemia was not different between insulin treatments (IRR=1.18, 95%CI 1.00-1.38; p=0.07). Detemir treatment was associated with a higher increase in body weight (p=0.008) and height (p=0.02) when compared with glargine. CONCLUSION: Detemir and glargine not show significant differential effects on the GH/IGFI axis. The greater weight gain and height associated with detemir treatment, apparently not related to the level of pubertal growth, deserve further investigation.

Perinatal outcome in a Caucasian population with gestational diabetes and preexisting diabetes first diagnosed in pregnancy.

AIM: Our objective was to compare, in a Caucasian population, the perinatal outcomes of pregnancies complicated by pregestational diabetes diagnosed in the first-trimester of pregnancy with those of pregnancies complicated by gestational diabetes. METHODS: A retrospective evaluation of maternal and neonatal outcomes was performed for all consecutive pregnancies complicated by gestational or pregestational diabetes that happened between 2005 and 2011. Pregestational diabetes was diagnosed for the first time in pregnancy if the first-trimester fasting glycaemia was ≥126 mg/dL. Gestational diabetes was diagnosed according to Carpenter-Coustan criteria until May 2010, and then according to the International Association of Diabetes and Pregnancy Study Groups (IADPSG) panel criteria modified by the American Diabetes Association. A specific diet, self-monitoring of blood glucose and, if required, insulin treatment were prescribed. RESULTS: Overall, 411 pregnant women were considered eligible for the study (379 with gestational diabetes and 32 with pregestational diabetes). Women with pregestational vs. gestational diabetes were diagnosed earlier in pregnancy (11.6±1.0 weeks vs. 25.9±1.7 weeks; P=0.0001), had a higher mean first-trimester fasting glycaemic level (129.5±3.6 mg/dL vs. 81.6±10.5mg/dL; P=0.0001), more often had a family history of diabetes (46.9% vs. 25.9%; P=0.02) and more often needed insulin treatment (78.1% vs. 14.0%; P=0.0001). Furthermore, a higher rate of fetal malformations in women with pregestational diabetes was detected (9.4% vs. 1.6%, P=0.02). No other differences in neonatal outcomes were identified. CONCLUSION: In a Caucasian population, the prevalence of fetal malformations and insulin requirements with pregestational diabetes first diagnosed in pregnancy were significantly higher compared with women with gestational diabetes. In any case, glucose impairment in pregnancy needs to be diagnosed in a timely fashion and appropriately treated to improve both maternal and fetal outcomes.

Severe hypoglycemia and ketoacidosis over one year in Italian pediatric population with type 1 diabetes mellitus: a multicenter retrospective observational study.

BACKGROUND AND AIMS: Evaluation of incidence and correlates of severe hypoglycemia (SH) and diabetes ketoacidosis (DKA) in children and adolescents with T1DM. METHODS AND RESULTS: Retrospective study conducted in 29 diabetes centers from November 2011 to April 2012. The incidence of SH and DKA episodes and their correlates were assessed through a questionnaire administered to parents of patients aged 0-18 years. Incidence rates and incident rate ratios (IRRs) were estimated through multivariate Poisson regression analysis and multilevel analysis. Overall, 2025 patients were included (age 12.4 ± 3.8 years; 53% males; diabetes duration 5.6 ± 3.5 years; HbA1c 7.9 ± 1.1%). The incidence of SH and DKA were of 7.7 and 2.4 events/100 py, respectively. The risk of SH was higher in females (IRR = 1.44; 95%CI 1.04-1.99), in patients using rapid acting analogues as compared to regular insulin (IRR = 1.48; 95%CI 0.97-2.26) and lower for patients using long acting analogues as compared to NPH insulin (IRR = 0.40; 95%CI 0.19-0.85). No correlations were found between SH and HbA1c levels. The risk of DKA was higher in patients using rapid acting analogues (IRR = 4.25; 95%CI 1.01-17.86) and increased with insulin units needed (IRR = 7.66; 95%CI 2.83-20.74) and HbA1c levels (IRR = 1.63; 95%CI 1.36-1.95). Mother's age was inversely associated with the risk of both SH (IRR = 0.95; 95%CI 0.92-0.98) and DKA (IRR = 0.94; 95%CI 0.88-0.99). When accounting for center effect, the risk of SH associated with the use of rapid acting insulin analogues was attenuated (IRR = 1.48; 95%CI 0.97-2.26); 33% and 16% of the residual variance in SH and DKA risk was explained by center effect. CONCLUSION: The risk of SH and DKA is mainly associated with treatment modalities and strongly depends on the practice of specialist centers.

Italian risk factor-based screening for gestational diabetes.

There is a debate about whether universal or risk factors-based screening is most appropriate for gestational diabetes diagnosis. The aim of our retrospective study was to compare in our population the universal screening test recommended by the International Association of Diabetes in Pregnancy Study Group (IADPSG) panel and the American Diabetes Association (ADA) versus the selective screening proposed by the United Kingdom National Institute for Health and Clinical Excellence guidelines (NICE) but modified by the Italian National Institute of Health. From May 2010 to October 2011 all consecutive pregnant women were screened for gestational diabetes according to the IADPSG's panel criteria, while all the risk factors for each patient were registered. Of the 1015 pregnant women included in the study, 113 (11%) were diagnosed with gestational diabetes and 26 (23%) of them would not have been identified by the selective screening proposed by the Italian National Institute of Health. However, all the risk factors considered by the selective screening revealed a good predictive role except for maternal age ≥ 35 years (OR: 0.98). In the group without the risk factors considered, it was reported the predictive role for gestational diabetes of prepregnancy BMI and nulliparity. The selective risk factors-based screening proposed by the Italian National Institute of Health has detected 77% of gestational diabetes cases in our population, sparing the oral glucose tolerance test for more than 40% of pregnant women at the same time. More information on the clinical impact of this choice could be obtained by a strict analysis of treatment, perinatal outcome and follow-up of an adequate sample size of "missed" gestational diabetes.

Cardiac diastolic evaluation in pregnant women with abnormal glucose tolerance: an opportunity to detect the early and subclinical alterations and prevent cardiovascular diseases.

OBJECTIVES: of this study were to assess diastolic function in pregnant women with abnormal glucose tolerance (AGT), compared with normal glucose tolerance (NGT) women, and to evaluate the insulin resistance status and its association with Doppler-echocardiographic indexes. Echocardiograms of 108 consecutive Caucasian women with singleton pregnancies were performed. Insulin resistance status was estimated by the homeostasis model assessment of insulin resistance (HOMA-IR) and the quantitative insulin sensitivity check index (QUICKI). All the studied women showed normal diastolic patterns. Patients with AGT (50.9%), as compared with NGT women, had higher HOMA-IR (1.70 ± 1.30 versus 1.01 ± 0.81, P = 0.003), lower QUICKI (0.36 ± 0.005 versus 0.40 ± 0.06, P = 0.004), higher lateral mitral annulus late diastolic velocity (13.6 ± 4.9 versus 11.9 ± 4.9, P = 0.03), and higher A-wave velocity, the wave responsible for the active atrial contraction component (75.2 ± 14.2 versus 67.7 ± 16.2, P = 0.01). At multivariate regression analysis HOMA-IR was the only parameter associated with A-wave velocity. In conclusion, women with AGT had an increased subclinical diastolic active participation, which is associated with higher levels of insulin resistance. For the increased risk of deterioration of cardiac diastolic function, earlier and more seriously than normal pregnancy, AGT women may have a careful followup to detect the early signs of cardiac alteration and to prevent cardiovascular diseases.

Phalangeal quantitative ultrasound and metabolic control in pre-menopausal women with type 1 diabetes mellitus.

BACKGROUND: Several studies have reported increased fracture risk in Type 1 diabetes mellitus (T1DM). Quantitative Ultrasound (QUS) provides information on the structure and elastic properties of bone, which are important determinants of fracture risk, along with bone mineral density. AIM: To study phalangeal sites by QUS, examine bone turnover markers and analyze association between these factors with metabolic control in a population of pre-menopausal women with T1DM. MATERIAL AND METHODS: Thirty-five T1DM pre-menopausal women (mean age 34.5 ± 6.8 yr) attending the Diabetic Outpatients Clinic in the Department of Internal Medicine, University of Messina, were consecutively enrolled and divided into two groups, taking into account the mean value of glycated hemoglobin in the last three years. Twenty healthy age-matched women served as controls. Phalangeal ultrasound measurements [Amplitude Dependent Speed of Sound (AD-SoS), Ultrasound Bone Profile Index (UBPI), TScore, Z-Score] were performed using a DBM Sonic Bone Profiler. Osteocalcin and deoxypyridinoline served as markers of bone formation and bone resorption, respectively. RESULTS: T1DM women with poor metabolic control showed lower phalangeal QUS values compared to healthy controls (p<0.01) and T1DM women with good metabolic control (p<0.05). No significant differences in QUS measurements were detected between T1DM women with good metabolic control and healthy controls. Lower bone formation and increased bone resorption, although not statistically significant, were observed in patients with poor metabolic control in comparison to patients with good metabolic control. CONCLUSIONS: Poor metabolic control may worsen the quality of bone in T1DM. Phalangeal QUS could be considered as a tool to screen T1DM women for osteoporosis in pre-menopausal age.

Correspondence between first-trimester fasting glycaemia, and oral glucose tolerance test in gestational diabetes diagnosis.

AIM: To evaluate the correspondence between first-trimester fasting glycaemia and the results of the OGTT in diagnosing gestational diabetes (GDM). METHODS: The medical records of all consecutive women who had undergone a diagnostic OGTT, performed according to the IADPSG, during the past year were retrospectively reviewed. All first-trimester fasting glucose values greater or equal to 5.1 mmol/L (92 mg/dL), recommended as a diagnostic value, were also verified for each patient in this cohort. Moreover, a ROC curve and a multiple logistic-regression model were constructed to calculate the predictive capability of this cut-off value in diagnosing GDM. RESULTS: In our population of 738 eligible pregnant women, an 11.9% prevalence of GDM was revealed by OGTT. However, when the first-trimester fasting glucose value for each patient was retrospectively considered, there were a further 29 patients who should have been diagnosed as GDM cases (glycaemia ≥ 5.1 mmol/L), although their OGTT was normal. Yet, when the value of fasting glucose was considered not diagnostic, but only predictive, an AUC of 0.614 (95% CI: 0.544-0.684) and an aOR of 7.1 (95% CI: 3.8-13.1) was obtained in these patients compared with the reference group (fasting glucose < 5.1 mmol/L). CONCLUSION: There was no complete correspondence in diagnosing GDM between the first-trimester fasting glucose value and the results of a 2-h 75-g OGTT performed early in the third trimester. However, albeit not diagnostic, a fasting glucose value greater or equal to 5.1 mmol/L may be considered a highly predictive risk factor for GDM.

One-year effects of myo-inositol supplementation in postmenopausal women with metabolic syndrome.

OBJECTIVE: To evaluate the 12-month effect of myo-inositol treatment on some biochemical parameters of women affected by metabolic syndrome. METHODS: Eighty outpatient postmenopausal women, affected by metabolic syndrome, were enrolled in a 12-month study. All women were treated with a low-energy diet, and then they were randomly assigned to myo-inositol 2 g b.i.d. (n = 40) or placebo (n = 40). All the women were evaluated for serum glucose, insulin, HOMA-IR (Homeostasis Model Assessment-Insulin Resistance), triglycerides, total and high density lipoprotein cholesterol, body mass index (BMI), waist circumference and blood pressure at baseline and after 12 months of treatment. RESULTS: With the exception of BMI and waist circumference, after 12 months of treatment, all the parameters studied showed a significant improvement in the myo-inositol group compared to the control group. At the end of the study, in the myo-inositol group, the number of women without metabolic syndrome was eight (20%) whereas, in the control group, only one woman no longer had the metabolic syndrome after 12 months of diet. CONCLUSIONS: Myo-inositol might be considered one of the insulin-sensitizing substances in the treatment of metabolic syndrome.

The effect of myoinositol supplementation on insulin resistance in patients with gestational diabetes.

AIM: To test the hypothesis that myoinositol supplementation will improve insulin sensitivity as measured by markers of insulin resistance such as homeostasis model assessment of insulin resistance and adiponectin in women with gestational diabetes. METHODS: The trial was carried out in diet-treated patients with gestational diabetes diagnosed in our department between April 2008 and September 2009. Subjects were randomly assigned to receive either myoinositol supplementation (4 g daily) plus folic acid (400 µg daily)-the study group-or folic acid only (400 µg daily)-the control group. Both groups received the same diet prescription. Homeostasis model assessment of insulin resistance and adiponectin were assayed while fasting at the time of the diagnostic oral glucose tolerance test and after 8 weeks of treatment. RESULTS: There were 69 evaluable patients, 24 in the study group and 45 in the control group. Fasting glucose and insulin, and consequently homeostasis model assessment of insulin resistance, decreased in both groups (50% in the study group vs. 29% in the control group), but the decline in the study group was significantly greater than that in the control group (P = 0.0001). Adiponectin increased in the myoinositol group while it decreased in the control group (P = 0.009). CONCLUSION: Myoinositol improves insulin resistance in patients with gestational diabetes.