Metformin for gestational diabetes study: metformin vs insulin in gestational diabetes: glycemic control and obstetrical and perinatal outcomes: randomized prospective trial.

BACKGROUND: Gestational diabetes that is not properly controlled with diet has been commonly treated with insulin. In recent years, several studies have published that metformin can lead to, at least, similar obstetrical and perinatal outcomes as insulin. Nevertheless, not all clinical guidelines endorse its use, and clinical practice is heterogeneous. OBJECTIVE: This study aimed to test whether metformin could achieve the same glycemic control as insulin and similar obstetrical and perinatal results, with a good safety profile, in women with gestational diabetes that is not properly controlled with lifestyle changes. STUDY DESIGN: The metformin for gestational diabetes study was a multicenter, open-label, parallel arms, randomized clinical trial performed at 2 hospitals in Málaga (Spain), enrolling women with gestational diabetes who needed pharmacologic treatment. Women at the age of 18 to 45 years, in the second or third trimesters of pregnancy, were randomized to receive metformin or insulin (detemir or aspart). The main outcomes were (1) glycemic control (mean glycemia, preprandial and postprandial) and hypoglycemic episodes and (2) obstetrical and perinatal outcomes and complications (hypertensive disorders, type of labor, prematurity, macrosomia, large for gestational age, neonatal care unit admissions, respiratory distress syndrome, hypoglycemia, jaundice). Outcomes were analyzed on an intention-to-treat basis. RESULTS: Between October 2016 and June 2019, 200 women were randomized, 100 to the insulin-treated group and 100 to the metformin-treated group. Mean fasting and postprandial glycemia did not differ between groups, but postprandial glycemia was significantly better after lunch or dinner in the metformin-treated-group. Hypoglycemic episodes were significantly more common in the insulin-treated group (55.9% vs 17.7% on metformin; odds ratio, 6.118; 95% confidence interval, 3.134-11.944; P=.000). Women treated with metformin gained less weight from the enrollment to the prepartum visit (36-37 gestational weeks) (1.35±3.21 vs 3.87±3.50 kg; P=.000). Labor inductions (45.7% [metformin] vs 62.5% [insulin]; odds ratio, 0.506; 95% confidence interval, 0.283-0.903; P=.029) and cesarean deliveries (27.6% [metformin] vs 52.6% [insulin]; odds ratio, 0.345; 95% confidence interval, 0.187-0.625; P=.001) were significantly lower in the metformin-treated group. Mean birthweight, macrosomia, and large for gestational age and babies' complications were not different between treatment groups. The lower cesarean delivery rate for women treated with metformin was not associated with macrosomia, large or small for gestational age, or other complications of pregnancy. CONCLUSION: Metformin treatment was associated with a better postprandial glycemic control than insulin for some meals, a lower risk of hypoglycemic episodes, less maternal weight gain, and a low rate of failure as an isolated treatment. Most obstetrical and perinatal outcomes were similar between groups.

Metformin action over gut microbiota is related to weight and glycemic control in gestational diabetes mellitus: A randomized trial.

BACKGROUND: Metformin, which is known to produce profound changes in gut microbiota, is being increasingly used in gestational diabetes mellitus (GDM). The aim of this study was to elucidate the differences in gut microbiota composition and function in women with GDM treated with metformin compared to those treated with insulin. METHODS: From May to December 2018, 58 women with GDM were randomized to receive insulin (INS; n = 28) or metformin (MET; n = 30) at the University Hospital Virgen de la Victoria, Málaga, Spain. Basal visits, with at least 1 follow-up visit and prepartum visit, were performed. At the basal and prepartum visits, blood and stool samples were collected. The gut microbiota profile was determined through 16S rRNA analysis. RESULTS: Compared to INS, women on MET presented a lower mean postprandial glycemia and a lower increase in weight and body mass index (BMI). Firmicutes and Peptostreptococcaceae abundance declined, while Proteobacteria and Enterobacteriaceae abundance increased in the MET group. We found inverse correlations between changes in the abundance of Proteobacteria and mean postprandial glycemia (p = 0.023), as well as between Enterobacteriaceae and a rise in BMI and weight gain (p = 0.031 and p = 0.036, respectively). Regarding the metabolic profile of gut microbiota, predicted metabolic pathways related to propionate degradation and ubiquinol biosynthesis predominated in the MET group. CONCLUSION: Metformin in GDM affects the composition and metabolic profile of gut microbiota. These changes could mediate, at least in part, its clinical effects. Studies designed to assess how these changes influence metabolic control during and after pregnancy are necessary.

Iodine intakes of 100-300 µg/d do not modify thyroid function and have modest anti-inflammatory effects.

Little information is available as to whether doses of iodide similar to those recommended in clinical practice for the prevention of iodine deficiency in pregnant women affect thyroid function. The aim of the present study was to analyse whether doses of iodide can affect thyroid function in adults, and evaluate its effect on plasma markers of oxidative stress, inflammation and acute-phase proteins. A total of thirty healthy volunteers (ten men and twenty women) with normal thyroid function were randomly assigned to three groups (n 10). Each group received a daily dose of 100, 200 or 300 µg of iodide in the form of KI for 6 months. Free tetraiodothyronine (FT4) levels at day 60 of the study were higher in the groups treated with 200 and 300 µg (P = 0·01), and correlated with the increase in urinary iodine (r 0·50, P = 0·007). This correlation lost its significance after adjustment for the baseline FT4. The baseline urinary iodine and FT4 correlated positively with the baseline glutathione peroxidase. On day 60, urinary iodine correlated with C-reactive protein (r 0·461, P = 0·018), and free triiodothyronine correlated with IL-6 (r - 0·429, P = 0·025). On day 60, the changes produced in urinary iodine correlated significantly with the changes produced in α1-antitrypsin (r 0·475, P = 0·014) and ceruloplasmin (r 0·599, P = 0·001). The changes in thyroid-stimulating hormone correlated significantly with the changes in α1-antitrypsin (r - 0·521, P = 0·005) and ceruloplasmin (r - 0·459, P = 0·016). In conclusion, the administration of an iodide supplement between 100 and 300 µg/d did not modify thyroid function in a population with adequate iodine intake. The results also showed a slight anti-inflammatory and antioxidative action of iodide.

[Depression in type 1 diabetes mellitus and associated factors]. / Depresión en la diabetes mellitus tipo 1 y factores asociados.

BACKGROUND AND OBJECTIVE: In recent years, there has been an increased interest in depression and diabetes risk factors. Our objectives were 1) Study the variables associated with the presence of depression in patients with type 1 diabetes mellitus (DM1), 2) to analyze potential risk factors for depression in these patients, and 3) to study a possible explanatory model of depression scores in these patients. PATIENTS AND METHODS: 207 patients with DM1. We evaluated sociodemographic and biomedical variables by means of a structured interview. We assessed psychological variables by means of the Scale for Depression in Type 1 Diabetes (EDDI-1) and the Spanish version of Diabetes Quality of Life (Es DQOL). RESULTS: Prevalence of depression was 21,7%. Variables associated with risk of depression in this sample were to be female; be unemployed; smoking; having complications of diabetes or other physical conditions; not perceiving family support or support from friends or colleagues in relation to diabetes; having a high number of weekly hyperglycemia; and a poor quality of life. A model based on previous research was obtained. This model explains a high percentage of the variability in the scores of patients in the EDDI-1. CONCLUSIONS: These results provide an empirical support to the knowledge of the risk factors associated with depression in patients with DM1. Glycemic control and quality of life have an important effect on the scores of depression in these patients, providing information for their treatment.

Bolus Calculator Reduces Hypoglycemia in the Short Term and Fear of Hypoglycemia in the Long Term in Subjects with Type 1 Diabetes (CBMDI Study).

BACKGROUND: In a previous study we demonstrated improvement in metabolic control and reduction in hypoglycemia in people with type 1 diabetes on multiple daily injections, after having used a bolus calculator for 4 months. OBJECTIVE: To demonstrate whether (1) extending its use (2) or introducing it in the control group, previously subjected to treatment intensification, could further improve metabolic control and related psychological issues. METHODS: After the previous clinical trial, in which the subjects were randomized either to treatment with the calculator or to control group for 4 months, both groups used the calculator during an additional 4-month period. RESULTS: In the previous control group, after using the device, HbA1c did not improve (7.86% ± 0.87% vs. 8.01% ± 0.93%, P 0.215), although a significant decrease in postprandial hypoglycemia was observed (2.3 ± 2 vs. 1.1 ± 1.2/2 weeks, P 0.002). In the group in which the treatment was extended from 4 to 8 months, HbA1c did not improve either (7.61 ± 0.58 vs. 7.73 ± 0.65, P 0.209); however this group had a greater perceived treatment satisfaction (12.03 ± 4.26 vs. 13.71 ± 3.75, P 0.007) and a significant decrease in fear of hypoglycemia (28.24 ± 8.18 basal vs. 25.66 ± 8.02 at 8 months, P 0.026). CONCLUSIONS: The extension in the use of the calculator or its introduction in a previously intensified control group did not improve metabolic control, although it did confirm a decrease in hypoglycemic episodes in the short term, while the extension of its use to 8 months was associated with a reduction in fear of hypoglycemia and greater treatment satisfaction.

Excess hospitalizations, hospital days, and inpatient costs among people with diabetes in Andalusia, Spain.

OBJECTIVE: The goal of this study was to estimate the excess hospitalizations, hospital days, and inpatient costs attributable to diabetes in Andalusia, Spain (37 hospitals, 7,236,459 inhabitants), during 1999 compared with those without diabetes. RESEARCH DESIGN AND METHODS: This study was an analysis of all hospital discharges. Those with an ICD-9-CM code of 250 as either the main or secondary diagnosis were considered to have been admissions of individuals with diabetes. An estimate of costs was applied to each inpatient admission by assigning a cost weight based on the diagnostic-related group (DRG) related to each admission. RESULTS: A total of 538,580 admissions generated 4,310,654 hospital bed-days and total costs of 940,026,949 euro. People with diabetes accounted for 9.7% of all hospital discharges, 13.8% of total stays, and 14.1% of the total cost. Of the total cost for individuals with diabetes (132,509,217 euro), 58.3% were excess costs, of which 47% was attributable to cardiovascular complications and 43% to admissions for comorbid diseases. Individuals 45-75 years of age accounted for 75% of the excess costs. The rate of admissions during the study year was 145 per 1,000 inhabitants for individuals with diabetes compared with 70 admissions per 1,000 inhabitants for individuals without diabetes. CONCLUSIONS: The costs arising from hospitalization of individuals with diabetes are disproportionate in relation to their prevalence. For those aged >or=45 years, cardiovascular complications were clearly the most important factor determining increased costs from diabetes.

Hypertension is related to the degradation of dietary frying oils.

BACKGROUND: The family kitchen resembles an uncontrolled laboratory experiment, and some discrepancies in the relation between the risk of hypertension and dietary fat may be partly due to the manipulation to which the fats were subjected. OBJECTIVE: We investigated whether deterioration in the quality of the cooking oils in the family household contributes to the risk of high blood pressure. DESIGN: The study was cross-sectional. Anthropometric measurements were obtained for 1226 persons aged 18-65 y who were selected randomly from the municipal census of Pizarra, Spain. An oral-glucose-tolerance test was given to 1020 of these persons. Samples of the cooking oil being used were taken from the kitchens of a random subset of 538 persons. The concentrations of polar compounds and polymers were used as markers of the deterioration of the oils. The strength of association between variables was measured by calculating the odds ratio from logistic models. RESULTS: Hypertension was strongly associated with obesity and was influenced by sex, diabetes, and age. The presence of excess polar compounds in the cooking oil and the use of sunflower oil were related to the risk of hypertension, whereas the concentration of monounsaturated fatty acids in the serum phospholipids was negatively related to this risk. These associations remained after inclusion in the models of age, sex, obesity, and the presence of carbohydrate metabolism disorder. CONCLUSIONS: The risk of hypertension is positively and independently associated with the intake of cooking oil polar compounds and inversely related to blood concentrations of monounsaturated fatty acids.

[Iodine deficiency and thyroid function in healthy pregnant women]. / Déficit de yodo y función tiroidea en una población de mujeres embarazadas sanas.

BACKGROUND AND OBJECTIVE: Studies from Spain suggest that the intake of iodine in pregnant women is below nutritional requirements. This study was designed to determine iodine intake and its relation with thyroid volume during pregnancy in women from southeast Spain. PATIENTS AND METHOD: A total of 520 healthy pregnant women were studied during the full three trimesters of their pregnancy. A control group was composed of 373 non-pregnant women. The following variables were measured: TSH, FT3, FT4, thyroglobulin, antiperoxidase antibodies, urinary iodine levels, and thyroid volume. RESULTS: Median urinary iodine levels were below 100 g/l in the controls and the pregnant women during their first trimester. These levels rose progressively and significantly over the second and third trimesters. Thyroid volume increased during the second and third trimesters compared with the first. TSH levels were lower during the first trimester compared to controls, and increased significantly during the third trimester. FT4 levels fell significantly during the third trimester. There was a significant negative correlation between TSH levels and thyroid volume (r = 0.22; p = 0.005). CONCLUSIONS: Iodine intake in pregnant women in Malaga is low. The results suggest a deficit in thyroid function secondary to iodine deficiency, which is worsened as pregnancy advances. The data support the convenience of systematic administration of an iodine supplement in healthy pregnant women.

Incidence of lower limb amputations in individuals with and without diabetes mellitus in Andalusia (Spain) from 1998 to 2006.

AIMS: We studied the changes in the incidence of lower limb amputation (LLA) in Andalusia from 1998 to 2006 in the population with and without diabetes. METHODS: We undertook a retrospective study of all LLA performed in Andalusia in people aged 30 years old, with or without diabetes, between 1 January 1998 and 31 December 2006. We obtained the crude and standardized incidence rates by year, and sex for three periods: 1998-2000, 2001-2003 and 2004-2006 and calculated the RR of requiring LLA in patients with diabetes. To test for time trend, Poisson regression models were fitted. RESULTS: A total of 16,210 LLA were carried out in Andalusia, 72.6% in patients with diabetes mellitus and 66.4% in men. In the population with diabetes the standardized incidence of all LLA was found to be 344.0 per 100,000 (95% CI, 315.4-372.4) in 2004-2006. There was an estimated incidence increase for all LLA by 14% and for minor LLA by 13.6% in 2004-2006. In people with diabetes the RR increased by 31.6% as compared to the first period. CONCLUSIONS: Despite the implementation of a care plan for patients with diabetes, the incidence of LLA has not fallen in Andalusia in recent years.

Iodine concentration in cow's milk and its relation with urinary iodine concentrations in the population.

BACKGROUND & AIMS: The importance of milk intake to the supply of dietary iodine is not fully known. We therefore undertook a study in Spain of the iodine concentration in cow's milk and the impact of the frequency of milk consumption on urinary iodine concentrations in three study populations. METHODS: We studied the iodine concentration in 362 samples of milk from 45 commercial brands and compared it with the milk iodine status in studies undertaken 17 years earlier. The epidemiologic studies were performed in three different places in the south of Spain: two in school-age children (N = 757 and N = 1205 children) and one in adults (N = 1051). A milk consumption questionnaire was given and urinary iodine concentrations measured. RESULTS: The mean concentration of iodine in the milk rose from 1991 (117 ± 37 µg/L) to 2008 (259 ± 58 µg/L) (P < 0.001). The iodine concentration was greater in skimmed milk (273 ± 52 µg/L) than in semi-skimmed milk (254 ± 57 µg/L) or whole milk (251 ± 61 µg/L) (P < 0.0001). The winter samples had a greater concentration of iodine (270 ± 55 µg/L) than the summer samples (247 ± 58 µg/L) (P < 0.0001), independently of the type of milk. The urinary iodine concentrations in all three epidemiologic studies were significantly associated with the frequency of milk intake. CONCLUSIONS: The concentration of iodine in cow's milk has risen over recent years, and it is higher in skimmed milk. The results also show that cow's milk is a relevant source of dietary iodine.

Development of a new fear of hypoglycemia scale: FH-15.

Hypoglycemia is the most common adverse event associated with insulin treatment in diabetes. The consequences of hypoglycemia can be quite aversive and potentially life threatening. The physical sequelae provide ample reason for patients to fear hypoglycemia and avoid episodes. For these reasons, our purpose in this study was to develop a new measure that explores specific fear of hypoglycemia (FH) in adult patients with type 1 diabetes and to examine its psychometric properties. The instrument developed to assess FH was initially made up of 20 items, of which 18 were negative and 2 were positive, assessed on a 5-point Likert scale (1-5). This scale was completed by 229 patients with type 1 diabetes. Additionally, a structured interview and a closed question called subjective fear of hypoglycemia were included as diagnostic criteria. A factor analysis employing the principal-components method and promax rotation was carried out, resulting in a new scale composed of 15 items. Three factors (fear, avoidance, and interference) were obtained and explained 58.27% of the variance. The scale showed good internal consistency (Cronbach's α = .891) and test-retest reliability (r = .908, p < .001), as well as adequate concurrent and predictive validity. The cutoff score that provided the highest overall sensitivity and specificity was set at 28 points. The Fear of Hypoglycemia 15-item scale (FH-15) demonstrated good reliability and validity. This study suggests that the new instrument may serve as a valuable measure of specific FH for use in research and clinical practice.

Continuous subcutaneous insulin infusion versus multiple daily injections in pregnant women with type 1 diabetes.

BACKGROUND: Continuous subcutaneous insulin infusion (CSII) may be an alternative to multiple daily injections (MDI) in pre-gestational diabetes during pregnancy. However, no clear improvement in obstetric and perinatal outcome has so far been established for CSII treatment. METHODS: In a case-control study, 35 pregnancies treated with CSII and 64 pregnancies treated with MDI treatment were evaluated. Metabolic control and obstetric and perinatal outcome were compared. RESULTS: Women in the CSII group improved their metabolic control (hemoglobin A1c before CSII, 7.83 +/- 0.97%; 3-6 months after, 6.77 +/- 0.61%; P < 0.05). Hemoglobin A1c before pregnancy was lower in the CSII group (6.62 +/- 0.60%) than in the MDI group (7.59 +/- 1.61%) (P < 0.05). No other significant differences, either in metabolic control of diabetes or in obstetric and perinatal outcome, were found. CONCLUSIONS: CSII treatment is safe in pregnancy, but it has not yet been associated with any improved pregnancy outcome.

Effect of iodine prophylaxis during pregnancy on neurocognitive development of children during the first two years of life.

CONTEXT: The association between thyroid function during pregnancy and the later mental and psychomotor development of the child is supported by numerous experimental, clinical, and epidemiological studies. OBJECTIVE: The aim of the study was to evaluate the psychological development of infants aged 3 to 18 months whose mothers had received 300 microg of potassium iodide during the first trimester of their pregnancy and compare with infants whose mothers had received no iodine supplements. DESIGN AND STUDY SUBJECTS: The study included 133 women who had received 300 microg of potassium iodine and 61 women who had received no iodine supplements. MAIN OUTCOME MEASURES: The neuropsychological status of the children was evaluated with the Bayley Scales of Infant Development, and measurements were made of TSH, free T(3), free T(4), and urinary iodine. RESULTS: Those children whose mothers had received an iodine supplement of 300 microg had a more favorable psychometric assessment than those of the other group of mothers. They had higher scores on the Psychomotor Development Index (P = 0.02) and the Behavior Rating Scale. CONCLUSIONS: Dietary iodine supplements not only have no harmful effect on the neurodevelopment of the children, they may even be beneficial. Given the possible presence of confounding variables not controlled for in this study, these findings should be considered as preliminary.