2023 UPDATE: Luso-Brazilian evidence-based guideline for the management of antidiabetic therapy in type 2 diabetes.

BACKGROUND: The management of antidiabetic therapy in people with type 2 diabetes (T2D) has evolved beyond glycemic control. In this context, Brazil and Portugal defined a joint panel of four leading diabetes societies to update the guideline published in 2020. METHODS: The panelists searched MEDLINE (via PubMed) for the best evidence from clinical studies on treating T2D and its cardiorenal complications. The panel searched for evidence on antidiabetic therapy in people with T2D without cardiorenal disease and in patients with T2D and atherosclerotic cardiovascular disease (ASCVD), heart failure (HF), or diabetic kidney disease (DKD). The degree of recommendation and the level of evidence were determined using predefined criteria. RESULTS AND CONCLUSIONS: All people with T2D need to have their cardiovascular (CV) risk status stratified and HbA1c, BMI, and eGFR assessed before defining therapy. An HbA1c target of less than 7% is adequate for most adults, and a more flexible target (up to 8%) should be considered in frail older people. Non-pharmacological approaches are recommended during all phases of treatment. In treatment naïve T2D individuals without cardiorenal complications, metformin is the agent of choice when HbA1c is 7.5% or below. When HbA1c is above 7.5% to 9%, starting with dual therapy is recommended, and triple therapy may be considered. When HbA1c is above 9%, starting with dual therapyt is recommended, and triple therapy should be considered. Antidiabetic drugs with proven CV benefit (AD1) are recommended to reduce CV events if the patient is at high or very high CV risk, and antidiabetic agents with proven efficacy in weight reduction should be considered when obesity is present. If HbA1c remains above target, intensification is recommended with triple, quadruple therapy, or even insulin-based therapy. In people with T2D and established ASCVD, AD1 agents (SGLT2 inhibitors or GLP-1 RA with proven CV benefit) are initially recommended to reduce CV outcomes, and metformin or a second AD1 may be necessary to improve glycemic control if HbA1c is above the target. In T2D with HF, SGLT2 inhibitors are recommended to reduce HF hospitalizations and mortality and to improve HbA1c. In patients with DKD, SGLT2 inhibitors in combination with metformin are recommended when eGFR is above 30 mL/min/1.73 m2. SGLT2 inhibitors can be continued until end-stage kidney disease.

Bone mineral density progression following long-term simultaneous pancreas-kidney transplantation in type-1 diabetes.

INTRODUCTION: Simultaneous pancreas-kidney transplantation (SPKT) has demonstrated favorable impact on the progression of chronic complications in type-1 diabetes (T1D) and terminal chronic kidney disease (CKD). However, some CKD mineral and bone disorders (CKD-MBD) may persist, even after transplantation. There are only a few studies addressing the long-term progression of bone mineral density (BMD) in these patients. Our aim was to assess baseline BMD and long-term progression and consequences in patients with T1D undergoing SPKT. METHODS: A retrospective cohort included patients undergoing SPKT in our tertiary center between 2000 and 2017. BMD progression was assessed on dual X-ray absorptiometry (DXA). Only patients with baseline data and a minimum follow-up of 2 years were included. RESULTS: Seventy-three patients were included, 53.4% male, with a median age at SPKT of 35 years (interquartile range [IQR] 31; 39). At transplantation, the median T-scores for the lumbar spine (LS) and femoral neck (FN) were -1.6 (IQR -2.6; -1.1) and --2.1 (IQR -2.7; -1.6), respectively. Seventy-five percent of patients presented low BMD (osteopenia or osteoporosis) in the LS and 90% in the FN, with 33% osteoporosis in the LS and 36% in the FN. On multivariate analysis, male gender (odds ratio [OR] 10.82, 95% confidence interval (CI) 2.88-40.70) and low body-mass index (BMI) (OR 0.73, 95% CI 0.55-0.97) were significantly associated with lumbar but not femoral osteoporosis. At long-term follow-up, BMD significantly improved in the LS (ΔT-score +0.41, P<0.001) and FN (ΔT-score +0.29, P=0.01), at a median 4 years after SPKT. Twelve (16.4%) and 9 (12.3%) patients showed persistent FN and LS osteoporosis, respectively. Multivariate linear regression showed that high BMI was predictive of improvement in BMD. CONCLUSIONS: This study demonstrated severe skeletal fragility in T1D patients with terminal CKD undergoing SPKT, more than a quarter of whom showed osteoporosis. The significant improvement in BMD may result from metabolic correction by SPKT and from physiological skeleton mineralization, which continues in this age group. BMD progression was positively associated with BMI, due to improved nutritional balance after transplantation.

Evaluation of Usage of a Fracture Risk Assessment by FRAX Tool in Adults With Type 2 Diabetes Mellitus.

BACKGROUND: Fragility fractures are increasingly recognized as a complication of type 2 diabetes mellitus (T2DM). The FRAX-Port® is a calculation tool that assesses the 10-year risk of either major and hip fracture, integrating several clinical risk factors, including T2DM. We aimed to evaluate the fracture risk in adults with T2DM and determine the rate of patients at high risk for fracture under anti-osteoporotic therapy. METHODS: We developed a cross-sectional study, including a convenience sample of adults with T2DM, followed in our tertiary center between 2019 and 2022. Fracture risk was evaluated according to FRAX-Port®. RESULTS: One hundred adults were included, 54% male, with a mean age of 68.4±9.2 years. Respecting fracture risk factors, 17% had a previous fragility fracture, 12% had a history of hip fracture in their parents, 9% had active alcohol consumption, and 4% had active smoking. Additionally, 17% presented secondary osteoporosis, being the most frequent cause of systemic corticosteroid exposure (10%). Regarding diabetes-specific risk factors, 94% had a diabetes duration longer than five years; HbA1c greater than 7% in 70%; 42% had diabetic retinopathy, 33% had diabetic chronic kidney disease, 18% had peripheral neuropathy, and 7% had autonomic neuropathy; 83% were on insulin, 2% on canagliflozin and 1% on pioglitazone. According to the FRAX-Port®, the median probability of major fracture was 6.8% (IQR 6.9), and hip fracture was 2.4% (IQR 3.9). Fracture risk was high, intermediate, and low at 41%, 15%, and 44%, respectively. Lastly, 56% of participants should undergo bone densitometry and 45% had a formal recommendation to begin an anti-osteoporotic treatment. However, only 6% were under anti-osteoporotic therapy: bisphosphonates (5%) and denosumab (1%). CONCLUSIONS: More than a third of T2DM patients evaluated had a high fracture risk. We found that FRAX-Port® is an easy-to-apply tool, which helps in the decision to perform densitometry or to institute anti-osteoporotic therapy. Given the increasing prevalence of T2DM and the associated risk of falls, this study highlights the need to recognize the fracture risk in these patients, usually a forgotten complication during the screening of risk factors for adverse events in adults with T2DM.

Inappropriate gestational weight gain impact on maternofetal outcomes in gestational diabetes.

OBJECTIVE: To evaluate the association between the dimension of deviation from appropriate gestational weight gain (GWG) and adverse maternofetal outcomes in women with gestational diabetes mellitus (GDM). METHODS: We performed a multicentric retrospective study based on the Portuguese GDM Database. Women were classified as within GWG, insufficient (IGWG) or excessive (EGWG) than the Institute of Medicine recommendations. EGWG and IGWG were calculated for each prepregnancy BMI category. Large-for-gestational-age (LGA) and macrosomia were defined as a birthweight more than the 90th percentile for the gestational age and newborn weight greater than 4000 g, respectively. Logistic regression models (adjusted odds ratio [aOR] plus 95% confidence interval [95%CI]) were derived to evaluate the association between EGWG or IGWG and adverse maternofetal outcomes. RESULTS: A total of 18961 pregnant women were included: 39.7% with IGWG and 27.8% with EGWG. An EGWG over 3 kg was associated with a higher risk of LGA infants (aOR 1.95, 95%CI 1.17-3.26) and macrosomia (aOR 2.01, 95%CI 1.23-3.27) in prepregnancy normal weight women. An EGWG greater than 4 kg was associated with a higher risk of LGA infants (aOR 1.67, 95%CI 1.23-2.23) and macrosomia (aOR 1.90, 95%CI 1.38-2.61) in obese women. In overweight women, an EGWG above 3.5 kg was associated with a higher risk of LGA infants (aOR 1.65, 95%CI 1.16-2.34), macrosomia (aOR 1.85, 95%CI 1.30-2.64), preeclampsia (aOR 2.40, 95%CI 1.45-3.98) and pregnancy-induced hypertension (aOR 2.21, 95%CI 1.52-3.21). An IGWG below -3.1 kg or -3kg was associated with a higher risk of small-for-gestational-age [SGA] infants in women with normal (OR 1.40, 95%CI 1.03-1.90) and underweight (OR 2.29, 95%CI 1.09-4.80), respectively. CONCLUSIONS: Inappropriate gestational weight gain seems to be associated with an increased risk for adverse maternofetal outcomes, regardless of prepregnancy BMI. Beyond glycemic control, weight management in women with GDM must be a focus of special attention to prevent adverse pregnancy outcomes.KEY MESSAGESThe dimension of deviation from appropriate gestational weight gain was associated with an increased risk for adverse maternofetal outcomes among women with gestational diabetes.Weight management must be a focus of special attention in women with gestational diabetes to prevent adverse pregnancy outcomes.

Liraglutide Effectiveness in Type 2 Diabetes: Insights from a Real-World Cohort of Portuguese Patients.

Liraglutide is a long-acting glucagon-like peptide-1 receptor agonist prescribed to diabetic patients for glycaemic control. To understand the impact of liraglutide in the real-world setting, this study analysed its effects in a Portuguese cohort of Type 2 diabetes patients. This was an observational, multicentric, and retrospective study that included 191 liraglutide-treated patients with at least 12 months of treatment. Patients' data were collected and analysed during a 24-month follow-up period. Overall, liraglutide treatment effectively reduced HbA1c levels from 8.3% to around 7.5%, after 6, 12, and 24 months (p < 0.001). In fact, 38.2%, 37.2%, and 44.8% of patients at 6, 12, and 24 months, respectively, experienced an HbA1c reduction of at least 1%. Moreover, a persistent reduction in anthropometric features was also observed, with 44.0%, 47.6%, and 54.4% of patients achieving a weight reduction of at least 3% at 6, 12, and 24 months, respectively. Finally, significant improvements were observed in the HDL-c and LDL-c levels. Our results demonstrate that liraglutide effectively promoted the reduction of HbA1c values during routine clinical practice, which was sustained throughout the study. In addition, there were significant improvements in anthropometric parameters and other cardiovascular risk factors.

Predictors of metformin monotherapy failure in gestational diabetes mellitus.

Objective: Metformin has emerged as a safe and effective pharmacological alternative to insulin in gestational diabetes mellitus (GDM), being associated with lower maternal weight gain and hypoglycemia risk. Nevertheless, glycemic control is unaccomplished in a considerable proportion of women only treated with metformin. We aim to determine the metformin monotherapy failure rate in GDM and to identify predictors of its occurrence. Design and methods: This was a retrospective multicenter study including pregnant women with GDM patients who started metformin as a first-line pharmacological treatment (n = 2891). A comparative analysis of clinical and analytical data between the group of women treated with metformin monotherapy and those needing combined therapy with insulin was performed. Results: In 685 (23.7%) women with GDM, combined therapy to achieve adequate glycemic control was required. Higher pregestational BMI (OR 1.039; CI 95% 1.008-1.071; P-value = 0.013), higher fasting plasma glucose (PG) levels in oral glucose tolerance test (OGTT) (OR 1.047; CI 95% 1.028-1.066; P-value <0.001) and an earlier gestational age (GA) at metformin introduction (0.839; CI 95% 0.796-0.885, P-value < 0.001) were independent predictive factors for metformin monotherapy failure. The best predictive cutoff values were a fasting PG in OGTT ≥87 mg/dL and GA at metformin introduction ≤29 weeks. Conclusions: In 685 (23.7%) women, combined therapy with insulin to reach glycemic control was required. Higher pre-gestational BMI, fasting PG levels in OGTT ≥87 mg/dL and introduction of metformin ≤29 weeks of GA were independent predictive factors for metformin monotherapy failure. The early recognition of these characteristics can contribute to the establishment of individualized therapeutic strategies and attain better metabolic control during pregnancy.

Characteristics and treatment outcomes of micromegaly - acromegaly with apparently normal basal GH: A retrospective study and literature review.

Objective. Micromegaly describes a subgroup of patients with clinically evident acromegaly and elevated insulin-like growth factor I (IGF-I) with apparently normal basal growth hormone (bGH) and often a glucose-suppressed growth hormone (GH) of <1 ng/mL at diagnosis. It is controversial whether this condition is a distinct clinical entity or a classic acromegaly in early stages. The aim of the present article was to characterize the prevalence, clinical and biochemical characteristics, and therapeutic outcomes of micromegaly. Methods. A retrospective study of patients with an acromegaly followed ≥1 year at a tertiary center from 1995 to 2019. Patients without IGF-I or GH measurements at diagnosis were excluded. At diagnosis, bGH was considered normal if <2 ng/mL. Results. From 74 patients with acromegaly, 6 (8.1%) had normal bGH levels. There was no difference in the gender distribution, median diagnostic delay, and follow-up time between patients with normal bGH and elevated bGH. Patients with normal bGH were significantly older at time of the first acromegalic manifestation and diagnosis they had significantly lower nadir post-glucose GH and IGF-I levels, and tended to have a higher prevalence of obesity than patients with the elevated bGH. The frequency of acromegalic symptoms, signs, and other comorbidities than obesity was similar between groups. Five patients (83.3%) with normal bGH presented microadenomas. Post-operative remission and outcomes at last visit were comparable between patients with or without normal bGH. Conclusions. Normal bGH acromegaly is relatively uncommon in our patients. These patients showed differentiating characteristics from the classical acromegaly with elevated bGH. Further studies are needed to extend the knowledge about its clinical behavior, therapeutic outcomes, morbidity, and mortality.

Severe Hyperthyroidism and Complete Hydatidiform Mole in Perimenopausal Woman: Case Report and Literature Review.

Gestational trophoblastic disease (GTD) represents a heterogeneous group of disorders within placental trophoblastic cells that are rather rare in perimenopausal ages. One of its complications is the development of secondary clinical hyperthyroidism, which can be potentially complicated if not properly and early recognized. We report the case of a 50-year-old perimenopausal woman, gravida 2 para 2, who presented to the emergency department with severe acute lower abdominal pain and abnormal uterine bleeding for one month. She also reported abnormal sweating and palpitation for a one-week duration and amenorrhea for the previous three months. Abdominal examination showed a pelvic mass resembling a 15-week sized uterus. Serum ß-hCG levels were strongly increased, and abdomen ultrasound displayed an enlarged uterus with "snow-storm" features, compatible with the diagnosis of GTD. Laboratory data revealed suppressed TSH levels and high free thyroxine and free triiodothyronine levels (4 and 1.5 times above the upper limit of normality, respectively). Thyrotropin-receptor antibodies (TRAb) levels were negative, and thyroid ultrasound excluded major structural disease. She was managed with anti-thyroid drugs, Lugol's iodine, beta-blockers, and steroids during preoperative care. Thereafter, she underwent surgery, being diagnosed with a hydatidiform mole postoperatively. Her thyroid function returned to normal after three months, without the further need for antithyroid drugs. This case highlights the importance of considering GTD as an aetiology for thyrotoxicosis in perimenopausal women, especially in the absence of findings suggesting primary thyroid disease.

Gestational diabetes in twin pregnancy: A predictor of adverse fetomaternal outcomes?

AIM: To compare fetomaternal outcomes between GDM pregnant women with twin versus singleton pregnancies and then between women with GDM versus non-GDM twin pregnancies. METHODS: We performed a retrospective study including GDM pregnant women with both twin and singleton pregnancies followed in our tertiary center between 2011 and 2018. The fetomaternal characteristics of each group were compared. We then compared women with GDM twin pregnancy followed at our institution between 2011 and 2018 to non-GDM twin pregnant women giving childbirth in 2018. RESULTS: A total of 1127 GDM pregnant women were evaluated: 42 with twin pregnancy and 1085 with singleton pregnancy. Preeclampsia (14.3% vs. 3.3%, p < 0.001) and cesarean delivery (76.2% vs. 36.9%, p < 0.001) were more frequent among women with twin pregnancy. Neonatal morbidity was also more common among neonates delivered from twin pregnant women, including preterm labor (73.8% vs. 7.8%, p < 0.001), hypoglycemia (6% vs. 4.8%, p = 0.043), hyperbilirubinemia (33.3% vs. 9.0%, p < 0.001), RDS (28.6% vs. 2.7%, p < 0.001), admission in NICU (32.1% vs. 4.5%, p < 0.001) and SGA (19.0% vs. 11.0%, p = 0.001). Overall there were no significant differences in fetomaternal morbidity parameters between GDM (n = 42) versus non-GDM (n = 83) twin pregnancies, although SGA infants were more frequent in the latter group (33.9% vs. 19.0%, p = 0.014). CONCLUSIONS: In GDM pregnant women, twin pregnancy seems to be associated with an increased prevalence of neonatal morbidity when compared to singleton pregnancy. On the other hand, in twin pregnancy, diagnosis of GDM does not seem to be associated with poorer fetomaternal outcomes. GDM seems to be protective for the occurrence of SGA neonates in twin pregnancies.

Characteristics of pregnant women with diabetes using injectable glucose-lowering drugs in the EVOLVE study.

AIMS: To examine clinical parameters, glycemic control, folic acid supplementation, and the presence of other chronic diseases during early pregnancy in the EVOLVE study population (women with pre-existing diabetes treated with injectable glucose-lowering drugs). METHODS: Cross-sectional baseline evaluation of EVOLVE: an international, multicenter, non-interventional study investigating the safety of injectable glucose-lowering drugs in pregnant women with pre-existing type 1 (T1D) or type 2 diabetes (T2D). Data were collected at enrollment visit interviews before gestational week 16. RESULTS: In total, 2383 women from 17 mainly European countries were enrolled in the study: 2122 with T1D and 261 with T2D; mean age was 31 and 33 years, and duration of diabetes was 15 and 6 years, respectively. For women with T1D or T2D, 63% and 75%, respectively, received basal and rapid-acting insulin, 36% and 3% rapid-acting insulin only, 0.7% and 14.0% basal insulin only, 0.2% and 5.4% premix insulin, 0.0% and 1.2% injectable glucagon-like peptide-1 receptor agonist treatment without insulin. In women with T1D or T2D, respectively, during early pregnancy, 59% and 62% had HbA1c <7.0% (53 mmol/mol); 16% and 36% reported not taking folic acid before or during early pregnancy. Overall, >40% of women had ≥1 chronic concomitant condition (predominantly thyroid disease or hypertension). Retinopathy was the most commonly reported diabetic complication. The most commonly reported previous pregnancy complication was miscarriage. CONCLUSIONS: Baseline data from this large multinational population of women with pre-existing diabetes indicate that sub-optimal glycemic control, poor pregnancy planning, and chronic concomitant conditions were common in early pregnancy.

Risk of Major Congenital Malformations or Perinatal or Neonatal Death With Insulin Detemir Versus Other Basal Insulins in Pregnant Women With Preexisting Diabetes: The Real-World EVOLVE Study.

OBJECTIVE: To compare the risk of severe adverse pregnancy complications in women with preexisting diabetes. RESEARCH DESIGN AND METHODS: Multinational, prospective cohort study to assess the prevalence of newborns free from major congenital malformations or perinatal or neonatal death (primary end point) following treatment with insulin detemir (detemir) versus other basal insulins. RESULTS: Of 1,457 women included, 727 received detemir and 730 received other basal insulins. The prevalence of newborns free from major congenital malformations or perinatal or neonatal death was similar between detemir (97.0%) and other basal insulins (95.5%) (crude risk difference 0.015 [95% CI -0.01, 0.04]; adjusted risk difference -0.003 [95% CI -0.03, 0.03]). The crude prevalence of one or more congenital malformations (major plus minor) was 9.4% vs. 12.6%, with a similar risk difference before (-0.032 [95% CI -0.064, 0.000]) and after (-0.036 [95% CI -0.081, 0.009]) adjustment for confounders. Crude data showed lower maternal HbA1c during the first trimester (6.5% vs. 6.7% [48 vs. 50 mmol/mol]; estimated mean difference -0.181 [95% CI -0.300, -0.062]) and the second trimester (6.1% vs. 6.3% [43 vs. 45 mmol/mol]; -0.139 [95% CI -0.232, -0.046]) and a lower prevalence of major hypoglycemia (6.0% vs. 9.0%; risk difference -0.030 [95% CI -0.058, -0.002]), preeclampsia (6.4% vs. 10.0%; -0.036 [95% CI -0.064, -0.007]), and stillbirth (0.4% vs. 1.8%; -0.013 [95% CI -0.024, -0.002]) with detemir compared with other basal insulins. However, differences were not significant postadjustment. CONCLUSIONS: Insulin detemir was associated with a similar risk to other basal insulins of major congenital malformations, perinatal or neonatal death, hypoglycemia, preeclampsia, and stillbirth.

Third trimester HbA1c and the association with large-for-gestational-age neonates in women with gestational diabetes

ABSTRACT Objective: To evaluate the association between HbA1c levels measured in the third trimester and the risk for large for gestational age (LGA) in neonates of mothers affected by gestational diabetes mellitus (GDM). Secondarily, we aimed to identify an ideal cut-off for increased risk of LGA amongst pregnant women with GDM. Materials and methods: Observational retrospective review of singleton pregnant women with GDM evaluated in a diabetes and pregnancy clinic of a tertiary and academic hospital. From January/2011 to December/2017, 1,085 pregnant women underwent evaluation due to GDM, of which 665 had an HbA1c test in the third trimester. A logistic regression model was performed to evaluate predictors of LGA. A receiver-operating-characteristic (ROC) curve was used to evaluate the predictive ability of third trimester HbA1c for LGA identification. Results: A total of 1,085 singleton pregnant women were evaluated during the study period, with a mean age of 32.9 ± 5.3 years. In the multivariate analysis, OGTT at 0 minutes (OR: 1.040; CI 95% 1.006-1.076, p = 0.022) and third trimester HbA1c (OR: 4.680; CI 95% 1.210-18.107, p = 0.025) were associated with LGA newborns. Using a ROC curve to evaluate the predictive ability of third trimester HbA1c for LGA identification, the optimal HbA1c cut-off point was 5.4% where the sensitivity was 77.4% and the specificity was 71.7% (AUC 0.782; p < 0.001). Conclusions: Few studies in the Mediterranean population have evaluated the role of HbA1c in predicting neonatal complications in women with GDM. A third trimester HbA1c > 5.4% was found to have good sensitivity and specificity for identifying the risk of LGA.

Third trimester HbA1c and the association with large-for-gestational-age neonates in women with gestational diabetes.

OBJECTIVE: To evaluate the association between HbA1c levels measured in the third trimester and the risk for large for gestational age (LGA) in neonates of mothers affected by gestational diabetes mellitus (GDM). Secondarily, we aimed to identify an ideal cut-off for increased risk of LGA amongst pregnant women with GDM. METHODS: Observational retrospective review of singleton pregnant women with GDM evaluated in a diabetes and pregnancy clinic of a tertiary and academic hospital. From January/2011 to December/2017, 1,085 pregnant women underwent evaluation due to GDM, of which 665 had an HbA1c test in the third trimester. A logistic regression model was performed to evaluate predictors of LGA. A receiver-operating-characteristic (ROC) curve was used to evaluate the predictive ability of third trimester HbA1c for LGA identification. RESULTS: A total of 1,085 singleton pregnant women were evaluated during the study period, with a mean age of 32.9 ± 5.3 years. In the multivariate analysis, OGTT at 0 minutes (OR: 1.040; CI 95% 1.006-1.076, p = 0.022) and third trimester HbA1c (OR: 4.680; CI 95% 1.210-18.107, p = 0.025) were associated with LGA newborns. Using a ROC curve to evaluate the predictive ability of third trimester HbA1c for LGA identification, the optimal HbA1c cut-off point was 5.4% where the sensitivity was 77.4% and the specificity was 71.7% (AUC 0.782; p < 0.001). CONCLUSION: Few studies in the Mediterranean population have evaluated the role of HbA1c in predicting neonatal complications in women with GDM. A third trimester HbA1c > 5.4% was found to have good sensitivity and specificity for identifying the risk of LGA.

Hypoglycemic episodes in hospitalized people with diabetes in Portugal: the HIPOS-WARD study.

BACKGROUND: We intended to estimate the proportion hypoglycemic/hyperglycemic emergency episodes in treated diabetes mellitus (DM) patients admitted to a hospital ward, and calculate the prevalence of risk factors for hypoglycemia and diabetic complications. METHODS: In this cross-sectional, multicentered study, the observational data was collected by physicians from patient's hospitalization to discharge/death. Statistical tests were 2-tailed considering 5% significance level. RESULTS: There were 646 ward admissions due to hyperglycemic emergencies and 176 hypoglycemic episodes with a ratio hypoglycemia/hyperglycemia 0.27 for all DM patients. In T2DM patients the ratio was 0.38. These were mainly female (55.1%), functionally dependent (61.4%) and retired/disabled (73.1%). Median age was 75 years and median duration of disease 11 years. Half the patients were on insulin-based therapy and 30.1% on secretagogue-based therapy. Approximately 57% of patients needed occasional/full assistance to manage the disease. The most frequent risk factor for hypoglycemia was polypharmacy (85.0%). Hypoglycemia in the 12 months before admission was higher in insulin-based therapy patients (66.1%; p = 0.001). CONCLUSIONS: Hyperglycemic emergencies are the most frequent cause of hospitalization in Portugal, although severe hypoglycemic events represent a health and social problem in elderly/frail patients. There is still the need to optimize therapy in terms of the potential for hypoglycemia in this patient group and a review of anti-hyperglycemic agents to add on to insulin.

Hospitalization Costs Due to Hypoglycemia in Patients with Diabetes: A Microcosting Approach.

INTRODUCTION: Hypoglycemia leading to hospitalization is associated with adverse economic outcomes, although the real burden is unknown. The HIPOS-WARD (Hypoglycemia In Portugal Observational Study-Ward) aimed to characterize ward admissions due to hypoglycemia episodes in treated patients with diabetes and assess their economic impact to the National Health System. METHODS: Observational, cross-sectional study, conducted in 16 Portuguese centers for 22 months. The applied microcosting approach was based on healthcare resource data, collected from patients' charts upon ward admission until discharge, and unitary costs from official/public data sources. Absenteeism was also estimated for active workers on the basis of the human capital approach. RESULTS: Of the 176 patients with diabetes mellitus enrolled, 86% had type 2 diabetes. Half of the patients (50.0%) were on insulin-based therapy, followed by 30.1% on a secretagogue-based regimen, 9.7% on non-secretagogue therapy, and 10.2% on a combination of insulin and secretagogue. Overall mean costs per patient were medication, 45.45 €; laboratory analysis, 218.14 €; examinations, 64.91 €; physician and nurse time, 268.55 € and 673.39 €, respectively. Bed occupancy was the main cost driver (772.09 €) and indirect cost averaged 140.44 €. Overall, the cost per hypoglycemia episode leading to hospitalization averaged 2042.52 € (range 194.76-16,762.87 €). Patients treated with insulin-based regimens (2267.76 €) and type 2 diabetes (2051.29 €) had the highest mean costs. The mean cost increased with repeated hypoglycemic events (2191.67 €), correlated complications (2109.26 €), and death (5253.38 €). CONCLUSION: HIPOS-WARD's findings confirm and support both the substantial clinical and economic impact of hospitalization due to hypoglycemia in Portugal.

Characteristics of hypoglycaemic episodes in diabetic patients treated at the emergency room of a Portuguese tertiary centre, 2012-2016.

OBJECTIVE: To analyse changes in the characteristics of hypoglycaemic episodes treated in the emergency room of a tertiary hospital in Portugal between 2012 and 2016. RESEARCH DESIGN AND METHODS: We retrospectively analysed all emergency room reports for patients discharged with a diagnosis of hypoglycaemia between 2012 and 2016 and analysed demographic characteristics, type of diabetes and treatments, causes of hypoglycaemia and discharge destination. Patients without diabetes were excluded. RESULTS: In total, 676 hypoglycaemic episodes were analysed. Most patients were female (59%) and the median age of the patients was 71 years (interquartile range, 57-81). The proportion of hypoglycaemic episodes relative to all emergency episodes decreased from 1.5% in 2012 to 1.0% in 2016 (P < .001). The proportion of patients with type 1 diabetes increased from 15.6% to 23.8%, while that of patients with type 2 diabetes decreased from 80.3% to 72.3% (nonsignificant differences). There was an increase in the use of insulin (67.1% to 85.4%, P = .02) and a decrease in the use of insulin secretagogues (26.6% to 11.5%, P = .03) over the study period. The rate of hospitalization dropped significantly from 11% in 2012 to 4.3% in 2015 and 5.4% in 2016 (P = .02). CONCLUSIONS: Despite the increasing use of newer diabetes medications associated with a lower risk of hypoglycaemia, these episodes still require emergency care. The proportion of patients receiving insulin increased over the years, probably due to the slight increase in the prevalence of type 1 diabetes and the increasing replacement of secretagogues with insulin in type 2 diabetes.

Metformin in gestational diabetes mellitus: predictors of poor response.

OBJECTIVE: Metformin can be regarded as a first-line treatment in gestational diabetes mellitus (GDM) due to its safety and effectiveness. However, a proportion of women do not achieve adequate glycemic control with metformin alone. We aim to identify predictors of this poor response to metformin. DESIGN AND METHODS: Retrospective multicentre cohort study of women with GDM who started metformin as first-line treatment. The assessed cohort was divided into a metformin group and metformin plus insulin group. Biometric and demographic characteristics, glycemic control data, obstetric, neonatal and postpartum outcomes were compared between groups and analysed in order to identify predictors of poor response to metformin. Data were analysed using STATA, version 13.1. RESULTS: Of the 388 women enrolled in the study, 135 (34.8%) required additional insulin therapy to achieve the glycemic targets. Higher age (aOR: 1.08 (1.03-1.13), P = 0.003), higher pre-pregnancy body mass index (BMI) (1.06 (1.02-1.10), P = 0.003) and earlier introduction of metformin (0.89 (0.85-0.94), P < 0.001) were independent predictors for insulin supplementation. Regarding all the analysed outcomes, only cesarean delivery rates and postpartum glucose levels were higher in women requiring insulin supplementation. CONCLUSIONS: Although almost 35% of women did not achieve adequate glycemic control with metformin, insulin supplementation was not associated with poor neonatal outcomes. Higher age, higher pre-pregnancy BMI and earlier introduction of metformin could be used as predictors of poor response to metformin.