Diabetic foot disease carries an intrinsic high risk of mortality and other severe outcomes in type 2 diabetes: a propensity score-matched retrospective population-based study.

BACKGROUND: To evaluate the association between diabetic foot disease (DFD) and the incidence of fatal and non-fatal events in individuals with type 2 diabetes (T2DM) from primary-care settings. METHODS: We built a cohort of people with a first DFD episode during 2010-2015, followed up until 2018. These subjects were 1 to 1 propensity score matched to subjects with T2DM without DFD. The incidence of all-cause mortality, the occurrence of new DFD, amputations, cardiovascular diseases, or composite outcome, including all-cause mortality and/or cardiovascular events during the follow-up period, were calculated. A Cox proportional hazard analysis was conducted to evaluate the hazard ratios (HR) for different events. RESULTS: Overall, 11,117 subjects with T2DM with a first episode of DFD were compared with subjects without DFD. We observed higher incidence rates (IRs) for composite outcome (33.9 vs. 14.5 IR per 100 person-years) and a new DFD episode event (22.2 vs. 1.1 IR per 100 person-years) in the DFD group. Compared to those without DFD, those with a first episode of DFD had a higher HR for all events, with excess rates particularly for amputation and new DFD occurrence (HR: 19.4, 95% CI: 16.7-22.6, HR: 15.1, 95% CI: 13.8-16.5, respectively) was found. CONCLUSIONS: Although DFD often coexists with other risk factors, it carries an intrinsic high risk of morbidity and mortality in individuals with T2DM. DFD should be regarded as a severe complication already at its onset, as it carries a poor clinical prognosis.

Weight-loss thresholds after bariatric surgery and cardiovascular outcomes: more is better.

BACKGROUND/OBJECTIVES: Whether the extent of weight loss (WL) modulates bariatric surgery (BS) cardiovascular benefits has scarcely been assessed. Several WL thresholds have been commonly used to classify BS patients as good or poor responders without a proven clinical relevance. We examined the relationship between the magnitude of WL after BS and post-surgery major adverse cardiovascular-event (MACE) incidence. We also compared the performance of three different insufficient weight-loss (IWL) criteria for their association with MACE. SUBJECTS AND METHODS: All individuals who underwent a primary Roux-en Y gastric bypass (RYGB) or sleeve gastrectomy (SG) in our institution at least six years before data analysis (12/2020) were included in the study. Data on MACE were available in 1638 of 1700 participants (96.4%). Proportional-hazard Cox analyses were performed to ascertain the association between MACE, WL, and the three IWL criteria. IWL was defined as: <50% excess weight loss (<50% EWL), <20% total body-weight loss (<20% TBWL), and -1 standard deviation of alterable weight-loss percentage (<1 SD% AWL). RESULTS: During a mean follow-up of 10.2 ± 2.8 years, 86 participants experienced a first post-surgery MACE. Higher WL at one year (HR: 0.77 (95% CI: 0.61-0.98)) and 5 years (HR: 0.63 (95% CI: 0.42-0.92)) was related to a lower incidence of MACE. All short-term criteria for defining IWL were similarly associated with MACE, yet <1 SD% AWL identified more at-risk subjects. Five-year TBWL < 20% and 5-year <1 SD-AWL% were significantly associated with a higher risk for CV events. TBWL < 20% identified more subjects at risk. CONCLUSIONS: The extent of WL is closely related to long-term MACE incidence. Patients who lost -1SD% AWL at one year or <20% TBWL at five years may be considered poor responders.

Thyroglobulin as early prognostic marker to predict remission at 18-24 months in differentiated thyroid carcinoma.

INTRODUCTION: Thyroglobulin (Tg), the most common marker to determine remission of differentiated thyroid carcinoma (DTC), can take 18 months or longer to be undetectable. We hypothesized that Tg stimulated after surgery and immediately before radioiodine treatment (baseline-stimulated Tg) could be a good predictor of remission at 18-24 months. The aim of this study was to evaluate the role of baseline-stimulated Tg as early prognostic marker of DTC. PATIENTS AND METHODS: Retrospective study of 133 patients with DTC from 1998 to 2010 (age at diagnosis 47·4 ± 16·8, follow-up 5·09 ± 3·2 years). Initial subset analysis was performed after excluding patients with positive TgAb, who were later included in the second. Baseline-stimulated Tg was divided into tertiles. Multivariate logistic regression analysis included baseline Tg and other known prognostic markers and receiver operating characteristic (ROC) curve to identify the best cut-off level of baseline Tg were performed. RESULTS: Baseline-stimulated Tg in the highest tertile was the only predictive variable of persistence of disease at 18-24 months in the initial analysis (OR 45·3, P < 0·01). In the second analysis, the predictive variables were baseline-stimulated Tg (OR 39·6, P < 0·001), presence of TgAb (OR 23·4, P < 0·005) and uptake outside of the thyroid bed post-treatment whole body scan (WBS; OR 5·3, P < 0·05) were predictive of persistence of disease. The ROC curve showed that baseline-stimulated Tg below 8·55 µg/l identified 95% of disease-free patients at 18-24 months after initial treatment. CONCLUSIONS: Baseline-stimulated Tg is a good predictor of remission of disease at 18-24 months after initial treatment and could be a useful marker to stratify risk immediately after surgery.

Continuous Glucose Monitoring Time-in-Range and HbA1c Targets in Pregnant Women with Type 1 Diabetes.

The CONCEPTT trial compared real-time Continuous Glucose Monitoring (RT-CGM) to capillary glucose monitoring in pregnant women with type 1 diabetes. We analyzed CGM and glycated hemoglobin (HbA1c) measures in first (n = 221), second (n = 197), and third (n = 172) trimesters, aiming to examine target glucose attainment and associations with pregnancy outcomes. CGM targets were Time-in-range (TIR) > 70%, Time-above-range (TAR) <25%, and Time-below-range (TBR) < 4%, and HbA1c targets < 6.5% (National Institute for Health and Care Excellence [NICE]) and HbA1c < 6.0% in second and third trimesters (American Diabetes Association [ADA]). TIR/TAR/TBR targets were achieved by 7.7/14.5/30.3% participants in first, 10.2/14.2/52.8% in second, and 35.5/37.2/52.9% in third trimesters. CGM target attainment was low but increased during pregnancy and with RT-CGM use. In the adjusted analyses, achieving TBR target was associated with a higher risk of pre-eclampsia and neonatal hypoglycemia. ADA HbA1c target attainment was low and unchanged during pregnancy (23.5/27.9/23.8%) but increased with RT-CGM use. In the adjusted analyses, HbA1c target attainment was associated with a lower risk of preterm birth, large-for-gestational age and neonatal hypoglycemia. We conclude that CONCEPTT trial participants had a low rate of CGM and of HbA1c target attainment. Attainment of CGM and NICE HbA1c targets increased throughout gestation and all targets (both NICE/ADA HbA1c and CGM) were more likely to be achieved by RT-CGM users, at 34 weeks' gestation. ADA HbA1c target achievement was independently associated with better perinatal outcomes, while the independent association of TBR target achievement with increased risk warrants further study. ClinicalTrials.gov Registration Identifier NCT01788527.

Novel Biochemical Markers of Glycemia to Predict Pregnancy Outcomes in Women With Type 1 Diabetes.

OBJECTIVE: The optimal method of monitoring glycemia in pregnant women with type 1 diabetes remains controversial. This study aimed to assess the predictive performance of HbA1c, continuous glucose monitoring (CGM) metrics, and alternative biochemical markers of glycemia to predict obstetric and neonatal outcomes. RESEARCH DESIGN AND METHODS: One hundred fifty-seven women from the Continuous Glucose Monitoring in Women With Type 1 Diabetes in Pregnancy Trial (CONCEPTT) were included in this prespecified secondary analysis. HbA1c, CGM data, and alternative biochemical markers (glycated CD59, 1,5-anhydroglucitol, fructosamine, glycated albumin) were compared at ∼12, 24, and 34 weeks' gestation using logistic regression and receiver operating characteristic (ROC) curves to predict pregnancy complications (preeclampsia, preterm delivery, large for gestational age, neonatal hypoglycemia, admission to neonatal intensive care unit). RESULTS: HbA1c, CGM metrics, and alternative laboratory markers were all significantly associated with obstetric and neonatal outcomes at 24 weeks' gestation. More outcomes were associated with CGM metrics during the first trimester and with laboratory markers (area under the ROC curve generally <0.7) during the third trimester. Time in range (TIR) (63-140 mg/dL [3.5-7.8 mmol/L]) and time above range (TAR) (>140 mg/dL [>7.8 mmol/L]) were the most consistently predictive CGM metrics. HbA1c was also a consistent predictor of suboptimal pregnancy outcomes. Some alternative laboratory markers showed promise, but overall, they had lower predictive ability than HbA1c. CONCLUSIONS: HbA1c is still an important biomarker for obstetric and neonatal outcomes in type 1 diabetes pregnancy. Alternative biochemical markers of glycemia and other CGM metrics did not substantially increase the prediction of pregnancy outcomes compared with widely available HbA1c and increasingly available CGM metrics (TIR and TAR).

Antenatal oral glucose tolerance test in women with gestational diabetes mellitus: fasting plasma glucose is the best predictor of both large for-gestational-age newborns and postpartum glucose tolerance.

BACKGROUND: Numerous studies have evaluated the predictors of large-for-gestational-age newborns (LGA) as well as abnormal glucose tolerance (AGT) after delivery in women with gestational diabetes mellitus, one at a time. The present study assesses the ability of glucose values on the antenatal oral glucose tolerance test (OGTT) to predict both outcomes. METHODS: Retrospective analysis of a prospectively collected database. Gestational diabetes was diagnosed with a two-step approach. After delivery, reevaluation was performed using 2006 WHO definition of glucose tolerance. SELECTION CRITERIA: 1) singleton pregnancies; 2) available information on: offspring weight for age, antenatal and follow-up OGTT and additional potential predictors of LGA and AGT. The study included 1241 women. Data were analyzed by multivariate logistic regression and ROC analyses. Logistic regression models were used to calculate adjusted and unadjusted odds ratios and corresponding 95% CI for 1 mmol/L increase in each glucose value (FPG, 1 h, 2 h, 3 h) of the diagnostic 100-g OGTT, associated to the main outcomes LGA and postpartum AGT. RESULTS: Analyzing each glucose value on antenatal OGTT, fasting plasma glucose (FPG) showed the highest OR for both outcomes: LGA (1.537, 95% CI 1.237-1.910) and AGT (2.288, 95% CI 1.869-2.801). On the adjusted analysis the association was attenuated, but FPG continued to be the best predictor for both outcomes. CONCLUSIONS: In women with gestational diabetes mellitus, FPG on the diagnostic OGTT was the glycemic value that best predicted both LGA and after delivery AGT.

Changes in Insulin Requirements From the Onset of Continuous Subcutaneous Insulin Infusion (CSII) Until Optimization of Glycemic Control.

The aim was to evaluate changes in insulin requirements from onset of continuous subcutaneous insulin infusion (CSII) until glucose optimization in type 1 diabetes and to determine patient characteristics to be considered when CSII is implemented. We retrospectively analyzed 74 type 1 diabetic patients over a follow-up of 5 months after starting CSII. Patients without a decrease in HbA1c levels at the end of follow-up were excluded. We compared total daily doses (TDD), basal/bolus distribution, basal diurnal/nocturnal proportion, number of basal segments, and HbA1c levels in relation to sex, age, body mass index (BMI), diabetes duration, and indication for CSII. At follow-up, HbA1c decreased by 0.75%, TDD decreased by 18%, basal rate was 60% of TDD, and diurnal basal rate was 60% of total basal rate. Insulin requirements were higher in males and in obese patients. Female patients and patients with longer diabetes duration showed a higher percentage of basal insulin. The number of basal segments was 4.9 ± 2.9. Basal requirements were higher in the second half of the nocturnal period. The dawn phenomenon was more relevant in men. Improvements in glycemic control were more marked in younger patients, in patients with higher HbA1c, in patients using more basal segments, and in patients initiating CSII for glucose control before pregnancy. Sex, diabetes duration, and BMI should be considered when initiating CSII. Our findings may help clinicians in clinical decision making regarding CSII therapy.

Perinatal maternal and neonatal outcomes in women with gestational diabetes mellitus according to fetal sex.

BACKGROUND: Male sex is a well-known risk factor for unfavorable perinatal outcomes. Fetal sex has been considered only occasionally in diabetic pregnancy. OBJECTIVE: Our aim was to evaluate perinatal outcomes in women with gestational diabetes mellitus (GDM) according to fetal sex. METHODS: We conducted a retrospective review of all singleton pregnancies of women with GDM progressing to >22 weeks and delivering in our center between 1981 and 2007. Evaluated maternal characteristics included anthropometrics, obstetric history, GDM diagnosis characteristics (ie, gestational age, blood glucose values), HbA(1c) (after diagnosis and in the third trimester). Outcomes variables were cesarean section (CS), gestational hypertension, preterm birth, abnormal Apgar, large and small for gestational age newborns, obstetric trauma, major and minor malformations, neonatal hypoglycemia, jaundice, respiratory distress, polycythemia, hypocalcemia, perinatal mortality, and a composite outcome. We used a descriptive and multiple logistic regression analysis (backwards method). RESULTS: A total of 2299 pregnancies were included (1125 female and 1174 male infants). Maternal characteristics were essentially similar in male and female newborns. For outcomes, unadjusted figures were higher in pregnancies of male newborns in 14 of 16 perinatal outcomes, but significance was only reached for CS. The logistic regression analyses revealed male sex as an independent predictor of CS (odds ratio = 1.48; 95% CI, 1.15-1.90) and neonatal hypoglycemia (odds ratio = 2.13; 95% CI, 1.02-4.43). CONCLUSIONS: In this group of women with GDM, perinatal outcomes in pregnancies of male newborns differ in only 2 of 16 evaluated variables: an increased frequency of CS and neonatal hypoglycemia. Male newborns of mothers with GDM could benefit from increased awareness of neonatal hypoglycemia.