Autoimmune thyroid diseases as a cost of physiological autoimmune surveillance.

Graves' disease (GD) and Hashimoto's thyroiditis (HT) are common autoimmune diseases of the thyroid gland, causing hyperthyroidism and hypothyroidism, respectively. Despite their opposing clinical manifestation, they have several enigmatic links. Here, we propose that GD and HT have the same fundamental origin: both diseases are the cost of a beneficial physiological process called autoimmune surveillance of hypersecreting mutants. Autoreactive T cells selectively eliminate mutant cells that hypersecrete the hormones and threaten to become toxic nodules. These T cells can trigger a humoral response in susceptible individuals, leading to the production of antibodies against thyroid antigens. This shared origin can explain similarities in incidence and risk factors between HT and GD, despite their opposite clinical phenotypes.

Greater risk of type 2 diabetes progression in multifetal gestations with gestational diabetes: the impact of obesity.

BACKGROUND: The relationship between gestational diabetes mellitus and adverse outcomes in multifetal pregnancies is complex and controversial. Moreover, limited research has focused on the risk of gestational diabetes mellitus progression to type 2 diabetes mellitus specifically in multifetal pregnancies, resulting in conflicting results from existing studies. OBJECTIVE: This study aimed to assess the risk of gestational diabetes mellitus progression to type 2 diabetes mellitus between singleton and multifetal pregnancies in a large cohort of parturients with a 5-year follow-up. STUDY DESIGN: A retrospective study was conducted on a prospective cohort of pregnant individuals with pregnancies between January 1, 2017, and December 31, 2020, followed up to 5 years after delivery. Glucose levels during pregnancy were obtained from the Meuhedet Health Maintenance Organization laboratory system and cross-linked with the Israeli National Diabetes Registry. The cohort was divided into 4 groups: singleton pregnancy without gestational diabetes mellitus, singleton pregnancy with gestational diabetes mellitus, multifetal pregnancy without gestational diabetes mellitus, and multifetal pregnancy with gestational diabetes mellitus. Gestational diabetes mellitus was defined according to the American Diabetes Association criteria using the 2-step strategy. Univariate analyses, followed by survival analysis that included Kaplan-Meier hazard curves and Cox proportional-hazards models, were used to assess differences between groups and calculate the adjusted hazard ratios with 95% confidence intervals for progression to type 2 diabetes mellitus. RESULTS: Among 88,611 parturients, 61,891 cases met the inclusion criteria. The prevalence of type 2 diabetes mellitus was 6.5% in the singleton pregnancy with gestational diabetes mellitus group and 9.4% in the multifetal pregnancy with gestational diabetes mellitus group. Parturients with gestational diabetes mellitus, regardless of plurality, were older and had higher fasting plasma glucose levels in the first trimester of pregnancy. The rates of increased body mass index, hypertension, and earlier gestational age at delivery were significantly higher in the gestational diabetes mellitus group among patients with singleton pregnancies but not among patients with multifetal pregnancies. Survival analysis demonstrated that gestational diabetes mellitus was associated with adjusted hazard ratios of type 2 diabetes mellitus of 4.62 (95% confidence interval, 3.69-5.78) in singleton pregnancies and 9.26 (95% confidence interval, 2.67-32.01) in multifetal pregnancies (P<.001 for both). Stratified analysis based on obesity status revealed that, in parturients without obesity, gestational diabetes mellitus in singleton pregnancies increased the risk of type 2 diabetes mellitus by 10.24 (95% confidence interval, 6.79-15.44; P<.001) compared with a nonsignificant risk in multifetal pregnancies (adjusted hazard ratio, 9.15; 95% confidence interval, 0.92-90.22; P=.059). Among parturients with obesity, gestational diabetes mellitus was associated with an increased risk of type 2 diabetes mellitus for both singleton and multifetal pregnancies (adjusted hazard ratio, 3.66; [95% confidence interval, 2.81-4.67; P<.001] and 9.31 [95% confidence interval, 2.12-40.76; P=.003], respectively). CONCLUSION: Compared with gestational diabetes mellitus in singleton pregnancies, gestational diabetes mellitus in multifetal pregnancies doubles the risk of progression to type 2 diabetes mellitus. This effect is primarily observed in patients with obesity. Our findings underscore the importance of providing special attention and postpartum follow-up for patients with multifetal pregnancies and gestational diabetes mellitus, especially those with obesity, to enable early diagnosis and intervention for type 2 diabetes mellitus.

Dynamics of thyroid diseases and thyroid-axis gland masses.

Thyroid disorders are common and often require lifelong hormone replacement. Treating thyroid disorders involves a fascinating and troublesome delay, in which it takes many weeks for serum thyroid-stimulating hormone (TSH) concentration to normalize after thyroid hormones return to normal. This delay challenges attempts to stabilize thyroid hormones in millions of patients. Despite its importance, the physiological mechanism for the delay is unclear. Here, we present data on hormone delays from Israeli medical records spanning 46 million life-years and develop a mathematical model for dynamic compensation in the thyroid axis, which explains the delays. The delays are due to a feedback mechanism in which peripheral thyroid hormones and TSH control the growth of the thyroid and pituitary glands; enlarged or atrophied glands take many weeks to recover upon treatment due to the slow turnover of the tissues. The model explains why thyroid disorders such as Hashimoto's thyroiditis and Graves' disease have both subclinical and clinical states and explains the complex inverse relation between TSH and thyroid hormones. The present model may guide approaches to dynamically adjust the treatment of thyroid disorders.

Flash Glucose Monitoring in Israel: Understanding Real-World Associations between Self-Monitoring Frequency and Metrics of Glycemic Control.

OBJECTIVE: Flash glucose monitoring has been widely used in Israel for diabetes treatment and since 2018, the cost is reimbursed for all people with type 1 diabetes nationally. In the current study, we present the daily scanning behavior for FreeStyle Libre users in Israel and how this was associated with a range of metrics for glycemic assessment. METHODS: Deidentified data from FreeStyle Libre readers were collected between September 2014 and October 2020. Scan-rate data from Israel was extracted and sorted into 10 equal-sized groups based on scan frequency. The glucose parameters derived for each group were: estimated HbA1c (eA1c), time in range (TIR) between 70 and 180 mg/dL, and time with glucose levels of <70 mg/dL, <54 mg/dL, and >180 mg/dL. RESULTS: The data set for Israel included 12 370 readers, with data from 131 639 separate glucose sensors representing 152 million automatically recorded individual glucose readings. Users performed an average of 15 daily glucose scans, ranging from a mean of 4.1 scans per day (lowest, 10%), rising to a mean of 38.7 scans/day (highest, 10%) (median, 12; IQR, 8-18 for all readers). As the scan rates increased, the eA1c decreased from 7.6% to 6.7% (P < .001). Mean TIR increased from 56.9% to 70.0% with increasing scan rates (P < .001). Concordantly, time with glucose levels of >180 mg/dL and <54 mg/dL decreased from 37.2% to 23.6% (P < .001) and from 2.23% to 1.99%, respectively, as scan frequency increased. CONCLUSION: In Israel, people with diabetes under real-world conditions record higher rates of FreeStyle Libre scanning. These are associated with improvements in TIR, eA1c, and reduced time with glucose levels of >180 mg/dL or <54 mg/dL.

Characterization of women with gestational diabetes who failed to achieve glycemic control by lifestyle modifications.

PURPOSE: To identify specific characteristics of women diagnosed with gestational diabetes who failed to achieve good glycemic control by lifestyle modifications only. METHODS: Retrospective analysis of women carrying a singleton pregnancy diagnosed with gestational diabetes. The cohort included 314 women who achieved good glycemic control by lifestyle modifications and 328 women who required anti-diabetic medications. Lifestyle modifications included medical nutrition therapy and physical exercise recommendations. Anti-diabetic medications included either oral treatment with metformin or glyburide and\or insulin. RESULTS: Women in the lifestyle modifications group were younger (32.87 vs. 33.79 years, p = 0.012) and had lower pre-pregnancy body-mass-index (25.86 vs. 27.93 kg/m2, p < 0.001). Glucose challenge test (GCT) was significantly lower in the lifestyle modifications group (158.31 vs. 171.04 mg/dL in the anti-diabetic treatment group, p < 0.001). Moreover, fasting oral-glucose-tolerance-test (fOGTT) results were significantly lower in the lifestyle modifications group (88.22 vs. 96.34 mg/dL in the anti-diabetic treatment group, p < 0.001). In a receiver-operator-curve analysis, GCT + 4*fOGTT, was the best model to predict lifestyle modifications failure with an area under the curve of 0.7419. Higher rates of vaginal delivery and lower rates of maternal hypoglycemia in the lifestyle modifications group were observed. CONCLUSIONS: Maternal baseline characteristics and diabetes diagnostic parameters may predict which women will fail to achieve good glycemic control solely by lifestyle modifications.

Hypoglycaemia and its management in primary care setting.

Hypoglycaemia is common in patients with type 1 diabetes and type 2 diabetes and constitutes a major limiting factor in achieving glycaemic control among people with diabetes. While hypoglycaemia is defined as a blood glucose level under 70 mg/dL (3.9 mmol/L), symptoms may occur at higher blood glucose levels in individuals with poor glycaemic control. Severe hypoglycaemia is defined as an episode requiring the assistance of another person to actively administer carbohydrate, glucagon, or take other corrective actions to assure neurologic recovery. Hypoglycaemia is the most important safety outcome in clinical studies of glucose lowering agents. The American Diabetes Association Standards of Medical Care recommends that a management protocol for hypoglycaemia should be designed and implemented by every hospital, along with a clear prevention and treatment plan. A tailored approach, using clinical and pathophysiologic disease stratification, can help individualize glycaemic goals and promote new therapies to improve quality of life of patients. Data from recent large clinical trials reported low risk of hypoglycaemic events with the use of newer anti-diabetic drugs. Increased hypoglycaemia risk is observed with the use of insulin and/or sulphonylureas. Vulnerable patients with T2D at dual risk of severe hypoglycaemia and cardiovascular outcomes show features of "frailty." Many of such patients may be better treated by the use of GLP-1 receptor agonists or SGLT2 inhibitors rather than insulin. Continuous glucose monitoring (CGM) should be considered for all individuals with increased risk for hypoglycaemia, impaired hypoglycaemia awareness, frequent nocturnal hypoglycaemia and with history of severe hypoglycaemia. Patients with impaired awareness of hypoglycaemia benefit from real-time CGM. The diabetes educator is an invaluable resource and can devote the time needed to thoroughly educate the individual to reduce the risk of hypoglycaemia and integrate the information within the entire construct of diabetes self-management. Conversations about hypoglycaemia facilitated by a healthcare professional may reduce the burden and fear of hypoglycaemia among patients with diabetes and their family members. Optimizing insulin doses and carbohydrate intake, in addition to a short warm up before or after the physical activity sessions may help avoiding hypoglycaemia. Several therapeutic considerations are important to reduce hypoglycaemia risk during pregnancy including administration of rapid-acting insulin analogues rather than human insulin, pre-conception initiation of insulin analogues, and immediate postpartum insulin dose reduction.

Perinatal outcome in gestational diabetes according to different diagnostic criteria.

Objectives To evaluate whether gestational diabetes mellitus (GDM) diagnosed by different criteria impacts perinatal outcome. Methods This was a retrospective study of deliveries with a diagnosis of GDM (2014-2016). Perinatal outcomes were compared between patients with: (1) GDM diagnosed according to a single abnormal value on the 100-g oral glucose tolerance test (OGTT); (2) two or more abnormal OGTT values; and (3) a 50-g glucose challenge test (GCT) value ≥200 mg/dL. Results A total of 1163 women met the inclusion criteria, of whom 441 (37.9%) were diagnosed according to a single abnormal OGTT value, 627 (53.9%) had two or more abnormal OGTT values and 95 (8.17%) had a GCT value ≥200 mg/dL. Diet-only treatment was significantly higher in the single abnormal value group (70.3% vs. 65.1% vs. 50.5%) and rates of medical treatment were significantly higher in the GCT ≥ 200 mg/dL group (P < 0.05). Women in the GCT ≥ 200 mg/dL group had higher rates of neonatal intensive care unit (NICU) admission (10.5% vs. 2.7% vs. 2.8%, P < 0.001) and neonatal hypoglycemia (5.3% vs. 0.5% vs. 0.8%, P < 0.001). On multivariate logistic regression, GCT ≥ 200 mg/dL was no longer associated with higher rates of NICU admission and neonatal hypoglycemia (P > 0.05). Conclusion No difference was noted in the perinatal outcome amongst the different methods used for diagnosing GDM.

Effect of prandial treatment timing adjustment, based on continuous glucose monitoring, in patients with type 2 diabetes uncontrolled with once-daily basal insulin: A randomized, phase IV study.

AIMS: To evaluate the glycaemic control achieved by prandial once-daily insulin glulisine injection timing adjustment, based on a continuous glucose monitoring sensor, in comparison to once-daily insulin glulisine injection before breakfast in patients with type 2 diabetes who are uncontrolled with once-daily basal insulin glargine. MATERIALS AND METHODS: This was a 24-week open-label, randomized, controlled, multicentre trial. At the end of an 8-week period of basal insulin optimization, patients with HbA1c ≥ 7.5% and FPG < 130 mg/dL were randomized (1:1) to either arm A (no sensor) or arm B (sensor) to receive 16-week intensified prandial glulisine treatment. Patients in arm A received pre-breakfast glulisine, and patients in arm B received glulisine before the meal with the highest glucose elevation based on sensor data. The primary outcome was mean HbA1c at week 24 and secondary outcomes included rates of hypoglycaemic events and insulin dosage. RESULTS: A total of 121 patients were randomized to arm A (n = 61) or arm B (n = 60). There was no difference in mean HbA1c at week 24 between arms A and B (8.5% ± 1.2% vs 8.4% ± 1.0%; P = .66). The prandial insulin glulisine dosage for arm A and arm B was 9.3 and 10.1 units, respectively (P = .39). The frequency of hypoglycaemic events did not differ between study arms (36.1% vs 51.7%; P = .08). CONCLUSION: Using a CGM sensor to identify the meal with the highest glucose excursion and adjusting the timing of prandial insulin treatment did not show any advantage in terms of glycaemic control or safety in our patients.

Admission blood glucose and 10-year mortality among patients with or without pre-existing diabetes mellitus hospitalized with heart failure.

BACKGROUND: High admission blood glucose (ABG) level has been associated with a poor short-term outcome among non-diabetic patients with heart failure (HF). We aimed to investigate the association between ABG levels and long-term (10 years) mortality in patients with or without pre-existing diabetes mellitus (DM) admitted with HF. METHODS: We analyzed data on 1811 patients with DM and 2182 patients without pre-existing DM who were hospitalized with HF during a prospective national survey. The relationship between ABG and 10-year mortality was assessed using the Cox proportional hazard model adjusting for multiple variables. ABG was analyzed both as a categorical (<110, 110-140, 140-200, and >200 mg/dL) and as a continuous variable. RESULTS: At 10 years of follow-up the cumulative probability of mortality was 85 and 78% among patients with DM and patients with no pre-existing DM (p < 0.001), respectively. Among patients with no pre-existing DM, glucose levels of 110-140, 140-200 and ≥200 mg/dL were associated with 9% (p = 0.140), 16% (p = 0.031) and 53% (p < 0.001) increased mortality risk compared to ABG < 110 mg/dL. Each 18-mg/dL (1-mmol/L) increase in glucose level was associated with a 5% increased risk of mortality (p < 0.001) among patients with no-pre-existing DM. In contrast, among patients with DM, only those with glucose levels >200 mg/dL had an increased mortality risk (>200 mg/dL versus <110 mg/dL; HR = 1.20, p = 0.032). CONCLUSION: Among hospitalized HF patients with no pre-existing DM there is a linear relationship between ABG level and long-term mortality, whereas among patients with DM only ABG level >200 mg/dL is associated with increased mortality risk.

Pharmacological Management of Gestational Diabetes Mellitus.

Gestational diabetes mellitus (GDM) is one of the most common morbidities complicating pregnancy, with short- and long-term consequences to the mothers, fetuses, and newborns. Management and treatment are aimed to achieve best possible glycemic control, while avoiding hypoglycemia and ensuring maternal and fetal safety. It involves behavioral modifications, nutrition and medications, if needed; concurrent with maternal and fetal surveillance for possible adverse outcomes. This review aims to elaborate on the pharmacological options for GDM therapy. We performed an extensive literature review of different available studies, published during the last 50 years, concerning pharmacological therapy for GDM, dealing with safety and efficacy, for both fetal and maternal morbidity consequences; as well as failure and success in establishing appropriate metabolic and glucose control. Oral medication therapy is a safe and effective treatment modality for GDM and in some circumstances may serve as first-line therapy when nutritional modifications fail. When oral agents fail to establish glucose control then insulin injections should be added. Determining the best oral therapy in inconclusive, although it seems that metformin is slightly superior to glyburide, in some aspects. As for parenteral therapy, all insulins listed in this article are considered both safe and effective for treatment of hyperglycemia during pregnancy. Importantly, a better safety profile, with similar efficacy is documented for most analogues. As GDM prevalence rises, there is a need for successful monitoring and treatment for patients. Caregivers should know the possible and available therapeutic options.

IGF-I levels reflect hypopituitarism severity in adults with pituitary dysfunction.

PURPOSE: To evaluate the utility of Insulin-like growth factor I (IGF-I) standard deviation score (SDS) as a surrogate marker of severity of hypopituitarism in adults with pituitary pathology. METHODS: We performed a retrospective data analysis, including 269 consecutive patients with pituitary disease attending a tertiary endocrine clinic in 1990-2015. The medical files were reviewed for the complete pituitary hormone profile, including IGF-I, and clinical data. Age-adjusted assay reference ranges of IGF-I were used to calculate IGF-I SDS for each patient. The main outcome measures were positive and negative predictive values of low and high IGF-I SDS, respectively, for the various pituitary hormone deficiencies. RESULTS: IGF-I SDS correlated negatively with the number of altered pituitary axes (p < 0.001). Gonadotropin was affected in 76.6 % of cases, followed by thyrotropin (58.4 %), corticotropin (49.1 %), and prolactin (22.7 %). Positive and negative predictive values yielded a clear trend for the probability of low/high IGF-I SDS for all affected pituitary axes. Rates of diabetes insipidus correlated with IGF-I SDS values both for the full study population, and specifically for patients with non-functioning pituitary adenomas. CONCLUSIONS: IGF-I SDS can be used to evaluate the somatotroph function, as a valid substitute to absolute IGF-I levels. Moreover, IGF-I SDS predicted the extent of hypopituitarism in adults with pituitary disease, and thus can serve as a marker of hypopituitarism severity.

VARIATIONS IN CLINICAL AND IMAGING FINDINGS BY TIME OF DIAGNOSIS IN FEMALES WITH HYPOPITUITARISM ATTRIBUTED TO LYMPHOCYTIC HYPOPHYSITIS.

OBJECTIVE: To describe the various patterns of presentation, including assisting analyses, associated with the timing of diagnosis of females with hypopituitarism and suspected clinical diagnosis of lymphocytic hypophysitis. METHODS: A retrospective study of 9 consecutive females with pituitary dysfunction developed during or after pregnancy. All subjects were treated in our clinics between 2008 and 2014. Data were collected on clinical characteristics, pituitary hormone levels, and imaging findings. RESULTS: The study group included 9 patients with a mean age 33.7 ± 7.8 years at delivery. The probable cause of disease was lymphocytic hypophysitis. Headache or specific symptoms/signs of hypopituitarism appeared within 1 year of delivery. Five patients had headache, and 8 had difficulty breastfeeding or amenorrhea. Laboratory findings included central hypocortisolism (8/9 patients), hypogonadotropic hypogonadism (8/9), and central hypothyroidism (6/7). Insulin-like growth factor-1 (IGF-1) levels were low in 8/8 patients. Prolactin levels were low in 3/9 patients, and 1 patient had diabetes insipidus. Seven patients were diagnosed less than 1 year from symptom onset; 4 (57%) complained of headaches, and 5 (71%) had panhypopituitarism. Two patients were diagnosed later. Both had difficulty breastfeeding and amenorrhea, and one also had headaches. Both had panhypopituitarism and reduced pituitary volume. None of the patients fully recovered pituitary function. Normalization of the thyrotroph axis occurred in 3 patients, gonadotroph function in 3, the corticotroph axis in 2, and IGF-1 normalized in 1 subject. CONCLUSION: Hypopituitarism attributed to lymphocytic hypophysitis may present during pregnancy or early postpartum period with a clear clinical picture, or later, with indolent and nonspecific symptoms and signs.

Insulin detemir versus glyburide in women with gestational diabetes mellitus.

AIM: To evaluate the safety, efficacy and pregnancy outcomes of insulin detemir (IDet) versus glyburide treatment in women with gestational diabetes mellitus (GDM). METHODS: We conducted a retrospective cohort study of women with GDM who were treated with either glyburide or IDet for GDM in a university-affiliated tertiary hospital. RESULTS: Ninety-one patients with GDM were enrolled, 62 were administered glyburide and 29 IDet. Maternal age, pregestational body mass index (BMI) and rate of abnormal oral glucose tolerance test (OGTT) blood glucose values were not significantly different between groups. Good glycemic control rates were comparable. Hypoglycemic episodes were reported only in the glyburide group (19.4% versus 0%, p = 0.01). Maternal weight gain during pregnancy was significantly higher among women in the glyburide group (8.8 ± 5.1 kg, p < 0.001) compared to those in the IDet group (2.1 ± 19.9 kg, p = 0.71). CONCLUSIONS: To the best of our knowledge, this is the first study on IDet treatment in patients with GDM. By our preliminary results, IDet is a viable treatment option in women with GDM. Further large prospective studies are needed to determine the efficacy and safety of IDet in GDM patients.

Pituitary imaging findings in male patients with hypogonadotrophic hypogonadism.

CONTEXT: Data on pituitary imaging in adult male patients presenting with hypogonadotrophic hypogonadism (HH) and no known pituitary disease are scarce. OBJECTIVE: To assess the usefulness of pituitary imaging in the evaluation of men presenting with HH after excluding known pituitary disorders and hyperprolactinemia. DESIGN: A historical prospective cohort of males with HH. PATIENTS: Men who presented for endocrine evaluation from 2011 to 2014 with testosterone levels <10.4 nmol/L (300 ng/mL), normal LH and FSH levels and no known pituitary disease. RESULTS: Seventy-five men were included in the analysis. Their mean age and BMI were 53.4 ± 14.8 years and 30.7 ± 5.2 kg/m2, respectively. Mean total testosterone, LH, and FSH were 6.2 ± 1.7 nmol/L, 3.4 ± 2 and 4.7 ± 3.1 mIU/L, respectively. Prolactin level within the normal range was obtained in all men (mean 161 ± 61, range 41-347 mIU/L). Sixty-two men had pituitary MRI and 13 performed CT. In 61 (81.3%) men pituitary imaging was normal. Microadenoma was found in 8 (10.7%), empty sella and thickened pituitary stalk in one patient (1.3%) each. In other four patients (5.3%) a small or mildly asymmetric pituitary gland was noted. No correlation was found between testosterone level and the presence of pituitary anomalies. CONCLUSIONS: This study suggests that the use of routine hypothalamic-pituitary imaging in the evaluation of IHH, in the absence of clinical characteristics of other hormonal loss or sellar compression symptoms, will not increase the diagnostic yield of sellar structural abnormalities over that reported in the general population.

Clinical course and outcome of nonfunctioning pituitary adenomas in the elderly compared with younger age groups.

OBJECTIVE: Nonfunctioning pituitary adenomas (NFPAs) are the most common type of pituitary adenomas diagnosed in older patients. However, there are insufficient data regarding the clinical course, risk of regrowth, and long-term prognosis in elderly versus younger patients. METHODS: This retrospective cohort study observed 105 adult patients with NFPAs diagnosed between 1995 and 2012. Patients were stratified into 3 age groups: 18 to 44 years (29 patients), 45 to 64 years (38 patients), and 65 years and over (38 patients). The impact of age on presenting symptoms, disease course, and outcome was analyzed. RESULTS: Adenoma size was larger in patients <45 years (mean, 2.9 ± 1.2 cm) compared to patients aged 45 to 64 years and those ≥65 years old (2.3 ± 0.9 and 2.5 ± 0.8 cm, respectively; P = .05), with transsphenoidal surgery being the treatment of choice in all 3 groups (83, 92, and 84%, not significant). After a mean follow-up of 6 years, there were higher recovery rates from hypopituitarism in patients <45 years old (58% vs. 27% and 24%; P = .04). Visual fields improved in most affected patients in each group following surgery (74, 94, and 86%), with a trend toward more full normalization in the youngest age group (58% vs. 44% and 41%; P = .09). There were no significant differences in the risk of remnant growth (29 to 39%), rates of radiation therapy, or need for repeated surgeries. There was no disease-related mortality. CONCLUSION: Elderly patients with NFPA have lower rates of recovery from hypopituitarism after treatment compared to younger patients, but the rates of regrowth and need for salvage surgery are similar.

First-trimester fasting plasma glucose levels and progression to type 2 diabetes: A 5-year cohort study.

OBJECTIVE: Impaired fasting glucose is a prediabetic condition defined as glucose levels of 100-125 mg/dL and is considered a risk factor for type 2 diabetes. However, this definition does not confer to pregnancy. The significance of first-trimester fasting glucose and future progression to diabetes is not well defined. Therefore, we aimed to evaluate the progression to type 2 diabetes according to first- trimester fasting plasma glucose levels, as compared with gestational diabetes, a well-established risk factor for diabetes, in up to 5-year follow-up postpartum. METHODS: A retrospective analysis of 69 001 parturients, evaluating fasting plasma glucose levels measured during the first trimester. The primary outcome was the incidence of type 2 diabetes within 5 years post-delivery. Fasting plasma glucose levels were categorized in 10 mg/dL increments. Receiver operating characteristic-area under the curve (ROC-AUC) statistics and the Youden index were employed to identify the optimal fasting plasma glucose cutoff for progression to type 2 diabetes. Survival analysis was applied to calculate the adjusted hazard ratios (aHRs) for type 2 diabetes progression with further stratification to maternal obesity status. RESULTS: The identified fasting plasma glucose cutoff for progression to type 2 diabetes was 86.5 mg/dL. This cut-off demonstrated superior performance compared with gestational diabetes diagnosis. Stratification by maternal obesity revealed enhanced predictive capabilities for type 2 diabetes, particularly among patients without obesity. CONCLUSIONS: Increased first-trimester fasting plasma glucose levels are associated with progression to type 2 diabetes, at least as gestational diabetes. For patients without obesity, first-trimester fasting plasma glucose has a more pronounced impact on progression to diabetes.

Hypoglycemia in Oral Glucose Tolerance Test during Pregnancy and Risk for Type 2 Diabetes-A Five-Year Cohort Study.

Objective: To evaluate the risk of progression to type 2 diabetes (T2D) following reactive hypoglycemia in 100 g oral glucose tolerance test (oGTT). Methods: A retrospective analysis of parturients with up to 5-year follow-up postpartum. Data were extracted from the computerized laboratory system of Meuhedet, an Israeli HMO and cross-linked with the Israeli National Registry of Diabetes. Included were parturients with no prior diabetesand available oGTT values during pregnancy. Reactive hypoglycemia was defined as glucose levels lower than 60 mg/dL in at least one of 3 post-glucose load values in oGTT. The cohort was divided into 3 groups: normal glucose status, reactive hypoglycemia, and GDM. Maternal characteristics, laboratory data, and progression to T2D over 5 years were compared. Univariate and survival analyses assessed the adjusted hazard ratio for T2D, stratified by obesity Results: Among 14,122 parturients, 16.8% had reactive hypoglycemia, 71% had normal glucose status, and 12.2% had GDM. Adjusted for age, obesity, and hypertension, Parturients with reactive hypoglycemia had similar T2D risk compared to normal glucose status and a lower risk compared to GDM patients, regardless of obesity status. Conclusions: Reactive hypoglycemia during oGTT does not increase the risk of progressing to T2D.

One abnormal value in oral glucose tolerance test during pregnancy and type 2 diabetes risk: Insights from a 5-Year Follow-Up study.

OBJECTIVES: To evaluate the risk of type 2 diabetes(T2D) following one abnormal value(OAbV) in an oral glucose tolerance test(oGTT) performed during pregnancy. STUDY DESIGN: A retrospective analysis of parturients between 01.01.2017 and 31.12.2020 with 5 years of follow-up after delivery. Glucose levels during pregnancy were extracted from the computerized laboratory system of Meuhedet HMO and cross-tabulated with the Israeli National Registry of Diabetes. Women with multiple gestations or pregestational diabetes were excluded. Maternal characteristics and risk of T2D were stratified and compared between 3 groups: normal glucose status, OAbV in oGTT, and gestational diabetes. Statistical analysis included univariate analysis followed by survival analysis. Further analysis was stratified to women with and without obesity. RESULTS: 58,693 women entered the analysis. Following an adjustment to maternal age, obesity, hypertension, and hyperlipidemia, OAbV in oGTT was associated with a 1.8-fold increased risk of T2D in a 5-year follow-up compared to normal glucose status. When stratified by obesity, OAbV was associated with a 3.7-fold increase in T2D in women without obesity, however, was no longer a statistically significant predictor of T2D among women with obesity. CONCLUSIONS: Women with OAbV oGTT during pregnancy are at increased risk for developing T2D over 5 years of follow-up.

Timing of gestational diabetes diagnosis and progression to type 2 Diabetes: A comparative analysis.

AIM: To evaluate and compare the risk of progressing to type 2 diabetes (T2DM) based on the timing of gestational diabetes (GDM) diagnosis during pregnancy. METHODS: Retrospective analysis of pregnant individuals with gestational diabetes and post-pregnancy follow up. Data sourced from Meuhedet HMO's computerized laboratory system, cross-tabulated with the Israeli National Diabetes Registry. The cohort was divided into normoglycemic, early GDM (diagnosed by fasting plasma glucose 92-125 mg/dL (5.1-6.9 mM) at < 15 weeks), 2nd trimester GDM (diagnosed at 24-28 weeks), and late GDM (diagnosed after 29 weeks). Statistics included univariate analysis followed by survival analysis. Risk was further analyzed for individuals by obesity status. RESULTS: 75,459 entered the analysis: 90 % normoglycemic, 7.9 % early GDM, 1.4 % 2nd trimester GDM, and 0.7 % late GDM. Median post-pregnancy follow-up time was 4.3 (IQR 3.3-5.1). 2nd trimester GDM showed the highest T2DM risk annually after pregnancy. Cox regression analysis, adjusted for confounders, revealed a significantly higher T2DM risk for 2nd-trimester GDM compared to early and late GDM. Late GDM did not confer additional significant T2DM risk. Stratification by obesity status highlighted that early GDM increased the risk of T2DM only in individuals without obesity. CONCLUSIONS: GDM diagnosis timing significantly impacts T2DM risk. 2nd trimester GDM carries the highest T2DM risk.

Oral Glucose Tolerance Test Performed after 28 Gestational Weeks and Risk for Future Diabetes-A 5-Year Cohort Study.

Gestational diabetes mellitus (GDM) is diagnosed by an oral glucose tolerance test (oGTT), preferably performed at 24 + 0-28 + 6 gestational weeks, and is considered a risk factor for type 2 diabetes (T2DM). In this study, we aimed to evaluate the risk of T2DM associated with abnormal oGTT performed after 28 weeks. We conducted a retrospective cohort study that included parturients with available glucose levels during pregnancy and up to 5 years of follow-up after pregnancy. Data were extracted from the computerized laboratory system of Meuhedet HMO and cross-tabulated with the Israeli National Registry of Diabetes (INRD). The women were stratified into two groups: late oGTT (performed after 28 + 6 weeks) and on-time oGTT (performed at 24 + 0-28 + 6 weeks). The incidence of T2DM was evaluated and compared using univariate analysis followed by survival analysis adjusted to confounders. Overall, 78,326 parturients entered the analysis. Of them, 6195 (7.9%) performed on-time oGTT and 5288 (6.8%) performed late oGTT. The rest-66,846 (85.3%)-had normal glucose tolerance. Women who performed late oGTT had lower rates of GDM and T2DM. However, once GDM was diagnosed, regardless of oGTT timing, the risk of T2DM was increased (2.93 (1.69-5.1) vs. 3.64 (2.44-5.44), aHR (95% CI), late vs. on-time oGTT, p < 0.001 for both). Unlike in oGTT performed on time, one single abnormal value in late oGTT was not associated with an increased risk for T2DM.