Consensus guidance for monitoring individuals with islet autoantibody-positive pre-stage 3 type 1 diabetes.

Given the proven benefits of screening to reduce diabetic ketoacidosis (DKA) likelihood at the time of stage 3 type 1 diabetes diagnosis, and emerging availability of therapy to delay disease progression, type 1 diabetes screening programmes are being increasingly emphasised. Once broadly implemented, screening initiatives will identify significant numbers of islet autoantibody-positive (IAb+) children and adults who are at risk of (confirmed single IAb+) or living with (multiple IAb+) early-stage (stage 1 and stage 2) type 1 diabetes. These individuals will need monitoring for disease progression; much of this care will happen in non-specialised settings. To inform this monitoring, JDRF in conjunction with international experts and societies developed consensus guidance. Broad advice from this guidance includes the following: (1) partnerships should be fostered between endocrinologists and primary-care providers to care for people who are IAb+; (2) when people who are IAb+ are initially identified there is a need for confirmation using a second sample; (3) single IAb+ individuals are at lower risk of progression than multiple IAb+ individuals; (4) individuals with early-stage type 1 diabetes should have periodic medical monitoring, including regular assessments of glucose levels, regular education about symptoms of diabetes and DKA, and psychosocial support; (5) interested people with stage 2 type 1 diabetes should be offered trial participation or approved therapies; and (6) all health professionals involved in monitoring and care of individuals with type 1 diabetes have a responsibility to provide education. The guidance also emphasises significant unmet needs for further research on early-stage type 1 diabetes to increase the rigour of future recommendations and inform clinical care.

Vitamin D Insufficiency and Epistemic Humility: An Endocrine Society Guideline Communication.

A long-held precept is that vitamin D supplementation primarily, if not exclusively, benefits individuals with low circulating 25-hydroxyvitamin D (25[OH]D) concentrations at baseline. However, the most appropriate 25(OH)D threshold to distinguish unacceptably low vs reliably adequate concentrations remains controversial. Such threshold proposals have largely been based on observational studies, which provide less robust evidence compared to randomized clinical trials (RCTs). Since the Endocrine Society's first vitamin D-related guideline was published in 2011, several large vitamin D-related RCTs have been published, and a newly commissioned guideline development panel (GDP) prioritized 4 clinical questions related to the benefits and harms of vitamin D supplementation in generally healthy individuals with 25(OH)D levels below a threshold. The GDP determined that available clinical trial evidence does not permit the establishment of 25(OH)D thresholds that specifically predict meaningful benefit with vitamin D supplementation. The panel noted important limitations in the available evidence, and the panel's overall certainty in the available evidence was very low. Nonetheless, based on the GDP's analyses and judgments, the Endocrine Society no longer endorses its previously proposed definition of vitamin D "sufficiency" (ie, at least 30 ng/mL [75 nmol/L]) or its previously proposed definition of vitamin D "insufficiency" (ie, greater than 20 ng/mL [50 nmol/L] but lower than 30 ng/mL [75 nmol/L]). The Endocrine Society's rationale for such is the subject of this Guideline Communication.

Navigating Complexities: Vitamin D, Skin Pigmentation, and Race.

Vitamin D plays a critical role in many physiological functions, including calcium metabolism and musculoskeletal health. This commentary aims to explore the intricate relationships among skin complexion, race, and 25-hydroxyvitamin D (25[OH]D) levels, focusing on challenges the Endocrine Society encountered during clinical practice guideline development. Given that increased melanin content reduces 25(OH)D production in the skin in response to UV light, the guideline development panel addressed the potential role for 25(OH)D screening in individuals with dark skin complexion. The panel discovered that no randomized clinical trials have directly assessed vitamin D related patient-important outcomes based on participants' skin pigmentation, although race and ethnicity often served as presumed proxies for skin pigmentation in the literature. In their deliberations, guideline panel members and selected Endocrine Society leaders underscored the critical need to distinguish between skin pigmentation as a biological variable and race and ethnicity as socially determined constructs. This differentiation is vital to maximize scientific rigor and, thus, the validity of resulting recommendations. Lessons learned from the guideline development process emphasize the necessity of clarity when incorporating race and ethnicity into clinical guidelines. Such clarity is an essential step toward improving health outcomes and ensuring equitable healthcare practices.

Consensus Guidance for Monitoring Individuals With Islet Autoantibody-Positive Pre-Stage 3 Type 1 Diabetes.

Given the proven benefits of screening to reduce diabetic ketoacidosis (DKA) likelihood at the time of stage 3 type 1 diabetes diagnosis, and emerging availability of therapy to delay disease progression, type 1 diabetes screening programs are being increasingly emphasized. Once broadly implemented, screening initiatives will identify significant numbers of islet autoantibody-positive (IAb+) children and adults who are at risk for (confirmed single IAb+) or living with (multiple IAb+) early-stage (stage 1 and stage 2) type 1 diabetes. These individuals will need monitoring for disease progression; much of this care will happen in nonspecialized settings. To inform this monitoring, JDRF, in conjunction with international experts and societies, developed consensus guidance. Broad advice from this guidance includes the following: 1) partnerships should be fostered between endocrinologists and primary care providers to care for people who are IAb+; 2) when people who are IAb+ are initially identified, there is a need for confirmation using a second sample; 3) single IAb+ individuals are at lower risk of progression than multiple IAb+ individuals; 4) individuals with early-stage type 1 diabetes should have periodic medical monitoring, including regular assessments of glucose levels, regular education about symptoms of diabetes and DKA, and psychosocial support; 5) interested people with stage 2 type 1 diabetes should be offered trial participation or approved therapies; and 6) all health professionals involved in monitoring and care of individuals with type 1 diabetes have a responsibility to provide education. The guidance also emphasizes significant unmet needs for further research on early-stage type 1 diabetes to increase the rigor of future recommendations and inform clinical care.

Reducing hypoglycemia from overtreatment of type 2 diabetes in older adults: The HypoPrevent study.

BACKGROUND: Hypoglycemia from overtreatment is a serious but underrecognized complication among older adults with type 2 diabetes. However, diabetes treatment is seldom deintensified. We assessed the effectiveness of a Clinical Decision Support (CDS) tool and shared decision-making (SDM) in decreasing the number of patients at risk for hypoglycemia and reducing the impact of non-severe hypoglycemic events. METHODS: HypoPrevent was a pre-post, single arm study at a five-site primary care practice. We identified at-risk patients (≥65 years-old, with type 2 diabetes, treated with insulin or sulfonylureas, and HbA1c < 7.0%). During three clinic visits over 6 months, clinicians used the CDS tool and SDM to assess hypoglycemic risk, set individualized HbA1c goals, and adjust use of hypoglycemic agents. We assessed the number of patients setting individualized HbA1c goals or modifying medication use, changes in the population at risk for hypoglycemia, and changes in impact of non-severe hypoglycemic events using a validated patient-reported outcome tool (TRIM-HYPO). RESULTS: We enrolled 94 patients (mean age-74; mean HbA1c (±SD)-6.36% ± 0.43), of whom 94% set an individualized HbA1c goal at either the baseline or first follow-up visit. Ninety patients completed the study. Insulin or sulfonylurea use was decreased or eliminated in 20%. An HbA1c level before and after goal setting was obtained in 53% (N = 50). Among these patients, the mean HbA1c increased 0.53% (p < 0.0001) and the number of patients at-risk decreased by 46% (p < 0.0001). Statistically significant reductions in the impact of hypoglycemia during daily activities occurred in both the total score and each functional domain of TRIM-HYPO. CONCLUSIONS: In a population of older patients at risk for hypoglycemia, the use of a CDS tool and SDM reduced the population at risk and decreased the use of insulin and sulfonylureas. Using a patient-reported outcome tool, we demonstrated significant reductions in the impact of hypoglycemia on daily life.

Enhancing the Trustworthiness of the Endocrine Society's Clinical Practice Guidelines.

In an effort to enhance the trustworthiness of its clinical practice guidelines, the Endocrine Society has recently adopted new policies and more rigorous methodologies for its guideline program. In this Clinical Practice Guideline Communication, we describe these recent enhancements-many of which reflect greater adherence to the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach to guideline development-in addition to the rationale for such changes. Improvements to the Society's guideline development practices include, but are not limited to, enhanced inclusion of nonendocrinologist experts, including patient representatives, on guideline development panels; implementation of a more rigorous conflict/duality of interest policy; a requirement that all formal recommendations must be demonstrably underpinned by systematic evidence review; the explicit use of GRADE Evidence-to-Decision frameworks; greater use and explanation of standardized guideline language; and a more intentional approach to guideline updating. Lastly, we describe some of the experiential differences our guideline readers are most likely to notice.

CLCN2 chloride channel mutations in familial hyperaldosteronism type II.

Primary aldosteronism, a common cause of severe hypertension 1 , features constitutive production of the adrenal steroid aldosterone. We analyzed a multiplex family with familial hyperaldosteronism type II (FH-II) 2 and 80 additional probands with unsolved early-onset primary aldosteronism. Eight probands had novel heterozygous variants in CLCN2, including two de novo mutations and four independent occurrences of a mutation encoding an identical p.Arg172Gln substitution; all relatives with early-onset primary aldosteronism carried the CLCN2 variant found in the proband. CLCN2 encodes a voltage-gated chloride channel expressed in adrenal glomerulosa that opens at hyperpolarized membrane potentials. Channel opening depolarizes glomerulosa cells and induces expression of aldosterone synthase, the rate-limiting enzyme for aldosterone biosynthesis. Mutant channels show gain of function, with higher open probabilities at the glomerulosa resting potential. These findings for the first time demonstrate a role of anion channels in glomerulosa membrane potential determination, aldosterone production and hypertension. They establish the cause of a substantial fraction of early-onset primary aldosteronism.

Missed opportunities for type 2 diabetes mellitus screening among women with a history of gestational diabetes mellitus.

OBJECTIVES: We sought to determine rates and factors associated with screening for type 2 diabetes mellitus (DM) in women with a history of gestational diabetes mellitus. METHODS: We retrospectively studied women with diagnosed gestational diabetes mellitus who delivered at a university-affiliated hospital (n=570). Data sources included medical and administrative record review. Main outcome measures were the frequency of any type of glucose testing at least 6 weeks after delivery and the frequency of recommended glucose testing. We assessed demographic data, past medical history, and prenatal and postpartum care characteristics. RESULTS: Rates of glucose testing after delivery were low. Any type of glucose testing was performed at least once after 38% of deliveries, and recommended glucose testing was performed at least once after 23% of deliveries. Among women with at least 1 visit to the health care system after delivery (n=447), 42% received any type of glucose test at least once, and 35% received a recommended glucose test at least once. Factors associated with testing were being married, having a visit with an endocrinologist after delivery, and having more visits after delivery. CONCLUSIONS: These findings suggest that most women with gestational diabetes mellitus are not screened for type 2 DM after delivery. Opportunities for DM prevention and early treatment are being missed.

Diagnosis and management of gestational diabetes mellitus.

Gestational diabetes occurs in 5 to 9 percent of pregnancies in the United States and is growing in prevalence. It is a controversial entity, with conflicting guidelines and treatment protocols. Recent studies show that diagnosis and management of this disorder have beneficial effects on maternal and neonatal outcomes, including reduced rates of shoulder dystocia, fractures, nerve palsies, and neonatal hypoglycemia. Diagnosis is made using a sequential model of universal screening with a 50-g one-hour glucose challenge test, followed by a diagnostic 100-g three-hour oral glucose tolerance test for women with a positive screening test. Treatment consists of glucose monitoring, dietary modification, exercise, and, when necessary, pharmacotherapy to maintain euglycemia. Insulin therapy is the mainstay of treatment, although glyburide and metformin may become more widely used. In women receiving pharmacotherapy, antenatal testing with nonstress tests and amniotic fluid indices beginning in the third trimester is generally used to monitor fetal well-being. The method and timing of delivery are controversial. Women with gestational diabetes are at high risk of subsequent development of type 2 diabetes. Lifestyle modification should therefore be encouraged, along with regular screening for diabetes.

Diagnosis and management of osteoporosis.

Osteoporosis is a common disorder with significant morbidity and mortality. Clinical risk factors can identify patients most likely to have osteoporosis. Patients who have decreased bone mass are candidates for calcium and vitamin D supplementation; those who have more severe bone loss should be screened for secondary causes and started on medical therapy. First-line therapy most often is a bisphosphonate. Estrogen reduces hip fractures in women. Recombinant parathyroid hormone is reserved for patients who have failed or are not candidates for bisphosphonate therapy. Follow-up dual-emission x-ray absorptiometry is reserved for when a change in bone mineral density will make a difference in therapy.