American Association of Clinical Endocrinology Clinical Practice Guideline: Developing a Diabetes Mellitus Comprehensive Care Plan-2022 Update.

OBJECTIVE: The objective of this clinical practice guideline is to provide updated and new evidence-based recommendations for the comprehensive care of persons with diabetes mellitus to clinicians, diabetes-care teams, other health care professionals and stakeholders, and individuals with diabetes and their caregivers. METHODS: The American Association of Clinical Endocrinology selected a task force of medical experts and staff who updated and assessed clinical questions and recommendations from the prior 2015 version of this guideline and conducted literature searches for relevant scientific papers published from January 1, 2015, through May 15, 2022. Selected studies from results of literature searches composed the evidence base to update 2015 recommendations as well as to develop new recommendations based on review of clinical evidence, current practice, expertise, and consensus, according to established American Association of Clinical Endocrinology protocol for guideline development. RESULTS: This guideline includes 170 updated and new evidence-based clinical practice recommendations for the comprehensive care of persons with diabetes. Recommendations are divided into four sections: (1) screening, diagnosis, glycemic targets, and glycemic monitoring; (2) comorbidities and complications, including obesity and management with lifestyle, nutrition, and bariatric surgery, hypertension, dyslipidemia, retinopathy, neuropathy, diabetic kidney disease, and cardiovascular disease; (3) management of prediabetes, type 2 diabetes with antihyperglycemic pharmacotherapy and glycemic targets, type 1 diabetes with insulin therapy, hypoglycemia, hospitalized persons, and women with diabetes in pregnancy; (4) education and new topics regarding diabetes and infertility, nutritional supplements, secondary diabetes, social determinants of health, and virtual care, as well as updated recommendations on cancer risk, nonpharmacologic components of pediatric care plans, depression, education and team approach, occupational risk, role of sleep medicine, and vaccinations in persons with diabetes. CONCLUSIONS: This updated clinical practice guideline provides evidence-based recommendations to assist with person-centered, team-based clinical decision-making to improve the care of persons with diabetes mellitus.

THE ENDOCRINOLOGY OF AGING: A KEY TO LONGEVITY "GREAT EXPECTATIONS".

ABBREVIATIONS: AMP = adenosine monophosphate CETP = cholesteryl ester transfer protein FOXO = Forkhead box O GH = growth hormone HDL = high-density lipoprotein IGF-1 = insulin-like growth factor 1 LDL = low-density lipoprotein miRNA = microRNA mTOR = mammalian target of rapamycin SIRT = sirtuin T4 = thyroxine TSH = thyroid-stimulating hormone "The Moving Finger writes; and, having writ, Moves on: nor all thy Piety nor Wit Shall lure it back to cancel half a Line, Nor all thy Tears wash out a Word of it." Omar Khayyam ( 1 ).

Diagnosis of Diabetes Mellitus in Older Adults.

In the United States, 4 out of 10 adults with diabetes are ≥65 years of age. The older adult with diabetes is very likely to be asymptomatic and also at higher risk of vascular disease. New concerns include new diagnosis of diabetes for older adults admitted to hospital and older adults in long-term care facilities. The pathophysiology for increased incidence of diabetes in older adults is multifactorial, but dominant features are increased likelihood of metabolic syndrome, dysfunctional insulin secretion, and peripheral insulin resistance. Society in general benefits from more cost-effective care of older adults with diabetes.

Improving Adherence in Type 2 Diabetes.

International Diabetes Federation estimates that there are more than a half-billion adults ages 20 to 79 years worldwide who have diabetes mellitus (DM) and that the global health care expenditure for adults with DM in 2015 was $673 billion. Nonadherence and nonpersistence to prescribed type 2 DM medications are common and remain a barrier to optimal health outcomes. There is a high prevalence of nonadherence among older adults. Research has focused on prevalence and predictors of adherence, research methodologies, and development of measures of adherence. Improvements hopefully will result in better disease monitoring, medication adherence, and reduced rates of diabetes complications.

Artificial Intelligence and Digital Tools: Future of Diabetes Care.

Diabetes mellitus has become a global threat, especially in the emerging economies. In the United States, there are about 24 million people with diabetes mellitus. Diabetes represents a trove of physiologic and sociologic data that are only superficially understood by the health care system. Artificial intelligence can address many problems posed by the prevalence of diabetes mellitus and the impact of diabetes on individual and societal health. We provide a brief overview of artificial intelligence and discuss case studies that illustrate how artificial intelligence can enhance diabetes care.

Academic collaborations with industry: lessons for the future.

Academic centers and industry partners have had love-hate relationships for more than a century. Despite many examples of socially beneficial collaborations between academia and industry, it has become increasingly difficult to find an arrangement where neither clinicians/researchers working with industry nor industry itself is demonized. Regardless, we must incentivize innovation. Preclinical research is primarily funded by the government, whereas 70% of clinical research is supported by industry. Due to external political pressure and industry's concern about lack of control over content, industry's support of continuing medical education (CME) has shrunk to 10% from 40% and has led to diversion of funding to non-CME events. Despite scrutiny of clinical faculty members' interactions with industry, corporate philanthropy is much sought after by academic institutions. Developing new therapeutics requires both academia and industry to transparently and ethically partner with creation of innovative start-ups, sharing of non-proprietary clinical trial data, and in postmarketing surveillance. The search continues for truly symbiotic relationships between academia and industry.

Metastatic malignant insulinoma in a patient with type 2 diabetes mellitus: case presentation and literature review.

OBJECTIVE: To describe the occurrence of metastatic malignant insulinoma in a patient with preexisting type 2 diabetes mellitus. METHODS: We present a detailed case report, with clinical, biochemical, and imaging findings, and summarize the data from 21 similar cases in the literature. RESULTS: The occurrence of malignant insulinoma in a patient with preexisting diabetes is very rare and thus can be a diagnostic challenge. In our patient with type 2 diabetes, endogenous hyperinsulinism was confirmed by demonstrating elevated insulin and C-peptide levels during hypoglycemic episodes in the absence of sulfonylurea on a blood screen. Abdominal computed tomographic scan and magnetic resonance imaging revealed a pancreatic mass as well as metastatic lesions in the liver. The pancreatic mass was removed and confirmed to be a malignant insulinoma. This procedure was followed by disappearance of the hypoglycemic episodes as well as the diabetes for a few months. On follow-up, however, more metastatic lesions appeared in conjunction with a protracted course of hypoglycemia that necessitated treatment with antihypoglycemic agents and, 3 years after the initial surgical intervention, culminated in the death of the patient. CONCLUSION: Our patient is one of the few subjects known to have a malignant insulinoma in conjunction with preexisting diabetes. A high degree of suspicion for the presence of an insulinoma should be maintained when unexplained hypoglycemic episodes occur in a patient with previously stable diabetes.

Endocrinology update 2006.

Endocrinology has recently witnessed several important developments: The Epidemiology of Diabetes Interventions and Complications study, a follow-up to the landmark Diabetes Control and Complications trial, found that strict glucose control early in the course of type 1 diabetes reduces the risk of microvascular and cardiovascular complications and provides prolonged benefits even if intensive control is not so tightly maintained. Inhaled insulin preparations are now available for mealtime coverage. We now have two new injectable medications for diabetes; pramlintide (Symlin) and exenatide (Byetta) are good adjuncts for patients with both type 1 and type 2 diabetes who have trouble reaching their hemoglobin A1c target, and they can help control and even reduce weight. Thyroxine (T4), instead of being merely a "prohormone," has been found to have direct actions on cells, leading to rapid clinical effects and possibly oncogenesis and angiogenesis. The therapeutic range for thyrotropin (TSH) may be much narrower than traditionally believed: some have proposed that the normal range should be redefined as 0.4 to 2.5 mIU/L. New evidence shows that vitamin D is important for more than calcium control and may help prevent type 1 diabetes.

Evolving to Personalized Medicine for Type 2 Diabetes.

Type 2 diabetes is an expensive public health problem threatening society at many levels. Despite many advances in classification of diabetes, we're still in early stages of developing an etio-pathologic ontology of diabetes. Recognizing the various biologic and social determinants of disease outcomes, precision medicine applies to medical interventions as well as psychosocial measures, nutrition, and exercise that may also affect individuals differently. Using this highly personalized approach, one hopes to achieve cost-effective care. The striking evolution in generating "Big Data," Biomarker Fingerprints, and the Internet of Things will force all clinicians to be familiar with the terminology and understand the clinical relevance.

Raloxifene causing malabsorption of levothyroxine.

To our knowledge, raloxifene hydrochloride, a selective estrogen receptor modulator, has never been reported to interfere with absorption of levothyroxine. We describe a 79-year-old woman with chronic, treated primary hypothyroidism, presenting with increasing levothyroxine requirement while taking raloxifene at the same time as levothyroxine. For two 6- to 8-week periods, we separated the ingestion of raloxifene and levothyroxine by about 12 hours. In addition, we tested the absorption of 1.0 mg of levothyroxine sodium with and without the coadministration of 60 mg of raloxifene hydrochloride on 2 separate occasions by collecting serial blood samples for 6 hours. Hypothyroidism occurred in a reproducible fashion whenever levothyroxine and raloxifene were administered together and improved whenever they were taken separately. Combined administration of levothyroxine and raloxifene resulted in lower levels of serum thyroxine compared with administration of levothyroxine alone. By a yet unknown mechanism, raloxifene caused malabsorption of levothyroxine in our patient when coadministered.

Basal and postglucagon C-peptide levels in Ethiopians with diabetes.

OBJECTIVE: To study basal C-peptide (BCP) and postglucagon C-peptide (PGCP) levels in Ethiopians with diabetes. RESEARCH DESIGN AND METHODS: A total of 56 subjects with type 1 diabetes, 97 subjects with type 2 diabetes, and 50 control subjects were recruited from a hospital in Ethiopia. BCP was determined in all subjects and PGCP in 86 subjects. RESULTS: Mean (+/- SEM) BCP, PGCP, and the increment after glucagon in type 1 diabetic subjects (0.14 +/- 0.04, 0.22 +/- 0.11, and 0.08 +/- 0.05 nmol/l, respectively) were lower (P < 0.001) than those in type 2 diabetic subjects (0.66 +/- 0.04, 1.25 +/- 0.10, and 0.56 +/- 0.06 nmol/l, respectively) or control subjects (0.54 +/- 0.04, 1.52 +/- 0.26, and 1.11 +/- 0.24 nmol/l, respectively). The mean BCP level was higher in type 2 diabetic subjects than control subjects (P=0.015), whereas the mean increment was lower (P=0.005). Insulin-treated type 2 diabetic subjects, compared with non-insulin-treated type 2 diabetic subjects, had lower mean BCP (0.55 +/- 0.08 nmol/l [n=37] vs. 0.73 +/- 0.04 [n=60], P=0.001), lower PGCP (0.97 +/- 0.20 nmol/l [n=18] vs. 1.40 +/- 0.11 [n=35], P=0.010), and a lower C-peptide increment (0.34 +/- 0.06 [n=18] vs. 0.67 +/- 0.07 nmol/l [n=35], P=0.003). In both the type 1 and type 2 diabetic groups, those with BCP levels <0.2 nmol/l had lower BMI than those with higher BCP levels (P=0.023 and P < 0.001, respectively). CONCLUSIONS: Combined with clinical criteria, C-peptide levels are good discriminators between type 1 and type 2 diabetes in Ethiopians and may also be useful in identifying subjects with type 2 diabetes who require insulin therapy. There is a subgroup of type 2 diabetic subjects with features of type 1 diabetes.

Management of nondiagnostic thyroid fine-needle aspiration biopsy: survey of endocrinologists.

OBJECTIVE: To evaluate the approach of endocrinologists in the setting of nondiagnostic thyroid fine-needle aspiration (FNA) biopsies. METHODS: In 2002, we surveyed physicians attending the national annual meetings of the American Association of Clinical Endocrinologists and the Endocrine Society of North America, using a 13-item questionnaire. The responses were tallied and analyzed. RESULTS: Of the 143 respondents, 139 were endocrinologists, with a male:female ratio of 2.5:1. Most respondents were involved in a medical practice in North America, but Europe, Asia, New Zealand, and Australia were also represented. Of those performing thyroid FNA biopsy, 31% used thyroid ultrasound guidance. Among the survey respondents, 16%, 49%, 20%, and 15% performed less than 2, 2 to 5, 6 to 10, and more than 10 thyroid FNA biopsies per month, respectively. Among the respondents, 13.5%, 44%, 28.5%, 10%, and 4% had non-diagnostic rates of less than 5%, 5 to 10%, 11 to 20%, 21 to 30%, and more than 30%, respectively. The approach of the respondents to an initially nondiagnostic FNA was repeated FNA biopsy in 87%, observation in 7%, levothyroxine suppression in 4%, and thyroid scintigraphy in 2%. Respondents believed that the most cost-effective approach in a patient with nondiagnostic FNA was repeated biopsy (82%), monitoring the size of the thyroid nodule (17%), and surgical referral (<1%). No one was willing to repeat the thyroid biopsy more than three times. CONCLUSION: On the basis of findings in our survey, most endocrinologists repeat thyroid FNA at least once when confronted with a nondiagnostic result. No published studies have demonstrated the cost-effectiveness of this approach versus proceeding to surgical intervention or observation. We hope that this survey will encourage further studies on this issue.

Development of diabetes mellitus several years after manifestation of diabetic nephropathy: case report and review of literature.

OBJECTIVE: To describe an unusual case of development of diabetes mellitus (DM) several years after manifestation of diabetic nephropathy and to review the related literature. METHODS: We present a case report, including detailed laboratory and pathologic findings in a 51-year-old man who was diagnosed as having DM several years after presenting with diabetic nephropathy. The pertinent literature is also reviewed. RESULTS: A 51-year-old African American man presented with proteinuria of 4 g/24 h. Past medical history was significant for impaired glucose tolerance diagnosed 2 years previously. Subsequent follow-up demonstrated fasting blood glucose levels ranging from 108 to 123 mg/dL and glycated hemoglobin levels ranging from 5.3 to 5.8%. The patient also had chronic hepatitis C, hypertension, a history of intravenous drug abuse, and a family history of DM and hypertension. On examination of the patient, his blood pressure was 180/90 mm Hg. Funduscopy revealed mild diabetic retinopathy. Work-up was negative for glomerulonephritis, connective tissue disease, vasculitis, or multiple myeloma. Kidney biopsy revealed thickened glomerular basement membranes and diffuse glomeru-losclerosis, consistent with diabetic nephropathy. During follow-up, 9 years after presenting with proteinuria and 4 years after diagnosis of biopsy-proven diabetic nephropathy, the patient had a blood glucose level of 890 mg/dL and diabetic ketoacidosis. CONCLUSION: This case provides one explanation for the natural course of patients who present with "diabetic complications" but have no diabetes. Some of those patients may have "prediabetes" and may manifest with DM during follow-up. We also conclude that hyperglycemia is not the only important factor in the pathogenesis of diabetic nephropathy.

Value of repeating a nondiagnostic thyroid fine-needle aspiration biopsy.

OBJECTIVE: To assess the value of repeating a biopsy when the initial thyroid fine-needle aspiration (FNA) biopsy is nondiagnostic. METHODS: Between 1990 and 2003, 4,311 thyroid FNAs were performed at the Cleveland Clinic Foundation, of which 220 (5%) were nondiagnostic. Among 189 patients whose medical records were available for retrospective review, 106 underwent a repeated FNA (FNA #2), and 14 had a second repeated FNA (FNA #3). Thyroid ultrasonography was used in the evaluation in 113 FNAs. RESULTS: The first and second repeated FNAs were diagnostic in 58% (62 of 106 patients) and 50% (7 of 14 patients), respectively. The rate of malignant disease in patients with no repeated FNAs versus 1 or more repeated FNAs was 4.8% (4 of 83) versus 11.3% (12 of 106), respectively. Ultrasound-guided FNA yielded a diagnosis among 33 of 113 biopsies (29.2%), and FNA without ultrasound guidance provided a diagnosis in 30 of 159 biopsies (18.9%). Thus, the use of thyroid ultrasonography significantly improved the likelihood of establishing a diagnosis (P = 0.017). We found that repeating the FNA up to 2 times provides a diagnosis in up to 60% of cases. CONCLUSION: The overall prevalence of thyroid cancer in patients with nondiagnostic FNA is not trivial--8.5% in our study group of 189 patients. An aggressive approach toward nondiagnostic FNA biopsies is recommended, with performance of at least 2 repeated FNA biopsies, preferably with the help of ultrasound guidance.