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1.
Efficacy of Semaglutide in a Subcutaneous and an Oral Formulation.
Meier, JJ
Frontiers in endocrinology. 2021;:645617
Abstract
Despite the benefits of early and effective glycemic control in the management of type 2 diabetes (T2D), achieving glycated hemoglobin (HbA1c) targets is challenging in some patients. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) provide effective reductions in HbA1c and body weight. Semaglutide is the only GLP-1RA that is available in both an injectable and oral formulation. The efficacy of once-weekly subcutaneous semaglutide and once-daily oral semaglutide has been investigated in the global SUSTAIN and PIONEER phase III clinical trial programs in a range of clinical settings, including early T2D managed with diet and exercise only, more established T2D uncontrolled on one to three oral antidiabetic drugs, and advanced disease treated with insulin. Across the SUSTAIN program, once-weekly subcutaneous semaglutide 1.0 mg reduced HbA1c by 1.5-1.8% after 30-56 weeks, which was significantly more than sitagliptin, liraglutide, exenatide extended release, dulaglutide, canagliflozin, or insulin glargine. Across the PIONEER program, once-daily oral semaglutide 14 mg reduced HbA1c by 1.0-1.4%, significantly more than sitagliptin or empagliflozin, and to a similar extent as liraglutide after 26 weeks. In addition, subcutaneous semaglutide reduced body weight significantly more than all active comparators tested, while oral semaglutide reduced body weight more than sitagliptin and liraglutide, and to a similar extent as empagliflozin. Neither formulation of semaglutide has been associated with an increased risk of hypoglycemia and both improve various measures of health-related quality of life. Semaglutide offers the benefits of a highly effective GLP-1RA in both injectable and oral formulations. Selection of the most appropriate formulation can be made on an individual basis to best suit the patient's preferences and needs.
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Is HbA1c an ideal biomarker of well-controlled diabetes?
Kaiafa, G, Veneti, S, Polychronopoulos, G, Pilalas, D, Daios, S, Kanellos, I, Didangelos, T, Pagoni, S, Savopoulos, C
Postgraduate medical journal. 2021;(1148):380-383
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Abstract
HbA1c is a biomarker with a central role in the diagnosis and follow-up of patients with diabetes, although not a perfect one. Common comorbidities encountered in patients with diabetes mellitus, such as renal insufficiency, high output states (iron deficiency anaemia, haemolytic anaemia, haemoglobinopathies and pregnancy) and intake of specific drugs could compromise the sensitivity and specificity of the biomarker. COVID-19 pandemic poses a pressing challenge for the diabetic population, since maintaining optimal blood glucose control is key to reduce morbidity and mortality rates. Alternative methods for diabetes management, such as fructosamine, glycosylated albumin and device-based continuous glucose monitoring, are discussed.
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Early Gestational Diabetes Mellitus: Diagnostic Strategies and Clinical Implications.
Bhattacharya, S, Nagendra, L, Krishnamurthy, A, Lakhani, OJ, Kapoor, N, Kalra, B, Kalra, S
Medical sciences (Basel, Switzerland). 2021;(4)
Abstract
Preexisting diabetes mellitus (DM) should be ruled out early in pregnancy in those at risk. During screening, a significant proportion of women do not reach the threshold for overt DM but fulfill the criteria used for diagnosing conventional gestational DM (cGDM). There is no consensus on the management of pregnancies with intermediate levels of hyperglycemia thus diagnosed. We have used the term early gestational DM (eGDM) for this condition and reviewed the currently available literature. Fasting plasma glucose (FPG), oral glucose tolerance test, and glycated hemoglobin (HbA1c) are the commonly employed screening tools in early pregnancy. Observational studies suggest that early pregnancy FPG and Hba1c correlate with the risk of cGDM and adverse perinatal outcomes. However, specific cut-offs, including those proposed by the International Association of the Diabetes and Pregnancy Study Group, do not reliably predict the development of cGDM. Emerging data, though indicate that FPG ≥ 92 mg/dL (5.1 mmol/L), even in the absence of cGDM, signals the risk for perinatal complication. Elevated HbA1c, especially a level ≥ 5.9%, also correlates with the risk of cGDM and worsened outcome. HbA1c as a diagnostic test is however besieged with the usual caveats that occur in pregnancy. The studies that explored the effects of intervention present conflicting results, including a possibility of fetal malnutrition and small-for-date baby in the early treatment group. Diagnostic thresholds and glycemic targets in eGDM may differ, and large multicenter randomized controlled trials are necessary to define the appropriate strategy.
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4.
Understanding Metabolic Memory: A Tale of Two Studies.
Miller, RG, Orchard, TJ
Diabetes. 2020;(3):291-299
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Abstract
The results of the Diabetes Control and Complications Trial (DCCT) have given rise to much encouragement in the battle to stave off the complications of type 1 diabetes, showing dramatic declines in the development of severe retinopathy, nephropathy, and neuropathy in those treated intensively compared with conventional therapy. Particularly encouraging has been the continuing difference between the two groups despite both having similar HbA1c (∼8%) since the end of DCCT, when 96% of participants entered the observational Epidemiology of Diabetes Interventions and Complications (EDIC) study. This continuing relative benefit has been termed "metabolic memory," which implies altered metabolic regulation. Based on evidence from both the Epidemiology of Diabetes Complications (EDC) prospective cohort study of childhood-onset type 1 diabetes and DCCT/EDIC, we show that the metabolic memory effect can be largely explained by lower cumulative glycemic exposure in the intensive therapy group, and, on average, the development of complications increases with greater glycemic exposure, irrespective of whether this results from a high exposure for a short time or a lower exposure for a longer time. Thus, there is no need for a concept like "metabolic memory" to explain these observations. Potential mechanisms explaining the cumulative glycemic effect are also briefly discussed.
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Racial/Ethnic Differences in Glycemic Control in Older Adults with Type 2 Diabetes: United States 2003-2014.
Smalls, BL, Ritchwood, TD, Bishu, KG, Egede, LE
International journal of environmental research and public health. 2020;(3)
Abstract
The aim of this study was to determine whether racial differences in HbA1c persist in older adults (≥65 years) living with type 2 diabetes. Data from The National Health and Nutrition Examination Survey (NHANES) 2003-2014 were used to examine the association between HbA1c and older adults (≥65 years) over time. Compared to non-Hispanic Whites, Mexican Americans had the greatest difference in average HbA1c among minority groups, followed by those with unspecified/mixed ethnicities and non-Hispanic Blacks. In the adjusted linear model, racial minorities had a statistically significant relationship with HbA1c. There was no relationship between HbA1c and older age and insulin use. Trends in mean HbA1c over time increased for non-Hispanic Blacks and Mexican Americans and decreased for non-Hispanic Whites. The findings suggest that racial differences in HbA1c persist into older age and compared to non-Hispanic Whites, non-Hispanic Blacks and Mexican Americans are at an increased risk of morbidity, mortality, and disability due to high HbA1c. Furthermore, alternate measures of glycemic control may be needed to screen and manage T2DM in racial minorities.
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6.
Glycemic Monitoring and Management in Advanced Chronic Kidney Disease.
Galindo, RJ, Beck, RW, Scioscia, MF, Umpierrez, GE, Tuttle, KR
Endocrine reviews. 2020;(5):756-74
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Abstract
Glucose and insulin metabolism in patients with diabetes are profoundly altered by advanced chronic kidney disease (CKD). Risk of hypoglycemia is increased by failure of kidney gluconeogenesis, impaired insulin clearance by the kidney, defective insulin degradation due to uremia, increased erythrocyte glucose uptake during hemodialysis, impaired counterregulatory hormone responses (cortisol, growth hormone), nutritional deprivation, and variability of exposure to oral antihyperglycemic agents and exogenous insulin. Patients with end-stage kidney disease frequently experience wide glycemic excursions, with common occurrences of both hypoglycemia and hyperglycemia. Assessment of glycemia by glycated hemoglobin (HbA1c) is hampered by a variety of CKD-associated conditions that can bias the measure either to the low or high range. Alternative glycemic biomarkers, such as glycated albumin or fructosamine, are not fully validated. Therefore, HbA1c remains the preferred glycemic biomarker despite its limitations. Based on observational data for associations with mortality and risks of hypoglycemia with intensive glycemic control regimens in advanced CKD, an HbA1c range of 7% to 8% appears to be the most favorable. Emerging data on the use of continuous glucose monitoring in this population suggest promise for more precise monitoring and treatment adjustments to permit fine-tuning of glycemic management in patients with diabetes and advanced CKD.
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Caution is Needed in Interpreting Hemoglobin A1c Levels in the Muslim Bedouin Population of Southern Israel.
Treister-Goltzman, Y, Peleg, R
The Israel Medical Association journal : IMAJ. 2019;(8):546-551
Abstract
The Bedouins living in southern Israel are a Muslim-Arab population that is transitioning from a nomadic lifestyle to life in permanent settlements. The population has unique characteristics that could affect hemoglobin A1c (HbA1c) measurements. The objective of this study was to describe the socio-demographic and unique morbidity characteristics of this community and their effect on HbA1c measurements. Consanguinity, especially among cousins in the Bedouin population, results in a high prevalence of autosomal recessive genetic diseases such as thalassemia (underestimate of HbA1c), hemoglobinopathies (underestimate and overestimate), Gilbert's disease, and glucose-6-phosphate dehydrogenase deficiency, an X-linked disorder, which can cause hyperbilirubinemia with an overestimate of HbA1c. Furthermore, nutritional deficiencies, autosomal recessive diseases, high birth rates, parasitic infections, and poverty can all cause high rates of anemia (iron and vitamin B12 deficiencies) that can raise HbA1c levels. Congenital dyserythropoietic anemia is found among Bedouin tribes in the Negev region and can lead to an underestimation of HbA1c levels. Pregnancy can also affect HbA1c levels. Medical teams working in the Bedouin community and in other Muslim populations with similar morbidity characteristics throughout the world should identify patients with medical conditions that can affect HbA1c measurements and be aware of possible measurement alternatives such as fructosamine and glycated albumin.
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Plant-based Diet for HbA1c Reduction in Type 2 Diabetes Mellitus: an Evidence-based Case Report.
Utami, DB, Findyartini, A
Acta medica Indonesiana. 2018;(3):260-267
Abstract
BACKGROUND diabetes has become a major public health concern with an estimated 180 million cases worldwide. Nutritional changes are one of the key aspects in the management of type 2 diabetes mellitus. Previous studies have suggested an association between vegetarian diets and improvements in glycemic control in type 2 diabetes mellitus, however the relationship is not well established. The aim of this report is to perform a critical appraisal to analyze whether plant-based diet reduces the HbA1c level compared to conventional diet. METHODS a comprehensive computer-based literature search was performed on June 20, 2016 using PubMed, Ovid, EBSCO, and the Cochrane Library. All abstracts and titles from the initial search results were screened, reviewed, and appraised using critical appraisal worksheets by Center of Evidence-Based Medicine, University of Oxford. RESULTS one systematic review and two RCTs met the inclusion criteria and were considered eligible for this case report. In patients with type 2 diabetes mellitus, HbA1c significantly yielded greater reduction in the plant-based group compared to conventional diet group after 22 weeks of follow up. Similarly, there was a statistically greater reduction in HbA1c level in the plant-based group after 72 weeks. Furthermore, consumption of plant-based diet was associated with a significant reduction in HbA1c. CONCLUSION in patients with type 2 diabetes mellitus, HbA1c reduction was greater in patients with plant-based diet compared to patients with conventional diet. Further research should be conducted with larger sample size and longer follow-up period.
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Standardizing Clinically Meaningful Outcome Measures Beyond HbA1c for Type 1 Diabetes: A Consensus Report of the American Association of Clinical Endocrinologists, the American Association of Diabetes Educators, the American Diabetes Association, the Endocrine Society, JDRF International, The Leona M. and Harry B. Helmsley Charitable Trust, the Pediatric Endocrine Society, and the T1D Exchange.
Agiostratidou, G, Anhalt, H, Ball, D, Blonde, L, Gourgari, E, Harriman, KN, Kowalski, AJ, Madden, P, McAuliffe-Fogarty, AH, McElwee-Malloy, M, et al
Diabetes care. 2017;(12):1622-1630
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Abstract
OBJECTIVE To identify and define clinically meaningful type 1 diabetes outcomes beyond hemoglobin A1c (HbA1c) based upon a review of the evidence, consensus from clinical experts, and input from researchers, people with type 1 diabetes, and industry. Priority outcomes include hypoglycemia, hyperglycemia, time in range, diabetic ketoacidosis (DKA), and patient-reported outcomes (PROs). While priority outcomes for type 1 and type 2 diabetes may overlap, type 1 diabetes was the focus of this work. RESEARCH AND METHODS A Steering Committee-comprising representatives from the American Association of Clinical Endocrinologists, the American Association of Diabetes Educators, the American Diabetes Association, the Endocrine Society, JDRF International, The Leona M. and Harry B. Helmsley Charitable Trust, the Pediatric Endocrine Society, and the T1D Exchange-was the decision-making body for the Type 1 Diabetes Outcomes Program. Their work was informed by input from researchers, industry, and people with diabetes through Advisory Committees representing each stakeholder group. Stakeholder surveys were used to identify priority outcomes. The outcomes prioritized in the surveys were hypoglycemia, hyperglycemia, time in range, DKA, and PROs. To develop consensus on the definitions of these outcomes, the Steering Committee relied on published evidence, their clinical expertise, and feedback from the Advisory Committees. RESULTS The Steering Committee developed definitions for hypoglycemia, hyperglycemia, time in range, and DKA in type 1 diabetes. The definitions reflect their assessment of the outcome's short- and long-term clinical impact on people with type 1 diabetes. Knowledge gaps to be addressed by future research were identified. The Steering Committee discussed PROs and concluded that further type 1 diabetes-specific development is needed. CONCLUSIONS The Steering Committee recommends use of the defined clinically meaningful outcomes beyond HbA1c in the research, development, and evaluation of type 1 diabetes therapies.
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Glycated albumin: a potential biomarker in diabetes.
Freitas, PAC, Ehlert, LR, Camargo, JL
Archives of endocrinology and metabolism. 2017;(3):296-304
Abstract
Diabetes mellitus (DM) is a chronic and metabolic disease that presents a high global incidence. Glycated hemoglobin (A1C) is the reference test for long-term glucose monitoring, and it exhibits an association with diabetic chronic complications. However, A1C is not recommended in clinical situations which may interfere with the metabolism of hemoglobin, such as in hemolytic, secondary or iron deficiency anemia, hemoglobinopathies, pregnancy, and uremia. The glycated albumin (GA) is a test that reflects short-term glycemia and is not influenced by situations that falsely alter A1C levels. GA is the higher glycated portion of fructosamine. It is measured by a standardized enzymatic methodology, easy and fast to perform. These laboratory characteristics have ensured the highlight of GA in studies from the last decade, as a marker of monitoring and screening for DM, as well as a predictor of long-term outcomes of the disease. The aim of this review was to discuss the physiological and biochemistry characteristics of the GA, as well as its clinical utility in DM.