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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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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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Sodium-glucose cotransporter 2 inhibitors for diabetes mellitus control after kidney transplantation: Review of the current evidence.
Kanbay, M, Demiray, A, Afsar, B, Karakus, KE, Ortiz, A, Hornum, M, Covic, A, Sarafidis, P, Rossing, P
Nephrology (Carlton, Vic.). 2021;(12):1007-1017
Abstract
Sodium-glucose cotransporter type 2 inhibitors (SGLT2i) are promising drugs to treat chronic kidney disease patients with or without diabetes mellitus (DM). Besides improving glycemic control, SGLT2i are cardioprotective and kidney protective and decrease bodyweight, serum uric acid, blood pressure, albuminuria and glomerular hyperfiltration. These effects may benefit graft function and survival in kidney transplant (KT) patients. In this review, we evaluate data on the efficacy and safety of SGLT2i for KT patients with DM. Eleven studies with 214 diabetic KT patients treated with SGLT2i have been reported. SGLT2i lowered haemoglobin A1c and bodyweight. While glomerular filtration rate may be reduced in the short-term, it remained similar to baseline after 3-12 months. In two studies, blood pressure decreased and remained unchanged in the others. There were no significant changes in urine protein to creatinine ratio. Regarding safety, 23 patients had urinary tract infections, 2 patients had a genital yeast infection, one had acute kidney injury, and one had mild hypoglycaemia. No cases of ketoacidosis or acute rejection were reported. In conclusion, the limited experience so far suggests that SGLT2i are safe in KT patients with DM, decrease bodyweight and improve glycemic control. However, some of the benefits observed in larger studies in the non-KT population have yet to be demonstrated in KT recipients, including preservation of kidney function, reduction in blood pressure and decreased proteinuria.
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4.
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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Identification of MODY among patients screened for gestational diabetes: a clinician's guide.
Urbanová, J, Brunerová, L, Nunes, M, Brož, J
Archives of gynecology and obstetrics. 2020;(2):305-314
Abstract
PURPOSE Screening of gestational diabetes/GDM (although different in different countries) represents a standard procedure allowing to identify women with pregnancy-associated diabetes. Some of the women with GDM (up to 5%) may, however, suffer from previously undiagnosed MODY (Maturity-Onset Diabetes of the Young). Currently, no international or local guidelines focused on the identification of MODY among GDM exist. Thus, the aim of this manuscript is to propose a clear guide for clinicians on how to detect MODY among pregnant women with gestational diabetes. METHODS Based on the available literature about diagnosis (in general population) of MODY and management of MODY (both, in general population and in pregnant women), we propose a clear clinical guide on how to diagnose and manage MODY in pregnancy. RESULTS The manuscript suggests a feasible clinical approach how to recognize MODY among patients with GDM and how to manage pregnancy of women with three most common MODY subtypes. CONCLUSION A correct classification of diabetes is, nonetheless, essential, particularly in case of MODY, as the management of pregnant women with MODY is different and the correct diagnosis of MODY enables individualized treatment with regard to optimal pregnancy outcomes.
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6.
Diagnosis of Diabetes Mellitus in Older Adults.
Reddy, SSK
Clinics in geriatric medicine. 2020;(3):379-384
Abstract
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.
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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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8.
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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Plant-derived natural agents as dietary supplements for the regulation of glycosylated hemoglobin: A review of clinical trials.
Rezaeiamiri, E, Bahramsoltani, R, Rahimi, R
Clinical nutrition (Edinburgh, Scotland). 2020;(2):331-342
Abstract
BACKGROUND & AIMS Type 2 diabetes mellitus (T2DM) is a metabolic disorder affecting a growing number of patients all over the world. T2DM complications are positively associated with HbA1c which is a long-term glycemic marker. Medicinal plants and their isolated phytochemicals have been extensively used as dietary supplements for the management of chronic disorders including T2DM. Current paper aims to review clinical trials evaluated the effect of phytochemicals for long-term management of T2DM considering the HbA1c level. METHODS Electronic databases including PubMed, Scopus and Cochrane were searched using the keywords "phytochemical", "extract", "herb", or "plant" and "HbA1c" or "glycosylated hemoglobin" in the title/abstract from the date of inception until May 2017. English and Persian language papers were included. References of the retrieved papers were also screened for relevant studies. RESULTS Of 2435 studies, 39 relevant clinical trials were finally included in which phytochemicals including berberine, curcumin, catechin, silymarin, resveratrol, pycnogenol, isoflavones, lignans, isohumulone, saponins, corn bran hemicellulose and pinitol were examined. Berberine and silymarin had the strongest evidence regarding their effectiveness in long-term management of HbA1c; however, lack of enough toxicological studies suggests to stay on the safe side for the administration of these agents in diabetic patients. CONCLUSIONS Current data regarding the efficacy of other phytochemicals are still controversial due to small follow-up period, methodological problems and small sample size. Future well-designed clinical trials are necessary to confirm the safety and efficacy of phytochemicals for long-term glycemic control of diabetic patients.