A Population-Based Cohort Study
AUDIENCE: Endocrinology, Ob/Gyn
KEY FINDINGS: Gestational glucose intolerance, including conditions not meeting gestational diabetes criteria of the two-step strategy, confers a high risk of type 2 diabetes in young adulthood. These conditions should be recognised as risk factors for type 2 diabetes, especially among women with abnormal fasting glucose concentrations during pregnancy.
BACKGROUND: The risk of type 2 diabetes among women with glucose intolerance during pregnancy that does not meet gestational diabetes criteria requires further investigation. We aimed to explore the associations between various degrees of gestational glucose intolerance and the risk of type 2 diabetes in young adulthood.
DETAILS: For this population-based cohort study, the national Israeli conscription database was linked to Maccabi Healthcare Services (MHS), the second-largest state-mandated health provider in Israel. Researcghers included 177,241 women who underwent a pre-recruitment evaluation at adolescence (age 16-20 years), 1 year before mandatory military service, and later underwent, from Jan 1, 2001, to Dec 31, 2019, two-step gestational diabetes screening with a 50 g glucose challenge test (GCT) based on a threshold of 140 mg/dL (7.8 mmol/L), followed as needed by a 100 g oral glucose tolerance test (OGTT). Abnormal OGTT values were defined according to the Carpenter-Coustan thresholds: 95 mg/dL (5.3 mmol/L) or higher in the fasting state; 180 mg/dL (10.0 mmol/L) or higher at 1 h; 155 mg/dL (8.6 mmol/L) or higher at 2 h; and 140 mg/dL (7.8 mmol/L) or higher at 3 h. The primary outcome was incident type 2 diabetes in the MHS diabetes registry. Cox proportional hazards models were applied to estimate adjusted hazard ratios (HRs) with 95% CIs for incident type 2 diabetes. During a cumulative follow-up of 1,882,647 person-years, and with a median follow-up of 10.8 (IQR 5.2-16.4) years, 1262 women were diagnosed with type 2 diabetes. Crude incidence rates of type 2 diabetes were 2.6 (95% CI 2.4-2.9) per 10,000 person-years in women with gestational normoglycaemia, 8.9 (7.4-10.6) per 10,000 person-years in women with an abnormal GCT and normal OGTT, 26.1 (22.4-30.1) per 10,000 person-years in women with one abnormal OGTT value (in the fasting state or 1 h, 2 h, or 3 h post-challenge), and 71.9 (66.0-78.3) per 10,000 person-years in women with gestational diabetes. After adjustment for sociodemographic characteristics, adolescent BMI, and age at gestational screening, the risk of type 2 diabetes was higher, compared to the gestational normoglycaemia group, in women with an abnormal GCT and normal OGTT (adjusted hazard ratio [HR] 3.39 [95% CI 2.77-4.16]; p<0.0001), in women with one abnormal OGTT value (9.11 [7.64-10.86]; p<0.0001), and in women with gestational diabetes (24.84 [21.78-28.34]; p<0.0001). The risk of type 2 diabetes was modestly increased in women with isolated elevated fasting glucose (adjusted HR 11.81 [95% CI 8.58-16.25]; p<0.0001), and in women with gestational diabetes and an abnormal fasting glucose (38.02 [32.41-44.61]; p<0.0001).
Copyright © Elsevier Ltd. All rights reserved.
Source: Bardugo, A., Bendor, C. D., Rotem, R. S., et al. (2023). Glucose Intolerance In Pregnancy and Risk Of Early-Onset Type 2 Diabetes: A Population-Based Cohort Study. The Lancet. 2023; 11(5): 333-344. Published: May, 2023. DOI: 10.1016/S2213-8587(23)00062-1.
AUDIENCE: Endocrinology, Pediatric, Family Medicine
KEY FINDINGS: The research analyses suggest parent DD is a strong predictor of child HbA1c and is another modifiable treatment target for lowering child HbA1c.
BACKGROUND: Diabetes distress (DD) describes the unrelenting emotional and behavioral challenges of living with, and caring for someone living with, type 1 diabetes (T1D). We investigated associations between parent-reported and child-reported DD, T1D device use, and child glycated hemoglobin (HbA1c) in 157 families of school-age children.
DETAILS: Parents completed the Parent Problem Areas in Diabetes-Child (PPAID-C) and children completed the Problem Areas in Diabetes-Child (PAID-C) to assess for DD levels. Parents also completed a demographic form where they reported current insulin pump or continuous glucose monitor (CGM) use (ie, user/non-user). Authors measured child HbA1c using a valid home kit and central laboratory. We used correlations and linear regression for our analyses. Children were 49% boys and 77.1% non-Hispanic white (child age (mean±SD)=10.2±1.5 years, T1D duration=3.8±2.4 years, HbA1c=7.96±1.62%). Most parents self-identified as mothers (89%) and as married (78%). Parents' mean PPAID-C score was 51.83±16.79 (range: 16-96) and children's mean PAID-C score was 31.59±12.39 (range: 11-66). Higher child HbA1c correlated with non-pump users (r=-0.16, p<0.05), higher PPAID-C scores (r=0.36, p<0.001) and higher PAID-C scores (r=0.24, p<0.001), but there was no association between child HbA1c and CGM use. A regression model predicting child HbA1c based on demographic variables, pump use, and parent-reported and child-reported DD suggested parents' PPAID-C score was the strongest predictor of child HbA1c.
Copyright © BMJ Publishing Group Ltd. All rights reserved.
Source: Patton, S. R., Kahhan, N., Pierce, J. S., et al. (2023). Parental Diabetes Distress Is A Stronger Predictor Of Child HbA1c Than Diabetes Device Use In School-Age Children With Type 1 Diabetes. BMJ Open Diabetes Research and Care. 2023; 11(5): e003607. Published: September, 2023. DOI: 10.1136/bmjdrc-2023-003607.
AUDIENCE: Oncology, Cardiology
KEY FINDINGS: The present study demonstrates that the use of metformin in patients with cancer is associated with a decreased incidence of HF in the year following anthracycline chemotherapy. The findings are consistent with previous experimental studies and provide impetus to develop further randomized controlled trials investigating the benefits of metformin in anthracycline-induced cardiotoxicity.
BACKGROUND: The prevention of heart failure (HF) is an important issue in patients treated with anthracyclines. Metformin, widely used to treat diabetes mellitus (DM), protects from anthracycline-induced cardiotoxicity in vitro and in animal models. The aim of the study was to test the association of metformin with the occurrence of symptomatic HF in patients with DM receiving anthracyclines.
DETAILS: A total of 561 patients with DM received new anthracycline therapy between 2008 and 2021 in a tertiary care center; propensity score matching was used to compare patients with or without metformin treatment. The primary outcome was new onset symptomatic HF occurring within 1 year of the initiation of anthracyclines. A total of 315 patients (65 ± 11 years of age, 33.7% male) were included. Patients with and without metformin were well matched for age, sex, type of cancer, medications, and cardiovascular risk factors. Six patients treated with metformin and 17 matched patients developed HF within 1 year of anthracycline initiation. The incidence of HF in patients treated with metformin was lower than patients without metformin within 1 year after anthracyclines (cumulative incidence: 3.6% vs 10.5%; P = 0.022; HR: 0.35; 95% CI: 0.14-0.90; P = 0.029). The use of metformin (HR: 0.71; 95% CI: 0.50-1.00; P = 0.049), was also associated with lower mortality.
Copyright © American College of Cardiology Foundation. All rights reserved.
Source: Onoue, T., Kang, Y., Lefebvre, B., et al. (2023). The Association of Metformin With Heart Failure in Patients With Diabetes Mellitus Receiving Anthracycline Chemotherapy. J Am Coll Cardiol CardioOnc. Published: August 29, 2023. DOI: 10.1016/j.jaccao.2023.05.013.
Clinical and Immunological Features
AUDIENCE: Nephrology, Internal Medicine
KEY FINDINGS: Concomitant C3GN and TMA is extremely rare and is associated with poor kidney outcomes. Genetic or acquired abnormalities of the alternative complement pathway are common as is the presence of monoclonal gammopathy, which may inform the selection of treatment approaches.
BACKGROUND: C3 glomerulopathy (C3GN) and atypical hemolytic uremic syndrome (aHUS) are 2 distinct rare kidney diseases caused by dysregulation of the alternative complement pathway. Patients with C3GN and concurrent kidney lesions of thrombotic microangiopathy (TMA) have been rarely reported. We characterized the clinical features and underlying immunological abnormalities in these patients.
DETAILS: Among 278 registered patients with C3GN, 16 (6%) had biopsy-proven glomerular and/or vascular TMA lesions. Their median age at diagnosis was 39 years (range, 7-76), and 59% were female. Fourteen of the 16 patients (88%) had an estimated glomerular filtration rate of 30 mL/min/1.73 m2 and 3 of 16 (19%) required dialysis. Twelve of the 14 evaluated patients (86%) showed evidence of mechanical hemolysis. Fifty percent of the patients had low C3 levels. Six of the 14 evaluated patients had a rare variant in complement genes, and 4 of the 16 patients (25%) had monoclonal gammopathy. Among the 16 patients, 10 (63%) received eculizumab, 5 (31%) received immunosuppressive therapy, and 4 (25%) received clone-targeted chemotherapy. Median kidney survival was 49 months.
Copyright © Elsevier Ltd. All rights reserved.
Source: Chabannes, M., Rabant, M., El Sissy, C., et al. (2023). C3 Glomerulopathy With Concurrent Thrombotic Microangiopathy: Clinical and Immunological Features. Am J Kidney Dis. 2023; 82(3): 279-289. Published: September, 2023. DOI: 10.1053/j.ajkd.2022.12.020.
AUDIENCE: Endocrinology, Family Medicine
KEY FINDINGS: MIB-626 administration in overweight or obese, middle-aged and older adults safely increased circulating NAD levels, and significantly reduced total LDL and non-HDL cholesterol, body weight, and diastolic blood pressure. These data provide the rationale for larger trials to assess the efficacy of NAD augmentation in improving cardiometabolic outcomes in older adults.
BACKGROUND: Nicotinamide adenine dinucleotide (NAD) levels decline with aging and age-related decline in NAD has been postulated to contribute to age-related diseases. The authors evaluated the safety and physiologic effects of NAD augmentation by administering its precursor, β-nicotinamide mononucleotide (MIB-626, Metro International Biotech, Worcester, MA), in adults at risk for age-related conditions.
DETAILS: Thirty overweight or obese adults, >= 45 years, were randomized in a 2:1 ratio to 2 MIB-626 tablets each containing 500 mg of microcrystalline β-nicotinamide mononucleotide or placebo twice daily for 28 days. Study outcomes included safety; NAD and its metabolome; body weight; liver, muscle, and intra-abdominal fat; insulin sensitivity; blood pressure; lipids; physical performance, and muscle bioenergetics. Adverse events were similar between groups. MIB-626 treatment substantially increased circulating concentrations of NAD and its metabolites. Body weight (difference -1.9 [-3.3, -0.5] kg, P = .008); diastolic blood pressure (difference -7.01 [-13.44, -0.59] mmHg, P = .034); total cholesterol (difference -26.89 [-44.34, -9.44] mg/dL, P = .004), low-density lipoprotein (LDL) cholesterol (-18.73 [-31.85, -5.60] mg/dL, P = .007), and nonhigh-density lipoprotein cholesterol decreased significantly more in the MIB-626 group than placebo. Changes in muscle strength, muscle fatigability, aerobic capacity, and stair-climbing power did not differ significantly between groups. Insulin sensitivity and hepatic and intra-abdominal fat did not change in either group.
Copyright © The Author(s). Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved.
Source: Pencina, K. M., Valderrabano, R., Wipper, B., et al. (2023). Nicotinamide Adenine Dinucleotide Augmentation in Overweight or Obese Middle-Aged and Older Adults: A Physiologic Study . The Journal of Clinical Endocrinology & Metabolism. 2023; 108(8): 1968-1980. Published: August, 2023. DOI: 10.1210/clinem/dgad027.
AUDIENCE: Family Medicine
KEY FINDINGS: Poststroke problems with mobility, balance, cognition, dysphagia, and depression are common. Rehabilitation involves a multidisciplinary, multimodal approach that includes physical therapy, speech therapy, and treatment of chronic pain and poststroke depression.
BACKGROUND: Ischemic stroke is the result of a sudden blockage of blood flow to the central nervous system due to thrombotic or embolic phenomena, and it is a major cause of morbidity and mortality worldwide. In 2019, stroke was the fifth leading cause of death in the United States. Although stroke can be hemorrhagic or ischemic, approximately 87% of strokes in the United States are ischemic. Almost 800,000 strokes occur annually in the United States, often leading to long-term disability.
DETAILS: Ischemic stroke is a major cause of morbidity and mortality worldwide. Ischemic stroke and transient ischemic attack exist on a continuum of the same disease process. Ischemic stroke is common, and more than 85% of stroke risk is attributed to modifiable risk factors. The initial management of acute stroke is usually performed in the emergency department and hospital settings. Family physicians have a key role in follow-up, ensuring that a complete diagnostic evaluation has been performed, addressing modifiable risk factors, facilitating rehabilitation, and managing chronic sequelae. Secondary prevention of ischemic stroke includes optimization of chronic disease management (e.g., hypertension, type 2 diabetes mellitus, dyslipidemia), nonpharmacologic lifestyle interventions (e.g., diet changes, exercise, substance use counseling), and pharmacologic interventions. Dual antiplatelet therapy with aspirin and clopidogrel is generally indicated for minor noncardioembolic ischemic strokes and high-risk transient ischemic attacks and should be converted to single antiplatelet therapy after 21 to 90 days. Secondary prevention of cardioembolic stroke requires long-term anticoagulation. Direct oral anticoagulants are preferred over warfarin for patients with nonvalvular atrial fibrillation.
Copyright © American Academy of Family Physicians. All rights Reserved.
Source: Larson, S. T., Ray, B. E., and Wlbur, J., (2023). Ischemic Stroke Management: Posthospitalization and Transition of Care. Am Fam Physician.. 2023; 108(1):70-77. Published: July, 2023. DOI: XXXXXXXX.