RESUMO
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.
Assuntos
Diabetes Mellitus Tipo 2 , Dislipidemias , Endocrinologia , Criança , Diabetes Mellitus Tipo 2/terapia , Feminino , Humanos , Hipoglicemiantes , Insulina , Gravidez , Estados UnidosRESUMO
SOURCE CITATION: Visser MM, Charleer S, Fieuws S, et al. Comparing real-time and intermittently scanned continuous glucose monitoring in adults with type 1 diabetes (ALERTT1): a 6-month, prospective, multicentre, randomised controlled trial. Lancet. 2021;397:2275-83. 34089660.
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Diabetes Mellitus Tipo 1 , Adulto , Glicemia , Automonitorização da Glicemia , Diabetes Mellitus Tipo 1/tratamento farmacológico , Controle Glicêmico , Humanos , Hipoglicemiantes/uso terapêutico , Estudos ProspectivosRESUMO
SOURCE CITATION: Pratley RE, Kanapka LG, Rickels MR, et al. Effect of continuous glucose monitoring on hypoglycemia in older adults with type 1 diabetes: a randomized clinical trial. JAMA. 2020;323:2397-406. 32543682.
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Diabetes Mellitus Tipo 1 , Hipoglicemia , Idoso , Glicemia , Automonitorização da Glicemia , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/tratamento farmacológico , Hemoglobinas Glicadas/análise , Humanos , Hipoglicemia/induzido quimicamente , Hipoglicemia/diagnóstico , Hipoglicemia/prevenção & controle , InsulinaRESUMO
Primary prevention of type 2 diabetes (T2D) should be achievable through the implementation of early and sustainable measures. Several randomized control studies that found success in preventing the progression to T2D in high-risk populations have identified early and intensive intervention based on an individualized prevention model as the key factor for participant benefit. The global prevalence of both overweight and obesity has now been widely recognized as the major epidemic of the 21st century. Obesity is a major risk factor for the progression from normal glucose tolerance to prediabetes and then to T2D. However, not all obese individuals will develop prediabetes or progress to diabetes. Intensive, multicomponent behavioural interventions for overweight and obese adults can lead to weight loss. Diabetes medications, including metformin, GLP-1 agonists, glitazones, and acarbose, can be considered for selected high-risk patients with prediabetes when lifestyle-based programmes are proven unsuccessful. Nutrition education is the cornerstone of a healthy lifestyle. Also, physical activity is an integral part of the prediabetes management plan and one of the main pillars in the prevention of diabetes. Mobile phones, used extensively worldwide, can facilitate communication between health professionals and the general population, and have been shown to be helpful in the prevention of T2D. Universal screening is needed. Noninvasive risk scores should be used in all countries, but they should be locally validated in all ethnic populations focusing on cultural differences around the world. Lifestyle interventions reduce the progression to prediabetes and diabetes. Nevertheless, many questions still need to be answered.
Assuntos
Consenso , Diabetes Mellitus Tipo 2/prevenção & controle , Saúde Global , Estado Pré-Diabético/terapia , Prevenção Primária , Diabetes Mellitus Tipo 2/epidemiologia , Saúde Global/normas , Saúde Global/tendências , Humanos , Guias de Prática Clínica como Assunto/normas , Estado Pré-Diabético/diagnóstico , Estado Pré-Diabético/epidemiologia , Estado Pré-Diabético/patologia , Prevenção Primária/métodos , Prevenção Primária/normas , Prevenção Primária/tendênciasRESUMO
BACKGROUND: Hepatic insulin gene therapy (HIGT) employing a glucose and insulin sensitive promoter to direct insulin transcription can lower blood sugars within 2 h of an intraperitoneal glucose challenge. However, post-challenge blood sugars frequently decline to below baseline. We hypothesize that this 'over-shoot' hypoglycemia results from sustained translation of long-lived transgene message, and that reducing pro-insulin message half-life will ameliorate post-challenge hypoglycemia. METHODS: We compared pro-insulin message content and insulin secretion from primary rat hepatocytes expressing insulin from either a standard construct (2xfur), or a construct producing a destabilized pro-insulin message (InsTail), following exposure to stimulating or inhibitory conditions. RESULTS: Hepatocytes transduced with a 2xfur construct accumulated pro-insulin message, and exhibited increased insulin secretion, under conditions that both inhibit or stimulate transcription. By contrast, pro-insulin message content remained stable in InsTail expressing cells, and insulin secretion increased less than 2xfur during prolonged stimulation. During transitions from stimulatory to inhibitory conditions, or vice versa, amounts of pro-insulin message changed more rapidly in InsTail expressing cells than 2xfur expressing cells. Importantly, insulin secretion increased during the transition from stimulation to inhibition in 2xfur expressing cells, although it remained unchanged in InsTail expressing cells. Use of the InsTail destabilized insulin message tended to more rapidly reduce glucose induced glycemic excursions, and limit post-load hypoglycemia in STZ-diabetic mice in vivo. CONCLUSIONS: The data obtained in the present study suggest that combining transcriptional and post-transcriptional regulatory strategies may reduce undesirable glycemic excursion in models of HIGT.
Assuntos
Glicemia/genética , Terapia Genética , Hepatócitos/metabolismo , Insulina/genética , Estabilidade de RNA , RNA Mensageiro/genética , Transcrição Gênica , Adenoviridae/genética , Animais , Diabetes Mellitus Experimental , Regulação da Expressão Gênica , Ordem dos Genes , Vetores Genéticos/administração & dosagem , Vetores Genéticos/genética , Humanos , Insulina/sangue , Insulina/metabolismo , Masculino , Camundongos , Cultura Primária de Células , Ratos , Transdução GenéticaRESUMO
BACKGROUND: Insulin self-administration is burdensome and can produce dangerous hypoglycemia. Insulin gene therapy may improve and simplify the treatment of diabetes mellitus. In rats, metabolically responsive hepatic insulin gene therapy (HIGT) delivered by adenovirus normalizes random blood sugars but with a limited duration. To prolong glycemic control, we delivered a metabolically regulated insulin transgene by adeno-associated virus (AAV). METHODS: We administered increasing doses of self-complementary (SC), pseudotyped AAV8 expressing the (GlRE)3 BP1-2xfur insulin transgene to streptozotocin-diabetic CD-1 mice, and monitored blood sugar and body weight. We also compared responses to intraperitoneal glucose and chow withdrawal, assessed for viral genomes in liver by Southern blotting, and measured hepatic glycogen. RESULTS: Glucose lowering required the combination of SC genomes and AAV capsid pseudotyping. HIGT controlled glycemia in diabetic mice (DM) for > 1 year. However, glycemic responses were variable. Approximately 30% of mice succumbed to hypoglycemia, and approximately 30% of mice again became hyperglycemic. During an intraperitoneal glucose tolerance test, blood sugars declined to normal within 180 min in HIGT-treated DM compared to 90 min in control mice. Hypoglycemia was common among HIGT-treated mice during a 24-h fast. However, HIGT mice lost less weight than either diabetic or nondiabetic controls as a result of increased water intake. HIGT treatment reduced the hepatic glycogen content of fed mice. CONCLUSIONS: Our studies demonstrate the possibility for long-term glycemic correction following AAV-mediated HIGT in mice. However, the dose-response relationship is irregular, and metabolic responsiveness may be less than that observed in rats.
Assuntos
Glicemia/genética , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/genética , Terapia Genética , Insulina/genética , Fígado/metabolismo , Animais , Peso Corporal , Dependovirus/genética , Diabetes Mellitus Experimental/terapia , Modelos Animais de Doenças , Expressão Gênica , Vetores Genéticos/administração & dosagem , Vetores Genéticos/genética , Teste de Tolerância a Glucose , Glicogênio/metabolismo , Humanos , Insulina/metabolismo , Masculino , Camundongos , TransgenesRESUMO
IMPORTANCE: Screening for diabetes might be more widespread if adverse associations with cardiovascular disease (CVD), resource use, and costs were known to occur earlier than conventional clinical diagnosis. OBJECTIVE: The purpose of this study was to determine whether adverse effects associated with diabetes begin prior to clinical diagnosis. DESIGN: Veterans with diabetes were matched 1:2 with controls by follow-up, age, race/ethnicity, gender, and VA facility. CVD was obtained from ICD-9 codes, and resource use and costs from VA datasets. SETTING: VA facilities in SC, GA, and AL. PARTICIPANTS: Patients with and without diagnosed diabetes. MAIN OUTCOME MEASURES: Diagnosed CVD, resource use, and costs. RESULTS: In this study, the 2,062 diabetic patients and 4,124 controls were 63 years old on average, 99 % male, and 29 % black; BMI was 30.8 in diabetic patients vs. 27.8 in controls (p<0.001). CVD prevalence was higher and there were more outpatient visits in Year -4 before diagnosis through Year +4 after diagnosis among diabetic vs. control patients (all p<0.01); in Year -2, CVD prevalence was 31 % vs. 24 %, and outpatient visits were 22 vs. 19 per year, respectively. Total VA costs/year/veteran were higher in diabetic than control patients from Year -4 ($4,083 vs. $2,754) through Year +5 ($8,347 vs. $5,700) (p<0.003) for each, reflecting underlying increases in outpatient, inpatient, and pharmacy costs (p<0.05 for each). Regression analysis showed that diabetes contributed an average of $1,748/year to costs, independent of CVD (p<0.001). CONCLUSIONS AND RELEVANCE: VA costs per veteran are higher--over $1,000/year before and $2,000/year after diagnosis of diabetes--due to underlying increases in outpatient, inpatient, and pharmacy costs, greater number of outpatient visits, and increased CVD. Moreover, adverse associations with veterans' health and the VA healthcare system occur early in the natural history of the disease, several years before diabetes is diagnosed. Since adverse associations begin before diabetes is recognized, greater consideration should be given to systematic screening in order to permit earlier detection and initiation of preventive management. Keeping frequency of CVD and marginal costs in line with those of patients before diabetes is currently diagnosed has the potential to save up to $2 billion a year.
Assuntos
Doenças Cardiovasculares/epidemiologia , Diabetes Mellitus/economia , Custos de Cuidados de Saúde , Recursos em Saúde/estatística & dados numéricos , Veteranos , Doenças Cardiovasculares/diagnóstico , Estudos de Casos e Controles , Diabetes Mellitus/diagnóstico , Feminino , Pesquisa sobre Serviços de Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Sudeste dos Estados Unidos/epidemiologiaRESUMO
The aims of this study were designed to determine whether liraglutide, a long-acting glucagon-like peptide, could reverse the adverse effects of a diet high in fat that also contained trans-fat and high-fructose corn syrup (ALIOS diet). Specifically, we examined whether treatment with liraglutide could reduce hepatic insulin resistance and steatosis as well as improve cardiac function. Male C57BL/6J mice were pair fed or fed ad libitum either standard chow or the ALIOS diet. After 8 wk the mice were further subdivided and received daily injections of either liraglutide or saline for 4 wk. Hyperinsulinemic-euglycemic clamp studies were performed after 6 wk, revealing hepatic insulin resistance. Glucose tolerance and insulin resistance tests were performed at 8 and 12 wk prior to and following liraglutide treatment. Liver pathology, cardiac measurements, blood chemistry, and RNA and protein analyses were performed. Clamp studies revealed hepatic insulin resistance after 6 wk of ALIOS diet. Liraglutide reduced visceral adiposity and liver weight (P < 0.001). As expected, liraglutide improved glucose and insulin tolerance. Liraglutide improved hypertension (P < 0.05) and reduced cardiac hypertrophy. Surprisingly, liver from liraglutide-treated mice had significantly higher levels of fatty acid binding protein, acyl-CoA oxidase II, very long-chain acyl-CoA dehydrogenase, and microsomal triglyceride transfer protein. We conclude that liraglutide reduces the harmful effects of an ALIOS diet by improving insulin sensitivity and by reducing lipid accumulation in liver through multiple mechanisms including, transport, and increase ß-oxidation.
Assuntos
Cardiomegalia/tratamento farmacológico , Dieta Hiperlipídica/efeitos adversos , Fígado Gorduroso/tratamento farmacológico , Peptídeo 1 Semelhante ao Glucagon/análogos & derivados , Adiposidade/efeitos dos fármacos , Animais , Cardiomegalia/etiologia , Fígado Gorduroso/etiologia , Peptídeo 1 Semelhante ao Glucagon/farmacologia , Peptídeo 1 Semelhante ao Glucagon/uso terapêutico , Teste de Tolerância a Glucose , Hipertensão/tratamento farmacológico , Hipertensão/etiologia , Resistência à Insulina , Liraglutida , Fígado/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BLRESUMO
The retina is nourished by two unique (retinal and choroidal) circulations. The lack of depth-resolved blood volume (BV) imaging techniques hampers investigation of vascular-specific regulation of the retina in vivo. This study presents a high-resolution, laminar-specific magnetic resonance imaging (MRI) study to image retinal and choroidal BVs, their responses to physiologic challenges in normal and Royal-College-of-Surgeons (RCS) rats (a model of retinal degeneration). Retinal and choroidal BVs were imaged by MRI (30×30×800 µm) with intravascular administration of monocrystalline iron oxide nanocolloid (MION) contrast agent. Relative baseline BV and BV changes due to physiologic challenges were calculated in normal and RCS rat retinas. BV-MRI revealed two well-resolved retinal and choroidal vascular layers located on either side of the retina and an intervening avascular layer. The ratio of choroidal:retinal BV in normal rats at baseline was 9.8±3.2 in control rat retinas (N=7). Hyperoxia decreased retinal BV (-51±17%, p<0.05) more than choroidal BV (-28±14%), and hypercapnia increased retinal BV (52±11%, p<0.01) more than choroidal BV (12±11%). BV-MRI in degenerated retinas of RCS rats (N=7) revealed thinning of the avascular layer and an increase in relative baseline retinal and choroidal BVs. Only hypercapnia-induced BV changes in the retinal vasculature of RCS rats were significantly different (smaller) from controls (p<0.05). These findings suggest that BV in both retinal vasculatures is regulated. The relative baseline BV in both vasculatures increased in retinal degeneration. BV-MRI provides clinically relevant data that may prove useful for early detection and longitudinal probing of retinal diseases, and could complement optical imaging techniques.
Assuntos
Corioide/irrigação sanguínea , Corioide/fisiologia , Artérias Ciliares/fisiologia , Retina/fisiologia , Vasos Retinianos/fisiologia , Animais , Modelos Animais de Doenças , Hipercapnia/fisiopatologia , Hiperóxia/fisiopatologia , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Masculino , Ratos , Ratos Long-Evans , Degeneração Retiniana/patologiaRESUMO
Obesity and age are risk factors for feline diabetes. This study aimed to test the hypothesis that age, long-term obesity, and dietary composition would lead to peripheral and hepatorenal insulin resistance, indicated by higher endogenous glucose production (EGP) in the fasted and postprandial state, higher blood glucose and insulin, and higher leptin, free thyroxine, and lower adiponectin concentrations. Using triple tracer-(2)H(2)O, [U-(13)C(3)] propionate, and [3,4-(13)C(2)] glucose infusion, and indirect calorimetry-we investigated carbohydrate and fat metabolic pathways in overnight-fasted neutered cats (13 young lean, 12 old lean, and 12 old obese), each fed three different diets (high protein with and without polyunsaturated fatty acids, and high carbohydrate) in a crossover design. EGP was lowest in fasted and postprandial obese cats despite peripheral insulin resistance, indicated by hyperinsulinemia. Gluconeogenesis was the most important pathway for EGP in all groups, but glycogen contributed significantly. Insulin and leptin concentrations were higher in old than in young lean cats; adiponectin was lowest in obese cats but surprisingly highest in lean old cats. Diet had little effect on metabolic parameters. We conclude that hepatorenal insulin resistance does not develop in the fasted or postprandial state, even in long-term obese cats, allowing the maintenance of euglycemia through lowering EGP. Glycogen plays a major role in EGP, especially in lean fasted cats, and in the postprandial state. Aging may predispose to insulin resistance, which is a risk factor for diabetes in cats. Mechanisms underlying the high adiponectin of healthy old lean cats need to be further explored.
Assuntos
Envelhecimento , Doenças do Gato/metabolismo , Glucose/metabolismo , Estado Nutricional/fisiologia , Obesidade/veterinária , Período Pós-Prandial , Ração Animal , Animais , Glicemia , Gatos , Dieta/veterinária , Ingestão de Energia , Feminino , Insulina , Masculino , Obesidade/metabolismoRESUMO
High-resolution magnetic resonance imaging (MRI) provides non-invasive images of retinal anatomy, physiology, and function with depth-resolved laminar resolution. Eye movement and drift, however, could limit high spatial resolution imaging, and anesthetics that minimize eye movement could significantly attenuate retinal function. The aim of this study was to determine the optimal anesthetic preparations to minimize eye movement and maximize visual-evoked retinal response in rats. Eye movements were examined by imaging of the cornea with a charge-coupled device (CCD) camera under isoflurane, urethane, ketamine/xylazine, and propofol anesthesia at typical dosages in rats. Combination of the paralytic pancuronium bromide with isoflurane or ketamine/xylazine anesthesia was also examined for the eye movement studies. Visual-evoked retinal responses were evaluated using full-field electroretinography (ERG) under isoflurane, ketamine/xylazine, urethane, and ketamine/xylazine + pancuronium anesthesia in rats. The degree of eye movement, measured as displacement per unit time, was the smallest under 1% isoflurane + pancuronium anesthesia. The ketamine/xylazine groups showed larger dark-adapted ERG a- and b-waves than other anesthetics tested. The isoflurane group showed the shortest b-wave implicit times. Photopic ERGs in the ketamine/xylazine groups showed the largest b-waves with the isoflurane group showing slightly shorter implicit times at the higher flash intensities. Oscillatory potentials revealed an early peak in the isoflurane group compared with ketamine/xylazine and urethane groups. Pancuronium did not affect the a- and b-wave, but did increase oscillatory potential amplitudes. Compared with the other anesthetics tested here, ketamine/xylazine + pancuronium was the best combination to minimize eye movement and maximize retinal function. These findings should set the stage for further development and application of high-resolution functional imaging techniques, such as MRI, to study retinal anatomy, physiology, and function in anesthetized rats.
Assuntos
Anestésicos/farmacologia , Eletrorretinografia/efeitos dos fármacos , Potenciais Evocados Visuais/efeitos dos fármacos , Movimentos Oculares/efeitos dos fármacos , Retina/efeitos dos fármacos , Retina/fisiologia , Análise de Variância , Anestésicos Dissociativos/farmacologia , Animais , Visão de Cores/efeitos dos fármacos , Visão de Cores/fisiologia , Combinação de Medicamentos , Eletrorretinografia/métodos , Ketamina/farmacologia , Masculino , Visão Noturna/efeitos dos fármacos , Visão Noturna/fisiologia , Pancurônio/farmacologia , Ratos , Ratos Sprague-Dawley , Xilazina/farmacologiaRESUMO
OBJECTIVE: To evaluate the effect of hepatic insulin gene therapy on diabetic enteric neuropathy. METHODS: Mice were randomly allocated into 3 groups: a normal control group, a diabetic group, and a diabetic gene therapy group. Diabetes were induced by penial vein injection of streptozocin (STZ). The gene therapy group received hepatic insulin gene therapy while the other 2 groups only received an empty virus expressing green fluorescent protein. Random blood glucose, body weight growth, gastric emptying, total bowel length, absolute and relative bowel transit, electric field stimulation of colon smooth muscle, colon nuclei staining and counting were measured. RESULTS: We successully established a mouse model of diabetic enteric neuropathy which manifests as: 8 weeks of continuous hyperglycemia,increased total bowel length, decreased relative bowel transit, impaired colon smooth muscle relaxation and loss of inhibitory neurons in colon. Through gene therapy, the above indexes were normalized or ameliorated, suggesting hepatic insulin gene therapy is capable of preventing diabetic enteric neuropathy. CONCLUSION: Hepatic insulin gene therapy can prevent STZ induced diabetic enteric neuropathy.
Assuntos
Diabetes Mellitus Experimental/terapia , Neuropatias Diabéticas/terapia , Sistema Nervoso Entérico/patologia , Terapia Genética , Insulina/genética , Adenoviridae , Animais , Diabetes Mellitus Experimental/complicações , Sistema Nervoso Entérico/metabolismo , Gastroenteropatias/etiologia , Gastroenteropatias/terapia , Técnicas de Transferência de Genes , Vetores Genéticos , Hepatócitos/metabolismo , Insulina/metabolismo , Camundongos , Proinsulina/genéticaRESUMO
OBJECTIVE: We investigated sex and racial differences in insulin sensitivity, ß-cell function, and glycated hemoglobin (HbA1c) and the associations with selected phenotypic characteristics. RESEARCH DESIGN AND METHODS: This is a cross-sectional analysis of baseline data from 3,108 GRADE (Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study) participants. All had type 2 diabetes diagnosed <10 years earlier and were on metformin monotherapy. Insulin sensitivity and ß-cell function were evaluated using the HOMA of insulin sensitivity and estimates from oral glucose tolerance tests, including the Matsuda Index, insulinogenic index, C-peptide index, and oral disposition index (DI). RESULTS: The cohort was 56.6 ± 10 years of age (mean ± SD), 63.8% male, with BMI 34.2 ± 6.7 kg/m2, HbA1c 7.5 ± 0.5%, and type 2 diabetes duration 4.0 ± 2.8 years. Women had higher DI than men but similar insulin sensitivity. DI was the highest in Black/African Americans, followed by American Indians/Alaska Natives, Asians, and Whites in descending order. Compared with Whites, American Indians/Alaska Natives had significantly higher HbA1c, but Black/African Americans and Asians had lower HbA1c. However, when adjusted for glucose levels, Black/African Americans had higher HbA1c than Whites. Insulin sensitivity correlated inversely with BMI, waist-to-hip ratio, triglyceride-to-HDL-cholesterol ratio (TG/HDL-C), and the presence of metabolic syndrome, whereas DI was associated directly with age and inversely with BMI, HbA1c, and TG/HDL-C. CONCLUSIONS: In the GRADE cohort, ß-cell function differed by sex and race and was associated with the concurrent level of HbA1c. HbA1c also differed among the races, but not by sex. Age, BMI, and TG/HDL-C were associated with multiple measures of ß-cell function and insulin sensitivity.
Assuntos
Diabetes Mellitus Tipo 2 , Resistência à Insulina , Glicemia , Peptídeo C , Criança , Pré-Escolar , Estudos Transversais , Feminino , Humanos , Lactente , Insulina , MasculinoRESUMO
Continuous glucose monitoring (CGM) has become a widely used tool in the ambulatory setting for monitoring glucose levels, as well as detecting uncontrolled hyperglycemia, hypoglycemia, and glycemic variability. The accuracy of some CGM systems has recently improved to the point of manufacture with factory calibration and Food and Drug Administration clearance for nonadjunctive use to dose insulin. In this commentary, we analyze the answers to six questions about what is needed to bring CGM into the hospital as a reliable, safe, and effective tool. The evidence to date indicates that CGM offers promise as an effective tool for monitoring hospitalized patients. During the current coronavirus disease 2019 crisis, we hope to provide guidance to healthcare professionals, who are seeking to reduce exposure to SARS-Cov-2, as well as preserve invaluable personal protective equipment. In this commentary, we address who, what, where, when, why, and how CGM can be adopted for inpatient use.
Assuntos
Automonitorização da Glicemia/métodos , Infecções por Coronavirus/epidemiologia , Complicações do Diabetes/terapia , Hiperglicemia/complicações , Hiperglicemia/diagnóstico , Pneumonia Viral/epidemiologia , Betacoronavirus , Glicemia/análise , COVID-19 , Calibragem , Controle de Doenças Transmissíveis , Diabetes Mellitus/sangue , Diabetes Mellitus/terapia , Registros Eletrônicos de Saúde , Hospitalização , Hospitais , Humanos , Hiperglicemia/sangue , Pacientes Internados , Sistemas de Infusão de Insulina , Monitorização Ambulatorial , Pandemias , SARS-CoV-2 , Estados Unidos , United States Food and Drug AdministrationRESUMO
Diabetic retinopathy (DR) is diagnosed clinically by directly viewing retinal vascular changes during ophthalmoscopy or through fundus photographs. However, electroretinography (ERG) studies in humans and rodents have revealed that retinal dysfunction is demonstrable prior to the development of visible vascular defects. Specifically, delays in dark-adapted ERG oscillatory potential (OP) implicit times in response to dim-flash stimuli (<-1.8 log cd · s/m2) occur prior to clinically recognized DR. Animal studies suggest that retinal dopamine deficiency underlies these early functional deficits. In this study, we randomized individuals with diabetes, without clinically detectable retinopathy, to treatment with either low- or high-dose Sinemet (levodopa plus carbidopa) for 2 weeks and compared their ERG findings with those of control subjects (no diabetes). We assessed dim-flash-stimulated OP delays using a novel handheld ERG system (RETeval) at baseline and 2 and 4 weeks. RETeval recordings identified significant OP implicit time delays in individuals with diabetes without retinopathy compared with age-matched control subjects (P < 0.001). After 2 weeks of Sinemet treatment, OP implicit times were restored to control values, and these improvements persisted even after a 2-week washout. We conclude that detection of dim-flash OP delays could provide early detection of DR and that Sinemet treatment may reverse retinal dysfunction.
Assuntos
Carbidopa/uso terapêutico , Retinopatia Diabética/tratamento farmacológico , Eletrorretinografia/métodos , Levodopa/uso terapêutico , Adulto , Idoso , Retinopatia Diabética/diagnóstico , Retinopatia Diabética/fisiopatologia , Combinação de Medicamentos , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Hepatic insulin gene therapy (HIGT) produces near-normal glycemia in diabetic rats. Hepatic insulin production is expected to stimulate glycogen storage. However, the effect of HIGT on hepatic glycogen metabolism in vivo is unknown. METHODS: After administration of an adenoviral vector capable of inducing glucose responsive insulin production from hepatocytes, we evaluated circulating hormones, cytokines, hepatic gene expression and hepatic glycogen content in diabetic CD-1 mice receiving intravenous streptozotocin. Nondiabetic mice and diabetic mice treated with empty adenovirus served as controls. RESULTS: Peripheral concentrations of human insulin in HIGT mice were less than concentrations of mouse insulin among controls. However, expression of insulin responsive genes in HIGT livers indicated a significant intra-hepatic insulin effect, with expression changes reflecting appropriate responses to fed-fasting transitions. Transcription factors (hepatocyte nuclear factor-4alpha and peroxisome proliferator-activated receptor gamma co-activator-1alpha), as well as target genes (phospho-enol-pyruvate carboxykinase, glucose-6-phosphatase and glucokinase) exhibited insulin responsive expression. Despite producing near normal glycemia, HIGT diminished hepatic glycogen content in both fasted and fed mice. Serum cytokine responses revealed both vector-related (monocyte chemoatractant protein-1, interleukin-6) and transgene specific (resistin, tumor necrosis factor alpha) effects. CONCLUSIONS: HIGT produces low circulating concentrations of insulin, but produces significant intra-hepatic effects on gene expression. Despite controlling hyperglycemia, HIGT exerts unexpected insulin effects on hepatic carbohydrate metabolism. Although the precise mechanisms remain to be determined, they may relate to vector-induced cytokine effects.
Assuntos
Diabetes Mellitus Experimental , Regulação da Expressão Gênica , Terapia Genética , Insulina , Glicogênio Hepático/metabolismo , Transcrição Gênica , Adipocinas/metabolismo , Animais , Peso Corporal , Citocinas/metabolismo , Diabetes Mellitus Experimental/genética , Diabetes Mellitus Experimental/metabolismo , Modelos Animais de Doenças , Humanos , Insulina/genética , Insulina/metabolismo , Insulina/uso terapêutico , Fígado/fisiologia , Masculino , Camundongos , RatosRESUMO
Previous studies of hepatic insulin gene therapy (HIGT) focused on glycemic effects of insulin produced from hepatocytes. In this study, we extend the observations of glycemic control with metabolically regulated HIGT to include systemic responses and whole-body metabolism. An insulin transgene was administered with an adenoviral vector [Ad/(GlRE)(3)BP1-2xfur] to livers of BB/Wor rats made diabetic with polyinosinic polycytidilic acid (poly-I:C) (HIGT group), and results compared with nondiabetic controls (non-DM), and diabetic rats receiving different doses of continuous-release insulin implants (DM-low BG and DM-high BG). Blood glucose and growth normalized in HIGT, with lower systemic insulin levels, elevated glucagon, and increased heat production compared with non-DM. Minimal regulation of systemic insulin levels were observed with HIGT, yet the animals maintained normal switching from carbohydrate to lipid metabolism determined by respiratory quotients (RQs), and tolerated 24-hour fasts without severe hypoglycemia. HIGT did not restore serum lipids as we observed increased triglycerides (TGs) and increased free fatty acids, but reduced weight of visceral fat pads despite normal total body fat content and retroperitoneal fat depots. HIGT favorably affects blood glucose, normalizes metabolic switching in diabetic rats, and reduces intra-abdominal fat deposition.
Assuntos
Diabetes Mellitus Experimental/terapia , Terapia Genética/métodos , Insulina/genética , Fígado/metabolismo , Gordura Abdominal/metabolismo , Adenoviridae , Animais , Glicemia , Composição Corporal , Ritmo Circadiano , Humanos , Insulina/sangue , Masculino , Oxirredução , Ratos , Ratos Endogâmicos , Transdução Genética , Triglicerídeos/sangue , Triglicerídeos/metabolismoRESUMO
BACKGROUND: Gene transfer can induce insulin production from non-beta-cells. Multiple gene transfer protocols have demonstrated efficacy correcting diabetes-associated hyperglycemia and growth abnormalities in vivo. OBJECTIVES: To review the literature reporting induction of insulin secretion from non-beta-cells by gene transfer. METHODS: Database search of literature in Ovid Medline. RESULTS/CONCLUSIONS: Gene transfer for the treatment of diabetes mellitus has advanced significantly, but remains premature for clinical translation. Approaches inducing metaplasia produce beta-like-cells that normalize glycemia in diabetic rodents. Insulin gene transfer strategies provide somewhat inferior glycemic control, but avoid the overproduction of counter-regulatory hormones. Both approaches will require extensive investigations into their effects on host cells and tissues, and the efficacy of neither has been satisfactorily verified in a large animal model.
Assuntos
Diabetes Mellitus/terapia , Terapia Genética , Insulina/genética , Técnicas de Transferência de Genes , Humanos , Insulina/biossíntese , MetaplasiaRESUMO
BACKGROUND: Increasing use of nurse practitioners and physician assistants is a possible solution to the shortage of primary care providers in the United States, but the quality of care they provide is not well understood. METHODS: Because the scope of practice of the 3 provider types is similar in the Veterans Health Administration, we determined whether patients managed by primary care nurse practitioners, physician assistants, or physicians had similar hemoglobin A1c levels at comparable times in the natural history of diabetes. Our retrospective cohort study examined veterans with newly diagnosed diabetes in 2008, continuous primary care from 2008 to 2012, and more than 75% of primary care visits with nurse practitioner, physician assistant, or physician. RESULTS: Of the 19,238 patients, 95.3% were male, 77.7% were white, and they had a mean age 68.5 years; 14.7%, 7.1%, and 78.2% of patients were managed by nurse practitioners, physician assistants, and physicians, respectively. Median hemoglobin A1c was comparable at diagnosis (6.6%, 6.7%, 6.7%, P > .05) and after 4 years (all 6.5%, P > .5). Hemoglobin A1c levels at initiation of the first (7.5%-7.6%) and second (8.0%-8.2%) oral medications for patients of nurse practitioners and physician assistants compared with that of physicians was also similar after adjusting for patient characteristics (all P > .05). Nurse practitioners started insulin at a lower hemoglobin A1c (9.4%) than physicians (9.7%), which remained significant after adjustment (P < .05). CONCLUSIONS: At diagnosis and during 4 years of follow-up, diabetes management by nurse practitioners and physician assistants was comparable to management by physicians. The Veterans Health Administration model for roles of nurse practitioners and physician assistants may be broadly useful to help meet the demand for primary care providers in the United States.
Assuntos
Diabetes Mellitus/terapia , Profissionais de Enfermagem , Assistentes Médicos , Atenção Primária à Saúde/organização & administração , Idoso , Diabetes Mellitus/sangue , Diabetes Mellitus/diagnóstico , Feminino , Hemoglobinas Glicadas/metabolismo , Humanos , Hipoglicemiantes/uso terapêutico , Insulina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Estados Unidos , VeteranosRESUMO
BACKGROUND: Many individuals with diabetes remain undiagnosed, leading to delays in treatment and higher risk for subsequent diabetes complications. Despite recommendations for diabetes screening in high-risk groups, the optimal approach is not known. We evaluated the utility of inpatient glucose levels as an opportunistic screening tool for identifying patients at high risk for diabetes. METHODS: We retrospectively examined 462,421 patients in the US Department of Veterans Affairs healthcare system, hospitalized on medical/surgical services in 2000-2010, for ≥3 days, with ≥2 inpatient random plasma glucose (RPG) measurements. All had continuity of care: ≥1 primary care visit and ≥1 glucose measurement within 2 years before hospitalization and yearly for ≥3 years after discharge. Glucose levels during hospitalization and incidence of diabetes within 3 years after discharge in patients without diabetes were evaluated. RESULTS: Patients had a mean age of 65.0 years, body mass index of 29.9 kg/m2, and were 96% male, 71% white, and 18% black. Pre-existing diabetes was present in 39.4%, 1.3% were diagnosed during hospitalization, 8.1% were diagnosed 5 years after discharge, and 51.3% were never diagnosed (NonDM). The NonDM group had the lowest mean hospital RPG value (112 mg/dL [6.2 mmol/L]). Having at least 2 RPG values >140 mg/dL (>7.8 mmol/L), the 95th percentile of NonDM hospital glucose, provided 81% specificity for identifying incident diabetes within 3 years after discharge. CONCLUSIONS: Screening for diabetes could be considered in patients with at least 2 hospital glucose values at/above the 95th percentile of the nondiabetic range (141 mg/dL [7.8 mmol/L]).