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1.
Ann Intern Med ; 174(10): JC119, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34606313

RESUMO

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.


Assuntos
Diabetes Mellitus Tipo 1 , Adulto , Glicemia , Automonitorização da Glicemia , Diabetes Mellitus Tipo 1/tratamento farmacológico , Controle Glicêmico , Humanos , Hipoglicemiantes/uso terapêutico , Estudos Prospectivos
2.
Diabetes Care ; 44(2): 340-349, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33334808

RESUMO

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 , Masculino
3.
Ann Intern Med ; 173(10): JC54, 2020 11 17.
Artigo em Inglês | MEDLINE | ID: mdl-33197347

RESUMO

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.


Assuntos
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 , Insulina
4.
J Diabetes Sci Technol ; 14(4): 822-832, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32536205

RESUMO

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 Administration
5.
Diabetes ; 69(7): 1518-1527, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32051147

RESUMO

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-Idade
6.
Diabetes Metab Res Rev ; 34(6): e3021, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29757486

RESUMO

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/tendências
7.
J Am Med Dir Assoc ; 19(5): 399-404.e3, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29289540

RESUMO

OBJECTIVES: Safe and easily implemented treatment regimens are needed for the management of patients with type 2 diabetes mellitus (T2DM) in long-term care (LTC) and skilled nursing facilities. DESIGN: This 6-month open-label randomized controlled trial compared the efficacy and safety of a DPP4 inhibitor (linagliptin) and basal insulin (glargine) in LTC residents with T2DM. SETTINGS: Three LTC institutions affiliated with a community safety-net hospital, US Department of Veterans Affairs and Emory Healthcare System in Atlanta, Georgia. PARTICIPANTS: A total of 140 residents with T2DM treated with oral antidiabetic agents or low-dose insulin (≤0.1 U/kg/d), with fasting or premeal blood glucose (BG) > 180 mg/dL and/or HbA1c >7.5%. INTERVENTION: Baseline antidiabetic therapy, except metformin, was discontinued on trial entry. Residents were treated with linagliptin 5 mg/d (n = 67) or glargine at a starting dose of 0.1 U/kg/d (n = 73). Both groups received supplemental rapid-acting insulin before meals for BG > 200 mg/dL. MEASUREMENTS: Primary outcome was mean difference in daily BG between groups. Main secondary endpoints included differences in frequency of hypoglycemia, glycosylated hemoglobin (HbA1c), complications, emergency department visits, and hospital transfers. RESULTS: Treatment with linagliptin resulted in no significant differences in mean daily BG (146 ± 34 mg/dL vs. 157 ± 36 mg/dL, P = .07) compared to glargine. Linagliptin treatment resulted in fewer mild hypoglycemic events <70 mg/dL (3% vs. 37%, P < .001), but there were no differences in BG < 54 mg/dL (P = .06) or <40 mg/dL (P = .05) compared to glargine. There were no significant between-group differences in HbA1c, length of stay, complications, emergency department visits, or hospitalizations. CONCLUSION: Treatment with linagliptin resulted in noninferior glycemic control and in significantly lower risk of hypoglycemia compared to insulin glargine in long-term care and skilled nursing facility residents with type 2 diabetes.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Inibidores da Dipeptidil Peptidase IV/uso terapêutico , Hipoglicemiantes/uso terapêutico , Insulina Glargina/uso terapêutico , Linagliptina/uso terapêutico , Idoso , Glicemia/análise , Feminino , Hemoglobinas Glicadas/análise , Humanos , Hipoglicemia/etiologia , Masculino , Instituições Residenciais , Instituições de Cuidados Especializados de Enfermagem
8.
Invest Ophthalmol Vis Sci ; 59(1): 572-581, 2018 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-29372256

RESUMO

Purpose: Electroretinograms (ERGs) are abnormal in diabetic retinas before the appearance of vascular lesions, providing a possible biomarker for diabetic vision loss. Previously, we reported that decreased retinal dopamine (DA) levels in diabetic rodents contributed to early visual and retinal dysfunction. In the current study, we examined whether oscillatory potentials (OPs) could serve as a potential marker for detecting early inner retinal dysfunction due to retinal DA deficiency. Methods: Retinal function was tested with dark-adapted ERGs, taken at 3, 4, and 5 weeks after diabetes induction with streptozotocin. Electrical responses were analyzed and correlations were made with previously reported retinal DA levels. The effect of restoring systemic DA levels or removing DA from the retina in diabetic mice on OPs was assessed using L-3,4-dihydroxyphenylalanine (L-DOPA) treatments and retina-specific tyrosine hydroxylase (Th) knockout mice (rTHKO), respectively. Results: Diabetic animals had significantly delayed OPs compared to control animals in response to dim, but not bright, flash stimuli. L-DOPA treatment preserved OP implicit time in diabetic mice. Diabetic rTHKO mice had further delayed OPs compared to diabetic mice with normal retinal Th, with L-DOPA treatment also providing benefit. Decreasing retinal DA levels significantly correlated with increasing OP delays mediated by rod pathways. Conclusions: Our data suggest that inner retinal dysfunction in early-stage diabetes is mediated by rod-pathway deficits and DA deficiencies. OP delays may be used to determine the earliest functional deficits in diabetic retinopathy and to establish an early treatment window for DA therapies that may prevent progressive vision loss.


Assuntos
Diabetes Mellitus Experimental/metabolismo , Retinopatia Diabética/metabolismo , Dopamina/deficiência , Células Fotorreceptoras Retinianas Bastonetes/patologia , Animais , Glicemia/metabolismo , Peso Corporal , Adaptação à Escuridão , Diabetes Mellitus Experimental/diagnóstico , Diabetes Mellitus Experimental/tratamento farmacológico , Retinopatia Diabética/diagnóstico , Retinopatia Diabética/tratamento farmacológico , Dopaminérgicos/uso terapêutico , Eletrorretinografia , Feminino , Levodopa/uso terapêutico , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Oscilometria , Tirosina 3-Mono-Oxigenase/genética
9.
Am J Med ; 131(4): 443.e11-443.e24, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-28993187

RESUMO

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]).


Assuntos
Glicemia/análise , Diabetes Mellitus Tipo 2/sangue , Hospitais de Veteranos , Pacientes Internados , Programas de Rastreamento/métodos , Idoso , Diabetes Mellitus Tipo 2/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Medição de Risco , Estados Unidos/epidemiologia
11.
J Diabetes Complications ; 31(9): 1430-1436, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28673663

RESUMO

AIMS: Clinical trials show lifestyle change programs are beneficial, yet large-scale, successful translation of these programs is scarce. We investigated the association between participation in the largest U.S. lifestyle change program, MOVE!, and diabetes control outcomes. METHODS: This longitudinal, retrospective cohort study used Veterans Health Administration databases of patients with diabetes who participated in MOVE! between 2005 and 2012, or met eligibility criteria (BMI ≥25kg/m2) but did not participate. Main outcomes were diabetic eye disease, renal disease, and medication intensification. RESULTS: There were 400,170 eligible patients with diabetes, including 87,366 (22%) MOVE! PARTICIPANTS: Included patients were 96% male, 77% white, with mean age 58years and BMI 34kg/m2. Controlling for baseline measurements and age, race, sex, BMI, and antidiabetes medications, MOVE! participants had lower body weight (-0.6kg), random plasma glucose (-2.8mg/dL), and HbA1c (-0.1%) at 12months compared to nonparticipants (each p<0.001). In multivariable Cox models, MOVE! participants had lower incidence of eye disease (hazard ratio 0.80, 95% CI 0.75-0.84) and renal disease (HR 0.89, 95% CI 0.86-0.92) and reduced medication intensification (HR 0.82, 95% CI 0.80-0.84). CONCLUSIONS: If able to overcome participation challenges, lifestyle change programs in U.S. health systems may improve health among the growing patient population with diabetes.


Assuntos
Diabetes Mellitus/epidemiologia , Diabetes Mellitus/terapia , Participação do Paciente/estatística & dados numéricos , Comportamento de Redução do Risco , Veteranos/estatística & dados numéricos , Programas de Redução de Peso , Idoso , Índice de Massa Corporal , Complicações do Diabetes/epidemiologia , Complicações do Diabetes/prevenção & controle , Diabetes Mellitus/sangue , Feminino , Humanos , Incidência , Estilo de Vida , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Serviços Preventivos de Saúde/estatística & dados numéricos , Estudos Retrospectivos , Resultado do Tratamento , Saúde dos Veteranos , Programas de Redução de Peso/estatística & dados numéricos
12.
J Gene Med ; 19(3)2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28181342

RESUMO

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 Genética
13.
Am J Prev Med ; 52(4): 459-468, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27939239

RESUMO

INTRODUCTION: Lifestyle change programs implemented within healthcare systems could reach many Americans, but their impact on cardiovascular disease (CVD) remains unclear. The MOVE! program is the largest lifestyle change program implemented in a healthcare setting in the U.S. This study aimed to determine whether MOVE! participation was associated with reduced CVD incidence. METHODS: This retrospective cohort study, analyzed in 2013-2015, used national Veterans Health Administration databases to identify MOVE! participants and eligible non-participants for comparison (2005-2012). Patients eligible for MOVE!-obese or overweight with a weight-related health condition, and no baseline CVD-were examined (N=1,463,003). Of these, 169,248 (12%) were MOVE! PARTICIPANTS: Patients were 92% male, 76% white, with mean age 52 years and BMI of 32. The main outcome was incidence of CVD (ICD-9 and procedure codes for coronary artery disease, cerebrovascular disease, peripheral vascular disease, and heart failure). RESULTS: Adjusting for age, race, sex, BMI, statin use, and baseline comorbidities, over a mean 4.9 years of follow-up, MOVE! participation was associated with lower incidence of total CVD (hazard ratio [HR]=0.83, 95% CI=0.80, 0.86); coronary artery disease (HR=0.81, 95% CI=0.77, 0.86); cerebrovascular disease (HR=0.87, 95% CI=0.82, 0.92); peripheral vascular disease (HR=0.89, 95% CI=0.83, 0.94); and heart failure (HR=0.78, 95% CI=0.74, 0.83). The association between MOVE! participation and CVD incidence remained significant when examined across categories of race/ethnicity, BMI, diabetes, hypertension, smoking status, and statin use. CONCLUSIONS: Although participation was limited, MOVE! was associated with reduced CVD incidence in a nationwide healthcare setting.


Assuntos
Doenças Cardiovasculares/prevenção & controle , Estilo de Vida , Programas de Redução de Peso/estatística & dados numéricos , Adulto , Doenças Cardiovasculares/epidemiologia , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Estados Unidos/epidemiologia , United States Department of Veterans Affairs , Saúde dos Veteranos
14.
J Clin Transl Endocrinol ; 4: 66, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29159132
15.
Mol Ther Methods Clin Dev ; 2: 15028, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26366426

RESUMO

Depending on the population examined, from 6 to 83% of people with diabetes mellitus exhibit symptoms of altered gut motility, manifesting as dysphagia, reflux, early satiety, nausea, abdominal pain, diarrhea, or constipation. Hyperglycemia-induced cell loss within the enteric nervous system has been demonstrated in both diabetic rodents and patients with diabetes. Glycemic control is recommended to prevent diabetic gastroenteropathy but is often difficult to achieve with current treatment modalities. We asked if hepatic insulin gene therapy (HIGT) could inhibit the development of diabetic gastroenteropathy in mice. Bowel length, bowel transit, colonic muscle relaxation, and the numbers of both stimulatory and inhibitory neurons in the colonic myenteric plexus were compared in groups of diabetic mice (DM), control nondiabetic mice (Con), and diabetic mice treated with HIGT (HIGT). Delivery of a metabolically responsive insulin transgene to the liver of STZ-diabetic mice with an adeno-associated virus, sero-type 8 (AAV8) produced near-normal blood sugars for over 1 month and prevented anatomic, functional, and neurohistologic changes observed in diabetic mice. We conclude that in addition to normalizing oxidative metabolism in diabetic rodents, HIGT is sufficient to prevent the development of diabetic gastroenteropathy.

16.
J Gene Med ; 17(8-9): 141-52, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26190010

RESUMO

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 , Transgenes
17.
J Diabetes Sci Technol ; 9(4): 857-64, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25759182

RESUMO

BACKGROUND: The most efficacious strategies to improve diabetes control include case management, health care team changes, patient education, and facilitated transmission of patient data to clinicians ("facilitated relay"), but these strategies have not been translated to permit general use in clinical practice. METHODS: A web-based decision support program was developed to include these features, and assessed in patients who had A1c ≥7.0% despite using metformin with/without sulfonylureas or insulin. Staff entered patients' glucose data, obtained management recommendations, reviewed the plan with a clinician, and discussed the new plan with patients. RESULTS: 113 subjects were 96% male and 32% black, with average age 65.6 years and BMI 32.8. During prior primary care, A1c averaged 8.32 ± 0.16% (SEM). In all patients, baseline A1c was 8.18 ± 0.11%, and decreased to 7.54 ± 0.12%, 7.16 ± 0.13%, and 7.54 ± 0.16% at 3, 6, and 12 months, respectively, all P < .001. In 42 subjects who provided glucose data and made requested changes in medications, A1c was 8.12 ± 0.09% at baseline and fell to 7.29 ± 0.11%, 6.98 ± 0.10%, and 7.05 ± 0.10% at 3, 6, and 12 months, respectively, all P < .001. Chart review of 16 subjects followed for 12 months demonstrated that hypoglycemia (symptoms and/or glucose <70 mg/dl) averaged less than 1 episode/patient/month, and there was no severe hypoglycemia. CONCLUSIONS: A novel decision support program improved A1c with little hypoglycemia. Use of this approach should allow primary care teams to keep patients well controlled, and reduce the need for specialist referrals.


Assuntos
Sistemas de Apoio a Decisões Clínicas , Diabetes Mellitus/terapia , Hemoglobinas Glicadas/análise , Pesquisa Translacional Biomédica/métodos , Idoso , Algoritmos , Glicemia/análise , Método Duplo-Cego , Exenatida , Feminino , Georgia , Hospitais de Veteranos , Humanos , Hipoglicemiantes/uso terapêutico , Insulina/administração & dosagem , Internet , Masculino , Metformina/administração & dosagem , Pessoa de Meia-Idade , Pacientes Ambulatoriais , Equipe de Assistência ao Paciente , Educação de Pacientes como Assunto , Peptídeos/administração & dosagem , Atenção Primária à Saúde/organização & administração , Desenvolvimento de Programas , Projetos de Pesquisa , Compostos de Sulfonilureia/administração & dosagem , Estados Unidos , Peçonhas/administração & dosagem , Veteranos
18.
Lancet Diabetes Endocrinol ; 3(3): 173-80, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25652129

RESUMO

BACKGROUND: Programmes for lifestyle change are aimed at improving health but little is known about their effectiveness in clinical settings. The Veterans Health Administration (VA) MOVE! lifestyle change programme is the largest in the USA. We investigated whether participation in MOVE! is associated with reduced incidence of diabetes. METHODS: We did a retrospective observational analysis of data from VA databases in overweight patients and obese patients with a weight-related disorder who had undergone at least 3 years of continuous outpatient care in 2005-12. We used generalised estimating equations to assess characteristics associated with MOVE! participation, and Cox's proportional hazards regression to analyse the association between participation and diabetes incidence. FINDINGS: Of 1·8 million eligible individuals, 238 540 (13%) participated in the MOVE! programme. 19 367 (1% overall, 8% of participants) met criteria for intense and sustained participation (at least eight sessions within 6 months over at least a 4-month span), which was associated with greater weight loss at 3 years than low-intensity or no participation (-2·2% vs -0·64% or 0·46%). Compared with non-participation, incidence of diabetes was reduced by intense and sustained participation (hazard ratio 0·67, 95% CI 0·61-0·74) and low-intensity participation (0·80, 0·77-0·83) in MOVE!. These patterns were consistent across sex, ethnic origin, and age. Participation was most beneficial in patients with high BMI or high random glucose concentrations at baseline (both pinteraction<0·0001). INTERPRETATION: Participation in the MOVE! programme was associated with weight loss and reduced incidence of diabetes, but the rate of participation was low and, therefore, selection bias could have exaggerated these effects. FUNDING: US Department of Veterans Affairs, National Institutes of Health.


Assuntos
Diabetes Mellitus/epidemiologia , Diabetes Mellitus/prevenção & controle , Comportamento de Redução do Risco , Saúde dos Veteranos/tendências , Programas de Redução de Peso/estatística & dados numéricos , Humanos , Incidência , Pacientes Ambulatoriais , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Estados Unidos/epidemiologia , United States Department of Veterans Affairs
19.
J Gen Intern Med ; 30(6): 749-57, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25608739

RESUMO

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/epidemiologia
20.
Diabetes Care ; 37(11): 2934-9, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25168125

RESUMO

OBJECTIVE: Effective treatment algorithms are needed to guide diabetes care at hospital discharge in general medicine and surgery patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: This was a prospective, multicenter open-label study aimed to determine the safety and efficacy of a hospital discharge algorithm based on admission HbA1c. Patients with HbA1c <7% (53.0 mmol/mol) were discharged on their preadmission diabetes therapy, HbA1c between 7 and 9% (53.0-74.9 mmol/mol) were discharged on a preadmission regimen plus glargine at 50% of hospital daily dose, and HbA1c >9% were discharged on oral antidiabetes agents (OADs) plus glargine or basal bolus regimen at 80% of inpatient dose. The primary outcome was HbA1c concentration at 12 weeks after hospital discharge. RESULTS: A total of 224 patients were discharged on OAD (36%), combination of OAD and glargine (27%), basal bolus (24%), glargine alone (9%), and diet (4%). The admission HbA1c was 8.7 ± 2.5% (71.6 mmol/mol) and decreased to 7.3 ± 1.5% (56 mmol/mol) at 12 weeks of follow-up (P < 0.001). The change of HbA1c from baseline at 12 weeks after discharge was -0.1 ± 0.6, -0.8 ± 1.0, and -3.2 ± 2.4 in patients with HbA1c <7%, 7-9%, and >9%, respectively (P < 0.001). Hypoglycemia (<70 mg/dL) was reported in 22% of patients discharged on OAD only, 30% on OAD plus glargine, 44% on basal bolus, and 25% on glargine alone and was similar in patients with admission HbA1c ≤7% (26%) compared with those with HbA1c >7% (31%, P = 0.54). CONCLUSIONS: Measurement of HbA1c on admission is beneficial in tailoring treatment regimens at discharge in general medicine and surgery patients with type 2 diabetes.


Assuntos
Algoritmos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hemoglobinas Glicadas/análise , Hipoglicemiantes/uso terapêutico , Adulto , Idoso , Glicemia/efeitos dos fármacos , Feminino , Seguimentos , Hospitalização , Humanos , Hipoglicemia/epidemiologia , Hipoglicemiantes/administração & dosagem , Insulina Glargina , Insulina de Ação Prolongada/uso terapêutico , Masculino , Pessoa de Meia-Idade , Alta do Paciente , Estudos Prospectivos , Resultado do Tratamento
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