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1.
Adv Exp Med Biol ; 1131: 943-963, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31646540

RESUMO

Insulin secretion in humans is usually induced by mixed meals, which upon ingestion, increase the plasma concentration of glucose, fatty acids, amino acids, and incretins like glucagon-like peptide 1. Beta-cells can stay in the off-mode, ready-mode or on-mode; the mode-switching being determined by the open state probability of the ATP-sensitive potassium channels, and the activity of enzymes like glucokinase, and glutamate dehydrogenase. Mitochondrial metabolism is critical for insulin secretion. A sound understanding of the intermediary metabolism, electrophysiology, and cell signaling is essential for comprehension of the entire spectrum of the stimulus-secretion coupling. Depolarization brought about by inhibition of the ATP sensitive potassium channel, together with the inward depolarizing currents through the transient receptor potential (TRP) channels, leads to electrical activities, opening of the voltage-gated calcium channels, and exocytosis of insulin. Calcium- and cAMP-signaling elicited by depolarization, and activation of G-protein-coupled receptors, including the free fatty acid receptors, are intricately connected in the form of networks at different levels. Activation of the glucagon-like peptide 1 receptor augments insulin secretion by amplifying calcium signals by calcium induced calcium release (CICR). In the treatment of type 2 diabetes, use of the sulfonylureas that act on the ATP sensitive potassium channel, damages the beta cells, which eventually fail; these drugs do not improve the cardiovascular outcomes. In contrast, drugs acting through the glucagon-like peptide-1 receptor protect the beta-cells, and improve cardiovascular outcomes. The use of the glucagon-like peptide 1 receptor agonists is increasing and that of sulfonylurea is decreasing. A better understanding of the stimulus-secretion coupling may lead to the discovery of other molecular targets for development of drugs for the prevention and treatment of type 2 diabetes.


Assuntos
Diabetes Mellitus Tipo 2 , Células Secretoras de Insulina , Cálcio/metabolismo , Diabetes Mellitus Tipo 2/fisiopatologia , Glucose , Humanos , Insulina , Células Secretoras de Insulina/enzimologia , Células Secretoras de Insulina/patologia
2.
Medicine (Baltimore) ; 98(44): e17736, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31689819

RESUMO

To explore associated risk factors and their interactions with type 2 diabetes (T2DM) among the elderly with prediabetes in rural areas in China.A nested case-control study was conducted in a fixed cohort to identify the risk factors for T2DM among the elderly with prediabetes in rural areas of Yiyang City in China. A total of 37 elderly with T2DM were included in the cases group and 111 elderly subjects with prediabetes were matched in the control group. Data related to sociodemographic characteristics, lifestyle behavior, and anthropometric variables were collected by trained staff using standard tools. The risk factors for T2DM were determined using conditional logistic regression analysis, and their additive interactions were also explored.Multivariable conditional logistic regression analysis results showed that overweight/obesity (odds ratio [OR] = 4.80, 95% confidence interval [CI]: 1.20-12.28), family history of diabetes (OR = 3.63, 95% CI: 1.03-12.81), physically inactive (OR = 3.08, 95% CI: 1.14-8.30), high waist-to-hip ratio (WHR) (OR = 3.15, 95% CI: 1.27-7.80), and inadequate diabetes-specific health literacy (DSHL) (OR = 3.92, 95% CI: 1.14-13.48) increased the risk for T2DM. Additive interactions for T2DM were observed between a family history of diabetes and high WHR with a relative excess risk of interaction (RERI) of 10.02 (95% CI: 4.25, 15.78), and between high WHR and overweight or obesity, with an RERI of 3.90 (95% CI: 0.36, 7.44).The independent risk factors for T2DM are overweight or obesity, high WHR, family history of diabetes, physically inactive, and inadequate DSHL. High WHR as a risk factor for T2DM has additive interactions with family history of diabetes and overweight or obesity.


Assuntos
Diabetes Mellitus Tipo 2/etiologia , Estado Pré-Diabético/etiologia , População Rural/estatística & dados numéricos , Idoso , Antropometria , Estudos de Casos e Controles , China/epidemiologia , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/fisiopatologia , Exercício , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estado Pré-Diabético/epidemiologia , Estado Pré-Diabético/fisiopatologia , Risco , Fatores de Risco , Comportamento Sedentário , Relação Cintura-Quadril
3.
Medicine (Baltimore) ; 98(44): e17805, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31689862

RESUMO

Carotid intima-media thickness (C-IMT) increases in patients with adult type-2 diabetes mellitus (DM) and is used for early detection of macrovascular complications. We aimed to investigate the change of C-IMT in prediabetes and type-2 DM patients compared to subjects with normal glucose metabolism (NGM).A total of 180 individuals (60 subjects with NGM, 60 patients with prediabetes and 60 patients with type-2 DM) were included in this study. Routine laboratory and micro-macrovascular involvement were investigated. Urine albumin-creatinine ratio (ACR) was measured for urinary albuminuria detection. In addition to routine laboratory examination, right-left common and internal C-IMT (CC-IMT and IC-IMT) were measured.Systolic and diastolic blood pressure values were found to be higher in prediabetes and type-2 DM groups than NGM group. The prevalence of nephropathy and presence of CAD were higher in type-2 DM groups than prediabetes. Glucose, glycated hemoglobin (HbA1c), total cholesterol, low-density lipoprotein (LDL) cholesterol, triglycerides, blood urea nitrogen, creatinine, high sensitive C reactive protein (hs-CRP) levels and urinary ACR were significantly higher in patients within prediabetes and type-2 DM groups than NGM group. Glucose, HbA1c and hs-CRP levels were found to be higher in type-2 DM groups than prediabetes. Estimated glomerular filtration rate and high-density lipoprotein (HDL) cholesterol level was found to be lower in patients within prediabetes and type-2 DM groups than NGM group. Right-left-mean CC-IMT and IC-IMT values were found to be higher in prediabetes and type-2 DM groups than NGM group. Left IC-IMT, left CC-IMT, and mean IC-IMT values were found to be higher in type-2 DM patients compared to prediabetes. LDL and HDL cholesterols, HbA1c, and hs-CRP levels were independently associated with IC-IMT and CC-IMT.C-IMT values were significantly higher in impaired glucose metabolism compared to NGM. C-IMT measurement may be used as part of routine screening of macrovascular complication in patients with prediabetes and newly diagnosed type-2 DM.


Assuntos
Espessura Intima-Media Carotídea , Diabetes Mellitus Tipo 2/diagnóstico por imagem , Angiopatias Diabéticas/diagnóstico , Estado Pré-Diabético/diagnóstico por imagem , Idoso , Glicemia/metabolismo , Pressão Sanguínea , Proteína C-Reativa/metabolismo , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Doença da Artéria Coronariana/diagnóstico , Estudos Transversais , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/fisiopatologia , Feminino , Hemoglobina A Glicada/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Estado Pré-Diabético/sangue , Estado Pré-Diabético/fisiopatologia
5.
Bratisl Lek Listy ; 120(7): 532-535, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31602990

RESUMO

AIM: The aim of this study is to evaluate the association between urinary megalin, renal function, blood pressure, lipid profile, vitamin D and glycemic control in patients with type 2 diabetes mellitus (T2DM). METHODS: . This was a cross-sectional study which recruited 209 patients with T2DM. Urinary megalin was positively associated with systolic blood pressure (SBP) (r=0.218, p=0.04) but negatively with glomerular filtration rate (GFR) (r=-0.16, p=0.023). The levels of urinary albumin, triglycerides (TGs) and glycosylated hemoglobin (HbA1c) were higher in the "high-megalin" group, compared to those in "low-megalin" group. Moreover, there was a significant inverse association between vitamin D3 levels and megalin levels in urine (OR=0.281, p=0.047). CONCLUSION: Our study showed for the first time that megalin is associated with progression factors of diabetic nephropathy as well as vitamin D deficiency (Tab. 3, Fig. 1, Ref. 15).


Assuntos
Nefropatias Diabéticas/urina , Proteína-2 Relacionada a Receptor de Lipoproteína de Baixa Densidade/análise , Albuminúria , Colecalciferol/urina , Estudos Transversais , Diabetes Mellitus Tipo 2/fisiopatologia , Diabetes Mellitus Tipo 2/urina , Nefropatias Diabéticas/fisiopatologia , Progressão da Doença , Taxa de Filtração Glomerular , Hemoglobina A Glicada/urina , Humanos , Triglicerídeos/urina , Deficiência de Vitamina D
6.
Pediatr Endocrinol Rev ; 17(1): 4-16, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31599132

RESUMO

Growth hormone (GH) is a pleiotropic hormone that coordinates an array of physiological processes including growth and metabolism. GH promotes anabolic action in all tissues except adipose, where it catabolizes stored fat to release energy for the promotion of growth in other tissues. However, chronic stimulation of lipolysis by GH results in an increased flux of free fatty acids (FFAs) into systemic circulation. Hence, a sustained release of high levels of GH contributes significantly to the development of insulin resistance by antagonizing the anti-lipolytic action of insulin. The molecular pathways associated with the lipolytic effect of GH in adipose tissue however, remain elusive. Recent studies have provided molecular insights into GH-induced lipolysis and impairment of insulin signaling. This review discusses the physiological and metabolic actions of GH on adipose tissue as well as GH-mediated deregulation of the FSP27-PPARγ axis which alters adipose tissue homeostasis and contributes to the development of insulin resistance and Type 2 diabetes.


Assuntos
Diabetes Mellitus Tipo 2 , Hormônio do Crescimento Humano , Resistência à Insulina , Lipólise , Tecido Adiposo/efeitos dos fármacos , Diabetes Mellitus Tipo 2/induzido quimicamente , Diabetes Mellitus Tipo 2/fisiopatologia , Hormônio do Crescimento Humano/metabolismo , Hormônio do Crescimento Humano/farmacologia , Humanos , Lipólise/efeitos dos fármacos
7.
Arch Endocrinol Metab ; 63(5): 509-515, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31482956

RESUMO

OBJECTIVE: We denote the four major factors related to the development of type 2 diabetes (T2D) as "diabetes factor" (DF); increased insulin resistance (IR); decreased glucose effectiveness (GE); and the first-and-second-phase of insulin secretion (FPIS, SPIS). The level of hemoglobin (Hb) was found to be related to IR and FPIS, but no-known studies focused on its role in relation to SPIS and GE. In this study, we aim to evaluate the relationships between Hb and all four DFs in the same individual. SUBJECTS AND METHODS: We randomly enrolled 24,407 men and 24,889 women between 30 and 59 years old. IR, FPIS, SPIS and GE were measured according to equations published in our previous studies. To compare the slopes between Hb and the four DFs with different units, we converted their units to percent of change per unit of increased Hb. RESULTS: Age, HDL-cholesterol and GE were higher in women; BMI, blood pressure, LDL-cholesterol, TG, Hb, FPIS, SPIS and IR were higher in men. After they were converted into percentage, the closeness of their relationships to Hb, from the highest to the lowest, were GE, IR, FPIS and SPIS for women and IR, GE, FPIS and SPIS for men. GE was the only one negatively related to Hb. CONCLUSIONS: Our data showed that IR, FPIS and SPIS were both positively and, GE negatively, related to the Hb in adult Chinese. For women, GE had the closest association with Hb; for men, it was IR. Both phases of insulin secretion had relatively weaker relationships than IR and GE.


Assuntos
Glicemia/fisiologia , Diabetes Mellitus Tipo 2/fisiopatologia , Resistência à Insulina/fisiologia , Secreção de Insulina/fisiologia , Adulto , Grupo com Ancestrais do Continente Asiático , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Distribuição Aleatória
8.
Medicine (Baltimore) ; 98(36): e16860, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31490370

RESUMO

BACKGROUND: The blood glucose response to moderate-intensity exercise remains unclear for patients with type 2 diabetes (T2DM). In addition, little is known about determinants of blood glucose response to a 12-week moderate-intensity exercise training. Therefore, this study aimed to explore trends in blood glucose in response to a 12-week moderate-intensity exercise training in patients with T2DM and to explore the predictors of post-exercise blood glucose (PEBG) and exercise-induced glucose response (EIGR). METHODS: A prospective longitudinal study was conducted. Of the 66 participants with T2DM recruited from outpatient clinics of a medical center, 20 were eligible to enroll in a 12-week moderate-intensity exercise training. Participants were randomly assigned to 1 of 3 exercise times (morning, afternoon, or evening). Blood glucose were measured pre- and post-exercise. The EIGR was calculated by subtracting the PEBG from the before-exercise blood glucose (BEBG). Generalized estimating equations were used to examine the trends and predictors of PEBG and EIGR. RESULTS: The BEBG declined progressively (ß = -1.69, P < .001); while the PEBG (ß = -0.18, P = .08) remained stable over time during the 12-week exercise training. Higher BEBG predicted higher (ß = 0.53, P < .001) PEBG. Higher baseline maximum oxygen uptake (VO2max) contributed to a larger magnitude of EIGR; higher HgbA1c and BEBG predicted higher EIGR (ß = 0.27, P = .02; ß = 0.45, P < .001); afternoon or evening exercise predicted lower (ß = -13.2, P = .04; ß = -5.96, P = .005) EIGR than did morning exercise. CONCLUSIONS: A 12-week moderate-intensity exercise training appears safe for patients with T2DM. Time of day for exercise, baseline VO2max, and baseline metabolic control may influence the impact of exercise for individuals with T2DM. These findings provide considerations for design of optimal exercise training for T2DM patients.


Assuntos
Glicemia/metabolismo , Diabetes Mellitus Tipo 2/fisiopatologia , Diabetes Mellitus Tipo 2/terapia , Exercício/fisiologia , Adulto , Índice de Massa Corporal , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Consumo de Oxigênio/fisiologia , Estudos Prospectivos
9.
Diabetes Res Clin Pract ; 155: 107805, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31377226

RESUMO

AIMS: Intrarenal Aquaporin 5 (AQP5) is upregulated in patients with diabetic nephropathy. Here we investigate whether urinary AQP5 is independently associated with estimated glomerular filtration rate (eGFR) decline in patients with type 2 diabetes and nephropathy. METHODS: Baseline urine samples (n = 997) from patients with type 2 diabetes and nephropathy of the sulodexide macroalbuminuria trial were measured for AQP5 through enzyme-linked immunosorbent assays. Pearson correlation and multiple linear regression between AQP5 with eGFR slope (calculated by ≥3 serum creatinine during follow-up) was performed, and association with fast renal function decline, defined as eGFR slope less than 3.0 mL/min/1.73 m2/year, was determined by logistic regression. RESULTS: Follow-up eGFR data >1.4 years from n = 700 were available for analyses. AQP5 was undetectable in 138 patients. Tertiles of AQP5 were 0.4 [0-2.2], 7.3 [5.9-9.1], and 16.0 [13.0-21.6] (ng/mL), respectively (p < 0.01). Patients in the highest tertile of AQP5 had significantly higher total cholesterol, lower baseline eGFR, and higher levels of albuminuria compared to the lowest tertile. AQP5 was inversely correlated with eGFR slope (Pearson's r = -0.12, p < 0.001), and independent of clinical risk factors age, sex, race, and baseline systolic and diastolic blood pressure, hemoglobin A1c, total cholesterol, eGFR, and urine albumin-to-creatinine ratio (ß = -0.05, p < 0.004). Furthermore, AQP5 was significantly associated with fast eGFR decline (Odds Ratio = 1.03 (95% Confidence Interval 1.003-1.06), p < 0.03). CONCLUSION: Our data suggest that baseline AQP5 is independently associated with the progression of eGFR decline in patients with type 2 diabetes and nephropathy.


Assuntos
Aquaporina 5/urina , Diabetes Mellitus Tipo 2/urina , Nefropatias Diabéticas/urina , Diabetes Mellitus Tipo 2/fisiopatologia , Nefropatias Diabéticas/fisiopatologia , Feminino , Taxa de Filtração Glomerular , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco
10.
Adv Exp Med Biol ; 1158: 143-182, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31452140

RESUMO

Mitochondrial dysfunction is discussed as a key player in the pathogenesis of type 2 diabetes mellitus (T2Dm), a highly prevalent disease rapidly developing as one of the greatest global health challenges of this century. Data however about the involvement of mitochondria, central hubs in bioenergetic processes, in the disease development are still controversial. Lipid and protein homeostasis are under intense discussion to be crucial for proper mitochondrial function. Consequently proteomics and lipidomics analyses might help to understand how molecular changes in mitochondria translate to alterations in energy transduction as observed in the healthy and metabolic diseases such as T2Dm and other related disorders. Mitochondrial lipids integrated in a tool covering proteomic and functional analyses were up to now rarely investigated, although mitochondrial lipids might provide a possible lynchpin in the understanding of type 2 diabetes development and thereby prevention. In this chapter state-of-the-art analytical strategies, pre-analytical aspects, potential pitfalls as well as current proteomics and lipidomics-based knowledge about the pathophysiological role of mitochondria in the pathogenesis of type 2 diabetes will be discussed.


Assuntos
Biologia Computacional , Diabetes Mellitus Tipo 2 , Fígado , Mitocôndrias , Músculo Esquelético , Proteômica , Diabetes Mellitus Tipo 2/fisiopatologia , Humanos , Metabolismo dos Lipídeos , Fígado/fisiopatologia , Mitocôndrias/metabolismo , Músculo Esquelético/fisiopatologia
11.
Diabetes Res Clin Pract ; 155: 107813, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31408665

RESUMO

AIMS: To assess cardiac autonomic control and its association with submaximal exercise measured using the 6-minute walk test (6MWT) in subjects with type-2 diabetes mellitus (DM2). METHODS: Cardiac autonomic control was assessed using Ewing's tests and heart rate variability (HRV) in DM2 volunteers (DG, n = 22) and sex-, age- and body mass index-matched non-diabetic controls (CG, n = 22) before, during and after 6MWT. RESULTS: Before the 6MWT, DG presented lower HRV represented by reduced SDNN [median 28.9 ms2 (IQR:18.6-35.4) vs. 45.1 (IQR:39.2-62.67), p < 0.001] and Total Power [median 785 ms2 (IQR:256-1264) vs. 1757 ms2 (IQR:1006-2912), p = 0.004]. Exercise capacity was reduced in DG [maximal predicted distance (%) = 88.4 ±â€¯6.4 vs. 95.2 ±â€¯11.0%, p = 0.018]. DG demonstrated lower global HRV during recovery and lower parasympathetic drive, represented by reduced RMSSD, during all phases of the 6MWT. Moreover, supine HR (r = -0.32), HR orthostatism (ρ = -0.40), SDNN pre-6MWT (ρ = 0.39), TP pre-6MWT (ρ = 0.38), Valsalva ratio (ρ = 0.39) and 30:15 ratio (ρ = 0.38) were all correlated with maximal walked distance. CONCLUSIONS: DM2 subjects presented abnormal HRV during and after submaximal exercise. Furthermore, autonomic control impairment in orthostatism, represented by lower global HRV (SDNN, Total power) and lower Ewing's indexes (Valsalva and 30:15 ratios), was associated with lower exercise capacity.


Assuntos
Sistema Nervoso Autônomo/fisiopatologia , Diabetes Mellitus Tipo 2/fisiopatologia , Teste de Esforço/métodos , Tolerância ao Exercício/fisiologia , Exercício/fisiologia , Frequência Cardíaca/fisiologia , Manobra de Valsalva/fisiologia , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
12.
Life Sci ; 233: 116746, 2019 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-31401313

RESUMO

AIM: Diabetes accelerates pro-atherogenic and pro-osteogenic phenotypes of vascular smooth muscle cells (VSMCs), an important process for vascular calcification. Reticulocalbin 2 (RCN2) is a candidate gene for atherosclerosis and involved in vascular remodeling in hypertension. However, the role of RCN2 in VSMCs calcification under diabetic conditions is unclear. MATERIALS AND METHODS: Expression of RCN2 and Runt-related transcription factor 2 (Runx2) in femoropopliteal arterial plaques was compared between type 2 diabetes mellitus (DM) and non-DM patients using immunohistochemical staining (IHCS). Human aortic VSMCs (HAVSMCs) were analyzed under RCN2 gene knockdown and overexpression conditions. Alizarin red staining and intracellular calcium deposition quantification were used to observe calcification induced in vitro under normal glucose or high glucose combined with ß-glycerol phosphoric acid conditions. The cells were investigated for gene modulation of osteogenic differentiation markers using Western blotting. KEY FINDINGS: The expression of RCN2 and Runx2 in femoropopliteal artery plaques was significantly higher in DM than in non-DM patients. In addition, a significant positive correlation was observed between RCN2 and Runx2 levels. RCN2 was highly expressed when HAVSMCs were treated with high glucose and the expression levels correlated with the calcification characteristics. RCN2 upregulated osteogenic transformation markers Runx2 and Osterix in HAVSMCs and downregulated contractile phenotype markers α-SMA and SM22α. SIGNIFICANCE: The results from this study indicate RCN2 is a major factor in mediating the calcification process of HAVSMCs in diabetic conditions. Thus, RCN2 may serve as a future therapeutic target for vascular calcification in diabetes.


Assuntos
Aterosclerose/complicações , Proteínas de Ligação ao Cálcio/metabolismo , Subunidade alfa 1 de Fator de Ligação ao Core/metabolismo , Diabetes Mellitus Tipo 2/fisiopatologia , Músculo Liso Vascular/citologia , Osteogênese , Calcificação Vascular/etiologia , Proteínas de Ligação ao Cálcio/genética , Estudos de Casos e Controles , Diferenciação Celular , Células Cultivadas , Subunidade alfa 1 de Fator de Ligação ao Core/genética , Humanos , Músculo Liso Vascular/metabolismo , Calcificação Vascular/metabolismo , Calcificação Vascular/patologia
13.
Expert Opin Investig Drugs ; 28(9): 741-747, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31398075

RESUMO

Introduction: Type 2 diabetes is a complex metabolic disorder defined by hyperglycemia which occurs because of impaired insulin secretion and sensitivity. There is an ongoing need to develop novel therapies that are effective and safe with minimal side effects and long-term durability. TTP399 is a hepatoselective, glucokinase activator with potential for treating type 2 diabetes. Areas covered: This is a review of the available data regarding the mechanism of action and the pharmacokinetics of TTP399. The efficacy and safety of the drug for treatment of type 2 diabetes will also be examined with an emphasis on the results of a randomized, controlled phase 2 study. Expert opinion: TTP399 could offer significant advantages over currently available therapies for type 2 diabetes. It successfully lowers glucose without side effects such as hypoglycemia, weight gain or dyslipidemia. Larger trials are required to understand long-term efficacy and safety of this medication in various patient populations and to elucidate its effect on the pathologic processes underpinning type 2 diabetes.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/farmacologia , Animais , Glicemia/efeitos dos fármacos , Diabetes Mellitus Tipo 2/fisiopatologia , Glucoquinase/efeitos dos fármacos , Glucoquinase/metabolismo , Humanos , Hipoglicemia/induzido quimicamente , Hipoglicemiantes/efeitos adversos , Fígado/metabolismo , Ensaios Clínicos Controlados Aleatórios como Assunto
14.
Expert Opin Investig Drugs ; 28(9): 811-820, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31402716

RESUMO

Introduction: More than 424 million adults have diabetes mellitus (DM). This number is expected to increase to 626 million by 2045. The majority (90-95%) of people with DM has type 2-diabetes (T2DM). The continued prevalence of DM and associated complications has prompted investigators to find new therapies. One of the most recent additions to the anti-diabetic armamentarium are inhibitors of sodium-glucose co-transporters 1 and 2 (SGLT1, SGLT2). Areas covered: The authors review the status of SGLT2 inhibitors for the treatment of T2DM and place an emphasis on those agents in early phase clinical trials. Data and information were retrieved from American Diabetes Association, Diabetes UK, ClinicalTrials.gov, PubMed, and Scopus websites. The keywords used in the search were T2DM, SGLT1, SGLT2, and clinical trials. Expert opinion: The benefits of SGLT inhibitors include reductions in serum glycated hemoglobin (HbA1c), body weight, blood pressure and cardiovascular and renal events. However, SGLT inhibitors increase the risk of genitourinary tract infections, diabetic ketoacidosis, and bone fractures. The development of SGLT inhibitors with fewer side effects and as combination therapies are the key to maximizing the therapeutic effects of this important class of anti-diabetic drug.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Transportador 1 de Glucose-Sódio/antagonistas & inibidores , Inibidores do Transportador 2 de Sódio-Glicose/farmacologia , Adulto , Animais , Diabetes Mellitus Tipo 2/fisiopatologia , Desenvolvimento de Medicamentos/métodos , Hemoglobina A Glicada/metabolismo , Humanos , Hipoglicemiantes/efeitos adversos , Hipoglicemiantes/farmacologia , Transportador 1 de Glucose-Sódio/metabolismo , Transportador 2 de Glucose-Sódio/efeitos dos fármacos , Transportador 2 de Glucose-Sódio/metabolismo , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos
15.
Orv Hetil ; 160(34): 1346-1352, 2019 Aug.
Artigo em Húngaro | MEDLINE | ID: mdl-31423831

RESUMO

Introduction: Some meta-analyses suggested a positive effect of metformin therapy on lipid parameters, but the potential beneficial effect of metformin on cardiovascular risk in type 2 diabetes is not entirely clear. Aim: We investigated the effect of metformin therapy on lipid parameters and cardiovascular risk in patients with type 2 diabetes. Method: In a cross-sectional, monocentric study, 102 patients with type 2 diabetes without lipid-lowering medication were analysed for lipid profile and cardiovascular risk (United Kingdom Prospective Diabetes Study Risk Calculator) depending on metformin therapy. The patients were divided into two subgroups regarding with (n = 52) or without metformin therapy (n = 50). Results: Patients with metformin therapy had significantly lower total cholesterol and LDL cholesterol levels than patients without metformin (p<0.01 and p<0.05). This effect was independent from glucose control. No intrinsic effect of metformin could be found on systolic blood pressure, HDL cholesterol, triglycerides, and long-term cardiovascular risk using a multivariable risk assessment score. Conclusion: Metformin therapy has beneficial effects on cholesterol levels without improving cardiovascular risk in patients with type 2 diabetes. Orv Hetil. 2019; 160(34): 1346-1352.


Assuntos
Doenças Cardiovasculares/prevenção & controle , HDL-Colesterol/efeitos dos fármacos , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/efeitos adversos , Metformina/efeitos adversos , Doenças Cardiovasculares/epidemiologia , Colesterol/sangue , HDL-Colesterol/sangue , Estudos Transversais , Diabetes Mellitus Tipo 2/fisiopatologia , Feminino , Humanos , Hipoglicemiantes/uso terapêutico , Lipídeos/sangue , Metformina/uso terapêutico , Estudos Prospectivos , Fatores de Risco , Reino Unido
16.
Rev Med Chil ; 147(4): 480-489, 2019 Apr.
Artigo em Espanhol | MEDLINE | ID: mdl-31344211

RESUMO

Physical training is recommended in several studies and guidelines for the control of type 2 diabetes mellitus (DM2) and its complications. We performed a systematic review about the effects of aerobic training (AT), resistance (RT) or the combination of both (AT/ RT), on glycated hemoglobin (HbA1c) in patients with DM2. Therefore, we included 15 clinical trials with at least 12 weeks duration about training program or recommendations of physical exercise, that evaluated the reduction in HbA1c levels in patients with DM2. Information was obtained on training modality (AT, RT or AT / RT), training parameters, duration and weekly training frequency. The results showed increases in peak or maximal oxygen uptake, exercise tolerance time and muscle strength, depending on the type of training, and a reduction in HbA1c levels. We conclude that exercise training is associated with reductions of HbA1c in patients with DM2. Thus, it can be a complementary tool in the management of these patients.


Assuntos
Diabetes Mellitus Tipo 2/prevenção & controle , Diabetes Mellitus Tipo 2/fisiopatologia , Condicionamento Físico Humano/métodos , Treinamento de Resistência/métodos , Diabetes Mellitus Tipo 2/metabolismo , Hemoglobina A Glicada/análise , Humanos , Condicionamento Físico Humano/fisiologia , Reprodutibilidade dos Testes , Fatores de Tempo , Resultado do Tratamento
17.
Hypertension ; 74(3): 687-696, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31327268

RESUMO

Metabolic syndrome is a cause of coronary artery disease and type 2 diabetes mellitus. Camk2n1 resides in genomic loci for blood pressure, left ventricle mass, and type 2 diabetes mellitus, and in the spontaneously hypertensive rat model of metabolic syndrome, Camk2n1 expression is cis-regulated in left ventricle and fat and positively correlates with adiposity. Therefore, we knocked out Camk2n1 in spontaneously hypertensive rat to investigate its role in metabolic syndrome. Compared with spontaneously hypertensive rat, Camk2n1-/- rats had reduced cardiorenal CaMKII (Ca2+/calmodulin-dependent kinase II) activity, lower blood pressure, enhanced nitric oxide bioavailability, and reduced left ventricle mass associated with altered hypertrophic networks. Camk2n1 deficiency reduced insulin resistance, visceral fat, and adipogenic capacity through the altered cell cycle and complement pathways, independent of CaMKII. In human visceral fat, CAMK2N1 expression correlated with adiposity and genomic variants that increase CAMK2N1 expression associated with increased risk of coronary artery disease and type 2 diabetes mellitus. Camk2n1 regulates multiple networks that control metabolic syndrome traits and merits further investigation as a therapeutic target in humans.


Assuntos
Proteínas de Transporte/genética , Hipertensão/genética , Hipertrofia Ventricular Esquerda/genética , Síndrome Metabólica/fisiopatologia , Adiposidade/genética , Animais , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/fisiopatologia , Modelos Animais de Doenças , Regulação da Expressão Gênica , Humanos , Hipertensão/fisiopatologia , Hipertrofia Ventricular Esquerda/fisiopatologia , Síndrome Metabólica/genética , Distribuição Aleatória , Ratos , Ratos Endogâmicos SHR , Medição de Risco , Sensibilidade e Especificidade
18.
Medicine (Baltimore) ; 98(28): e16255, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31305406

RESUMO

RATIONALE: Hemichorea-hemiballism, a rare manifestation of non-ketotic hyperglycemia, characterized by involuntary arrhythmic motions involving one side of the body, results from focal lesions in the contralateral caudate nucleus and putamen. Hyperkinetic disorders can be complications of uncontrolled diabetes mellitus and should not be ignored. PATIENT CONCERNS: We present the case of a 39-year-old woman who presented to the emergency department with a 3-day history of left-sided hemichorea-hemiballism. She had type 2 diabetes mellitus with poor control and maintenance of regular hemodialysis. DIAGNOSES: The patient was diagnosed as hyperglycemia, normal ketone body and hemichorea-hemiballism based on laboratory examination, computed tomography (CT) scan, and brain magnetic resonance image (MRI). INTERVENTIONS: Intensive glycemic control via insulin injection was prescribed for correction of hyperglycemia. OUTCOMES: The unilateral involuntary movements subsided progressively over four weeks. The patient's hemichorea had completely resolved at the three-month follow-up. LESSONS: This unusual clinical presentation is often accompanied by severe hyperglycemia. Appropriate blood glycemic control is important. If physicians recognize and provide early treatment for this disease, it is usually treatable and has a good prognosis.


Assuntos
Coreia/complicações , Diabetes Mellitus Tipo 2/complicações , Discinesias/complicações , Hiperglicemia/complicações , Adulto , Coreia/diagnóstico , Coreia/tratamento farmacológico , Coreia/fisiopatologia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/fisiopatologia , Diagnóstico Diferencial , Discinesias/diagnóstico , Discinesias/tratamento farmacológico , Discinesias/fisiopatologia , Feminino , Humanos , Hiperglicemia/diagnóstico , Hiperglicemia/tratamento farmacológico , Hiperglicemia/fisiopatologia
19.
Vasc Health Risk Manag ; 15: 101-107, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31190848

RESUMO

Introduction: Theoretically, first-degree relatives (FDRs) of type 2 diabetes mellitus (T2DM) are predisposed to have earlier and more severe atherosclerosis than non-FDR due to hereditary insulin resistance. A previous study reported that atherosclerotic plaques were found in 45.2% of young adults FDR of T2DM, but the study did not include non-FDR as control group. The aim of this study was to compare subclinical atherosclerosis (carotid intima-media thickness, CIMT) between FDR of T2DM and non-FDR. Method: This was a cross-sectional study involving 16 FDR subjects and 16 age-sex matched non-FDR subjects, aged 19-40 years, with normal glucose tolerance and no hypertension. Collected data included demographic characteristic, anthropometric measurement (BMI and waist circumference), laboratory analysis (fasting blood glucose, HbA1c, lipid profile), and CIMT examination (using B-mode ultrasound). Results: The mean of CIMT in the FDR group was higher than that in the non-FDR group (0.44 mm vs 0.38 mm, p=0.005). After adjusting for waist circumference, BMI, low-density lipoprotein cholesterol, and triglyceride, CIMT maintained significant difference between FDR and non-FDR subjects. BMI and waist circumference showed moderate correlation with CIMT. Conclusion: CIMT in young adult FDR of T2DM is thicker than that in age-and sex-matched non-FDR population.


Assuntos
Artérias Carótidas/diagnóstico por imagem , Doenças das Artérias Carótidas/diagnóstico por imagem , Espessura Intima-Media Carotídea , Diabetes Mellitus Tipo 2/genética , Adulto , Doenças Assintomáticas , Biomarcadores/sangue , Glicemia/análise , Pressão Sanguínea , Artérias Carótidas/patologia , Doenças das Artérias Carótidas/genética , Doenças das Artérias Carótidas/patologia , Estudos de Casos e Controles , Estudos Transversais , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/fisiopatologia , Feminino , Predisposição Genética para Doença , Hereditariedade , Humanos , Masculino , Linhagem , Fenótipo , Placa Aterosclerótica , Valor Preditivo dos Testes , Fatores de Risco , Adulto Jovem
20.
Fisioter. Pesqui. (Online) ; 26(2): 137-144, abr.-jun. 2019. tab
Artigo em Português | LILACS | ID: biblio-1012143

RESUMO

RESUMO O objetivo deste trabalho foi comparar o pico de torque e flexibilidade dos membros inferiores de indivíduos com e sem diabetes mellitus tipo 2 (DM2). O método foi o estudo com grupos expostos e não expostos ao DM2. Foram incluídos indivíduos com diagnóstico médico de DM2, encaminhados para eletroneuromiografia, e não expostos ao DM2. Foram excluídos da pesquisa indivíduos com idade superior a 70 anos ou que, por algum motivo, não conseguiram realizar um ou dois dos testes. A amostra foi não probabilística, composta por 64 indivíduos: 34 (53,1%) expostos ao DM2 e 30 não expostos; 50 (78,1%) eram do sexo feminino, a idade média era de 60,7±7,1 anos, e o membro inferior dominante era o direito em 57 (89,1%) dos indivíduos. Comparando indivíduos com e sem diagnóstico de DM2, observou-se redução do torque de flexão à esquerda, em velocidade angular de 120° (25,94±2,26 vs. 33,79±2,4nm, p=0,027, respectivamente). Relatou-se menor valor do torque de dorsiflexão à direita, em velocidade angular de 60°, dos diabéticos em relação aos não diabéticos (10,95±0,89 vs. 13,95±0,96nm, p=0,033, respectivamente). Ao comparar indivíduos com DM2, com e sem diagnóstico de neuropatia diabética periférica (NDP), notou-se maior déficit de flexão entre os indivíduos neuropatas em comparação com não neuropatas (46,57±9,47 vs. 11,63±13,85nm, p=0,049, respectivamente). Não foram encontradas diferenças estatisticamente significativas ao comparar os grupos de expostos e não expostos ao DM2 e diabéticos neuropatas e não neuropatas.


RESUMEN El objetivo de este trabajo fue comparar el pico de torque y la flexibilidad de los miembros inferiores de individuos con y sin diabetes mellitus tipo 2 (DM2). El método fue el estudio con grupos expuestos y no expuestos al DM2. Se incluyeron individuos con diagnóstico médico de DM2, encaminados para electroneuromiografía, y no expuestos al DM2. Se excluyeron de la investigación a individuos mayores de 70 años o que, por algún motivo, no pudieron realizar una o dos de las pruebas. La muestra fue no probabilística, compuesta por 64 individuos: 34 (53,1%) expuestos al DM2 y 30 no expuestos; 50 (78,1%) eran de sexo femenino, la edad media era de 60,7±7,1 años, y el miembro inferior dominante era el derecho en 57 (89,1%) de los individuos. En comparación con individuos con y sin diagnóstico de DM2, se observó reducción del torque de flexión a la izquierda, en velocidad angular de 120° (25,94±2,26 frente a 33,79±2,4nm, p=0,027, respectivamente). Se ha reportado un menor valor del torque de dorsiflexión a la derecha, en velocidad angular de 60°, de los diabéticos con relación a los no diabéticos (10,95±0,89 frente a 13,95±0,96nm, p=0,033, respectivamente). Al comparar individuos con DM2, con y sin diagnóstico de neuropatía diabética periférica (NDP), se notó mayor déficit de flexión entre los individuos neuropáticos en comparación con no neuropáticos (46,57±9,47 vs. 11,63±13,85nm, p=0,049, respectivamente). No se encontraron diferencias estadísticamente significativas al comparar los grupos de expuestos y no expuestos al DM2 y los diabéticos neuropáticos y no neuropáticos.


ABSTRACT To compare the muscle strength and flexibility of the lower limbs of individuals with and without T2DM. The method was a study of the types exposed and unexposed to T2DM. Individuals diagnosed with T2DM, individuals referred to electromyography, and those unexposed to T2DM were included. The exclusion criteria were: individuals over 70 years old; those who for some reason failed to complete one or both tests. The study population consisted of 64 individuals; 34 (53.1%) exposed to DM and 30 unexposed, 50 (78.1%) were female, the mean age was 60.7±7.1 and the dominant lower limb was right in 57 (89.1%) individuals. Comparing individuals with and without a diagnosis of DM, one observed a reduction in the flexion torque on the left at a 120 ° angular velocity in diabetics individuals compared with nondiabetic patients, 25.94±2.26 vs 33.79±2, 4nm, p=0.027, respectively. The reduction in dorsiflexion torque on the right, at a 60 ° angular velocity was observed in diabetics compared with nondiabetic patients, 10.95±0.89 vs. 13.95±0.96nm, p=0.033, respectively. When comparing diabetic individuals with and without a diagnosis of PDN, one observed a greater flexion deficit among neuropathic individuals when compared with non-neuropathic individuals, 46.57±9.47 vs 11.63±13.85nm, p=0.049, respectively. No statistically significant differences were found when comparing groups exposed and unexposed to T2DM, and neuropathic and non-neuropathic diabetics.


Assuntos
Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Amplitude de Movimento Articular/fisiologia , Torque , Extremidade Inferior/fisiologia , Diabetes Mellitus Tipo 2/fisiopatologia , Fenômenos Biomecânicos/fisiologia , Neuropatias Diabéticas/fisiopatologia , Dinamômetro de Força Muscular
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