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1.
J Diabetes Complications ; 25(1): 63-72, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-19781960

RESUMO

The purpose of this article is to provide reasons to start looking more critically at the existing glucose-lowering therapies in diabetes, from the point of their effect on cardiac metabolism. The presented arguments begin with the description of major differences between metabolism in myocardium and the skeletal muscle and of examples of myocardial metabolic inflexibility observed in heart failure and Type 2 diabetes. It is proposed that the metabolic inflexibility of diabetic myocardium should be taken into consideration as a factor to explain causes of unexpected cardiovascular mortality observed in the recently published outcome studies such as Action to Control Cardiovascular Risk in Diabetes (ACCORD) and Veterans Affairs Diabetes Feasibility Trial. The same reasoning was applied to challenge the "legacy effect" of the UK Prospective Diabetes Study and Steno-2 trials. A striking paucity of data on the effects of antihyperglycemic therapies on cardiac metabolism is brought to attention in spite of the fact that the technology to study human cardiac metabolism in vivo is available. It is hoped that increased focus on research in this area could contribute to improved cardiovascular safety monitoring of various antihyperglycemic regimens and thereby enhance our ability to save more lives of patients with Type 2 diabetes.


Assuntos
Diabetes Mellitus/tratamento farmacológico , Coração/efeitos dos fármacos , Hipoglicemiantes/efeitos adversos , Miocárdio/metabolismo , Doenças Cardiovasculares/induzido quimicamente , Doenças Cardiovasculares/mortalidade , Diabetes Mellitus/metabolismo , Cardiomiopatias Diabéticas/metabolismo , Glucose/metabolismo , Humanos , Insulina/efeitos adversos , Insulina/uso terapêutico , Resistência à Insulina/fisiologia , Músculo Esquelético/metabolismo
2.
Expert Rev Endocrinol Metab ; 5(6): 875-889, 2010 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30780830

RESUMO

Leptin, a pluripotent adipokine, has been discovered as a hormone controlling energy balance in hypothalamic neuroendocrine centers. In addition, recent studies provided ample evidence that leptin can be produced by cells other than adipocytes, and that the hormone can regulate many physiological processes other than energy balance and appetite. In this context, it is not surprising that both leptin excess as well as leptin insufficiency have been implicated in various pathologies. Consequently, despite initially disappointing results with recombinant leptin as the drug for obesity management, new leptin receptor modifiers have been developed and emerged as potential treatment modalities for numerous metabolic, immunological and neoplastic diseases. The major focus of this paper is a systematic review of current experimental leptin-based therapies, including pharmacological advantages and limitations of each prodrug category.

3.
Diabetes Care ; 28(3): 533-8, 2005 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-15735183

RESUMO

OBJECTIVE: Multiple daily injection (MDI) therapy of bolus insulin aspart and basal insulin glargine was compared with continuous subcutaneous insulin infusion (CSII) with aspart in type 1 diabetic patients previously treated with CSII. RESEARCH DESIGN AND METHODS: One hundred patients were enrolled in a randomized, multicenter, open-label, crossover study. After a 1-week run-in period with aspart by CSII, 50 subjects were randomly assigned to MDI therapy (aspart immediately before each meal and glargine at bedtime) and 50 subjects continued CSII. After 5 weeks of the first treatment, subjects crossed over to the alternate treatment for 5 weeks. During the last week of each treatment period, subjects wore a continuous glucose monitoring system for 48-72 h. RESULTS: Mean serum fructosamine levels were significantly lower after CSII therapy than after MDI therapy (343 +/- 47 vs. 355 +/- 50 micromol/l, respectively; P = 0.0001). Continuous glucose monitoring profiles over a 24-h time period showed that glucose exposure was 24 and 40% lower for CSII than MDI as measured by area under the curve (AUC) glucose >/=80 mg/dl (1,270 +/- 742 vs. 1,664 +/- 1,039 mg . h . dl(-1); P < 0.001) and AUC glucose >/=140 mg/dl (464 +/- 452 vs. 777 +/- 746 mg . h . dl(-1), CSII vs. MDI, respectively; P < 0.001). Similar percentages of subjects reported hypoglycemic episodes (CSII: 92%, MDI: 94%) and nocturnal (12:00 a.m. to 8:00 a.m.) hypoglycemic episodes (CSII: 73%, MDI: 72%). Major hypoglycemia was infrequent (CSII: two episodes, MDI: five episodes). CONCLUSIONS: In a trial of short duration, CSII therapy with insulin aspart resulted in lower glycemic exposure without increased risk of hypoglycemia, as compared with MDI with insulin aspart and glargine.


Assuntos
Diabetes Mellitus Tipo 1/tratamento farmacológico , Sistemas de Infusão de Insulina , Insulina/análogos & derivados , Insulina/uso terapêutico , Adulto , Biomarcadores/sangue , Glicemia/metabolismo , Índice de Massa Corporal , Esquema de Medicação , Feminino , Frutosamina/sangue , Hemoglobinas Glicadas/análise , Humanos , Insulina/administração & dosagem , Insulina Aspart , Insulina Glargina , Insulina de Ação Prolongada , Masculino
4.
Diabetes Care ; 26(7): 2027-31, 2003 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-12832307

RESUMO

OBJECTIVE: To compare insulin levels and actions in patients with type 1 diabetes after subcutaneous injection of the rapid-acting insulin analogs aspart and lispro. RESEARCH DESIGN AND METHODS: Seven C-peptide-negative patients with type 1 diabetes (two men and five women) were studied at the General Clinical Research Center at Temple University Hospital two times, 1 month apart. Their plasma glucose was normalized overnight by intravenous infusion of insulin. The next morning, they received subcutaneous injections of either aspart or lispro (9.4 +/- 1.9 U) in random order. For the next 4-5 h, their plasma glucose was clamped at approximately 5.5 mmol/l with a variable infusion of 20% glucose. The study was terminated after 8 h. RESULTS: Both insulin analogs produced similar serum insulin levels (250-300 pmol/l) at approximately 30 min and disappeared from serum after approximately 4 h. Insulin aspart and lispro had similar effects on glucose and fat metabolism. Effects on carbohydrate metabolism (glucose uptake, glucose oxidation, and endogenous glucose production) peaked after approximately 2-3 h and disappeared after approximately 5-6 h. Effects on lipid metabolism (plasma free fatty acid, ketone body levels, and free fatty acid oxidation) appeared to peak earlier (at approximately 2 h) and disappeared earlier (after approximately 4 h) than the effects on carbohydrate metabolism. CONCLUSIONS: We conclude that both insulin aspart and lispro are indistinguishable from each other with respect to blood levels and that they are equally effective in correcting abnormalities in carbohydrate and fat metabolism in patients with type 1 diabetes.


Assuntos
Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/tratamento farmacológico , Hipoglicemiantes/farmacocinética , Insulina/análogos & derivados , Insulina/farmacocinética , Adulto , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Índice de Massa Corporal , Peptídeo C/sangue , Calorimetria Indireta , Feminino , Glucose/metabolismo , Teste de Tolerância a Glucose , Humanos , Hipoglicemiantes/uso terapêutico , Insulina/uso terapêutico , Insulina Aspart , Insulina Lispro , Masculino
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