High Risk Population Isolate Reveals Low Frequency Variants Predisposing to Intracranial Aneurysms

Peer reviewe

Analogi insulina

Первым инсулиновым аналогом, ставшим доступным для клинического применения, является аналог короткого действия - инсулин лизпро, в котором остатки лизина и пролина в конце В цепи молекулы инсулина были заменены местами. Инсулин лизпро обладает более точным профилем действия на период приема пищи, так как его максимальный эффект наступает примерно через 1 ч и практически исчезает через 3-4 ч после подкожной инъекции. Средняя частота гипогликемии при СД 2 типа у больных, получавших инсулин лизпро, ниже, чем у больных, получавших инсулин регуляр; различия наиболее выражены ночью. У больных СД 2 типа с плохой компенсацией на одних только препаратах сульфонилмочевины улучшение контроля гликемии с помощью инсулина лизпро сопровождалось значительным снижением уровня триглицеридов сыворотки крови и повышением концентрации холестерина липопротеинов высокой плотности. Данные мультицентровых исследований показывают, что, если больные СД 1 и 2 типов переводятся с человеческого инсулина регуляра на инсулин лизпро без каких-либо изменений дозы инсулина или диеты, показатели постпрандиальной гликемии и удовлетворенности лечением улучшаются, а частота гипогликемии слегка снижается. Инсулин аспарт - это инсулиновый аналог короткого действия с замещением остатка аспарагиновой кислоты на остаток пролина в положении B28 молекулы инсулина. Инсулин гларгин (Гли А21, Apr В31, Apr В32) представляет собой один из аналогов продленного действия, произведенный с помощью технологии рекомбинантной ДНК и имеющий изоэлектрическую точку при нейтральном рН. Эти аналоги обладают пролонгированным действием благодаря связыванию с альбумином в крови

Improved mealtime treatment of diabetes mellitus using an insulin analogue

The absorption of regular human insulin from subcutaneous injection sites is delayed due to the self-association of insulin to multimeric forms. The insulin analogue insulin lispro has a weak self-association and a fast absorption rate. We examined the safety and efficacy of insulin lispro in the premeal treatment of patients with diabetes mellitus. A 12-month study was performed in 336 patients with insulin-dependent diabetes mellitus (IDDM) and 295 patients with non-insulin-dependent diabetes mellitus (NIDDM). The patients were randomized to inject either regular human insulin 30 to 45 minutes before eating, or insulin lispro immediately before each meal, in addition to basal insulin. The postprandial rise in serum glucose was lower in patients receiving insulin lispro than in those receiving regular human insulin therapy. At end point, the increment was significantly lower at 1 hour (35%) and at 2 hours (64%) after the meal in IDDM patients; in NIDDM patients, the increment was nonsignificantly lower at 1 hour (19%) and significantly lower at 2 hours (48%). IDDM patients receiving insulin lispro achieved significantly lower glycated hemoglobin (HbA 1c) levels in patients receiving regular human insulin (8.1% vs 8.3%. In NIDDM patients, HbA 1c levels decreased equally in both treatment groups. Due to its fast absorption rate, insulin lispro improves postprandial control in diabetes. Insulin lispro can be considered one step toward optimal insulin therapy and improved patient convenience

Sodium nitroprusside increases human skeletal muscle blood flow, but does not change flow distribution or glucose uptake

The role of blood flow as a determinant of skeletal muscle glucose uptake is at present controversial and results of previous studies are confounded by possible direct effects of vasoactive agents on glucose uptake. Since increase in muscle blood flow can be due to increased flow velocity or recruitment of new capillaries, or both, it would be ideal to determine whether the vasoactive agent affects flow distribution or only increases the mean flow.In the present study blood flow, flow distribution and glucose uptake were measured simultaneously in both legs of 10 healthy men (aged 29 ± 1 years, body mass index 24 ± 1 kg m−2) using positron emission tomography (PET) combined with [15O]H2O and [18F]fluoro-2-deoxy-D-glucose (FDG). The role of blood flow in muscle glucose uptake was studied by increasing blood flow in one leg with sodium nitroprusside (SNP) and measuring glucose uptake simultaneously in both legs during euglycaemic hyperinsulinaemia (insulin infusion 6 pmol kg−1 min−1).SNP infusion increased skeletal muscle blood flow by 86 % (P < 0·01), but skeletal muscle flow distribution and insulin-stimulated glucose uptake (61·4 ± 7·5 vs. 67·0 ± 7·5 μmol kg−1 min−1, control vs. SNP infused leg, not significant), as well as flow distribution between different tissues of the femoral region, remained unchanged. The effect of SNP infusion on blood flow and distribution were unchanged during infusion of physiological levels of insulin (duration, 150 min).Despite a significant increase in mean blood flow induced by an intra-arterial infusion of SNP, glucose uptake and flow distribution remained unchanged in resting muscles of healthy subjects. These findings suggest that SNP, an endothelium-independent vasodilator, increases non-nutritive, but not nutritive flow or capillary recruitment

Insulin action on heart and skeletal muscle glucose uptake in essential hypertension.

Essential hypertension is characterized by skeletal muscle insulin resistance but it is unknown whether insulin resistance also affects heart glucose uptake. We quantitated whole body (euglycemic insulin clamp) and heart and skeletal muscle (positron emission tomography and 18F-fluoro-2-deoxy-D-glucose) glucose uptake rates in 10 mild essential hypertensive (age 33 +/- 1 yr, body mass index 23.7 +/- 0.8 kg/m2, blood pressure 146 +/- 3/97 +/- 3 mmHg, VO2max 37 +/- 3 ml/kg per min) and 14 normal subjects (29 +/- 2 yr, 22.5 +/- 0.5 kg/m2, 118 +/- 4/69 +/- 3 mmHg, 43 +/- 2 ml/kg per min). Left ventricular mass was similar in the hypertensive (155 +/- 15 g) and the normotensive (164 +/- 13 g) subjects. In the hypertensives, both whole body (28 +/- 3 vs 44 +/- 3 mumol/kg per min, P < 0.01) and femoral (64 +/- 11 vs 94 +/- 8 mumol/kg muscle per min, P < 0.05) glucose uptake rates were decreased compared to the controls. In contrast, heart glucose uptake was 33% increased in the hypertensives (939 +/- 51 vs 707 +/- 46 mumol/kg muscle per min, P < 0.005), and correlated with systolic blood pressure (r = 0.66, P < 0.001) and the minute work index (r = 0.48, P < 0.05). We conclude that insulin-stimulated glucose uptake is decreased in skeletal muscle but increased in proportion to cardiac work in essential hypertension. The increase in heart glucose uptake in mild essential hypertensives with a normal left ventricular mass may reflect increased oxygen consumption and represent an early signal which precedes the development of left ventricular hypertrophy