I m p a i red Skin Microvascular Function in C h i l d ren, Adolescents, and Young Adults With Type 1 Diabetes O R I G I N A L A R T I C L EO B J E C T I V E -Vascular disease in type 1 diabetes is a complex and multifactorial pro c e s s , which probably begins in childhood in association with the onset of diabetes. To determine the possible factors involved, we measured microvascular responses to endothelium-dependent (acetylcholine) and endothelium-independent (sodium nitro p russide) vasodilators in 56 patients with type 1 diabetes (aged 9-22 years) and 22 control subjects.RESEARCH DESIGN AND METHODS -Skin perfusion was measured at the dorsum of the foot using laser Doppler flowmetry during low-current iontophoresis of acetylcholine and sodium nitro p russide. Maximum vasodilator function was measured during local 44°C skin heating. R E S U LT S -Vascular responses were significantly reduced in patients with type 1 diabetes c o m p a red with responses in control subjects: acetylcholine (P 0.01, analysis of variance [ A N O VA]), sodium nitro p russide (P 0.01, ANOVA), and local heating (P 0.02. MannWhitney U test). Endothelium-dependent responses were related to duration of diabetes (r = 0.38, P 0.01) and to glycemic control (r = 0.37, P 0.01). Significant correlations were found in the patient group between responses to acetylcholine and sodium nitro p russide (r = 0.28, P 0.05) but not to heating, suggesting that a common factor (e.g., nitric oxide activity) may be responsible for the abnormal vascular responses to these chemicals.C O N C L U S I O N S -Early changes in microvascular function are present in young patients with type 1 diabetes, long before the initial clinical presentation. These abnormalities may be related to complex interactions between structural abnormalities and functional changes in the endothelium, smooth muscle, and nitric oxide activity. Diabetes P a t h o p h y s i o l o g y / C o m p l i c a t i o n s 216DIABETES CARE, VOLUME 23, NUMBER 2, FEBRUARY 2000Vascular impairment in young type 1 diabetic patients young adult categories were classified as adolescents. Accord i n g l y, in the gro u p with type 1 diabetes, there were 13 prep u b e rtal children, 19 adolescents, and 24 young adults.Glycemic control was assessed by measuring HbA 1 c using ion-liquid chro m a t o gr a p h y. Five of the young adults with diabetes and none of the control gro u p w e re current smokers. None of the patients had any clinical evidence of diabetic re t i n o p a t h y, and all but one had urinary albumin excretion values within the normal re f e rence range.Endothelium-dependent and -independent microvascular responses Studies were conducted in a temperaturec o n t rolled room (25-26°C) in the morn i n g , 2 h after a light breakfast. Patients took their usual morning insulin. Subjects were lying in the supine position with their feet at h e a rt level. After a 25-min equilibration, skin perfusion (termed skin ery t h rocyte flux [SkEF]) was measured continuously at the dorsum of the right foot...
There is still uncertainty about what is the most appropriate test for assessment of the integrity of the hypothalamo-pituitary-adrenal (HPA) axis. Many advocate the insulin tolerance test (ITT), but this is unpleasant and resource intensive, and may occasionally give misleading results. The conventional [250 microg tetracosactrin, ACTH-(1-24)] short synacthen test (SST) has been used as a simple alternative to the ITT, but it has produced some falsely reassuring results with potentially serious consequences. A low dose [1 microg tetracosactrin, ACTH-(1-24)] short synacthen test (LDSST) has recently been advocated as a more reliable and safer alternative to ITT. Some studies, however, have failed to demonstrate any difference between SST and LDSST. The purpose of this study was to assess the clinical usefulness of LDSST compared to SST and ITT in patients with pituitary disease. We studied 64 patients with suspected or proven pituitary disease. All patients underwent SST and LDSST. Forty-two patients underwent ITT. There was a high correlation between the ITT and LDSST peak cortisol responses (r = 0.89; P < 0.0001), the ITT and SST 30 min cortisol levels (r = 0.83; P < 0.0001), and the LDSST peak cortisol response and the SST 30 min cortisol level (r = 0.85; P < 0.0001). In the LDSST, all but six patients achieved maximal cortisol response by 30 min. A plasma cortisol cut-off of 600 nmol/L is more helpful than 500 nmol/L for clinical decision-making using either the SST 30 min cortisol level or the LDSST peak cortisol response. The sensitivity of the LDSST was 100% (cortisol response of >600 nmol/L indicates intact HPA axis), with no falsely reassuring results. SST (pass cortisol level, >600 nmol/L) was less sensitive than LDSST, it produced 2 of 64 (3%) falsely reassuring results. Even the ITT (pass cortisol level, >500 nmol/L) failed to identify one patient with clinically evident cortisol deficiency. The results of this study indicate that both SST and LDSST, at a cortisol cut-off of 600 nmol/L, are safe for the purpose of clinical decision-making with regard to steroid replacement therapy in patients with pituitary disease. As the LDSST produced no falsely reassuring decisions, we suggest that this could replace the SST and ITT for initial evaluation of the HPA axis in patients with pituitary disease. We suggest administering 1 microg tetracosactrin, i.v., with sampling at 0, 20, and 30 min.
Diabetes mellitus is emerging as a major public health probelm in Saudi Arabia in parallel with the worldwide diabetes pandemic, which is having a particular impact upon the Middle East and the third world. This pandemic has accompanied the adoption of a modern lifestyle and the abandonment of a traditional lifestyle, with a resultant increase in rates of obesity and other chronic non-communicable diseases. The indigenous Saudi population seems to have a special genetic predisposition to develop type 2 diabetes, which is further amplified by a rise in obesity rates, a high rate of consanguinity and the presence of other variables of the insulin resistance syndrome. We highlight the epidemiology, clinical and complications profiles of diabetes in Saudi people. Diabetes is well studied in Saudi Arabia; however, there seems to be little research in the area of education and health care delivery. This is of paramount importance to offset the perceived impact on health care delivery services, to lessen chronic diabetes complications, and to reduce the expected morbidity and mortality from diabetes.
Changes in lipid levels help to explain the results from risk factor modelling which show increased coronary risk in growth hormone deficient hypopituitary patients, particularly females. The abnormal lipid profile is characterized in both genders by an increase in the total to HDL ratio [corrected], an important parameter in the Framingham equation. The lipid abnormalities conferring increased risk is related to growth hormone deficiency either directly (LDL) or indirectly through increased central obesity (HDL) [corrected]. Adverse calculated coronary risk might provide a new objective indication for consideration of GH replacement therapy in adults.
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