Publications (109) View all
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Article: Evidence of increased inflammation and microcirculatory abnormalities in patients with type 1 diabetes and their role in microvascular complications.
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ABSTRACT: Type 1 diabetes is associated with increased microvascular complications and inflammation. The monocyte-macrophage is a pivotal cell in atherogenesis. There are scanty data on noninvasive measures of microvascular abnormalities and inflammation in type 1 diabetic subjects with microvascular complications. Thus, we examined systemic and cellular biomarkers of inflammation in type 1 diabetic patients with microvascular complications (T1DM-MV patients) and type 1 diabetic patients without microvascular complications (T1DM patients) compared with matched control subjects and determined the microcirculatory abnormalities in the T1DM and T1DM-MV patients using computer-assisted intravital microscopy (CAIM). Fasting blood, 24-h urine, and CAIM measurements were obtained from the T1DM and T1DM-MV patients and matched control subjects. C-reactive protein, E-selectin, nitrotyrosine, monocyte superoxide, and cytokines were elevated in the T1DM and T1DM-MV patients compared with control subjects (P < 0.01). Severity index, as assessed by CAIM, was significantly increased in the T1DM and T1DM-MV patients compared with the control subjects (P < 0.001). There was a significant increase in C-reactive protein, nitrotyrosine, vascular cell adhesion molecule and monocyte superoxide anion release, and interleukin-1 release in T1DM-MV compared with T1DM patients (P < 0.05). T1DM-MV patients had significantly increased CAIM severity index and microalbumin-to-creatinine ratio compared with T1DM patients (P < 0.05). Furthermore, pp38MAPK, pp65, and pERK activity were significantly increased in monocytes from the T1DM and T1DM-MV patients compared with those from the controls subjects, and pp38MAPK and pp65 activity were significantly increased in the T1DM-MV compared with the T1DM patients (P < 0.01). T1DM-MV patients have increased inflammation compared with T1DM patients. CAIM provides an effective biomarker of microvascular complications, since it is significantly elevated in T1DM-MV compared with T1DM patients and can be monitored following therapies targeted at improving inflammation and/or microvascular complications of type 1 diabetes.Diabetes 11/2007; 56(11):2790-6. · 8.29 Impact Factor -
Article: Chronic intermittent intravenous insulin therapy: a new frontier in diabetes therapy.
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ABSTRACT: The limited success achieved in controlling diabetes and its complications with conventional insulin therapy suggests the need for reevaluation of the appropriateness of insulin administration protocols. Indeed, conventional subcutaneous insulin administration produces slowly changing blood insulin levels and suboptimal hepatocyte insulinization resulting in impaired hepatic capacity for processing incoming dietary glucose. The novel approach to insulin administration known as chronic intermittent intravenous insulin therapy (CIIIT) delivers insulin in a pulsatile fashion and achieves physiological insulin concentration in the portal vein. Done as a weekly outpatient procedure combined with daily intensive subcutaneous insulin therapy, this procedure has been shown to (1) significantly improve glycemic control while decreasing the incidence of hypoglycemic events, (2) improve hypertension control, (3) slow the progression of overt diabetic nephropathy, and (4) reverse some manifestations of diabetic autonomic neuropathy (e.g., abnormal circadian blood pressure pattern, severe postural hypotension, and hypoglycemia unawareness).Diabetes Technology & Therapeutics 02/2001; 3(1):111-23. · 1.93 Impact Factor -
Article: Practical guidelines on the use of insulin lispro in elderly diabetic patients.
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ABSTRACT: Glucose tolerance deteriorates, and the prevalence of diabetes mellitus increases, with advancing age. Most elderly diabetic patients have type 2 (non-insulin-dependent) diabetes mellitus, but the prolonged survival of young people with type 1 (insulin-dependent) diabetes mellitus increases the prevalence of type 1 diabetes among the elderly. Approximately 25 to 29% of patients with type 2 diabetes mellitus are treated with insulin. Conventional therapy with regular and intermediate-acting insulin preparations does not mimic physiological insulin secretion. Subcutaneous administration of insulin lispro, a recently introduced insulin analogue, more closely mimics the time-action curve of endogenous insulin that is produced in response to meals. Its rapid onset and short duration of action allow for adequate control of postprandial glucose levels while reducing the risk of late postprandial hypoglycaemia. Insulin lispro offers improved glycaemic control, convenience and increased flexibility in insulin-treated patients with diabetes.Drugs & Aging 03/1998; 12(2):103-13. · 2.67 Impact Factor -
Article: Anterior pitutiary and pitutiary-dependent target organ function in men infected with the human immunodeficiency virus.
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ABSTRACT: To evaluate pituitary and pituitary-dependent target organ function in men infected with the human immunodeficiency virus (HIV), 26 ambulatory HIV-positive men (13 with acquired immunodeficiency syndrome [AIDS]) and nine healthy control men were administered rapid sequential injections of thyrotropin (TSH)-releasing hormone (TRH), gonadotropin-releasing hormone (GnRH), ovine corticotropin (ACTH)-releasing hormone (oCRH), and human growth hormone-(GH)-releasing hormone (hGHRH). Blood samples were collected before and for 90 minutes after the injections for immunoassay of pituitary hormones, cortisol, testosterone, and free thyroxine (fT(4)). Data were analyzed for each group of men considering basal, peak, and incremental responses to the releasing hormones, as well as the time course of response of each hormone. Mean basal serum GH concentrations were the same in all groups (control, AIDS, and non-AIDS HIV-positive), but stimulated GH levels were substantially higher at all time points in both groups of HIV-positive subjects. Results for prolactin (PRL) were similar, although stimulated PRL levels were increased significantly only in the AIDS group. The mean basal serum TSH concentration and stimulated TSH levels at 60 and 90 minutes were significantly greater in the AIDS group than in the control group. Basal mean fT(4) concentration in the AIDS group was significantly less than in the control group. Mean basal and stimulated serum (total) testosterone concentrations in all groups were the same. However, basal serum luteinizing hormone (LH) concentrations in both groups of HIV-infected men were significantly greater than in controls; stimulated (peak) LH levels were not different from control levels. Basal and peak stimulated plasma ACTH concentrations were significantly increased in both HIV-infected groups. Basal serum cortisol levels were also greater, on average, in HIV-infected groups, although stimulated (peak) cortisol responses were not different. These results indicate that basal serum concentrations of TSH, LH, ACTH, and cortisol are modestly increased in men with AIDS, and that maximum levels of GH, PRL, TSH, and ACTH stimulated by the releasing hormones are also increased in this group. Measurements obtained in the non-AIDS HIV-infected men showed a pattern generally similar to that obtained in men with AIDS, but less marked. The basis for the increased pituitary activity is unknown; we speculate that it is due to modestly impaired target organ function and to increased hypothalamic stimulation.Metabolism 07/1996; 45(6):738-46. · 2.66 Impact Factor -
Article: Chronic intermittent intravenous insulin therapy corrects orthostatic hypotension of diabetes.
The American Journal of Medicine 01/1996; 99(6):683-4. · 5.43 Impact Factor
