Chronic intermittent intravenous insulin therapy: a new frontier in diabetes therapy.

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).

Prevalence of osteoporosis in women: variation with skeletal site of measurement of bone mineral density.

OBJECTIVE: To determine retrospectively the prevalence of osteoporosis in a referral population of female patients and to compare the sensitivity for diagnosing osteoporosis by dual-energy x-ray absorptiometry (DXA) measurements of bone mineral density (BMD) at multiple skeletal sites. METHODS: We studied the data from 625 consecutive women (mean age, 57.3 +/- 13.9 years), who had been referred to our center for lumbar spine (anteroposterior [AP] and lateral region) and hip (femoral neck [FN], Ward's triangle [WT], trochanter, intertrochanteric region, and total hip) BMD measurements with use of DXA (Hologic QDR-2000) between June 1994 and July 1998. RESULTS: Osteoporosis (based on the World Health Organization definition--T-score of -2.5 or lower for BMD) was diagnosed by DXA at the following sites: AP spine in 21.7%, lateral spine in 43.2%, FN in 33.6%, WT in 49.1%, trochanter in 26.1%, intertrochanteric region in 25.9%, and total hip in 28.4% of study patients. Significant site differences were found in the prevalence of osteoporosis between the lateral and AP spine (P < 0.001), as well as between WT and the FN, trochanter, intertrochanteric region, and total hip (P < 0.001). In a subgroup of 71 women, forearm (ultradistal radius and radius 1/3 region) BMD results indicated low sensitivity for diagnosing osteoporosis, similar to that seen at the AP spine, trochanter, and intertrochanteric region. Not surprisingly, the prevalence of osteoporosis increased with advancing age (15.5% in patients younger than 50 years, in comparison with 59.6% in those older than 69 years of age). The frequency of misclassification of patients (osteoporosis at one site and normal BMD at another) with use of the seven measurement sites was 16.6% (104 of the 625 patients). CONCLUSIONS: For diagnosis of osteoporosis, DXA BMD measurements are significantly more sensitive at the lateral spine than at the AP spine, as well as at WT than at the FN, trochanter, intertrochanteric region, and total hip sites.

Effect of intensive insulin therapy on progression of overt nephropathy in patients with type 1 diabetes mellitus.

OBJECTIVE: To assess the effects of chronic (long-term) intermittent intravenous insulin therapy (CIIIT) on the progression of overt nephropathy in patients with type 1 diabetes mellitus. METHODS: We undertook a retrospective longitudinal three-center study of 31 patients with type 1 diabetes mellitus and overt nephropathy, who were receiving intensive subcutaneous insulin therapy (four insulin injections daily) and weekly CIIIT. All study patients had follow-up consultations weekly for at least 12 months (mean duration, 37.0 +/- 4.6 months). Each patient had monthly hemoglobin A(1c) (by high-performance liquid chromatography) and semiannual creatinine clearance determinations. RESULTS: The hemoglobin A(1c) levels declined significantly from 8.6 +/- 0.6% to 7.6 +/- 0.3% (P = 0.0062) during the study period. The creatinine clearance remained essentially unchanged (from 46.1 +/- 3.0 mL/min per 1.73 m 2 at baseline to 46.0 +/- 3.9 mL/min per 1.73 m 2 at the end of the observation period, with an average annualized slope increase of 3.39 +/- 1.5 mL/min per year--no significant difference). CONCLUSION: The addition of CIIIT to intensive subcutaneous insulin therapy in patients with type 1 diabetes mellitus seems to arrest or appreciably reduce the progression of overt diabetic nephropathy, as well as substantially improve their glycemic control.

Practical guidelines on the use of insulin lispro in elderly diabetic patients.

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.

Effect of the stress of medical residency training on the overnight dexamethasone suppression test.

Forty-two medical residents and interns were studied to evaluate the effect of the stress of medical residency training on-call nights on the hypothalamic-pituitary-adrenal axis. Dexamethasone 1 mg was given at 11:00 p.m. on two separate occasions; a control (off-call) night and on on-call night. Plasma cortisol was measured between 8:00-9:00 a.m. the following morning. The number of patient admissions during the on-call night and the number of hours of sleep during both on-call and control nights were recorded. Plasma cortisol decreased to < 138 nmol/l (< 5 micrograms/dl) in 41 out of 42 (97.6%) of the participants following an on-call day and in 40 out of 42 (95.2%) participants after the control day. The number of hours of sleep during the on-call night was 3.9 +/- 0.29 and during the control night 7.0 +/- 0.11 hours and the number of patient admissions was 3.1 +/- 0.3. In conclusion General Internal Medicine on-call experience does not produce significant alteration on the hypothalamic-pituitary-adrenal axis.

Long-term intermittent intravenous insulin therapy and type 1 diabetes mellitus.

An important defect in insulin-dependent diabetes mellitus (IDDM) is that the liver does not meet its full fuel-processing function, because many of the enzymes involved depend on high insulin concentrations in the portal vein. We tried to reactivate the liver by long-term treatment of IDDM patients with intravenous insulin in pulses, with the aim of achieving high portal-vein concentrations during and after a glucose meal. We studied 20 IDDM patients with brittle disease; despite use of a four-injection regimen with manipulation of insulin doses, diet, and physical activity, and frequent clinic visits for at least a year, these patients still had wide swings in blood glucose and frequent hypoglycaemic reactions. The intermittent therapy consisted of 7-10 pulses of intravenous insulin, infused while the patient was ingesting carbohydrate, primarily glucose, during the first hour of a 3 h treatment; three treatments were given in a day. After 2 consecutive days' treatment, patients were treated for 1 day per week. No patient was withdrawn from the study. At the time of this analysis the duration of intermittent treatment ranged from 7 to 71 months (mean 41 [SE 5] months). Haemoglobin A1C concentrations declined from 8.5 (0.4)% at the end of the stabilisation phase to 7.0 (0.2)% at the analysis point (p = 0.0003). During the same time the frequencies of major and minor hypoglycaemic events also fell significantly (major 3.0 [1.1] to 0.1 [0], minor 13.0 [2.6] to 2.4 [0.8] per month; both p < 0.0001). Because the use of saline rather than insulin pulses would have led to unacceptable hyperglycaemia we opted for a historical control design. The absence of a true control group limits the interpretation of these preliminary results, but we believe further studies of hepatic and muscle metabolism before and after long-term intermittent intravenous insulin therapy would be worth while.

Prolactin responses in dexamethasone suppression test in patients with anorexia nervosa.

In anorexia nervosa (AN), abnormalities are present in the hypothalamic-pituitary-adrenal axis, but the prolactin (PRL) response to dexamethasone suppression test (DST) has not yet been studied. In order to study the interrelationships between the various endocrine abnormalities, we investigated the responses of PRL and cortisol to DST (1 mg of dexamethasone at 2300) in AN patients. The subjects were 12 female inpatients with AN and 8 age- and sex-matched healthy controls. The percentage suppression and absolute change in PRL levels before and after dexamethasone administration were significantly different in the 2 groups. In the control group PRL levels suppressed to 36.5 +/- 3.7% of basal, while AN levels declined to 79.4 +/- 8.9% of basal. When the percentage suppression of PRL was compared between patients with and without cortisol suppression, the mean PRL level was 68.9 +/- 7.8% of the basal level for the cortisol-suppressed patients and 100.4 +/- 19.1% for the nonsuppressed patients. Hence in both groups, the percentage PRL suppression was significantly reduced compared with the control group, and indeed nonexistent in cortisol-nonsuppressed patients. The finding that there was less PRL suppression in the cortisol-suppressed patients than in the controls suggests that, in AN, there may be an abnormality in PRL secretion not related to the hypothalamic-pituitary-adrenal axis. Further work is needed to distinguish between the PRL response to stress and potential hypothalamic abnormality.