The Veterans Affairs Implantable Insulin Pump Study: effect on cardiovascular risk factors.

OBJECTIVE: To determine whether implantable insulin pump (IIP) and multiple-dose insulin (MDI) therapy have different effects on cardiovascular risk factors in insulin-requiring patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: A randomized clinical trial was conducted at seven Veterans Affairs medical centers in 121 male patients with type 2 diabetes between the ages of 40 and 69 years receiving at least one injection of insulin per day and with HbA1c, levels of > or =8% at baseline. Weights, blood pressures, insulin use, and glucose monitoring data were obtained at each visit. Lipid levels were obtained at 0, 4, 8, and 12 months, and free and total insulin levels were obtained at 0, 6, and 12 months. All medications being taken were recorded at each visit. RESULTS: No difference in absolute blood pressure, neither systolic nor diastolic, was seen between patients receiving MDI or IIP therapy, but significantly more MDI patients required anti-hypertensive medications. When blood pressure was modeled against weight and time, IIP therapy was significantly better than MDI therapy for systolic blood pressure in patients with BMI <33 and for diastolic blood pressure in patients with BMI >34 kg/m2. Total cholesterol levels decreased in the overall sample, but IIP patients exhibited significantly higher levels than MDI patients. Triglyceride levels increased over time for both groups, with IIP patients having significantly higher levels than patients in the MDI group. BMI was a significant predictor of, and inversely proportional to, HDL cholesterol level. No difference in lipid-lowering drug therapy was seen between the two groups. Free insulin and insulin antibodies tended to decrease in the IIP group as compared with the MDI group. C-peptide levels decreased in both groups. CONCLUSIONS: IIP therapy in insulin-requiring patients with type 2 diabetes has advantages over MDI therapy in decreasing the requirement for antihypertensive therapy and for decreasing total and free insulin and insulin antibodies. Both therapies reduce total cholesterol and C-peptide levels.

Implantable insulin pump vs multiple-dose insulin for non-insulin-dependent diabetes mellitus: a randomized clinical trial. Department of Veterans Affairs Implantable Insulin Pump Study Group.

OBJECTIVE: To determine whether implantable insulin pump (IIP) therapy and multiple daily insulin (MDI) injections could equally attain improved blood glucose control, and to compare the 2 treatments with respect to reducing daily blood glucose fluctuations, reducing serious hypoglycemic insulin reactions, and improving patients' quality of life. DESIGN: Randomized clinical trial. SETTING: Seven Veterans Affairs medical centers. PATIENTS: One hundred twenty-one male type II diabetic patients between the ages of 40 and 69 years, receiving at least 1 injection of insulin per day and having hemoglobin A1c (HbA1c) levels of 8% or above. INTERVENTION: Intensive therapy (IIP or MDI) for 1 year. MAIN OUTCOME MEASURES: Hemoglobin A1c and blood glucose levels. RESULTS: Blood glucose levels declined to 7.96+/-1.08 mmol/L (143.4+/-19.5 mg/dL) and 8.30+/-1.52 mmol/L (149.6+/-27.4 mg/dL) (mean +/- SD) for IIP and MDI, respectively (P=.57). Hemoglobin A1c levels improved in both groups (time effect P<.001), to means of 7.54%+/-0.83% (MDI) vs 7.34%+/-0.79% (IIP). IIP reduced blood glucose fluctuations compared with MDI (P<.001), and reduced the incidence of mild clinical hypoglycemia by 68% (P<.001); IIP also eliminated the weight gain associated with MDI therapy and yielded better overall quality-of-life (P=.03) and impact-of-disease subscale scores (P=.05). Adverse events included 25% of subjects with episodes of insulin underdelivery due to microprecipitates of insulin within the pump. CONCLUSIONS: Intensive insulin therapy with IIP and MDI is effective in controlling non-insulin-dependent diabetes mellitus. IIP has significant advantages in reducing glycemic variability, clinical hypoglycemia, and weight gain, while improving aspects of quality of life.

Computer-focused modification of physician prescribing behavior.

Prescribing data downloaded from the MUMPS-based hospital information system of the Department of Veterans Affairs has been used to target specific interventions aimed at changing physician prescribing patterns. Focused interventions aimed at specific groups of physicians, patients, clinics, and drugs have proven effective in reducing pharmaceutical costs by rationalizing prescribing patterns. The results indicate the potential usefulness of a microcomputer with a commercial database program in manipulating hospital information system data.

Electrical stimulation of the liver cell: activation of glycogenolysis.

To examine the role of ionic factors in the regulation of glycogen metabolism, we examined the effects of electrical stimulation on liver glycogen cycle enzymes. Passage of electric current through a suspension of rat hepatocytes caused the conversion of glycogen phosphorylase to its active (a) form and the simultaneous conversion of glycogen synthase to its inactive (D) form. The rise in phosphorylase a activity was dependent on the magnitude of current flow, was detectable after 5 s of current flow, and was rapidly reversible on cessation of stimulation. The activation of phosphorylase by shocking was completely eliminated by depletion of cellular Ca2+ and was restored by readdition of Ca2+. Cyclic AMP and cyclic GMP levels were unaffected by shocking. It is concluded that shocking, in the absence of any hormone or exogenous chemical, causes an increase in cytosol Ca2+, which in turn leads to activation of phosphorylase and inactivation of synthase. Electrical stimulation may serve as a model system for studying the role of ions in metabolic regulation.

Splenic protein synthesis in magnesium deficiency: mechanism of the inhibition.

To investigate the basis for the depressed protein synthesis in vivo in magnesium deficient spleens, the activities of splenic subcellular fractions in polypeptide synthesis were studied in vitro. Splenic ribosomes from Mg deficient animals were normal structurally and functionally. In contrast, supernatant fractions from the deficient spleens had a reduced ability to incorporate labeled amino acids into protein, both in the presence of endogenous mRNA and in the presence of added polyuridylic acid. The specific defects observed in the Mg deficient supernatants were twofold: There was a modest reduction in the rate of acylation of tRNA and a more marked reduction in the activity of the elongation factors, EF-I and EF-II. The reduction in elongation factor activity was quantitatively sufficient to account for the inhibition of protein synthesis in vivo.

Effects of magnesium deficiency on protein and nucleic acid synthesis in vivo.

The effects of magnesium deficiency on the in vivo incorporation of labeled precursors into tissue macromolecules were studied. In severe Mg deficiency developing over 4 months, total protein synthesis in spleen and thymus was depressed by 40% to 50%, while DNA synthesis was increased by as much as 350%. RNA synthesis was not significantly altered. Protein synthesis in kidney was also reduced. In the intact liver, DNA synthesis was increased and RNA synthesis reduced, but protein synthesis was unchanged. The regeneration of the liver after partial hepatectomy was impaired, however, which suggested that the capacity of the liver protein synthetic system was reduced. The effects of magnesium deficiency were unaltered by the ingestion of ethanol that comprised approximately 25% of total energy. Each of the organs enlarged in Mg deficiency, and the spleen was strikingly hyperplastic. The increase in splenic DNA synthesis in the presence of depressed protein synthesis may be an early stage in a lymphoproliferative process leading ultimately to neoplasia.

Human intoxication following inhalation exposure to synthetic jet lubricating oil.

A previously healthy member of an aircraft flight crew was acutely incapacitated during flight with neurologic impairment and gastrointestinal distress. His clinical status returned to normal within 24 hr. The etiology of his symptoms was related to an inhalation exposure to aerosolized or vaporized synthetic lubricating oil arising from a jet engine of his aircraft.