Diabetes autoantibodies do not predict progression to diabetes in adults: the Diabetes Prevention Program.

AIMS: To determine if the presence of diabetes autoantibodies predicts the development of diabetes among participants in the Diabetes Prevention Program. METHODS: A total of 3050 participants were randomized into three treatment groups: intensive lifestyle intervention, metformin and placebo. Glutamic acid decarboxylase (GAD) 65 autoantibodies and insulinoma-associated-2 autoantibodies were measured at baseline and participants were followed for 3.2 years for the development of diabetes. RESULTS: The overall prevalence of GAD autoantibodies was 4.0%, and it varied across racial/ethnic groups from 2.4% among Asian-Pacific Islanders to 7.0% among non-Hispanic black people. There were no significant differences in BMI or metabolic variables (glucose, insulin, HbA(1c), estimated insulin resistance, corrected insulin response) stratified by baseline GAD antibody status. GAD autoantibody positivity did not predict diabetes overall (adjusted hazard ratio 0.98; 95% CI 0.56-1.73) or in any of the three treatment groups. Insulinoma-associated-2 autoantibodies were positive in only one participant (0.033%). CONCLUSIONS: These data suggest that 'diabetes autoimmunity', as reflected by GAD antibodies and insulinoma-associated-2 autoantibodies, in middle-aged individuals at risk for diabetes is not a clinically relevant risk factor for progression to diabetes.

Long-term effects of the Diabetes Prevention Program interventions on cardiovascular risk factors: a report from the DPP Outcomes Study.

AIMS: Whether long-term cardiovascular risk is reduced by the Diabetes Prevention Program interventions is unknown. The aim of this study was to determine the long-term differences in cardiovascular disease risk factors and the use of lipid and blood pressure medications by the original Diabetes Prevention Program intervention group. METHODS: This long-term follow-up (median 10 years, interquartile range 9.0-10.5) of the three-arm Diabetes Prevention Program randomized controlled clinical trial (metformin, intensive lifestyle and placebo), performed on 2766 (88%) of the Diabetes Prevention Program participants (who originally had impaired glucose tolerance), comprised a mean of 3.2 years of randomized treatment, approximately 1-year transition (during which all participants were offered intensive lifestyle intervention) and 5 years follow-up (Diabetes Prevention Program Outcomes Study). During the study, participants were followed in their original groups with their clinical care being provided by practitioners outside the research setting. The study determined lipoprotein profiles and blood pressure and medication use annually. RESULTS: After 10 years' follow-up from Diabetes Prevention Program baseline, major reductions were seen for systolic (-2 to -3) and diastolic (-6 to -6.5 mmHg) blood pressure, and for LDL cholesterol (-0.51 to -0.6 mmol/l) and triglycerides (-0.23 to -0.25 mmol/l) in all groups, with no between-group differences. HDL cholesterol also rose significantly (0.14 to 0.15 mmol/l) in all groups. Lipid (P = 0.01) and blood pressure (P = 0.09) medication use, however, were lower for the lifestyle group during the Diabetes Prevention Program Outcomes Study. CONCLUSION: Overall, intensive lifestyle intervention achieved, with less medication, a comparable long-term effect on cardiovascular disease risk factors, to that seen in the metformin and placebo groups.

Assessment of glycemia in diabetes mellitus: hemoglobin A1c.

The monitoring of glycemia is an essential component of diabetes care. It may be divided into self-monitoring of blood glucose (SMBG), which measures the immediate level of glycemia, and measurement of hemoglobin A1c (HbA1c), which reflects longer-term glycemia. SMBG was discussed in an earlier review. HbA1c is a measure of erythrocyte hemoglobin glycation, and since erythrocytes have about a 120 day life span, HbA1c reflects mean glycemia for the previous 3 months (weighted to the most recent month). There are several conditions that confound the HbA1c measurement such as hemolytic anaemia (lowers HbA1c) or aplastic anaemia (raises it), but in most circumstances HbA1c is a valid index of glycemia. The recommendation is to measure HbA1c every 3-6 months, and treat to a target level of < 7%. If these recommendations were successfully followed in most people with diabetes, long-term complications, especially microvascular complications, would be markedly reduced.

Assessment of glycemia in diabetes mellitus--self-monitoring of blood glucose.

Self-monitoring of blood glucose (SMBG) is an integral component of diabetes self-care and, if use optimally, essential to obtaining glycemic control. There are many methods currently available and the use of glucometers can provide readily available information on blood glucose patterns over time. However, some barriers to the use of SMBG, such as its cost, are significant. Other barriers, such as pain, patient denial or insufficient encouragement from the health care professional, should be overcome. While we find pre-prandial testing to be more informative, there are instances where post-prandial testing may be useful such as in pregnancy or in patients with early stages of glucose intolerance. In the future, continuous glucose monitoring will become available, and ultimately an insulin delivery device will be linked to continuous monitoring making the "closed loop" artificial pancreas a reality. At present, SMBG is an under-utilized but important part of modern diabetes care and should be recommended for all people with diabetes.

Intraperitoneal delivery of insulin via mechanical pump: surgical implications.

Between November 1986 and January 2000, 28 patients with insulin-dependent diabetes mellitus were enrolled in the implanted insulin pump study at Johns Hopkins Hospital. An additional two patients underwent pump implantation under compassionate use guidelines due to apparent resistance to subcutaneously administered insulin uptake. The mean patient age was 44 +/- 10.5 years. Eleven patients (39%) were female and the mean duration of diabetes was 25.7 +/- 8.9 years. Diabetic retinopathy, neuropathy, and nephropathy were present in 43%, 25% and 11 % of patients, respectively. The insulin pumps functioned safely for a total of 189 patient years. Mean pump life was 26 +/- 1.2 months. There was no mortality. Morbidity was limited to pump-site infections [n=y (4%) of all pumps placed], one case of pump migration and skin erosion, and one small bowel obstruction associated with the pump catheter. Mean serum hemoglobin AIC levels before and after pump placement were 9.0 +/- 2.9% and 7.5 +/- 0.7% (P=0.0023), respectively. Correspondingly, the mean daily blood glucose levels decreased from l61 +/- 40 mg/dl before placement to 141 +/- 27 mg/dl after pump placement (P=0.0063). Intraperitoneal delivery of insulin by a mechanical pump appears to be an attractive alternative for the treatment of insulin-dependent diabetes mellitus.

Predicting expenditures for Medicare beneficiaries with diabetes. A prospective cohort study from 1994 to 1996.

OBJECTIVE: To describe health care expenditures and utilization patterns among older adults with diabetes and to examine factors associated with expenditures over a 3-year period. RESEARCH DESIGN AND METHODS: We conducted a prospective cohort study of health care expenditures and utilization by diabetic patients from a random nationwide sample of aged Medicare beneficiaries from 1994 to 1996. All services covered by the Medicare program were examined. Multivariate regression was used to assess the contribution of patient characteristics in 1994 on Part B, inpatient, and total expenditures in 1995 and 1996. RESULTS: Per capita expenditures for beneficiaries with diabetes (n = 169,613) were 1.7 times greater than those for those beneficiaries without diabetes (n = 968,832) in 1994. This ratio remained fairly constant over the 2 years of follow-up. Expenditures for beneficiaries with diabetes were highly skewed. However, few of these individuals remained in the highest expenditure quintile over the 2 years of follow-up. Using multiple regression analysis to adjust for demographic and clinical characteristics, we were able to explain 7% of the variation in total expenditures in 1995 and 6% of the variation in 1996. Using the same model, we were able to explain 10.7% of the variation in Part B expenditures in 1995 and 8% in 1996. CONCLUSIONS: Beneficiaries with diabetes are consistently more expensive than beneficiaries without diabetes. Demographic and clinical factors at baseline are able to predict only a small portion of future expenditures among this population, and the most expensive patients in one year were often not the most expensive in subsequent years. More work is necessary to assure equitable risk adjustment in the calculation of capitation rates for health plans and practitioners who specialize in the care of individuals with diabetes.

Feasibility and outcomes of insulin therapy in elderly patients with diabetes mellitus.

The use of insulin in elderly patients raises special considerations. Most people who develop diabetes mellitus late in life have type 2 diabetes mellitus, in which there is some residual endogenous insulin secretion. This pancreatic insulin secretion, when present, stabilises their metabolic status. However, some elderly people lose virtually all their endogenous insulin secretory capacity over time, or may even have type 1 (autoimmune) diabetes mellitus with no endogenous insulin. Generally, older patients with diabetes mellitus can be managed for years, often decades, with nutritional therapy and oral agents. More options exist now than did previously. In addition to a variety of sulfonylureas, there is metformin, troglitazone, and/or alpha-glucosidase inhibitors, that are viable options to be used before turning to insulin. The goals of insulin therapy in the elderly must be considered. When hyperglycaemia causes symptoms (polyuria, polydypsia and bodyweight loss) blood glucose levels are generally >200 mg/dl, and insulin is needed if maximal doses of oral agents have been used. Insulin is also indicated when hyperglycaemia puts patients at risk of hyperosmolar states, for example, when blood glucose is >300 mg/dl during a normal day. Clinical judgement dictates whether to use insulin to control glycaemia in the attempt to avoid long term complications such as neuropathy, retinopathy or nephropathy. In people with relatively short life expectancy, major comorbities and no sign of diabetic complications, the risk may be small. On the other hand, in patients for whom neuropathy, in particular, is a major risk, controlling glycaemia (with insulin if necessary) does reduce that risk. Most patients with type 2 diabetes mellitus can be managed with relatively simple insulin regimens thanks to their endogenous insulin secretion. A single bedtime dose of neutral protamine Hagedorn (NPH) insulin, with or without continuation of daytime oral agents, may control fasting blood glucose. A pre-mix combination of NPH and Regular insulin such as 70/30 or 50/50 may be used pre-meal. More customised, 'intensive' insulin regimens are needed when the glycaemia is unstable. Hypoglycaemia is clearly the most significant risk of insulin therapy. If mild and easily treated, it is of no real concern. On the other hand, nocturnal hypoglycaemia, and, in particular, hypoglycaemia unawareness, are clear signs that the insulin regimen should be modified. In summary, insulin therapy may be necessary, and can be used effectively, in elderly patients. However, risk:benefit considerations must be taken into account when deciding which patients to treat with insulin and what insulin regimen to use.

Effect of insulin therapy on macrovascular risk factors in type 2 diabetes.

Many patients with type 2 diabetes require insulin therapy for improved glycemic control after beta-cell failure. However, many physicians are reluctant to institute insulin therapy in type 2 diabetes for fear of accelerating atherosclerosis. The epidemiological evidence is reasonably sound that hyperinsulinism correlates with increased cardiovascular disease in nondiabetic people and those with early type 2 diabetes. It is much less clear, however, that insulin concentration plays a negative role when less well controlled diabetes is considered. The data are more consistent, in fact, with the glucose hypothesis, i.e., that hyperglycemia is a risk factor, although the magnitude of the glucose effect is not well defined. Certainly, the dysmetabolism associated with poor glycemic control could increase the risk of macrovascular events through well-known mechanisms. There is direct evidence that insulin therapy can reduce the risk of macrovascular events by improving glycemic control and diabetes-associated dyslipidemias, although the beneficial effects may be significantly compromised by excessive weight gain. Insulin therapy does not appear to induce hypertension independent of changes in body weight. It is concluded that optimal glycemic control confers a known benefit and can only be achieved with insulin therapy in some people with type 2 diabetes. In these circumstances, the use of insulin has a net benefit on cardiovascular risk, mediated primarily through improvement in dyslipidemia and glycemia itself.

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.

Patterns of expenditures and use of services among older adults with diabetes. Implications for the transition to capitated managed care.

OBJECTIVE: To examine health care use and expenditures among older adults with diabetes, investigate factors that are associated with higher expenditures, and describe the policy implications of caring for this population under managed care. RESEARCH DESIGN AND METHODS: A cross-sectional analysis of expenditures for individuals with diabetes over age 65 years from a nationwide 5% random sample of Medicare beneficiaries was conducted during 1992. All components of medical care covered under Medicare were examined. Multivariate analysis was used to assess the contribution of age, race, sex, number of diabetic complications, and comorbidity (Charlson Index) on total expenditures. RESULTS: On average, individuals with diabetes (n = 188,470) were 1.5 times (P < 0.0001) as expensive as all Medicare beneficiaries (n = 1,371,960). However, there were wide variations, with the most expensive 10% of beneficiaries with diabetes accounting for 56% of expenditures for individuals with diabetes and the least expensive 50% accounting for 4%. Acute care hospitalizations accounted for the majority (60%) of total expenditures, whereas outpatient and physician services accounted for 7 and 33%, respectively. There were no differences in the number of complications for all older adults with diabetes compared with those with the highest expenditures. However, the average number of hospitalizations was 1.6 times (0.53 vs. 0.34; P < 0.0001) higher, and the average length of stay was 2 days longer, among older adults with diabetes (P < 0.0001). In the regression model, age and male sex (factors currently used to set payment rates for Medicare managed care enrollees), and number of diabetic complications, but not race, were positively related to expenditures, yet had minimal predictive power (R2 = 0.0006). The addition of the Charlson Index, also positively related to expenditures, was able to explain up to 20% of the variation in total expenditures (R2 = 0.196). CONCLUSIONS: There are large variations in expenditures among older adults with diabetes. Because elderly beneficiaries with diabetes are more expensive than the average older adult, current Medicare capitation rates may be inadequate. To avoid selection bias and under-treatment of this vulnerable population under managed care, methods to construct fair payment rates and safeguard quality of care are desirable.

Surgical experience with implantable insulin pumps. Department of Veterans Affairs Implantable Insulin Pump Study Group.

BACKGROUND: A recent Veterans Affairs cooperative trial demonstrated that intensive insulin therapy via an implantable pump with intraperitoneal insulin delivery reduced glycemic variability and improved quality of life compared with multiple daily insulin injections. Our aim was to determine perioperative morbidity and assess long-term function of the implantable insulin pump. METHODS: Fifty-one adult patients with type 2 diabetes had infusion pumps placed over a 2-year period at seven VA Medical Centers as part of a randomized prospective study. RESULTS: All pumps were placed successfully. There were two (4%) perioperative complications. There were no wound complications. Duration of pump use ranged from 12 to 25 months (mean 20). Catheter obstruction (57%) and pump malfunction (25%) were the most common reasons for pump explantation. Catheter occlusions increased after 12 months. Catheter occlusion was treated by percutaneous rinse procedure in 75% and revisional procedures in 31% of patients. CONCLUSIONS: Implantable insulin pumps can be placed with minimal surgical morbidity. Attention to surgical detail and infusion protocol permits satisfactory long-term function. Pump/catheter complications increase with time but are usually resolvable by either operative or percutaneous manipulations.

Novel forms of insulin delivery.

Despite its widespread use, much is wrong with conventional subcutaneous insulin injection. It is more-or-less painful and inconvenient; it delivers insulin slowly with highly inconsistent pharmacokinetics into the peripheral venous system rather than directly to the liver via the portal vein; and, once delivered into the skin, it cannot be "turned off". This review has focused on novel alternative approaches to insulin delivery. The clinically available insulin delivery devices, such as pen injectors and external insulin pumps, are probably underutilized. Pen injectors offer convenience, whereas external pumps offer a basal/bolus approach to insulin delivery unlike that achieved by injections. Of the approaches currently under development, IPPs are closet to general availability. They have been extremely popular in more than 600 patients worldwide, however, an insulin problem has delayed application for their PMA in the United States. Feasibility studies of inhaled insulin, nasal insulin, and oral insulin have produced interesting preliminary findings, with pulmonary delivery for meal coverage with short-acting insulin having perhaps the brightest prospects. Encapsulated islets and biohybrid systems that place live islets into an implanted device are in earlier stages of development. Closing the loop with a continuous glucose sensor will be the only way to achieve truly normal blood glucose homeostasis by directing insulin delivery automatically on demand. Glucose sensors would have many other clinical applications in diabetes management in addition to driving a mechanical delivery system. However, the development of glucose sensing devices has been a formidable technical challenge. Based on an evaluation of current technologic development, glucose oxidase-based, needle-type sensors may become available within the next few years. Clinicians, the research community, and persons with diabetes can join in rejecting the notion that standard regimens of insulin injection do not need to be improved. If there is adequate incentive to continue a broad-based research effort into novel approaches to insulin delivery, the quality of life of persons with diabetes can be improved in the not too distant future.

Implanted programmable insulin pumps: one hundred fifty-three patient years of surgical experience.

BACKGROUND: Implanted insulin pumps (IIPs) are an alternative treatment for diabetes mellitus. To maintain good glycemic control, patients with an IIP require frequent surgical interventions. METHODS: Since November 1986, 21 patients with insulin-dependent diabetes mellitus at the Johns Hopkins Hospital have undergone implantation of pumps subcutaneously with a catheter delivering insulin into the peritoneal space. Patients were followed up with self-monitoring of blood glucose levels two to four times daily and percutaneous refills of the pump with U-400 insulin every 6 to 12 weeks. RESULTS: In 153 patient-years, 77 pumps were placed. The mean pump life was 29 +/- 2 months. Morbidity was limited to pump site infections (3.9%) and one small bowel obstruction. Inadvertent insulin overdelivery has never occurred. Episodes of insulin underdelivery were caused by backflow anomalies (n = 67), which were cleared by percutaneous rinses, or catheter obstructions (n = 12), which required catheter replacements. Ninety-one operations were required to maintain pump function. All patients are alive and report improvements in quality of life. Significant reductions in hemoglobin A1C and plasma glucose levels were also seen. CONCLUSIONS: Long-term use of IIPs results in significant improvements in clinical parameters and quality of life for individuals with insulin-dependent diabetes mellitus. Relatively frequent operations are required for maintaining pump function, which are done with a local anesthetic with minimal morbidity.

Cyclic vomiting: association with multiple homeostatic abnormalities and response to ketorolac.

Cyclic vomiting is a rare syndrome that over the years has variously been ascribed to psychogenic causes, sensory seizures, abdominal migraine, and more recently, to mechanical or electrical disturbances in gastric physiology. We describe the case of a 65-year-old white diabetic female with a 10-yr history of recurrent episodes of nausea and vomiting, occurring every 10-12 days and lasting approximately 1-3 days at a time. These episodes were accompanied by edema, mild temperature elevations, and remarkable elevations in blood pressure. In between these episodes, the patient remained asymptomatic. Initial screening tests were also negative except for moderate gastroparesis. However, antral motility was found to be normal, as was an electrogastrogram. Detailed neurological and psychiatric evaluations were negative. Trials of erythromycin, metoclopramide, naloxone, ondansetron, and amitryptiline were unsuccessful. Serial endocrinological testing revealed that an episode of vomiting was always preceded by an abnormal elevation in at least one of the following: serum adrenocorticotropic hormone, serum cortisol, or urinary cortisol. In the midst of an episode, all three values were exceedingly high (e.g., > 10-fold increases in 24-hr urinary cortisol levels). Fluctuations of a milder degree, though still abnormally high, were also noted in between cycles at times when the patient was completely asymptomatic. High-dose dexamethasone suppressed these hormonal surges completely but not the clinical symptoms, which continued undisturbed. The patient was finally given a trial of intramuscular ketorolac during one of her episodes, which produced prompt and sustained relief. During the next few weeks, she was given this drug each time her symptoms commenced, and each time it appeared that her cycle had been aborted. She has since been able to terminate her episodes promptly and completely by self-administration of ketorolac. We speculate that her syndrome is caused by a poorly characterized disorder of endogenous prostaglandin release, resulting not only in derangements in the hypothalamic pituitary system but also in nausea and vomiting.

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.

Evaluation of the psychosocial impact of the MiniMed variable-rate implantable insulin pump.

We examined the psychosocial impact of treatment with an implantable insulin pump among persons with insulin-dependent diabetes mellitus (IDDM). Of specific interest was whether use of the MiniMed implantable insulin pump (MIP) resulted in changes in functional status, performance of diabetes self-care behavior, psychologic symptoms, and perceived level of stress. From a sample of 36 patients with IDDM, 10 persons were randomly selected to receive the MIP, while the remaining 26 served as control subjects. Additionally, a nonrandom sample of three MIP recipients from an additional site were included in the MIP group. At regular assessment intervals, all participants completed self-report questionnaires regarding psychosocial functioning and monitored blood glucose levels. After 4 months of MIP use, MIP recipients did not significantly differ from control subjects on any measure of psychosocial functioning; however, MIP use did have an impact on diabetes self-care. The MIP users monitored their blood glucose levels more frequently and had lower average blood glucose levels than control subjects. Additional follow-up is needed to determine the long-term psychosocial impact of implantable insulin pump therapy.

Non-ophthalmologic findings of the Diabetes Control and Complications Trial.

The Diabetes Control and Complications Trial (DCCT) was a large and rigorously conducted trial which definitively established that longterm hyperglycemia causes longterm diabetic complications. In this review the author considers the non-ophthalmologic results of the DCCT and the applications of these findings to current and future care of diabetic patients. It is concluded that people with diabetes do not need to anticipate a future of diabetic complications, and that improved glycemic control can be achieved through the education and cooperation of physicians, patients, and health care payers.

Intraperitoneal insulin delivery decreases the levels of chylomicron remnants in patients with IDDM.

OBJECTIVE: To investigate whether intraperitoneal insulin (IPII) decreases the levels of circulating chylomicron remnants in patients with insulin-dependent diabetes mellitus (IDDM). RESEARCH DESIGN AND METHODS: Eight nonobese, normolipidemic IDDM patients were studied twice: before (while on subcutaneous insulin) and 6 months after initiation of IPII by a programmable implanted medication system. Fasting and mean blood glucose, HbA1, and lipid values were determined. Blood samples were also drawn before and every 2 h for 10 h after ingestion of a fat meal (corn oil + Vitamin A). Triglycerides (TGs), apolipoprotein B (apoB), and retinyl esters were determined over time in two TG-rich lipoprotein subfractions (Sf > 100 and Sf20-100) isolated from plasma by density-gradient ultracentrifugation. RESULTS: IPII slightly decreased the mean blood glucose from 7.8 +/- 1.1 to 7.4 +/- 1.1 mmol/l (mean +/- SD, P = 0.027, paired Student's t test) and the HbA1 from 9.4 +/- 1.5 to 8.7 +/- 1.2 (NS). TG and apoB levels in postprandial Sf > 100 and Sf20-100 were not changed by IPII. On IPII, however, retinyl ester levels in Sf > 100 decreased (P = 0.05, analysis of variance [ANOVA]) and tended to be lower in Sf20-100 (P = 0.075). In addition, following IPII, the retinyl ester:apoB ratio was lower in Sf > 100 (P = 0.0002) and marginally lower (P = 0.06) in Sf 20-100. CONCLUSIONS: IPII decreased chylomicron remnant levels, which might decrease the atherosclerotic risk in IDDM. Since glycemic control was only slightly improved, the effect was most likely due to the intraperitoneal route of delivery.