Real-world weight change among patients treated with glucagon-like peptide-1 receptor agonist, dipeptidyl peptidase-4 inhibitor and sulfonylureas for type 2 diabetes and the influence of medication adherence.

AIMS: The study aims to examine real-world weight change and the role of medication adherence among patients with type 2 diabetes who initiated one of three drug classes: glucagon-like peptide-1 receptor agonist (GLP-1RA), dipeptidyl peptidase-4 inhibitor (DPP4) and sulfonylureas (SUs). MATERIALS AND METHODS: A cohort of patients initiating one of the three drug classes was selected from a large US database of integrated electronic medical record and administrative claims. Adherence was defined as per cent of days covered ≥80% during the year following drug initiation. Weight change was calculated from drug initiation (-180, +30 d) to 1 year (±90 d) later. Multivariate regression controlled for baseline differences between adherent and poorly adherent patients and the addition of another drug class during follow-up. RESULTS: The study included 833 GLP-1RA, 2,272 DPP4 and 2,713 SU patients who contributed 2,279, 6,602 and 7,429 observations respectively. Patients initiating a GLP-1RA achieved the largest weight change (-2.46 kg of GLP-1RA, -1.26 kg of DPP4 and 0.18 kg of SU, P < 0.01). Adherent GLP-1 patients lost 1.73 kg more than poorly adherent patients, and adherent SU patients gained 1.11 kg more than poorly adherent patients (all P < 0.01). Adherent and poorly adherent DPP4 patients experienced approximately the same amount of weight loss. CONCLUSIONS: Medication adherence can mediate observed weight loss in patients treated with a GLP1-RA or weight gain in those treated with an SU. Medication adherence was low in a real-world population, particularly for GLP-1RA, which displayed the strongest weight loss benefit. Because recent American Diabetes Association guidelines recommend selecting drug therapies that have a weight loss or weight neutral effect for the management of type 2 diabetes patients, patients should be encouraged to enhance their adherence to benefit the most from therapies that have weight loss properties.

Evaluation of immunogenicity of LY2963016 insulin glargine compared with Lantus® insulin glargine in patients with type 1 or type 2 diabetes mellitus.

AIMS: To compare the immunogenicity profiles and the potential effects on clinical outcomes of LY2963016 insulin glargine (LY IGlar) and Lantus® insulin glargine (IGlar), products with identical primary amino acid sequences, in patients with type 1 or type 2 diabetes mellitus (T1DM or T2DM). METHODS: To assess immunogenicity, anti-insulin glargine antibodies (measured as percent binding) were compared between treatments in 52-week (open-label) and 24-week (double-blind) randomized studies in total study populations of patients with T1DM (N = 535) and T2DM (N = 756), respectively, and two subgroups of patients with T2DM: insulin-naïve patients and those reporting prestudy IGlar treatment (prior IGlar). Relationships between insulin antibody levels and clinical outcomes were assessed using analysis of covariance and partial correlations. Insulin antibody levels were assessed using Wilcoxon rank sum. Treatment comparisons for treatment-emergent antibody response (TEAR) and incidence of detectable antibodies were analysed using Fisher's exact test. RESULTS: No significant treatment differences were observed for insulin antibody levels, incidence of detectable anti-insulin glargine antibodies, or incidence of TEAR [overall and endpoint, by last-observation-carried-forward (LOCF)] in patients with T1DM or patients with T2DM, including the insulin-naïve subgroup. A statistically significant difference was noted in the overall incidence of detectable antibodies but not at endpoint (LOCF) nor in TEAR for the prior IGlar subgroup of patients with T2DM. Insulin antibody levels were low (<5%) in both treatment groups. Insulin antibody levels or developing TEAR was not associated with clinical outcomes. CONCLUSIONS: LY IGlar and IGlar have similar immunogenicity profiles; anti-insulin glargine antibody levels were low for both treatments, with no observed effect on efficacy and safety outcomes.

Identifying the worries and concerns about hypoglycemia in adults with type 2 diabetes.

AIMS: To identify the hypoglycemic concerns of adults with type 2 diabetes (T2D) and examine how these concerns are associated with key patient characteristics. METHODS: Qualitative interviews with 16 T2D adults and 11 diabetes care providers were conducted. Survey items were then developed and submitted to exploratory factor analyses (EFAs). Construct validity was assessed by correlations with diabetes distress, anxiety and depressive symptoms, well-being, hypoglycemic fear, hypoglycemia history and glycemic control (A1C). RESULTS: An EFA with 226 insulin users and 198 non-insulin users yielded 3 factors (14 items): Hypoglycemia Anxiety, Avoidance and Confidence. For both T2D groups, higher Anxiety and Avoidance were significantly associated with more hypoglycemia, lower well-being, and greater diabetes distress, depressive symptoms and hypoglycemic fear. Similar associations, in the converse direction, were found for Confidence. Among insulin users only, Anxiety was independently associated with greater emotional distress and more hypoglycemia, while Confidence was independently linked to less emotional distress and lower A1C. Avoidance was independently associated with greater emotional distress in both groups. CONCLUSIONS: Using the new 14-item Hypoglycemic Attitudes and Behavior Scale (HABS), we found that hypoglycemic concerns are significant in T2D adults, are linked to emotional distress and A1C, and merit attention in clinical practice.

What is so tough about self-monitoring of blood glucose? Perceived obstacles among patients with Type 2 diabetes.

AIMS: To identify patient-reported obstacles to self-monitoring of blood glucose among those with Type 2, both insulin users and non-insulin users, and to investigate how obstacles are associated with frequency of self-monitoring and use of self-monitoring data. METHODS: Patients with Type 2 diabetes (n = 886, 65% insulin users) who attended a 1-day diabetes education conference in cities across the USA completed a survey on current and recommended self-monitoring of blood glucose frequency, how they used self-monitoring results and perceived obstacles to self-monitoring use. Exploratory factor analysis examined 12 obstacle items to identify underlying factors. Regression analyses examined associations between self-monitoring of blood glucose use and the key obstacle factors identified in the exploratory factor analysis. RESULTS: Three obstacle factors emerged: Avoidance, Pointlessness and Burden. Avoidance was the only significant independent predictor of self-monitoring frequency (ß = -0.23, P < 0.001). Avoidance (ß = -0.12, P < 0.01) and Pointlessness (ß = -0.15, P < 0.001) independently predicted how often self-monitoring data were shared with healthcare professionals and whether or not data were used to make management adjustments (Avoidance: odds ratio = 0.74, P < 0.001; Pointlessness: odds ratio = 0.75, P < 0.01). Burden was not associated with any of the self-monitoring behavioural measures. Few differences between insulin users and non-insulin users were noted. CONCLUSIONS: Obstacles to self-monitoring of blood glucose use, both practical and emotional, were common. Higher levels of Avoidance and Pointlessness, but not Burden, were associated with less frequent self-monitoring use. Addressing patients' self-monitoring-related emotional concerns (Avoidance and Pointlessness) may be more beneficial in enhancing interest and engagement with self-monitoring of blood glucose than focusing on day-to-day, behavioural issues (Burden).

Pramlintide in the treatment of diabetes.

Diabetes treatment has traditionally focused on correcting insulin deficiency with exogenous insulin and oral agents designed to enhance insulin secretion or insulin sensitivity in peripheral tissues. The more recent view of diabetes as a disease that affects multiple hormones in addition to insulin has led to the development of new therapies more broadly aimed at restoring glucose homeostasis by correcting abnormalities in additional glucoregulatory hormones. Pramlintide, a synthetic analogue of the beta-cell hormone amylin, regulates the appearance of glucose in the circulation following meals through several mechanisms of action: slowing gastric emptying, preventing inappropriate postprandial secretion of glucagon and increasing satiety. Long-term studies have demonstrated that pramlintide improves postprandial glucose fluctuations and A1C while reducing insulin dose and body weight. This combination of benefits associated with pramlintide makes it an attractive new treatment option for patients with diabetes. Clinical Trial Registry Numbers: 137-155 open-label clinical trial: NCT00108004 (Pramlintide long-term, placebo-controlled clinical trials were completed prior to the requirement for NCT registry).

Insulin therapy in type 2 diabetes.

Type 2 diabetes is a common disorder often accompanied by numerous metabolic abnormalities leading to a high risk of cardiovascular morbidity and mortality. Results from the UKPDS have confirmed that intensive glucose control delays the onset and retards the progression of microvascular disease and possibly of macrovascular disease in patients with type 2 diabetes. In the early stages of the disease, insulin resistance plays a major role in the development of hyperglycemia and other metabolic abnormalities, and patients with type 2 diabetes often benefit from measures to improve insulin sensitivity such as weight loss, dietary changes, and exercise. Later, the use of oral insulin secretagogues and insulin sensitizers as monotherapy and in combination helps maintain glycemia for varying periods of time. Ultimately, because of the progressive nature of the disease and the progressive decline in pancreatic beta-cell function, insulin therapy is almost always obligatory to achieve optimal glycemic goals. Not all patients are candidates for aggressive insulin management; therefore, the goals of therapy should be modified, especially in elderly individuals and those with co-morbid conditions. Candidates for intensive management should be motivated, compliant, and educable, without other major medical conditions and physical limitations that would preclude accurate and reliable HGM and insulin administration. In selected patients, combination therapy with insulin and oral antidiabetic medications can be an effective method for normalizing glycemia without the need for rigorous multiple-injection regimens. The patients for whom combination therapy is most commonly successful are those who do not achieve adequate glycemic control using daytime oral agents but who still show some evidence of responsiveness to the medications. Bedtime intermediate-acting or predinner premixed intermediate- and rapid-acting insulin is administered and progressively increased until the FPG concentration is normalized. If combination therapy is not successful, a split-mixed regimen of intermediate- and rapid-acting insulin equally divided between the prebreakfast and pre-dinner periods is advised for oese patients, and more intensive regimens are advised for thin patients. Insulin therapy is invariably associated with weight gain and hypoglycemia. The use of metformin or glitazones in combination with insulin has been demonstrated to have insulin-sparing properties. Also, metformin use may ameliorate weight gain. The use of continuous subcutaneous insulin infusion pumps can be particularly beneficial in treating patients with type 2 diabetes mellitus who do not respond satisfactorily to more conventional treatment strategies. Intraperitoneal insulin delivery systems hold considerable promise in type 2 diabetes because of their more physiologic delivery of insulin and their ability to inhibit hepatic glucose production selectively, with less peripheral insulinemia than with subcutaneous insulin injections. Newer insulin analogues such as the rapidly acting Lispro insulin and the peakless, long-acting glargine insulin are increasingly being used because of their unique physiologic pharmacokinetics. New developments such as inhaled and buccal insulin preparations will also make it easier for many patients to initiate and maintain a proper insulin regimen. Finally, a new generation of gut peptides such as amylin and GLP-1 will add a new dimension to glycemic control through modification of nutrient delivery and other mechanisms; however, the ultimate goal in the management of type 2 diabetes is the primary prevention of the disease. The Diabetes Prevention Program (DPP) sponsored by the National Institutes of Health has currently randomly assigned more than 3000 persons with impaired glucose tolerance and at high risk of developing diabetes into three treatment arms: metformin arm, an intensive lifestyle-modification arm, and a placebo arm. The study will conclude in 2002 after all participants have been followed for 3 to 6 years.

Home testing of fructosamine improves glycemic control in patients with diabetes.

OBJECTIVE: To determine whether weekly fructosamine testing at home by patients with type 2 diabetes, combined with therapeutic intervention when necessary on the basis of the results, would lead to improved glycemic control in comparison with usual care during a 3-month period. METHODS: In a prospective study, 25 patients with glycosylated hemoglobin (HbA1c) values above 8.0% were randomized into 2 groups. Both groups, a glucose-only testing group (14 patients with an initial mean HbA1c of 9.4 +/- 0.9%) and a combined glucose plus fructosamine testing group (11 patients with an initial mean HbA1c of 9.2 +/- 0.7%), received therapeutic intervention at the time of randomization. Both groups were instructed to perform blood glucose testing up to four times per day. The combined glucose plus fructosamine testing group was also instructed to perform weekly fructosamine testing in addition to the glucose testing and to telephone the investigator if their home-testing fructosamine value exceeded 350 mmol/L (approximately equivalent to HbA1c of 7.8%), whereupon the investigator implemented further interventions. Both groups returned in 3 months, at which time HbA1c testing was repeated in order to determine whether glycemic control had changed. RESULTS: The study results after 3 months showed that the HbA1c values in the combined glucose plus fructosamine testing group decreased from 9.2 +/- 0.7% to 8.0 +/- 0.5% (P<0.0001). In contrast, the HbA1c values in the glucose-only testing group declined from 9.4 +/- 0.9% to 9.1 +/- 1.3%, a difference that was not significant. CONCLUSION: In the 3 months after a change in therapy for type 2 diabetes, weekly home testing of fructosamine, combined with therapeutic interventions based on the results, led to a more rapid and significant improvement in glycemic control than did the usual regimen of glucose-only testing.

Benchmark data from the literature for evaluation of new glucose sensing technologies.

New glucose sensors based on various technologies are being developed to provide information for improved therapy in diabetes. There is a need to establish rational performance standards for these sensors. Frequently sampled, direct blood glucose recordings representative of blood glucose excursions in diabetes are the "gold standard." An extensive literature search revealed a limited number of diabetic and nondiabetic blood glucose recordings suitable for this purpose. Certain blood glucose recordings reflect the diversity of glycemic dynamics and provide sufficient challenge for evaluation of sensor systems. These recordings were converted into an accessible electronic format. An example is given of the use of these benchmark data to estimate aliasing error, or the error due to insufficient sampling frequency, based on a hypothetical sensor system having some properties of conventional "fingerstick" systems. Discrete sampling systems accumulate substantial aliasing error as the sampling period increases.

Maintenance of the long-term effectiveness of tramadol in treatment of the pain of diabetic neuropathy.

OBJECTIVE: The objective of this study was to evaluate the efficacy and safety of tramadol in a 6-month open extension following a 6-week double-blind randomized trial. RESEARCH DESIGN AND METHODS: Patients with painful diabetic neuropathy who completed the double-blind study were eligible for enrollment in an open extension of up to 6 months. All patients received tramadol 50-400 mg/day. Self-administered pain intensity scores (scale 0-4; none to extreme pain) and pain relief scores (scale -1-4; worse to complete relief) were recorded the first day of the open extension (last day of the double-blind phase) and at 30, 90, and 180 days. RESULTS: A total of 117 patients (56 former tramadol and 61 former placebo) entered the study. On the first day of the study, patients formerly treated with placebo had a significantly higher mean pain intensity score (2. 2+/-1.02 vs. 1.4+/-0.93, P<0.001) and a lower pain relief score (0. 9+/-1.43 vs. 2.2+/-1.27, P<0.001) than former tramadol patients. By Day 90, both groups had mean pain intensity scores of 1.4, which were maintained throughout the study. Mean pain relief scores (2. 4+/-1.09 vs. 2.2+/-1.14) were similar after 30 days in the former placebo and former tramadol groups, respectively and were maintained for the duration of the study. Four patients discontinued therapy due to ineffective pain relief; 13 patients discontinued due to adverse events. The most common adverse events were constipation, nausea, and headache. CONCLUSIONS: Tramadol provides long-term relief of the pain of diabetic neuropathy.

Multisite evaluation of a new diabetes self-test for glucose and glycated protein (fructosamine).

BACKGROUND: In diabetes management, the true average blood glucose is best obtained using glycated protein tests that give the average blood glucose over a previous time window of either weeks (fructosamine tests) or months (glycated hemoglobin tests). Until now, glycated protein tests have only been available as laboratory tests and have therefore been underutilized in diabetes management. Recently, a fructosamine self-test for use by diabetes patients at home was cleared for marketing by the U.S. Food and Drug Administration (FDA). We have studied the performance of this test in three geographically distinct diabetes clinics to confirm the performance and accuracy of both glucose and fructosamine testing with this device. This new self-testing system has the potential to improve glycemic control dramatically in patients with diabetes, including those patients with type 2 diabetes using oral drug therapy. METHODS: Three geographically different sites (San Diego, CA, Tallahassee, FL, and Minneapolis, MN) were selected for the study. Sixty male and 56 female adult patients, with both type 1 (59) and type 2 (57) diabetes, were selected for participation in the study (total patients = 116). Fingerstick puncture capillary blood glucose was tested using the YSI Model 1500 and the Duet Glucose test. A fingerstick puncture capillary blood test was also tested with the Duet GlucoProtein (fructosamine) test strip in duplicate. For fructosamine comparison, a venipuncture blood sample of ethylene diaminetetraacetic acid (EDTA) plasma was collected and tested using the Roche Unimate laboratory test. RESULTS: The glucose test gave excellent correlation to the reference laboratory method (r = 0.98) and the GlucoProtein test gave a correlation of 0.72 compared to the laboratory method. The bias of both tests compared to the laboratory tests was 10% or less at all concentrations. Error grid analysis of the glucose test showed that 97.5% of test results were in the accurate zone and 2.5% were in the clinically neutral or benign errors zone. Analysis of fructosamine test results using a two-by-two grid yielded sensitivity of 100%, specificity of 92% and accuracy of 94%. CONCLUSIONS: The Duet Glucose Control System is accurate for both measuring glucose and GlucoProtein (fructosamine) using a fingerstick blood sample. This new testing system has the potential to provide useful information to both healthcare specialists in their office and also to patients at home to help them achieve better long-term glucose control and avoid the potential acute and chronic complications of diabetes.

The natural history of type 2 diabetes. Implications for clinical practice.

This article reviews the natural history of type 2 diabetes and emphasizes that the disease is a continuum from impaired glucose tolerance and impaired fasting glucose to frank diabetes. Understanding this natural history aids the clinician in identifying those individuals most at risk for developing type 2 diabetes. Early intervention may significantly limit the severity of the microvascular and macrovascular complications of diabetes. Additionally, this article discusses oral antidiabetic agents and reviews their potential effectiveness at the different stages in the continuum to aid the clinician in developing a treatment strategy.

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.

Importance of glucose control.

The importance of glycemic control in reducing the microvascular complications of type 1 diabetes has been clearly demonstrated with a long-term prospective, randomized interventional trial. The data are not as strong with regards to type 2 diabetes. The results of several prospective studies and one interventional study, however, all report benefits of improved glycemic indices on reducing microvascular complications. The available literature evaluating the relationship between glycemic control and macrovascular disease in type 1 and type 2 diabetes demonstrates the importance of glucose control. One could make rational scientific arguments or criticize the design and interpretations of any one individual study. Yet collectively the evidence is powerful. Additionally, there have been no negative studies reported. Lowering the glycosylated hemoglobin to less than 2 percentage points above the upper limit of normal should be the first glycemic goal for most patients with diabetes. Obviously, some patients cannot obtain this degree of control for a variety of reasons. Moreover, the intensity of therapy needs to be individualized and tailored to each patient. In addition, intensive glycemic control does not necessarily mean multiple injections or insulin pumps or home glucose monitoring 10 times a day. Intensive glycemic control means that the glycohemoglobin (hemoglobin and A1C and blood glucose values are in a normal or near-normal range, no matter how simple or how complex the treatment regimen. The most controversial issue is with regards to the relationship between hyperinsulinemia and accelerated atherosclerosis. This association is not consistently found in many of the large prospective studies, and certainly there has never been a direct cause-and-effect relationship proven. Most experts in the field recommend that insulin be reserved for patients with type II diabetes when oral therapy cannot achieve near-normal glycemic control. Weight gain and hypoglycemia are adverse effects of sulfonylurea and insulin therapy. These adverse effects are dwarfed, however, by the acute and chronic complications of poorly controlled diabetes. Lastly, estimates on the economic benefits of reducing long-term microvascular and macrovascular complications in populations are staggering. Based on the available literature, all patients with diabetes should be educated and have access to an appropriate individualized treatment regimen with the goal to normalize or near-normalize glycemic control. This should be the standard of care until proven otherwise.

Type II diabetes mellitus.

Type II diabetes is a common disorder whose prevalence is increasing in the United States and throughout the world. Type II diabetes is also associated with several other metabolic abnormalities such as central obesity, hypertension, and dyslipidemia, which contributes to the very high rate of cardiovascular morbidity and mortality. The main pathologic defects in diabetes consist of excessive hepatic glucose production, peripheral insulin resistance, and defective beta-cell secretory function. The duration and severity of the hyperglycemia dictate the microvascular complications, no matter what the etiology of the glucose intolerance, and the goals of therapy should be similar to those of insulin-dependent type I diabetic patients. Initiation of nonpharmacologic therapy should be started as soon as the diagnosis is made. Pharmacologic agents should be initiated if the glycemic goals are not met with a 3-month trial of diet and exercise. The cornerstone of therapy consists of a regular exercise routine along with a diet consisting of 40% to 50% complex carbohydrates, 10% to 20% protein, and monounsaturated fats such as canola oil and olive oil. If nonpharmacologic therapy does not achieve adequate glycemic control, initiation of an oral antidiabetic agent is warranted. In addition to the sulfonylureas, which work by stimulating insulin secretion, we now have metformin, which inhibits excessive hepatic glucose production; acarbose, which delays the absorption of carbohydrates in the gut; and troglitazone, which reduces insulin, resistance primarily in skeletal muscle. The selection of an initial oral antidiabetic agent depends on patient characteristics such as the presence of obesity and dyslipidemia, the duration of diabetes, and other concomitant conditions. Combination therapy with two or three of the different classes of oral antidiabetic agents is effective and has been used throughout the world. When maximum doses of oral antidiabetic agents do not adequately control glycemia, insulin therapy is necessary. In selected patients, combination therapy consisting of bedtime intermediate-acting insulin in addition to daytime oral antidiabetic agent(s) can be an effective method to normalize glucose control without the need for rigorous insulin regimens. When combination therapy fails, a split-mixed regimen using premixed 70/30 insulin prebreakfast and predinner can be very effective in obese subjects. In thin insulin-requiring subjects with type II diabetes, more intensive regimens may be required. In general, the risk of severe hypoglycemia is quite low in patients with type II diabetes, and the main adverse effect of insulin therapy is weight gain. Prevention and aggressive treatment of glucose intolerance and the other adverse metabolic conditions associated with type II diabetes will not only have a positive effect on the quality of life but also provide long-term cost savings.

Acute effects of intraperitoneal versus subcutaneous insulin delivery on glucose homeostasis in patients with NIDDM. Veterans Affairs Implantable Insulin Pump Study Group.

OBJECTIVE: The objective of this study is to compare the effect of intraperitoneal versus subcutaneous insulin injection on hepatic glucose production (HGP) and systemic glucose utilization (Rd) in patients with NIDDM. RESEARCH DESIGN AND METHODS: Eight male volunteers with NIDDM, each of whom had a programmable-rate, implantable insulin pump, were given an injection of insulin (0.15 units/kg body wt) by intraperitoneal or subcutaneous injection on separate days in randomized order. Plasma glucose was kept constant for 5 h using the glucose clamp technique, and HGP and Rd were measured using isotope dilution. RESULTS: Intraperitoneal insulin injection resulted in higher and earlier peak systemic insulin concentrations (1,469 +/- 245 vs. 454 +/- 48 pmol/l, P < 0.01). Glucose Rd doubled within 1 h after intraperitoneal injection and was greater than that attained with subcutaneous injection (3.91 +/- 0.27 vs. 2.60 +/- 0.19 mg.kg-1.min-1, P < 0.01). Intraperitoneal and subcutaneous injections suppressed HGP and plasma free fatty acid to a similar extent during the first 3 h, effects tht persisted through 5 h after subcutaneous insulin injection but waned 3-4 h after intraperitoneal injection. CONCLUSIONS: In patients with NIDDM, intraperitoneal insulin injection achieves more rapid and greater peak values for stimulation of glucose Rd than subcutaneous insulin injection. With regard to HGP and lipolysis, intraperitoneal and subcutaneous injections achieve similar initial suppression but this is maintained for a more limited duration with intraperitoneal as compared with subcutaneous injection. These differences in insulin action seem directly related to the rapidity of insulin absorption with intraperitoneal injection.

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.