Is insulin pump therapy effective in Type 1 diabetes?

There continues to be uncertainty about the effectiveness in Type 1 diabetes of insulin pump therapy (continuous subcutaneous insulin infusion, CSII) vs. multiple daily insulin injections (MDI). This narrative review discusses the reasons for this uncertainty, summarizes the current evidence base for CSII and suggests some future research needs. There are difficulties in interpreting trials of CSII because effectiveness varies widely due to factors such as differing baseline control, suboptimal use of best CSII practices, and psychological factors, for example, high external locus of control, non-adherence and lack of motivation. Many summary meta-analyses are also misleading because of poor trial selection (e.g. short duration, obsolete pumps, low baseline rate of hypoglycaemia) and reliance on mean effect size for decision-making. Both MDI and CSII can achieve strict glycaemic control without hypoglycaemia in some people with Type 1 diabetes, especially those who are motivated and have undergone structured diabetes education, and with high levels of ongoing input from healthcare professionals. CSII is particularly effective in those people with Type 1 diabetes who have not achieved target HbA1c levels without disabling hypoglycaemia using best attempts with MDI, and here there can be valuable and substantial improvement. Insulin pumps are safe, effective and accepted when used in newly diagnosed diabetes, particularly in children, where MDI may not be practicable. Future research needs include more studies on mortality associated with insulin pumps where registry data have suggested lower rates vs. MDI; and psychological strategies to improve non-adherence and suboptimal glycaemic outcomes on CSII.

A modelling study of the budget impact of improved glycaemic control in adults with Type 1 diabetes in the UK.

AIMS: To develop a novel interactive budget impact model that assesses affordability of diabetes treatments in specific populations, and to test the model in a hypothetical scenario by estimating cost savings resulting from reduction in HbA1c from ≥69 mmol/mol (8.5%) to a target of 53 mmol/mol (7.0%) in adults with Type 1 diabetes in the UK. METHODS: A dynamic, interactive model was created using the projected incidence and progression over a 5-year horizon of diabetes-related complications (micro- and macrovascular disease, severe hypoglycaemia and diabetic ketoacidosis) for different HbA1c levels, with flexible input of population size, complications and therapy costs, HbA1c distribution and other variables. The model took a National Health Service and societal perspective. RESULTS: The model was developed, and in the proposed hypothetical situation, reductions in complications and expected costs evaluated. Achievement of target HbA1c in individuals with HbA1c ≥69 mmol/mol (8.5%) would reduce expected chronic complications from 6.8 to 1.2 events per 100 person-years, and diabetic ketoacidosis from 14.5 to 1.0 events per 100 person-years. Potential cumulative direct cost savings achievable in the modelled population were estimated at £687 m over 5 years (£5,585/person), with total (direct and indirect) savings of £1,034 m (£8,400/person). CONCLUSIONS: Implementation of strategies aimed at achieving target glucose levels in people with Type 1 diabetes in the UK has the potential to drive a significant reduction in complication costs. This estimate may provide insights into the potential for investment in achieving savings through improved diabetes care in the UK.

Banting Memorial Lecture 2014* Technology and diabetes care: appropriate and personalized.

Continuous subcutaneous insulin infusion was initially developed as a research procedure in the 1970s but quickly became a routine treatment for selected people with Type 1 diabetes. Continuous subcutaneous insulin infusion and other diabetes technologies, such as continuous glucose monitoring, are now an established and evidence-based part of diabetes care, but there has been some confusion about effectiveness and best use, particularly because of conflicting results from meta-analyses. This is because literature summary meta-analyses (including all trials) are inappropriate for therapeutic and economic decision-making; such meta-analyses should only include trials representative of groups likely to benefit. For example, for continuous subcutaneous insulin infusion, this would be those with continued disabling hypoglycaemia or elevated HbA1c levels. Alternatively, individual patient data meta-analysis allows modelling of covariates that determine effect size, e.g. in the case of continuous glucose monitoring, baseline HbA1c and frequency of sensor usage. Diabetes technology is therefore an example of personalized medicine, where evaluation and use should be both appropriate and targeted. This will also apply to future technologies such as new 'patch' pumps for Type 2 diabetes, closed-loop insulin delivery systems and nanomedicine applications in diabetes that we are currently researching. These include fluorescence lifetime-based non-invasive glucose monitoring and nanoencapsulation of islets for improved post-transplant survival.

Cost-effectiveness of continuous subcutaneous insulin infusion versus multiple daily injections of insulin in Type 1 diabetes: a systematic review.

AIM: Continuous subcutaneous insulin infusion (CSII) is increasingly used in clinical practice for the management of selected patients with Type 1 diabetes. Several cost-effectiveness studies comparing CSII vs. multiple insulin injections (MDI) have been reported. The aim was systematically to review these analyses and test the hypothesis that CSII is a cost-effective use of healthcare resources across settings. METHODS: A literature review was performed using MEDLINE, Cochrane Library and other databases. No time limit or language restrictions were applied. After two rounds of screening, 11 cost-effectiveness analyses were included in the final review, of which nine used the CORE Diabetes Model. A narrative synthesis was conducted and mean cost effectiveness calculated. RESULTS: CSII was considered cost-effective vs. MDI in Type 1 diabetes in all 11 studies in 8 countries, with a mean (95% CI) incremental cost effectiveness ratio of €30 862 (17 997-43 727), US$40 143 (23 409-56 876) per quality-adjusted life year (QALY) gained. CSII was associated with improved life expectancy and quality-adjusted life expectancy (0.4-1.1 QALYs in adults), driven by lower HbA(1c) and lower frequency of hypoglycaemic events vs. MDI. CSII was associated with higher lifetime direct costs due to higher treatment costs but this was partially offset by cost-savings from reduced diabetes-related complications. CONCLUSIONS: Published cost-effectiveness analyses show that in Type 1 diabetes CSII is cost-effective vs. MDI across a number of settings for patients who have poor glycaemic control and/or problematic hypoglycaemia on MDI, with cost-effectiveness highly sensitive to the reduction in HbA1c and hypoglycaemia frequency associated with CSII.

Variations in the quality and sustainability of long-term glycaemic control with continuous subcutaneous insulin infusion.

AIMS: To investigate the pattern of changes in HbA1c in people with Type 1 diabetes managed by long-term Continuous subcutaneous insulin infusion. METHODS: We studied HbA1c changes using computerized clinic records in 35 adult people with Type 1 diabetes and an elevated HbA1c (≥ 64 mmol/mol, 8.0%) on multiple daily insulin injections, who were then switched to continuous subcutaneous insulin infusion for at least 5 years. RESULTS: We identified three subgroups with similar baseline HbA1c but different long-term responses to pump therapy: group A--those with improvement followed by deterioration (57%); group B--those with improvement that was sustained throughout the 5 years (31%); and group C-those where HbA1c did not change significantly from baseline (12%). The patients in group C had a higher BMI: 31.0 ± 5.2 vs. 25.9 ± 3.3 vs. 25.2 ± 3.1 kg/m² (group C vs. group A and group B; P = 0.02). CONCLUSIONS: Improved glycaemic control with continuous subcutaneous insulin infusion was maintained over 5 years by 88% of people with Type 1 diabetes in this study, but there were variations in the long-term efficacy, with some people improving and worsening, others maintaining strict control and a few subcutaneous insulin infusion 'non-responders'.

Innate immunity, insulin resistance and type 2 diabetes.

In this edition of 'Then and now' the initial studies by J.C. Pickup and colleagues supporting the hypothesis that type 2 diabetes is caused by activated innate immunity, published in Diabetologia in 1997 (40:1286-1292), are discussed. These initial findings led to research that has uncovered links between insulin resistance, obesity, circulating immune markers, immunogenetic susceptibility, macrophage function and chronic infection. Genetic variations leading to the altered production or function of circulating innate immune proteins, cellular pattern recognition receptors and inflammatory cytokines are linked to obesity, insulin resistance and type 2 diabetes. Components of the innate immune system in the muscle, bone, liver and adipose tissue, as well as macrophages, have been revealed to play a role in systemic insulin action. Evolutionary pressures, such as acute infections at the population level (pandemics) and chronic low exposure to environmental products or infectious agents, may have contributed to increased susceptibility and to the current increase in the prevalence of insulin resistance and type 2 diabetes.

Nano-scale encapsulation enhances allograft survival and function of islets transplanted in a mouse model of diabetes.

AIMS/HYPOTHESIS: The success of islet transplantation as a treatment for type 1 diabetes is currently hampered by post-transplantation loss of functional islets through adverse immune and non-immune reactions. We aimed to test whether early islet loss can be limited and transplant survival improved by the application of conformal nano-coating layers to islets. METHODS: Our novel coating protocol used alternate layers of phosphorylcholine-derived polysaccharides (chitosan or chondroitin-4-sulphate) and alginate as coating materials, with the binding based on electrostatic complexation. The in vitro function of encapsulated mouse islets was studied by analysing islet secretory function and cell viability. The in vivo function was evaluated using syngeneic and allogeneic transplantation in the streptozotocin-induced mouse model of diabetes. RESULTS: Nano-scale encapsulated islets retained appropriate islet secretory function in vitro and were less susceptible to complement- and cytokine-induced apoptosis than non-encapsulated control islets. In in vivo experiments using a syngeneic mouse transplantation model, no deleterious responses to the coatings were observed in host animals, and the encapsulated islet grafts were effective in reversing hyperglycaemia. Allo-transplantation of the nano-coated islets resulted in preserved islet function post-implantation in five of seven mice throughout the 1 month monitoring period. CONCLUSIONS/INTERPRETATION: Nano-scale encapsulation offers localised immune protection for implanted islets, and may be able to limit early allograft loss and extend survival of transplanted islets. This versatile coating scheme has the potential to be integrated with tolerance induction mechanisms, thereby achieving long-term success in islet transplantation.

Severe hypoglycaemia and glycaemic control in Type 1 diabetes: meta-analysis of multiple daily insulin injections compared with continuous subcutaneous insulin infusion.

AIMS: Continuous subcutaneous insulin infusion (CSII) is a recommended treatment for reducing severe hypoglycaemia in Type 1 diabetes, but the change in hypoglycaemia compared with multiple daily insulin injections (MDI) is unclear. We therefore conducted a meta-analysis comparing severe hypoglycaemia and glycaemic control during CSII and MDI. METHODS: Databases and literature (1996-2006) were searched for randomized controlled trials (RCTs) and before/after studies of > or = 6 months' duration CSII and with severe hypoglycaemia frequency > 10 episodes/100 patient years on MDI. RESULTS: In 22 studies (21 reports), severe hypoglycaemia during MDI was related to diabetes duration (P = 0.038) and was greater in adults than children (100 vs. 36 events/100 patient years, P = 0.036). Severe hypoglycaemia was reduced during CSII compared with MDI, with a rate ratio of 2.89 (95% CI 1.45 to 5.76) for RCTs and 4.34 (2.87 to 6.56) for before/after studies [rate ratio 4.19 (2.86 to 6.13) for all studies]. The reduction was greatest in those with the highest initial severe hypoglycaemia rates on MDI (P < 0.001). The mean difference in glycated haemoglobin (HbA(1c)) between treatments was less for RCTs [0.21% (0.13-0.30%)] than in before/after studies [0.72% (0.55-0.90%)] but strongly related to the initial HbA(1c) on MDI (P < 0.001). CONCLUSIONS: The severe hypoglycaemia rate in Type 1 diabetes was markedly less during CSII than MDI, with the greatest reduction in those with most severe hypoglycaemia on MDI and those with the longest duration of diabetes. The biggest improvement in HbA(1c) was in those with the highest HbA(1c) on MDI.

Investigating incretin-based therapies as a novel treatment for depression in type 2 diabetes: Findings from the South London Diabetes (SOUL-D) Study.

We aimed to investigate the association between incretin-based therapies and 1-year change in depressive symptoms in a cohort of 1735 patients with newly diagnosed type 2 diabetes. The incretin group experienced significant reduction in depressive symptoms compared to controls. This was independent of HbA1c and may be mediated by an anti-inflammatory mechanism.

Correction of exercise-induced microalbuminuria in insulin-dependent diabetics after 3 weeks of subcutaneous insulin infusion.

The effect of metabolic near-normalization, induced by continuous subcutaneous insulin infusion, on the exaggerated microalbuminuria of exercise was studied in eight insulin-dependent diabetic men selected for normal resting albuminuria. Patients were studied in randomized order during the ordinary glycemic control of conventional insulin treatment (CIT) and after 3 wk of "super-control" with continuous subcutaneous insulin infusion (CSII). Seven age-matched healthy men were used as controls. In the diabetics the albuminuric response to fixed-load bicycle exercise (600 kpm/min for 20 min) during CIT greatly exceeded that of the normal controls (P less than 0.01). After 3 wk of optimal plasma glucose control, urinary albumin excretion rates in response to the same exercise load were significantly reduced (P less than 0.02) in the diabetics and became statistically indistinguishable from that of the normal controls. The urinary excretion rate of beta 2-microglobulin, an index of tubular function, was not increased significantly by exercise either during CIT or CSII. The plasma glucose fall after exercise was greater (P greater than 0.001) on CIT (8.5 +/- 0.9 mmol/L) than on CSII (4.0 +/- 0.6 mmol/L). The pulse rate acceleration in response to exercise was significantly reduced after 3 wk of CSII (P less than 0.05). The exercise-induced systolic blood pressure rise was similar in controls and diabetics on both therapeutic regimens. Thus, a period of metabolic near-normalization in the diabetic corrects the abnormal transglomerular passage of albumin induced by moderately strenuous muscular exercise and reduces the exercise tachycardia. Improved control with CSII appears to reduce greatly the risk of exercise-induced hypoglycemia, despite much tighter glycemic control.

Conference on insulin pump therapy in diabetes. Multicenter study of effect on microvascular disease. The pump life. Patient responses and clinical and technological problems.

As part of a randomized, prospective trial in subjects with insulin-dependent diabetes assigned to either continuous subcutaneous insulin infusion (CSII) or to their unchanged conventional insulin treatment (CIT) for 8 mo, patients completed questionnaires dealing with general responses and clinical and technological problems. Although there was no significant difference between treatment groups with respect to the number of patients experiencing severe hypoglycemia (i.e., requiring intravenous glucose or intramuscular glucagon injection), there were nine episodes in six patients during CSII compared with one episode during CIT. Diabetic ketoacidosis occurred significantly more often in the CSII group (nine episodes in eight patients) than in the CIT group (no episodes). A number of CSII-related failures occurred, including omission of premeal bolus, needle dislodgement, pump accidentally turned off, and leakage at the infusion site. At 8 mo, 85% of CSII-treated patients wished to continue indefinitely on the pump, and almost all would continue with self-monitoring of blood glucose even if they stopped CSII.

Conference on insulin pump therapy in diabetes. Multicenter study of effect on microvascular disease. Origin and design of the Kroc Collaborative Study.

Although the benefits of metabolic intervention on the microvascular complications of diabetes mellitus remain unproven, it is generally assumed though not proven that prognosis in terms of blindness and renal failure will reflect the long-term glycemic response to therapy. Treatment goals however remain poorly defined. Costs and hazards of achieving near-normoglycemia in insulin-dependent diabetes mellitus (IDDM) are major. A multicenter trial was proposed to test the hypothesis that in IDDM two levels of mean glycemia, sufficiently separated to examine the control/complications relationship, could be maintained by the six collaborating centers, using randomized patient allocation to conventional insulin therapy (CIT) and continuous subcutaneous insulin infusion (CSII) as the alternative treatment modalities. Methods of maintaining and monitoring metabolic control and of assessing renal and retinal responses were to be applied, evaluated, and possibly improved. All clinics shared a common experimental protocol, which received ethical approval at each treatment center. Retinal assessment facilities were provided by the Fundus Photograph Reading Center at the University of Wisconsin in Madison, and at the Diabetic Retinopathy Department, Royal Postgraduate Medical School, Hammersmith, United Kingdom. The Central Biochemistry Laboratory was at the University of Newcastle, United Kingdom. Collaborators agreed on policy for recruitment, baseline assessment, and randomization of patients with IDDM, complicated by early microvascular disease. CIT took the form of the unchanged prestudy regimen; glycemic goals were set for CSII and their achievement based on inpatient and outpatient sampling of plasma glucose. Glycosylated hemoglobin was measured, retinal abnormalities recorded photographically, and urinary albumin excretion quantitated at baseline, 4, and 8 mo in all patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Glucose-dependent changes in NAD(P)H-related fluorescence lifetime of adipocytes and fibroblasts in vitro: potential for non-invasive glucose sensing in diabetes mellitus.

The aim of this study was to test the hypothesis that glucose can be monitored non-invasively by measuring NAD(P)H-related fluorescence lifetime of cells in an in vitro cell culture model. Autofluorescence decay functions were measured in 3T3-L1 adipocytes by time-correlated single-photon counting (excitation 370nm, emission 420-480nm). Free NADH had a two-exponential decay but cell autofluorescence fitted best to a three-exponential decay. Addition of 30mM glucose caused a 29% increase in autofluorescence intensity, a significantly shortened mean lifetime (from 7.23 to 6.73ns), and an increase in the relative amplitude and fractional intensity of the short-lifetime component at the expense of the two longer-lifetime components. Similar effects were seen with rotenone, an agent that maximizes mitochondrial NADH. 3T3-L1 fibroblasts stained with the fluorescent mitochondrial marker, rhodamine 123 showed a 16% quenching of fluorescence intensity when exposed to 30mM glucose, and an increase in the relative amplitude and fractional intensity of the short lifetime at the expense of the longer lifetime component. We conclude that, though the effect size is relatively small, glucose can be measured non-invasively in cells by monitoring changes in the lifetimes of cell autofluorescence or of a dye marker of mitochondrial metabolism. Further investigation and development of fluorescence intensity and lifetime sensing is therefore indicated for possible non-invasive metabolic monitoring in human diabetes.

Preliminary evaluation of a skin conductance meter for detecting hypoglycemia in diabetic patients.

A portable device (the Diabalert), which measures the electrical conductivity of the skin surface and sounds an alarm at a preset conductivity, was evaluated as a possible detector of hypoglycemia-induced sweating in diabetic subjects. Insulin was infused intravenously into seven insulin-dependent diabetic subjects, and the course of the plasma glucose decline, hypoglycemic symptoms, and state of consciousness of the patients frequently monitored. In five patients sweating occurred with hypoglycemia, and the Diabalert alarm was activated at plasma glucose concentrations between 1.6 and 3.7 mmol/L. Three of these five diabetic patients were by then unaware of the alarm and would have failed to take corrective action to restore normoglycemia. Two further patients had virtually no symptoms despite marked biochemical hypoglycemia and the alarm was not triggered. Studies are needed in larger numbers of diabetic patients at home to fully assess the clinical usefulness of this device.

Salivary insulin in normal and type I diabetic subjects.

We studied the relationship of salivary insulin to serum insulin concentrations in normal subjects and type I (insulin-dependent) diabetic patients to test the hypothesis that salivary insulin might be a simple measure of insulinemia in diabetes. In 8 nondiabetic subjects, salivary insulin levels increased after an oral glucose load but with a delay in peak concentrations of approximately 45 min in comparison with serum insulin levels. There was a significant correlation (r = .810, P less than .01) between mean serum insulin and the salivary insulin 30 min later. In 12 type I diabetic patients, day profiles of saliva and serum insulin were obtained during usual insulin treatment, diet, and physical activity. In serum, the mean (+/- SE) percentage of bound insulin was 58.8 +/- 5.2%, and in saliva it was 45 +/- 3.5%. The mean ratio of salivary to serum free insulin throughout the day was 1:1.6. Although there was a significant correlation (r = .913, P less than .001) between mean serum free insulin for all patients and the corresponding mean free salivary insulin, several individual profiles showed marked discrepancies between the timing and magnitude of insulin changes in the two compartments. We would not, therefore, recommend salivary insulin concentrations as a reliable index of insulinemia in individuals with type I diabetes.

Elevated serum sialic acid concentration in NIDDM and its relationship to blood pressure and retinopathy.

OBJECTIVE: In view of the possible link between serum sialic acid and cardiovascular disease in the general population, we investigated whether serum total and lipid-associated sialic concentrations are elevated in NIDDM patients compared with normal subjects. We also investigated how sialic acid levels relate to glycemic control, blood pressure, microalbuminuria, retinopathy, and serum lipid levels. RESEARCH DESIGN AND METHODS: We selected 20 NIDDM patients at random and matched them for age and sex with 20 normal subjects. The patients also had a similar BMI as the control subjects. A first morning blood sample was taken for sialic acid, glucose, fructosamine, and lipid analysis, as was a first morning urine sample for assessment of microalbuminuria. Retinopathy was assessed by fundoscopy. RESULTS: Both total and lipid-associated sialic acid levels were elevated in the NIDDM patients compared with control subjects (mean +/- SD, total: 0.74 +/- 0.11 vs. 0.60 +/- 0.22 g/L, P < 0.02; lipid-associated: 0.18 +/- 0.04 vs 0.12 +/- 0.04 g/L, P < 0.001). Total serum sialic acid was correlated with systolic blood pressure (r = 0.58, P < 0.01) and diastolic blood pressure (r = 0.58, P < 0.02). There was no significant relationship of total sialic acid with age, duration of diabetes, BMI, microalbuminuria, serum triglyceride, blood glucose, or serum fructosamine. A relationship of lipid-associated sialic acid levels and systolic blood pressure did not reach significance (P = 0.09). In 9 patients with background retinopathy with or without maculopathy, the total serum sialic acid concentration was higher than in those without retinopathy (0.81 +/- 0.09 vs. 0.69 +/- 0.10 g/L, P < 0.008). Lipid-associated sialic acid levels were similar in those with and without retinopathy. (The conversion factor for standard units to SI units is 1 gL = 3.2 mM.) CONCLUSIONS: Total serum sialic acid levels were significantly elevated in a relatively small group of NIDDM patients and were correlated with hypertension and retinopathy. A larger study of circulating sialic acid concentrations as a risk factor for the development or marker of diabetic angiopathy is therefore justified.

Continuous intravenous insulin infusion in the management of brittle diabetes: etiologic and therapeutic implications.

Continuous intravenous insulin infusion (CIVII) was used to treat five brittle insulin-dependent diabetic women (aged 16-29 yr) who had failed to achieve satisfactory glycemic control during intensified subcutaneous insulin treatment including continuous subcutaneous insulin infusion (CSII). Insulin was infused through an indwelling central venous catheter by a portable pump for 3-16 mo. During CIVII, only three subjects obtained satisfactory glycemic control and only for short periods. Generally, as with CSII, control was erratic and unpredictable and three subjects intermittently had high insulin requirements (200 U/day). By contrast, three stable insulin-dependent diabetic subjects achieved near-normoglycemia within 1-3 days of starting CIVII with daily insulin dosages of 30-90 U. The lives of all five brittle subjects continued to be disrupted by frequent hospital admissions during CIVII treatment. Deliberate interference with their own treatment (including tampering with pumps and central venous catheters) was thought to be a major contribution to instability in two of the brittle subjects. In the others, the ineffectiveness of CIVII suggests that brittleness was not due solely to defective subcutaneous insulin absorption, as had previously been suggested in other CSII-unresponsive brittle subjects. Although CIVII has reportedly been successful in managing brittle diabetes, the technique may not be useful in all brittle individuals, as illustrated by the poor glycemic responses of these subjects and the serious complications (including local infection, septicemia, and thrombosis) they suffered.

Rarity of a marked "dawn phenomenon" in diabetic subjects treated by continuous subcutaneous insulin infusion.

We assessed the quality of overnight glycemic control and the frequency of the "dawn phenomenon" (nadir-0800 h glycemic increase) in 41 insulin-dependent diabetic patients treated by continuous subcutaneous insulin infusion (CSII). Mean plasma glucose levels were near-normal during the 24 h and, in particular, constant throughout the night. In a subset of six patients overnight plasma free insulin concentrations were also constant during CSII. The majority of profiles (88%) showed a glucose nadir from 2.0 to 5.9 mmol/L (most frequently at 0600 h) and had an 0800 h value from 2.0 to 6.9 mmol/L (92%). A large proportion (46%) of profiles showed a zero or negative nadir-0800 h glycemic increase. In 22 patients with three or more profiles recorded at the same basal insulin infusion rate, only one of 103 profiles had a fasting glycemic increase greater than an arbitrary value of 5.0 mmol/L (5.3), although many patients exhibited small dawn glycemic increases (e.g., 14 of 22 had a mean increase of from 0 to 2 mmol/L). In 12 subjects a 15% reduction in basal insulin infusion rate increased the mean +/- SEM dawn glycemic increase from 0.58 +/- 0.25 mmol/L to 2.7 +/- 0.76 mmol/L (P less than 0.025) as well as significantly increasing the nocturnal nadir and 0800 h plasma glucose concentrations. Thus, a marked dawn phenomenon is rare when a single but adequate basal infusion rate is used for CSII, and this questions the need in the majority of patients for preprogrammable pumps with nocturnal infusion rate changes.

Serum sialic acid, a risk factor for cardiovascular disease, is increased in IDDM patients with microalbuminuria and clinical proteinuria.

OBJECTIVE: An elevated serum sialic acid concentration has recently been shown to be a potent cardiovascular risk factor in the general population. Because clinical proteinuria is associated with a high frequency of cardiovascular disease, and because microalbuminuria predicts the development of renal and cardiovascular disease in diabetes, we investigated whether serum sialic acid levels are increased in insulin-dependent diabetes mellitus (IDDM) patients with microalbuminuria or clinical proteinuria. RESEARCH DESIGN AND METHODS: We studied 23 patients with IDDM who had a normal urinary albumin excretion rate, 23 patients who had microalbuminuria, and 23 patients with clinical proteinuria. The patients were matched for age, sex, duration of diabetes, GHb levels, and body mass index (BMI). Fasting blood samples were taken for measurement of sialic acid, cholesterol, triglyceride, creatinine, and GHb. RESULTS: Serum sialic acid was significantly higher in the microalbuminuric patients compared with the normoalbuminuric group (mean +/- SD: 1.93 +/- 0.26 vs. 1.76 +/- 0.27 mM, P < 0.01). Moreover, serum sialic acid was also significantly higher in the group with clinical proteinuria compared with the microalbuminuric patients (2.34 +/- 0.24 vs. 1.93 +/- 0.26 mM, P < 0.001). Serum sialic acid was not related independently to age, BMI, diabetes duration, GHb, blood pressure, serum cholesterol, triglyceride, or creatinine concentration in any of the diabetic groups. CONCLUSIONS: These observations suggest that the serum sialic acid concentration is raised in IDDM patients with both microalbuminuria and clinical proteinuria and may play a role as a cardiovascular risk factor or disease marker in these conditions.

Meeting the problems of first-generation insulin infusion pumps: clinical trial of a new miniature infuser.

We designed and constructed a new miniature, open-loop insulin infusion pump specifically to overcome the problems of many first generation insulin infusers. Special features are small size, adjustable volumetric basal infusion rate, rapid electronically mediated prandial insulin boosts, facility for doubling and halving the basal infusion rate and/or prandial delivery, and alarms for low battery state, motor over-run, stoppage, and control circuit malfunction. The infuser takes a specially designed syringe prefilled with short-acting insulin, sufficient in most diabetic patients for at least 7 days treatment with 100 U/ml insulin. To test clinical efficacy nine insulin-dependent diabetic patients received continuous subcutaneous insulin infusion (CSII) with the new infuser for periods up to 6 mo. Four patients previously CSII-treated with a first-generation pump and five who were new to CSII achieved and maintained the expected degree of near-normoglycemia. There were no pump breakdowns and a questionnaire completed by patients during the study confirmed ease and simplicity of operation and an appreciation of the advantages of the new pump compared with one widely used first-generation infuser.