Suzanne M. Strowig

Improved Glycemic Control in Intensively Treated Type 1 Diabetic Patients Using Blood Glucose Meters With Storage Capability and Computer-Assisted Analyses

OBJECTIVE To determine the effect on glycemic control in intensively treated type 1 diabetic patients using a blood glucose meter with storage capability and computer-assisted analyses. RESEARCH DESIGN AND METHODS Glycemic control was assessed in 22 intensively treated adults with type 1 diabetes for 12 months while using a meter without memory, followed by 12 months while using a meter with memory. Log books were used to assist patients in managing aspects of the diabetes treatment plan during the first 12-month period, and computer-assisted analyses were used when the meter with memory was used. GHb levels were measured monthly throughout the 24 months of observation. RESULTS The mean GHb level averaged across all patients during the period of memory meter use (6.4%) was significantly lower than that during the period of meter use without memory (6.9%) (P = 0.0004). The change in GHb levels from each period-specific baseline level occurred at significantly different slopes (P = 0.046) when adjusted for baseline GHb level. In addition, the downward trend in GHb level was greater in those patients who increased the frequency of testing the most (r = −0.54, P = 0.01). CONCLUSIONS Use of a meter with memory in conjunction with computer-generated analyses of stored blood glucose test results can lead to improved glycemic control when used by a group of intensively treated adult diabetic patients. Improvement in glycemic control was related to frequency of blood glucose testing.

Relationship between diabetes control and pulmonary function in insulin-dependent diabetes mellitus

PURPOSE To evaluate the effect of different levels of glycemic control on the pulmonary function of subjects with type I insulin-dependent diabetes mellitus. PATIENTS AND METHODS Eighteen subjects with type I insulin-dependent diabetes mellitus with no history or physical findings of respiratory disease. Patients were given insulin therapy with a standard twice-daily insulin injection regimen (standard treatment group) or a subcutaneous insulin infusion device (insulin pump) (intensive treatment group). Glycosylated hemoglobin (HbA1c) levels were determined at quarterly intervals in both groups of patients (standard treatment group, n = 10; intensive treatment group, n = 8). Pulmonary function and diffusing capacity for carbon monoxide (DLCO) were measured after 6 years of continuous follow-up. RESULTS The average HbA1c in the standard treatment group was significantly higher than that of the intensive treatment group throughout the 6 years of follow-up (p less than 0.001). The forced vital capacity of the standard treatment group was 85 +/- 3% of predicted as compared with 106 +/- 4% of predicted in the intensive treatment group (p less than 0.001). The DLCO was also significantly diminished in the standard treatment group as compared with that in the intensive treatment group (65 +/- 2% versus 87 +/- 4% of predicted) (p less than 0.001). CONCLUSION These data confirm previous reports of abnormal respiratory function in subjects with insulin-dependent diabetes mellitus and suggest that long-term near-normoglycemia may be beneficial in preventing the deterioration of pulmonary function associated with diabetes mellitus.

A comparison of insulin lispro and buffered regular human insulin administered via continuous subcutaneous insulin infusion pump

This study compared glycemic control achieved with insulin lispro or buffered regular human insulin in patients with Type 1 diabetes treated with continuous subcutaneous insulin infusion (CSII) using an external insulin pump. In this 24-week multicenter, randomized, two-way crossover, open-label trial, 58 patients on CSII with adequate glycemic control received either insulin lispro or buffered regular human insulin for 12 weeks, followed by the alternate treatment for another 12 weeks. Efficacy and safety measures included hemoglobin A(1c) (HbA(1c)) at baseline and endpoint, home blood glucose monitoring, hypoglycemia, and frequency of pump catheter occlusion. Patients consumed a standard test meal on three occasions, with determinations of fasting, 1- and 2-h postprandial glucose values. Insulin lispro use was associated with a significantly lower HbA(1c) than was buffered regular human insulin (7.41+/-0.97 vs. 7.65+/-0.85 mmol/l; P=.004). Fasting serum glucose values before the test meal were similar between the two therapies. The 1-h (11.16+/-4.29 vs. 13.20+/-4.68 mmol/l; P=.012) and 2-h (9.64+/-4.10 vs. 12.53+/-4.64 mmol/l; P=.001) postprandial glucose concentrations were significantly lower during treatment with insulin lispro. No differences between treatments were observed in basal or bolus insulin doses, weight gain, or the incidence and rate of hypoglycemia, hyperglycemia, or pump occlusions. When used in external pumps, insulin lispro provides better glycemic control than buffered regular human insulin with a similar adverse event profile.

Glycemic Control and Diabetic Complications

The relationship between glycemic control and diabetic complications remains unclear. Epidemiological studies reveal that ∼25% of diabetic individuals do not develop complications, irrespective of degree of glycemic control. Studies of genetic factors, including HLA type, capillary basement membrane thickness, genetic predisposition to hypertension, and familial clustering of diabetic complications, suggest that there is a genetic component to developing the complications of diabetes. On the other hand, clinical trials have demonstrated that the progression of early, mild background retinopathy, microalbuminuria, and parameters of nervous system function are stabilized with improved glycemic control. Other metabolic parameters, such as serum lipoprotein levels, are significantly improved with near normoglycemia. No studies to date have evaluated the effect of blood glucose control on the prevention of diabetic complications. The degree of glycemic control required to impact on diabetic complications is unknown. In addition, achieving near normoglycemia carries increased risk for severe hypoglycemia and weight gain. Further study is needed to determine the long-term benefits of blood glucose control and to weigh that against the risks of improving glycemic control. Further investigation also is needed to address the probable interrelationship of genetic factors and glycemic control on the development of diabetic complications.

Combination therapy using metformin or thiazolidinediones and insulin in the treatment of diabetes mellitus

The biguanide, metformin, sensitizes the liver to the effect of insulin, suppressing hepatic glucose output. Thiazolidinediones such as rosiglitazone and pioglitazone enhance insulin‐mediated glucose disposal, leading to reduced plasma insulin concentrations. These classes of drugs may also have varying beneficial effects on features of insulin resistance such as lipid levels, blood pressure and body weight. Metformin in combination with insulin has been shown to significantly improve blood glucose levels while lowering total daily insulin dose and body weight. The thiazolidinediones in combination with insulin have also been effective in lowering blood glucose levels and total daily insulin dose. Triple combination therapy using insulin, metformin and a thiazolidinedione improves glycaemic control to a greater degree than dual therapy using insulin and metformin or insulin and a thiazolidinedione. There is insufficient evidence to recommend the use of metformin or thiazolidinediones in type 1 diabetic patients. Although these agents are largely well tolerated, some subjects experience significant gastrointestinal problems while using metformin. Metformin is associated with a low risk of lactic acidosis, but should not be used in patients with elevated serum creatinine or those being treated for congestive heart failure. The thiazolidinediones are associated with an increase in body weight, although this can be avoided with careful lifestyle management. Thiazolidinediones may also lead to oedema and are associated with a low incidence of hepatocellular injury. Thiazolidinediones are contraindicated in patients with underlying heart disease who are at risk of congestive heart failure and in patients who have abnormal hepatic function. The desired blood glucose‐lowering effect and adverse event profiles of these agents should be considered when recommending these agents to diabetic patients. The potential for metformin or the thiazolidinediones to impact long‐term cardiovascular outcomes remains under investigation.

Iatrogenic hyperinsulinemia in type 1 diabetes: Its effect on atherogenic risk markers☆

AIMS Insulin is lipogenic and may invoke inflammation. We wished to determine if well controlled human and mice with type 1 diabetes had iatrogenic hyperinsulinemia as an explanation for the increased rate of coronary artery disease (CAD) in type 1 diabetes. METHODS Type 1 diabetic subjects with HbA1C less than 7.0% had plasma insulin measured before and one hour after a Boost® challenge and a dose of subcutaneously administered insulin. These levels were compared with non-diabetic humans. Plasma insulin levels in well controlled NOD mice with type 1 diabetes were measured 3 h and 17 h after their usual dose of insulin. Hepatic cholesterol-relevant CAD and inflammation markers were measured in the NOD mice. RESULT Marked iatrogenic hyperinsulinemia was observed in patients at levels of approximately two times higher than in non-diabetic controls. Similar findings were present in the NOD mice. Hepatic CAD risk markers were increased by insulin, but did not exceed normal expression levels in non-diabetic mice with lower insulin. In contrast, insulin-mediated stimulation of pro-inflammatory mediators TNF-α and IL-1β remained significantly higher in hyperinsulinemic NOD than non-diabetic mice. CONCLUSION Optimal insulin therapy in mice and humans with type 1 diabetes causes iatrogenic hyperinsulinemia and subsequently promotes pro-inflammatory macrophage response independent of hepatic cholesterol-relevant CAD markers. The tight glycemic control in type 1 diabetes may thus increase the risk for atherogenesis via inflammation.

Reduction in Cardiovascular Risk Factors With Intensive Diabetes Treatment in Insulin-Dependent Diabetes Mellitus

We measured plasma lipid and lipoprotein levels at baseline and at 6-mo intervals in 47 normolipidemic patients with classic insulin-dependent diabetes mellitus treated either with a conventional (n = 21) or intensive (n = 26) diabetes-treatment program. Patients were followed for a mean of 3 yr (range 1–4 yr). Intensive diabetes treatment resulted in a significant improvement in glycemic control that caused sustained changes in plasma lipid and lipoprotein levels that were not evident with the conventional- treatment program. These changes, which persisted for periods averaging 3 yr, can potentially reduce predicted risk for the development of premature atherosclerosis. Thus, long-term near normoglycemia may have a role in the prevention of atherosclerosis in insulin-dependent diabetic patients.

Comparison of a novel insulin bolus-patch with pen/syringe injection to deliver mealtime insulin for efficacy, preference, and quality of life in adults with diabetes: a randomized, crossover, multicenter study.

OBJECTIVE This study compared the efficacy, safety, device satisfaction, and quality of life (QOL) in people with diabetes using an insulin bolus-patch versus current devices (pen/syringe) to deliver mealtime insulin. RESEARCH DESIGN AND METHODS Thirty-eight subjects with diabetes (26 with type 1 and 12 with type 2) were randomized to bolus-patch or current injection device (55% pen and 45% syringe) to deliver mealtime insulin in a multicenter, 6-week crossover study. Efficacy was assessed by equivalence in mean daily seven-point blood glucose (MDBG). Safety assessments included severe hypoglycemia episodes, adverse device effects (ADEs), and adverse events (AEs). Device satisfaction was determined by the validated Insulin Delivery System Rating Questionnaire (IDSRQ) and QOL by the validated Diabetes Specific QOL Scale (DSQOLS). RESULTS Using bolus-patch, MDBG (mean±SE) was equivalent to that using pen/syringe (8.61±0.28 vs. 9.02±0.26 mmol/L; P=0.098). SD of the seven-point blood glucose measurements was lower using bolus-patch (3.18±0.18 vs. 3.63±0.17 mmol/L; P=0.004), as was the coefficient of variation (CV) (37.2±1.7 vs. 40.3±1.7%; P=0.046). Hemoglobin A1c, 1,5-anhydroglucitol, fructosamine, and insulin use were similar between groups. There were no severe hypoglycemia episodes or serious ADEs. Between-device AEs were comparable. Subjects scored better on six of seven subscales on the DSQOLS and five of six subscales on the IDSRQ while using bolus-patch versus pen/syringe. At study completion, 76% of subjects would choose to switch to bolus-patch (P=0.001). CONCLUSIONS Delivery of mealtime insulin with bolus-patch compared with pen/syringe resulted in equivalent MDBG, lower SD and CV of seven-point blood glucose measurements, good safety, significant device satisfaction, and improved QOL.

Personality traits as predictors of good diabetic control

To identify personality characteristics that might contribute to overall good control of type I diabetes mellitus, we used a biological correlate of control, glycosylated hemoglobin A1c values, as a means of selecting patients. Patients with evidence of good control (HbA1c less than 7.5%) were compared with patients with evidence of poor control (HbA1c greater than 10.4%). All patients were administered the Personality Research Form E. Need for achievement and a socially desirable response style were associated with good glycemic control. This finding is placed in the context of the complexity of health care behaviors required for adequate self-management.

Patient-reported experience with velosulin® Human insulin in continuous subcutaneous insulin infusion

A multicenter, retrospective survey of 339 patients with insulin-dependent diabetes mellitus was done to evaluate patient experience with Velosulin Human insulin, a regular insulin in a phosphate buffer, used in continuous subcutaneous insulin infusion. Patients had used this insulin exclusively for 3 months preceding the survey. Responses were elicited through interviews conducted by physicians or nurses. Patients were queried as to the occurrence of specific complications associated with pump therapy that occurred while using Velosulin Human insulin, including hypoglycemia, diabetic ketoacidosis, unexplained hyperglycemia, tubing obstruction, and infection or abscess at the infusion site. Most patients reported that they did not experience any of these complications during the preceding 3 months. The most frequently cited complication was hyperglycemia unexplained by dosage, exercise, or dietary changes, reported by 110 (32%) patients. The second most frequently reported complication was tubing obstruction, reported by 99 (29%) patients. The reported frequencies of the other complications were: severe hypoglycemia, 45 (13%) patients; diabetic ketoacidosis, 28 (8%) patients; and infection or abscess at the infusion site, 26 (8%) patients. The low morbidity reported by the patients in this survey probably was due in large part to careful patient selection, a high level of motivation on the part of the patients, and experience and education on the part of the health care team, as well as to the use of buffered regular human insulin.