Insulin Injections In Patients Research Articles

Pharmacotherapy in Type 1 Diabetes

Pharmacotherapy in Type 1 Diabetes

New insulins and insulin therapy

New insulins and insulin therapy

A Case of Insulin Resistance Secondary to Insulin Induced Localized Cutaneous Amyloidosis.

Abstract 4908Insulin resistance can be a major problem in patients with diabetes mellitus. Although multiple reasons can result in this problem, one of the rare causes is localized insulin induced cutaneous amyloidosis. Lack of recognition of this may result in fatal hypoglycemia if a higher dose of insulin is given at a different site.A 43-year-old female diagnosed with diabetes mellitus in 1986 after acute pancreatitis secondary to hypertriglyceridemia presented to our hospital in December of 2008 with a 2 year history of low grade fever of 99-100F. This was associated with chills and fatigue. Over the same time period she had noticed anterior abdominal wall nodularity, particularly at sites where she has been injecting her insulin. Her insulin requirement had also increased from a total of 60 units of NPH in a day to 170 units per day. Because of the subcutaneous nodularity at the site of injection a decision was made to switch the site of the insulin which resulted in lower blood glucose level and subsequently significant decrease in her insulin requirement to 120 units a day. This suggested poor absorption from the infiltrated site. At our clinic laboratory data showed normal white count of 5.4 × 10(9)/L with normal differential, normal hemoglobin of 12.9 g/dL with an ESR of 11 mm/hour, creatinine of 0.8 mg/dL and C-reactive protein of less than 3. As part of the work up for fever of unknown origin a CT-scan of the abdomen was obtained which showed infiltrative lesion in the anterior abdominal subcutaneous tissue with few calcifications Fig 1 & 2. Biopsy of the anterior abdominal wall nodular infiltrate was performed. Tissue cultures came out negative for infection. The biopsy showed eosinophilic material positive with Congo red staining and showing apple green birefringence when viewed under polarized light. Immunohistochemical staining showed this to be negative for AA, AL, or TTR amyloidosis. Liquid chromatography tandem mass spectrometry (LC MS/MS) detected peptides representing apolipoprotein E, apolipoprotein A-IV, SAP and Insulin. The amyloid deposits stained positive with anti-insulin. The presence of peptides from insulin and immunohistochemical reactivity with an anti-insulin antibody indicated that the amyloid deposits were caused by insulin injection at this site. Work up for systemic amyloidosis including serum protein electrophoresis with immunofixation was negative for a monoclonal protein. Quantitative immunoglobulins were within normal range. Her 24-hour urine protein was 65 mg within normal range. Her serum free light chains were unremarkable. Echocardiogram did not show any evidence of infiltrative cardiomyopathy. This was therefore consistent with localized insulin induced cutaneous amyloidosis. The recommendation was to change the insulin type and to rotate the insulin injection site. Because of occasional hemorrhage and pain the long term plan will be to surgically remove the amyloid deposits.Insulin mediated iatrogenic localized amyloidosis has been described previously in the literature at the sites of insulin injection in patients with diabetes. This is a rare complication of insulin therapy and must be considered in the differential diagnosis of patients with insulin resistance to prevent fatal hypoglycemia. [Display omitted] [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Switch to oral hypoglycemic agent therapy from insulin injection in patients with type 2 diabetes

We aimed to determine the feasibility of substituting thiazolidinedione-based therapy for insulin injection therapy in patients with type 2 diabetes. Thirty-six subjects (17 men and 19 women) aged 67.8 +/- 11.3 years with an average insulin dose of 0.46 +/- 0.17 U/kg bodyweight, a duration of insulin therapy of 6.1 +/- 8.2 years and an average hemoglobin A1c (HbA1c) of 6.8 +/- 1.3% were switched from insulin injection therapy to pioglitazone, glimepiride and voglibose combination therapy. The number of subjects achieving HbA1c levels of less than 7% at 4 months was 30. The success rate of switch therapy was 83% (30/36). HbA1c was significantly reduced from 6.7 +/- 1.3% to 5.9 +/- 0.7% at 4 months after the switch (P < 0.01) in 32 patients who completed the planned 4-month study. No adverse effects including heart failure, liver dysfunction or severe hypoglycemia were observed. The insulin dose and the maximum blood glucose on the switch day were significantly lower and the age was significantly higher in the subjects who achieved HbA1c less than 7% at 4 months compared to those who did not (P < 0.05). Thiazolidinedione-based oral combination therapy may efficiently and safely substitute relatively high-dose insulin injection therapy in patients with type 2 diabetes.

Continuous subcutaneous insulin infusion versus multiple daily insulin injections in patients with diabetes mellitus: systematic review and meta-analysis

We compared the effects of continuous subcutaneous insulin infusion (CSII) with those of multiple daily insulin (MDI) injections on glycaemic control, risk of hypoglycaemic episodes, insulin requirements and adverse events in type 1 and type 2 diabetes mellitus. The electronic databases MEDLINE, EMBASE and CENTRAL were systematically searched for randomised controlled trials up to March 2007. A systematic review and meta-analysis were performed. Overall, 22 studies were included (17 on type 1 diabetes mellitus, two on type 2 diabetes mellitus, three on children). With regard to adults with type 1 diabetes mellitus, our meta-analysis found a between-treatment difference of -0.4% HbA(1c) (six studies) in favour of CSII therapy. Available median rates of mild or overall hypoglycaemic events were comparable between the different interventions (1.9 [0.9-3.1] [CSII] vs 1.7 [1.1-3.3] [MDI] events per patient per week). Total daily insulin requirements were lower with CSII than with MDI therapy. In patients with type 2 diabetes mellitus, CSII and MDI treatment showed no statistically significant difference for HbA(1c). The incidence of mild hypoglycaemic events was comparable between the treatment groups. In adolescents with type 1 diabetes mellitus, glycated haemoglobin and insulin requirements were significantly lower in the CSII groups; no data were available on hypoglycaemic events. The only study performed in younger children did not provide enough data for conclusive inferences. No overall conclusions were possible for severe hypoglycaemia and adverse events for any of the different patient groups due to rareness of such events, different definitions and insufficient reporting. CSII therapy in adults and adolescents with type 1 diabetes mellitus resulted in a greater reduction of glycated haemoglobin, in adult patients without a higher rate of hypoglycaemia. No beneficial effect of CSII therapy could be detected for patients with type 2 diabetes mellitus.

Improved motor development and good long-term glycaemic control with sulfonylurea treatment in a patient with the syndrome of intermediate developmental delay, early-onset generalised epilepsy and neonatal diabetes associated with the V59M mutation in the KCNJ11 gene

Activating mutations in the KCNJ11 gene encoding the Kir6.2 subunit of the K(ATP) channels in pancreatic beta cells are a common cause of neonatal diabetes. One-third of patients also have developmental delay, which probably results from mutated K(ATP) channels in muscle, nerve and brain. Sulfonylureas, which bind to the sulfonylurea receptor 1 subunit of the K(ATP) channel, can replace insulin injections in patients with KCNJ11 mutations. The aim of this study was to investigate the long-term outcome and impact on neurological features of sulfonylurea treatment. We report the response to sulfonylurea treatment in a boy with neonatal diabetes and marked developmental delay resulting from the KCNJ11 mutation V59M. Glibenclamide (glyburide) treatment was started at 23 months and resulted in insulin being discontinued, lower overall glycaemia, reduced glucose fluctuations and reduced hypoglycaemia. Good control (HbA(1c) 6.5%) was maintained 2 years after discontinuing insulin, despite a reduction in the glibenclamide dose (from 0.41 to 0.11 mg.kg(-1).day(-1)). Within 1 month of starting glibenclamide there was marked improvement in motor function, resulting in the patient progressing from being unable to stand unaided to walking independently, but there was no improvement in mental function. This 2-year follow-up of a patient highlights that sulfonylurea treatment can result in prolonged, excellent glycaemic control and may improve motor features, but not mental features, associated with KCNJ11 mutations. This suggests that the neurological actions of sulfonylurea are initially principally on peripheral (nerve or muscle) rather than on central (brain) K(ATP) channels. Early molecular diagnosis is important in patients with neonatal diabetes and neurological features.

A multicenter, randomized, open-label, comparative, two-period crossover trial of preference, efficacy, and safety profiles of a prefilled, disposable pen and conventional vial/syringe for insulin injection in patients with type 1 or 2 diabetes mellitus

Background: The accuracy and convenience of pen devices for insulin injection have improved quality of life for patients with insulin-treated diabetes mellitus (DM). Prefilled, disposable pens have the advantage of simplicity, with minimal training and attention required and no installation of new cartridges necessary. Objective: The aim of this study was to assess patient preference, efficacy, and safety profiles of a prefilled, disposable pen (FlexPen®) and conventional vial/syringe injection method for insulin injection therapy among patients with DM. Methods: In a multicenter, randomized, open-label, crossover study, patients with type 1 or 2 DM were transferred from previous QD or BID conventional insulin therapy to a mixture of 70% insulin aspart protamine suspension and 30% insulin aspart injection (NovoLog® Mix 70 30 ) for 4 weeks of dose optimization using their usual type of syringe. Patients were then randomly assigned to use either vial/syringe or a prefilled, disposable pen to inject the biphasic insulin aspart 70 30 mixture for the next 4 weeks, followed by 4 weeks of use of the other injection device. Efficacy, safety profiles, and patient preference for the delivery systems were compared. Results: A total of 121 patients (mean [SD] age, 57.0 [12.4] years; age range, 28–81 years; mean [SD] body mass index, 31 [5.5] kg/m 2) were enrolled. One hundred three patients completed the study. Seventy-four percent of patients ( 78 105 ) indicated a preference for the pen over the vial/syringe method (95% CI, 71%–87%), compared with 20% ( 21 105 ) who preferred the vial/syringe. Eighty-five percent ( 88 104 ) considered the pen more discreet for use in public (compared with 9% [ 9 104 ] for the vial/syringe), 74% ( 77 104 ) considered it easier to use overall (compared with 21% [ 22 104 ] for the vial/syringe), and 85% ( 89 105 ) found the insulin dose scale on the pen easier to read (compared with 10% [ 10 105 ] for the vial/syringe). Patients had statistically significant improvement in glycosylated hemoglobin values during the study ( P < 0.05). No statistically significant differences in fasting plasma glucose, mean 4-point blood glucose profiles, or serum fructosamine values were found between groups. Overall, the safety profiles during treatment periods with the pen were comparable to those with the vial/syringe. Conclusions: In this trial, differences in efficacy and safety profiles between the vial/syringe and prefilled, disposable pen appeared negligible. However, more patients expressed a preference to continue use of the pen.

Review: Intensive insulin pump therapy slightly improves glycemic control in type 1 diabetes

Source Citation Pickup J, Mattock M, Kerry S. Glycaemic control with continuous subcutaneous insulin infusion compared with intensive insulin injections in patients with type 1 diabetes: meta-analysis of randomised controlled trials. BMJ. 2002 Mar 23;324:705-8. 11909787

Glycaemic control with continuous subcutaneous insulin infusion compared with intensive insulin injections in patients with type 1 diabetes: meta-analysis of randomised controlled trials

Objective: To compare glycaemic control and insulin dosage in people with type 1 diabetes treated by continuous subcutaneous insulin infusion (insulin infusion pump therapy) or optimised insulin injections.Design: Meta-analysis of...

Pre-meal inhaled insulin treatment is an effective alternative to regular meal-related insulin injections in patients with type 1 diabetes

Pre-meal inhaled insulin treatment is an effective alternative to regular meal-related insulin injections in patients with type 1 diabetes

Coronary hyperreactivity to adrenergic stimulation and increased nocturnal vagal tone trigger coronary vasospasm.

The relationship between autonomic nervous system activity (ANA) and coronary vasoreactivity during transient myocardial ischemia was determined in patients with vasospastic angina (VA). ANA was measured by power spectral analysis of heart rate variability and humoral factors following intravenous infusion of insulin in 24 patients with VA and 6 control patients. Nine (38%) of the VA patients had significant ST segment depression (STD), and 4 of these patients had symptomatic STD. The frequency of anginal episodes in the 9 patients with VA and STD was significantly greater than that in the 15 VA patients without STD (3.4 +/- 3.1 vs 0.5 +/- 0.8 episodes/week, p < 0.05). The increase in the LF/HF ratio 30 min after insulin injection in patients with STD was significantly greater than that in patients without STD (34 +/- 31% vs 4 +/- 34%, p < 0.05). All of the patients with VA and STD had significant coronary vasospasm in response to the infusion of < or = 20 micrograms of acetylcholine, higher levels of nocturnal parasympathetic activity, and greater norepinephrine production in response to insulin stimulation than the VA patients without STD. These findings suggest that increased vagal tone and hyperreactivity to adrenergic stimulation may trigger vasospasm in patients with VA.

New Orally Administered Antihyperglycemic Agents for the Management of Patients with Type II Diabetes and the Syndrome of Insulin Resistance

To describe several newly developed orally administered antidiabetic drugs, which are effective for type II diabetes. Detailed clinical information about three types of antihyperglycemic agents--carbohydrase inhibitors, biguanides, and thiazolidinediones--is presented. Miglitol and acarbose, two a-glucosidase inhibitors, effectively reduce postprandial blood glucose values and do not cause hypoglycemia. The biguanide metformin has been shown to suppress hepatic glucose production, augment glucose uptake, and enhance insulin action in peripheral tissues. Metformin is effective alone or in combination with other orally administered antidiabetic agents or insulin. A new class of antidiabetic agents called the thiazolidinediones (not yet available for clinical use) apparently works by mainly reducing insulin resistance in skeletal muscle. The most extensively studied drug in this category is troglitazone. Carbohydrase inhibitors as well as biguanides may be useful in patients with the insulin resistance syndrome, especially those with obesity, hypertension, and hyperinsulinemia. Because of the development of new antihyperglycemic agents for oral administration, the need for insulin injections in patients with type II diabetes will be minimized, and the clinical management of such patients will be improved.

Metformin

The biguanide metformin (dimethylbiguanide) is an oral antihyperglycaemic agent used in the management of non-insulin-dependent diabetes mellitus (NIDDM). It reduces blood glucose levels, predominantly by improving hepatic and peripheral tissue sensitivity to insulin without affecting the secretion of this hormone. Metformin also appears to have potentially beneficial effects on serum lipid levels and fibrinolytic activity, although the long term clinical implications of these effects are unclear. Metformin possesses similar antihyperglycaemic efficacy to sulphonylureas in obese and nonobese patients with NIDDM. Additionally, interim data from the large multicentre United Kingdom Prospective Diabetes Study (UKPDS) indicated similar antihyperglycaemic efficacy for metformin and insulin in newly diagnosed patients with NIDDM. Unlike the sulphonylureas and insulin, however, metformin treatment is not associated with increased bodyweight. Addition of metformin to existing antidiabetic therapy confers enhanced antihyperglycaemic efficacy. This may be of particular use in improving glycaemic control in patients with NIDDM not adequately controlled with sulphonylurea monotherapy, and may serve to reduce or eliminate the need for daily insulin injections in patients with NIDDM who require this therapy. The acute, reversible gastrointestinal adverse effects seen with metformin may be minimised by administration with or after food, and by using lower dosages, increased slowly where necessary. Lactic acidosis due to metformin is rare, and the risk of this complication may be minimised by observance of prescribing precautions and contraindications intended to avoid accumulation of the drug or lactate in the body. Unlike the sulphonylureas, metformin does not cause hypoglycaemia. Thus, metformin is an effective antihyperglycaemic agent which appears to improve aberrant plasma lipid and fibrinolytic profiles associated with NIDDM. Possible long term clinical benefits of this drug with regard to cardiovascular mortality and morbidity are not yet established but are being assessed in a major ongoing study. Since metformin does not promote weight gain or hypoglycaemia it should be considered first-line pharmacotherapy in obese patients with NIDDM inadequately controlled by nonpharmacological measures. Metformin appears similarly effective for the pharmacological management of NIDDM in nonobese patients.