[Individualized therapy. Insulin therapy requirements in pregnancy and old age].
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Aged↗
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[Which form of therapy (insulin therapy or oral antidiabetics) is best for a patient with newly diagnosed type 2 diabetes mellitus?].
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Diabetes Mellitus, Type 2↗
[Insulin therapy: insulin varieties and usage tactics].
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Insulin↗
Increased cholesteryl ester transfer protein and changes in lipid metabolism from initiating insulin therapy.
Insulin therapy is often necessary for glycemic control, and its effect on plasma lipids is an important issue with respect to arteriosclerosis. Previous reports suggested that increased cholesteryl ester transfer protein (CETP) appeared in diabetic patients with hyperinsulinemia or given a lot of insulin is atherogenic. We investigated whether insulin always increases CETP and whether increased CETP by insulin is always atherogenic. In 40 patients the amount and activity of CETP were assessed before and 2 weeks after initiation of insulin therapy. After starting insulin, plasma concentrations of total cholesterol, triglycerides, LDL-cholesterol, and remnant lipoprotein cholesterol decreased. No change occurred in HDL-cholesterol. Starting insulin therapy increased the amount and activity of CEIP. No significant correlation was observed between changes in CETP and in lipids including HDL-cholesterol or apolipoprotein concentrations. This is the first prospective study to show increased CETP activity after initiation of insulin therapy. After initiating insulin, CETP increases without accompanying atherogenic changes in lipid metabolism. Based on the changes observed, CETP in itself does not have atherogenicity and the increase, but no excess, of CETP by appropriate insulin therapy cannot be atherogenic.
Apolipoproteins↗
Insulin therapy improves insulin actions on glucose metabolism and aortic wave reflection in type 2 diabetic patients.
BACKGROUND: Normal insulin action in vivo involves a decrease in aortic systolic blood pressure as a result of an insulin-induced decrease in the amplitude of the second systolic (reflected) pressure wave. This action of insulin and insulin action on glucose metabolism is impaired in insulin-resistant and type 2 diabetic subjects. We determined whether 6 months of insulin therapy affects insulin actions on glucose metabolism and vascular function. MATERIALS AND METHODS: Thirteen type 2 diabetic patients (age 53 +/- 2 years, body mass index 30.8 +/- 1.2 kg m(-2), HbA1C 8.8 +/- 0.2%) were studied before and after insulin therapy. Central aortic pressure waveforms were reconstructed from those recorded in the periphery using applanation tonometry every 30 min. This allowed determination of augmentation, i.e. the pressure difference between the second and first systolic pressure peaks and the augmentation index (AgI, augmentation divided by pulse pressure). The measurements were performed basally and during euglycaemic hyperinsulinaemic conditions. RESULTS: Insulin therapy increased whole body glucose disposal by 35% from 5.1 +/- 0.7 to 6.8 +/- 0.6 mg kg ffm(-1) min(-1) (P<0.001 for 0 vs. 60 months). 6 months of insulin therapy decreased basal AgI from 26.2 +/- 1.8 to 22.7 +/- 2.3% (P<0.05). The change in AgI by insulin infusion was similar before and after insulin therapy at all time points. Peripheral blood flow, heart rate and blood pressures remained unchanged. CONCLUSIONS: Insulin therapy improves insulin action on glucose metabolism and decreases basal AgI. These data support the idea that insulin therapy has beneficial effects on vascular function.
Adult↗
[Progress in insulin therapy. V. Insulin therapy in noninsulin dependent diabetes mellitus].
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C-Peptide↗
Correlates of insulin antibodies in newly diagnosed children with insulin-dependent diabetes before insulin therapy.
Insulin antibodies, as measured by plasma radiolabeled insulin-binding capacity, were determined in 124 newly diagnosed insulin-dependent diabetic (IDDM) children before and after 1, 3, and 5 days of insulin therapy. Controls were 35 nondiabetic children with plasma insulin binding capacity of 1.0 +/- 0.7%. The patients were divided into three groups according to their plasma insulin-binding capacity. Group 1 (N = 79) had binding within two standard deviations (SD) of the control mean, group 2 (N = 20) had insulin binding 2-6 SD above controls, and group 3 (N = 25) showed insulin-binding capacity of more than 6 SD above the control mean. After exogenous insulin therapy, plasma 125I-insulin-binding capacity dropped significantly in both groups 2 and 3, concurrent with significant increases in plasma insulin levels. The three groups differed from each other in that patients in group 3 were significantly younger than in the other groups and clinically seemed to be more severely dehydrated, as reflected in their higher levels of serum urea nitrogen, plasma glucose, potassium, and elevated pulse rate. The three groups did not differ in respect to sex, HLA-DR antigens, Coxsackie-B antibody titers, islet cell cytoplasmic antibodies, immunoglobulin level, and C-peptide levels. Only two of 446 siblings of IDDM children showed elevated insulin binding, one of whom developed IDDM 6 wk later. The presence of an insulin-binding substance probably representing insulin antibodies in some cases of newly diagnosed IDDM suggests that autoimmunity in this disorder is not limited to the B-cell membrane and cytoplasm and lends further support to the heterogeneity of IDDM.
Adolescent↗
Insulin therapy.
Insulin therapy is the most important treatment aspect of diabetes mellitus. Since the discovery of insulin in 1921, a variety of insulin formulations have been developed. The purpose of this article is to describe the current sources, formulations, and types of insulins available for therapy of diabetes mellitus in small animals and to provide the veterinarian with guidelines for insulin therapy in dogs and cats.
Animals↗
[Brazilian Diabetes Society consensus statement--intensive insulin therapy and insulin pump therapy].
This article reports the Brazilian Diabetes Society consensus statement on intensive insulin therapy and insulin pump therapy, arrived at during an update symposium held in 2003 for this specific purpose. The concepts underlying these modalities of diabetes treatment are outlined, their fundaments are given, and practical issues about their indications, feasibility, limits, techniques and cost-benefit relationships are analyzed. The techniques comprise the suggested self-monitoring schedules and the insulin doses, types, forms of administration and correction factors used in each modality of intensive treatment, for both type 1 and 2 diabetes. The roles of SBD in the implementation of these treatments and of the different professionals involved are discussed and commented. The conclusions are based on consensual answers to some orienting questions formulated during the symposium's presentation.
Blood Glucose Self-Monitoring↗
Intensive insulin therapy in insulin dependent diabetes and combination therapy.
Intensive insulin therapy (IIT) and combination therapy using sulfonylurea and insulin are two insulin regimens being used more frequently to improve glycemic control. For those patients with insulin-dependent diabetes, IIT or multiple daily injection therapy mimics normal pancreatic function by its timing of insulin delivery. The improvement in glycemic control carries with it the risk of a two- to threefold increase in episodes of hypoglycemia. For those with non-insulin-dependent diabetes, combination therapy attempts to provide a bridge between maximal dose oral hypoglycemic agents and aggressive insulin therapy. Although this therapy remains controversial, it has proved useful in select patient groups. This article discusses the rationale for IIT, and its implementation. Variables that affect IIT are discussed. The combination therapy section provides guidelines for patient selection and insulin protocols for evening insulin administration. The health care provider is familiarized with these alternative therapies and their successful applications.
Blood Glucose↗
Short term intensive insulin therapy improves insulin secretion significantly in type 2 diabetic patients.
To investigate the effects of short-term (1 week) intensive insulin therapy, on glycemic control, insulin secretion, and insulin sensitivity in type 2 diabetic patients, an open prospective study was conducted in sixteen type 2 diabetic patients receiving diet therapy alone or treatment with oral hypoglycemic agents. Of the study subjects, 8 patients were treated with insulin, the remaining 8 patients served as the control group. The metabolic parameters were evaluated once before treatment and once during one of the following treatments : glycemic control as measured by 1,5-anhydro-D-glucitol (1,5-AG) and area under curve of glucose (AUCglucose), insulin secretion as measured by area under curve of daily serum insulin (AUCinsulin), and insulin sensitivity as measured by the K index of the insulin tolerance test (K(ITT)). Post-treatment plasma glucose (AUCglucose) and 1,5-AG levels in patients who had received intensive insulin therapy were comparable to those of the control group. A statistically significant increase in AUCinsulin occurred after intensive insulin therapy for just 1 week, while no change occurred in the control group. Insulin sensitivity (K(ITT)) did not improve significantly in patients treated with insulin or patients from the control group. These results indicate that intensive insulin therapy for 1 week improves insulin secretion remarkably but has little effect on insulin sensitivity in type 2 diabetic patients. Clinically, this suggests that intensive insulin therapy for one week might be one of the initial treatments of choice for such patients.
Aged↗
Failure and efficacy of insulin therapy in insulin dependent (type I) diabetic patients.
In order to determine the degree of metabolic control (HbA1c [normal less than 5.8%], mean blood glucose [MBG], glucosuria and lipids) and the prevalence of late diabetic complications in insulin-dependent diabetic patients treated by conventional insulin therapy both patients of a diabetes center (DC: n = 130; age 37.1 +/- 1.4 years) and a rural area (RA: n = 73; age 38.4 +/- 2.4 years) were examined within their local setting. Eighty such insulin-dependent diabetic patients were also taught a technique of near normal glycemic insulin substitution (NIS), which separates basal from prandial insulin replacement and instructs the patients to immediately correct self-controlled (3.8 +/- 0.1/day) aberrant blood glucose values. None of the groups on conventional insulin therapy was able to achieve satisfactory metabolic control or to avoid late diabetic complications, but rural patients were even worse off (BG 240 +/- 10 mg/dl; HbA1c 8.7 +/- 0.2% [normal: 3/73 = 4%]) than those of the DC (MBG 191 +/- 5 mg/dl; HbA1c 7.1 +/- 0.2% [normal: 27/130 = 21%]), while the prevalence of late diabetic complications was almost identical (RA/DC: neuropathy 22%/25%; retinopathy 41%/38%; macroangiopathy 15%/13%; but proteinuria 14%/5.4%). Metabolic control was improved by NIS with twice daily injections of basal (long acting) and separately of prandial (regular) insulin (total: 4.8 +/- 0.1 injections/day; MBG 130 +/- 2 mg/dl; HbA1c 5.8 +/- 0.1% [normal: 41/80 = 51%]. We conclude (1) that conventional insulin therapy just prevents metabolic catastrophe but in more than 79% of insulin-dependent diabetic patients lacks the ability to provide good metabolic control, while (2) NIS, a more physiological form of insulin therapy, improves this deplorable situation 5- to 12.4-fold.
Adult↗
3.5 years of insulin therapy with insulin glargine improves in vivo endothelial function in type 2 diabetes.
OBJECTIVE: To determine long-term effects of insulin glargine on vascular function in patients with type 2 diabetes. METHODS AND RESULTS: A total of 49 in vivo endothelial function tests, intrabrachial artery infusions of endothelium-dependent (acetylcholine [ACh]) and endothelium-independent (sodium nitroprusside [SNP]) vasoactive agents, were performed in 11 patients with type 2 diabetes (age: 59+/-2 years; BMI: 29.7+/-0.9 kg/m2; fasting plasma glucose: 226+/-14 mg/dL) and 16 matched normal subjects. The tests in the type 2 diabetic patients were performed before and after 6 months and 3.5 years of combination therapy with insulin glargine and metformin. A control group of type 2 diabetic patients not treated with insulin was studied twice at 6-month intervals. Before treatment, blood flow during infusions of low and high doses of ACh were significantly lower in the type 2 diabetic patients than in the normal subjects (P=0.021 for ANOVA). In the patients with type 2 diabetes, blood flow during infusion of the low dose of ACh averaged 7.1+/-0.8 mL/dL per minute at baseline, 8.8+/-1.0 mL/dL per minute at 6 months (NS), and then increased compared with baseline by 87+/-29% to 11.6+/-1.4 mL/dL per minute at 3.5 years (P<0.02 versus baseline). Blood flow during infusion of the high dose of ACh increased from 8.8+/-0.9 at baseline to 13.0+/-1.9 mL/dL per minute at 6 months (P<0.05) and by 86+/-25% to 14.7+/-1.6 mL/dL per minute at 3.5 years (P<0.01 versus baseline), which was not different from normal subjects. Blood flow during infusion of low (blood flow at 0 months: 7.7+/-0.5; at 6 months: 9.9+/-0.6; P<0.01 for 6 versus 0 months; and 3.5 years: 11.6+/-1.1 mL/dL per minute; P<0.02 for 3.5 years versus 0 months) and high (blood flow at 0 months: 10.7+/-0.9; 6 months: 13.4+/-1.0; P<0.05 for 6 versus 0 months; and 3.5 years: 16.6+/-1.5 mL/dL per minute; P<0.05 for 3.5 years versus 0 months) doses of SNP also increased significantly during insulin therapy. CONCLUSIONS: We conclude that insulin glargine therapy improves endothelium-dependent and endothelium-independent vasodilatation. These data support the idea that long-term insulin therapy has beneficial rather than harmful effects on vascular function in type 2 diabetes.
Acetylcholine↗
[Metabolic control in labile type I diabetes with conventional insulin therapy, basal bolus insulin therapy using pens and continuous subcutaneous insulin infusion with the pump].
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Adolescent↗
A quality-of-life assessment of intensive insulin therapy using insulin lispro switched from short-acting insulin and measured by an ITR-QOL questionnaire: a prospective comparison of multiple daily insulin injections and continuous subcutaneous insulin infusion.
We examined quality-of-life (QOL) of patients with a prospective comparison of multiple daily insulin injections therapy (16 patients in MDI group) and continuous subcutaneous insulin infusion therapy (12 patients in CSII group) using insulin lispro (LP), which was switched from short-acting insulin on the basis of a questionnaire about insulin-therapy-related QOL measure (ITR-QOL). The overall score of ITR-QOL before using LP in the CSII group was significantly higher (P<0.02) than the MDI group. In four subscales of ITR-QOL, the scores of social and daily activities and of therapy-related feelings in the CSII group were significantly higher (P<0.02) than those in the MDI group, respectively, while there was no significant difference in the score of physical function between the two groups. Three months after using LP, the score of daily activities in the MDI group was significantly higher (P<0.02) than that before using LP, while there were no significant differences in other scores of the two groups. There were no significant differences in HbA1c between two groups before and after using LP. The frequency of hypoglycemic events in the MDI group before using LP was higher than that in the CSII group and decreased after using LP. These results show that QOL of patients treated by CSII is superior to that treated by MDI and demonstrate that insulin lispro has a more beneficial effect on daily activities in patients treated by MDI than short-acting insulin.
Blood Glucose↗
Combined therapy with insulin lispro Mix 75/25 plus metformin or insulin glargine plus metformin: a 16-week, randomized, open-label, crossover study in patients with type 2 diabetes beginning insulin therapy.
OBJECTIVE: This study aimed to assess glycemic response to a mixture of 75% insulin lispro protamine suspension and 25% insulin lispro (Mix 75/25) BID plus metformin versus insulin glargine QD plus metformin in patients with type 2 diabetes mellitus (DM). METHODS: Adults new to insulin therapy were enrolled in a multicenter, randomized, prospective, open-label, crossover study with 16 weeks on each treatment. Variables included glycosylated hemoglobin (HbA(1c)), hypoglycemia rate, fasting blood glucose (FBG), 2-hour postprandial blood glucose (ppBG), and rise in blood glucose after meals. RESULTS: One hundred five patients (mean age, 55 years) were randomized. There was no difference in baseline mean values for either treatment sequence group for body mass index, duration of DM, or HbA(1c). Ninety-five patients completed the study and 67 were included in the efficacy analysis. Mix 75/25 was associated with lower mean (SD) HbA(1c) at end point (7.4% [1.1%] vs 7.8% [1.1%]; P = 0.002). More patients using Mix 75/25 achieved target HbA(1c) < or =7.0% (42% [30/71] vs 18% [13/71]; P < 0.001). With Mix 75/25, the mean (SD) 2-hour ppBG was similar after lunch but lower after breakfast (156.4 [43.6] vs 171.1 [44.9] mg/dL; P = 0.012) and dinner (164.8 [42.5] mg/dL vs 193.8 [51.0] mg/dL; P < 0.001), although FBG was higher (139.3 [36.6] mg/dL vs 123.9 [34.9] mg/dL; P < 0.001). Rise in ppBG was lower with Mix 75/25 after breakfast (16.9 [47.0] mg/dL vs 47.4 [34.8] mg/dL; P < 0.001) and dinner (14.2 [44.1] mg/dL vs 45.9 [41.3] mg/dL; P < 0.001). Gain in mean (SD) body weight was greater with Mix 75/25 than insulin glargine (2.3 [4.0] kg vs 1.6 [4.0] kg; P = 0.006). For all randomized patients, mean (SD) hypoglycemia rates were lower with insulin glargine (0.68 [1.38] vs 0.39 [1.24] episodes/patient per 30 days; P = 0.041), although nocturnal hypoglycemia was similar. CONCLUSION: In this study population, Mix 75/25 plus metformin was associated with lower HbA(1c) than insulin glargine plus metformin, smaller rise in ppBG after breakfast and dinner, and higher proportion of patients achieving HbA(1c) < or =7.0%, with a slight increase in overall (but not nocturnal) hypoglycemia.
Adult↗
Intensive insulin therapy with insulin lispro: a randomized trial of continuous subcutaneous insulin infusion versus multiple daily insulin injection.
OBJECTIVE: To evaluate glycemic control, hypoglycemic events, and quality of life in patients treated with continuous subcutaneous insulin infusion (CSII) and multiple daily insulin injection (MDI), with insulin lispro as the principal insulin. RESEARCH DESIGN AND METHODS: This clinical trial enrolled 27 patients with type 1 diabetes. They were randomly assigned to CSII (n = 13) or MDI (n = 14) treatment regimens. Glycemic control (HbA(1c) level) was the primary outcome and was measured monthly for 9 months. Secondary outcomes were patient reports of hypoglycemic events (recorded monthly for 9 months) and quality of life assessed at 9 months using the Diabetes Quality of Life (DQOL) questionnaire. RESULTS: A significant decrease in HbA(1c) from baseline was shown for both groups. However, the overall treatment effect (CSII - MDI) for HbA(1c) was +0.08% (95% CI -0.23 to +0.39, P > 0.10). This was significantly less than the a priori limit of +/-0.5% (P = 0.004). The relative treatment effect ([CSII - MDI]/MDI) for the overall number of hypoglycemic events was +9% (95% CI -37 to +87, P > 0.10). There were no statistically significant differences between treatment groups for any of the DQOL subscales. CONCLUSIONS: No statistically significant differences in glycemic control, reported hypoglycemic events, or quality of life were found in this study. Furthermore, a clinically significant difference of more than +/-0.5% HbA(1c) between the two regimens can be confidently ruled out. We conclude that the choice of intensive insulin therapy should be a matter of patient preference, consistent with lifestyle.
Adolescent↗
Advances in insulin therapy for insulin-dependent diabetic children.
During the last two decades new forms of insulin and a better understanding of the physiological insulin secretion profile have led to great changes in insulin therapy. New insulin regimens mimicking the normal insulin secretory pattern, called intensive insulin therapy, and new insulin-delivery systems have been introduced. Self-monitoring of blood glucose levels and the use of glycosylated hemoglobin determination for objective evaluation of long-term control have made the achievement of near normoglycemia a practical goal for most patients taking insulin. 1. New forms of insulin: Beef and pork insulin were replaced by monocomponent pork insulin and now monocomponent human insulin is most popularly used. 2. Intensive insulin therapy: Intensified conventional insulin therapy, that is a multiple injection regimen and a twice a-day insulin regimen using a mixture of intermediate- and short-acting insulins has been commonly accepted. New devices such as pen-type injectors and jet-injectors have also been introduced for simplifying the multiple injection regimen. Continuous subcutaneous insulin injection (CSII) has also been adopted by adolescents and young adults.
Child↗