Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0011860 (type 2 diabetes)
 57,723 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The treatment of NIDDM patients with secondary failure to sulfonylureas is still a debated problem. In this study we compared in NIDDM patients with secondary failure to glyburide, the effect of adding a single, low-dose bed time either NPH or ultralent insulin injection (0.15-0.2 U/kg) to the previously ineffective sulfonylurea treatment. Both NPH and ultralent insulin therapy have been demonstrated to be effective in ameliorating metabolic control in NIDDM patients with secondary failure to sulfonylureas. However, the addition of bed-time ultralent insulin caused a greater and significant decrease in post prandial plasma glucose. In contrast, the average fasting plasma glucose decrease was significantly greater after NPH insulin administration. These results indicate that in NIDDM patients with secondary failure to glyburide bed-time ultralent insulin administration is a better tool to improve the post prandial plasma glucose.
 ...
PMID:[Comparative study of the efficiency of ultralente insulin and NPH insulin combined with sulfonylurea in type 2 diabetes patients with secondary tolerance to sulfonylurea. Possible selection criteria]. 902 80

A decision support system has been developed, Diabetes Insulin Advisory System for patients with non-insulin dependent diabetes mellitus (DIAS-NIDDM), assisting in the adjustment of insulin doses in insulin-treated subjects. DIAS-NIDDM uses a causal probabilistic network (CPN) model of carbohydrate metabolism to make stochastic predictions of blood glucose (BG) excursions. The CPN model is an extension of an existing model with an added component representing endogenous insulin secretion. A linear relationship between BG and insulin concentration due to BG stimulated insulin secretion is assumed. Model parameters (pancreatic sensitivity, insulin sensitivity, and time-to-peak of NPH insulin) are estimated by Bayesian probability updating from patient's specific data (food intake, insulin doses, BG measurements) recorded over a period of 4 days. The estimated parameters allow the system to be potentially used as a diagnostic tool to identify abnormalities of carbohydrate metabolism: impaired insulin secretion, insulin resistance and the severity of the impairments. DIAS-NIDDM was used to predict patient-specific BG profiles and advise on insulin doses during a pilot study in eight patients with NIDDM of whom five were treated with insulin. Compared to the administered insulin amount, daily insulin amount advised by DIAS-NIDDM was similar (within 4 U) in three patients, higher by 20% (19 U) in one patient and lower by 40% (18 U) and 50% (11 U) in two patients, respectively. The inter-day coefficient of variation of the daily insulin advice suggests that, at least according to DIAS-NIDDM criteria, day-to-day adjustment of insulin doses is necessary to maintain optimum control.
 ...
PMID:DIAS-NIDDM--a model-based decision support system for insulin dose adjustment in insulin-treated subjects with NIDDM. 970 Apr 32

The treatment of NIDDM patients with secondary failure to sulphonylurea is a common problem. We performed a crossover study in 50 NIDDM patients with secondary failure to glibenclamide by comparing the addition to sulphonylurea of either a low-dose bedtime NPH insulin or a t.i.d. oral metformin and by analyzing treatment efficacy in relation to patient and disease characteristics. Both combined therapies clearly improved glycaemic control. HbA1 c were similarly reduced by the addition of either bedtime NPH insulin (7.6+/-0.34 vs 8.7+/-0.35, p<0.01) or metformin (7.6+/-0.22 vs 8.6+/-0.31, p<0.01). Also fasting plasma glucose (FPG) and post-prandial plasma glucose (PPPG) significantly decreased (p<0.01) with both treatments. Bed-time NPH insulin was more effective on FPG reduction than metformin (-36+/-2% vs -25+/-2%, p<0.01); in contrast, metformin addition was more effective on PPPG reduction than bedtime NPH insulin addition (-30+/-2% vs 20+/-3%, p<0.01). Serum cholesterol was marginally but significantly decreased after metformin (5.49+/-0.19 vs 5.91 +/-0.18 mM, p<0.05) but not after NPH insulin. Body weight increase was significantly greater after insulin addition than after metformin (1.47+/-0.25 Kg vs 0.64+/-0.17 p=0.02). All patients preferred the addition of metformin rather than NPH insulin. None of the measured clinical and metabolic variables (before treatment FPG and PPPG, HbA1 c, post-glucagon C-peptide levels, insulin sensitivity, patient age, BMI and diabetes duration) significantly correlated to the efficacy of the two combined treatments studied. In conclusion, in NIDDM patients with secondary failure to sulphonylureas the addition of either low-dose bedtime NPH insulin or t.i.d. metformin is similarly effective in improving glycaemic control. Metformin is better accepted by patients and provides a modest advantage in terms of body weight and cholesterol levels. The most common clinical and metabolic variables are not useful for predicting the efficacy of these two combined treatments.
 ...
PMID:Efficacy of combined treatments in NIDDM patients with secondary failure to sulphonylureas. Is it predictable? 997 73

The objective of this 6-month, open-label, randomized, two-period crossover study was to compare glycemic control when patients were treated with (1) 2 manufactured premixed insulin formulations containing insulin lispro and a novel insulin lispro-protamine formulation, neutral protamine lispro (NPL), and (2) 2 manufactured premixed human insulin formulations, human insulin 50/50 and human insulin 30/70. One hundred individuals, 37 with type 1 diabetes mellitus (12 females, 25 males; mean age, 39.4 years; mean body mass index [BMI], 24.8; mean duration of diabetes, 12.9 years) and 63 with type 2 diabetes mellitus (33 females, 30 males; mean age, 59.0 years; mean BMI, 28.4; mean duration of diabetes, 12.6 years), were treated with insulin lispro mixtures. Insulin lispro Mix50 (50% insulin lispro/50% NPL) and human insulin 50/50 (50% regular insulin/50% neutral protamine Hagedorn [NPH] insulin) were administered before breakfast; insulin lispro Mix25 (25% insulin lispro/75% NPL) and human insulin 30/70 (30% regular insulin/70% NPH) were administered before dinner. Blood glucose (BG), hypoglycemic episodes (hypoglycemic signs or symptoms or BG <3.0 mmol/L), insulin dose and timing of dose before meals, and hemoglobin A1c were measured. Mean doses of insulin lispro and human insulin mixtures were similar overall and for both diabetes subgroups. However, compared with human insulin mixtures, twice-daily administration of insulin lispro mixtures resulted in improved postprandial glycemic control, similar overall glycemic control, and less nocturnal hypoglycemia, as well as offering the convenience of dosing closer to meals.
 ...
PMID:Improved postprandial blood glucose control and reduced nocturnal hypoglycemia during treatment with two novel insulin lispro-protamine formulations, insulin lispro mix25 and insulin lispro mix50. Mix50 Study Group. 1032 21

The treatment of type 2 diabetes mellitus remains controversial. Since most patients are overweight or obese, regimens based on dietary modification and increased physical exercise are logical and safe treatment approaches. However, the long term impact of these interventions is frequently disappointing and pharmacotherapy is therefore required in the majority of patients. Oral antidiabetic agents, principally the sulphonylureas and biguanides, are often only partially effective, even in combination. Insulin is the treatment of choice for certain clinical situations, for example, pregnancy. Often insulin will be a temporary measure. Safety considerations will also point to the preferential use of insulin in other circumstances, for example, in patients with pronounced renal impairment. In addition, a significant proportion of patients with type 2 diabetes mellitus will ultimately require insulin therapy in the long term because of failure of oral agents to provide adequate glycaemic control (i.e. secondary failure). Reservations about insulin therapy in patients with type 2 diabetes mellitus, particularly elderly patients with cardiovascular complications, include hypoglycaemia and bodyweight gain. However, severe hypoglycaemia occurs with considerably lower frequency than in patients with type 1 diabetes mellitus. To date, no clear evidence has emerged implicating exogenous insulin therapy in the promotion of cardiovascular disease. On the contrary, recent clinical and experimental studies suggest anti-atherogenic effects. Insulin therapy can be successful in type 2 diabetes mellitus if patients are carefully selected. Twice daily isophane (neutral protamine Hagedom; NPH) or pre-mixed insulin is used routinely in many centres. The role of combinations of insulin and oral agents remains an area of controversy. Combined therapy with sulphonylureas may be more expensive and clear clinical advantages have not been consistently demonstrated. Bodyweight gain may be lessened by the concomitant use of metformin and troglitazone may improve glycaemic control in obese patients. Procrastination about transfer to insulin is not uncommon. Patient acceptance may be facilitated by a positive attitude from the diabetes care team and discussion of the possibility at a relatively early stage. Adequate support from a multidisciplinary team is important for safe and effective insulin therapy. Even so, in the long term, attainment of glycaemic targets may prove difficult to sustain with present therapeutic strategies.
 ...
PMID:Benefits and risks of transfer from oral agents to insulin in type 2 diabetes mellitus. 1043 50

In this prospective study we aimed to compare insulin plus acarbose with insulin plus gliclazide with respect to their effect on insulin requirement, lipid profiles and body mass index (BMI) while achieving good glycemic control. Forty patients with type 2 diabetes mellitus who were on conventional insulin therapy (subcutaneous insulin therapy consisting of regular and NPH insulin, two times a day) were included in the study. They were randomized to double blind treatment with insulin in combination with gliclazide or acarbose for 6 months. For both groups, acceptable glycemic control was achieved at the end of study period. The mean HbA(1c) levels decreased from 8.32+/-0.26 to 7.13+/-0.18% in acarbose group and 8. 6+/-0.15 to 7.48+/-0.21% in the gliclazide group. The difference between groups was not significant (P 0.29). In the acarbose group, total cholesterol and LDL concentration decreased significantly while other parameters did not change. In the gliclazide group, HDL levels decreased significantly from 46.6+/-2.48 mg/dl to 41.3+/-2.09 mg/dl (P 0.001) BMI increased significantly from 27.60+/-1.21 kg/m(2) to 28.69+/-1.26 kg/m(2). (P 0.003) Total daily insulin dose was not changed in the acarbose group significantly, but increased from 42.6+/-2.73 to 49.27+/-3.58 U/day, which was significant in gliclazide group of (P 0.016). In the acarbose group, there were no significant differences between responders and nonresponders with respect to fasting and stimulated C-peptide, HbA(1c) levels and baseline BMI values. But in the gliclazide group, baseline BMI values were significantly higher in the nonresponding group compared to responders (P 0.02). In conclusion, combination of insulin with acarbose can be a good alternative for type 2 diabetic patients on insulin therapy; seems more beneficial than combination with gliclazide; may have advantage of achieving good glycemic control without increasing insulin dose and BMI; also may have the advantage of providing a decrease in LDL level, which are all important to prevent atherosclerosis.
 ...
PMID:Effects of combination of insulin and acarbose compared with insulin and gliclazide in type 2 diabetic patients. 1043 59

Long-term micro- and macrovascular complications cause major morbidity and mortality in patients with type 2 diabetes mellitus. Up to the present it is not clear whether intensified or conventional insulin treatment is more effective to keep blood glucose concentrations close to the normal range. In the present trial 90% (n = 117) of all insulin-treated type 2 diabetic patients aged 16 to 60 years and living in the city of Jena (100,247 inhabitants), Thuringia, Germany were examined. Fourty patients (34%) were on intensive insulin therapy (ICT, > or = 2 injections of normal- and > or = 1 injection of NPH-/mixed-insulin/day, > or = 1 insulin-dose adjustments/week, > or = 2 blood-glucose self-tests/day) and 77 patients (66%) were on conventional insulin therapy (CIT). Patients with ICT had more injections/d (4.3 +/- 0.7 vs CIT 2.4 +/- 0.7, p < 0.001), more insulin-dose adjustments/week < or = 11.5 +/- 8.2 vs 2.2 +/- 5.2, p < 0.001) and more blood-glucose self-tests/week (25.2 +/- 5.7 vs 9.6 +/- 8.8, p < 0.001). Patients with ICT had higher insulin doses (0.71 +/- 0.32 vs 0.47 +/- 0.2 IU/kg body wt/d, p < 0.001), were younger (50.5 +/-6.7 vs 54.0 +/- 5.9 years, p = 0.004) and they had a non-significant tendency to a better HbAlc (8.7 +/- 2.2 vs 9.2 +/- 2.0%, p = 0.23, HPLC, Diamat, normal range 4.4-5,9%). There was a negative correlation between HbAlc and the frequency of blood-glucose self-tests/week (r = -0.23, p = 0.019) and the number of insulin-dose adjustments/week (r = -0.33, p < 0.001). There were no differences between the groups as regards body-mass index (29.7 +/-4.9 vs 28.0 +/- 4.5 kg/m2, p = 0.06), diabetes duration (12.3 +/- 6.9 vs 12.2 +/- 7.5 years, p = 0.96), duration of insulin therapy (4.2 +/-3.5 versus 4.5 +/- 4.8 years, p = 0.67), incidence of acute complications (severe hypoglycaemia, diabetic coma), prevalence of retino-, nephro- and neuropathy (assessed according to Young et al.) and education or socio-economic factors. Also, in respect of quality of life and treatment satisfaction, assessed with standardized questionnaires according to Bradley et al. and Lewis et al., there were no differences between the two groups. In conclusion, in type 2 diabetic patients, ICT seems to be indicated in a second step in "problem-patients" with bad metabolic control under CIT and/or individual's need for more flexibility. Perhaps, in these patients ICT leads to an improvement in the quality of metabolic control.
 ...
PMID:Intensive or conventional insulin therapy in type 2 diabetic patients? A population-based study on metabolic control and quality of life (The JEVIN-trial). 1061 81

To determine causes of interindividual variation in insulin requirements, we recruited 20 type 2 diabetic patients with stable glucose control and insulin doses for >1 year on combination therapy with bedtime NPH insulin and metformin. Insulin absorption (increase in free and total insulin over 8 h after a subcutaneous dose of regular insulin) and actions of intravenous (6-h 0.3 mU x kg(-1) x min(-1) euglycemic insulin clamp combined with [3-3H]glucose) and subcutaneous (glucose infusion rate required to maintain isoglycemia and suppression of free fatty acids [FFAs]) insulin, liver fat content (proton spectroscopy), visceral fat (magnetic resonance imaging), weight, and body composition were determined. We found the following variation in parameters: insulin dose range 10-176 U (mean 42 U, fold variation 17.6x) or 0.13-1.39 U/kg (0.44 U/kg, 10.7x), absorbed insulin 10.6x, action of subcutaneous insulin to suppress FFAs 7.5 x and to stimulate glucose metabolism (M value) 11.5x, body weight 67-127 kg (91 kg, 1.9x), liver fat 2-28% (12%, 14x), and visceral fat 179-2,053 ml (1,114 ml, 11.5x). The amount of insulin absorbed, measured as either free or total insulin, was significantly correlated with its ability to suppress FFAs and stimulate glucose metabolism but not with the insulin dose per se. The actions of absorbed insulin were, on the other hand, significantly correlated with the daily insulin dose (r = 0.70 for action on FFAs, P < 0.001, and r = -0.61 for M value, P < 0.005). Actions of subcutaneous and intravenous insulin to suppress FFAs were significantly correlated (r = 0.82, P < 0.001, R2 = 67%). Of the measures of adiposity, the percent hepatic fat was the parameter best correlated with the daily insulin dose (r = 0.76, P < 0.001). The percent hepatic fat was also significantly correlated with the ability of intravenous insulin to suppress endogenous glucose production (r = 0.72, P < 0.005). We conclude that the major reason for interindividual variation in insulin requirements in type 2 diabetes is the variation in insulin action. Variation in hepatic fat content may influence insulin requirements via an effect on the sensitivity of endogenous glucose production to insulin.
 ...
PMID:Hepatic fat content and insulin action on free fatty acids and glucose metabolism rather than insulin absorption are associated with insulin requirements during insulin therapy in type 2 diabetic patients. 1090 83

To determine the effects of combined therapy of gliclazide and bedtime insulin on glycemic control and C-peptide secretion, we studied 25 patients with type 2 diabetes and sulfonylurea secondary failure, aged 56.8 +/- 8.3 years, with a duration of diabetes of 10.6 +/- 6.6 years, fasting plasma glucose of 277.3 +/- 64.6 mg/dl and a body mass index of 27.4 +/- 4.8 kg/m2. Patients were submitted to three therapeutic regimens lasting 2 months each: 320 mg gliclazide (phase 1), 320 mg gliclazide and bedtime NPH insulin (phase 2), and insulin (phase 3). At the end of each period, glycemic and C-peptide curves in response to a mixed meal were determined. During combined therapy, there was a decrease in all glycemic curve values (P<0.01). Twelve patients (48%) reached fasting plasma glucose <140 mg/dl with a significant weight gain of 64.8 kg (43.1-98.8) vs 66.7 kg (42.8-101.4) (P<0.05), with no increase in C-peptide secretion or decrease in HbA1. C-Peptide glucose score (C-peptide/glucose x 100) increased from 0.9 (0.2-2.1) to 1.3 (0.2-4.7) during combined therapy (P<0.01). Despite a 50% increase in insulin doses in phase 3 (12 U (9-30) vs 18 U (11-60); P<0.01) only 3 patients who responded to combined therapy maintained fasting plasma glucose <140 mg/dl (P<0.02). A tendency to a higher absolute increase in C-peptide (0.99 (0.15-2.5) vs 0.6 (0-2.15); P = 0.08) and C-peptide incremental area (2.47 (0.22-6.2) vs 1.2 (0-3.35); P = 0.07) was observed among responders. We conclude that combined therapy resulted in a better glucose response to a mixed meal than insulin alone and should be tried in type 2 diabetic patients before starting insulin monotherapy, despite difficulties in predicting the response.
 ...
PMID:Gliclazide and bedtime insulin are more efficient than insulin alone for type 2 diabetic patients with sulfonylurea secondary failure. 1115 Oct 28

Type 2 diabetes mellitus is a complex heterogenous metabolic disorder in which peripheral insulin resistance and impaired insulin release are the main pathogenetic factors. The rapid response of the pancreatic beta-cells to glucose is already markedly disturbed in the early stages of type 2 diabetes mellitus. The consequence is often postprandial hyperglycaemia, which seems to be extremely important in the development of secondary complications, especially macrovascular disease. Therefore one of the main aims of treatment is to minimise blood glucose oscillations and attain near-normal glycosylated haemoglobin levels. Meglitinide analogues belong to a new family of insulin secretagogues which stimulate insulin release by inhibiting ATP-sensitive potassium channels of the beta-cell membrane via binding to a receptor distinct from that of sulphonylureas (SUR1/KIR 6.2). The pharmacokinetic and pharmacodynamic properties of repaglinide, the first drug of these new antihyperglycaemic agents on the market, and of nateglinide, which will be available soon, differ markedly from the currently used sulphonylureas [mainly glibenclamide (glyburide) and glimepiride]. Repaglinide and nateglinide are absorbed rapidly, stimulate insulin release within a few minutes, are rapidly metabolised in the liver and are mainly excreted in the bile. Therefore, following preprandial administration of these drugs, insulin is more readily available during and just after the meal. This leads to a significant reduction in postprandial hyperglycaemia without the danger of hypoglycaemia between meals. The short action of these compounds and biliary elimination makes repaglinide and nateglinide especially suitable for patients with type 2 diabetes mellitus who would like to have a more flexible lifestyle, need more flexibility because of unplanned eating behaviour (e.g. geriatric patients) or in whom one of the other first-line antidiabetic drugs, i.e. metformin, is strictly contraindicated (e.g. nephropathy with creatinine clearance < or = 50 ml/min). Meglitinide analogues act synergistically with metformin and thiazolidinediones (pioglitazone and rosiglitazone) and can be also combined with long-acting insulin (NPH insulin at bedtime). Therefore, these drugs enrich the palette of antidiabetic drugs and make the treatment more flexible and better tolerated, which both add to better metabolic control and support the empowerment and compliance of the patient. However, this will only be the case if the patient and the diabetes care team are trained for this new therapeutic schedule and the healthcare system is able to pay for these rather expensive drugs.
 ...
PMID:Meglitinide analogues in the treatment of type 2 diabetes mellitus. 1119 Apr 20


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>