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

Insulin glargine is a biosynthetic human insulin analogue that controls blood glucose levels over 24 hours without a pronounced peak. In most studies in patients with type 2 diabetes mellitus (DM), insulin glargine did not significantly reduce fasting blood glucose, fasting plasma glucose or hemoglobin A1c compared to NPH insulin. Most trials showed a statistically significant decrease in the incidence of nocturnal and symptomatic hypoglycemia. This may not be as much of a concern in most patients with type 2 DM compared to type 1 DM. Current evidence suggests that patients who are adequately controlled with NPH insulin will not gain additional benefit from insulin glargine.
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PMID:Insulin glargine for type 2 diabetes. 1531 41

Suboptimal glycemic control in individuals with type 1 and type 2 diabetes mellitus is associated with an increased risk of microvascular and macrovascular complications. Even brief periods of hyperglycemia increase the risk of complications. Fasting hyperglycemia is a phenomenon that has been observed in essentially all individuals with diabetes and may be due to dysregulation of the normal circadian hormonal patterns resulting in increased hepatic glucose output. Controlling hepatic glucose output and disposal is essential for effectively managing fasting hyperglycemia. Fasting hyperglycemia generally can be attributed to inadequate or inappropriate hepatic insulinization or the dawn phenomenon (fasting hyperglycemia occurring in the absence of antecedent hypoglycemia). Less commonly, the Somogyi effect (marked fasting hyperglycemia following antecedent hypoglycemia) can cause fasting hyperglycemia. Accurate diagnosis with overnight home blood glucose monitoring is important in developing an appropriate treatment strategy. Manipulation of the individual's diet or oral agent therapy may be all that is required in some individuals to reduce fasting hyperglycemia. Hepatic glucose output and disposal in the fasting state may be controlled via bedtime administration of either an intermediate-acting insulin such as NPH or a long-acting true basal insulin such as insulin glargine. Attention to fasting hyperglycemia coupled with appropriate individualization of treatment should improve the long-term outcome of individuals with type 1 and type 2 diabetes by reducing the risk of complications. Normalization of the fasting blood glucose, through whatever strategy, minimizes glucotoxicity and insulin resistance, profoundly influences daytime glycemic control, and profoundly reduces the risk of the complications of diabetes.
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PMID:Fasting hyperglycemia: etiology, diagnosis, and treatment. 1532 Oct 11

Decreased first-phase secretion of insulin may play a role in the development of insulin resistance. In the development of type 2 diabetes an abnormal function of the beta-cells and insulin resistance of liver, fat cells and muscle play the main role. An early sign of beta-cell damage can be the loss of first-phase insulin response. This is supposed to precede the development of insulin resistance. Decrease of first-phase secretion of insulin can induce early postprandial hyperglycaemia and hypertriglyceridaemia damaging endothelium of precapillary arterioles of the nutritive capillaries. Insulin-induced endothelium-dependent dilation of these arterioles is inhibited by high glucose and triglyceride levels preventing metabolic effect of insulin on the parenchymal cells surrounded by nutritive capillaries and leading this way to insulin resistance. Second-phase hyperinsulinaemia develops in the impaired glucose tolerance. With the progression of the disease into the type 2 diabetes, insulin secretion decreases in the second-phase, as well. Because of decrease of first-phase insulin secretion in type 2 diabetic patients, early insulin therapy could be a choice of treatment in type 2 diabetes. Results of the UKPDS suggest that insulin-treated type 2 diabetic patients are longer in the near-euglycaemic state compared to those treated by oral hypoglycaemic agents. Recent data support that early insulin therapy of type 2 diabetic patients retains their own insulin secretion capacity and results in lower haemoglobin A1c. A comparison of before-meal rapid-acting insulin analogue and bedtime NPH insulin regimens verified that rapid-acting insulin analogue decreased haemoglobin A1c compared to NPH insulin treatment in type 2 diabetes. On the basis of these data arises the possibility of the change of the attitude "Oh no, not insulin in type 2 diabetes" to the "early rapid-acting insulin analogue treatment" of these patients.
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PMID:[Decreased first-phase secretion of insulin may play a role in the development of insulin resistance]. 1557 90

We studied the efficacy of four different treatment regimens (sulphonylurea and metformin+/-acarbose versus glimepiride and rosiglitazone versus glimepiride and bedtime NPH insulin versus multiple actrapid and NPH insulin injections) in poorly controlled type 2 diabetes subjects on hs-CRP, VCAM-1 and AGE at 4, 8 and 12 weeks of treatment. Multiple insulin injections rapidly improved HbA(1c) by 0.6+/-0.9% (p<0.005), 1.2+/-1.3% (p<0.0005) and 1.3+/-1.4% (p<0.0005) at week 4, at week 8 and week 12, respectively. Subjects who continued their existing combination treatment of sulphonylurea, metformin+/-acarbose also showed a significant reduction in HbA(1c) (p<0.05). Although effective in reducing glycemic parameters, there was no reduction in CRP levels in either treatment group. The treatment regimen consisting of rosiglitazone and glimepiride significantly lowered hs-CRP by -2.6 (3.9) mg/L (p<0.05) at week 12 in spite of no improvement in blood glucose. AGE improved in all groups irrespective of type of treatment, glycaemic control and CRP levels. Our data indicate rapid glycaemic control alone does not necessarily result in improvement in markers of inflammation in type 2 diabetes patients.
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PMID:Improvement in C-reactive protein and advanced glycosylation end-products in poorly controlled diabetics is independent of glucose control. 1625 80

(1) There are few clinical trials comparing combination therapy with a sulphonylurea and metformin after oral antidiabetic monotherapy fails to provide adequate glycaemic control. The UKPDS study suggested that this combination had a negative impact on mortality. (2) The assessment of insulin therapy in patients in whom oral antidiabetic therapy fails is based solely on surrogate endpoints: mainly HbA1c (glycated haemoglobin), bodyweight, and the frequency of hypoglycaemia. (3) In a comparative randomised trial involving patients whose glucose levels were no longer controlled by a sulphonylurea, the addition of metformin or a daily injection of insulin isophane (NPH) was similarly effective in reducing HbA1c levels. However, metformin caused less weight gain. (4) There are no randomised controlled trials comparing the addition of insulin versus a sulphonylurea when ongoing metformin monotherapy is inadequate. (5) Randomised comparative trials show that, when glycaemia is no longer controlled by a sulphonylurea plus metformin, adding a daily insulin injection is more effective in lowering HbA1c levels than the addition of acarbose and as effective as adding a glitazone. The adjunction of insulin appears to have a better risk-benefit balance than an oral three-drug regimen. (6) Several randomised controlled trials have shown that the addition of an oral antidiabetic to ongoing insulin therapy reduces HbA1c levels in patients with type 2 diabetes. The addition of metformin is also beneficial in terms of body weight changes. (7) Nine randomised controlled trials involving patients whose glycaemia was inadequately controlled by a sulphonylurea, alone or in combination with metformin, have compared the addition of a bedtime injection of insulin isophane versus replacement of the oral antidiabetics by several daily insulin injections. The two strategies had a similar impact on HbA1c (-1.5% to -2.5%), but patients experienced less weight gain when the oral antidiabetics were continued and a single insulin injection was added. (8) The few available comparative trials fail to show which oral treatment (a sulphonylurea, metformin, or a combination of the two) has the best risk-benefit balance when combined with a bedtime injection of insulin isophane. (9) Insulin isophane is the first-choice insulin for combination therapy with an oral antidiabetic. In comparative trials, when combined with an oral antidiabetic, insulin glargine was no more effective than insulin isophane in terms of HbA1c levels or weight gain. Insulin glargine seems to provoke less hypoglycaemia but, in the absence of adequate follow-up, its long-term adverse effects are not known. (10) When a bedtime insulin injection plus an oral antidiabetic fail to control hyperglycaemia, indirect comparisons support the use of several daily insulin injections plus metformin, or three injections of an ultrarapid insulin analogue plus a sulphonylurea.
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PMID:Insulin in type 2 diabetes: a useful alternative despite limited assessment based on surrogate endpoints. 1628 76

Insulin detemir (Levemir) is a soluble long acting human insulin analogue acylated with a 14-carbon fatty acid. The fatty acid modification allows insulin detemir to reversibly bind to albumin, thereby providing slow absorption and a prolonged metabolic effect (up to 24 hours) with low variability. Indeed, in patients with type 1 or type 2 diabetes mellitus, insulin detemir has a more predictable, protracted and consistent effect, with less intrapatient variability in glycaemic control (particularly fasting plasma glucose levels), compared with NPH (Neutral Protamine Hagedorn) insulin. Insulin detemir, is at least as effective as NPH insulin in maintaining overall glycaemic control, with a lower risk of nocturnal hypoglycaemia. It also provides the additional benefit of less body weight gain as compared to other basal insulins. Levemir, presented in cartridges for the pen device NovoPen 3 and administered preferably at bedtime (if necessary morning and evening), is a promising new option for basal insulin therapy in diabetic patients, especially those on a basal-bolus scheme.
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PMID:[Insulin detemir (Levemir)]. 1635 71

Insulin treated diabetic patients have often to contend with variability in the action of injected insulin and to some unpredictibility in glycemic control. The variability in blood glucose control seems particularly important with long-acting insulins. Insulin detemir belongs to a new class of non-crystalline form of long-acting insulin analogs. Absorption of insulin detemir is dependent on neither appropriate resuspension before injection and dissolution of crystals in the subcutaneous tissue, as is the case for NPH insulin, nor on formation and dissolution of microprecipitates, as is the case for insulin glargine. In euglycemic glucose clamp studies, insulin detemir was associated with significantly less within-subjects variability for the pharmacodynamic endpoints than both NPH insulin and insulin glargine. Three, up to 6 months trials, carried out in patients with type 1 diabetes have shown that the day-to-day within-subject variations in plasma glucose were significantly lower with insulin detemir than with human NPH insulin. Similar results have been reported in patients with type 2 diabetes. Nightly 8-h plasma glucose recordings showed a smoother and more stable profile with insulin detemir than with NPH insulin. In patients with type 1 diabetes the combination of insulin detemir with mealtime insulin aspart, a fast-acting insulin analog, provides a smoother and more stable profile with lower post-prandial plasma glucose levels that the combination of NPH insulin with regular human insulin before each meal. In several trials, the risk of hypoglycemia, particularly of nocturnal hypoglycemia, was significantly lower with insulin detemir than with NPH insulin. In conclusion insulin detemir offers a better reproducibility as compared with other basal insulins, reduces the risk of hypoglycemia, and may lead the patients to titrate their insulin doses more easily and therefore to achieve more often glycemic objectives. The combination of rapid- and long-acting insulin analogs reproduces a more physiological insulin secretion and thereby reduces the risk of hypoglycemia and improves the overall 24-h glycemic profile.
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PMID:Is insulin detemir able to favor a lower variability in the action of injected insulin in diabetic subjects? 1638 96

This review presents recent data on weight gain when on insulin treatment in type 1 and type 2 diabetic patients. In both types of diabetes, the excess weight gain with intensified insulin therapy compared with conventional insulin or sulfonylurea remains modest: 2.6 kg over 7.5 years in the Stockholm study (type 1 diabetic patients) and 1.7 kg when compared to glibenclamide over 10 years in the UKPDS (type 2 diabetic patients). Patients who gain the most weight after insulin initiation are those who: (1) had the worst metabolic control before the intensification of treatment, (2) had the greater weight loss prior to insulin initiation, and (3) in the case of patients with type 1 diabetes, have a family history of type 2 diabetes. This suggests that most of the weight gain observed after the insulin initiation is a "catch-up" weight re-gain. There is no evidence that weight gain after insulin therapy initiation is associated with a deterioration in the lipid profile or arterial hypertension or an excess risk for cardiovascular events, contrary to common beliefs. All clinical studies performed to date with the insulin analogue detemir have shown that this analogue is associated with lesser weight gain than NPH insulin. There is no explanation yet for these intriguing results. If confirmed on the long-term, this favourable effect on weight might be an interesting feature of this new insulin analogue.
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PMID:Weight gain and insulin treatment. 1638 99

Premixed insulin analogues, consisting of rapid-acting and intermediate-acting insulin analogues, were developed to more closely mimic physiological endogenous insulin secretion and meet the needs of patients who require both basal and prandial insulin but wish to limit the number of daily injections. There is considerable variability in onset and duration of action, as well as peak insulin levels, obtained with human insulin formulations such as premixed human insulin 70/30. To overcome these limitations, premixed insulin analogues were developed. Peak insulin levels are twice as high and reached in half the time with the rapid-acting insulin component of a premixed insulin analogue. In the US, two premixed insulin analogue formulations are currently available: insulin lispro 75/25 (75% insulin lispro protamine suspension and 25% insulin lispro) and biphasic insulin aspart 70/30 (BIAsp 70/30; 70% insulin aspart protamine suspension and 30% insulin aspart). They are generally administered twice daily, just before breakfast and dinner. Data from various randomised trials show that both insulin lispro 75/25 and BIAsp 70/30 provide more effective postprandial control of blood glucose than premixed human insulin 70/30 or human insulin isophane suspension (NPH insulin). Longer-term glycaemic control, evaluated as changes in glycosylated haemoglobin, is comparable for premixed insulin analogues and premixed human insulin 70/30 in most studies. Three comparative, randomised trials have shown that patients with type 2 diabetes mellitus using premixed insulin analogues twice daily are more likely to reach glycaemic goals than those using only insulin glargine once daily. Some patients can also reach glycaemic goals with once-daily administration of a premixed insulin analogue. Although the incidence of hypoglycaemia is low, direct comparison across trials of premixed insulin analogues is difficult because of inconsistencies in reporting. Within trials, the incidence of both major (rare) and minor hypoglycaemic episodes during treatment with premixed insulin analogues is low and comparable with rates found with human insulin 70/30. Premixed insulin analogues can be safely used, and are effective and convenient for achieving overall glycaemic control in patients with diabetes. In addition, given the convenience of mealtime dose administration, compliance with insulin therapy may increase with premixed insulin analogues.
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PMID:Premixed insulin analogues for the treatment of diabetes mellitus. 1639 67

We previously reported that lipoprotein lipase mass level in preheparin serum (preheparin LPL mass) was significantly lower in type 2 diabetes mellitus compared to healthy subjects and increased by conventional insulin therapy using NPH (intermediate-acting) insulin. The aim of this study was to investigate the effects of intensive insulin therapy on preheparin LPL mass. Thirty-two subjects (total group) with type 2 diabetes receiving treatment by NPH insulin injection twice a day in the morning and evening were switched to basal bolus insulin (BBI) therapy (fast-acting insulin after each meal and NPH insulin before bedtime). In 14 subjects, the total daily insulin dose was not change after switching to BBI therapy (iso-dose group). After 3 months of BBI therapy, preheparin LPL mass increased significantly from 47 to 56 ng/ml in total group. Glycosylated hemoglobin and serum triglyceride levels decreased significantly, and high-density lipoprotein-cholesterol increased significantly. Low-density lipoprotein levels did not changed but increase in size was suggested by PAG disc electrophoresis. Similar changes were observed in the iso-dose group. These results suggest that BBI therapy enhances preheparin LPL mass, accompanied by antiatherogenic changes in glucose and lipid metabolism.
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PMID:Enhancement of serum lipoprotein lipase mass levels by intensive insulin therapy. 1644 9


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