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Query: UMLS:C0011860 (type 2 diabetes)
 57,723 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Prandial glucose regulation represents a new concept in the management of type 2 diabetes: targeting postprandial glycaemic excursions as a means of achieving long-term glycaemic control. Although control of the overall glycaemic load is the most important factor for the success of long-term management of type 2 diabetes, control of postprandial hyperglycaemia also has positive implications for preventing the development of diabetic complications. Repaglinide is the first prandial glucose regulator to become available in the clinical setting. It has a rapid and short-lived insulinotropic action and can therefore reduce postprandial glucose excursions without increasing the risk of hypoglycaemia. Short-term clinical studies showed that repaglinide is superior to glibenclamide in improving postprandial glycaemic control. Longer-term studies confirmed that improved PGR is accompanied by improved overall glycaemic control that is at least equivalent to that achieved by sulphonylurea treatment. Moreover, because repaglinide can be used with flexible meal patterns without compromising glucose control, it can improve quality of life as indicated by overall treatment satisfaction, well-being and health status. Repaglinide has few contraindications or drug interactions and can be used in a wide range of patients. Although careful titration of repaglinide dose is recommended for patients with mild to moderate renal impairment, no dosage adjustment is otherwise needed in the elderly. In addition to being an effective first-line hypoglycaemic agent, repaglinide is highly effective in combination therapy for patients with type 2 diabetes who require more intensive treatment. When glucose targets are not met using repaglinide monotherapy, the combination of repaglinide with metformin can further improve glycaemic control by enhancing insulin secretion and improving insulin sensitivity. Similarly, when required combination of repaglinide with troglitazone or NPH-insulin can produce better glycaemic control than monotherapy alone. Given that most patients with type 2 diabetes require a multitherapy approach to achieve and sustain adequate glycaemic control, repaglinide will be an important element in future intensive therapy regimens.
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PMID:Repaglinide: prandial glucose regulation in clinical practice. 1122 59

Repaglinide is a novel insulin secretagogue that was developed as a prandial glucose regulator for the treatment of people with Type 2 diabetes mellitus. It is used flexibly, taken prior to meals, in order to limit subsequent postprandial blood glucose excursions as well as the dependent basal blood glucose concentration. In theory, the pharmacological profile of repaglinide is well suited for this role. Taken at mealtimes, its relatively rapid-onset and short-duration of action counteract a fundamental pathophysiological aspect of this disease: attenuation of the prandial insulin response. The predominantly hepatic elimination profile and a lack of drug-drug interactions with repaglinide are also properties well suited for patients with Type 2 diabetes. Importantly, the pharmacokinetic properties of repaglinide, are expected to reduce the risk of hypoglycaemia in comparison to the conventional insulin secretagogues (sulphonylureas). A reduced risk of hypoglycaemia carries the advantage that patients are not obliged to consume meals at regular intervals supplemented by snacks, so caloric restriction is feasible and lifestyle not compromised. These theoretical advantages have now been largely borne-out by clinical studies and empirical experience. Placebo-controlled studies have consistently demonstrated the antidiabetic efficacy of repaglinide, with improvements having been shown in all indicators of glycaemic control. Double-blind, active-comparator studies have shown repaglinide to have an antidiabetic efficacy that is at least equivalent to sulphonylureas, even when food intake and dosing intervals were controlled according to the requirements of sulphonylureas. Pooled data from these studies have shown that the risk of severe hypoglycaemia is reduced by 60% (p = 0.03) when repaglinide is used in preference to sulphonylureas. There is also evidence that the blood glucose threshold at which symptoms of hypoglycaemia are perceived by patients may be better preserved during treatment with repaglinide than with sulphonylureas. Studies examining flexible prandial dosing with repaglinide have shown that good glycaemic control and a low risk of hypoglycaemia are achievable goals that are independent of the meal (and, hence, dosing) pattern chosen by the patient. Furthermore, when used in this way, repaglinide has not been associated with weight gain. In combination therapy, repaglinide has been shown to act in synergy with both metformin and troglitazone. The possibility of a 'new' basal-bolus regimen combining repaglinide and exogenous (neutral protamine hagedorn) NPH insulin strategy has also been investigated.
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PMID:A review of clinical experience with the prandial glucose regulator, repaglinide, in the treatment of type 2 diabetes. 1124 78

It has been suggested that insulin has an effect on nerve regeneration similar to that of nerve growth factor (NGF). Therefore, we aimed to evaluate the effectiveness of local insulin injection on median nerve in patients with non-insulin-dependent diabetes (NIDDM) mellitus who have mild-to-moderate carpal tunnel syndrome (TS). We carried out a prospective, randomized, double-blind, placebo-controlled study in these patients. At the baseline, 20 mg methylprednisolone was injected directly into the carpal tunnel in all patients [n=43 (62 hands)]. A week after prednisolone, the placebo or NPH insulin (12 U) was injected into the carpal tunnel weekly for 7 weeks. The patients were followed up for 23 weeks. A significant improvement in mean median nerve motor distal latency (MNMDL), median nerve sensory velocity (MNSV), and global symptom score (GSS) occurred in both groups (with the exception of mean MNMDL in the placebo group). A more significant improvement in the mean MNMDL, MNSV, and GSS was observed in the insulin group when compared with the placebo group. This study suggests that local insulin treatment may be of great potential benefit in the improvement of nerve functions in NIDDM patients with mild-to-moderate CTS who opt for conservative treatment.
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PMID:Local insulin injection improves median nerve regeneration in NIDDM patients with carpal tunnel syndrome. 1142 29

The DCCT and UKPDS studies have definitely established that in type 1 as well as in type 2 diabetes mellitus, long-term near-normoglycaemia strongly protects against onset and/or progression of microangiopathic complications. Therefore, implementation of insulin strategies to maintain long-term near-normoglycaemia is of key importance in the management of diabetes mellitus. To successfully reach the goal of near-normoglycaemia, insulin therapy has to be physiological, i.e. it has to mimic nature by providing a bolus of insulin at meal ingestion, and by replacing the need for basal insulin between meals and during the night. The meal-time insulin needs can be best met by s.c. injection of a short-acting insulin analogue (lispro, aspart). Short-acting insulin analogues should be preferred to human regular insulin for three main reasons. First, convenience (meal-time injection, better adaptation of insulin dose to carbohydrate content of the meal); second, lower blood glucose 2-hour after meals; third, less risk for late post-prandial hypoglycaemia. However, the benefits of meal-time treatment with short-acting insulin analogues become apparent only by the extent to which replacement of basal insulin is optimised as well. The interprandial (especially nocturnal) need for basal insulin can be best met by the continuous s.c. insulin infusion by an external minipump, the gold standard of basal insulin replacement. Continuous s.c. insulin infusion in the basal state is so good because it uses a short-acting insulin analogue (low variability in s.c. absorption, flat and peak-less action profile), not insulin preparations with retarded action (high variability of s.c. absorption, peak of action) likewise the model of multiple daily insulin injections. A second choice option is s.c. injection of an insulin preparation with retarded action. At present, the long-acting insulin analogue glargine is the retarded insulin preparation of choice because its action profile is flat, peakless and long-lasting (approximately 24 hours). This is in contrast with the peak action profile of NPH insulin which exhibits a short duration of action (10-15 h). Thus, the modern insulin strategies for intensive therapy always include use of a short-acting insulin analogue at meal-time, and use of either continuous s.c. insulin infusion, or a s.c. injection of insulin glargine to replace basal insulin. Insulin glargine reproduces closely the pharmacokinetics and pharmacodynamics of continuous s.c. insulin infusion, and should always be preferred to NPH in all insulin-requiring diabetic patients, both type 1 and type 2.
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PMID:Physiological insulin replacement in type 1 diabetes mellitus. 1146 May 80

Repaglinide, a carbamoylmethyl benzoic acid derivative, is the first of a new class of oral antidiabetic agents designed to normalise postprandial glucose excursions in patients with type 2 diabetes mellitus. Like the sulphonylureas, repaglinide reduces blood glucose by stimulating insulin release from pancreatic beta-cells, but differs from these and other antidiabetic agents in its structure, binding profile, duration of action and mode of excretion. In clinical trials of up to 1-year's duration, repaglinide maintained or improved glycaemic control in patients with type 2 diabetes mellitus. In comparative, 1-year, double-blind, randomised trials (n = 256 to 544), patients receiving repaglinide (0.5 to 4mg before 3 daily meals) achieved similar glycaemic control to that in patients receiving glibenclamide (glyburide) < or = 15 mg/day and greater control than patients receiving glipizide < or = 15 mg/day. Changes from baseline in glycosylated haemoglobin and fasting blood glucose levels were similar between patients receiving repaglinide and glibenclamide in all studies; however, repaglinide was slightly better than glibenclamide in reducing postprandial blood glucose in I short term study (n = 192). Patients can vary their meal timetable with repaglinide: the glucose-lowering efficacy of repaglinide was similar for patients consuming 2, 3 or 4 meals a day. Repaglinide showed additive effects when used in combination with other oral antidiabetic agents including metformin, troglitazone, rosiglitazone and pioglitazone, and intermediate-acting insulin (NPH) given at bedtime. In 1-year trials, the most common adverse events reported in repaglinide recipients (n = 1,228) were hypoglycaemia (16%), upper respiratory tract infection (10%), rhinitis (7%), bronchitis (6%) and headache (9%). The overall incidence of hypoglycaemia was similar to that recorded in patients receiving glibenclamide, glipizide or gliclazide (n = 597) [18%]; however, the incidence of serious hypoglycaemia appears to be slightly higher in sulphonylurea recipients. Unlike glibenclamide, the risk of hypoglycaemia in patients receiving repaglinide was not increased when a meal was missed in 1 trial. In conclusion, repaglinide is a useful addition to the other currently available treatments for type 2 diabetes mellitus. Preprandial repaglinide has displayed antihyperglycaemic efficacy at least equal to that of various sulphonylureas and is associated with a reduced risk of serious hypoglycaemia. It is well tolerated in a wide range of patients, including the elderly, even if a meal is missed. Furthermore, glycaemic control is improved when repaglinide is used in combination with metformin. Thus, repaglinide should be considered for use in any patient with type 2 diabetes mellitus whose blood glucose cannot be controlled by diet or exercise alone, or as an adjunct in patients whose glucose levels are inadequately controlled on metformin alone.
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PMID:Repaglinide: a review of its therapeutic use in type 2 diabetes mellitus. 1157 98

Modern diabetes therapy is positively introduced insulin administration including intensive insulin therapy to type 1 and type 2 diabetes to prevent or delay the development of long-term complications. However, conventional insulin derivatives could not mimic more closely physiological insulin secretion profiles, resulting in frequent hypoglycemia attacks and brittle diabetes. Recent advanced technologies have allowed to modify insulin molecules to obtain several insulin analogues. Lys.Pro insulin and insulin aspart, rapid-acting insulin analogues, have demonstrated improved post-prandial glucose control in comparison with regular insulin, even although they are usually administered immediately prior to the meal. Insulin glargine and SoLongln, long-acting insulin analogues, could preserve the stable basic insulin profiles during a day as compared with NPH insulin. These insulin analogues are very useful to supply the post-prandial and basic insulin secretions in type 1 and type 2 diabetics.
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PMID:[Recent trends of development of rapid-acting and long-acting human insulin analogues--its biological characteristics and clinical availability]. 1171 96

Since 1995 there have been several new medications approved for the treatment of type 2 diabetes. The availability of these new medications has made the treatment regiment for type 2 diabetes complex. There are currently five classes of oral antidiabetic agents available in the United States. These classes include: sulfonylureas, meglitinides, alpha-glucosidase inhibitors, thiazolidinediones, and biguanides. Additionally there are several types of insulin and insulin analogs available for the treatment of hyperglycemia: regular, lispro, aspart, NPH, lente, ultralente, glargine, 70/30, 50/50, and 75/25. In this article, the mechanism, site of action, and adverse effects of these classes will be reviewed. The efficacy and important management issues of these glucose-lowering drugs used in monotherapy and in combination will be discussed.
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PMID:Treatment of type 2 diabetes mellitus: pharmacologic intervention. 1180 68

Although obesity is a frequent feature of type 2 diabetes mellitus (DM), many patients with type 1 DM are prone to high body mass index (BMI). We measured serum leptin concentrations in a cohort of children (n = 55) with type 1 diabetes mellitus (DM), as well as their anthropometric parameters including BMI, skin fold thickness at multiple sites, and midarm circumference. Glycemic control was assessed by blood glucose (BG) monitoring before meals, and measurement of glycated hemoglobin (HbA1c) and insulin dose/kg/d was recorded. Dietary evaluation and assessment of caloric intake (kg/d) was performed by an expert dietitian. In the newly diagnosed children (n = 10) before initiation of insulin therapy, circulating leptin concentration was significantly lower (1.1 +/- 0.8 ng/dL) versus 5 days after insulin therapy (1.45 +/- 0.7 ng/dL). The decreased leptin level appears to be related to insulinopenia in these patients. In 45 children with type 1 DM on conventional therapy (2 doses of insulin mixture (NPH and regular) subcutaneous (SC) before breakfast and dinner for more than 2 years), serum leptin concentration was significantly higher (2.15 +/- 1 ng/dL) compared with age-matched normal children (1.3 +/- 1 ng/dL). Diabetic children were further divided into 2 groups according to their HbA1c level: group 1 with HbA1C less than 7.5% (less than 2 SD above the mean for normal population) (n = 29) and group 2 with HbA1c greater than 7.5%. (greater than 2 SD above the mean for normal population) (n = 16). Patients with a higher HbA1c level (group 2) had a higher leptin concentration (2.3 +/- 0.8 ng/dL), higher BMI (17.8 +/- 1.7), and were receiving higher insulin dose/kg (0.92 +/- 0.2 U/kg/d) compared with group 1 (lower HbA1c) (1.78 +/- 0.8 ng/dL, 16.7 +/- 1.5, and 0.59 +/- 0.2 U/kg/d, respectively). Group 2 patients had a higher incidence of late morning hypoglycemia (9/29) versus group 1 patients (2/16). Analysis of dietary intake showed that patients with a higher HbA1c (group 2) consumed more calories (73.5 +/- 10.5 kcal/kg/d) versus patients with lower HbA1c (64.2 +/- 8.7 kcal/kg/d). These findings pointed to the unphysiologic nature of injecting a mixture of insulin twice daily. To cover the relatively big lunch meal (40% to 50% of the total caloric intake in the Arab countries) and prevent afternoon hyperglycemia, there is a great tendency to increase NPH dose before breakfast. This, in turn, induces late-morning hypoglycemia and increases appetite and food intake at that time. Multiple regression analysis showed that circulating leptin concentrations (the dependent variable) were best correlated with the mean skinfold thickness (SFT), BMI, and caloric intake/kg/d (together they explained 65% of the variability in leptin concentrations). It appears that oversubstitution by insulin and increased food intake stimulate fat synthesis and subsequently BMI. Increased appetite and BMI contribute to increased leptin secretion and explains the higher leptin levels in undercontrolled diabetic children (higher circulating HbA1c concentrations) who were oversubstituted by insulin.
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PMID:Serum leptin concentrations in children with type 1 diabetes mellitus: relationship to body mass index, insulin dose, and glycemic control. 1188 62

Type 2 diabetes natural history and progressive deterioration requires a therapeutic approach starting with diet and physical activity changes, then associated with pharmacological interventions (monotherapy, then multiple therapy). When oral anti-diabetics at optimal dosage have failed to maintain good diabetic control (HbA1c 6.5% Pounds), insulin treatment has to be considered and should be used when diabetic controls remain poor (HbA1c > 8%). The most adequate insulin regimen are bedtime NPH associated or not with oral anti-diabetics, or alternatively 2 daily injections (morning and evening) of intermediate insulin. Intensive insulin (3 daily injections or more), and particularly the use of short-acting analogues is an effective regimen when bedtime or conventional regimen have failed. Insulin glargin could be an interesting alternative to bedtime NPH but needs further data in type 2 diabetes. Insulin treatment has to be initiated with an adequate patient (and family) education. Glycaemic objectives (fasting blood glucose and HbA1c) should be regularly assessed and adapted taking into consideration diabetic control, clinical effects and safety assessments (weight gain, hypoglycaemic events...).
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PMID:[Present and future of insulin therapy in type 2 diabetic patients]. 1191 Sep 75

The pharmacodynamics, pharmacokinetics, clinical efficacy, adverse effects, and dosage and administration of insulin glargine are reviewed. Current treatment regimens for patients with type 1 diabetes mellitus and some with type 2 are designed to provide a basal insulin level with intermittent preprandial insulin coverage. Insulin glargine precipitates after subcutaneous injection, slowing absorption. Insulin glargine is used as a basal insulin and exhibits a flat pharmacokinetic profile, with a duration of action of at least 24 hours. Hypoglycemia is the most commonly reported adverse effect, especially within the first four weeks after a switch to insulin glargine. Insulin glargine should not be mixed with any other insulin product and should be administered with a syringe that has not been used for other insulin products or other medications. Insulin glargine is administered once daily at bedtime. Patients previously receiving twice-daily isophane insulin (NPH) should receive an insulin glargine dosage 20% less than the total daily dose of NPH insulin. Clinical trials did not consistently show improvements in hemoglobin A1c levels when patients with type 1 diabetes mellitus were switched from NPH insulin once or twice daily to insulin glargine. Insulin glargine should be considered for patients who continue to have elevated morning blood glucose levels and problems with nocturnal hypoglycemia despite receiving NPH insulin at bedtime. In patients with type 2 diabetes mellitus, insulin glargine significantly improved glycemic control compared with once-daily NPH insulin, but not when it was compared with combined treatment with once- or twice-daily NPH insulin. Clinical trials assessing progression of retinopathy and nephropathy and comparing insulin glargine therapy with continuous subcutaneous insulin infusion therapy are needed to more clearly determine insulin glargine's role. Insulin glargine is a new long-acting formulation that can provide prolonged basal glucose control in patients with diabetes mellitus.
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PMID:Insulin glargine: a new long-acting insulin product. 1194 2


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