Home About us Contact
|
Home About us Contact | ||
|
|
||
Metformin
Kinds of Metformin Terms modified by Metformin Selected AbstractsEffects of insulin resistance on endothelial function: possible mechanisms and clinical implicationsDIABETES OBESITY & METABOLISM, Issue 10 2008D Tousoulis Insulin resistance (IR) is defined as a reduced responsiveness of peripheral tissues to the effects of the hormone, referring to abated ability of insulin in stimulating glucose uptake in peripheral tissues and in inhibiting hepatic glucose output. Insulin has both a vasodilatory effect, which is largely endothelium dependent through the release of nitric oxide, and a vasoconstrictory effect through the stimulation of the sympathetic nervous system and the release of endothelin-1. IR and endothelial dysfunction (ED) are not only linked by common pathogenetic mechanisms, involving deranged insulin signalling pathways, but also by other, indirect to the hormone's actions, mechanisms. Different treatment modalities have been proposed to affect positively both the metabolic effects of insulin and ED. Weight loss has been shown to improve sensitivity to insulin as a result of either altered diet or exercise. Exercise has favourable effects on endothelial function in normal states and in states of disease, in men and women, and throughout the age spectrum and, hence, in IR states. Metformin improves sensitivity to insulin and most likely affects positively ED. Studies have shown that inhibitors of the renin,angiotensin system alter IR favourably, while Angiotensin converting enzyme (ACE) inhibitors and Angiotensin receptor type II (ATII) inhibitors improve ED. Ongoing studies are expected to shed more light on the issue of whether treatment with the thiazolidinediones results in improvement of endothelial function, along with the accepted function of improving insulin sensitivity. Finally, improved endothelial function by such treatments is not in itself proof of reduced risk for atherosclerosis; this remains to be directly tested in clinical trials. [source] Metformin inhibits intracellular lipid accumulation in the murine pre-adipocyte cell line, 3T3-L1DIABETES OBESITY & METABOLISM, Issue 8 2008K. B. Alexandre No abstract is available for this article. [source] Combination therapy using metformin or thiazolidinediones and insulin in the treatment of diabetes mellitusDIABETES OBESITY & METABOLISM, Issue 6 2005Suzanne M. Strowig The biguanide, metformin, sensitizes the liver to the effect of insulin, suppressing hepatic glucose output. Thiazolidinediones such as rosiglitazone and pioglitazone enhance insulin-mediated glucose disposal, leading to reduced plasma insulin concentrations. These classes of drugs may also have varying beneficial effects on features of insulin resistance such as lipid levels, blood pressure and body weight. Metformin in combination with insulin has been shown to significantly improve blood glucose levels while lowering total daily insulin dose and body weight. The thiazolidinediones in combination with insulin have also been effective in lowering blood glucose levels and total daily insulin dose. Triple combination therapy using insulin, metformin and a thiazolidinedione improves glycaemic control to a greater degree than dual therapy using insulin and metformin or insulin and a thiazolidinedione. There is insufficient evidence to recommend the use of metformin or thiazolidinediones in type 1 diabetic patients. Although these agents are largely well tolerated, some subjects experience significant gastrointestinal problems while using metformin. Metformin is associated with a low risk of lactic acidosis, but should not be used in patients with elevated serum creatinine or those being treated for congestive heart failure. The thiazolidinediones are associated with an increase in body weight, although this can be avoided with careful lifestyle management. Thiazolidinediones may also lead to oedema and are associated with a low incidence of hepatocellular injury. Thiazolidinediones are contraindicated in patients with underlying heart disease who are at risk of congestive heart failure and in patients who have abnormal hepatic function. The desired blood glucose-lowering effect and adverse event profiles of these agents should be considered when recommending these agents to diabetic patients. The potential for metformin or the thiazolidinediones to impact long-term cardiovascular outcomes remains under investigation. [source] Metabolic and haemodynamic effects of metformin in patients with type 2 diabetes mellitus and hypertensionDIABETES OBESITY & METABOLISM, Issue 5 2001M. H. Uehara SUMMARY Background Since metformin improves insulin sensitivity, it has been indicated for patients with diabetes and hypertension, which are insulin-resistant conditions. In contrast to its well-known effects on carbohydrate metabolism, its potential for reducing blood pressure (BP) and its effect on leptin levels have been investigated less frequently. Patients and Methods A double-blind, randomized, placebo-controlled trial was carried out with 26 overweight diabetic subjects with mild-to-moderate hypertension to assess the effects of metformin-induced glycaemic control on BP and metabolic parameters. After a 4-week placebo period, when BP was stabilized by calcium channel blockers, they received either metformin (MG) or placebo (PG) for 12 weeks. Results Neither group showed any change in weight throughout the study. Only metformin-treated patients reduced fasting plasma glucose (8.54 + 1.72 to 7.54 + 1.33 mmol/l, p <,0.05), although HbA1c had decreased in both groups (PG: 6.7±3.0 to 5.9±2.6%; MG: 5.3±1.5 to 4.6±0.9%; p <,0.05). The initial office mean BPs were similar and decreased at the end of the treatment period in both groups, reaching statistical significance only in MG (105.7±8.0 to 99.2±9.3 mmHg, p <,0.05). No difference was observed when comparing baseline and final values obtained by 24-h ambulatory BP monitoring. Metformin induced a reduction in both insulinaemia (71.0±62.4 to 38.0±23.0 pmol/l, p <,0.05) and the insulin resistance index (3.5±2.7 to 1.8±1.0, p <,0.05). The two groups had similar baseline leptin levels which remained unchanged after treatment (PG: 16.8±7.9 to 21.4±14.6 ,g/l; MG: 18.5±10.3 to 18.4±8.9 ,g/l). Dopamine levels increased significantly only in metformin-treated subjects. Conclusions Reductions in both the insulin levels and the resistance index reinforced metformin capacity to improve peripheral sensitivity. Moreover, such benefits were not accompanied by any hypotensive effects. Since leptin levels were affected neither by metformin per se nor by the induced insulinaemia reduction, our data support the role of body weight as the major determinant of circulating leptin levels. [source] Why insulin sensitizers but not secretagogues should be retained when initiating insulin in type 2 diabetesDIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 1 2008Philip Raskin Abstract The stringent targets set for HbA1c levels in type 2 diabetes are currently achieved by fewer than half the patients in the United States. Failure to manage hyperglycaemia in the early stages of disease results in progressive loss of ,-cell function, which ultimately necessitates the initiation of insulin therapy. At this point, choices have to be made on whether to continue oral anti-diabetic drug therapy and, if so, with which agent(s). Historically, sulfonylureas have been the mainstay of oral anti-diabetic drug therapy; however, their long-term efficacy in patients with depleted ,-cell capacity is doubtful, and other classes of oral anti-diabetic drugs, notably the insulin sensitizers, may prove more reliable. These agents (metformin and thiazolidinediones) appear to provide various benefits over and above sustained glycaemic control, which may variably include reduced loss of ,-cell function as well as improvements to cardiovascular risk factors, morbidity, and mortality. Metformin also limits weight gain associated with insulin therapy. This manuscript presents the case that when insulin therapy is initiated it should be tailored to individual needs through combination with one or more insulin sensitizers rather than a secretagogue. Copyright © 2007 John Wiley & Sons, Ltd. [source] Metformin use and diabetic pregnancy,has its time come?DIABETIC MEDICINE, Issue 3 2006G. Hawthorne Abstract The prevalence of Type 2 diabetes in women of childbearing age continues to grow as the incidence of Type 2 diabetes increases. Recent evidence shows that treatment of gestational diabetes ensures the best possible outcome for pregnancy complicated by gestational diabetes. Metformin is a logical treatment in these circumstances but there has always been concern about its safety for the fetus, particularly as it crosses the placenta and it may increase the risk of teratogenesis. Although evidence is accumulating that metformin is useful and has a role in polycystic ovary syndrome, a condition of insulin resistance, it is not yet accepted as treatment for Type 2 diabetes in pregnancy and gestational diabetes. Observational data supports the use of metformin in Type 2 diabetes in pregnancy and its role in gestational diabetes is currently under investigation. Metformin may become an important treatment for women with either gestational or Type 2 diabetes in pregnancy and indeed may have additional important benefits for women, including reducing insulin resistance, body weight and long-term risk of diabetes. There is a need for a randomized controlled trial in women with Type 2 diabetes in pregnancy with long-term follow-up of both mothers and children. Until then the best advice remains that optimized glycaemic control prior to conception and during pregnancy is the most important intervention for best possible pregnancy outcome. [source] Low-dose metformin improves hyperglycaemia related to myotonic dystrophyDIABETIC MEDICINE, Issue 3 2005T. Kouki Abstract Background One of the clinical features of myotonic dystrophy is insulin resistance with non-obese diabetes mellitus (DM). Recently, the mechanism of insulin resistance in patients with myotonic dystrophy was revealed. The optimal treatment of DM with myotonic dystrophy has not been established. We report the effect of metformin in a patient with myotonic dystrophy without obesity. Case report A 58-year-old woman (BMI = 22.1 kg/m2) with myotonic dystrophy and DM was followed at our clinic. She had been treated with glimepiride for DM for the last 6 months, without achieving good control (HbA1c 9.3%). She was admitted with congestive heart failure and cholecystitis. She was treated with diuretics, antibiotics and insulin. As her blood glucose fell, we discontinued insulin and started glimepiride, but her glycaemic control had worsened. We started metformin instead of glimepiride. After 4 weeks of metformin, HbA1c was decreased to 7.4%, while HOMA-IR during glimepiride treatment was 4.9, and 3.7 with metformin. Three months later, HbA1c was maintained (7.5%). Conclusion It is important to choose the optimal treatment for DM in myotonic dystrophy, because the patients have hyperinsulinemia caused by specific mechanism and could not reduce the insulin resistance. Metformin improved hyperglycemia through increased insulin-independent glucose uptake in peripheral muscle. We believe metformin is the optimal agent for these patients. [source] Metabolic effects of metformin in patients with impaired glucose toleranceDIABETIC MEDICINE, Issue 7 2001M. Lehtovirta Abstract Aims To assess the effect of metformin on insulin sensitivity, glucose tolerance and components of the metabolic syndrome in patients with impaired glucose tolerance (IGT). Methods Forty first-degree relatives of patients with Type 2 diabetes fulfilling WHO criteria for IGT and participating in the Botnia study in Finland were randomized to treatment with either metformin 500 mg b.i.d. or placebo for 6 months. An oral glucose tolerance test (OGTT) and a euglycaemic hyperinsulinaemic clamp in combination with indirect calorimetry was performed at 0 and 6 months. The patients were followed after stopping treatment for another 6 months in an open trial and a repeat OGTT was performed at 12 months. Results Metformin treatment resulted in a 20% improvement in insulin-stimulated glucose metabolism (from 28.7 ± 13 to 34.4 ± 10.7 µmol/kg fat-free mass (FFM)/min) compared with placebo (P = 0.01), which was primarily due to an increase in glucose oxidation (from 16.6 ± 3.6 to 19.1 ± 4.4 µmol/kg FFM; P = 0.03) These changes were associated with a minimal improvement in glucose tolerance, which was maintained after 12 months. Conclusions Metformin improves insulin sensitivity in subjects with IGT primarily by reversal of the glucose fatty acid cycle. Obviously large multicentre studies are needed to establish whether these effects are sufficient to prevent progression to manifest Type 2 diabetes and associated cardiovascular morbidity and mortality. Diabet. Med. 18, 578,583 (2001) [source] The effect of metformin on measurements of insulin sensitivity and , cell response in 18 horses and ponies with insulin resistanceEQUINE VETERINARY JOURNAL, Issue 5 2008A. E. Durham Summary Reasons for performing study: Laminitis in equids is a very common debilitating disease, and insulin resistance (IR) and hyperinsulinaemia are increasingly recognised as important predisposing factors. Pharmacological modification of IR and hyperinsulinaemia might reduce the risk of laminitis. Hypothesis: Metformin, a drug commonly prescribed for treatment of human IR, may also decrease IR in equids. Methods: Eighteen horses and ponies with IR and recurrent laminitis were treated with 15 mg/kg bwt metformin per os q. 12 h. Each animal served as its own control by comparing pre- and post treatment proxies for IR, insulin sensitivity (IS) and pancreatic , cell function while controlling for possible dietary and managemental influences on IR. Results: Evidence of significantly improved IS and decreased pancreatic , cell secretion was found following metformin treatment. The magnitude of effect was greater at earlier resampling (6,14 days) than at later times (23,220 days). Apparent subjective clinical benefits were good but less favourable than effects on IR. Conclusions: Metformin is safe and appears to increase IS in equids. Potential relevance: Metformin may be indicated as a treatment for IR in equids. Further studies are required to define appropriate selection of subjects warranting therapy, dosing schedule and pharmacokinetics. [source] A randomized placebo-controlled trial of metformin for the treatment of HIV lipodystrophyHIV MEDICINE, Issue 7 2007R Kohli Objective We conducted a randomized placebo-controlled trial to examine the effects of metformin on visceral adipose tissue (VAT), appendicular fat, lipid profile and insulin sensitivity in HIV-infected persons with central adiposity and mild insulin resistance. Methods Forty-eight HIV-infected men and women with a self-reported increase in abdominal girth and an abnormal waist-to-hip ratio were randomly assigned in double-blind fashion to receive metformin 1500 mg or placebo daily for 24 weeks. Persons with diabetes were excluded. The following measures were obtained at baseline and 24 weeks: single-slice computed tomography (CT) scan, dual-energy X-ray absorptiometry (DEXA), lipid profile and oral glucose tolerance test. Results The median fasting insulin concentration of all participants was 12.3 ,U/mL. The percentage change in VAT was not significantly different between the metformin and placebo groups in univariate analysis and linear regression analysis adjusting for age, height, baseline VAT and insulin area under the curve (10.1% vs 3.2%; P=0.58). Metformin was associated with a significant decrease in appendicular fat mass compared with placebo (,686.0 vs 161.0 g; P=0.03). There was no significant change in lipid profile or insulin sensitivity between the two groups at 24 weeks. Conclusion Metformin should be used with caution in the treatment of HIV lipodystrophy, and, if used, should be reserved for persons with adequate peripheral fat and marked insulin resistance. [source] Avandamet: combined metformin,rosiglitazone treatment for insulin resistance in type 2 diabetesINTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 9 2004C.J. Bailey Summary Insulin resistance is a major endocrinopathy underlying the development of hyperglycaemia and cardiovascular disease in type 2 diabetes. Metformin (a biguanide) and rosiglitazone (a thiazolidinedione) counter insulin resistance, acting by different cellular mechanisms. The two agents can be used in combination to achieve additive glucose-lowering efficacy in the treatment of type 2 diabetes, without stimulating insulin secretion and without causing hypoglycaemia. Both agents also reduce a range of atherothrombotic factors and markers, indicating a lower cardiovascular risk. Early intervention with metformin is already known to reduce myocardial infarction and increase survival in overweight type 2 patients. Recently, a single-tablet combination of metformin and rosiglitazone, Avandamet, has become available. Avandamet is suitable for type 2 diabetic patients who are inadequately controlled by monotherapy with metformin or rosiglitazone. Patients already receiving separate tablets of metformin and rosiglitazone may switch to the single-tablet combination for convenience. Also, early introduction of the combination before maximal titration of one agent can reduce side effects. Use of Avandamet requires attention to the precautions for both metformin and rosiglitazone, especially renal, cardiac and hepatic competence. In summary, Avandamet is a single-tablet metformin,rosiglitazone combination that doubly targets insulin resistance as therapy for hyperglycaemia and vascular risk in type 2 diabetes. [source] Metformin,pioglitazone and metformin,rosiglitazone effects on non-conventional cardiovascular risk factors plasma level in type 2 diabetic patients with metabolic syndromeJOURNAL OF CLINICAL PHARMACY & THERAPEUTICS, Issue 4 2006G. Derosa MD PhD Summary Background and objective:, Metformin is considered the gold standard for type 2 diabetes treatment as monotherapy and in combination with sulphonylureas and insulin. The combination of metformin with thiazolidinediones is less well studied. The aim of the present study was to assess the differential effect, and tolerability, of metformin combined with pioglitazone or rosiglitazone on glucose, coagulation and fibrinolysis parameters in patients with type 2 diabetes mellitus and metabolic syndrome. Methods:, This 12-month, multicentre, double-blind, randomized, controlled, parallel-group trial was conducted at three study sites in Italy. We assessed patients with type 2 diabetes mellitus (duration ,6 months) and with metabolic syndrome. All patients were required to have poor glycaemic control with diet, or experienced adverse effects with diet and metformin, administered up to the maximum tolerated dose. Patients were randomized to receive either pioglitazone or rosiglitazone self-administered for 12 months. We assessed body mass index (BMI), glycaemic control [glycosylated haemoglobin (HbA1c), fasting and postprandial plasma glucose and insulin levels (FPG, PPG, FPI, and PPI respectively), homeostasis model assessment (HOMA) index], lipid profile [total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C) and triglycerides (TG)], lipoprotein (a) [Lp(a)] and homocysteine (HCT) at baseline and at 3, 6, 9 and 12 months of treatment. Results and discussion:, No BMI change was observed at 3, 6, 9 and 12 months in either group. Significant HbA1c decreases were observed at 9 and 12 months in both groups. After 9 and 12 months, mean FPG and PPG levels decreased in both groups. Decreases in FPI and PPI were observed at 9 and 12 months compared with the baseline in both groups. Furthermore, in both groups, the HOMA index improved but only at 12 months. Significant TC, LDL-C, HDL-C, TG improvement was present in the pioglitazone group at 12 months compared with the baseline values, and these variations were significantly different between groups. No TC, LDL-C, TG improvement was present in the rosiglitazone group after 12 months. Significant Lp(a) and HCT improvement was present in the pioglitazone group at 12 months compared with the baseline values, and Lp(a) change was significant compared with the rosiglitazone group. Significant HCT decrease was observed in the rosiglitazone group at the end of the study. In our type 2 diabetic patients, both drugs were safe and effective for glycaemic control and improving HCT plasma levels. However, long-term treatment with metformin plus pioglitazone significantly reduced Lp(a) plasma levels, whereas metformin + rosiglitazone did not. Conclusion:, For patients with type 2 diabetes mellitus and metabolic syndrome, combined treatment with metformin and rosiglitazone or pioglitazone is safe and effective, However, the pioglitazone combination also reduced the plasma Lp(a) levels whereas the rosiglitazone combination did not. [source] Effects of cysteine on metformin pharmacokinetics in rats with protein-calorie malnutrition: partial restoration of some parameters to control levelsJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 2 2008Young H. Choi Metformin is metabolized primarily via hepatic microsomal cytochrome P450 (CYP)2C11, CYP2D1 and CYP3A1/2 in rats. The expression and mRNA levels of hepatic CYP2C11 and CYP3A1/2 are decreased in rats with protein-calorie malnutrition (PCM), but these levels are fully or partially restored to control levels in PMC rats by oral cysteine supplementation (PCMC rats). Thus, it would be expected that the pharmacokinetic parameters of metformin in PCM rats would be returned to control levels in PCMC rats. Metformin was administered i.v. (100 mg kg,1) and orally (100 mg kg,1) to control, CC (control rats with oral cysteine supplementation), PCM and PCMC rats. The following pharmacokinetic parameters of metformin following i.v. administration were restored from levels in PCM rats to levels in control rats in PCMC rats: intrinsic clearance (0.0350, 0.0309, 0.0253 and 0.0316 mL min,1 mg,1 protein for control, CC, PCM, and PCMC rats, respectively), total area under the plasma concentration-time curve from time zero to time infinity (AUC; 4110, 4290, 5540 and 4430 ,g min mL,1, respectively), and time-averaged non-renal clearance (8.12, 7.95, 5.94 and 8.17 mL min,1 kg,1, respectively). AUC values following oral administration were comparable between control and PCMC rats (1520, 1480, 2290 and 1680 ,g min mL,1, respectively). [source] Uptake and Dispersion of Metformin in the Isolated Perfused Rat LiverJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 8 2000CHEN-HSI CHOU Although metformin is a widely used oral antihyperglycaemic, the exact mechanisms of its cellular uptake and action remain obscure. In this study the hepatic extraction and disposition kinetics of metformin were investigated by use of an isolated in-situ rat liver preparation. The liver was perfused in single-pass mode with protein-free Krebs bicarbonate medium at a flow rate of 20mLmin,1. During constant infusion with 1 mgL,1 metformin hydrochloride the hepatic uptake of metformin approached equilibrium within 10 min. The steady-state availability, F, determined from the ratio of outflow concentration to input concentration, was 0.99±0.02 (mean±s.d., n=4). The outflow profile of metformin resulting from a bolus injection of 25 ,g into the portal vein, had a sharp peak then a slower declining terminal phase. The mean transit time (MTT; 49.5±14.5, n = 6) and normalized variance (CV2; 4.13±0.05) of the hepatic transit times of metformin were estimated by numerical integration from the statistical moments of the outflow data. The volume of distribution of metformin in the liver (1.58±0.28 mL (g liver),1) was estimated from its MTT. The volume of distribution is greater than the water space of liver, indicating that metformin enters the hepatic aqueous space and becomes distributed among cellular components. The magnitude of CV2 for metformin is greater than for the vascular marker sucrose, suggesting that distribution of metformin into hepatic tissue is not instantaneous. In conclusion, hepatic uptake of metformin is rate-limited by a permeability barrier. Although metformin is accumulated in the liver, the organ does not extract it. [source] Clinical trial: pilot study of metformin for the treatment of non-alcoholic steatohepatitisALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 2 2009R. LOOMBA Summary Background, Non-alcoholic steatohepatitis (NASH) is a form of progressive fatty liver disease that is strongly associated with insulin resistance, which suggests that insulin sensitizing agents such as metformin may be beneficial for NASH. Aim, To assess the effects of metformin on insulin sensitivity, body composition, serum alanine aminotransferase (ALT) levels and liver histology in patients with NASH. Methods, Patients underwent liver biopsy, metabolic profiling and imaging studies before and at the end 48 weeks of metformin (2000 mg/day) therapy. The primary endpoint was a three-point improvement in the histological NASH activity index. Results, Of 28 patients enrolled, 26 (13 females; average age 44 years) completed 48 weeks of treatment and underwent repeat metabolic studies, imaging and liver biopsy. Thirty per cent achieved a histological response. Most patients lost weight, the average being 6 kg. There was a marked association between weight loss and improvements in NASH activity index and ALT levels (both, P < 0.01). Insulin sensitivity also improved, but the degree of change did not correlate with histological improvement. Conclusion, Metformin leads to improvements in liver histology and ALT levels in 30% of patients with NASH, probably by its effects in causing weight loss. [source] Balancing Risk and Benefit with Oral Hypoglycemic DrugsMOUNT SINAI JOURNAL OF MEDICINE: A JOURNAL OF PERSONALIZED AND TRANSLATIONAL MEDICINE, Issue 3 2009Ole-Petter R. Hamnvik MB Abstract Clinicians are faced with an expansive array of treatment choices when caring for patients with type 2 diabetes. Because patient compliance may be affected when media sensationalism about controversial findings is misunderstood, we sought to clarify the recent controversy surrounding the cardiovascular and bone-health risks of thiazolidinediones, the risk of lactic acidosis with metformin, and the risk of hypoglycemia with oral therapies. The side effect profile of thiazolidinediones includes fluid retention, heart failure; and an increased risk of fracture. A recent controversial meta-analysis suggested that rosiglitazone increases the risk of myocardial infarction, which is possibly related to thiazolidinedione-induced lipid changes, weight gain, congestive heart failure, and anemia. Metformin is restricted to patients with normal renal function because of concerns that metformin may cause lactic acidosis. However, few cases of metformin-associated lactic acidosis have been reported, and most have occurred in patients with other reasons for developing lactic acidosis, such as sepsis or renal failure. Although the use of metformin continues to increase, observational studies have not been able to demonstrate an increased incidence of lactic acidosis in metformin-treated patients, even when it is used in populations with relative contraindications. Some oral hypoglycemic medications can cause hypoglycemia. Hypoglycemia is especially common in older patients, alcoholics, and patients with liver or renal disease. Patients on sulfonylureas and meglitinides have the highest incidence of hypoglycemia because of their pharmacological action of increasing insulin secretion. Of the sulfonylureas, glyburide presents the highest risk of hypoglycemia. Combination therapies, especially those regimens containing a sulfonylurea, increase the risk of hypoglycemia. Mt Sinai J Med 76:234,243, 2009. © 2009 Mount Sinai School of Medicine [source] Usefulness of the addition of metformin to insulin in pediatric patients with type 1 diabetes mellitusPEDIATRICS INTERNATIONAL, Issue 4 2005Tatsuhiko Urakami Abstract, Background:,The aim of this study was to evaluate the effect of metformin in addition to insulin therapy in adolescents and young adults with type 1 diabetes mellitus. Methods:,Nine patients, two males and seven females, aged 18.1 ± 3.0 years, with type 1 diabetes mellitus were studied. They were relatively overweight with a body mass index (BMI) of 24.2 ± 1.8 and had high levels of HbA1c at 9.5 ± 1.2% despite high doses of insulin of 74.0 ± 31.2 U/day. Metformin at the dose of 500,750 mg daily was administered to the patients in addition to insulin therapy for 1 year. Results:,HbA1c, BMI and insulin dose were compared before 1 year without metformin therapy, at baseline, and at 3, 6 and 12 months during the use of metformin in addition to insulin therapy. HbA1c lowered (8.6 ± 1.4**, 8.4 ± 1.3**, 8.4 ± 1.2*%), BMI was reduced (23.9 ± 1.7*, 23.8 ± 1.8, 23.5 ± 1.8*), and insulin requirement decreased (69.8 ± 29.7*, 68.7 ± 29.8**, 67.3 ± 29.1**U/d) significantly after the start of metformin therapy (*P < 0.05, **P < 0.01 vs at baseline). There were no adverse events, not even lactic acidosis, during the study period. Conclusion:,Metformin is safe and may represent a useful adjunct to the management of type 1 diabetes mellitus in adolescents and young adults who have poor glycemic control despite a large amount of insulin. [source] DPP-4-Inhibitoren in der Klinik.PHARMAZIE IN UNSERER ZEIT (PHARMUZ), Issue 2 2010Therapie ohne Hypoglykämie-Gefahr Mit den DPP-4-Hemmern stehen seit 2007 zugelassene orale Antidiabetika zur Verfügung, die im Gegensatz zu anderen insulinotropen Medikamenten glucoseabhängig bei Hyperglykämie die Insulinsekretion stimulieren und daher kein eigenes Hypoglykämierisiko haben. Zusätzlich hemmen sie die Glucagonsekretion und sind gewichtsneutral. DPP-4-Hemmer sind in Monotherapie und in Kombination mit Metformin, Glitazonen und Sulfonylharnstoffen wirksam, ihre Wirksamkeit bezüglich der Blutzuckersenkung ist mit der anderer oraler Antidiabetika vergleichbar. Zugelassen und auf dem Markt sind derzeit Sitagliptin, Saxagliptin und Vildagliptin für die Kombinationstherapie mit den oben genannten Substanzen. Die Verträglichkeit ist gut, spezifische Nebenwirkungen sind nicht bekannt. Weitere Substanzen sind im Zulassungsverfahren oder in klinischer Prüfung. [source] Type 2 diabetes in adolescence , unearthed at the time of registration with the general practitioner (GP)PRACTICAL DIABETES INTERNATIONAL (INCORPORATING CARDIABETES), Issue 8 2000GYT Ng Abstract Type 2 diabetes, or non-insulin-dependent diabetes mellitus (NIDDM), is often considered to be a diagnosis of adulthood. We present a 13 year old boy who was noted to have glycosuria on routine general practitioner (GP) urine testing. Clinical examination upon referral showed massive obesity, hypertension and prominent acanthosis nigricans, and investigations confirmed hyperinsulinaemia and hyperglycaemia. Metformin and a programme of weight reduction comprise the management of this young adolescent with type 2 diabetes. Such early diagnosis should permit the institution of appropriate management to avoid the early emergence of the complications of type 2 diabetes. Copyright © 2000 John Wiley & Sons, Ltd. [source] Latest news and product developmentsPRESCRIBER, Issue 11 2008Article first published online: 18 JUN 200 New asthma guideline The BTS/SIGN guideline for the management of asthma has been updated. The diagnosis section has been rewritten, there is a new section on difficult asthma and the treatment sections have been updated. A new option at Step 3 (initial add-on therapy) is now the use of a combined budesonide/formoterol inhaler (Symbicort) as a reliever in addition to regular use as a preventer. This reflects evidence from the SMART trials, which showed that an average of one extra puff per day significantly reduced exacerbations and admissions (Br Med J 2007;335:513). Metformin matches insulin in pregnancy Metformin does not worsen perinatal outcomes compared with insulin in gestational diabetes and mothers prefer it, a study from Australia and New Zealand shows (N Engl J Med 2008;358:2003,15). Of the women randomised to metformin treatment, 93 per cent were still taking it at term and 46 had supplemental insulin. The combined incidence of neonatal hypoglycaemia, respiratory distress, need for phototherapy, birth trauma, five-minute Apgar score less than 7 or prematurity was 32 per cent with both treatments. There were no serious adverse events. More women said they would choose the same treatment again for metformin than insulin (77 vs 27 per cent). Same CV protection with antihypertensives There is no difference in protection against major cardiovascular events between different types of antihypertensives in young or older (65 or over) adults, according to the Blood Pressure Lowering Treatment Trialists' Collaboration. Its meta-analysis of 31 trials involving over 190 000 patients (BMJ Online 2008; doi:10.1136/bmj.39548.738 368.BE) found no significant difference by age on blood pressure reduction or risk reduction. Treatment may be chosen according to tolerability and cost as long as effective blood pressure reduction is achieved, the authors conclude. Older people are at greater absolute risk and treatment therefore offers larger reductions in serious vascular events. HPV vaccination starts in September Vaccination against human papilloma virus will be part of the national immunisation programme from the start of the new school year in September. The vaccine, administered as three doses over six months, will initially be offered to girls aged 12,13 (school year 8) to reduce their risk of cervical cancer. A two-year catch-up campaign for all girls up to 18 years old will begin in 2009. MHRA: pancreatitis with exenatide warning The incretin mimetic exenatide (Byetta), licensed for the treatment of type 2 diabetes, may rarely be associated with pancreatitis, warns the MHRA (Drug Safety Update 2008;1:Issue 10). One case has been reported in the UK and 89 in the USA and Germany. The MHRA advises that patients should be warned of the symptoms of pancreatitis (severe abdominal pain, back pain). Treatment should be discontinued if pancreatitis is suspected and the case reported on a yellow card. 2007 prescribing bill Primary-care expenditure on drugs in England in 2007 totalled £8.37 billion, only 2 per cent more than in 2006, according to the latest statistics from the Information Centre (www.ic.nhs.uk). Prescription numbers increased by almost 6 per cent. Prescribing increased in most BNF categories but changed little in musculoskeletal drugs and immunological products and vaccines. Calceos: calcium/ vitamin D3 price match Manufacturer Galen has pledged to continue to price-match its calcium/vitamin D3 supplement Calceos with Adcal-D3 or Calcichew D3 Forte. If the price of either product falls below that of Calceos chewable tablets, Galen will match it within six months. The company says it will honour the pledge until at least 2011. Copyright © 2008 Wiley Interface Ltd [source] Latest news and product developmentsPRESCRIBER, Issue 8 2008Article first published online: 12 MAY 200 Glargine preferred to lispro as type 2 add-on Basal insulin glargine (Lantus) and insulin lispro (Humalog) at mealtimes improved glycaemic control equally well in patients with type 2 diabetes poorly controlled by oral agents, but patient satisfaction was greater with basal insulin (Lancet 2008;371:1073-84). The 44-week APOLLO trial, funded by Sanofi Aventis, was a nonblinded randomised comparison of basal and prandial insulin regimens added to oral treatment in 418 patients. It found similar reductions in HbA1C (,1.7 vs ,1.9 per cent respectively). Fasting and nocturnal glucose levels were lower with insulin glargine and postprandial levels were lower with insulin lispro. The basal regimen was associated with fewer hypoglycaemic events (5.2 vs 24 per patient per year), less weight gain (3.01 vs 3.54kg) and greater improvement in patient satisfaction scores. Treating hypertension cuts mortality in over-80s Treating hypertension in the over-80s reduces all-cause mortality by 21 per cent, the HYVET study has shown (N Engl J Med online: 31 March 2008; doi: 10.1056/NEJMoa 0801369). Compared with placebo, treatment with indapamide alone or with perindopril for an average of 1.8 years also reduced the incidence of fatal stroke by 39 per cent, cardiovascular death by 23 per cent and heart failure by 64 per cent. The incidence of stroke was reduced by 30 per cent but this was of borderline statistical significance. Fewer serious adverse events were reported with treatment than with placebo. New work for NICE The DoH has announced the 18th work programme for NICE. Seven public health interventions include preventing skin cancer, smoking by children and excess weight gain during pregnancy. Public health guidance will include the provision of contraceptive services for socially disadvantaged young people. Two new clinical guidelines are sedation in young people and management of fractured neck of femur. New technology appraisals may include eight therapies for cancer, two new monoclonal antibodies for psoriasis and rheumatoid arthritis, an oral retinoid for severe chronic hand eczema and methylnaltrexone for opioid-induced bowel dysfunction. Combinations no better against CV disease Taking ezetimibe and simvastatin (Inegy) does not appear to slow the progression of atherosclerosis more than high-dose simvastatin alone, say researchers from The Netherlands (N Engl J Med 2008;358: 1431-43). In patients with hypercholesterolaemia, there was no difference in regression or progression of atherosclerosis after two years' treatment with simvastatin 80mg per day alone or combined with ezetimibe 10mg per day. Adverse event rates were similar. In patients with vascular disease or high-risk diabetes, there was no difference between the ACE inhibitor ramipril 10mg per day or the ARB telmisartan (Micardis) 80mg per day as monotherapy, or their combination, in the risk of a composite outcome of cardiovascular death, MI, stroke and admission for heart failure (N Engl J Med 2008;358:1547-59). Combined treatment was associated with higher risks of hypotensive symptoms, syncope and renal dysfunction. Twice-daily celecoxib increases CV risk Taking celecoxib (Celebrex) twice daily carries a higher risk of cardiovascular events than the same total dose taken once daily, a metaanalysis suggests (Circulation 2008; doi: 10.1161/ CIRCULATIONAHA.108. 764530). The analysis of six placebo-controlled trials involving a total of 7950 patients taking celecoxib for indications other than rheumatoid arthritis found that the combined risk of cardiovascular death, myocardial infarction, stroke, heart failure or thromboembolic event increased with dose over the range 400-800mg per day. The risk was significantly greater with 200mg twice daily (HR 1.8) than 400mg once daily (HR 1.1). Patients at greatest baseline risk were at disproportionately increased risk from celecoxib. Long-term etanercept effective in AS An open-label study suggests that etanercept (Enbrel) remains effective in the treatment of ankylosing spondylitis in the long term (Ann Rheum Dis 2008;67:346-52). Of 257 patients who completed six months' treatment with etanercept and who entered the nonblinded extension study, 126 completed a total of 168-192 weeks' treatment. The commonest adverse events were injection-site reactions (22 per cent), headache (20 per cent) and diarrhoea (17.5 per cent). The annual rate of serious infections was 0.02 per person. Response and partial remission rates after 192 weeks were similar to those reported after 96 weeks. Metformin reduces risk Metformin reduces the risk of developing diabetes in individuals at increased risk, a meta-analysis suggests (Am J Med 2008;121:149-57.e2). The study included 31 mostly small, randomised, controlled trials involving a total of 4570 participants and lasting at least eight weeks (8267 patient-years of treatment). Metformin was associated with reductions in body mass (,5.3 per cent), fasting glucose (,4.5 per cent) and insulin resistance (,22.6 per cent); lipid profiles also improved. The odds of developing diabetes were reduced by 40 per cent,an absolute risk reduction of 6 per cent over 1.8 years. MHRA clarifies cough and colds advice Press reports mistakenly suggested that the MHRA had banned some cough and cold remedies when it issued new guidance on treating young children, the MHRA says. The Agency's advice followed a review of over-thecounter cough and cold medicines for children by the Commission on Human Medicines. Children under two are at increased risk of adverse reactions and should no longer be treated with products containing antihistamine (chlorphenamine, brompheniramine, diphenhydramine), antitussives (dextromethorphan, pholcodine), expectorants (guaifenesin, ipecacuanha) and decongestants (phenylephrine, pseudoephedrine, ephedrine, oxymetazoline and xylometazoline). The MHRA said these products, which are classified as general sale medicines, should be removed from open shelves until available in new packaging that complies with the advice. They may still be supplied by a pharmacist for the treatment of older children. Coughs and colds should be treated with paracetamol or ibuprofen for fever, a simple glycerol, honey or lemon syrup for cough, and vapour rubs and inhalant decongestants for stuffy nose. Saline drops can be used to thin and clear nasal secretions in young babies. Parents are being urged not to use more than one product at a time to avoid inadvertently administering the same constituent drug twice. Perindopril brand switch Servier Laboratories is replacing its current formulations of perindopril (Coversyl, Coversyl Plus) with a new product that is not bioequivalent. The current Coversyl brand contains perindopril erbumine (also known as tert -butylamine). The new formulation contains perindopril arginine; it will be distinguished by new brand names (Coversyl Arginine, Coversyl Arginine Plus) and new packaging. Coversyl 2, 4 and 8mg tablets are equivalent to Coversyl Arginine 2.5, 5 and 10mg. Servier says the change is part of the simplification and harmonisation of global manufacturing; the arginine salt is already used in other countries and offers greater stability and a longer shelf-life. Both Coversyl and Coversyl Arginine will be in the supply chain for the next few weeks. Generic perindopril will continue to be the erbumine salt and prescriptions for generic perindopril are not affected. New from NICE Diabetes in pregnancy: management of diabetes and its complications from preconception to the postnatal period. Clinical Guidance No. 63, March 2008 This clinical guideline focuses on additional aspects of care for women with gestational diabetes (88 per cent of cases) or pre-existing diabetes (of which about 40 per cent is type 2 diabetes) and their babies. To date, insulin aspart (NovoRapid) is the only drug in the guideline specifically licensed for use in pregnancy and NICE advises obtaining informed consent to implement its recommendations for using other insulins and oral hypoglycaemic agents. As with other guidelines, NICE begins by stressing the importance of patient-centred care and involving women in decisions about their treatment. The guideline is divided into six sections, dealing with consecutive periods of pregnancy. Preconceptual planning should include empowering women to help them reduce risks, optimising glycaemic control (after retinal assessment) and increasing monitoring intensity, and providing information about the effects of pregnancy on diabetes. Metformin may be recommended as an adjunct or alternative to insulin, but other oral hypoglycaemic agents should be replaced with insulin, although glibenclamide is an option during pregnancy. Isophane insulin is the preferred long-acting insulin; lispro (Humalog) and aspart are considered safe to use. ACE inhibitors and angiotensin-II receptor blockers should be replaced with other antihypertensive agents and statins should be discontinued. Recommendations for screening and treatment of gestational diabetes build on previous guidance (CG62). Drug treatment will be needed by 10-20 per cent , this includes insulin (soluble, aspart or lispro) and/or metformin or glibenclamide, tailored to individual need. Antenatal care includes optimising glycaemic control. Insulin lispro or aspart should be considered in preference to soluble insulin. If glycaemic control cannot be achieved with insulin injections, an insulin pump may be indicated. The guideline includes a timetable for appointments and the care that should offered after each interval. Recommendations for intrapartum care, which supplement those in CG55, include frequent monitoring of blood glucose. Neonatal care includes recommendations for monitoring and screening the infant and the management of hypoglycaemia. Postnatal care (supplementing CG37) involves adjusting maternal treatment to avoid hypoglycaemia and recommendations for returning to community care. Metformin and glibenclamide are the only oral agents suitable for breastfeeding women. Women with gestational diabetes need advice about glycaemic control and planning for future pregnancies. Lifestyle advice and measurement of annual fasting plasma glucose should be offered. Inhaled corticosteroids for the treatment of chronic asthma in adults and in children aged 12 years and over. Technology Appraisal No. 138, March 2008 The latest technology appraisal of asthma treatments covers inhaled steroids for adults and children over 12 with chronic asthma. It makes only two recommendations. First, the cheapest appropriate option is recommended. Second, when a steroid and a long-acting beta2-agonist are indicated, the decision to prescribe a combined inhaler or separate devices should take into account therapeutic need and likely adherence. Combined inhalers are currently less expensive than separate devices, though they may not remain so. When a combined inhaler is chosen it should be the cheapest. NICE concludes that, at equivalent doses, there is little difference in the effectiveness or adverse event profile of the available steroids or the fixed-dose combinations. According to specialist advice, choosing the best device for an individual remains the overriding concern. Continuous positive airway pressure for the treatment of obstructive sleep apnoea/hypopnoea syndrome. Technology Appraisal No. 139, March 2008 NICE recommends continuous positive airway pressure (CPAP) for adults with moderate or severe obstructive sleep apnoea, and for those with a milder disorder if quality of life and functioning are impaired and alternative strategies such as lifestyle change have failed. Diagnosis and treatment is the responsibility of a specialist team. A CPAP device costs £250-£550 and lasts for seven years. Copyright © 2008 Wiley Interface Ltd [source] The Effect of Metformin in Overweight Patients with Type 1 Diabetes and Poor Metabolic ControlBASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 3 2009Iben Brock Jacobsen Double-blinded intervention with 2000 mg metformin or placebo daily in 24 type 1 diabetic patients as adjunct to intensive insulin therapy. Primary endpoint was HbA1c, while secondary endpoints were body weight, frequency of hypoglycaemia, blood pressure, lipids, insulin dosage and self-monitored blood glucose profiles were measured. After 24 weeks, no difference in HbA1c was seen between the metformin and placebo groups (,0.5 ± 0.3 vs. ,0.2 ± 0.2%, P = 0.26. , mean ± S.E.M). Mean diurnal blood glucose profiles showed no statistical significant difference between the groups. The total daily insulin dose (IU) was significantly reduced in the metformin group compared to placebo after 24 weeks (,5.9 ± 2.2 vs. 2.9 ± 1.7, P = 0.004. , mean ± S.E.M). An increase in the frequency of hypoglycaemia was seen in the metformin group (0.7 ± 0.9 vs. 0.3 ± 0.5 events patient,1 week,1, P = 0.005), and a reduction in body weight was found using metformin compared to placebo (,3.0 ± 1.0 vs. 0.8 ± 1.1, P = 0.02. , mean ± S.E.M). Lipids and blood pressure did not differ significantly after intervention. Metformin, as adjunct to intensive insulin therapy, was associated with a reduction in the total daily insulin dose and a significant weight loss in patients with type 1 diabetes mellitus. [source] Metformin Induces Cardioprotection against Ischaemia/Reperfusion Injury in the Rat Heart 24 Hours after AdministrationBASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 1 2008Lasse Solskov The energy sensing enzyme AMP-activated protein kinase (AMPK) has been indicated to play an important protective role in the ischaemic heart and is activated by metformin. The aim of this study was to determine whether a single dose of metformin protects the myocardium against experimentally induced ischaemia 24 hr after the administration, and furthermore to determine whether a single dose of metformin results in an acute increase in myocardial AMPK activity. Wistar rats were given either a single oral dose of metformin (250 mg/kg body weight), or a single oral dose of saline. After 24 hr, the hearts were Langendorff-perfused and subjected to 45 min. of coronary artery occlusion. Infarct size was determined by staining with triphenyltetrazoliumchloride (TTC) and Evans Blue and expressed as a percentage of the risk zone (IS/AAR %). Isoform specific AMPK activity was measured 2 hr after administration of metformin or saline. Infarct size was significantly reduced in the metformin treated (I/R: 19.9 ± 3.9%versus 36.7 ± 3.6%, P < 0.01, n = 8,14) compared to the control group. A single oral dose of metformin resulted in an approximately ~2-fold increase in AMPK-,2 activity 2 hr after administration (P < 0.015, n = 10). In conclusion, a single dose of metformin results in an acute increase in myocardial AMPK activity measured 2 hr after administration and induces a significant reduction in myocardial infarct size 24 hr after metformin administration. Increased AMPK activity may be an important signal mediator involved in the mechanisms behind the cardioprotective effects afforded by metformin. [source] Expanding roles for AMP-activated protein kinase in neuronal survival and autophagyBIOESSAYS, Issue 9 2009Jeroen Poels Abstract AMP-activated protein kinase (AMPK) is an evolutionarily conserved cellular switch that activates catabolic pathways and turns off anabolic processes. In this way, AMPK activation can restore the perturbation of cellular energy levels. In physiological situations, AMPK senses energy deficiency (in the form of an increased AMP/ATP ratio), but it is also activated by metabolic insults, such as glucose or oxygen deprivation. Metformin, one of the most widely prescribed anti-diabetic drugs, exerts its actions by AMPK activation. However, while the functions of AMPK as a metabolic regulator are fairly well understood, its actions in neuronal cells only recently gained attention. This review will discuss newly emerged functions of AMPK in neuroprotection and neurodegeneration. Additionally, recent views on the role of AMPK in autophagy, an important catabolic process that is also involved in neurodegeneration and cancer, will be highlighted. [source] Protective role of the antidiabetic drug metformin against chronic experimental pulmonary hypertensionBRITISH JOURNAL OF PHARMACOLOGY, Issue 5 2009C Agard Background and purpose:, Pulmonary arterial hypertension (PAH) is associated with increased contraction and proliferation of pulmonary vascular smooth muscle cells. The anti-diabetic drug metformin has been shown to have relaxant and anti-proliferation properties. We thus examined the effect of metformin in PAH. Experimental approach:, Metformin effects were analysed in hypoxia- and monocrotaline-induced PAH in rats. Ex vivo and in vitro analyses were performed in lungs, pulmonary artery rings and cells. Key results:, In hypoxia- and monocrotaline-induced PAH, the changes in mean pulmonary arterial pressure and right heart hypertrophy were nearly normalized by metformin treatment (100 mg·kg,1·day,1). Pulmonary arterial remodelling occurring in both experimental models of PAH was also inhibited by metformin treatment. In rats with monocrotaline-induced PAH, treatment with metformin significantly increased survival. Metformin increased endothelial nitric oxide synthase phosphorylation and decreased Rho kinase activity in pulmonary artery from rats with PAH. These effects are associated with an improvement of carbachol-induced relaxation and reduction of phenylephrine-induced contraction of pulmonary artery. In addition, metformin inhibited mitogen-activated protein kinase activation and strongly reduced pulmonary arterial cell proliferation during PAH. In vitro, metformin directly inhibited pulmonary artery smooth muscle cell growth. Conclusions and implications:, Metformin protected against PAH, regardless of the initiating stimulus. This protective effect may be related to its anti-remodelling property involving improvement of endothelial function, vasodilatory and anti-proliferative actions. As metformin is currently prescribed to treat diabetic patients, assessment of its use as a therapy against PAH in humans should be easier. [source] Liver dysfunction in paediatric obesity: a randomized, controlled trial of metforminACTA PAEDIATRICA, Issue 9 2007Michael Freemark Abstract Aim: In a previous study we showed that metformin reduced BMI z -scores and fasting glucose and insulin concentrations, and increased whole body insulin sensitivity in obese adolescents with fasting hyperinsulinemia and a family history of type 2 diabetes. We analyzed the data from this study to determine (a) if metformin reduced serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) concentrations during the 6-month trial, and (b) if the response to pharmacotherapy varied along gender or ethnic lines. Methods: The 6-month trial was randomized, double blinded and placebo controlled; a total of 14 metformin-treated (500 mg bid) and 15 placebo-treated subjects completed the study. There were no dietary restrictions. Results: In obese adolescents fed ad libitum, metformin (a) prevented the rise in ALT concentrations that were observed in placebo-treated subjects at the 3 to 5 month time-points (p < 0.05); (b) reduced (p < 0.01) the percentage of all ALT values exceeding 40 U/L; and (c) caused a modest (10%) but statistically significant (p < 0.05) reduction in serum ALT in Caucasian subjects. Metformin had no effect on ALT levels or the ALT to AST ratio in the five African American adolescents enrolled in the study but reduced their fasting insulin concentrations from 26.1 to 19.5 ,U/mL (p < 0.05). Conclusions: Our findings suggest that metformin might reduce the rates or severity of liver dysfunction in selected high-risk adolescents. [source] Prevalence of diabetic peripheral neuropathy and relation to glycemic control therapies at baseline in the BARI 2D cohortJOURNAL OF THE PERIPHERAL NERVOUS SYSTEM, Issue 1 2009Rodica Pop-Busui Abstract We evaluated the associations between glycemic therapies and prevalence of diabetic peripheral neuropathy (DPN) at baseline among participants in the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trial on medical and revascularization therapies for coronary artery disease (CAD) and on insulin-sensitizing vs. insulin-providing treatments for diabetes. A total of 2,368 patients with type 2 diabetes and CAD was evaluated. DPN was defined as clinical examination score >2 using the Michigan Neuropathy Screening Instrument (MNSI). DPN odds ratios across different groups of glycemic therapy were evaluated by multiple logistic regression adjusted for multiple covariates including age, sex, hemoglobin A1c (HbA1c), and diabetes duration. Fifty-one percent of BARI 2D subjects with valid baseline characteristics and MNSI scores had DPN. After adjusting for all variables, use of insulin was significantly associated with DPN (OR = 1.57, 95% CI: 1.15,2.13). Patients on sulfonylurea (SU) or combination of SU/metformin (Met)/thiazolidinediones (TZD) had marginally higher rates of DPN than the Met/TZD group. This cross-sectional study in a cohort of patients with type 2 diabetes and CAD showed association of insulin use with higher DPN prevalence, independent of disease duration, glycemic control, and other characteristics. The causality between a glycemic control strategy and DPN cannot be evaluated in this cross-sectional study, but continued assessment of DPN and randomized therapies in BARI 2D trial may provide further explanations on the development of DPN. [source] AMP-activated protein kinase and cancerACTA PHYSIOLOGICA, Issue 1 2009W. Wang Abstract AMP-activated protein kinase (AMPK) is a cellular energy sensor that is conserved in eukaryotes. Elevated AMP/ATP ratio activates AMPK, which inhibits energy-consuming processes and activates energy-producing processes to restore the energy homeostasis inside the cell. AMPK activators, metformin and thiazolidinediones, are used for the treatment of type II diabetes. Recently, reports have indicated that AMPK may also be a beneficial target for cancer treatment. Cancer cells have characteristic metabolic changes different from normal cells and, being a key metabolic regulator, AMPK may regulate the switch. AMPK may act to inhibit tumorigenesis through regulation of cell growth, cell proliferation, autophagy, stress responses and cell polarity. [source] The metabolic syndrome and schizophreniaACTA PSYCHIATRICA SCANDINAVICA, Issue 1 2009J. M. Meyer Objective:, To summarize the accumulated data on metabolic syndrome prevalence in patients with schizophrenia, examine evidence for a biological contribution of the mental illness to metabolic risk and review novel options available for management of prediabetic states. Method:, A Medline search using metabolic syndrome, insulin resistance and insulin sensitivity cross-referenced with schizophrenia was performed on articles published between 1990 and May 2008. Results:, Recent evidence indicates that schizophrenia increases predisposition towards metabolic dysfunction independent of environmental exposure. Both fasting and non-fasting triglycerides have emerged as important indicators of cardiometabolic risk, while metformin, thiazolidinediones and GLP-1 modulators may prove promising tools for managing insulin resistance. Conclusion:, Because of lifestyle, disease and medication effects, schizophrenia patients have significant risk for cardiometabolic disease. Routine monitoring, preferential use of metabolically neutral antipsychotics and lifestyle education are critical to minimizing risk, with a possible role for antidiabetic medications for management of insulin resistant states that do not respond to other treatment strategies. [source] Initial short-term intensive insulin therapy as a strategy for evaluating the preservation of beta-cell function with oral antidiabetic medications: a pilot study with sitagliptinDIABETES OBESITY & METABOLISM, Issue 10 2010R. Retnakaran Aim: Studies evaluating the effects of oral antidiabetic drugs (OADs) on beta-cell function in type 2 diabetes mellitus (T2DM) are confounded by an inability to establish the actual baseline degree of beta-cell dysfunction, independent of the deleterious effects of hyperglycaemia (glucotoxicity). Because intensive insulin therapy (IIT) can induce normoglycaemia, we reasoned that short-term IIT could enable evaluation of the beta-cell protective capacity of OADs, free from confounding hyperglycaemia. We applied this strategy to assess the effect of sitagliptin on beta-cell function. Methods: In this pilot study, 37 patients with T2DM of 6.0 + 6.4 years duration and A1c 7.0 + 0.8% on 0,2 OADs were switched to 4,8 weeks of IIT consisting of basal detemir and premeal insulin aspart. Subjects achieving fasting glucose <7.0 mmol/l 1 day after completing IIT (n = 21) were then randomized to metformin with either sitagliptin (n = 10) or placebo (n = 11). Subjects were followed for 48 weeks, with serial assessment of beta-cell function [ratio of AUCCpep to AUCgluc over Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) (AUCCpep/gluc/HOMA-IR)] on 4-h meal tests. Results: During the study, fasting glucagon-like-peptide-1 was higher (p = 0.003) and A1c lower in the sitagliptin arm (p = 0.016). Nevertheless, although beta-cell function improved during the IIT phase, it declined similarly in both arms over time (p = 0.61). By study end, AUCCpep/gluc/HOMA-IR was not significantly different between the placebo and sitagliptin arms (median 71.2 vs 80.4; p = 0.36). Conclusions: Pretreatment IIT can provide a useful strategy for evaluating the beta-cell protective capacity of diabetes interventions. In this pilot study, improved A1c with sitagliptin could not be attributed to a significant effect on preservation of beta-cell function. [source] | |||||||||||||||||||||||||||||||||||||