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G Schernthaner

Publications and source records attributed to G Schernthaner.

At least 19 recordsLinked to original sources
PubMed2007

Asymmetrical dimethylarginine is related to renal function, chronic inflammation and macroangiopathy in patients with Type 2 diabetes and albuminuria.

AIMS: Patients with Type 2 diabetes mellitus (T2DM) and micro- and macroalbuminuria are at increased cardiovascular risk. The endogenous nitric oxide synthase inhibitor asymmetrical dimethylarginine (ADMA) is increased in renal failure and could promote atherosclerosis. To determine the relationship between ADMA, renal albumin excretion rate (AER) and cardiovascular risk, we studied 103 T2DM patients. METHODS: ADMA, symmetrical dimethylarginine (SDMA) and L-arginine were determined by high-performance liquid chromatography in plasma from 36 normo-, 40 micro- and 27 macroalbuminuric patients with T2DM (age 64 +/- 11 years; 38 women) who had comparable age, sex and metabolic parameters. Forty-six patients had macrovascular disease (MVD). RESULTS: ADMA was significantly increased in patients with micro- and macroalbuminuria [median 0.61 (interquartile range 0.55-0.70) micromol/l and 0.62 (0.50-0.79) micromol/l, respectively] compared with those with normoalbuminuria [0.55 (0.48-0.63) micromol/l; both P < 0.05]. SDMA was elevated in micro- and macroalbuminuria [0.57 (0.42-0.80) micromol/l and 0.64 (0.50-0.96) micromol/l] compared with normoalbuminuric subjects [0.44 (0.37-0.53) micromol/l; both P < 0.01]. Patients with increased AER and MVD had higher ADMA and SDMA compared with those without MVD (both P < 0.001). L-arginine was comparable between all groups. ADMA correlated significantly with high-sensitivity C-reactive protein (hsCRP) and glomerular filtration rate (GFR) but not with the extent of albumin excretion, body mass index, fasting glucose, HbA(1c) or plasma lipids. CONCLUSIONS: Increased ADMA in T2DM patients with albuminuria is linked to cardiovascular disease and is associated with renal dysfunction and subclinical inflammation.

Aged↗
PubMed2006

[Success of blood pressure reduction in diabetic patients].

Diabetes and hypertension frequently coexist, and their combination provides additive increases in the risk of life-threatening cardiovascular events. Recent guidelines agree (JN-VII) on the need for early, aggressive reduction of blood pressure, with a goal of < 130/80 mmHg, in patients with diabetes. The mechanism responsible for the increased sensitivity of diabetics to hypertension is not known, but may involve attenuated nocturnal decrease (non-dipping) of blood pressure. Treatment of hypertension in type 2 diabetes provides dramatic cardiovascular benefit. Aggressive blood pressure control may be the most important factor in preventing adverse outcomes in patients with type 2 diabetes. Target diastolic blood pressures of less than 80 mm Hg and systolic targets less than 135 mm Hg appear optimal. All classes of antihypertensive agents are effective in reducing blood pressure in patients with diabetes, and all show evidence of a concomitant reduction in cardiovascular risk. Although there is evidence that agents that interrupt the renin-angiotensin system system may be superior in both the nephroprotection and cardioprotection, however the data are not totally conclusive. However, most diabetics and especially diabetic patients with nephropathy will require combination therapy ("antihypertensive cocktail") to reach goal blood pressure. Hypertensive patients have a significantly increased risk for the development of type 2 diabetes, and antihypertensive drugs can also significantly influence the risk for that. While diuretics and ss-blockers have a prodiabetic effect, angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers may prevent diabetes more effectively than the metabolically neutral calcium channel blockers.

Antihypertensive Agents↗
PubMed2006

No effect of homocysteine-lowering therapy on vascular inflammation and haemostasis in peripheral arterial occlusive disease.

BACKGROUND: Although peripheral arterial occlusive disease (PAOD) is significantly associated with elevated homocysteine levels, the clinical relevance of hyperhomocysteinaemia for the prevention and progression of PAOD is still unknown. MATERIALS AND METHODS: A total of 65 patients suffering from symptomatic PAOD with elevated homocysteine levels were randomized onto placebo or B-vitamins (50 mg thiaminhydrochlorid, 50 mg pyridoxine, and 0.05 mg cyanocobalamin), plus 5 mg folic acid daily for 6 weeks. Serum levels of folic acid, vitamin B12, creatinine, ultra-sensitive C-reactive protein (usCRP), interleukin (IL)-6, IL-8, IL-18, monocyte-chemo-attractant-protein-1 (MCP-1) and plasma levels of homocysteine, tissue factor (TF) and tissue factor pathway inhibitor (TFPI) were determined on the 1st day and 42nd day. Primary outcome was reduction of homocysteine, secondary outcomes were reduction of usCRP, IL-6, IL-8, Il-18, MCP-1, TF and TFPI. RESULTS: The mean reduction of homocysteine concentration was 33% (95%CI 33.36-55.76, or 18.9+/-5.4 micromol L-1-12.6+/-2.8 micromol L-1, P=0) in the B-vitamin group compared with 1% in the placebo group. Folic acid (P=0) and vitamin B12 (P=0) increased significantly in the verum group, but both remained unchanged in the control group. No treatment effect of lowering of homocysteine on any markers of haemostasis (TF, TFPI) or inflammation (usCRP, IL-6, IL-8, IL-18 and MCP-1) was observed. CONCLUSION: Although homocysteine is associated with vascular disease risk in the general population and in particular with PAOD, marked lowering of homocysteine concentrations by folic acid and B-vitamin supplementation does not influence inflammatory responses involving usCRP, IL-6, IL-8, IL-18 and MCP-1, nor tissue factor. These results provide evidence against a major effect of hyperhomocysteinaemia on vascular chronic inflammation or coagulation in patients with symptomatic peripheral arterial occlusive disease.

Aged↗
PubMed2006

Soluble CD40L in patients with morbid obesity: significant reduction after bariatric surgery.

BACKGROUND: Morbid obesity is associated with increased cardiovascular morbidity and mortality. Recent studies suggest that soluble CD40 Ligand (sCD40L) may play a pathogenetic role in atherothrombotic complications in cardiovascular disease as well as in inflammation and thrombosis. As morbid obesity is closely associated with chronic inflammation and insulin resistance (IR), it was of interest to study sCD40L in patients with morbid obesity before and after massive weight loss induced by bariatric surgery. PATIENTS AND METHODS: A total of 34 patients (mean age 40 +/- 12 years) with morbid obesity were studied before and 27.2 months after bariatric surgery. High sensitivity assays were used to measure concentrations of fasting sCD40L, monocyte-chemoattractant-protein-1 (MCP-1) and high-sensitive C-reactive protein (hsCRP). To investigate the associations of concentration changes of the parameters studied, differences between pre- and post-operative data were assessed and tested by univariate and multivariate linear regression analysis. RESULTS: After a mean weight loss of 33.1 +/- 18.4 kg, circulating sCD40L decreased significantly from (3.7 +/- 1.5) ng mL(-1) to (2.2 +/- 0.7) ng mL(-1), (P < 0.001). The decline in sCD40L after weight loss correlated significantly with the decrease in fasting insulin, 2-h insulin, HOMA insulin resistance (HOMA-IR), triglycerides, and the inflammatory biomarkers MCP-1 and hsCRP. CONCLUSIONS: We have shown a marked decrease in circulating sCD40L in association with an improvement of both insulin resistance and chronic inflammation in morbidly obese patients after bariatric surgery. As high sCD40L was shown to predict cardiovascular death and myocardial infarction in several prospective studies, the observed marked lowering of sCD40L might be of clinical relevance in morbidly obese patients.

Adult↗
PubMed2005

Long-term efficacy and tolerability of add-on pioglitazone therapy to failing monotherapy compared with addition of gliclazide or metformin in patients with type 2 diabetes.

AIMS/HYPOTHESIS: The aim of this analysis was to examine the long-term effects of pioglitazone or gliclazide addition to failing metformin monotherapy and pioglitazone or metformin addition to failing sulphonylurea monotherapy in patients with type 2 diabetes. METHODS: Two 2-year, randomised, multicentre trials were performed in patients with inadequately controlled type 2 diabetes (HbA1c 7.5-11% inclusive), who were receiving either metformin or a sulphonylurea at > or = 50% of the maximum recommended dose or at the maximum tolerated dose. In the first study, patients on metformin received add-on therapy with pioglitazone (15-45 mg/day, n = 317) or gliclazide (80-320 mg/day, n = 313). In the second study, patients on sulphonylurea therapy were randomised to receive add-on therapy with either pioglitazone (15-45 mg/day, n = 319) or metformin (850-2,550 mg/day, n = 320). HbA(1)c, fasting plasma glucose, insulin and lipids were investigated. RESULTS: At week 104, the mean reduction from baseline in HbA(1)c was 0.89% for pioglitazone and 0.77% for gliclazide addition to metformin (p = 0.200). There was a statistically significant between-group difference for the change in mean fasting plasma glucose at week 104 (-1.8 mmol/l for pioglitazone vs -1.1 mmol/l for gliclazide, p < 0.001). There were no significant differences in changes from baseline in glycaemic parameters for pioglitazone compared with metformin addition to sulphonylurea therapy. Whether added to metformin or sulphonylurea, pioglitazone caused significantly greater decreases in triglycerides and significantly greater increases in HDL cholesterol than the comparator regimens (p < or = 0.001). There were decreases in LDL cholesterol in the comparator groups and these were significantly different from the small changes observed with pioglitazone (p < 0.001). All treatment regimens were well tolerated. There were weight increases of 2.5 kg and 3.7 kg in the pioglitazone and 1.2 kg in the gliclazide add-on groups, and there was a mean decrease of 1.7 kg in the metformin add-on group. CONCLUSIONS/INTERPRETATION: As add-on therapy to existing sulphonylurea or metformin therapy, pioglitazone improved glycaemic control and this improvement was sustained over 2 years. Furthermore, there were potential benefits in terms of improvements in specific lipid abnormalities. This could offer an advantage over the addition of other oral agents in the long-term treatment of diabetes.

Adult↗
PubMed2005

Effects of marked weight loss on plasma levels of adiponectin, markers of chronic subclinical inflammation and insulin resistance in morbidly obese women.

OBJECTIVE: Obesity is linked to the insulin resistance syndrome (IRS), type 2 diabetes (T2D) and cardiovascular disease. Markers of chronic subclinical inflammation such as high-sensitive C-reactive protein (hs-CRP) and interleukin 6 (IL-6) are closely related to insulin resistance and obesity. Recent evidence suggests that adiponectin, a protein whose circulating levels are decreased in obesity, has anti-inflammatory properties, and also appears to enhance potently insulin action and therefore appears to function as a signal produced by adipose tissue that influences whole-body glucose metabolism. SUBJECTS AND METHODS: We investigated the cross-sectional and longitudinal association of adiponectin with CRP and IL-6 in 41 morbidly obese women with different stages of glucose tolerance before and 17 months after significant weight loss induced by gastric surgery. Adiponectin was measured by RIA. CRP and IL-6 were determined by commercially available ELISA systems. RESULTS: Weight loss induced a significant shift from T2D (preoperatively 34% vs postoperatively 2%) to impaired glucose tolerance (IGT) (37% preoperatively vs 30% postoperatively) and normal glucose tolerance (NGT) (29% preoperatively vs 68% postoperatively). Preoperatively adiponectin levels were negatively correlated with CRP (r=-0.59, P<0.0006), IL-6 (r=-0.42, P<0.02) and leukocytes (r=-0.41, P<0.007). After gastroplasty, adiponectin concentrations increased significantly (15.4+/-8.2 vs 19.8+/-6.2 microg/ml, P<0.005) associated with changes of weight and body mass index (r=-0.45, P<0.007; r=-0.35, P<0.04). Furthermore, preoperative CRP was significantly associated with changes in adiponectin even after adjustment for sex, age, preoperative body mass index (BMI) impaired glucose metabolism and changes in BMI and changes in BMI (standardized beta 0.61, P=0.005). CONCLUSION: Levels of adiponectin, which are associated with markers of chronic subclinical inflammation, could be significantly increased after weight loss in morbidly obese patients. This increase was more pronounced in patients with NGT compared to those with T2D and IGT. Preoperative levels of CRP are predictive for changes of adiponectin after weight loss.

Adiponectin↗
PubMed2005

High prevalence of abnormal circadian blood pressure regulation and impaired glucose tolerance in adults with hypopituitarism.

Patients with hypopituitarism have an increased mortality from cardiovascular events. Reduced nocturnal blood pressure decline (non-dipping) and impaired glucose tolerance are considered as cardiovascular risk factors. To evaluate the role of these risk factors in patients with hypopituitarism we determined the 24-hour blood pressure regulation and glucose tolerance status in hypopituitary patients with and without growth hormone (GH) deficiency. Sixty-one hypopituitary subjects 5 +/- 3 years after brain surgery because of macroadenoma, 61 patients with type 2 diabetes mellitus (T2DM), and 20 healthy controls were included. Forty-four hypopituitary patients were GH deficient and 28 of these on GH treatment. Non-dipping was observed in 41 % (n = 7) of hypopituitary subjects with normal GH release, in 46 % (n = 13) of patients on GH therapy, and in 69 % (n = 11) of untreated GH deficient patients. Untreated GH deficient patients had a higher systolic night/day ratio (1.00 +/- 0.03) compared to non GH deficient (0.92 +/- 0.02; p < 0.02) and GH treated hypopituitary patients (0.93 +/- 0.01; p < 0.02). The rate of non-dipping in hypopituitarism was comparable to that in T2DM. Pathologic glucose tolerance was diagnosed in 30 % of the hypopituitary patients. The prevalence of non-dipping was independent of glucose metabolism in hypopituitary patients. All controls had normal night time blood pressure fall and glucose metabolism. The high prevalence of nocturnal non-dipping and glucose intolerance detected in this cohort might contribute to the increased cardiovascular risk of hypopituitary patients.

Adenoma↗
PubMed2005

Improvement of glucose tolerance in type 2 diabetic patients: traditional vs. modern insulin regimens (results from the Austrian Biaspart Study).

OBJECTIVE: Major advantages of modern insulin regimens containing premixed insulin analogues in comparison to traditional insulin regimens have not been evaluated yet. The aim of the present study was to investigate whether meal-related (breakfast, lunch, dinner) application of biphasic insulin aspart 30 (BIAsp 30) provides better glycaemic control than administration of biphasic human insulin 30 (BHI 30) twice per day. RESEARCH DESIGN AND METHODS: In a multi-centre, randomized, open-label parallel trial, a total of 177 patients with type 2 diabetes mellitus were exposed to the two different insulin regimens described above over a study period of 24 weeks. HbA1c and glycemic exposure parameters were measured at predefined intervals. RESULTS: The mean difference between treatment groups in HbA1c after 24 weeks of treatment was 0.08% (p = 0.6419). Analysing the 7-point blood-glucose (BG) profiles, significant differences in BG levels were observed after lunch (156 vs. 176 mg/dl, p = 0.0289), before dinner (142 vs. 166 mg/dl p = 0.006) and after dinner (154 vs. 182 mg/dl p = 0.002) in favour of BIAsp 30 insulin. Prandial BG increment was lower in the BIAsp 30 group at breakfast (p = 0.057) and lunch (p < 0.0005). No difference was found regarding safety parameters in the two treatment groups. CONCLUSIONS: This study demonstrates that meal-related BIAsp 30-insulin maintains postprandial BG control more effectively than traditional BHI 30 insulin twice per day in type 2 diabetic patients.

Adult↗
PubMed2005

Circulating ADMA concentrations are elevated in hypopituitary adults with and without growth hormone deficiency.

BACKGROUND: Cardiovascular mortality is increased in patients with hypopituitarism. Elevated concentrations of the endogenous NO synthase antagonist asymmetrical dimethylarginine (ADMA) may be related to the development of atherosclerosis and are associated with cardiovascular risk. We studied the concentrations of ADMA in hypopituitary patients with and without growth hormone deficiency (GHD) and in healthy subjects. MATERIALS AND METHODS: Plasma from 44 patients with hypopituitarism with (n = 30) and without GHD (n = 14) and from 25 age- and sex-matched healthy controls was taken for analysis of L-arginine, ADMA, symmetrical dimethylarginine (SDMA) and clinical parameters. Further plasma from 10 hypopituitary patients was examined before and after treatment with 9 g of oral L-arginine for 14 days. RESULTS: Asymmetrical dimethylarginine was significantly higher in the hypopituitary patients than in the controls (0.63 +/- 0.12 vs. 0.51 +/- 0.15 micromol L(-1); P < 0.005). L-arginine and the L-arginine/ADMA ratios were lower in the subjects with hypopituitarism (53 +/- 18 vs. 90 +/- 29 micromol L(-1) and 87 +/- 31 vs. 185 +/- 59; both P < 0.0001). Symmetrical dimethylarginine was comparable between the patients and the controls. L-arginine and dimethylarginines were associated with 2-h stimulated glucose levels in a glucose tolerance test (r = 0.33; P < 0.05), but not other cardiovascular risk factors. Oral L-arginine supplementation normalized the reduced L-arginine/ADMA ratio in the hypopituitary patients. CONCLUSION: Asymmetrical dimethylarginine is elevated in patients with hypopituitarism independent of GHD and traditional risk factors. This might contribute to the increased cardiovascular morbidity in hypopituitary patients.

Arginine↗
PubMed2005

A long-term comparison of pioglitazone and gliclazide in patients with Type 2 diabetes mellitus: a randomized, double-blind, parallel-group comparison trial.

AIMS: This study compared the effects of pioglitazone and gliclazide on metabolic control in drug-naive patients with Type 2 diabetes mellitus. METHODS: A total of 1270 patients with Type 2 diabetes were randomized in a parallel-group, double-dummy, double-blind study. Patients with poorly controlled Type 2 diabetes (HbA1c 7.5-11%), despite dietary advice, received either pioglitazone up to 45 mg once daily or gliclazide up to 160 mg two times daily. Primary efficacy endpoint was change in HbA1c from baseline to the end of the study. Secondary efficacy endpoints included change in fasting plasma glucose, fasting plasma insulin and plasma lipids. At selected centres, oral glucose tolerance tests were performed and C-peptide and pro-insulin levels were measured. RESULTS: Mean HbA1c values decreased by the same amount in the two treatment groups from baseline to week 52 [pioglitazone: -1.4%; gliclazide: -1.4%; (90% CI: -0.18 to 0.02)]. A significantly greater mean reduction in fasting plasma glucose was observed in the pioglitazone group (2.4 mmol/l) than in the gliclazide group [2.0 mmol/l; treatment difference -0.4 mmol/l in favour of pioglitazone; P = 0.002; (95% CI: -0.7 to -0.1)]. Improvements in high-density lipoprotein cholesterol (HDL-C) and total cholesterol/HDL-C were greater with pioglitazone than with gliclazide (P < 0.001). The frequencies of adverse events were comparable between the two treatment groups, but more hypoglycaemic events were reported for gliclazide, whereas twice as many patients reported oedema with pioglitazone than with gliclazide. CONCLUSIONS: Pioglitazone monotherapy was equivalent to gliclazide in reducing HbA1c, with specific differences between treatments in terms of mechanism of action, plasma lipids and adverse events.

Adult↗
PubMed2005

Changes in liver tests during 1-year treatment of patients with Type 2 diabetes with pioglitazone, metformin or gliclazide.

AIMS: Patients with Type 2 diabetes are at increased risk of liver damage. Therefore, it is of particular importance to investigate the hepatic effects of drugs used to treat such patients. METHODS: Liver testing results performed in four 1-year, randomized, double-blind studies comparing effects of pioglitazone, metformin or a sulphonylurea, gliclazide, in the treatment of over 3700 patients with Type 2 diabetes have been analysed. RESULTS: Pioglitazone caused reductions in mean levels of hepatic enzymes of between 3 and 18%, whilst gliclazide caused small increases of between 3 and 13%. Metformin treatment showed either small mean increases or decreases. More patients receiving pioglitazone had liver tests within the normal range at the end of treatment (> or = 87%) compared with patients receiving metformin (> or= 80%) or gliclazide (> or = 75%). Slightly fewer patients with pioglitazone than with comparators showed a large increase (> 3 upper limit of normal) in alanine aminotransferase levels at any time during treatment (pioglitazone 0.9%, metformin 1.9%, gliclazide 1.9%). CONCLUSIONS: During pioglitazone treatment there is a reduction in liver enzyme levels. Although the mechanism of this effect is not clear, the results demonstrate potential beneficial effects on the liver during treatment of patients with Type 2 diabetes with pioglitazone.

Aged↗
PubMed2004

Individualized risk management in diabetics: how to implement best practice guidelines--design and concept of the IRIDIEM studies.

The prevalence of type 2 diabetes mellitus is rising rapidly in all developed countries, particularly in the growing population of persons >50 years of age. As a dangerous consequence, this is accompanied by a proportionate increase in the incidence of chronic renal disease. Evidence-based medicine has shown that tight blood glucose control can delay the onset and retard the progression of diabetic complications, and while it is a challenge to closely manage the complexity of diabetes, it is more difficult to effectively treat the multiple associated comorbidities that develop. Best practice guidelines support early intervention and aggressive treatment of hypertension, hyperglycaemia, proteinuria, hypercholesterolemia, and anaemia. To date, guideline-based management has been proven to be difficult. This article describes the concept of the IRIDIEM studies. The objective of these studies is to endorse and facilitate the use of current best practice guidelines for the management of frequent comorbid diseases and established risk factors in the treatment of type 2 diabetes associated with chronic kidney disease. Additionally, IRIDIEM will assess the impact of this improved disease management model on the progression of chronic kidney disease that can result from electronically prompting clinicians with evidence-based treatment advice.

Diabetic Nephropathies↗
PubMed2004

Metabolic control in patients with type 2 diabetes using Humalog Mix50 injected three times daily: crossover comparison with human insulin 30/70.

OBJECTIVE: Patients with type 2 diabetes most frequently use injections of premixed insulin formulations twice daily, but intensified insulin therapy may provide better control. This study was designed to compare metabolic control with three daily injections of Humalog Mix50 or premixed human insulin 30/70 (30 % regular/70 % NPH) twice daily in accordance with normal prescription practice. RESEARCH DESIGN AND METHODS: The study cohort of 40 patients with type 2 diabetes used a two-way, crossover design. Patients were randomized to either Mix50 at each main meal or human insulin 30/70 at breakfast and dinner for 3 months, followed by the alternate treatment for 3 months. Blood glucose was measured by the patients at baseline and at the end of each treatment sequence. No significant carryover effects were observed, so treatment sequences were combined and data analyzed by unpaired t-tests. RESULTS: Mean blood glucose level was significantly (p = 0.010) decreased with Mix50 but not with 30/70 (p = 0.237), and there was a significant difference between treatments at the endpoint (p = 0.035). Fasting blood glucose was increased pre-breakfast and decreased at bedtime with Mix50 but was not significantly changed pre-lunch or dinner or at any time with 30/70 insulin. Blood glucose excursions were significantly decreased with Mix50 after breakfast (p = 0.002), lunch (p < 0.001) and dinner (p = 0.037) but not significantly changed from baseline with 30/70 insulin. The decrease from baseline in HbA (1c) was significantly (p = 0.021) greater with Mix50 than with 30/70 insulin. There were no significant differences between treatments regarding incidence of hypoglycemia or adverse events. CONCLUSIONS: In patients with type 2 diabetes, a regimen of Humalog Mix50 administered three times daily before meals maintains glucose control more effectively than premixed human insulin 30/70 administered before breakfast and dinner.

Aged↗
PubMed2004

Improved metabolic control decreases platelet activation markers in patients with type-2 diabetes.

BACKGROUND: Cardiovascular disease is associated with platelet dysfunction in patients with diabetes. Hyperglycaemia is known as an independent risk factor for micro- and macrovascular complications, and improvement of metabolic control has shown beneficial effects on diabetic late complications. Our study attempts to clarify the effect of improved metabolic control on platelet activation markers in patients with type-2 diabetes. MATERIALS AND METHODS: Thirty patients were studied at baseline and 3 months after improvement of metabolic control and compared with an age-matched nondiabetic control group. Platelet activation markers (CD31, CD36, CD49b, CD62P and CD63) were assessed by flow cytometry analysis. RESULTS: Significantly more activated platelets were detected in patients with diabetes compared with controls. After 3 months' improvement of metabolic control, a significant decline of all platelet activation markers except CD36 was noted. Furthermore a significant correlation between CD62P, CD63 and HbA(1c) levels was observed. CONCLUSIONS: We conclude therefore that improvement of metabolic control has a beneficial effect on platelet activation. This may have an implication in the pathogenesis of vascular disease in patients with type-2 diabetes.

Adult↗
PubMed2004

GUIDE study: double-blind comparison of once-daily gliclazide MR and glimepiride in type 2 diabetic patients.

BACKGROUND: Progressive beta-cell failure is a characteristic feature of type 2 diabetes; consequently, beta-cell secretagogues are useful for achieving sufficient glycaemic control. The European GUIDE study is the first large-scale head-to-head comparison of two sulphonylureas designed for once-daily administration used under conditions of everyday clinical practice. DESIGN: Eight hundred and forty-five type 2 diabetic patients were randomized to either gliclazide modified release (MR) 30-120 mg daily or glimepiride 1-6 mg daily as monotherapy or in combination with their current treatment (metformin or an alpha-glucosidase inhibitor) according to a double-blind, 27-week, parallel-group design. Efficacy was evaluated by HbA1c and safety by hypoglycaemic episodes using the European Agency definition. RESULTS: HbA1c decreased similarly in both groups from 8.4% to 7.2% on gliclazide MR and from 8.2% to 7.2% on glimepiride. Approximately 50% of the patients achieved HbA1c levels less than 7%, and 25% less than 6.5%. The mean difference between groups of the final HbA1c was -0.06% (noninferiority test P < 0.0001). No hypoglycaemia requiring external assistance occurred. Hypoglycaemia with blood glucose level < 3 mmol L(-1) occurred significantly less frequently (P = 0.003) with gliclazide MR (3.7% of patients) compared with glimepiride (8.9% of patients). The distribution of the sulphonylurea doses was similar in both groups. CONCLUSIONS: This study provides new insights into therapeutic strategies using sulphonylureas. It shows that gliclazide MR is at least as effective as glimepiride, either as monotherapy or in combination. The safety of gliclazide MR was significantly better, demonstrating approximately 50% fewer confirmed hypoglycaemic episodes in comparison with glimepiride.

Diabetes Mellitus, Type 2↗
PubMed2004

Preprandial vs. postprandial insulin lispro-a comparative crossover trial in patients with Type 1 diabetes.

AIMS: Administration of bolus insulin after eating may be a useful therapeutic option for some patients. This 6-month, crossover study compared metabolic effects of routine use of preprandial vs. postprandial injection of bolus insulin lispro. METHODS: Thirty-one patients with Type 1 diabetes injected insulin lispro either preprandially or postprandially for a 3-month period followed by the alternate regimen for a further 3 months. HbA1c, fructosamine and eight-point self-determined blood glucose profiles were measured and analysed using an anova model appropriate for a crossover design. RESULTS: Mean HbA1c decreased slightly from baseline with preprandial (-0.15 +/- 0.41%) and increased slightly with postprandial (0.11 +/- 0.48%) insulin lispro so that there was a significant (P = 0.008) difference between treatments in final HbA1c level. Mean fructosamine also decreased slightly with preprandial (-15 +/- 31 micro mol/l) but was almost unchanged (1 +/- 39 micro mol/l) with postprandial insulin lispro. Overall daily blood glucose was not different (P = 0.312) for preprandial compared with postprandial administration. However, mean preprandial glucose was lower (7.5 +/- 2.01 vs. 6.6 +/- 1.22 mmol/l; P = 0.026), whereas mean postprandial glucose was higher (7.7 +/- 1.8 vs. 8.7 +/- 2.1 mmol/l; P = 0.031) with postprandial insulin lispro administration. Mean blood glucose excursions were higher with postprandial compared with preprandial insulin lispro, indicating greater daily fluctuations. No difference in incidence of hypoglycaemia was observed with the two treatment regimens. CONCLUSIONS: Postprandial insulin lispro administration appeared to be an acceptable treatment regimen and may be of benefit in certain situations. However, the benefits of postprandial administration may have to be balanced against poorer glycaemic control with continuous long-term use.

Adult↗
PubMed2004

Efficacy and safety of pioglitazone versus metformin in patients with type 2 diabetes mellitus: a double-blind, randomized trial.

Pioglitazone increases the insulin sensitivity of peripheral tissues and may provide an alternative first-line treatment for type 2 diabetes. This study compared metabolic control in drug-naive type 2 diabetes patients given either pioglitazone or metformin. Eleven hundred and ninety-nine patients with poorly controlled type 2 diabetes mellitus [glycosylated hemoglobin (HbA1c), 7.5-11%; normal, 4.3-6.1%] were randomized to receive either pioglitazone (< or =45 mg/d) or metformin (< or =850 mg, three times daily). HbA1c, fasting plasma glucose (FPG), insulin levels, total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol, triglycerides, free fatty acids, and urinary albumin/creatinine ratio were measured. Mean HbA1c decreased in both treatment groups from baseline to wk 52 (-1.4% and -1.5%). Significantly greater mean reductions in FPG were observed in the pioglitazone group (-45.0 mg/dl; -2.5 mmol/liter) than in the metformin (-39.6 mg/dl; -2.2 mmol/liter) group (P = 0.016). Favorable changes in triglycerides and HDL-C were more pronounced with pioglitazone. Although low density lipoprotein cholesterol and TC levels increased with pioglitazone, TC/HDL-C ratios decreased similarly with both treatments. The urinary albumin/creatinine ratio was reduced by 19% with pioglitazone treatment, but remained unchanged with metformin therapy (-1%; P = 0.002). There was an increase in body weight of 1.9 kg in the pioglitazone group and a decrease of 2.5 kg in the metformin group. The overall frequency of adverse events was similar between treatment groups, but adverse event profiles were different between treatment groups. HbA1c reduction is similar after pioglitazone and metformin monotherapies, but differences in FPG, plasma lipids, and adverse effects between the two compounds may influence decision-making in individual prescribers.

Adult↗
PubMed2003

Impact of weight loss on inflammatory proteins and their association with the insulin resistance syndrome in morbidly obese patients.

OBJECTIVE: Obesity is closely linked to the insulin resistance syndrome (IRS), type 2 diabetes, and cardiovascular disease, the primary cause of morbidity and mortality in these patients. Elevated levels of C-reactive protein (CRP) and interleukin-6 (IL-6), indicating chronic subclinical inflammation, have been associated with features of the IRS and incident cardiovascular disease. METHODS AND RESULTS: We studied the cross-sectional and longitudinal relation of CRP, IL-6, and tumor necrosis factor-alpha (TNF-alpha) with features of the IRS in 37 morbidly obese patients with different stages of glucose tolerance before and 14 months after gastric surgery. Weight loss after gastric surgery induced a significant shift from diabetes (37% vs 3%) to impaired glucose tolerance (40% vs 33%) and normal glucose tolerance (23% vs 64%). The baseline concentration of IL-6 was correlated with TNF-alpha (r=0.59, P<0.01) and CRP (r=0.44, P<0.05) levels. TNF-alpha, IL-6, and CRP were significantly correlated with insulin resistance estimated by the homeostatic model assessment (r=0.48, P<0.05; r=0.56, P<0.01; and r=0.35, P<0.05, respectively). Concentrations of CRP and IL-6 decreased after weight loss (median, 8.6 and interquartile range, 2.7/14.5 vs 2.5 and 1.2/4.1 mg/L; P<0.006, and 5.13 and 2.72/12.15 vs 3.95 and 1.97/5.64 pg/mL, P<0.02, respectively), whereas serum levels of TNF-alpha remained unchanged (8.6 and 6.3/18.8 vs 11.7 and 5.8/17.2 pg/mL; NS.). Multiple regression analysis revealed that the decrease in insulin resistance remained independently and significantly correlated with the decrease in IL-6 concentrations (P<0.01) and the decrease in body mass index with the decrease in CRP (P<0.05), respectively. CONCLUSIONS: Weight loss in morbidly obese patients induces a significant decrease of CRP and IL-6 concentrations in association with an improvement of the IRS.

Adult↗