Carsta Koehler

Acarbose Slows Progression of Intima-Media Thickness of the Carotid Arteries in Subjects With Impaired Glucose Tolerance

Background and Purpose— Impaired glucose tolerance (IGT)–a prediabetic state–is an important risk factor for atherosclerosis. Acarbose, an &agr;-glucosidase inhibitor, was shown in the placebo-controlled prospective study to prevent noninsulin-dependent diabetes mellitus (STOP-NIDDM) trial to reduce the risk of diabetes by 36% in IGT subjects. This article reports on a placebo-controlled subgroup analysis of the STOP-NIDDM study to examine the efficacy of acarbose to slow progression of intima-media thickness (IMT) in subjects with IGT. Methods— One hundred thirty-two IGT subjects were randomized to placebo (n=66) or acarbose (n=66) 100 mg 3 times daily; the study duration was at least 3 years, mean follow-up time 3.9 (SD 0.6) years. Carotid IMT was determined at study entry and the end of the trial. The intent-to-treat analysis included 56 subjects in the acarbose and 59 in the control group who had a baseline and endpoint measurement. Results— A significant reduction of the progression of IMTmean was observed in the acarbose group versus placebo. After an average time of 3.9 years, IMTmean increased by 0.02 (0.07) mm in the acarbose group versus 0.05 (0.06) mm in the placebo group (P =0.027). The annual increase of IMTmean was reduced by ≈50% in the acarbose group versus placebo. Multiple linear regression revealed IMT progression as significantly related to acarbose intake. Conclusions— Acarbose slows progression of IMT in IGT subjects, a high-risk population for diabetes and atherosclerosis. This is the first placebo-controlled prospective subgroup analysis, demonstrating that counterbalancing of postprandial hyperglycemia may be vasoprotective.

Postprandial plasma glucose is an independent risk factor for increased carotid intima-media thickness in non-diabetic individuals

Postprandial (pp) hyperglycemia--frequently associated with an increase in cardiovascular risk factors--may be damaging for the endothelium. So far, little information exists how glucose, insulin and lipids may affect atherosclerosis in the pp state. Therefore, we evaluated the relationship of pp hyperglycemia, insulin secretion and coronary risk factors to intima-media thickness (IMT) in a non-diabetic risk population. In 403 subjects (147 males, 256 females), aged 40-70 years, in the majority relatives of index cases with type 2 diabetes--a 75 g oral glucose tolerance test was performed together with measurement of insulin fractions, various risk factors and IMT of the common carotid artery. We found a continuous rise of 2h pp insulin fractions along the quintiles of 2h pp plasma glucose. A significant increase of body mass index, waist to hip ratio, triglycerides and decrease of HDL-cholesterol was observed in the top quintile of 2h pp plasma glucose (8.24 > or = pp plasma glucose < 11.1 mmol/l). Albuminuria was significantly enhanced in the 5th quintile. In parallel, IMT was significantly increased in the 5th quintile versus the bottom quintile of 2 h and maximal glucose (range 11.7-15.3 mmol/l) postprandially. After age and sex adjustment pp glucose and C-peptide, total cholesterol, triglycerides and HDL-cholesterol but not fasting plasma glucose were significantly correlated to IMT. In multivariate analysis age, male sex, pp plasma glucose, total and HDL-cholesterol were found to be independent risk factors for increased IMT. In conclusion, our data in a non-diabetic European risk population show that the two top quintiles of pp plasma glucose are associated with a clustering of standard risk factors. Corresponding to this clustering of risk factors IMT was significantly increased in the top quintile of 2 h and maximal pp plasma glucose. These data show that pp hyperglycemia may exert a noxious impact on the arterial wall together with a cluster of anomalies typical for the metabolic syndrome.

Post‐challenge hyperglycaemia relates more strongly than fasting hyperglycaemia with carotid intima‐media thickness: the RIAD Study

SUMMARY

Extended abdominoperineal excision vs. standard abdominoperineal excision in rectal cancer—a systematic overview

BackgroundAfter introduction of total mesorectal excision (TME) as the gold standard for rectal cancer surgery, oncologic results appeared to be inferior for abdominoperineal excision (APE) as compared to anterior resection. This has been attributed to the technique of standard APE creating a waist at the level of the tumor-bearing segment. This systematic review investigates outcome of both standard and extended techniques of APE regarding inadvertent bowel perforation, circumferential margin (CRM) involvement, and local recurrence.MethodsA literature search was performed to identify all articles reporting on APE after the introduction of TME using Medline, Ovid, and Embase. Extended APE was defined as operations that resected the levator ani muscle close to its origin. All other techniques were taken to be standard. Studies so identified were evaluated using a validated instrument for assessing nonrandomized studies. Rates for perforation, CRM involvement, and local recurrence were compared using chi-square statistics.ResultsIn the extended group, 1,097 patients, and in the standard group, 4,147 patients could be pooled for statistical analysis. The rate of inadvertent bowel perforation and the rate of CRM involvement for extended vs. standard APE was 4.1% vs. 10.4% (relative risk reduction 60.6%, p = 0.004) and 9.6% vs. 15.4% (relative risk reduction 37.7%, p = 0.022), respectively. The local recurrence rate was 6.6% vs. 11.9% (relative risk reduction 44.5%, p < 0.001) for the two groups.ConclusionThis systematic review suggests that extended techniques of APE result in superior oncologic outcome as compared to standard techniques.

Relationship Between Hypoglycemic Episodes and Ventricular Arrhythmias in Patients With Type 2 Diabetes and Cardiovascular Diseases: Silent Hypoglycemias and Silent Arrhythmias

OBJECTIVE In patients with type 2 diabetes and cardiovascular diseases (CVDs), intensive treatment with insulin and/or sulfonylurea (SU) may be associated with excessive increased risk of hypoglycemic episodes. To evaluate the risk of critical arrhythmias related to glycemic variability, we carried out an observational study in type 2 diabetes patients with CVD. RESEARCH DESIGN AND METHODS Thirty patients with type 2 diabetes and documented CVD who had been treated with insulin and/or SU underwent 5 days of monitoring with a continuous glucose measurement system along with parallel electrocardiogram recording for monitoring of ventricular arrhythmias. Twelve age-matched patients with documented CVD who received treatment with metformin and/or dipeptidyl peptidase-4 inhibitor served as the control group. Patients were receiving stable treatment, and were instructed to notice symptoms of arrhythmias and hypoglycemia, respectively. RESULTS We observed a high incidence of asymptomatic severe episodes of hypoglycemia (<3.1 mmol/L) in patients receiving treatment with insulin and/or SU, whereas severe hypoglycemia did not develop in any of the control subjects. Patients with severe hypoglycemia (n = 12) had a higher number of severe ventricular arrhythmias (patients with versus without severe hypoglycemia, respectively: ventricular couplets 41.7 ± 81.8 vs. 5.5 ± 16.7; ventricular tachycardia 1.0 ± 1.9 vs. 0.1 ± 0.3). No direct correlation could be found among different variables of glucose profile, corrected QT interval, and ventricular arrhythmias. CONCLUSIONS Our results suggest that severe episodes of hypoglycemia are associated with an increased risk of severe ventricular arrhythmias.

Impaired fasting glucose is not a risk factor for atherosclerosis

Aim To determine a new category of dysfunctional glucose homeostasis – impaired fasting glucose (IFG) – introduced by the American Diabetes Association (ADA) and the World Health Organization (WHO) defining those with abnormal but nondiabetic fasting glucose values and with a possible risk for developing diabetes. It is not known whether IFG is a risk factor for atherosclerosis, as is impaired glucose tolerance (IGT).

Impact of the individual components of the metabolic syndrome and their different combinations on the prevalence of atherosclerotic vascular disease in type 2 diabetes: the Diabetes in Germany (DIG) study.

BackgroundOne of the major controversies surrounding the metabolic syndrome (MetS) in type 2 diabetes is whether its single components act synergistically as risk factors for atherosclerotic vascular disease (AVD). We aimed to answer this by evaluating the relationship, and its various combinations to AVD in comparison to single traits in a population-based study with type 2 diabetes in Germany.Methods and results4020 unselected patients with type 2 diabetes aged 35 – 80 years. MetS was: diabetes plus ≥ 2 traits of the MetS by AHA/NHBLI definition.AVD was: history of myocardial infarction and/or coronary revascularization and/or stroke. The occurrence of AVD in relation to overall MetS/single traits/combinations was presented as OR (95% CI). Multiple logistic regression, including established cardiovascular risk factors, modeled their associations.The prevalence of overall MetS was 74.4% and the OR for AVD was 1.41 (1.12–1.78), which however was higher for hypertension as single trait (OR 4.76). Different combinations of MetS presented a wide range of ORs (0.47 to 10.90) and strong sex differences. Some clusters of MetS including hypertension and low HDL-cholesterol presented a higher risk factor than single traits or their sum, whereas the others out of 11 possible carried no increased AVD risk. Multiple logistic regression showed independent association between AVD and overall MetS.ConclusionThe overall MetS in type 2 diabetes comprises 11 heterogenous clusters of traits. Overall MetS increases the risk of AVD in type 2 diabetes and individual traits in some clusters with hypertension and low HDL-cholesterol may act synergistically as risk factors particularly in women.

Leukocyte count and fibrinogen are associated with carotid and femoral intima-media thickness in a risk population for diabetes

OBJECTIVE To investigate the relationship of the inflammatory parameters--leukocyte count and fibrinogen level--to the intima-media thickness (IMT) of the common carotid artery and the common femoral artery, as well as to a variety of risk factors within the metabolic syndrome in a risk population for diabetes. METHODS A total of 597 subjects were analyzed from the Risk factors in Impaired glucose tolerance for Atherosclerosis and Diabetes (RIAD) study, who were at risk for the development of type 2 diabetes. IMT of the common carotid and common femoral artery was determined by B-mode ultrasound. Leukocyte count and fibrinogen level, as well as various risk factors for atherosclerosis, were measured by established methods. RESULTS In univariate analysis, leukocyte count and fibrinogen level correlated significantly to carotid and femoral IMT. Leukocyte count was significantly correlated to body mass index, waist to hip ratio, blood pressure, plasma triglycerides, high-density lipoprotein cholesterol (inversely), fasting and postprandial plasma glucose, insulin and proinsulin, PAI(active), tPA and microalbuminuria, as well as to smoking and physical activity (inversely). Fibrinogen level was significantly correlated with body mass index, systolic blood pressure, plasma triglycerides, fasting plasma glucose, HbA1c, PAI(active), tPA and von Willebrandt factor, as well as with smoking and low physical activity. In multivariate analysis, leukocyte count was an independent determinant of the maximal carotid IMT and fibrinogen level of femoral IMT. CONCLUSIONS Our study indicates that low-grade inflammation is correlated to IMT, as an indicator of early atherosclerosis, and is strongly associated to a variety of risk factors within the metabolic syndrome in a population at risk for type 2 diabetes.

Structured health care for subjects with diabetic foot ulcers results in a reduction of major amputation rates.

ObjectiveWe tested the effects of structured health care for the diabetic foot in one region in Germany aiming to reduce the number of major amputations.Research design and methodsIn a prospective study we investigated patients with diabetic foot in a structured system of outpatient, in-patient and rehabilitative treatment. Subjects were recruited between January 1st, 2000 and December 31, 2007. All participants underwent a two-year follow-up. The modified University of Texas Wound Classification System (UT) was the basis for documentation and data analysis. We evaluated numbers of major amputations, rates of ulcer healing and mortality. In order to compare the effect of the structured health care program with usual care in patients with diabetic foot we evaluated the same parameters at another regional hospital without interdisciplinary care of diabetic foot (controls).Results684 patients with diabetic foot and 508 controls were investigated. At discharge from hospital 28.3% (structured health care program, SHC) vs. 23.0% (controls) of all ulcers had healed completely. 51.5% (SHC) vs. 49.8% (controls) were in UT grade 1.Major amputations were performed in 32 subjects of the structured health care program group (4.7%) vs. 110 (21.7%) in controls (p<0.0001). Mortality during hospitalization was 2.5% (SHC) vs. 9.4% in controls (p<0.001).ConclusionsWith the structured health care program we achieved a significant reduction of major amputation rates by more than 75% as compared to standard care.

Effect of Acarbose on Vascular Disease in Patients with Abnormal Glucose Tolerance

IntroductionExcessive postprandial (pp) glucose excursion in people with IGT and type 2 diabetes is associated with a cascade of proatherogenic events. Acarbose, a potent competitive inhibitor of α-glucosidases of the small intestine specifically reduces pp hyperglycemia with an average reduction of HbA1c by 0.8% in Cochrane metaanalysis. This is associated with pleiotropic effects on a broad spectrum of cardiovascular (CV) risk factors: reduction of overweight, lowering of blood pressure, triglycerides, hsCRP, fibrinogen and other biomarkers of low grade inflammation.Results and discussionFlow mediated vasodilation was improved and progression of intima media thickness was reduced by acarbose. In the STOP-NIDDM trial in people with IGT acarbose decreased the incidence of diabetes by 36%. The STOP-NIDDM trial with CV events as secondary objective is the only intervention trial in people with IGT so far with a significant benefit for CV disease inclusive hypertension. In a metaanalysis of controlled studies (MeRIA) in patients with type 2 diabetes, treatment with acarbose was associated with a 64% lower rate of myocardial infarction and 35% less CV events.ConclusionThus results so far available prove that acarbose is an effective and safe drug to treat abnormal glucose tolerance. They suggest that acarbose can help to control a broad spectrum of CV risk factors and may prevent CV disease.