Kerstin Kempf

Effects of coffee consumption on subclinical inflammation and other risk factors for type 2 diabetes: a clinical trial

BACKGROUND Coffee consumption is associated with a decreased risk of type 2 diabetes. Suggested mechanisms underlying the association have included attenuation of subclinical inflammation and a reduction in oxidative stress. OBJECTIVE The aim was to investigate the effects of daily coffee consumption on biomarkers of coffee intake, subclinical inflammation, oxidative stress, glucose, and lipid metabolism. DESIGN Habitual coffee drinkers (n = 47) refrained for 1 mo from coffee drinking; in the second month they consumed 4 cups of filtered coffee/d and in the third month 8 cups of filtered coffee/d (150 mL/cup). Blood samples were analyzed by gas chromatography-mass spectrometry, bead-based multiplex technology, enzyme-linked immunosorbent assay, or immunonephelometry. RESULTS Coffee consumption led to an increase in coffee-derived compounds, mainly serum caffeine, chlorogenic acid, and caffeic acid metabolites. Significant changes were also observed for serum concentrations of interleukin-18, 8-isoprostane, and adiponectin (medians: -8%, -16%, and 6%, respectively; consumption of 8 compared with 0 cups coffee/d). Serum concentrations of total cholesterol, HDL cholesterol, and apolipoprotein A-I increased significantly by 12%, 7%, and 4%, respectively, whereas the ratios of LDL to HDL cholesterol and of apolipoprotein B to apolipoprotein A-I decreased significantly by 8% and 9%, respectively (8 compared with 0 cups coffee/d). No changes were seen for markers of glucose metabolism in an oral-glucose-tolerance test. CONCLUSIONS Coffee consumption appears to have beneficial effects on subclinical inflammation and HDL cholesterol, whereas no changes in glucose metabolism were found in our study. Furthermore, many coffee-derived methylxanthines and caffeic acid metabolites appear to be useful as biomarkers of coffee intake.

ROSSO-in-praxi: A Self-Monitoring of Blood Glucose-Structured 12-Week Lifestyle Intervention Significantly Improves Glucometabolic Control of Patients with Type 2 Diabetes Mellitus

BACKGROUND As healthy diet and physical activity can improve glucometabolic control in patients with type 2 diabetes, lifestyle changes should be the basis for each therapy. The only tool to visualize immediate effects of food pattern and exercise on blood glucose levels is self-monitoring of blood glucose (SMBG). Therefore, the aim of the 12-week lifestyle intervention ROSSO-in-praxi was to evaluate the impact of an SMBG-structured motivation and education program on glucometabolic and health parameters in diabetes patients not treated with insulin. METHODS Participants (n = 405) generated a seven-point blood glucose diurnal profile every 4 weeks, including actual weight, waist circumference, and steps/day. At baseline and the end of the study, glycated hemoglobin A1c (HbA1c), blood pressure, and cholesterol levels, lifestyle changes, and well-being (SF36 and Center for Epidemiologic Studies Depression Scale questionnaires) were assessed. RESULTS Three hundred twenty-seven participants (81%) completed the program and significantly improved quality of diet and physical activity, accompanied by an increase of >2,300 steps/day. Participants significantly reduced weight, body mass index, waist circumference, blood glucose, blood pressure, low-density lipoprotein cholesterol, and HbA1c by 0.3% (all P < 0.001), accompanied by increased physical and mental health and reduced depression measurements. Weight loss was significantly associated with overall improvements of glucometabolic and health parameters and mean reduction of 0.05% HbA1c/kg. CONCLUSIONS The evaluated SMBG-structured lifestyle intervention is applicable to motivate individuals with type 2 diabetes for lifestyle changes. Integration of this short-term, highly motivational, and low-cost intervention into basic therapy for patients without insulin therapy could strengthen patient empowerment in order to change lifestyle and to improve glucometabolic and general health.

Immune Mediators in Patients With Acute Diabetic Foot Syndrome

OBJECTIVE Subclinical inflammation is an important risk factor for type 2 diabetes and diabetes complications. However, data on the association between inflammation and acute diabetic foot syndrome are scarce. The aim of this study was to compare systemic immune mediators in diabetic patients with and without an ulcer and to identify modulating factors. RESEARCH DESIGN AND METHODS Circulating levels of acute-phase proteins, cytokines, and chemokines were measured in diabetic patients with an ulcer (n = 170) and without an ulcer (n = 140). Of the patients, 88% had type 2 diabetes. RESULTS Patients with an acute foot ulcer had higher levels of C-reactive protein (CRP), fibrinogen, interleukin (IL)-6, macrophage migration inhibitory factor, macrophage inflammatory protein-1α, and interferon-γ–inducible protein-10 as well as lower levels of RANTES (regulated on activation normal T-cell expressed and secreted) (all P < 0.01). No differences were found for IL-8, IL-18, and monocyte chemoattractant protein-1. Most of these associations persisted after adjustment for demographic and anthropometric data, metabolic confounders, and diabetes complications. In multivariate models, size of ulcer according to the University of Texas classification but not the grade of infection was independently associated with three markers of subclinical inflammation (CRP, IL-6, and fibrinogen). CONCLUSIONS We demonstrate in our cross-sectional study that acute foot ulcers and their severity are associated with a marked upregulation of acute-phase proteins, cytokines, and chemokines independently of the concomitant infection. Further studies should investigate whether an activation of the immune system precedes the development of foot ulcer and whether anti-inflammatory therapies might be effective.

Impaired glucose regulation and type 2 diabetes in children and adolescents.

Diabetes mellitus in paediatric patients used to be almost exclusively type 1, but in recent years, case series as well as hospital‐based and population‐based studies indicated that the number of children and adolescents with type 2 diabetes (T2DM) has been increasing. This development is alarming since T2DM in youth is usually not an isolated condition, but accompanied by other cardiovascular risk factors such as obesity, dyslipidaemia, hypertension and low‐grade inflammation. In adults, numerous studies provided detailed data on prevalence, incidence and risk factors for the development of T2DM, but for children and adolescents clinical and experimental data are still rather limited. This review provides an overview about the epidemiology and pathogenesis of T2DM in youth and about impaired glucose regulation as major risk factor for diabetes development with a special focus on the recent literature on clinical and lifestyle‐related risk factors. Differences in incidence and prevalence across different populations indicate that ethnic background and genetic pre‐disposition may be important risk determinants. In addition, epigenetic factors and foetal programming appear to confer additional risk before birth. Among the environmental and lifestyle‐related risk factors there is evidence that obesity, hypercaloric diet, physical inactivity, socio‐economic position (SEP), smoking, low‐grade inflammation, psychosocial stress and sleeping patterns contribute to the risk for T2DM. However, the assessment of the relevance of risk factors and of incidence or prevalence estimates in youth is complicated by methodological issues that are also discussed. Copyright

Inflammation in metabolic syndrome and type 2 diabetes : Impact of dietary glucose

Abstract:  Chronic overnutrition combined with a lack of exercise is the main cause for the rapidly increasing prevalence of overweight and obesity. It seems accepted that adipositis (macrophage infiltration and inflammation of adipose tissue in obesity) and systemic low grade inflammation affect the pathogenesis of the metabolic syndrome or type 2 diabetes mellitus (T2DM). Therefore, modern weight reduction programs additionally focus on strategies to attenuate the inflammation state. Exercise is one major factor, which contributes to the reduction of both the incidence of T2DM and inflammation, and the immunomodulatory effects of exercise are supported by similarly beneficial effects of dietary changes. In this context, glucose is the most extensively studied nutrient and current investigations focus on postprandial glucose‐induced inflammation, one possible reason why hyperglycemia is detrimental. Indeed, glucose may modulate the mRNA expression and serum concentrations of immune parameters but these alterations rapidly normalize in normoglycemic subjects. In case of an impaired metabolic state, however, postprandial hyperglycemia increases magnitude and duration of systemic inflammatory responses, which probably promotes the development of T2DM and of cardiovascular disease.

ROSSO-in-praxi follow-up: long-term effects of self-monitoring of blood glucose on weight, hemoglobin A1c, and quality of life in patients with type 2 diabetes mellitus.

BACKGROUND Self-monitoring of blood glucose (SMBG) is a simple tool to monitor the effects of lifestyle change on blood glucose. Recently, the ROSSO-in-praxi Study demonstrated that addition of SMBG to a 12-week lifestyle intervention was associated with significant improvements in glucometabolic control and quality of life in insulin-naive patients with type 2 diabetes mellitus (T2DM). So far it is unknown if this short-term intervention also has long-term effects. Therefore, participants were followed up for a mean period of 2 years. METHODS Participants (n=327) were asked by mail for current weight, hemoglobin A1c (HbA1c), performance of SMBG, and quality of life (SF36 and CES-D questionnaires). Participants who did not reply were contacted by phone. RESULTS Two hundred twenty-eight participants (70%) completed the follow-up. During the 12-week lifestyle intervention they had significantly reduced weight (2.2 kg) and HbA1c (0.3%; P<0.001 each). After 2 years they achieved a further reduction of weight (0.2 kg; P<0.001), whereas HbA1c increased again, remaining 0.1% lower than baseline. The numbers of depressed participants remained stable during follow-up, whereas physical and mental health-related quality of life remained better compared with baseline. During follow-up 20% of participants continued SMBG daily, 35% several times a week, and 33% irregularly. It is interesting that participants with daily SMBG demonstrated an HbA1c decrease of 0.3% at time of follow-up, whereas in those who stopped SMBG HbA1c increased by 0.1% (P=0.05). CONCLUSIONS Integration of a short-term, motivational, and low-cost intervention into basic therapy of T2DM has had beneficial long-term effects on weight and quality of life and, if SMBG was continued daily, also on HbA1c.

Sfrp5 correlates with insulin resistance and oxidative stress

Secreted frizzled‐related protein 5 (Sfrp5) has been described as novel adipokine in mice with insulin‐sensitising and anti‐inflammatory properties similar to adiponectin. The aim of this study was to compare serum concentrations and determinants of Sfrp5, its pro‐inflammatory antagonist wingless‐type MMTV integration site family member (Wnt)5a and adiponectin in humans and their regulation by coffee.

Self-monitoring of blood glucose in type 2 diabetes: a new look at published trials

To the Editor: Published randomised controlled trials (RCTs) of self-monitoring of blood glucose (SMBG) in type 2 diabetes have not reached a consistent conclusion with regard to the benefit of using SMBG, especially in non-insulin-treated patients. As a consequence, there is worldwide variability in the use of glucose test strips and policies on reimbursement [1]. We analysed 18 relevant RCTs [2–19], some of which had not been included in previous meta-analyses [20–25]. Why do these trials not provide a reliable answer? The main reason appears to be conceptual. SMBG per se is a diagnostic procedure and not an intervention. Clinical trials, though, compare different types of intervention vs outcome. Hence, the 18 RCTs did not simply compare the same treatment protocol plus/minus SMBG but compared intervention strategies, which differed in many aspects, i.e. SMBG-guided disease management strategies. Each of the RCTs studied a different strategy for SMBG-guided disease management. As a consequence, the clinical outcomes of the different trials can hardly be combined in a metaanalysis. This renders safe conclusions virtually impossible. An SMBG-guided disease management strategy should include some type of algorithm enabling the patient to translate SMBG readings into changes of diet, daily exercise and/or of dose of glucose-lowering medication. Next there should be some guidance for patients during their first months of using SMBG, and, finally, decisions on medication and advice from nurses or doctors should also make use of documented SMBG results. For this advice, some rules or an algorithm on how to translate blood glucose profiles into medical advice should exist in the context of a RCT. We have analysed the RCTs for the SMBG-based disease management strategy employed. Unfortunately, information on this crucial point is quite brief in most reports. Only seven of the 18 study protocols included an algorithm or some guideline to teach patients how to respond to elevated SMBG readings, whether they were fasting or postprandial (Table 1). Reinforcement of patient education by guidance during the study ranged from one visit in 6 months to initially weekly meetings, to continuous support via the Internet. Six trials did not report a procedure for consideration of documented SMBG data for making medical treatment decisions by doctors or nurses; a further two trials apparently evaluated fasting but not postprandial values (Table 1). We conclude that most RCTs of SMBG in type 2 diabetes do not provide a sufficiently detailed description of the SMBG-guided disease management strategy used, even though it is this intervention strategy that is analysed in the trial. As judged from the information provided, there is Diabetologia (2008) 51:686–688 DOI 10.1007/s00125-008-0946-7

On what evidence-base do we recommend self-monitoring of blood glucose?

Self-monitoring of blood glucose (SMBG) has been considered one major breakthrough in diabetes therapy because, for the first time, patients were able to determine their blood glucose levels during daily life. It seems obvious that this must be of advantage to disease management and clinical outcome, but it has become a nightmare for those trying to provide evidence. Randomised controlled trials have yielded inconsistent results on a benefit of SMBG-based treatment strategies not only in type 2 but - surprisingly - also in type 1 and gestational diabetes. Despite this, SMBG is being considered indispensible in intensive insulin treatment, but is being debated for other clinical settings. When considering the non-RCT based reasons for recommending SMBG in type 1 and gestational diabetes it becomes apparent that the same reasons also apply to type 2 diabetes.

ROSSO-in-praxi-international: Long-Term Effects of Self-Monitoring of Blood Glucose on Glucometabolic Control in Patients with Type 2 Diabetes Mellitus Not Treated with Insulin

BACKGROUND Effects of lifestyle change on blood glucose levels can be monitored by self-monitoring of blood glucose (SMBG) in type 2 diabetes mellitus (T2DM) patients. We analyzed whether the SMBG-structured lifestyle intervention program ROSSO-in-praxi-international can improve glucometabolic control in the short and the long term. SUBJECTS AND METHODS One hundred twenty-four SMBG-naive ambulatory non-insulin-treated T2DM patients were randomly assigned to an SMBG group (n=63) and a control group (n=61). Both groups received a 12-week structured lifestyle guidance manual. The SMBG group additionally got a blood glucose meter with 150 test strips and was instructed to measure blood glucose regularly as well as event-driven. Glucometabolic parameters were assessed at baseline, after 12 weeks, and after 1.5 years. RESULTS During the 12 weeks of intervention the SMBG group significantly improved glycated hemoglobin (HbA1c) levels (from 7.4 ± 1.6% to 6.9 ± 1.1% [P<0.001]) and weight (-0.9 ± 1.9 kg [P<0.05]), whereas HbA1c reduction (from 7.5 ± 1.0% to 7.3 ± 1.0%) and weight loss (-0.6 ± 2.4 kg) were not significant in the control group. Of the 124 patients, 122 completed the 1.5-year follow-up. In the control group HbA1c increased again, reaching baseline values (7.5 ± 0.7%). In the SMBG group HbA1c remained stable (6.9 ± 0.9% [P=0.0003 for trend]), and weight (-1.6 ± 3.0 kg vs. baseline [P=0.0003 for trend]) improved further. Eighty-seven percent of participants in the SMBG group continued to perform SMBG. Those who measured their blood glucose more than three times per week (n=24) demonstrated an overall reduction in HbA1c of 1.0% (P=0.006 vs. three times or fewer per week) after 1.5 years. CONCLUSIONS Integration of SMBG into basic therapy of T2DM for monitoring the effect of lifestyle changes improves glucometabolic control and has long-term effects.