A progressive increase in cardiovascular risk assessed by coronary angiography in non-diabetic patients at sub-diabetic glucose levels

<p>Abstract</p> <p>Objective</p> <p>Diabetes mellitus type 2 (DM2) is a risk factor for coronary heart disease (CHD). While there is a clear correlation of fasting blood glucose (FBG) and 2 h post-challenge blood glucose values (2h-BG) with microvascular complications, the risk for CHD conferred by glucose dysregulation antecedent to DM2 is less clear. Therefore, we investigated associations of FBG and 2h-BG values with the prevalence of CHD assessed by coronary angiography as the most sensitive diagnostic tool.</p> <p>Research Design and Methods</p> <p>Coronary angiography was performed in 1394 patients without known DM. Capillary blood glucose was analyzed before and 2 h after an oral glucose tolerance test. Associations between FBG as well as 2h-BG levels and the risk for CHD were assessed by logistic regression analysis.</p> <p>Results</p> <p>1064 (75%) of patients were diagnosed with CHD. 204 (15%) were diagnosed with so far unknown DM2, 274 (20%) with isolated impaired fasting glucose (IFG), 188 (13%) with isolated impaired glucose tolerance (IGT) and 282 (20%) with both, IGT and IFG. We found a continuous increase in the risk for CHD with fasting and post-challenge blood glucose values even in the subdiabetic range. This correlation did however not suggest clear cut-off values. The increase in risk for CHD reached statistical significance at FBG levels of > 120 mg/dl (Odds Ratio of 2.7 [1.3-5.6] and 2h-BG levels > 140 mg/dl (141-160 mg/dl OR 1.8 [1.1-2.9], which was however lost after adjusting for age, sex and BMI.</p> <p>Conclusions</p> <p>In our study population we found a continuous increased risk for CHD at fasting and 2h-BG levels in the sub-diabetic glucose range, but no clear cut-off values for cardiovascular risk.</p

Prediabetes conversion to Normoglycemia is superior adding a low-carbohydrate and energy deficit formula diet to lifestyle intervention - a 12-month subanalysis of the ACOORH trial

Lifestyle interventions have been shown to reverse hyperglycemia to normoglycemia. However, these effects are not long-lasting and are accompanied with high dropout rates. As formula diets have been shown to be simple in usage and effective in improving glycemic control, we hypothesised that adding a low-carbohydrate and energy deficit formula diet to a low-intensity lifestyle intervention is superior in reversing prediabetes compared with lifestyle intervention alone. In this predefined subanalysis of an international, multicenter randomised controlled trial (Almased Concept against Overweight and Obesity and Related Health Risk (ACOORH) study (ID DRKS00006811)), 141 persons with prediabetes were randomised (1:2) into either a control group with lifestyle intervention only (CON, n = 45) or a lifestyle intervention group accompanied with a formula diet (INT, n = 96). Both groups were equipped with telemonitoring devices. INT received a low-carbohydrate formula diet substituting three meals/day (~1200 kcal/day) within the first week, two meals/day during week 2–4, and one meal/day during week 5–26 (1300–1500 kcal/day). Follow-up was performed after 52 weeks and 105 participants (75%, INT: n = 74; CON: n = 31) finished the 26-week intervention phase. Follow-up data after 52 weeks were available from 93 participants (66%, INT: n = 65; CON: n = 28). Compared with CON, significantly more INT participants converted to normoglycemia after 52 weeks (50% vs. 31%; p 0.05). The risk reduction led to a number-needed-to-treat of 5.3 for INT. Lifestyle intervention with a low-carbohydrate formula diet reduces prediabetes prevalence stronger than lifestyle intervention alone and is effective for type 2 diabetes prevention

High-protein, low-glycaemic meal replacement decreases fasting insulin and inflammation markers — a 12-month subanalysis of the ACOORH trial

Abstract: Lifestyle interventions, including meal replacement, are effective in the prevention and treatment of type-2-diabetes and overweight. Since insulin is the key weight regulator, we hypothesised that addition of meal replacement to a lifestyle intervention reduces insulin levels more effective than lifestyle intervention alone. In the international, multicenter randomised-controlled ACOORH-trial (Almased-Concept-against-Overweight-and-Obesity-and-Related-Health-Risk) overweight or obese persons with criteria of metabolic syndrome (n=463) were randomised into two groups. Both groups received nutritional advice focussing on carbohydrate restriction and telemonitoring devices. The intervention group substituted all three main meals/day in week 1, two meals/day in week 2–4, and one meal/day in week 5–26 with a protein-rich, low-glycaemic meal replacement. Data were collected at baseline, after 1, 3, 6 and 12 months. All datasets providing insulin data (n=446) were included in this predefined subanalysis. Significantly stronger reductions of insulin (-3.3±8.7μU/ml vs. -1.6±9.8μU/ml), weight (-6.1±5.kg vs. -3.2±4.6kg) and inflammation markers were observed in the intervention group. Insulin reduction correlated with weight reduction and strongest weight loss (-7.6±4.9kg) was observed in those participants with insulin decrease >2μU/ml. These results underline the potential of meal replacement-based lifestyle interventions in diabetes prevention, and measurement of insulin may serve as an indicator for adherence to carbohydrate restriction

Effects of a protein-rich, low-glycaemic meal replacement on changes in dietary intake and body weight following a weight-management intervention—the ACOORH trial

Although meal replacement can lead to weight reduction, there is uncertainty whether this dietary approach implemented into a lifestyle programme can improve long-term dietary intake. In this subanalysis of the Almased Concept against Overweight and Obesity and Related Health Risk (ACOORH) study (n = 463), participants with metabolic risk factors were randomly assigned to either a meal replacement-based lifestyle intervention group (INT) or a lifestyle intervention control group (CON). This subanalysis relies only on data of participants (n = 119) who returned correctly completed dietary records at baseline, and after 12 and 52 weeks. Both groups were not matched for nutrient composition at baseline. These data were further stratified by sex and also associated with weight change. INT showed a higher increase in protein intake related to the daily energy intake after 12 weeks (+6.37% [4.69; 8.04] vs. +2.48% [0.73; 4.23], p 0.001) of intervention compared to CON. Fat and carbohydrate intake related to the daily energy intake were more strongly reduced in the INT compared to CON (both p 0.01). After sex stratification, particularly INT-women increased their total protein intake after 12 (INT: +12.7 g vs. CON: −5.1 g, p = 0.021) and 52 weeks (INT: +5.7 g vs. CON: −16.4 g, p = 0.002) compared to CON. Protein intake was negatively associated with weight change (r = −0.421; p 0.001) after 12 weeks. The results indicate that a protein-rich dietary strategy with a meal replacement can improve long-term nutritional intake, and was associated with weight loss

Early and strong leptin reduction is predictive for long-term weight loss during high-protein, low-glycaemic meal replacement: a subanalysis of the randomised-controlled ACOORH trial

Lifestyle interventions including meal replacement are suitable for prevention and treatment of obesity and type-2-diabetes. Since leptin is involved in weight regulation, we hypothesised that a meal replacement-based lifestyle intervention would reduce leptin levels more effectively than lifestyle intervention alone. In the international, multicentre, randomised-controlled ACOORH-trial (Almased-Concept-against-Overweight-and-Obesity-and-Related- Health-Risk), overweight or obese participants with metabolic syndrome criteria ( = 463) were randomised into two groups and received telemonitoring devices and nutritional advice. The intervention group additionally used a protein-rich, low-glycaemic meal replacement. Data were collected at baseline, after 1, 3, 6, and 12 months. All datasets providing leptin data ( = 427) were included in this predefined subanalysis. Serum leptin levels significantly correlated with sex, body mass index, weight, and fat mass at baseline ( &lt; 0.0001). Stronger leptin reduction has been observed in the intervention compared to the control group with the lowest levels after 1 month of intervention (estimated treatment difference -3.4 µg/L [1.4; 5.4] for females; -2.2 µg/L [1.2; 3.3] for males; &lt; 0.001 each) and was predictive for stronger reduction of body weight and fat mass ( &lt; 0.001 each) over 12 months. Strongest weight loss was observed after 6 months (-5.9 ± 5.1 kg in females of the intervention group vs. -2.9 ± 4.9 kg in the control group ( &lt; 0.0001); -6.8 ± 5.3 kg vs. -4.1 ± 4.4 kg ( = 0.003) in males) and in those participants with combined leptin and insulin decrease. A meal replacement-based lifestyle intervention effectively reduces leptin which is predictive for long-term weight loss

Structure of the Head of the Bartonella Adhesin BadA

Trimeric autotransporter adhesins (TAAs) are a major class of proteins by which pathogenic proteobacteria adhere to their hosts. Prominent examples include Yersinia YadA, Haemophilus Hia and Hsf, Moraxella UspA1 and A2, and Neisseria NadA. TAAs also occur in symbiotic and environmental species and presumably represent a general solution to the problem of adhesion in proteobacteria. The general structure of TAAs follows a head-stalk-anchor architecture, where the heads are the primary mediators of attachment and autoagglutination. In the major adhesin of Bartonella henselae, BadA, the head consists of three domains, the N-terminal of which shows strong sequence similarity to the head of Yersinia YadA. The two other domains were not recognizably similar to any protein of known structure. We therefore determined their crystal structure to a resolution of 1.1 Å. Both domains are β-prisms, the N-terminal one formed by interleaved, five-stranded β-meanders parallel to the trimer axis and the C-terminal one by five-stranded β-meanders orthogonal to the axis. Despite the absence of statistically significant sequence similarity, the two domains are structurally similar to domains from Haemophilus Hia, albeit in permuted order. Thus, the BadA head appears to be a chimera of domains seen in two other TAAs, YadA and Hia, highlighting the combinatorial evolutionary strategy taken by pathogens

Coffee and Lower Risk of Type 2 Diabetes: Arguments for a Causal Relationship

Prospective epidemiological studies concur in an association between habitual coffee consumption and a lower risk of type 2 diabetes. Several aspects of these studies support a cause–effect relationship. There is a dependency on daily coffee dose. Study outcomes are similar in different regions of the world, show no differences between sexes, between obese versus lean, young versus old, smokers versus nonsmokers, regardless of the number of confounders adjusted for. Randomized controlled intervention trials did not find a consistent impact of drinking coffee on acute metabolic control, except for effects of caffeine. Therefore, lowering of diabetes risk by coffee consumption does not involve an acute effect on the post-meal course of blood glucose, insulin or insulin resistance. Several studies in animals and humans find that the ingestion of coffee phytochemicals induces an adaptive cellular response characterized by upregulation and de novo synthesis of enzymes involved in cell defense and repair. A key regulator is the nuclear factor erythroid 2-related factor 2 (Nrf2) in association with the aryl hydrocarbon receptor, AMP-activated kinase and sirtuins. One major site of coffee actions appears to be the liver, causing improved fat oxidation and lower risk of steatosis. Another major effect of coffee intake is preservation of functional beta cell mass via enhanced mitochondrial function, lower endoplasmic reticulum stress and prevention or clearance of aggregates of misfolded proinsulin or amylin. Long-term preservation of proper liver and beta cell function may account for the association of habitual coffee drinking with a lower risk of type 2 diabetes, rather than acute improvement of metabolic control

Health Effects of Coffee: Mechanism Unraveled?

The association of habitual coffee consumption with a lower risk of diseases, like type 2 diabetes mellitus, chronic liver disease, certain cancer types, or with reduced all-cause mortality, has been confirmed in prospective cohort studies in many regions of the world. The molecular mechanism is still unresolved. The radical-scavenging and anti-inflammatory activity of coffee constituents is too weak to account for such effects. We argue here that coffee as a plant food has similar beneficial properties to many vegetables and fruits. Recent studies have identified a health promoting mechanism common to coffee, vegetables and fruits, i.e., the activation of an adaptive cellular response characterized by the upregulation of proteins involved in cell protection, notably antioxidant, detoxifying and repair enzymes. Key to this response is the activation of the Nrf2 (Nuclear factor erythroid 2-related factor-2) system by phenolic phytochemicals, which induces the expression of cell defense genes. Coffee plays a dominant role in that regard because it is the major dietary source of phenolic acids and polyphenols in the developed world. A possible supportive action may be the modulation of the gut microbiota by non-digested prebiotic constituents of coffee, but the available data are still scarce. We conclude that coffee employs similar pathways of promoting health as assumed for other vegetables and fruits. Coffee beans may be viewed as healthy vegetable food and a main supplier of dietary phenolic phytochemicals