Strength Training Affects Lower Extremity Gait Kinematics, Not Kinetics, in People With Diabetic Polyneuropathy

Increased forefoot loading in diabetic polyneuropathy plays an important role in the development of plantar foot ulcers and can originate from alterations in muscle strength, joint moments and gait pattern. The current study evaluated whether strength training can improve lower extremity joint moments and spatiotemporal gait characteristics in patients with diabetic polyneuropathy. An intervention group receiving strength training during 24 weeks and a control group receiving no intervention. Measurements were performed in both groups at t= 0, t= 12, t= 24 and t= 52 weeks at an individually preferred and standardized imposed gait velocity. The strength training did not affect the maximal amplitude of hip, knee and ankle joint moments, but did result in an increase in stance phase duration, stride time and stride length of approximately 5 %, during the imposed gait velocity. In addition, both groups increased their preferred gait velocity over one year. Future longitudinal studies should further explore the possible effects of strength training on spatiotemporal gait characteristics. The current study provides valuable information on changes in gait velocities and the progressive lower extremity problems in patients with polyneuropathy

Increased forefoot loading is associated with an increased plantar flexion moment

The aim of this study was to identify the cascade of effects leading from alterations in force generation around the ankle joint to increased plantar pressures under the forefoot. Gait analysis including plantar pressure measurement was performed at an individually preferred and a standardized, imposed gait velocity in diabetic subjects with polyneuropathy (n=94), without polyneuropathy (n=39) and healthy elderly (n=19). The plantar flexion moment at 40% of the stance phase was negatively correlated with the displacement rate of center of pressure (r=-.749, p<.001 at the imposed, and r=-.693, p<.001 at the preferred gait velocity). Displacement rate of center of pressure was strongly correlated with forefoot loading (r=-.837, p<.001 at the imposed, and r=-.731, p<.001 at the preferred gait velocity). People with a relatively high plantar flexion moment at 40% of the stance phase, have a faster forward transfer of center of pressure and consequently higher loading of the forefoot. This indicates that interventions aimed at increasing the control of the roll-off of the foot may contribute to a better plantar pressure distribution

Sex difference in the incidence of microvascular complications in patients with type 2 diabetes mellitus: a prospective cohort study

Aims: Type 2 diabetes mellitus is a major cause of death and disability due to its long-term macro- and microvascular diseases. Although women with type 2 diabetes have more macrovascular diseases, it is unclear whether there are sex differences in the occurrence of microvascular disease. The aim of our study was to investigate sex differences in the incidence of microvascular complications in type 2 diabetes. Methods: Analyses were performed in the DiaGene study, a prospective cohort study for complications of type 2 diabetes, collected in the city of Eindhoven, the Netherlands (n = 1886, mean follow-up time = 6.93 years). Cox proportional hazard models adjusted for risk factors for complications (age, smoking, hypertension, dyslipidemia, HbA1c and duration of type 2 diabetes) were used to analyze the incidence of microvascular complications in men and women. Results: The incidence of microalbuminuria was significantly higher in men (HR microalbuminuria 1.64 [CI 1.21–2.24], p = 0.002). Additionally, men are more likely to develop two or three microvascular complications compared to women (OR 2.42 [CI 1.69–3.45], p < 0.001). Conclusions: This study shows that men with type 2 diabetes are more likely to develop microvascular complications, especially microalbuminuria. Furthermore, men seem to have a higher chance of developing multiple microvascular complications. Our results highlight that men and women may not benefit to a similar extent from current treatment approaches to prevent diabetes-related microvascular diseases

The effect of guideline revisions on vascular complications of type 2 diabetes

Background: The aim of this study was to investigate the impact of implementation and revision of the ‘Diabetes Mellitus type II’ guideline by the Dutch College of General Practitioners (DCGP) on the prevalence and incidence of macrovascular and microvascular complications. Methods: The DiaGene study is a case-control study (n = 1886 patients of type 2 diabetes) with extensive, retrospectively collected complication data, as well as prospective follow up of complications. The study incorporates all lines of diabetes care. Cases were divided into categories according to the date of onset of diabetes and publication dates of the DCGP. Logistic regression models were used to investigate the associations between guideline version and complications. To investigate a possible trend between guideline version and complications, the ‘guideline category’ was also used as a continuous variable. All models were adjusted for clinical covariables. Results: The 1999 and 2006 guidelines versions were associated with significantly lower risk of retinopathy than the group that started without a guideline [OR 0.32 (95% CI 0.14–0.72, p = 0.006) and 0.31 (95% CI 0.11–0.91, p = 0.034), respectively]. A significant trend in reduction of peripheral artery disease (PAD) over the guideline versions was found, adjusted for age, sex and diabetes duration (odds ratio (OR) 0.70, 95% CI 0.51-0.97, p trend = 0.029) and for retinopathy in all models (OR = 0.52, 95% CI 0.37-0.73, p trend < 0.001). Conclusions: The introduction of the first diabetes guideline and subsequent revisions have reduced the risk of macrovascular and microvascular complications of type 2 diabetes, most strongly in diabetic retinopathy. This indicates that real-time diabetes care has improved over time

Lipoprotein(a) plasma levels are not associated with incident microvascular complications in type 2 diabetes mellitus

Aims/hypothesis: Microvascular disease in type 2 diabetes is a significant cause of end-stage renal disease, blindness and peripheral neuropathy. The strict control of known risk factors, e.g. lifestyle, hyperglycaemia, hypertension and dyslipidaemia, reduces the incidence of microvascular complications, but a residual risk remains. Lipoprotein (a) [Lp(a)] is a strong risk factor for macrovascular disease in the general population. We hypothesised that plasma Lp(a) levels and the LPA gene SNPs rs10455872 and rs3798220 are associated with the incident development of microvascular complications in type 2 diabetes. Methods: Analyses were performed of data from the DiaGene study, a prospective study for complications of type 2 diabetes, collected in the city of Eindhoven, the Netherlands (n = 1886 individuals with type 2 diabetes, mean follow-up time = 6.97 years). To assess the relationship between plasma Lp(a) levels and the LPA SNPs with each newly developed microvascular complication (retinopathy n = 223, nephropathy n = 246, neuropathy n = 236), Cox proportional hazards models were applied and adjusted for risk factors for microvascular complications (age, sex, mean arterial pressure, non-HDL-cholesterol, HDL-cholesterol, BMI, duration of type 2 diabetes, HbA1c and smoking). Results: No significant associations of Lp(a) plasma levels and the LPA SNPs rs10455872 and rs3798220 with prevalent or incident microvascular complications in type 2 diabetes were found. In line with previous observations the LPA SNPs rs10455872 and rs3798220 did influence the plasma Lp(a) levels. Conclusions/interpretation: Our data show no association between Lp(a) plasma levels and the LPA SNPs with known effect on Lp(a) plasma levels with the development of microvascular complications in type 2 diabetes. This indicates that Lp(a) does not play a major role in the development of microvascular complications. However, larger studies are needed to exclude minimal effects of Lp(a) on the development of microvascular complications

Patients with chronic gastrointestinal ischemia have a higher cardiovascular disease risk and mortality

Objectives: We determined the prevalence of classical risk factors for atherosclerosis and mortality risk in patients with CGI. Methods: A case-control study was conducted. Patients referred with suspected CGI underwent a standard work-up including risk factors for atherosclerosis, radiological imaging of abdominal vessels and tonometry. Cases were patients with confirmed atherosclerotic CGI. Controls were healthy subjects previously not known with CGI. The mortality risk was calculated as standardized mortality ratio derived from observed mortality, and was estimated with ten-year risk of death using SCORE and PREDICT. Results: Between 2006 and 2009, 195 patients were evaluated for suspected CGI. After a median follow-up of 19 months, atherosclerotic CGI was diagnosed in 68 patients. Controls consisted of 132 subjects. Female gender, diabetes, hypercholesterolemia, a personal and family history of cardiovascular disease (CVD), and current smoking are highly associated with CGI. After adjustment, female gender (OR 2.14 95% CI 1.05-4.36), diabetes (OR 5.59, 95% CI 1.95-16.01), current smoking (OR 5.78, 95% CI 2.27-14.72), and history of CVD (OR 21.61, 95% CI 8.40-55.55) remained significant. CGI patients >55 years had a higher median ten-year risk of death (15% vs. 5%, P = 0.001) compared to controls. During follow-up of 116 person-years, standardized mortality rate was higher in CGI patients (3.55; 95% CI 1.70-6.52). Conclusions: Patients with atherosclerotic CGI have an increased estimated CVD risk, and severe excess mortality. S

Association of the IgG N-glycome with the course of kidney function in type 2 diabetes

Introduction Inflammatory processes are thought to be involved in kidney function decline in individuals with type 2 diabetes. Glycosylation of immunoglobulin G (IgG) is an important post-translation process affecting the inflammatory potential of IgG. We investigated the prospective relationship between IgG N-glycosylation patterns and kidney function in type 2 diabetes. Research design and methods In the DiaGene study, an all-lines-of-care case–control study (n=1886) with mean prospective follow-up of 7.0 years, the association between 58 IgG N-glycan profiles and estimated glomerular filtration rate (eGFR) and albumin-to-creatinine ratio (ACR) per year and during total follow-up was analyzed. Models were adjusted for clinical variables and multiple comparisons. Results Eleven traits were significantly associated with eGFR change per year. Bisecting GlcNAc in fucosylated and fucosylated disialylated structures and monosialylation of fucosylated digalactosylated structures were associated with a faster decrease of eGFR. Fucosylation of neutral and monogalactosylated structures was associated with less eGFR decline per year. No significant associations between IgG glycans and ACR were found. Conclusions In type 2 diabetes, we found IgG Nglycosylation patterns associated with a faster decline of kidney function, reflecting a pro-inflammatory state of IgG. eGFR, but not ACR, was associated with IgG glycans, which suggests these associations may represent renal macroangiopathy rather than microvascular disease

Plasma protein N-glycosylation is associated with cardiovascular disease, nephropathy, and retinopathy in type 2 diabetes

Introduction Although associations of total plasma N-glycome (TPNG) with type 2 diabetes have been reported, little is known on the role of TPNG in type 2 diabetes complications, a major cause of type 2 diabetes-related morbidity and mortality. Here, we assessed TPNG in relation to type 2 diabetes complications in subsamples of two Dutch cohorts using mass spectrometry (n=1815 in DiaGene and n=1518 in Hoorn Diabetes Care System).Research design and methods Blood plasma samples and technical replicates were pipetted into 96-well plates in a randomized manner. Peptide:N-glycosidase F (PNGase F) was used to release N-glycans, whereafter sialic acids were derivatized for stabilization and linkage differentiation. After total area normalization, 68 individual glycan compositions were quantified in total and were used to calculate 45 derived traits which reflect structural features of glycosylation. Associations of glycan features with prevalent and incident microvascular or macrovascular complications were tested in logistic and Cox regression in both independent cohorts and the results were meta-analyzed.Results Our results demonstrated similarities between incident and prevalent complications. The strongest association for prevalent cardiovascular disease was a high level of bisection on a group of diantennary glycans (A2FS0B; OR=1.38, p=1.34x10(-11)), while for prevalent nephropathy the increase in 2,6-sialylation on triantennary glycans was most pronounced (A3E; OR=1.28, p=9.70x10(-6)). Several other TPNG features, including fucosylation, galactosylation, and sialylation, firmly demonstrated associations with prevalent and incident complications of type 2 diabetes.Conclusions These findings may provide a glance on how TPNG patterns change before complications emerge, paving the way for future studies on prediction biomarkers and potentially disease mechanisms.Molecular Epidemiolog

Lifetime risk to progress from pre-diabetes to type 2 diabetes among women and men: comparison between American

INTRODUCTION: Pre-diabetes, a status conferring high risk of overt diabetes, is defined differently by the American Diabetes Association (ADA) and the WHO. We investigated the impact of applying definitions of pre-diabetes on lifetime risk of diabetes in women and men from the general population. RESEARCH DESIGN AND METHODS: We used data from 8844 women without diabetes and men aged ≥45 years from the prospective population-based Rotterdam Study in the Netherlands. In both gender groups, we calculated pre-diabetes prevalence according to ADA and WHO criteria and estimated the 10-year and lifetime risk to progress to overt diabetes with adjustment for competing risk of death. RESULTS: Out of 8844 individuals, pre-diabetes was identified in 3492 individuals (prevalence 40%, 95% CI 38% to 41%) according to ADA and 1382 individuals (prevalence 16%, 95% CI 15% to 16%) according to WHO criteria. In both women and men and each age category, ADA prevalence estimates doubled WHO-defined pre-diabetes. For women and men aged 45 years having ADA-defined pre-diabetes, the 10-year risk of diabetes was 14.2% (95% CI 6.0% to 22.5%) and 9.2% (95% CI 3.4% to 15.0%) compared with 23.2% (95% CI 6.8% to 39.6%) and 24.6% (95% CI 8.4% to 40.8%) in women and men with WHO-defined pre-diabetes. At age 45 years, the remaining lifetime risk to progress to overt diabetes was 57.5% (95% CI 51.8% to 63.2%) vs 80.2% (95% CI 74.1% to 86.3%) in women and 46.1% (95% CI 40.8% to 51.4%) vs 68.4% (95% CI 58.3% to 78.5%) in men with pre-diabetes according to ADA and WHO definitions, respectively. CONCLUSION: Prevalence of pre-diabetes differed considerably in both women and men when applying ADA and WHO pre-diabetes definitions. Women with pre-diabetes had higher lifetime risk to progress to diabetes. The lifetime risk of diabetes was lower in women and men with ADA-defined pre-diabetes as compared with WHO. Improvement of pre-diabetes definition considering appropriate sex-specific and age-specific glycemic thresholds may lead to better identification of individuals at high risk of diabetes

Dental calculus is not equivalent to bone collagen for isotope analysis: a comparison between carbon and nitrogen stable isotope analysis of bulk dental calculus, bone and dentine collagen from same individuals from the Medieval site of El Raval (Alicante, Spain).

Palaeodietary reconstruction using the carbon and nitrogen isotope values of bone and dentine collagen is a well-established method and the biochemical processes involved are well known. Researchers have recently explored using bulk samples of dental calculus as a substitute for bone and dentine collagen in dietary analyses, because calculus can be sampled without causing damage to the teeth, and may be useful in situations where more destructive analyses are not possible, or where collagen is poorly preserved. Several questions remain about the use of bulk calculus as a source of carbon and nitrogen isotope data, however. It is not yet clear how much of an individual¿s life span dental calculus represents, what portions of the diet it records, and how diagenesis effects the carbon and nitrogen isotope values of this material. Most importantly, there have been no comparative studies of collagen and calculus isotope values, which are necessary to establish the value of bulk calculus as a source of accurate isotope values. Here we report the comparison of carbon and nitrogen stable isotope analyses of bulk calculus to those from bone and dentine collagen. These analyses have been performed on individuals from the El Raval Mudéjar Medieval Cemetery (Eastern Iberia, 15th century A.D.). Although calculus isotope values may be broadly similar to expected values at the population level, we report here no correlation between collagen and bulk dental calculus values at the individual level. As a result, we recommend that carbon and nitrogen analysis on bulk dental calculus should only be used as a last resource archaeological dietary marker, if at all