The storage of triglyceride (TG) droplets in nonadipose tissues is called ectopic fat storage. Ectopic fat is associated with insulin resistance and type 2 diabetes mellitus (T2DM). Not the ...triglycerides per se but the accumulation of intermediates of lipid metabolism in organs, such as the liver, skeletal muscle, and heart seem to disrupt metabolic processes and impair organ function. We describe the mechanisms of ectopic fat depositions in the liver, skeletal muscle, and in and around the heart and the consequences for each organs function. In addition, we systematically reviewed the literature for the effects of diet-induced weight loss and exercise on ectopic fat depositions.
Aim
To describe the prevalence and characteristics of polypharmacy in a Dutch cohort of individuals with type 2 diabetes.
Methods
We included people with type 2 diabetes from the Diabetes Pearl ...cohort, of whom 3886 were treated in primary care and 2873 in academic care (secondary/tertiary). With multivariable multinomial logistic regression analyses stratified for line of care, we assessed which sociodemographic, lifestyle and cardiometabolic characteristics were associated with moderate (5–9 medications) and severe polypharmacy (≥10 medications) compared with no polypharmacy (0–4 medications).
Results
Mean age was 63 ± 10 years, and 40% were women. The median number of daily medications was 5 (IQR 3–7) in primary care and 7 (IQR 5–10) in academic care. The prevalence of moderate and severe polypharmacy was 44% and 10% in primary care, and 53% and 29% in academic care respectively. Glucose‐lowering and lipid‐modifying medications were most prevalent. People with severe polypharmacy used a relatively large amount of other (i.e. non‐cardiovascular and non‐glucose‐lowering) medication. Moderate and severe polypharmacy across all lines of care were associated with higher age, low educational level, more smoking, longer diabetes duration, higher BMI and more cardiovascular disease.
Conclusions
Severe and moderate polypharmacy are prevalent in over half of people with type 2 diabetes in primary care, and even more in academic care. People with polypharmacy are characterized by poorer cardiometabolic status. These results highlight the significance of polypharmacy in type 2 diabetes.
Abstract Background and Aims South Asians have an exceptionally high risk of developing cardiovascular disease compared to white Caucasians. A contributing factor might be dysfunction of high density ...lipoprotein (HDL). We aimed to compare HDL function in different age groups of both ethnicities. Methods and Results HDL functionality with respect to cholesterol efflux, anti-oxidation and anti-inflammation was determined using fasting, apoB-depleted, plasma samples from South Asian and white Caucasian neonates (n=14 each), adolescent healthy men (n=12 each, 18-25y), and adult overweight men (n=12 each, 40-50y). Adolescents were subjected to a 5-day high fat high calorie diet (HCD) and adults to an 8-day very low calorie diet (LCD). Additionally, HDL composition was measured in adolescents and adults using1 H-NMR spectroscopy. Anti-oxidative capacity was lower in South Asian adults before LCD (19.4±2.1 vs. 25.8±1.2%, p=0.045, 95%-CI=0.1;12.7) and after LCD (16.4±2.4 vs. 27.6±2.7%, p=0.001, 95%-CI=4.9;17.5). Anti-inflammatory capacity was reduced in South Asian neonates (23.8±1.2 vs. 34.9±1.3%, p=0.000001, 95%-CI=-14.6;-7.5), and was negatively affected by an 8-day LCD only in South Asian adults (-12.2±4.3%, p=0.005, 95%-CI=-5.9;-1.2). Cholesterol efflux capacity was increased in response to HCD in adolescents (South Asians: +6.3±2.9%, p=0.073, 95%-CI=-0.02;0.46, Caucasians: +11.8±3.4%, p=0.002, 95%-CI=0.17;0.65) and decreased after LCD in adults (South Asians: -10.3±2.4%, p<0.001, 95%-CI=-0.57;-0.20, Caucasians: -13.7±1.9%, p<0.00001, 95%-CI=-0.67;-0.33). Although subclass analyses of HDL showed no differences between ethnicities, cholesterol efflux correlated best with cholesterol and phospholipid within small HDL compared to other HDL subclasses and constituents. Conclusion Impaired HDL functionality in South Asians may be a contributing factor to their high CVD risk. Clinical Trial Registration NTR 2473 (URL: http://www.trialregister.nl/ )
Background: Sphingolipids, like phytosphingosine (PS) are part of cellular membranes of yeasts, vegetables and fruits. Addition of PS to the diet decreases serum cholesterol and free fatty acid (FFA) ...levels in rodents and improves insulin sensitivity. Objective: To study the effect of dietary supplementation with PS on cholesterol and glucose metabolism in humans. Methods: Twelve men with the metabolic syndrome (MetS) (according to the International Diabetes Federation (IDF) criteria; age 51±2 years (mean±s.e.m.); body mass index (BMI) 32±1 kg/m2) were randomly assigned to 4 weeks of PS (500 mg twice daily) and 4 weeks of placebo (P) in a double-blind cross-over study, with a 4-week wash-out period between both interventions. At the end of each intervention anthropometric measures and serum lipids were measured and an intravenous glucose tolerance test (IVGTT) was performed. Results: Phytosphingosine did not affect body weight and fat mass compared with P. PS decreased serum total cholesterol (5.1±0.3 (PS) vs 5.4±0.3 (P) mmol/l; P<0.05) and low-density lipoprotein (LDL)-cholesterol levels (3.1±0.3 (PS) vs 3.4±0.3 (P) mmol/l; P<0.05), whereas it did not alter serum triglyceride and high-density lipoprotein (HDL)-cholesterol levels. In addition, PS lowered fasting plasma glucose levels (6.2±0.3 (PS) vs 6.5±0.3 (P) mmol/l; P<0.05). PS increased the glucose disappearance rate (K-value) by 9.9% during the IVGTT (0.91±0.06 (PS) vs 0.82±0.05 (P) %/min; P<0.05) at similar insulin levels, compared with P, thus implying enhanced insulin sensitivity. PS induced only minor gastrointestinal side effects. Conclusion: Dietary supplementation of PS decreases plasma cholesterol levels and enhances insulin sensitivity in men with the MetS.
•Data extraction from general practice health records provided a follow-up rate of 97%.•ICPC-coded diagnoses diabetes had an excellent agreement with the reference standard.•ICPC-coded diagnoses DM ...were more accurate compared to self-reported DM.•ICPC-coded diagnoses DM are feasible and valid for case definition in cohort studies.
To examine the feasibility and validity of obtaining International Classification of Primary Care (ICPC)-coded diagnoses of diabetes mellitus (DM) from general practice electronic health records for case definition in epidemiological studies, as alternatives to self-reported DM.
The Netherlands Epidemiology of Obesity study is a population-based cohort study of 6671 persons aged 45–65 years at baseline, included between 2008−2012. Data from electronic health records were collected between 2012−2014. We defined a reference standard using diagnoses, prescriptions and consultation notes and investigated its agreement with ICPC-coded diagnoses of DM and self-reported DM.
After a median follow-up of 1.8 years, data from 6442 (97%) participants were collected. With the reference standard, 506 participants (79/1000 person-years) were classified with prevalent DM at baseline and 131 participants (11/1000 person-years) were classified with incident DM during follow-up. The agreement of prevalent DM between self-report and the reference standard was 98% (kappa 0.86), the agreement between ICPC-coded diagnoses and the reference standard was 99% (kappa 0.95). The agreement of incident DM between ICPC-coded diagnoses and the reference standard was >99% (kappa 0.92).
ICPC-coded diagnoses of DM from general practice electronic health records are a feasible and valid alternative to self-reported diagnoses of DM.
Aims/hypothesis Both energy restriction (ER) per se and weight loss improve glucose metabolism in obese insulin-treated type 2 diabetic patients. Short-term ER decreases basal endogenous glucose ...production (EGP) but not glucose disposal. In contrast the blood glucose-lowering mechanism of long-term ER with substantial weight loss has not been fully elucidated. The aim of this study was to investigate the effect of loss of 50% of excess weight 50% excess weight reduction (EWR) on EGP, whole-body insulin sensitivity and the disturbed myocellular insulin-signalling pathway in ten obese insulin-treated type 2 diabetic patients. Methods A euglycaemic-hyperinsulinaemic clamp with stable isotopes (6,6-²H₂glucose and ²H₅glycerol) combined with skeletal muscle biopsies was performed during a very low energy diet (VLED; 1,883 kJ/day) on day 2 and again after 50% EWR. Oral blood glucose-lowering agents and insulin were discontinued 3 weeks prior to the VLED and at the start of the VLED, respectively. Results Loss of 50% EWR (20.3 ± 2.2 kg from day 2 to day of 50% EWR) normalised basal EGP and improved insulin sensitivity, especially insulin-stimulated glucose disposal (18.8 ± 2.0 to 39.1 ± 2.8 μmol kg fat-free mass-¹ min-¹, p = 0.001). The latter was accompanied by improved insulin signalling at the level of the recently discovered protein kinase B/Akt substrates AS160 and PRAS40 along with a decrease in intramyocellular lipid (IMCL) content. Conclusions/interpretation Considerable weight loss in obese, insulin-treated type 2 diabetic patients normalises basal EGP and improves insulin sensitivity resulting from an improvement in insulin signal transduction in skeletal muscle. The decrease in IMCL might contribute to this effect.
Abstract Background and aims South Asians have a higher risk of developing cardiovascular disease than white Caucasians. The underlying cause is unknown, but might be related to higher cardiac ...susceptibility to metabolic disorders. Short-term caloric restriction (CR) can be used as a metabolic stress test to study cardiac flexibility. We assessed whether metabolic and functional cardiovascular flexibility to CR differs between South Asians and white Caucasians. Methods and results Cardiovascular function and myocardial triglycerides were assessed using a 1.5T-MRI/S-scanner in 12 middle-aged overweight male South Asians and 12 matched white Caucasians before and after an 8-day very low calorie diet (VLCD). At baseline South Asians were more insulin resistant than Caucasians. Cardiac dimensions were smaller, despite correction for body surface area, and pulse wave velocity (PWV) in the distal aorta was higher in South Asians. Systolic and diastolic function, myocardial triglycerides and pericardial fat did not differ significantly between groups. After the VLCD body weight reduced on average by 4.0 ± 0.2 kg. Myocardial triglycerides increased in both ethnicities by 69 ± 18%, and diastolic function decreased although this was not significant in South Asians. However, pericardial fat and PWV in the proximal and total aorta were reduced in Caucasians only. Conclusion Myocardial triglyceride stores in middle-aged overweight and insulin resistant South Asians are as flexible and amenable to therapeutic intervention by CR as age-, sex- and BMI-matched but less insulin resistant white Caucasians. However, paracardial fat volume and PWV showed a differential effect in response to an 8-day VLCD in favor of Caucasians. Clinical Trial Registration NTR 2473 (URL: http://www.trialregister.nl/trialreg/admin/rctsearch.asp?Term=2473 ).
It is well known that obesity is associated with insulin resistance and an increased risk for type 2 diabetes mellitus. Formerly it was postulated that increased lipolysis and consequently free fatty ...acid (FFA) production, from with triglycerides overloaded fat cells, would disrupt glucose homeostasis via Randle's hypothesis. Lipodystrophy, however, also leads to insulin resistance. Recently it has become clear that adipose tissue functions as an endocrine organ and secretes numerous proteins in response to a variety of stimuli. These secreted proteins exert a pleiotropic effect. The proteins that are involved in glucose and fat metabolism and hence can influence insulin resistance are discussed in this paper. They include leptin, resistin, adiponectin, acylation-stimulating protein, tumour necrosis factor-alpha and interleukin-6. The stimuli for production and the site and mechanism of action in relation to insulin resistance will be discussed. None of these proteins are, however, without controversy with regard to their mechanism of action. Furthermore, some of these proteins may influence each other via common signalling pathways. A theory is presented to link the interrelationship between these adipocyte secretory products and their effect on insulin resistance.
Objective To identify factors which predict the blood glucose lowering effect of monotherapy with a 30‐day very low calorie diet (VLCD) in obese Type 2 diabetic patients. A responder was a priori ...defined as a patient with a fasting plasma glucose (FPG) level < 10 mmol/l on day 30.
Research design and methods In 17 obese patients (BMI 37.6 ± 5.6 (mean ± SD) kg/m2) with Type 2 diabetes, all blood glucose lowering medication (including insulin) was discontinued on day −1 followed by a 30‐day VLCD. On day 2 and 30 of the VLCD an intravenous glucose tolerance test (IVGTT) was performed.
Results Of the 14 patients who completed the 30‐day VLCD, eight qualified as responder. Responders and non‐responders could be distinguished by day 2. Responders had a shorter duration of Type 2 diabetes and higher fasting serum insulin, C‐peptide and HOMA‐β‐values. In addition, responders displayed a more prominent second‐phase insulin response following i.v. glucose loading and higher k‐values. In a stepwise discriminant analysis, the change in FPG from day 0 to day 2 (responders +0.64 ± 2.3, non‐responders +4.15 ± 3.3 mmol/l, P = 0.035) in combination with the area under the curve of insulin (AUC) above baseline during an IVGTT on day 2 (responders 571 ± 236, non‐responders 88 ± 65 mU*50 min, P < 0.001), distinguished responders completely from non‐responders.
Conclusion Preservation of the capacity of β‐cells to secrete insulin predicts a favourable metabolic response to a VLCD in obese Type 2 diabetic patients.
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