Females are more prone to obesity than males. This may lead to different outcomes. We studied if sex differences were seen in mortality outcomes in a longitudinal T2D cohort study.
Data from a ...regional UK database (Salford) was taken between 2010-2020. Standardised Mortality Ratio (SMR) was established from actual versus expected deaths calculated from national annual statistics for mortality rate by sex and age. The SMR was then calculated for by each sex, year, age group, HbA1c level, and diabetes medication as taken by a patient in previous years.
We included 9,558 patients with 88,102 patient years and 2,909 recorded deaths against 1,851 expected, SMR men 1.46 and women 1.72 (18% higher than men) . SMR increased slightly over time (Figure 1a) . SMR in younger females (<75 years) was higher than older females (Figure 1b) . SMR in females with high HbA1c (>86mmol/mol) was higher (Figure 1c) than lower HbA1c. Patients currently on insulin and GLP1 had much higher SMR than oral alone (Figure 1d) .SMR analysis of the oral drug use had SGLT2i 1.28; metformin 1.50; thiazolinedione 1.61; DPP4i 1.74; sulphonylurea 1.78. Note that average age and HbA1c varied across therapies.
Diabetes has greater impact on women’s mortality than men for both age, and HbA1c. Indication bias will impact drug choice but lower SMR with SGLT2i and higher with sulphonylureas concords with trial data. Despite newer therapies, SMR for diabetes has not improved over time.
Disclosure
A. H. Heald: None. M. Stedman: None. I. Laing: None. A. Robinson: None. G. Rayman: None. M. B. Whyte: Consultant; AstraZeneca, Research Support; AstraZeneca, Sanofi.
Chronic kidney disease (CKD) is a complex disease which affects approximately 13% of the world’s population. Over time, CKD can cause renal dysfunction and progression to end-stage kidney disease and ...cardiovascular disease. Complications associated with CKD may contribute to the acceleration of disease progression and the risk of cardiovascular-related morbidities. Early CKD is asymptomatic, and symptoms only present at later stages when complications of the disease arise, such as a decline in kidney function and the presence of other comorbidities associated with the disease. In advanced stages of the disease, when kidney function is significantly impaired, patients can only be treated with dialysis or a transplant. With limited treatment options available, an increasing prevalence of both the elderly population and comorbidities associated with the disease, the prevalence of CKD is set to rise. This review discusses the current challenges and the unmet patient need in CKD.
There has been uncertainty whether SGLT2 inhibition predisposes to hyperkalaemia or is protective from it. We therefore performed a meta-analysis to assess effects of SGLT2 inhibition on ...serum-potassium and hyperkalaemia-events in T2DM.
MEDLINE and PubMed databases were searched for ‘hyperkalaemia’ or ‘potassium’, with SGLT2 inhibitors in T2DM, to 31st December 2020. Randomised controlled trials, with potassium or hyperkalaemia as primary or secondary outcomes, were included. Cochran’s Q test and I2 statistic assessed statistical heterogeneity. Meta-analyses were performed using Cochrane-RevMan with two outcomes: i) Odds ratio (OR) of hyperkalaemia-events between SGLT2 inhibitor and placebo (fixed-effects), ii) Mean difference (MD) in change from baseline potassium between SGLT2 inhibitor and placebo (random-effects).
Of 1724 identified publications, nine were included in the meta-analysis (n = 3 hyperkalaemia event; n = 5 serum-potassium; n = 1 reported both outcomes). Pooled OR for hyperkalaemia-events for SGLT2 inhibitor vs placebo was 0.72 95% confidence interval (CI) 0.61 to 0.85, P < 0.001, I2 of 9%. The pooled MD in serum-potassium concentration with SGLT2 inhibitor vs placebo was −0.04 mmol/L 95% CI −0.08 to 0.00 mmol/L; P = 0.04, I2 of 89%.
Use of SGLT2 inhibitors in T2DM reduced odds of inducing hyperkalaemia but had a minimal effect of lowering serum potassium.
Aim
The COVID‐19 pandemic has resulted in the near‐complete loss of routine endoscopy services. We describe a major reorganization of service at a regional referral centre (Royal Surrey NHS ...Foundation Trust) to manage the crisis. Faecal immunochemical testing (FIT) was implemented for triage to make optimum use of limited diagnostic resources. Consultations were switched from face‐to‐face to telephone. Our aim was to evaluate the impact FIT had on resource allocation and patient diagnoses in the first 3 months of use.
Method
All colorectal 2‐week‐wait patient referrals were posted a pack requesting FIT and notification of telephone consultation. A prepaid envelope was included for return of the samples. At consultation, FIT was incorporated with the presenting symptoms to guide the choice of investigation and triage urgency. FIT ≥10 μg/g was interpreted as positive. Outcome data were collected prospectively and compared with retrospective audit data from prepandemic levels across 3 months.
Results
From 26 March 2020 to 2 July 381 patients were referred who were invited to provide FIT samples and underwent telephone consultations. Three hundred and fifty eight FIT samples were returned (94%). Onward referral for colonoscopy reduced from 62% to 34% (P < 0.001). There were 14 colorectal cancers (CRC) (3.7%) diagnosed, which was not statistically different from the prepandemic level of 3.9% (P = 0.995). Twelve of the 14 patients with a CRC diagnosis had provided samples; all 12 had FIT ≥10 μg/g and were offered fast‐track investigations.
Conclusions
The incorporation of FIT optimized the allocation of limited resources to triage those who required urgent colonic investigation for detecting CRC.
A high fructose intake exacerbates postprandial plasma triacylglycerol (TAG) concentration, an independent risk factor for cardiovascular disease, although it is unclear whether this is due to ...increased production or impaired clearance of triacylglycerol (TAG)-rich lipoproteins. We determined the in vivo acute effect of fructose on postprandial intestinal and hepatic lipoprotein TAG kinetics and de novo lipogenesis (DNL). Five overweight men were studied twice, 4 weeks apart. They consumed hourly mixed-nutrient drinks that were high-fructose (30% energy) or low-fructose (<2% energy) for 11 h. Oral
H
O was administered to measure fasting and postprandial DNL. Postprandial chylomicron (CM)-TAG and very low-density lipoprotein (VLDL)-TAG kinetics were measured with an intravenous bolus of
H
-glycerol. CM and VLDL were separated by their apolipoprotein B content using antibodies. Plasma TAG (
< 0.005) and VLDL-TAG (
= 0.003) were greater, and CM-TAG production rate (PR,
= 0.046) and CM-TAG fractional catabolic rate (FCR,
= 0.073) lower when high-fructose was consumed, with no differences in VLDL-TAG kinetics. Insulin was lower (
= 0.005) and apoB48 (
= 0.039), apoB100 (
= 0.013) and non-esterified fatty acids (NEFA) (
= 0.013) were higher after high-fructose. Postprandial hepatic fractional DNL was higher than intestinal fractional DNL with high-fructose (
= 0.043) and low-fructose (
= 0.043). Fructose consumption had no effect on the rate of intestinal or hepatic DNL. We provide the first measurement of the rate of intestinal DNL in humans. Lower CM-TAG PR and CM-TAG FCR with high-fructose consumption suggests lower clearance of CM, rather than elevated production, may contribute to elevated plasma TAG, possibly due to lower insulin-mediated stimulation of lipoprotein lipase.
Abstract
Context
Glucagon-like peptide-1 (GLP-1) agonists control postprandial glucose and lipid excursion in type 2 diabetes; however, the mechanisms are unclear.
Objective
To determine the ...mechanisms of postprandial lipid and glucose control with lixisenatide (GLP-1 analog) in type 2 diabetes.
Design
Randomized, double-blind, cross-over study.
Setting
Centre for Diabetes, Endocrinology, and Research, Royal Surrey County Hospital, Guildford, United Kingdom.
Patients
Eight obese men with type 2 diabetes age, 57.3 ± 1.9 years; body mass index, 30.3 ± 1.0 kg/m2; glycosylated hemoglobin, 66.5 ± 2.6 mmol/mol (8.2% ± 0.3%).
Interventions
Two metabolic studies, 4 weeks after lixisenatide or placebo, with cross-over and repetition of studies.
Main Outcome Measures
Study one: very-low-density lipoprotein (VLDL) and chylomicron (CM) triacylglycerol (TAG) kinetics were measured with an IV bolus of 2H5glycerol in a 12-hour study, with hourly feeding. Oral 13Ctriolein, in a single meal, labeled enterally derived TAG. Study two: glucose kinetics were measured with U-13Cglucose in a mixed-meal (plus acetaminophen to measure gastric emptying) and variable IV 6,6-2H2glucose infusion.
Results
Study one: CM-TAG (but not VLDL-TAG) pool-size was lower with lixisenatide (P = 0.046). Lixisenatide reduced CM 13Coleate area under the curve (AUC)60–480min concentration (P = 0.048) and increased CM-TAG clearance, with no effect on CM-TAG production rate. Study two: postprandial glucose and insulin AUC0–240min were reduced with lixisenatide (P = 0.0051; P < 0.05). Total glucose production (P = 0.015), rate of glucose appearance from the meal (P = 0.0098), and acetaminophen AUC0–360min (P = 0.006) were lower with lixisenatide than with placebo.
Conclusions
Lixisenatide reduced 13Coleate concentrations, derived from a single meal in CM-TAG and glucose rate of appearance from the meal through delayed gastric emptying. However, day-long CM production, measured with repeated meal feeding, was not reduced by lixisenatide and decreased CM-TAG concentration resulted from increased CM-TAG clearance.
Using stable isotopes, lixisenatide acutely slowed gastric emptying, lowering postprandial TAG levels. A more prolonged effect of reduced chylomicron TAG was from increased clearance.
Black African-Caribbean (BAC) populations are at greater risk of cardiometabolic disease than White Europeans (WE), despite lower fasting triacylglycerol (TAG) concentrations. However, limited data ...exist regarding postprandial fatty acid metabolism in BAC populations. This study determined the ethnic differences in postprandial fatty acid metabolism between overweight and obese WE and BAC men. WE ( n=10) and BAC ( n=9) men consumed two consecutive moderate-to-high fat meals; the first labelled with U- 13 C palmitate. The plasma concentration and appearance of meal-derived fatty acids in very-low density lipoprotein (VLDL)-TAG, chylomicron-TAG, and NEFA were determined over 8-hours. Indirect calorimetry with 13 CO 2 enrichment determined total and meal-derived fatty acid oxidation rates, and plasma b-hydroxybutyrate (3-OHB) concentration was measured to assess ketogenesis. BAC exhibited lower postprandial TAG ( P=0.006) and VLDL-TAG ( P=0.002) concentrations than WE. The appearance of meal-derived fatty acids in VLDL-TAG was lower in BAC than WE ( P=0.004). Following the second meal, BAC showed a trend for lower chylomicron-TAG concentration ( P=0.057). There were no ethnic differences in the appearance of meal-derived fatty acids in chylomicron-TAG. Cumulative fatty acid oxidation and the NEFA:3-OHB ratio were similar in WE and BAC. In conclusion, BAC exhibit lower postprandial TAG concentrations compared with WE men, driven by lower VLDL-TAG concentrations and possibly lower chylomicron-TAG in the late postprandial period. In BAC, the lower VLDL-TAG concentration was partially driven by a lower appearance of meal-derived fatty acids in VLDL-TAG. These findings suggest that postprandial fatty acid trafficking may be a less important determinant of cardiometabolic risk in BAC than WE men.
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