Machines that can learn and correct themselves already perform better than doctors at some tasks, says Jörg Goldhahn, but Vanessa Rampton and Giatgen A Spinas maintain that machines will never be ...able to replicate the inter-relational quality of the therapeutic nature of the doctor-patient relationship
Excessive fructose intake is associated with increased de novo lipogenesis, blood triglycerides, and hepatic insulin resistance. We aimed to determine whether fructose elicits specific effects on ...lipid metabolism independently of excessive caloric intake.
A total of 94 healthy men were studied in this double-blind, randomized trial. They were assigned to daily consumption of sugar-sweetened beverages (SSBs) containing moderate amounts of fructose, sucrose (fructose-glucose disaccharide) or glucose (80 g/day) in addition to their usual diet or SSB abstinence (control group) for 7 weeks. De novo fatty acid (FA) and triglyceride synthesis, lipolysis and plasma free FA (FFA) oxidation were assessed by tracer methodology.
Daily intake of beverages sweetened with free fructose and fructose combined with glucose (sucrose) led to a 2-fold increase in basal hepatic fractional secretion rates (FSR) compared to control (median FSR %/day: sucrose 20.8 (p = 0.0015); fructose 19.7 (p = 0.013); control 9.1). Conversely, the same amounts of glucose did not change FSR (median of FSR %/day 11.0 (n.s.)). Fructose intake did not change basal secretion of newly synthesized VLDL-triglyceride, nor did it alter rates of peripheral lipolysis, nor total FA and plasma FFA oxidation. Total energy intake was similar across groups.
Regular consumption of both fructose- and sucrose-sweetened beverages in moderate doses – associated with stable caloric intake – increases hepatic FA synthesis even in a basal state; this effect is not observed after glucose consumption. These findings provide evidence of an adaptative response to regular fructose exposure in the liver.
This study investigated the metabolic effects of daily sugar-sweetened beverage consumption for several weeks in healthy lean men. It revealed that beverages sweetened with the sugars fructose and sucrose (glucose and fructose combined), but not glucose, increase the ability of the liver to produce lipids. This change may pave the way for further unfavorable effects on metabolic health.
NCT01733563.
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•It is debated whether fructose drives the metabolic syndrome or non-alcoholic fatty liver disease.•Fructose in a liquid form, within sugar-sweetened beverages, may impact liver metabolism.•Herein, consumption of beverages containing fructose or sucrose increased hepatic lipogenesis.•Increased hepatic lipogenic activity may promote long-term metabolic perturbations.
Up to 50% of the people who have died from COVID-19 had metabolic and vascular disorders. Notably, there are many direct links between COVID-19 and the metabolic and endocrine systems. Thus, not only ...are patients with metabolic dysfunction (eg, obesity, hypertension, non-alcoholic fatty liver disease, and diabetes) at an increased risk of developing severe COVID-19 but also infection with SARS-CoV-2 might lead to new-onset diabetes or aggravation of pre-existing metabolic disorders. In this Review, we provide an update on the mechanisms of how metabolic and endocrine disorders might predispose patients to develop severe COVID-19. Additionally, we update the practical recommendations and management of patients with COVID-19 and post-pandemic. Furthermore, we summarise new treatment options for patients with both COVID-19 and diabetes, and highlight current challenges in clinical management.
Adverse effects of hypercaloric, high-fructose diets on insulin sensitivity and lipids in human subjects have been shown repeatedly. The implications of fructose in amounts close to usual daily ...consumption, however, have not been well studied. This study assessed the effect of moderate amounts of fructose and sucrose compared with glucose on glucose and lipid metabolism.
Nine healthy, normal-weight male volunteers (aged 21-25 years) were studied in this double-blind, randomized, cross-over trial. All subjects consumed four different sweetened beverages (600 mL/day) for 3 weeks each: medium fructose (MF) at 40 g/day, and high fructose (HF), high glucose (HG), and high sucrose (HS) each at 80 g/day. Euglycemic-hyperinsulinemic clamps with 6,6-(2)H(2) glucose labeling were used to measure endogenous glucose production. Lipid profile, glucose, and insulin were measured in fasting samples.
Hepatic suppression of glucose production during the clamp was significantly lower after HF (59.4 ± 11.0%) than HG (70.3 ± 10.5%, P < 0.05), whereas fasting glucose, insulin, and C-peptide did not differ between the interventions. Compared with HG, LDL cholesterol and total cholesterol were significantly higher after MF, HF, and HS, and free fatty acids were significantly increased after MF, but not after the two other interventions (P < 0.05). Subjects' energy intake during the interventions did not differ significantly from baseline intake.
This study clearly shows that moderate amounts of fructose and sucrose significantly alter hepatic insulin sensitivity and lipid metabolism compared with similar amounts of glucose.
Sugar-sweetened beverages (SSBs) have unfavorable effects on glucose and lipid metabolism if consumed in high quantities by obese subjects, but the effect of lower doses in normal-weight subjects is ...less clear.
The aim was to investigate the effects of SSBs consumed in small to moderate quantities for 3 wk on LDL particle distribution and on other parameters of glucose and lipid metabolism as well as on inflammatory markers in healthy young men.
Twenty-nine subjects were studied in a prospective, randomized, controlled crossover trial. Six 3-wk interventions were assigned in random order as follows: 600 mL SSBs containing 1)40 g fructose/d medium fructose (MF), 2) 80 g fructose/d high fructose (HF), 3) 40 g glucose/d medium glucose (MG), 4) 80 g glucose/d high glucose (HG), 5) 80 g sucrose/d high sucrose (HS), or 6) dietary advice to consume low amounts of fructose. Outcome parameters were measured at baseline and after each intervention.
LDL particle size was reduced after HF by -0.51 nm (95% CI: -0.19, -0.82 nm) and after HS by -0.43 nm (95% CI: -0.12, -0.74; P < 0.05 for both). Similarly, a more atherogenic LDL subclass distribution was seen when fructose-containing SSBs were consumed (MF, HF, and HS: P < 0.05). Fasting glucose and high-sensitivity C-reactive protein (hs-CRP) increased significantly after all interventions (by 4-9% and 60-109%, respectively; P < 0.05); leptin increased during interventions with SSBs containing glucose only (MG and HG: P < 0.05).
The present data show potentially harmful effects of low to moderate consumption of SSBs on markers of cardiovascular risk such as LDL particles, fasting glucose, and hs-CRP within just 3 wk in healthy young men, which is of particular significance for young consumers. This trial was registered at clinicaltrials.gov as NCT01021969.
Human fibroblast growth factor 21 (FGF21) is a multifaceted metabolic regulator considered to control sugar intake and to exert beneficial effects on glucose and lipid metabolism. Elevated serum ...FGF21 levels are associated with metabolic syndrome, suggesting a state of FGF21 resistance. Further, given the evidence of a hepatic ChREBP and FGF21 signaling axis, it can be assumed that SSBs containing fructose would possibly increase FGF21 concentrations. We investigated the effects of sugar-sweetened beverage (SSB) consumption on fasting FGF21 levels in healthy, lean men, discriminating the effects of glucose, fructose, and their disaccharide sucrose by secondary data analysis from a randomized controlled trial. Seven weeks of daily SSB consumption resulted in increased fasting FGF21 in healthy, lean men, irrespective of the sugar type. Medians of ΔFGF21 between post-SSB intervention values (week 7) and no-intervention period values (IQR) in pg/mL were: glucose 17.4 (0.4–45.8), fructose 22.9 (−8.6–35.1), and sucrose 13.7 (2.2–46.1). In contrast, this change in FGF21 concentration was only 6.3 (−20.1–26.9) pg/mL in the control group. The lack of a fructose-specific effect on FGF21 concentrations is contrary to our assumption. It is concluded that SSB intake may impact FGF21 concentrations and could contribute to the increased FGF21 concentrations observed in subjects suffering from metabolic syndrome that is possibly associated with decreased FGF21 responsiveness.
In patients with type 1 diabetes and end-stage renal disease, combined transplantation of a kidney together with a pancreas or isolated pancreatic islets are options to improve glycemic control. The ...aim of this study was to compare their long-term outcome with regard to metabolic control and surgical complication rate, as well as function of the transplanted kidney.
We conducted a prospective cohort study in consecutive patients receiving either a pancreas or islet transplant simultaneously with or after kidney transplantation (simultaneous pancreas-kidney SPK/pancreas-after-kidney PAK or simultaneous islet-kidney SIK/islet-after-kidney IAK transplantation).
Ninety-four patients who had undergone SPK/PAK transplantation were compared with 38 patients who had undergone SIK/IAK transplantation over a period of up to 13 years. HbA1c levels declined from 7.8 ± 1.3% (62 ± 14 mmol/mol) to 5.9 ± 1.1% (41 ± 12 mmol/mol), and from 8.0 ± 1.3% (64 ± 14 mmol/mol) to 6.5 ± 1.1% (48 ± 12 mmol/mol), respectively, in the SPK/PAK and SIK/IAK groups (P < 0.001 for both) and remained stable during follow-up, despite a reduction in the rate of severe hypoglycemia by >90%. The 5-year insulin independence rate was higher in the SPK/PAK group (73.6 vs. 9.3% in the SIK/IAK group), as was the rate of relaparotomy after transplantation (41.5 vs. 10.5% in the SIK/IAK group). There was no difference in the rate of kidney function decline.
During a long-term follow-up, SPK/PAK transplantation as well as SIK/IAK transplantation resulted in a sustained improvement of glycemic control with a slightly higher glycated hemoglobin level in the SIK/IAK group. While insulin independence is more common in whole-organ pancreas recipients, islet transplantation can be conducted with a much lower surgical complication rate and no difference in kidney function decline.
Aim of the present Consensus Statement is to provide a comprehensive and up to-date document on the pathophysiology, atherogenicity and clinical significance of low density liproproteins (LDL) ...subclasses. We sub-divided our statement in 2 sections. section I discusses the pathophysiology, atherogenicity and measurement issues, while section II is focused on the effects of drug and lifestyle modifications. Suggestions for future research in the field are highlighted at the end of section II. Each section includes Conclusions.
The association of small, dense low-density lipoprotein (sdLDL) particles with an increased cardiovascular risk is well established. However, its predictive value with regard to glucose metabolism ...and arterial disease in patients with type 2 diabetes has not been thoroughly investigated. We conducted a prospective longitudinal cohort study in patients with (pre)diabetes who were seen at baseline and after two years. sdLDL particles were determined by gradient gel electrophoresis. Insulin resistance was estimated by using the homeostatic model assessment 2 (HOMA2). Intima media thickness (IMT) and flow-mediated dilation (FMD) were assessed by ultrasound measurements. Fifty-nine patients (mean age 63.0 ± 12.2 years) were enrolled and 39 were seen at follow-up. IMT increased in the whole cohort during follow-up. The change in IMT was predicted by the proportion of sdLDL particles at baseline (p=0.03), and the change in FMD was predicted by LDL-cholesterol levels at baseline (p=0.049). HOMA2 and changes in HOMA2 correlated with the proportion of sdLDL particles and changes in this proportion, respectively (p<0.05 for both). Serum resistin levels increased in parallel with the increasing sdLDL particle number, while serum adiponectin increased only in patients with unaltered sdLDL particle number at follow-up (p<0.01 for both). In conclusion, the proportion of small, dense LDL particles and changes in this proportion are predictive of changes in intima media thickness and insulin resistance, and are closely associated with other determinants of an adverse metabolic status. Thus, this parameter extends the individual risk assessment beyond the limitations of traditional risk markers in patients with dysglycemia.
Many factors influence the outcome of islet transplantation. As islets in the early posttransplant setting are supplied with oxygen by diffusion only and are in a hypoxic state in the portal system, ...we tested whether small human islets are superior to large islets both in vitro and in vivo. We assessed insulin secretion of large and small islets and quantified cell death during hypoxic conditions simulating the intraportal transplant environment. In the clinical setting, we analyzed the influence of transplanted islet size on insulin production in patients with type 1 diabetes. Our results provide evidence that small islets are superior to large islets with regard to in vitro insulin secretion and show a higher survival rate during both normoxic and hypoxic culture. Islet volume after 48 h of hypoxic culture decreased to 25% compared with normoxic culture at 24 h due to a preferential loss of large islets. In human islet transplantation, the isolation index (islet volume as expressed in islet equivalents/islet number), or more simply the islet number, proved to be more reliable to predict stimulated C-peptide response compared with islet volume. Thus, islet size seems to be a key factor determining human islet transplantation outcome.
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