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Background and Aims: Type 2 diabetes is associated with a heightened risk of cardiovascular complications, including myocardial steatosis. Fasting-mimicking diets (FMDs) may mimic the metabolic benefits of fasting, while being less intensive than fasting. This study aims to investigate the effect of following an FMD program on myocardial triglyceride content (MTGC), as assessed by Magnetic Resonance Spectroscopy (MRS), in patients with type 2 diabetes., Methods and Results: 100 patients with type 2 diabetes, who used metformin as the only glucose-lowering drug or no medication were randomly assigned to either an FMD group or a control group. The FMD group received the FMD program for 5 consecutive days a month alongside usual care, while the control group received usual care only. Both groups underwent baseline, 6-months and 12-months examinations, including single voxel cardiac 1H-MRS to assess MTGC. N = 13 participants of the FMD and n = 13 of the control group had complete data at baseline and twelve month follow-up. The FMD group exhibited a significant reduction in MTGC over the twelve month period (-0.235 % MTGC, p = 0.027), while the control group saw no significant change (0.143 % MTGC, p = 0.236). The decrease of MTGC in the FMD group was statistically different (p = 0.018) from control., Conclusion: Following an FMD program reduces MTGC, which indicates a favorable effect on cardiac metabolism and thereby may be an effective strategy to reduce the cardiovascular risk in patients with type 2 diabetes., Clinical Trials Registration Number: NCT03811587., Trial Registration: ClinicalTrials.gov; NCT03811587, submitted January 13th, 2019., (Copyright © 2025 The Authors. Published by Elsevier B.V. All rights reserved.)

The prevalence of type 2 diabetes (T2D) has increased rapidly. Adopting a heathy diet is suggested as one of the effective behaviors to prevent or delay onset of T2D. Dairy consumption has been recommended as part of a healthy diet, but there remains uncertainty in both the scientific community and the public about the effect of different dairy products on T2D risk. In a recent workshop, the evidence on dairy products and T2D risk was presented and discussed by a group of experts. The main conclusions from the workshop are presented in this position paper and are as follows. 1) Available evidence from large prospective cohort studies and limited randomized controlled trials (RCTs) suggests that total dairy consumption has a neutral or moderately beneficial effect on T2D risk. 2) Increasing evidence from prospective cohort studies indicates that yogurt is most strongly associated with a lower T2D risk, but evidence from RCTs is scarce. 3) Fatty acids from dairy (medium-chain, odd, and very long-chain SFAs as well as trans-palmitoleic acid) are associated with lower T2D risk and improved metabolic health, but more research is needed on studies that explore cause and effect relations to exclude the possibility that the dairy fatty acids simply serve as markers of overall dairy consumption. 4) The food matrix can be a stronger determinant of health effects than SFA content. This review further identifies research gaps in the existing knowledge and highlights key research questions that need to be addressed to better understand the impact of dairy consumption on future T2D risk., (Copyright © American Society for Nutrition 2019.)

Background: It remains uncertain which diet is best for people with type 2 diabetes (T2D)., Objective: We compared the effects of dietary carbohydrate restriction with fat restriction on markers of metabolic syndrome and quality of life in people with T2D., Design: This systematic review of randomized controlled trials (RCTs) and controlled clinical trials (CCTs) compares the effects of a low-carbohydrate [≤40% of energy (%)] diet with those of a low-fat (≤30%) diet over a period of ≥4 wk in patients with T2D. Two investigators independently selected studies, extracted data, and assessed risk of bias. The GRADE (Grading of Recommendations Assessment, Development, and Evaluation) approach was used to assess the certainty of evidence. Pooled mean differences (MDs) and 95% CIs were calculated with the use of a random-effects model., Results: Thirty-three RCTs and 3 CCTs (n = 2161) were included. Glycated hemoglobin declined more in people who consumed low-carbohydrate food than in those who consumed low-fat food in the short term (MD: -1.38%; 95% CI: -2.64%, -0.11%; very-low-certainty evidence). At 1 y, the MD was reduced to -0.36% (95% CI: -0.58%, -0.14%; low-certainty evidence); at 2 y, the difference had disappeared. There is low to high (majority moderate) certainty for small improvements of unclear clinical importance in plasma glucose, triglycerides, and HDL concentrations favoring low-carbohydrate food at half of the prespecified time points. There was little to no difference in LDL concentration or any of the secondary outcomes (body weight, waist circumference, blood pressure, quality of life) in response to either of the diets (very-low- to high-certainty evidence)., Conclusions: Currently available data provide low- to moderate-certainty evidence that dietary carbohydrate restriction to a maximum of 40% yields slightly better metabolic control of uncertain clinical importance than reduction in fat to a maximum of 30% in people with T2D. This systematic review is registered at http://www.crd.york.ac.uk/PROSPERO/display_record.php?ID=CRD42017052467 as CRD42017052467.

Background: Excessive consumption of sugar-sweetened beverages (SSBs) has been associated with obesity and related diseases. SSBs are often consumed cold, and both the energy content and temperature might influence the consumption behavior for SSBs., Objective: The main aim of this study was to elucidate whether consumption temperature and energy (i.e., glucose) content modulate homeostatic (hypothalamus) and reward [ventral tegmental area (VTA)] responses., Design: Sixteen healthy men participated in our study [aged 18-25 y; body mass index (kg/m2): 20-23]. High-resolution functional magnetic resonance imaging data were collected after ingestion of 4 different study stimuli: plain tap water at room temperature (22°C), plain tap water at 0°C, a glucose-containing beverage (75 g glucose dissolved in 300 mL water) at 22°C, and a similar glucose drink at 0°C. Blood oxygen level-dependent (BOLD) changes from baseline (7 min preingestion) were analyzed over time in the hypothalamus and VTA for individual stimulus effects and for effects between stimuli., Results: In the hypothalamus, water at 22°C led to a significantly increased BOLD response; all other stimuli resulted in a direct, significant decrease in BOLD response compared with baseline. In the VTA, a significantly decreased BOLD response compared with baseline was found after the ingestion of stimuli containing glucose at 0°C and 22°C. These responses were not significantly modulated by consumption temperature. The consumption of plain water did not have a significant VTA BOLD effect., Conclusions: Our data show that glucose at 22°C, glucose at 0°C, and water at 0°C lowered hypothalamic activity, which is associated with increased satiation. On the contrary, the consumption of water at room temperature increased activity. All stimuli led to a similar VTA response, which suggests that all drinks elicited a similar hedonic response. Our results indicate that, in addition to glucose, the low temperature at which SSBs are often consumed also leads to a response from the hypothalamus and might strengthen the response of the VTA. This trial was registered at www.clinicaltrials.gov as NCT03181217., (© 2018 American Society for Nutrition. All rights reserved.)

Background: Paleolithic nutrition, which has attracted substantial public attention lately because of its putative health benefits, differs radically from dietary patterns currently recommended in guidelines, particularly in terms of its recommendation to exclude grains, dairy, and nutritional products of industry., Objective: We evaluated whether a Paleolithic nutritional pattern improves risk factors for chronic disease more than do other dietary interventions., Design: We conducted a systematic review of randomized controlled trials (RCTs) that compared the Paleolithic nutritional pattern with any other dietary pattern in participants with one or more of the 5 components of metabolic syndrome. Two reviewers independently extracted study data and assessed risk of bias. Outcome data were extracted from the first measurement time point (≤6 mo). A random-effects model was used to estimate the average intervention effect. The quality of the evidence was rated with the use of the Grading of Recommendations Assessment, Development and Evaluation approach., Results: Four RCTs that involved 159 participants were included. The 4 control diets were based on distinct national nutrition guidelines but were broadly similar. Paleolithic nutrition resulted in greater short-term improvements than did the control diets (random-effects model) for waist circumference (mean difference: -2.38 cm; 95% CI: -4.73, -0.04 cm), triglycerides (-0.40 mmol/L; 95% CI: -0.76, -0.04 mmol/L), systolic blood pressure (-3.64 mm Hg; 95% CI: -7.36, 0.08 mm Hg), diastolic blood pressure (-2.48 mm Hg; 95% CI: -4.98, 0.02 mm Hg), HDL cholesterol (0.12 mmol/L; 95% CI: -0.03, 0.28 mmol/L), and fasting blood sugar (-0.16 mmol/L; 95% CI: -0.44, 0.11 mmol/L). The quality of the evidence for each of the 5 metabolic components was moderate. The home-delivery (n = 1) and dietary recommendation (n = 3) RCTs showed similar effects with the exception of greater improvements in triglycerides relative to the control with the home delivery. None of the RCTs evaluated an improvement in quality of life., Conclusions: The Paleolithic diet resulted in greater short-term improvements in metabolic syndrome components than did guideline-based control diets. The available data warrant additional evaluations of the health benefits of Paleolithic nutrition. This systematic review was registered at PROSPERO (www.crd.york.ac.uk/PROSPERO) as CRD42014015119., (© 2015 American Society for Nutrition.)

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)., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Background: The brain is crucial for the control of food intake, reward, and energy homeostasis., Objective: We hypothesized that 1) brain circuits involved in energy homeostasis and reward show different functional connectivity patterns between obese and lean individuals and 2) food intake affects functional connectivity differentially in obese and lean individuals. Therefore, we compared the connectivity of the hypothalamus, amygdala, and posterior cingulate cortex, each probing a distinct network related to energy homeostasis and reward, between obese subjects and lean subjects in the fasting state and after meal ingestion., Design: We acquired 3 Tesla resting-state functional magnetic resonance imaging scans after an overnight fast and after ingestion of a liquid mixed meal in 46 obese female participants [19 with normal glucose tolerance and 27 with type 2 diabetes mellitus (T2DM)] and 12 lean subjects. Functional connectivity of our regions of interest was assessed by using a seed-based correlation approach., Results: No significant differences between normal-glucose-tolerant and T2DM subjects were observed. In the fasting state, the total obese group had stronger hypothalamic connectivity with the medial prefrontal cortex and the dorsal striatum than did the lean subjects. The amygdala was differentially connected to the right insula in obese compared with lean subjects. Food intake dampened hypothalamic connectivity with the frontal regions in lean subjects, whereas these connections were barely affected in obese subjects., Conclusions: Our results indicate that functional connectivity in several brain networks, particularly the homeostatic and cognitive control network and the reward network, was different between obese and lean subjects. In the fasting state, obesity appears to be associated with stronger functional connectivity between brain areas involved in cognitive control, motivation, and reward, whereas these connections are largely unaffected by food intake in obese compared with lean subjects., (© 2014 American Society for Nutrition.)

Insulin signaling in the central nervous system (CNS) is required for the inhibitory effect of insulin on glucose production. Our aim was to determine whether the CNS is also involved in the stimulatory effect of circulating insulin on the tissue-specific retention of fatty acid (FA) from plasma. In wild-type mice, hyperinsulinemic-euglycemic clamp conditions stimulated the retention of both plasma triglyceride-derived FA and plasma albumin-bound FA in the various white adipose tissues (WAT) but not in other tissues, including brown adipose tissue (BAT). Intracerebroventricular (ICV) administration of insulin induced a similar pattern of tissue-specific FA partitioning. This effect of ICV insulin administration was not associated with activation of the insulin signaling pathway in adipose tissue. ICV administration of tolbutamide, a K(ATP) channel blocker, considerably reduced (during hyperinsulinemic-euglycemic clamp conditions) and even completely blocked (during ICV administration of insulin) WAT-specific retention of FA from plasma. This central effect of insulin was absent in CD36-deficient mice, indicating that CD36 is the predominant FA transporter in insulin-stimulated FA retention by WAT. In diet-induced insulin-resistant mice, these stimulating effects of insulin (circulating or ICV administered) on FA retention in WAT were lost. In conclusion, in insulin-sensitive mice, circulating insulin stimulates tissue-specific partitioning of plasma-derived FA in WAT in part through activation of K(ATP) channels in the CNS. Apparently, circulating insulin stimulates fatty acid uptake in WAT but not in BAT, directly and indirectly through the CNS.

AutoDecon is a fully automatic, multiparameter deconvolution procedure that can be used to estimate various hormone secretion kinetics. We propose a strategy based on the application of the corrected Akaike's information criterion to select the optimal deconvolution model from a class of candidates generated by applying different combinations of initializing values. Using simulated cortisol time series, we show that, particularly in cases of diminished hormone half-life, this approach can yield estimates that are closer to the true underlying secretion kinetics compared with the commonly used approach based on a single set of initializing values. However, although we provide proof of principle, more extensive elaboration and validation of this approach are necessary.

Background: This study aims to quantitatively and qualitatively assess microvascular complications and their risk factors in patients with cystic fibrosis-related diabetes (CFRD) compared to those with type 1 diabetes mellitus (DM1)., Methods: 79 patients with CFRD were matched with 79 patients with DM1 according to sex, age and duration of insulin therapy. Retinopathy, peripheral neuropathy, nephropathy and microalbuminuria were the microvascular complications assessed. Risk factors studied were: smoking, BMI, HbA1c, cholesterol, cholesterol/HDL ratio, diastolic and systolic blood pressure., Results: Both groups had the same number of microvascular complications (29%). CFRD patients showed more microalbuminuria (21% versus 4.1%; p=0.003), while retinopathy was more common in patients with DM1 (24% versus 10%; p=0.044). The prevalences of peripheral neuropathy and nephropathy were similar. Patients with CFRD had lower BMI (p<0.0001), total cholesterol (p<0.0001) and HbA1c (p=0.056) levels, and a lower prevalence of smokers (p<0.0001). Cholesterol/HDL ratio and diastolic and systolic blood pressure were similar in both groups., Conclusions: The microvascular complications shown by patients with CFRD are similar to those seen in patients with DM1 but with a lower prevalence of retinopathy and a higher prevalence of microalbuminuria. The latter may reflect the influence of other cystic fibrosis-related factors on renal function.

Obese obob mice with strong overexpression of the human apolipoprotein C1 (APOC1) exhibit excessive free fatty acid (FFA) and triglyceride (TG) levels and severely reduced body weight (due to the absence of subcutaneous adipose tissue) and skin abnormalities. To evaluate the effects of APOC1 overexpression on hepatic and peripheral insulin sensitivity in a less-extreme model, we generated obob mice with mild overexpression of APOC1 (obob/APOC1(+/-)) and performed hyperinsulinemic clamp analysis. Compared with obob littermates, obob/APOC1(+/-) mice showed reduced body weight (-25%) and increased plasma levels of TG (+632%), total cholesterol (+134%), FFA (+65%), glucose (+73%), and insulin (+49%). Hyperinsulinemic clamp analysis revealed severe whole-body and hepatic insulin resistance in obob/APOC1(+/-) mice and, in addition, increased hepatic uptake of FFA and hepatic TG content. Treatment of obob/APOC1(+/-) mice with rosiglitazone strongly improved whole-body insulin sensitivity as well as hepatic insulin sensitivity, despite a further increase of hepatic fatty acid (FA) uptake and a panlobular increase of hepatic TG accumulation. We conclude that overexpression of APOC1 prevents rosiglitazone-induced peripheral FA uptake leading to severe hepatic steatosis. Interestingly, despite rosiglitazone-induced hepatic steatosis, hepatic insulin sensitivity improves dramatically. We hypothesize that the different hepatic fat accumulation and/or decrease in FA intermediates has a major effect on the insulin sensitivity of the liver.

Dietary interventions with fish oil have been found to protect against the development of high-fat diet-induced insulin resistance and to decrease the expression of tumor necrosis factor (TNF)-alpha. However, the effect of fish oil administration on preexisting insulin resistance is subject to debate. In the present study, we examined the mechanism by which fish oil affects preexisting insulin resistance. High fat diet-induced insulin-resistant ApoE*3-Leiden transgenic mice were treated for 10 wk as follows: 1) high fat diet (control group), 2) high fat diet with 3 g/100 g fish oil and 3) high fat diet but food intake restricted to 75% of the ad libitum food intake. We measured plasma glucose, insulin, free fatty acids (FFA) and triglyceride (TG) levels throughout the study. After the 10-wk dietary intervention period we performed hyperinsulinemic euglycemic analyses and measured insulin sensitivity and FFA turnover. Furthermore, we then determined the VLDL-TG production rate and TNF-alpha protein expression in white adipose tissue (WAT). Compared with control mice, the insulin sensitivity of mice treated with fish oil was not affected, whereas it was improved (P < 0.05) for energy-restricted mice. FFA turnover was unaffected in both fish oil-treated and energy-restricted mice. Compared with controls, hepatic VLDL-TG production was lower (P < 0.05) with fish oil feeding but greater with energy restriction (P < 0.05). Interestingly, the level of TNF-alpha protein in WAT was lower (P < 0.05) in both groups. We conclude that partial replacement of saturated fat by fish oil does not improve preexisting high fat diet-induced insulin resistance, although it lowers TNF-alpha protein levels in WAT.

Background: Abdominal obesity is associated with a blunted lipolytic response to fasting that may contribute to the preservation of adipose tissue mass., Objective: To further explore the pathophysiology of blunted lipolysis during fasting in obesity, we simultaneously measured lipolysis and distinct neuroendocrine regulatory hormones in abdominally obese and normal-weight (NW) women., Design: Eight abdominally obese [x +/- SD body mass index (BMI; in kg/m(2)): 32.1 +/- 2.6] and 6 NW (BMI: 22.7 +/- 1.5) women were studied during the last 8 h of a 20-h fast. The glycerol appearance rate and the serum and plasma concentrations of insulin, leptin, cortisol, and growth hormone were measured regularly., Results: At 13 h of fasting, the mean (+/-SD) glycerol appearance rate corrected for fat mass was greater in NW women than in obese women (7.2 +/- 1.0 and 5.1 +/- 0.6 micro mol.kg(-1).min(-1), respectively; P = 0.001). After a 20-h fast, lipolysis increased to 8.9 +/- 1.5 mmol.kg(-1).min(-1) in NW women (23%), whereas it did not change significantly in obese women (-2%). Fasting decreased insulin concentrations by approximately 30% in both groups, but it did not induce significant changes in leptin concentrations. Mean cortisol concentrations and urinary catecholamine excretion were comparable in both groups. However, mean plasma growth hormone concentrations were higher in NW women than in obese women (1.81 +/- 0.98 compared with 0.74 +/- 0.52 mU/L; P = 0.046). The relative change in lipolysis tended to correlate with mean plasma growth hormone concentrations (r = 0.515, P = 0.059)., Conclusion: Abdominal obesity-associated hyposomatotropism may be involved in the blunted increase in lipolysis during fasting.

Background: A high dietary fat intake is involved in the pathogenesis of insulin resistance., Objective: The aim was to compare the effect of different amounts of dietary fat on hepatic and peripheral insulin sensitivity., Design: Six healthy men were studied on 3 occasions after consuming for 11 d diets with identical energy and protein contents but different percentages of energy as fat and carbohydrate as follows: 0% and 85% [low-fat, high-carbohydrate (LFHC) diet], 41% and 44% [intermediate-fat, intermediate-carbohydrate (IFIC) diet], and 83% and 2% [high-fat, low-carbohydrate (HFLC) diet]. Insulin sensitivity was quantified by using a hyperinsulinemic euglycemic clamp (plasma insulin concentration: approximately 190 pmol/L)., Results: During hyperinsulinemia, endogenous glucose production was higher after the HFLC diet (2.5 +/- 0.3 micromol x kg(-1) x min(-1); P < 0.05) than after the IFIC and LFHC diets (1.7 +/- 0.3 and 1.2 +/- 0.4 micromol x kg(-1) x min(-1), respectively). The ratio of dietary fat to carbohydrate had no unequivocal effects on insulin-stimulated glucose uptake. In contrast, insulin-stimulated, nonoxidative glucose disposal tended to increase in relation to an increase in the ratio of fat to carbohydrate, from 14.8 +/- 5.1 to 20.6 +/- 1.9 to 26.2 +/- 2.9 micromol x kg(-1) x min(-1) (P < 0.074 between the 3 diets). Insulin-stimulated glucose oxidation was significantly lower after the HFLC diet than after the IFIC and LFHC diets: 1.7 +/- 0.8 compared with 13.4 +/- 2.1 and 19.0 +/- 2.1 micromol x kg(-1) x min(-1), respectively (P < 0.05). During the clamp study, plasma fatty acid concentrations were higher after the HFLC diet than after the IFIC and LFHC diets: 0.22 +/- 0.02 compared with 0.07 +/- 0.01 and 0.05 +/- 0.01 mmol/L, respectively (P < 0.05)., Conclusion: A high-fat, low-carbohydrate intake reduces the ability of insulin to suppress endogenous glucose production and alters the relation between oxidative and nonoxidative glucose disposal in a way that favors storage of glucose.

This study examined the relationship between borderline and impulsive personality traits on the one hand, and monoamine function on the other in 15 women with bulimia nervosa and 15 women with recurrent suicidal behavior. Platelet serotonin (5-HT) and platelet monoamine oxidase (MAO) activity were used as peripheral measures of monoaminergic function. All suicide attempters were diagnosed as having a borderline personality disorder, whereas this diagnosis was less frequent in bulimics. Bulimics with borderline comorbidity resembled recurrent suicide attempters with borderline personality disorder more closely in both psychological (anger, impulsive behavior) and biochemical characteristics (platelet 5-HT) than bulimics without borderline personality disorder. Platelet 5-HT was higher in patients with borderline personality than in normal female controls and was positively correlated with the disposition to experience anger. Impulsive personality traits were consistently negatively correlated with platelet MAO activity. Our findings support the subdivision of bulimics according to the presence of borderline or "multi-impulsive" personality disorder.

Fifteen bulimic women (BN) and 19 healthy female controls (CO) were studied. The subjects were cross-over treated with either fluoxetine (FXT) or placebo during 4 days. They received, in randomized order, a breakfast containing pure carbohydrate (CHO) or a protein-rich (PROT) breakfast following day 3 and 4 of each treatment period. Twenty-nine different food items were offered for lunch. The fasting serum glucose and insulin concentrations and the fasting plasma tryptophan (Trp)/large neutral amino acid (LNAA) ratio were slightly higher in BN. The changes of these metabolic parameters in response to a CHO or PROT breakfast were similar in both groups. Across breakfast type, the plasma (Trp)/(LNAA) ratio at 120 min after breakfast was higher in BN. Total caloric intake at lunchtime was less in BN. In CO, less carbohydrate was selected at lunchtime following the CHO breakfast, an effect that was abolished by FXT. Breakfast type or FXT did not have any apparent effect on food intake at lunchtime in BN. This might indicate that bulimic subjects are less sensitive to serotoninergic stimuli than control subjects.