French Recommendations for Sugar Intake in Adults: A Novel Approach Chosen by ANSES.

This article presents a systematic review of the scientific evidence linking sugar consumption and health in the adult population performed by a group of experts, mandated by the French Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement, et du travail (ANSES). A literature search was performed by crossing search terms for overweight/obesity, diabetes/insulin resistance, dyslipidemia/cardiovascular diseases, non-alcoholic fatty liver diseases (NAFLD), and uric acid concentrations on one hand and for intake of sugars on the other. Controlled mechanistic studies, prospective cohort studies, and randomized clinical trials were extracted and assessed. A literature analysis supported links between sugar intake and both total energy intake and body weight gain, and between sugar intake and blood triglycerides independently of total energy intake. The effects of sugar on blood triglycerides were shown to be mediated by the fructose component of sucrose and were observed with an intake of fructose >50 g/day. In addition, prospective cohort studies showed associations between sugar intake and the risk of diabetes/insulin resistance, cardiovascular diseases, NAFLD, and hyperuricemia. Based on these observations, ANSES proposed to set a maximum limit to the intake of total sugars containing fructose (sucrose, glucose⁻fructose syrups, honey or other syrups, and natural concentrates, etc.) of 100 g/day.

Skin collagen pentosidine and fluorescence in diabetes were predictors of retinopathy progression and creatininemia increase already 6years after punch-biopsy.

OBJECTIVE: Advanced glycation end products (AGEs) of collagens appear to contribute to microvascular complications in diabetes. Do high concentrations of AGEs in skin collagen predict accelerated progression of these complications after 6 years and indicate the need for tighter anti-diabetic treatment? DESIGN AND METHODS: We measured two AGE parameters in collagen extracted from skin punch-biopsies: pentosidine and fluorescence at 370/440nm, as markers and predictors of microvascular complications, in 30 patients with diabetes (14 type-1, 16 type-2) without renal insufficiency, and in age- and gender-matched normoglycemic controls, followed at Hôtel-Dieu in Paris. RESULTS: At the time of biopsy, marked increases in pentosidine (p=0.0014) and fluorescence (p=0.0001) expressed per collagen hydroxyproline, were found in the patients with diabetes versus the controls. A significant effect of age was found for pentosidine, but not fluorescence, measurements in the normoglycemic controls. Therefore pentosidine but not fluorescence results were corrected for age in the patients. Pentosidine and fluorescence were correlated with diabetes duration. Fluorescence was significantly dependent on retinopathy presence and score in type-1 and type-2 diabetes, whereas pentosidine was not. Fluorescence was correlated with microalbuminuria only in type-1 diabetes. Neither fluorescence nor pentosidine were correlated with creatininemia. Already six years after biopsy, retinopathy score progression and creatininemia increase were significantly correlated with initial pentosidine and fluorescence measurements. CONCLUSIONS: These AGEs are good predictors of progression of microvascular complications and appear to be pathogenic. High skin concentrations of AGEs should induce tighter anti-diabetic treatment.

Erratum to: Review of the nutritional benefits and risks related to intense sweeteners.

[This corrects the article DOI: 10.1186/s13690-015-0092-x.].

Pathophysiology of hypertension: interactions between macro and microvascular alterations through endothelial dysfunction.

Hypertension is a multifactorial systemic chronic disorder through functional and structural macrovascular and microvascular alterations. Macrovascular alterations are featured by arterial stiffening, disturbed wave reflection and altered central to peripheral pulse pressure amplification. Microvascular alterations, including altered wall-to-lumen ratio of larger arterioles, vasomotor tone abnormalities and network rarefaction, lead to disturbed tissue perfusion and susceptibility to ischemia. Central arterial stiffness and microvascular alterations are common denominators of organ damages. Vascular alterations are intercorrelated, amplifying the haemodynamic load and causing further damage in the arterial network. A plausible precursor role of vascular alterations in incident hypertension provides new insights for preventive and therapeutic strategies targeting macro and microvasculature. Cumulative metabolic burden and oxidative stress lead to chronic endothelial injury, promoting structural and functional vascular alterations, especially in the microvascular network. Pathophysiology of hypertension may then be revisited, based on both macrovascular and microvascular alterations, with a precursor role of endothelial dysfunction for the latter.

Treatment for 2 mo with n 3 polyunsaturated fatty acids reduces adiposity and some atherogenic factors but does not improve insulin sensitivity in women with type 2 diabetes: a randomized controlled study.

BACKGROUND: Information is lacking on the potential effect of n-3 polyunsaturated fatty acids (PUFAs) on the adipose tissue of patients with type 2 diabetes. OBJECTIVE: We evaluated whether n-3 PUFAs have additional effects on adiposity, insulin sensitivity, adipose tissue function (production of adipokines and inflammatory and atherogenic factors), and gene expression in type 2 diabetes. DESIGN: Twenty-seven women with type 2 diabetes without hypertriglyceridemia were randomly allocated in a double-blind parallel design to 2 mo of 3 g/d of either fish oil (1.8 g n-3 PUFAs) or placebo (paraffin oil). RESULTS: Although body weight and energy intake measured by use of a food diary were unchanged, total fat mass (P < 0.019) and subcutaneous adipocyte diameter (P < 0.0018) were lower in the fish oil group than in the placebo group. Insulin sensitivity was not significantly different between the 2 groups (measured by homeostasis model assessment in all patients and by euglycemic-hyperinsulinemic clamp in a subgroup of 5 patients per group). By contrast, atherogenic risk factors, including plasma triacylglycerol (P < 0.03), the ratio of triacylglycerol to HDL cholesterol (atherogenic index, P < 0.03), and plasma plasminogen activator inhibitor-1 (P < 0.01), were lower in the fish oil group than in the placebo group. In addition, a subset of inflammation-related genes was reduced in subcutaneous adipose tissue after the fish oil, but not the placebo, treatment. CONCLUSIONS: A moderate dose of n-3 PUFAs for 2 mo reduced adiposity and atherogenic markers without deterioration of insulin sensitivity in subjects with type 2 diabetes. Some adipose tissue inflammation-related genes were also reduced. These beneficial effects could be linked to morphologic and inflammatory changes in adipose tissue. This trial was registered at clinicaltrials.gov as NCT0037.

[Apollinaire Bouchardat and diabetes]. / Apollinaire Bouchardat et le diabète.

Apollinaire Bouchardat (1806-1886) begins its hospital formation by the pharmacy internship and then starts his medical studies. He becomes chief pharmacist of the Hôtel-Dieu in 1835 and during 20 years, he devotes his life to the study of diabetes. Through observations and experiments, he builds new concepts allowing to establish the bases of clinical diabetology due to a solid competence in fundamental sciences and his intelligence in semiologic observations. He studied urine glucose as a reflect of the clinical state of the patients and, in order to carry out its exact measurement, he recommended the use of the polarimeter. He engaged himself in many studies concerning well as the patients diet as to their way of life. Thus he recommended a large decrease in starchy foods and sugars, he encouraged physical exercise and considered that, since the assumption of responsibility of the diabetic was serious, it could foresee the remission of disease. Due to encouraging results, he developed self-monitoring by the patients by the means of simple chemical reagents, convinced that making patients responsible, despite difficulties of the diet, could modify their attitude. Precursor of the modern diabetology, one can consider that he founded it as a true medical discipline. Its major work: De la Glycosurie ou diabète sucré, son traitement hygénigue is pro-bably the first textbook on diabetes, associating clinical observations, experimental steps and proposals for a treatment based on the patients' way of life: mainly diet and exercise: still preached steps, a hundred and fifty years later.

Low glycemic index foods should play a role in improving overall glycemic control in type-1 and type-2 diabetic patients and, more specifically, in correcting excessive postprandial hyperglycemia.

There is a large bulk of evidence that using low glycemic index (GI) foods has a very significant impact on the amelioration of metabolic disturbances observed in diabetic and/or hyperlipidemic patients and in subjects affected by the metabolic syndrome. Studies bringing convincing evidence against this concept are very rare if any. Improvement is observed not only in postprandial blood glucose and insulin variations but also in circulating plasma lipid levels and the morphology and function of adipocytes. Using the concept of low GI foods in diet counseling of diabetic patients is not exclusive of other measures to improve postprandial and overall blood glucose control. On the contrary, the use of low GI foods should be considered as one of other means and tools available to improve diabetes control (such as other dietary modifications, use of specific and nonspecific drug therapy altering postprandial blood glucose). Among these therapies, the most promising ones are alpha-glucosidase inhibitors, glynides, rapid insulin analogues and in the near future the GLP1 analogue. Again, all these classes of drugs could be associated with one another in order to obtain a postprandial delta excursion target of not below 20 and not above 40-50 mg/dl blood glucose.

Dietary fish oil positively regulates plasma leptin and adiponectin levels in sucrose-fed, insulin-resistant rats.

Insulin resistance and adiposity induced by a long-term sucrose-rich diet (SRD) in rats could be reversed by fish oil (FO). Regulation of plasma leptin and adiponectin levels, as well as their gene expression, by FO might be implicated in these findings. This study was designed to evaluate the long-term regulation of leptin and adiponectin by dietary FO in a dietary model of insulin resistance induced by long-term SRD in rats and to determine their impact on adiposity and insulin sensitivity. Rats were randomized to consume a control diet (CD; n = 25) or an SRD (n = 50) for 7 mo. Subsequently, the SRD-fed rats were randomized to consume SRD+FO or to continue on SRD for an additional 2 mo. Long-term SRD induced overweight and decreased both plasma leptin and adiponectin levels without change in gene expression. Dyslipidemia, adiposity, and insulin resistance accompanied these modifications. Shifting the source of fat to FO for 2 mo increased plasma levels of both adipokines, reversed insulin resistance and dyslipidemia, and improved adiposity. These results were not associated with modifications in gene expression. These results suggest that increasing both adipokines by dietary FO might play an essential role in the normalization of insulin resistance and adiposity in dietary-induced, insulin-resistant models.

Association between a protein polymorphism in the start codon of the vitamin D receptor gene and severe diabetic retinopathy in C-peptide-negative type 1 diabetes.

CONTEXT: The vitamin D (VD) receptor (VDR) is extensively expressed in retina. The plasma concentration of 1,25-dihydroxyvitamin D3 has been inversely correlated with the severity of diabetic retinopathy (DR), which raises the possibility that VD, through its antiinflammatory, antioxidant, antiproliferative, and antiangiogenic properties, may protect diabetic retina. The TaqI VDR polymorphism has been associated with severe DR. The FokI VDR polymorphism is a T-to-C substitution in the first codon (f allele), abolishing the first translation initiation site and resulting in a peptide lacking three amino acids (F allele), which increases the transcriptional activity of VDR. OBJECTIVE AND DESIGN: To examine whether FokI polymorphism is involved in severe DR, 254 Caucasians with longstanding C-peptide-negative type 1 diabetes, 128 patients with absent/mild DR (control group), and 126 patients with preproliferative/proliferative DR (study group) were genotyped using PCR-restriction fragment length polymorphism analysis. RESULTS: The genotype distribution was in Hardy-Weinberg equilibrium and was different between groups (P = 0.046). The frequency of F allele was significantly higher in the control (66.4%) than in the study group (56%, odds ratio = 0.64, 95% confidence interval 0.44-0.92, P = 0.016). In subjects with fewer than 25 yr of diabetes duration (median value, n = 134), this association was strongly increased (P = 0.0008). CONCLUSIONS: In conclusion, we observed, in a cohort of Caucasians with C-peptide-negative type 1 diabetes, a novel association between the functional FokI VDR polymorphism and severe DR, especially among subjects with fewer than 25 yr of diabetes duration.

The T-786C and C774T endothelial nitric oxide synthase gene polymorphisms independently affect the onset pattern of severe diabetic retinopathy.

Genetic factors could be implicated in the pathogenesis of severe diabetic retinopathy (DR). Recently, we reported a strong association between the eNOS4b/a endothelial nitric oxide synthase (eNOS) polymorphism and severe DR. To examine whether T-786C and C774T eNOS polymorphisms are involved in severe DR, 254 Caucasians with longstanding C-peptide-negative type 1 diabetes, 128 patients with absent/mild DR (control group), and 126 patients with preproliferative/proliferative DR (study group) were genotyped. The distribution of T-786C and C774T eNOS polymorphisms was in Hardy-Weinberg equilibrium and did not differ between the study and control groups. However, in case patients (n=126), T-786C and C774T polymorphisms influenced the onset pattern of severe DR (P=0.0169 and P=0.0257, respectively). The C-786C genotype was associated with early-onset severe DR (duration of diabetes: 15.2+/-5.9 vs. 19.4+/-6.3 years, P=0.0105), and the homozygous T774T genotype was associated with late-onset severe DR (24.3+/-7.0 vs. 18.4+/-6.2 years, P=0.0067). In the case of patients with high glycosylated hemoglobin levels (HbA1c >8%, n=88), the association between the T-786C polymorphism and early-onset severe DR was stronger (P=0.0068). Case patients carrying the C-786C genotype had higher HbA1c values (9.61+/-1.89%) than those carrying the T-786T genotype (8.93+/-1.47%, P=0.0173). Multivariate analysis showed that T-786C polymorphism was the best independent factor for onset pattern of severe DR (P<0.001). These findings, supported by previous associations between eNOS4b/a polymorphism and DR, suggest that T-786C and C774T eNOS polymorphisms affect the onset pattern of severe DR.

Improved plasma glucose control, whole-body glucose utilization, and lipid profile on a low-glycemic index diet in type 2 diabetic men: a randomized controlled trial.

OBJECTIVE: To determine whether a chronic low-glycemic index (LGI) diet, compared with a high-glycemic index (HGI) diet, has beneficial effects on plasma glucose control, lipid metabolism, total fat mass, and insulin resistance in type 2 diabetic patients. RESEARCH DESIGN AND METHODS: Twelve type 2 diabetic men were randomly allocated to two periods of 4 weeks of an LGI or HGI carbohydrate diet separated by a 4-week washout interval, in a crossover design. RESULTS: The LGI diet induced lower postprandial plasma glucose and insulin profiles and areas under the curve than after the HGI diet. At the end of the two dietary periods, the 7-day dietary records demonstrated equal daily total energy and macronutrient intake. Body weight and total fat mass were comparable. Four-week LGI versus HGI diet induced improvement of fasting plasma glucose (P < 0.01, Delta changes during LGI vs. HGI), HbA(1c) (P < 0.01), and whole-body glucose utilization measured by the euglycemic-hyperinsulinemic clamp (P < 0.05). LGI diet induced a decrease in fasting plasma total and LDL cholesterol (Delta changes LGI vs. HGI, P < 0.01), free fatty acids (P < 0.01), apolipoprotein B, and plasminogen activator inhibitor 1 activity. CONCLUSIONS: Only 4 weeks of an LGI diet was able to improve glycemic control, glucose utilization, some lipid profiles, and the capacity for fibrinolysis in type 2 diabetes. Even if changes in glycemic control were modest during the 4-week period, the use of an LGI diet in a longer-term manner might play an important role in the treatment and prevention of diabetes and related disorders.

Dietary fish oil increases lipid mobilization but does not decrease lipid storage-related enzyme activities in adipose tissue of insulin-resistant, sucrose-fed rats.

Fish oil feeding has been shown to limit visceral fat accumulation in insulin-resistant rats. Our goal was to determine whether this finding is due to increased fat mobilization or decreased lipid storage. Adipocytes were isolated from rats fed for 3 wk a diet containing 57.5 g/100 g sucrose and 14 g/100 g lipids as either fish oil (SF) or a mixture of standard oils (SC); there was also a reference group (R). Substituting fish oil for standard oils protected rats from visceral fat hypertrophy, hypertriglyceridemia and hyperglycemia. The stimulation of lipolysis was greater in adipocytes isolated from SF-fed rats than in those from SC-fed rats. Fatty acid synthase (FAS) activity was markedly lower in the liver but not in the adipose tissues of rats fed SF. Lipoprotein lipase (LPL) activity was 2.2-fold higher in the adipose tissues but not in the muscle in rats fed the SF diet than in those fed the SC diet. The decrease in visceral fat in rats fed fish oil could be attributed to decreased plasma triacylglycerol concentration and/or increased lipid mobilization rather than to reduced lipid storage.

Dietary (n-3) polyunsaturated fatty acids up-regulate plasma leptin in insulin-resistant rats.

The study was designed to evaluate the chronic regulation of plasma leptin by dietary (n-3) polyunsaturated fatty acids (PUFA) in insulin-resistant, sucrose-fed rats. Male Sprague-Dawley rats were randomly assigned to consume for 3 or 6 wk a diet containing 57.5% (g/100 g) sucrose and 14% lipids as either fish oil (SF) or control oils (SC). After 3 and 6 wk of consuming the SF diet, plasma leptin was 70% (P < 0.001) and 75% (P < 0.05) greater, respectively, than in rats fed the SC diet. The same result was found when plasma leptin was adjusted by total fat mass, as measured by dual-energy X-ray absorptiometry. Despite high leptin levels, food intake of rats fed the SF diet was greater than in SC-fed rats without any difference in body weight or total fat mass. After 3 wk, accumulated leptin in epididymal and retroperitoneal adipose tissue was higher in the SF-fed rats than in the SC-fed rats. However, after 6 wk, tissue leptin in the SF-fed rats did not differ from that of the SC-fed rats. The SF diet increased adipose tissue glucose transporter-4 protein quantity and prevented the sucrose-induced elevations in plasma triglycerides and free fatty acids. When all SC- and SF-fed rats (both diets and feeding durations) were considered, plasma leptin levels were positively correlated with body weight (r = 0.5, P < 0.0001) and with total fat mass (r = 0.5, P < 0.0005). These results suggest that plasma leptin at a given time could be inappropriately high for a given fat mass in insulin-sensitive rats fed (n-3) PUFA.

Four-week low-glycemic index breakfast with a modest amount of soluble fibers in type 2 diabetic men.

Low-glycemic index diets are associated with a wide range of benefits when followed on a chronic basis. The chronic effects, however, of the substitution of 1 meal per day are not well known in diabetic subjects. Therefore, we aimed to evaluate whether the chronic use of a low-glycemic index breakfast (low-GIB) rich in low-GI carbohydrates and a modest amount of soluble fibers could have an effect on lipemia at a subsequent lunch, and improve glucose and lipid metabolism in men with type 2 diabetes. A total of 13 men with type 2 diabetes were randomly allocated in a double-blind cross-over design to a 4-week daily intake of a low-GI versus a high-GI breakfast separated by a 15-day washout interval. The low-GI breakfast was composed of whole grain bread and muesli containing 3 g beta-glucan from oats. Low-GIB induced lower postprandial plasma glucose peaks than the high-GIB at the beginning (baseline, P <.001) and after the 4-week intake (P <.001). The incremental area under the plasma glucose curve was also lower (P <.001, P <.01, baseline, and 4 weeks, respectively). There was no effect on fasting plasma glucose, insulin, fructosamine, or glycosylated hemoglobin (HbA(1c)). Fasting plasma cholesterol, as well as the incremental area under the cholesterol curve, were lower (P <.03, P <.02) after the 4-week low-GIB period than after the high-GIB period. Apolipoprotein B (apo B) was also decreased by the 4-week low-GIB. There was no effect of the low-GI breakfast on triacylglycerol excursions or glucose and insulin responses at the second meal. The high-GIB, however, tended to decrease the amount of mRNA of leptin in abdominal adipose tissue, but had no effect on peroxisome proliferator-activated receptor gamma (PPARgamma) and cholesterylester transfer protein (CETP) mRNA amounts. In conclusion, the intake of a low-GI breakfast containing a modest amount (3 g) of beta-glucan for 4 weeks allowed good glycemic control and induced low plasma cholesterol levels in men with type 2 diabetes. The decrease in plasma cholesterol associated with low-GI breakfast intake may reduce the risk of developing cardiovascular complications in subjects with type 2 diabetes.

The effect of Type I diabetes on the eating patterns of free-living French: a diet diary study.

In order to investigate the changes produced by Type I diabetes on the ad libitum eating behavior of free-living humans, 56 French participants with diabetes and 28 healthy controls were paid to maintain detailed food intake diaries for four 7-day periods. The participants with diabetes ate more protein and more frequent meals, ate slightly later and with fewer other people, were less hungry, thirsty, and depressed, but more elated than the healthy participants. Responses to social facilitation, the diurnal rhythm, subjective hunger, the palatability of the food, and the weekend were not affected by the presence of diabetes. The participants with diabetes had significantly larger correlations and regression coefficients for the relationship between meal size and the duration of the before-meal interval. The relationship between meal size and the after-meal interval was strong and positive in all participants. The recorded behavioral characteristics of diabetics may, in part, be accounted for by the nutritional education that is provided as an integral part of treatment. Based upon these results, it was theorized that the glucose regulatory system is an influence on intake, but only one of many that are responsible for the coordination, control, and regulation of nutrient intake in free-living humans.

Five-week, low-glycemic index diet decreases total fat mass and improves plasma lipid profile in moderately overweight nondiabetic men.

OBJECTIVE: To evaluate whether a 5-week low-glycemic index (LGI) diet versus a high-glycemic index (HGI) diet can modify glucose and lipid metabolism as well as total fat mass in nondiabetic men. RESEARCH DESIGN AND METHODS: In this study, 11 healthy men were randomly allocated to 5 weeks of an LGI or HGI diet separated by a 5-week washout interval in a crossover design. RESULTS: The LGI diet resulted in lower postprandial plasma glucose and insulin profiles and areas under the curve (AUCs) than the HGI diet. A 5-week period of the LGI diet lowered plasma triacylglycerol excursion after lunch (AUC, P < 0.05 LGI vs. HGI). These modifications were associated with a decrease in the total fat mass by approximately 700 g (P < 0.05) and a tendency to increase lean body mass (P < 0.07) without any change in body weight. This decrease in fat mass was accompanied by a decrease in leptin, lipoprotein lipase, and hormone-sensitive lipase RNAm quantities in the subcutaneous abdominal adipose tissue (P < 0.05). CONCLUSIONS: We concluded that 5 weeks of an LGI diet ameliorates some plasma lipid parameters, decreases total fat mass, and tends to increase lean body mass without changing body weight. These changes were accompanied by a decrease in the expression of some genes implicated in lipid metabolism. Such a diet could be of benefit to healthy, slightly overweight subjects and might play a role in the prevention of metabolic diseases and their cardiovascular complications.