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Biomedical subjects

B Guerci

Publications and source records attributed to B Guerci.

At least 19 recordsLinked to original sources

Differences in serum GH cut-off values for pharmacological tests of GH secretion depend on the serum GH method. Clinical validation from the growth velocity score during the first year of treatment.

BACKGROUND: The serum GH cut-off value for pharmacological tests of GH secretion (PhT GH) depends on the type of test and also on the method used for determining serum GH. Cut-off serum GH values as different as 5-10 ng/ml, have been reported, and have been validated biochemically. We have used the growth velocity (GV)-standard deviation score (SDS) during the first year of treatment with rhGH to validate these cut-offs on a biological basis. METHODS: Fifty pre-pubertal patients with short stature (height < or =-2 SDS and GV < or =-1.2 SDS) were studied. GH deficiency (GHD) was diagnosed in 39 patients, on the basis of clinical and auxological parameters and on the serum concentration of IGF-1, and non-GHD in the other 11 patients. Two PhT GH (arginine and clonidine) were carried out in the 50 patients. Serum GH was determined by two different methods: one detecting most of serum GH isoforms, named Total GH (HGH Bio-Tech, MAIA Clone), and another one, only detecting the 22 kDa GH, named 22K GH (GH-22K IFMA, Wallac). RESULTS: Basal data: all patients with GHD and with non-GHD had maximal serum GH response (MaxR) values below and above the cut-off, respectively, for the serum Total GH and 22K GH. The mean 22K GH/Total GH ratio was similar to previous publications. Post-rhGH treatment data: the two groups improved their height SDS during the first year of treatment, particularly patients with GHD. A receiver-operator curve was used to define the best threshold for post-treatment GV-SDS that separates GHD from non-GHD patients. This value was 1.91 GV-SDS. A negative correlation between first year treatment GV-SDS and pre-treatment serum GH MaxR was found for the two assays (p < 0.001). Then, the best cut-off GV-SDS, previously calculated with the receiver-operator curve (1.91 SDS) was used to interpolate the corresponding serum GH values, as determined by the two methods. For Total GH, the value was 10.8 ng/ml, and for 22K GH, it was 5.4 ng/ml. CONCLUSION: The cut-off values calculated by biological means to separate GHD from non-GHD were remarkably similar to those calculated biochemically (10.0 and 4.8 ng/ml, respectively) for Total and 22K GH. This is a biological validation for using different cut-off values, appropriate for each assay, to diagnose GHD.

Adolescent↗

Continuous intraperitoneal insulin infusion does not increase the risk of organ-specific autoimmune disease in type 1 diabetic patients: results of a multicentric, comparative study.

AIM: The purpose of this national multicenter prospective study by the French EVADIAC group was to investigate the possibility that continuous intraperitoneal insulin infusion using an implanted pump (CIpii) increases the risk of autoimmune disease in type 1 diabetic patients as it increased anti-insulin immunogenicity. METHODS: Prevalence of clinical (Hashimoto's disease, hyperthyroidism, gastric atrophic disease and vitiligo) and subclinical (presence of anti-thyroperoxidase antibodies, anti-intrinsic factor antibodies, abnormal TSH levels) autoimmune diseases was estimated by comparing two groups of patients already treated by either CIpii (n=154) or external pump (CSII) (n=121) for an average of 6 years. Incidence of autoimmune disease was determined by comparing the same measurements one year after inclusion. RESULTS: No significant difference was observed for the total prevalence of clinical and subclinical auto-immune thyroid and gastric di-seases (35.6% and 3.2% respectively in the CIpii group versus 40.4% and 2.6% in the CSII group). No significant difference for the incidence of clinical and subclinical auto-immune diseases was observed: 7.2% and 0% in CIpii and 7.3% and 1.7% in CSII. CONCLUSION: As previously shown AIA (anti-insulin antibodies) levels were higher in CIpii than in CSII (32.9% vs 20.2%, P<0.0001) but no correlation was observed with either clinical or subclinical autoimmune disease. This large-scale study eliminates the possibility that CIpii increases the risk of autoimmune disease.

Adult↗

Subcutaneous insulin: pharmacokinetic variability and glycemic variability.

The therapeutic goal in insulin-treated diabetic patients is to maintain on the long-term a tight glucose control (HbA1, < 6.5-7% or less) through an insulin regimen which "mimic" the physiological insulin profile: a basal insulin secretion to maintain glucose homeostasis and an acute post-prandial secretion in response to meal intake. Such goal represents a challenge for the clinician as conventional human insulins have major drawbacks: slow absorption and too late peak with regular insulins, delayed peak and often occuring at an unwanted time with intermediate and long-acting insulins. Furthermore, these insulins are characterised by a large within- and between-subjects variability, which complicate patients' task to self-adapt their daily doses, even for those well educated and compliants. These limitations and unpredictable variations in insulin action are responsible for an increased risk of hypoglycemic events, between meals as well as during the night period. As a consequence, glucose control is frequently insufficient in type 1 diabetic patients, and these limitations may contribute also to the delayed initiation of insulin therapy in type 2 diabetics when oral antidiabetic agents fail. This variability and the non-reproducibility of the conventional insulin pharmacodynamics are explained by several exogenous and endogenous factors describe in this review. Availability of new short-acting (lispro, aspart and glulisine) and long-acting analogs (glargine, detemir) of human insulin, with improved pharmacokinetic characteristics, and a lesser variability and better reproducibility, should facilitate a tight glucose control in insulin-treated patients. The main pharmacokinetic and pharmacodynamic characteristics of these new insulin analogs are presented and discussed in the light of there intra- and inter-individual variability. Their reduced variability should permit to reinforce near "physiological" insulin regimen such as "basal-bolus" technique and to consider new approaches and therapeutic strategies in type 1 and type 2 diabetic patients.

Blood Glucose↗

Advantages to using capillary blood beta-hydroxybutyrate determination for the detection and treatment of diabetic ketosis.

Ketone body determination is indicated in all diabetic patients when the risk of ketotic decompensation exists. New methods of screening for ketosis, in particular capillary blood ketone body determination, provide analytical, technical and clinical advantages compared to the conventional ketonuria. It is proposed that a diabetic patient with hyperglycaemia (capillary blood glucose > 2.50 g.l(-1)) and capillary blood ketone bodies exceeding 0.5 mmol.l(-1) requires therapeutic management. For values greater than 3 mmol.l(-1) or in case of more serious clinical symptoms, hospitalisation is indicated, considering the high probability of ketoacidotic decompensation. The advantages of capillary blood ketone body determination including easy use, and rapid and objective results may improve management of the diabetic patient, especially in emergency situations. However, prescription by a physician of capillary blood ketone body determination should be offered to targeted populations that have a high risk of ketoacidotic decompensation, after providing education to patients that is above all aimed at preventing this metabolic complication. In this context of determining ketone bodies in capillary blood, the term "capillary blood ketone bodies" is therefore preferable to the term "capillary blood beta-hydroxybutyrate determination". Indeed, it appears more appropriate, simple, descriptive and significant both for health-care staff and for patients.

3-Hydroxybutyric Acid↗

[Glitazones clinical data: an update].

The thiazolidinediones (or glitazones) were recently added to the oral treatments for type 2 diabetes. Several recent studies, either in in vitro models or in animal models, lead to a better understanding of their mechanism of action. Recent, long term, controlled clinical studies, permit to define better their place and their condition of use (including adverse event prevention), as a monotherapy, or in association with metformin or a sulfonylurea when these drugs failed to achieve an optimal glycemic control. The beneficial metabolic effects of glitazones, generate great hopes for the prevention of the progressive beta-pancreatic cell function decline observed in type 2 diabetics, and possibly to prevent and/or to delay type 2 diabetes in high at-risk subjects. This review describe and discuss the most recent studies and their results.

Blood Glucose↗

[Continuous glucose monitoring: which benefits?].

Continuous glucose monitoring is a recent technique which appears to be highly useful in diabetic patients, particularly in children and adolescents. Its potential interest to study unstable diabetes, to detect asymptomatic and nocturnal hypoglycaemias, to adapt and/or to adjust insulin treatment, etc. has lead to several recent clinical studies, conducted in various conditions. The different techniques, the studies conducted in children and adult diabetic patients, as well as the main current indications for continuous glucose monitoring are described in this article.

Blood Glucose Self-Monitoring↗

Heterogeneity of diabetes phenotype in patients with 3243 bp mutation of mitochondrial DNA (Maternally Inherited Diabetes and Deafness or MIDD).

OBJECTIVE: In patients with maternally inherited diabetes and deafness (MIDD), due to 3 243 A > G mutation of mitochondrial DNA (mtDNA), diabetes may present with variable phenotypes. OBJECTIVE: To ascertain the existence of two distinct phenotypes, MIDD1 and MIDD2, in a series of patients with MIDD. DESIGN: Multicenter prospective study. PATIENTS: 77 patients with diabetes and the mtDNA 3243 mutation and 139 control patients with type 1 (T1D) or type 2 (T2D) diabetes, matched according to initial presentation of diabetes, age at onset, sex, and duration of diabetes (24 T1D and 115 T2D, including 55 treated with insulin). MEASUREMENTS: Anthropometric characteristics (height, body weight, body mass index [BMI], sex), family history of diabetes, and characteristics of diabetes (age at onset, treatment, hemoglobin A1c [HbA1c]), extrapancreatic manifestations. RESULTS: In 13 cases (17%, MIDD1), diabetes presented as insulin-dependent from the onset, with ketoacidosis in 6 cases. In 64 cases (83%, MIDD2), diabetes resembled T2D, and was treated with diet in 12 cases, oral hypoglycemic agents in 21 cases, or insulin in 31 cases. Compared with patients with MIDD2, patients with MIDD1 were characterized by lower age at onset of first manifestation of MIDD (25.4 +/- 9.6 vs 33.7 +/- 13.2 Years, P<0.0005), lower body weight (49.1 +/- 7.4 vs 56.3 +/- 10.9 kg, P<0.0025), lower BMI (18.2 +/- 2.3 vs 20.9 +/- 3.6 kg/m2, P<0.0005), and higher HbA1c levels (9.5 +/- 2.0 vs 7.5 +/- 1.6%, P<0.0005). Frequency of family history of diabetes and of extrapancreatic manifestations was the same in both MIDD subtypes. No difference was found within the MIDD2 subtype when comparing patients treated with or without insulin. Compared with matched controls, patients with MIDD had a lower BMI (MIDD1/T1D 18.2 +/- 2.3 vs 24.0 +/- 3.6 kg/m2 and MIDD2/T2D 20.9 +/- 3.6 vs 30.2 +/- 5.9 kg/m2, P<0.0025). Lastly, male patients with MIDD had a shorter height than controls (MIDD1/T1D: 166.1 +/- 3.2 vs 177.3 +/- 6.6 cm and MIDD2/T2D: 168.4 +/- 7.2 vs 173.6 +/- 6.6 cm P<0.025). CONCLUSIONS: These results confirm the existence of two different phenotypes in MIDD, MIDD1 and MIDD2, which may be related to the severity of the mitochondrial disease. The role of other genetic and/or environmental factors in the variable phenotype of MIDD remains to be elucidated.

Adult↗

Self-monitoring of blood glucose significantly improves metabolic control in patients with type 2 diabetes mellitus: the Auto-Surveillance Intervention Active (ASIA) study.

OBJECTIVE: Self monitoring of blood glucose (SMBG) in type 2 diabetes is a topic of current interest (imbalance between increased health-care costs and improvement in compliance with treatment and diet). An open label randomized prospective study was designed to compare changes in metabolic control over 6 months in patients managed with usual recommendations alone (conventional assessment group) or combined with SMBG. RESEARCH DESIGN AND METHODS: Patients not treated with insulin or previously self monitored, 40 to 75 years of age, with a diagnosis of type 2 diabetes > 1 year and standardized HbA(1c) level > =7.5 and< =11% were randomized to either a control group or SMBG group. They were followed up every 6 weeks over 24 weeks. Patients in the SMBG group were given the same device (Ascensia Esprit Discmeter, Bayer) and were required to perform at least 6 capillary assays a week (3 different days of the week, including weekend). Management of patients was standardized, including drugs, diet and physical activity. The primary efficacy criterion was change in HbA(1c) level in Intent To Treat (ITT) patients. Assays were performed at baseline, at 3 and 6 months using the calibrated DCA 2000(R) device (Bayer). RESULTS: Two hundred sixty five general practitioners randomized 988 patients (ITT Population), but 689 patients were evaluable for the primary criterion. At the endpoint, HbA(1c) was lower in the SMBG group (8.1 +/- 1.6%) than in the conventional treatment group (8.4 +/- 1.4%, P=0.012). The change in HbA(1c) levels between baseline and endpoint was classified into two classes: improvement if a change > 0.5% occurred, stability or worsening in case of a change< =0.5%; 57.1% of patients in the SMBG group vs 46.8% in the control group had an improvement in HbA(1c) level (P=0.007) after 3 months. A steady state was reached during the last 3 months. A multivariate logistic regression analysis was performed and identified factors predictive of improvement in HbA(1c) levels: HbA(1c) at baseline: odd ratio (OR)=1.749 (P<0.001), SMBG group (reference value: SMBG group): OR=0.665 (P=0.015), duration of diabetes: OR=0.953 (P=0.001) and BMI: OR=0.962 (P=0.039). CONCLUSIONS: This study is the first multicenter, controlled, prospective trial conducted on a large number of patients demonstrating that SMBG was statistically associated with a better quality of metabolic control than usual traditional recommendations alone in type 2 diabetes.

Adult↗

Combined improvements in implantable pump technology and insulin stability allow safe and effective long term intraperitoneal insulin delivery in type 1 diabetic patients: the EVADIAC experience.

OBJECTIVE: To report a long-term multicentre experience with implantable insulin pumps in type 1 diabetic patients, and to test safety and accuracy of the systems following improvements in infused insulin solutions and peritoneal catheter. RESEARCH DESIGN AND METHODS: Forty MiniMed Implantable Pumps model 2001 were consecutively implanted over a two-month period in type 1 diabetic volunteers. The systems were equipped by a new compliant sideport catheter and were refilled at 45-day intervals with HOE 21 PH ETP insulin batches showing enhanced physical stability in vitro. Safety was assessed from the incidence of acute adverse events and effectiveness from quarterly HbA(1c) assays. Accuracy of delivery was measured at each pump refill by comparing residual insulin in the pump reservoir with expected amount according to programmed infusion. The study lasted until pump battery depletion or premature pump explantation. RESULTS: Cumulated experience was 106 patient-years. Premature explantations occurred in 3 cases, due to one electronic pump failure and two "pump-pocket" infections. Near-normal insulin delivery was sustained until expected battery depletion in 13 cases. Forty underdelivery events occurred in 24 pumps, but 36 among them were related to pump slowdowns due to insulin aggregation in pumps that were promptly solved by an outpatient NaOH rinse procedure. Only 4 underdeliveries were caused by catheter obstructions that required laparoscopy to remove peritoneal tissue overgrowth around the catheter. Over pump lifetime, HbA(1c) was 7.2 +/- 0.2% in the 13 patients with no underdelivery and 7.7 +/- 0.5% in the other ones. Only one severe hypoglycemia and one ketoacidosis occurred during the whole study. CONCLUSION: Our current experience with improved implantable pumps and insulin solutions shows both long-term safety and effectiveness of this treatment in type 1 diabetic patients following improvement in infused insulin solutions and catheter. This therapy may be a good alternative for patients that experience frequent severe hypoglycemia with intensive subcutaneous insulin therapy.

Adult↗

[Asymptomatic glycemic instability: how to measure it and which clinical applications? ].

The glycemic variations observed in nondiabetic subjects are primarily related to the post-prandial metabolic responses generated by the food intake. This physiological glycemic variability is reproducible between two successive days under conditions of similar meals and activities. In insulin-treated diabetic patients, glycemic instability is directly related to loss of glucose homeostasis due to the failure then the deficiency of endogenous insulin secretion, but its physiopathological implication in term of diabetic angiopathy risk remains to be determined. Other exogenous glycemic instability factors are known and have to be corrected (not adapted repartition of the meals and/or the insulin doses during the day, inappropriate choices in insulin regimens, errors in insulin adjustments, inadequate insulin injection). Classical glycemic measurements used to appreciate the quality of the glycemic control do not provide or give partial and erroneous information on quality of glycemic stability. It's particularly the case for glycated hemoglobin and glycemic average. In order to exactly quantify glycemic variability, specific tools of measurement or calculation can evaluate the intra-day glycemic variations or excursions (MAGE), the day-to-day glycemic variations or excursions (MODD), the meal-related glycemic excursions (MIME) or the risk of severe hypoglycemia (LBGI). Some of these tools are easy to use, other much complex or difficult to apply in clinical practice, even by using new methods such as the continuous glucose monitoring system (CGMS). Thus, asymptomatic glycemic variability is related to loss of glucose homeostasis, but also to irrelevant or incompatibility of the treatments used to obtain glucose control in insulin-treated diabetic patients. The evaluation of glucose instability can be provided using new methods of glucose monitoring and could be useful to optimize the therapeutic regimens in some of these diabetic patients.

Blood Glucose↗

Maternally inherited diabetes and deafness: a multicenter study.

BACKGROUND: Maternally inherited diabetes and deafness (MIDD), which is seen in 0.5% to 2.8% of patients with type 2 diabetes mellitus, is related to a point mutation at position 3243 of mitochondrial (mt) DNA. Its clinical description is incomplete. OBJECTIVE: To study the clinical presentation and complications of diabetes in patients with MIDD and to identify clinical characteristics that may help select diabetic patients for mtDNA mutation screening. DESIGN: Multicenter prospective descriptive study. SETTING: 16 French departments of internal medicine, diabetes and metabolic diseases, or both. PATIENTS: 54 patients with type 2 diabetes mellitus and the mtDNA 3243 mutation. MEASUREMENTS: Characteristics of diabetes, metabolic control (glycosylated hemoglobin level), complications of diabetes, and involvement of other organs. RESULTS: On average, patients with MIDD were young at diabetes onset and presented with a normal or low body mass index. None were obese. Seventy-three percent of probands had a maternal family history of diabetes. Diabetes was non-insulin-dependent at onset in 87% of patients; however, 46% of patients had non-insulin-dependent disease at onset but progressed to insulin therapy after a mean duration of approximately 10 years. Neurosensory hearing loss was present in almost all patients. Eighty-six percent of patients who received an ophthalmologic examination had macular pattern dystrophy (a specific retinal lesion). Forty-three percent of patients had myopathy, 15% had cardiomyopathy, and 18% (9 of 51) had neuropsychiatric symptoms. Although the prevalence of diabetic retinopathy was 8% among patients who received an ophthalmologic examination, lower than expected after a mean 12-year duration of diabetes, prevalence of kidney disease was 28%. This suggests that a specific renal involvement was the result of mitochondrial disease. CONCLUSIONS: Maternally inherited diabetes and deafness has a specific clinical profile that may help identify diabetic patients for mtDNA testing.

Adolescent↗

Effect of the inflammation, chronic hyperglycemia, or malabsorption on the apolipoprotein A-IV concentration in type 1 diabetes mellitus and in diabetes secondary to chronic pancreatitis.

The metabolism of apolipoprotein (apo) A-IV in diabetes mellitus (DM) is poorly understood. Several factors, such as dietary fat intake, fat malabsorption, acute inflammation, and hormonal dysregulation can disturb the plasma apo A-IV concentration. We have compared the plasma apo A-IV concentrations in patients with type 1 DM and DM secondary to chronic pancreatitis to determine the effects of combinations of these factors. We examined 4 groups of male patients with chronic pancreatitis without diabetes (ND-CP) (n = 12), diabetes secondary to chronic pancreatitis and insulin-treated (CP-DM) (n = 32), type 1 diabetes (n = 25), and controls (n = 20). Plasma apo A-IV was significantly lower in the chronic pancreatitis patients (ND-CP and CP-DM) than in the other patients. Inflammatory proteins (fibrinogen, ceruloplasmin, and haptoglobin) were significantly elevated in the 2 chronic pancreatitis groups. The apo A-IV concentration was positively correlated with hemoglobin A(1c) (HbA(1c)) percentage in each group of diabetic patients (CP-DM, r =.35; P =.046; type 1 DM, r =.53; P =.010), in both groups of diabetic patients (r =.472; P <.0001) and negatively correlated with ceruloplasmin concentration in each group of diabetic patients (CP-DM, r = -.48; P =.0052; type 1 DM, r = -.66; P =.003), in both groups of diabetic patients (r = -.561; P <.0001), and in the whole population (r = -.463; P <.0001). Apo A-IV was also negatively correlated with haptoglobin in type 1 DM patients (r = -.434; P =.0435), in the both groups of diabetic patients (r = -.349; P =.0154), and in the whole population (r = -.351; P =.0019). Multiple linear regression analysis revealed that only HbA(1c) and ceruloplasmin were independent explanatory variables. Plasma apo A-IV is positively correlated with HbA(1c) suggesting that hyperglycemia per se selectively affects apo A-IV metabolism. The correlation between the concentrations of inflammatory protein and apo A-IV suggest a link between chronic inflammation and apo A-IV synthesis or catabolism. As apo A-IV is involved in reverse cholesterol transport, its low level in CP-DM may contribute to the accelerated development of atherosclerosis in these patients.

Adult↗

Basal and postprandial serum-promoted cholesterol efflux in normolipidemic subjects: Importance of fat mass distribution.

Excess of adipose tissue may affect the reverse cholesterol transport mediated by high-density lipoprotein (HDL). Impairments in this system may be one possible factor favoring atherosclerosis development in obesity. To investigate if gender and regional fat mass distribution independently influence reverse cholesterol transport (RCT), we studied in vitro the capacity of serum to promote the cell cholesterol efflux. Measurements were performed both in the fasting state and in the postprandial state, a setting known to stimulate cholesterol transport and altered in obesity. Thirteen obese women with an android phenotype, waist-to-hip ratio (WHR): 0.98 to 0.85 and 51 normal-weight subjects: 25 women and 26 men, with a similar WHR range: 0.96 to 0.67, were recruited. All the participants were normolipoproteinemic in the fasting state and were given an oral fat load. Blood samples were taken before giving the oral fat load and after every 2 hours. The measurements of the ability of serum to promote cholesterol efflux from cells were performed using 3H-cholesterol labeled Fu5AH hepatoma cells in the fasting state 6 and 8 hours after the lipid rich meal. Incremental serum triglyceride (TG), area under the curve (iAUC) and AUC of retinyl palmitate (RP) for the obese women and nonobese subjects were similar. Basal cholesterol efflux was reduced in obese women compared with normal-weight women (26.75% +/- 3.1% v 30.81% +/- 4.2%, P =.004). However, the magnitude of cholesterol efflux promoted by whole serum increased similarly in all the groups. In the subjects with similar WHR, no gender difference was observed in the postprandial TG response and in the first step of RCT. Multivariate regression analyses indicated that plasma HDL-cholesterol (HDL-C) concentration is the best predictor of cholesterol efflux in the fasting state with an independent mild additive effect of WHR. Conversely, postprandial efflux appeared to be mostly related to the WHR with a mild additive effect of HDL-C. Our results indicate that alterations in the first step of RCT can occur in normolipidemic obese subjects and are tightly associated with the abdominal distribution of fat mass. Android obesity in women brings them to the level of men with respect to RCT.

Administration, Oral↗

Evidence that diabetes mellitus favors impaired metabolism of zinc, copper, and selenium in chronic pancreatitis.

Diabetes mellitus, a common complication of chronic pancreatitis, can disturb the metabolism of zinc, copper, and selenium. We analyzed the effects of hyperglycemia, malabsorption, and dietary intake on these factors in 35 men with alcohol-induced chronic pancreatitis complicated by insulin-treated diabetes mellitus (CP-D), 12 men with chronic pancreatitis but no diabetes (nondiabetic CP), 25 men with type 1 diabetes mellitus (type 1 DM), and 20 control subjects. Diabetes due to chronic pancreatitis was associated with decreased plasma zinc and selenium concentrations and with increased urinary copper excretion. Of the chronic pancreatitis patients, 17% had low plasma zinc, and 41% of them had low plasma selenium. None of the type 1 diabetic patients had low plasma concentrations of zinc, but 12% of them had a low selenium concentration. Hyperglycemia, as assessed by fasting plasma glucose and by plasma HbAlc, was responsible for the increased zinc excretion and the decreased superoxide dismutase activity. The perturbations of the copper, selenium, and zinc metabolism were particularly pronounced in subjects with chronic pancreatitis plus diabetes mellitus. We have yet to determine whether the differences in trace-element status contribute to the clinical expression of the disease.

Adult↗

[Macronutrients, fat mass, fatty acid flux and insulin sensitivity].

Obesity and visceral or upper body fat distribution, have a major impact on insulin sensitivity. There is strong evidence to suggest that free fatty acids (FFA) contribute to the pathogenesis of insulin resistance and the metabolic syndrome. Increased FFA release from adipose tissue or failure of FFA using tissues to remove them normally, lead to increased triglycerides (TG) and FFA fluxes. Increased delivery of FFA to muscle reduces muscle glucose uptake and utilisation by substrate competition or direct inhibition of glucose transport. Insulin resistance has been correlated with the size of intramuscular TG store. Intracellular TG have been involved in beta cell failure the so called lipotoxicity phenomena. The rate of FFA to the liver is a major determinant of hepatic TG secretion. So the regulation of FFA distribution between FFA using tissues and the partition of FFA between storage and oxidation could be involved in the developpment of insulin resistance. The dietary macronutrients could play a role in nutrient partitioning but their role in the etiology of insulin resistance is poorly understood due to a paucity of credible intervention studies in humans. However deleterious effects of saturated fatty acids on insulin action and the beneficial effects of polyunsaturated fatty acids (PUFAs) could be suspected from animal studies, and from epidemiological or clinical studies in humans. A very high intake of sucrose or fructose could be deleterious but low glycemic index foods, and fibers could have protective effects. Weight loss can induce marked improvement in insulin resistance, but weight maintenance is also required to keep long term good metabolic results.

Adipose Tissue↗