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Mean amplitude of glucose excursion (MAGE) is considered as the "gold standard" for assessing the short-term within-day glycemic variability (GV), which is an important component of overall glycemic control. A 14-day continuous glucose monitoring system is now widely used and allows easier assessment of GV. However, it is still unknown whether MAGE, usually calculated on a 48-hour period is identical whatever the time during the 14-day lifespan of the sensor and whether a longer time period might give additional information. We evaluated in 68 patients with type 1 diabetes, MAGE during three 2-day periods (day1-day3; day6-day8; day11-day13) and during periods of 3 days and 4 days. MAGE calculated at the three 2-day periods were identical and not different from MAGE of the 3-day or 4-day periods.

Objective: Dyslipidemia observed in type 2 diabetes (T2D) is atherogenic. Important features of diabetic dyslipidemia are increased levels of triglyceride-rich lipoproteins and small dense LDL particles, which all have apolipoprotein B100 (apoB100) as a major apolipoprotein. This prompted us to study the effect of the GLP-1 agonist liraglutide on the metabolism of apoB100-containing lipoproteins., Research Design and Methods: We performed an in vivo kinetic study with stable isotopes (L-[1- 13 C]leucine) in 10 patients with T2D before and after 6 months of treatment with liraglutide (1.2 mg/day). We also evaluated in mice the effect of liraglutide on the expression of genes involved in apoB100-containing lipoprotein clearance., Results: In patients with T2D, liraglutide treatment significantly reduced plasma apoB100 (0.93 ± 0.13 vs. 1.09 ± 0.11 g/L, P = 0.011) and fasting triglycerides (1.76 ± 0.37 vs. 2.48 ± 0.69 mmol/L, P = 0.005). The kinetic study showed a significant increase in indirect catabolism of VLDL 1 -apoB100 (4.11 ± 1.91 vs. 2.96 ± 1.61 pools/day, P = 0.005), VLDL 2 -apoB100 (5.17 ± 2.53 vs. 2.84 ± 1.65 pools/day, P = 0.008), and IDL-apoB100 (5.27 ± 2.77 vs. 3.74 ± 1.85 pools/day, P = 0.017) and in catabolism of LDL-apoB100 (0.72 ± 0.22 vs. 0.56 ± 0.22 pools/day, P = 0.005). In mice, liraglutide increased lipoprotein lipase (LPL) gene expression and reduced proprotein convertase subtilisin/kexin type 9 (PCSK9), retinol-binding protein 4 (RBP4), and tumor necrosis factor-α (TNF-α) gene expression in adipose tissue and decreased PCSK9 mRNA and increased LDL receptor protein expression in liver. In vitro, liraglutide directly reduced the expression of PCSK9 in the liver., Conclusions: Treatment with liraglutide induces a significant acceleration of the catabolism of triglyceride-rich lipoproteins (VLDL 1 , VLDL 2 , IDL) and LDL. Liraglutide modifies the expression of genes involved in apoB100-containing lipoprotein catabolism. These positive effects on lipoprotein metabolism may reduce cardiovascular risk in T2D., (© 2021 by the American Diabetes Association.)

Obesity is increasing in patients with type 2 diabetes. A possible reduced association between fructosamine and glycated hemoglobin (HbA1c) in obese individuals has been previously discussed, but this has never been specifically evaluated in type 2 diabetes, and the potential influence of body fat mass and fat distribution has never been studied. We studied 112 type 2 diabetes patients with assessment of fat mass, liver fat and fat distribution. Patients with body mass index (BMI) above the median (34.9 kg/m 2 ), versus BMI below the median, had a correlation coefficient between fructosamine and HbA1c significantly reduced (r = 0.358 vs r = 0.765). In the whole population, fructosamine was correlated negatively with BMI and fat mass. In multivariate analysis, fructosamine was associated with HbA1c (positively) and fat mass (negatively), but not with BMI, liver fat or fat distribution. The association between fructosamine and HbA1c is significantly reduced in the most obese type 2 diabetes patients, and this is mostly driven by increased fat mass., (© 2020 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.)

Aim: The aim of the present study was to identify the affected gene in a French family with maturity-onset diabetes of the young (MODY) using whole-exome sequencing (WES)., Methods: WES was performed in one patient with MODY, and candidate variants were confirmed in members of the immediate family by Sanger sequencing., Results: In the proband, a new heterozygous missense mutation (c.340A>C) was identified in the NEUROD1 gene by WES analysis and confirmed by Sanger sequencing. Additional Sanger sequencing of the proband's sister and mother revealed the same heterozygous mutation. The proband and his sister displayed typical clinical characteristics of MODY, while their mother had the same typical MODY features except for later onset. When clinical and biological profiles were established for all three patients, the severity of diabetes-related complications varied substantially from one family member to another., Conclusion: A novel missense mutation found in NEUROD1 was associated with MODY 6 features in a single French family., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

Objective- Treatment with liraglutide, a GLP-1 (glucagon-like peptide-1) agonist, has been shown to reduce postprandial lipidemia, an important feature of diabetic dyslipidemia. However, the underlying mechanisms for this effect remain unknown. This prompted us to study the effect of liraglutide on the metabolism of ApoB48 (apolipoprotein B48). Approach and Results- We performed an in vivo kinetic study with stable isotopes (D 8 -valine) in the fed state in 10 patients with type 2 diabetes mellitus before treatment and 6 months after the initiation of treatment with liraglutide (1.2 mg/d). We also evaluated, in mice, the effect of a 1-week liraglutide treatment on postload triglycerides and analysed in vitro on jejunum, the direct effect of liraglutide on the expression of genes involved in the biosynthesis of chylomicron. In diabetic patients, liraglutide treatment induced a dramatic reduction of ApoB48 pool (65±38 versus 162±87 mg; P=0.005) because of a significant decrease in ApoB48 production rate (3.02±1.33 versus 6.14±4.27 mg kg -1 d -1 ; P=0.009) and a significant increase in ApoB48 fractional catabolic rate (5.12±1.35 versus 3.69±0.75 pool d -1 ; P=0.005). One-week treatment with liraglutide significantly reduced postload plasma triglycerides in mice and liraglutide, in vitro, reduced the expression of ApoB48, DGAT1 (diacylglycerol O-acyltransferase 1), and MTP (microsomal transfer protein) genes. Conclusions- We show that treatment with liraglutide induces a significant reduction of the ApoB48 pool because of both a reduction of ApoB48 production and an increase in ApoB48 catabolism. In vitro, liraglutide reduces the expression of genes involved in chylomicron synthesis. These effects might benefit cardiovascular health. Clinical Trial Registration- URL: https://www.clinicaltrials.gov . Unique identifier: NCT02721888.

Background: Continuous glucose monitoring (CGM) and sensor-augmented pump (SAP) therapy improve glucose control provided good adherence. In France, not only diabetologists, nurses, and dieticians but also nurses employed by homecare providers (HCPNs) are together involved in the initiation and/or follow-up of continuous subcutaneous insulin injection (CSII) and SAP training. The SENLOCOR Study is an observational study designed to assess SAP adherence over 6 months (primary objective). Secondary objectives included the impact of SAP on metabolic control and patients' satisfaction., Materials and Methods: CGM initiation (M0) was performed within 3 months after CSII. CGM adherence, defined by sensor wear >70% of the time, glycated hemoglobin (HbA1c) levels, and satisfaction questionnaires were collected at inclusion and at 3 (M3) and 6 (M6) months., Results: The analysis population was 234 patients, including 27 children. Of the physicians, 88.0% were involved in SAP education for the whole cohort (median time, 45 min), whereas HCPNs were involved in CGM training for 190 patients (81.2%) (median time: at M0, 156 min; at M3, 20 min). Good adherence was obtained in 86.1% (M0-M3) and 68.9% (M3-M6) of the patients. The HbA1c level decreased from 8.16 ± 1.35% (M0) to 7.67 ± 1.01% (M6) in 189 patients (change, -0.48%; 95% confidence interval, -0.64, -0.33). The percentage of patients who experienced severe hypoglycemia decreased from 20.7% (M0) to 13.6% (M3) and 13.3% (M6). Satisfaction scores were high., Conclusions: In patients with type 1 diabetes, a 6-month training on SAP involving a multidisciplinary team, and especially HCPNs, improved metabolic control with a high level of adherence and satisfaction.

Aim: The benefits of retrospective continuous glucose monitoring (retroCGM) recording have been widely explored in clinical studies, and many diabetes physicians routinely use this examination. However, the method of interpretation of CGM recordings has never been precisely described., Method: An expert French panel of physicians met for two days to discuss several aspects of retroCGM use and to produce a position statement., Results: The guidelines cover the indications for retroCGM, the general organization and practical implementation of CGM recordings, a description of the different devices available and guidelines for the interpretation of retroCGM recordings., Conclusion: This consensus document should help clinicians in the proper use of retroCGM., (Copyright © 2015 Elsevier Masson SAS. All rights reserved.)

Context: Apelin is an adipokine expressed in several tissues and it appears to be involved in energy metabolism., Objective: The aim of this study was to determine serum apelin levels in a large cohort of patients with type 1 and type 2 diabetes and control subjects and to correlate the results with glycaemic control., Design and Participants: One hundred and thirty patients with type 1 diabetes, 98 patients with type 2 diabetes and 162 controls were enrolled in the study. Apelin levels were measured by enzyme-linked immunosorbent assay., Results: Serum apelin levels were significantly higher in type 1 and type 2 diabetic patients than in controls (P < 0·0001). Serum apelin levels were higher in type 1 than in type 2 diabetic patients (P = 0·02). In multivariate analysis, serum apelin levels were higher in patients with type 1 diabetes and in patients with type 2 diabetes versus controls. We found a negative correlation between glycosylated haemoglobin and serum apelin levels in all diabetic patients (r = -0·17, P = 0·008) and in patients with type 2 diabetes (r = -0·24 P = 0·01). No correlation was found in type 1 diabetic patients., Conclusion: Our study showed that apelin concentrations were increased in diabetic patients. This rise, which was greater in type 1 than in type 2 diabetic patients, suggests that obesity is not the main determinant of plasma apelin levels. The negative correlation with glycosylated haemoglobin in patients with type 2 diabetes could indicate that apelin plays a role in glycaemic balance and even insulin sensitivity., (© 2014 John Wiley & Sons Ltd.)

Background: Implanted insulin pumps using the peritoneal route provide long-term improvement of glucose control compared with subcutaneous insulin therapy in type 1 diabetes (T1D) patients. The stability of insulin preparation is critical for a safe use in implanted pumps. Insuman implantable(®) (400 IU/mL) (Sanofi-Aventis Deutschland GmbH, Frankfurt am Main, Germany), a recombinant human insulin, has been developed as a replacement for Insuplant(®) (Aventis Pharma, Frankfurt am Main, Germany), a semisynthetic insulin, the only one used so far. The aim of the study was to demonstrate the noninferiority of Insuman versus Insuplant, in terms of safety and effectiveness when used in implanted pumps., Subjects and Methods: The patients enrolled, currently treated for T1D by the Medtronic MiniMed (Northridge, CA) implantable pump model 2007 with Insuplant, were randomized into two study arms and received either Insuman or Insuplant for four pump refill cycles. Each pump refill cycle was 40±5 days. The co-primary end points included glycated hemoglobin (HbA1c) change from baseline and pump infusion accuracy., Results: In total, 169 patients were randomized. Noninferiority of Insuman versus Insuplant was demonstrated both for the HbA1c change from baseline (as a percentage) with intergroup difference of 95% confidence interval (-0.36;+0.11) and for the infusion accuracy assessed by the measured percentage of error at pump refill, as shown by intergroup difference of 95% confidence interval (-5.81; -0.50), in per-protocol populations, although the insulin daily dose was similar. Severe hypoglycemia occurred at least once in 12 versus 11 patients, respectively, and metabolic or technical adverse events were comparable., Conclusions: Findings suggest that Insuman can safely and effectively replace Insuplant in implanted pumps.

Objective: In vitro studies showed that insulin stimulates the production of apolipoprotein AI (apoAI). Thus, we hypothesized that chronic hyperinsulinemia could contribute to the increase in the production of high-density lipoprotein apoAI that is observed in metabolic syndrome., Approach and Results: We performed an in vivo kinetic study with stable isotope in 7 patients with insulinoma who showed hyperinsulinemia but no insulin resistance, 8 patients with insulin resistance, and 16 controls. Insulinemia was 3.1× (P<0.01) higher in patients with insulinoma or insulin resistance than in controls in the fasting state and, respectively, 3.5× and 2.6× (P<0.05) higher in the fed state. The high-density lipoprotein apoAI pool size was smaller in patients with insulin resistance than in controls (49.3 ± 5.4 versus 59.6 ± 7.7 mg · kg(-1); P<0.01), whereas both the high-density lipoprotein apoAI fractional catabolic rate and the high-density lipoprotein apoAI production rate were higher (0.30 ± 0.07 versus 0.20 ± 0.04 pool · d(-1); P<0.0001 and 14.6 ± 1.5 versus 11.5 ± 1.9 mg · kg(-1) · d(-1); P<0.01, respectively). In contrast, no significant difference was observed for these parameters between patients with insulinoma and controls. In patients with insulinoma, the apoAI pool size tended to be greater than in patients with insulin resistance (56.3 ± 8.6 versus 49.3 ± 5.4 mg · kg(-1); P=0.078), whereas both the apoAI fractional catabolic rate and the production rate were lower (0.20 ± 0.06 versus 0.30 ± 0.07 pool · d(-1); P<0.01 and 11.1 ± 1.6 versus 14.6 ± 1.5 mg·kg(-1) · d(-1); P<0.01, respectively). The apoAI fractional catabolic rate was the only variable associated with the apoAI production rate in multivariate analysis and explained 80% of its variance., Conclusions: Chronic endogenous hyperinsulinemia does not induce any increase in the apoAI production rate, which seems to be more dependent on the apoAI fractional catabolic rate.

Objective: It is currently suggested that chronic hyperinsulinemia is a causal factor for the increased production rate of very-low-density lipoproteins (VLDL) associated with metabolic syndrome. However, the involvement of hyperinsulinemia independently of the other abnormalities also observed in metabolic syndrome has never been proven in humans., Design: We used patients with insulinoma showing hyperinsulinemia but no insulin resistance as a model and conducted an apolipoprotein B (apoB) kinetic study in seven patients with insulinoma, seven insulin-resistant (IR) obese patients, and 12 controls., Results: Insulinemia was higher in patients with insulinoma or IR than in controls both in the fasting state [2.4-fold (P = 0.039) and 3.1-fold (P = 0.003), respectively] and in the fed state [3.5-fold (P = 0.006) and 2.6-fold (P = 0.05), respectively]. Patients with insulinoma were not IR (steady state plasma glucose = 80 ± 46 mg/dl, a value lower than in IR subjects (231 ± 75, P = 0.0013). In the fed state, triglyceridemia and VLDL apoB pool size were higher in IR subjects compared with controls and patients with insulinoma [208 ± 56 vs. 89 ± 30 mg/dl (P < 0.0001) and 96 ± 42 mg/dl (P < 0.0001), respectively, for triglyceridemia and 3.56 ± 0.60 vs. 1.85 ± 0.88 mg/kg (P = 0.004) and 2.32 ± 1.79 (P = 0.052) mg/kg for VLDL apoB pool size]. The production rate of VLDL apoB in subjects with insulinoma was not significantly different from that in controls (14.56 ± 7.43 vs. 16.40 ± 7.70 mg/kg · d) but was higher in IR subjects compared with these two groups [25.66 ± 12.84 mg/kg · d (P = 0.046 and 0.035, respectively)]., Conclusion: Chronic endogenous hyperinsulinemia is not directly responsible for any increase in the production rate of VLDL apoB in humans.

We performed a study in 102 people with type 2 diabetes aiming to determine "easy-to-use" predictive factors for glycemic response to glitazones. We found that low baseline HDL-cholesterol (<40 mg/L [1.04 mmol/L] in males, <50 mg/L [1.30 mmol/L] in females) was a strong independent predictor of glycemic response to glitazones (OR=2.67 [2.02-3.52], p=0.0004)., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Objective: Ethanol injection under ultrasound (US) guidance has been proposed as an alternative to surgery in the treatment of recurrent benign thyroid cysts following aspiration. We aimed to set up a new procedure of ethanol sclerotherapy without US guidance for the treatment of pure thyroid cysts in order to make this useful treatment, available to more patients, more particularly when access to centers specialized in thyroid ultrasonography is limited., Patients and Methods: Nine patients with recurrent large thyroid cysts following aspiration, and showing symptoms of compression and/or cosmetic complaints were treated by ethanol injection without US guidance and followed for up to 11 years., Results: After ethanol injection, mean cyst volume was significantly reduced (9.9 ± 13.6 vs. 31.3 ± 34.1 ml, P=0.007) and the mean percentage volume reduction was 72.7%. A size reduction of the thyroid lesion more than 50% was achieved in eight of the nine patients (89%). Compressive symptoms and cosmetic complaints totally disappeared after sclerotherapy in all patients. During a mean follow-up of 48 months (ranging from 12 to 135 months), no recurrences were observed. The treatment was well tolerated with no major side effects., Conclusion: Non-US-guided ethanol sclerotherapy is a safe and "easy-to-use" procedure to treat benign thyroid cysts effectively. Because this new treatment does not need US-guidance, it can be performed by endocrinologists during outpatient visits. This new procedure may be useful in some areas, such as developing countries, where access to US examination is limited., (Copyright © 2011 Elsevier Masson SAS. All rights reserved.)

Catabolism of HDL particles is accelerated in type 2 diabetes, leading to a reduction in plasma residence time, which may be detrimental. Rosuvastatin is the most powerful statin to reduce LDL-cholesterol, but its effects on HDL metabolism in type 2 diabetes remain unknown. We performed a randomized double-blind cross-over trial of 6-week treatment period with placebo or rosuvastatin 20 mg in eight patients with type 2 diabetes. An in vivo kinetic study of HDL-apolipoprotein A-I (apoA-I) with (13)C leucine was performed at the end of each treatment period. Moreover, a similar kinetic study was carried out in eight nondiabetic normolipidemic controls. Rosuvastatin significantly reduced plasma LDL-cholesterol (-51%), triglycerides (TGs) (-38%), and HDL-TG (-23%). HDL-apoA-I fractional catabolic rate (FCR) was decreased by rosuvastatin (0.25 +/- 0.06 vs. 0.32 +/- 0.07 pool/day, P = 0.011), leading to an increase in plasma HDL-apoA-I residence time (4.21 +/- 1.02 vs. 3.30 +/- 0.73 day, P = 0.011). Treatment with rosuvastatin was associated with a concomitant reduction of HDL-apoA-I production rate. The decrease in HDL-apoA-I FCR, induced by rosuvastatin, was correlated with the reduction of plasma TGs and HDL-TG. HDL apoA-I FCR and production rate values in diabetic patients on rosuvastatin were not different from those found in controls. Rosuvastatin is responsible for a 22% reduction of HDL-apoA-I FCR and restores to normal the increased HDL turnover observed in type 2 diabetes. These kinetic modifications may have beneficial effects by increasing HDL plasma residence time.

Aims/hypothesis: In addition to its efficacy in reducing LDL-cholesterol, rosuvastatin has been shown to significantly decrease plasma triacylglycerol. The use of rosuvastatin may be beneficial in patients with type 2 diabetes, who usually have increased triacylglycerol levels. However, its effects on the metabolism of triacylglycerol-rich lipoproteins in type 2 diabetic patients remains unknown., Methods: We performed a randomised double-blind crossover trial of 6-week treatment with placebo or rosuvastatin 20 mg in eight patients with type 2 diabetes who were being treated with oral glucose-lowering agents. In each patient, an in vivo kinetic study of apolipoprotein B (ApoB)-containing lipoproteins with [13C]leucine was performed at the end of each treatment period. A central randomisation centre used computer-generated tables to allocate treatments. Participants, caregivers and those assessing the outcomes were blinded to group assignment., Results: Rosuvastatin 20 mg significantly reduced plasma LDL-cholesterol, triacylglycerol and total ApoB. It also significantly reduced ApoB pool sizes of larger triacylglycerol-rich VLDL particles (VLDL1; p = 0.011), smaller VLDL particles (VLDL2; p = 0.011), intermediate density lipoprotein (IDL; p = 0.011) and LDL (p = 0.011). This reduction was associated with a significant increase in the total fractional catabolic rate of VLDL1-ApoB (6.70 +/- 3.24 vs 4.52 +/- 2.34 pool/day, p = 0.049), VLDL2-ApoB (8.72 +/- 3.37 vs 5.36 +/- 2.64, p = 0.011), IDL-ApoB (7.06 +/- 1.68 vs 4.21 +/- 1.51, p = 0.011) and LDL-ApoB (1.02 +/- 0.27 vs 0.59 +/- 0.13, p = 0.011). Rosuvastatin did not change the production rates of VLDL2-, IDL- or LDL-, but did reduce VLDL1-ApoB production rate (12.4 +/- 4.5 vs 19.5 +/- 8.4 mg kg(-1) day(-1), p = 0.035). No side effects of rosuvastatin were observed during the study., Conclusions/interpretation: In type 2 diabetic patients rosuvastatin 20 mg not only induces a significant increase of LDL-ApoB catabolism (73%), but also has favourable effects on the catabolism of triacylglycerol-rich lipoproteins, e.g. a significant increase in the catabolism of VLDL1-ApoB (48%), VLDL2-ApoB (63%) and IDL-ApoB (68%), and a reduction in the production rate of VLDL1-ApoB (-36%). The effects of rosuvastatin on the metabolism of triacylglycerol-rich lipoproteins may be beneficial for prevention of atherosclerosis in type 2 diabetic patients.

In type 1 diabetic patients, the replacement of subcutaneous insulin infusion by intraperitoneal insulin infusion restores the normal physiological gradient between the portal vein and the peripheral circulation, which is likely to modify HDL metabolism. This stable isotope kinetic study was designed to compare HDL apolipoprotein (apo) AI metabolism in seven type 1 diabetic patients first treated by continuous subcutaneous insulin infusion by an external pump and then 3 months after the beginning of intraperitoneal insulin infusion by an implantable pump. Glycaemic control was comparable under subcutaneous and intraperitoneal insulin infusion (HbA1c=7.34+/-0.94% versus 7.24+/-1.00%, NS). HDL composition was similar under both insulin regimens (esterified cholesterol=20.1+/-2.5% versus 24.0+/-3.0% (NS), free cholesterol=3.4+/-1.1% versus 3.3+/-0.9% (NS), triglycerides=2.4+/-0.9% versus 2.1+/-0.9% (NS), phospholipids=22.7+/-5.3% versus 25.2+/-6.5% (NS) and proteins=51.2+/-6.3% versus 45.5+/-4.7% (NS)). The replacement of subcutaneous insulin infusion by intraperitoneal insulin infusion induced significant changes neither in apoAI fractional catabolic rate, nor in apoAI production rate, nor in apoAI pool size (respectively, 0.199+/-0.051 pool d(-1) versus 0.211+/-0.017 pool d(-1), 12.0+/-3.2 mg kg(-1)d(-1) versus 12.1+/-1.8 mg kg(-1)d(-1), 60.4+/-5.0 mg kg(-1) versus 57.5+/-7.5 mg kg(-1)). In conclusion, HDL metabolism is not modified by the replacement of subcutaneous insulin infusion by intraperitoneal insulin infusion when glycaemia is well controlled under both insulin regimens. As far as HDL metabolism is concerned there is no advantage in favour of one way of insulin administration or another.

Objective: In type 1 diabetic patients, the replacement of s.c. insulin infusion with i.p. insulin infusion restores the normal physiological gradient between the portal vein and the peripheral circulation, which is likely to modify lipoprotein metabolism., Design: To check this hypothesis, we performed two apolipoprotein (apo) B100 kinetic studies in seven type 1 diabetic patients, first under s.c. insulin infusion and then 3 months after the beginning of i.p. insulin infusion., Results: Glycemic control was similar under s.c. insulin infusion and i.p. insulin infusion, as assessed by glycated hemoglobin A1c and the capillary glycemic curve determined during the kinetic study. Very low-density and intermediate-density lipoprotein apoB100 pool size, production rate, and fractional catabolic rate (FCR) were similar under s.c. insulin infusion and i.p. insulin infusion. The low-density lipoprotein apoB100 FCR tended to decrease under ip insulin (0.45 +/- 0.06 vs. 0.55 +/- 0.11 pool/d), but the difference did not reach statistical significance (95% confidence interval for the difference, -0.33, 0.11). The low-density lipoprotein apoB100 pool size and production rate remained unchanged under i.p. insulin infusion compared with s.c. insulin infusion., Conclusion: In type 1 diabetic patients, the replacement of s.c. insulin infusion with i.p. insulin infusion does not induce profound modifications of apoB100-containing lipoprotein production and FCRs.

Aims/hypothesis: Type 1 diabetic subjects are at increased risk of cardiovascular disease and exhibit multiple qualitative abnormalities of apolipoprotein (apo) B100-containing lipoproteins. This stable isotope kinetic experiment was designed to study whether these abnormalities are associated with changes in the synthesis and fractional catabolic rates of VLDL-, IDL- and LDL-apoB100., Methods: Using a bolus followed by a 16-h constant infusion of 13C-leucine, we performed a kinetic study in eight men with type 1 diabetes treated with a continuous subcutaneous insulin infusion administered by an external pump and in seven healthy men, in the fed state., Results: The mean HbA1c level in the type 1 diabetic patients was 8.00+/-1.48%. Plasma triglyceride, and total, LDL and HDL cholesterol levels were similar in patients and control subjects. VLDL were less triglyceride rich in type 1 diabetic patients than in control subjects (VLDL triglyceride : apoB 6.91+/-0.81 vs 8.29+/-1.24 mmol/g, p=0.05). Conversely, the IDL and LDL of the type 1 diabetic patients contained relatively higher levels of triglycerides (IDL triglycerides : apoB 2.16+/-0.36 vs 1.57+/-0.30 mmol/g, p<0.01; LDL triglycerides : apoB 0.27+/-0.06 vs 0.16+/-0.04 mmol/g, p<0.05). The apoB100 pool size, production and fractional catabolic rates in the two groups of subjects were similar for all lipoprotein fractions., Conclusions/interpretation: Despite qualitative abnormalities, especially abnormalities of triglyceride content, the metabolism of apoB100-containing lipoproteins is not altered in type 1 diabetic men with fair glycaemic control with continuous subcutaneous insulin infusion. The high risk of atherosclerosis in these patients cannot be explained by kinetic abnormalities of apoB100-containing lipoproteins.