Richard Marechaud

Glycaemic control in type 2 diabetic patients on chronic haemodialysis: use of a continuous glucose monitoring system

BACKGROUND The proportion of diabetic patients undergoing haemodialysis is rapidly increasing. Glucose control among such patients is difficult to assess. We aimed to evaluate the clinical performance of a continuous glucose monitoring system (CGMS) in type 2 diabetic patients on chronic haemodialysis. METHODS We used a 4-day CGMS to monitor glucose levels in 19 haemodialysed type 2 diabetic patients (HD T2) including 2 days with and 2 days without dialysis session, and 39 non-HD T2 in a double-centre study. RESULTS The glucose concentration according to the glucose meter and CGMS were correlated in HD T2 patients (r = 0.90, P < 0.0001) and in non-HD T2 patients (r = 0.81, P < 0.0001). The relative absolute difference (RAD) between glucose determined by a glucose meter and glucose determined by the CGMS did not differ between HD T2 and non-HD T2 patients (9.2 +/- 10.5 vs. 8.2 +/- 7.6%; P = 0.165). Glycated haemoglobin (A1c) and mean glucose concentration were strongly correlated in non-HD T2 patients (r = 0.71; P < 0.0001) but weakly correlated in HD T2 patients (r = 0.47; P = 0.042). Fructosamine was correlated with the mean glucose concentration in non-HD T2 (r = 0.67; P < 0.0001) but not in HD T2 patients (r = 0.04; P = 0.88). CONCLUSION CGM is a validated marker of glycaemic control in HD diabetic patients. This tool showed that A1c and fructosamine, despite being good markers of glycaemic control in non-HD diabetic patients, are of poor value in HD diabetic patients.

Risk Factors for Recurrent Nodular Goiter after Thyroidectomy for Benign Disease: Case-control Study of 244 Patients

Surgery for recurrent nodular goiter is associated with a significant risk of parathyroid and recurrent laryngeal nerve (RLN) morbidity. Total thyroidectomy for benign disease is assessed. The aim of this study was to evaluate the risk factors for recurrence and the morbidity associated with reoperation. From 1969 to 1996 a total of 4334 thyroidectomies were performed, of which 122 were for recurrent nodular goiter (group I: 116 women, 6 men). A matched case-control study of 122 patients operated on for nonrecurrent multinodular goiter was performed (group II: 112 women, 10 men). Age, family history, initial surgery, pathology, and morbidity were compared in the two groups by ċ2 test, Fisher’s exact test, and the Mantel-Haenszel test. The mean age was 39.88 years in group I and 47.89 years in group II. There was no statistical difference in relation to the extent of thyroidectomy or morbidity after initial surgery. Statistical differences were identified regarding age (p = 0.000002) and the multinodular nature of the initial goiter (p = 0.005). Bilaterality and family history were less significant (p = 0.09 and p = 0.08, respectively). Temporary RLN palsy and temporary hypoparathyroidism were higher in group I (12.3% vs. 5.7%, p = 0.0737; 10.6% vs. 1.7%, p = 0.00337). Permanent RLN palsy was found in 0.8% in group I and in none in group II (p = 0.5, NS). Young age and multiple nodules at initial surgery are risk factors for recurrence. A higher rate of temporary morbidity was demonstrated after surgery for recurrent goiter. Total thyroidectomy for multinodular goiter is advisable.

Impact of Natriuretic Peptide Clearance Receptor (NPR3) Gene Variants on Blood Pressure in Type 2 Diabetes

OBJECTIVE Hypertension in diabetes is characterized by abnormal sodium homeostasis, suggesting a particular role of natriuretic peptide pathway. Natriuretic peptides can affect blood pressure (BP) through their plasma concentrations, which are dependent on their receptor activities. We thus assessed the association between nine NPR3 gene polymorphisms and BP levels in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS Nine single nucleotide polymorphisms (SNPs) tagging the haplotype structure of the NPR3 gene were genotyped in the 3,126 French Non-insulin-dependent Diabetes, Hypertension, Microalbuminuria or Proteinuria, Cardiovascular Events, and Ramipril (DIABHYCAR) trial participants. We then used a second population (Diabete de type 2, Nephropathie et Genetique [DIAB2NEPHROGENE]/Survie, Diabete de type 2 et Genetique [SURDIAGENE] study) of 2,452 patients for the purpose of replication. Finally, we separately investigated subjects selected according to their rs 2270915SNP genotypes for their BP response to salt restriction. RESULTS In DIABHYCAR patients, three SNPs (rs6889608, rs1173773, and rs2270915) were significantly associated with systolic BP (SBP). The effect of the rs2270915 was replicated in the second step population: AA homozygotes had a lower SBP than G carriers (137.4 ± 19.1 vs. 140.0 ± 20.2 mmHg, P = 0.004). The rs2270915 influenced the response of SBP to salt reduction, with AA homozygous patients showing greater reductions after restriction of salt intake compared with G carriers: −20 mmHg (−43 to −8) vs. −3 (−20 to +7); P = 0.006. CONCLUSIONS We found a consistent and significant association between the rs2270915 polymorphism of the NPR3 gene and SBP in diabetic patients. This genetic variation may affect pressure response to changes in dietary sodium.

Acute Kidney Injury Predicts Major Adverse Outcomes in Diabetes: Synergic Impact With Low Glomerular Filtration Rate and Albuminuria

OBJECTIVE Subjects with diabetes are prone to the development of cardiovascular and noncardiovascular complications. In separate studies, acute kidney injury (AKI), albuminuria, and low estimated glomerular filtration rate (eGFR) were shown to predict adverse outcomes, but, when considered together, their respective prognostic value is unknown. RESEARCH DESIGN AND METHODS Patients with type 2 diabetes consecutively recruited in the SURDIAGENE cohort were prospectively followed up for major diabetes-related events, as adjudicated by an independent committee: death (with cause), major cardiovascular events (myocardial infarction, stroke, congestive heart failure, amputation, and arterial revascularization), and renal failure (i.e., sustained doubling of serum creatinine level or end-stage renal disease). RESULTS Intrahospital AKI occurred in 411 of 1,371 patients during the median follow-up period of 69 months. In multivariate analyses, AKI was significantly associated with cardiovascular and noncardiovascular death, including cancer-related death. In multivariate analyses, AKI was a powerful predictor of major adverse cardiovascular events, heart failure requiring hospitalization, myocardial infarction, stroke, lower-limb amputation or revascularization, and carotid artery revascularization. AKI, eGFR, and albuminuria, even when simultaneously considered in multivariate models, predicted all-cause and cardiovascular deaths. All three renal biomarkers were also prognostic of most adverse outcomes and of the risk of renal failure. CONCLUSIONS AKI, low eGFR, and elevated albuminuria, separately or together, are compelling biomarkers of major adverse outcomes and death in diabetes.

Prognostic Value of Resting Heart Rate on Cardiovascular and Renal Outcomes in Type 2 Diabetic Patients A competing risk analysis in a prospective cohort

OBJECTIVE Epidemiological studies and randomized clinical trials have demonstrated in various populations that resting heart rate (RHR) was an independent predictor of cardiovascular (CV) risk and all-cause mortality. However, few data specifically evaluated the relationship between RHR and long-term CV and renal complications in a large population of type 2 diabetic (T2D) patients. RESEARCH DESIGN AND METHODS We performed a single-center, prospective analysis in 1,088 T2D patients. RHR was determined at baseline by electrocardiogram. The primary outcome was a composite criterion of CV and renal morbi-mortality (CV death, nonfatal myocardial infarction and/or stroke, hospitalization for heart failure, renal replacement therapy), which was adjusted for death from non-CV cause as a competing event. The secondary outcome was a renal composite criterion (renal replacement therapy or doubling of baseline serum creatinine) adjusted for all-cause death as a competing event. RESULTS During median follow-up of 4.2 years, 253 patients (23%) and 62 patients (6%) experienced the primary and secondary outcomes, respectively. In the subgroup of patients with CV disease history at baseline (n = 336), RHR was found to be associated with the incidence of primary outcome (P = 0.0002) but also with renal risk alone, adjusted for all-cause death as a competing event (secondary outcome; P < 0.0001). In patients without history of CV disease, no relation was found between RHR and the incidence of CV and/or renal events. CONCLUSIONS In the real-life setting, RHR constitutes an easy and less time-consuming factor that would permit identification of CV disease diabetic patients with an increased risk for long-term CV and renal complications.

Association Between Diabetic Macular Edema and Cardiovascular Events in Type 2 Diabetes Patients: A Multicenter Observational Study

AbstractDiabetic macular edema (DME) is the main cause of visual loss associated with diabetes but any association between DME and cardiovascular events is unclear.This study aims to describe the possible association between DME and cardiovascular events in a multicenter cross-sectional study of patients with type 2 diabetes.Two thousand eight hundred seven patients with type 2 diabetes were recruited from diabetes and nephrology clinical institutional centers participating in the DIAB 2 NEPHROGENE study focusing on diabetic complications. DME (presence/absence) and diabetic retinopathy (DR) classification were based on ophthalmological report and/or on 30° color retinal photographs. DR was defined as absent, nonproliferative (background, moderate, or severe) or proliferative. Cardiovascular events were stroke, myocardial infarction, and lower limb amputation.Details regarding associations between DME and cardiovascular events were evaluated.The study included 2807 patients with type 2 diabetes, of whom 355 (12.6%) had DME. DME was significantly and independently associated with patient age, known duration of diabetes, HbA1c, systolic blood pressure, and DR stage. Only the prior history of lower limb amputation was strongly associated with DME in univariate and multivariate analyses, whereas no association was found with regard to myocardial infarction or stroke. Moreover, both major (n = 32) and minor lower limb (n = 96) amputations were similarly associated with DME, with respective odds ratio of 3.7 (95% confidence interval [CI], 1.77–7.74; P = 0.0012) and of 4.29 (95% CI, 2.79–6.61; P < 0.001).DME is strongly and independently associated with lower limb amputation in type 2 diabetic patients.

Urinary Sodium Concentration Is an Independent Predictor of All-Cause and Cardiovascular Mortality in a Type 2 Diabetes Cohort Population

Objective. Sodium intake is associated with cardiovascular outcomes. However, no study has specifically reported an association between cardiovascular mortality and urinary sodium concentration (UNa). We examined the association of UNa with mortality in a cohort of type 2 diabetes (T2D) patients. Methods. Patients were followed for all-cause death and cardiovascular death. Baseline UNa was measured from second morning spot urinary sample. We used Cox proportional hazard models to identify independent predictors of mortality. Improvement in prediction of mortality by the addition of UNa to a model including known risk factors was assessed by the relative integrated discrimination improvement (rIDI) index. Results. Participants (n = 1,439) were followed for a median of 5.7 years, during which 254 cardiovascular deaths and 429 all-cause deaths were recorded. UNa independently predicted all-cause and cardiovascular mortality. An increase of one standard deviation of UNa was associated with a decrease of 21% of all-cause mortality and 22% of cardiovascular mortality. UNa improved all-cause and cardiovascular mortality prediction beyond identified risk factors (rIDI = 2.8%, P = 0.04 and rIDI = 4.6%, P = 0.02, resp.). Conclusions. In T2D, UNa was an independent predictor of mortality (low concentration is associated with increased risk) and improved modestly its prediction in addition to traditional risk factors.

Glycaemic control influences the relationship between plasma PCSK9 and LDL cholesterol in type 1 diabetes.

Pro‐protein convertase subtilisin/kexin type 9 (PCSK9) is a critical regulator of LDL cholesterol metabolism. Little is known, however, about the regulation of PCSK9 in patients with type 1 diabetes (T1D). In the present study, we aimed to determine the relationship between circulating PCSK9 and metabolic variables in T1D. Plasma PCSK9 levels were measured in 195 people with T1D (mean age 38.8 years, mean diabetes duration 17.2 years, mean glycated haemoglobin [HbA1c] 8.3%), who were free of any lipid‐lowering agent. Plasma PCSK9 was positively correlated with LDL cholesterol (P = .0007), triglycerides (P = .004), apolipoprotein B (P = .005), HbA1c (P = .003), systolic (P = .003) and diastolic (P = .001) blood pressure and body mass index (0.02). In multivariate analysis, PCSK9 concentration was independently associated with HbA1c (P = .02) and LDL cholesterol (P = .03). After classifying patients according to HbA1c tertile, the correlation between PCSK9 and LDL cholesterol was only observed in the highest tertile (P = .0006; Rho = 0.43), whereas no correlation was found in the lowest and intermediate tertiles. This study suggests that good glycaemic control abolishes the positive relationship between PCSK9 and LDL cholesterol in patients with T1D; however, the underlying molecular mechanisms remain to be established.

Effect of dietary calcium intake on weight gain in type 2 diabetic patients following initiation of insulin therapy.

OBJECTIVES This pilot study analyses weight gain in type 2 diabetic patients at initiation of insulin therapy, according to daily calcium intake. METHODS Type 2 diabetic patients consecutively admitted for initiation of insulin therapy were studied between January and March 2004 in a monocenter study. Dietary intake was assessed by a 7-day food history before insulin treatment (initial visit) and 4 to 6 months later (final visit). RESULTS Thirty-one patients were studied (18 males and 13 females; mean age 62+/-9 years, with diabetes duration 14+/-10 years). Weight significantly increased between initial and final visits (81.9+/-16.2 vs. 84.8+/-17.8 kg; P=0.0272). Median weight gain was 2.4 kg (IQR: -1.15 to +5.27 kg). Waist circumference increased by 2 cm (IQR: 0 to +4 cm). There was no difference between weight change and tertile of calcium intake adjusted on energy intake. We did not find any correlation between weight change and total calcium intake (Rho=0.186; P=0.3165) or dairy calcium intake (Rho=0191; P=0.3040). Similarly, we did not find any correlation between waist circumference change and total calcium intake (Rho=0.324; P=0.1205) or dairy calcium intake (Rho=0.285; P=0.0755). CONCLUSION We found no relation between total or dairy calcium intake and weight change during initiation of insulin therapy in type 2 diabetic patients. Dietary calcium intake does probably not play a major role on insulin-induced body weight gain.

Cardiovascular prognosis in patients with type 2 diabetes: Contribution of heart and kidney subclinical damage

BACKGROUND Left ventricular hypertrophy (LVH) and kidney damage (abnormal urinary albumin-to-creatinine ratio [uACR] or estimated glomerular filtration rate [eGFR]) are predictive of major cardiovascular events (MACE) in patients with type 2 diabetes (T2D) but are rarely used in cardiovascular score calculators. Our study aimed to assess their respective prognostic values for MACE and the additive information they provide to score calculators. METHODS A total of 1298 T2D (43% women) aged 65 (SD 11) years were followed up for a median of 65 months, with MACE as a primary composite end point: cardiovascular death, nonfatal myocardial infarction, or stroke. Electrocardiogram (ECG)-derived LVH was defined using Sokolow, Gubner, and Cornell product indexes; uACR was considered as abnormal if >2.5 mg/mmol in men or >3.5 mg/mmol in women and eGFR if <60 mL/min per 1.73 m(2). RESULTS Urinary albumin-to-creatinine ratio was higher in subjects with electrocardiographic LVH (ECG-LVH) than in subjects without (median [interquartile range] 7.61 [43.48] and 2.56 [10.53], respectively; P < .0001). After adjustment for age, history of myocardial infarction, and peripheral artery disease, ECG-LVH and kidney damage were strong predictors for MACE (adjusted hazard ratio [1.64; 95% CI 1.23-2.20], [1.90; 95% CI 1.43-2.53], and [1.85; 95% CI 1.42-2.41] for ECG-LVH, uACR, and eGFR, respectively). Net reclassification improvement was higher with the model including both ECG-LVH and uACR than models with ECG-LVH alone (P < .0001) or uACR alone (P < .0001). In addition, using cardiovascular risk calculators (Framingham score and others), we observed an additional prognostic value of ECG-LVH for each one of them. CONCLUSIONS Electrocardiographic LVH is complementary to kidney damage for MACE prediction in T2D.