Low Dosage and Long Treatment Duration of {beta}-Lactam: Risk Factors for Carriage of Penicillin-Resistant Streptococcus pneumoniae

Context.— The spread of drug-resistant Streptococcus pneumoniae in the community is a public health problem in developed and developing nations, but whether antibiotic use is responsible for the increase in drug resistance is not known. Objective.— To analyze the relationship between penicillin-resistant S pneumoniae (PR Sp) pharyngeal carriage and characteristics of -lactam use. Design.— Observational study of children attending 20 randomly sampled schools. Setting.— The Loiret, in the center of France. Participants.— A total of 941 children, 3 to 6 years old. Main Outcome Measure(s).— Pharyngeal carriage of S pneumoniae, antibiotic use, and medical events during the preceding 30 days. Pneumococcal penicillin G sodium minimal inhibitory concentrations and serotyping were performed. Results.— Medical illnesses and the use of antibiotics were not associated with PR Sp carriage. However, oral -lactam use was associated with an increased risk of PR Sp carriage (odds ratio [OR], 3.0; 95% confidence interval [CI], 1.1-8.3; P=.03). Children treated by low daily doses of an oral -lactam (defined as lower than clinical recommendations) had an increased risk of PR Sp carriage, as compared with children who did not (OR, 5.9; 95% CI, 2.1-16.7; P =.002). A treatment of long duration (>5 days) with a -lactam was associated with an increased risk of PR Sp carriage (OR, 3.5; 95% CI, 1.3-9.8; P=.02). Conclusions.— Our results suggest that a low daily dose and a long duration of treatment with an oral -lactam contribute to the selective pressure in promoting pharyngeal carriage of PR Sp.      

Analysis of common PTPN1 gene variants in type 2 diabetes, obesity and associated phenotypes in the French population

Background  

The protein tyrosine phosphatase-1B, a negative regulator for insulin and leptin signalling, potentially modulates glucose and energy homeostasis. PTP1B is encoded by the PTPN1 gene located on chromosome 20q13 showing linkage with type 2 diabetes (T2D) in several populations. PTPN1 gene variants have been inconsistently associated with T2D, and the aim of our study was to investigate the effect of PTPN1 genetic variations on the risk of T2D, obesity and on the variability of metabolic phenotypes in the French population.     

Urinary albumin excretion is a risk factor for diabetes mellitus in men, independently of initial metabolic profile and development of insulin resistance. The DESIR Study

BACKGROUND: Elevated urinary albumin excretion (UAE) is more frequent in patients with the metabolic syndrome or insulin resistance. Whether UAE predicts the development of diabetes mellitus, independently of the presence or the development of the metabolic syndrome, is unclear, in particular, in women. OBJECTIVE: We prospectively assessed the association between baseline UAE and subsequent diabetes mellitus in participants selected from the general population. PARTICIPANTS AND METHODS: Four thousand and seventy-four nondiabetic patients (aged 30-64 years) included in the Data from an Epidemiological Study on the Insulin Resistance syndrome Study had a baseline UAE. Among them, 3851 patients had complete data regarding diabetes mellitus. RESULTS: Diabetes mellitus occurred in 171 out of 3851 patients during the 9-year follow-up (132/2056 men and 39/1795 women). UAE was associated with diabetes mellitus in a dose-dependent manner in men [as compared to men with UAE<9 mg/l, hazard ratios were 1.81 (P=0.0160), 1.83 (P=0.0134), 2.31 (P=0.0008) and 4.43 (P=0.0005) for men with UAE: 9-12 mg/l, 12-19 mg/l, 20-200 mg/l and >200 mg/l, respectively] but not in women; the association was more marked after exclusion of men with baseline impaired fasting glucose [hazard ratios were 3.28 (P=0.0007), 3.08 (P=0.0012), 3.27 (P=0.0022), 9.23 (P<0.0001), respectively]. The association remained significant after adjustments on BMI, sporting activity, diet, smoking, waist circumference, insulin and homeostasis model assessment of insulin resistance, lipids, C-reactive protein and family of history of diabetes mellitus. Adjustment on the first 3-year change in weight, glucose, insulin and homeostasis model assessment of insulin resistance did not modify the results. CONCLUSION: Elevated UAE predicts the 9-year risk of diabetes mellitus in men, independent of baseline or early development of metabolic abnormalities or insulin resistance.     

Age and sex variations of HbA(1C) in a French population without known diabetes aged 6 to 79 years

HbA(1C) is being used for screening and diagnosing diabetes. We determined mean values of HbA(1C) according to age and sex in a large population without known diabetes, in a wide age range 6-79 years. 5,138 men and women without known diabetes aged 6-79 years participated in a routine health examination provided by their medical insurance. HbA(1C) was assessed on an HPLC analyzer aligned with a DCCT method. HbA(1C) was approximately normally distributed in both men and women. Mean (SD) HbA(1C) were, for men vs women, in percentages 5.3 (0.4) vs 5.2 (0.3), in mmol/mol 34 (5) vs 34 (4) and in estimated blood glucose in mmol/L 5.83 (0.67) vs 5.75 (0.53). HbA(1C) increased with age by 0.08% every 10 years and this was attenuated to a 0.04% increase after adjustment on fasting plasma glucose. Between 15 and 49 years, women had lower values than men (p < 0.0001), but no sex differences were observed before and after this age range. In our population, 0.6% had HbA(1C) greater or equal to 6.5% and 88% (96% of men and 73% of women) of them had fasting plasma glucose greater or equal to 6,1 mmol/L. Threshold of 6.0% selected 2.8% of our population.     

Number of children and change in markers of metabolic health over 9-years in men and women. Data from the DESIR study

Aim

Parity is associated with an increased risk of coronary heart disease and type 2 diabetes, possibly mediated by long-term modification of metabolic health. Studying associations between the number of children with health and disease in men in addition to women allows for differentiation between the social and lifestyle influences of child-rearing, and the biological influences of childbearing. We sought to determine whether the number of children is associated with the incidence of raised fasting glucose (fasting plasma glucose ≥ 6.1 mmol/L) and changes in glucose, insulin, insulin resistance and β-cell function over 9-years.

Methods

Analysis of 1798 women and 1737 men from the DESIR study.

Results

The number of children was associated with change in fasting glucose for women (P_trend = 0.02) and men (P_trend = 0.03), and increased incidence of raised fasting glucose by 30% (95% CI: 15, 47%) per child for men, but not women (3% [95% CI: −8, 15%]). There was a J-shaped association between number of children and change in insulin (P = 0.01) and insulin resistance (P = 0.005) for women, and a reduction in β-cell function in parous women (P = 0.07). Men with children had increases in insulin (P = 0.02), insulin resistance (P = 0.02), and β-cell function (P = 0.07).

Conclusions

The number of children a person has is associated with changes in metabolic health indices long after childbirth for both men and women. The distinct gender differences in deterioration of metabolic health indices emphasize that childbearing and child-rearing are likely to have differential influences on metabolic health.     

Polymorphisms of the lamina maturation pathway and their association with the metabolic syndrome: the DESIR prospective study

Laminopathies are rare monogenic diseases, some of them exhibiting features of the metabolic syndrome. These diseases are mainly due to mutations in LMNA, encoding A-type lamins. One LMNA polymorphism, rs4641, has been associated with the metabolic syndrome, but results have been controversial. We therefore investigated the effect of single nucleotide polymorphisms (SNPs) in the LMNA gene in combination with four other genes encoding enzymes influencing lamin post-translational maturation on risk of metabolic syndrome (MS). Twenty-three tagging SNPs characterising the haplotypic variability of five genes (LMNA, ICMT, ZMPSTE24, FNTA and FNTB) were genotyped in 3,916 French men and women who took part in the prospective DESIR study. Single locus and haplotype analyses were performed but did not detect any significant association with the risk of MS. No robust interaction between SNPs located in different genes on the risk of MS was identified. In conclusion, we did not observe any convincing evidence that common polymorphisms of the lamina pathway could modulate the risk of MS.     

The burden of diabetes-related mortality in France in 2002: an analysis using both underlying and multiple causes of death

Aim To describe the burden of diabetes-related mortality in France. Methods Underlying and multiple causes (all causes listed) of death were extracted from the 2002 French national mortality registry. Death rates were standardized on the age structure of the European population. Results Diabetes was reported as the underlying cause of death in 11,177 certificates (2.1%), and as multiple causes in 29,357 certificates (5.3%), giving a ratio (multiple/underlying causes) of 2.6. When diabetes was a multiple cause, the mean age at death was 75 years in men, 81 years in women. The age-standardized mortality rates were 41.0/100,000 in men, 24.6/100,000 in women. The excess mortality observed in men (men/women ratio = 1.7) decreased with age. Geographic differences were observed: higher rates in the North-East, lower rates in the West of the country. In certificates mentioning diabetes, the most frequent cause of death was diseases of the circulatory system (76%). Coronary heart diseases, foot ulcers and renal diseases were more likely to be mentioned in certificates referring to diabetes than in those that did not. Discussion The use of multiple rather than underlying causes of death more than doubled diabetes-related mortality rates. While probably still under-estimated, the burden of diabetes-related mortality corresponds to a high proportion of the total mortality, especially in men. Geographic differences partially reflect disparities in diabetes prevalence. Causes more frequently associated with diabetes include coronary heart disease and complications related to neuropathy and nephropathy.     

Anthropometrics,body shape over 12 years and risk of cancer events in pre‐ and post‐menopausal women

Studies of anthropometry and cancer have focused on body mass index (BMI). Relations between weight, waist (WC) and hip circumferences (HC), birth length and adult height with cancer are less well studied. Women from the French E3N study, born between 1925 and 1950, were followed biennially from 1995 until 2008. Body shape was classed into four groups based on median WC and HC at baseline. Hazard ratios (HRs) were estimated by Cox proportional hazards regression models. Over the 12 years of follow‐up, 7,247 of 63,798 women developed cancer. As WC increased, we found a trend for decreasing cancer risk in pre‐menopausal women, which reversed to an increasing risk in post‐menopausal women. This remained unchanged after further adjustment for HC /or height [HR: 0.72 (0.52–1.00) before menopause and 1.17 (1.04–1.31) in the 5th vs. 1st quintile of HC], and were similar after exclusion of breast cancer. We showed that large body shape decreased cancer risk before menopause and increased it after [HR: 0.87 (0.73–1.02) and 1.11 (1.04–1.17), respectively, in women with large waist and hips compared to small waist and hips]. Adult height was associated with an non‐significant increase in cancer in pre‐menopause and a significant cancer risk in menopause, independent of other anthropometric characteristics [5th vs. 1st quintile [HR: 1.24 (0.98–1.56) and 1.20 (1.10–1.30)], respectively as was long birth length in post‐menopausal women [HR: 1.18 (1.07–1.30) compared to medium birth length]. These results suggest independent roles of height and WC on cancer risk, through different pathways.     

Reproducibility of the diagnosis of diabetes over a 30-month follow-up: the Paris Prospective Study.

OBJECTIVE: To describe the change in diabetic status over 30 months. RESEARCH DESIGN AND METHODS: Cohort study of 5,400 Caucasian men from the Paris Prospective Study, aged 44-55 years, who were not known as having diabetes at baseline. Oral glucose tolerance tests were performed at baseline and after 30 months. RESULTS: At baseline, diabetes was diagnosed in 2.9% of the men by fasting plasma glucose (FPG) > or =7.0 mmol/l and in 0.9% by isolated postchallenge hyperglycemia (IPH) (FPG <7.0 mmol/l and 2-h plasma glucose concentration > or =11.1 mmol/l), i.e., one in four of all men with newly diagnosed diabetes. Thirty months later, 42% of the men with diabetes diagnosed by FPG reverted to nondiabetic status, compared with 72% of those with diabetes diagnosed by IPH (P < 0.0001). For the men with diabetes diagnosed by FPG at baseline, diabetes had been diagnosed by a physician at 30 months in 11.5%, in contrast to only 3.9% of those with diabetes diagnosed by IPH (P < 0.05). For the 51 men with diabetes diagnosed by IPH at baseline, those who reverted to nondiabetic status had a lower frequency of family history of diabetes (P < 0.1), a higher mean corpuscular volume (P < 0.08), and a significantly higher total cholesterol concentration (P < 0.006) at baseline; in contrast, for the 156 men with diabetes diagnosed by FPG at baseline, the men who reverted to nondiabetic status and those who remained diabetic had similar characteristics. CONCLUSIONS: In this epidemiological study, diabetes diagnosed by one FPG concentration was more stable than diabetes diagnosed by one IPH; in clinical practice, the diagnosis of diabetes requires confirmation of the hyperglycemia.