B. Bauduceau

Diabetes and inflammation: Fundamental aspects and clinical implications

AIM The aim of this paper is to provide the fundamental background of the inflammation theory associated with type 2 diabetes, to discuss the clinical consequences of low-grade inflammation, particularly in terms of cardiovascular risk, and to infer some clinical therapeutic strategies deriving from drugs that already exist or are in development. METHODS This non-exhaustive work is the result of a Pubmed(®) research, based on requests including the following keywords: diabetes, inflammation, innate immunity, obesity, reticulum endoplasmic stress, cytokines, endothelial dysfunction. RESULTS Obesity and type 2 diabetes are linked with a low-grade inflammation state that reflects the activation of innate immunity where metabolic, environmental and genetic factors are implicated. The role of endoplasmic reticulum stress and unfold protein response is underlined. Inflammation markers are predictive for the risk to develop diabetes, and are associated with an increased cardiovascular risk. While lifestyle modifications are followed by an improvement in inflammation markers, treatments inferred from the inflammation theory are of great interest, although quite moderate effects on glycaemic control have been observed with some of them. CONCLUSION The development of molecules targeting different inflammatory mechanisms could lead in diabetic patients to improvement of both glycaemia and cardiovascular prognosis.

Should pancreas imaging be recommanded in patients over 50 years when diabetes is discovered because of acute symptoms

The relationship between diabetes mellitus and cancer of the pancreas is complex and incompletely understood. Nevertheless, it is generally agreed that new-onset diabetes in a patient over 50 Years old is a classical indication of pancreatic cancer. But there is no official directive in France that a scan should routinely be performed in such cases. We have studied 115 patients aged over 50 who were hospitalized for new-onset diabetes (fewer than 30 days) whose instability required insulin treatment. Routine imaging revealed abdominal disorders in 14 patients, 6 (5.2%) of whom were suffering from pancreatic adenocarcinomas. No clinical indication or laboratory test, apart from an unusually severe anorexia, suggested the discovered disorders. We therefore routinely carry out a pancreas scan, preferably by MRI, on all patients over 50 Years old presenting with new-onset diabetes, even if there are not clinical or laboratory indications of cancer. This is the only way in which small pancreatic cancers can be detected, thus providing the best hopes for successful treatment. Unfortunately, too often, this approach also detects only tumors that are already well developed. However, nowadays, it is not conceivable for a clinical team to discharge a patient from hospital with such a serious disease undiagnosed.

Hypoglycaemia and dementia in diabetic patients.

Diabetes and dementia, which have a complex relationship between them, are undergoing extensive growth in their fields. The occurrence of hypoglycaemia, the potential severity of which has just been pointed out in some recent studies, must be included in these relationships. In fact, diabetes is the cause of decline in cognitive functions and most certainly is involved in the occurrence of vascular dementia. The brain, which is highly dependent on glucose for its metabolism, is particularly vulnerable to hypoglycaemia in children and the elderly. Animal studies and pathoanatomical observations confirm the clinical impression of the reality of genuine post-hypoglycaemic encephalopathy. The impact of mild hypoglycaemia however is being debated. Lastly, the existence of dementia promotes the occurrence of hypoglycaemia due to disorders related to eating habits or poor treatment management. This hypoglycaemic risk however must not constitute a pretext for exaggerated laxity in achieving the blood glucose objectives.

Screening of cardiovascular autonomic neuropathy in patients with diabetes using non-invasive quick and simple assessment of sudomotor function

AIM Cardiovascular autonomic neuropathy (CAN) is a common but often overlooked complication of diabetes. Sympathetic C-fibers innervating sweat glands can be impaired early on in patients with diabetes. In this study, SUDOSCAN, a new non-invasive device that assesses sudomotor function was compared to methods generally used for the investigation of CAN. PATIENTS A total of 232 patients with diabetes were measured for heart rate variability (HRV) at rest and during moderate activity. Time and frequency domain analysis techniques, including measurement of the low-frequency (LF) domain component, were assessed during HRV testing. Ewing tests, as recommended by the French Health Authority, were also done. Electrochemical sweat conductance (ESC) was measured on the hands and feet, and a risk-score was calculated. RESULTS Using two abnormal Ewing tests as a reference for the area under the curve (AUC) of the receiver operating characteristics (ROC) curve for SUDOSCAN, the risk-score was 0.74, with a sensitivity of 92% and specificity of 49% for a risk-score cut-off value of 35%. For the ROC curve analysis using the LF power component during moderate activity at a threshold of 90 ms(2) (first quartile) as reference, the AUC was higher for the SUDOSCAN risk-score (0.77) compared with the standard Ewing tests [E:I ratio (0.62), 30:15 ratio (0.76) and blood pressure change on standing (0.55)]. Using a cut-off value of 35%, risk-score sensitivity and specificity were 88 and 54%, respectively. CONCLUSION SUDOSCAN, which allows quick quantitative assessment of sudomotor function, may be used for early screening of CAN in everyday clinical practice before resorting to the more sophisticated and specific, but ultimately more time-consuming, Ewing tests.

A Prevalence Survey of Diabetes in Mauritania

OBJECTIVE To perform an epidemiological study of the prevalence of diabetes in Mauritania, West Africa, with little data available on diabetes in West Africa. RESEARCH DESIGN AND METHODS The study was performed with a representative sample of the Mauritanian population. A random selection of the study population (n = 744) was drawn by a cluster sampling method. Screening for diabetes was made by capillary blood glucose (CBG) measurement, using strips analyzed by reflectance meter. Criteria for the diagnosis of diabetes were those of the World Health Organization (WHO). RESULTS The survey performed a screening of 744 subjects whose sex distribution was 307 men and 437 women. Their mean age was 34.6 ± 15.2 years, and their mean BMI was 22.7 ± 5.1 kg/m2, with a significant difference for BMI between men (20.0 ± 2.9 kg/m2) and women (24.3 ± 5.5 kg/m2). According to the study criteria, we found 14 diabetic patients (4 men, 10 women). The crude prevalence of diabetes was 1.88% (95% CI 0.90–2.86). The difference in prevalence by sex was 1.30% (95% CI 0.00–2.60) for men and 2.29% (95% CI 0.89–3.43) for women. For the truncated 30- to 64-year-old age-group, the crude prevalence was 2.84%; the age-adjusted prevalence for the same 30- to 64-year-old age-group, using the standardized age distribution of Segi (10), was 2.61%. CONCLUSIONS With a crude prevalence of diabetes of 1.88% and an age-adjusted prevalence of 2.61%, Mauritania may be classified among the countries with a low prevalence of diabetes, a finding which is not surprising, considering the low level of development of this region of Africa.

Normative Values for Electrochemical Skin Conductances and Impact of Ethnicity on Quantitative Assessment of Sudomotor Function

BACKGROUND Sudomotor dysfunction is one of the earliest pathophysiologic abnormalities in diabetes. Sudoscan™ (Impeto Medical, Paris, France) was developed as a noninvasive, rapid, and quantitative assessment of sudomotor function and has been shown to be sensitive in the detection of neuropathy. This global collaborative analysis aimed to establish reference values in healthy subjects of different ethnic groups, age, and gender, to define factors potentially affecting results, and to provide standardization of the methodology. MATERIALS AND METHODS Data from 1,350 generally healthy study participants who underwent sudomotor function testing were collected and analyzed. The relationship between age, height, weight, gender, glycemic and lipid profiles, ethnicity, and hand and foot electrochemical skin conductance (ESC) was assessed among subgroups of participants. RESULTS Lower mean hands and feet ESC values were observed in African American, Indian, and Chinese subjects (P < 0.0001). No participant discomfort or safety concern was reported in 1,376 tests. No significant difference in ESC was observed between women and men at the hands (75 [57-87] vs. 76 [56-89] μS; P = 0.35) or feet (83.5 [71-90] vs. 82.5 [70-91] μS; P = 0.12). The coefficient of correlation between right and left side ESC was r = 0.96, P < 0.0001 for hands and r = 0.97, P < 0.0001 for feet. A significant but weak correlation was observed between ESC and age: for hands, r = -0.17, P < 0.0001; for feet, r = -0.19, P < 0.0001. CONCLUSIONS A normative reference range was established in whites showing that there was no effect of sex or body mass index and a slight decrease in ESC with age. Ethnicity influenced ESC scores, but additional studies are necessary to validate this effect and determine its mechanism and impact on nerve function.

Prise de position de la Société Francophone du Diabète (SFD) sur la prise en charge médicamenteuse de l'hyperglycémie du patient diabétique de type 2

Composition du groupe de relecture Mme Carole Avril, Directrice Générale de la Fédération Française des Diabétiques (Paris) Dr Éric Drahi, médecin généraliste (Saint-Jean-de-Braye) Pr Jean Doucet, interniste gériatre et diabétologue, Professeur de Thérapeutique (Rouen) Pr Serge Halimi, endocrinologue-diabétologue, Professeur Émérite de Nutrition (Grenoble) Pr Anne-Marie Magnier, Professeur Honoraire de Médecine Générale (Paris, Sorbonne) Dr Laurent Meyer, endocrinologue-diabétologue (Strasbourg) Pr Ronan Roussel, endocrinologue-diabétologue (Paris, Diderot) Dr Pierre Serusclat, endocrinologue-diabétologue (Vénissieux) Pr Charles Thivolet, endocrinologue-diabétologue (Lyon) Composition du groupe de travail de la SFD Pr Bernard Bauduceau (endocrinologuediabétologue, Saint-Mandé), Pr Lyse Bordier (endocrinologue-diabétologue, Saint-Mandé), Pr Bernard Charbonnel (endocrinologue-diabétologue, Nantes), Pr Emmanuel Cosson (endocrinologuediabétologue, Bobigny), Pr Patrice Darmon (endocrinologue-diabétologue, Marseille), Dr Bruno Detournay (CEMKA-EVAL, Bourg-la-Reine), Pr Pierre Fontaine (endocrinologue-diabétologue, Lille), Pr André Grimaldi (endocrinologue-diabétologue, Paris), Pr Pierre Gourdy (endocrinologue-diabétologue, Toulouse), Pr Bruno Guerci (endocrinologue-diabétologue, Nancy), Pr Hélène Hanaire (endocrinologue-diabétologue, Toulouse ; présidente de la SFD), Pr Alfred Penfornis (endocrinologue-diabétologue, Corbeil-Essonnes), Pr André Scheen (endocrinologue-diabétologue, Liège, Belgique).

Retinopathy, nephropathy, peripheral neuropathy and geriatric scale scores in elderly people with Type 2 diabetes.

To analyse the relationships between retinopathy, nephropathy, peripheral neuropathy and geriatric scale scores in elderly people with Type 2 diabetes.

Rilmenidine in the hypertensive type-2 diabetic: a controlled pilot study versus captopril.

Background Rilmenidine is an innovative antihypertensive agent that binds specifically to I1 imidazoline receptors. The antihypertensive efficacy of rilmenidine in treating type-2 diabetics has been demonstrated, and is associated with very good clinical and laboratory tolerance. Design This was a 6-month, double-blind, randomized, controlled study comparing the effects of rilmenidine and captopril on the progression of microalbuminuria in a population of patients with mild-to-moderate hypertension [90 mmHg < diastolic blood pressure (DBP) < 110 mmHg], type-2 diabetes, and microalbuminuria (30 mg/24 h < urine albumin excretion ≤ 300 mg/24 h). Results Between month 0 and month 6, the mean supine blood pressure was reduced in a similar manner by rilmenidine (systolic blood pressure from 159 to 141 mmHg and diastolic blood pressure from 98 to 84 mmHg) and captopril (systolic blood pressure from 157 to 144 mmHg and diastolic blood pressure from 101 to 82 mmHg). The median value for microalbuminuria was reduced from 160 (90–260) to 56 (27–87) mg per 24 h by rilmenidine and from 144 (51–200) to 54 (41–123) mg per 24 h by captopril. Rate of clearance of creatinine was not significantly changed during the study by either treatment (with rilmenidine it varied from 95.2 to 95.6 ml/min; with captopril it varied from 86.2 to 90.4 ml/min). There was no statistical difference between the changes in levels of glycosylated hemoglobin for the groups treated with rilmenidine and captopril. Clinical and laboratory acceptabilities were good, and those for the two groups were comparable. Conclusion Rilmenidine exerts similar antihypertensive effects to those of captopril on the hypertensive with type-2 diabetes. Decreases in microalbuminuria elicited by the two treatments do not differ. That administration of rilmenidine decreases microalbuminuria suggests that it could exert nephroprotective effects.

Military Community: A Privileged Site for Clinical Research: Epidemiological Study of Metabolic Syndrome Risk Factors in the Military Environment

The metabolic syndrome is considered to be an important public health problem. The Epidemiological Study of Metabolic Syndrome Risk Factors in the Military Environment is a prospective epidemiological study that is designed to identify clinical and laboratory parameters of metabolic syndrome and cardiovascular risk factors with an initial 1-year cross-sectional study followed by a 10-year follow-up and patient care. One hundred eight-five (9%) of 2,045 military personnel subjects presented at least three of the five National Cholesterol Education Program Expert Panel on Detection, Evaluation and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) criteria. They were significantly older (42.2 +/- 8.5 years) than the other subjects (37.3 +/- 8.7 years, p < 0.001), had a higher body mass index (BMI) (29.5 +/- 3.4 vs. 24.8 +/- 2.9, p < 0.001), and a greater body weight at age 20 (75.4 +/- 11 vs. 70.4 +/- 8.5 kg, p < 0.001). Smoking, little physical activity, and family histories of diabetes and arterial hypertension were more frequent in these subjects. Total plasma cholesterol and C-reactive protein were higher. Plasma insulin and BMI (r = 0.456, p < 0.0001) and plasma insulin and waist circumference (r = 0.446, p < 0.0001) were well correlated. Plasma insulin and homeostasis model assessment increased with the number of metabolic syndrome criteria. These results demonstrate a strong association with insulin resistance. Men with several risk factors require specific care especially for hypertension and dyslipidemia that will be evaluated during the follow-up period. Genotyping of subjects having metabolic syndrome vs. controls for genes, presumably involved should enlarge the area of exploration of this syndrome.