Diabetes mellitus and vascular lesions.

Cardiovascular complications represent by far the most severe manifestations of diabetes mellitus. Treatment aimed at stopping progression of vascular lesions may fall short if initiated when the disease becomes clinically evident. Therefore, identification of the earliest vascular disfunctions may offer the best opportunity to interfere with pathogenic mechanisms and avoid progression of diabetic vasculopathy. In this report, we present a few mechanisms that alter hemodynamic and metabolic homeostasis in the course of diabetes mellitus. Endothelial function with special emphasis on nitric oxide and oxidative stress, advanced glycation end products, and the renin angiotensin system are briefly discussed. New pharmacological agents that may favorably influence these parameters are presently undergoing clinical trials. However, tight control of plasma glucose and cardiovascular risk factors represent the cornerstone of the treatment in diabetes to slow progression of vascular disease.

Cloning and functional expression of the human islet GLP-1 receptor. Demonstration that exendin-4 is an agonist and exendin-(9-39) an antagonist of the receptor.

A complementary DNA for a glucagon-like peptide-1 receptor was isolated from a human pancreatic islet cDNA library. The isolated clone encoded a protein with 90% identity to the rat receptor. In stably transfected fibroblasts, the receptor bound [125I]GLP-1 with high affinity (Kd = 0.5 nM) and was coupled to adenylate cyclase as detected by a GLP-1-dependent increase in cAMP production (EC50 = 93 pM). Two peptides from the venom of the lizard Heloderma suspectum, exendin-4 and exendin-(9-39), displayed similar ligand binding affinities to the human GLP-1 receptor. Whereas exendin-4 acted as an agonist of the receptor, inducing cAMP formation, exendin-(9-39) was an antagonist of the receptor, inhibiting GLP-1-induced cAMP production. Because GLP-1 has been proposed as a potential agent for treatment of NIDDM, our present data will contribute to the characterization of the receptor binding site and the development of new agonists of this receptor.

Diabète de type 2: n'oubliez pas les troubles du comportement alimentaire [Patient with type 2 diabetes: don't forget eating disorders!]

The coexistence of diabetes and eating disorder (ED) is more prevalent than we think; indeed it seems to occur in 10 to 20% of cases. Therefore ED deserve attention to be detected and treated in order to permit a decreased in morbidity and better outcomes in body weight loss. The association of type 2 diabetes and ED is frequently seen in younger, overweighed or obese patients suffering of at least one psychiatric co-morbidities and frequently in a difficult psychosocial setting. To succeed in ED treatment, a multidisciplinary and specialised team in eating disorder is requested, however these patients are highly fragile and complex and therapeutic failure has to be feared.

Glucagon-like peptide-1 and control of insulin secretion.

Although glucose is the major regulator of insulin secretion by pancreatic beta cells, its action is modulated by several neural and hormonal stimuli. In particular, hormones secreted by intestinal endocrine cells stimulate glucose-induced insulin secretion very potently after nutrient absorption. These hormones, called gluco-incretins or insulinotropic hormones, are major regulators of postprandial glucose homeostasis. The main gluco-incretins are GIP (gastric inhibitory polypeptide or glucose-dependent insulinotropic polypeptide) and GLP-1 (glucagon-like polypeptide-1). The secretion of GIP, a 42 amino acid polypeptide secreted by duodenal K cells, is triggered by fat and glucose. GIP stimulation of insulin secretion depends on the presence of specific beta-cell receptors and requires glucose at a concentration at least equal to or higher than the normoglycaemic level of approximately 5 mM. GIP accounts for about 50% of incretin activity, and the rest may be due to GLP-1 which is produced by proteolytic processing of the preproglucagon molecule in intestinal L cells. GLP-1 is the most potent gluco-incretin characterized so far. As with GIP, its stimulatory action requires a specific membrane receptor and normal or elevated glucose concentrations. Contrary to GIP, the incretin effect of GLP-1 is maintained in non-insulin-dependent diabetic patients. This peptide or agonists of its beta-cell receptor could provide new therapeutic tools for the treatment of Type II diabetic hyperglycaemia.

Stratégies thérapeutiques en présence d'un diabète de type 2 [Therapeutic strategies in type 2 diabetes]

UKPDS and DCCT studies have demonstrated the critical role of tight glycaemic control to reduce the micro- and macro-vascular damage linked to diabetes. Unfortunately, the insulin requirement of type 2 diabetic patients remains elevated since 5 to 7% of these patients will required, yearly, a change from oral antidiabetic drug to insulin treatment to maintain a good glycaemic control. This manuscript is intended to review the currently available oral antidiabetic drugs, their benefits as well as potential arms and to propose a simplified therapeutic strategy in presence of type 2 diabetes.

Association of poorly controlled diabetes with low serum leptin in morbid obesity.

OBJECTIVES: Leptin may be involved in the regulation of body weight, food intake, and energy expenditure. In view of a possible link between leptin concentrations and diabetes that has been suggested in obese rodents, we investigated the potential relationship between serum leptin concentrations and hyperglycaemia in French patients with morbid obesity. SUBJECTS: Fasting leptin concentrations were measured in 241 morbidly obese patients with various degrees of glucose tolerance in a cross-sectional study. RESULTS: Fasting serum leptin concentrations did not differ between normoglycaemia (NG, 61.5 +/- 24.0 ng/ml) and glucose intolerant morbidly obese subjects (IGT, 56.5 +/- 18.5 ng/ml) and were slightly lower in those with controlled diabetes (55.1 +/- 30.3 ng/ml, P = 0.06 when compared to NG subjects). In contrast, leptin concentrations were 30% lower in patients with poorly controlled diabetes (43.0 +/- 22.2 ng/ml, P = 0.001 vs NG subjects). Leptin concentrations were negatively correlated with fasting glucose in all groups combined (p = -0.24, P = 0.0001) and particularly in NIDDM subjects (p = 0.31, P = 0.0054). Although leptin concentrations were higher in women than in men, similar significant correlation with fasting glucose was found when females were analyzed separately. A positive correlation was found with BMI (p = 0.25, P = 0.0001) in all groups. Multivariate analysis revealed that fasting glucose was independently associated with serum leptin concentrations (F = 12.5, P = 0.0005). Sex, age, BMI, waist/hip ratio, fasting glucose and insulin, total cholesterol and triglycerides, tested in the model, explained 42% of the leptin variability in this population. CONCLUSIONS: Poorly controlled diabetes was accompanied by a significant reduction of serum leptin concentrations in morbidly obese subjects. We suggest that a relative leptin deficiency (lower than expected for the BMI) associated with insulin deficiency in this population might contribute to a vicious cycle maintaining (or even worsening) obesity itself and/or its metabolic complications.

Quette place pour l'automesure glycémique dans la prise en charge du diabète de type 2 [Which role for self-monitoring of blood glucose in type 2 diabetes?]

There is a sustained controversy in the literature about the role and utility of self-monitoring of blood glucose (SMBG) in type 2 diabetes. The study results in this field do not provide really useful clues for the integration of SMBG in the follow-up of the individual patient, because they are based on a misconception of SMBG. It is studied as if it was a medical treatment whose effect on glycemic control is to be isolated. However, SMBG has no such intrinsic effect. It gains its purpose only as an inseparable component of a comprehensive and structured educational strategy. To be appropriate this strategy cannot be based on the health care professionals' view on diabetes only. It rather has to be tailored to the individual patient's needs through an ongoing process of shared reflection with him.

Diabetes mellitus, periapical inflammation and endodontic treatment outcome

The possible connection between chronic oral inflammatory processes, such as apical periodontitis and periodontal disease (PD), and systemic health is one of the most interesting aspects faced by the medical and dental scientific community. Chronic apical periodontitis shares important characteristics with PD: 1) both are chronic infections of the oral cavity, 2) the Gram-negative anaerobic microbiota found in both diseases is comparable, and 3) in both infectious processes increased local levels of inflammatory mediators may have an impact on systemic levels. One of the systemic disorders linked to PD is diabetes mellitus (DM); is therefore plausible to assume that chronic apical periodontitis and endodontic treatment are also associated with DM. The status of knowledge regarding the relationship between DM and endodontics is reviewed. Upon review, we conclude that there are data in the literature that associate DM with a higher prevalence of periapical lesions, greater size of the osteolityc lesions, greater likelihood of asymptomatic infections and worse prognosis for root filled teeth. The results of some studies suggest that periapical disease may contribute to diabetic metabolic dyscontrol

Mortality associated with diabetes mellitus in comparison with history of cardiovascular disease in older women.

Current treatment guidelines consider diabetes to be equivalent to existing cardiovascular disease (CVD), but few data exist about the relative importance of these risk factors for total and CVD mortality in older women.We studied 9704 women aged >= 65 years enrolled in a prospective cohort study (Study of Osteoporotic Fracture) during a mean follow-up of 13 years and compared all-cause and CVD mortality among non-diabetic women without and with history of CVD at baseline and diabetic women without and with history of CVD. Diabetes mellitus and CVD were defined as self-report of physician diagnoses. Cause of death was adjudicated from death certificates and medical records when available. Ascertainment of vital status was 99% complete. Multivariate Cox hazard models adjusted for age, smoking, physical activity, systolic blood pressure, waist girth and education were used to compare mortality among the four groups with non-diabetic women without CVD as the referent group. At baseline mean age was 71.7 &#129;} 5.3 years, 7.0% reported diabetes mellitus and 14.5% reported prior CVD. 4257 women died during follow-up, 36.6% were attributed to CVD. Compared to non-diabetic women without prior CVD, the risk of CVD mortality was elevated among both non-diabetic women with CVD (HR = 1.82, 95% CI: 1.60-2.07, P <0.001) and diabetic women without prior CVD (HR = 2.24, CI: 1.87-2.69, P <0.001). CVD mortality was highest among diabetic women with CVD (HR = 3.41, CI: 2.61-4.45, P <0.001). Compared to non-diabetic women with CVD, diabetic women without prior CVD had a significantly higher adjusted HR for total and CVD mortality (P < 0.001 and P <0.05 respectively). Older diabetic women without prior CVD have a higher risk of all-cause and CVD mortality compared to nondiabetic women with pre-existing CVD. For older women, these data support the equivalence of prior CVD and diabetes mellitus in current guidelines for the prevention of CVD in primary care.

Diabetes mellitus: la pandemia del siglo XXI

La diabetes mellitus (DM) constituye uno de los principales problemas de salud pública debido a su elevada prevalencia, al hecho de que puede afectar a personas de cualquier edad, sexo, clase social y área geográfica, a su elevada morbilidad y mortalidad y a su elevado coste sanitario. Tanto la DM tipo 1 (DM1) como la DM tipo 2 (DM2) cursan con hiperglucemia lo que puede originar complicaciones agudas hiperglucémicas e hipogucémicas, debido al tratamiento, y graves complicaciones crónicas macrovasculares y microvasculares, que pueden producir infarto de miocardio, accidente vascular...