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Impaired secretion of parathyroid hormone, but not refractoriness of osteoblast, is a major mechanism of low bone turnover in hemodialyzed patients with diabetes mellitus.

Diabetic bone disease is characterized by low bone turnover resulting from either impaired secretion of parathyroid hormone (PTH) or refractoriness of osteoblasts to PTH. The present study was performed to elucidate which factor contributes more to the reduction in bone turnover by comparison between 64 hemodialyzed patients with diabetes mellitus and 106 hemodialyzed patients without diabetes mellitus. Only men were enrolled to avoid the influence of the menstrual cycle on bone metabolism. Serum intact PTH (iPTH) levels were significantly lower in hemodialyzed patients with diabetes than those without diabetes, although no significant difference existed in age, duration of hemodialysis therapy, or serum calcium or phosphate levels. Of the biochemical markers measured, serum intact osteocalcin (iOC) and deoxypyridinoline levels were significantly lower in patients with diabetes, although serum bone-specific alkaline phosphatase (BAP) and pyridinoline levels did not differ significantly between the two groups of patients. When patients were restricted to those with serum iPTH levels greater than 180 pg/mL, this parameter correlated significantly in a positive manner with both serum iOC and BAP levels and negatively with bone mineral density at distal radius 1/3. Regression slopes between iPTH levels and these parameters were not significantly different between the two groups of patients, indicating the absence of refractoriness of bone to PTH in patients with diabetes. In conclusion, our findings suggest that impaired PTH secretion, but not refractoriness of osteoblasts to PTH, may be responsible for the low bone turnover in hemodialyzed patients with diabetes.

Adult↗

Osteomyelitis associated with peripheral vascular disease secondary to diabetes mellitus.

Diabetes mellitus and arteriosclerotic vascular disease have been found to be the predisposing factors of osteomyelitis associated with peripheral vascular disease (10). A diabetic person is more susceptible to osteomyelitis because of the microangiopathy, peripheral neuropathy and decreased resistance to infection. In diabetes mellitus there can be microangiopathy which results from the proliferation of the endothelium of the intima and thickening of the basement membrane. This further contributes to a sluggish blood flow. In the patient with arteriosclerotic vascular disease, the lumens of the arterioles and arterioles are compromised by the atheromatous plaques. The anatomic structure of the blood supply to bone along with the pathologic membrane thickening, allows for slowing of blood. This slowing of blood flow causes micro-thrombi and enhances bacterial growth. In diabetes mellitus it has been shown that there is a decreased immunologic response which, along with the above, contributes to the sheltering and proliferation of bacteria in the small bones of the foot.

Adolescent↗

Diabetes mellitus.

Diabetes mellitus is a group of metabolic diseases characterized by hyperglycemia resulting from defects in insulin secretion, insulin action, or both. The chronic hyperglycemia of diabetes mellitus is associated with long-term damage, dysfunction, and failure of various organs, especially the eyes, kidneys, nerves, heart, and blood vessels. The management of this disease process is complicated. Good diabetic control depends on diligence in blood glucose monitoring, frequent adjustment of medications, adherence to a regular diet and exercise plan, and treatment of comorbid conditions such as hypertension and hyperlipidemia.

Adolescent↗

Juvenile onset diabetes mellitus, central diabetes insipidus and optic atrophy (Wolfram syndrome)--neurological findings and prognostic implications.

The authors report on one case of Wolfram syndrome, a rare condition, which is characterized by juvenile onset diabetes mellitus, diabetes insipidus, optic atrophy and sensorineural deafness. The findings of this 13-year follow-up show that this patient developed typical neurological complications of long-standing diabetes mellitus as in the common type 1 variant. Moreover, some peculiar signs occurred such as anosmia, ophthalmoplegia interna, and central nystagmus. Since Wolfram syndrome is probably part of a more generalized neurodegenerative disorder, long-term prognosis will depend both upon the severity of chronic diabetic complications and upon the rapidity, by which degeneration of cerebellar, pontine and brain stem structures appear. Prognosis of the cardinal clinical signs is such that optic atrophy, though usually quite rapid in the beginning, generally does not lead to complete blindness. Sensorineural hearing loss progresses very slowly so that deafness might be expected exceptionally only. The hearing deficit in classical diabetics, however, is of retrocochlear origin. Therefore, in Wolfram syndrome, a combined inner-ear and retrocochlear hearing loss may occur.

Adolescent↗

Dominant Western health care: type 2 diabetes mellitus.

Diabetes is a major public health problem with serious complications. In 2002, the Centers for Disease Control estimated that 18.2 million people in the United States had diabetes. One in every 400 to 500 adolescents is diagnosed with type 1 diabetes mellitus (T1DM), and pediatric type 2 diabetes mellitus (T2DM) represents an emerging public health concern. The Children's Hospital of Philadelphia (CHOP) identified 337 children with T2DM through 2004. These children were mostly female and obese with a strong family history of T2DM. One patient's course of treatment for 1.5 years after initial presentation is described. Nineteen percent of the patients at CHOP were diagnosed with a neuropsychiatric illness before T2DM onset, further complicating their treatment. There is an imperative need for large-scale studies investigating the pathophysiology, treatment, and complications of T2DM in adolescents and youth.

Adolescent↗

Oral health care in diabetes mellitus.

Diabetes mellitus produces many complex changes in the lives of those affected. Elevated blood glucose levels, which may occur in the absence of symptoms, lead to late complications from tissue damage. There is an increased susceptibility to infection, poor wound healing and periodontal disease. Furthermore, chronic oral infection itself may contribute to raised blood glucose levels and hence to the later complications of diabetes. Acute infection in the oral cavity needs specific and aggressive management, just as in the acutely infected diabetic foot.' The dental team may not have made a significant contribution to the shared management of the person with diabetes in the past; however, recent findings suggest that the dental team may contribute greatly to the shared care of diabetes with the diabetic team itself, and regular liaison is strongly recommended.

Blood Glucose↗

Comparison of left ventricular function in insulin- and non-insulin-dependent diabetes mellitus.

Diabetes mellitus has been reported to have controversial effects on left ventricular (LV) function in patients with no evidence of coronary artery disease. In this study, LV function at rest was evaluated in 2 groups of diabetic patients, with insulin-dependent (IDD; n = 16) and non-insulin-dependent (NIDD; n = 23) diabetes mellitus, with no evidence of coronary artery disease. All patients underwent an electrocardiographic stress test, and first-pass and equilibrium radionuclide angiography at rest and during supine exercise. Data in each group of diabetic patients were compared with those obtained from age- and sex-matched normal subjects. In both groups of diabetic patients plasma catecholamine levels were significantly greater than in control subjects. Ejection fraction at rest and during exercise did not differ between each group of diabetic patients and their respective control group. In patients with IDD, peak ejection rate (4 +/- 1 end-diastolic count/s) was significantly greater than in control subjects (2.6 +/- 0.1 end-diastolic count/s; p < 0.001); similarly, peak filling rate (4.3 +/- 1.0 end-diastolic count/s) was significantly greater than in controls (3.0 +/- 0.2 end-diastolic count/s; p < 0.001). Cardiac output and systemic vascular resistances did not differ between patients with IDD and control subjects. In contrast, patients with NIDD had significantly reduced cardiac output compared with that of control subjects (5.7 +/- 0.2 vs 5.9 +/- 0.2 liter/min; p < 0.01), and increased systemic vascular resistances (1,422 +/- 137 vs 1,314 +/- 68 dynes.s.cm-5; p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Small molecule activators of the insulin receptor: potential new therapeutic agents for the treatment of diabetes mellitus.

Diabetes mellitus refers to a spectrum of syndromes characterized by abnormally high levels of glucose in blood. These syndromes are associated with an absolute (Type 1 diabetes) or relative (Type 2 diabetes) deficiency of insulin, coupled with varying degrees of peripheral resistance to the actions of insulin. Clinical studies have shown that controlling hyperglycemia significantly reduces the appearance and progression of the vascular complications associated with diabetes. Insulin's regulation of glucose homeostasis is mediated by a cascade of signaling events that take place upon insulin binding to its cell surface receptor. Autophosphorylation of the receptor and activation of its intrinsic tyrosine kinase are critical processes for transmitting these intracellular signals. Type 1 diabetes patients depend on exogenous insulin to achieve these effects, whereas Type 2 diabetes patients can accomplish a similar response through oral medications that increase the production of endogenous insulin or enhance its actions on the target tissues. Current biochemical and clinical evidence suggests that defects within the insulin receptor itself may be a cause of insulin resistance leading to Type 2 diabetes. This review focuses on the insulin receptor as a target for therapeutic intervention, and describes the recent discovery of small molecules that act on the receptor and either enhance or directly emulate the actions of insulin both in vitro and in vivo.

Diabetes Mellitus↗

Apoptosis in the pathophysiology of diabetes mellitus.

Diabetes mellitus is one of the most common non-communicable diseases, and if uncontrolled, targets multi-organ systems with serious debilitating and life-threatening sequela. Most diabetic cases fall under the Type 2 category, characterized by relatively late onset, development of insulin resistance and/or deficiency, and amyloidosis. Type 1 diabetes, on the other hand, manifests early during childhood and has an autoimmune component to it that causes a severe deficiency in the circulating levels of insulin. Despite the heterogeneity in etiology and clinical presentation, hyperglycemia is the most common metabolic abnormality in diabetic patients. At the molecular level, pancreatic beta-cell loss by apoptosis appears to play an important role in the development of insulin deficiency and the onset and/or progression of the disease. Here, we provide a short review on the apoptotic death circuitry in the pathogenesis of diabetes.

Apoptosis↗

[Nasal mucosa in patients with diabetes mellitus].

Diabetes mellitus is the most common endocrinologic disease all over the world. 150 million people suffer from this disease, in Poland about 2 million. The disease on the basis of the onset and pathophysiology may be divided into type I and type II. Pathophysiologic changes include diabetic microangiopathy, macroangiopathy and neuropathy. The most common presentations in head and neck are otitis externa, hypoacusis, vertigo, disequilibrium, xerostomia, dysphagia, fungal and recurrent infections. The changes in nasal mucosa are not very well known. Only few papers concerned the problem. The main complaints of patients regarding the nose are xeromycteria, hyposmia and various degree of decreased patency of the nose. Chronic atrophic rhinitis, septal perforation, ulceration of nasal mucosa, alar necrosis, symptoms of staphylococcal or fungal infection can be found during otolaryngologic examination. The treatment in this group of patients should consist of systemic therapy of diabetes mellitus and on the other hand focal therapy with the use of a solution to moisten the nasal mucosa.

Chronic Disease↗

Salt intake, hypertension and diabetes mellitus.

Diabetes mellitus affects approximately 135 million people in the world. Diabetes and hypertension are both relatively common diseases in westernised countries. Both entities increase with age. Essential hypertension accounts for the majority of hypertension in people with type 2 diabetes, who constitute more than 90% of those with a dual diagnosis of diabetes and hypertension. The benefit conferred per mm Hg blood pressure reduction appears to be greater in persons with type 2 diabetes than in those with hypertension and non-coexistent diabetes mellitus. Similar to a subset of patients with essential hypertension, type 2 diabetic patients manifest dietary NaCl-induced exacerbation of hypertension. Recent guidelines have emphasised that the target blood pressure levels for patients with diabetes should be lower than in other hypertensive groups. An increased total body sodium and enhanced vascular reactivity are found in people with diabetes and most type 2 diabetic patients are salt sensitive. Type 2 diabetes with hypertension is associated with reduced renal plasma flow when dietary salt intake is high. Experimental, observational and interventional evidence support the benefits of sodium restriction in hypertensives. However, the full effects of sodium restriction are usually not obvious for at least 5 weeks. Other favourable effects of moderate reduction in sodium intake are a regress left ventricular hypertrophy, decrease in diuretic-induced potassium wastage, reduction in proteinuria, protection against stroke and from osteoporosis and renal stones, and enhancement of the antihypertensive effect of the antihypertensive agents.

Antihypertensive Agents↗

[Insulin secretion and aging. Implications for insulin therapy in the geriatric patient with diabetes mellitus].

Diabetes mellitus has become a global epidemic. With diabetes prevalence highest in old age groups and aging populations, it is the prevalence among the elderly, above all, where most dramatic increases can be expected. The present paper summarizes the age-related metabolic abnormalities resulting in diabetes mellitus, specifically the progressive decline in beta-cell function. In addition, insulin therapy in the elderly is described. Among the many different insulins and therapeutic algorithms, advantages and disadvantages pertaining to the elderly will be highlighted. Specifics in frequency, pathophysiology, and avoidance of severe hypoglycemia in the elderly are discussed.

Age Factors↗

Limitation of finger joint mobility in diabetes mellitus.

Diabetes mellitus, both insulin dependent and non-insulin dependent, is associated with limitation of joint mobility of the fingers, which can be due to connective tissue changes, neuropathy, vasculopathy, or combinations of these problems. Distinct clinical problems include Dupuytren disease, flexor tenosynovitis, carpal tunnel syndrome (diabetic hand), stiff hand syndrome, shoulder-hand syndrome (reflex dystrophy) and limited joint mobility (LJM). Stiff hand and LJM syndromes are only seen with diabetes; the others have distinct clinical characteristics in those with diabetes compared to the nondiabetic presentation. LJM is of particular interest because it is common in young patients and associated with an increased risk for the serious complications of nephropathy and retinopathy.

Diabetes Mellitus↗

Psychological aspects of diabetes mellitus.

Diabetes mellitus (DM) presents itself in two forms: insulin-dependent (type 1 DM) and non-insulin-dependent (type 2 DM). Although type 2 DM usually has an adult onset, in recent years there has been a significant rise in the number of children diagnosed with type 2 DM in the United States. Reasons for this increased frequency are believed to be a larger percentage of children who are overweight, a family history of diabetes, and a considerable increase in the use of psychotropic medication in children. The diagnosis of DM is a significant stressor not only for patients but also for their environment. Children with DM are sometimes stigmatized by their peers and relatives who do not understand the illness or are frightened by it. Some children also may need to alter several of their customary routines and are often scared to participate in activities in which they were previously engaged. The family's response to the diagnosis of DM may have a negative effect on glycemic control. Differences have been found in the way patients with type 1 DM and type 2 DM cope with and adapt to their diagnosis.

Adolescent↗

The molecular genetics of diabetes mellitus.

Diabetes mellitus is a clinically heterogeneous disorder which is characterized by hyperglycaemia due to an absolute or relative deficiency of insulin. Both genetic and non-genetic factors contribute to its development and, as such, it represents a multifactorial disorder. In addition, it may also be, in some instances, a polygenic disorder resulting from the cumulative effects of several genes with or without environmental factors. Serological and/or DNA markers for genes that confer susceptibility to the insulin-dependent form of the disorder (IDDM; type 1) have been identified in the HLA-D region of chromosome 6 and near the insulin gene on chromosome 11. Patients with non-insulin-dependent diabetes mellitus (NIDDM; type 2) make up a more heterogeneous group than those with IDDM and it is likely that in these patients similar clinical phenotypes may be produced by different genetic defects. The synthesis of either an abnormal insulin/proinsulin molecule or an abnormal insulin receptor can confer susceptibility to NIDDM. The genes encoding insulin and the insulin receptor are on chromosomes 11 and 19, respectively. In addition, studies of restriction fragment length polymorphism and disease associations suggest that two other genes may contribute to the development of NIDDM on chromosome 11, one near the insulin gene on the short arm of this chromosome and the other near the apolipoprotein A-I gene on the long arm. None of the susceptibility genes that have been identified to date causes diabetes in the absence of other genetic or non-genetic contributing factors, which is consistent with a multifactorial or polygenic origin for this disorder.

Alleles↗

[Diabetes mellitus].

Diabetes mellitus is a group of diseases characterized by high levels of blood glucose resulting from defects in insulin production, insulin action, or both. Diabetes is a serious health concern. The number of cases of diabetes mellitus is estimated to grow at a rate of 50% between 2000 and 2010. There are several types of diabetes: type 1 diabetes, type 2 diabetes, gestational diabetes, and other specific types of diabetes. Beta cell dysfunction plays a key role in the physiopathology of diabetes, even when insulin resistance, which is often present in several diabetes-related diseases, is considered among the causes of hyperglycemic type 2 diabetes. The prolonged hyperglycemia that is peculiar to all kind of diabetes has long term complications on several organs and systems. The diagnosis of diabetes is based on the evaluation of glucose plasma levels performed under fasting conditions or two hours after the oral ingestion of 75 grams of glucose. Currently, achieving and maintaining normal plasma levels of glucose are the aims of therapy for both type 1 and type 2 diabetes. Particularly, the therapy for type 1 diabetes is based on the administration of insulin, whereas that of type 2 diabetes changes over the time: diet and physical activity are the first treatments; oral hypoglycemic drugs are used as a second therapeutic step; and the administration of insulin is the last therapeutic option. The principal therapeutic innovation of the past ten years is represented by the tight and flexible control of glucose plasma level obtained by using the insulin analogues produced by recombinant DNA technology.

Diabetes Mellitus↗

[Diagnosis, classification and cathogenesis of diabetes mellitus].

Diabetes mellitus (DM) is a metabolic disorder characterized by the presence of chronic hyperglycemia accompanied by greater or lesser impairment in the metabolism of carbohydrates, lipids and proteins. The origin and etiology of DM can vary greatly but always include defects in either insulin secretion or response or in both at some point in the course of disease. When characteristic symptoms of DM are clearly present and blood glucose levels are high enough, the diagnosis is usually unequivocal. However, it is important to remember that the diagnosis is made in asymptomatic patients in most cases, based on the results of routine tests. The prevalence of DM, its specific complications and the presence of other diseases that often accompany DM make this disease one of today's main social and public health problems. The great increase in information available on the etiology and pathophysiology of DM and its chronic complications has led necessarily to the revision of diagnostic criteria and reclassification of the processes involved. Revised diagnostic criteria and classifications were agreed upon in 1997 and 1998 by the American Diabetes Association and the World Health Organization, respectively, and new recommendations were published. Thanks to cross-representation on the committees, the conclusions and final recommendations are, in general, very similar, although a few minor differences are present. Clarification of diagnostic criteria and better classification of patients suffering from DM should allow us to make better choices among the various treatment options available and to improve prognosis.

Blood Glucose↗

Hypercoagulability and high lipoprotein(a) levels in patients with type II diabetes mellitus.

Diabetes mellitus is associated with disturbances in hemostasis that could contribute to the development of diabetic vascular disease. We investigated the changes in parameters of blood coagulation and the fibrinolytic system and in plasma levels of lipoprotein(a)(Lp(a)) in 124 patients with type II diabetes mellitus and 44 healthy control subjects matched for age and body mass index (BMI) to determine whether hemostatic disturbances may lead to increased cardiovascular mortality. Median levels of fibrinogen (P < 0.0001), thrombin-antithrombin III complex (TAT) (P < 0.005), and plasminogen activator inhibitor-1 (PAI-1) activity (P < 0.05) in plasma were significantly elevated in diabetic patients compared with controls. The median concentration of Lp(a) was significantly higher in diabetic patients than in normal controls (18.2 vs. 12.6 mg/dl. P < 0.0005). Lp(a) levels tended to be elevated in patients with a prolonged history of diabetes. There was no evidence that Lp(a) levels were affected by metabolic control or by type of treatment. Twenty-two diabetics with coronary heart disease (CHD) had significantly higher levels of fibrinogen (P < 0.05), TAT (P < 0.05), and Lp(a) (24.7 vs. 13.7 mg/dl, P < 0.01) than the 51 patients without diabetic angiopathy. Our data indicate that impaired hemostatic balance in diabetes may cause hypercoagulability and may thus contribute to the increased cardiovascular mortality in diabetes.

Aged↗