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PubMed1986

Sodium-hydrogen exchange and glucose transport in renal microvillus membrane vesicles from rats with diabetes mellitus.

Diabetes mellitus is associated with important changes in renal hemodynamics and transport function. Disturbances in solute transport have also been characterized in nonrenal tissues during hyperglycemia and insulinopenia. The purpose of this study was to determine if diabetes is associated with adaptive changes in function of the brush-border membrane of the proximal tubule. We studied Na+ and glucose transport in rat microvillus membrane vesicles isolated from the renal cortex of streptozotocin-induced and BB/W autoimmune diabetic rats. Untreated diabetes was associated with an increase in pH-stimulated total and amiloride-sensitive 22Na+ uptake into vesicles. Insulin treatment returned vesicle 22Na+ uptake to control levels. The increased Na+/H+ exchange was shown to be a result of increased net renal acid production rather than a specific response to insulinopenia because treatment with NaHCO3 also returned 22Na+ uptake to control levels. On the other hand, Na+-glucose cotransport, which was depressed in vesicles from untreated diabetics, returned to control levels with insulin but not NaHCO3 administration. This decreased Na+-glucose cotransport was not secondary to reduction in transport sites in untreated diabetics. These results show that in diabetes mellitus, increased Na+/H+ exchange activity is not the direct result of insulinopenia. However, the diabetic state appears to alter the functioning of the luminal Na+-glucose cotransporter.

Acid-Base Equilibrium↗

PubMedDate not supplied

The psychophysiologic aspects of stress in juvenile diabetes mellitus.

Diabetes Mellitus is the most common endocrine disease found in children, and its reported incidence is increasing. Most investigators now agree that improved diabetic control is effective in decreasing both long and short term complications. The delineation of factors which affect control are, therefore, of importance. Classically, the physician has emphasized insulin dose, presence of infection, diet, and exercise. Emotional factors have long been thought to play a role in diabetes mellitus. The exact nature of this role, however, has been rather elusive and controversial. The authors review this literature, summarize the major viewpoints, and conclude that physiological factors can influence the physiology of the disease. The focus of this paper is the synthesis of recent advances in basic metabolic, endocrinologic, and stress research, relevant to juvenile diabetes, into a psychophysiologic model. The authors discuss future research directions necessary for clarification of the model, as well as its psychological and physiological therapeutic implications.

Adrenocorticotropic Hormone↗

PubMed1997

Recent advances in the treatment of type II diabetes mellitus.

Diabetes mellitus needs to be managed early to prevent the onset and progression of complications. Diet and exercise may not be sufficient to achieve and maintain good glycemic control. Currently, no pharmacologic agent addresses all of the fundamental abnormalities in the pathogenesis of type II diabetes mellitus. However, the newer agents do not exacerbate the hyperinsulinemia that often occurs with type II diabetes, and they may help reduce the risk of cardiovascular disease that is associated with high insulin levels. Two of these agents, metformin and acarbose, have recently become available in the United States for the treatment of type II diabetes. With the availability of agents that differ in their mechanisms of action and side effect profiles, regimens can be individualized to address the variety of pathophysiologic abnormalities in type II diabetes. For this purpose, agents can be used alone or in combination.

Acarbose↗

PubMed1993

Glycometabolic control, lipids, and coagulation parameters in patients with non-insulin-dependent diabetes mellitus.

Diabetes mellitus and hyperlipidemia are associated with coronary heart disease and with hypercoagulability, another independent risk factor for coronary heart disease. In 65 non-insulin-dependent diabetes mellitus patients [41 females, 24 males, median age 66 years (range 43-81 years)] treated with antidiabetic agents glycometabolic control (HbA1c), lipids (Quetelet index and blood lipids), and several coagulation parameters were studied in comparison with a reference group. Serum triglycerides were elevated [median (interquartile range) 2.3 (1.3) mmol/l vs. 1.6 (0.7) mmol/l in the controls (P < 0.001)], whereas the median lipoprotein(a) concentration was 65 (157) mg/l in the diabetic patients versus 44 (114) mg/l in the control group (not significantly different). Median high-density lipoprotein-cholesterol concentrations were slightly decreased in the diabetic patients: 1.2 (0.3) mmol/l compared with 1.3 (0.4) mmol/l in the control group (P < 0.02). Elevated levels of fibrinogen, fibrin monomers, thrombin-antithrombin III complex, and factor VIIIc were found in the diabetic patients and factor VII in male diabetic patients. These elevated coagulation parameters are indicators of an activated coagulation system in this patient group. By Spearman's rank test, only HbA1c values correlated with anti-thrombin III (r = 0.27, P < 0.03) and showed a tendency towards a correlation with lipoprotein(a) (r = 0.23, P < 0.07). Triglycerides correlated with the Quetelet index (r = 0.27, P < 0.03), high-density lipoprotein-cholesterol (r = -0.41, P < 0.001), and factor VII (r = 0.35, P < 0.01), whereas serum cholesterol concentrations correlated with factor VII (r = 0.27, P < 0.04) and with fibrin monomers (r = 0.29, P < 0.03).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1997

Using the World Wide Web--a new approach to risk identification of diabetes mellitus.

Diabetes mellitus is a major health problem with a rising tendency world-wide. A new strategy for risk evaluation and data collection of undiagnosed non-insulin-dependent diabetes mellitus (NIDDM) using the World Wide Web (WWW) is presented. An easy-to-handle questionnaire on typical risk factors was converted into an interactive WWW document. The Internet provides the suitable platform for the net-based distribution of the questionnaire form as well as the computer-assisted entering and interpretation of the data (http:(/)/www.uni-leipzig.de/-diabetes). The analysis program, installed on our WWW server, interprets the information and sends the assessment on-line back to the inquiring user PC. The data are also collected anonymously in a database for epidemiological studies. In the test period, 744 world-wide accesses were registered: 433 men, mean age 39.8 +/- 14.4 years (range 10-83) and 311 women, mean age 36.7 +/- 12.7 years (range 11-77). An increased risk for undiagnosed diabetes was identified to 43.6%. The risk profile of male and female users showed no significant gender-related differences. Using the WWW technology can support early detection and adequate treatment of undiagnosed diabetes. This innovative strategy to screen for a high risk profile is an useful, cost-effective and up-to-date tool for broad community health education and epidemiological studies world-wide.

Adolescent↗

PubMed2001

[Diabetes mellitus].

Diabetes mellitus is a group of metabolic disorders characterized by hyperglycemia resulting from defects in insulin secretion, insulin action or both. Genetic factors contribute to the development of diabetes. Some forms such as the condition called maturity-onset diabetes of the young(MODY) result from mutations in a single gene. Other forms such as type 1 or type 2 diabetes are multifactorial in origin with different combinations of genes together with non-genetic factors contributing to the development of hyperglycemia. MODY has been a good model for studying the genetics and pathophysiology of diabetes. This form of diabetes can result from mutations in at least seven different genes: hepatocyte nuclear factor(HNF)-4 alpha/MODY1, glucokinase/MODY2, HNF-1 alpha/MODY3, insulin promoter factor(IPF-1)/MODY4, HNF-1 beta/MODY5, NeuroD1/MODY6 and Islet(Isl)-1/MODY7. Mutations in HNF-1 alpha/MODY3 are the most common cause of MODY in Japanese identified to date accounting for about 15% of cases of MODY. Mutations in the HNF-4 alpha/MODY1, glucokinase/MODY2, HNF-1 beta/MODY5 and Isl-1/MODY7 genes have also been found in Japanese; however, they are rare causes of MODY. Clinical studies indicate that patients with MODY are generally not obese and that all forms of MODY are characterized by pancreatic beta-cell dysfunction. Patients who have mutations in the HNF-1 beta/MODY5 gene have non-diabetic kidney dysfunction including renal cysts. Female carriers may also exhibit abnormalities in the upper vagina and uterus. Genetic approach for type 2 diabetes had done by using non-parameteric linkage analysis such as sibpair analysis which worked well and NIDDM1 and NIDDM2 have been identified to date. The responsible gene for NIDDM1 was recently identified to be Calpain 10, and SNP43 in this gene could explain all of the evidence for linkage in Mexican American type 2 diabetes.

Diabetes Mellitus↗

PubMedDate not supplied

Intracellular calcium and hydrogen ions in diabetes mellitus.

Diabetes mellitus is a multi-component syndrome that is often complicated by angiopathy which is partly due to enhanced platelet functions. Using fluorescent dyes 2',7'-bis(carboxyethyl)-5(6)-carboxyfluorescein (BCECF) and Fura-2 AM, changes was evaluated in the concentration of baseline and thrombin-stimulated increases in intracellular ionized calcium (Ca2+i) relative to hydrogen ions in the platelets from control, insulin-treated, and non-treated diabetic rats. The cytosol of platelets from the diabetic rats were more acidic compared to the insulin-treated and normal control rats. The increased intracellular hydrogen ion concentration [H+] or decreased pH (pH) in the diabetic rat platelets is associated with an increased baseline [Ca2+]i. Upon stimulation with thrombin, the mean peak [Ca2+]i for the insulin-treated (309 +/- 97 nmol/L) and untreated (339 +/- 135 nmol/L) diabetic rats was significantly higher than the concentration for the normal rats (213 +/- 101 nmol/L). Treatment with insulin attempts to correct the diabetes-induced elevation in the baseline of [Ca2+]i and intracellular H+. These results suggest that the relationships between Ca2+ and H+ relative to binding sites are similar in the intra- and extracellular compartments. It is our conclusion that the enhanced platelet activity and associated development of vascular diseases in diabetes may be due to an increased intracellular H+ that caused an increased baseline [Ca2+]i in diabetes mellitus.

Animals↗

PubMed1999

Using baseline data to improve care of the patient with type 2 diabetes mellitus.

Diabetes mellitus affects approximately 16 million people in the United States. Despite the publication of multiple guidelines, the delivery of care has not substantially changed. This article describes a program at Advocate Health Care to improve the delivery of care to individuals with Type 2 diabetes mellitus in an ambulatory setting. Using a variety of continuous quality improvement tools, this project enhances partnerships between patients and health care providers.

Ambulatory Care↗

PubMed1980

Genetic patterns in diabetes mellitus.

Diabetes comprises many syndromes whose only common feature is a high blood glucose level. Some are entirely genetic, some partially so, and others not at all. Perhaps the most important advance in the past 10 years is proof that insulin dependent diabetes is genetically different from the insulin independent form. Most progress has been made in unraveling the etiology of insulin dependent diabetes, although more information is needed before the mode of inheritance is finally settled. The last few years have produced a plethora of new facts about insulin dependent diabetes mellitus, providing geneticists, clinicians, and epidemiologists with the fascinating challenge of a disease with an apparently genetic susceptibility to external (environmental) triggers. Little progress has been made in the field of insulin independent diabetes, and one might safely predict that the diabetic syndrome will still produce some nightmares for researchers who take up the challenge of trying to unravel its various etiologies and methods of inheritance.

Adolescent↗

PubMed2006

Estrogen receptors: new players in diabetes mellitus.

Diabetes mellitus type 2 is a systemic disease characterized by imbalance of energy metabolism, which is mainly caused by inadequate insulin action. Recent data have revealed a surprising role for estradiol in regulating energy metabolism and opened new insights into the role of the two estrogen receptors, ERalpha and ERbeta, in this context. New findings on gene modulation by ERalpha and ERbeta of insulin-sensitive tissues indicate that estradiol participates in glucose homeostasis by modulating the expression of genes that are involved in insulin sensitivity and glucose uptake. Drugs that can selectively modulate the activity of either ERalpha or ERbeta in their interactions with target genes represent a promising frontier in diabetes mellitus coadjuvant therapy.

Animals↗

PubMed2002

[Treatment of patients with destructive pulmonary tuberculosis with concomitant diabetes mellitus].

Diabetes mellitus accompanying tuberculosis complicates the course of the latter and remains a topical problem of phthisiology. Surgical treatment of patient with both conditions presents a high risk and is employed unreasonably rarely. The results of medical (173 patients) and surgical (107 patients) treatments were studied in patients with destructive tuberculosis concurrent with diabetes mellitus. Analyzing early and late results of treatment showed a more steady-state effect in the group of surgically treated patients. Thus, surgery should be desirably used in all patients with preserving destructive changes after the basic course of antibacterial therapy.

Adult↗

PubMed1989

[State of insulin receptors and carbohydrate metabolism in children with diabetes mellitus].

Diabetes mellitus children demonstrate the lowering of insulin binding by lymphocytes on appearance of the signs of insulin overdosage. After standard breakfast preceded by insulin injection such patients show a lower blood content of ATP as compared to children without metabolic signs of insulin overdosage, which may be of importance in the pathogenesis of insulin resistance development. Patients with type I diabetes mellitus and hyperlactatemia manifested the lowering of glucose assimilation by lymphocytes whatever the presence of the signs of insulin overdosage, pointing to insulin resistance.

Adenosine Triphosphate↗

PubMed1977

Genetic, acquired, and related factors in the etiology of diabetes mellitus.

Diabetes mellitus is not a single disease entity, but a heterogenous group of disorders with a striking diversity of etiopathogenetic mechanisms as well as clinical manifestations. Lack of a known genetic marker for the disease(s) and variable influences of environmental factors on the expression of a putative diabetic genome have resulted in considerable debate over its etiology. Over the past few years, systematic epidemiologic studies, along with knowledge gained from a close association of certain human-leukocyte-antigens with the diabetic diathesis and possible role of host-immune factors, and gene-virus interaction have led to considerable advancement in the understanding of the disease-complex. Pending the availability of definite genetic marker(s), we propose a new, tentative classification based on the etiologic mechanisms. We also suggest that the term "prediabetes" be abandoned as a prospective entity, since as presently employed, this connotation carries a risk probability no different than the terms like prehypertension or precoronary thrombosis.

Adolescent↗

PubMed2000

[Cardiac complications in diabetes mellitus].

Diabetes mellitus as a disease of epidemiological impact leads to diabetic cardiopathy by modulation of myocardial, vascular and metabolic components. This includes the development of a coronary microangiopathy and a decrease of diastolic and systolic function of the left ventricle as well as the development of an autonomic diabetic neuropathy. Patients with diabetes show an increased mortality concerning cardiovascular events. They more often suffer from myocardial infarction as non-diabetics mostly with a more serious course. Moreover, the post-infarction course is affected with a worse prognosis as in non-diabetics. For diagnosis of cardial involvement in diabetes electrocardiographic and echocardiographic procedures are of use. Special tests of the autonomic function complete the diagnostic ensemble. An early therapy with ACE-inhibitors and beta blocking agents as well as a strong diabetes therapy, in particular with insulin, can influence the mortality favorably. Moreover, the diagnosis and therapy of additional cardiovascular risk factors (arterial hypertension, dyslipidemia) are very important, because these are correlated with a for diabetic patients markedly increased risk of mortality. The clinical relevance of the term diabetic cardiopathy is justified by the 6 factors: macroangiopathy, microangiopathy, disturbances of the myocardial metabolism, myocardial fibrosis, autonomic diabetic neuropathy and disturbances of the coagulability. Diagnostic and therapeutic goals are discussed.

Arteriosclerosis↗

PubMedDate not supplied

Gestational diabetes mellitus.

Diabetes sometimes appears for the first time during pregnancy. It is important that all cases are detected, so all pregnant woman should be screened for this condition. Screening protocols vary but usually involve urinalysis at all clinic visits plus a blood glucose test, taken after a meal, at 24-28 weeks. Risk factors include increasing maternal age (25 years upwards); obesity; family history of diabetes; and previous unexplained stillbirths or babies with congenital abnormalities. There is an increased frequency of gestational diabetes in Oriental women and those from the Indian subcontinent and the Middle East Once diagnosed, careful monitoring of diabetes is essential during pregnancy to minimise complications to mother and baby Mothers should be taught to monitor their own blood glucose levels. There is no place for urinalysis in the management of gestational diabetes mellitus. Advice from a dietitian is important and there should be easy access to a diabetes specialist nurse. The baby may be born large (macrosomia), with an increased risk of respiratory distress syndrome and hypoglycaemia. Hypocalcaemia and hyper-bilirubinaemia are other complications. Mothers may suffer birth trauma and require an assisted delivery because of the baby's large size. Although most women return to normal blood glucose levels in the puerperium, they are at considerably increased risk of developing non-insulin dependent diabetes mellitus in the following years. General education about recognising the symptoms of diabetes should be given, as well as advice about future pregnancies-including the need to seek preconceptual advice.

Blood Glucose Self-Monitoring↗

PubMed1989

[Disorders of lipid metabolism in diabetes mellitus].

Diabetes mellitus is the most frequent endogenous cause of fat metabolism-disorder. In diabetics the risk for arteriosclerosis is significantly higher and the clinical significance of hyperlipidemia should be estimated more serious as in non-diabetics. The predominant abnormality of fat metabolism in diabetes is hypertriglyceridemia due to an increase of triglyceride-carrying lipoproteins, the chylomicrons and the very-low-density lipoproteins. In type I-diabetics the decisive pathogenetic factor for hypertriglyceridemia is the impaired degradation of VLDL and the reduced chylomicron-clearance, caused by decreased activity of the lipoproteinlipase. In ketoacidosis there is an additional increase in hepatic VLDL-triglyceride-production due to increased lipolysis with elevated free-fatty-acid flux. Total cholesterol in type I-diabetics is only significantly elevated when metabolic control is poor, low-density lipoprotein (LDL-)-cholesterol-levels can be increased and high-density lipoprotein (HDL-)cholesterol decreased in dependence on the metabolic control. In type II-diabetics the decisive pathogenetic factor for hypertriglyceridemia is increased VLDL-triglyceride-synthesis in the liver especially due to augmented free-fatty-acid flux. Additionally the activity of the lipoproteinlipase can be reduced. Usually in non-insulin-dependent diabetics LDL-cholesterol-levels can be seen elevated and HDL-cholesterol-concentration decreased in correlation with the metabolic control. Primary hyperlipoproteinemia appears frequently in diabetics, but this can be explained by the association with obesity in type II-diabetics.

Arteriosclerosis↗

PubMed2003

Wound healing and diabetes mellitus.

Diabetes mellitus is one of the major contributors to chronic wound healing problems. When diabetic patients develop an ulcer, they become at high risk for major complications, including infection and amputation. The pathophysiologic relationship between diabetes and impaired healing is complex. Vascular, neuropathic, immune function, and biochemical abnormalities each contribute to the altered tissue repair. Despite treatment of these chronic wounds, which involves tight glucose control and meticulous wound care, the prognosis for their healing is quite poor. Newer modalities that deliver natural or engineered growth factors show a great deal of promise. All of the studies clearly show the continued need for well-controlled clinical trials.

Chronic Disease↗

PubMed1994

Mastopathy in insulin-requiring diabetes mellitus.

Diabetic mastopathy is a recently described collection of histopathological features found in dense fibrous breast masses in insulin-requiring diabetics. Fifty-seven breast biopsy specimens showing nonspecific benign disease were examined in a blinded fashion from 21 diabetics (seven insulin-requiring, 14 non-insulin-requiring), 30 age-matched controls and six patients with thyroid disease. Five diabetics had the constellation of extensive keloidal fibrosis, mononuclear perivasculitis, and mononuclear ductitis and/or lobulitis, whereas none of the controls or patients with thyroid disease had all of these features. All five patients with diabetic mastopathy were insulin-requiring (two type I, three type II). Epithelioid fibroblasts in the stroma, a previously described component of this constellation, were present in three of the five cases but do not appear to be essential in making the diagnosis. Four of the five diabetics were hypertensive, and three had secondary diabetic complications. The mean duration of diabetes in the five patients was greater than 13 years. Based on a previous report and the current study, this constellation of histological features appears to be relatively specific for insulin-requiring diabetes mellitus. The single clinical factor common to all patients with diabetic mastopathy in this article and in a previous study was exogenous insulin use.

Biopsy↗