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We investigated the effect of repeated high volume plasma exchange with fresh donor plasma in 11 patients with fulminant hepatic failure, all initially in stage 3 or 4 encephalopathy. A daily exchange of a volume equal to the extracellular volume (20% of body weight) on three consecutive days was intended. We obtained an average of 2.6 exchanges each with a mean volume equal to 16% of the body weight. Five patients (46%, 95% confidence limits 17%-77%) survived, all with acetaminophen induced liver failure. Four of the 6 non-survivors showed a temporary improvement in cerebral function. Two of the patients woke up completely. The 6 non-survivors maintained a stable condition with a systolic blood pressure >110 mm Hg for a mean of 6.9 days after initiating plasma exchange. Plasma exchange may be considered in acute liver failure in patients with residual liver function before transplantation is finally decided. In addition, plasmapheresis may be used to keep patients with definite liver failure clinically stable until a transplant can be performed.

Data on body composition in patients with insulin-dependent diabetes mellitus (IDDM) are scarce. Dual X-ray absorptiometry (DXA) scanning has proved useful for this purpose in other groups of patients. We tested the validity of the DXA scanner for the determination of fat-free mass (FFM) and fat mass in IDDM patients and control subjects, as compared to other reference methods, i.e. total body potassium by 40K whole body counting (TBK), total body water by tritiated water (TBW), bioelectrical impedance analysis (BIA) and 24-h urinary creatinine excretion (Ucrea). A total of 13 healthy controls, 5 males and 8 females, aged 34.2 years ± SD 10.4, and 11 IDDM patients, 5 males, 6 females, aged 28.1 years ± 7.3, diabetes duration 4.2 ± 2.9 (1.0-9.9), were examined. The patients had no long-term diabetic complications and they had normal ophthalmoscopy and urine albumin excretion. The agreement between FFM estimated by DXA and the other methods, expressed as mean difference ± 2 SD was; for DXA vs. TBK, 0.09 ± 6.26 and 0.50 ± 5.26 kg for controls and IDDM patients respectively; DXA vs. TBW, -2.07 ± 2.56 and -1.07 ± 4.58 kg; DXA vs. Ucrea, -2.62 ± 8.02 and 2.00 ± 10.0 kg; DXA vs. BIA, -7.90 ± 8.92 and -7.85 ± 2.32 kg. The results obtained with BIA were significantly different from the other methods for both control subjects and IDDM patients. In conclusion, DXA scanning is a precise and valid method for estimation of fat-free mass in IDDM patients.

In a 14-day multiple-dose study the pharmacokinetics of paroxetine was investigated in 12 patients with alcoholic cirrhosis and in 6 subjects without liver disease. The dose of 20–30 mg paroxetine daily was adjusted to the reduction in liver function, as assessed by the galactose elimination capacity. Accordingly, all but two of the cirrhotic patients received 20 mg, while all six control subjects received 30 mg.

Glutathione and amino acid concentrations were measured in arterial and hepatic vein plasma in four healthy volunteers and two patients with cirrhosis. There was no significant splanchnic efflux of glutathione (95% confidence limits,-0.501 to 0.405 μmol/min). After infusion of N-acetylcysteine (NAC) in a high dose (150 mg/kg body weight primer plus 15 mg/(h × kg BW), corresponding to treatment of acetaminophen overdose, there was no change in the splanchnic glutathione efflux (95% confidence limits,-0.531 to 0.375 μmol/min). NAC increased hepatic plasma flow rate from 0.90 ± 0.531 min-1 to 0.97 ± 0.11 (mean ± SEM; p < 0.05). The effects of NAC treatment on plasma amino acids corresponded to an increased load on hepatic metabolic N conversion and transamination among non-essential amino acids. Splanchnic uptake of serine, alanine, cystine, isoleucine, and phenylalanine increased after NAC compatible with stimulated hepatic glutathione synthesis. In contrast to the rat, plasma glutathione in man probably originates mainly from extrahepatic tissues.

It is unknown whether interleukin-1 exerts a bimodal effect on Beta-cell function in vivo, and whether interleukin-1 has a diabetogenic action in normal animals. We therefore studied: (a) acute effects 2 h after an intraperitoneal bolus injection of 4 μg of recombinant human interleukin-1βper kg body weight on blood glucose, plasma levels of insulin, glucagon and corticosterone in Wistar Kyoto rats, either untreated or pre-treated with 4 μg/kg of interleukin-1 daily for 3 or 5 days; (b) the cumulative effects of repetitive intraperitoneal injections of 4 μg/kg interleukin-1 on blood glucose, glucose tolerance, plasma levels of insulin, glucagon and corticosterone, pancreatic insulin content and pancreatic ultrastructure; and (c) blood glucose and plasma concentrations of insulin, glucagon and corticosterone 10 h after the last of five intraperitoneal injections of interleukin-1, at which time point the inhibitory effect of short-term interleukin-1 exposure on insulin secretion reaches its nadir in vitro. A single injection of 4 μg/kg of interleukin-1 caused a slight, but significant lowering of blood glucose 2 h after interleukin-1 injection with no significant changes in plasma insulin and in spite of increases in plasma glucagon and corticosterone. A lowering of blood glucose 2 h after interleukin-1 administration was reproduced with 40, but not 0.4 μg/kg of interleukin-1, and was also seen in interleukin-1 pre-treated rats. Two hours after the fifth injection of interleukin-1, intraperitoneal glucose tolerance was impaired with elevated plasma insulin and corticosterone levels and increased pancreatic insulin content, indicating a state of insulin resistance. Blood glucose levels significantly increased time-dependently 4–10 h after the third and fifth injection of interleukin-1, and diabetic values (blood glucose >11.0 mmol/l) were observed 6 and 10 h after the fifth injection of interleukin-1. Ten hours after the fifth injection of interleukin-1, diabetic blood glucose levels were observed together with a 50% reduction in plasma insulin concentration. Ultrastructural examination showed no signs of Betacell lysis. In conclusion, interleukin-1 has bimodal effects on glucose homeostasis in vivo, a slight lowering of the blood glucose followed by impaired glucose tolerance and later by diabetic blood glucose levels. Two hours after the last of five daily injections of interleukin-1 impaired glucose tolerance is primarily caused by a state of insulin resistance, whereas diabetic blood glucose levels are associated with inhibition of insulin secretion. Thus, interleukin-1 causes a diabetic state in normal animals, but it remains to be demonstrated that administration of interleukin-1 to normal animals leads to permanent diabetes due to Beta-cell destruction.

Diabetes was induced in Wistar rats by intravenous streptozotocin, 75 mg/kg. Four and 14 days after streptozotocin, fasting insulin decreased to about one-third, and fasting glucagon increased three-fold. The urea-N synthesis rate, stimulated by infusion of alanine, was measured at different amino acid concentrations 14 days after streptozotocin in 24 rats. The relationship was compatible with a barrier limited substrate inhibition kinetics. Data were examined accordingly by non-linear regression analysis. Among the estimated kinetic constants, only the 70% increase in Vmax was different from control values. In control rats the capacity of urea nitrogen synthesis, as measured within the amino acid concentration interval 7.3–11.6 mmol/1, was 10.2 ± 1.1 μmol · (min 100 g BW)−1(mean ± SEM). The capacity was not different in 4 day diabetic rats, whereas it doubled in 14 day diabetic rats, 20.9 ± 1.7 μmol (min 100 g BW)−1. The alanine elimination rate was 35% higher in the 14 day diabetic rats compared both to 4 day diabetic and control rats. The increase of urea synthesis is suggested to be due to enzyme induction by glucagon. The net nitrogen balance was negative at amino acid concentrations up to 25 mmol/1, indicating that the urea synthesis was increased at the expense of amino nitrogen.

In order to study the effect of hyperglucagonaemia on nitrogen metabolism in diabetes, zinc protamin glucagon 60 μg was injected subcutaneously 3 times daily for 4 weeks into streptozotocindiabetic rats (n=5), adequately treated with long acting insulin. This raised the plasma concentration of glucagon to 725±125 (mean±SEM), which is not different from that found in portal blood of uncontrolled diabetic rats: 400±75 ng/l. The controls were 5 diabetic rats treated with insulin alone and 5 non-diabetic rats. Compared with control rats the nitrogen balance was reduced (p<0.05) and the nitrogen contents of carcass, heart, intestines, and kidneys were reduced by 15–30% (p<0.05) in the glucagon treated rats. The hepatic capacity of urea synthesis and the alanine elimination rate were determined in the 3 above-mentioned groups, and confirmed in 3 identical groups followed for only 2 weeks; and in addition in a group of glucagon treated diabetic rats, where the long acting glucagon was substituted by neutral insulin the last two days before investigation. The capacity of urea-N synthesis and the alanine elimination rate were, respectively, in control rats: 9.6±0.8 and 5.9±0.3 μmol/(min 100 g body weight), in insulin treated diabetic rats: 8.5±0.7 and 5.4±0.6 μmol/(min 100g body weight), in glucagon treated rats: 6.3±0.4 (lower than controls, p<0.05) and 10.4±0.4 (higher than controls, p<0.05) (μmol/(min 100 g body weight), and in glucagon treated rats given neutral insulin: 20.7±1.6 and 10.9±0.3 μmol/(min 100 g body weight) (both higher than controls, p<0.05). Hyperglucagonaemia in itself leads to loss of nitrogen from organs, probably by an increased hepatic conversion of amino-nitrogen to urea-nitrogen, as evidenced by the increased urea excretion. This proceeds despite an insulin induced decrease in the capacity of urea synthesis and may thus rather be attributed to changes in the affinity of urea synthesis for amino-nitrogen.

Rats with experimental diabetes due to streptozotocin (75 mg/kg body weight) and free access to food were divided into two groups. One group (n=9) was optimally treated with insulin (glucosuria <4.0 mmol/24 h), using heat treated very long-acting ultralente insulin. The other group (n=10) was poorly treated with insulin (glucosuria 20–30 mmol/24 h). The nitrogen balance and energy balance of optimally treated diabetic rats was positive and not different from the control group (n=6). In the poorly treated diabetic rats the nitrogen balance was reduced whereas the energy balance was not different from that of control rats. After 4 weeks the fasting glucagon was: 50±21 ng/l (mean±SEM) in control rats, 62±18 ng/l in optimally treated diabetic rats and 249±58 ng/l in poorly treated diabetic rats (p<0.01). The capacity of urea nitrogen synthesis determined during alanine loading was: 9.6±1.0 umol/(min 100 g body weight) in control rats, 10.6±1.7 umol/(min 100 g body weight) in optimally treated diabetic rats and 17.3±1.3 umol/(min 100 g body weight) in poorly treated diabetic rats (p<0.01). Nitrogen contents of carcass, heart, intestines, liver, and kidneys as determined by Kjeldahl analyses were identical in control rats and optimally treated diabetic rats. In the poorly treated diabetic rats carcass-nitrogen and heart-nitrogen contents were reduced to 89% of the control value (p<0.01), whereas the kidney-nitrogen content was increased to 112% of the control value (p<0.01). Strict insulin therapy in experimental diabetes leads to a normalisation of nitrogen metabolism and hyperglucagonaemia, whereas less than optimally insulin treated rats show marked abnormalities in nitrogen metabolism as well as hyperglucagonaemia.

Rats with experimental streptozotocin-induced diabetes (75 mg/kg) were divided into two groups. One group was free fed (n=8), the other group (n=7) pair fed to a group of control animals (n=8). The nitrogen and energy balances of the control rats were positive. In the free-fed diabetic rats the nitrogen balance was neutral and the energy balance higher than in controls. In the pair-fed diabetic rats the nitrogen balance was negative and the energy balance reduced. After 4 weeks the capacity of urea-nitrogen synthesis was: 8.1±0.6 μmol/(min 100 g body weight) (mean±SEM) in controls and 22.2±2.2 μmol/(min 100 g body weight) in both groups of diabetic rats. Initially, the whole body nitrogen content was 453±9 mmol. Four weeks later it was 536±19 mmol in controls, 410±21 mmol in the free-fed diabetic rats, and 315±6 mmol in the pair-fed diabetic rats. The largest changes occurred in the muscles, initially containing 278±6 mmol, 4 weeks later 328±8 mmol, compared to 234±19 in the free-fed diabetic rats and 166±18 mmol in the pair-fed diabetic rats. In conclusion uncontrolled diabetes is characterised by loss of nitrogen from muscles and most other organs. The losses from some organs are preventable by increased food intake. Irrespective of food intake the hepatic dynamics of amino nitrogen conversion is changed in a way that favours protein catabolism.

The purpose of the present investigation was to study changes in cerebral blood flow (CBF) in hepatic encephalopathy, to ascertain whether this was related to the changes in liver function and whether these changes gave any prognostic information. CBF, determined by the intravenous xenon-133 method, and liver functions, assessed by the prothrombin index, bilirubin concentration, and the galactose elimination capacity, were studied in patients with acute fulminant liver failure and in patients with encephalopathy due to chronic liver diseases - that is, cirrhosis of various etiologies. The CBF range in healthy young subjects (age, 23-42 years) was 44-61 m1/100 g/min; in patients with grade I + II encephalopathy (mean ± SEM) it was 32.8 23.6 m1/100 g/min in acute (n = 4; age, 28 ± 8 years) and 37.0 ×.3.3 m1/100 g/ min in chronic liver patients (n = 10; age, 51 ± 2 years). In grade III ± IV encephalopathy it was 28.7 ± 3.8 m1/100 g/min in acute (n = 8; age, 28 ± 3 years) and 32.9 ± 3.7 m1/100 g/min in chronic patients (n = 12; age, 49 ± 3 years). CBF did not correlate with the liver function and was of no prognostic value. The liver function was markedly reduced in all the patients, without any differences between patients with acute or chronic liver diseases or the different degrees of hepatic encephalopathy. In conclusion, a marked reduction of the CBF was seen in hepatic encephalopathy, irrespective of the etiology of the disease.

Among 342 consecutive patients admitted to the hospital with cirrhosis of the liver 68 (17%) had ascites and had a diagnostic paracentesis performed. Fourteen episodes of peritonitis were diagnosed in 13 patients, which is an overall incidence of peritonitis of 19%. The incidence of peritonitis was 36% in patients with hepatic encephalopathy and 10% in patients without hepatic encephalopathy (P < 0.01). In all except one case the infecting organism was most likely of enteric origin-that is, gram-negative or anaerobic species. The infected patients had lower mean ascites pH and higher mean ascites leukocyte and polymorphonuclear cell counts than non-infected patients. However, there was a considerable overlap between the two groups, and the diagnostic sensitivity did not exceed 65% for any of these three features. The survival of infected patients without encephalopathy was 33%, which was significantly lower (P < 0.05) than that the 89% for non-infected patients. In patients with encephalopathy the survival was identical for infected and non-infected patients.

The effect of metabolic alkalosis was studied in 10 healthy volunteers. In each person urea synthesis was determined in two periods of 2 h as urinary excretion corrected for accumulation in body water and for intestinal hydrolysis. Infusion of bicarbonate (115 mmol/h) increased pH of the venous blood by 0.10 units. In four subjects fasting urea synthesis was 24 mmol N/h at normal pH and unaffected by alkalosis (mean difference δδ was 1.04±±4.1). In six subjects alanine was infused so as to increase blood alanine concentration from 0.4 to 2.5 mmol/1 and urea synthesis to 107 mmol N/h. Alkalosis did not change urea synthesis (mean difference δδ was 1.5±±7.4 mmol N/h). The results favour the view that urea synthesis mainly serves to eliminate nitrogen, but do not support the hypothesis that urea synthesis is an important immediate and direct regulatory process in acute acid-base disturbances.

In a five-year retrospective study, there were 57 episodes of bacteremia among 1623 admissions (3.5%) of patients suffering from cirrhosis. Gram-positive bacteria were found in 70% of the episodes, gram-negative bacteria in 30%. All of the gram-positive bacteria found were fully sensitive to methicillin and to gentamicin. The gram-negative bacteria found were all sensitive to gentamicin, but only 50% were sensitive to ampicillin. The distribution between gram-positive and gram-negative bacteria was the same, irrespective of whether the patients acquired the infection inside or outside the hospital. More than 50% of the patients suffered from one or more of the following complications of cirrhosis: ascites, encephalopathy and haematemesis. Twenty-one patients died within seven days after the bacteremia was diagnosed. Bacteremia is a serious complication of advanced cirrhosis, and it is recommended that adequate antibiotic treatment is started when septicemia is suspected. Im Rahmen einer retrospektiven Fünfjahres-Studie wurden unter 1623 Einweisungen 57 Bakteriämien bei Patienten mit Zirrhose gefunden (3,5%). Bei 70% der Bakteriämien fanden sich grampositive Bakterien, bei 30% gramnegative Bakterien. Alle isolierten grampositiven Bakterien waren voll empfindlich gegenüber Methicillin und Gentamicin. Gegenüber Gentamicin waren alle gramnegativen Isolate empfindlich, gegenüber Ampicillin jedoch nur 50%. Die Verteilung von grampositiven und gramnegativen Bakterien war unabhängig davon, ob die Infektion im Krankenhaus oder außerhalb erworben war. Eine oder mehrere der folgenden Komplikationen der Zirrhose traten bei mehr als 50% der Patienten auf: Aszites, Enzephalopathie und Hämatemesis. 21 Patienten verstarben innerhalb von sieben Tagen nach Diagnose der Bakteriämie. Die Bakteriämie ist eine ernsthafte Komplikation der fortgeschrittenen Leberzirrhose, und es wird empfohlen, bereits bei Verdacht auf eine Septikämie mit einer adäquaten Antibiotikatherapie zu beginnen.

The effect of epidermal growth factor (EGF) on liver regeneration was investigated in rats subjected to partial hepatectomy. In a dose-response study EGF in doses of 6 and 24 nmol/kg X day increased liver regeneration after treatment for 48 h compared with controls, whereas a dose of 48 nmol/kg X day had no effect. In a subsequent study EGF, 6 nmol/kg X day, accelerated liver regeneration significantly after 36, 48, and 72 h of treatment. A possible influence of EGF on other hepatotrophic factors was investigated. No changes in the concentration of gastrin, insulin, or glucagon was found in portal venous blood. This study has shown that EGF in small doses can stimulate liver regeneration, whereas higher doses are ineffective. The study suggests that EGF should be regarded as a hepatotrophic factor.

A clinical trial, NCT06674161, is being conducted in Saudi Arabia to study the impact of cardiovascular disease (CVD) and Type 2 diabetes mellitus (T2DM) on the population. The study aims to quantify incidence and mortality rates of CVD and T2DM, analyze risk factors, understand cultural influences on health behaviors, develop predictive models, and evaluate the impact of the ICD11 classification of CVD. The project involves experts from various institutions and aims to improve epidemiological knowledge and support the health goals of Saudi Vision 2030. [Extracted from the article]

Diabetes is a complex disease that affects an estimated 29.1 million adults (9.3%) in the United States. The prevalence of diagnosed diabetes is higher among certain minorities, including American Indians [...], The keys to optimal glycemic control in patients with type 2 diabetes are early diagnosis and interventions that include lifestyle changes and pharmacotherapy. This review discusses therapeutic goals and current options for treatment of type 2 diabetes.

INTRODUCTION Obesity is a public health concern that affects children, adolescents and adults. The current prevalence of overweight in the U.S. is 35.9% [Body Mass Index (BMI) of 25-29.9], and [...], The purpose of this study was to evaluate the role of social support and social connectedness for five weight control behaviors among overweight/obese adults (N = 118)participating in an online weightloss community. The five weight control behaviors investigated were physical activity, screen time, and the consumption of sugar-free drinks, sugar-sweetened drinks, and fruits and vegetables. Step-wise multiple regression was used to predict each weight control behavior with constructs of social support and social connectedness. Social support was highly predictive of all behaviors under investigation. Furthermore, interactions within the community (active or passive users) were significant for two behaviors (screen time and fruit and vegetable consumption), and number of minutes engaged in the community per week was significant for fruit and vegetable consumption only. These results suggest that promoting social support is likely the most important feature for online weight loss communities.

OBJECTIVE--Type 2 diabetes is a risk factor for other forms of stroke, but its association with subarachnoid hemorrhage (SAH) from ruptured saccular intracranial aneurysm (sIA) has remained unclear. RESEARCH DESIGN [...]

OBJECTIVE--Current guidelines for intensive treatment of type 1 diabetes base the mealtime insulin bolus calculation exclusively on carbohydrate counting. There is strong evidence that free fatty acids impair insulin sensitivity. [...]

Hypertension and type 2 diabetes (T2D) commonly coexist, and both conditions are major risk factors for cardiovascular disease (CVD). We aimed to examine the association between genetic predisposition to high [...]

OBJECTIVE--To estimate the impact of diabetes on mortality in patients after first stroke event. RESEARCH DESIGN AND METHODS--Using claims data from a nationwide statutory health insurance fund (Gmunder ErsatzKasse), we [...]

The effectiveness of medical nutrition therapy (MNT) in the management of diabetes has been well established (1). Previous reviews have provided comprehensive recommendations for MNT in the management of diabetes [...]

Although the existence of mitochondrial abnormalities in patients with type 2 diabetes has been extensively reported during the last decade (1-5), there is no evidence that a reduced mitochondrial function [...], OBJECTIVE--Type 2 diabetes and insulin resistance have been associated with mitochondrial dysfunction, but it is debated whether this is a primary factor in the pathogenesis of the disease. To test the concept that mitochondrial dysfunction is secondary to the development of insulin resistance, we employed the unique model of prolonged fasting in humans. Prolonged fasting is a physiologic condition in which muscular insulin resistance develops in the presence of increased free fatty acid (FFA) levels, increased fat oxidation and low glucose and insulin levels. It is therefore anticipated that skeletal muscle mitochondrial function is maintained to accommodate increased fat oxidation unless factors secondary to insulin resistance exert negative effects on mitochondrial function. RESEARCH DESIGN AND METHODS--While in a respiration chamber, twelve healthy males were subjected to a 60 h fast and a 60 h normal fed condition in a randomized crossover design. Afterward, insulin sensitivity was assessed using a hyperinsulinemic-euglycemic clamp, and mitochondrial function was quantified ex vivo in permeabilized muscle fibers using high-resolution respirometry. RESULTS--Indeed, FFA levels were increased approximately ninefold after 60 h of fasting in healthy male subjects, leading to elevated intramuscular lipid levels and decreased muscular insulin sensitivity. Despite an increase in whole-body fat oxidation, we observed an overall reduction in both coupled state 3 respiration and maximally uncoupled respiration in permeabilized skeletal muscle fibers, which could not be explained by changes in mitochondrial density. CONCLUSIONS--These findings confirm that the insulin-resistant state has secondary negative effects on mitochondrial function. Given the low insulin and glucose levels after prolonged fasting, hyperglycemia and insulin action per se can be excluded as underlying mechanisms, pointing toward elevated plasma FFA and/or intramuscular fat accumulation as possible causes for the observed reduction in mitochondrial capacity. Diabetes 59: 2117-2125, 2010

OBJECTIVE--Sleep restriction results in decreased insulin sensitivity and glucose tolerance in healthy subjects. We hypothesized that deep duration is also a determinant of insulin sensitivity in patients with type 1 [...]

Recent evidence implicates leptin not only in the regulation of energy balance but also in glucose homeostasis as well. In addition to hyperphagia and obesity, insulin resistance is a prominent [...], OBJECTIVE--Depletion of body fat stores during uncontrolled, insulin-deficient diabetes (uDM) results in markedly reduced plasma leptin levels. This study investigated the role of leptin deficiency in the genesis of severe insulin resistance and related metabolic and neuroendocrine derangements induced by uDM. RESEARCH DESIGN AND METHODS--Adult male Wistar rats remained nondiabetic or were injected with the β-cell toxin, streptozotocin (STZ) to induce uDM and subsequently underwent subcutaneous implantation of an osmotic minipump containing either vehicle or leptin at a dose (150 µg/kg/day) designed to replace leptin at nondiabetic plasma levels. To control for leptin effects on food intake, another group of STZ-injected animals were pair fed to the intake of those receiving leptin. Food intake, body weight, and blood glucose levels were measured daily, with body composition and indirect calorimetry performed on day 11, and an insulin tolerance test to measure insulin sensitivity performed on day 16. Plasma hormone and substrate levels, hepatic gluconeogenic gene expression, and measures of tissue insulin signal transduction were also measured. RESULTS--Physiologic leptin replacement prevented insulin resistance in uDM via a mechanism unrelated to changes in food intake or body weight. This effect was associated with reduced total body fat and hepatic triglyceride content, preservation of lean mass, and improved insulin signal transduction via the insulin receptor substrate--phosphatidylinositol-3-hydroxy kinase pathway in the liver, but not in skeletal muscle or adipose tissue. Although physiologic leptin replacement lowered blood glucose levels only slightly, it fully normalized elevated plasma glucagon and corticosterone levels and reversed the increased hepatic expression of gluconeogenic enzymes characteristic of rats with uDM. CONCLUSIONS--We conclude that leptin deficiency plays a key role in the pathogenesis of severe insulin resistance and related endocrine disorders in uDM. Treatment of diabetes in humans may benefit from correction of leptin deficiency as well as insulin deficiency. Diabetes 59:1626-1634, 2010

OBJECTIVE--Reduction of bone marrow-derived circulating progenitor cells has been proposed as a novel mechanism of cardiovascular disease in type 2 diabetes. The present study was designed to describe the extent [...]

Type 2 diabetes is the most frequent metabolic disease and the leading cause of human morbidity and mortality (1,2). Based on epidemiologic data, patients with diabetes are immunocompromised and have [...], OBJECTIVE--Although patients with diabetes suffer from increased infections and a higher incidence of cancer due to impaired immune function, details on diabetes-induced decrease in immunity are lacking. We assessed how immune-mediating peripheral blood mononuclear cells (PBMCs) are affected in diabetes. RESEARCH DESIGN AND METHODS--From 33 patients with type 2 diabetes and 28 healthy volunteers, we obtained PBMCs and investigated their susceptibility to apoptosis and functional alteration. RESULTS--In a subpopulation of PBMCs, monocytes derived from patients with diabetes were more susceptible to apoptosis than monocytes from healthy volunteers. Monocytes from patients with diabetes had decreased phagocytotic activity and were less responsive to Toll-like receptor (TLR) ligands, although the expression of TLRs did not differ significantly between the two groups. Furthermore, monocytes from patients with diabetes had a distinctly different gene expression profile compared with monocytes from normal volunteers as assessed with DNA microarray analysis. Specifically, quantitative real-time detection PCR measurements showed an elevated expression of the markers of endoplasmic reticulum (ER) stress in diabetic monocytes, and electron microscopic examination of monocytes revealed morphologic alterations in the ER of cells derived from patients with diabetes. Consistently, the ER stress inducer tunicamycin increased apoptosis of otherwise healthy monocytes and attenuated the proinflammatory responses to TLR ligands. CONCLUSIONS--These data suggest that monocytes comprise a substantially impaired subpopulation of PBMCs in patients with diabetes and that ER stress is involved in these pathologic changes mechanistically. This implies that the affected monocytes should be investigated further to better understand diabetic immunity. Diabetes 59:634-643, 2010

A though type 2 diabetes is a heterogeneous condition encompassing multiple metabolic and vascular alterations, it can be easily described as a disease characterized by chronic hyperglycemia and increased cardiovascular [...]

The American Heart Association (AHA) (Rosamond et al., 2008) defined modifiable cardiovascular risk factors as risk determinants that individuals can alter by specific interventions to reduce the probability of a [...], Older women uniquely experience a "double jeopardy" for heart disease. Evidence-based risk factor information to enhance the prevention of coronary heart disease in older women is provided.

Stroke affects more than 700,000 individuals each year; it is the third largest cause of death and the largest cause of adult disability in the U.S. Diabetes is a major [...]

OBJECTIVE--The aim of this study was to examine the relationship between type 1 and type 2 diabetes and risk of stroke subtypes in women. RESEARCH DESIGN AND METHODS--We followed 116,316 [...]

OBJECTIVE--Cardiovascular disease (CVD) is the main cause of morbidity/mortality in diabetes. We set forth to determine incidence and identify predictors (including microvascular complications and treatment) of first coronary heart disease [...]

OBJECTIVE--We sought to develop stroke risk equations for Chinese patients with type 2 diabetes in Hong Kong. RESEARCH DESIGN AND METHODS--A total of 7,209 Hong Kong Chinese type 2 diabetic [...]

OBJECTIVE--Type 2 diabetes leads to cognitive impairment and dementia, which may reflect microvascular and macrovascular complications as well as neurodegenerative processes. There are few studies on the anatomical basis for [...]

OBJECTIVE--The Treating to New Targets study showed that intensive lipid-lowering therapy with atorvastattn 80 mg/day provides significant clinical benefit beyond that afforded by atorvastatin 10 mg/day in patients with stable [...]

Abstract Sedentary lifestyles and increased pollution brought about by industrialization pose major challenges to the prevention of both obesity and chronic respiratory diseases such as chronic obstructive pulmonary disease (COPD), [...]

OBJECTIVE--Diabetes may influence the outcome of complicated peptic ulcer disease, due to angiopathy, blurring of symptoms, and increased risk of sepsis. We examined whether diabetes increased 30-day mortality among Danish [...]

OBJECTIVE--To determine whether the hyperbolic relationship between insulin sensitivity and the acute insulin response to glucose (AI[R.sub.g]) exists in subjects with impaired fasting glucose (IFG) or decreased glucose tolerance. RESEARCH [...]

Diabetic nephropathy (DN) is a primary cause of excess mortality in type 1 diabetic patients (1). It affects about one-third of diabetic patients (2,3), increases the risk of cardiovascular diseases, [...], We determined the magnitude of familial aggregation in the development of diabetic nephropathy (DN) among a population-based cohort of Finnish type 1 diabetic patients. Probands with type 1 diabetes were identified from the nationwide register of all Finnish cases diagnosed during 1965-1979. By 1998, there were 537 families with at least two siblings with type 1 diabetes. These 537 probands and their 616 diabetic siblings were followed for a diagnosis of DN until the end of 2001. We identified 323 cases of DN in these families. If the proband had DN, 38% of the siblings also had DN, whereas out of the diabetic siblings of the probands without DN, only 17% had DN (P = 0.001). Diabetic siblings of the nephropathic probands had a 2.3 times (95% CI 1.4-2.7) higher risk of DN compared with siblings of probands free of DN. The presence of a severe form of DN in the proband increases the risk threefold for diabetic siblings. Sex, the DN of the proband, the age at the onset of diabetes, and parental type 2 diabetes were significant predictors of DN among diabetic siblings. Although the majority of sibpairs with type 1 diabetes are discordant for DN, its presence in one sibling doubles the risk for the other diabetic siblings.