Diabetes mellitus - Wikipedia

«Diabetes mellitus (DM), commonly known as diabetes, is a group of metabolic disorder characterized by high blood sugar levels over a prolonged period.^[9] Symptoms of high blood sugar include frequent urination, increased thirst, and increased hunger.^[2] If left untreated, diabetes can cause many complications.^[2]Acute complications can include diabetic ketoacidosis, hyperosmolar hyperglycemic state, or death.^[3] Serious long-term complications include cardiovascular disease, stroke, chronic kidney disease, foot ulcers, and damage to the eyes.^[2]

Diabetes is due to either the pancreas not producing enough insulin, or the cells of the body not responding properly to the insulin produced.^[10] There are three main types of diabetes mellitus:^[2]

Prevention and treatment involve maintaining a healthy diet, regular physical exercise, a normal body weight, and avoiding use of tobacco.^[2] Control of blood pressure and maintaining proper foot care are important for people with the disease.^[2] Type 1 DM must be managed with insulin injections.^[2] Type 2 DM may be treated with medications with or without insulin.^[12] Insulin and some oral medications can cause low blood sugar.^[13]Weight loss surgery in those with obesity is sometimes an effective measure in those with type 2 DM.^[14] Gestational diabetes usually resolves after the birth of the baby.^[15]

As of 2017^[update], an estimated 425 million people had diabetes worldwide,^[8] with type 2 DM making up about 90% of the cases.^[16][17] This represents 8.8% of the adult population,^[8] with equal rates in both women and men.^[18] Trend suggests that rates will continue to rise.^[8] Diabetes at least doubles a person's risk of early death.^[2] In 2017, diabetes resulted in approximately 3.2 to 5.0 million deaths.^[8] The global economic cost of diabetes related health expenditure in 2017 was estimated at US$727 billion.^[8] In the United States, diabetes cost nearly US$245 billion in 2012.^[19]

The classic symptoms of untreated diabetes are unintended weight loss, polyuria (increased urination), polydipsia (increased thirst), and polyphagia (increased hunger).^[20] Symptoms may develop rapidly (weeks or months) in type 1 DM, while they usually develop much more slowly and may be subtle or absent in type 2 DM. Other symptoms of diabetes mellitus include weight loss and tiredness.^[21]

Several other signs and symptoms can mark the onset of diabetes although they are not specific to the disease. In addition to the known ones above, they include blurred vision, headache, fatigue, slow healing of cuts, and itchy skin. Prolonged high blood glucose can cause glucose absorption in the lens of the eye, which lead to changes in its shape, resulting in vision changes. Long-term vision loss can also be caused by diabetic retinopathy. A number of skin rashes that can occur in diabetes are collectively known as diabetic dermadromes.^[22]

Low blood sugar (hypoglycemia) is common in people with type 1 and type 2 DM. Most cases are mild and are not considered medical emergencies. Effects can range from feelings of unease, sweating, trembling, and increased appetite in mild cases to more serious effects such as confusion, changes in behavior such as aggressiveness, seizures, unconsciousness, and (rarely) permanent brain damage or death in severe cases.^[23][24] Moderately low blood sugar may easily be mistaken for drunkenness;^[25]rapid breathing and sweating, cold, pale skin are characteristic of low blood sugar but not definitive.^[26] Mild to moderate cases are self-treated by eating or drinking something high in sugar. Severe cases can lead to unconsciousness and must be treated with intravenous glucose or injections with glucagon.^[27]

People (usually with type 1 DM) may also experience episodes of diabetic ketoacidosis (DKA), a metabolic disturbance characterized by nausea, vomiting and abdominal pain, the smell of acetone on the breath, deep breathing known as Kussmaul breathing, and in severe cases a decreased level of consciousness.^[28]

A rare but equally severe possibility is hyperosmolar hyperglycemic state (HHS), which is more common in type 2 DM and is mainly the result of dehydration.^[28]

All forms of diabetes increase the risk of long-term complications. These typically develop after many years (10–20) but may be the first symptom in those who have otherwise not received a diagnosis before that time.

The major long-term complications relate to damage to blood vessels. Diabetes doubles the risk of cardiovascular disease^[29] and about 75% of deaths in diabetics are due to coronary artery disease.^[30] Other macrovascular diseases include stroke, and peripheral artery disease.

The primary complications of diabetes due to damage in small blood vessels include damage to the eyes, kidneys, and nerves.^[31] Damage to the eyes, known as diabetic retinopathy, is caused by damage to the blood vessels in the retina of the eye, and can result in gradual vision loss and eventual blindness.^[31] Diabetes also increases the risk of having glaucoma, cataracts, and other eye problems. It is recommended that diabetics visit an eye doctor once a year.^[32] Damage to the kidneys, known as diabetic nephropathy, can lead to tissue scarring, urine protein loss, and eventually chronic kidney disease, sometimes requiring dialysis or kidney transplantation.^[31] Damage to the nerves of the body, known as diabetic neuropathy, is the most common complication of diabetes.^[31] The symptoms can include numbness, tingling, pain, and altered pain sensation, which can lead to damage to the skin. Diabetes-related foot problems (such as diabetic foot ulcers) may occur, and can be difficult to treat, occasionally requiring amputation. Additionally, proximal diabetic neuropathy causes painful muscle atrophy and weakness.»

2018 Association of Cardiorespiratory Fitness With Long-term Mortality Among Adults Undergoing Exercise Treadmill Testing

«This study assesses the association between cardiorespiratory fitness and long-term mortality in adults undergoing exercise treadmill testing.»

2014 Arterial Stiffening Provides Sufficient Explanation for Primary Hypertension

2018 Plasma 25-hydroxyvitamin D concentration and risk of type 2 diabetes and pre-diabetes: 12-year cohort study

«Results according to continuous variable at baseline are shown in Table 1. Median follow-up time until diagnosis of diabetes or pre-diabetes was as follows: 4.5 years for diabetes cases; 4.1 years for pre-diabetes cases; and 12.5 years for the total cohort. Range of age of the cohort at baseline was 38–97 years, with a mean of 74 years. Body mass index, waist circumference, fasting plasma glucose, triglyceride concentration and systolic blood pressure were higher in individuals who became cases of diabetes during the follow-up period than in those who did not, as shown in Table 1.»

2014 Serum 25‐hydroxyvitamin D concentration does not independently predict incident diabetes in older women

1989 Association of oral candidiasis with diabetic control.

«Factors associated with oral candidiasis in 51 diabetics were examined. The prevalence of oral yeast infection was 49 (n = 25)%. The association with diabetic control, as measured by fasting blood glucose concentration, urinary glucose concentration, and glycosylated haemoglobin, with the presence of yeast was analysed in the 51 diabetic patients. Glycosylated haemoglobin above 12% was strongly associated with oral yeast infection (odds ratio = 13.00) (p less than 0.001), while fasting blood and urinary glucose concentration were not. The risk of oral candidiasis among diabetics wearing dentures was significantly higher than among dentate diabetics (odds ratio = 4.78). After controlling for the effect of denture wearing, glycosylated haemoglobin greater than 12% remained highly predictive of oral yeast infection, particularly among diabetics without dentures.»

2008 From here to eternity - the secret of Pharaohs: Therapeutic potential of black cumin seeds and beyond

«Over many centuries humans have been mining the bounties of nature for discovering substances that have been used for the treatment of all human diseases; many such remedies are useful even today as modern day medicine. Emerging evidence also suggests ...»

2012 Bilirubin, Renal Hemodynamics, and Blood Pressure

Using this mouse model, we demonstrated that moderate hyperbilirubinemia achieved with indinavir prevented the development of Ang II mediated hypertension (Figure ​5B; Vera et al., 2009). Similar effects on the development of Ang II hypertension were also observed in mice which received direct intravenous infusion of bilirubin which increased the levels of unconjugated bilirubin to levels observed in indinavir treated mice (Vera et al., 2009).

2012 Infections in patients with diabetes mellitus: A review of pathogenesis

«Oral and esophageal candidiasis The most common etiological agent is Candida albicans.[4,55] Its pathogenesis is related to a combination of factors that increase its virulence, with emphasis on the production of extracellular enzymes such as proteinase and phospholipase.[55] Candidiasis manifests in different ways: median rhomboid glossitis or central papillary atrophy, atrophic glossitis, denture stomatitis, pseudomembranous candidiasis, and angular cheilitis.[55] The diagnosis is eminently clinical. However, in case of esophageal candidiasis, endoscopy is needed.[55]»

2013 Oral Candida spp carriers: its prevalence
in patients with type 2 Diabetes Mellitus


«Prevalence of oral candidiasis in diabetic patients is 13.7-64%. Candida albicans was the most frequently isolated species (75-86.5%). To obtain the prevalence of Candida carriers among patients with type 2
diabetes mellitus to identify the species of ...»

2013 VO2max Trainability and High Intensity Interval Training in Humans: A Meta-Analysis

«A total of 211 articles were identified in the initial search. After screening titles and abstracts, 181 articles were discarded as it was apparent that they did not meet the study criteria. Figure 1 is a schematic of our search strategy and displays the criteria for exclusion. The full text of the remaining 30 articles was examined in detail. An additional 70 articles were identified through reference searches. The systematic review resulted in 37 articles for the Meta-analysis. Within these 37 articles were 334 participants (120 women) and 40 unique training groups (i.e., three articles each contained the results of two training programs). In brief, all studies contained between 3 to 19 healthy subjects with an age range of 18 to 42 years and pre training VO₂max values ranging from ∼26 to 52 ml · kg⁻¹ · min⁻¹.»

2014 On the potential of acarbose to reduce cardiovascular disease

«In the emerging landscape of cardiovascular (CV) outcome trials evaluating the effects of blood glucose lowering drugs in individuals with type 2 diabetes, it is becoming increasingly apparent that since the promising signals coming from the United Kingdom Prospective Diabetes Study (UKPDS) no unequivocal benefits have been established for any single therapy thus far. There is an unmet need for introducing an effective pharmacological agent which could target both correlates of glycaemic regulation and CV risk factors, to ameliorate the enormous burden of fatal and non-fatal CV events in diabetic patients. Acarbose, like other alpha-glucosidase inhibitors (AGIs), has been proven to be an effective antidiabetic treatment for decades, but the overall significant impact of this class of drugs on modulating CV risk has only recently been appreciated. Accumulating evidence has shown that apart from its multiple effects on primarily postprandial glucose dysmetabolism, a key component of mechanisms linked to increased incidence of CV events, acarbose therapy also associates with a favorable impact on an array of surrogate markers of CV disease. Data stemming from in vitro testing of human cell lines as well as from preliminary trials in diabetic populations, like the Study to Prevent Non-Insulin-Dependent Diabetes Mellitus (STOP-NIDDM) trial, have highlighted – though not undisputed – the potential beneficial effects of the drug on CV morbidity. Large scale trials, like the ongoing Acarbose Cardiovascular Evaluation (ACE) trial, aim at conclusively establishing such a positive effect in patients with coronary heart disease and impaired glucose tolerance. In view of its usually acceptable level of side effects that are, if they occur, mostly limited to transient gastrointestinal symptoms, acarbose could well be a strong future player in CV disease secondary prevention. Current discouraging results from many trials of antidiabetic medications to significantly lower CV event rates in diabetic patients, should only draw further attention on alternative glucose lowering agents, among which acarbose is indeed promising.»

2014 Effects of aldosterone on insulin sensitivity and secretion

«Dr. Conn originally reported an increased risk of diabetes in patients with hyperaldosteronism in the 1950’s, although the mechanism remains unclear. Aldosterone-induced hypokalemia was initially described to impair glucose tolerance by impairing insulin secretion. Correction of hypokalemia by potassium supplementation only partially restored insulin secretion and glucose tolerance, however. Aldosterone also impairs glucose-stimulated insulin secretion in isolated pancreatic islets via reactive oxygen species in a mineralocorticoid receptor-independent manner. Aldosterone-induced mineralocorticoid receptor activation also impairs insulin sensitivity in adipocytes and skeletal muscle. Aldosterone may produce insulin resistance secondarily by altering potassium, increasing inflammatory cytokines, and reducing beneficial adipokines such as adiponectin. Renin-angiotensin system antagonists reduce circulating aldosterone concentration and also the risk of type 2 diabetes in clinical trials. These data suggest that primary and secondary hyperaldosteronism may contribute to worsening glucose tolerance by impairing insulin sensitivity or insulin secretion in humans. Future studies should define the effects of MR antagonists and aldosterone on insulin secretion and sensitivity in humans.»

2015 Acarbose: safe and effective for lowering postprandial hyperglycaemia and improving cardiovascular outcomes

«α-Glucosidase inhibitors (AGIs) are a class of oral glucose-lowering drugs used exclusively for treatment or prevention of type 2 diabetes mellitus. AGIs act by altering the intestinal absorption of carbohydrates through inhibition of their conversion into simple sugar (monosaccharides) and thus decrease the bioavailability of carbohydrates in the body, significantly lowering blood glucose levels. The three AGIs used in clinical practice are acarbose, voglibose and miglitol. This review will focus on the cardiovascular properties of acarbose. The current available data suggest that AGIs (particularly acarbose) may be safe and effective for the treatment of prediabetes and diabetes.»

2016 Longer telomeres in chronic, moderate, unconjugated hyperbilirubinaemia: insights from a human study on Gilbert’s Syndrome

Baseline inflammation markers in serum such as CRP and SAA were only weakly inversely associated with UCB (r = −0.2, P = 0.02 and r = −0.19, P = 0.04, respectively), whereas IL-6 and IL-1β in monocytes showed a stronger inverse correlation (r = −0.301, P = 0.001 and r = −0.211, P = 0.023 respectively) which remained significant after age correction.

UCB might affect the immune response by downregulating intracellular production of cytokines, as evident from the lower levels of IL6 and IL-1β in monocytes from GS individuals, in particularly males (sup. Table S1).

2016 Statin-induced diabetes: incidence, mechanisms, and implications

«Persuasive data from many randomized controlled trials and large, long-term observational studies indicate a modestly increased risk for the emergence of new diabetes after statin initiation. Several meta-analyses of many statin trials as well as longitudinal population-based studies suggest that the risk factors for diabetes in statin-treated persons include underlying risk for diabetes at baseline (specifically features of metabolic syndrome), the intensity of statin therapy, certain genetic traits independent of diabetes risk, and adherence to lifestyle factors. Limited data suggest statins modestly worsen hyperglycemia and A1c levels in those with pre-existing diabetes or glucose intolerance. The precise mechanism(s) of diabetogenesis with statin therapy are unclear, but impaired insulin sensitivity and compromised β cell function via enhanced intracellular cholesterol uptake due to inhibition of intracellular cholesterol synthesis by statins, as well as other mechanisms, may be involved. Furthermore, while statins are known to have anti-inflammatory effects, it is hypothesized that, under dysmetabolic conditions, they might have pro-inflammatory effects via induction of certain inflammasomes. This concept requires further elucidation in the human. Finally, it is clear that the risk–benefit ratio for cardiovascular disease events is strongly in favor of statin therapy in those at risk, despite the emergence of new diabetes. Adherence to lifestyle regimen is critical in the prevention of new diabetes on statins.»

2016 Effects of Nigella sativa supplementation on blood parameters and anthropometric indices in adults: A systematic review on clinical trials

«RESULTS: After analyzing 23 articles including 1531 participants, these results were achieved: In 4 trials, N. sativa reduced BP, but in 5 trials it could not. Fasting blood sugar (FBS) was reduced significantly in 13 studies. In addition, N. sativa reduced levels of glycosylated hemoglobin (HbA1c). Although weight and waist circumference (WC) in 2 articles were reduced significantly, in 6 articles they were not. Fluctuation in lipid profile in the articles was very controversial, being significant in many of them but not in others.

CONCLUSION: Our systematic review revealed that N. sativa supplementation might be effective in glycemic control in humans.»

2017 The Role of Vitamin D in the Prevention of Type 2 Diabetes: To D or Not to D?

«Evidence on biological plausibility from mechanistic studies and highly consistent data from observational studies raise the possibility that optimizing vitamin D status may reduce the risk of type 2 diabetes. However, the observational nature of cohort studies precludes a definitive assessment of cause and effect because residual confounding or reverse causation cannot be excluded. Confounding is especially problematic with studies of vitamin D because blood 25-hydoxyvitamin D concentration is not only an excellent biomarker of vitamin D status, reflecting intake or biosynthesis, but also an excellent marker of good overall health. Results from underpowered trials and post hoc analyses of trials designed for nondiabetic outcomes do not support a role of vitamin D supplementation for prevention of type 2 diabetes among people with normal glucose tolerance. Whether vitamin D supplementation may have a role in the prevention of diabetes in high-risk populations remains to be seen. Adequately powered, randomized trials in well-defined populations (e.g., prediabetes) are ongoing and expected to establish whether vitamin D supplementation lowers risk of diabetes.»

2017 The Potential Liver, Brain, and Embryo Toxicity of Titanium Dioxide Nanoparticles on Mice

Lower doses (5, 10, 50, and 100 mg/kg) of nano-TiO2 did not change any blood biochemistry index (Fig. ​(Fig.3).3). High doses of nano-TiO2 (150 to 200 mg/kg) elevated liver function biomarkers alkaline phosphatase (ALP) and alanine aminotransferase (ALT), albumin (ALB), leucine aminopeptidase (LAP), butyrylcholinesterase (PChe), total bilirubin (TBIL), and total protein (TP) levels (Fig. ​(Fig.3).3). High doses decreased serum uric acid (UA) and blood urea nitrogen (BUN) levels, which are biomarkers for kidney function. They increased serum aspartate aminotransferase (AST), creatine kinase (CK), lactate dehydrogenase (LDH), and alpha hydroxybutyrate dehydrogenase (HBDH) levels, which are indices for myocardial damage (Fig. ​(Fig.33).

The treatment of mice with 5 mg/kg nano-TiO2 for 60 days did not change the levels of ROS such as O2−, H2O2, nitric oxide (NO), and MDA (Fig. ​(Fig.6),6), or the mRNA levels of SOD, CAT, GSHPx, MT, GST, HSP70, P53, and TF genes in liver tissues (Fig. ​(Fig.7).7). Treatment of mice with 10 or 50 mg/kg nano-TiO2 for 60 days resulted in significant increases in the levels of O2−, H2O2, NO, and MDA (Fig. ​(Fig.6),6), decreases in the mRNA levels of SOD, CAT, MT, GST, HSP70, P53, TF, and GSHPx genes, and increases in the mRNA levels of CYP1A genes in the liver of mice (Fig. ​(Fig.7).7). The results showed that high doses of nano-TiO2-induced oxidative stress and changes in the expression of protective genes in the liver of exposed mice.

We further evaluated brain toxicity of nano-TiO2. We first examined the ratios of brain/body weight in the mice exposed to nano-TiO2 (i.p. for 14 days). Low doses (5, 10, 50 mg/kg) did not change the ratios of brain/body weight, and higher doses (100, 150, 200 mg/kg) significantly decreased the ratios of brain/body weight in a dose-dependent manner (Fig. ​(Fig.2).2). The concentration of Ti in the brain tissues was significantly increased in a dose-dependent manner (Fig. ​(Fig.11).

2017 Isolation and Speciation of Candida in Type II Diabetic Patients using CHROM Agar: A Microbial Study

«Results: All the species of Candida, namely, Candida albicans, Candida glabrata, Candida dubliniensis, Candida krusei, Candida parapsilosis except for Candida tropicalis showed a significantly higher (p<0.001) occurrence in the diabetic group compared to the healthy group. The highest identified species is C. parapsilosis, second being C. albicans in both the groups.»

2018 β-glucans and cholesterol (Review)

«Hypercholesterolemia is one of primary risk factors of cardiovascular disease, together with metabolic syndrome, hypertension and diabetes. Although progress has been made, the search for novel methods of preventing and treating dyslipidemia is ongoing and current therapies for cardiovascular disease induce various side effects. β-glucans are linear unbranched polysaccharides found in various natural sources, such as mushrooms. Due to their structure they are able to interact with innate immunity receptors, however they also act as dietary fiber in the digestive tract. As there are two forms of β-glucans, insoluble and soluble forms, they are able to interact with lipids and biliary salts in the bowel and consequently reduce cholesterol levels. Therefore, they may be developed as a suitable therapeutic option to treat patients with dyslipidemia, as they are natural molecules that do not induce any significant side effects. The current review discusses the evidence supporting the effects of β-glucans on cholesterol levels.»

«None of the cholesterol lowering drugs currently used are free of side effects. By contrast, it is generally accepted that different types of dietary fiber, including β-glucans, have positive effects on health without inducing significant side effects (92). The results of experimental studies in animals and clinical trials in humans have demonstrated that dietary fiber supplements not only improve general health but also reduce the risk of various chronic diseases associated with lifestyle, including CVD, cancer and type 2 diabetes (93), which all have a large impact on public health and society in general. Due to their variety, accurately defining the different types of dietary fiber has been challenging. »

2018 Black Seed Thymoquinone Improved Insulin Secretion, Hepatic Glycogen Storage, and Oxidative Stress in Streptozotocin-Induced Diabetic Male Wistar Rats

«RESULTS: The body weight of the STZ-induced diabetic group rats reduced significantly (P < 0.05) than did those of the control nondiabetic rats at the 3rd and 4th weeks of the experiment. However, NSO 2 mL/kg treatment of diabetic rats increased their body weight (P < 0.05) compared to those of diabetic nontreated rats at the 4th week of the experimental period (Table 1).

CONCLUSION: Based on the current results, NSO was found to be an effective protection against the adverse consequences of STZ-induced diabetes in Wistar rats. NSO exerts its effect through thymoquinone antioxidant potential, which improved pancreatic and hepatic integrity, thus increasing pancreatic islet immunoreactivity, therefore increasing the serum insulin level, increasing hepatic glycogen content, reducing the elevated blood glucose level, and counteracting diabetic dyslipidemia.»

2019 The Role of Vitamin D Binding Protein, Total and Free 25-Hydroxyvitamin D in Diabetes

«Vitamin D is important for bone health, but may also have extra-skeletal effects. Vitamin D and its binding protein DBP have immunological effects and may therefore be important in the development of type 1 diabetes (T1DM), and low serum levels of 25-hydroxyvitamin D (25(OH)D) are associated with later development of type 2 diabetes (T2DM). However, it has so far been difficult to convincingly show an effect of vitamin D supplementation on prevention or treatment of diabetes. The serum level of 25(OH)D has traditionally been used as a marker of a subject's vitamin D status. This measurement includes both 25(OH)D bound to DBP and albumin as well as the free from of 25(OH)D. However, according to the free hormone hypothesis, the free form is the biologically active. Previously the free form of 25(OH)D had to be calculated based on measurements of 25(OH)D, DBP, and albumin, but recently a method for direct measurement of free 25(OH)D has become commercially available. This is important in clinical conditions where the amount of DBP is affected, and has caused a renewed interest in which vitamin D metabolite to measure in clinical situations. In the present review the relations between DBP, total and free 25(OH)D in T1DM and T2DM are described.»

1999 1,25-dihydroxyvitamin D3 regulates the synthesis of gamma-glutamyl transpeptidase and glutathione levels in rat primary astrocytes.

«Astrocytes play a pivotal role in CNS detoxification pathways, where glutathione (GSH) is involved in the elimination of oxygen and nitrogen reactive species such as nitric oxide. We have previously demonstrated that the specific activity of gamma-glutamyl transpeptidase (gamma-GT), an enzyme of central significance in GSH metabolism, is regulated in vivo in astrocytes by 1,25-dihydroxyvitamin D3 (1,25-D3). The aim of the present work was to investigate, in primary cultures of newborn rat astrocytes, the effects of this hormone on gamma-GT synthesis and on GSH and nitrite levels after lipopolysaccharide (LPS) treatment. This study demonstrates that both gamma-GT gene expression and specific activity, induced by LPS, are potentiated by 1,25-D3. In contrast, 1,25-D3 does not regulate the expression of other enzymes involved in astrocyte detoxification processes, such as superoxide dismutase or GSH peroxidase. In parallel, 1,25-D3 enhanced intracellular GSH pools and significantly reduced nitrite production induced by LPS. Taken together, these results suggest that gamma-GT, GSH, and 1,25-D3 play a fundamental role in astrocyte detoxification pathways.»

1999 Effects of exercise training on oxygen uptake kinetic responses in women with type 2 diabetes.

«RESULTS: On entry, women with type 2 diabetes had the lowest VO2max and slowest VO2 kinetics of the three groups. After exercise training, the women with type 2 diabetes improved their VO2max more than the lean and overweight control women: 28 vs. 5 and 8%, respectively (P < 0.05 for the diabetic group vs. both control groups). In the group with diabetes, VO2 kinetics improved by 39 and 22% at 20 and 30 W, respectively. For the control subjects, VO2 kinetics did not improve at any workload in either group.

CONCLUSIONS: Despite beginning with the lowest VO2max and slowest VO2 kinetics, subjects with type 2 diabetes benefited more from an exercise training program than did control subjects. These findings suggest that in addition to its known metabolic effects, exercise training in individuals with type 2 diabetes may be an effective therapy to improve the cardiovascular response to exercise and to overcome low-level exercise impairment as reflected by improved VO2max and VO2 kinetics. If the ability to make circulatory adjustments at the beginning of exercise at low workloads is improved by an exercise training program, as suggested by the VO2 kinetics data, the clinical significance of exercise for people with type 2 diabetes is clear.»

2000 Antioxidant activity of Nigella sativa essential oil.

«The essential oil of black cumin seeds, Nigella sativa L., was tested for a possible antioxidant activity. A rapid evaluation for antioxidant, using two TLC screening methods, showed that thymoquinone and the components carvacrol, t-anethole and 4-terpineol demonstrated respectable radical scavenging property. These four constituents and the essential oil possessed variable antioxidant activity when tested in the diphenylpicrylhydracyl assay for non-specific hydrogen atom or electron donating activity. They were also effective.OH radical scavenging agents in the assay for non-enzymatic lipid peroxidation in liposomes and the deoxyribose degradation assay. GC-MS analysis of the essential oil obtained from six different samples of Nigella sativa seeds and from a commercial fixed oil showed that the qualitative composition of the volatile compounds was almost identical. Differences were mainly restricted to the quantitative composition.»

2006 Epigallocatechin gallate supplementation alleviates diabetes in rodents.

«As the prevalence of type 2 diabetes mellitus is increasing at an alarming rate, effective nutritional and exercise strategies for the prevention of this disease are required. Specific dietary components with antidiabetic efficacy could be one aspect of these strategies. This study investigated the antidiabetic effects of the most abundant green tea catechin, epigallocatechin gallate (EGCG, TEAVIGO), in rodent models of type 2 diabetes mellitus and H4IIE rat hepatoma cells. We assessed glucose and insulin tolerance in db/db mice and ZDF rats after they ingested EGCG. Using gene microarray and real-time quantitative RT-PCR we investigated the effect of EGCG on gene expression in H4IIE rat hepatoma cells as well as in liver and adipose tissue of db/db mice. EGCG improved oral glucose tolerance and blood glucose in food-deprived rats in a dose-dependent manner. Plasma concentration of triacylglycerol were reduced and glucose-stimulated insulin secretion was enhanced. In H4IIE cells, EGCG downregulated genes involved in gluconeogenesis and the synthesis of fatty acids, triacylgycerol, and cholesterol. EGCG decreased the mRNA expression of phosphoenolpyruvate carboxykinase in H4IIE cells as well as in liver and adipose tissue of db/db mice. Glucokinase mRNA expression was upregulated in the liver of db/db mice in a dose-dependent manner. This study shows that EGCG beneficially modifies glucose and lipid metabolism in H4IIE cells and markedly enhances glucose tolerance in diabetic rodents. Dietary supplementation with EGCG could potentially contribute to nutritional strategies for the prevention and treatment of type 2 diabetes mellitus.»

2009 Soluble CD40 ligand and soluble P-selectin levels in Gilbert's syndrome: a link to protection against atherosclerosis?

«RESULTS: sCD40L and hs-CRP levels were significantly lower in GS compared to the controls (0.33+/-0.27 vs 0.71+/-0.37 ng/mL, p<0.001 and 0.51+/-0.45 vs 1.16+/-1.31 mg/L, p=0.046, respectively). Both sCD40L and hs-CRP were negatively correlated with total bilirubin (r=-0.5, p<0.001 and r=-0.34, p=0.002, respectively). sP-selectin levels were lower in GS when compared to the controls but the difference did not reach statistical significance (p=0.052). No correlation was found between the plasma levels of sCD40L, sP-selectin and hs-CRP.

CONCLUSION: These novel findings suggest that reduced sCD40L and hs-CRP concentration may have a role in the mechanism of protection against atherosclerosis in GS.»

2010 Decreased small dense LDL levels in Gilbert's syndrome.

«RESULTS: Age, gender and body mass index (BMI) distributions were similar between the two groups. sd-LDL-C, ox-LDL and hs-CRP levels were lower in GS than the healthy controls (p<0.001, p<0.001 and p=0.001, respectively). Unconjugated bilirubin was negatively correlated with sd-LDL-C, ox-LDL and hs-CRP (r=-0.594, p<0.001; r=-0.249, p=0.016 and r=-0.373, p<0.001 respectively). In addition, sd-LDL-C was positively correlated with ox-LDL (r=0.307, p=0.003).

CONCLUSIONS: The findings of this preliminary study suggest that reduced sd-LDL-C, ox-LDL and hs-CRP levels may have a role in preventing atherosclerosis in subjects with GS.»

2011 Effect of Nigella sativa seeds on the glycemic control of patients with type 2 diabetes mellitus.

«CONCLUSION: the results of this study indicate that a dose of 2 gm/ day of Nigella sativa might be a beneficial adjuvant to oral hypoglycemic agents in type 2 diabetic patients.»

2011 Relationship between unconjugated hyperbilirubinemia and lipoprotein spectrum.

«RESULTS: We found significantly higher levels of total bilirubin and unconjugated bilirubin in patients with Gilbert's syndrome. In the control group, probands had significantly higher triglycerides levels, VLDL cholesterol levels, IDL cholesterol level, and small dense LDL levels compared to the group with Gilbert\'s syndrome. Probands with Gilbert's syndrome had significantly lower presence of atherogenic lipoprotein spectrum than probands in control group (5% vs. 18%). We found significantly negative correlation between serum unconjugated bilirubin levels and LDL 3-7 (r = - 0.594, p <0.01), as well as between bilirubin and triglycerides (r = -0.540, p<0.01). Serum bilirubin concentration and LDL 1-2 concentration correlated significantly positively (r = 0.451, p <0.05).

CONCLUSION: The presence of atherogenic lipoprotein spectrum is determined by the particular representation of small dense LDL. Atherogenic spectrum was presented significantly less in patients with Gilbert\'s syndrome compared with the control group (5% vs. 18%). In our study, we have not followed the risk of coronary heart disease or other manifestations of atherosclerotic arteries disability. However, we found the inverse relationship of serum bilirubin levels and atherogenic small dense LDL. We found out that the protective antiatherogenic effect of hyperbilirubinemia is potentiated by low occurence of strongly atherogenic small dense LDL and persons with byperbilirubionemia (in our case represented Gilbert's syndrome), could be protected against the development of atheroscleosis.»

2013 The effects of Gilbert's syndrome on the mean platelet volume and other hematological parameters.

«The protective effect of increased levels of indirect bilirubin on atherosclerotic heart disease in patients of Gilbert's syndrome is well known. The aim of the study was to investigate the effects of increased levels of bilirubin on the mean platelet volume (MPV) and other hematological parameters. Thirty-two men and 36 women (a total of 68 Gilbert's syndrome patients) and a similar age group of 68 healthy individuals (32 men and 36 women) were included in the study. Hematologic tests, C-reactive protein (CRP) and biochemical values of the two groups were checked. MPV level of Gilbert's syndrome group was 7.8±1.0fl and CRP 0.2±0.27mg/dl. In the control group MPV was 8.6±1.0fl and CRP 0.3±0.38mg/dl. MPV of patients group (P<0.001) and CRP (P=0.037) were significantly lower than the control group. When dividing Gilbert's syndrome and control groups according to sex into subgroups the level of indirect bilirubin in men with Gilbert's syndrome (1.8±0.8mg/dl) was found to be higher than other groups. Healthy men had higher levels of MPV (8.8±0.9fl) whereas Gilbert's syndrome male patients had lower levels (7.7±1.1fl), (P<0.001). The elevated levels of bilirubin and decreasing levels of MPV and CRP in Gilbert's syndrome patients may have an effect on the slowing down of the atherosclerotic process.»

2013 Protection from age-related increase in lipid biomarkers and inflammation contributes to cardiovascular protection in Gilbert's syndrome.

IL-6 (interleukin 6), a pro-inflammatory cytokine, induces the hepatic synthesis of pro-inflammatory CRP (C-reactive protein), which is a known independent risk factor for CVD and Type 2 diabetes [22–23]

2013 Gilbert's syndrome and the risk of death: a population-based cohort study.

«RESULTS: During the 350 000 PYs of follow up across the Gilbert's and comparison cohorts, there were 1174 deaths. Mortality rates were 24/10 000 PYs in the Gilbert's cohort versus 50/10 000 PYs in the comparison cohort. Mortality rates were around half in patients with Gilbert's syndrome after accounting for sociodemographics and general health indicators (adjusted mortality rate ratio: 0.5 [95% confidence interval; 0.4-0.7; P < 0.001]).

CONCLUSIONS: Mortality rates observed for people with Gilbert's syndrome in the general population are almost half those of people without evidence of Gilbert's syndrome.»

2013 Oral Candida spp carriers: its prevalence in patients with type 2 diabetes mellitus.

«We examined 141 patients (mean age 57 years): 103 women (73%) and 38 men (26.9%). Exfoliative cytology was positive in 32 cases (23 with oral lesions); 78 had oral lesions but no Candida (93.9%). Candida was isolated in 58 patients (41.1%), 21 (45.6 %) had blood glucose greater than 126 mg/dl, and 37 (38.9%) had less than 126 mg/dl. The most frequent species was C. albicans (82.7%). Forty-two Candida carriers had salivary flow greater than 20 mm (72.4%), and 16 (27.5%) had hyposalivation. Candida was isolated in 25 of 79 patients with dental prosthesis (31.6%), 9 of 15 were smokers (60%), and 22 of 71 had symptoms (30.9%).»

2013 Curcumin improves expression of ghrelin through attenuating oxidative stress in gastric tissues of streptozotocin-induced diabetic gastroparesis rats.

«The study was performed to investigate the improved effect of curcumin on gastrointestinal function in streptozotocin-induced diabetic rats. Curcumin was administrated intragastrically at a dose of 100, 200 and 400 mg/kg/day to diabetic rats. After 28 days of treatment, the activity of superoxide dismutase (SOD), catalase (CAT), the content of reduced glutathione (GSH) and malondialdehyde (MDA) in gastric mucosa was assayed. Furthermore, the gastric function was evaluated by hormone secretion and gastric emptying tests. The results indicated that: (i) the diabetic rats exhibited significant decreases in the above mentioned antioxidative enzymes activities and GSH level and exhibited a high level of MDA. After administration of curcumin, the parameters were ameliorated to a large extent; (ii) curcumin treatment dose-dependently augmented the ghrelin levels of stomach and plasma, which were earlier depleted in the diabetic control rats. Conversely, the expression of ghrelin mRNA was decreased after curcumin treatment; and (iii) the gastric emptying in curcumin treated diabetic rats was notably accelerated compared with the diabetic control rats. These findings showed an improved effect of curcumin against streptozotocin-induced gastroparesis possibly by its antioxidant property.»

2015 Bilirubin, platelet activation and heart disease: a missing link to cardiovascular protection in Gilbert's syndrome?

Significant dose dependent reduction in C-reactive protein (CRP; a chronic inflammatory biomarker) is consistently reported in individuals with elevated circulating bilirubin, being lowest in individuals with GS

2017 Mildly elevated unconjugated bilirubin is associated with reduced platelet activation-related thrombogenesis and inflammation in Gilbert's syndrome.

«Gilbert's syndrome (GS) is associated with a mild unconjugated hyperbilirubinemia, increased circulating antioxidant capacity, and reduced cardiovascular disease (CVD) risk. The current study investigated whether mildly elevated circulating unconjugated bilirubin (UCB) is negatively associated with multiple thrombotic risk factors including platelet activity, hemostatic function, and inflammation in individuals with GS. Blood samples were collected from matched GS and control subjects (14 per group). Activation-dependent platelet surface marker expression of PAC-1 (binds to GPIIb/IIIa surface receptors on activated platelet) and CD62P (marker for P-selectin released from activated degranulated platelet) was assessed in adenosine diphosphate (ADP)-stimulated platelet using flow cytometry. Exogenous agonists, ADP, collagen, and arachidonic acid (AA), were used to stimulate platelet aggregation. A statistically significant decrease in the expression of P-selectin (P = 0.030) on activated platelet was observed in GS subjects. Collagen and AA-induced platelet aggregation were significantly (P = 0.018; P = 0.032 for respective agonists) reduced in GS versus control group. Elevated UCB (P = 0.001) and high density lipoprotein (P = 0.033) in addition to reduced low density lipoprotein (P = 0.024) and high sensitive C-reactive protein (P = 0.043) were also observed in GS when compared to the control group. Reduced P-selectin expression suggests decreased platelet activation-dependent degranulation, while reduced platelet aggregation by AA and collagen indicates a quantitative decrease in platelet aggregation consequently targeting the cyclooxygenase-1 and GP VI pathways, respectively. These findings are the first to demonstrate that the activation of platelet is mildly inhibited in individuals with GS, an effect that might contribute to protection from platelet hyperactivation-induced thrombosis and thus cardiovascular mortality in individuals with benign hyperbilirubinemia.»

2017 Mild hyperbilirubinaemia as an endogenous mitigator of overweight and obesity: Implications for improved metabolic health.

«RESULTS: BMI, hip circumference (HC), and lipid profile were significantly lower in GS. UCB was inversely correlated with BMI (p <0 .001), HC as well as with fat mass (FM) and lipid variables (p < 0.05). Moreover, DM2 patients had significantly lower UCB compared to GS and healthy controls. Older GS subjects (≥35 years) had significantly reduced anthropometric data and improved lipid profile.

CONCLUSIONS: Our results propose that the health promoting potential of mild hyperbilirubinaemia may extend to protection from age-related weight gain and dyslipidaemia.»

2018 Telmisartan Improves Insulin Resistance: A Meta-Analysis.

«A total of 21 RCTs, which included 1679 patients, were included. Results revealed that telmisartan was superior in improving homeostasis model assessment of insulin resistance (mean difference = -0.23, 95% confidence interval [CI], -0.40 to -0.06), reducing fasting blood glucose level (mean difference = -0.32, 95% CI, -0.57 to -0.07), reducing fasting insulin level (mean difference = -1.01, 95% CI, -1.63 to -0.39), and decreasing diastolic blood pressure (mean difference = -1.46, 95% CI, -2.10 to -0.82) compared with other ARB. However, for the decrease in systolic pressure, the difference was not statistically significant (mean difference = -0.73, 95% CI, -1.53 to 0.07).»

2018 Bilirubin acts as a multipotent guardian of cardiovascular integrity: more than just a radical idea.

«Bilirubin, a potentially toxic catabolite of heme and indicator of hepatobiliary insufficiency, exhibits potent cardiac and vascular protective properties. Individuals with Gilbert's syndrome (GS) may experience hyperbilirubinemia in response to stressors including reduced hepatic bilirubin excretion/increased red blood cell breakdown, with individuals usually informed by their clinician that their condition is of little consequence. However, GS appears to protect from all-cause mortality, with progressively elevated total bilirubin associated with protection from ischemic heart and chronic obstructive pulmonary diseases. Bilirubin may protect against these diseases and associated mortality by reducing circulating cholesterol, oxidative lipid/protein modifications, and blood pressure. In addition, bilirubin inhibits platelet activation and protects the heart from ischemia-reperfusion injury. These effects attenuate multiple stages of the atherosclerotic process in addition to protecting the heart during resultant ischemic stress, likely underpinning the profound reduction in cardiovascular mortality in hyperbilirubinemic GS. This review outlines our current knowledge of and uses for bilirubin in clinical medicine and summarizes recent progress in revealing the physiological importance of this poorly understood molecule. We believe that this review will be of significant interest to clinicians, medical researchers, and individuals who have GS.»

2018 Association of Type 2 Diabetes with Submicron Titanium Dioxide Crystals in the Pancreas

In this pilot study of 11 pancreatic specimens, 8 of the type 2 diabetic pancreas and 3 of the nondiabetic pancreas, we show that particles comprising 110 ± 70 nm average diameter TiO2 monocrystals abound in the type 2 diabetic pancreas, but not in the nondiabetic pancreas. In the type 2 diabetic pancreas, the count of the crystals is as high as 108–109 per gram.

2018 The Association between Vitamin D Deficiency and Sleep Disorders: A Systematic Review and Meta-Analysis.

«Epidemiology studies have investigated the association between vitamin D and the risk of sleep disorders, but the results remain controversial. Therefore, we conducted this meta-analysis with the goal of clarifying the association between vitamin D and sleep disorders risk. All relevant studies were searched using PubMed, EMBASE, and Web of Science from inception to January 2018. Pooled odds ratios (ORs) and 95% confidence interval (CIs) were calculated using a fixed-effect model A total of nine studies (6 cross-sectional, 2 case-control, and 1 cohort studies) involving 9397 participants were included. By comparing the lowest verse highest levels of serum vitamin D, we found that participants with vitamin D deficiency (VDD) had a significantly increased risk of sleep disorders (OR: 1.50, 95% CI: 1.31, 1.72). Subgroup analysis showed that VDD also was associated with poor sleep quality (OR: 1.59, 95% CI: 1.23, 2.05), short sleep duration (OR: 1.74, 95% CI: 1.30, 2.32), and sleepiness (OR: 1.36, 95% CI: 1.12, 1.65). Subgroup analyses further indicated that serum 25(OH)D <20 ng/mL could significantly increase the risk of unhealthy sleep. This meta-analysis suggest that vitamin D deficiency is associated with a higher risk of sleep disorders. More high-quality cohort studies and randomized controlled trials (RCTs) are needed to verify this association.»

2018 Life-threatening vitamin D intoxication due to intake of ultra-high doses in multiple sclerosis: A note of caution.

«Knowledge about complications of chronic ultra-high dose vitamin D supplementation is limited. We report a patient with primary progressive multiple sclerosis (MS) who presented with generalized weakness caused by hypercalcemia after uncontrolled intake of more than 50,000 IU of cholecalciferol per day over several months. Various treatment strategies were required to achieve normocalcemia. However, renal function improved only partly and further progression of MS was observed. We conclude that patients need to be informed about the risks of uncontrolled vitamin D intake and neurologists need to be alert of biochemical alterations and symptoms of vitamin D toxicity.»

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