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Can Cranberry Supplementation Reduce Risks for Diabetes?
Abstract
Diabetes affects approximately 250 million people worldwide and health care costs related to diabetes equal approximately $98 billion each year. Aldose reductase has been shown to contribute to the side effects of diabetes including kidney disease, nerve disease, and retinopathy. Cranberries contain anthocyanins and other flavonoids that have been shown in vitro to inhibit the enzyme aldose reductase and to inhibit protein glycosylation. It is believed that daily cranberry supplementation could reduce side effects of diabetes. Twenty-seven adults with type 2 diabetes were recruited for this 12 week double-blind, placebo-controlled study. Fasting blood analysis was done at weeks 0, 6, and 12. The blood analyses included: cholesterol (total cholesterol, triglycerides, HDL, LDL, and percent HDL), glycosylated hemoglobin (HbA, c), blood glucose, insulin, fructosamine, aldose reductase activity, and hexanal. The subjects were asked to take 6 capsules each day that contained either spray-dried cranberry powder or a placebo. The placebo consisted of cellulose and artificial food coloring, as well as sucrose, fructose, magnesium hydroxide, and ascorbic acid in the same concentrations as in the cranberry powder. Improvements were seen in blood glucose levels, HbAic, fructosamine, insulin, total cholesterol, triglycerides, and percent HDL for some subjects. Glucose levels were significantly lower (p = 0.036) at week 12 in subjects who had diabetes more than 5 years in the cranberry group compared to the placebo group. At week 6, in subjects less than 50 years of age, blood glucose levels decreased significantly (p = 0.030) in the cranberry group compared to the placebo group. HbAlc levels decreased significantly (p = 0.031) in the cranberry group at week 6 in subjects who had diabetes more than 5 years. Fructosamine levels improved significantly in patients less than age of 50 in the cranberry group compared to the placebo group from week 0 to week 6 (p = 0.027). Triglyceride and total cholesterol levels were significantly lower (p = 0.013 and p = 0.007 respectively) in the cranberry group than the placebo group in subjects who had diabetes more than 5 years. Cranberry supplementation may be beneficial for individuals with diabetes. More research is needed in subjects with poor glycemic control and to determine proper dosages.
... 12 studies met the eligibility criteria and were included in the systematic review. Of these, two studies [38,39] did not contain appropriate data for pooling results in all outcomes they reported, and one study [40] did not provided suitable information for SBP, and were only presented in the systematic review. One study [41] used 2 different doses of cranberry for intervention, considering each one as a separate arm. ...
... The primary characteristics of the included trials are shown in Table 2. Twelve RCTs [29,30,[38][39][40][41][42][43][44][45][46][47] comprising 496 participants with a mean age of nearly 48.5 provided data on the effects of cranberry consumption on blood lipid profiles, markers of glycemic status, blood pressure and inflammatory markers. Studies were conducted in the USA [29,30,38,39,44], Czech Republic [41], Iran [43,46,47], Canada [45], Scotland [42] and Taiwan [40]. ...
... The primary characteristics of the included trials are shown in Table 2. Twelve RCTs [29,30,[38][39][40][41][42][43][44][45][46][47] comprising 496 participants with a mean age of nearly 48.5 provided data on the effects of cranberry consumption on blood lipid profiles, markers of glycemic status, blood pressure and inflammatory markers. Studies were conducted in the USA [29,30,38,39,44], Czech Republic [41], Iran [43,46,47], Canada [45], Scotland [42] and Taiwan [40]. Two trials [30,45] used a cross-over methodology, while the rest [29,[38][39][40][41][42][43][44]46,47] had parallel designs. ...
Background & aims:
The impetus for the current study was to evaluate the efficacy of cranberry supplementation on cardiovascular disease metabolic risk factors in adult populations.
Methods:
A systematic review was conducted on PubMed, Scopus, Web of Science and Google Scholar up to June 2018, to identify randomized controlled trials investigating the effect of cranberry supplementation on cardiovascular metabolic risk factors.
Results:
The results of the pooled effect size indicated that cranberry administration significantly reduced systolic blood pressure and body mass index. No statistically significant change was observed in triacylglycerol, total cholesterol, low-density lipoprotein, high-density lipoprotein, fasting plasma glucose, fasting insulin, homeostasis model assessment of insulin resistance, diastolic blood pressure, waist circumference, C-reactive protein, and intercellular adhesion molecule. Stratified analysis showed that SBP reduction was more pronounced in studies with ≥50 mean age participants. Also, subgroup analysis suggested a significant increase in high-density lipoprotein concentrations in subgroups with subjects <50 mean age, and triacylglycerol levels in subsets with cranberry administered in juice form.
Conclusions:
This systematic review and meta-analysis suggests cranberry supplementation may be effective in managing systolic blood pressure, body mass index and high-density lipoprotein in younger adults. Further high-quality studies are needed to confirm these results.
... Different animal studies showed the promising effect of cranberry on liver enzymes and hepatic steatosis [8,9]. Moreover, various human studies have also focused on the effect of Cranberry capsules (240-1500 mg/day) [9][10][11][12] and Cranberry juice (240-750 ml/ days) [13][14][15][16][17][18][19] on cardiometabolic risk factors and providing mixed results. Some studies reported the protective effect of cranberry on TC [11], LDL-C [11], HDL-C [19], FPG [16], and blood pressure [15]. ...
Background
We aimed to evaluate the effect of cranberry supplementation on serum liver enzymes, hepatic steatosis, and cardiometabolic risk factors in patients with non-alcoholic fatty liver (NAFLD).
Methods
In the present parallel-designed randomized controlled clinical trial, 110 patients with NAFLD were enrolled. The patients were randomized to receive 144 mg cranberry capsule or placebo for 6 months. The primary efficacy of the treatment was lipid profile, glycemic measurements, and liver enzyme levels.
Results
The data were reported for 46 in the supplementation group and 48 in the placebo group. The patient’s mean (SD) age was 43.16 (11.08) years. No significant differences between groups were observed regarding the post-intervention level of liver enzyme. The mean after-intervention levels of total cholesterol ( p < 0.001) and triglyceride ( p = 0.01) were significantly lower in the intervention group compared with the placebo group. At the end of the study, the mean insulin and HOMA-IR levels were significantly lower in the cranberry group compared with the placebo group. Significantly more patients in the cranberry group experienced a decrease in steatosis level compared with the control group.
Conclusion
The results of the present study showed that cranberry supplementation had a positive effect on some lipid profiles, insulin resistance, and hepatic steatosis in patients with NAFLD.
Trial registration
IRCT20200725048200N1 ; first registration date: 11.8.2020.
... Blueberry is considered as one of the richest sources of anthocyanins among common fruits [80,83], which are responsible for a variety of health promoting values [42,77]. Several studies have shown that blueberry can be used in treatment of many diseases such as diabetes [13,16,20,26], preventing diabetic retinopathy and neuro protection [29,34,62,79], malignant tumors [7,11,23,67], chronic diseases [46], prevention of cardiovascular diseases [15,41,84], having antimicrobial activity [70,73,74], improving memory and protection against Alzheimer's disease [34,40,78]. All these properties of blueberry and its unique set of anthocyanins content, make it especially attractive for food and pharmaceutical preparations. ...
Blueberry is considered as a health-promoting food with a high content of anthocyanins. The extraction of anthocyanins from callus has been used to solve some problems of anthocyanins production, being more effective for commercial application and high production of anthocyanins. One of the most important aims of our study is to enhance anthocyanin synthesis in callus cultures. The results showed that callus induction from the highbush blueberry V. corymbosum L. cv. Sunt Blue Giant depends on the type of explant (leaf, root, and stem segments) and culture medium. Maximum callus induction was established on Woody Plant nutrient medium (WPM) containing 2.0 mg/L ɑ–naphthalene acetic acid (NAA) in combination with 1.0 mg/L 6-benzylaminopurine/benzyl adenine (BAP) from all used explants and the maximum fresh weight (for leaf, 1.03; root, 1.0; and stem, 0.8 g/jar) was recorded. After four subcultures on the same medium composition, we studied the effect of different light types on the accumulation of anthocyanins in callus culture. The highest levels of anthocyanin content were observed in callus from root origin (5.7 fold) and leaf origin (4.8 fold) grown under red light comparing with callus grown in dark as a control. The anthocyanins composition were evaluated using high-performance liquid chromatography, under the influence of red light the qualitative composition of anthocyanins significantly expanded in comparison with the dark condition. In addition, the red light increased the qualitative composition of anthocyanins in callus obtained from leaf origin largely than in callus obtained from root origin. From callus cultures obtained from root and leaf origin growing under red light were isolated ten anthocyanins and three proanthocyanidins. The present study could suggest an important protocol for improving the production of anthocyanins from callus culture of V. corymbosum L. cv. Sunt Blue Giant.
Objective: To estimate the cost effectiveness of conventional versus intensive blood glucose control in patients with type 2 diabetes.
Design: Incremental cost effectiveness analysis alongside randomised controlled trial.
Setting: 23 UK hospital clinic based study centres.
Participants: 3867 patients with newly diagnosed type 2 diabetes (mean age 53 years).
Interventions: Conventional (primarily diet) glucose control policy versus intensive control policy with a sulphonylurea or insulin.
Main outcome measures: Incremental cost per event-free year gained within the trial period.
Results: Intensive glucose control increased trial treatment costs by £695 (95% confidence interval £555 to £836) per patient but reduced the cost of complications by £957 (£233 to £1681) compared with conventional management. If standard practice visit patterns were assumed rather than trial conditions, the incremental cost of intensive management was £478 (-£275 to £1232) per patient. The within trial event-free time gained in the intensive group was 0.60 (0.12 to 1.10) years and the lifetime gain 1.14 (0.69 to 1.61) years. The incremental cost per event-free year gained was £1166 (costs and effects discounted at 6% a year) and £563 (costs discounted at 6% a year and effects not discounted).
Conclusions: Intensive blood glucose control in patients with type 2 diabetes significantly increased treatment costs but substantially reduced the cost of complications and increased the time free of complications.
The aim of the Finnish Diabetes Prevention Study is to assess the efficacy of an intensive diet–exercise programme in preventing or delaying type 2 diabetes in individuals with impaired glucose tolerance (IGT) and to evaluate the effect of the programme on the risk factors of atherosclerotic vascular diseases and the incidence of cardiovascular events. In this ongoing study, a total of 523 overweight subjects with IGT based on two oral glucose tolerance tests were randomized to either an intervention group or a control group. The main measure in the intervention group is individual dietary advice aimed at reducing weight and intake of saturated fat and increasing intake of dietary fibre. The intervention subjects are individually guided to increase their level of physical activity. The control group receives general information about the benefits of weight reduction, physical activity and healthy diet in the prevention of diabetes. A pilot study began in 1993, and recruitment ended in 1998. By the end of April 1999 there were 65 new cases of diabetes, 34 drop-outs and one death. The weight reduction was greater (-4.6 kg) at 1 year in the intervention group (n = 152) than in the control group (n = 143, -0.9 kg, P < 0.0001), and this difference was sustained in the second year of follow-up. At 1 year 43.4 % and at 2 years 41.8 % of the intervention subjects had achieved a weight reduction of at least 5 kg, while the corresponding figures for the control subjects were 14.0 and 12.0 % (P < 0.001 between the groups). At 1 year the intervention group showed significantly greater reductions in 2 h glucose, fasting and 2 h insulin, systolic and diastolic blood pressure, and serum triglycerides. Most of the beneficial changes in cardiovascular risk factors were sustained for 2 years. These interim results of the ongoing Finnish Diabetes Prevention Study demonstrate the efficacy and feasibility of the lifestyle intervention programme.
To evaluate baseline risk factors for coronary artery disease in patients with type 2 diabetes mellitus.
A stepwise selection procedure, adjusting for age and sex, was used in 2693 subjects with complete data to determine which risk factors for coronary artery disease should be included in a Cox proportional hazards model.
3055 white patients (mean age 52) with recently diagnosed type 2 diabetes mellitus and without evidence of disease related to atheroma. Median duration of follow up was 7.9 years. 335 patients developed coronary artery disease within 10 years.
Angina with confirmatory abnormal electrocardiogram; non-fatal and fatal myocardial infarction.
Coronary artery disease was significantly associated with increased concentrations of low density lipoprotein cholesterol, decreased concentrations of high density lipoprotein cholesterol, and increased triglyceride concentration, haemoglobin A1c, systolic blood pressure, fasting plasma glucose concentration, and a history of smoking. The estimated hazard ratios for the upper third relative to the lower third were 2.26 (95% confidence interval 1.70 to 3.00) for low density lipoprotein cholesterol, 0.55 (0.41 to 0.73) for high density lipoprotein cholesterol, 1.52 (1.15 to 2.01) for haemoglobin A1c, and 1.82 (1.34 to 2.47) for systolic blood pressure. The estimated hazard ratio for smokers was 1.41 (1.06 to 1.88).
A quintet of potentially modifiable risk factors for coronary artery disease exists in patients with type 2 diabetes mellitus. These risk factors are increased concentrations of low density lipoprotein cholesterol, decreased concentrations of high density lipoprotein cholesterol, raised blood pressure, hyperglycaemia, and smoking.
Br J Nutr 2000; 83 (Suppl 1): 137-142.
A rapid, sensitive and convenient capillary gas chromatographic-headspace method was developed to determine hexanal as an important volatile decomposition product of hydroperoxides formed from n-6 polyunsaturated fatty acids in rat liver samples. Total volatiles were also determined as a measure of overall lipid peroxidation. Samples of headspace taken from sealed serum bottles incubated at 37 degrees C were injected into a gas chromatograph. It was possible to make 15 determinations per hour. This method is convenient because no special sample manipulations are necessary. The addition of 0.5 mM ascorbic acid prior to gas chromatographic analysis significantly increased hexanal production. The applicability of the method was demonstrated in studies of the effect of iron in the presence or absence of hydroperoxides of methyl linoleate and methyl linolenate and tert-butyl hydroperoxide on rat liver homogenates, slices and microsomes. A rapid silica cartridge chromatographic procedure was used to purify hydroperoxides from autoxidized methyl linoleate and methyl linolenate, and hydroperoxy epidioxides (cyclic peroxides) from autoxidized methyl linolenate in 20-40 mg quantities. The hydroperoxides and hydroperoxy epidioxides of methyl linolenate were effective inducers of n-6 polyunsaturated fatty acid peroxidation in liver homogenates. Hexanal and thiobarbituric acid-reacting substances were significantly correlated in liver homogenates and microsomes but not in slices. This specific method for hexanal, a known product of peroxidation of n-6 polyunsaturated fatty acids, can be used as a good measure of lipid peroxidation.
Glucose molecules are joined to protein molecules to form stable ketoamines, or fructosamines, through glycation, a nonenzymatic mechanism involving a labile Schiff base intermediate and the Amadori rearrangement. The amount of fructosamine in serum is increased in diabetes mellitus owing to the abnormally high concentration of sugar in blood. The concentration of fructosamine in serum thus reflects the degree of glycemic control attained by the diabetic patient and is useful in monitoring the effectiveness of therapy in diabetes over a period of several weeks, in a manner analogous to the determination of glycated hemoglobin. Of the analytical approaches used to measure fructosamine, affinity chromatography with m-aminophenylboronic acid and the nitroblue tetrazolium reduction method appear to be the most practical means for clinical chemists to assay fructosamine quickly, economically, and accurately. Fructosamine values can readily distinguish normal individuals and diabetic patients in good glycemic control from diabetics in poor control. Unlike glycated hemoglobin, which reflects the average blood sugar concentration over the past six to eight weeks, fructosamine reflects the average blood sugar concentration over the past two to three weeks. Thus a clinical advantage is that fructosamine responds more quickly to changes in therapy, thereby allowing for improved glycemic control. Used in conjunction with determinations of blood sugar and (or) of glycated hemoglobin, or by itself, the fructosamine assay can provide clinically useful information for the detection and control of diabetes.
To identify risk factors for diabetic lower-extremity peripheral sensory neuropathy prospectively in a cohort of U.S. veterans with diabetes.
General medicine clinic outpatients with diabetes were followed prospectively for the development of insensitivity to the 5.07 monofilament on the foot.
Of 775 subjects, 388 (50%) had neuropathy at baseline. Of the 387 subjects without neuropathy at baseline, 288 were followed up, and of these, 58 (20%) developed neuropathy. Multivariate logistic regression modeling of prevalent neuropathy controlling for sex and race revealed independent and significant associations with age, duration of diabetes, glycohemoglobin level, height, history of lower-extremity ulceration, callus, and edema; an independent and inverse correlation was noted with ankle-arm index. Risk factors for incident neuropathy in multivariate logistic regression included age, baseline glycohemoglobin level, height, history of ulcer, and CAGE screening instrument alcohol score; current smoking and albumin level were inversely associated with risk.
Poorer glycemic control increases the risk of neuropathy and is amenable to intervention. Height and age directly increase risk of neuropathy and may help identify patients at risk. A proportion of neuropathy in diabetic veterans is probably due to or worsened by alcohol ingestion. Neuropathy was less common in current smokers than subjects not currently smoking.
The antioxidative activity of three anthocyanin pigments, extracted from the fruits of chokeberry, honeysuckle and sloe, were studied. Lipid oxidation in the liposome membrane, induced by UV radiation, was evaluated with a thiobarbituric acid-reactive substances assay. The antioxidant efficiency of the studied compounds follows this sequence: chokeberry > sloe > honeysuckle. The extract concentrations at which a 50% reduction of phosphatidylcholine oxidation was observed, were respectively: 48, 54 and 60 mg/l. The end products of lipid membrane oxidation were evaluated using HPLC. It was found that the antioxidative potency of anthocyanin extracts is concentration-dependent. As shown by EPR technique the efficiency of the extracts to eliminate free radicals from the solution follows the order of the antioxidant activity.
To investigate the association between consumption of certain foods and macronutrients and urinary glucose excretion, which is a predictor of non-insulin-dependent diabetes mellitus.
A cross-sectional study, Denmark, 1993-97.
Participants in the Danish study 'Diet, Cancer and Health'. After exclusion of persons with postprandial urine samples and persons with diabetes or other diseases potentially resulting in glycosuria, the study population included 14 743 men and 18 064 women aged 50-64 y. We identified 183 men and 43 women with glucose in their urine.
Consumption of poultry was negatively associated with glycosuria in both men (odds ratio, OR=0.87; 95% confidence interval, 95% CI=0.77-0.98) and women (OR=0.69; 0.48-1.00). Fiber from fruit showed a weak negative association with glycosuria in both men (0. 95; 0.90-1.01) and women (0.89; 0.78-1.02), whereas a significant negative association with total fiber (0.68; 0.51-0.91) and fiber from vegetables (0.94; 0.88-0.99) was seen in men. Intake of fish tended to reduce the risk of glycosuria in women only (0.80; 0.63-1. 02), whereas ingestion of milk products increased their risk significantly (1.15; 1.06-1.24).
Although statistical significance and consistency in the two sexes were not achieved for all end-points, the study indicates a protective effect of dietary products like poultry, fruit and cereals against glycosuria and suggests a promoting effect of milk.
The Danish National Board of Health and the Danish Cancer Society.
To assess whether consumption of 500 ml of blueberry juice or cranberry juice by healthy female subjects increased plasma phenolic content and antioxidant capacity.
Latin square arrangement to eliminate ordering effects. After an overnight fast, nine volunteers consumed 500 ml of blueberry juice, cranberry juice or a sucrose solution (control); each volunteer participated on three occasions one week apart, consuming one of the beverages each time. Blood samples were obtained by venipuncture at intervals up to four hours after consumption of the juices. Urine samples were also obtained four hours after consuming the juice.
Consumption of cranberry juice resulted in a significant increase in the ability of plasma to reduce potassium nitrosodisulphonate and Fe(III)-2,4, 6-Tri(2-pyridyl)-s-triazine, these measures of antioxidant capacity attaining a maximum after 60-120 min. This corresponded to a 30% increase in vitamin C and a small but significant increase in total phenols in plasma. Consumption of blueberry juice had no such effects.
The increase in plasma antioxidant capacity following consumption of cranberry juice could mainly be accounted for by an increase in vitamin C rather than phenolics. This also accounted for the lack of an effect of the phenolic-rich but vitamin C-low blueberry juice. Sponsorship: Funded by the Scottish Executive Rural Affairs Department and the Danish Government.
To determine the relation between exposure to glycaemia over time and the risk of macrovascular or microvascular complications in patients with type 2 diabetes.
Prospective observational study. Setting: 23 hospital based clinics in England, Scotland, and Northern Ireland. Participants: 4585 white, Asian Indian, and Afro-Caribbean UKPDS patients, whether randomised or not to treatment, were included in analyses of incidence; of these, 3642 were included in analyses of relative risk.
Primary predefined aggregate clinical outcomes: any end point or deaths related to diabetes and all cause mortality. Secondary aggregate outcomes: myocardial infarction, stroke, amputation (including death from peripheral vascular disease), and microvascular disease (predominantly retinal photo-coagulation). Single end points: non-fatal heart failure and cataract extraction. Risk reduction associated with a 1% reduction in updated mean HbA(1c) adjusted for possible confounders at diagnosis of diabetes.
The incidence of clinical complications was significantly associated with glycaemia. Each 1% reduction in updated mean HbA(1c) was associated with reductions in risk of 21% for any end point related to diabetes (95% confidence interval 17% to 24%, P<0.0001), 21% for deaths related to diabetes (15% to 27%, P<0.0001), 14% for myocardial infarction (8% to 21%, P<0.0001), and 37% for microvascular complications (33% to 41%, P<0.0001). No threshold of risk was observed for any end point.
In patients with type 2 diabetes the risk of diabetic complications was strongly associated with previous hyperglycaemia. Any reduction in HbA(1c) is likely to reduce the risk of complications, with the lowest risk being in those with HbA(1c) values in the normal range (<6.0%).
To clarify the role of the polyol pathway in the intracellular formation of advanced glycation end products in human tissues, we examined the effects of epalrestat, an aldose reductase inhibitor, on the level of Nepsilon-(carboxymethyl)lysine (CML) along with 3-deoxyglucosone (3-DG) and triosephosphates in erythrocytes from diabetic patients. Plasma thiobarbituric acid-reactive substances (TBARS) were also determined as indicators of oxidative stress.
Blood samples were collected from 12 nondiabetic volunteers, 38 untreated type 2 diabetic patients, and 16 type 2 diabetic patients who had been treated with 150 mg epalrestat/day. Blood samples were also collected from 14 of the untreated type 2 diabetic patients before and after the administration of epalrestat for 2 months. The amount of erythrocyte CML was determined by a competitive enzyme-linked immunosorbent assay, and 3-DG was measured by high-performance liquid chromatography
In diabetic patients not treated with epalrestat, the erythrocyte CML level was significantly elevated above levels seen in nondiabetic individuals (49.9 +/- 5.0 vs. 31.0 +/- 5.2 U/g protein, P < 0.05) and was significantly lower in patients receiving epalrestat (33.1 +/- 3.8 U/g protein, P < 0.05). Similar results were observed with 3-DG. The treatment of patients with epalrestat for 2 months significantly lowered the level of erythrocyte CML (46.2 +/- 5.6 at baseline vs. 34.4 +/- 5.0 U/g protein, P < 0.01) along with erythrocyte 3-DG (P < 0.05), triosephosphates (P < 0.05), fructose (P < 0.05), sorbitol (P < 0.05), and plasma TBARS (P < 0.05) without changes in plasma glucose and HbA(1c) levels. A positive correlation was evident between the erythrocyte CML and sorbitol (r = 0.49, P < 0.01) or fructose (r = 0.40, P < 0.05) levels in diabetic patients.
The results indicate that epalrestat administration lowers CML and associated variables and that polyol metabolites are correlated with CML in the erythrocytes of diabetic patients. The observed results suggest that aldose reductase activity may play a substantial role in the intracellular formation of CML in the mediation of reactive intermediate metabolites and oxidative stress.
Hyperglycemia is considered a key causal factor in the development of diabetic vascular complications and can mediate its adverse effects through multiple pathways. This was confirmed for microangiopathy in the Diabetes Control and Complications Trial study for type 1 diabetes and corroborated for type 2 diabetes by the United Kingdom Prospective Diabetes Study published in 1998. Prevention of diabetic complications requires at least control of glycemia. This article briefly summarizes the evidence that strongly supports the role of hyperglycemia in vascular complications. After outlining the role of the polyol pathway, protein kinase C, and oxidative stress, the author focuses on one of the key biochemical mechanisms for this pathologic process: the direct deleterious action of glucose and other sugars on proteins, known as glycation or nonenzymatic glycosylation. Results of animal studies and phase III clinical trials reveal that the inhibition of this process attenuates the development of a range of these complications.
Although diet and nutrition are widely believed to play an important part in the development of Type II (non-insulin-dependent) diabetes mellitus, specific dietary factors have not been clearly defined. Much controversy exists about the relations between the amount and types of dietary fat and carbohydrate and the risk of diabetes. In this article, we review in detail the current evidence regarding the associations between different types of fats and carbohydrates and insulin resistance and Type II diabetes. Our findings indicate that a higher intake of polyunsaturated fat and possibly long-chain n-3 fatty acids could be beneficial, whereas a higher intake of saturated fat and trans-fat could adversely affect glucose metabolism and insulin resistance. In dietary practice, exchanging nonhydrogenated polyunsaturated fat for saturated and trans-fatty acids could appreciably reduce risk of Type II diabetes. In addition, a low-glycaemic index diet with a higher amount of fiber and minimally processed whole grain products reduces glycaemic and insulinaemic responses and lowers the risk of Type II diabetes. Dietary recommendations to prevent Type II diabetes should focus more on the quality of fat and carbohydrate in the diet than quantity alone, in addition to balancing total energy intake with expenditure to avoid overweight and obesity.
This study compared the prevalence and pattern of use of complementary and alternative medicine (CAM) in individuals with and without diabetes and identified factors associated with CAM use.
The 1996 Medical Expenditure Panel Survey, a nationally representative sample of the U.S. noninstitutionalized civilian population, was analyzed. Estimates of CAM use in individuals with common chronic conditions were determined, and estimates of CAM use in patients with diabetes were compared with that in individuals with chronic medical conditions. Patterns of use and costs of CAM use in patients with diabetes were compared with those in nondiabetic individuals. Multiple logistic regression was used to determine independent predictors of CAM use in individuals with diabetes, controlling for age, sex, race/ethnicity, household income, educational level, and comorbidity.
Individuals with diabetes were 1.6 times more likely to use CAM than individuals without diabetes (8 vs. 5%, P < 0.0001). In the general population, estimates of CAM use were not significantly different across selected chronic medical conditions, but diabetes was an independent predictor of CAM use. Among individuals with diabetes, older age (> or =65 years) and higher educational attainment (high school education or higher) were independently associated with CAM use.
Diabetes is an independent predictor of CAM use in the general population and in individuals with diabetes. CAM use is more common in individuals aged > or =65 years and those with more than high school education.
The number of people with diabetes mellitus worldwide is estimated to be 221 million in 2010 compared to about 124 million in 1997. The dominant part of diabetic persons was in 1997 represented by Type 2 (97%). WHO expect the number of adults (20 years and older) with diabetes (i.e. a mix of Type I and 2) to rise to 300 millions in 2025 from 135 millions in year 1995. On average people with diabetes are three times more likely to be hospitalized than non-diabetic individuals. The risk for hospitalization is slightly diversified, venous complications being the least risky (1.7 times) and heart-related complications the most risky (3.1 times). The risk of premature death is higher for persons with diabetes compared to those without diabetes,. and the life time expectancy is 10-15 times shorter. US data shows that diabetes is the leading cause of blindness and accounts for 40% of the new cases of end-stage renal disease. The risk for leg amputation is 15-40 times higher and the risk for heart disease and stroke is two to four times higher for people with diabetes compared with people without diabetes. Recent studies show that the health care expenditures are as much as five times higher for individuals with diabetes compared to individuals without diabetes. In Sweden in 1994. three times more resources were spent on treating complications compared to what was spent on control of the disease. Studies show that intensive treatments cost more than traditional treatment, but also cut costs substantially for the treatment of late complications. The main message was that early intervention and intensified treatment had a better effect on the late complications. The basic message is quite simple: dia.-nose more persons with diabetes earlier, introduce and improve treatment.
Objective:
Diabetes is a significant public health problem resulting in substantial morbidity and mortality. The objectives of this study were 1) to determine the direct medical and indirect costs attributable to diabetes and 2) to calculate total and per capita expenditures of people with and without diabetes.
Research design and methods:
Direct medical and indirect expenditures attributable to diabetes in 1997 were estimated at $98 billion. Medical expenditures for the treatment of diabetes were estimated for all individuals in the U.S. in 1997 by age-group, sex, race, type of condition, and site of service. Productivity costs due to disability and premature mortality were also estimated for selected patient cohorts. Etiological fractions based on national health care survey data and published literature were used to estimate the proportion of health service utilization and mortality associated with diabetes-related chronic complications and general medical conditions.
Results:
Direct medical expenditures attributable to diabetes in 1997 totaled $44.1 billion and comprised $7.7 billion for diabetes and acute glycemic care, $11.8 billion due to the excess prevalence of related chronic complications, and $24.6 billion due to the excess prevalence of general medical conditions. The majority of attributable expenditures were for inpatient care (62%), followed by outpatient services (25%) and nursing home care (13%). Two-thirds of all medical costs for diabetes were borne by elderly people. Attributable indirect costs totaled $54.1 billion and comprised $17.0 billion resulting from premature mortality and $37.1 billion from disability. Total medical expenditures incurred by people with diabetes totaled $77.7 billion or $10,071 per capita, compared with $2,669 for people without diabetes.
Conclusions:
The economic burden of diabetes mellitus in the U.S. is enormous. Medical innovations that can delay the onset and slow the progression of diabetes have tremendous potential to mitigate the associated clinical and cost repercussions.
BACKGROUND
Long-term microvascular and neurologic complications cause major morbidity and mortality in patients with insulin-dependent diabetes mellitus (IDDM). We examined whether intensive treatment with the goal of maintaining blood glucose concentrations close to the normal range could decrease the frequency and severity of these complications.
METHODS
A total of 1441 patients with IDDM -- 726 with no retinopathy at base line (the primary-prevention cohort) and 715 with mild retinopathy (the secondary-intervention cohort) were randomly assigned to intensive therapy administered either with an external insulin pump or by three or more daily insulin injections and guided by frequent blood glucose monitoring or to conventional therapy with one or two daily insulin injections. The patients were followed for a mean of 6.5 years, and the appearance and progression of retinopathy and other complications were assessed regularly.
RESULTS
In the primary-prevention cohort, intensive therapy reduced the adjusted mean risk for the development of retinopathy by 76 percent (95 percent confidence interval, 62 to 85 percent), as compared with conventional therapy. In the secondary-intervention cohort, intensive therapy slowed the progression of retinopathy by 54 percent (95 percent confidence interval, 39 to 66 percent) and reduced the development of proliferative or severe nonproliferative retinopathy by 47 percent (95 percent confidence interval, 14 to 67 percent). In the two cohorts combined, intensive therapy reduced the occurrence of microalbuminuria (urinary albumin excretion of ≥ 40 mg per 24 hours) by 39 percent (95 percent confidence interval, 21 to 52 percent), that of albuminuria (urinary albumin excretion of ≥ 300 mg per 24 hours) by 54 percent (95 percent confidence interval, 19 to 74 percent), and that of clinical neuropathy by 60 percent (95 percent confidence interval, 38 to 74 percent). The chief adverse event associated with intensive therapy was a two-to-threefold increase in severe hypoglycemia.
CONCLUSIONS
Intensive therapy effectively delays the onset and slows the progression of diabetic retinopathy, nephropathy, and neuropathy in patients with IDDM.
To determine whether flavonoid intake explains differences in mortality rates from chronic diseases between populations.
Cross-cultural correlation study.
Sixteen cohorts of the Seven Countries Study in whom flavonoid intake at baseline around 1960 was estimated by flavonoid analysis of equivalent food composites that represented the average diet in the cohorts.
Mortality from coronary heart disease, cancer (various sites), and all causes in the 16 cohorts after 25 years of follow-up.
Average intake of antioxidant flavonoids was inversely associated with mortality from coronary heart disease and explained about 25% of the variance in coronary heart disease rates in the 16 cohorts. In multivariate analysis, intake of saturated fat (73%; P = 0.0001), flavonoid intake (8%, P = .01), and percentage of smokers per cohort (9%; P = .03) explained together, independent of intake of alcohol and antioxidant vitamins, 90% of the variance in coronary heart disease rates. Flavonoid intake was not independently associated with mortality from other causes.
Average flavonoid intake may partly contribute to differences in coronary heart disease mortality across populations, but it does not seem to be an important determinant of cancer mortality.
The antioxidant activity of phenolic compounds present in berries was investigated by two copper-catalyzed in vitro oxidation assays: human low-density lipoproteins (LDL) and lecithin liposomes. The amount of total phenolics varied between 617 and 4350 mg/kg in fresh berries, as gallic acid equivalents (GAE). In LDL at 10 μM GAE, berry extracts inhibited hexanal formation in the order: blackberries > red raspberries > sweet cherries > blueberries > strawberries. In lecithin liposomes, the extracts inhibited hexanal formation in the order: sweet cherries > blueberries > red raspberries > blackberries > strawberries. Red raspberries were more efficient than blueberries in inhibiting hydroperoxide formation in lecithin liposomes. HPLC analyses showed high anthocyanin content in blackberries, hydroxycinnamic acid in blueberries and sweet cherries, flavonol in blueberries, and flavan-3-ol in red raspberries. The antioxidant activity for LDL was associated directly with anthocyanins and indirectly with flavonols, and for liposome it correlated with the hydroxycinnamate content. Berries thus contribute a significant source of phenolic antioxidants that may have potential health effects. Keywords: Berries; antioxidants; LDL oxidation; liposomes; flavonoids; hydroxycinnamates; anthocyanins; flavan-3-ols; flavonols
We previously described a rapid headspace gas chromatographic method for the determination of hexanal, an important decomposition product of n-6 polyunsaturated fatty acid (PUFA) peroxidation in rat liver samples and human red blood cell membranes. This method was applied to the measurement of Cu2+ catalyzed-oxidation of freshly prepared human low density lipoproteins (LDL) from 10 healthy adult volunteers. A twofold variation in oxidative susceptibility was found by this assay for hexanal and other volatiles. Hexanal values correlated significantly (P < 0.05) with total polyunsaturated fatty acid (PUFA), 18:2 and n-6 PUFA contents of LDL; but poorly with 20:4 and with vitamin E. Therefore, in addition to alpha-tocopherol, other endogenous antioxidants and factors may contribute to LDL's resistance to oxidation. This simple, rapid and sensitive method for oxidative susceptibility provides a useful component in the analysis of the prooxidant/antioxidant status of biological samples. The method is used routinely in our laboratories to determine specific peroxidation products of n-6 and n-3 PUFA.
Aldose reductase is a rate limiting enzyme in the polyol pathway associated with the conversion of glucose to sorbitol. The enzyme is located in the eye (cornea, retina, lens), kidney, myelin sheath, and also in other tissues less involved in diabetic complications. Experiments in diabetic animals have implicated sorbitol accumulation in the lens to the development of cataracts. The use of inhibitors of aldose reductase in animal studies has demonstrated that diabetic complications such as cataracts, nephropathy, and slowing of nerve conduction can be ameliorated. While an osmotic effect can explain the physical changes in the lens leading to cataract formation, the effect of sorbitol accumulation in other tissues and the resulting diabetic complications has been linked to the depletion of myoinositol content resulting in a derangement of sodium-potassium adenosine triphosphatase activity. Since glucose and other hexoses are poor substrates for aldose reductase, it is only in hyperglycemia when the enzyme hexokinase is saturated that aldose reductase is activated, leading to accumulation of sorbitol. The kinetics of inhibition of aldose reductase by a variety of inhibitors has been delineated. The dose required varies from inhibitor to inhibitor and is consistent with their inhibition constants. Toxicity is a consideration in the use of some of the inhibitors, as was demonstrated with sorbinil which caused hypersensitivity reactions in 10 percent of patients. Other inhibitors such as tolerant have shown efficacy and are under clinical investigation. Interpretation of results obtained with aldose reductase inhibitor therapy in human subjects suggest that these inhibitors are effective at early stages of diabetic complications.
Oxidative modifications of low density lipoproteins (LDL) are now recognised as one of the major processes in atherogenesis. Various drugs, as well as a number of natural products, have been proposed to inhibit such processes. Among the naturally-occurring constituents of plants which appear to possess antioxidant activity are polyphenolic compounds such as flavonoids. The aqueous extract of Vaccinium myrtillus is rich in such molecules. In this report, we describe the in vitro antioxidative potential of this extract on human LDL. The copper-induced oxidative modification of these lipoproteins was assessed using 1) measurement of oxidative resistance as determined by the lag-phase preceding conjugated diene formation; 2) quantification of the amount of lipoperoxides and thiobarbituric acid-reactive substances generated, and measurement of the modification in the net negative electrical charge of the lipoproteins, over a 7-hour time course experiment. Trace amounts of V myrtillus extract (15 to 20 micrograms/mL) induce statistically significant changes in the oxidation behaviour of LDL, which include 1) prolongation of the lag-phase of conjugated diene production (P < 0.01); 2) reduction in the formation of lipoperoxides and of thiobarbituric acid-reactive substances up to 7 hours and especially between 1 and 5 hours (P < 0.01); and 3) inhibition of modification in the net negative charge of LDL. These results demonstrate that V myrtillus extract exerts potent protective action on LDL particles during in vitro copper-mediated oxidation. Calculation of IC50 values indicates that, on a molar basis, this extract may indeed be more potent than either ascorbic acid or butylated hydroxytoluene in the protection of LDL particles from oxidative stress.
Despite numerous attempts over 16 years, the results of aldose reductase inhibitor (ARI) trials for the treatment of diabetic neuropathy have not proven efficacy. This paper reviews each of the ARI trials, examines confounding factors, and proposes a future course. The confounding factors considered are pharmacokinetics (ARI penetration of human nerve), length of trial (in terms of the natural history of diabetic neuropathy), trial endpoints (reversibility or slowing of progression), reproducibility of clinical measurements (in terms of power calculations), standardization and quality control of endpoints, and clinically meaningful differences in endpoints. We conclude that ARIs are most likely to have a beneficial effect in the management of diabetic distal symmetrical polyneuropathy and autonomic neuropathy but that the clinical role of ARIs is to slow the progression of diabetic neuropathy rather than to reverse it. Future trials should be designed with adequate statistical power, with consideration of the variability of the endpoint measurements for long enough duration, and with rigorous quality control to definitively confirm the utility of ARIs in the treatment of diabetic distal symmetrical polyneuropathy and autonomic neuropathy.
We tested the hypothesis that level of glycemic control is related to medical care costs in adults with diabetes.
Regression analysis was used to estimate the relationship between glycemic control and medical care charges for 3,017 adults with diabetes who were continuously enrolled in a large health maintenance organization (HMO) over a 4-year period. Diagnosis of diabetes was ascertained from diagnostic and pharmaceutical databases using a method with an estimated sensitivity of 0.91 and an estimated specificity of 0.99. Charges for care included defined outpatient and inpatient services. Patients who disenrolled or who died during the 4-year period were excluded from the main analysis.
Charges for medical care for patients with diabetes from 1993 to 1995 were closely related to HbA1c level in 1992 before and after adjustment for age, sex, coronary heart disease, and hypertension. Standardized 3-year estimates of charges ranged from $10,439 for patients without comorbid conditions to $44,417 for those with heart disease and hypertension. Medical care charges increased significantly for every 1% increase above HbA1c of 7%. For a person with an HbA1c value of 6%, successive 1% increases in HbA1c resulted in cumulative increases in charges of approximately 4, 10, 20, and 30%. The increase in charges accelerated as the HbA1c value increased. For patients with diabetes only, or with diabetes plus other chronic conditions, the rate of increase in charges with HbA1c was consistent.
HbA1c provides useful information to providers and patients regarding both health status and future medical care charges. Economic data suggest that clinicians should assign high importance to low HbA1c results and aggressively maintain the HbA1c status of patients who have low HbA1c values. For economic as well as clinical reasons, it may be beneficial to lower HbA1c when it is > 8% and to reduce cardiovascular risk factors. The medical charge data suggest that investment in clinical systems to improve diabetes care may benefit both payers and patients.
Cranberry juice consumption is often used for the treatment of urinary tract infections, but the effect of cranberry juice on heart disease has not been investigated. We evaluated how a cranberry extract containing 1,548 mg gallic acid equivalents/liter (initial pH=2.50) affected low density lipoprotein (LDL) oxidation induced by 10 micromolar cupric sulfate. When LDL oxidation took place in the presence of diluted cranberry extracts, the formation of thiobarbituric acid reactive substances (TBARS) and LDL electrophoretic mobility were reduced. LDL electrophoretic migration was also reduced when the cranberry extract had a pH of 7.00 prior to dilution. This study suggests that cranberry extracts have the ability to inhibit the oxidative modification of LDL particles.
Although the level of hyperglycemia is clearly a risk factor for microvascular complications in diabetic patients, its role in macrovascular complications remains controversial. We followed 4,875 subjects (65% Mexican-American) for 7-8 years to investigate the effects of diabetes and hyperglycemia on all-cause and cardiovascular disease (CVD) mortality. These end points were also analyzed according to quartiles of baseline fasting plasma glucose among diabetic participants.
The Cox proportional hazards model was used to estimate the relative risks (RRs) for all-cause and CVD mortality.
Diabetes was significantly associated with increased all-cause mortality (RR [95% CI] = 2.1 [1.3-3.5] in men; 3.2 [1.9-5.4] in women) and increased CVD mortality (3.2 [1.4-7.1] in men; 8.5 [2.8-25.2] in women). Among diabetic subjects, those in quartile 4 had a 4.2-fold greater risk of all-cause mortality (P < 0.001) and a 4.7-fold greater risk of CVD mortality (P = 0.01) than those in quartiles 1 and 2 combined. After further adjustment for other potential risk factors, subjects in quartile 4 had a 4.9-fold greater risk of all-cause mortality and a 4.9-fold greater risk of CVD mortality than those in quartiles 1 and 2. In addition, hypertension, current smoking, and cholesterol > 6.2 mmol/l were significant predictors of CVD mortality using Cox models.
We conclude that diabetes is a predictor of both all-cause and CVD mortality in the general population and that both hyperglycemia and common CVD risk factors are important predictors of all-cause and CVD mortality in diabetic subjects.
The objective of the U.K. Prospective Diabetes Study (UKPDS), initiated in 1977, was set up to determine whether improved blood glucose control in people with type 2 diabetes will prevent the complications of diabetes. The UKPDS was also designed to determine whether there are differences between conventional policy (diet therapy) and three different regimens of intensive treatment policy, based on sulfonylurea, metformin, or insulin. Interim efficacy analyses revealed that the intensive policies with sulfonylurea, insulin, and metformin were equally effective in reducing fasting plasma glucose concentrations. However, glucose and HbA1c measurements steadily increased with time, reflecting ongoing deterioration of beta-cell function. Cardiovascular disease was the major cause of complications, and the risk factors included raised LDL cholesterol concentrations, low HDL cholesterol concentrations, elevated blood pressure, elevated HbA1c concentrations, and smoking. A final study report was issued in September 1998, when the median duration of therapy was 11 years.
A high glucose concentration has been found to lead to the glycosylation of amino groups of lysine residue in proteins. The addition of reducing agent not only prevents this reaction but also reverses it. On the other hand, flavonoids which found in plant sources have antioxidant properties. Since the glycosylation of protein is an oxidation reaction, therefore, antioxidants should be able to prevent this reaction. In this study, the best concentration and time to incubate glucose with hemoglobin was investigated. Then the glycosylation degree of hemoglobin in the presence of flavonoids and their absence was measured by means of a colorimetric method. Different concentration of flavonoids (Quercetin, Rutin, Kaempferol) were used. The preventing effect on hemoglobin glycosylation by the three concentrations; 0.5, 5, 10 micrograms/ml was estimated as follows: for Rutin; 11%, 27%, 42%, Quercetin; 3%, 37%, 52%, Kaempferol; 10%, 12%, 15% respectively. So, the in vivo effect should be investigated and then plants that containing flavonoids can be utilized to prevent or treat complication of diabetes.
Ascorbic acid, or vitamin C, has been reported to lower erythrocyte sorbitol concentrations, and present studies were performed to determine the mechanism of this effect. Incubation of erythrocytes with increasing concentrations of glucose (5-40 mM) progressively increased erythrocyte sorbitol contents, reflecting increased flux through aldose reductase. At extracellular concentrations of 90 microM, both ascorbic acid and its oxidized form, dehydroascorbate, decreased intracellular sorbitol by 25 and 45%, respectively. This inhibition was not dependent on the extracellular glucose concentration, or on erythrocyte contents of free NADPH or GSH. To test for a direct effect of ascorbate on aldose reductase, erythrocyte hemolysates were prepared and supplemented with 100 microM NADPH. Hemolysates reduced glucose to sorbitol in a dose-dependent manner that was inhibited with a Ki of 120 microM by the aldose reductase inhibitor tetramethylene glutaric acid. Above 100 microM, ascorbic acid also lowered hemolysate sorbitol generation by about 30%. Studies with ascorbic acid derivatives showed that the reducing capacity of ascorbic acid was not required for inhibition of sorbitol production from glucose in erythrocyte hemolysates. These results show that high, but physiologic, concentrations of ascorbic acid can directly inhibit erythrocyte aldose reductase, and provide a rationale for the use of oral vitamin C supplements in diabetes.
Hyperglycemia, a well recognized pathogenetic factor of long-term complications in diabetes mellitus, not only generates more reactive oxygen species but also attenuates antioxidative mechanisms through glycation of the scavenging enzymes. Therefore, oxidative stress has been considered to be a common pathogenetic factor of the diabetic complications including nephropathy. A causal relationship between oxidative stress and diabetic nephropathy has been established by observations that (1) lipid peroxides and 8-hydroxydeoxyguanosine, indices of oxidative tissue injury, were increased in the kidneys of diabetic rats with albuminuria; (2) high glucose directly increases oxidative stress in glomerular mesangial cells, a target cell of diabetic nephropathy; (3) oxidative stress induces mRNA expression of TGF-beta1 and fibronectin which are the genes implicated in diabetic glomerular injury, and (4) inhibition of oxidative stress ameliorates all the manifestations associated with diabetic nephropathy. Proposed mechanisms involved in oxidative stress associated with hyperglycemia are glucose autooxidation, the formation of advanced glycosylation end products, and metabolic stress resulting from hyperglycemia. Since the inhibition of protein kinase C (PKC) effectively blocks not only phorbol ester-induced but also high glucose- and H2O2-induced fibronectin production, the activation of PKC under diabetic conditions may also have a modulatory role in oxidative stress-induced renal injury in diabetes mellitus.
Amongst the numerous co-adjuvant therapies which could influence the incidence and progression of diabetic complications, antioxidants and flavonoids are currently being tested in several clinical trials. In this study we investigated the effects of Daflon 500, which is made up of the flavonoids diosmin (90%) and hesperidin (10%), in a group of 28 Type 1 diabetic patients in a double blind placebo-controlled study. Parameters of glycation and oxidative stress were measured before and after the intervention. Treatment with this flavonoid had no side effects and was followed by a decrease in HbA1c, from 8.85+/-1.57 to 8.47+/-1.40% (p=0.017). This decrease was more pronounced in the patients with higher initial HbA1c but was unrelated to glycaemic control as monitored by the mean and fluctuations of daily glycaemia. Decrease in HbA1c was accompanied by an increase in glutathione peroxidase activity, from 119+/-68 to 145+/-42 U/l haemolysate (p=0.015), a tendency for increase in plasma protein thiols and an increase in the lag time of the copper-induced in vitro oxidability of non-HDL lipoproteins, from 96+/-24 to 111+/-28 min (p=0.005). These parameters did not change significantly after receiving placebo. Other parameters of antioxidant capacity such as blood GSH, catalase and superoxide dismutase activities, as well as in vitro formation of thiobarbituric acid reactive substances (TBARS), were unaffected by either flavonoid or placebo. Our results suggest that the flavonoid-induced decrease in glycation is associated with an increase in the antioxidant component dependent on the levels and activities of thiol-containing proteins such as glutathione peroxidase. One mechanism which could explain these effects is the protection of vitamin C and E from consumption by oxidative processes.
The amounts of quercetin, myricetin, and kaempferol aglycons in 25 edible berries were analyzed by an optimized RP-HPLC method with UV detection and identified with diode array and electrospray ionization mass spectrometry detection. Sixteen species of cultivated berries and nine species of wild berries were collected in Finland in 1997. Quercetin was found in all berries, the contents being highest in bog whortleberry (158 mg/kg, fresh weight), lingonberry (74 and 146 mg/kg), cranberry (83 and 121 mg/kg), chokeberry (89 mg/kg), sweet rowan (85 mg/kg), rowanberry (63 mg/kg), sea buckthorn berry (62 mg/kg), and crowberry (53 and 56 mg/kg). Amounts between 14 and 142 mg/kg of myricetin were detected in cranberry, black currant, crowberry, bog whortleberry, blueberries, and bilberry. Kaempferol was detected only in gooseberries (16 and 19 mg/kg) and strawberries (5 and 8 mg/kg). Total contents of these flavonols (100-263 mg/kg) in cranberry, bog whortleberry, lingonberry, black currant, and crowberry were higher than those in the commonly consumed fruits or vegetables, except for onion, kale, and broccoli.
BACKGROUND; In diabetic renal complications, hyperglycemia may cause damage at a cellular level in both glomerular and tubular locations, often preceding overt dysfunction. Our previous work has implicated aldose reductase in a pathway whereby aldose reductase-induced use of nicotinamide adenine dinucleotide phosphate (reduced form) (NADPH) drives the pentose phosphate pathway, which culminates in a protein kinase C-induced increase in glomerular prostaglandin production and loss of mesangial cell contractility as a possible cause of hyperfiltration and glomerular dysfunction in diabetes. In this model, aldose reductase inhibition in vitro redresses all aspects of the pathway proposed to lead to hyperfiltration; aldose reductase inhibition in vivo gives only a partial amelioration over the short-term or is without effect in the longer term on microalbuminuria, which follows glomerular and tubular dysfunction. In diabetes, hyperglycemia-induced renal polyol pathway activity does not occur in isolation but instead in tandem with oxidative changes and the production of reactive dicarbonyls and alpha,beta-unsaturated aldehydes. Aldose reductase may detoxify these compounds. We investigated this aspect in a transgenic rat model with human aldose reductase cDNA under the control of the cytomegalovirus promoter with tubular expression of transgene.
Tubules (S3 region-enriched) from transgenic and control animals were prepared, exposed to oxidative stress, and analyzed to determine the cellular protein dicarbonyl content.
In tubules from transgenic animals, oxidative stress-induced dicarbonyls were significantly reduced, an effect not seen when an aldose reductase inhibitor was present.
Aldose reductase may both exacerbate and alleviate the production of metabolites that lead to hyperglycemia-induced cellular impairment, with the balance determining the extent of dysfunction.
The antioxidant activities against superoxide radicals (O(2)(*)(-)), hydrogen peroxide (H(2)O(2)), hydroxyl radicals (OH(*)), and singlet oxygen ('O(2)) was evaluated in fruit juice from different cultivars of thornless blackberries (Rubus sp.), blueberries (Vaccinium spp.), cranberries (Vaccinium macrocarpon Aiton), raspberries (Rubus idaeus L. and Rubus occidentalis L.), and strawberries (Fragaria x ananassa Duch.). Among the different cultivars, juice of 'Hull Thornless' blackberry, 'Earliglow' strawberry, 'Early Black' cranberry, 'Jewel' raspberry, and 'Elliot' blueberry had the highest antioxidant capacity against superoxide radicals (O(2)(*)(-)), hydrogen peroxide (H(2)O(2)), hydroxyl radicals (OH(*)), and singlet oxygen ('O(2)). In general, blackberries had the highest antioxidant capacity inhibition of O(2)(*)(-), H(2)O(2), and OH(*). Strawberry was second best in the antioxidant capacity assay for these same free radicals. With regard to 'O(2) scavenging activity, strawberry had the highest value, while blackberry was second. Cranberries had the lowest inhibition of H(2)O(2) activity. Meanwhile, blueberries had the lowest antioxidant capacity against OH(*) and 'O(2). There were interesting and marked differences among the different antioxidants in their abilities to scavenge different reactive oxygen species. beta-Carotene had by far the highest scavenging activity against 'O(2) but had absolutely no effect on H(2)O(2). Ascorbic acid was the best at inhibiting H(2)O(2) free radical activity. For OH(*), there was a wide range of scavenging capacities from a high of 15.3% with alpha-tocopherol to a low of 0.88% with ascorbic acid. Glutathione had higher O(2)(*)(-) scavenging capacity compared to the other antioxidants.
Patients with type 2 diabetes (formerly known as non-insulin-resistant diabetes) have a significantly increased risk of developing cardiovascular disease. Once clinical cardiovascular disease develops, these patients have a poorer prognosis than normoglycemic patients. By inducing endothelial changes, hyperglycemia contributes directly to atherosclerosis. Type 2 diabetes is also associated with atherogenic dyslipidemias. This form of diabetes, or the precursor state of insulin resistance, commonly occurs as a metabolic syndrome (formerly known as syndrome X) consisting of hypertension, atherogenic dyslipidemia and a procoagulant state, in addition to the disorder of glucose metabolism. All cardiovascular risk factors except smoking are more prevalent in patients with type 2 diabetes. In addition to exercise, weight control, aspirin therapy and blood pressure control, therapy to modify lipid profiles is usually necessary. The choice of agent or combination of statin, bile acid sequestrant, fibric acid derivative and nicotinic acid depends on the lipid profile and characteristics of the individual patient.
Adequate fruit and vegetable intake may lower the risk of several chronic diseases, but little is known about how it affects the risk of diabetes mellitus.
We examined whether fruit and vegetable consumption was associated with diabetes incidence in a cohort of U. S. adults aged 25-74 years who were followed for about 20 years.
In the analytic sample of 9,665 participants, 1,018 developed diabetes mellitus. The mean daily intake of fruits and vegetables as well as the percentage of participants consuming five or more fruits and vegetables per day was lower among persons who developed diabetes than among persons who remained free of this disease (P < 0.001). After adjustments for age, race or ethnicity, cigarette smoking, systolic blood pressure, use of antihypertensive medication, serum cholesterol concentration, body mass index, recreational exercise, nonrecreational exercise, and alcohol consumption, the hazard ratio for participants consuming five or more servings of fruits and vegetables per day compared with those consuming none was 0.73 (95% confidence interval (CI), 0.54-0.98) for all participants, 0.54 (95% CI, 0.36-0.81) for women, and 1.09 (95% CI, 0.63-1.87) for men. Adding education to the model changed the hazard ratios to 0.79 (95% CI, 0.59-1.06) for all participants, 0.61 (95% CI, 0.42-0.88) for women, and 1.14 (95% CI, 0.67-1.93) for men.
Fruit and vegetable intake may be inversely associated with diabetes incidence particularly among women. Education may explain partly this association.
Blueberries and cranberries were analyzed for procyanidins using normal-phase HPLC/MS. Monomers, identified as (+)-catechin and (-)-epicatechin, and a series of oligomers were detected in blueberries, and MS data confirmed that the oligomers consisted of (epi)catechin units that were exclusively singly linked (B-type). The procyanidin "fingerprints" were similar for Tifblue and Rubel but higher than that for lowbush blueberries. In whole cranberries, (-)-epicatechin was present, along with a complex series of oligomers. Both A-type (contained only one double linkage per oligomer) and B-type oligomers were present. Two commercial cranberry juices exhibited similar procyanidin profiles, except that one contained increased quantities. There were processing effects on the procyanidin content of cranberry extract and juices when compared to those of the unprocessed fruits. Monomer, dimers, and A-type trimers were the primary procyanidins, with only trace levels of the B-type trimers and A-type tetramers and with an absence of the higher oligomers in cranberry extract and juices.
Enormous advances have been made in medical care but more people are still using herbal or alternative remedies. In chronic conditions such as diabetes patients may turn to alternative remedies that have been purported to improve glycaemic control. This study surveyed diabetic and control subjects about their use of all prescribed medication, over-the-counter supplements, and alternative medications.
Subjects were prospectively contacted in person or by telephone. Five hundred and two diabetic subjects and 201 control subjects were asked to provide details about themselves, their diabetes (for the diabetic subjects) and their use of prescribed medication, over-the-counter supplements and alternative medications. Subjects were asked to rank their assessment of the effectiveness of each medication. Costs were calculated on a per month basis from average prices obtained from five alternative health stores and five chemist shops.
Of the diabetic subjects, 78% were taking prescribed medication for their diabetes, 44% were taking over-the-counter supplements and 31% were taking alternative medications. Of the control subjects, 63% were taking prescribed medication, 51% were taking over-the-counter supplements, and 37% were taking alternative medications. Multivitamins, vitamin E, vitamin C, calcium and aspirin were the most commonly used over the counter supplements. Garlic, echinacea, herbal mixtures, glucosamine were the most commonly used alternative medications. Chromium was used only by diabetic subjects and then only rarely. Subjects rated the effectiveness of the alternative medications significantly lower than for prescribed medications but still thought them efficacious. Alternative medications purported to have some hypoglycaemic effect were little used by diabetic subjects. Diabetic subjects spent almost as much money on over-the-counter supplements and alternative medications together as they did on their diabetic medications.
One-third of diabetic patients are taking alternative medications that they consider efficacious but this is no more than in the control group. The money spent on alternative and non-prescription supplements nearly equals that spent on prescription medications. In view of the money spent in this area the time is past due to evaluate these remedies and to establish what merit they have.
In the work an effect of anthocyanins of red wine type Cabernet on the course and intensity of symptoms of the experimental diabetes in the rats has been examined. The estimation of the course of experimental diabetes was based on: determination of sugar concentration in urine and blood serum, determination of concentration of the unsaturated fatty acids peroxidation in urine and blood serum, also on the change of body mass during the experiment. The examination was carried out on 80, weighing 200-250 g, rats. They lived in the animal quarters with a stable temperature and humidity being fed with standard fodder (Murigan) with water supply in ever quantity. The rats were divided into the following four group: I--control group, II--group of animals receiving intraperitoneal streptozotocin in concentration 70 mg/kg m.c., III--group of animals receiving intragastric 10 mg/kg m.c. of natural anthocyanin dye of red wine type Cabernet, IV--group of animals receiving intraperitoneal 70 mg/kg m.c. of streptozotocin and simultaneously receiving intragastric 1 mg/kg m.c. of natural anthocyanin dye. An essential increase of glucose concentration in urine was found in the rats after streptozotocin injection. A simultaneous daily administration of anthocyanins obtained from red wine type Cabernet and streptozotocin substantially decreased sugar concentration in urine and blood serum. Those anthocyanins also inhibited loss of body mass caused by the former injection of streptozotocin. Simultaneously antocyan pigment was stated to considerably prevent generation of free oxygen radicals. The decrease of peroxidation of lipids, the measure of which was lowering of the concentration of the products of unsaturated fatty acids oxidation in urine and blood serum was also observed.
Phenolic profiles of a total of 26 berry samples, together with 2 apple samples, were analyzed without hydrolysis of glycosides with HPLC. The phenolic contents among different berry genera varied considerably. Anthocyanins were the main phenolic constituents in bilberry, bog-whortleberry, and cranberry, but in cowberries, belonging also to the family Ericaceae genus Vaccinium, flavanols and procyanidins predominated. In the family Rosaceae genus Rubus (cloudberry and red raspberry), the main phenolics found were ellagitannins, and in genus Fragaria (strawberry), ellagitannins were the second largest group after anthocyanins. However, phenolic acids were dominant in rowanberries (genus Sorbus) and anthocyanins in chokeberry (genus Aronia). In the family Grossulariaceae genus Ribes (currants and gooseberry), anthocyanins predominated, as well as in crowberries (family Empetraceae genus Empetrum). In apples, hydroxycinnamic acids were the main phenolic subgroup. Extraction methods for berries and apples were studied to produce phenolic extracts with high antioxidant activity. Evaluation of antioxidant activity was performed by autoxidazing methyl linoleate (40 degrees C, in the dark). The extraction method affected remarkably both the phenolic composition and the antioxidant activity, but with statistical analysis the observed activity could not be well explained with the contents of individual phenolic subgroups.
The number of people with diabetes mellitus worldwide is estimated to be 221 million in 2010 compared to about 124 million in 1997. The dominant part of diabetic persons was in 1997 represented by Type 2 (97%). WHO expect the number of adults (20 years and older) with diabetes (i.e. a mix of Type 1 and 2) to rise to 300 millions in 2025 from 135 millions in year 1995. On average people with diabetes are three times more likely to be hospitalized than non-diabetic individuals. The risk for hospitalization is slightly diversified, venous complications being the least risky (1.7 times) and heart-related complications the most risky (3.1 times). The risk of premature death is higher for persons with diabetes compared to those without diabetes, and the life time expectancy is 10-15 times shorter. US data shows that diabetes is the leading cause of blindness and accounts for 40% of the new cases of end-stage renal disease. The risk for leg amputation is 15-40 times higher and the risk for heart disease and stroke is two to four times higher for people with diabetes compared with people without diabetes. Recent studies show that the health care expenditures are as much as five times higher for individuals with diabetes compared to individuals without diabetes. In Sweden in 1994, three times more resources were spent on treating complications compared to what was spent on control of the disease. Studies show that intensive treatments cost more than traditional treatment, but also cut costs substantially for the treatment of late complications. The main message was that early intervention and intensified treatment had a better effect on the late complications. The basic message is quite simple: diagnose more persons with diabetes earlier, introduce and improve treatment.
Aldose reductase inhibitors (ARIs) prevent peripheral nerve dysfunction and morphological abnormalities in diabetic animal models. However, some experimental intervention studies and clinical trials of ARIs on diabetic neuropathy appeared disappointing because of either 1) their inadequate design and, in particular, insufficient correction of the sorbitol pathway activity or 2) the inability to reverse established functional and metabolic deficits of diabetic neuropathy by AR inhibition in general. We evaluated whether diabetes-induced changes in nerve function, metabolism, and antioxidative defense are corrected by the dose of ARI (sorbinil, 65 mg/kg/d in the diet), resulting in complete inhibition of increased sorbitol pathway activity. The groups included control rats and streptozotocin-diabetic rats treated with/without ARI for 2 weeks after 4 weeks of untreated diabetes. ARI treatment corrected diabetes-induced nerve functional changes; that is, decrease in endoneurial nutritive blood flow, motor and sensory nerve conduction velocities, and metabolic abnormalities (i.e., mitochondrial and cytosolic NAD+/NADH redox imbalances and energy deficiency). ARI restored nerve concentrations of two major non-enzymatic antioxidants, reduced glutathione (GSH) and ascorbate, and completely arrested diabetes-induced lipid peroxidation. In conclusion, treatment with adequate doses of ARIs (that is, doses that completely inhibit increased sorbitol pathway activity) is an effective approach for reversal of, at least, early diabetic neuropathy.