Efficacy of Low-Carbohydrate Ketogenic Diet in the Treatment of Type 2 Diabetes.

Low-carbohydrate ketogenic diet (LCKD), originally used as a treatment for childhood epilepsy is currently gaining acceptance as a nutritional therapy for obesity and type 2 diabetes. In addition, this diet has a positive effect on body weight, blood glucose level, glycosylated hemoglobin, plasma lipid profile, and neurological disorders. This review focuses on the therapeutic effectiveness, negative effects, and the rationale of using LCKD for the treatment of type 2 diabetes. It is shown that LCKD contributes to the reduction in the intake of insulin and oral antidiabetic drugs in patients with type 2 diabetes. Furthermore, the data presented in this review reveal the efficacy and cost-effectiveness of LCKD in the management of type 2 diabetes.

Fundamental studies of adrenal retinoid-X-receptor: Protein isoform, tissue expression, subcellular distribution, and ligand availability.

Adrenal gland reportedly expresses many nuclear receptors that are known to heterodimerize with retinoid-X-receptor (RXR) for functions, but the information regarding the glandular RXR is not adequate. Studies of rat adrenal homogenate by Western blotting revealed three RXR proteins: RXRα (55kDa), RXRß (47kDa) and RXR (56kDa). RXRγ was not detectable. After fractionation, RXRα was almost exclusively localized in the nuclear fraction. In comparison, substantial portions of RXRß and RXR were found in both nuclear and post-nuclear particle fractions, suggesting genomic and non-genomic functions. Cells immunostained for RXRα were primarily localized in zona fasciculata (ZF) and medulla, although some stained cells were found in zona glomerulosa (ZG) and zona reticularis (ZR). In contrast, cells immunostained for RXRß were concentrated principally in ZG, although some stained cells were seen in ZR, ZF, and medulla (in descending order, qualitatively). Analysis of adrenal lipid extracts by LC/MS did not detect 9-cis-retinoic acid (a potent RXR-ligand) but identified all-trans retinoic acid. Since C20 and C22 polyunsaturated fatty acids (PUFAs) can also activate RXR, subcellular availabilities of unesterified fatty acids were investigated by GC/MS. As results, arachidonic acid (C20:4), adrenic acid (C22:4), docosapentaenoic acid (C22:5), and cervonic acid (C22:6) were detected in the lipids extracted from each subcellular fraction. Thus, the RXR-agonizing PUFAs are available in all the main subcellular compartments considerably. The present findings not only shed light on the adrenal network of RXRs but also provide baseline information for further investigations of RXR heterodimers in the regulation of adrenal steroidogenesis.

Green Tea Induced Cellular Proliferation and the Expression of Transforming Growth Factor-ß1 in the Jejunal Mucosa of Fasting Rats.

OBJECTIVE: The aim of this study was to understand whether or not the protective effect of green tea after fasting-induced damage in the jejunal mucosa of rat is dependent on cell proliferation and the stimulation of specific growth factors. MATERIALS AND METHODS: Sixty adult male Wistar rats were used in this study. The animals were divided randomly into 5 groups, with 12 in each group (G1-5). The animals in G1 (control group) were fed a rat chow diet and water ad libitum. The animals in G2 (fasting group) were fasted for 3 days. The animals in the G3, G4, and G5 groups were fasted for 3 days as G2, but were given water (G3), green tea (G4), or a vitamin E (G5) solution, respectively, for another 7 days. The animals were euthanized, and the jejunum was removed and processed for histological and immunohistochemical analysis. RESULTS: Compared to the G3 group, the jejunal mucosa of G4 rats showed a 70.6% higher level (p < 0.001) of expression of proliferating cell nuclear antigen and 98% higher level (p = 0.0001) of the expression of transforming growth factor-ß1 (TGF-ß1), whereas the level of fibroblast growth factor-1 (FGF-1) and insulin-like growth factor-1 (IGF-1) expression was 22 and 11% lower, respectively, in G4 animals as compared to G3 rats. These differences in the expression of FGF-1 and IGF-1 in G4 animals were not statistically significant. CONCLUSION: In this study, green tea repaired the fasting-induced damage in the jejunal mucosa of rats, mainly by inducing a significant expression of TGF-ß1 in the jejunal mucosa.

Erythrocyte membranes convert monomeric ferriprotoporphyrin IX to ß-hematin in acidic environment at malarial fever temperature.

Hemozoin production makes it possible for intraerythrocytic malaria parasites to digest massive quantities of hemoglobin but still avoid potential ferriprotoporphyrin IX (FP) toxicity, which they cannot decompose further. Some antimalarial drugs, such as chloroquine, work by inhibiting this production, forcing the parasite to starve to death. As part of the efforts to identify possible biological mechanisms of FP polymerization, we have used normal human erythrocyte membranes as a model, to promote ß-hematin (ß-h) synthesis. Hemin in 35% aqueous dimethyl sulfoxide (DMSO) was reacted with isolated erythrocyte membranes and incubated overnight in sodium acetate buffer, pH 4.8, at 41°C. Infrared spectroscopy and electron microscopy showed that ß-h was produced. Hemin in 10% was less effective as the substrate than when it was in 35% DMSO. A high malarial temperature seemed to be necessary, because FP polymerization was less at 37°C than at 41°C. Production was partially inhibited by chloroquine. These observations are of interest because other investigators have reported that membrane lipids mediated FP polymerization, but whole membranes were ineffective. On the other hand, our hypothesis is that the transport vesicles (TV) in malaria parasites could provide the receptor for FP and the lipids that promote hemozoin formation. Erythrocyte membranes may not be directly involved, but Plasmodium species transport hemoglobin in membrane-bound TV into food vacuoles, where hemoglobin catabolism is completed and hemozoin crystals are stored.

Effect of low-calorie versus low-carbohydrate ketogenic diet in type 2 diabetes.

OBJECTIVE: Effective diabetic management requires reasonable weight control. Previous studies from our laboratory have shown the beneficial effects of a low-carbohydrate ketogenic diet (LCKD) in patients with type 2 diabetes after its long term administration. Furthermore, it favorably alters the cardiac risk factors even in hyperlipidemic obese subjects. These studies have indicated that, in addition to decreasing body weight and improving glycemia, LCKD can be effective in decreasing antidiabetic medication dosage. Similar to the LCKD, the conventional low-calorie, high nutritional value diet is also used for weight loss. The purpose of this study was to understand the beneficial effects of LCKD compared with the low-calorie diet (LCD) in improving glycemia. METHODS: Three hundred and sixty-three overweight and obese participants were recruited from the Al-Shaab Clinic for a 24-wk diet intervention trial; 102 of them had type 2 diabetes. The participants were advised to choose LCD or LDKD, depending on their preference. Body weight, body mass index, changes in waist circumference, blood glucose level, changes in hemoglobin and glycosylated hemoglobin, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, uric acid, urea and creatinine were determined before and at 4, 8, 12, 16, 20, and 24 wk after the administration of the LCD or LCKD. The initial dose of some antidiabetic medications was decreased to half and some were discontinued at the beginning of the dietary program in the LCKD group. Dietary counseling and further medication adjustment were done on a biweekly basis. RESULTS: The LCD and LCKD had beneficial effects on all the parameters examined. Interestingly, these changes were more significant in subjects who were on the LCKD as compared with those on the LCD. Changes in the level of creatinine were not statistically significant. CONCLUSION: This study shows the beneficial effects of a ketogenic diet over the conventional LCD in obese diabetic subjects. The ketogenic diet appears to improve glycemic control. Therefore, diabetic patients on a ketogenic diet should be under strict medical supervision because the LCKD can significantly lower blood glucose levels.

Morphologic changes in fibroadenoma of breast due to chickenpox: a case report with suspicious cytology in fine needle aspiration smears.

BACKGROUND: Fibroadenomas with stromal giant cell reaction have been described in the literature, but cytologic atypia including giant cell reaction due to chickenpox giving rise to suspicious cytology has not been reported. CASE REPORT: A 25-year-old woman, recovering from chickenpox, presented with a 1.5 x 1.5-cm mass in the lower outer quadrant of her right breast. Fine needle aspiration smears showed sheets of benign ductal cells with overlapping myoepithelial cells and many bipolar bare nuclei. Cells showing nuclear enlargement, prominent nucleoli and multilobated or multinucleated giant cell formation occurred in separate sheets or dispersed among groups of benign ductal cells. Cytodiagnosis was suspicion for malignancy; excision biopsy was advised. Histopathologic examination showed fibroadenoma with evidence of epithelial hyperplasia, nuclear enlargement and multilobated giant cell formation. Atypical ductal cells, including the giant cells, were immunohistochemically positive for epithelial membrane antigen, estrogen receptor and progesterone receptor and negative for smooth muscle actin, indicating epithelial origin. Both cytologic and histologic specimens showed focal positive reaction with HSV-1 and HSV-2 antibodies. Ultrastructural examination of aspirated material revealed cytoplasmic viral particles with characteristic surface projections. CONCLUSION: Herpes zoster virus can produce morphologic alteration mimicking a malignancy. Pathologists should be aware of these changes to avoid a false positive diagnosis.

Low carbohydrate ketogenic diet enhances cardiac tolerance to global ischaemia.

UNLABELLED: The cardio-protective effects of a low carbohydrate ketogenic diet following global ischaemic injury as compared to rats fed a normal and high carbohydrate diet for a period of 19 weeks, were investigated. The reperfusion recovery of coronary flow was highly significant in the low carbohydrate ketogenic diet group. Although the initial reperfusion recovery of the pressure developed in the left ventricle, Pmax was similar in all groups, after 15 minutes, the momentum for faster recovery was maintained in the low carbohydrate ketogenic diet group. Ultrastructural observations of the cardiac muscles have shown that there was a decrease in the number of mitochondria in rats fed a high carbohydrate diet and an increase in the number of mitochondria in those fed a low carbohydrate ketogenic diet as compared to the normal diet group. This study demonstrates that a low carbohydrate ketogenic diet is cardio-protective functionally. INTRODUCTION: Ischaemia and reperfusion lead to cell death. These pathways are regulated and hence are subjected to therapeutic intervention. Previously, we have shown that a low carbohydrate ketogenic diet (LCKD) reduces the risk factors for heart disease in obese patients. This study is aimed at understanding the cardio-protective effects of LCKD following global ischaemic injury in rats. MATERIALS AND METHODS: Rats weighing 190-250 g were divided into normal diet (ND), LCKD and high carbohydrate diet (HCD) groups consisting of six animals in each group. Specific diets were given to each group for a period of 19 weeks. Changes in body weight, ultrastructure of the cardiac muscles and the cardio-protective effects of the LCKD group as compared to the ND and HCD groups were investigated in rats following global ischaemic injury. RESULTS: Electron microscopic studies have shown that there was a decrease in the number of mitochondria in rats fed a high carbohydrate diet and an increase in the number of mitochondria in those fed a low carbohydrate ketogenic diet as compared to the normal diet group. Rats on LCKD had a remarkable tolerance to ischaemia and a faster recovery of cardiac function following reperfusion. The initial reperfusion recovery of the pressure developed in the left ventricle, Pmax was similar in all groups. However, after 15 minutes, the momentum for faster recovery was significantly maintained in the LCKD group (P < 0.05). The reperfusion recovery of coronary flow was highly significant (P < 0.05) in the LCKD regime. The increase in left ventricle end diastolic pressure, coronary vascular resistance and the changes in body weight were not significant between the experimental groups. DISCUSSION AND CONCLUSION: This is a unique study showing ultrastructural variation in cardiac muscle in relation to cardio-protective function in rats fed a low carbohydrate ketogenic diet. This study suggests that the LCKD is cardio-protective functionally. The underlying mechanism of the cardio-protective effect of an LCKD needs to be elucidated.

Beneficial effects of ketogenic diet in obese diabetic subjects.

OBJECTIVE: Obesity is closely linked to the incidence of type II diabetes. It is found that effective management of body weight and changes to nutritional habits especially with regard to the carbohydrate content and glycemic index of the diet have beneficial effects in obese subjects with glucose intolerance. Previously we have shown that ketogenic diet is quite effective in reducing body weight. Furthermore, it favorably alters the cardiac risk factors even in hyperlipidemic obese subjects. In this study the effect of ketogenic diet in obese subjects with high blood glucose level is compared to those with normal blood glucose level for a period of 56 weeks. MATERIALS AND METHODS: A total of 64 healthy obese subjects with body mass index (BMI) greater than 30, having high blood glucose level and those subjects with normal blood glucose level were selected in this study. The body weight, body mass index, blood glucose level, total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides, urea and creatinine were determined before and at 8, 16, 24, 48, and 56 weeks after the administration of the ketogenic diet. RESULTS: The body weight, body mass index, the level of blood glucose, total cholesterol, LDL-cholesterol, triglycerides, and urea showed a significant decrease from week 1 to week 56 (P < 0.0001), whereas the level of HDL-cholesterol increased significantly (P < 0.0001). Interestingly these changes were more significant in subjects with high blood glucose level as compared to those with normal blood glucose level. The changes in the level of creatinine were not statistically significant. CONCLUSION: This study shows the beneficial effects of ketogenic diet in obese diabetic subjects following its long-term administration. Furthermore, it demonstrates that in addition to its therapeutic value, low carbohydrate diet is safe to use for a longer period of time in obese diabetic subjects.

Long term effects of ketogenic diet in obese subjects with high cholesterol level.

OBJECTIVE: Various studies have convincingly shown the beneficial effect of ketogenic diet (in which the daily consumption of carbohydrate is less than 20 grams, regardless of fat, protein and caloric intake) in reducing weight in obese subjects. However, its long term effect on obese subjects with high total cholesterol (as compared to obese subjects with normal cholesterol level is lacking. It is believed that ketogenic diet may have adverse effect on the lipid profile. Therefore, in this study the effect of ketogenic diet in obese subjects with high cholesterol level above 6 mmol/L is compared to those with normocholesterolemia for a period of 56 weeks. MATERIALS AND METHODS: In this study, 66 healthy obese subjects with body mass index (BMI) greater than 30, having high cholesterol level (Group I; n = 35) and those subjects with normal cholesterol level (Group II; n = 31) were selected. The body weight, body mass index, total cholesterol, LDL-cholesterol, HDL-cholesterol, urea, creatinine, glucose and triglycerides were determined before and after the administration of the ketogenic diet. Changes in these parameters were monitored at 8, 16, 24, 32, 40, 48 and 56 weeks of the treatment. RESULTS: The body weight and body mass index of both groups decreased significantly (P < 0.0001). The level of total cholesterol, LDL cholesterol, triglycerides and blood glucose level decreased significantly (P < 0.0001), whereas HDL cholesterol increased significantly (P < 0.0001) after the treatment in both groups. CONCLUSION: This study shows the beneficial effects of ketogenic diet following its long term administration in obese subjects with a high level of total cholesterol. Moreover, this study demonstrates that low carbohydrate diet is safe to use for a longer period of time in obese subjects with a high total cholesterol level and those with normocholesterolemia.

Long-term effects of a ketogenic diet in obese patients.

BACKGROUND: Although various studies have examined the short-term effects of a ketogenic diet in reducing weight in obese patients, its long-term effects on various physical and biochemical parameters are not known. OBJECTIVE: To determine the effects of a 24-week ketogenic diet (consisting of 30 g carbohydrate, 1 g/kg body weight protein, 20% saturated fat, and 80% polyunsaturated and monounsaturated fat) in obese patients. PATIENTS AND METHODS: In the present study, 83 obese patients (39 men and 44 women) with a body mass index greater than 35 kg/m(2), and high glucose and cholesterol levels were selected. The body weight, body mass index, total cholesterol, low density lipoprotein (LDL) cholesterol, high density lipoprotein (HDL) cholesterol, triglycerides, fasting blood sugar, urea and creatinine levels were determined before and after the administration of the ketogenic diet. Changes in these parameters were monitored after eight, 16 and 24 weeks of treatment. RESULTS: The weight and body mass index of the patients decreased significantly (P<0.0001). The level of total cholesterol decreased from week 1 to week 24. HDL cholesterol levels significantly increased, whereas LDL cholesterol levels significantly decreased after treatment. The level of triglycerides decreased significantly following 24 weeks of treatment. The level of blood glucose significantly decreased. The changes in the level of urea and creatinine were not statistically significant. CONCLUSIONS: The present study shows the beneficial effects of a long-term ketogenic diet. It significantly reduced the body weight and body mass index of the patients. Furthermore, it decreased the level of triglycerides, LDL cholesterol and blood glucose, and increased the level of HDL cholesterol. Administering a ketogenic diet for a relatively longer period of time did not produce any significant side effects in the patients. Therefore, the present study confirms that it is safe to use a ketogenic diet for a longer period of time than previously demonstrated.